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)

1. Developmental enzyme alterations were investigated in skeletal muscle of the hereditary progressive muscular dystrophy (PMD) mice of C57BL/6J strain. 2. Enzymes examined were classified into three groups according to changes of activities in dystrophy muscle during ageing. Activities of creatine kinase (EC 2.7.3.2), pyruvate kinase (EC 2.7.1.40), glycogen phosphorylase (EC 2.4.1.1), and fructose-biphosphate aldolase (EC 4.1.2.13), each of which had the respective muscle specific isoenzyme of extremely high activity in normal adult skeletal muscle, decreased rapidly in dystrophy muscle from the early stage of the disease with ageing. Activities of glycogen synthase (EC 2.4.1.11) and hexokinase (EC 2.7.1.1) were higher in dystrophy muscle in the early stage but decreased gradually to lower levels than those in the control with ageing. Activities of glucose-6-phosphate dehydrogenase (EC 1.1.1.49) were always much higher in dystrophy muscle than in the control, with no relation to ageing. 3. Isoenzymes of creatine kinase, pyruvate kinase and phosphorylase in dystrophy muscle were mainly the muscle types, indicating that muscle differentiation was not blocked profoundly even in dystrophy muscle. In limited cases, especially in the early stage of the disease, very weak activities of the non-muscle fetal type isoenzymes of creatine kinase and phosphorylase were detected, apparently associated with partial muscle regeneration in dystrophy muscle.
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PMID:Enzyme alteration in skeletal muscle of mice with muscular dystrophy. 41 23

Isoforms of creatine kinase (CK) MM have been analysed in plasma from normal subjects and patients with muscular dystrophy using isoelectric focusing techniques. Most plasma samples analysed contained three isoforms of CK-MM of isoelectric points 7.26 (MMI), 6.85 (MMII) and 6.45 (MMIII) although in some plasma samples two additional isoforms of isoelectric points 7.12 and 6.65 were seen. Patients with muscular dystrophy were found to have a generally higher proportion of CK-MMI in their plasma than normal subjects and this was relatively unaffected by large variations in the total creatine kinase activity. By comparison eccentric exercise in normal subjects was found to result in a large increase in total plasma CK activity which then declined to normal over a period of approximately 6 days. CK-MMI was found to increase initially followed by CK-MMII and CK-MMIII. Analysis of the isoforms in biopsy samples of human muscle revealed the presence of two of the bands found in plasma (CK-MMI and MMII) and a third muscle specific isoform, while incubation of muscle homogenates in plasma induced the formation of CK-MMIII and the two isoforms of pI 7.12 and 6.65. It is concluded that analyses of CK-MM isoforms in human plasma can provide useful information on the extent and relative time course following an episode of muscle damage but that in patients with muscular dystrophy the large variations in plasma CK activity are not reflected in the proportion of CK found in each isoform.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Isoforms of creatine kinase: MM in the study of skeletal muscle damage. 249 78

A radioimmunosorbent technique was used for the assay of the skeletal muscle specific enzyme, carbonic anhydrase III (CA III). The usefulness of serum CA III determinations for detecting skeletal muscle damage was evaluated by comparing the serum levels of this enzyme and of myoglobin and creatine kinase in 64 patients with neuromuscular disorders and in 13 healthy volunteers before and after a long-distance run. Increased serum CA III levels were found in all patients with muscular dystrophy, chronic polymyositis and amyotrophic lateral sclerosis and in many with myasthenia gravis. In patients with polymyositis who were followed up with repeated blood sampling, the time courses of serum CA III levels, myoglobin levels and clinical symptoms were closely related. In all the runners the serum CA III level immediately after the run was increased. In the present study serum CA III and myoglobin seemed to be equally sensitive as biochemical markers of muscular damage and more sensitive than creatine kinase.
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PMID:Serum carbonic anhydrase III in neuromuscular disorders and in healthy persons after a long-distance run. 393 1

A case of muscular dystrophy in a 1-year-old male castrated Domestic Shorthair cat is presented. The most striking clinical features were regurgitation, a stiff gait, an increased muscle tone and exercise intolerance. Serum biochemistry panels showed a marked increase in the muscle specific enzyme creatine kinase, and moderately elevated levels of LDH, AST and ALT. Spontaneous electrical activity of skeletal muscles in the form of "bizarre high frequency discharges" and "myotonia-like repetitive discharges" were registered. Gross pathology revealed a marked hypertrophy of the skeletal muscles. The main histopathological changes were myofiber necrosis and calcification, variation in fiber size, hypertrophied muscle fibers of type I and type II and fiber splitting. Indirect immunofluorescence showed dystrophin deficiency. Feline muscular dystrophy resembles the X-linked human Duchenne muscular dystrophy (DMD). Besides the X-linked muscular dystrophy in the mouse and Golden Retriever the feline muscular dystrophy could represent another valuable animal model for the study of DMD.
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PMID:[Muscular dystrophy in a cat]. 824 6

A reclassification of the limb-girdle types of autosomal recessive muscular dystrophy based on genetic and protein information has been made possible by major advances over the past 2 years. At least six different forms of limb-girdle types of autosomal recessive muscular dystrophy can be defined by their genetic basis, with at least two pathogenic mechanisms involved. Three forms are defined by involvement of different proteins of the sarcoglycan complex, while a muscle specific protease (calpain 3) is implicated in another form of the recessive disease. These findings provide the basis for a new diagnostic approach to the group, with molecular techniques now an essential part of the diagnostic process. A scheme for diagnosis in this group is proposed.
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PMID:Advances in the molecular genetics of the limb-girdle type of autosomal recessive progressive muscular dystrophy. 901 5

Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disorder characterized by an insidious onset and progressive course. The disease has a frequency of about 1 in 20,000 and is transmitted in an autosomal dominant fashion with almost complete penetrance. Deletion of an integral number of tandemly arrayed 3.3-kb repeat units (D4Z4) on chromosome 4q35 is associated with FSHD but otherwise the molecular basis of the disease and its pathophysiology remain obscure. Comparison of mRNA populations between appropriate cell types can facilitate identification of genes relevant to a particular biological or pathological process. In this report, we have compared mRNA populations of FSHD and normal muscle. Unexpectedly, the dystrophic muscle displayed profound alterations in gene expression characterized by severe underexpression or overexpression of specific mRNAs. Intriguingly, many of the deregulated mRNAs are muscle specific. Our results suggest that a global misregulation of gene expression is the underlying basis for FSHD, distinguishing it from other forms of muscular dystrophy. The experimental approach used here is applicable to any genetic disorder whose pathogenic mechanism is incompletely understood.
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PMID:Profound misregulation of muscle-specific gene expression in facioscapulohumeral muscular dystrophy. 1053 77

Myostatin, a TGF-beta family member, is a negative regulator of muscle growth. Here, we generated transgenic mice that expressed myostatin mutated at its cleavage site under the control of a muscle specific promoter creating a dominant negative myostatin. These mice exhibited a significant (20-35%) increase in muscle mass that resulted from myofiber hypertrophy and not from myofiber hyperplasia. We also evaluated the role of myostatin in muscle degenerative states, such as muscular dystrophy, and found significant downregulation of myostatin. Thus, further inhibition of myostatin may permit increased muscle growth in muscle degenerative disorders.
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PMID:Dominant negative myostatin produces hypertrophy without hyperplasia in muscle. 1082 54

Limb girdle muscular dystrophy (LGMD) type 2A (LGMD2A) is caused by mutations in the CAPN3 gene encoding for calpain-3, a muscle specific protease. While a large number of CAPN3 gene mutations have already been described in calpainopathy patients, the diagnosis has recently shifted from molecular genetics towards biochemical assay of defective protein. However, an estimate of sensitivity and specificity of protein analysis remains to be established. Thus, we first correlated protein and molecular data in our large LGMD2A patient population. By a preliminary immunoblot screening for calpain-3 protein of 548 unclassified patients with various phenotypes (LGMD, myopathy, or elevated levels of serum creatine kinase [hyperCKemia]), we selected 208 cases for CAPN3 gene mutation analysis: 69 had protein deficiency and 139 had normal expression. Mutation search was conducted using SSCP, denaturing high performance liquid chromatography (DHPLC), amplification refractory mutation system (ARMS-PCR), and direct sequencing methods. We identified 58 LGMD2A mutant patients: 46 (80%) had a variable degree of protein deficiency and 12 (20%) had normal amount of calpain-3. We calculated that the probability of having LGMD2A is very high (84%) when patients show a complete calpain-3 deficiency and progressively decreases with the amount of protein; this new data offers an important tool for genetic counseling when only protein data are available. A total of 37 different CAPN3 gene mutations were detected, 10 of which are novel. In our population, 87% of mutant alleles were concentrated in seven exons (exons 1, 4, 5, 8, 10, 11, and 21) and 61% correspond to only eight mutations, indicating the regions where future molecular analysis could be restricted. This study reports the largest collection of LGMD2A patients so far in which both protein and gene mutations were obtained to draw genotype-protein-phenotype correlations and provide insights into a critical protein domain.
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PMID:Molecular diagnosis in LGMD2A: mutation analysis or protein testing? 1522 89

The muscular dystrophies are a genetically heterogeneous group of progressive disorders that lead to the breakdown of the integrity of skeletal muscle. Numerous recent advances made in research into the molecular genetics of muscular dystrophy have highlighted the diversity of this family of disorders. Muscle biopsy allows the immunohistochemical analysis of various muscle specific proteins, and can provide important data enabling definitive diagnosis. Muscle biopsy is not always necessary, such as in the case of Duchenne or Fukuyama type dystrophies, which are relatively easy to diagnose by genetic testing; in such cases, however, consideration must given to the ethical implications of testing. The future promises the development of new therapeutic approaches and clinical applications based on genetic diagnostic data.
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PMID:[Muscular dystrophy]. 1577 40

Skeletal muscles in mdx mice exhibit differential degrees of pathological changes and fibrosis. The purpose of this study was to examine differences in various indices of collagen metabolism in skeletal muscles with widely different functions and activity profiles in mdx mice, and to determine whether pirfenidone would attenuate the development of fibrosis. Mice in the pirfenidone group were orally fed pirfenidone (500 mg/kg) daily for 4 weeks. Marked differences were noted in hydroxyproline concentration between muscles, which could not be explained solely by the level of type I collagen and transforming growth factor-beta1 (TGF-beta1) mRNA. In normal mice, matrix metalloproteinase (MMP)-2 mRNA was significantly higher in the gastrocnemius than in the diaphragm or genioglossus muscles, suggesting that collagen degradation plays an important role in regulating collagen accretion in skeletal muscle. In mdx mice, the levels of both MMP-2 and MMP-9 mRNA were significantly elevated relative to control, although the response was muscle specific. Pirfenidone treatment resulted in a significant reduction in the level of hydroxyproline concentration across all muscles, although the effect was small. Results from this study reveal intrinsic dissimilarities in collagen metabolism between functionally different skeletal muscles. Moreover, the pharmacological use of pirfenidone may be beneficial in preventing fibrosis in muscular dystrophy.
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PMID:A comparison of factors associated with collagen metabolism in different skeletal muscles from dystrophic (mdx) mice: impact of pirfenidone. 1705 74


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