MUSCLES A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Muscles: 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: 0-497-11073-3 1. Muscles-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 muscles. 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 MUSCLES ................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Muscles ......................................................................................... 7 E-Journals: PubMed Central ....................................................................................................... 66 The National Library of Medicine: PubMed ................................................................................ 87 Academic Periodicals covering Muscles .................................................................................... 132 Dissertations on Muscles........................................................................................................... 132 CHAPTER 2. NUTRITION AND MUSCLES ....................................................................................... 145 Overview.................................................................................................................................... 145 Finding Nutrition Studies on Muscles...................................................................................... 145 Federal Resources on Nutrition ................................................................................................. 153 Additional Web Resources ......................................................................................................... 154 CHAPTER 3. ALTERNATIVE MEDICINE AND MUSCLES ................................................................. 163 Overview.................................................................................................................................... 163 The Combined Health Information Database............................................................................. 163 National Center for Complementary and Alternative Medicine................................................ 164 Additional Web Resources ......................................................................................................... 164 General References ..................................................................................................................... 204 CHAPTER 4. PATENTS ON MUSCLES ............................................................................................. 205 Overview.................................................................................................................................... 205 Patents on Muscles .................................................................................................................... 205 Patent Applications on Muscles ................................................................................................ 240 Keeping Current ........................................................................................................................ 270 CHAPTER 5. BOOKS ON MUSCLES ................................................................................................. 271 Overview.................................................................................................................................... 271 Book Summaries: Federal Agencies............................................................................................ 271 Book Summaries: Online Booksellers......................................................................................... 276 Chapters on Muscles .................................................................................................................. 276 CHAPTER 6. MULTIMEDIA ON MUSCLES ...................................................................................... 281 Overview.................................................................................................................................... 281 Video Recordings ....................................................................................................................... 281 Audio Recordings....................................................................................................................... 287 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................. 289 Overview.................................................................................................................................... 289 U.S. Pharmacopeia..................................................................................................................... 289 Commercial Databases ............................................................................................................... 298 Researching Orphan Drugs ....................................................................................................... 299 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 303 Overview.................................................................................................................................... 303 NIH Guidelines.......................................................................................................................... 303 NIH Databases........................................................................................................................... 305 Other Commercial Databases..................................................................................................... 307 The Genome Project and Muscles .............................................................................................. 307 APPENDIX B. PATIENT RESOURCES ............................................................................................... 313 Overview.................................................................................................................................... 313 Patient Guideline Sources.......................................................................................................... 313 News Services and Press Releases.............................................................................................. 322 Newsletter Articles .................................................................................................................... 323 Finding Associations.................................................................................................................. 327
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APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 329 Overview.................................................................................................................................... 329 Preparation................................................................................................................................. 329 Finding a Local Medical Library................................................................................................ 329 Medical Libraries in the U.S. and Canada ................................................................................. 329 ONLINE GLOSSARIES................................................................................................................ 335 Online Dictionary Directories ................................................................................................... 340 MUSCLES DICTIONARY............................................................................................................ 341 INDEX .............................................................................................................................................. 435
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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 muscles 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 muscles, 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 muscles, 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 muscles. 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 muscles, 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 muscles. 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 MUSCLES Overview In this chapter, we will show you how to locate peer-reviewed references and studies on muscles.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and muscles, 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 “muscles” (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: •
Characterization of Esophageal Striated Muscle in Patients with Achalasia Source: Digestive Diseases and Sciences. 45(2): 285-288. February 2000. Summary: Many studies have been conducted analyzing the manometric properties of patients with achalasia, but the striated portion of the esophagus has never been analyzed and is often overlooked. This article reports on a retrospective review of 120 manometric tracings (20 achalasia, 100 controls) performed between 1994 and 1997. Tracings were excluded from patients with chronic cough and nutcracker esophagus. The data were assessed for age, sex, symptoms, duration of symptoms, lower esophageal sphincter (LES) pressure, gastroesophageal gradient, upper esophageal sphincter pressure, smooth muscle contraction amplitude and duration, striated muscle contraction amplitude and duration, length from upper esophageal sphincter to maximal striated muscle contraction, and esophageal length. The maximum striated
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muscle contraction amplitude was significantly decreased in achalasia patients with a median amplitude of 45 mm Hg versus 76 mm Hg in the control group. Although the wave forms were similar, the maximum striated muscle contraction duration and the distance from the upper esophageal sphincter in achalasia patients was not significantly different from controls. The length of the esophagus was significantly longer in achalasia patients than in the control group. The authors conclude that patients with achalasia have significantly lower maximum striated muscle contraction amplitudes and longer esophagi, but the duration of the contractions and the configuration of the wave forms are not different. 2 figures. 2 tables. 12 references. •
Significance of Pelvic Floor Muscles in Anal Incontinence Source: Gastroenterology. 123(5): 1441-1450. November 2002. Contact: Available from W.B. Saunders Company. 6277 Sea Harbor Drive, Orlando, FL 32887-4800. (800) 654-2452. Website: www.gastrojournal.org. Summary: The pathophysiology of anal incontinence may be elusive using current measurements. This article reports on a study undertaken to establish the role of the levator ani muscles in anal incontinence. The study included 53 patients with anal incontinence, 30 with constipation as disease controls, and 15 healthy controls. The authors evaluated incontinence severity by a 0-12 scale, anorectal function by standard manometric tests, and levator ani contraction by a perineal dynamometer. Patients with incontinence exhibited various physiological abnormalities, but analysis showed that levator ani contraction was the independent variable with strongest relation to the severity of incontinence. Furthermore, in contrast to other physiological parameters, clinical improvement in response to treatment was associated with a marked and significant strengthening of levator ani contraction. The authors conclude by reiterating the importance of levator ani failure in understanding the etiology (cause) of anal incontinence and in predicting response to treatment. 5 figures. 3 tables. 34 references.
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Anatomic Plane of Separation Between External Anal Sphincter and Puborectalis Muscle: Clinical Implications Source: Diseases of the Colon and Rectum. 42(3): 374-379. March 1999. Contact: Available from Williams and Wilkins. 352 West Camden Street, Baltimore, MD 21201-2436. Summary: The possible existence of an anatomic and functional separation between the external sphincter and the puborectalis muscle has been reported in the medical literature. In this article, the authors confirm, by means of anatomic and clinical observations, the presence of such a separation and focus on its importance in understanding the pathway of diffusion for some suppurative anal lesions and in planning advanced procedures to spare the sphincter. Twenty adult anatomic specimens of the anal region (from 12 women, and 8 men) were cut in the sagittal, coronal, and paracoronal planes, stained with hematoxylin and eosin, and examined. The pelvic floor musculature was examined in 3 patients undergoing postanal repair operations. Primary posterior and posterolateral anal fistulas in 11 women and 19 men were carefully traced during and after staged fistulotomy. An attempted was made peranally to separate the external sphincter from the puborectalis muscle to spare the sphincter in 4 patients (3 women) aged 56 to 65 years with rectal cancers 4 to 5 cm from the anal verge. The results of these investigations showed a connective plane of separation between the puborectalis muscle and the external sphincter. An anatomicofunctional separation between the puborectalis muscle and the external sphincter was easily
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demonstrated during anal repair operations. The authors conclude that the presence of this plane is important to help understand the diffusion of some suppurative anal lesions and to plan advanced procedures to spare the sphincter. 9 figures. 26 references. (AA-M). •
Effects of Adductor Muscle Stimulation on Speech in Abductor Spasmodic Dysphonia Source: Laryngoscope. 110(11): 1943-1949. November 2000. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2300. Fax (301) 824-7390. Summary: This article reports on a study undertaken to determine whether adductor laryngeal muscle stimulation might be a beneficial treatment alternative for abductor spasmodic dysphonia (ABSD). Baseline comparisons were made of measures of voiceless consonant and syllable duration between patients with ABSD (n = 10, two men and eight women, aged 36 to 69 years) and normal control subjects. Speech and voice production with and without muscle stimulation were compared within 10 patients with ABSD. Baseline group comparisons were conducted on measures of syllable and voiceless consonant duration between the patients and the control subjects. Neuromuscular stimulation was applied to the thyroarytenoid or lateral cricoarytenoid muscles in the patients during extended phonation, and measures were made of fundamental frequency and sound pressure level in the stimulated and nonstimulated conditions. Voiceless consonant duration was compared with and without adductor laryngeal muscle stimulation during syllable repetitions and sentences in the patients. Before stimulation, the patients had increased syllable durations in comparison with control subjects. Repeated within patient comparisons with and without stimulation demonstrated significant reductions in voiceless consonant durations during syllable repetition. The more severely affected patients had the greatest reductions in voiceless consonant duration during sentence production. The authors conclude that adductor muscle stimulation improved speech production in patients with ABSD, and the improvement was greatest in the most severely affected patients. Therefore, adductor muscle stimulation has potential for benefiting patients with ABSD. 8 figures. 2 tables. 22 references.
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Diabetic Muscle Infarction: An Underdiagnosed Complication of Long-Standing Diabetes Source: Diabetes Care. 26(1): 211-215. January 2003. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reports on a systematic review of all the reported cases of diabetic muscle infarction (DMI) and its pathogenesis, clinical features, prognostic implications, and management. The authors searched databases (MEDLINE and EMBASE) from their inception to August 2001 and reviewed bibliographies in reports retrieved. A total of 47 references were retrieved; 115 patients and 166 episodes were included. Clinical presentation of DMI is uniform, with acute onset of painful swelling of the affected muscle. DMI was more frequent in women. Of the cases, 59 percent had type 1 diabetes; the mean duration of disease was 14.3 years; and multiple diabetic end-organ complications were noted. DMI affects the lower limbs with abrupt onset of pain and local swelling. Diagnosis is made by biopsy, but the characteristic features in magnetic
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resonance imaging (MRI) are very typical. Treatment includes bed rest and administration of analgesics, but recurrence is common. 3 figures. 1 table. 49 references. •
Basic Clinical Management of Muscle Strains and Tears Source: Journal of Musculoskeletal Medicine. 20(6): 303-307. June 2003. Summary: This journal article discusses prevention, diagnosis, and treatment of muscle strains and tears. Muscle strains and tears are injuries to a muscle or tendon that occur when the muscle is stretched excessively. Muscle strains are more common than tears. These injuries, especially hamstring strain, are common in athletes. Most patients with muscle strain injuries present after an acute onset of pain during activity. Physical examination may reveal local swelling or ecchymosis; palpitation usually reveals localized tenderness over the myotendinous junction. Radiographs may only show soft tissue swelling but should be obtained if there is any concern about fracture. MRIs may be helpful if the diagnosis is unclear. Acute management of muscle strain injuries includes rest, ice, compression, elevation cryotherapy, and NSAIDs. Prolonged immobilization after strain injury should be avoided, and an exercise program should be instituted after pain and swelling subside to recover range of motion, strength, endurance, and eventually, normal athletic skills. Surgery may be required in the rare case of a complete tear with significant retraction of the muscle from the tendon. Flexible, strong, and warmed-up muscles are the key to strain rehabilitation and injury prevention. 11 references and 2 figures. (AAM).
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Muscle Tone Abnormalities Source: Rehabilitation Nursing. 22(3):118-123,130; May/June 1997. Summary: This journal article for health professionals presents current information about alterations in muscle tone. Rehabilitation nurses frequently encounter clients with neurological disorders that adversely affect muscle tone, so, if they understand the physiological etiology of abnormal muscle tone, they can design nursing interventions for various care settings. Topics discussed include the basis of motor control; the relationship between the type of muscle tone alteration and the location of neurological damage; the differences between spasticity, rigidity, and flaccidity; the medical and physical treatment approaches to muscle tone problems; and the nurse's role in managing alterations in muscle tone. 20 references, 2 figures, and 3 tables. (AA-M).
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The Effects of Muscle Fatigue on Neuromuscular Function and Anterior Tibial Translation in Healthy Knees Source: American Journal of Sports Medicine. 24(5):615-621. 1996. Summary: This journal article for physicians investigated the effect of quadriceps and hamstring muscle fatigue on anterior tibial translation and muscle reaction time in 6 men and 4 women, all healthy, with an average age of 21.3 years with no known pathologic knee conditions. Each patient underwent a knee examination, arthrometer measurements of tibial translation, subjective functional assessment, and an anterior tibial translation stress test before and after quadriceps and hamstring muscle-fatiguing exercise. The recruitment order of the lower extremity muscles in response to anterior tibial translation did not change with muscle fatigue. However, results showed that an average increase of 32.5 percent in anterior tibial translation (range, 11.4 percent to 85.2 percent) after fatigue. Muscle responses in the gastrocnemius, hamstring, and quadriceps originating at the spinal cord and cortical level showed significant slowing and, in some cases, an absence of activity after the quadriceps and hamstring muscles
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were fatigued. The authors indicate that increases in displacement after fatigue strongly correlated (0.62 to 0.96) with a delay in cortical activity (intermediate and voluntary). Muscle fatigue, which appears to affect the dynamic stability of the knee, alters the neuromuscular response to anterior tibial translation. It is suggested that fatigue may play an important role in the pathomechanics of knee injuries in physically demanding sports. 3 tables, 1 figure, and 26 references. (AA) •
How To Evaluate the Patient Who Has Muscle Disease Source: Journal of Musculoskeletal Medicine. 17(7): 407-410,413. July 2000. Summary: This journal article provides health professionals with information on the evaluation of a patient who complains of muscle weakness, pain, dysfunction, or fatigue. Many conditions can affect the skeletal muscles, including inflammatory diseases such as polymyositis or one of the connective tissue disorders; endocrine, genetic, and metabolic disorders; and central and peripheral nervous system diseases. The patient history can help establish the severity of the symptoms. When questioning patients about their symptoms, the physician should list the tasks they now have difficulty performing and also quantify as much as possible their degree of weakness or strength. An additional area of inquiry that is crucial for the diagnosis of muscle disease is the family history. Facts gained from the family history may be of great value in suggesting the presence, or at least the strong possibility, of a particular disease. The physical examination should attempt to quantify the patient's muscle strength, assess other aspects of muscle function, and detect abnormal movements and reflex changes. During the examination, the physician should look for abnormal movements and reflex changes, as well as changes in muscle volume. Biochemical analyses of muscle enzymes and serum myoglobin, electromyographic studies, magnetic resonance imaging, sonography, and muscle biopsy can help confirm the diagnosis. 3 tables. (AA-M).
Federally Funded Research on Muscles The U.S. Government supports a variety of research studies relating to muscles. 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 muscles. 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 muscles. The following is typical of the type of information found when searching the CRISP database for muscles:
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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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Project Title: A RODENT MODEL FOR LOCOMOTOR TRAINING WITH FNS Principal Investigator & Institution: Jung, Ranu; Associate Professor; Ctr for Biomedical Engineering; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 17-JAN-2002; Project End 31-OCT-2002 Summary: The long-term goal of this work is to develop strategies for using functional neuromuscular stimulation (FNS) of paralyzed muscles to enhance the recovery of individuals with incomplete spinal cord injury. The proposed work is motivated by three important developments. First, recent basic science and clinical studies have demonstrated that the degree of functional recovery of the injured spinal cord depends on the activity patterns of neural inputs to the spinal cord. Second, recent advances have produced adaptive controllers for FNS systems that provide a means of automatically adjusting stimulation parameters to reliably achieve specified rhythmic movements. Third, rodent models of spinal cord injury (complete and incomplete lesions) are extensively being used at the molecular, cellular, and systems level to investigate the effects of traumatic injury and to assess the results of therapeutic intervention. A combination therapy that utilizes locomotor training with FNS and pharmacological intervention is likely to be the most effective in enhancing the reorganization (plasticity) of the spinal circuitry that is spared after spinal trauma. A rodent model for FNSassisted locomotion would facilitate quantitative evaluation of therapeutic regimens that include FNS and would provide the ability to characterize effects of FNS-assisted locomotion on the neuroanatomy and neurophysiology of the injured spinal cord. This biomedical engineering research grant proposal will develop a rodent model of locomotor training that utilizes treadmill walking and functional neuromuscular stimulation (FNS) with fixed-pattern and adaptive controllers. Kinematic and electromyogram (EMG) patterns of intact animals will be examined and then used to develop stimulation patterns for FNS-assisted movement. A series of tasks will be performed using FNS stimulation of hindlimb muscles in spinalized rats. These tasks will progress in difficulty from controlling suspended hindlimb movements to controlling hindlimb movements during treadmill locomotion in spinalized rats with partial weight support. Two different FNS control strategies will be used for each movement: a fixed-pattern, or open-loop, stimulation pattern and an adaptive stimulation control system. The adaptive stimulation control system will build upon our previous work and is expected to provide movement patterns that are more accurate and more repeatable. Successful completion of the proposed project will result in a novel animal model for FNS-assisted locomotor training and provide quantitative methods for evaluating locomotor behavior. In future studies, we plan to use a rodent model of incomplete spinal cord injury with FNS-assisted locomotion to test the hypothesis that FNS-assisted locomotor training enhances motor recovery after incomplete spinal cord injury. We anticipate that the improved performance provided by the adaptive control system may enhance the therapeutic effects of the technique. This locomotor training could also be combined with pharmacological intervention, tissue transplant, and neural repair therapies to determine if locomotor training can enhance the effectiveness of these therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ACL DEFICIENT KNEE--MRI AND BIOMECHANICAL MODELING Principal Investigator & Institution: Buchanan, Thomas S.; Professor and Director; Mechanical Engineering; University of Delaware Newark, De 19716 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2004
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Summary: The overall goal of this work is to provide a detailed understanding of the effect of anterior cruciate ligament injury on knee movement in those who compensate well for the injury and those who do not. Some persons (copers) are able to fully compensate for the absence of the anterior cruciate ligament (ACL) while others (noncopers) are not. Non-copers demonstrate quadriceps femoris weakness, and use kinematic, kinetic, and muscle activity patterns that stiffen the knee joint for stability. They accomplish the joint stiffening via general cocontraction of the muscles around the knee and by reducing the force with which the foot hits the ground. Copers have no quadriceps weakness, normal ground reaction forces, and possess an ability to coordinate the activity of the lower extremity muscles to efficiently distribute control of the knee among the hip, knee and ankle while maintaining normal knee motion. Even using sophisticated motion analysis techniques, copers are indistinguishable from uninjured subjects. A new approach to in vivo analysis of musculoskeletal dynamics uses Cine-phase contrast (Cine-PC) magnetic resonance imaging (MRI) to image and track the moving knee. Cine-PC MRI, a non-invasive technique, is capable of measuring 3D muscle fiber and skeletal velocity, in vivo, during dynamic tasks. Through integration, 3D musculoskeletal movement can be tracked. A combination of the use of this new technology and conventional MRI, electromyography, and musculoskeletal modeling will provide a unique opportunity to elucidate the compensation strategies employed by the copers. There are two aims to this proposal. Aim I is to identify differences in knee kinematics, ligament lengths, tendon lengths, and muscle activation patterns of ACL deficient patients using Cine-phase contrast MRI and electromyographic analysis that characterize the mechanisms with which the copers, in altering their muscle activation pattern, alter their knee joint kinematics in order to stabilize their knees. Aim II is to identify differences in muscle activation patterns in ACL deficient copers and non-copers using electromyography and biomechanical modeling. Patient specific models of the ACL deficient knee using T1-weighted MRI will be developed and used as input to a biomechanical analysis. Previous work suggests that patients with ACL deficiencies balance knee joint loads between muscles and ligaments using a strategy that is different than that employed by unimpaired subjects. This will be examined for copers and non-copers in this study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALTERATIONS IN NEUROMUSCULAR FUNCTION FOLLOWING BURNS Principal Investigator & Institution: Martyn, J A.; Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 01-DEC-1983; Project End 31-MAR-2007 Summary: (provided by applicant): Muscle weakness accompanies all forms of critical illnesses including burns, resulting in hypoventilation, dependence on respirators, and decreased mobilization, all of which lead to increased morbidity and mortality. The loss of muscle strength is out of proportion to loss of muscle mass. It is hypothesized (a) since prolonged open channel time of acetylcholine receptors (AChRs) due to congenital mutations of AChRs results in muscle weakness, the weakness of muscles in close proximity to bums is related to the expression of gamma subunits containing an "immature" isoform of AChRs, which also have a longer mean open-channel time; (b) that akin to that seen in many congenital muscular dystrophies (CMDs), the weakness in muscles at sites distant from burn occurs as a result of changes in muscle membrane structural components termed dystrophin associated complexes (DACs). It is postulated that the pathophysiological bases for the neuromuscular changes following burns are
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related to (a) decreased signaling via agrin, important for clustering, expression, and maturation of the AChRs, and (b) decreased growth factor signaling via Akt/PKB, important for stabilization and maintenance of DACs, respectively. Related to the above: Specific Aim 1 tests the hypotheses (1) that muscles in close proximity to burn injury express an immature isoform of AChRs at the neuromuscular junction (NMJ), resulting in aberrant neurotransmission, (2) that these AChR changes are related to increased expression of iNOS, resulting in decreased signaling of agrin, and (3) that iNOS inhibitors and/or exogenous agrin will reverse the AChR changes and enhance muscle function. Specific Aim 2 tests the hypothesis that the diminished contractility of skeletal muscle at sites distant from bum is due to changes in muscle membrane DAC, independent of AChRs, since AChRs are unaltered at sites distant from burn. Muscle membrane costamere integrity will be determined by confocal microscope. Biochemical fractionation techniques (velocity gradients) will be utilized to detect molecular localization of each DAC component (dystrophin, dystroglycan, caveolin-3, and integrin), since abnormal localization of these membranes will result in disruption of costamere integrity. Specific Aim 3 using the rat in vivo model and the in vitro cell culture model, tests the hypothesis that bum injury-induced malformation of DAC is due to decreased pro-anabolic signaling via Akt/PKB. Specific Aim 4 tests the hypothesis that the attenuated Akt/PKB activity at sites distant from burn can be rectified by parenteral IGF-I or adenovirus transfer of Akt/PKB, both of which will restore the DAC integrity and function to normal. Delineation of the pathophysiology of burn-induced muscle dysfunction will provide a scientific rationale for therapeutic approaches to prevent muscular complications of burns. These mechanistic studies will also help to understand the molecular etiology of other acquired and congenital diseases of muscle, which affect muscle function in a vast number of adult and pediatric patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANATOMICAL SPECIALIZATIONS OF THE HUMAN PHARYNX Principal Investigator & Institution: Mu, Liancai; Otolaryngology; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2005 Summary: (Applicant's abstract): What variables in the neuromuscular properties of the human pharynx make some patients more susceptible to aspiration, obstructive sleep apnea (OSA), acid reflux, cricopharyngeal spasm and other disorders of the pharyngeal region? In most mammals (and neonatal humans) the respiratory system is protected by overlapping the epiglottis and soft palate, however with separation of these structures the human at risk of aspiration, and this is often the cause of death in the elderly and neurologically impaired. At present the basic neuromuscular specializations of the human pharynx are poorly understood. In preliminary work numerous novel observations were made, one example is that of the human cricopharyngeus (CP) muscle; That the CP receives its innervation from multiple nerves, each of which supplies a distinct region within the muscle, and that it contains specialized muscle fibers. One of these, slow tonic muscle fibers (STMF) has a unique physiology. STMF are extremely rare in mammals but preliminary work has shown that they are widespread in human upper airway structures including the tongue and larynx. Moreover the particular distribution of these fiber suggests that they are directly related to distinct biomechanics. The proposed work will focus on clarifying the peripheral organization patterns of the human pharyngeal plexus and characterizing the intrinsic properties of the CP and the muscles surrounding the pharynx to answer the questions: what
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anatomic specializations are present that appear specific to humans and possibly speech and swallowing related? What variations in these specializations correlate with certain ethnic (black males OSA), genders (males reflux, OSA) and especially geriatric (CP spasm and aspiration) susceptibility to specific disorders? All studies will be done in human post-mortem tissue. The motor and sensory nerve supply to the pharyngeal region will be studied using Sihler's stain. An additional hypothesis to be tested is that the human glossopharyngeal nerve (IX) provides motor innervation not only to the traditionally described stylopharyngeus, but also to the CP and pharyngeal constrictor muscles as demonstrated by our preliminary studies. This will be studied by triple approaches: Sihler's stain whole-mount acetylcholinesterase (AChE) and silver stain, and Karnovsky-Roots' method. Another hypothesis to be tested is that most swallowingrelated muscles are specialized and composed of neuromuscular compartments (NMC) as functional requirements. Our preliminary studies provided evidence for the existence of the NMC within the human CP inferior constrictor and geniohyoid muscles. In addition, the human CP appears to be a specialized skeletal muscle as it contains slow tonic and a-cardiac myosin heavy chain isoforms that are not normally present in limb muscles. The muscular specializations of the upper esophageal sphincter, pharyngeal constrictor and suprahyoid muscles will be explored using a wide variety of histochemical, immunohistochemical, electrophoretic and immunoblotting techniques The muscle fiber architecture, distribution of the fiber types and the major and unusual myosin heavy chain isoforms will be studied. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANKLE STRENGTHENING TO IMPROVE GAIT AND FUNCTION IN CP Principal Investigator & Institution: Engsberg, Jack R.; Associate Professor; Neurological Surgery; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-MAY-2005 Summary: (provided by the applicant): Many treatments exist to improve the gait and function of persons with Cerebral Palsy (CP). Despite recognizing that muscle weakness is a major impairment in CP, none of the treatments have the direct aim of strengthening muscles. Our results from an NIH investigation (R01-NS035830) indicated high correlations between ankle strength and function, with greater strength correlated with higher function. The idea of strengthening muscles has been controversial for safety issues. The purposes of this pilot investigation are to: 1) establish sample sizes for a future randomized clinical trial determining if intensive ankle strength training programs can improve strength, gait, and function without increasing spasticity; and 2) investigate potential safety issues arising from the training programs. Aim 1: Establish sample sizes for a future randomized clinical trial determining if intensive ankle strength training programs can improve ankle strength, gait, and function without increasing spasticity. Twenty ambulatory subjects with spastic diplegia CP will be randomly assigned to one of 4 groups: 1) Dorsi-flexor strength training group; 2) Plantar-flexor strength training group; 3) Dorsi-plantarflexor strength training group; and 4) the group undergoing no intensive strength training program. Subjects in the strength training groups will participate in a 12-week progressive, resistance strengthtraining program. Prior to, and at the end of the training program, all subjects will be objectively assessed for ankle Plantar-flexor spasticity, ankle strength, gait, and GMFM. The data will be used in a repeated measures power analysis to establish sample sizes for the clinical trial. Aim 2: Investigate potential safety issues arising from the training programs. The aim has 2 components. The first is the weekly measurement of Plantar-
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flexor spasticity and tightness. The data will permit continuous monitoring of spasticity and tightness, and alert investigators to potential problems during each subject's participation. In the second component, both the pre- and post-intervention measures, and the weekly monitoring of spasticity and tightness, will determine if potential changes could be a concern for the future clinical trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOMECHANICS
ANTERIOR
CRUCIATE
LIGAMENT-FUNCTIONAL
Principal Investigator & Institution: Andriacchi, Thomas P.; Professor; Mechanical Engineering; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-APR-1988; Project End 31-MAY-2005 Summary: The long-term goal of this project is to provide information that can be applied to the prevention and treatment of injury to the anterior cruciate ligament (ACL) of the knee. The annual incidence of acute ACL disruptions is approximately 1 in 3000. Treatment of the ruptured anterior cruciate ligament is often complicated by the difficulty in predicting from passive physical examination of the knee which patients will be functionally impaired by the loss of this ligament and which patients will have minimal symptoms. Is it possible that altered patterns of locomotion dynamically compensate for loss of the ACT? Quantifying the relationship between altered patterns of locomotion and changes in the anterior-posterior displacement (AP) and internalexternal rotation (IE) of the knee is a fundamental step towards answering this question. This information is clinically important since the AP and IE components of knee motion influence strains in secondary restraints (to anterior laxity) such as the medial meniscus of altered patterns of locomotion for ACL deficient knees. A newly developed point cluster technique will be used to quantify knee kinematics during locomotion. The first hypothesis will test if altered patterns of locomotion (characterized by the magnitude of the moment generated by net quadriceps/knee flexor muscles) are correlated with AP and IE displacements at the knee. Another consideration in this study is the possibility that individual anatomical variations can influence the effect of altered patterns of locomotion on knee kinematics. Previous work has implicated the extensor mechanism as a possible cause of these adaptations. The second hypothesis will test if the magnitude of the altered pattern of locomotion (defined by the reduction from normal) in the net quadriceps/knee flexor moment) is correlated with knee extensor anatomy. This study will generate fundamental new information on the patient's ability to dynamically control anterior posterior stability of the knee joint in the absence of anterior cruciate ligament. This study will also help to identify critical variables that should be considered in a larger prospective clinical outcome study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BINOCULAR COORDINATION IN MONKEYS WITH STRABISMUS Principal Investigator & Institution: Das, Vallabh E.; Neurology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2007 Summary: (provided by applicant): Binocular alignment must be maintained in the horizontal, vertical and torsional planes to ensure binocular sensory fusion. Normal development ensures binocular alignment during fixation and binocular coordination during eye movements. Unfortunately, abnormal visual experience during development usually leads to ocular misalignment (strabismus). In fact, various studies have reported
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the incidence of strabismus to be about 2-5% of the infant population. Data from strabismic humans and from strabismic monkeys in our laboratory have shown that ocular misalignment is accompanied by a lack of conjugate eye movements. Though strabismus is most often associated with a horizontal misalignment, often a combined horizontal, vertical and torsional misalignment is observed. Along with the static horizontal, vertical and torsional misalignment, there appears to be substantial dynamic cross-talk between the principal eye movement planes. In the clinical literature these apparent cross-axis interactions are usually described as 'A' and 'V' patterns of strabismus. Unfortunately, there is a lack of understanding of the neural or mechanical bases for these cross-axis movements, the putative relationship or lack thereof to the neural control of horizontal, vertical or torsional eye movements and the relationship to the etiology of the strabismus. Competing hypotheses include static malpositioning of extraocular muscle pulleys, sideslip of extraocular muscles and muscle pulleys, torsional control of eye movements gone awry leading to apparent muscle dysfunction and finally simply unexplained overaction/underaction of individual extraocular muscles. The goal of our studies is to clarify static and dynamic properties of cross-axis movements and examine its source in animals with a sensory induced strabismus. Our approach will include structural imaging of extraocular muscle to determine role of muscle pulleys; behavioral experiments to examine control of torsion and Listing's laws; neurophysiological experiments to examine the role of motor and pre-motor structures in the brain and biomechanical modeling of extraocular musculature to simulate experimental data. Completion of our studies will be of benefit to the understanding and treatment of certain types of strabismus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BINOCULAR MATCHING AND DISPARITY VERGENCE. Principal Investigator & Institution: Stevenson, Scott; Vision Sciences; University of Houston 4800 Calhoun Rd Houston, Tx 77004 Timing: Fiscal Year 2002; Project Start 10-APR-2001; Project End 31-MAR-2004 Summary: (adapted from applicant's abstract): Proper alignment of the eyes is essential for clear, single vision. Misalignment during early development can lead to amblyopia, a permanent visual impairment. Eye alignment during gaze changes is determined both by the anatomical organization of extraocular muscles and by the coordinated, visuallyguided control of those muscles. The detection and correction of alignment errors from binocular comparison of retinal images is referred to as Disparity Vergence, and has both reflexive and voluntary aspects. The reflexive component of disparity vergence corrects horizontal, vertical and cyclotorsional errors of alignment, while voluntary control is restricted to horizontal vergence. This project is concerned with the visual information processing that provides the basis for reflexive disparity vergence, as revealed by vertical vergence responses. Previous work by the Principal Investigator has shown that the vertical vergence controller can extract vertical disparity signals from dynamic random dot stereograms, but that vertical vergence is not influenced by visual attention or subject effort and often occurs without conscious awareness. These movements thus reflect visual processes that are binocular, most probably cortical, but pre-conscious. The experiments in this project provide a way to study processing at an intermediate stage of the visual system. These processes are central to the control of eye alignment, but cannot be studied with conventional psychophysical techniques because they do not necessarily contribute to visual perception. An eye tracking device is used to detect small changes in eye alignment made in response to imposed vertical image misalignment, allowing for measurement of the vergence system's sensitivity to a
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variety of image parameters. Proposed experiments will determine the role of contrast, spatial and temporal frequency, and visual feature type in the control of reflexive vergence eye movements. Measurements in subjects with abnormal binocularity will follow up on preliminary evidence that reflex vergence is intact in some cases of stereoblindness. Comparison to results from conventional psychophysical sensitivity measures will highlight differences between early (pre-conscious) and later (perceptual) visual processes. The long-term benefit of this research will be improvements in the diagnosis and treatment of binocular visual disorders of eye alignment and depth perception. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOARTIFICIAL MUSCLES FOR GENE THERAPY Principal Investigator & Institution: Vandenburgh, Herman H.; Associate Professor; Cell Based Delivery, Inc. 4 Richmond Square, 5Th Fl Providence, Ri 02906 Timing: Fiscal Year 2002; Project Start 15-APR-1998; Project End 31-MAR-2003 Summary: Recombinant proteins are used to treat a number of human disorders including diabetes, neutropenia, anemia, and musculoskeletal disorders of the elderly. Muscle atrophy and bone wasting associated with aging can be attenuated using growth hormone (GH), insulin-like growth factor-1 (IGF-1), and parathyroid hormone (PTH) but delivery by daily injection is problematic since the proteins degrade rapidly in vivo, are expensive to manufacture, and have detrimental side effects when delivered at pharmacological doses. Cell based delivery of proteins from genetically-modified implanted cells may provide a more effective and cost-saving alternative. The long-term objective of this project is to develop and optimize the surgical techniques for reversible delivery of proteins from bioartificial muscle platforms. Muscle stem cells (myoblasts) can be isolated by simple needle biopsy and genetically modified to express foreign proteins. When tissue engineered in vitro into skeletal muscle-like bioartificial muscles (BAMs) and implanted in vivo, they serve as a long-term delivery system for biologically active proteins. Advantages of this technology over currently used injected myoblasts or plasmid DNA gene therapy techniques include efficient in vitro fusion of myoblasts into BAMs, preimplantation monitoring of growth factor secretion levels, and reversibility. BAMs secreting recombinant human GH (rhGH) and engineered from a murine C2C12 muscle cell line successfully attenuate skeletal muscle disuse atrophy when implanted subcutaneously under tension in mice. In the current project, primary myoblasts from inbred Fisher 344 rats will be transduced to constitutively express rhGH or IGF-1 using retroviral expression constructs under the control of the LTR viral promoter. New replication defective retrovirus expression vectors with the GH, IGF-1, and PTH genes under control of the regulatable human skeletal alpha -actin (HSA) promoter will also be constructed. BAMs from transduced primary rat myoblasts will be engineered using previously developed protocols and their morphology and protein secretion rates evaluated in vitro and in vivo. Rat BAM (R-BAM) myofiber survival, differentiation, innervation, and vascularization in subcutaneous and muscular sites will be studied by quantitative histological, immunocytochemical and biochemical techniques. The ability of GH, IGF-1 and PTH secreted from R-BAMs to attenuate muscle atrophy and bone wasting will be assessed in hindlimb unloaded adult Fisher rats. New therapeutic treatments with recombinant proteins for chronic musculoskeletal wasting disorders will lead to enhanced quality of life and reduced costs in this 150 billion dollar annual U.S. healthcare market. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOMECHANICALLY BASED SHOULDER REHABILITATION STRATEGIES Principal Investigator & Institution: Ludewig, Paula M.; Phys Med and Rehabilitation; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The candidate's long-term career objective is to investigate biomechanical factors contributing to musculoskeletal dysfunction, in order to refine current clinical treatment approaches and develop novel scientifically founded rehabilitation interventions. A five-year research and training plan developed with the primary mentor and a team of experienced scientists will expand the candidate's scientific background in biomechanics and musculoskeletal modeling, enrich her direct research skills and experience in the scientific process, promote integration of research findings to clinical practice, and advance skills necessary for becoming an independent investigator. The long-term objective of the research plan is to develop and test the effectiveness of biomechanically based rehabilitation strategies for improving upper extremity function and reducing pain and disability in persons with shoulder pathologies related to abnormal shoulder movement patterns. In-vivo 3-D full shoulder complex kinematics (thorax, clavicle, scapula, and humerus) during arm elevation will be collected from healthy and symptomatic subjects and integrated with a state of the art shoulder model to describe the 3-D muscle function of selected shoulder muscles, allowing comparisons among muscles for their relative biomechanical ability to reduce shoulder kinematic deviations, or contribute to deviations if producing excess or inadequate force (Aim 1). Computerized Tomography scans of the shoulder complex structures will be taken and imaging data combined with the kinematic data, allowing determination of the effects of abnormal kinematics on the available volume of the subacromial space, providing insight into how specific kinematic deviations create impingement of soft tissue structures (Aim 2). Determining and demonstrating muscle activations that can improve scapular kinematics and reduce subacromial impingement can provide a template for scientifically based intervention approaches that can be further tested through clinical trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BODY COMPOSITION CHANGES IN THE ELDERLY--SARCOPENIA Principal Investigator & Institution: Baumgartner, Richard N.; Professor; Medicine; University of New Mexico Albuquerque Controller's Office Albuquerque, Nm 87131 Timing: Fiscal Year 2002; Project Start 30-SEP-1993; Project End 31-MAY-2004 Summary: (Adapted from Investigator's Abstract) The main objectives of this competing continuation application are to develop methods of estimating the prevalence and incidence rates of sarcopenia, or deficient relative muscle mass, and to determine sex and ethnic differences in risk factors and consequences of sarcopenia in communitydwelling elderly. It is accepted that muscle mass and strength are gradually lost with age. Because there are few methods of quantifying muscle mass in population studies, and criteria for defining "deficient" muscle mass remain to be established, estimates of the prevalence and incidence of sarcopenia are lacking and the extent of the public health problem posed is unknown. Age-related loss of muscle mass is undoubtedly multifactorial. Although a variety of possible mechanisms and etiological factors have been indicated, there are few data for multivariate associations of risk factors with sarcopenia. Sarcopenia is believed to be a major factor associated with physical functional impairment, and a number of studies have reported that indicators of muscle
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strength and function (e.g., balance, gait speed, etc.) are associated with disability and falls in elderly people. There are few reports, however, for direct associations between sarcopenia and disability or falls. Sex and ethnic differences in rates of loss for muscles mass and strength, risk factors and consequences remain to be established. The proposed study will establish methods for defining sarcopenia using cross-sectional data collected previously in the New Mexico Elder Health Survey (NMEHS, 1993-1996, n = 883) and reference data to be collected for a population-based sample of 300 young adults 20 to 40 years of age. Risk factors and long-term consequences of sarcopenia will be studied using 4 to 10 years of follow up data by continuation of the New Mexico Aging Process Study (NMAPS, current n = 404). The following variables have been measured in the NMAPS since 1993: muscle mass from dual-energy X-ray absorptiometry, serum nutrient and hormone levels (e.g. free-T, estrone, IGF1, DHEAs, leptin), dietary intake, physical activity and resting energy expenditure, cognitive and physical functional status, disability, incident falls and morbidity. Data collected for these variables will be extended another 5 years. The NMEHS included Hispanic elderly men and women: 200 new Hispanic participants will be recruited in the NMAPS to further facilitate ethnic comparisons for risk factors and consequences of sarcopenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BONE GROWTH, PERIOSTEAL MIGRATION AND MUSCLE FUNCTION Principal Investigator & Institution: Herring, Susan W.; Professor & Acting Chair; Orthodontics; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-MAY-1990; Project End 31-MAR-2008 Summary: (provided by applicant): Our overall goal is to clarify the influence of function on the growth and ultimate morphology of the head. The mechanical environment influences skull growth at every level from individual cells to gross structure. Although usually neglected, soft tissues such as muscles, ligaments and cartilages play a critical role in cranial mechanics and growth. This proposal focuses on two ways in which soft tissue mechanics may direct the growth of skull bones, using the pig as a model. First, the osteogenic activity of the periosteum is linked to its blood supply, which originates from muscles and ligaments. We hypothesize that the deformation of these soft tissues during function can modify periosteal perfusion. In Specific Aim 1, new methodology will be employed to map the three-dimensional deformation of muscles and ligaments during awake mastication and to test whether buccinator contraction places significant pressure on the alveolar periosteum. Specific Aim 2 addresses the periosteal vascular system directly with both immunocytochemical assays of cellular activity and in vivo measures of blood flow. These studies will provide evidence for or against a causal linkage between soft tissue behavior and periosteal perfusion. The second way in which soft tissues may direct skull growth involves the nasal septum. Despite being an unmineralized cartilage, the septum has been considered an important mechanical support of the face. Moreover, forces generated by septal growth are claimed to separate the sutures between facial bones, causing compensatory growth. These assertions have never been tested directly. In Specific Aim 3 a novel indwelling transducer will be used to reveal the mechanical loading pattern of the septum and to investigate the timing of its growth in relation to that of facial sutures. Specific Aim 4 will test the mechanical plausibility of the hypothesis that the septum controls facial growth by comparing the viscoelastic stiffness of the cartilaginous septum to the resistance of the facial sutures. Taken together, these studies will develop new techniques for monitoring soft tissue function, provide fundamental new information
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about the mechanical behavior of the head, and test hypotheses about how soft tissues influence skull growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CARDIAC CONTRACTILE PROTEIN COOPERATIVITY Principal Investigator & Institution: Tobacman, Larry S.; Professor; Internal Medicine; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-AUG-1987; Project End 31-JUL-2006 Summary: (provided by applicant): This proposal concerns the mechanism controlling the repetitive contraction and relaxation of the heart, at the level of the protein assemblies that comprise the contractile apparatus. Cyclical variation in the calcium concentration causes calcium binding to and dissociation from troponin, which interacts with the other thin filament proteins tropomyosin and actin so that the thin filament switches between states that will or will not support contraction. A comparable system also exists in skeletal muscles. The long term goal of this work is to understand how troponin and tropomyosin exert this direct regulation, because of its fundamental physiological importance, because this regulation is altered in disease states, and because this is a potential target for therapy. Tropomyosin has an extended coiled-coil structure, and in striated muscles it spans seven actins. We will examine striated muscle alpha-tropomyosin segment by segment, to test hypotheses concerning its function and structure, to circumvent previous difficulties in understanding tropomyosin when using the entire molecule, and to evaluate evidence for major functional heterogeneity within this elongated protein. This will involve host-guest studies of function, and additionally both structural and functional studies of tropomyosin fragments. The structure and conformation of the thin filament also will be investigated by electron microscopy with 3-D reconstruction. This will involve filaments with altered forms of tropomyosin or troponin C (the calcium binding subunit), and short actin filaments created with the filament severing protein gelsolin. Solution studies of these altered filaments will be correlated with the structural results, and used to investigate the conformational transitions of the thin filament, and the spatial propagation of these transitions. Further, permeabilized muscle fibers containing altered forms of TnC will be used to investigate the mechanism of calcium-dependent cooperativity in the intact sarcomere. Finally, the mechanism of cooperative thin filament activation also will be investigated with statistical mechanical modeling of the effects of the non-homogeneous relationship between the regulatory proteins and the seven actins with each regulatory unit. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CARDIOVASCULAR SEQUELLAE OF RESPIRATORY MUSCLE WORK Principal Investigator & Institution: Dempsey, Jerome A.; Professor; Population Health Sciences; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-SEP-1977; Project End 31-MAR-2007 Summary: (provided by applicant): We propose to determine the physiological and clinical importance of metaboreflexes originating in the inspiratory and expiratory respiratory muscles in regulating blood flow and its distribution at rest and exercise. The rationale for this proposal is based on findings in humans which show that: a) mechanical unloading of the respiratory muscles in heavy exercise causes a reduction in stroke volume and cardiac output and vasodilation and increased blood flow in locomotor muscles; b) that fatiguing the diaphragm causes a time-dependent increases
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in muscle sympathetic nerve activity (MSNA) in the resulting limb; and c) that central inspiratory motor output has no influence on MSNA in the intact human. Aim 1: We will voluntarily increase inspiratory and expiratory muscle effort in healthy humans at rest, during plantar flexion exercise and in hypoxia to determine the threshold and sensitivity of the respiratory muscle metaboreflex in response to progressive increases in respiratory muscle force output and fatigue. We will also determine the combined effects - additive or multiplicative - of combinations of forearm and diaphragm submaximal and fatiguing exercise. Outcome measures include: a) MSNA (via peroneal nerve microneurography); b) femoral arterial blood flow and vascular conductance (measured beat-by-beat with a Doppler ultrasound imaging technique). Aim 2: We will use local infusions of metabolites into the diaphragm and abdominal expiratory muscles in a chronically instrumented dog model in order to quantify the sensitivity and compensatory capabilities of the respiratory muscle metaboreflex and its effect on blood flow distribution at rest and exercise. This animal model will also be used to address the effects of the limb locomotor muscle metaboreflex on distribution of blood flow to the respiratory muscles during exercise. Aim 3: In patients with chronic heart failure of varying etiology, we will apply ventilatory assist in the form of pressure support or proportional assist mechanical ventilation to determine the influence of respiratory muscle work and intra-thoracic pressure on exercise performance, on stroke volume and cardiac output and on limb locomotor muscle blood flow and vascular resistance at rest and exercise. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CATCH: MECHANOCHEMISTRY AND REGULATION IN SMOOTH MUSCLE Principal Investigator & Institution: Siegman, Marion J.; Professor; Physiology; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2002; Project Start 01-DEC-1994; Project End 31-JUL-2004 Summary: A unique and important characteristic of all smooth muscles (mammalian and invertebrate) is the ability to vary the energy cost of force production and maintenance during the time course of isometric contractions. The basic mechanisms controlling force maintenance, or tone in smooth muscle are not well understood. Our discovery that the phosphorylation state of twitchin (a mini-titin) regulates catch and force production in the anterior byssus retractor muscle (ABRM) of Mytilus edulis, has opened the way to new studies described here on the molecular basis of its function. Our overall goal is to determine the mechanisms whereby twitchin controls actinmyosin interaction and resulting mechanical output. The ubiquitous presence of twitchin in invertebrate striated, smooth catch and phasic muscles suggests that twitchin may serve as a regulator in all of these muscle types. The understanding of the basic mechanisms underlying this regulation may very well provide new insights on the control of other muscle types, especially mammalian smooth muscle, which shows very similar mechanical characteristics as the smooth muscles from invertebrates. In the proposed studies the smooth ABRM of M. edulis, and striated adductor of the sea scallop (P. magellanicus) will serve as experimental models. Intact and permeabilized invertebrate muscles will be used, as needed. The Specific Aims are to (1) Determine the mechanism by which twitchin phosphorylation gives rise to an increase in the detachment rate constant of the myosin crossbridge; (2) Determine the relationship between the degree of phosphorylation of twitchin and its mechanical effect in intact and permeabilized ABRM; (3) Test the hypothesis that the intrinsic rate of actin movement by myosin is attenuated by the presence of twitchin, and that the
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phosphorylation of twitchin restores the intrinsic fast rate, using in vitro motility studies of actin movement on native thick filaments from ABRM and the body wall of C. elegans. Nucleotide turnover on the thick filaments will be measured in order to learn how twitchin phosphorylation alters the ATPase activity when calcium concentration is varied. (4) Determine of the effect of twitchin phosphorylation on fast striated scallop adductor muscle in order to learn whether this is a generalized mechanism for the modulation of crossbridge kinetics in invertebrate muscle. (5) Biochemical studies on twitchin will characterize the twitchin molecule and determine the mechanism by which its phosphorylation by protein kinase A controls the interaction of contractile proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CENTRAL AUDITORY PATHWAY OF THE MIDDLE EAR REFLEX Principal Investigator & Institution: Lee, Daniel; Otolaryngology; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The goal of this project is to understand the anatomic and physiologic features of interneurons of the mammalian middle ear muscle (MEM) reflex pathway. The neurons of this reflex coordinate the activity of the MEMs to protect the inner ear from intense acoustic stimuli as well as reduce masking. This reflex arc is composed of primary auditory afferents originating in the cochlea, a single or series of interneurons originating in the cochlear nucleus and ultimately synapsing on MEM motoneurons, and efferent fibers of the facial and trigeminal nerves that terminate on the stapedius and tensor tympani muscles, respectively. Although features of primary auditory afferents and the motoneuron efferents have been well characterized, little is known about the reflex interneurons. Which subdivision of the cochlear nucleus contains the reflex interneurons? Is there a single or a series of interneurons from the cochlear nucleus to the facial and trigeminal nuclei? For Aim 1, we will perform focal lesioning studies of the cochlear nucleus using kainic acid, an excitatory neurotoxin. We will correlate focal lesioning of the cochlear nucleus with loss of the MEM electromyography (EMG) response, to determine which division of the cochlear nucleus is involved in the MEM reflex pathway. Since the anatomical cell types of the cochlear nucleus subdivisions are well known, these studies will narrow down the identity of the cochlear nucleus interneurons. For Aim 2, we will examine the cochlear nucleus interneurons by double-injection experiments. We will inject retrograde tracer into either the stapedius or tensor tympani muscles to label their respective motoneurons, and, at the same time, inject an anterograde tracer into the cochlear nucleus to label the interneurons of the MEM reflex. Injections of the cochlear nucleus will be guided by our lesion studies described in Aim 1. Labeled projections from the cochlear nucleus will be identified as interneurons of the MEM reflex if they terminate on labeled MEM motoneurons. Such terminations would reveal a direct connection between the cochlear nucleus and the MEM motoneurons. Overall, the proposed project will improve our understanding of the brainstem connections that comprise the MEM reflex pathway. These findings may provide a basis for refining and extending our interpretation of clinical tests of MEM reflex integrity and brainstem auditory processing in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHARACTERIZATION ELASTOGRAPHY
OF
SKELETAL
MUSCLE
BY
MR
Principal Investigator & Institution: An, Kai-Nan; Professor & Chair; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905
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Timing: Fiscal Year 2003; Project Start 01-APR-1999; Project End 31-MAR-2008 Summary: (provided by applicant): The goal of this proposal is two-fold: (1) to further develop and validate a technology, magnetic resonance elastography (MRE), for quantitatively imaging mechanical properties and tension distribution in muscle and (2) to apply the technique for in vivo evaluation of patients with four common, and clinically significant muscle disorders (spasticity, disuse atrophy, myofascial pain and a metabolic myopathy). These studies will employ a magnetic resonance imaging sequence with synchronous motion-sensitizing gradients to map propagating shear waves in the muscle. The technique will assess the mechanical properties of the muscle and its tension distribution. Specifically, the study can be divided into three specific aims. Aim 1: Optimize MRE methods of acquisition and analysis for the assessment of muscle, including electromechanical drivers, data acquisition techniques, and methods for image analysis. Advanced techniques for very rapid MRE assessment of muscle will continue to be developed. Aim 2: Validate the MRE assessment of muscle properties and tension with phantom, ex-vivo muscle, and Finite Element Modeling (FEM) techniques. Finite Element Analysis will be performed by using both phantom and bovine muscles to better correlate MRE wave-length findings as function of muscle properties, tension and fiber architecture. Aim 3: Study In Vivo Normal and Abnormal Muscle. The MRE technique will be applied in vivo to provide elastographic images of abnormal muscle with known disorders. The patient groups chosen for study are each important in their own right, and furnish unique information across the spectrum of muscular disease and dysfunction. Groups to be studied include individuals with new onset of spasticity following an ischemic, hemispheric stroke, disuse atrophy as a result of immobilization, metabolic (hyperthyroid) myopathy and myofascial pain for trigger point identification. The overall hypothesis of this work is that will bring benefits to both basic research and clinical care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CI-2 MODULATION OF SPINAL PROCESSES: SUPRASPINAL EFFECTS Principal Investigator & Institution: Foreman, Robert D.; Professor & Chair; Physiology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002; Project Start 01-SEP-1996; Project End 31-MAY-2007 Summary: (provided by applicant): The purpose of this study is to examine how neurons of propriospinal pathway(s) originating in the C1-C2 region process information from amygdala, subcoeruleus/parabrachial (SC/PB) nuclei, and vagal afferent fibers to modulate sensory-motor integration in the spinal cord. We previously demonstrated that chemical stimulation of C1-C2 neurons modulated spontaneous and visceral-evoked activity in lumbosacral spinal neurons and EMG activity of thoracic paraspinal muscles. Our preliminary data further demonstrate that chemical stimulation of C1 C2 neurons can strongly influence the activity of T3-T4 respiratoryrelated interneurons. Especially critical to this application are our preliminary results indicating that excitotoxic blockade of C1-C2 neurons with ibotenic acid, attenuated amygdalar and SC/PB modulation of lumbosacral spinal cells. The same lesion reduced vagal effects on lumbosacral neurons and paraspinal muscles. Our results challenge the assumption that descending pathways from supraspinal regions modulate activity of thoracic and lumbosacral neurons through direct projections only. The present application addresses the hypothesis that C1-C2 neurons process information from amygdala, SC/PB and vagal afferents. In turn, C1-C2 neurons strongly influence activity
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of spinal sensory neurons, thoracic respiration-related interneurons, and somatomotor reflexes. We also hypothesize that amygdala and vagal afferents transmit information to C1-C2 neurons via SC/PB nuclei. Specific aims are designed to answer the following questions: 1) Are discharge patterns and activities of C1-C2 neurons affected by stimulating specific supraspinal nuclei? 2) Do neurons in C1-C2 segments process information from specific supraspinal nuclei to change sensory and integrative/motor activity in the spinal cord? 3) Do neurons in C1-C2 segments process information from vagal afferents to change integrative/motor and sensory activity in the spinal cord? 4) Do SC/PB nuclei relay information from amygdala and vagal afferent fibers to the C1C2 segments to change sensory and integrative/motor activity in the spinal cord? Neurophysiological studies to examine extracellular discharge patterns and studies using c-fos as a marker of neuronal activation will be conducted in anesthetized rats. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEFINING HETEROPLASMY AT THE SINGLE MITOCHONDRION LEVEL Principal Investigator & Institution: Arriaga, Edgar A.; Assistant Professor; Chemistry; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant): Our long-term goal is to understand how mitochondrial DNA (mtDNA) mutations appear, propagate, and are distributed among the thousands of mtDNA molecules in a cell, a condition called heteroplasmy. While these mutations are associated with age-related diseases and the aging process, predicting the degree of heteroplasmy at which disease symptoms or age-related phenotypes will appear is practically impossible because the dynamics of heteroplasmy are not well understood. The central hypothesis of this application is that individual mitochondria, containing anywhere from 2 to 10 mtDNA copies, can be heteroplasmic, a condition resulting from the segregation of mtDNA molecules upon mitochondrial replication, and likely modified by the dynamic exchange of genomic material among mitochondria within a given cell. If this hypothesis is correct, a heteroplasmic mitochondrion will have both mutated and wild-type mtDNA, all the peptides encoded by the mitochondrial genome, and a normal mitochondrial membrane potential. We propose to develop the first bioanalytical technologies capable of investigating heteroplasmy in individual mitochondria. We will continue to use and improve upon an instrument based on capillary electrophoresis with laser-induced fluorescence detection (CE-LI F) to determine the properties of individual mitochondria that can then be collected and subjected to PCR amplification of their DNA. In addition, peptide profiles from mitochondria containing mutated mtDNA that will be determined by in situ matrix-assisted laser-desorption time-of-flight mass spectrometry will provide a more comprehensive characterization of heteroplasmy. As testing models, we will use NS-1 cells lines, two cybrid cell lines harboring 7522 and 4977 deletions, and rectus femoris and soleous muscles from Fisher 344 Rats, aged 6, 24, and 28 months. The NS-1 model will mainly be used to develop technologies and methods. The cybrid models have a defined degree of heteroplasmy (> 50 percent) and host deletions that omit the expression of the genes ND5, ND4, ND3, ND4L, COIII, A6, A8, and tRNAL, tRNAS, tRNAH, tRNAR, and tRNAG. In addition to these genes the cybrid hosting the 7522 base pair deletion further omits expression of the cytb, ND6, COIl (2), tRNAR, and tRNAK genes. These cybrid models will be used to study the progression of heteroplasmy in cell lines. The two muscle models will be used to study the progression of heteroplasmy along red ragged fibers that have been identified by (COX-, SDH++)
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phenotype. Our individual mitochondrial determinations will be the basis for monitoring (1) the progression of heteroplasmy after the formation and propagation of a cybrid clone, and (2) the degree of heteroplasmy along skeletal muscle fibers. The data resulting from the cybrid and muscle tissue models will be used to refine existing mathematical models that predict the clonal expansion of heteroplasmy. The determination of mtDNA mutations at the single mitochondrion level in the cybrid and muscle models will bring us closer to uncovering the intricacies of heteroplasmy and its implications in disease and aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF INNERVATION TOPOGRAPHY IN MUSCLE Principal Investigator & Institution: Laskowski, Michael B.; Biological Sciences; University of Idaho Moscow, Id 838443020 Timing: Fiscal Year 2002; Project Start 01-JUL-1988; Project End 31-MAY-2005 Summary: (From the Applicant's Abstract): Over the last several years, we have shown that motor neuron pools map onto muscles with a rostrocaudal positional bias. Detailed studies from our lab revealed that this topographic map is detectable in embryonic muscles upon first contact between nerve and muscle, and is partially restored after denervation. We have developed an important model of synaptic competition during reinnervation, where we can predict with 95 percent accuracy the survivor between two competing nerve terminals. We have also developed an in vitro model to identify muscle membrane-bound labels that may be responsible for the positional bias. We have found selective growth of embryonic spinal cord neurites on membranes derived from embryonic rostral or caudal muscles or from transgenic muscle cell lines bearing a heritable memory for rostrocaudal position. We have recently focused our attention on the Eph A/ephrin A subfamily of tyrosine kinase receptors as a class of candidate molecules that regulate neuromuscular topography. We have found that all five members of the ephrin A subfamily are expressed in embryonic muscles, and that membrane expression of ephrin A ligands progressively diminishes during postnatal development. We have further found that overexpression of ephrin A5 or deletion of ephrin A5 and A2 degrades the topographic map. We propose to build on this series of observations in three ways. First, we will study the physiological basis for the altered topographic map by ephrins A using intracellular recording and uptake of activity dependent dyes into living nerve terminals. Second, we will extend our in vitro model for innervation topography using a wide array of neurite growth assays. In particular, we will examine growth on membranes of two particularly selective muscles, the gluteus and serratus anterior where 87 percent to 95 percent of the neurites making a choice grew selectively on membranes of similar axial position. We will also explore selective neurite growth within compartments of a single muscle. Third, we will use this in vitro model to search for molecular guidance cues other than ephrin A ligands that may cooperate in establishing the neuromuscular map. This will include the use of ephrin A5 fusion proteins to block endogenous ephrin A ligands. In addition, we will isolate membranes from mutant mice where ephrin A5 or A2/A5 genes have been deleted. In both cases we will search for residual selective growth by spinal motor neurites as a first step toward isolation of additional guidance molecules. Results of these studies will provide unique insight into how neurites in the peripheral nervous system recognize and synapse with their positionally matched partners. We will also learn whether positional labels in the neuromuscular system are part of a general strategy for encoding position in the nervous system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DIABETES ENDOCRINOLOGY RESEARCH CENTER Principal Investigator & Institution: Barrett, Eugene J.; Professor; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-JAN-2008 Summary: (provided by applicant) We propose to establish a DERC within the University of Virginia Diabetes Center. The research base of the proposed DERC includes 43 scientists with distinguished research accomplishments in the fields of diabetes, endocrinology, immunology, cell signaling and vascular disease. Their research is organized in 3 thematic areas autoimmunity, insulin secretion and action and vascular complications of diabetes. These are areas of current strength and future growth for diabetes at Virginia. The proposed DERC will be a magnet to attract faculty and research support in diabetes and its complications to the institution. The proposed DERC will center around 5 scientific core laboratories, and the Pilot and Feasibility and Enrichment Programs. Organizational structure and grants management by an Administrative Core will support these activities. The Cores include a Genetics Core that will give DERC members facilities for genotyping, linkage analysis and generating speed congenics; a Biomolecular Research Core with tools for DNA sequencing and peptide and oligonucleotide synthesis as well as unique capabilities for protein sequencing using mass spectroscopy; an Animal Characterization Core that will facilitate detailed metabolic, imaging and behavior assessment of nutritionally, genetically, pharmacologically or behaviorally treated rodents as well as facilities for immune assay and phospho and fluoro imaging; a Cell and Islet Isolation Core that will provide facilities to isolate and characterize islets, adipocytes, and isolated muscles, as well as routine access to tissue culture reagents; and a Integrated Data Management Core that will bring mathematical tools to analyze, integrate and archive data from individual laboratories and from other Cores to enhance research programs of center investigators. These capabilities in our scientific cores promise to drive a period of discovery in diabetes and endocrine research at the University of Virginia. Pilot and Feasibility and Enrichment Programs will introduce new investigators to diabetes research in an environment of research excellence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DIETARY RESTRICTION, MT DNA ABNORMALITIES AND AGING Principal Investigator & Institution: Aiken, Judd M.; Professor; Animal Hlth & Biomedical Scis; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 10-JUL-1995; Project End 31-JAN-2006 Summary: (Verbatim from application) Aging is recognized as an intricate web of global, physiological attrition. Many of the physiologically significant age-related changes are exhibited in non-replicative tissues such as brain, heart and skeletal muscle that rely heavily on oxidative metabolism for energy. In skeletal muscle, we hypothesize that mitochondrial genetic and enzymatic abnormalities, possibly secondary to life-long oxidative damage, may ultimately disrupt cellular processes or trigger cell death. The ensuing skeletal muscle fiber dysfunction or loss may contribute to sarcopenia, the agerelated loss of skeletal muscle mass and function. We are addressing, by the in situ analyses of skeletal muscle from aged rodents, the question of the biological impact of mitochondrial abnormalities. Our studies suggest a specific sequence of events linking mtDNA deletions to sarcopenia. Concomitant with decreased muscle mass and fiber number, we have observed increases in segmental mitochondrial abnormalities that
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contain specific rntDNA deletion mutations as revealed by laser capture microdissection and whole mitochondrial genome amplification. Muscle fibers harboring mtDNA deletion mutations often display atrophy, splitting and oxidative damage demonstrating a cellular impact of these abnormalities. These correlations suggest a causal role for mtDNA deletion mutations in sarcopenia. The aims of the present proposal are fourfold: 1) characterize ETS abnormalities, fiber atrophy, fiber splitting and oxidative damage during the progression of sarcopenia in selected rat muscles; 2) ascertain the cellular impact of age-associated ETS abnormal segments by gene expression profiling of laser-capture microdissected muscle fibers 3) Assess the effect of early- and adultonset caloric restriction on the progression of sarcopenia and the accumulation of mitochondrial abnormalities in selected muscles of F344BNF1 rats; 4) determine whether mitochondrial genomes harboring deletion mutations are causally related to age-associated ETS abnormalities and subsequent cellular impact. The outcome of this work will shed additional light on the biological significance of these mutations and the effects they have on the age-related changes in muscle physiology and structure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIFFERENCES IN SWALLOW MECHANICS IN INFANTS Principal Investigator & Institution: German, Rebecca Z.; Professor; Biological Sciences; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2002; Project Start 01-JUL-1998; Project End 31-JUL-2006 Summary: (provided by applicant): Swallowing requires the coordination of a large number of muscles; this complexity arises partly from the need for airway protection. In the previous funding period, we added to the understanding of muscle activity and oropharyngeal kinematics in infant deglutition. However, the role of the majority of muscles during emptying of the valleculae and in the transport of the bolus past the laryngeal opening or the natural stimuli that initiate the emptying of the valleculae over maturation is not well understood. Our preliminary data suggest that two distinct pathways of bolus movement exist, either around the epiglottis/laryngeal opening (in the newborn) or over it (by the age of weaning). However the timing of the transition, from one path to the other and the associated changes in the kinematics or motor patterns, are unknown. The decerebrate pig is an excellent model for studying vallecular emptying because this phase of the swallow can be isolated experimentally. We propose to apply our existing techniques both to this model and to intact animals, in order to answer the following questions. What natural stimuli initiate vallecular emptying, and do they change during maturation? What is the pattern of muscle activity during vallecular emptying in terms of the order and amplitude of muscle activation? Does change in the consistency of the bolus alter the motor pattern during vallecular emptying, and does this change over developmental time? Does epiglottal movement result from: (i) direct muscle contraction; (ii) indirect movement of the rest of the larynx, (iii) the mechanical action of food on the epiglottis, or a combination of all three? Current studies of human dysphagia and rehabilitation rely heavily on several older studies of oral function in adult man and animal; these studies did not have the means to examine the ontogeny of vallecular function in detail. The proposed study of the maturation of motor patterns will provide an important baseline for treatment strategies aimed at human infant dysphagia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DISEASE AND CONTINUOUS MYOFIBER REMODELING IN EOM Principal Investigator & Institution: Mcloon, Linda K.; Associate Professor; Ophthalmology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2005 Summary: (Applicant's Abstract) Extraocular muscles (EOM) are spared or preferentially involved in various skeletal muscle diseases. We propose a novel and controversial alternative mechanism that may form the basis for the differences between extraocular muscles and limb skeletal muscles. We have strong preliminary evidence to suggest that there is ongoing, continuous myofiber remodeling in the adult extraocular muscles. This would involve both myogenic and apoptotic components. These conclusions are based on 4 lines of evidence. In this proposal we are asking questions to confirm our original observations. We have shown that the EOM continue to express cells positive for myogenic regulatory factors, such as myoD. Activated satellite cells are always present in adult EOM. BrdU labeling experiments using both 2 week and 4 week continuous labeling protocols followed by various brdU-free periods, a protocol that labels dividing cells, demonstrated mature myofibers with brdU-positive nuclei within them. Our working hypothesis is that there are mechanisms present in adult EOM that allow continuous satellite cell activation and division, resulting in either continuous remodeling of existing myofibers by fusion of new myoblasts with existing adult myofibers or formation of entirely new myofibers by the fusion of myoblasts with each other. This proposal asks the following questions: What are the mechanisms of myofiber remodeling in adult EOM? What is the time course and extent of fiber remodeling? What role does apoptosis play in myofiber remodeling and by what mechanism? How do surgical and chemodenervation manipulations simulating strabismus treatments cause changes in myofiber remodeling that may be affecting long-term surgical outcomes? The ability of adult EOM to continuously remodel provides a wealth of testable hypotheses for some long-standing enigmas involving the EOM and their preferential sparing or involvement in various muscle diseases. Ultimately, we hope to use this information to develop new therapeutic strategies.for the treatment of strabismus and other ocular and non-ocular muscle diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DO LIGHT CHAIN EXTENSIONS ENHANCE MUSCLE POWER OUTPUT? Principal Investigator & Institution: Maughan, David W.; Research Professor; Molecular Physiol & Biophysics; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2005 Summary: Oscillatory power production is a general feature of striated muscle. Enhanced oscillatory power output is correlated with the presence of extensions of the amino terminus of myosin light chains. Homologous extensions exist in myosin essential light chains of vertebrate myocardium and the regulatory light chain of Drosophila jump and flight muscles. The exact function of these protein extensions is unknown, but preliminary results suggest that they augment power during contraction. Our central hypothesis is that the light chain extensions make molecular contacts that help pre-position the motor subunit of myosin near its target zone on actin for optimal interaction and power generation. Light chain constructs will be created in mouse myocardium and flies to assess the extent to which power output is diminished by
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removing or replacing residues thought to be involved in thin filament interaction. The following hypotheses will be tested: 1) intact ventricular strips lacking the essential light chain N-terminal extension produce lower oscillatory power output at submaximal calcium levels than strips with full length light chains, 2) the essential light chain extension exhibits its effect on power only at in vivo lattice spacing, 3) the light chain extension exerts its effect on power by specific, electrostatic interactions with the thin filament, and 4) comparable alterations of the N-terminal extension of the regulatory light chain in Drosophila flight and jump muscles produce structural and functional phenotypes comparable to those observed in mouse hearts. Interfilament spacing, lattice order, and indices of myosin head alignment will be measured in both intact and demembranated (skinned) preparations using low-angle X-ray diffraction, aided by electron microscopy. Isometric force, unloaded shortening velocity, and dynamic stiffness (oscillatory power output) will be measured in skinned preparations under conditions in which the otherwise swollen lattice is restored by osmotic compression to its in vivo spacing. This research will contribute to understanding and treating human muscle diseases in which power output is compromised. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOES SPINAL MANIPULATION SPEED DETERMINE NEURAL RESPONSE Principal Investigator & Institution: Pickar, Joel G.; Research and Development; Palmer Chiropractic Universtiy 1000 Brady St Davenport, Ia 52803 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2004 Summary: The goal of this R21 PROJECT is two-fold: 1) to increase our understanding regarding the effects of spinal manipulation on the nervous system and 2) to seek a scientific basis for the continued investigation of the role of proprioceptors in the effects of spinal manipulation. The specific aim of this project is to determine if the speed of a spinal manipulation is an important determinant of the neural response from paraspinal muscle proprioceptors. Strong evidence supports using spinal manipulation to help patients with acute low back pain and neck pain. A theory common to the practice of spinal manipulation proposes that spinal manipulation alters paraspinal sensory input (ie, neural input from tissues of the vertebral column). Preliminary data demonstrate that spinal manipulative impulses stimulate proprioceptive afferents from lumbar paraspinal muscles. These afferents could contribute to the therapeutic effects of manipulation. The proposed experiments will determine how muscle spindles and Golgi tendon organs in lumbar paraspinal muscle respond to the time-varying impulse of a spinal manipulation. Slow and fast impulses will be given. A Fourier transform will be used to analyze, in the time domain, the force-time and displacement-time profile of each manipulative impulse. The resulting power spectra for a range of impulse durations will enable us to determine if the speed of a spinal manipulation is an important determinant of proprioceptive sensory input from paraspinal muscles during spinal manipulation. The experiments will provide information regarding the neural systems impacted by spinal manipulation and can lead to improved training methods for the proper application of spinal manipulation. Teaching the manual skill of spinal manipulation could be approached from the perspective of quantifying the velocity with which the clinician applies a spinal manipulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DYNAMICS LOCOMOTION
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Principal Investigator & Institution: Roberts, Thomas J.; Zoology; Oregon State University Corvallis, or 973391086 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (adapted from Investigator's abstract) The mechanical and metabolic energetics of locomotion are ultimately determined by the mechanical properties of skeletal muscles and the pattern of contraction they undergo. The link between muscle properties and movement energetics is poorly developed because we lack information about how muscles contract in vivo. The proposed research will use a particularly suitable locomotor model to measure force, power and activity of muscles and tendons directly during running, walking and acceleration. Direct measurements of muscle contraction in vivo, measurements of tissue properties, and inverse dynamics will be used to determine how muscle contractile power is translated into movement. Independent measurements of muscle and tendon work will be used to test the hypothesis that tendon energy recovery supplies the majority of the positive work of movement during steady-speed level walking and running. The force-velocity and length-tension properties of muscles will be used to test the hypothesis that muscles operate at lengths and shortening velocities that allow for economical force production during steady-speed walking and running. The role of passive force development during movement will also be investigated to test the hypotheses that muscles produce force passively over a range of muscle lengths and velocities where active force capacity is low. These studies will provide insight into how the cellular and molecular properties of muscles and tendons determine the energetics and mechanics of normal gait. A basic understanding of muscle mechanical function during normal gait is important for developing rehabilitative therapies for individuals with musculoskeletal injuries or gait disorders, the design of prosthetic devices, and an understanding of the mechanical forces that influence the regulation of muscle properties. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTROGEN EFFECTS ON CARDIOVASCULAR RESPONSE TO EXERCISE Principal Investigator & Institution: Kaufman, Marc P.; Professor of Internal Medicine & Human p; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: (Applicant's abstract): Static and moderate dynamic exercise are known to increase heart rate, myocardial contractility, arterial blood pressure, breathing and muscle sympathetic nerve discharge. These effects, which are believed to increase the delivery of oxygen to metabolically active tissues (i.e., the exercising muscles), appear to be less in women than in men. This difference is often attributed to the effect of estrogen on neuronal function. Consequently, the aim of the experiments proposed in this application is to identify the effect of estrogen on "central command" and the muscle reflex, the two neural mechanisms responsible for evoking the autonomic responses to exercise. The proposed studies will be done in decerebrate unanesthetized female and male cats, which have been either ovariectomized or castrated, respectively two to four weeks prior to the experiment. In this preparation, the two neural mechanisms, central command and the muscle reflex, can be investigated separately without the influence of anesthesia. The effect of estrogen (i.e., 17-beta-estradiol) on the central command to
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exercise will be studied while the cats are paralyzed with vecuronium, and will be evoked by both electrical and chemical stimulation of the hypothalamic and mesencephalic locomotor regions. Motoneuron discharge to agonist and antagonist hindlimb muscles will be recorded. The criterion for elicitation of central command will be "fictive locomotion." Likewise, the effect of estrogen on the muscle reflex will be studied, but the cats will not be paralyzed. The muscle reflex will be evoked both while the hindlimb muscles are freely perfused and while they are ischemic. Dose response relationships for the effect of estrogen on both the cardiovascular and respiratory responses to central command and the muscle reflex will be determined. Moreover, studies will be extended to estrogen pretreatment with timed release pellets implanted into castrated male cats and ovariectomized females. In addition, the effect of microinjections of 17beta-estradiol into the hypothalamic and mesencephalic locomotor regions will be determined because preliminary data suggest that central command, but not the muscle reflex, is responsible for the estrogen-induced attenuation of the cardiovascular and ventilatory responses to exercise. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXPIRATORY MUSCLE ACTIVATION TO PRODUCE COUGH Principal Investigator & Institution: Dimarco, Anthony F.; Physiology and Biophysics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-FEB-1986; Project End 31-JUL-2004 Summary: (Applicant's abstract):Patients with spinal cord injury frequently suffer from respiratory complications due to their inability to cough and clear secretions. In recent animal studies, we have demonstrated that lower thoracic spinal cord stimulation (SCS) and magnetic stimulation (MS) results in the generation of large increases in airway pressure and high peak flow rates. These techniques, therefore, have the potential to produce an effective cough mechanism in spinal cord injured patients. The purpose of these studies is to resolve important basic science issues concerning these techniques in animal studies. In OBJECTIVE I, the efficacy of cough by these techniques will be assessed by radiolabeled clearance studies. In OBJECTIVE II, the pathway(s) by which the motor nerves innervating the expiratory muscles are activated during SCS and MS will be determined. The importance of motor root activation via stimulation of spinal cord pathways will be assessed by monitoring pressure generation before and after sequential section of the ventral roots. The specific pathways responsible for pressure generation will be localized anatomically by evaluating the effects of spinal cord section. Nerve compound action potentials will also be recorded from the motor roots during stimulation. In OBJECTIVE III, the electric field generated around and within the spinal cord during SCS and MS will be measured and used in conjunction with finite element analysis modeling techniques to determine optimum electrode and coil design. In OBJECTIVE IV, we will characterize the changes in expiratory muscle structure and function following upper motoneuron denervation. An effective cough is dependent upon optimal function of the expiratory muscles which are most likely atrophied in patients with spinal cord injury. Therefore, we will also assess the capacity or SCS and MS to maintain expiratory muscle function in a chronic animal model of spinal cord injury. In OBJECTIVE V, the safety profile of SCS will be assessed in chronic animals. The results of these studies should provide important information relevant to the potential use of these techniques in human clinical trials. Restoration of affective cough mechanism may allow patients with spinal cord injury to clear secretions more easily, reduce the incidence of respiratory complication and, ultimately, improve their life quality.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EYELID SENSORIMOTOR NETWORKS Principal Investigator & Institution: Ledoux, Mark S.; Associate Professor; Neurology; University of Tennessee Health Sci Ctr Memphis, Tn 38163 Timing: Fiscal Year 2002; Project Start 04-AUG-2000; Project End 31-MAY-2004 Summary: Normal eyelid motor function depends on neurons that innervate the orbicularis oculi muscles that clone the eyes during blinks and levator palpebrae muscles that open the eyes. Neural structures afferent to orbicularis oculi and levator palpebrae motoneurons control the parameters of voluntary eyelid opening and closure, spontaneous and reflexive blinks, and eyelid activity that accompanies eye movements. The motor circuitry mediating spontaneous and reflex blinking is critical for the maintenance of normal ocular function and prevention of ocular injury. Disorders of the nervous system associated with abnormal blinking such as blepharospasm and apraxia of eyelid opening can produce significant functional disability including blindness. Lid retraction and decreased blink frequency seen in neurodegenerative disorders such as progressive supranuclear palsy can cause dry eye and exposure keratitis. Blepharospasm is an involuntary, typically bilateral, closure of the eyes secondary to spasmodic contractions of the orbicularis oculi musculature. Blepharospasm, although usually idiopathic, has been associated with structural lesions of the central nervous system, particularly the rostral brainstem and mesencephalon. Light sensitivity (photophobia) is a symptom with most patients. Some patients with blepharospasm have a history of irritative ocular stimuli such as blepharitis or dry eye; one hypothesis is that maladaptive responses to these stimuli are critical to the development of blepharospasm. Pharmacological, physiological, and postmortem-pathological evidence suggest that monoaminergic systems, particularly serotonergic, may play a role in the pathophysiology of blepharospasm. The neural circuits premotor to orbicularis oculi and levator palpebrae motoneurons will be defined anatomically in both rats and primates using both standard and viral transneuronal tracers. These experiments will also determine the relationship of orbicularis oculi premotor neurons to the central terminations of trigeminal afferents from the eyelid and cornea. The simultaneous use of two transneuronal tracers will localize neural structures critical to the bilateral coordination of orbicularis oculi and levator palpebrae motoneuron activity. Finally, the components of the orbicularis oculi premotor network activated either acutely or chronically by irritative ocular stimuli will be determined in rats. The data generated from these experiments will contribute to the development of models of eyelid motor function and dysfunction, improve understanding of clinical blink reflex testing and conditioning studies of the blink reflex, and provide important information regarding the cell-specific transport of viruses into rodent and primate nervous systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FACTORS THAT MODIFY INSULIN ACTION Principal Investigator & Institution: Buse, Maria G.; Professor; Medicine; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-MAY-1978; Project End 31-MAR-2003 Summary: "Glucose toxicity" accounts for insulin resistance in uncontrolled Type I diabetes (IDDM) and contributes to insulin resistance in Type II diabetes (NIDDM). Sustained hyperglycemia or hyperinsulinemia cause insulin resistance; glucose and insulin act synergistically in down- regulating insulin-stimulated glucose transport. A
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hypothesis to be tested in 3T3-Ll adipocytes is that glucose/insulin induced glucose transport desensitization reflects altered subcellular trafficking of the glucose transporter, GLUT4, which may involve impaired GLUT4 translocation and inappropriate association of GLUT4 containing vesicles (GCV) with the plasma membrane. Products of the hexosamine synthesis pathway (HNSP) have been implicated in glucose-induced insulin resistance; glutamine-fructose-6-P amidotransferase (GFAT) is the rate limiting enzyme and UDP-N-acetyl glucosamine (UDP-GlcNAc) the major product. The role of HNSP will be tested by examining whether conditions which increase or decrease flux via HNSP augment or mitigate, respectively, glucose induced insulin resistance. O-GlcNAcylation is a reversible process, involving O-glycosylation of proteins on Ser/Thr residues with monosaccharide GlcNAc. It usually involves phosphorylation sites and may be regulatory. Based on preliminary data in muscles of a mouse model of insulin resistance, over-expressing GLUTI in muscle, the hypothesis will be tested that increased flux via HNSP promotes O-GlcNAcylation of critical proteins involved in insulin- stimulated glucose transport. These may include GSV-associated proteins, possibly GLUT4 itself and/or proteins associated with GSV docking and fusion. Since adaptive regulation usually involves multiple sites, we will test the hypothesis that glucose-induced insulin resistance represents in part down-regulation of the insulin receptor (IR) signaling cascade, attempt to identify the major regulatory sites and critically assess the possible contribution of HNSP to the glucose effect. If warranted, the involvement of modulators of IR signal transduction, I.E. protein kinase C (PKC) isoforms, and candidate protein tyrosine phosphatases (PTP-ases: PTP-1B, SH-PTP2 and LAR) will be examined. GFAT activity is allosterically regulated by UDP-GlcNAc, and is modulated in vivo in muscle by the hormonal and metabolic milieu. The pre- and posttranslational regulation of GFAT expression will be studied in muscles of rodent models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FAILED RESCUE OF OLD SKELETAL MUSCLE FROM ATROPHY Principal Investigator & Institution: Booth, Frank W.; Professor; Veterinary Biomedical Sciences; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2002; Project Start 15-AUG-2001; Project End 31-JUL-2005 Summary: A common clinical problem is that in many nursing homes there are mobile and functioning aged individuals who, upon being subjected to one or more periods of immobility due to illness or injury, are unable to return back to mobility. Even with extensive rehabilitative therapy, many of these individuals are unable to recover to preinjury functioning levels. An animal model mimics this human condition. Both young and old rats who undergo a 10-day period of hindlimb immobilization exhibit disuse atrophy, but only skeletal muscle from young rats successfully regrows from this disuse atrophy as old muscle had no regrowth after 77 days of recovery. Hypothesis 2 reads: "Ten of the 200 mRNAs corresponding to growth factors, growth factor receptors, or post-receptor signaling that are present on the employed microarray will differ between young and old rats during the failure of old skeletal muscle to rescue itself from immobilization-induced atrophy during reloading. Specific aim 1 will identify a pool of mRNAs associated with the failure of old skeletal muscle to rescue itself from immobilization-induced atrophy during reloading. Another observation is that shortterm IGF-I application will rescue the failure of old muscle to regrow after disuse atrophy. However, this effect is only transient as continued IGF-I application to old muscle depletes remaining satellite cell proliferations and muscle wastes. Thus, all
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defective growth factor responses must be identified. Specific aim 2 will apply IGF-I to old muscle after hindlimb immobilization in order to further identify those genes that failed to respond in old muscles, but had responded in young muscles. Specific aim 3 will begin to characterize for those differentially expressed ESTs between young and old muscles after ending immobilization in Specific aims 1 and 2. To support data analysis in Specific aims 1 and 2, Specific aim 4 will develop a computer-based, automated system for analysis of microarray data, data warehousing system for high capacity data storage, and tools for querying microarray data across experiments. Identifying the inappropriately expressed mRNAs associated with failed muscle regrowth of old muscles will permit a more scientifically-based growth factor rescue of old atrophied muscle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONAL DYNAMICS OF MOTOR CONTROL Principal Investigator & Institution: Brezina, Vladimir; Physiology and Biophysics; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 15-JUN-2001; Project End 31-MAY-2005 Summary: from applicant's abstract) The long-term goal of this research is to understand the basic computational and control principles which the central nervous system uses to generate functional behavior. Some fundamental principles are implicit in the interaction of the central controller with its peripheral effectors, most importantly muscles. The motor commands of the nervous system and the peripheral response characteristics of the neuromuscular system must be mutually matched for optimal performance. In many systems this matching is accomplished by peripheral modulation which dynamically tunes the properties of the muscle so as to enable it to perform the behavior being commanded by the nervous system. But, although set up as part of the behavior, the modulation generally has much slower dynamics than those of the behavior. In effect, the modulatory state represents a memory, maintained peripherally in the muscle, of past behavior. This memory then prepares the muscle to perform future behavior. It facilitates performance especially of the same kind of behavior as in the past, but may complicate performance if the nervous system commands a different behavior without its presence into account. This peripheral memory and its consequences for control of motor performance and behavior by the nervous system will be studied in a well known, experimentally advantageous model neuromuscular system. The system participates in several behaviors and exhibits a rich variety of neuromuscular modulation on a wide range of time scales. Preliminary studies demonstrate prominent peripheral memory in the system. A strategy combining experiments with mathematical modeling will be used to address the following questions: What motor commands does the nervous system send in the different behaviors? What corresponding modulation occurs? How do the commands and modulation interact to produce functional movement? How does the functional movement change when on the one hand the motor commands, and on the other hand the modulation, are altered? Altogether, this work will test a two-part hypothesis, reflecting the mutual interdependence of controller and effector: that the peripheral memory is required for smooth, efficient integration of successive cycles of a behavior and even for transitions from one behavior to another; but that, at the same time, its existence requires modification of the commands sent by the central nervous system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FUNCTIONAL RESPONSES OF EXTRAOCULAR EYE MUSCLES TO T3 Principal Investigator & Institution: Rubinstein, Neal A.; Associate Professor; Anatomy; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-DEC-1997; Project End 31-MAR-2003 Summary: Thyroid dysfunction affects some 10 million Americans; and although the extraocular muscles (EOMs) are often involved in thyroid disease, little is known about the effects of T3 on the properties or development of EOM fibers. The effects of dysthyroidisms on the function of appendicular muscle fibers suggest that altered T3 levels should have profound influences on the performance of EOM fibers; however, there unique developmental origin, structural and functional properties and singular reactions to diseases suggest that EOMs have unique rules governing gene expression. T3 regulates the contractile properties of muscle fibers by differentially activating or repressing isoforms of the myosin heavy chains (MyHCs). The transcriptional control is mediated by the thyroid receptors (TRs) and the retinoid X receptors (RXRs) which themselves exist as multiple isoforms. Preliminary data, as well as susceptibilities to disease, suggest that the response of genes to T3 in EOMs will differ from that in other muscles. We hypothesize this differential response will be related to unusual distributions of TR and RXR isoforms among fibers; altered T3 levels will lead to the expression of inappropriate MyHC isoforms, abnormal contractile characteristics and impaired vision. Proving this hypothesis requires (a) determining which MyHC genes are expressed in each EOM fiber type during development and in the adult, (b) correlating the MyHC complement of each fiber to the contractile properties of that fiber, (c) determining whether hypo-and hyperthyroidism after the expression of MyHC genes and contractile properties, (d) discriminating the TR and RXR isoforms synthesized in euthyroid and pathological conditions. Studies will isoform-specific cRNA probes and antibodies will be combined with contractile measurements of individual skinned EOM fibers to accomplish these aims. To understand how the eye performs its repertoire of motions under both normal and pathological circumstances, one must understand the synthetic capacity of each fiber and how it defines the functional properties of each fiber. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE THERAPY FOR A SEVERE DMD ANIMAL MODEL Principal Investigator & Institution: Xiao, Xiao; Associate Professor; Molecular Genetics & Biochem; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2004; Project Start 15-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is the most common, disabling and lethal muscle disease, afflicting one of every 3500 males. Recently, we have generated a series of highly truncated mini-dystrophin genes that had large deletions in the "non-essential" regions including part of the central rod domain and the very C-terminus domain. These minigenes were small enough to be packaged into adeno-associated virus (AAV) vectors and large enough to preserve high functionality, when tested in mdx mice after local intramuscular gene delivery. However, the mdx mice are far from an ideal DMD animal model although it is a commonly used one. While manifesting many similar symptoms of the human patients such as the muscle pathology, the mdx mice do not suffer shortened lifespan and do not show overall muscle weakness and skeletal contractures
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as do the human patients. This phenomenon is due to the up-regulation of utrophin gene (a dystrophin analogue) that partially compensates the defects of dystrophin in the mdx mice. By knocking out both dystrophin and utrophin genes (double-KO), two teams have recently developed a severe DMD mouse model that closely reflects every major deficiency seen in the human patients including much shortened life-span, severe muscle weakness and skeletal contractures, offering a more truthful small animal model for more stringent tests of new therapeutics. In this grant proposal, we will use the newly available double-KO mice to vigorously test the hypothesis whether the novel mini-dystrophin genes are able to rescue the muscle functions locally and systemically, and more importantly, to improve the overall health and prolong the life-span of the severe DMD animal, which is key to the development of a clinically efficacious gene therapy strategy. In this proposal, we will investigate 1) biological/therapeutic functions of mini-dystrophin genes in the double-KO mice using the transgenic mouse technology; 2) therapeutic effects of mini-dystrophin genes in both young and adult double-KO mice after local intramuscular injection of AAV vectors; 3) systemic gene delivery and its therapeutic effects in large groups of muscles and the entire body; 4) alternative therapeutic genes that may offer synergistic effects along with the minigenes to benefit the dystrophic muscles. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETICS AND MOLECULAR BIOLOGY OF MYOSIN Principal Investigator & Institution: Bernstein, Sanford I.; Biology; San Diego State University 5250 Campanile Dr San Diego, Ca 92182 Timing: Fiscal Year 2002; Project Start 01-JUL-1983; Project End 31-MAR-2004 Summary: (adapted from investigator's abstract): The investigators are using an integrative and multidisciplinary approach to determine how the myosin heavy chain (MHC) protein drives muscle function. Myosin is the molecular motor of muscle and the major component of myofibrillar thick filaments. Its ATP-dependent interaction with actin-containing thin filaments powers muscle contraction. They will test a series of hypotheses that predict myosin properties encoded by alternative exons, and how these properties dictate the different mechanical functions of various muscles. They use the model organism Drosophila melanogaster because it has a single gene coding for muscle MHC, but produces multiple forms of the protein (isoforms) by alternative RNA splicing. Using MHC null mutants in conjunction with germline transformation, they created a series of "isoform-switch" organisms that accumulate versions of MHC differing in single domains. To determine how each alternative structural domain defines the biochemical and biophysical properties of myosin and the ultrastructural and physiological properties of muscle, they are employing a battery of in vitro and in vivo assays: ATPase, actin and nucleotide binding, in vitro motility, optical trapping, electron microscopy, whole organism muscle function and isolated fiber mechanics. As appropriate, they will create a second series of chimeric constructs, to more specifically link functional properties with structural subdomains within each alternative region of the myosin head. Defining whether in vitro properties dictate in vivo functions is difficult, since a biochemical activity of a protein may always correlate with a particular mechanical property of a muscle without there being a causal relationship. The Drosophila muscle system is unique in that the effects of individual functional domains can be tested in muscle cells and intact organisms. Therefore, they can determine directly and to what degree a specific biochemical property defines a mechanical characteristic. They will also use these assays to test hypotheses regarding the molecular, biochemical, physiological and ultrastructural defects associated with two
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Mhc mutations that affect key amino acid residues. Their results will be interpreted in relation to the three-dimensional structure of the myosin molecule and models for the mechanochemical cycle. Overall, their novel approach will yield direct insight into how the myosin protein functions in muscle and permit testing of models for the transduction of chemical energy into movement. Since mutations in the myosin head cause defects in human cardiac and skeletal muscle, these studies are relevant to understanding human myopathies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GTPASE REGULATION OF SMOOTH MUSCLE CONTRACTION Principal Investigator & Institution: De Lanerolle, Primal; Professor; Physiology and Biophysics; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2005 Summary: Small GTP binding proteins transduce signals that control a host of cellular responses. The activation of protein kinases by the GTP-bound form of small G proteins and highly regulated changes in the actin cytoskeleton appear to be important characteristics of the signalling properties of specific GTPases. Myosin II is an actin based molecular motor that converts chemical energy into mechanical work. The actinmyosin II interaction in smooth muscles is regulated by the phosphorylation of ser 19 on the 20 kDa light chain of smooth muscle myosin by the calcium-calmodulin dependent enzyme myosin light chain kinase. Recent reports have suggested that GTPases and myosin phosphorylation interact to regulate the actin cytoskeleton and smooth muscle contraction. Experiments performed by Somlyo, Kaibuchi and Narumiya and their coworkers have shown that GTPases regulate the calcium sensitivity of smooth muscle contraction. We have recently discovered that myosin light chain kinase is regulated by phosphorylation by PAK 1, a member of a family of protein kinases that is activated by the binding of the p21 GTPase. Although PAKs are generally thought to be involved in responding to stress, substrates for PAK's are not well characterized and myosin light chain kinase represents an important one. Based on extensive preliminary data, we propose that PAKs regulate the calcium sensitivity of smooth muscle contraction by a mechanism that involves the phosphorylation of myosin light chain kinase. We now propose experiments to test this hypothesis. The experiments described in Specific Aim 1 will investigate the kinetics of myosin light chain kinase phosphorylation by PAK 1, in vitro. Specific Aim 2 will test the hypothesis by performing studies on skinned smooth muscles. Specific Aim 3 will test the hypothesis by performing experiments on intact blood vessels. These experiments represent a powerful test of our hypothesis and they will provide important insights into the molecular mechanisms that regulate the calcium sensitivity of smooth muscle contraction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IGF-1 GENE TRANSFER TO ACCELERATE MUSCLE RECOVERY Principal Investigator & Institution: Vandenborne, Krista H.; Chair and Associate Professor; Physical Therapy; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2006 Summary: Muscle weakness is a common clinical phenomina observed following bed rest, surgery, cast immobilization and injury or disease. The consequences of loss of muscle strength are far reaching and include decrease of motor control and overall fitness, development of functional limitations and impairment, and long term disability. As such, the objective of this study is to investigate the potential of virus-mediated gene
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transfer of IGF-1 to guard skeletal muscle from the deleterious impact of disuse or forced inactivity and to accelerate the subsequent recovery in muscle size and strength. For this purpose the left or right hindlimb (randomized) muscles of young adult mice will be injected with a recombinant adeno-associated virus vector for IGF-1. 3 months post-injection, both hindlimbs (injected and control) of the animals will be immobilized in a plaster cast for a period of 2 weeks. After removal of the cast the animals are allowed to reambulate and resume their normal cage activity. Cage restricted levels of weight-bearing activity have been shown to be sufficient to induce muscle regeneration and hypertrophy. Morphometric and functional measurements will be performed bilaterally (injected and control limb) at baseline, 3 months post-injection, following 2 weeks of cast immobilization, during reloading and at several time points during reambulation (2, 4 and 10 weeks). Morphological measures will include fiber crosssectional area and fiber number, wet weight and protein content. Functional measures (twitch and tetanic force) will be performed in vitro on superfused muscles. The secondary objective of this study is to elucidate the mechanisms by which IGF-1 overexpression modulates muscle size and function under varying loading/activity conditions. For this purpose we will measure IGF-1 peptide levels, in vivo protein synthesis and degradation rates, and markers of muscle regeneration and satellite cell proliferation. We anticipate that the ability to locally manipulate muscle regeneration and hypertrophy during disuse and subsequent rehabilitation will be of great clinical importance. In addition, we anticipate that this study will help elucidate the role of IGF1 in the regulation of muscle size under varying loading/activation conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INJECTABLE SENSORS FOR CONTROL OF FES Principal Investigator & Institution: Loeb, Gerald E.; Professor and Director; Biomedical Engineering; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 10-JUN-2000; Project End 31-MAY-2004 Summary: (adapted from the Investigator's abstract): In order to reanimate a paralyzed limb to produce clinically useful movements, three functions must be provided: 1) Electrical stimulators to cause muscles to contract; 2) A controller to coordinate the stimulation; and 3) Sensors of command and feedback signals from the patient to the controller. The investigators have recently completed development and preclinical testing of a novel stimulation technology that permits large numbers of individual muscles to be precisely controlled by injectable, wireless microstimulators that receive power and data by RF transmission from an external controller. They propose to extend that technology by incorporating and testing various types of sensors in similar injectable modules. These will use a novel, compatible system for RF back-telemetry to send signals out of the limb for command and feedback purposes. Their immediate goal is a family of generic "BIONs" (bionic neurons)-that can be configured flexibly to serve a wide range of Functional Electrical Stimulation (FES) applications. The investigators have selected the following basic sensing modalities: 1) Low-level bioelectric signal recording such as electromyography, to monitor (the) level of electrical recruitment (Mwaves) and spontaneous activity from muscles with some remaining voluntary control (useful as myoelectric commands for prostheses);and 2) Triangulation of relative position between devices, to be used for determining limb posture Acceleration and inclination (vs. gravity), using microelectromachined silicon (MEMS) sensor technology. The research will proceed in overlapping stages, the first of which is already underway in pilot work: 1) Design, build and test the basic circuit functions for low-level, low-
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power signal detection, digitization and telemetric transmission; 2) Design, build and test specialized MEMS sensors; 3) Build complete injectable BIONs with sensing and back-telemetry capabilities; 4) Perform preclinical tests of sensor BIONs for biocompatibility; 5) Test sensing and telemetry functions in vitro with artificiallygenerated inputs; and 6) Test sensing and telemetry functions in alert, behaving animals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INSTABILITY AND MUSCULAR DEMAND DURING OBSTACLE CROSSING Principal Investigator & Institution: Chou, Li-Shan; Exercise & Movement Science; University of Oregon Eugene, or 97403 Timing: Fiscal Year 2003; Project Start 04-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Falls are among the most serious problems facing the aging population and have become the largest single cause of accidental death. Moreover, the total direct cost of fall injuries in 1994 among people 65 and older was $20.2 billion. Most falls in the elderly stem from interactions between environmental hazards and increased individual susceptibility to hazards from accumulated effects of age and intrinsic factors. Research on biomechanics of selected physical tasks, that take both environmental and intrinsic factors into account, is needed to quantify impairment magnitudes, to determine what elements are critical to the impairment, and ultimately to design more effective interventions for preventing falls in the elderly. The long-term goals of this proposed project are to advance the understanding of the mechanisms underlying the increased incidence of falls in the elderly, to determine a more effective method of identifying aged persons at risk of falling, and eventually to design more effective exercise/strengthening programs for the prevention of falls in the elderly. Specific aims of this project are to (1) demonstrate that motion of the whole body center of mass (COM) during obstacle crossing could better distinguish fallers from non-fallers when compared to individual segmental motion, (2) examine the relationship between ability to accommodate to environmental hazards during locomotion and muscle weakness, and (3) to identify quantitative, biomechanical indices (muscular demand-tocapacity ratios) that can better indicate the level of mechanical challenge imposed on selected muscles. Motion analysis and muscle strength testing will be performed on 24 elderly non-fallers and 24 elderly fallers (65 years or older). Body segment motion, ground reaction forces, and electromyography will be collected during unobstructed walking and stepping over obstacles of heights corresponding to 2.5% and 10% of each subject's height. Isometric strength of selected lower extremity muscles will be measured bilaterally. A thirteen-link biomechanical model, with kinematic inputs of each body segment and ground reaction forces will be used to compute the threedimensional motion of the whole body COM and three-dimensional joint moments (torques) of the lower limbs. Data analysis will be performed on both mechanical and neuromuscular levels, including the isometric muscle strength, electromyography, motion of the COM, and it's interaction with the center of pressure (COP) of the stance foot derived from ground reaction forces and moments. Finally, correlation between muscle strength and dynamic balance control (indicated by the motion of the whole body COM) will be examined. This proposed project is expected to identify/define more sensitive biomechanical measures (both intrinsic and extrinsic) for better quantification of age-related mobility impairment and functional challenges imposed on our musculoskeletal system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTERACTION DIFFERENTIATIO
AFFECTING
CRANIOFACIAL
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Principal Investigator & Institution: Noden, Drew M.; Professor; Biomedical Sciences; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2005 Summary: (provided by applicant): Craniofacial muscles show great structural and functional diversity, and anomalies in their development contribute to a wide range of problems in vision, facial expression, mastication, and phonation. However, little is known about processes controlling the differentiation and maturation of branchial and extra-ocular muscles. Head muscles arise in mesenchyme adjacent to the brain then migrate and differentiate in connective tissues derived from the neural crest. Trunk and limb muscles arise in epithelial myotomes, then differentiate in paraxial and lateral mesoderm. This research will characterize tissue interactions necessary (1) to promote early differentiation of branchial and extra-ocular muscle myoblasts and (2) to direct expression of fiber typespecific myosins in primary myotubes in these muscles. These interactions will be identified by transplanting specific muscle precursors, at different stages and with or without putative muscle-inducing tissues, between head and trunk axial levels. Assays of tissue response include expression of myoblast markers (e.g., my, about, myoD), of trunk or head muscle-specific markers (e.g., parc aboutcis, pax3; podl, barx2, Ibxl,en2), and at later stages of muscle-specific myosin heavy chains. Surgeries are done on quail and chick embryos, which are ideally suited for in vivo tissue recombination experiments and for which detailed cellular and molecular biographies of head muscles are uniquely available. A third specific aim will characterize the processes by which craniofacial muscles change their attachments during later growth and maturation stages. EM studies reveal that primary myotubes undergo focal degeneration at their myotendinous tips and also at mid-myotube regions during embryonic days 12-15. I propose that these focal degenerations are essential for normal remodeling of head muscles, but nothing is known of the processes or provocations for these focal losses. Assays for elements of the pathways known to be active during programmed cell death of mononucleated cells will be applied to normal and functionor growth-arrested head muscles. Collectively, these experiments will provide the first insights into the signals necessary for initiation and diverse differentiations of craniofacial muscles and the mechanisms by which remodeling of these head muscles occurs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ISCHEMIC MITRAL REGURGITATION:FROM MECHANISMS TO THERAPY Principal Investigator & Institution: Levine, Robert A.; Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 10-JUL-2001; Project End 31-MAY-2006 Summary: (provided by applicant) Immediate Goals: To examine the mechanism of ischemic mitral regurgitation (MR) with the goal of designing and implementing more effective therapy to reduce adverse impact on patients. Career Development Goals: To provide sufficient time for mentoring and research activities. Research Project: Mitral valve function can be understood in terms of the force-balance concept in which tethering forces from the papillary muscles balance left ventricular valve closing forces. In ischemic MR, this force balance may be altered in ways that impair the ability of the mitral leaflets to close effectively at the annular level. This proposal uses a combined,
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parallel clinical and experimental approach to evaluate the mechanism, progression and therapy of ischemic MR, all relating to the central hypothesis that ischemic MR is caused by an abnormal relationship of the mitral valve to its supporting ventricular structures. These altered relationships involve both abnormal tethering forces due to displacement of the papillary muscles as well as reduced closing forces due to LV contractile dysfunction. Specific testable questions related to this hypothesis include: 1) The progression of mitral regurgitation in patients with acute myocardial infarction relates to abnormalities in the mitral valve-ventricular relationship; 2) These mechanisms also cause persistent MR despite coronary revascularization surgery, thereby impairing exercise capacity and raising pulmonary pressures; 3) Both an externally applied device and afterload reduction provide effective means of reducing ischemic mitral regurgitation by normalizing these relationships between the valve and the ventricle; cutting a minimum number of critically positioned strut chordae also has the potential to relieve tethering, and opens the way to potential minimally invasive percutaneous approaches. The aims of the mentored award will be met by allowing the PI to translate his experimental expertise to direct clinical studies of progression and functional outcome of ischemic MR, and to make the transition from mechanism to therapy in models reflecting the clinical situation, with the ultimate goal of patient applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LOCOMOTOR DYNAMICS OF MUSCLE FUNCTION Principal Investigator & Institution: Biewener, Andrew A.; Professor & Chair; Organismic & Evolutionary Biol; Harvard University Holyoke Center 727 Cambridge, Ma 02138 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2008 Summary: (provided by applicant): The proposed research addresses the central question of how muscles function under dynamic conditions of locomotor activity. It does so in the context of how muscle function is modulated in relation to muscle architecture and fiber composition to accommodate changes in locomotor requirement. These questions will be addressed by making in vivo recordings of force (tendon buckle transducers), length change (sonomicrometry) and neural activation (electromyography) of key limb muscles in two animal models: quadrupedal goats and bipedal guinea fowl. Measurements will be obtained from animals trained to move over a range of speeds on a treadmill at different gaits and grades (level vs incline vs decline) to address the following hypotheses: (i) regional activation and fractional length change within muscles that have focal skeletal attachments is uniform both along a fascicle axis and between differing fascicle regions, but may vary in muscles with broader attachments and more complex architectures; as a result, (ii) the timing and strain of activated fascicles are homogeneous within a muscle performing a given motor task; and (iii) proximal muscles with long fibers account for the majority of mechanical work modulation; whereas distal short-fibered muscles with long tendons contract isometrically for more economical force production and tendon elastic savings. Differences in mechanical work rate with locomotor grade will be related to observed changes in the in vivo force-length behavior of key limb muscles. Recordings made while animals accelerate from rest will provide a second context to evaluate work modulation in relation to muscle architecture. Ground reaction force-platform and highspeed video recordings will also be carried out to integrate the in vivo force, length and EMG measurements of individual muscles into whole-limb mechanics. These studies have important consequences for understanding patterns of motor recruitment in relation to locomotor strategy and how regional differences in motor unit organization
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(and fiber type) may influence the neural control of movement. Prior work in this area has been limited by studies of motor function under more quasi-steady ranges of movement and/or indirect assessment of muscle length change and force development. Although an overarching goal is to understand factors that influence normal and agerelated changes in human motor function, animal studies allow direct experimental approaches for assessing the dynamics of motor function that are likely to apply to humans. Consequently, the proposed studies will have value for developing more effective physical, occupational and rehabilitative therapies, as well as for sports and exercise training, and prosthetics design. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LUNG GROWTH AT HIGH ALTITUDE AND MAXIMAL O2 TRANSPORT Principal Investigator & Institution: Johnson, Robert Lee.; Professor; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-JUN-1996; Project End 31-MAR-2006 Summary: (Applicant's abstract): Human natives of high altitude (HA) develop increased lung volume and diffusing capacity consistent with enhanced alveolar growth, and increase blood volumes that facilitate 02 transport. However, other adaptation to HA (muscularization of pulmonary arterioles, dysanaptic airway growth and retardation of thoracic growth) may impair O2 transport. The interplay among these factors at different altitudes is not known. Functional consequences of these structural changes can be isolated only after re-acclimatization to sea level (SL) when reversible changes in blood volume and pulmonary vascular reactivity have subsided. We employ this approach to address long-term structure-function relationships of maturation at HA in dogs. Hypotheses are 1) Hypoxia stimulates alveolar hyperplasia and enhances diffusive gas exchange. 2) Airway growth lags behind alveolar growth at HA, leading to uneven distribution of ventilation and increased ventilatory work. 3) Pulmonary vascular changes at HA significantly limits maximal cardiac output at SL. 4) Structural changes at HA persist after reacclimatization to SL and exert opposing effects on O2 transport, i.e., persistent vascular and airway abnormalities offset benefits derived from enhanced alveolar growth. 5) Growth of thorax is impaired in an altitudedependent way; at extreme altitude, the restricted thoracic size sets an upper limit to lung growth and O2 transport. We plan to raise immature dogs (age 2 mo.) to somatic maturity (12 mo.) at 3 levels of HA (3, 100m, 3,800m or 4,500m in separate groups) compared with controls raised at SL. Dogs will be returned to SL at maturity for cardiopulmonary testing at rest and exercise, including pressure-volume curves, maximal 02 uptake, efficiency of gas exchange and diffusing capacity of lungs (DL) and muscles, ventilatory work, hemodynamics and blood volume. Dimensions of airways, diaphragm, rib cage, lungs and spleen will be assessed by spiral CT scan. Components of DL, septal tissue volume and pulmonary blood flow will be measured at regular intervals and correlated with blood volume. After 1 yr. of re-acclimatization to SL, studies will be repeated to determine regression of changes. Terminally, detailed structural analysis will be performed on the lungs, respiratory, locomotive and ventricular muscles, as well as ribs and long bones. Growth patterns of the acini, airways, vasculature, thoracic structures and their functional correlates will be compared at the 3 levels of hypoxia to determine the altitude-dependence of adaptation in O2 transport. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANICAL FUNCTION OF MUSCLE DURING MOVEMENT Principal Investigator & Institution: Marsh, Richard L.; Professor; Biology; Northeastern University 360 Huntington Ave Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: The performance of a skeletal muscle during movement is determined by the interaction of its intrinsic properties with the mechanical properties of the system to which it is linked. These interactions are complex and predictive equations are limited in some respects by the lack of empirical data on the performance of muscle under loading conditions that replicate those found during movement. Muscles serve three major mechanical functions during movement: producing force, producing work, and providing stability. These different functions are linked to differences in the length trajectory (sequence of length change) in relation to the motor activity of the muscles. Although we know that all three of these functions are performed by humans in walking and running, we know little of the conditions under which individual muscles operate while performing each function. Further we have no empirical data on the quantitative importance of each function to the cost of locomotion. The specific aims of this project are to: 1) Examine the in vivo contractile parameters (operational lengths, length trajectories, and amounts of series elasticity) for muscles that are active only while performing positive work in running and jumping; 2) Examine the prediction that during running and jumping actively lengthening muscles function to help stabilize the movement; 3) Quantify the relative energetic importance of the different mechanical functions served by muscles during running; 4) Measure the efficiency of fast and slow muscles under conditions of varying power output; 5) Quantify the influence of velocity dependent activation and deactivation on mechanical function of fast and slow muscles. The mechanical function of muscles used in running and jumping will be assessed in vivo using sonomicrometry and electromyography. Blood flow measurements using fluorescently labeled microspheres will be used in conjunction with other measures to estimate the relative contribution of the different limb muscles to the energy cost of running. In vitro work with the muscles used in jumping and running and computer modeling will examine the optimum conditions for accelerating inertial loads. Mouse muscles will be used to examine the influence of length trajectory and cycle frequency on mechanical performance and efficiency. This project is predicated on the assumption that examining how muscles are used in animals during movement allows us to better predict the design parameters important in human movement and will improve our understanding of both normal and dysfunctional human movement. Such studies will eventually assist in designing rehabilitative strategies that require an understanding of the diverse roles of muscles during movement. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANICAL VENTILATION AND RESPIRATORY MUSCLES Principal Investigator & Institution: Powers, Scott K.; Professor and Chair; Exercise and Sport Sciences; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2005 Summary: (Applicant's abstract): Mechanical ventilation (MV) is used clinically to sustain ventilation in patients who are incapable of independently maintaining adequate alveolar ventilation. Unfortunately, the withdrawal of MV, or weaning, can be difficult in a large number of cases. Strong evidence exists that MV-induced respiratory muscle weakness contributes significantly to these difficulties in weaning. Indeed, we have recently demonstrated that prolonged MV results in diaphragmatic atrophy and a
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significant reduction in diaphragmatic maximal force production. Further, we have observed that prolonged MV results in oxidative injury (i.e. protein oxidation) to the diaphragm; this is significant because oxidized proteins become targets for proteases. The mechanisms responsible for this MV-induced atrophy and protein oxidation are unknown and comprise the focus of our proposed experiments. To determine the factors that contribute to diaphragmatic atrophy during prolonged MV, we will test the following hypotheses: 1a) MV-induced diaphragmatic atrophy occurs due to a decrease in synthesis of muscle proteins as well as an increased rate of proteolysis; 1b) proteolysis is the major contributor to diaphragmatic protein loss during prolonged MV; 2a) The increased activity of calpain, lysosomal, and ATP ubiquitin-dependent proteases are collectively responsible for the protein degradation observed in diaphragms from MV animals; and 2b) Although calpain, lysosomal, and ATP-ubiquitin-dependent proteases all contribute to diaphragmatic protein loss during MV, the ATP-ubiquitindependent and calpain proteolytic pathways are dominant. To resolve which chemical pathways are responsible for diaphragmatic protein oxidation during MV we will test the hypothesis that MV-induced protein oxidation in the diaphragm is caused by several reactive chemical species including hypochlorous acid, tyrosyl radicals and hydroxyl radicals. To test these postulates, we will perform both in vitro and in vivo studies using an animal model and utilize the tools of molecular biology, biochemistry, and physiology. These experiments will improve our understanding of the mechanisms associated with MV-induced diaphragmatic atrophy. The long-term goal of our experiments is to provide the knowledge required to develop clinical strategies to oppose the deleterious effects of MV on respiratory muscles. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISMS OF SEXUAL DIFFERENTIATION IN NEURAL SYSTEMS Principal Investigator & Institution: Forger, Nancy G.; Professor; Psychology; University of Massachusetts Amherst 408 Goodell Building Amherst, Ma 01003 Timing: Fiscal Year 2002; Project Start 12-JUN-2000; Project End 31-MAY-2005 Summary: (adapted from applicant's abstract): A large number of sex differences in the central nervous systems (CNS) of vertebrates have now been described. Such morphological dimorphisms may underlie well documented sex differences in behavior, in susceptibility to certain drugs, and in the incidence of some human mental disorders including autism, depression and schizophrenia. In many cases, neural sex differences have been shown to be due to differential exposure to gonadal steroid hormones in males and females. However, the cellular and molecular mechanisms governed by hormones in the nervous system are not well understood. The identification and cloning of several new neurotrophic molecules has fueled an explosion of research into the actions of trophic molecules in the CNS, and recent findings indicate a role for neurotrophic factors in sexually dimorphic development. Experiments in the first half of this proposal will test the idea that effects of gonadal steroids are mediated by trophic factors in a well-characterized model system. The spinal nucleus of the bulbocavernosus (SNB) and its target muscles constitute an anatomically simple system that is sexually dimorphic in many mammals. SNB motoneurons reside in the lumbar spinal cord and innervate striated perineal muscles attached to the phallus. Androgens regulate SNB motoneuron survival during perinatal development, and SNB cell size in adulthood. Recent observations suggest that some effects of androgens on this system are mediated by protein neurotrophic factors. Trophic factor antagonists will be administered to developing and adult rats in order to identify endogenously produced factors
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controlling SNB cell survival and morphological plasticity. In the second half of this proposal, the intracellular events regulated by hormones and neurotrophic factors will be explored. Specifically, a role for the death-regulatory protein, Bcl-2, in sexually dimorphic cell death will be tested in the SNB and in the anteroventral periventricular nucleus (AVPV) of the hypothalamus. Because the neurotrophic factors and deathregulatory proteins to be examined are expressed throughout the nervous systems of many vertebrates, including humans, information gained from this work will be relevant to our overall understanding of the extracellular and intracellular molecules mediating hormone regulated development and plasticity in neural tissues. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MENTAL EFFORT EFFECT ON LARGE MUSCLE STRENGTHENING Principal Investigator & Institution: Yue, Guang H.; Associate Staff; Cleveland Clinic Foundation 9500 Euclid Ave Cleveland, Oh 44195 Timing: Fiscal Year 2002; Project Start 27-SEP-1999; Project End 31-MAY-2004 Summary: It is well known that to strengthen a muscle one should perform training involving heavy loads or resistance. Recently we have found that substantial voluntary strength gains can be achieved with training involving low resistance but strong mental effort. In contrast, individuals who trained with the same low-intensity contractions but with low mental effort had no improvement in strength. Based on these preliminary findings, we hypothesize that muscle strength improvements depend primarily on the level of mental effort during training, not the training intensity (resistance) per se. The reason that high-intensity training always increases strength is because mental effort is high during high-intensity muscle contractions. Aim 1 of the project is to compare the effects of training with different levels of mental effort on the improvement in muscle strength. Four groups of elderly subjects (greater than or equal to 65 years) will participate in a 12-week training study involving elbow-flexor muscles. One group will be trained with an intensity near the level of maximal voluntary contraction (MVC group); a second group will be trained with high mental-effort, low muscle-intensity elbow-flexion contractions (LME group); and the fourth (control) group will not be trained will participate in the strength tests. We expect that the strength improvement after training will be: MVC group > HME group > LME group = control group. We also expect that the strength increase in the MVC and HME groups will result in an improvement in daily living function. Aim 2 is determine the neural mechanisms underlying muscle strength improvements. We hypothesize that an increase in the central nervous system (CNS) drive is the primary mechanism that mediates strength improvements induced by low-intensity training (HME group). To evaluate the CNS drive, four measurements will be made using the same subjects and groups as in Ami 1: brain activation level examined by functional MRI (fMRI) and EEG-derived motor activity-related cortical potential (MRCP), surface EMG signals, and the MRI T2 relaxation time obtained from the trained muscles. We expect to find that after training: (1) the brain activation level (fMRI and MRCP), EMG, and MRI T2 will significantly increase in the MVC and HME groups; and (2) the amplitude of increases in these measurements will be: MVC group = HME group > LME group = control group. The knowledge gained from these studies will substantially advance the current understanding of mechanisms underlying human voluntary muscle strengthening and will have direct application in neuromuscular rehabilitation for older adults and individuals who are physically handicapped and unable to perform repeated, forceful muscle contractions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR AND BIOCHEMICAL STUDY OF COLLAGEN IN PROLAPSE Principal Investigator & Institution: Visco, Anthony G.; Assistant Professor; Obstetrics and Gynecology; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from Applicant's Description): Pelvic floor dysfunction including urinary incontinence and pelvic organ prolapse is a major health issue for women resulting in an 11 percent lifetime risk of requiring surgery. The cost of urinary incontinence alone in 1995 alone was estimated at $26 billion in the United States. Several studies have identified pregnancy related risk factors for pelvic floor dysfunction including vaginal parity, increased infant birth weight, forceps and vacuum assisted vaginal delivery, episiotomy and prolonged second stage of labor. However, vaginal delivery fails to fully explain the genesis and progression of pelvic floor dysfunction since severe pelvic organ prolapse has been observed in nulliparous women and most women who deliver vaginally do not develop prolapse. Pelvic organ prolapse and urinary incontinence result from failure of the support mechanism derived from pelvic fascia and muscles. Many researchers have hypothesized that a parturitionrelated denervation injury to the female pelvic floor leads to weakness of the levator ani muscles which in turn results in marked stress placed on the uterosacral cardinal ligaments and endopelvic fascia, ultimately leading to secondary failure of the fascia and development of prolapse. Other studies suggest a primary failure of the fascia. Associations have been reported between prolapse, joint hypermobility and abdominal striac suggesting a generalized connective tissue defect affecting pelvic organ support, joints and skin. One explanation is a defect in collagen biosynthesis. Such a generalized connective tissue disorder might affect collagen's biomechanical strength and be explained at the genetic level. The long-term objective, therefore, is to gain insight into the mechanisms of pelvic floor dysfunction through the study of collagen at the molecular and biochemical levels. Collagen cross-linking is critical for the stability and mechanical strength of the collagen molecule and for the cohesiveness of the collagen fibrils. Hydroxylation of lysine is critical for the cross-linking process and the level of hydroxylation varies among tissues, Lysyl oxidase and lysyl hydroxylase are two enzymes involved in the early steps of the cross-linking process. We hypothesize that alterations in the intermolecular cross-linking may result in weakened connective tissue which may lead to pelvic floor dysfunction. Few studies have examined the biochemical nature of connective tissue or genetic differences in women with pelvic floor dysfunction. The specific aims are to compare: 1. total collagen content, 2. the six characterized collagen cross-links, 3. the ratio of Type I/III collagen, 4. the level of lysine hydroxylation, 5. collagen solubility, and 6. the genes coding for lysyl oxidase and the three isoforms of lysyl hydroxylase (LH1, LH2, LH3), in patients with advanced-stage pelvic organ prolapse and age and parity matched controls. This study would be the first large-scale comprehensive description of collagen cross-linking, lysine hydroxylation, and of genes coding for enzymes involved in the cross-linking process, in patients with pelvic organ prolapse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR BASIS FOR MUSCLE PROTEIN LOSS IN CACHEXIA Principal Investigator & Institution: Lecker, Stewart H.; Assistant Professor of Medicine; Cell Biology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115
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Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Muscle wasting, which occurs mainly by an activation of the ubiquitinproteasome degradative pathway, is a prominent, debilitating feature of many disease states, including diabetes mellitus and renal failure. Recently, using a newly established cell-free system, we have been able to demonstrate that rates of ubiquitin (Ub) conjugation increase in atrophying muscles from septic; tumor-bearing, diabetic and uremic rats, and that a subset of Ub conjugating enzymes, the N-end rule pathway, is responsible for most of the enhanced Ub conjunction in these atrophying muscles. This is an interesting, unexpected discovery because the N-end rule pathway has been viewed as a minor ubiquitination system that was only involved in the elimination of certain abnormal polypeptides. These results raise the possibility that in cachexia, muscle proteins may be modified to become substrates for this pathway. We propose to use our newly developed cell-free system to further characterize this process. We will measure the abundance and activity of the N-end rule pathway enzymes (E1, E2/14K, and E3alpha) to identify the ones which are responsible for the enhanced proteolysis, and identify the substrates in muscle for these enzymes. In collaborative studies, we will genetically produce animals in which these enzymes are deleted to directly show their requirement in muscle atrophy. Finally, since most of the loss of muscle protein during muscle atrophy is from myofibrillar components, we will begin to study how the myofibril may serve as a source of substrates of the Ub-proteasome pathway by developing an assay for myofibril disassembly. Defining the components of the Ubproteasome pathway and myofibril disassembly which are modulated in diabetes and renal failure should not only help to illuminate the regulation of muscle protein turnover, but also may allow the development of inhibitors that could combat the morbidity of these catabolic diseases. These studies will be performed in the laboratory of Dr. Alfred Goldberg, a leader in the fields of muscle proteolysis and the Ubproteasome pathway. The applicant is a graduate of the M.D./Ph.D. program at UCLA, completing a Nephrology fellowship at the Beth Israel Deaconess Medical Center and Harvard Medical School. His long-term goal is to develop a research program centered on problems of protein folding and degradation relevant to kidney disease. This proposal offers the unique opportunity for the applicant to obtain further cell biology training, gaining experience in animal physiology, DNA technology, and biochemistry, while studying clinically relevant problems in renal disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR GENETICS OF MUSCLES SPECIALIZATION Principal Investigator & Institution: Williams, R S.; Professor of Medicine; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-APR-1991; Project End 31-MAR-2006 Summary: (Applicant's abstract): In the previous project period, we proposed that calcineurin and CaMK serve as nodal points in signal transduction pathways by which specific patterns of motor nerve activity lead to changes in gene expression that establish specialized metabolic and physiologic properties in adult skeletal myofibers. Our basic mechanistic model has been supported by evidence from our own lab, and from others, but features of the model remain conjectural or controversial, and the mechanisms we have described so far provide only a partial view of the relevant biological processes. In the next project period, we propose new experiments that seek to achieve a more complete understanding of the molecular basis for fiber type determination in mammalian skeletal muscles. To this end, we will address the following specific aims: 1) To define the set of specific molecular signals that are necessary and sufficient to
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promote complete fiber type transformation in skeletal muscles of adult transgenic mice; 2) To define quantitative relationships between specific patterns of neural activity and the activation state of specific signaling cascades in skeletal myofibers of intact animals; 3) To define other signaling molecules and pathways pertinent to transcriptional regulation of fiber type-specific genes. These aims are distinctive within the field of muscle biology for several reasons. Activity-dependent inter-conversion of specialized skeletal muscle subtypes was observed many decades ago, but identifying the molecular mechanisms that underlie this physiologically important response has been an elusive goal. Our recent hypothesis that calcineurin is important to the process has stimulated a fresh look at the problem. The subsequent experiments we propose are hypothesis-driven and focused, and major conclusions will be buttressed by results from both reductionisticand integrative approaches. We have incorporated new experimental methods so as to capitalize on recent technological advances. Finally, the knowledge to be gained may provide opportunities for development of new therapeutic measures to alter the specialized properties of skeletal myofibers, for the benefit of patients with primary and secondary myopathies or with metabolic diseases in which skeletal muscle plays an important role. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR PHYSIOLOGY OF RECOVERY FROM MUSCLE ATROPHY Principal Investigator & Institution: Pavlath, Grace K.; Associate Professor; Pharmacology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-MAY-2006 Summary: A loss of skeletal muscle functional capacity occurs in disease, disuse and aging mostly attributable to a loss of muscle mass. Such losses of muscle mass contribute to weakness, impaired mobility and/or respiratory function, low quality of life and high health care costs. The overall goal of this proposal is to delineate cellular and molecular mechanisms that regulate growth of atrophied muscles. The relative importance of muscle precursor cell (mpc) pathways vs. myofiber pathways can vary depending on the type of muscle growth and may differ for the growth of an atrophied myofiber. Determining how much of the recovery from atrophy is dependent on mpc is important for designing therapeutic strategies to treat muscle atrophy. This proposal has 3 integrated parts: (1) To delineate the contribution of mpc and other muscle progenitor cells to growth of atrophied muscle (Aims 1 and 2). We will define the timing of mpc proliferation and fusion with myofibers during growth. Subsequently, we will analyze growth in muscles lacking mpc due to local irradiation. Finally, we will determine if the abundance and/or in vitro properties of newly identified muscle progenitor populations change in response to muscle atrophy or growth. (2) To enhance mpc proliferation and fusion using the drug curcumin as a means of stimulating recovery from atrophy (Aim 3). We have previously shown that curcumin effectively enhances the growth of regenerating muscles and now extend these studies to growth of atrophied muscle; (3) To study molecular signals that are activated during the growth of atrophied muscles (Aims 4 and 5). We will delineate the contribution of a known signaling pathway (calcineurin) as well as identify new molecules using microarray analysis, which may play a role in regulating muscle growth. The experiments in this proposal will reveal new information about growth of atrophied muscle and possibly new avenues of rehabilitative therapy for manipulating this growth process in disease, disuse and aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MUSCLE LOCOMOTION
ACTIVITY
INITIATION
DURING
HEMIPARETIC
Principal Investigator & Institution: Brown, David A.; Programs in Physical Therapy; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 10-SEP-2000; Project End 31-MAY-2004 Summary: (adapted from Investigator's abstract) During locomotion in persons with post-stroke hemiparesis, muscle activity is initiated at inappropriate points in the cycle. As a consequence, movements are less-forceful and are slower, and movement function is impaired. The investigators propose that an interaction between two key underlying mechanisms, heightened motoneuron excitability and abnormal position-dependent modulation of motoneuron excitability, result in inappropriately-timed muscle activity. With their earlier work, the investigators have shown that paretic uniarticular knee muscles and biarticular hip and knee muscles are inappropriately activated at an earlier phase in the pedaling cycle. Since these muscles are lengthening at these points in the cycle and, since this effect is speed-dependent, they first propose that heightened motoneuron excitability results in muscle being activated when it is stretched at a specific threshold length and velocity. They will systematically vary the ranges of length and velocity of uniarticular knee muscles during cyclical leg motion to identify threshold muscle stretch parameters that trigger inappropriate initiation of uniarticular muscle activity. They will also systematically vary the ranges of length and velocity of uni- and biarticular muscles crossing the hip to identify muscle stretch parameters that, secondarily, contribute to inappropriate initiation of uniarticular knee muscle activity. They will use a computer model of the musculoskeletal system to calculate each muscle's length and velocity characteristics from kinematic patterns and develop a comprehensive statistical model of the relative contributions from multiple muscle stretch parameters. Also, normally during cycling, uniarticular knee extensors are activated during knee extension, regardless of hip position. However, preliminary work in post-stroke subjects has demonstrated abnormal activation that is dependent on hip position. They propose that the position of the hip can abnormally modulate motoneuron excitability and, hence, influence timing of muscle activity in uniarticular knee extensor muscles. They will systematically vary the relative position of the hip versus knee using a unique linkage attached to the feet. This experiment will result in kinematic patterns that generate more appropriate timings of uniarticlar knee extensors. The intent is that the experimental apparatus and principles developed within this study will form the basis of a new therapeutic modality that targets deficits in locomotor control, post-stroke, and with other neurologic conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MYOFILAMENT PROTEIN ISOFORMS IN NEUROMUSCULAR REFLEX Principal Investigator & Institution: Jin, J-P P.; Physiology and Biophysics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 20-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): Neuromuscular reflex plays a central role in the maintenance of muscle tone and hypertonia forms a basis of muscle contracture. As a sensory organ for muscle length in the peripheral neuromuscular reflex loop, muscle spindle produces positive feedback (la and II afferent) to simulate alpha-motor neuron activity. The sensitivity of a spindle is filtered by the tension of intrafusal muscle fibers under gamma-efferent regulation. Much attention has been paid to the spindle function
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in muscle function and spasticity and the contractility of intrafusal fibers is an essential link in the reflex loop. The intrafusal fibers contain unique myosin isoforms as compared with the extrafusal fibers, but little is known for their Ca 2+ regulation and contractile features. The regulation of intrafusal myofilament protein isoform expression during muscle development, adaptation and diseases is largely unknown. Based on our previous studies, we plan to investigate the role of myofilament protein isoforms in neuromuscular reflex. Our research plan is focused on testing a hypothesis in which the changes in fiber type-specific myofilament protein isoforms, especially the actin filament-associated regulatory protein troponin T (TnT), in intrafusal fibers may play a role in the pathophysiology of muscle contracture. It has been found that spastic muscles have increased type I (slow) fibers. Cerebral palsy, joint immobilization and tenotomy, three very different original conditions which cause muscle contracture, have a common consequence that is a fixed shortening of the resting muscle length. We have found an increased expression of slow myosin in a tenotomy model and the expression of myosin and thin filament regulatory protein isoforms is coordinated in the muscle. As an acidic TnT isoform, an up-regulation of slow TnT would increase the sensitivity of myofilaments to Ca2+ activation. The increase in intrafusal fiber Ca2+ responsiveness will increase spindle tension and sensitivity, which in turn increases the positive feedback to stimulate alpha-motor neuron to activate the extrafusal fibers and result in hypertonia. To test this hypothesis will help to understand the pathophysiology of muscle contracture. Three specific aims will be pursued in this pilot study: I. To examine the thin filament regulatory protein isoforms expressed in intrafusal fibers in adult and developing muscles. II. To investigate whether fixed shortening of muscle length originated from different conditions induces similar changes in the expression of intrafusal myofilament protein isoforms. III. To test whether elevated slow TnT expression in transgenic mouse muscles will produce increased Ca2+ sensitivity of intrafusal fibers and increased alpha-motor neuron activity. To explore this largely unknown area of neuromuscular reflex, this research initiative will lay groundwork for understanding the molecular mechanism of muscle contracture and improving treatment of this disabling condition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEURAL CONTROL OF GRASPING Principal Investigator & Institution: Santello, Marco; Exercise Science; Arizona State University P.O. Box 873503 Tempe, Az 852873503 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: Neurological and musculo-skeletal diseases severely impair the complex coordination of finger motion and forces that characterizes our ability to grasp and manipulate objects. Knowledge of the physiological control mechanisms of prehension is essential for an understanding of the pathologies that affect hand function. The longterm objective of the present proposal is to characterize the normal patterns of muscle activation responsible for the control of grasping movements, in particular the strategies used by the nervous system to coordinate the large number of muscles of the hand. This objective will be pursued by studying the simultaneous activation of multiple hand muscles and the coordination of grip forces. The present proposal has three specific aims: to characterize the organization of hand muscle activity as a function of hand and wrist posture (Aim number 1); to determine whether motor unit synchronization is dependent on task constraints (object's size and center of mass location; Aim number 2) and grip type (power vs. precision grip, and object shape; Aim number 3). The proposed studies are based on the hypothesis, supported by previous work, that the coordination
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of multiple grip forces is based on synergies reducing the number of degrees of freedom that has to be controlled independently. We will determine how the activity of multiple hand muscles is coordinated as a function of finger/wrist posture and task constraints. Hand muscle activity will be measured by intramuscular electromyographic recording as (a) interference multi-unit EMG and (b) single motor unit activity. Contact forces exerted by each finger will be measured in three dimensions by force sensors. The issues examined by this basic research are relevant to efforts in rehabilitation and restoration of hand function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEURAL CONTROL OF MUSCLE ACTIVITY Principal Investigator & Institution: Fetz, Eberhard E.; Professor; Physiology and Biophysics; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 30-SEP-1978; Project End 31-JUL-2006 Summary: We plan to investigate the neural mechanisms controlling voluntary hand and arm movement in primates. The functional roles of premotor (PreM) cells in motor cortex and spinal cord will be directly compared. PreM cells with a correlational linkage to forelimb motoneurons will be identified by post-spike effects in spike-triggered averages of EMG activity. The activity of PreM cells and multiple muscles will be documented during multidirectional wrist movements. Monkeys will operate a multijointed manipulandum that will allow wrist movements in three directions: flexionextension, radial-ulnar deviation and pronation-supination. In addition a grip handle will transduce force during a power grip. This repertoire of movements will activate muscles in different synergistic combinations and resolve whether PreM cells and nonPreM cells are organized primarily in terms of muscles or movement parameters. The directional tuning of forearm muscles will be compared with the tuning curves of PreM cells and non-PreM cells. We anticipate finding functionally significant differences between motor cortex cells and spinal interneurons with regard to their relation to muscles and movements. Spinal cord interneurons have been studied largely in immobilized animals; our study will provide new information about the involvement of interneurons in preparation and execution of voluntary movements. These interneurons will be identified by their synaptic inputs from different forelimb muscles and from functionally identified cortical sites. We will also systematically map the movements of arm and hand evoked by electrical stimulation of spinal cord sites; the modulations of these responses during an instructed delay task will reveal the interaction of intraspinally evoked responses with preparation and execution of voluntary movements. Activity of dorsal root afferent fibers also will be recorded during an instructed delay task to document the afferent input to the central nervous system during movement. The axonal excitability of afferent fibers will be tested to investigate task-related modulation of presynaptic inhibition. These studies of the primate motor system will provide unique information essential to understanding and effectively treating clinical motor disorders, like cerebral palsy, stroke and spinal cord injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEURAL DEVELOPMENT
FACTORS
AND
UPPER
AIRWAY
MUSCLE
Principal Investigator & Institution: Millhorn, David E.; Joseph Eichberg Prof. & Chairman; Molecular and Cellular Physio; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221
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Timing: Fiscal Year 2002; Project Start 10-JUL-2000; Project End 31-MAY-2004 Summary: Breathing is a highly regulated process that requires precise coordination among the muscles that cause ventilation and those responsible for maintenance of upper airway patency. Failure to properly activate the upper airway dilator muscles in response to an increase in inspiratory drive can result in obstruction of the upper airways. High fidelity synaptic signaling across the neuromuscular junction is required for precise regulation of upper airway patency that corresponds to the level of inspiratory drive. The major synaptic component of the neuromuscular junction is the nicotinic acetylcholine receptor (nAChR), a ligand (ACh)- gated channel that is composed of four homologous trans-membrane subunits (alpha2, beta, epsilon, gamma) arranged in a pentamer. During early postnatal development the nAChR undergoes a structural modification which impacts on its ability to respond to ACh released from motoneurons. In the neonate, the nAChR contains a gamma- instead of the epsilonsubunit. The nAChR-gamma exhibits a lower single channel conductance than the adult nAChR-epsilon. Thus, muscles that express more nACh-gamma and less nAChRepsilon might be prone to hypotonicity and less responsive to synaptic input. We hypothesize that discordant regulation of the nAChR-gamma and nAChR-epsilon isoforms could lead to reduced upper airway patency and airway obstruction There is growing evidence that opposing kinase and phosphatase pathways in muscle regulate the nAChR-gamma to nAChR-epsilon transition during early postnatal development. Moreover, recent findings indicate that both the kinase and phosphatase activities are regulated by "trophic" factors released from the motoneurons. The proposed research will investigate the role of the tetradecapeptide somatostatin (SST) in the regulation of tyrosyl phosphatase (PTPase) activities in muscle. Preliminary results show that SST, which is expressed developmentally in the motoneurons that innervate the upper airways, prevents induction of -subunit gene expression by the kinase pathway. The specific aims are: 1) Identify and characterize the protein tyrosyl phosphatases that are activated by SST and cause inhibition of epsilon-subunit gene expression; 2) Determine the mechanism by which SST-induced PTPases oppose kinase pathways to prevent activation of epsilon-subunit gene expression; and 3) Determine the effect of continuous expression of the SST-SSTR-PTPase pathway on epsilon-subunit gene expression in genetically engineered mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEURAL MECHANISMS IN MUSCLE FATIGUE Principal Investigator & Institution: Enoka, Roger M.; Professor; Kinesiology & Appld Physiology; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2002; Project Start 15-APR-2002; Project End 31-MAR-2005 Summary: The endurance capacity of muscle varies with the task that is performed. We found that the endurance time for a submaximal isometric contraction with the elbow flexor muscles was twice as long when the wrist was attached to a force transducer compared with when it supported an equivalent inertial load. Although the subject sustained a constant force when the wrist was restrained by a force transducer and maintained a constant elbow angle when supporting the inertial load, the resultant muscle torque and the rate of increase in the average EMG were identical for the two tasks. Nonetheless, additional results suggested that the descending drive to the motor neurons was greater during the constant-position contraction. We hypothesize that endurance time of the elbow flexor muscles is less for a constant- position contraction compared with a constant-force contraction due to greater excitatory descending drive to the motor neurons and greater inhibitory feedback from the muscles. According to
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this hypothesis, the difference in endurance time for the two tasks is attributable to differences in the input received by the spinal motor neurons. We propose three specific aims (Aims 1 to 3) to examine the, descending- drive component of the hypothesis and two aims (Aims 4 and 5) to assess the inhibitory-feedback component. The hypothesis predicts that motor unit activity will be greater during the constant-position contraction (Aim 1) and that endurance time will be briefer when the gain of the position-feedback signal is increased (Aim 2) and vibration is applied to the active muscles (Aim 3). Furthermore, the hypothesis predicts that the decline in maximum discharge rate of motor units in the contralateral muscles (Aim 4) and that the increase in mean arterial pressure (Aim 5) will be greater after the constant-position contraction. We are not aware of another study that has examined the contribution of neural mechanisms to the fatigue experienced during constant-force and constant-position isometric contractions. The outcomes will provide novel information on the physiological adjustments that occur during isometric contractions, which are the most common form of muscle activity, and will have direct application to the design of work tasks in ergonomics and the prescription of physical activities in rehabilitation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROMUSCULAR CONTROL OF THE PHARYNGEAL AIRWAY Principal Investigator & Institution: Fregosi, Ralph F.; Associate Professor; Physiology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 10-APR-1998; Project End 31-MAR-2004 Summary: (Adapted from the applicant's abstract): The long-term objective of this proposal is to test the hypothesis that the muscles that protrude and retract the tongue (genioglossus and hypoglossus/styloglossus muscles, respectively) are co-activated during inspiration, and that co-contraction contributes significantly to the maintenance of pharyngeal airway patency. The conceptual model is that co-contraction during inspiration stiffens the tongue as the antagonist muscles work against one another, thereby minimizing backward displacement of the tongue and subsequent occlusion of the pharynx. Significant new data showing respiratory-related co-activation of the protrudor and retractor muscles in animal models, as well as recent evidence showing improved inspiratory airflow with co-activation in human subjects with obstructive sleep apnea, provide strong support for this conceptual framework. Accordingly, the following Specific Aims are designed to rigorously test the co-activation hypothesis using an anesthetized rat model: Aim 1 is to demonstrate that the protrudor and retractor muscles of the tongue are co-activated during breathing and that they respond similarly to changes in respiratory related stimuli. Aim 2 is to show that co-activation of the extrinsic tongue muscles will improve pharyngeal airway mechanics more than the independent activation of either the protrudor or retractor muscles. Aim 3 is to demonstrate that the initial operating length of the tongue muscles will influence: a) the magnitude of respiratory related tongue movements, b) the ability of the tongue muscles to modulate pharyngeal airway flow mechanics, c) the fatigability of the tongue muscles. These experiments will lay the foundation for new and improved treatment strategies for persons with obstructive sleep apnea or with other conditions that are caused by malfunction of the tongue motor system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOVEMENT
NEUROMUSCULAR
STRATEGIES
FOR
HUMAN
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TONGUE
Principal Investigator & Institution: Sokoloff, Alan J.; Physiology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: The tongue is essential in normal oromotor function, and is of pre-eminent importance in the production of human speech. Tongue dysfunction is associated with many human clinical syndromes. Yet the design of effective treatments for recovery from tongue dysfunction is hindered by our limited understanding of the neuromuscular bases for tongue motor control. Most critically, we lack information on the organization of the fundamental output elements of the tongue motor system, i.e., tongue muscles, tongue muscle compartments and tongue motor units. The long term goals of this study are to determine the neuromuscular organization of these functional output elements in the human tongue motor system and to improve clinical treatments for recovery from tongue dysfunction. To achieve these goals this study applies anatomical and physiological techniques directly to investigations of the human and non-human primate tongue. The results of these investigations will meet three general aims. First, the architecture of human tongue muscles and the pattern of their motor innervation will be studied to determine the neuroanatomical bases of muscle biomechanical diversity in the human tongue. Second, the identity and distribution of muscle fiber types in the human tongue will be determined to test the hypothesis of parallel anatomical systems for human tongue movement. Third, the morphology and physiology of tongue motor units and muscle compartments will be determined in the non-human primate to allow physiological correlation of anatomical organization. These studies will provide the first detailed understanding of the functional output elements of the human and non-human primate tongue. This understanding is essential if we are to develop accurate models of tongue motor control and if we are to design rational interventions for recovery of tongue function in human disease Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROMUSCULAR SYNAPTOGENESIS IN ZEBRAFISH Principal Investigator & Institution: Balice-Gordon, Rita J.; Associate Professor; Neuroscience; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2005 Summary: (provided by applicant): The goal of this proposal is to isolate vertebrate genes that play a role in neuromuscular synapse formation and maintenance, using zebrafish as a model system. Previous fish mutagenesis screens have not focused on mutants that affect neuromuscular synaptogenesis, in part because these synapses need to be labeled with antibodies or toxins that specifically label different synaptic components and visualized using light microscopy at relatively high magnification. Over the last year, my lab has participated in a pilot mutagenesis screen conducted by Drs. Mary Mullins and Michael Granato in the Dept. of Cell and Developmental Biology at the University of Pennsylvania. My lab developed an assay for neuromuscular synapses in zebrafish utilizing antibodies against synaptic vesicles to mark presynaptic terminals, fluorescent conjugated alpha-bungarotoxin to label acetylcholine receptor (AChR) clusters, and high resolution fluorescence microscopy in intact fish at 48 hours post fertilization (hpf). Preliminary results demonstrate that we have identified several mutants with defects in different aspects of neuromuscular synaptogenesis at 48 hpf, and that some of these mutants also have motility defects. These mutants fall into three
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overlapping categories: aberrant synapse formation (too many, too few or mislocalized pre- and/or postsynaptic specializations); normal synapse formation, followed by synapse loss and/or redistribution; and aberrant primary and/or secondary motor axon branching within body wall musculature, resulting in aberrant endplate bands within individual muscles. Based on our success with this small, pilot screen, we propose to first, define the primary defect in 2-3 of the isolated mutants by analyzing synaptic structure and function; second, to determine the genetic map position of mutated genes for 2-3 mutants using complementation, mapping using an established set of molecular markers, and linkage analyses; and third, to isolate new mutations in genes required for neuromuscular synapse formation and maintenance by continuing and expanding our screen of mutant fish. Taken together, these approaches will allow us to study the genetic, molecular and cellular mechanisms of these processes in vertebrates. This R21 proposal will allow us to use mutagenesis in zebrafish to identify some of the genes required for neuromuscular synapse formation and maintenance, and expand the repertoire of tools available in my lab to address these fundamental questions in zebrafish and mice in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRECISE CONTOL OF TONGUE MOVEMENT Principal Investigator & Institution: Goldberg, Stephen J.; Professor; Anatomy and Neurobiology; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 01-JUN-1994; Project End 31-MAY-2006 Summary: The normal development of the complex neuromuscular system used to control tongue movement is critical to the immediate survival of all terrestrial mammals. Voluntary control in this motor system involves a sequence of neural and muscular events beginning in the motor cortex. Coordinated tongue movements are needed for eating (mastication and swallowing), drinking, licking (suckling), breathing, grooming and vocalization. Clinically, and in contrast to a normal developmental progression, premature human infants often need to be fed intravenously or with a nasogastric tube for extended periods of time (weeks or months) to insure their survival. Attempts to begin bottle feeding these infants can result in apnea, bradycardia, hypoxia, fatigue and agitation and there can also be the long term consequence of delayed oral feeding milestones which results in longer hospital stays. A later impact on motor speech has also been documented. It may be that the interrupted normal maturation of the neuromuscular control system for appropriate suckling plays an important role here. In addition, infants born at term who also need non-oral nutrition due to system disorders or surgical interventions may also exhibit delayed oral feeding. We propose, therefore, to continue our studies of rat hypoglossal nucleus anatomy and tongue muscle contractile measures with a new emphasis on system development. We also propose to add morphological and biochemical studies of individual developing tongue muscles. The normal development of this system, and its cortical control, will then be compared and contrasted to that in rat pups who have been fed, for varying postnatal times, using a gastric cannula. Some animals will experience a near total absence of suckling while others will have their normal suckling sequence interrupted. This has been termed "artificial rearing" and is modeled on the human infant interventions mentioned above. New preliminary data indicates that artificial rearing from postnatal days 4 to 13 results in striking changes in tongue contractile strength, speed, endurance, muscle fiber diameter and a persistence of developmental myosin heavy chain (MHC) isoforms, similar to changes observed in other skeletal muscles after a period of disuse. These studies should help to lay a firm foundation for an understanding of how the
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hypoglossal motor system develops, especially since many aspects of its normal development have simply not yet been studied. In addition, we hypothesize that the neuroanatomical organization within the hypoglossal nucleus, muscle morphology plus MHC expression, muscle contractile characteristics and afferent input from the motor cortex are altered in animals that have been artificially reared. The degree to which each of these components is altered needs to be ascertained for a clearer view of this motor system and to delineate those postnatal time periods that are the most critical for normal development. It is also hoped, for the long run, that these basic findings can have an application for a speedier and more complete rehabilitation of human infants that are necessarily deprived of normal suckling and eating. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRE-PATTERNING OF SKELETAL MUSCLE Principal Investigator & Institution: Burden, Steven J.; Professor; Pharmacology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 15-MAY-2001; Project End 31-MAR-2005 Summary: (From the Applicant's Abstract): Current ideas of synapse formation suggest that muscle is patterned by signals, such as agrin, provided by motor neurons. Our recent studies, however, have revealed that muscle is pre-patterned in the absence of innervation. We found that motor axons in top 2b mutant embryos reach their targets but fail to grow or branch within limb or diaphragm muscles. To our surprise, we found that AChRs are clustered in the central region of muscle, despite the absence of motor axons within the muscle. These results suggest that the expression pattern of AChRs in skeletal muscles is determined, at least in part, by mechanisms that are autonomous to muscle and suggest that muscle is pre-patterned, independent from signals provided by motor neurons. The experiments described in this proposal are designed to determine how pre-patterning of muscle is established, whether muscle pre-patterning might regulate where axons terminate and form synapses and how innervation might regulate muscle pre-patterning. We will determine (1) whether motor innervation requires neural or muscle expression of top 2b, (2) whether signals from motor axons are required to pre-pattern AChRs in skeletal muscle, (3) whether MuSK or agrin are required to establish muscle pre-patterning, (4) whether additional skeletal muscle proteins are pre-patterned in muscle, (5) whether genes encoding synaptic proteins are pre-patterned in muscle, (6) whether pre-patterned molecules might have a role in specifying the site of motor innervation, (7) whether motor axons or electrical activity suppress muscle pre-patterning, and (8) whether a distinct myoblast lineage might be a source of the pre-pattern. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROGESTERONE /MELATONIN AS NEUROPROTECTANTS IN NERVE INJ Principal Investigator & Institution: Yu, Wan-Hua A.; City College of New York 138Th St and Convent Ave New York, Ny 10031 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: Motor neurons of adult animals, despite resistance to axotomy-induced cell death, undergo apoptotic cell death after nerve injury with removal of axon associated Schwann cells, indicating that neurotrophic factors from central glial cells may not be adequate to support the survival of injured neurons. This proposal aims to test the hypothesis that glial synthesis of neurotrophic factors can be up-regulated by steroid
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hormones, and that death of injured neurons is preventable by agents which scavenge free radicals and remove reactive oxygen species. Adult rat hypoglossal nerve innervating the tongue muscles will be lesioned on one side by crush (for reversible injury), ligation (to permanently disconnect neurons from target muscles but retain the proximal nerve segment), and avulsion (to deprive neurons of Schwann cell-derived neurotrophic factors). The vagus nerve will be crushed or transected to include parasympathetic motor neurons for comparison. Since progesterone (PG) and melatonin (MT) possess antioxidant activities; and in cerebral ischemia and truamatic injuries, reduce tissue damage, attenuate brain edema and cell loss, and facilitate functional recovery; and glial cells have PG receptors, nerve lesioned rats will receive PG injection daily via s.c. route, MT by osmotic pump infusion, combined treatment of the two agents, PG antagonist RU486 to block endogenous PG activities, and no treatment as control. Specific questions to be addressed are: (1) Will PG increase the synthesis of brain-derived neurotrophic factor (BDNF) and glial cell-line derived neurotrophic factor (GDNF)? (2) Will PG and MT prevent the loss of neurons after nerve avulsion? (3) What is the status of PG receptors in motor neurons before and after axotomy? Will PG affect the expression of PG receptors ininjured neurons? (4) Will a "death receptor" FAS be induced in neurons after nerve avulsion? Will PG and MT block the induction or reduce the expression of FAS and p75 in injured neurons? To answer these questions, tissue sections will be prepared for neuronal cell counting, and for immunostaining of BDNF, GDNF, PG receptors, FAS and p75, and quantify their levels by computerized image analysis. These studies will provide insight into the cellular and molecular events responsible for the initiation and activation of apoptotic pathways in injured neurons, and offer therapeutic potential for treating traumatic injuries and other neuropathological conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REDOX MECHANISMS OF RESPIRATORY MUSCLE STRESS ADAPTATION Principal Investigator & Institution: Clanton, Thomas L.; Professor; Internal Medicine; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 01-DEC-1994; Project End 31-JAN-2005 Summary: During intense exercise, skeletal muscles must withstand stress in the form of heat, tissue hypoxia, reactive oxygen, steep osmotic gradients, elevated tissue pressure, sheer stress and over-stimulation. Few cells of the body could survive such punishment and yet skeletal muscles survive and adapt to it. To accomplish this, they must be pre-programmed in some primordial way to sense when the environment is threatening and make rapid adaptations in contractile and metabolic activity to reduce the threat to survival. We hypothesize that reactive oxygen is an important signal used for this purpose, particularly under conditions of metabolic stress, such as high energy demand (over-stimulation), low energy supply (hypoxia) or overheating (thermal stress). In this funding period, we will investigate the mechanisms by which reactive oxygen participates in muscle adaptation to stress. The study will focus on isolated, perfused mouse diaphragm. SPECIFIC AIM 1 will test the hypothesis that reactive oxygen is formed as an acute response to hypoxia, heat stress and over-stimulation (resulting in fatigue) and that conditions of disordered O2 supply and demand are necessary prerequisites for this response. Both tissue fluorescence and confocal imaging techniques will be used in these experiments. SPECIFIC AIM 2 will test the hypothesis that reactive oxygen plays an important role as a signaling agent to modify metabolic pathways during stress in such a way as to favor of accumulation of metabolites,
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preservation of ATP and reduction of creatine phosphate. This will be tested by blocking the effects or reactive oxygen with antioxidants and by using transgenic species with antioxidant over-expression. Measures phosphate metabolism, mitochondrial function, creatine kinase function and activity of other metabolic enzymes will be assessed. SPECIFIC AIM 3 will test the hypothesis that reactive oxygen plays a role in acute changes in the cytoskeleton during stress that promote an increase in muscle "stiffness" and favor preservation of muscle structural integrity. Biophysical measurements of the viscoelastic properties of muscle will be tested before and during stress. These studies should provide new information regarding the adaptive mechanisms muscle in stressful environments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF ALS AND ITS ROLE IN THE IGF SYSTEM Principal Investigator & Institution: Boisclair, Yves R.; Animal Science; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2003; Project Start 26-SEP-1997; Project End 31-MAR-2007 Summary: (provided by applicant): Gene deletion studies have demonstrated the importance of IGF-I and II (IGFs), particularly during fetal life when local IGFs production predominates. After birth, the liver becomes the most important site of IGFs synthesis, resulting in the development of a substantial plasma reservoir. This reservoir is dependent on the postnatal production of the acid labile subunit (ALS), a protein that recruits IGFs and IGF Binding Protein-3 in long-lived ternary complexes. The significance of this reservoir has been uncertain until we showed that ALS and the plasma IGF-I reservoir are required for early postnatal growth and bone development. We now will extend these studies to normal and diseased states of later postnatal life. This is relevant to malnutrition and catabolic illnesses in which decreased plasma IGF-I is associated with erosion of lean mass. Despite this association, IGF-I-based therapies have had limited success, reflecting the need for their incorporation into ternary complexes for effectiveness. Three specific aims wilt be pursued to address the role of ALS and the circulating IGFs reservoir during diseased states. AIM A: IGF-I is a potent positive regulator of skeletal muscle mass. Null ALS mice will be subjected to challenges known to induce changes in plasma IGF-I and to alter the mass of skeletal muscles (i.e., sudden increase in GH, nutritional deficiency or sepsis). AIM B: Humans have 3 times as much plasma IGF-II than IGF-I. In contrast, mice have little IGF-II and null ALS mice have normal carbohydrate homeostasis. To determine the role of ALS in containing the metabolic effects of IGF-II, we will study null ALS mice over-expressing human IGF-II. AIM C: GH stimulates ALS synthesis by increasing transcription. In vitro, this effect is conveyed by STAT5, but the importance of this mechanism remains to be established in vivo. Using null STAT5 mice and liver cells, we will evaluate the contribution of direct and indirect mechanisms mediating the effects of GH on ALS synthesis. Studying the GH-regulation of ALS transcription will provide clues to mechanisms responsible for development of hepatic GH resistance during catabolic diseases. Overall, these studies will significantly advance our understanding of the roles played by ALS and the circulating IGF reservoir in diseases of postnatal life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION OF PROTEIN TURNOVER IN SEPSIS Principal Investigator & Institution: Vary, Thomas C.; Professor; Cellular/Molecular Physiology; Pennsylvania State Univ Hershey Med Ctr 500 University Drive Hershey, Pa 170332390
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Timing: Fiscal Year 2002; Project Start 01-JUL-1989; Project End 31-JUL-2003 Summary: The objectives of the studies described herein are to identify the loci responsible for the inhibition of protein synthesis in skeletal muscle during sepsis and to establish the mechanism(s) by which the inhibition can be reversed in order to develop treatment strategies to combat the severe muscle wasting associated with the septic process. Sustained muscle wasting contributes to the morbidity and mortality associated with sepsis. The defect in protein synthesis is localized to an impaired translation of mRNA at the level of peptide-chain initiation. Translation initiation is regulated at two steps: formation of the 43S pre-initiation complex (controlled by eukaryotic initiation factor 2 (eIF2) and eIF2B); and the binding of mRNA to the 40S ribosome (controlled by elF4E). We have identified a decreased activity of eIF2B as one defect in peptide-chain initiation and have shown that the muscle content of eIF2B protein is diminished 40 percent by sepsis. Therefore, reduced expression of eIF2B appeared a likely cause of the sepsis-induced inhibition of peptide-chain initiation in muscles of septic rats. However, protein synthesis can be stimulated 2-fold by perfusion of muscles from septic rats with buffer containing either IGF-I or elevated concentrations of amino acids by accelerating peptide-chain initiation without increasing the muscle content of eIF2B. Thus, effects of a reduced eIF2B expression on protein synthesis can be overridden, but the mechanisms responsible remain unknown. The hypothesis to be tested is that altered regulation of eIF2B and/or eIF4E mediates the changes in protein synthesis in sepsis. The specific aims of the studies proposed for the next project period are: (1) to evaluate the role of altered phosphorylation of eIF2B activity in controlling translation initiation during sepsis; (2) to investigate the effect of sepsis on eIF4E by measuring the amount of eIF4E found in the inactive 4E-BPI eIF4E complex and the active eIF4G eIF4E complex in muscle; (3) to investigate the mechanisms by which IGF-I stimulates translation initiation and contrast the response of skeletal muscle protein synthesis to IGF-I with that of insulin during sepsis; (4) to investigate the mechanisms by which amino acids stimulate translation initiation, and hence protein synthesis, during sepsis; and (5) to investigate the mechanisms by which chronic infusion of TNF or IL-1 cause an inhibition of protein synthesis in skeletal muscle. The research design will be to correlate changes in eukaryotic factor activity with rates of protein synthesis to establish which control mechanisms are important for regulating protein synthesis in skeletal muscle during sepsis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CALPONIN
REGULATION
OF
SMOOTH
MUSCLE
ACTOMYOSIN
BY
Principal Investigator & Institution: Haeberle, Joe R.; Associate Professor; Molecular Physiol & Biophysics; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 01-APR-1995; Project End 31-JUL-2004 Summary: The proposed studies constitute part of a larger effort to understand how the contraction of smooth muscle is regulated at the level of contractile proteins, actin and myosin. The focus of this proposal is to elucidate the mechanism by which the putative regulatory protein calponin interacts with the actin filament to modulate contraction. In particular, thee studies will attempt to determine if calponin regulates a well described state of smooth muscle contraction called a "latch- state". The latch-state allows smooth muscles to remain contracted for long periods with relatively low expenditure of chemical energy. The high-economy of smooth muscle contraction is essential for normal physiologic function. In spite of the central importance of this contractile state
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for normal function of smooth muscle, the molecular basis for the regulation of the latch-state is unknown. Our central hypothesis is that calponin slows the rate of crossbridge dissociation from actin, and this leads to activation of unphosphorylated cross bridges via a thin filament-linked mechanism. To test this hypothesis we will measure 1) actin filament sliding velocity, 2) changes in the level of force exerted on regulated actin filaments by a field of immobilized myosin molecules, 3) the force, displacement (step size), and attachment time for single myosin molecules interact with single actin filaments, and 4) the rate of myosin dissociation from actin using stopped-flow techniques. These measurements will provide insights into the physiologic parameters of isometric force and unloaded shortening velocity that characterize the contractile state of intact smooth muscles. These assays, in conjunction with recent x-ray diffraction data and high resolution electron microscopic images of actin myosin, tropomyosin, and calponin allow us to formulate and test specific molecular models for how calponin might interact with actin, tropomyosin, and/or myosin. The proposed studies will begin to address the issue of how calponin might interact with actin, tropomyosin, and/or myosin. The proposed studies will begin to address the issue of how calponin-mediated regulation interacts with the now well established myosin phosphorylation regulatory system. A major goal of the proposed studies will be to elucidate the role of calponin in thin-filament linked regulation of unphosphorylated myosin (i.e. the latch-state). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RESPIRATORY ACTIVITIES OF INTRINSIC TONGUE MUSCLES Principal Investigator & Institution: Bailey, Elizabeth F.; Physiology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Tongue movement depends on the actions of both intrinsic (origin and insertion in the tongue) and extrinsic (attached to bone and inserted into the tongue) muscles. These muscles play a key role in swallowing, breathing, chewing, and speaking. Contraction of the extrinsic muscles is generally considered to change tongue position (protrusion or retrusion), whereas contraction of the intrinsic tongue muscles changes tongue shape. To date, research that examines the respiratoryrelated effects of tongue function in mammals has focused exclusively on the respiratory control and function of the extrinsic tongue muscles. The respiratory-related control and function of the intrinsic tongue muscles and their bearing on extrinsic tongue muscle activity are still unknown. Recent findings indicate that the intrinsic tongue muscles may contribute to tongue protrusion and retraction, and facilitate the actions of the extrinsic tongue muscles in swallowing. In light of these findings, our objective is to characterize the respiratory-related activities of the intrinsic tongue muscles in vivo. The specific goals of the present application are to test the following hypotheses: (1) intrinsic tongue muscles are co-activated with extrinsic tongue muscles during resting tidal breathing; (2) intrinsic and extrinsic tongue muscle activities are modulated in parallel by central and peripheral chemoreceptors and airway mechanoreceptors; and (3) the EMG of intrinsic and extrinsic tongue muscles exhibit similar onset times and burst characteristics during perturbations of chemoreceptor and mechanoreceptor feedback. Experiments will be conducted on urethane anesthetized, spontaneously breathing male Sprague-Dawley rats. Simultaneous EMG recordings of the hyoglossus, internal intercostal muscles and superior longitudinal muscles will be obtained under each of the following conditions: (1) hypoxia, hypercapnia, and asphyxia, to assess the effects of central and peripheral chemoreceptor stimulation of intrinsic tongue muscle activities; (2) before and after superior laryngeal nerve section, and before and after lingual nerve
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section, to quantify the influence of upper airway mechanosensory modulation of intrinsic tongue muscle activities; (3) with and without single-breath airway occlusion, to quantify the influence of phasic lung volume changes on drive to intrinsic tongue musculature. The results of this work will enhance our understanding of the functions of the tongue musculature and provide broad insights into the modulation of tongue muscle activities in breathing and other behaviors such as chewing and swallowing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RESPIRATORY RELATED MOTOR OUTPUT TO UPPER AIRWAY MUSLCES Principal Investigator & Institution: Kuna, Samuel T.; Associate Professor of Medicine; Medicine; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUL-1981; Project End 31-MAR-2004 Summary: (Adapted from the Applicant's Abstract): The purpose of this proposal is to perform experiments in decerebrate cats to examine four specific aims: 1. To determine the neural input from the Kolliker-Fuse nucleus (KFN) to pharyngeal respiratory muscle motoneurons located in the hypoglossal nucleus (HGN). In addition, to neural pathways, neuromediator activity of the KLN will be explored. 2. To determine the effect of airway length on the mechanical effects of pharyngeal constrictor muscle contraction. It is hypoothesized that upper airway shortening may alter the mechanical effect of contraction of these muscles, such that they will have dilatory instead of constricting action. 3. To determine the effect of vagal afferent activity on pharyngeal muscle constrictor action. It is proposed that the pharyngeal muscles that are usually pharyngeal constrictors may become dilator muscles during hypercapnia in the absence of afferent vagal feedback. 4. To determine the changes in regional structure during contracture of various pharyngeal muscles by the use of retrograde fiberoptic imaging in a closed upper airway. This work is an expansion of work conducted to date by the PI, who has recently relocated to the University of Pennsylvania. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SARCOLEMMAL ORGANIZATION OF EXTRACULAR MUSCLE Principal Investigator & Institution: Porter, John D.; Professor; Ophthalmology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: Extraocular muscle (EOM) is specifically tailored to serve a diverse repertoire of eye movement control systems. Many aspects of the molecular biology, cell biology, morphology, and function of EOM are very different from the well-describe skeletal muscles of the limb and axial skeleton. Genotype and/or phenoptypic differences in the EOMs may either predispose or protect them in disease. Thus, knowledge of EOM biology is critical in design of theoretical and practical models of eye movements and in preventing or treating disorders. of eye alignment or movement. We currently have almost no knowledge of the cell/molecular substrate for stabilizing the EOM membrane, or sarcolemma, and for formation and maintenance of specializations at the neuromuscular function. What we do know strongly suggests that the transmembrane protein complex that plays these roles in skeletal muscle may exhibit adaptations in EOM. We propose to test the hypothesis that the unique phenotype, and functional properties, of EOM require muscle group-specific adaptations at the level of the intricate complex of proteins that spans the sarcolemma to stabilize during muscle contraction and to organize the neuromuscular junction. First, we will determine the
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spatial/temporal relationships in maturation EOM and visuomotor systems. Data will establish similarities and differences between EOM and the pattern that has been well described in other muscles. Second, we will investigate the regulatory mechanisms for the specializations in the transmembrane protein complex at neuromuscular junctions in EOM. These studies will allow use to identify the extent to which EOM utilizes general muscle regulatory mechanisms and identify any protein complex in EOM using natural mutant and gene knockout models that generate loss of function in most muscles. Our pilot data establish that EOM responds to loss of components of the transmembrane protein system in ways that other skeletal muscles do not. Proposed studies will begin to understand the molecular mechanisms used by EOM in sarcolemmal organization for the day-to-day function of these novel muscles. An overall knowledge of the properties and regulation of the EOM sarcolemma will be important for understanding and treating ocular motility disorders in myasthenia gravis, congenital fibrosis of EOM, and strabismus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SMOOTH MUSCLE THIN FILAMENT Principal Investigator & Institution: Graceffa, Philip J.; Boston Biomedical Research Institute 64 Grove St Watertown, Ma 02472 Timing: Fiscal Year 2002; Project Start 20-AUG-2001; Project End 31-JUL-2005 Summary: (provided by the applicant): Smooth muscles, which surround the periphery of hollow organs, contract to change organ shape or maintain tension to fix the shape and thereby control the flow of vital fluids, which are essential to the normal functioning of the cardiovascular, respiratory, digestive, and reproductive systems. If the regulation of smooth muscle contraction does not function properly, it could contribute to such diseases as high blood pressure, asthma, and premature birth. The goal of our work is to understand the molecular basis of the normal regulation of contraction. Smooth muscle contraction is primarily regulated by the Ca2+ controlled phosphorylation of myosin in the thick filament. However there is not a strict coupling between phosphorylation levels and the level of the resulting contractile force. Evidence indicates that there is additional regulation in the actin thin filament possibly involving tropomyosin (Tm). However the mechanism of this function is poorly understood. The long-range goal of this project is to uncover the molecular mechanisms whereby Tm, in concert with other thin filament proteins, regulates smooth muscle contraction. The main hypothesis of this proposal is that thin filament regulation occurs mainly by controlling the movement of Tm on the thin filament by myosin in the thick filament and by the other thin filament proteins, caldesmon and calponin, which are in turn regulated by phosphorylation and Ca2+binding proteins. This will be tested by monitoring Tm's position, and movement by measuring the Tm-actin distances as a function of myosin, caldesmon and calponin by fluorescence resonance energy transfer and correlated with actomyosin ATPase activity, an in vitro analogue of contraction. The results of these studies, which will be conducted on reconstituted thick and thin filaments, will help to further our understanding of the switching on/off of smooth muscle contraction and of smooth muscle's unique ability, especially vascular muscle, to maintain tension, and thus organ shape, at the cost of very little energy. These studies will compare myosin from vascular and gastrointestinal smooth muscles in order to better understand the ability of vascular muscle to maintain this tension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SPATIAL AND TEMPORAL CONTROL OF TARGETED LIMB MOVEMENTS Principal Investigator & Institution: Cordo, Paul J.; Senior Scientist; None; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-DEC-1983; Project End 31-MAY-2007 Summary: The long-range goal of this project is to determine how the human central nervous system (CNS) coordinates voluntary movement and ultimately to use this information to develop treatments for motor disorders, such as stroke. The goal of the research proposed in this application is to determine how proprioception at the receptor level-in this case, the muscle spindle-leads to perception. The central hypothesis to be investigated is that, in active movement, the primary source of proprioceptive input is muscle spindles in the lengthening, "antagonist" muscles, rather than muscle spindles in the contracting, "agonist" muscles. Three specific aims are addressed: Specific Aim 1 is to contrast the information signaled by agonist and antagonist muscle spindles to determine which of these populations provides the CNS with the most accurate information about limb position and movement. Unlike agonist muscle spindles, little is known about how antagonist muscle spindles respond to active joint rotation. We will characterize how agonist and antagonist muscle spindles signal joint position and movement to test the hypothesis that the CNS uses the input from both populations, but that the information provided by antagonist muscle spindles is the most accurate. Specific Aim 2 is to investigate how antagonist muscle spindles encode position and movement variables, to inform the CNS of the location and movement of the limbs in space. The proposed experiments are designed to test the hypothesis that, during a movement, antagonist muscle spindles signal the CNS information about the starting position, movement velocity, and limb position during movement by three distinctive features within the firing pattern. Specific Aim 3 is to characterize the influence of fusimotor input on antagonist muscle spindles. Past research on agonist muscle spindles has failed to explain why the CNS activates the fusimotor system during voluntary movement. The proposed experiments are designed to test the hypothesis that fusimotor input increases the precision with which antagonist muscle spindles signal limb position and movement during precise movements and during motor learning, but that fusimotor input does not decrease the precision of signaling from antagonist muscle spindles during loaded movements. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SPATIAL AND TEMPORAL PROCESSING IN PROPRIOCEPTION Principal Investigator & Institution: Jones, Lynette A.; Mechanical Engineering; Massachusetts Institute of Technology Room E19-750 Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 16-FEB-2001; Project End 31-JAN-2005 Summary: (Adapted from the Investigator's Abstract) The proprioceptive system converts information from receptors in muscles, skin and joints for the purposes of perceiving both the internal state of the neuromuscular system (e.g. the position of limbs, the forces generated by muscles) and the properties of objects (e.g., weight, stiffness) encountered in the external world. There is considerable kinematic ambiguity in these afferent signals as mechanoreceptors in muscles, skin and joints do not simply encode a single stimulus but respond to a number of variables both mechanical and temporal. Despite this ambiguity, the proprioceptive system can still extract the necessary information, such as joint velocity or angular position, from the sensory input and use this both to control and perceive muscle force and limb movements. The long-
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term goal of the present research is to understand The principles and mechanisms underlying these perceptual processes and to determine the commonalities in information processing shared by the proprioceptive system with other sensory modalities whose inputs arise externally. The present proposal uses human psychophysical techniques to address these issues in several series of experiments that will examine the nature and extent of spatial summation of forces in the hand using the contralateral limb-matching procedure, the temporal processing of limb movements and the motor and sensory mechanisms involved in perceiving derived percepts such as stiffness. The movement studies will initially focus on determining whether frequency selectivity, a property of many sensory modalities, characterizes proprioceptive processing. This will be measured in terms of tuning curves and peripheral filtering processes (i.e. critical bands). Related studies will determine what factors influence the perception of movement velocity under active and passive conditions, during fast and slow movements and when cutaneous signals are masked. The final series experiments will determine how subjects perceive properties such as stiffness, viscosity and inertia on the basis of muscle force and limb displacement signals, and whether, as predicted, the motor strategies used to derive this information differs for each of these variables. This research program will elucidate the basic operations of the human proprioceptive system, improve our understanding of normal perceptual functioning and provide a basis for interpreting neuromuscular and neurological disorders that impact human movement control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURE AND FUNCTION OF SARCOPLASMIC RETICULUM Principal Investigator & Institution: Ikemoto, Noriaki; Senion Scientist; Boston Biomedical Research Institute 64 Grove St Watertown, Ma 02472 Timing: Fiscal Year 2002; Project Start 01-JUN-1976; Project End 31-MAR-2007 Summary: (provided by applicant): The overall goal of this project is to resolve the molecular mechanism of Excitation (E)-Contraction (C) Relaxation (R) coupling in normal and diseased muscles. Skeletal muscle-type E-C-R coupling appears to occur in several sequential steps. The proposed experiments aim to elucidate the mechanism for each of these steps. (1) Upon depolarization of the surface membrane (excitation of muscle cell), the activator domain of the dihydropyridine receptor II-III loop binds to, and its blocker domain dissociates from, the ryanodine receptor (RyR)/calcium release channel protein; T-tubule polarization reverses these processes (hypothesis). The investigator will test this model (and alternative models as well) by examining how the peptides corresponding to these domains (activator and blocker) compete with their in vivo counterparts during E-C coupling in triads and skinned or permeabilized fibers. To further define the mechanism, the pattern of peptide activation/inhibition will be correlated with the pattern of peptide binding. (2) The binding of these II-III loop domains to their specific binding sites on the RyR produces local conformational changes in the signal reception region. The investigator will localize the binding sites of these loop domains, and will monitor the dynamic conformational changes occurring in the signal reception region during E-C coupling using the site-specific fluorescence probe. (3) The conformational change in the signal reception region is coupled with a global conformational change in the RyR and calcium release (contraction). This process seems to involve interactions of a number of regulatory sub-domains within the RyR. Using a novel peptide probe technique, this investigator has uncovered several subdomains involved in the regulation of the RyR calcium channel. Efforts will be made to uncover a sufficient number of sub-domains to deduce the global structure of the intra-
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molecular communication network. (4) Soon after the induction of calcium release (contraction), the calcium ATPase is activated to facilitate re-uptake of the released calcium (relaxation). The investigator hypothesizes that the communication between the RyR and the calcium ATPase is mediated by the transient changes occurring in the luminal calcium. This will be tested by correlating the time course of the changes in the activity of the calcium ATPase with those in the luminal calcium concentration. This program will likely resolve the basic mechanisms governing individual steps of E-C coupling, and will provide a better understanding of abnormal channel regulation in skeletal and cardiac muscles. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ALPHA-1C CALCIUM CHANNEL IN MUSCLE Principal Investigator & Institution: Palade, Philip T.; Professor; Physiology and Biophysics; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 27-SEP-2000; Project End 31-JUL-2005 Summary: (Adapted from the applicant's abstract): L-type voltage-gated calcium channels also known as dihydropyridine receptors (DHPRs) are critical for excitationcontraction coupling in both skeletal and cardiac muscle. Each of these muscle types expresses its own isoform of the DHPR. The role of the alpha1C cardiac DHPR in cardiac muscle is unquestionable to both provide the influx of Ca2+ needed to trigger Ca2+ release from intracellular stores as well as to provide a means to refill those stores when they become depleted. In vascular smooth muscle these same channels are the site of action of nearly all Ca2+ channel blockers used therapeutically in the treatment of hypertension and heart disease. Recently certain adult skeletal muscles have been shown to exhibit not only the alpha1S skeletal isoform of the DHPR, but also the alpha1C cardiac isoform, although at lower levels of expression. This grant tests several hypotheses for the role of the cardiac DHPR in adult skeletal muscle. The hypotheses to be tested include refilling of partially depleted intracellular Ca2+ stores, forestalling fatigue, and serving to turn off other genes. Methods will include tension, (Ca2+)i and electrophysiology measurements and measurements of gene expression. The results may suggest additional roles for the alpha1C cardiac DHPRs in the heart as well as in many smooth muscles. This grant also seeks to determine how the steroid hormone dexamethasone, the protein kinase C inhibitor staurosporine, and electrical stimulation regulate the expression of the cardiac DHPR in muscle, and to determine the response elements for the transcription factors involved and for tissue-specific expression within the gene promoter. Additional methods will include traditional assays used for promoter work. These results will enhance understanding of the transcriptional regulation of this extremely important receptor for therapeutic agents in the treatment of hypertension and heart disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE ANATOMICAL BASIS OF HUMAN TONGUE BIOMECHANICS Principal Investigator & Institution: Sanders, Ira; Associate Professor; Otolaryngology; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JUL-2004 Summary: (provided by applicant): What is special about the human tongue that allows it to perform the movements that are unique to human speech and swallowing? The biomechanics of the tongue are dependent on its anatomy, and some of the most basic
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facts of human tongue anatomy are unknown. It is hypothesized that the human tongue contains specialized anatomy related to the movements of human speech and swallowing. Studying this anatomy will increase our understanding of tongue movements; provide a normative baseline from which to compare pathological conditions, and provide the detail required for progress in surgical procedures on the tongue, including transplantation. The human tongue presents formidable challenges for the anatomist: the small muscle groups that interweave in complex ways are technically difficult to trace; it is often difficult to identify specific muscles in histological sections; and many techniques routinely used in animal studies cannot be used on human post mortem tissue. However, based on experience studying the human larynx, a systematic approach is proposed with a variety of techniques that have all been successfully tested in the preliminary work. Tongue anatomy will simultaneously be studied on the gross anatomical, microscopic and molecular level using the following methods: 1) high-resolution magnetic resonance microscopy of tongue tissue to study 3D structural detail; 2) Sihler's stain, a process that renders whole tongue specimens translucent while counterstalning the nerve supply and outlines of muscle groups; 3) serial sectioning of whole tongues followed by staining to show details of muscle structure and insertion into connective tissue; 4) micro dissection of muscle fibers followed by silver and acetylcholinesterase staining to study details of muscle fiber size and shape, motor endplate types, and terminal axon branching; 5) myofibrillar ATPase, to type the muscle fibers of each muscle; 6) immunohistochemistry, to identify the myosin heavy chain (MHC) within tongue muscles; and 7) immunoelectrophoresis and immunoblotting, to confirm the immunohistochemistry. Preliminary work has supported the presence of specialized anatomy in the human tongue. Certaln muscles are significantly different in size and position when compared to other mammalian tongues. The genioglossus muscle, for example, is greatly enlarged while the inferior longitudinal is comparatively smaller. In addition, human tongue muscles have unusual internal structure: some appear to be compartmentalized into smaller groups of muscle fibers arranged in series. In the superior longitudinal muscle preliminary work suggests that these muscle compartments are surprisingly short and that the muscle fibers are interconnected in complex webs. Overall, the human tongue has the highest proportion of slow twitch muscle fibers yet reported in any mammalian tongue, and these are arranged in a gradient with the higher proportions found medially and in the tongue base. Among these slow muscle fibers are large numbers of slow tonic muscle fibers, an extremely rare type of muscle fiber with unique contractile properties. In summary, the dearth of information about the human tongue appears to offer an opportunity to increase our understanding of the special nature of speech and swallowing as well as the pathophysiology of dysphagia and dysarthria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE ELECTROPHYSIOLOGY OF MOTOR NEURON DISEASES Principal Investigator & Institution: Bromberg, Mark B.; Professor; Neurology; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2003 Summary: (provided by applicant): Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders of unknown etiology. They have in common death of lower motor neurons (LMN) causing muscle weakness, and both disorders are fatal. Mechanisms of LMN death differ for SMA and ALS. In SMA, LMN death may occur over a limited period of time. Unanswered is whether there is late or continued LMN loss. Recent genetic studies in SMA indicate a relationship between
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survival motor neuron gene (SMN2) copy number and SMA type. Unanswered is the relationship between copy number and LMN number. In ALS, no single mechanism of LMN death explains known features, and a cascade of events ultimately leading to LMN death is likely. Unanswered in ALS is the natural pattern of progression of LMN loss from muscle to muscle. Although muscle weakness is the clinical manifestation of LMN loss for both disorders, the rate of loss of strength does not accurately reflect the rate of loss of LMNs. The discrepancy is due to the compensatory effects of reinnervation of denervated fibers by collateral sprouting from surviving motor nerve terminals. Similarly, routine electrophysiologic tests do not accurately measure LMN loss. Unanswered for both disorders is the dynamics of the compensatory process that determines the clinical state and level of function. Motor unit number estimation (MUNE) is a special electrophysiologic test that can directly assess the number of LMNs innervating a muscle. There are no data on the natural course of LMN loss for SMA, and little data for ALS. We propose to develop and refine MUNE and other electrophysiologic techniques to study, and follow the course of LMN loss and associated compensatory changes. For SMA, we will adapt MUNE techniques to study infants and children. For older SMA and ALS, we will refine MUNE techniques to optimize data collection. For SMA, we will correlate LMN loss with clinical type and SMN2 copy number. We will begin, in the two years of the grant-performing serial studies, to assess whether there is continued LMN loss. For ALS, we will determine and compare the rate and pattern of LMN loss in distal and proximal muscles. In older SMA and ALS, we will assess relationships between LMN loss and measures of collateral reinnervation and strength. We anticipate that MUNE and other electrophysiologic techniques will have direct applicability to the design of clinical trials for SMA and ALS, because these techniques can be used as informative end-point measures. To facilitate the use of MUNE in clinical trials, we will develop and refine the techniques in a form that can be used in any clinical center participating in trials. Currently, most MUNE techniques rely on proprietary software. We will develop software for use on PC-based computer systems, making them available to all laboratories. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSGENIC MICE WITH ALTERED CALCIUM HANDLING Principal Investigator & Institution: Kranias, Evangelia G.; Professor; Pharmacology & Cell Biophysics; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2003; Project Start 01-AUG-1997; Project End 31-JUL-2003 Summary: The sarcoplasmic recticulum (SR) is an internal membrane system in muscle, which functions as a Ca2+-sink during relaxation as as a Ca2+-source during contraction. Relaxation is mediated by the transport of Ca2+into the SR lumen by the Ca2+-ATPase (SERCA2), which is under regulation by phospholamban (PLB) in cardiac, slow-twitch skeletal and smooth muscles. Dephosphorylated PLB is an inhibitor of the affinity of the SR Ca2+-pump for Ca2+and phosphorylation relieves this inhibition. Alterations is in the expression levels of PLB or the SR Ca2+-ATPasehave been linked to altered Ca2+ homeostasis and deterioration of cellular function in several diseases. While transgenic mice have been rccently generated, which elucidated the functional role of altered PLB expression in vivo, focused on cardiac muscle and the physiological significance of PLB in other muscle and non-muscle tissues is not well understood. Thus, the objectives of the present proposal are to generate mouse models, with altered expressionof PLB or the SR Ca2+-ATPase to better define the function of each of these two key Ca2+-handling protein in vivo. Specifically, we will generate mice: a) overexpressing PLB and its phosphorylation mutants in either smooth or soleus muscle.
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Studies in these models coupled with studies in the PLB knockout mouse will elucidate the functional role of PLB in smooth and soleus muscles and define the second messanger pathways regulating these muscles through phosphorylation of PLB; b) overexpressing PLB in multiple tissues and under the control of an inducible promoter to achieve tight temporal and quantitative control of PLB expression in a reversible manner. These models will permit evaluation of the role of temporal alterations in PLB expression levels on cellular function; and c) overexpressing each of the SERCA2 isoforms (SERCA2a or SERCA2b) or conditionally ablating SERCA2 expression in a tissue specific manner. The models with altered SERCA2 expression levels will elucidate the role of this protein in the intact animal. Overall, the proposed animal models will provide valuable and unique systems for the biomedical community at large to carry out further studies on elucidating the functional role of PLB and SERCA2 in intracellular calcium handling in health and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TROPHIC MANIPULATIONS OF THE OCULOMOTOR SYSTEM Principal Investigator & Institution: Von Bartheld, Christopher S.; Associate Professor; Physiology and Cell Biology; University of Nevada Reno 204 Ross Hall Mailstop 325 Reno, Nv 89557 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-JUL-2005 Summary: (Adapted from applicant's abstract): Strabismus is a misalignment of the visual axis, which can lead to severe deficiencies such as loss of central vision from one eye, known as amblyopia. Strabismus is relatively common in the general population with estimates of 5-6 percent. The etiology of strabismus is multifactorial. Current therapies for restoration of visual alignment include muscle weakening by surgical recession or pharmacological denervation with botulinum toxin and muscle tightening by surgical resection. In the proposed research project, the trophic regulation between eye muscles an innervating oculomotor neurons will be explored with the long-term goal to supplement surgical treatment of strabismus with a pharmacological treatment targeted at trophic interactions. Injections of trophic factors or trophic antagonists into selected eye muscles may restore balanced eye movements by mimicking intrinsic trophic mechanisms. The proposed studies will test in an animal model how trophic manipulations of oculomotor neurons and eye muscles can adjust the strength of these muscles, increase the survival of oculomotor neurons during development, increase numbers of collateral axonal branches of oculomotor neurons, and maintain axon collaterals and endplates. Studies will determine which trophic factors are produced in the eye muscles, which functions they have on muscle mass, muscle strength, nerve sprouting, and maintenance of axons or endplates. Additional studies will determine whether the muscle-derived factors are transported retrogradely to the oculomotor neurons and support the survival of these neurons. The time course of trophic interactions between eye muscles and their nerves will be explored with the goal to understand and manipulate the trophic responses which are induced by denervation with botulinum toxin or in chronically paralyzed muscle such as the avian genetic mutant, crooked neck dwarf (cn/cn). These studies will focus on four trophic factors, brain-derived neurotrophic factor (BDNF), glial cell-line-derived neurotrophic factor (GDNF), and the insulin-like growth factors (IGF I, II), and, added in the resubmission, cardiotrophin-1 (CT-1). Additional trophic factors will be screened for their potential to modify the strength of eye muscles. A combined pharmacological, molecular, physiological and morphological approach including the ultrastructural level will provide a meaningful assessment of the prospects for a trophic, pharmacological
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treatment of strabismus and other eye muscle disorders as a supplement to current resection and denervation procedures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VULNERABILITY OF MOTOR NERVE TERMINALS IN AN ALS MODEL Principal Investigator & Institution: Barrett, Ellen F.; Professor; Physiology and Biophysics; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): Motor nerve terminals are especially vulnerable to ischemic stress. The proposed experiments will test the hypothesis that even at early ages motor terminals in mice that overexpress a mutant human superoxide dismutase I (SODIG93A, a model of familial amyotrophic lateral sclerosis) are more vulnerable to stress than terminals in mice that overexpress wild-type human superoxide dismutase (hSOD1). We will test three stresses that might sometimes be encountered by motor terminals in vivo: (1) hindlimb ischemia/reperfusion stress in vivo, (2) hypoxia/ reoxygenation stress in vitro, and (3) in vivo intense stimulation of a single motor nerve. Structural integrity of the stressed motor terminals will be assessed by a fluorescence endplate occupancy assay, testing the extent to which labeled skeletal muscle endplates in fast and slow muscles are occupied by an innervating motor nerve terminal. Preliminary results indicate that both the ischemic and stimulation stresses increase endplate denervation. The function of motor terminals will be assessed during and/or after the stress by measuring resting and stimulation-induced changes in cytosolic and mitochondrial [Ca2+] and mitochondrial membrane potential using fluorescent indicators, and by measuring quantal transmitter release using electrophysiological recording. Preliminary results show disruptions in all these functional parameters during the hypoxia/ reoxygenation stress. Other experiments will test whether stresses that damage motor terminals also produce immunohistochemical signs of damage in the parent motoneurons. We will also test whether agents shown to be neuroprotective for motoneurons (e.g. vascular endothelial growth factor, VEGF; insulin-like growth factor, IGF-1) can protect motor nerve terminals during these stresses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “muscles” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for muscles in the PubMed Central database: 3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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14-3-3[tau] associates with and activates the MEF2D transcription factor during muscle cell differentiation. by Choi SJ, Park SY, Han TH.; 2001 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55772
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20-Hydroxyeicosatetraenoic acid mediates calcium/calmodulin-dependent protein kinase II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells. by Muthalif MM, Benter IF, Karzoun N, Fatima S, Harper J, Uddin MR, Malik KU.; 1998 Oct 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22894
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A Calcineurin-NFATc3-Dependent Pathway Regulates Skeletal Muscle Differentiation and Slow Myosin Heavy-Chain Expression. by Delling U, Tureckova J, Lim HW, De Windt LJ, Rotwein P, Molkentin JD.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86143
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A conserved CATTCCT motif is required for skeletal muscle-specific activity of the cardiac troponin T gene promoter. by Mar JH, Ordahl CP.; 1988 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281980
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A Gene Therapy Strategy Using a Transcription Factor Decoy of the E2F Binding Site Inhibits Smooth Muscle Proliferation in vivo. by Morishita R, Gibbons GH, Horiuchi M, Ellison KE, Nakajima M, Zhang L, Kaneda Y, Ogihara T, Dzau VJ.; 1995 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41600
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A novel E box/AT-rich element is required for muscle-specific expression of the sarcoplasmic reticulum Ca2+-ATPase (SERCA2) gene. by Baker DL, Dave V, Reed T, Misra S, Periasamy M.; 1998 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=147358
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A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification. by Pallafacchina G, Calabria E, Serrano AL, Kalhovde JM, Schiaffino S.; 2002 Jul 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123120
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A Role for Nitric Oxide in Muscle Repair: Nitric Oxide --mediated Activation of Muscle Satellite Cells. by Anderson JE.; 2000 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14889
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A serum response factor-dependent transcriptional regulatory program identifies distinct smooth muscle cell sublineages. by Kim S, Ip HS, Lu MM, Clendenin C, Parmacek MS.; 1997 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=232076
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A single MEF-2 site is a major positive regulatory element required for transcription of the muscle-specific subunit of the human phosphoglycerate mutase gene in skeletal and cardiac muscle cells. by Nakatsuji Y, Hidaka K, Tsujino S, Yamamoto Y, Mukai T, Yanagihara T, Kishimoto T, Sakoda S.; 1992 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=360362
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Abnormal Junctions Between Surface Membrane and Sarcoplasmic Reticulum in Skeletal Muscle with a Mutation Targeted to the Ryanodine Receptor. by Takekura H, Nishi M, Noda T, Takeshima H, Franzini-Armstrong C.; 1995 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42170
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Absence of the [beta] subunit (cchb1) of the skeletal muscle dihydropyridine receptor alters expression of the [alpha]1 subunit and eliminates excitation-contraction coupling. by Gregg RG, Messing A, Strube C, Beurg M, Moss R, Behan M, Sukhareva M, Haynes S, Powell JA, Coronado R, Powers PA.; 1996 Nov 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19477
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Abundant expression of parathyroid hormone-related protein in primary rat aortic smooth muscle cells accompanies serum-induced proliferation. by Hongo T, Kupfer J, Enomoto H, Sharifi B, Giannella-Neto D, Forrester JS, Singer FR, Goltzman D, Hendy GN, Pirola C, et al.; 1991 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=295751
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Actinin-Associated LIM Protein-Deficient Mice Maintain Normal Development and Structure of Skeletal Muscle. by Jo K, Rutten B, Bunn RC, Bredt DS.; 2001 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86714
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Activation and Cellular Localization of the Cyclosporine A-sensitive Transcription Factor NF-AT in Skeletal Muscle Cells. by Abbott KL, Friday BB, Thaloor D, Murphy TJ, Pavlath GK.; 1998 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25565
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Activation of Protein Kinase C[zeta] Induces Serine Phosphorylation of VAMP2 in the GLUT4 Compartment and Increases Glucose Transport in Skeletal Muscle. by Braiman L, Alt A, Kuroki T, Ohba M, Bak A, Tennenbaum T, Sampson SR.; 2001 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99955
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Activation of Ras and the Mitogen-Activated Protein Kinase Pathway Promotes Protein Degradation in Muscle Cells of Caenorhabditis elegans. by Szewczyk NJ, Peterson BK, Jacobson LA.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133852
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Adeno-associated virus site-specifically integrates into a muscle-specific DNA region. by Dutheil N, Shi F, Dupressoir T, Linden RM.; 2000 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18323
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Adenovirus-mediated over-expression of the cyclin/cyclin-dependent kinase inhibitor, p21 inhibits vascular smooth muscle cell proliferation and neointima formation in the rat carotid artery model of balloon angioplasty. by Chang MW, Barr E, Lu MM, Barton K, Leiden JM.; 1995 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185876
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Adenylate kinase1 gene deletion disrupts muscle energetic economy despite metabolic rearrangement. by Janssen E, Dzeja PP, Oerlemans F, Simonetti AW, Heerschap A, Haan AD, Rush PS, Terjung RR, Wieringa B, Terzic A.; 2000 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=305872
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Administration of endotoxin, tumor necrosis factor, or interleukin 1 to rats activates skeletal muscle branched-chain alpha-keto acid dehydrogenase. by Nawabi MD, Block KP, Chakrabarti MC, Buse MG.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296413
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Alpha 1-adrenergic receptor stimulation of sarcomeric actin isogene transcription in hypertrophy of cultured rat heart muscle cells. by Long CS, Ordahl CP, Simpson PC.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303787
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Alteration of Myosin Cross Bridges by Phosphorylation of Myosin-Binding Protein C in Cardiac Muscle. by Weisberg A, Winegrad S.; 1996 Aug 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38584
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Altered Extracellular Signal-Regulated Kinase Signaling and Glycogen Metabolism in Skeletal Muscle from p90 Ribosomal S6 Kinase 2 Knockout Mice. by Dufresne SD, Bjorbaek C, El-Haschimi K, Zhao Y, Aschenbach WG, Moller DE, Goodyear LJ.; 2001 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=88782
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Altered Skeletal Muscle Phenotypes in Calcineurin A[alpha] and A[beta] GeneTargeted Mice. by Parsons SA, Wilkins BJ, Bueno OF, Molkentin JD.; 2003 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156151
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AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. by Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ, Shulman GI.; 2002 Dec 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=138551
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An alternative, nonkinase product of the brain-specifically expressed Ca2+/calmodulin-dependent kinase II alpha isoform gene in skeletal muscle. by Bayer KU, Lohler J, Harbers K.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=230975
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An in vitro assay reveals essential protein components for the "catch" state of invertebrate smooth muscle. by Yamada A, Yoshio M, Kojima H, Oiwa K.; 2001 Jun 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34405
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An intronic enhancer containing an N-box motif is required for synapse- and tissuespecific expression of the acetylcholinesterase gene in skeletal muscle fibers. by Chan RY, Boudreau-Lariviere C, Angus LM, Mankal FA, Jasmin BJ.; 1999 Apr 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16383
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An N-terminal fragment of titin coupled to green fluorescent protein localizes to the Z-bands in living muscle cells: overexpression leads to myofibril disassembly. by Turnacioglu KK, Mittal B, Dabiri GA, Sanger JM, Sanger JW.; 1997 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=276120
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Analysis of SM22[alpha]-Deficient Mice Reveals Unanticipated Insights into Smooth Muscle Cell Differentiation and Function. by Zhang JC, Kim S, Helmke BP, Yu WW, Du KL, Lu MM, Strobeck M, Yu QC, Parmacek MS.; 2001 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99586
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Analysis of the rabbit cardiac/slow twitch muscle sarcoplasmic reticulum calcium ATPase (SERCA2) gene promoter. by Sukovich DA, Shabbeer J, Periasamy M.; 1993 Jun 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=309608
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Association of calcium channel [alpha]1S and [beta]1a subunits is required for the targeting of [beta]1a but not of [alpha]1S into skeletal muscle triads. by Neuhuber B, Gerster U, Doring F, Glossmann H, Tanabe T, Flucher BE.; 1998 Apr 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20205
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Association of titin and myosin heavy chain in developing skeletal muscle. by Isaacs WB, Kim IS, Struve A, Fulton AB.; 1992 Aug 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=49737
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Caenorhabditis elegans UNC-98, a C2H2 Zn Finger Protein, Is a Novel Partner of UNC-97/PINCH in Muscle Adhesion Complexes. by Mercer KB, Flaherty DB, Miller RK, Qadota H, Tinley TL, Moerman DG, Benian GM.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=194897
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Calcineurin controls nerve activity-dependent specification of slow skeletal muscle fibers but not muscle growth. by Serrano AL, Murgia M, Pallafacchina G, Calabria E, Coniglio P, Lomo T, Schiaffino S.; 2001 Nov 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60832
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Cardiac actin is the major actin gene product in skeletal muscle cell differentiation in vitro. by Bains W, Ponte P, Blau H, Kedes L.; 1984 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=368933
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CArG elements control smooth muscle subtype --specific expression of smooth muscle myosin in vivo. by Manabe I, Owens GK.; 2001 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=199571
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Carvedilol, a Cardiovascular Drug, Prevents Vascular Smooth Muscle Cell Proliferation, Migration, and Neointimal Formation Following Vascular Injury. by Ohlstein EH, Douglas SA, Sung CP, Yue T, Louden C, Arleth A, Poste G, Ruffolo RR Jr, Feuerstein GZ.; 1993 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46893
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Caspase 3 activity is required for skeletal muscle differentiation. by Fernando P, Kelly JF, Balazsi K, Slack RS, Megeney LA.; 2002 Aug 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123204
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Characterization of a rat myosin alkali light chain gene expressed in ventricular and slow twitch skeletal muscles. by Periasamy M, Wadgaonkar R, Kumar C, Martin BJ, Siddiqui MA.; 1989 Oct 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=334880
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Characterization of Muscle Sarcoplasmic and Myofibrillar Protein Hydrolysis Caused by Lactobacillus plantarum. by Fadda S, Sanz Y, Vignolo G, Aristoy MC, Oliver G, Toldra F.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91531
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Characterization of the AB (AF-1) region in the muscle-specific retinoid X receptorgamma: evidence that the AF-1 region functions in a cell-specific manner. by Dowhan DH, Muscat GE.; 1996 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=145623
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Common core sequences are found in skeletal muscle slow- and fast-fiber-typespecific regulatory elements. by Nakayama M, Stauffer J, Cheng J, Banerjee-Basu S, Wawrousek E, Buonanno A.; 1996 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231230
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Consequences of DNA-Dependent Protein Kinase Catalytic Subunit Deficiency on Recombinant Adeno-Associated Virus Genome Circularization and Heterodimerization in Muscle Tissue. by Duan D, Yue Y, Engelhardt JF.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152118
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Contraction Stimulates Translocation of Glucose Transporter GLUT4 in Skeletal Muscle Through a Mechanism Distinct from that of Insulin. by Lund S, Holman GD, Schmitz O, Pedersen O.; 1995 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41592
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d-[alpha]-Tocopherol Inhibition of Vascular Smooth Muscle Cell Proliferation Occurs at Physiological Concentrations, Correlates with Protein Kinase C Inhibition, and is Independent of Its Antioxidant Properties. by Tasinato A, Boscoboinik D, Bartoli G, Maroni P, Azzi A.; 1995 Dec 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40322
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Development of a porcine skeletal muscle cDNA microarray: analysis of differential transcript expression in phenotypically distinct muscles. by Bai Q, McGillivray C, da Costa N, Dornan S, Evans G, Stear MJ, Chang KC.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=152649
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Developmental Expression of Spectrins in Rat Skeletal Muscle. by Zhou D, Ursitti JA, Bloch RJ.; 1998 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25216
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Dexamethasone enhances insulin-like growth factor-I effects on skeletal muscle cell proliferation. Role of specific intracellular signaling pathways. by Giorgino F, Smith RJ.; 1995 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185771
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Differential Activation of Mitogen-Activated Protein Kinase in Response to Basic Fibroblast Growth Factor in Skeletal Muscle Cells. by Campbell JS, Wenderoth MP, Hauschka SD, Krebs EG.; 1995 Jan 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42722
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Differential Epitope Tagging of Actin in Transformed Drosophila Produces Distinct Effects on Myofibril Assembly and Function of the Indirect Flight Muscle. by Brault V, Sauder U, Reedy MC, Aebi U, Schoenenberger CA.; 1999 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25159
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Differential localization of HDAC4 orchestrates muscle differentiation. by Miska EA, Langley E, Wolf D, Karlsson C, Pines J, Kouzarides T.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55849
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Differential Requirement for the Nonhelical Tailpiece and the C Terminus of the Myosin Rod in Caenorhabditis elegans Muscle. by Hoppe PE, Andrews RC, Parikh PD.; 2003 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153131
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Direct Involvement of N-Cadherin --mediated Signaling in Muscle Differentiation. by Goichberg P, Geiger B.; 1998 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25598
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Disruption of Sur2-containing KATP channels enhances insulin-stimulated glucose uptake in skeletal muscle. by Chutkow WA, Samuel V, Hansen PA, Pu J, Valdivia CR, Makielski JC, Burant CF.; 2001 Sep 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58803
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Distinct regulatory elements control muscle-specific, fiber-type-selective, and axially graded expression of a myosin light-chain gene in transgenic mice. by Rao MV, Donoghue MJ, Merlie JP, Sanes JR.; 1996 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231388
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Doxorubicin selectively inhibits muscle gene expression in cardiac muscle cells in vivo and in vitro. by Ito H, Miller SC, Billingham ME, Akimoto H, Torti SV, Wade R, Gahlmann R, Lyons G, Kedes L, Torti FM.; 1990 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=54091
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Effect Of DNA-dependent protein kinase on the molecular fate of the rAAV2 genome in skeletal muscle. by Song S, Laipis PJ, Berns KI, Flotte TR.; 2001 Mar 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=31183
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Effect of extraction time and acid concentration on the separation of proglycogen and macroglycogen in horse muscle samples. by Brojer JT, Stampfli HR, Graham TE.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=227005
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Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts. by Stump CS, Short KR, Bigelow ML, Schimke JM, Nair KS.; 2003 Jun 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164701
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Effect of thymol on kinetic properties of Ca and K currents in rat skeletal muscle. by Szentandrassy N, Szentesi P, Magyar J, Nanasi PP, Csernoch L.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=183846
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Elevated arginase I expression in rat aortic smooth muscle cells increases cell proliferation. by Wei LH, Wu G, Morris SM Jr, Ignarro LJ.; 2001 Jul 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55408
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Elevated expression of monocyte chemoattractant protein 1 by vascular smooth muscle cells in hypercholesterolemic primates. by Yu X, Dluz S, Graves DT, Zhang L, Antoniades HN, Hollander W, Prusty S, Valente AJ, Schwartz CJ, Sonenshein GE.; 1992 Aug 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=49623
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Elevated Glucose and Angiotensin II Increase 12-Lipoxygenase Activity and Expression in Porcine Aortic Smooth Muscle Cells. by Natarajan R, Gu J, Rossi J, Gonzales N, Lanting L, Xu L, Nadler J.; 1993 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46630
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Elevated subsarcolemmal Ca2 + in mdx mouse skeletal muscle fibers detected with Ca2 +-activated K + channels. by Mallouk N, Jacquemond V, Allard B.; 2000 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18338
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Elimination of smooth muscle cells in experimental restenosis: targeting of fibroblast growth factor receptors. by Casscells W, Lappi DA, Olwin BB, Wai C, Siegman M, Speir EH, Sasse J, Baird A.; 1992 Aug 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=49665
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Endothelial cell expression of vasoconstrictors and growth factors is regulated by smooth muscle cell-derived carbon monoxide. by Morita T, Kourembanas S.; 1995 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185974
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Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: Acetyl --CoA carboxylase inhibition and AMP-activated protein kinase activation. by Tomas E, Tsao TS, Saha AK, Murrey HE, Zhang CC, Itani SI, Lodish HF, Ruderman NB.; 2002 Dec 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=138607
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Enhancement of Muscle Gene Delivery with Pseudotyped Adeno-Associated Virus Type 5 Correlates with Myoblast Differentiation. by Duan D, Yan Z, Yue Y, Ding W, Engelhardt JF.; 2001 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=115001
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Epigallocathechin-3 Gallate Selectively Inhibits the PDGF-BB --induced Intracellular Signaling Transduction Pathway in Vascular Smooth Muscle Cells and Inhibits Transformation of sis-transfected NIH 3T3 Fibroblasts and Human Glioblastoma Cells (A172). by Ahn HY, Hadizadeh KR, Seul C, Yun YP, Vetter H, Sachinidis A.; 1999 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25235
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Epiregulin is a potent vascular smooth muscle cell-derived mitogen induced by angiotensin II, endothelin-1, and thrombin. by Taylor DS, Cheng X, Pawlowski JE, Wallace AR, Ferrer P, Molloy CJ.; 1999 Feb 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15542
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ErbB2 Is Required for Muscle Spindle and Myoblast Cell Survival. by Andrechek ER, Hardy WR, Girgis-Gabardo AA, Perry RL, Butler R, Graham FL, Kahn RC, Rudnicki MA, Muller WJ.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133917
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Evidence for the load-dependent mechanical efficiency of individual myosin heads in skeletal muscle fibers activated by laser flash photolysis of caged calcium in the presence of a limited amount of ATP. by Sugi H, Iwamoto H, Akimoto T, Ushitani H.; 1998 Mar 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19317
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Expression and Partial Characterization of Kinesin-related Proteins in Differentiating and Adult Skeletal Muscle. by Ginkel LM, Wordeman L.; 2000 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15063
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Expression of bovine myf5 induces ectopic skeletal muscle formation in transgenic mice. by Santerre RF, Bales KR, Janney MJ, Hannon K, Fisher LF, Bailey CS, Morris J, Ivarie R, Smith CK 2nd.; 1993 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=364664
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Expression of high and low molecular weight caldesmons during phenotypic modulation of smooth muscle cells. by Ueki N, Sobue K, Kanda K, Hada T, Higashino K.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299689
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Expression of myogenic factors in denervated chicken breast muscle: isolation of the chicken Myf5 gene. by Saitoh O, Fujisawa-Sehara A, Nabeshima Y, Periasamy M.; 1993 May 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=309553
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Expression of the troponin complex genes: transcriptional coactivation during myoblast differentiation and independent control in heart and skeletal muscles. by Bucher EA, Maisonpierre PC, Konieczny SF, Emerson CP Jr.; 1988 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=365482
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Expression of utrophin A mRNA correlates with the oxidative capacity of skeletal muscle fiber types and is regulated by calcineurin/NFAT signaling. by Chakkalakal JV, Stocksley MA, Harrison MA, Angus LM, Deschenes-Furry J, St-Pierre S, Megeney LA, Chin ER, Michel RN, Jasmin BJ.; 2003 Jun 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=164666
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Expression profiling reveals altered satellite cell numbers and glycolytic enzyme transcription in nemaline myopathy muscle. by Sanoudou D, Haslett JN, Kho AT, Guo S, Gazda HT, Greenberg SA, Lidov HG, Kohane IS, Kunkel LM, Beggs AH.; 2003 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153613
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Extraocular muscle is defined by a fundamentally distinct gene expression profile. by Porter JD, Khanna S, Kaminski HJ, Rao JS, Merriam AP, Richmonds CR, Leahy P, Li J, Andrade FH.; 2001 Oct 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59827
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Flight muscle function in Drosophila requires colocalization of glycolytic enzymes. by Wojtas K, Slepecky N, von Kalm L, Sullivan D.; 1997 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=305727
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From intestine to muscle: Nuclear reprogramming through defective cloned embryos. by Byrne JA, Simonsson S, Gurdon JB.; 2002 Apr 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122901
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Full Functional Rescue of a Complete Muscle (TA) in Dystrophic Hamsters by Adeno-Associated Virus Vector-Directed Gene Therapy. by Xiao X, Li J, Tsao YP, Dressman D, Hoffman EP, Watchko JF.; 2000 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111478
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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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Functional Protection of Dystrophic Mouse (mdx) Muscles after AdenovirusMediated Transfer of a Dystrophin Minigene. by Deconinck N, Ragot T, Marechal G, Perricaudet M, Gillis JM.; 1996 Apr 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39651
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G protein-mediated inhibition of myosin light-chain phosphatase in vascular smooth muscle. by Kitazawa T, Masuo M, Somlyo AP.; 1991 Oct 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52703
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Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscle. by Haslett JN, Sanoudou D, Kho AT, Bennett RR, Greenberg SA, Kohane IS, Beggs AH, Kunkel LM.; 2002 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137534
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Gene transfer establishes primacy of striated vs. smooth muscle sarcoglycan complex in limb-girdle muscular dystrophy. by Durbeej M, Sawatzki SM, Barresi R, Schmainda KM, Allamand V, Michele DE, Campbell KP.; 2003 Jul 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166412
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Genetic Fate of Recombinant Adeno-Associated Virus Vector Genomes in Muscle. by Schnepp BC, Clark KR, Klemanski DL, Pacak CA, Johnson PR.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149530
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Glucose transport in cultured human skeletal muscle cells. Regulation by insulin and glucose in nondiabetic and non-insulin-dependent diabetes mellitus subjects. by Ciaraldi TP, Abrams L, Nikoulina S, Mudaliar S, Henry RR.; 1995 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185992
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GLUT4, AMP kinase, but not the insulin receptor, are required for hepatoportal glucose sensor --stimulated muscle glucose utilization. by Burcelin R, Crivelli V, Perrin C, Costa AD, Mu J, Kahn BB, Birnbaum MJ, Kahn CR, Vollenweider P, Thorens B.; 2003 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155044
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High-efficiency gene transfer into skeletal muscle mediated by electric pulses. by Mir LM, Bureau MF, Gehl J, Rangara R, Rouy D, Caillaud JM, Delaere P, Branellec D, Schwartz B, Scherman D.; 1999 Apr 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16320
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HIV envelope gp120 activates human arterial smooth muscle cells. by Schecter AD, Berman AB, Yi L, Mosoian A, McManus CM, Berman JW, Klotman ME, Taubman MB.; 2001 Aug 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=56929
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Human and murine dystrophin mRNA transcripts are differentially expressed during skeletal muscle, heart, and brain development. by Bies RD, Phelps SF, Cortez MD, Roberts R, Caskey CT, Chamberlain JS.; 1992 Apr 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=312263
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Human cytomegalovirus IE1 promoter/enhancer drives variable gene expression in all fiber types in transgenic mouse skeletal muscle. by Hallauer PL, Hastings KE.; 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29077
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Hypoxia Extends the Life Span of Vascular Smooth Muscle Cells through Telomerase Activation. by Minamino T, Mitsialis SA, Kourembanas S.; 2001 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100255
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Identification of a myocyte nuclear factor that binds to the muscle-specific enhancer of the mouse muscle creatine kinase gene. by Buskin JN, Hauschka SD.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=362335
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Identification of the coupling between skeletal muscle store-operated Ca2 + entry and the inositol trisphosphate receptor. by Launikonis BS, Barnes M, Stephenson DG.; 2003 Mar 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151445
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Immune interferon inhibits proliferation and induces 2'-5'-oligoadenylate synthetase gene expression in human vascular smooth muscle cells. by Warner SJ, Friedman GB, Libby P.; 1989 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303804
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Impairment of sympathetic activation during static exercise in patients with muscle phosphorylase deficiency (McArdle's disease). by Pryor SL, Lewis SF, Haller RG, Bertocci LA, Victor RG.; 1990 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296590
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In vitro infection of smooth muscle cells by Chlamydia pneumoniae. by Knoebel E, Vijayagopal P, Figueroa JE 2nd, Martin DH.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176087
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In vivo and in vitro Analysis of Electrical Activity-Dependent Expression of Muscle Acetylcholine Receptor Genes Using Adenovirus. by Bessereau J, Stratford-Perricaudet LD, Piette J, Poupon CL, Changeux J.; 1994 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43146
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In Vivo Regulation of Human Skeletal Muscle Gene Expression by Thyroid Hormone. by Clement K, Viguerie N, Diehn M, Alizadeh A, Barbe P, Thalamas C, Storey JD, Brown PO, Barsh GS, Langin D.; 2002 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155277
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In vivo Suppression of Injury-Induced Vascular Smooth Muscle Cell Accumulation Using Adenovirus-Mediated Transfer of the Herpes Simplex Virus Thymidine Kinase Gene. by Guzman RJ, Hirschowitz EA, Brody SL, Crystal RG, Epstein SE, Finkel T.; 1994 Oct 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=45096
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Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle. by Kim JK, Gimeno RE, Higashimori T, Kim HJ, Choi H, Punreddy S, Mozell RL, Tan G, Stricker-Krongrad A, Hirsch DJ, Fillmore JJ, Liu ZX, Dong J, Cline G, Stahl A, Lodish HF, Shulman GI.; 2004 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=351314
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Induction by agrin of ectopic and functional postsynaptic-like membrane in innervated muscle. by Jones G, Meier T, Lichtsteiner M, Witzemann V, Sakmann B, Brenner HR.; 1997 Mar 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20144
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Inhibitors of soluble epoxide hydrolase attenuate vascular smooth muscle cell proliferation. by Davis BB, Thompson DA, Howard LL, Morisseau C, Hammock BD, Weiss RH.; 2002 Feb 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122346
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Insulin action on heart and skeletal muscle glucose uptake in essential hypertension. by Nuutila P, Maki M, Laine H, Knuuti MJ, Ruotsalainen U, Luotolahti M, Haaparanta M, Solin O, Jula A, Koivisto VA, et al.; 1995 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185288
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Insulin and glucose 6-phosphate stimulation of Ca2+ uptake by skinned muscle fibers. by Brautigan DL, Kerrick WG, Fischer EH.; 1980 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=348397
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Insulin Control of Glycogen Metabolism in Knockout Mice Lacking the MuscleSpecific Protein Phosphatase PP1G/RGL. by Suzuki Y, Lanner C, Kim JH, Vilardo PG, Zhang H, Yang J, Cooper LD, Steele M, Kennedy A, Bock CB, Scrimgeour A, Lawrence JC Jr, DePaoli-Roach AA.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86899
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Insulin increases near-membrane but not global Ca2 + in isolated skeletal muscle. by Bruton JD, Katz A, Westerblad H.; 1999 Mar 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15933
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Insulin-induced cortical actin remodeling promotes GLUT4 insertion at muscle cell membrane ruffles. by Tong P, Khayat ZA, Huang C, Patel N, Ueyama A, Klip A.; 2001 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=209359
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Insulin-Like Growth Factor I Stimulates Myofibril Development and Decreases Smooth Muscle [alpha]-Actin of Adult Cardiomyocytes. by Donath MY, Zapf J, Eppenberger-Eberhardt M, Froesch ER, Eppenberger HM.; 1994 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43228
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Interference fine structure and sarcomere length dependence of the axial x-ray pattern from active single muscle fibers. by Linari M, Piazzesi G, Dobbie I, Koubassova N, Reconditi M, Narayanan T, Diat O, Irving M, Lombardi V.; 2000 Jun 20; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16527
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Intravenous administration of phosphorylated acid alpha-glucosidase leads to uptake of enzyme in heart and skeletal muscle of mice. by Van der Ploeg AT, Kroos MA, Willemsen R, Brons NH, Reuser AJ.; 1991 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296338
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Invertebrate connectin spans as much as 3.5[micro]m in the giant sarcomeres of crayfish claw muscle. by Fukuzawa A, Shimamura J, Takemori S, Kanzawa N, Yamaguchi M, Sun P, Maruyama K, Kimura S.; 2001 Sep 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125597
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Isoproterenol Stimulates Rapid Extrusion of Sodium from Isolated Smooth Muscle Cells. by Moore ED, Fay FS.; 1993 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=47287
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Long-term systemic therapy of Fabry disease in a knockout mouse by adenoassociated virus-mediated muscle-directed gene transfer. by Takahashi H, Hirai Y, Migita M, Seino Y, Fukuda Y, Sakuraba H, Kase R, Kobayashi T, Hashimoto Y, Shimada T.; 2002 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129774
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Lymphocyte antigen Leu-19 as a molecular marker of regeneration in human skeletal muscle. by Schubert W, Zimmermann K, Cramer M, Starzinski-Powitz A.; 1989 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286453
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M-CAT binding factor, a novel trans-acting factor governing muscle-specific transcription. by Mar JH, Ordahl CP.; 1990 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=360969
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Mice Lacking Skeletal Muscle Actin Show Reduced Muscle Strength and Growth Deficits and Die during the Neonatal Period. by Crawford K, Flick R, Close L, Shelly D, Paul R, Bove K, Kumar A, Lessard J.; 2002 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133984
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Mitochondrial DNA deletion mutations are concomitant with ragged red regions of individual, aged muscle fibers: analysis by laser-capture microdissection. by Cao Z, Wanagat J, McKiernan SH, Aiken JM.; 2001 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=60181
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Modulation of L-type Ca2+ current but not activation of Ca2+ release by the gamma1 subunit of the dihydropyridine receptor of skeletal muscle. by Ahern CA, Powers PA, Biddlecome GH, Roethe L, Vallejo P, Mortenson L, Strube C, Campbell KP, Coronado R, Gregg RG.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=37314
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Molecular Dissection of DNA Sequences and Factors Involved in Slow MuscleSpecific Transcription. by Calvo S, Vullhorst D, Venepally P, Cheng J, Karavanova I, Buonanno A.; 2001 Dec 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=100012
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Molecular genetics of muscle development andneuromuscular diseases Kloster Irsee, Germany, September 26 --October 1, 1999. by Brand T, Butler-Browne G, Fuchtbauer EM, Renkawitz-Pohl R, Brand-Saberi B.; 2000 May 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=305694
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Molecular organization of transverse tubule/sarcoplasmic reticulum junctions during development of excitation-contraction coupling in skeletal muscle. by Flucher BE, Andrews SB, Daniels MP.; 1994 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=301134
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Monoclonal antibody specific for the transverse tubular membrane of skeletal muscle activates the dihydropyridine-sensitive Ca2+ channel. by Malouf NN, Coronado R, McMahon D, Meissner G, Gillespie GY.; 1987 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=305238
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Mouse Limb Muscle is Determined in the Absence of the Earliest Myogenic Factor myf-5. by Tajbakhsh S, Buckingham ME.; 1994 Jan 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43026
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Mouse Pop1 Is Required for Muscle Regeneration in Adult Skeletal Muscle. by Andree B, Fleige A, Arnold HH, Brand T.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134701
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Multiple defects in muscle glycogen synthase activity contribute to reduced glycogen synthesis in non-insulin dependent diabetes mellitus. by Thorburn AW, Gumbiner B, Bulacan F, Brechtel G, Henry RR.; 1991 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296335
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Multiple thyroid hormone-induced muscle growth and death programs during metamorphosis in Xenopus laevis. by Das B, Schreiber AM, Huang H, Brown DD.; 2002 Sep 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=129427
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Muscle degeneration without mechanical injury in sarcoglycan deficiency. by Hack AA, Cordier L, Shoturma DI, Lam MY, Sweeney HL, McNally EM.; 1999 Sep 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17950
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Muscle LIM Proteins Are Associated with Muscle Sarcomeres and Require dMEF2 for Their Expression during Drosophila Myogenesis. by Stronach BE, Renfranz PJ, Lilly B, Beckerle MC.; 1999 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25449
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Muscle-regulated expression and determinants for neuromuscular junctional localization of the mouse RI[alpha] regulatory subunit of cAMP- dependent protein kinase. by Barradeau S, Imaizumi-Scherrer T, Weiss MC, Faust DM.; 2001 Apr 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33159
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Muscle-specific inactivation of the IGF-I receptor induces compensatory hyperplasia in skeletal muscle. by Fernandez AM, Dupont J, Farrar RP, Lee S, Stannard B, Le Roith D.; 2002 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150853
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Muscle-specific PPAR[gamma]-deficient mice develop increased adiposity and insulin resistance but respond to thiazolidinediones. by Norris AW, Chen L, Fisher SJ, Szanto I, Ristow M, Jozsi AC, Hirshman MF, Rosen ED, Goodyear LJ, Gonzalez FJ, Spiegelman BM, Kahn CR.; 2003 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=171387
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Myf5 is a direct target of long-range Shh signaling and Gli regulation for muscle specification. by Gustafsson MK, Pan H, Pinney DF, Liu Y, Lewandowski A, Epstein DJ, Emerson CP Jr.; 2002 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=155306
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Myocardin Is a Critical Serum Response Factor Cofactor in the Transcriptional Program Regulating Smooth Muscle Cell Differentiation. by Du KL, Ip HS, Li J, Chen M, Dandre F, Yu W, Lu MM, Owens GK, Parmacek MS.; 2003 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=150745
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Myocardin is a master regulator of smooth muscle gene expression. by Wang Z, Wang DZ, Pipes GC, Olson EN.; 2003 Jun 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165841
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Myocyte-Specific Enhancer Factor 2 Acts Cooperatively with a Muscle Activator Region to Regulate Drosophila Tropomyosin Gene Muscle Expression. by Lin M, Nguyen HT, Dybala C, Storti RV.; 1996 May 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39328
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MyoD is functionally linked to the silencing of a muscle-specific regulatory gene prior to skeletal myogenesis. by Mal A, Harter ML.; 2003 Feb 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149902
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Neural agrin controls acetylcholine receptor stability in skeletal muscle fibers. by Bezakova G, Rabben I, Sefland I, Fumagalli G, Lomo T.; 2001 Aug 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=55554
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NMR Studies of Muscle Glycogen Synthesis in Insulin-Resistant Offspring of Parents with Non-Insulin-Dependent Diabetes Mellitus Immediately after GlycogenDepleting Exercise. by Price TB, Perseghin G, Duleba A, Chen W, Chase J, Rothman DL, Shulman RG, Shulman GI.; 1996 May 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39245
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Obscurin Is a Ligand for Small Ankyrin 1 in Skeletal Muscle. by KontrogianniKonstantopoulos A, Jones EM, van Rossum DB, Bloch RJ.; 2003 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151585
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Ontogenesis and localization of Ca2+ channels in mammalian skeletal muscle in culture and role in excitation-contraction coupling. by Romey G, Garcia L, Dimitriadou V, Pincon-Raymond M, Rieger F, Lazdunski M.; 1989 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287034
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Opposing mitogenic and anti-mitogenic actions of parathyroid hormone-related protein in vascular smooth muscle cells: A critical role for nuclear targeting. by Massfelder T, Dann P, Wu TL, Vasavada R, Helwig JJ, Stewart AF.; 1997 Dec 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28357
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Origin of neointimal endothelium and [alpha]-actin --positive smooth muscle cells in transplant arteriosclerosis. by Hillebrands JL, Klatter FA, van den Hurk BM, Popa ER, Nieuwenhuis P, Rozing J.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=209313
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Overexpression of myogenin in muscles of transgenic mice: interaction with Id-1, negative crossregulation of myogenic factors, and induction of extrasynaptic
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Overexpression of the LAR (leukocyte antigen-related) protein-tyrosine phosphatase in muscle causes insulin resistance. by Zabolotny JM, Kim YB, Peroni OD, Kim JK, Pani MA, Boss O, Klaman LD, Kamatkar S, Shulman GI, Kahn BB, Neel BG.; 2001 Apr 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33185
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Pharmacogenetic heterogeneity of transgene expression in muscle and tumours. by Lefesvre P, Attema J, van Bekkum D.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=194725
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Platelet-Derived Growth Factor Stimulates the Secretion of Hyaluronic Acid by Proliferating Human Vascular Smooth Muscle Cells. by Papakonstantinou E, Karakiulakis G, Roth M, Block LH.; 1995 Oct 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40906
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Precise determination of mitochondrial DNA copy number in human skeletal and cardiac muscle by a PCR-based assay: lack of change of copy number with age. by Miller FJ, Rosenfeldt FL, Zhang C, Linnane AW, Nagley P.; 2003 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=156738
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Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sarcospan complex. by Cohn RD, Durbeej M, Moore SA, Coral-Vazquez R, Prouty S, Campbell KP.; 2001 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=199179
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Prions in skeletal muscle. by Bosque PJ, Ryou C, Telling G, Peretz D, Legname G, DeArmond SJ, Prusiner SB.; 2002 Mar 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122606
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Promotion of Vascular Smooth Muscle Cell Growth by Homocysteine: A Link to Atherosclerosis. by Tsai J, Perrella MA, Yashizumi M, Hsieh C, Haber E, Schlegel R, Lee M.; 1994 Jul 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44203
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Proteolytic disruption of laminin-integrin complexes on muscle cells during synapse formation. by Anderson MJ, Shi ZQ, Zackson SL.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231499
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Radial and longitudinal diffusion of myoglobin in single living heart and skeletal muscle cells. by Papadopoulos S, Endeward V, Revesz-Walker B, Jurgens KD, Gros G.; 2001 May 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33311
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Rapid neural regulation of muscle urokinase-like plasminogen activator as defined by nerve crush. by Hantai D, Rao JS, Festoff BW.; 1990 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53806
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Rates of ubiquitin conjugation increase when muscles atrophy, largely through activation of the N-end rule pathway. by Solomon V, Baracos V, Sarraf P, Goldberg AL.; 1998 Oct 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22877
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Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. by Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, Entman ML, Michael LH, Hirschi KK, Goodell MA.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=209322
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Regulation of Myosin Heavy Chain Expression during Rat Skeletal Muscle Development In Vitro. by Torgan CE, Daniels MP.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34600
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Regulation of skeletal muscle stiffness and elasticity by titin isoforms: a test of the segmental extension model of resting tension. by Wang K, McCarter R, Wright J, Beverly J, Ramirez-Mitchell R.; 1991 Aug 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52241
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Relationship of insulin-like growth factor II gene expression in muscle to synaptogenesis. by Ishii DN.; 1989 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287027
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Release of Hepatocyte Growth Factor from Mechanically Stretched Skeletal Muscle Satellite Cells and Role of pH and Nitric Oxide. by Tatsumi R, Hattori A, Ikeuchi Y, Anderson JE, Allen RE.; 2002 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117951
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Requirement for Down-Regulation of the CCAAT-binding Activity of the NF-Y Transcription Factor during Skeletal Muscle Differentiation. by Gurtner A, Manni I, Fuschi P, Mantovani R, Guadagni F, Sacchi A, Piaggio G.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165670
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Rescue of dystrophin expression in mdx mouse muscle by RNA /DNA oligonucleotides. by Rando TA, Disatnik MH, Zhou LZ.; 2000 May 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25834
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Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1. by Michael LF, Wu Z, Cheatham RB, Puigserver P, Adelmant G, Lehman JJ, Kelly DP, Spiegelman BM.; 2001 Mar 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=31136
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Role of Guanine Nucleotide-Binding Proteins--ras-Family or Trimeric Proteins or both--in Ca2+ Sensitization of Smooth Muscle. by Gong MC, Iizuka K, Nixon G, Browne JP, Hall A, Eccleston JF, Sugai M, Kobayashi S, Somlyo AV, Somlyo AP.; 1996 Feb 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40082
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Role of HuR in Skeletal Myogenesis through Coordinate Regulation of Muscle Differentiation Genes. by Figueroa A, Cuadrado A, Fan J, Atasoy U, Muscat GE, Munoz-Canoves P, Gorospe M, Munoz A.; 2003 Jul 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=162217
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Role of platelets in smooth muscle cell proliferation and migration after vascular injury in rat carotid artery. by Fingerle J, Johnson R, Clowes AW, Majesky MW, Reidy MA.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298292
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Role of the arginine-nitric oxide pathway in the regulation of vascular smooth muscle cell proliferation. by Ignarro LJ, Buga GM, Wei LH, Bauer PM, Wu G, del Soldato P.; 2001 Mar 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=31203
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Role of the short isoform of myosin light chain kinase in the contraction of cultured smooth muscle cells as examined by its down-regulation. by Bao J, Oishi K, Yamada T, Liu L, Nakamura A, Uchida MK, Kohama K.; 2002 Jul 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=123179
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Rostrocaudal gradient of transgene expression in adult skeletal muscle. by Donoghue MJ, Merlie JP, Rosenthal N, Sanes JR.; 1991 Jul 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=51975
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Sarcoglycan, the heart, and skeletal muscles: new treatment, old drug? by Towbin JA, Bowles NE.; 2001 Jan 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=199185
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Sarcolemmal Organization in Skeletal Muscle Lacking Desmin: Evidence for Cytokeratins Associated with the Membrane Skeleton at Costameres. by O'Neill A, Williams MW, Resneck WG, Milner DJ, Capetanaki Y, Bloch RJ.; 2002 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=117318
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Sarcomere length-dependence of activity-dependent twitch potentiation in mouse skeletal muscle. by Rassier DE, MacIntosh BR.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140028
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Sarcospan-Deficient Mice Maintain Normal Muscle Function. by Lebakken CS, Venzke DP, Hrstka RF, Consolino CM, Faulkner JA, Williamson RA, Campbell KP.; 2000 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85350
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Scorpion toxins targeted against the sarcoplasmic reticulum Ca(2+)-release channel of skeletal and cardiac muscle. by Valdivia HH, Kirby MS, Lederer WJ, Coronado R.; 1992 Dec 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=50723
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Single-cell transplantation determines the time when Xenopus muscle precursor cells acquire a capacity for autonomous differentiation. by Kato K, Gurdon JB.; 1993 Feb 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=45862
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Skeletal muscle dysfunction in chronic obstructive pulmonary disease. by Jeffery Mador M, Bozkanat E.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59579
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Skeletal muscle engraftment potential of adult mouse skin side population cells. by Montanaro F, Liadaki K, Volinski J, Flint A, Kunkel LM.; 2003 Aug 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=170919
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Skeletal muscle membrane lipid composition is related to adiposity and insulin action. by Pan DA, Lillioja S, Milner MR, Kriketos AD, Baur LA, Bogardus C, Storlien LH.; 1995 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=185990
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Smooth muscle cell --extrinsic vascular spasm arises from cardiomyocyte degeneration in sarcoglycan-deficient cardiomyopathy. by Wheeler MT, Allikian MJ, Heydemann A, Hadhazy M, Zarnegar S, McNally EM.; 2004 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=351323
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Spontaneously hypertensive rat vascular smooth muscle cells in culture exhibit increased growth and Na+/H+ exchange. by Berk BC, Vallega G, Muslin AJ, Gordon HM, Canessa M, Alexander RW.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303754
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Stability of the human dystrophin transcript in muscle. by Tennyson CN, Shi Q, Worton RG.; 1996 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=146056
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Stable expression of calpain 3 from a muscle transgene in vivo: Immature muscle in transgenic mice suggests a role for calpain 3 in muscle maturation. by Spencer MJ, Guyon JR, Sorimachi H, Potts A, Richard I, Herasse M, Chamberlain J, Dalkilic I, Kunkel LM, Beckmann JS.; 2002 Jun 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124391
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Stearoyl-CoA desaturase 1 deficiency elevates insulin-signaling components and down-regulates protein-tyrosine phosphatase 1B in muscle. by Rahman SM, Dobrzyn A, Dobrzyn P, Lee SH, Miyazaki M, Ntambi JM.; 2003 Sep 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=196935
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Subcellular analysis of Ca2+ homeostasis in primary cultures of skeletal muscle myotubes. by Brini M, De Giorgi F, Murgia M, Marsault R, Massimino ML, Cantini M, Rizzuto R, Pozzan T.; 1997 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=276065
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Subcellular localization of myosin light chain kinase in skeletal, cardiac, and smooth muscles. by Cavadore JC, Molla A, Harricane MC, Gabrion J, Benyamin Y, Demaille JG.; 1982 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=346443
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Substance P Responsiveness of Smooth Muscle Cells is Regulated by the Integrin Ligand, Thrombospondin. by Dahm LM, Bowers CW.; 1996 Feb 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40070
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Surfactant-induced sealing of electropermeabilized skeletal muscle membranes in vivo. by Lee RC, River LP, Pan FS, Ji L, Wollmann RL.; 1992 May 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=49115
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Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors. by Song S, Morgan M, Ellis T, Poirier A, Chesnut K, Wang J, Brantly M, Muzyczka N, Byrne BJ, Atkinson M, Flotte TR.; 1998 Nov 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24382
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Tagging muscle cell lineages in development and tail regeneration using Cre recombinase in transgenic Xenopus. by Ryffel GU, Werdien D, Turan G, Gerhards A, Goosses S, Senkel S.; 2003 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153756
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Telomerase reverse transcriptase promotes cardiac muscle cell proliferation, hypertrophy, and survival. by Oh H, Taffet GE, Youker KA, Entman ML, Overbeek PA, Michael LH, Schneider MD.; 2001 Aug 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=56957
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Temporal correlation between maximum tetanic force and cell death in postischemic rat skeletal muscle. by Suzuki H, Poole DC, Zweifach BW, Schmid-Schonbein GW.; 1995 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=186000
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The "glycogen shunt" in exercising muscle: A role for glycogen in muscle energetics and fatigue. by Shulman RG, Rothman DL.; 2001 Jan 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=14608
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The Cell Adhesion Molecule M-Cadherin Is Not Essential for Muscle Development and Regeneration. by Hollnagel A, Grund C, Franke WW, Arnold HH.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=133893
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The development expression of the rat alpha-vascular and gamma-enteric smooth muscle isoactins: isolation and characterization of a rat gamma-enteric actin cDNA. by McHugh KM, Lessard JL.; 1988 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=365625
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The distribution of blood flow, oxygen consumption, and work output among the respiratory muscles during unobstructed hyperventilation. by Robertson CH Jr, Pagel MA, Johnson RL Jr.; 1977 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=333330
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The serum response factor coactivator myocardin is required for vascular smooth muscle development. by Li S, Wang DZ, Wang Z, Richardson JA, Olson EN.; 2003 Aug 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=170924
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The Thrombospondin Receptor CD47 (IAP) Modulates and Associates with [alpha]2[beta]1 Integrin in Vascular Smooth Muscle Cells. by Wang XQ, Frazier WA.; 1998 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25313
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The transduction properties of intercostal muscle mechanoreceptors. by Holt GA, Johnson RD, Davenport PW.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137590
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The Whistle and the Rattle: The Design of Sound Producing Muscles. by Rome LC, Syme DA, Hollingworth S, Lindstedt SL, Baylor SM.; 1996 Jul 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=38881
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Theiler's murine encephalomyelitis virus-induced cardiac and skeletal muscle disease. by Gomez RM, Rinehart JE, Wollmann R, Roos RP.; 1996 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=190990
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Topology of the Ca2 + release channel of skeletal muscle sarcoplasmic reticulum (RyR1). by Du GG, Sandhu B, Khanna VK, Guo XH, MacLennan DH.; 2002 Dec 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139211
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Transcription Enhancer Factor 1 Binds Multiple Muscle MEF2 and A/T-Rich Elements during Fast-to-Slow Skeletal Muscle Fiber Type Transitions. by Karasseva N, Tsika G, Ji J, Zhang A, Mao X, Tsika R.; 2003 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165722
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Transdifferentiation of Chicken Embryonic Cells into Muscle Cells by the 3' Untranslated Region of Muscle Tropomyosin. by L'Ecuyer TJ, Tompach PC, Morris E, Fulton AB.; 1995 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41371
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Transfer of [beta]-Amyloid Precursor Protein Gene Using Adenovirus Vector Causes Mitochondrial Abnormalities in Cultured Normal Human Muscle. by Askanas V, McFerrin J, Baque S, Alvarez RB, Sarkozi E, Engel WK.; 1996 Feb 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40077
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Transformation by Rous sarcoma virus prevents acetylcholine receptor clustering on cultured chicken muscle fibers. by Anthony DT, Schuetze SM, Rubin LL.; 1984 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=345479
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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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Trichinella spiralis-Infected Muscle Cells: Abundant RNA Polymerase II in Nuclear Speckle Domains Colocalizes with Nuclear Antigens. by Yao C, Jasmer DP.; 2001 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98470
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Two Forms of Acetylcholine Receptor [gamma] Subunit in Mouse Muscle. by Mileo AM, Monaco L, Palma E, Grassi F, Miledi R, Eusebi F.; 1995 Mar 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42283
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Two mechanisms for termination of individual Ca2 + sparks in skeletal muscle. by Lacampagne A, Klein MG, Ward CW, Schneider MF.; 2000 Jul 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=16629
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Type 3 ryanodine receptors of skeletal muscle are segregated in a parajunctional position. by Felder E, Franzini-Armstrong C.; 2002 Feb 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122253
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Vimentin mRNA Location Changes During Muscle Development. by Cripe L, Morris E, Fulton AB.; 1993 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46168
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Viral mediated expression of insulin-like growth factor I blocks the aging-related loss of skeletal muscle function. by Barton-Davis ER, Shoturma DI, Musaro A, Rosenthal N, Sweeney HL.; 1998 Dec 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28090
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Voltage dependence of inositol 1,4,5-trisphosphate-induced Ca2+ release in peeled skeletal muscle fibers. by Donaldson SK, Goldberg ND, Walseth TF, Huetteman DA.; 1988 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281839
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Voltage dependence of the pattern and frequency of discrete Ca2 + release events after brief repriming in frog skeletal muscle. by Klein MG, Lacampagne A, Schneider MF.; 1997 Sep 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23600
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 muscles, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “muscles” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for muscles (hyperlinks lead to article summaries): •
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A delta-conotoxin from Conus ermineus venom inhibits inactivation in vertebrate neuronal Na+ channels but not in skeletal and cardiac muscles. Author(s): Barbier J, Lamthanh H, Le Gall F, Favreau P, Benoit E, Chen H, Gilles N, Ilan N, Heinemann SH, Gordon D, Menez A, Molgo J. Source: The Journal of Biological Chemistry. 2004 February 6; 279(6): 4680-5. Epub 2003 November 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14615484
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 dynamic recurrent neural network for multiple muscles electromyographic mapping to elevation angles of the lower limb in human locomotion. Author(s): Cheron G, Leurs F, Bengoetxea A, Draye JP, Destree M, Dan B. Source: Journal of Neuroscience Methods. 2003 October 30; 129(2): 95-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14511813
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A Japanese family with FEOM1-linked congenital fibrosis of the extraocular muscles type 1 associated with spinal canal stenosis and refinement of the FEOM1 critical region. Author(s): Uyama E, Yamada K, Kawano H, Chan WM, Andrews C, Yoshioka M, Uchino M, Engle EC. Source: Neuromuscular Disorders : Nmd. 2003 August; 13(6): 472-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12899874
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A novel PHOX2A/ARIX mutation in an Iranian family with congenital fibrosis of extraocular muscles type 2 (CFEOM2). Author(s): Yazdani A, Chung DC, Abbaszadegan MR, Al-Khayer K, Chan WM, Yazdani M, Ghodsi K, Engle EC, Traboulsi EI. Source: American Journal of Ophthalmology. 2003 November; 136(5): 861-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14597037
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A retrospective analysis of the gluteal muscles contracture and discussion of the relative problems. Author(s): Liu G, Du J, Yang S, Zheng Q, Li J. Source: J Tongji Med Univ. 2000; 20(1): 70-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12845763
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Activation varies among the knee extensor muscles during a submaximal fatiguing contraction in the seated and supine postures. Author(s): Rochette L, Hunter SK, Place N, Lepers R. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2003 October; 95(4): 151522. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12970375
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Activity patterns of leg muscles in periodic limb movement disorder. Author(s): de Weerd AW, Rijsman RM, Brinkley A. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2004 February; 75(2): 3179. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742617
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Adaptations in muscular activation of the knee extensor muscles with strength training in young and older adults. Author(s): Knight CA, Kamen G. Source: Journal of Electromyography and Kinesiology : Official Journal of the International Society of Electrophysiological Kinesiology. 2001 December; 11(6): 405-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11738953
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Altered aquaporin 4 expression in muscles of Fukuyama-type congenital muscular dystrophy. Author(s): Wakayama Y, Jimi T, Inoue M, Kojima H, Yamashita S, Kumagai T, Murahashi M, Hara H, Shibuya S. Source: Virchows Archiv : an International Journal of Pathology. 2003 December; 443(6): 761-7. Epub 2003 August 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12942324
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An electromyographic analysis of the deep cervical flexor muscles in performance of craniocervical flexion. Author(s): Falla D, Jull G, Dall'Alba P, Rainoldi A, Merletti R. Source: Physical Therapy. 2003 October; 83(10): 899-906. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519061
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An integrated AMLAB-based system for acquisition, processing and analysis of evoked EMG and mechanical responses of upper limb muscles. Author(s): Jaberzadeh S, Nazeran H, Scutter S, Warden-Flood A. Source: Australas Phys Eng Sci Med. 2003 June; 26(2): 70-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12956188
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Anatomical partitioning of three human forearm muscles. Author(s): Segal RL, Catlin PA, Krauss EW, Merick KA, Robilotto JB. Source: Cells, Tissues, Organs. 2002; 170(2-3): 183-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11731706
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Anterior and nasal transposition of the inferior oblique muscles. Author(s): Stager DR Jr, Beauchamp GR, Wright WW, Felius J, Stager D Sr. Source: J Aapos. 2003 June; 7(3): 167-73. Erratum In: J Aapos. 2003 December; 7(6): 450. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12825055
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Anticipatory activation of postural muscles associated with bilateral arm flexion in subjects with different quiet standing positions. Author(s): Fujiwara K, Toyama H, Kunita K. Source: Gait & Posture. 2003 June; 17(3): 254-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12770639
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Anticipatory postural adjustment in selected trunk muscles in post stroke hemiparetic patients. Author(s): Dickstein R, Shefi S, Marcovitz E, Villa Y. Source: Archives of Physical Medicine and Rehabilitation. 2004 February; 85(2): 261-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14966711
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Applied psychophysiology: beyond the boundaries of biofeedback (mending a wall, a brief history of our field, and applications to control of the muscles and cardiorespiratory systems). Author(s): Lehrer P. Source: Applied Psychophysiology and Biofeedback. 2003 December; 28(4): 291-304. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14686082
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Ask the doctor. I am a 64-year-old woman with high cholesterol caused by bad genes (familial hypercholesterolemia). Without medication, my cholesterol is above 450 mg/dL. So I am taking high-dose Lipitor (80 mg/day), WelChol, and Zetia to lower my cholesterol. I sometimes have pain and stiffness in my knees, and my shoulder, elbow, and wrist joints, plus the muscles in between, are stiff in the morning and hurt during the day. Two years ago I was diagnosed with bursitis in my hips. Could these problems be from the Lipitor? If so, is there another statin I could take that wouldn't do this? Author(s): Pasternak R. Source: Harvard Heart Letter : from Harvard Medical School. 2003 October; 14(2): 8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14576039
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Assessment of voluntary activation by stimulation of one muscle or two synergistic muscles. Author(s): Williams DM, Bilodeau M. Source: Muscle & Nerve. 2004 January; 29(1): 112-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14694506
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Atrophy of the abdominal wall muscles after extraperitoneal approach to the aorta. Author(s): Yamada M, Maruta K, Shiojiri Y, Takeuchi S, Matsuo Y, Takaba T. Source: Journal of Vascular Surgery : Official Publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter. 2003 August; 38(2): 346-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12891119
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Attitudinally correct designation of papillary muscles. Author(s): Frater RW. Source: J Heart Valve Dis. 2003 September; 12(5): 548-50. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14565703
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Beneficial effects of chronic low-frequency stimulation of thigh muscles in patients with advanced chronic heart failure. Author(s): Nuhr MJ, Pette D, Berger R, Quittan M, Crevenna R, Huelsman M, Wiesinger GF, Moser P, Fialka-Moser V, Pacher R. Source: European Heart Journal. 2004 January; 25(2): 136-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720530
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Benign asymmetric hypertrophy of the masticator muscles. Author(s): Palacios E, Valvassori G, D'Antonio M. Source: Ear, Nose, & Throat Journal. 2000 December; 79(12): 915. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11191429
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Bilateral aberrant biceps brachii muscles with special reference to their common nerve trunks. Author(s): Kawashima T, Yoshitomi S, Ito M, Hoshino Y, Oh-Ishi E, Ikeda E, Igarashi M, Yoshimura Y, Sato F, Sasaki H. Source: Okajimas Folia Anat Jpn. 2003 October; 80(4): 77-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14964467
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Bilateral anomaly of anterior bellies of digastric muscles. Author(s): Peker T, Turgut HB, Anil A. Source: Surgical and Radiologic Anatomy : Sra. 2000; 22(2): 119-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10959680
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Bilateral cortical control of the human anterior digastric muscles. Author(s): Gooden BR, Ridding MC, Miles TS, Nordstrom MA, Thompson PD. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 1999 December; 129(4): 582-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10638432
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Bilateral inferior insertion of lateral rectus muscles associated with schizencephaly. Author(s): Wine SB, Saad N, Vella ME. Source: Clinical & Experimental Ophthalmology. 2000 February; 28(1): 69-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11345352
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Bilateral interactions during contractions of intrinsic hand muscles. Author(s): Zijdewind I, Kernell D. Source: Journal of Neurophysiology. 2001 May; 85(5): 1907-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11353007
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Bilateral posterior fixation sutures on the medial rectus muscles for correction of nonaccommodative esotropia with infantile onset criteria. Author(s): Rizk A. Source: Journal of Pediatric Ophthalmology and Strabismus. 1999 November-December; 36(6): 320-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11132663
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Bilateral recession of superior rectus muscles: its influence on A and V pattern strabismus. Author(s): Melek NB, Mendoza T, Ciancia AO. Source: J Aapos. 1998 December; 2(6): 333-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10532719
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Bilateral recurrent focal myositis of gastrocnemius muscles after BCG vaccination. Author(s): Manganelli S, De Stefano R, Malandrini A, Selvi E, Frati E, Gambelli S, Marcolongo R. Source: Rheumatology (Oxford, England). 2002 September; 41(9): 1074-6. Erratum In: Rheumatology (Oxford) 2002 December; 41(12): 1461. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12209048
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Binding of an ankyrin-1 isoform to obscurin suggests a molecular link between the sarcoplasmic reticulum and myofibrils in striated muscles. Author(s): Bagnato P, Barone V, Giacomello E, Rossi D, Sorrentino V. Source: The Journal of Cell Biology. 2003 January 20; 160(2): 245-53. Epub 2003 Jan 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12527750
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Biomechanical model predicting electromyographic activity in three shoulder muscles from 3D kinematics and external forces during cleaning work. Author(s): Laursen B, Sogaard K, Sjogaard G. Source: Clinical Biomechanics (Bristol, Avon). 2003 May; 18(4): 287-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12689778
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Biomechanical model predicts directional tuning of spindles in finger muscles facilitates precision pinch and power grasp. Author(s): Biggs J, Horch K. Source: Somatosensory & Motor Research. 1999; 16(3): 251-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10527373
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Blocking of cloned and native delayed rectifier K channels from visceral smooth muscles by phencyclidine. Author(s): Frey BW, Lynch FT, Kinsella JM, Horowitz B, Sanders KM, Carl A. Source: Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society. 2000 December; 12(6): 509-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11123705
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Body position effects on EMG activity of the temporal and suprahyoid muscles in healthy subjects and in patients with myogenic cranio-cervical-mandibular dysfunction. Author(s): Ormeno G, Miralles R, Loyola R, Valenzuela S, Santander H, Palazzi C, Villanueva P. Source: Cranio. 1999 April; 17(2): 132-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10425940
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Booty camp. The fitness biz has bold new ways to trim your butt (and build muscles). Author(s): Streisand B. Source: U.S. News & World Report. 2003 January 13; 134(1): 54-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12530128
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Botox for contraction of pectoral muscles. Author(s): Richards A, Ritz M, Donahoe S, Southwick G. Source: Plastic and Reconstructive Surgery. 2001 July; 108(1): 270-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11420550
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Botulinum toxin-induced paralysis of frontotemporal muscles improves seizure focus localization. Author(s): Eisenschenk S, Gilmore RL, Uthman B, Valenstein E, Gonzalez R. Source: Neurology. 2002 January 22; 58(2): 246-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11805252
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Brains over muscles: the meaning of intelligence and race in American history. Author(s): Takaki R. Source: Halcyon. 1984; 6: 45-54. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11617025
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Breathing frequency and use of expiratory muscles do influence the dynamic positive end-expiratory pressure. Author(s): El Khawand Ch, Vanpee D, Rousseau L, Jamart J, Delaunois L. Source: Respiratory Medicine. 2003 April; 97(4): 388-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12693799
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Calcium-dependent and calcium-independent contractions in smooth muscles. Author(s): Harnett KM, Biancani P. Source: The American Journal of Medicine. 2003 August 18; 115 Suppl 3A: 24S-30S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12928071
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Carpal tunnel syndrome due to gouty infiltration of the lumbrical muscles and flexor tendons. Author(s): Tan G, Chew W, Lai CH. Source: Hand Surgery : an International Journal Devoted to Hand and Upper Limb Surgery and Related Research : Journal of the Asia-Pacific Federation of Societies for Surgery of the Hand. 2003 July; 8(1): 121-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12923948
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Caveolin-3 helps build muscles. Author(s): Marx J. Source: Science. 2001 November 30; 294(5548): 1864. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11729301
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Changes in motor planning of feedforward postural responses of the trunk muscles in low back pain. Author(s): Hodges PW. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 2001 November; 141(2): 261-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11713638
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Characteristics of the responses of smooth muscles of the uterus, coronary artery, and trachea to ozone and the ability of beta-adrenergic receptor sensitizers to decrease its beta-adrenergic blocking effect. Author(s): Sizova EN, Nozdrachev AD, Tsirkin VI. Source: Doklady Biological Sciences : Proceedings of the Academy of Sciences of the Ussr, Biological Sciences Sections / Translated from Russian. 2003 May-June; 390: 200-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12940140
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Characteristics of tone burst-evoked myogenic potentials in the sternocleidomastoid muscles. Author(s): Welgampola MS, Colebatch JG. Source: Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2001 November; 22(6): 796-802. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11698798
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Chronic transcutaneous electrical stimulation of calf muscles improves functional capacity without inducing systemic inflammation in claudicants. Author(s): Anderson SI, Whatling P, Hudlicka O, Gosling P, Simms M, Brown MD. Source: European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery. 2004 February; 27(2): 201-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718904
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Clinical and experimental studies of large amplitude action potential of the suffered facial muscles in intratemporal facial nerve paralysis. Author(s): Ren Z, Hui L. Source: Chinese Medical Sciences Journal = Chung-Kuo I Hsueh K'o Hsueh Tsa Chih / Chinese Academy of Medical Sciences. 1999 September; 14(3): 180-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12903822
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Comparative anatomical study of the gracilis and coracobrachialis muscles: implications for facial reanimation. Author(s): Taylor GI, Cichowitz A, Ang SG, Seneviratne S, Ashton M. Source: Plastic and Reconstructive Surgery. 2003 July; 112(1): 20-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12832872
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Comparative evaluation of effectiveness of different motor muscles in modified lasso procedure for correction of finger clawing. Author(s): Malaviya GN. Source: Journal of Hand Surgery (Edinburgh, Lothian). 2003 December; 28(6): 597-601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14599837
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Comparison of motor unit action potentials using monopolar vs. concentric needle electrodes in the middle deltoid and abductor digiti minimi muscles. Author(s): Nelson RM, Shedlock M, Kaczmarek C, Gahrs J, MacLaughlin H. Source: Electromyogr Clin Neurophysiol. 2003 December; 43(8): 459-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14717026
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Comparison of phosphocreatine concentration in the human masseter and medial pterygoid muscles by 31P-CSI. Author(s): Kanayama T, Minowa K, Inoue N, Yamaguchi T, Tamura T, Yoshida S, Kawasaki T. Source: Journal of Oral Rehabilitation. 2001 November; 28(11): 1075-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11722725
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Compliance changes of the series elastic component of elbow flexor muscles with age in humans. Author(s): Valour D, Pousson M. Source: Pflugers Archiv : European Journal of Physiology. 2003 March; 445(6): 721-7. Epub 2003 January 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12632193
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Contralateral reinnervation of midline muscles in facial paralysis. Author(s): Gilhuis HJ, Beurskens CH, Marres HA, de Vries J, Hartman EH, Zwarts MJ. Source: Muscle & Nerve. 2001 December; 24(12): 1703-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11745982
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Contralateral reinnervation of midline muscles in nonidiopathic facial palsy. Author(s): Gilhuis HJ, Beurskens CH, de Vries J, Marres HA, Hartman EH, Zwarts MJ. Source: Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society. 2003 April; 20(2): 151-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766689
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Conversion of biarticular to monoarticular muscles as a component of multilevel surgery in spastic diplegia. Author(s): Metaxiotis D, Wolf S, Doederlein L. Source: The Journal of Bone and Joint Surgery. British Volume. 2004 January; 86(1): 1029. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14765875
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Coupling between “hand” primary sensorimotor cortex and lower limb muscles after ulnar nerve surgical transfer in paraplegia. Author(s): Babiloni C, Vecchio F, Babiloni F, Brunelli GA, Carducci F, Cincotti F, Pizzella V, Romani GL, Tecchio FT, Rossini PM. Source: Behavioral Neuroscience. 2004 February; 118(1): 214-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14979799
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Cross-correlation analyses of mechanomyographic signals from the superficial quadriceps femoris muscles during concentric and eccentric isokinetic muscle actions. Author(s): Cramer JT, Housh TJ, Weir JP, Ebersole KT, Perry-Rana SR, Bull AJ, Johnson GO. Source: Electromyogr Clin Neurophysiol. 2003 July-August; 43(5): 293-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12964257
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Cross-sectional area of the lumbar back muscles as a function of torso flexion. Author(s): Jorgensen MJ, Marras WS, Gupta P. Source: Clinical Biomechanics (Bristol, Avon). 2003 May; 18(4): 280-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12689777
Studies
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Cystatin C colocalizes with amyloid-beta and coimmunoprecipitates with amyloidbeta precursor protein in sporadic inclusion-body myositis muscles. Author(s): Vattemi G, Engel WK, McFerrin J, Askanas V. Source: Journal of Neurochemistry. 2003 June; 85(6): 1539-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12787072
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Decomposition-based quantitative electromyography: methods and initial normative data in five muscles. Author(s): Doherty TJ, Stashuk DW. Source: Muscle & Nerve. 2003 August; 28(2): 204-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872325
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Decremental response of the nasalis and hypothenar muscles in myasthenia gravis. Author(s): Niks EH, Badrising UA, Verschuuren JJ, Van Dijk JG. Source: Muscle & Nerve. 2003 August; 28(2): 236-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872330
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Degradation of human hair keratin scaffold implanted for repairing injured skeletal muscles. Author(s): Qiao DF, Lu YM, Fu WY, Piao YJ. Source: Di Yi June Yi Da Xue Xue Bao. 2002 October; 22(10): 902-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12377613
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Descending control of muscles in patients with cervical dystonia. Author(s): Tijssen MA, Munchau A, Marsden JF, Lees A, Bhatia KP, Brown P. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2002 May; 17(3): 493-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12112196
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Desmin and actin alterations in human muscles affected by delayed onset muscle soreness: a high resolution immunocytochemical study. Author(s): Yu JG, Thornell LE. Source: Histochemistry and Cell Biology. 2002 August; 118(2): 171-9. Epub 2002 June 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12189520
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Development and characterisation of electromechanical muscles for driving transhumeral myoelectric prostheses. Author(s): Escudero AZ, Alvarez J, Leija L. Source: Prosthet Orthot Int. 2002 December; 26(3): 226-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12562070
98
Muscles
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Diagnostic value of vibration-induced nystagmus obtained by combined vibratory stimulation applied to the neck muscles and skull of 300 vertiginous patients. Author(s): Michel J, Dumas G, Lavieille JP, Charachon R. Source: Rev Laryngol Otol Rhinol (Bord). 2001; 122(2): 89-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11715267
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Differences in coenzyme Q10 content in deltoid and quadriceps muscles. Author(s): Benoist JF, Rigal O, Nivoche Y, Martin C, Biou D, Lombes A. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2003 March; 329(1-2): 147-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12589978
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Differential expression of myosin heavy chain isoforms between abductor and adductor muscles in the human larynx. Author(s): Li ZB, Lehar M, Nakagawa H, Hoh JF, Flint PW. Source: Otolaryngology and Head and Neck Surgery. 2004 February; 130(2): 217-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14990919
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Differential fatigue of paralyzed thenar muscles by stimuli of different intensities. Author(s): Godfrey S, Butler JE, Griffin L, Thomas CK. Source: Muscle & Nerve. 2002 July; 26(1): 122-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12115957
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Differential sensitivity of abdominal muscles and the diaphragm to mivacurium: an electromyographic study. Author(s): Kirov K, Motamed C, Dhonneur G. Source: Anesthesiology. 2001 December; 95(6): 1323-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11748387
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Direct neurotization of muscles by presynaptic motoneurons. Author(s): Brunelli GA. Source: Journal of Reconstructive Microsurgery. 2001 November; 17(8): 631-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11740660
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Disorders of the respiratory muscles. Author(s): Laghi F, Tobin MJ. Source: American Journal of Respiratory and Critical Care Medicine. 2003 July 1; 168(1): 10-48. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12826594
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Distention of venous structures in muscles as a controller of respiration. Author(s): Haouzi P, Chenuel B, Chalon B, Huszczuk A. Source: Advances in Experimental Medicine and Biology. 2001; 499: 349-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11729906
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Distribution of inspiratory drive to the external intercostal muscles in humans. Author(s): De Troyer A, Gorman RB, Gandevia SC. Source: The Journal of Physiology. 2003 February 1; 546(Pt 3): 943-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12563017
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Do Golgi tendon organs really inhibit muscle activity at high force levels to save muscles from injury, and adapt with strength training? Author(s): Chalmers G. Source: Sports Biomech. 2002 July; 1(2): 239-49. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14658379
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Do middle ear muscles trigger attacks of Meniere's disease? Author(s): Franz P, Hamzavi JS, Schneider B, Ehrenberger K. Source: Acta Oto-Laryngologica. 2003 January; 123(2): 133-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12701727
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Double-blind comparison study of two doses of botulinum toxin A injected into calf muscles in children with hemiplegic cerebral palsy. Author(s): Polak F, Morton R, Ward C, Wallace WA, Doderlein L, Siebel A. Source: Developmental Medicine and Child Neurology. 2002 August; 44(8): 551-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12206622
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Dynamic modeling of the neck muscles during horizontal head movement. Part II: Model construction in Pro/Engineer. Author(s): Haapala SA, Enderle JD. Source: Biomed Sci Instrum. 2003; 39: 71-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12724871
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Dynamic nature of fibre-type specific expression of myosin heavy chain transcripts in 14 different human skeletal muscles. Author(s): Smerdu V, Erzen I. Source: Journal of Muscle Research and Cell Motility. 2001; 22(8): 647-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12222825
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Effect of aging on fatigue characteristics of elbow flexor muscles during sustained submaximal contraction. Author(s): Bilodeau M, Henderson TK, Nolta BE, Pursley PJ, Sandfort GL. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2001 December; 91(6): 2654-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11717231
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Effect of sex on preactivation of the gastrocnemius and hamstring muscles. Author(s): DeMont RG, Lephart SM. Source: British Journal of Sports Medicine. 2004 April; 38(2): 120-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15039243
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Effect of static stretch training on neural and mechanical properties of the human plantar-flexor muscles. Author(s): Guissard N, Duchateau J. Source: Muscle & Nerve. 2004 February; 29(2): 248-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14755490
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Effect of step and ramp static contractions on the median frequency of electromyograms of back muscles in humans. Author(s): Lariviere C, Arsenault AB, Gravel D, Gagnon D, Loisel P. Source: European Journal of Applied Physiology. 2001 October; 85(6): 552-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11718284
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Effects of aging on muscle T2 relaxation time: difference between fast- and slowtwitch muscles. Author(s): Hatakenaka M, Ueda M, Ishigami K, Otsuka M, Masuda K. Source: Investigative Radiology. 2001 December; 36(12): 692-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11753139
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Effects of increased muscle mass on bone in male mice overexpressing IGF-I in skeletal muscles. Author(s): Banu J, Wang L, Kalu DN. Source: Calcified Tissue International. 2003 August; 73(2): 196-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14565602
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Effects of the use of cross-education to the affected side through various resistive exercises of the sound side and settings of the length of the affected muscles. Author(s): Arai M, Shimizu H, Shimizu ME, Tanaka Y, Yanagisawa K. Source: Hiroshima J Med Sci. 2001 September; 50(3): 65-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11720165
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Electromyographic activity of lower lip muscles when chewing with the lips in contact and apart. Author(s): Tomiyama N, Ichida T, Yamaguchi K. Source: Angle Orthod. 2004 February; 74(1): 31-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15038488
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Electromyographic activity of selected trunk muscles during dynamic spine stabilization exercises. Author(s): Souza GM, Baker LL, Powers CM. Source: Archives of Physical Medicine and Rehabilitation. 2001 November; 82(11): 15517. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11689975
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Electromyographic activity of voluntarily activated trunk flexor and extensor muscles in post-stroke hemiparetic subjects. Author(s): Dickstein R, Shefi S, Marcovitz E, Villa Y. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2004 April; 115(4): 790-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15003758
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Electromyographic analysis of the arm muscles in “front support” exercises. Author(s): Dias GA, Guazzelli Filho J, Rodrigues JA, Goncalves M, Bull ML. Source: Electromyogr Clin Neurophysiol. 2003 December; 43(8): 465-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14717027
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Electromyographic analysis of the pectoralis major and deltoideus anterior muscles in horizontal “flyer” exercises with loads. Author(s): Rodrigues JA, Bull ML, Dias GA, Goncalves M, Guazzelli JF. Source: Electromyogr Clin Neurophysiol. 2003 October-November; 43(7): 413-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14626721
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Electromyography of respiratory muscles in amyotrophic lateral sclerosis. Author(s): Stewart H, Eisen A, Road J, Mezei M, Weber M. Source: Journal of the Neurological Sciences. 2001 October 15; 191(1-2): 67-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11676994
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EMG activities of facial and chewing muscles of human adults in response to taste stimuli. Author(s): Horio T. Source: Percept Mot Skills. 2003 August; 97(1): 289-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14604052
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EMG characteristics of low back and lower limb muscles during forward bending posture. Author(s): Sakamoto K, Swie YW. Source: Electromyogr Clin Neurophysiol. 2003 September; 43(6): 335-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14535046
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Evaluation of extraocular muscles in the edematous phase of Graves ophthalmopathy on contrast-enhanced fat-suppressed magnetic resonance imaging. Author(s): Cakirer S, Cakirer D, Basak M, Durmaz S, Altuntas Y, Yigit U. Source: Journal of Computer Assisted Tomography. 2004 January-February; 28(1): 80-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14716237
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Evaluation of the peak torque, total work, average power of flexor-estensor and prono-supinator muscles of the elbow in baseball players. Author(s): Costantino C, Vaienti E, Pogliacomi F. Source: Acta Biomed Ateneo Parmense. 2003 August; 74(2): 88-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14509917
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Examination of pain ratings associated with elicitation of the maximal H-wave and maximal M-wave in the soleus and flexor carpi radialis muscles. Author(s): Motl RW, Knowles BD, O'Connor PJ. Source: The International Journal of Neuroscience. 2003 November; 113(11): 1477-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14585748
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Expiratory-synchronized sleep in a quadriplegic patient using inspiratory neck muscles to breathe. Author(s): Arnulf I, Straus C, Delafosse C, Derenne JP, Similowski T. Source: Sleep & Breathing = Schlaf & Atmung. 2003 September; 7(3): 143-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14569525
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Expression of lysosome-related proteins and genes in the skeletal muscles of inclusion body myositis. Author(s): Kumamoto T, Ueyama H, Tsumura H, Toyoshima I, Tsuda T. Source: Acta Neuropathologica. 2004 January; 107(1): 59-65. Epub 2003 September 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14513262
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Fascicle arrangements of vastus lateralis and gastrocnemius muscles in highly trained soccer players and swimmers of both genders. Author(s): Kanehisa H, Muraoka Y, Kawakami Y, Fukunaga T. Source: International Journal of Sports Medicine. 2003 February; 24(2): 90-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12669252
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Fascicle length of gastrocnemius muscles in monozygous twins. Author(s): Abe T. Source: Journal of Physiological Anthropology and Applied Human Science. 2002 November; 21(6): 291-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12612401
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Fast MRI used to evaluate the effect of abdominal belts during contraction of trunk muscles. Author(s): Miyamoto K, Shimizu K, Masuda K. Source: Spine. 2002 August 15; 27(16): 1749-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12195066
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Fatigability and variable-frequency train stimulation of human skeletal muscles. Author(s): Bickel CS, Slade JM, Warren GL, Dudley GA. Source: Physical Therapy. 2003 April; 83(4): 366-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12665407
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Fatigue of paralyzed and control thenar muscles induced by variable or constant frequency stimulation. Author(s): Thomas CK, Griffin L, Godfrey S, Ribot-Ciscar E, Butler JE. Source: Journal of Neurophysiology. 2003 April; 89(4): 2055-64. Epub 2002 December 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12611940
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Fatigue-induced change in corticospinal drive to back muscles in elite rowers. Author(s): Fulton RC, Strutton PH, McGregor AH, Davey NJ. Source: Experimental Physiology. 2002 September; 87(5): 593-600. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12481934
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FDG uptake by tongue and muscles of mastication reflecting increased metabolic activity of muscles after chewing gum. Author(s): Kawabe J, Higashiyama S, Okamura T, Torii K, Koyama K, Kawamura E, Ishizu H, Inoue Y, Shiomi S. Source: Clinical Nuclear Medicine. 2003 March; 28(3): 220-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12592130
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Fibre composition of human intrinsic tongue muscles. Author(s): Stal P, Marklund S, Thornell LE, De Paul R, Eriksson PO. Source: Cells, Tissues, Organs. 2003; 173(3): 147-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12673097
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First description of ocular counterrolling in 1786. The use of the oblique muscles. Author(s): Hunter J. Source: Strabismus. 2002 December; 10(4): 279-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12660852
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Flap tear of rectus muscles: an underlying cause of strabismus after orbital trauma. Author(s): Ludwig IH, Brown MS. Source: Ophthalmic Plastic and Reconstructive Surgery. 2002 November; 18(6): 443-9; Discussion 450. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12439059
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Focal pyomyositis of the perisciatic muscles in children. Author(s): Hernandez RJ, Strouse PJ, Craig CL, Farley FA. Source: Ajr. American Journal of Roentgenology. 2002 November; 179(5): 1267-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12388511
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Force and contraction time relation in skeletal muscles of children and adults. Author(s): Gatev V, Stefanova-Uzunova M, Stamatova L. Source: Agressologie. 1979; 20(5): 301-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12679962
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Foster-type modification of the Knapp procedure for anomalous superior rectus muscles in syndromic craniosynostoses. Author(s): Rattigan S, Nischal KK. Source: J Aapos. 2003 August; 7(4): 279-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12917616
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Frequency of M-cadherin-stained satellite cells declines in human muscles during aging. Author(s): Sajko S, Kubinova L, Cvetko E, Kreft M, Wernig A, Erzen I. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 2004 February; 52(2): 179-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14729869
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Frequency of occurrence of the F wave in distal flexor muscles as a function of hypnotic susceptibility and hypnosis. Author(s): Santarcangelo EL, Busse K, Carli G. Source: Brain Research. Cognitive Brain Research. 2003 March; 16(1): 99-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12589894
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From the electrodiagnosis lab.H-reflexes in hand muscles after cervical spinal cord disease. Author(s): Leppanen RE. Source: The Spine Journal : Official Journal of the North American Spine Society. 2003 September-October; 3(5): 405. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14598812
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Function and bulk of respiratory and limb muscles in patients with cystic fibrosis. Author(s): Pinet C, Cassart M, Scillia P, Lamotte M, Knoop C, Casimir G, Melot C, Estenne M. Source: American Journal of Respiratory and Critical Care Medicine. 2003 October 15; 168(8): 989-94. Epub 2003 June 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12829457
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Functional magnetic resonance image finding of cortical activation by neuromuscular electrical stimulation on wrist extensor muscles. Author(s): Han BS, Jang SH, Chang Y, Byun WM, Lim SK, Kang DS. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2003 January; 82(1): 17-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12510180
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Further debate regarding surgery for esotropia, +/- accommodative; cyclovertical muscles, Gobin's theories re “sagitallization”; letters No. 3,4 & 5. Author(s): Kushner BJ. Source: Binocul Vis Strabismus Q. 2001; 16(4): 246-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11720587
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Further insights into post-exercise effects on H-reflexes and motor evoked potentials of the flexor carpi radialis muscles. Author(s): Kato T, Takeda Y, Tsuji T, Kasai T. Source: Motor Control. 2003 January; 7(1): 82-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12536164
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Ga-67 scintigram in the diagnosis of infection of masticator muscles due to an odontogenic infection. Author(s): Sakamoto H, Suzuki Y, Watanabe D, Yanagimachi N, Sasaki J. Source: Clinical Nuclear Medicine. 2000 May; 25(5): 383-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10795706
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Gastric mucosal smooth muscles may explain oscillations in glandular pressure: role of vasoactive intestinal peptide. Author(s): Synnerstad I, Ekblad E, Sundler F, Holm L. Source: Gastroenterology. 1998 February; 114(2): 284-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9453488
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Gastrointestinal smooth muscles and sphincters spasms: treatment with botulinum neurotoxin. Author(s): Brisinda G, Civello IM, Albanese A, Maria G. Source: Current Medicinal Chemistry. 2003 April; 10(7): 603-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12678792
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Gating of segmental and transcortical reflexes to human hand muscles depends on the mode of innervation. Author(s): Wagner S, von Waldenfels A, Meinck HM. Source: Neuroscience Letters. 2000 February 18; 280(2): 127-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10686394
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Gender influence on the oxygen consumption of the respiratory muscles in young and older healthy individuals. Author(s): Topin N, Mucci P, Hayot M, Prefaut C, Ramonatxo M. Source: International Journal of Sports Medicine. 2003 November; 24(8): 559-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14598190
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Generation second messengers by prostanoids in the iris-sphincter and ciliary muscles of cows, cats and humans. Author(s): Bhattacherjee P, Smithson M, Paterson CA. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 1997 June; 56(6): 443-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9223655
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Geometric structure of the human and canine cricothyroid and thyroarytenoid muscles for biomechanical applications. Author(s): Cox KA, Alipour F, Titze IR. Source: The Annals of Otology, Rhinology, and Laryngology. 1999 December; 108(12): 1151-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10605920
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Geometrical factors in surface EMG of the vastus medialis and lateralis muscles. Author(s): Rainoldi A, Nazzaro M, Merletti R, Farina D, Caruso I, Gaudenti S. Source: Journal of Electromyography and Kinesiology : Official Journal of the International Society of Electrophysiological Kinesiology. 2000 October; 10(5): 327-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11018442
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Getting muscles moving again after botulinum toxin: novel therapeutic challenges. Author(s): Foran PG, Davletov B, Meunier FA. Source: Trends in Molecular Medicine. 2003 July; 9(7): 291-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12900216
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Glucose uptake by individual skeletal muscles during running using whole-body positron emission tomography. Author(s): Fujimoto T, Itoh M, Tashiro M, Yamaguchi K, Kubota K, Ohmori H. Source: European Journal of Applied Physiology. 2000 November; 83(4 -5): 297-302. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11138567
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GLUT-4 expression is not consistently higher in type-1 than in type-2 fibres of rat and human vastus lateralis muscles; an immunohistochemical study. Author(s): Borghouts LB, Schaart G, Hesselink MK, Keizer HA. Source: Pflugers Archiv : European Journal of Physiology. 2000 December; 441(2-3): 3518. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11211123
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Glycogen depletion and lactate accumulation in human intercostal muscles after administration of succinylcholine. Author(s): Mizuno M, Secher NH. Source: British Journal of Anaesthesia. 1998 March; 80(3): 302-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9623428
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Grand rounds #68: a case of consecutive exotropia after recession of all four horizontal rectus muscles for the treatment of nystagmus. Author(s): Kushner BJ, Coats DK, Kodsi SR, Repka MX, Richard JM, Saunders RA, Wang FM. Source: Binocul Vis Strabismus Q. 2002 Winter; 17(4): 304-11. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12470293
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Grandad, it ain't what you eat, it depends when you eat it--that's how muscles grow! Author(s): Rennie MJ. Source: The Journal of Physiology. 2001 August 15; 535(Pt 1): 2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11507153
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Group I projections from intrinsic foot muscles to motoneurones of leg and thigh muscles in humans. Author(s): Marque P, Nicolas G, Marchand-Pauvert V, Gautier J, Simonetta-Moreau M, Pierrot-Deseilligny E. Source: The Journal of Physiology. 2001 October 1; 536(Pt 1): 313-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11579179
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Guidelines for the intramuscular positioning of EMG electrodes in the semispinalis capitis and cervicis muscles. Author(s): Kramer M, Schmid I, Sander S, Hogel J, Eisele R, Kinzl L, Hartwig E. Source: Journal of Electromyography and Kinesiology : Official Journal of the International Society of Electrophysiological Kinesiology. 2003 June; 13(3): 289-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12706608
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Habitual level of physical activity and muscle fatigue of the elbow flexor muscles in older men. Author(s): Seghers J, Spaepen A, Delecluse C, Colman V. Source: European Journal of Applied Physiology. 2003 June; 89(5): 427-34. Epub 2003 April 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12684808
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Having it both ways? Vasoconstriction in contracting muscles. Author(s): Joyner MJ, Thomas GD. Source: The Journal of Physiology. 2003 July 15; 550(Pt 2): 333. Epub 2003 May 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12777450
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Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1). Author(s): Yamada K, Andrews C, Chan WM, McKeown CA, Magli A, de Berardinis T, Loewenstein A, Lazar M, O'Keefe M, Letson R, London A, Ruttum M, Matsumoto N, Saito N, Morris L, Del Monte M, Johnson RH, Uyama E, Houtman WA, de Vries B, Carlow TJ, Hart BL, Krawiecki N, Shoffner J, Vogel MC, Katowitz J, Goldstein SM, Levin AV, Sener EC, Ozturk BT, Akarsu AN, Brodsky MC, Hanisch F, Cruse RP, Zubcov AA, Robb RM, Roggenkaemper P, Gottlob I, Kowal L, Battu R, Traboulsi EI, Franceschini P, Newlin A, Demer JL, Engle EC. Source: Nature Genetics. 2003 December; 35(4): 318-21. Epub 2003 November 02. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14595441
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High mutational burden in the mtDNA control region from aged muscles: a singlefiber study. Author(s): Del Bo R, Crimi M, Sciacco M, Malferrari G, Bordoni A, Napoli L, Prelle A, Biunno I, Moggio M, Bresolin N, Scarlato G, Pietro Comi G. Source: Neurobiology of Aging. 2003 October; 24(6): 829-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12927765
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High spatial resolution in vivo 2D (1)H magnetic resonance spectroscopic imaging of human muscles with a band-selective technique. Author(s): Hu J, Jiang Q, Xia Y, Zuo C. Source: Magnetic Resonance Imaging. 2001 October; 19(8): 1091-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11711233
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Histological changes to palatal and paratubal muscles in oral submucous fibrosis. Author(s): Gupta SC, Khanna S, Singh M, Singh PA. Source: The Journal of Laryngology and Otology. 2000 December; 114(12): 947-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11177364
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Histological pictures of muscles and an evaluation of cellular infiltrations in human polymyositis/dermatomyositis, as compared to the findings in experimental Guinea pig myositis. Author(s): Gendek-Kubiak H, Gendek EG. Source: Cellular & Molecular Biology Letters. 2003; 8(2): 297-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12813563
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Histology of nerves and muscles in adductor spasmodic dysphonia. Author(s): Chhetri DK, Blumin JH, Vinters HV, Berke GS. Source: The Annals of Otology, Rhinology, and Laryngology. 2003 April; 112(4): 334-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12731628
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Homozygous mutations in ARIX(PHOX2A) result in congenital fibrosis of the extraocular muscles type 2. Author(s): Nakano M, Yamada K, Fain J, Sener EC, Selleck CJ, Awad AH, Zwaan J, Mullaney PB, Bosley TM, Engle EC. Source: Nature Genetics. 2001 November; 29(3): 315-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11600883
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How muscles know how to adapt. Author(s): Rennie MJ. Source: The Journal of Physiology. 2001 August 15; 535(Pt 1): 1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11507152
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Human elbow joint torque is linearly encoded in electromyographic signals from multiple muscles. Author(s): Kutch JJ, Buchanan TS. Source: Neuroscience Letters. 2001 September 28; 311(2): 97-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11567787
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Human hamstring muscles adapt to eccentric exercise by changing optimum length. Author(s): Brockett CL, Morgan DL, Proske U. Source: Medicine and Science in Sports and Exercise. 2001 May; 33(5): 783-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11323549
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Human lower limb muscles: an evaluation of weight and fiber size. Author(s): Ito J, Moriyama H, Inokuchi S, Goto N. Source: Okajimas Folia Anat Jpn. 2003 August; 80(2-3): 47-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14604153
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Human MYO18B, a novel unconventional myosin heavy chain expressed in striated muscles moves into the myonuclei upon differentiation. Author(s): Salamon M, Millino C, Raffaello A, Mongillo M, Sandri C, Bean C, Negrisolo E, Pallavicini A, Valle G, Zaccolo M, Schiaffino S, Lanfranchi G. Source: Journal of Molecular Biology. 2003 February 7; 326(1): 137-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12547197
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Human postural responses to different frequency vibrations of lower leg muscles. Author(s): Polonyova A, Hlavacka F. Source: Physiological Research / Academia Scientiarum Bohemoslovaca. 2001; 50(4): 405-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11551147
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Human SM22 alpha BAC encompasses regulatory sequences for expression in vascular and visceral smooth muscles at fetal and adult stages. Author(s): Xu R, Ho YS, Ritchie RP, Li L. Source: American Journal of Physiology. Heart and Circulatory Physiology. 2003 April; 284(4): H1398-407. Epub 2003 January 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12521938
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Hyperbaric oxygen increases the contractile function of regenerating rat slow muscles. Author(s): Gregorevic P, Williams DA, Lynch GS. Source: Medicine and Science in Sports and Exercise. 2002 April; 34(4): 630-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11932571
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Hypercapnic acidosis activates KATP channels in vascular smooth muscles. Author(s): Wang X, Wu J, Li L, Chen F, Wang R, Jiang C. Source: Circulation Research. 2003 June 13; 92(11): 1225-32. Epub 2003 May 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12738754
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Hypertrophied papillary muscles mimicking left ventricular mass on Tc-99m MIBI myocardial perfusion scintigraphy. Author(s): Berk F, Demir H, Agacdiken A, Ural D, Aktolun C. Source: Journal of Nuclear Cardiology : Official Publication of the American Society of Nuclear Cardiology. 2002 July-August; 9(4): 441-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12161722
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Hypoalgesia to pressure pain in referred pain areas triggered by spatial summation of experimental muscle pain from unilateral or bilateral trapezius muscles. Author(s): Ge HY, Madeleine P, Wang K, Arendt-Nielsen L. Source: European Journal of Pain (London, England). 2003; 7(6): 531-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14575666
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Idiopathic inflammatory myopathies: why do the muscles become weak? Author(s): Lundberg IE. Source: Current Opinion in Rheumatology. 2001 November; 13(6): 457-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11698720
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Impact of papillary muscles in ventricular volume and ejection fraction assessment by cardiovascular magnetic resonance. Author(s): Sievers B, Kirchberg S, Bakan A, Franken U, Trappe HJ. Source: Journal of Cardiovascular Magnetic Resonance : Official Journal of the Society for Cardiovascular Magnetic Resonance. 2004; 6(1): 9-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15054924
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In vivo characterisation of the human UCP3 gene minimal promoter in mice tibialis anterior muscles. Author(s): Riquet FB, Rodriguez M, Guigal N, Dromaint S, Naime I, Boutin JA, Galizzi JP. Source: Biochemical and Biophysical Research Communications. 2003 November 21; 311(3): 583-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14623310
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In vivo determination of fascicle curvature in contracting human skeletal muscles. Author(s): Muramatsu T, Muraoka T, Kawakami Y, Shibayama A, Fukunaga T. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2002 January; 92(1): 12934. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11744651
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Increased blood pressure can reduce fatigue of thenar muscles paralyzed after spinal cord injury. Author(s): Butler JE, Ribot-Ciscar E, Zijdewind I, Thomas CK. Source: Muscle & Nerve. 2004 April; 29(4): 575-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15052623
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Increased jitter and blocking in normal muscles due to doubly innervated muscle fibers. Author(s): Lateva ZC, McGill KC, Johanson ME. Source: Muscle & Nerve. 2003 October; 28(4): 423-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506713
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Influence of acute alcohol load on metabolism of skeletal muscles--expired gas analysis during exercise. Author(s): Shiraishi K, Watanabe M, Motegi S, Nagaoka R, Matsuzaki S, Ikemoto H. Source: Alcoholism, Clinical and Experimental Research. 2003 August; 27(8 Suppl): 76S78S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12960513
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Influence of occlusal stabilization splint on the asymmetric activity of masticatory muscles in patients with temporomandibular dysfunction. Author(s): Alajbeg IZ, Valentic-Peruzovic M, Alajbeg I, Illes D. Source: Coll Antropol. 2003 June; 27(1): 361-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12974166
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Innervation of calf muscles in relation to calf reduction. Author(s): Hwang K, Kim YJ, Chung IH, Won HS, Tanaka S, Lee SI. Source: Annals of Plastic Surgery. 2003 May; 50(5): 517-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12792543
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Innervation of the sternocleidomastoid and trapezius muscles by the accessory nucleus. Author(s): DeToledo JC, David NJ. Source: Journal of Neuro-Ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society. 2001 September; 21(3): 214-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11725190
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Innervation zones of the upper and lower limb muscles estimated by using multichannel surface EMG. Author(s): Saitou K, Masuda T, Michikami D, Kojima R, Okada M. Source: J Hum Ergol (Tokyo). 2000 December; 29(1-2): 35-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12696320
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Integrated approach for in vivo evaluation of respiratory muscles mechanics. Author(s): Ratnovsky A, Zaretsky U, Shiner RJ, Elad D. Source: Journal of Biomechanics. 2003 December; 36(12): 1771-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14614931
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Interaction of fibre type, potentiation and fatigue in human knee extensor muscles. Author(s): Hamada T, Sale DG, MacDougall JD, Tarnopolsky MA. Source: Acta Physiologica Scandinavica. 2003 June; 178(2): 165-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12780391
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Internal/external rotation moment arms of muscles at the knee: moment arms for the normal knee and the ACL-deficient knee. Author(s): Buford WL Jr, Ivey FM Jr, Nakamura T, Patterson RM, Nguyen DK. Source: The Knee. 2001 December; 8(4): 293-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11706692
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Intramuscular hemangiomas of extraocular muscles. Author(s): Kiratli H, Bilgic S, Caglar M, Soylemezoglu F. Source: Ophthalmology. 2003 March; 110(3): 564-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12623822
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Intramuscular innervation of upper-limb skeletal muscles. Author(s): Lim AY, Pereira BP, Kumar VP, De Coninck C, Taki C, Baudet J, Merle M. Source: Muscle & Nerve. 2004 April; 29(4): 523-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15052617
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Investigation of the distribution and changes of VLDLR subtype in fibrotic cardiac muscles. Author(s): Yang G, Bao L, Zhao J, Qu S. Source: J Tongji Med Univ. 2000; 20(4): 297-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12840916
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Is the normal content of sulfhydryl groups attributable to sparing from dystrophic pathology in dystrophin-deficient muscles? Author(s): Niebroj-Dobosz I, Fidzianska A, Glinka Z, Hausmanowa-Petrusewicz I. Source: Folia Neuropathol. 2002; 40(3): 143-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12572920
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Isokinetic eccentric-to-concentric strength ratios of the shoulder rotator muscles in throwers and nonthrowers. Author(s): Noffal GJ. Source: The American Journal of Sports Medicine. 2003 July-August; 31(4): 537-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12860541
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Isolated flexor muscles of the little toe in the feet of an individual with atrophied or lacking 4th head of the M. extensor digitorum brevis and lacking the 4th tendon of the M. extensor digitorum longus. Author(s): Claassen H, Wree A. Source: Ann Anat. 2003 January; 185(1): 81-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12597131
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Jaw muscles in older overdenture patients. Author(s): Newton JP, McManus FC, Menhenick S. Source: Gerodontology. 2004 March; 21(1): 37-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15074538
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Juvenile xanthogranuloma invading the muscles in the head and neck: clinicopathological case report. Author(s): Margulis A, Melin-Aldana H, Bauer BS. Source: Annals of Plastic Surgery. 2003 April; 50(4): 425-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12671388
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Kegel exercises. Strengthening the weak pelvic floor muscles that cause urinary incontinence. Author(s): Kolcaba K, Dowd T, Winslow EH, Jacobson AF. Source: The American Journal of Nursing. 2000 November; 100(11): 59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11103639
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Kinematics and electromyography of lower limb muscles in overground and treadmill running. Author(s): Wank V, Frick U, Schmidtbleicher D. Source: International Journal of Sports Medicine. 1998 October; 19(7): 455-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9839841
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Kocher Debre Semelaigne syndrome: regression of pesudohypertrophy of muscles on thyroxine. Author(s): Mehrotra P, Chandra M, Mitra MK. Source: Archives of Disease in Childhood. 2002 March; 86(3): 224. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11861255
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Lactate transporters (MCT proteins) in heart and skeletal muscles. Author(s): Bonen A. Source: Medicine and Science in Sports and Exercise. 2000 April; 32(4): 778-89. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10776897
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Less calcium in cremaster muscles of boys with undescended testis supports a deficiency in sympathetic innervation. Author(s): Tanyel FC, Ulusu NN, Tezcan EF, Buyukpamukcu N. Source: Urologia Internationalis. 2002; 69(2): 111-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12187040
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Limitation to exercise tolerance in chronic obstructive pulmonary disease: look to the muscles of ambulation. Author(s): Casaburi R. Source: American Journal of Respiratory and Critical Care Medicine. 2003 August 15; 168(4): 409-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12912729
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Loads applied tangential to a fingertip during an object restraint task can trigger short-latency as well as long-latency EMG responses in hand muscles. Author(s): Macefield VG, Johansson RS. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 2003 September; 152(2): 143-9. Epub 2003 July 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12898103
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Local injection into mimetic muscles of botulinum toxin A for the treatment of facial lines. Author(s): Guerrissi J, Sarkissian P. Source: Annals of Plastic Surgery. 1997 November; 39(5): 447-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9374139
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Localization of the motor nerve branches and motor points of the triceps surae muscles in korean cadavers. Author(s): Sook Kim H, Hye Hwang J, Lee PK, Kwon JY, Yeon Oh-Park M, Moon Kim J, Ho Chun M. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2002 October; 81(10): 765-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12362117
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Location of innervation zones of sternocleidomastoid and scalene muscles--a basis for clinical and research electromyography applications. Author(s): Falla D, Dall'Alba P, Rainoldi A, Merletti R, Jull G. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2002 January; 113(1): 57-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11801425
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Locomotor-specific measure of spasticity of plantarflexor muscles after stroke. Author(s): Lamontagne A, Malouin F, Richards CL. Source: Archives of Physical Medicine and Rehabilitation. 2001 December; 82(12): 1696704. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11733885
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Long-loop reflex from arm afferents to remote muscles in normal man. Author(s): Kagamihara Y, Hayashi A, Masakado Y, Kouno Y. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 2003 July; 151(1): 136-44. Epub 2003 May 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12743676
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Long-term activity in upper- and lower-limb muscles of humans. Author(s): Kern DS, Semmler JG, Enoka RM. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2001 November; 91(5): 2224-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11641365
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Lung function and surface electromyography of intercostal muscles in cement mill workers. Author(s): Meo SA, Azeem MA, Ghori MG, Subhan MM. Source: International Journal of Occupational Medicine and Environmental Health. 2002; 15(3): 279-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12462455
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Mice expressing only covalent dimeric heparin binding-deficient lipoprotein lipase: muscles inefficiently secrete dimeric enzyme. Author(s): Lutz EP, Kako Y, Yagyu H, Heeren J, Marks S, Wright T, Melford K, BenZeev O, Radner H, Merkel M, Bensadoun A, Wong H, Goldberg IJ. Source: The Journal of Biological Chemistry. 2004 January 2; 279(1): 238-44. Epub 2003 October 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570890
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Modulation of human cervical premotoneurons during bilateral voluntary contraction of upper-limb muscles. Author(s): Stinear JW, Byblow WD. Source: Muscle & Nerve. 2004 April; 29(4): 506-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15052615
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Motor and sensory innervation of extraocular eye muscles. Author(s): Buttner-Ennever JA, Eberhorn A, Horn AK. Source: Annals of the New York Academy of Sciences. 2003 October; 1004: 40-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662446
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Motor unit action potential analysis of the paraspinal muscles. Paraspinal MUAP analysis is not useful. Author(s): Trojaborg W. Source: Muscle & Nerve. 2004 March; 29(3): 454-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14981749
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Motor unit action potential analysis of the paraspinal muscles. Paraspinal MUAP analysis is useful. Author(s): Bromberg MB. Source: Muscle & Nerve. 2004 March; 29(3): 451-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14981748
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MR imaging of the accessory muscles around the ankle. Author(s): Cheung Y, Rosenberg ZS. Source: Magn Reson Imaging Clin N Am. 2001 August; 9(3): 465-73, X. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11694421
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Muscle activation patterns of selected lower extremity muscles during stepping and cutting tasks. Author(s): Houck J. Source: Journal of Electromyography and Kinesiology : Official Journal of the International Society of Electrophysiological Kinesiology. 2003 December; 13(6): 545-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14573369
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Muscle fatigue of the elbow flexor muscles during two intermittent exercise protocols with equal mean muscle loading. Author(s): Seghers J, Spaepen A. Source: Clinical Biomechanics (Bristol, Avon). 2004 January; 19(1): 24-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14659926
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Muscles flex, axons die. Author(s): Wrathall JR. Source: Nature Medicine. 2003 November; 9(11): 1347-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14595422
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Muscular bridge between the inferior oblique and inferior rectus muscles. Author(s): Yalcin B, Kocabiyik N, Ozan H, Kutoglu T. Source: American Journal of Ophthalmology. 2004 January; 137(1): 121-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14700654
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Neck vibration causes short-latency electromyographic activation of lower leg muscles in postural reactions of the standing human. Author(s): Andersson G, Magnusson M. Source: Acta Oto-Laryngologica. 2002 April; 122(3): 284-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12030575
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Nerve growth factor expression in human dystrophic muscles. Author(s): Toti P, Villanova M, Vatti R, Schuerfeld K, Stumpo M, Barbagli L, Malandrini A, Costantini M. Source: Muscle & Nerve. 2003 March; 27(3): 370-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12635125
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Neural control of rhythmic human arm movement: phase dependence and task modulation of hoffmann reflexes in forearm muscles. Author(s): Zehr EP, Collins DF, Frigon A, Hoogenboom N. Source: Journal of Neurophysiology. 2003 January; 89(1): 12-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12522155
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Neuroblastoma with atypical metastases to cardiac and skeletal muscles: MRI features. Author(s): Faingold R, Babyn PS, Yoo SJ, Dipchand AI, Weitzman S. Source: Pediatric Radiology. 2003 August; 33(8): 584-6. Epub 2003 May 24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12768251
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Neuromuscular effects of rapacuronium on the diaphragm and skeletal muscles in anaesthetized patients using cervical magnetic stimulation for stimulating the phrenic nerves. Author(s): Moerer O, Baller C, Hinz J, Buscher H, Crozier TA. Source: European Journal of Anaesthesiology. 2002 December; 19(12): 883-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12510907
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Neurovascular territories of the external and internal oblique muscles. Author(s): Yang D, Morris SF, Geddes CR, Tang M. Source: Plastic and Reconstructive Surgery. 2003 November; 112(6): 1591-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14578789
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New relationship between electrical characteristics of evoked contractions in skeletal muscles during necrobiosis. Author(s): Babinkov VI. Source: Bulletin of Experimental Biology and Medicine. 2000 October; 130(10): 934-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11177285
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Nicotinic acetylcholine receptors of muscles and nerves: comparison of their structures, functional roles, and vulnerability to pathology. Author(s): Lindstrom JM. Source: Annals of the New York Academy of Sciences. 2003 September; 998: 41-52. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14592862
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Non-invasive quantitative assessment of oxidative metabolism in quadriceps muscles by near infrared spectroscopy. Author(s): Ding H, Wang G, Lei W, Wang R, Huang L, Xia Q, Wu J. Source: British Journal of Sports Medicine. 2001 December; 35(6): 441-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11726485
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Normalized force, activation, and coactivation in the arm muscles of young and old men. Author(s): Klein CS, Rice CL, Marsh GD. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2001 September; 91(3): 1341-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11509534
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Older adults are less steady during submaximal isometric contractions with the knee extensor muscles. Author(s): Tracy BL, Enoka RM. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2002 March; 92(3): 100412. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11842033
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On the mechanics of the ocular muscles. Part I. 1869. Author(s): Volkmann AW, Blanken RR. Source: Strabismus. 2002 March; 10(1): 45-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12185646
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Organization of the central control of muscles of facial expression in man. Author(s): Root AA, Stephens JA. Source: The Journal of Physiology. 2003 May 15; 549(Pt 1): 289-98. Epub 2003 April 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12692176
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Original histologic findings in arteries of the right ventricle papillary muscles in human hearts. Author(s): Nerantzis CE, Koutsaftis PN, Marianou SK, Karakoukis NG, Cafiris NA, Kontogeorgos G. Source: The Anatomical Record. 2002 March 1; 266(3): 146-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11870597
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Orthologous myosin isoforms and scaling of shortening velocity with body size in mouse, rat, rabbit and human muscles. Author(s): Pellegrino MA, Canepari M, Rossi R, D'Antona G, Reggiani C, Bottinelli R. Source: The Journal of Physiology. 2003 February 1; 546(Pt 3): 677-89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12562996
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Oscillatory interaction between human motor cortex and trunk muscles during isometric contraction. Author(s): Murayama N, Lin YY, Salenius S, Hari R. Source: Neuroimage. 2001 November; 14(5): 1206-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11697952
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Outcomes after trans-tibial amputation: the relationship between quiet stance ability, strength of hip abductor muscles and gait. Author(s): Nadollek H, Brauer S, Isles R. Source: Physiotherapy Research International : the Journal for Researchers and Clinicians in Physical Therapy. 2002; 7(4): 203-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12528576
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Overexpression of neural cell adhesion molecule (NCAM) antigens on intestinal smooth muscles in hypoganglionosis: is hypoganglionosis a disorder of the neuromuscular junction? Author(s): Kobayashi H, Li Z, Yamataka A, Lane GJ, Miyano T. Source: Pediatric Surgery International. 2003 May; 19(3): 190-3. Epub 2003 March 29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12811479
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Overexpression of peroxisome proliferator-activated receptor gamma coactivator1alpha down-regulates GLUT4 mRNA in skeletal muscles. Author(s): Miura S, Kai Y, Ono M, Ezaki O. Source: The Journal of Biological Chemistry. 2003 August 15; 278(33): 31385-90. Epub 2003 May 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12777397
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Oxygen dynamics at paraspinal muscles during exertion using near-infrared spectroscopy in patients with degenerative lumbar scoliosis. Author(s): Miyake M, Harada Y, Senda M, Oda K, Inoue H. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2003; 8(2): 187-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12665955
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Participation of the deltoid (anterior portion) and pectoralis major (clavicular portion) muscles in different modalities of supine and frontal elevation exercises with different grips. Author(s): Ferreira MI, Bull ML, Vitti M. Source: Electromyogr Clin Neurophysiol. 2003 April-May; 43(3): 131-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12712801
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Pharmacologic denervation of frown muscles enhances baseline expression of happiness and decreases baseline expression of anger, sadness, and fear. Author(s): Heckmann M, Teichmann B, Schroder U, Sprengelmeyer R, CeballosBaumann AO. Source: Journal of the American Academy of Dermatology. 2003 August; 49(2): 213-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12894067
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Pharmacological techniques for the in vitro study of intestinal smooth muscles. Author(s): Daniel EE, Kwan CY, Janssen L. Source: Journal of Pharmacological and Toxicological Methods. 2001 March-April; 45(2): 141-58. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11687381
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Polyarteritis nodosa limited to calf muscles: a case report and review of the literature. Author(s): Nakamura T, Tomoda K, Yamamura Y, Tsukano M, Honda I, Iyama K. Source: Clinical Rheumatology. 2003 May; 22(2): 149-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740683
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Poor results after recession of both medial rectus muscles in unilateral small-angle Duane's syndrome, type I. Author(s): Greenberg MF, Pollard ZF. Source: J Aapos. 2003 April; 7(2): 142-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12736629
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Potential of phosphorus nuclear magnetic resonance spectroscopy in studies of the energy metabolism of skeletal muscles. Author(s): Ternovoi SK, Veselova TN, Sinitsin VE. Source: Neuroscience and Behavioral Physiology. 2003 September; 33(7): 723-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14552542
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Precision of a needle localization technic in the lumbosacral multifidus muscles for segmental specific needle electromyographic study: a cadaveric study. Author(s): Chinsethagij K, Wongphaet P, Su-archawaratana S, Dangprasert T. Source: J Med Assoc Thai. 2003 August; 86(8): 722-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12948270
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Principles of force gradation in skeletal muscles. Author(s): Kernell D. Source: Neural Plast. 2003; 10(1-2): 69-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14640309
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Provision of tricuspid valve leaflets by septal papillary muscles in the right ventricle of human and other mammal hearts. Author(s): Jezyk D, Jerzemowski J, Grzybiak M. Source: Folia Morphol (Warsz). 2003; 62(3): 309-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14507075
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Pulsatile control of the human masticatory muscles. Author(s): Jaberzadeh S, Brodin P, Flavel SC, O'Dwyer NJ, Nordstrom MA, Miles TS. Source: The Journal of Physiology. 2003 March 1; 547(Pt 2): 613-20. Epub 2003 January 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12562913
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Quadriceps concentric and eccentric exercise 2: differences in muscle strength, fatigue and EMG activity in eccentrically-exercised sore and non-sore muscles. Author(s): Hamlin MJ, Quigley BM. Source: J Sci Med Sport. 2001 March; 4(1): 104-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11339487
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Quadriceps muscles vastus medialis obliques, rectus femoris and vastus lateralis compared via electromyogram bicoherence analysis. Author(s): Simeoni RJ, Mills PM. Source: Australas Phys Eng Sci Med. 2003 September; 26(3): 125-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14626852
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Quantifying the magnitude of torque physiotherapists apply when stretching the hamstring muscles of people with spinal cord injury. Author(s): Harvey LA, McQuade L, Hawthorne S, Byak A. Source: Archives of Physical Medicine and Rehabilitation. 2003 July; 84(7): 1072-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12881837
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Quantitative assessment of myositis in thigh muscles using magnetic resonance imaging. Author(s): Bartlett ML, Ginn L, Beitz L, Villalba ML, Plotz P, Bacharach SL. Source: Magnetic Resonance Imaging. 1999 February; 17(2): 183-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10215472
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Quantitative electromyographic analysis of levator ani and external anal sphincter muscles of nulliparous women. Author(s): Weidner AC, Sanders DB, Nandedkar SD, Bump RC. Source: American Journal of Obstetrics and Gynecology. 2000 November; 183(5): 124956. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11084574
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Quantitative EMG analysis to investigate synergistic coactivation of ankle and knee muscles during isokinetic ankle movement. Part 1: time amplitude analysis. Author(s): Hwang IS, Abraham LD. Source: Journal of Electromyography and Kinesiology : Official Journal of the International Society of Electrophysiological Kinesiology. 2001 October; 11(5): 319-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11595551
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Quantitative EMG analysis to investigate synergistic coactivation of ankle and knee muscles during isokinetic ankle movement. Part 2: time frequency analysis. Author(s): Hwang IS, Abraham LD. Source: Journal of Electromyography and Kinesiology : Official Journal of the International Society of Electrophysiological Kinesiology. 2001 October; 11(5): 327-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11595552
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Quantitative features of the stretch response of extrinsic finger muscles in hemiparetic stroke. Author(s): Kamper DG, Rymer WZ. Source: Muscle & Nerve. 2000 June; 23(6): 954-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10842274
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Quantitative study of muscle spindles in suboccipital muscles of human foetuses. Author(s): Kulkarni V, Chandy MJ, Babu KS. Source: Neurology India. 2001 December; 49(4): 355-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11799407
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Quantitative ultrasonography of skeletal muscles in children: normal values. Author(s): Scholten RR, Pillen S, Verrips A, Zwarts MJ. Source: Muscle & Nerve. 2003 June; 27(6): 693-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766980
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Reduced jaw opening from paradoxical activity of mandibular elevator muscles treated with botulinum toxin. Author(s): Bakke M, Werdelin LM, Dalager T, Fuglsang-Frederiksen A, Prytz S, Moller E. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2003 November; 10(6): 695-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14641515
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Reflex and non-reflex elements of hypertonia in triceps surae muscles following acquired brain injury: implications for rehabilitation. Author(s): Singer B, Dunne J, Allison G. Source: Disability and Rehabilitation. 2001 November 20; 23(17): 749-57. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11762877
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Reflex inhibition of human inspiratory muscles in response to contralateral phrenic nerve stimulation. Author(s): Butler JE, McKenzie DK, Gandevia SC. Source: Respiratory Physiology & Neurobiology. 2003 October 16; 138(1): 87-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14519380
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Rehabilitation of pelvic floor muscles utilizing trunk stabilization. Author(s): Sapsford R. Source: Manual Therapy. 2004 February; 9(1): 3-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14723856
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Relative activity of abdominal muscles during commonly prescribed strengthening exercises. Author(s): Willett GM, Hyde JE, Uhrlaub MB, Wendel CL, Karst GM. Source: Journal of Strength and Conditioning Research / National Strength & Conditioning Association. 2001 November; 15(4): 480-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11726260
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Repeatability of maximal voluntary force and of surface EMG variables during voluntary isometric contraction of quadriceps muscles in healthy subjects. Author(s): Rainoldi A, Bullock-Saxton JE, Cavarretta F, Hogan N. Source: Journal of Electromyography and Kinesiology : Official Journal of the International Society of Electrophysiological Kinesiology. 2001 December; 11(6): 425-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11738955
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Re-recession of the medial rectus muscles in patients with recurrent esotropia. Author(s): Felius J, Stager DR Jr, Beauchamp GR, Stager DR. Source: J Aapos. 2001 December; 5(6): 381-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11753260
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Respiratory muscles in chronic obstructive pulmonary disease and asthma. Author(s): Barbarito N, Ceriana P, Nava S. Source: Minerva Anestesiol. 2001 September; 67(9): 653-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11731756
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Respiratory muscles in chronic obstructive pulmonary disease. Author(s): Fitting JW. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2001 August 25; 131(33-34): 483-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11683076
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Robin Hood for the lungs? A respiratory metaboreflex that “steals” blood flow from locomotor muscles. Author(s): Seals DR. Source: The Journal of Physiology. 2001 November 15; 537(Pt 1): 2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11711555
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Safety of a combined strength and endurance training using neuromuscular electrical stimulation of thigh muscles in patients with heart failure and bipolar sensing cardiac pacemakers. Author(s): Crevenna R, Mayr W, Keilani M, Pleiner J, Nuhr M, Quittan M, Pacher R, Fialka-Moser V, Wolzt M. Source: Wiener Klinische Wochenschrift. 2003 October 31; 115(19-20): 710-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14650946
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Scaling of peak moment arms of elbow muscles with upper extremity bone dimensions. Author(s): Murray WM, Buchanan TS, Delp SL. Source: Journal of Biomechanics. 2002 January; 35(1): 19-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11747879
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Selective blocks of the motor nerve branches to the soleus and tibialis posterior muscles in the management of the spastic equinovarus foot. Author(s): Deltombe T, De Wispelaere JF, Gustin T, Jamart J, Hanson P. Source: Archives of Physical Medicine and Rehabilitation. 2004 January; 85(1): 54-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14970968
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Selective denervation and resection of cervical muscles in the treatment of spasmodic torticollis: long-term follow-up results in 207 cases. Author(s): Chen X, Ma A, Liang J, Ji S, Pei S. Source: Stereotactic and Functional Neurosurgery. 2000; 75(2-3): 96-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11740176
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Sensible manual muscle strength testing to evaluate and monitor strength of the intrinsic muscles of the hand: a commentary. Author(s): Brandsma JW, Schreuders TA. Source: J Hand Ther. 2001 October-December; 14(4): 273-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11762727
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Sex differences in the fatigability of arm muscles depends on absolute force during isometric contractions. Author(s): Hunter SK, Enoka RM. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2001 December; 91(6): 2686-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11717235
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Simultaneous determination of neuromuscular block at the larynx, diaphragm, adductor pollicis, orbicularis oculi and corrugator supercilii muscles. Author(s): Hemmerling TM, Schmidt J, Hanusa C, Wolf T, Schmitt H. Source: British Journal of Anaesthesia. 2000 December; 85(6): 856-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11732519
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Sleep-disordered breathing, control of breathing, respiratory muscles, pulmonary function testing in AJRCCM 2003. Author(s): Tobin MJ. Source: American Journal of Respiratory and Critical Care Medicine. 2004 January 15; 169(2): 254-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718239
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Sleep-disordered breathing, control of breathing, respiratory muscles, pulmonary function testing, nitric oxide, and bronchoscopy in AJRCCM 2000. Author(s): Tobin MJ. Source: American Journal of Respiratory and Critical Care Medicine. 2001 October 15; 164(8 Pt 1): 1362-75. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11704580
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Slipped and lost extraocular muscles. Author(s): Lenart TD, Lambert SR. Source: Ophthalmology Clinics of North America. 2001 September; 14(3): 433-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11705143
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The effect of foot wedging on electromyographic activity in the erector spinae and gluteus medius muscles during walking. Author(s): Bird AR, Bendrups AP, Payne CB. Source: Gait & Posture. 2003 October; 18(2): 81-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14654211
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The effects of various therapeutic measures on shoulder range of motion and crosssectional areas of rotator cuff muscles after baseball pitching. Author(s): Yanagisawa O, Miyanaga Y, Shiraki H, Shimojo H, Mukai N, Niitsu M, Itai Y. Source: The Journal of Sports Medicine and Physical Fitness. 2003 September; 43(3): 35666. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14625518
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The fundamental thumb-tip force vectors produced by the muscles of the thumb. Author(s): Pearlman JL, Roach SS, Valero-Cuevas FJ. Source: Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society. 2004 March; 22(2): 306-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15013089
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The responses of leg and trunk muscles to sudden unloading of the hands: implications for balance and spine stability. Author(s): Brown SH, Haumann ML, Potvin JR. Source: Clinical Biomechanics (Bristol, Avon). 2003 November; 18(9): 812-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14527807
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The role of selected extrinsic foot muscles during running. Author(s): O'Connor KM, Hamill J. Source: Clinical Biomechanics (Bristol, Avon). 2004 January; 19(1): 71-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14659933
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The validity and reliability of surface EMG to assess the neuromuscular response of the abdominal muscles to rapid limb movement. Author(s): Marshall P, Murphy B. Source: Journal of Electromyography and Kinesiology : Official Journal of the International Society of Electrophysiological Kinesiology. 2003 October; 13(5): 477-89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12932422
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Three silent periods in the orbiculari oculi muscles of man: normal findings and some clinical vignettes. Author(s): Leon-Sarmiento FE, Arimura K, Osame M. Source: Electromyogr Clin Neurophysiol. 2001 October-November; 41(7): 393-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11721294
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Transient elastography in anisotropic medium: application to the measurement of slow and fast shear wave speeds in muscles. Author(s): Gennisson JL, Catheline S, Chaffai S, Fink M. Source: The Journal of the Acoustical Society of America. 2003 July; 114(1): 536-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12880065
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Treatment of osteitis pubis via the pelvic muscles. Author(s): McCarthy A, Vicenzino B. Source: Manual Therapy. 2003 November; 8(4): 257-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14559050
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Trunk muscles in persons with hemiparetic stroke evaluated with computed tomography. Author(s): Tsuji T, Liu M, Hase K, Masakado Y, Chino N. Source: Journal of Rehabilitation Medicine : Official Journal of the Uems European Board of Physical and Rehabilitation Medicine. 2003 July; 35(4): 184-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12892245
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Ubiquitin conjugation by the N-end rule pathway and mRNAs for its components increase in muscles of diabetic rats. Author(s): Lecker SH, Solomon V, Price SR, Kwon YT, Mitch WE, Goldberg AL. Source: The Journal of Clinical Investigation. 1999 November; 104(10): 1411-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10562303
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Ultrasound measurement of the horizontal external eye muscles in patients with thyroid disease. Is orbital involvement associated with thyroid autoantibodies? Author(s): Zimmermann-Belsing T, Feldt-Rasmussen U, Fledelius H. Source: Eur J Ophthalmol. 2002 September-October; 12(5): 351-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12474915
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Ultrasound of muscles. Author(s): Peetrons P. Source: European Radiology. 2002 January; 12(1): 35-43. Epub 2001 October 19. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11868072
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Ultrastructural changes in paravertebral muscles associated with degenerative spondylolisthesis. Author(s): Ramsbacher J, Theallier-Janko A, Stoltenburg-Didinger G, Brock M. Source: Spine. 2001 October 15; 26(20): 2180-4; Discussion 2185. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11598503
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Unilateral fibroadipose degeneration of the masticatory muscles. Author(s): Pomatto E, Castellano S, Bianchi SD. Source: Dento Maxillo Facial Radiology. 2001 November; 30(6): 346-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11641735
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Upper airway muscles awake and asleep. Author(s): Series F. Source: Sleep Medicine Reviews. 2002 June; 6(3): 229-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12531123
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Use of a cold cathode for percutaneous stimulation of human plantarflexor muscles. Author(s): Galea V. Source: European Journal of Applied Physiology. 2001 July; 85(1-2): 141-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11513307
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Use of P-31 magnetic resonance spectroscopy to detect metabolic abnormalities in muscles of patients with fibromyalgia. Author(s): Park JH, Phothimat P, Oates CT, Hernanz-Schulman M, Olsen NJ. Source: Arthritis and Rheumatism. 1998 March; 41(3): 406-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9506567
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Using morphologic parameters of extraocular muscles for diagnosis and follow-up of Graves' ophthalmopathy: diameters, areas, or volumes? Author(s): Szucs-Farkas Z, Toth J, Balazs E, Galuska L, Burman KD, Karanyi Z, Leovey A, Nagy EV. Source: Ajr. American Journal of Roentgenology. 2002 October; 179(4): 1005-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12239055
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Using weights in abdominal exercises: electromyography response of the Rectus Abdominis and Rectus Femoris muscles. Author(s): Moraes AC, Bankoff AD, Almeida TL, Simoes EC, Rodrigues CE, Okano AH. Source: Electromyogr Clin Neurophysiol. 2003 December; 43(8): 487-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14717029
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Variability in fibre properties in paralysed human quadriceps muscles and effects of training. Author(s): Gerrits HL, Hopman MT, Offringa C, Engelen BG, Sargeant AJ, Jones DA, Haan A. Source: Pflugers Archiv : European Journal of Physiology. 2003 March; 445(6): 734-40. Epub 2003 January 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12632195
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Variability in human quadriceps muscles: quantitative study and review of clinical literature. Author(s): Willan PL, Ransome JA, Mahon M. Source: Clinical Anatomy (New York, N.Y.). 2002 March; 15(2): 116-28. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11877790
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Vascular anatomy of the metacarpal bones and the interosseous muscles. Author(s): Uysal AC, Alagoz MS, Tuccar E, Sensoz O. Source: Annals of Plastic Surgery. 2003 July; 51(1): 63-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12838127
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Vertical dimension. Part 2: the changes in electrical activity of the cervical muscles upon varying the vertical dimension. Author(s): Miralles R, Dodds C, Manns A, Palazzi C, Jaramillo C, Quezada V, Cavada G. Source: Cranio. 2002 January; 20(1): 39-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11831343
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Vertical visual disparity and the human oblique muscles. Author(s): Brodsky MC. Source: Binocul Vis Strabismus Q. 2001; 16(4): 251-2. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11720588
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Vestibular actions on back and lower limb muscles during postural tasks in man. Author(s): Ali AS, Rowen KA, Iles JF. Source: The Journal of Physiology. 2003 January 15; 546(Pt 2): 615-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12527747
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Visual performance after congenital nystagmus surgery using extended hang back recession of the four horizontal rectus muscles. Author(s): Alio JL, Chipont E, Mulet E, De La Hoz F. Source: Eur J Ophthalmol. 2003 June; 13(5): 415-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12841563
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Volume and shape of masticatory muscles in patients with hemifacial microsomia. Author(s): Takashima M, Kitai N, Murakami S, Furukawa S, Kreiborg S, Takada K. Source: The Cleft Palate-Craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association. 2003 January; 40(1): 6-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12498600
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Volume changes in human masticatory muscles between jaw closing and opening. Author(s): Goto TK, Tokumori K, Nakamura Y, Yahagi M, Yuasa K, Okamura K, Kanda S. Source: Journal of Dental Research. 2002 June; 81(6): 428-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12097437
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Volume estimation of extensor muscles of the lower leg based on MR imaging. Author(s): Lund H, Christensen L, Savnik A, Boesen J, Danneskiold-Samsoe B, Bliddal H. Source: European Radiology. 2002 December; 12(12): 2982-7. Epub 2002 April 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12439580
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Wasting of the small hand muscles in upper and mid-cervical cord lesions. Author(s): Mathews JA. Source: Qjm : Monthly Journal of the Association of Physicians. 1998 October; 91(10): 691-700. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10024928
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Water exchange induced by unilateral exercise in active and inactive skeletal muscles. Author(s): Nygren AT, Kaijser L. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2002 November; 93(5): 1716-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12381759
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Weakness of respiratory and skeletal muscles after a short course of steroids in patients with acute lung rejection. Author(s): Nava S, Fracchia C, Callegari G, Ambrosino N, Barbarito N, Felicetti G. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2002 August; 20(2): 497-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12212986
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Weight bearing through flexed upper limbs in quadriplegics with paralyzed triceps brachii muscles. Author(s): Harvey LA, Crosbie J. Source: Spinal Cord : the Official Journal of the International Medical Society of Paraplegia. 1999 November; 37(11): 780-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10578249
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Weight loss of respiratory muscles during mechanical ventilation. Author(s): Hering R, Viehofer A, Berg A, Kreyer S, Zinserling J, Wrigge H, Putensen C. Source: Intensive Care Medicine. 2003 September; 29(9): 1612. Epub 2003 July 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12897988
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What might the brain know about muscles, limbs and spinal circuits? Author(s): Loeb GE. Source: Prog Brain Res. 1999; 123: 405-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10635735
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When active muscles lengthen: properties and consequences of eccentric contractions. Author(s): Lindstedt SL, LaStayo PC, Reich TE. Source: News in Physiological Sciences : an International Journal of Physiology Produced Jointly by the International Union of Physiological Sciences and the American Physiological Society. 2001 December; 16: 256-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11719600
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When the embryonic genome flexes its muscles. Author(s): Rupp RA, Singhal N, Veenstra GJ. Source: European Journal of Biochemistry / Febs. 2002 May; 269(9): 2294-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11985611
Academic Periodicals covering Muscles Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to muscles. 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, 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.”
Dissertations on Muscles 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 muscles. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “muscles” (or a synonym) in their titles. The following covers recent dissertations found when using this search procedure: •
A biomechanical model of the spine to predict trunk muscle forces: Optimizing the relationship between spinal stability and spinal loading by Brown, Stephen Hadley Morgan; MHK from University of Windsor (Canada), 2003, 142 pages http://wwwlib.umi.com/dissertations/fullcit/MQ82859
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A COMPARATIVE ELECTROMYOGRAPHIC ANALYSIS OF THREE ABDOMINAL MUSCLES (RECTUS ABDOMINIS, INTERNAL OBLIQUE AND EXTERNAL OBLIQUE), WHILE RUNNING AND PERFORMING SIT-UPS by SEVIER, BARBARA ANN, PHD from The University of Utah, 1969, 73 pages http://wwwlib.umi.com/dissertations/fullcit/6917644
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A comparison of the short-term and long-term recall of human muscles for college anatomy and physiology students with regard to cadaver-based versus computerbased instruction by Roulette, Sterling Ralph; EdD from University of La Verne, 1999, 93 pages http://wwwlib.umi.com/dissertations/fullcit/9960968
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A morphological analysis of neuromuscular topography in serratus anterior muscle of rats by Potluri, Srilatha; PhD from University of Idaho, 2003, 93 pages http://wwwlib.umi.com/dissertations/fullcit/3089436
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Alterations in fast and slow-twitch muscles of genetically dystrophic mice with special reference to parvalbumin by Johnson, Marjorie Isabelle; PhD from The University of British Columbia (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL41834
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An analysis of trunk kinematics in the sagittal plane and of the roles of erector spinae and rectus abdominis muscles in five types of locomotion by Cooper, Juliette E; PhD from The University of Manitoba (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL37439
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An electrogoniometric analysis of knee joint movement and electromyographic study of the peak activity of the thigh muscles during the stair cycle in normals and syme amputees by Tata, Jal A; PhD from The University of Manitoba (Canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK47247
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AN ELECTROMYOGRAPHIC - ELECTROGONOMETRIC COMPARISON: FREE WEIGHTS, UNIVERSAL APPARATUS, NAUTILUS APPARATUS, USING SELECTED MUSCLES OF THE UPPER AND LOWER EXTREMITIES. by PEDERSON, NICHOLAS LAWRENCE, EDD from Brigham Young University, 1979, 170 pages http://wwwlib.umi.com/dissertations/fullcit/8000104
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AN ELECTROMYOGRAPHIC ANALYSIS OF SELECTED MUSCLES PERFORMING THE SOCCER INSTEP KICK FOLLOWING LEVELS OF PHYSIOLOGICAL STRESS by TAUBE, FREDERICK WILLIAM, PHD from The University of Utah, 1972, 88 pages http://wwwlib.umi.com/dissertations/fullcit/7221644
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AN ELECTROMYOGRAPHIC ANALYSIS OF THE SARTORIUS, GRACILIS AND SEMITENDINOSUS MUSCLES DURING ISOMETRIC CONTRACTIONS AT SELECTED ANGLES OF THE KNEE JOINT FOLLOWING PES ANSERINUS TRANSPLANTATION. by CUERRIER, JEAN-PIERRE, PHD from University of Oregon, 1975, 118 pages http://wwwlib.umi.com/dissertations/fullcit/7605153
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AN ELECTROMYOGRAPHIC ANALYSIS OF THE TRICEPS BRACHII AND ANCONEUS MUSCLES DURING ISOMETRIC CONTRACTION AT VARIED POSITIONS by CURRIER, DEAN PAGE, PHD from University of Maryland College Park, 1971, 141 pages http://wwwlib.umi.com/dissertations/fullcit/7212835
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AN ELECTROMYOGRAPHIC EXAMINATION OF SELECTED MUSCLES IN THE RIGHT ARM DURING TROMBONE PERFORMANCE by LAMMERS, MARK EDWARD, PHD from University of Minnesota, 1983, 149 pages http://wwwlib.umi.com/dissertations/fullcit/8404186
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AN ELECTROMYOGRAPHIC INVESTIGATION OF MUSCLE ACTION POTENTIALS OF SELECTED MUSCLES CONTRACTING ISOMETRICALLY AT
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VARIOUS JOINT ANGLES by WILLIAMSON, CHARLES BENNETT, EDD from The University of North Carolina at Greensboro, 1972, 105 pages http://wwwlib.umi.com/dissertations/fullcit/7218369 •
AN ELECTROMYOGRAPHIC INVESTIGATION OF MUSCLE ACTION POTENTIALS OF SELECTED MUSCLES CONTRACTING ISOMETRICALLY AT VARIOUS JOINT ANGLES by WILLIAMSON, CHARLES BENNETT, EDD from The University of North Carolina at Greensboro, 1972, 105 pages http://wwwlib.umi.com/dissertations/fullcit/7218369
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AN ELECTROMYOGRAPHIC STUDY OF FOUR BI-ARTICULAR MUSCLES OF THE THIGH IN COLLEGE MALES DURING A STATIC CONTRACTION TASK by CHRISTENSEN, CARL SOREN, JR., PHD from University of Maryland College Park, 1967, 152 pages http://wwwlib.umi.com/dissertations/fullcit/6806522
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AN ELECTROMYOGRAPHIC STUDY OF SELECTED LATERAL MUSCLES DURING EXERCISE by HINZ, IDA A., PHD from The University of Iowa, 1967, 107 pages http://wwwlib.umi.com/dissertations/fullcit/6716806
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AN ELECTROMYOGRAPHIC STUDY OF SPECIFIC MUSCLES INVOLVED IN THE LACROSSE CRADLE by RICE, MARY AGNES, EDD from Temple University, 1969, 99 pages http://wwwlib.umi.com/dissertations/fullcit/7016680
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AN ELECTROMYOGRAPHIC STUDY OF THE RESPONSES OF SELECTED MUSCLES TO VARIOUS RHYTHMIC PATTERNS by STAHR, DIXIE LEE, PHD from The University of Iowa, 1967, 85 pages http://wwwlib.umi.com/dissertations/fullcit/6800983
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AN ELECTROMYOGRAPHICAL ANALYSIS OF SPECIFIC MUSCLES WHILE USED IN PERFORMING SELECTED ISOTONIC WEIGHT TRAINING ACTIVITIES by SANTOMIER, JAMES PHILIP, JR., PHD from The University of Utah, 1971, 77 pages http://wwwlib.umi.com/dissertations/fullcit/7202130
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An exploratory study of the functioning of selected masticatory muscles during clarinet playing as observed through electromyography by Campbell, Bonnie Heather; DM from Indiana University, 1999, 320 pages http://wwwlib.umi.com/dissertations/fullcit/9982776
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AN INVESTIGATION OF EXTRINSIC LARYNGEAL MUSCLE RESPONSES TO AUDITORY STIMULATION (ELECTROMYOGRAPHIY, MUSCLE RESPONSES, EARTRAINING) by WALLACE, JERRY DON, PHD from University of North Texas, 1985, 220 pages http://wwwlib.umi.com/dissertations/fullcit/8527396
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AN INVESTIGATION OF PEAK TORQUE VALUES OF THE KNEE FLEXOR AND EXTENSOR MUSCLES OF FEMALES by DIBREZZO, ROSALIE, PHD from Texas Woman's University, 1983, 176 pages http://wwwlib.umi.com/dissertations/fullcit/8401195
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AN INVESTIGATION OF SELECTED MUSCLE POTENTIAL ACTIVITY IN VIOLIN/VIOLA VIBRATO by WEBER, MATTHEW JOSEPH, PHD from University of North Texas, 1995, 388 pages http://wwwlib.umi.com/dissertations/fullcit/9543248
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An investigation of the stretch reflex in wrist flexor and extensor muscles of awake human subjects by O'Riain, Micheal D; PhD from University of Toronto (Canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK35096
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Axon content and central afferent projections of nerves supplying suboccipital muscles in the cat by Bakker, Debra Ann; PhD from Queen's University at Kingston (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK61574
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CALCIUM ANTAGONISTS: EFFECT ON SKELETAL MUSCLE FUNCTION AND WORKING CAPACITY IN NORMAL MALES by LEHNHARD, ROBERT ALLEN, PHD from The Ohio State University, 1984, 71 pages http://wwwlib.umi.com/dissertations/fullcit/8426433
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Caracterisation des proteines cytosoliques de haute affinite liant les androgenes et l'estradiol-17beta dans les muscles stries du rat (French text) by Dionne, France Thérèse; PhD from Universite Laval (Canada), 1979 http://wwwlib.umi.com/dissertations/fullcit/NK41856
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CELLULAR ADAPTATIONS IN HUMAN MUSCLE FOLLOWING TWO OPPOSING MODES OF TRAINING IN THE SAME INDIVIDUAL by JACKSON, CATHERINE G. RATZIN, PHD from University of Colorado at Boulder, 1982, 143 pages http://wwwlib.umi.com/dissertations/fullcit/8309851
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Cellular and molecular mechanisms involved in skeletal muscle adaptation by Mitchell, Patrick Oliver James; PhD from Emory University, 2003, 194 pages http://wwwlib.umi.com/dissertations/fullcit/3080344
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CHANGES IN LEG STRENGTH AND MUSCLE FIBER HYPERTROPHY FOLLOWING ISOKINETIC STRENGTH TRAINING by CARR, LARRY STEVEN, PHD from Brigham Young University, 1980, 122 pages http://wwwlib.umi.com/dissertations/fullcit/8027371
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Changes in the constituents of four bovine muscles during growth by Peschiera, Jaime Alfonso; ADVDEG from University of Alberta (Canada), 1969 http://wwwlib.umi.com/dissertations/fullcit/NK05129
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CHANGES THAT OCCUR IN THE STRENGTH AND WORK CAPACITY OF THE MUSCLES THAT FLEX THE FOREARM FOLLOWING A PERIOD OF ISOKINETIC EXERCISE by EVANS, ANTHONY JOHN, PHD from University of Oregon, 1973, 75 pages http://wwwlib.umi.com/dissertations/fullcit/7320202
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Computational modeling of skeletal muscle glycogenolysis dynamics by Lambeth, Melissa Jo; PhD from University of Washington, 2003, 120 pages http://wwwlib.umi.com/dissertations/fullcit/3091024
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CONTRIBUTIONS OF ARM AND TRUNK MUSCLES TO POSTURE CONTROL (REFLEX, AUTOMATIC RESPONSES, SYNERGIES) by MCNAUGHTON, LARS ROBERT, PHD from University of Oregon, 1985, 113 pages http://wwwlib.umi.com/dissertations/fullcit/8514804
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Control and organization of cat intercostal muscles during respiration by Greer, John James; PhD from University of Alberta (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL45657
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Crystallographic studies of two regulatory muscle proteins: Structures of cardiac troponin C and the C-terminal region of striated muscle tropomyosin by Li, Yu; PhD from Brandeis University, 2003, 122 pages http://wwwlib.umi.com/dissertations/fullcit/3073878
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Effect of load placement on select trunk, shoulder, and leg muscle activity using two backpack designs by Howells, Justin John; MS from Utah State University, 2003, 37 pages http://wwwlib.umi.com/dissertations/fullcit/1413326
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Effects of aging and exercise training on endothelium-dependent vasodilation of skeletal muscle arterioles by Spier, Scott Alan; PhD from Texas A&m University, 2003, 63 pages http://wwwlib.umi.com/dissertations/fullcit/3102508
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Effects of ankle bracing on ground reaction forces and myoelectrical activity of selected lower extremity muscles during inversion stress by Cordova, Mitchell L., PhD from The University of Toledo, 1997, 155 pages http://wwwlib.umi.com/dissertations/fullcit/9804282
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EFFECTS OF CONCENTRIC AND ECCENTRIC ISOKINETIC HEAVYRESISTANCE TRAINING ON QUADRICEPS MUSCLE STRENGTH, CROSSSECTIONAL AREA AND NEURAL ACTIVATION IN WOMEN (MUSCLE HYPERTROPHY, MAGNETIC RESONANCE IMAGING) by HIGBIE, ELIZABETH JOHNSON, PHD from University of Georgia, 1994, 110 pages http://wwwlib.umi.com/dissertations/fullcit/9504388
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Effects of myosin heavy chain isoform composition on muscle fiber ATPase activity, postmortem metabolism, and meat quality in porcine muscle by Bowker, Brian Christopher; PhD from Purdue University, 2003, 193 pages http://wwwlib.umi.com/dissertations/fullcit/3108323
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EFFECTS OF STATICALLY PERFORMED TOE TOUCH STRETCHES ON TORQUE PRODUCTION OF THE HAMSTRING AND QUADRICEPS MUSCLE GROUPS by THIGPEN, LYDIA KAY, PHD from Texas A&m University, 1988, 183 pages http://wwwlib.umi.com/dissertations/fullcit/8815930
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ELECTRICAL STIMULATION OF PAIRED MUSCLES AS A DIAGNOSTIC TEST OF HANDEDNESS by COLE, RICHARD MELVIN, PHD from Northwestern University, 1965, 115 pages http://wwwlib.umi.com/dissertations/fullcit/6602692
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Electromyographic analysis of the lumbar erector spinae muscles: Influence of position, a history of low back pain, gender and muscle location on fatigue and recovery by Fall, Michael Paul; PhD from The University of Connecticut, 2001, 104 pages http://wwwlib.umi.com/dissertations/fullcit/3030666
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ELECTROMYOGRAPHIC POTENTIALS OF SELECTED FACIAL MUSCLES AND LABIAL MOUTHPIECE PRESSURE MEASUREMENTS IN THE EMBOUCHURE OF TRUMPET PLAYERS by WHITE, ELMER RUSSELL, EDD from Columbia University, 1972, 158 pages http://wwwlib.umi.com/dissertations/fullcit/7302634
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ELECTROMYOGRAPHIC RESPONSE OF PERONEAL MUSCLES IN SURGICAL AND NONSURGICAL INJURED ANKLES DURING SUDDEN INVERSION (ANKLE SPRAIN) by JOHNSON, MARY BLACK, PHD from The University of Utah, 1990, 78 pages http://wwwlib.umi.com/dissertations/fullcit/9111548
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137
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ELECTROMYOGRAPHIC STUDY OF THE ACTIONS OF SELECTED MUSCLES USED IN THE FENCING LUNGE by DREES, DORIS ANN, PHD from The University of Iowa, 1968, 148 pages http://wwwlib.umi.com/dissertations/fullcit/6908726
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Electrophysiological studies of quadriceps muscle activation in healthy subjects and subjects with anterior cruciate ligament injury or reconstruction by Alrowayeh, Hesham Nasser; PhD from Texas Woman's University, 2003, 155 pages http://wwwlib.umi.com/dissertations/fullcit/3103320
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Electrophysiological studies of quadriceps muscle activation in healthy subjects and subjects with anterior cruciate ligament injury or reconstruction by Alrowayeh, Hesham Nasser; PhD from Texas Woman's University, 2003, 155 pages http://wwwlib.umi.com/dissertations/fullcit/3103320
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Etudes sur l'ADN mitochondrial au cours du developpement des sarcosomes dans les muscles thoraciques de Schistocerca gregaria (Orthoptere) by Tanguay, Robert; DSc from Universite Laval (Canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK14225
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Expiratory muscle strength training and detraining: Effects on speech and cough prediction by Baker, Susan Elizabeth; PhD from University of Florida, 2003, 117 pages http://wwwlib.umi.com/dissertations/fullcit/3105584
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Fetus to adult: The development and evolutionary significance of pedal muscle variation by Fisher, Rebecca Elizabeth; PhD from Yale University, 2002, 679 pages http://wwwlib.umi.com/dissertations/fullcit/3068278
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Function of muscles about the hip during normal level walking: an electromyographic and biomechanical study by Greenlaw, Robert King; PhD from Queen's University at Kingston (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK15010
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Genotypic and phenotypic analysis of muscles from dystrophic--normal mouse chimeras by Peterson, Alan Clarke; PhD from The University of British Columbia (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK15144
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High force contractions as a countermeasure to muscle atrophy by Wenke, Joseph Carl; PhD from Texas A&m University, 2003, 92 pages http://wwwlib.umi.com/dissertations/fullcit/3088194
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Investigation of fibre atrophy, substrate availability and anaerobic capacity in fast and slow twitch muscles from malnourished rats by Nishio, Mary Lou; PhD from University of Toronto (Canada), 1989 http://wwwlib.umi.com/dissertations/fullcit/NL54555
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ISOMETRIC MUSCLE FORCE PRODUCTION CHARACTERISTICS AS A FUNCTION OF CHRONOLOGICAL AGE IN NORMAL, HEALTHY MEN, AGE 20 TO 80 YEARS (TWENTY-YEAR-OLDS, EIGHTY-YEAR-OLDS) by BEMBEN, MICHAEL GEORGE, PHD from University of Illinois at Urbana-champaign, 1989, 480 pages http://wwwlib.umi.com/dissertations/fullcit/9010803
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Leg spring model related to muscle activation, force, and kinematic patterns during endurance running to voluntary exhaustion by Dutto, Darren John; PhD from Oregon State University, 1999, 181 pages http://wwwlib.umi.com/dissertations/fullcit/9954855
138
Muscles
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LOAD SHARING IN THE FOREARM MUSCLES PRIOR TO IMPACT IN TENNIS BACKHAND STROKES. by MCLAUGHLIN, THOMAS MICHAEL, PHD from University of Illinois at Urbana-champaign, 1978, 236 pages http://wwwlib.umi.com/dissertations/fullcit/7821012
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Magnetic resonance imaging of skeletal muscle geometry and motion after surgery by Asakawa, Deanna Schmidt; PhD from Stanford University, 2003, 103 pages http://wwwlib.umi.com/dissertations/fullcit/3085253
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Making muscles: Representations of women's muscles in the 1970s by Holland, Mary Cecily; PhD from The University of Iowa, 2002, 220 pages http://wwwlib.umi.com/dissertations/fullcit/3050809
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MASTICATORY MUSCLE ARCHITECTURE AND BONE MORPHOLOGY IN PRIMATES (MACACA) by ANTON, SUSAN CAROL, PHD from University of California, Berkeley, 1994, 334 pages http://wwwlib.umi.com/dissertations/fullcit/9529205
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Mechanical properties of the extraocular muscles of the cat by Vilis, Tutis; PhD from Mcgill University (Canada), 1973 http://wwwlib.umi.com/dissertations/fullcit/NK18405
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Molecular genetic analysis of Drosophila melanogaster paramyosin in muscle development, structure, and function by Liu, Hongjun; PhD from University of California, San Diego and San Diego State University, 2003, 128 pages http://wwwlib.umi.com/dissertations/fullcit/3091354
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Muscle tenderness in women: Pressure pain thresholds in the trapezius and deltoid muscles at rest, after muscle exertion and after noxious stimulation by Persson, Ann Larsdotter; PhD from Lunds Universitet (Sweden), 2003 http://wwwlib.umi.com/dissertations/fullcit/f400657
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Muscle tenderness in women: Pressure pain thresholds in the trapezius and deltoid muscles at rest, after muscle exertion and after noxious stimulation by Persson, Ann Larsdotter; PhD from Lunds Universitet (Sweden), 2003 http://wwwlib.umi.com/dissertations/fullcit/f400657
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Muscle tenderness in women: Pressure pain thresholds in the trapezius and deltoid muscles at rest, after muscle exertion and after noxious stimulation by Persson, Ann Larsdotter; PhD from Lunds Universitet (Sweden), 2003 http://wwwlib.umi.com/dissertations/fullcit/f400657
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MYOFIBRILLAR ATPASE ACTIVITY IN RAT HEART AND SKELETAL MUSCLE FOLLOWING EXERCISE by SCHAFFER, WILLIAM FREDERICK, PHD from Washington State University, 1984, 61 pages http://wwwlib.umi.com/dissertations/fullcit/8413902
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Myosin heavy chain in mice and men: Gene regulation, protein expression, and muscle plasticity by Harrison, Brooke Chance; PhD from University of Colorado at Boulder, 2003, 325 pages http://wwwlib.umi.com/dissertations/fullcit/3087547
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Nonlinear analysis of muscle fatigue in low back pain patients before and after exercise therapy by Liu, Yiwei; MS from Loyola University of Chicago, 2003, 56 pages http://wwwlib.umi.com/dissertations/fullcit/1413570
Studies
139
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Nonlinear analysis of muscle fatigue in low back pain patients before and after exercise therapy by Liu, Yiwei; MS from Loyola University of Chicago, 2003, 56 pages http://wwwlib.umi.com/dissertations/fullcit/1413570
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Partial or complete loss of GLUT4: Close-up on skeletal muscle glucose transport by Gorovits, Naira; PhD from Yeshiva University, 2003, 193 pages http://wwwlib.umi.com/dissertations/fullcit/3075582
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Prediction of dynamic muscle forces across the elbow using three-dimensional vector modelling by Weiss-Bundy, Karyn Melita Anne; MSc from The University of Manitoba (Canada), 2003, 211 pages http://wwwlib.umi.com/dissertations/fullcit/MQ80082
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Pressure-lung volume relationship and electromyography of inspiratory muscles in man during partial curarization by Buick, Fred; PhD from Mcmaster University (Canada), 1985 http://wwwlib.umi.com/dissertations/fullcit/NK66170
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Prosthetic voice controlled by muscle electromyographic signals by Goldstein, Ehab Alfred; PhD from Harvard University, 2003, 184 pages http://wwwlib.umi.com/dissertations/fullcit/3106637
