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)

Dystrophia myotonica (Steinert's disease) is the most common hereditary disease of the neuromuscular system in adults. Its mode of inheritance is autosomal dominant. The gene responsible for its is located on chromosome 19 in the linkage domain of the loci for the apolipoproteins C2, C1 und E and of the creatine kinase of skeletal muscle (CKMM). Myotonic dystrophy is categorized in an adult and in a congenital form. In the adult form, the characteristic findings are muscular atrophy in certain regions of the body (face, neck and distally in the extremities) and myotonia. Cataract, intraocular hypotension, gonadal atrophy, conduction abnormalities in the heart and hearing deficiencies appear quite often in the course of the disease. In the congenital form, general muscle weekness (particularly pronounced in the face) is the leading finding, combined with retarded loco motor and mental development. A decisive criterion for the diagnosis of this form is the occurrence of myotonic dystrophy in the patient's mother. Electromyographic investigation is indicated when a suspicion of myotonic dystrophy cannot be ascertained on the basis of clinical and genetic findings. Myotonic runs in the EMG will then corroborate the suspicion. Recent electrophysiological investigations have indicated that at least three different types of channels for the passage of ions through the membrane of the skeletal muscle cells show abnormal behaviour, i.e. the channel for Cl-, Na+ and K+. These findings corroborate the hypothesis that the abnormality responsible for myotonic dystrophy is situated in the membrane systems. A pharmacological treatment of the muscular dystrophy has not yet been developed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Dystrophia myotonica (Steinert disease)--a frequently misdiagnosed disease]. 219 75

Changes in plasma electrolyte levels upon ischemic forearm exercise were studied in myotonic muscular dystrophy (MyD) patients, disease control groups, and healthy volunteers. Significant differences were observed in the pH and the concentrations of creatine kinase and Na+ before exercise between healthy volunteers and MyD patients. In comparison with healthy volunteers a lower pH and higher concentrations of both CK and Na+ were found in MyD patients. The concentrations of K+, inorganic phosphate, lactate, and ammonia increase upon exercise in all groups. The mean increase in plasma K+ for healthy volunteers amounted to 0.8 mM (= 23%). In MyD patients a significantly higher increase in plasma K+ was found [mean 2.2 mM (= 65%)]. No abnormal release of K+ from muscular tissue was found in the disease control groups. Data on the postexercise increase in the concentration of other muscular constituents such as creatine kinase, inorganic phosphate, or creatine exclude the possibility of a generally increased membrane permeability in MyD. The abnormally high increase of plasma K+ upon muscular exercise seems to be specific for MyD and may be related to the biochemical defect in this disease.
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PMID:Excessive plasma K+ increase after ischemic exercise in myotonic muscular dystrophy. 232 99

Variations in the content and translatability of the poly(A)+ RNA and mRNA molecules coding for myosin (M) were studied in the hind leg muscles of genetically dystrophic mice. The poly(A)+ RNA content of total skeletal muscle failed to increase normally during progression of the disease. M mRNA, isolated from dystrophic normally during progression of the disease. M mRNA, isolated from dystrophic murine muscle poly(A)+ RNA, was mostly found to be associated with the 26S RNA species. The translation of M mRNA in an in vitro heterologous wheat germ system was lower at 8 and 16 weeks in the dystrophic group as compared with the controls. Analysis of the translation products via sodium dodecyl sulfate-polyacrylamide gel electrophoresis, autoradiography, and densitometric autoradiographic tracing demonstrated the gradual disappearance of a protein band corresponding to M, the major component of skeletal muscle. cDNA was synthesized, using M mRNA that was isolated and purified from normal and dystrophic mouse muscle as a template. Total radioactivity was measured in some cDNA fractions produced from normal and dystrophic mouse muscle, while other fractions were utilized for separation and sizing of cDNA by disc gel electrophoresis. The cDNA from normal muscle was hybridized with M mRNA from normal and 16-week-old dystrophic mouse muscles. The cDNA probe, hybridization experiments, and studies involving the content and synthesis of M mRNA suggest that murine muscular dystrophy elicited a shorter species of mRNA or shorter sequences of the same species of mRNA coding for M. Not all poly(A)+ mRNA sequences coding for M, found in control mice, were present in their dystrophic counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemical changes in progressive muscular dystrophy. XIV. Skeletal muscle myosin mRNA translatability in dystrophic mice. 244 99

We studied selenium metabolism in patients with Duchenne muscular dystrophy and in contrast to previous reports found no significant abnormalities in these patients. Supplementation of muscular dystrophy patients and control subjects with sodium selenite (1 mg selenium/day) induced a variable rise in the activity of the selenium-dependent enzyme glutathione peroxidase in plasma and red cells, but no significant change in muscle glutathione peroxidase activities. There was no effect of selenium supplementation on disease activity in the patients with muscular dystrophy. Thiobarbituric acid-reacting substances (an index of free radical-mediated lipid peroxidation) were elevated in the muscle of patients with Duchenne muscular dystrophy in contrast to patients with other forms of muscular dystrophy and control subjects. This elevation was unaffected by selenium supplementation.
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PMID:Selenium metabolism and supplementation in patients with muscular dystrophy. 254 Apr 51

Skeletal muscles from healthy dogs and Labrador Retrievers with hereditary muscular dystrophy were examined morphologically and histochemically and were analyzed biochemically for Na+, K+, Ca2+, Mg2+, Zn2+, Cu2+, Cl-, total muscle water, and total neutral lipid content. Flame atomic absorption spectrophotometer was used for elemental quantitation of hydrochloric acid tissue extracts. Muscle samples from dystrophic dogs contained substantially increased concentrations of Na+, Ca2+, Zn2+, Cu2+, and Cl-, and a considerable reduction in the content of K+ and Mg2+ compared with samples from healthy dogs. Total muscle water and total fat content was higher in muscles from dystrophic dogs. Most muscle samples from dystrophic dogs had a type-2 fiber deficiency and an increase in number of fibers with internalized nuclei.
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PMID:Analysis of muscle elements, water, and total lipids from healthy dogs and Labrador retrievers with hereditary muscular dystrophy. 272 11

Skeletal muscles from normal dogs and labrador retrievers with a hereditary muscular dystrophy were examined morphologically and histochemically and were analysed for sodium (Na+), potassium (K+) and chloride (Cl-) ions and total muscle water. The partition of total muscle water and electrolytes between intracellular and extracellular phases was calculated on the basis of the chloride space method as the estimate of extracellular fluid volume. Muscle samples from dystrophic dogs contained significantly increased concentrations of Na+, Cl-, total muscle water, and a significant reduction in the level of K+ compared with normal values. There was a significant increase in the intracellular water and Na+ levels with a concomitant reduction of intracellular K+ content. Most dystrophic muscle samples had a pronounced type 2 fibre deficiency and a marked increase in numbers of fibres with internalised nuclei.
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PMID:Intracellular electrolytes and water analysis in dystrophic canine muscles. 277 3

In support of the widely held belief that membrane defects are present in the muscular dystrophies, alterations have been found in some transport-related enzymes of cells from affected donors. Cell membranes were isolated from cultured dermal fibroblasts of victims of myotonic muscular dystrophy, and of Duchenne's muscular dystrophy, and from cells of normal age- and sex-matched donors. Myotonic cells had an elevated Na+, K+ ATPase. gamma-Glutamyl transpeptidase was elevated in Duchenne cells. Among all cells' 5'nucleotide phosphatase exhibited a remarkably constant specific activity.
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PMID:Transport enzymes in the cell membranes of cultured fibroblasts; alterations in dystrophic cells. 286 29

Hypernatremia has occasionally been observed in patients with myotonic muscular dystrophy (MyD). To elucidate the possibility of osmoregulatory dysfunction, we investigated hypothalamo-posterior pituitary function as well as serum electrolytes in eight patients with MyD. Blood samples were obtained early in the morning after overnight dehydration. Renal function was estimated by blood urea nitrogen, serum creatinine and creatinine clearance. Posterior pituitary function was evaluated by direct measurement of plasma vasopressin (AVP) during a 5% hypertonic saline infusion. Plasma AVP concentrations were determined by sensitive radioimmunoassay. In five patients, circulating blood volume (CBV), plasma renin activity (PRA) and serum aldosterone (S-Aldo.) were also measured. The mean serum sodium level (143.9 +/- 1.7mEq/1: Mean +/- SD) was significantly higher than in the controls (139.4 +/- 2.2mEq/1). A 5% hypertonic saline infusion showed a subnormal increase in AVP and diminished thirst, despite sufficient elevation of plasma osmolality, in all patients as compared with healthy adults. Renal function was intact. Biochemical evidence of dehydration, estimated by PRA, S-Aldo and CBV, was unremarkable in four of the five patients. These findings suggest that patients with MyD have neurogenic disorders of osmoregulation in addition to previously reported endocrine abnormalities. Impaired AVP secretion in response to osmotic stimuli and reduced thirst might be responsible for such failure.
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PMID:[Impaired vasopressin secretion in patients with myotonic dystrophy]. 328 99

In the avian model of muscular dystrophy, electrophysiologic studies have shown alterations in the action potential characteristics of dystrophic muscle in vitro, supporting the notion that a membrane defect exists in avian dystrophy. As neurogenic and vascular etiologies have also been proposed, we examined the characteristics of action potentials recorded in a novel in vivo preparation of the extensor digitorum communis muscle in 8-week-old normal and dystrophic chickens. To facilitate intracellular recording, dantrolene sodium was used to attenuate the muscle twitch. Results showed that although the resting membrane potential, action potential amplitude and the action potential maximum rate of rise were similar in normal and dystrophic cells, the action potential duration at half the maximum amplitude was increased in dystrophic cells. This observation has not been previously reported for dystrophic avian muscle and suggests that a defect in the sarcolemmal potassium conductance is an early change in dystrophic avian muscle.
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PMID:Electrophysiologic differences between normal and dystrophic avian muscle. 377 Jan 30

6-Mercaptopurine (6-MP) was injected daily (2 mg/kg sc) into 24 Sprague-Dawley rats during the first three weeks of life. There were 23 saline-injected control animals. Atrophy of the muscles of the hindquarters in the 6-MP-treated rats began at about 4 months of age. The membrane potentials (Em) of the isolated extensor digitorum longus (EDL) and the caudofemoralis (CF) muscle (in situ) were measured with intracellular microelectrodes at 6-18 months of age. It was found that there was a wide spectrum of fibers with respect to electrical abnormalities in the 6-MP-treated muscles, some fibers having perfectly normal parameters. However, the mean resting Em of fibers in the EDL muscle of 6-MP-treated rats (-61.1 +/- 0.7 mV) was lower than that of the control rats (-69.7 +/- 0.6 mV). The same was true for the fibers of the CF muscle (-64.9 +/- 1.5 mV for 6-MP-treated fibers vs -71.6 +/- 1.3 mV for controls). Experiments done in the presence and absence of ouabain indicated that the contribution of the electrogenic pump potential to Em was similar in 6-MP-treated and control rats, and therefore could not account for the depolarization observed in 6-MP-treated rats. The data also demonstrated that this depolarization was not due to a decreased intracellular K+ concentration. The Na+/K+ permeability ratio (PNa/PK) was higher in the 6-MP-treated rats, and could account for the decreased resting Em. The APs of 6-MP-treated rats (elicited from the natural Em of the fiber) had more fibers with a lower maximum rate of rise (+Vmax) (330 +/- 20 vs 391 +/- 17 V/sec) and lower amplitude (65.1 +/- 2.9 vs 73.3 +/- 1.8 mV) than in the control muscles. When hyperpolarized to -90 mV before eliciting the AP, fibers from 6-MP-treated rats still displayed depressed AP rates of rise (+Vmax of 382 +/- 19 vs 511 +/- 21 V/sec in controls), depressed AP amplitudes (97 +/- 2.1 vs 105 +/- 1.6 mV in controls) and slightly prolonged duration at 50% amplitude (APD50) (0.66 +/- 0.03 vs 0.60 +/- 0.02 sec in controls). These electrophysiological alterations produced by this chemically-induced myopathy are similar to those observed in murine muscular dystrophy.
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PMID:6-Mercaptopurine treatment affects the membrane potentials of rat skeletal muscle fibers. 378 53


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