Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The number of putative calcium channels in cardiac muscle from young adult hamsters (60 days old) was compared in normal (F1B) hamsters and two different mutant strains (CHF 146 and Bio 14.6) which express cardiomyopathy and muscular dystrophy. Equilibrium binding assays of high affinity sites for [3H]-nitrendipine in ventricular homogenate preparations showed that the maximum number of [3H]-nitrendipine binding sites (Bmax), which corresponds to the number of putative calcium channels, was not significantly different in normal and cardiomyopathic hearts: 79(SEM 9), 64(14) and 69(10) fmol.mg-1 protein in 4-6 hearts from F1B, Bio 14.6 and CHF 146 hamster strains, respectively. Similar results were obtained with binding data after partial purification of the preparation. These data are in agreement with earlier studies comparing two normal strains (CHF 148 and random bred Syrian hamsters) with cardiomyopathic (CHF 146) hamsters, and conflict with other studies comparing normal and cardiomyopathic hamsters. Comparisons with the conflicting data suggest (a) that change in the number of high affinity [3H]-nitrendipine binding sites is not responsible for calcium overload and cell necrosis in cardiomyopathy, and (b) that increased numbers of low affinity [3H]-nitrendipine binding sites may emerge in cardiomyopathic hearts.
Cardiovasc Res 1988 Nov
PMID:[3H]-nitrendipine binding sites in normal and cardiomyopathic hamsters: absence of a selective increase in putative calcium channels in cardiomyopathic hearts. 285 22

The myopathic Syrian hamster is a genetic model of congestive heart failure that exhibits focal myocytolytic necrosis in both heart and skeletal muscle. Previous investigations of microvascular morphology in heart and skeletal muscle have shown severe arteriolar constrictions without fixed anatomical vessel lesions. This study tested the hypothesis that these constrictions indicate a hyperreactivity of the myopathic microvasculature in vivo and that the reactivity corresponds to the developmental course of myocyte pathology. The microcirculation of the cremaster muscle was studied in eight myopathic and six control hamsters in the active stage of necrosis (39-81 days of age) and five myopathic and six control hamsters in the later stage of muscle healing (150-213 days of age). The internal diameter of second order arterioles was measured during topically applied noradrenaline. The myopathic arterioles of the younger group constricted at significantly lower concentrations of noradrenaline (p less than 0.01) and constricted to 35-50% of their resting internal diameter over a narrower range of noradrenaline (p less than 0.01). This indicated both a reduced threshold to noradrenaline and an enhanced response to the agonist. Active myocytolytic necrosis was found in the contralateral cremaster muscle of each myopathic hamster. The older myopathic and control hamsters showed no significant differences in arteriolar responsiveness to applied noradrenaline and no active necrosis. These results indicate a relation between a hyperreactive microvasculature and active necrosis and a normal reacting microvasculature and diminished necrosis in the two phases of the disease. Thus a general correspondence between vascular responsiveness and myocyte pathology exists in this model of heart failure and muscular dystrophy.
Cardiovasc Res 1987 Nov
PMID:Microvascular reactivity of the myopathic Syrian hamster cremaster muscle. 337 Jun 64

We performed a sleeve lobectomy on a patient with squamous-cell carcinoma of the lung who had poor pulmonary function and could not move his extremities or trunk, due to a muscular dystrophy. Lung cancer in a highly disabled patient can be resected even with a bronchoplastic procedure.
Thorac Cardiovasc Surg 1996 Oct
PMID:Sleeve lobectomy for lung carcinoma in a patient with muscular dystrophy. 894 57

p94, a muscle-specific member of the calpain family, also called calpain3 (CAPN3), has been identified as the gene product responsible for limb-girdle muscular dystrophy type 2A (LGMD2A). To elucidate the molecular mechanism of LGMD2A, the effects of missense point mutations found in LGMD2A on the unique properties of p94 were studied. All of the mutants examined to date lose their proteolytic activity against fodrin, a cytoskeletal protein, strongly suggesting that of the specific properties of p94, the loss of protease activity is the prime cause of LGMD2A. Studies of LGMD2A and p94 suggest a novel molecular mechanism for muscular dystrophy, showing that a combined pathologic and biochemical approach is effective.
Trends Cardiovasc Med 1999 Jul
PMID:New aspect of the research on limb-girdle muscular dystrophy 2A: a molecular biologic and biochemical approach to pathology. 1063 25

The mouse has become the principal animal model for studying biologic processes in mammals. Major advances in transgene and gene targeting technology enabled manipulation of the mouse genome in a predictable fashion. Mutant mouse strains provide important insights into the molecular mechanisms underlying normal and disordered cardiac conduction and sudden cardiac death. A variety of mouse strains harboring gene mutations leading to inherited developmental disorders have been designed. Structural protein abnormalities, connexin protein defects, and ion channelopathies associated with human clinical phenotypes, including congenital heart disease, cardiomyopathies, long QT syndrome, and muscular dystrophy, have been engineered into the mouse genome, creating models of human electrophysiologic disease. Functional analyses of the underlying molecular mechanisms of resultant phenotypes require appropriate and sophisticated experimental methodology. In this review, genetic mouse models pertinent to human arrhythmogenic disorders and their application to present-day ex vivo and in vivo murine electrophysiologic technology at the whole organ and animal levels are discussed.
J Cardiovasc Electrophysiol 2000 Mar
PMID:Cardiac electrophysiology in genetically engineered mice. 1074 60

The calpains form a growing family of structurally related intracellular multidomain cysteine proteinases containing a papain-related catalytic domain, whose activity depends on calcium. The calpains are believed to play important roles in cytoskeletal remodeling processes, cell differentiation, apoptosis and signal transduction, but are also implicated in muscular dystrophy, cardiac and cerebral ischemia, platelet aggregation, restenosis, neurodegenerative diseases, rheumatoid arthritis and cataract formation. The best characterized calpains, the ubiquitously expressed mu- and m-calpains, are heterodimers consisting of a common 30-kDa small and a variable 80-kDa subunit. The recently determined crystal structures of human and rat m-calpain crystallized in the absence of calcium essentially explain the inactivity of the apoform by catalytic domain disruption, indicate several sites where calcium could bind causing reformation of a papain-like catalytic domain, and additionally reveal modes by which phospholipid membranes could reduce the calcium requirement. Current evidence points to a cooperative interaction of several sites, which, upon calcium binding, trigger the reformation of a papain-similar catalytic domain.
Trends Cardiovasc Med 2001 Aug
PMID:The structure of calcium-free human m-calpain: implications for calcium activation and function. 1167 52

In the past decade, advances in molecular genetics have shown that many familial neuromuscular and cardiovascular diseases share a common pathophysiology. They are caused by inherited mutations in the cellular cytoskeleton of cardiac and skeletal muscle cells. The clinical manifestation of cardiac disease in neuromuscular disorders is common and their management should include both periodic cardiac assessment and appropriate symptomatic and definitive therapy. Dilated cardiomyopathy is a common complication of neuromuscular diseases. Cardiac function may decline progressively as part of the natural history of the disease, but current medical therapy, including angiotensin-converting enzyme inhibitors, beta-blockers, and diuretics, can be used to alleviate symptoms of left ventricular dysfunction. Conduction disturbances may be an important cause of mortality, especially in patients with Emery Dreifuss muscular dystrophy, Kearns-Sayre syndrome, and myotonic dystrophy, and thus pacemaker implantation can be life-saving. Rhythm disturbances, such as atrial fibrillation and ventricular tachyarrhythmias, have been reported in patients with neuromuscular diseases. Treatment is based on preventing sudden death and embolic phenomena and cardioverting or controlling atrial fibrillation. In these patients, problems may arise with anticoagulation and antiarrhythmic therapy due to the inherent locomotor instability associated with the disease, and the presence of concomitant atrioventricular disease. Although uncommon, hypertrophic cardiomyopathy may be a feature of some neuromuscular disorders. Patients should undergo regular risk stratification for sudden cardiac death and symptoms such as heart failure can be treated with medical therapy.
Curr Treat Options Cardiovasc Med 2002 Apr
PMID:Cardiovascular Complications of Neuromuscular Disorders. 1185 79

Intermediate filament (IF) proteins and the dystrophin-associated protein complex (DPC) play important roles in cardiac and skeletal muscle. Both systems are mutated in several different forms of inherited muscular dystrophy and cardiomyopathy. Recently two articles have been published that propose a physical link between the DPC and the IF network in muscle. Two novel IF proteins, syncoilin and desmuslin, have been identified as binding partners for the dystrophin-associated protein, alpha-dystrobrevin, in muscle. These novel interactions suggest that alpha-dystrobrevin may tether the IF protein network to the DPC. Mice lacking alpha-dystrobrevin develop muscular dystrophy without perturbing the assembly of the DPC at the muscle membrane, suggesting the involvement of other non-DPC proteins in the disease. The interaction between the DPC and the IF network may be disrupted in patients with Duchenne muscular dystrophy and in mice lacking alpha-dystrobrevin.
Trends Cardiovasc Med 2002 Jul
PMID:Intermediate filaments and the function of the dystrophin-protein complex. 1216 Oct 77

Alterations in mitochondrial distribution and morphology are associated with normal cellular processes such as cell division and differentiation, as well as a variety of pathological conditions, including muscular dystrophy and cardiomyopathy. These observations have illuminated the necessity for a cellular machinery that mediates mitochondrial behavior and function. One important candidate member of this machinery is the cytoskeleton, all three members of which seem to associate with mitochondria. The role and significance of such association with the intermediate filament (IF) cytoskeleton in muscle was until recently completely unknown. Recent studies with desmin-deficient mice revealed the importance of desmin IFs in mitochondrial behavior and function. This review summarizes recent findings that link desmin cytoskeleton to muscle mitochondrial distribution and function. In particular, hypotheses are presented on the potential mechanism by which desmin's absence from cardiac muscle leads to abnormal mitochondrial behavior and compromised function, potentially responsible for the development of dilated cardiomyopathy and heart failure in desmin-null mice.
Trends Cardiovasc Med 2002 Nov
PMID:Desmin cytoskeleton: a potential regulator of muscle mitochondrial behavior and function. 1253 20

Sarcoglycans are transmembrane proteins important in the maintenance of proper muscle function. Together, the sarcoglycans form a heteromeric complex that interacts with dystrophin, dystroglycan, and filamin C to form a mechanosignaling complex. Mutations in the genes encoding sarcoglycan can produce cardiomyopathy and muscular dystrophy. Studies of patients and animal models have emphasized the variability in penetrance and severity of cardiomyopathy. In animal models of sarcoglycan mutations, muscular dystrophy develops owing to loss of the sarcoglycan complex at the membrane of skeletal myocytes. Cardiomyopathy similarly develops with evidence of focal areas of degeneration and necrosis, as well as loss of sarcoglycan at the cardiomyocyte membrane. Vascular spasm has been noted as a feature of sarcoglycan-mediated cardiomyopathy. Recent evidence suggests that disruption of the smooth muscle sarcoglycan complex is not required for the development of vascular spasm and that vascular spasm arises from a vascular smooth muscle cell-extrinsic process.
Trends Cardiovasc Med 2003 Aug
PMID:Sarcoglycans in vascular smooth and striated muscle. 1292 20


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