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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Avian muscular dystrophy is an autosomal recessive genetic disease characterized by early hypertrophy and loss of function of pectoralis major. The disease is progressive, ultimately resulting in atrophy and heavy lipid deposition. Previous investigators have noted a decrease in the ability of the dystrophic sarcoplasmic reticulum to concentrate Ca2+. More recently, other investigators have shown an abnormal calcium uptake in avian dystrophic sarcoplasmic reticulum. They indicated, using freeze-fracture techniques, that a 90 A particle of the vesicle membrane exhibited a decreased population and suggested that they might be the ATPase involved in calcium transport. Our studies confirm earlier observations of a decreased rate of Ca2+ uptake and Ca2+ binding capacity of dystrophic fragmented sarcoplasmic reticulum vesicles which are isolated from both embryonic and adult pectoralis. These observations correlate in turn with a 75% drop in the Ca:ATP transport efficiency of the dystrophic sarcoplasmic reticulum determined by measuring the rate of 32Pi liberation from gamma-ATP32 during active calcium transport by the isolated sarcoplasmic reticulum SR. In addition, we have found a quantitative deficiency in a 65,000 dalton component of the dystrophic fragmented SR at the time of myoblast fusion by measuring 35S-Methionine incorporation into the SR, coupled to high resolution polyacrylamide gel electrophoresis and radioautography. Analysis of total tissue calcium by atomic absorption spectroscopy revealed a decrease in the total calcium content of dystrophic muscle.
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PMID:Ca2+ binding, ATP-dependent Ca2+ transport, and total tissue Ca2+ in embryonic and adult avian dystrophic pectoralis. 75 24

Two groups of sheep fed a diet of hay known to produce nutritional muscular dystrophy, one group of which received selenium supplementation, were used to study the effects of selenium on the metabolism of administered L-(35S) methionine by rumen microflora. Rumen bacterial proteins of the Se supplemented sheep contained significantly higher levels of radiosulfur than the bacterial protein of the non-supplemented sheep. Of hte L-(35S) methionine present in the rumen liquor samples from Se-supplemented sheep 2 h after administration, 13.3% of the amino acid, which was measured as methionine sulfone, was found in the microbial proteins. A large proportion of the administered labeled methionine was resynthesized as cyst(e)ine which may account in part for that determined as cysteic acid in rumen bacterial and plasma proteins. The observed low levels of radiosulfur found in rumen microflora from selenium deficient wethers, indicates that the presence of selenium profoundly affects the rate of methionine metabolism and the distribution of methionine in rumen bacterial and protozoal proteins. In another experiment, the effect of selenium on the metabolism of L-(Me-3H) methionine was studied. The selenium status of the sheep had no significant effect (P greater than 0.05) on the distribution of 35S radioactivity in the blood plasma and tissues.
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PMID:The effects of selenium on the metabolism of methionine in sheep. 95 63

We have studied the structure of myosin heavy chain (MHC) in the pectoralis muscle of genetically dystrophic (Connecticut Strain) and White Leghorn chicks. MHC was alkylated with N-ethylmaleimide, purified by Sepharose-4B chromatography, and cleaved with cyanogen bromide. The MHC CNBr peptides were analyzed by one-dimensional and two-dimensional isoelectric focusing/sodium dodecyl sulfate gradient gels and by amino acid sequencing. Specific changes were detected in the gel patterns which could be correlated with the loss of muscle function as measured by the exhaustion score (the ability of chicks to rise from a reclining position) in three experimental groups (exhaustion scores: less than 3, 10-20, greater than 30). We have also examined the amino acid sequence of a 3-methyl-histidine-containing peptide which originates from the 20-kDa fragment of pectoralis muscle MHC in dystrophic chicks: Val-Leu-Asn-Ala-Ser-Ala-Ile-Pro-Glu-Gly-*Gln-Phe-*Ile-Asp-Ser-Lys-Lys- Ala-Ser-Leu-Gln-Lys-Leu-Gly-Ser-Ile-Asp-Val-(Asp, 3-methylhistidine, Gln). Comparison of the homologous MHC sequences shows two positions at which MHC from dystrophic chicks differs from that of the White Leghorn chicks *(Glu----Gln and Met----Ile). Thus, both the peptide map and sequence analyses demonstrate that in avian muscular dystrophy an abnormal pectoralis MHC is synthesized. It is not yet clear whether the "dystrophic" MHC is a variant MHC or if it arises from the abnormal expression of an earlier developmental form (embryonic or neonatal) of pectoralis muscle MHC.
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PMID:Structure of myosin heavy chain in avian muscular dystrophy. 399 78

Forty-eight weanling S.P.F. Yorshire pigs were used to study the influence of supplemental vitamin E (25 IU per kg of diet) selenium (0.5 ppm in diet) and methionine (0.1% in diet) on the incidence of hepatosis dietetica and mulberry heart disease when fed a torula yeast-corn diet. Vitamin E and/or selenium increased pig survival. Supplemental selenium resulted in increased liver selenium concentrations. No hepatosis dietetica was observed in any of the pigs. The addition of vitamin E and/or selenium at the levels used did not reduce the frequency of myocardial lesions; however, they prevented skeletal muscular dystrophy and exudative diathesis. The myocardial lesions were less severe in supplemented pigs compared with unsupplemented controls.
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PMID:Vitamin E, selenium and methionine supplementation of dystrophogenic diets for pigs. 426 22

To elucidate the metabolic abnormality of musclar dystrophy, 27 kinds of enzyme activity in various organs of control and dystrophic mice were examined. The organs examined included muscle, bone, heart, testis, uterus, spleen, thymus, submaxillary gland, stomach, pancreas, liver, kidney, brain, and lung. The activities of 14 different aminopeptidases, 5 endopeptidases, 4 glycosidases, phosphatase, esterase, and ribonuclease were measured. Most of the enzyme activities were significantly elevated in muscles and bones of dystrophic mice. These organs were similar in their patterns of enzyme abnormality. Among the 14 kinds of aminopeptidase activity studied, the degree of increased activity was greater for the aminopeptidases (AP):Ala-AP, Leu-AP, Met-AP, Phe-AP, Trp-AP, Gly-Pro-Leu-AP. In addition to aminopeptidases, there were significant increases in activities of chymotrypsinlike enzyme, cathepsin C, cathepsin D, several glycosidases and neutral ribonuclease in the muscles of dystrophic mice. Similarly increased enzyme activity was also observed in organs other than muscle and bone. Furthermore, protein content in most organs was higher in dystrophic mice than in those of control mice. These abnormalities were seen in both males and females. The present results suggest that there are extensive abnormalities in the protein metabolism in dystrophic mice. It seems therefore that the therapeutic approach to muscular dystrophy should be studies not only from the well-known abnormality of intramuscular endopeptidases, but from other aspects as well.
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PMID:Various enzyme activities in muscle and other organs of dystrophic mice. 625 14

Interactins between skeletal muscle protein and amino acid metabolism were investigated using C57BL and 129ReJ mice with hereditary muscular dystrophy. On incubation, hind limb muscle preparations from dystrophic mice released large quantities of amino acids, particularly alanine and glutamine which were increased 70% and 40% compared to muscles from carrier or control mice. The increased alanine release did not result from altered alanine oxidation to CO2 or reincorporation into protein. Alanine and glutamine formation from added amino acids were equal with dystrophic and control muscles. Incorporation in vitro of leucine, alanine, and glutamate into proteins of dystrophic muscle was 3- to 7-fold greater than control muscle, and the incorporation in vivo of [3H]- or [14C]arginine into muscle proteins was greater in extent and earlier in time with dystrophic as compared to control muscle. Proteins were also labeled in vivo using [guanido-14C]arginine. On incubation of these muscles in vitro, a 100% greater loss of label from protein was observed with dystrophic as compared to control preparations, and the appearance of label in the media was correspondingly increased. Sodium dodecyl sulfate-gel electrophoresis of dystrophic skeletal muscle showed numerous protein bands to be reduced in density, but autoradiographic studies demonstrated that these same bands were more highly labeled in vitro by [35S]methionine in dystrophic than in control muscle. Although insulin stimulation of glucose uptake was markedly blunted in dystrophic muscle, insulin inhibited alanine and glutamine release equally from both control and dystrophic muscle. These data indicate that alanine and glutamine formation and release are increased in hereditary mouse muscular dystrophy. An accelerated degradation and an increased resynthesis of many muscle proteins were also observed in dystrophic compared to control animals. This increased proteolysis may account for the increased alanine and glutamine formation in dystrophic muscle.
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PMID:Skeletal muscle protein and amino acid metabolism in hereditary mouse muscular dystrophy. Accelerated protein turnover and increased alanine and glutamine formation and release. 689 25

Duchenne and Becker muscular dystrophies (D/BMD) are caused by mutations in the dystrophin gene. Two-thirds of patients have large intragenic deletions or duplications and the remaining one-third have point mutations, small deletions or insertions. Point mutations are more difficult to detect due to the enormous size (2.4 Mb) of the gene and its large transcript (14 kb). In the present study, a total of 50 DNA samples from unrelated D/BMD (38 DMD and 12 BMD) patients who did not show intragenic deletions by multiplex PCR, were analyzed for detection of point mutations. Single stranded conformation analysis and heteroduplex analysis observed electrophoretic mobility shifts in one (BMD) and two (DMD and BMD) patients, respectively. The mobility shift and heteroduplexes were observed in exon 17 in all of the three patients. Sequencing of the amplified PCR products revealed a nucleotide change (-37 g to t) in the intronic region in two of the patients while a C2268T substitution in the exonic region in one. Mutation database search for D/BMD mutations showed the nucleotide substitution in the exonic region as a novel change in the human dystrophin gene, which was not reported earlier. It resulted in an amino acid transition from threonine to methionine in the 687th position of the dystrophin protein. This novel substitution has been included in the mutation database of Leiden muscular dystrophy pages (http://www.dmd.nl) in the rare polymorphism/mutation category. The substituted nucleotide segregated with the disease phenotype in the family suggesting that it can be directly used for carrier detection and prenatal diagnosis without identification of disease causing mutation.
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PMID:Point mutation and polymorphism in Duchenne/Becker muscular dystrophy (D/BMD) patients. 1179 88

Met-myoglobin isolated from gluteal muscle of cases with Duchenne type of progressive muscular dystrophy showed an abnormal ultraviolet spectrum. The maximum of the spectrum at pH 7.0 was at 275 mmicro, in contrast to that at 281 m/ A in normal met-myoglobin. Such an abnormality was not found in the limb-girdle type of dystrophy and in progressive spinal muscular atrophy. The results indicate the presence of an abnormal myoglobin in the Duchenne type of progressive muscular dystrophy.
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PMID:ABNORMAL MYOGLOBIN ULTRAVIOLET SPECTRUM IN DUCHENNE TYPE OF PROGRESSIVE MUSCULAR DYSTROPHY. 1406 46

Creatine and phosphocreatine serve not only as an intracellular buffer for adenosine triphosphate, but also as an energy shuttle for the movement of high-energy phosphates from mitochondrial sites of production to cytoplasmic sites of utilization. The spontaneous loss of creatine and of phosphocreatine to creatinine requires that creatine be continuously replaced; this occurs by a combination of diet and endogenous synthesis. Vegetarians obtain almost no dietary creatine. Creatine synthesis makes major demands on the metabolism of glycine, arginine, and methionine. Large doses of creatine monohydrate are widely taken, particularly by athletes, as an ergogenic supplement; creatine supplements are also taken by patients suffering from gyrate atrophy, muscular dystrophy, and neurodegenerative diseases. Children with inborn errors of creatine synthesis or transport present with severe neurological symptoms and a profound depletion of brain creatine. It is evident that creatine plays a critical, though underappreciated, role in brain function.
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PMID:Creatine: endogenous metabolite, dietary, and therapeutic supplement. 1743 86

Albeit genetically highly heterogeneous, muscular dystrophies (MDs) share a convergent pathology leading to muscle wasting accompanied by proliferation of fibrous and fatty tissue, suggesting a common MD-pathomechanism. Here we show that mutations in muscular dystrophy genes (Dmd, Dysf, Capn3, Large) lead to the spontaneous formation of skeletal muscle-derived malignant tumors in mice, presenting as mixed rhabdomyo-, fibro-, and liposarcomas. Primary MD-gene defects and strain background strongly influence sarcoma incidence, latency, localization, and gender prevalence. Combined loss of dystrophin and dysferlin, as well as dystrophin and calpain-3, leads to accelerated tumor formation. Irrespective of the primary gene defects, all MD sarcomas share non-random genomic alterations including frequent losses of tumor suppressors (Cdkn2a, Nf1), amplification of oncogenes (Met, Jun), recurrent duplications of whole chromosomes 8 and 15, and DNA damage. Remarkably, these sarcoma-specific genetic lesions are already regularly present in skeletal muscles in aged MD mice even prior to sarcoma development. Accordingly, we show also that skeletal muscle from human muscular dystrophy patients is affected by gross genomic instability, represented by DNA double-strand breaks and age-related accumulation of aneusomies. These novel aspects of molecular pathologies common to muscular dystrophies and tumor biology will potentially influence the strategies to combat these diseases.
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PMID:DNA damage, somatic aneuploidy, and malignant sarcoma susceptibility in muscular dystrophies. 2160 39


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