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

Muscle biopsies from nine patients with polymyositis, six with muscular dystrophy, six with other muscle diseases and three controls have been studied with a panel of 10 monoclonal antibodies (MoAb) identifying T lymphocytes, HLA-class I antigens, alpha, beta and gamma interferons and interleukin 2 (IL-2). The result confirm that the staining of the sarcolemma with anti-HLA class I antibody is weak or negative, except in areas adjacent to infiltrating leucocytes or where muscle fibre damage is evident. The very similar tissue distribution of alpha, beta and gamma interferons in the polymyositis biopsies supports the hypothesis that interferons are released by the inflammatory infiltrate and induce the class I antigen expression. In contrast, little interferon was demonstrated in the dystrophic muscle implying that class I expression in these disorders must occur by a different mechanism. Little IL-2 was demonstrated in any of the biopsies though some unexplained small dense accumulations were identified by one of the anti IL-2 MoAb.
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PMID:Localization of interferons and interleukin 2 in polymyositis and muscular dystrophy. 242 51

We applied a simple lead salt-based stain for interstitial and vascular 5'-nucleotidase to 150 muscle biopsy specimens. No reaction was obtained with 2'- or 3'-adenosine monophosphate, indicating that the stain was specific, and distinct from phosphatases. Staining was not inhibited by alpha, beta-methylene adenosine 5'-diphosphate, but was prevented by formaldehyde fixation or by brief immersion in octoxynol 9 (Triton X-100). Nucleotidase stains the following specific histologic sites that distinguish it from alkaline phosphatase: the intima and adventitia of medium-sized and large arteries, perineural and muscle spindle sheaths, and tendon insertions. Aside from these structures, normal muscle shows little reaction, as the sarcoplasm and sarcolemma do not stain. Neither of these enzymes shows a compensatory increase, histochemically, in myo-adenylate deaminase deficiency. In Duchenne's muscular dystrophy, however, and particularly in inflammatory myopathy, interstitial staining of 5'-nucleotidase is increased, leading to investment of most muscle fibers in the affected area. The stain rarely identifies regenerating fibers. Although alkaline phosphatase commonly shows a corresponding increase in interstitial staining, we encountered six cases of inflammatory myopathy in which this was absent, despite pronounced endomysial staining in the 5'-nucleotidase reaction. 5'-Nucleotidase thus appears to provide a valuable adjunct in the diagnosis of inflammatory myopathy.
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PMID:Interstitial 5'-nucleotidase stain for frozen biopsy specimens of skeletal muscle. A useful adjunct in the diagnosis of polymyositis. 619 1

Mutations in any of the genes encoding the alpha, beta or gamma-sarcoglycan components of dystrophin-associated glycoproteins result in both sporadic and familial cases of either limb-girdle muscular dystrophy or severe childhood autosomal recessive muscular dystrophy. The collective name 'sarcoglycanopathies' has been proposed for these forms. We report the identification of a fourth member of the human sarcoglycan family. We named this novel cDNA delta-sarcoglycan. Its mRNA expression is abundant in striated and smooth muscles, with a main 8 kb transcript, encoding a predicted basic transmembrane glycoprotein of 290 amino acids. Antibodies specifically raised against this protein recognized a single band at 35 kDa on western blots of human and mouse muscle. Immunohistochemical staining revealed a unique sarcolemmal localization. FISH, radiation hybrid and YAC mapping concordantly linked the delta-sarcoglycan gene to 5q33, close to D5S487 and D5S1439. The gene spans at least 100 kb and is composed of eight exons. The identification of a novel sarcoglycan component modifies the current model of the dystrophin-glycoprotein complex.
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PMID:Identification of a novel sarcoglycan gene at 5q33 encoding a sarcolemmal 35 kDa glycoprotein. 884 38

The majority (approximately 70%) of cases of childhood and adult onset muscular dystrophies in males, and approximately 10% of dystrophy in girls and women, show underlying primary abnormalities of dystrophin. Approximately 2% of childhood/adult onset muscular dystrophy patients have a primary defect of one of the three sarcoglycan proteins identified to date (alpha, beta, gamma). The finding of a sarcoglycan deficiency in muscle generally does not reflect the primary underlying defect, and thus testing of biopsies for sarcoglycans should be used only after normal dystrophin findings, and in conjunction with gene mutation testing. Approximately 30% of neonatal onset congenital muscular dystrophy has been shown to be due alpha 2-laminin (merosin) deficiency. alpha 2-laminin is a component of the myofiber basal lamina, and this protein interacts with the dystrophin-based membrane cytoskeleton. Due to the similar clinical and histopathological features of the different etiologies of muscular dystrophies, molecular testing of peripheral blood DNA and muscle biopsy protein are a critical part of the clinical work-up of dystrophy patients. Many patients carrying a Becker dystrophy or limb-girdle dystrophy diagnosis should be re-evaluated with molecular tests to provide accurate genetic counseling to their families.
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PMID:Clinical and histopathological features of abnormalities of the dystrophin-based membrane cytoskeleton. 886 47

The laminins are a family of structural basement membrane components with major influences on cells. They are high molecular weight glycoproteins composed of three different but homologous chains, alpha, beta and gamma. At present 10 different chains have been identified. Each chain has a distinct structural organization of domains, some of which have been assigned biological activities, including self-assembly and interactions with other proteins. The particular importance of laminins for the formation and stability of cell adhesion complexes is highlighted in severe inherited diseases of muscle and skin. Merosin is the collective name for laminins that share a common subunit, the laminin alpha 2 chain. Merosin-deficient congenital muscular dystrophy (CMD) is caused by mutations in the laminin alpha 2 chain gene. The skin disease Herlitz junctional epidermolysis bullosa is caused by mutations in any of the laminin alpha 3, beta 3 or gamma 2 chain genes. The medical importance of laminins provides a further impetus to study the basic structure-function relationships in laminins in order to understand genotype-phenotype relationships and to design prenatal diagnostic tests and therapies aimed at compensating for specific defects.
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PMID:Merosin/laminin-2 and muscular dystrophy. 902 48

Mutations in the genes encoding the dystrophin-associated sarcoglycan proteins (alpha, beta, gamma, and delta) (primary sarcoglycanopathies) have recently been shown to cause some cases of the genetically heterogeneous autosomal recessive muscular dystrophies (limb-girdle muscular dystrophy (LGMD) types 2D, 2E, 2C and 2F, respectively). Patients with a primary sarcoglycanopathy are clinically indistinguishable from those with the primary dystrophinopathies. Consequently, a definitive diagnosis can only be achieved through biochemical and molecular analysis. Patient biopsies showing normal dystrophin immunostaining (and/or immunoblot) can be immunostained with antibodies directed against any component of the sarcoglycan complex, and biochemical deficiencies of the sarcoglycan complex can be detected. We have shown, however, that only some of the biochemically-deficient patients are affected with alpha-, beta-, gamma- and delta-sarcoglycan mutations. Many will show mutations of an, as yet, unidentified protein. The primary sarcoglycanopathies have been estimated to account for about 5 per cent of muscular dystrophy in patients with normal dystrophin findings.
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PMID:Autosomal recessive muscular dystrophy and mutations of the sarcoglycan complex. 902 58

Mutations in genes coding for dystrophin, for alpha, beta, gamma, and delta-sarcoglycans, or for the alpha2 chain of the basement membrane component merosin (laminin-2/4) cause various forms of muscular dystrophy. Analyses of integrins showed an abnormal expression and localization of alpha7beta1 isoforms in myofibers of merosin-deficient human patients and mice, but not in dystrophin-deficient or sarcoglycan-deficient humans and animals. It was shown previously that skeletal muscle fibers require merosin for survival and function (Vachon, P.H., F. Loechel, H. Xu, U.M. Wewer, and E. Engvall. 1996. J. Cell Biol. 134:1483-1497). Correction of merosin deficiency in vitro through cell transfection with the merosin alpha2 chain restored the normal localization of alpha7beta1D integrins as well as myotube survival. Overexpression of the apoptosis-suppressing molecule Bcl-2 also promoted the survival of merosin-deficient myotubes, but did not restore a normal expression of alpha7beta1D integrins. Blocking of beta1 integrins in normal myotubes induced apoptosis and severely reduced their survival. These findings (a) identify alpha7beta1D integrins as the de facto receptors for merosin in skeletal muscle; (b) indicate a merosin dependence for the accurate expression and membrane localization of alpha7beta1D integrins in myofibers; (c) provide a molecular basis for the critical role of merosin in myofiber survival; and (d) add new insights to the pathogenesis of neuromuscular disorders.
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PMID:Integrins (alpha7beta1) in muscle function and survival. Disrupted expression in merosin-deficient congenital muscular dystrophy. 931 89

The muscular dystrophy is a progressive genetically determined disease of skeletal muscles. Thanks to the development of molecular genetics there have been identified genes responsible for synthesis of the corresponding proteins of the muscular membrane, whose deficiency causes certain types of muscular dystrophy. Thus, recently has been reported that deficiency of sarcoglycan (alpha, beta, gamma and sigma) is responsible for the appearance of four different types of autosomal recessive limb-girdle muscular dystrophies (2D, 2E, 2C, 2F), and that the lack of merosin is the cause of serious merosin deficiency, of congenital muscular dystrophy. The paper presents the nature, function and importance of the main components of sarcolemma, as well as the basic characteristics of muscular dystrophies caused by their deficiency. It is important to know the genetic product whose deficiency is responsible for certain types of muscular dystrophy as only by confirming their deficiency in the biopsy material the precise diagnosis can be established even without molecular-genetic analyses. This is of great importance for accurate genetic advising.
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PMID:[Significance of merosin and sarcoglycan in manifestations of certain forms of muscular dystrophy]. 952 81

Abnormalities of dystrophin, the sarcoglycans, and laminin alpha2 are responsible for a subset of the muscular dystrophies. In this study we aim to characterise the nature and frequency of abnormalities of these proteins in an Australian population and to formulate an investigative algorithm to aid in approaching the diagnosis of the muscular dystrophies. To reduce ascertainment bias, biopsies with dystrophic (n=131) and non-dystrophic myopathic (n=71) changes were studied with antibodies to dystrophin, alpha, beta, and gamma sarcoglycan, beta dystroglycan, and laminin alpha2, and results were correlated with clinical phenotype. Abnormalities of dystrophin, the sarcoglycans, or laminin alpha2 were present in 61/131 (47%) dystrophic biopsies and in 0/71 myopathic biopsies, suggesting that immunocytochemical study of dystrophin, the sarcoglycans, and laminin alpha2 may, in general, be restricted to patients with dystrophic biopsies. Two patients with mutations identified in gamma sarcoglycan had abnormal dystrophin (by immunocytochemistry and immunoblot), showing that abnormalities of dystrophin may be a secondary phenomenon. Therefore, biopsies should not be excluded from sarcoglycan analysis on the basis of abnormal dystrophin alone. The diagnostic yield was highest in those with severe, rapidly progressive limb-girdle weakness (92%). Laminin alpha2 deficiency was identified in 5/131 (4%) patients; 215 patients presented after infancy, indicating that abnormalities of laminin alpha2 are not limited to the congenital muscular dystrophy phenotype. Overall patterns of immunocytochemistry and immunoblotting provided a guide to mutation analysis and, on the basis of this study, we have formulated a diagnostic algorithm to guide the investigation of patients with muscular dystrophy.
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PMID:Abnormalities of dystrophin, the sarcoglycans, and laminin alpha2 in the muscular dystrophies. 961 Aug

The sarcoglycans are a complex of four transmembrane proteins (alpha, beta, gamma, and delta) which are primarily expressed in skeletal muscle and are closely associated with dystrophin and the dystroglycans in the muscle membrane. Mutations in the sarcoglycans are responsible for four autosomal recessive forms of muscular dystrophy. The function and the organization of the sarcoglycan complex are unknown. We have used coimmunoprecipitation and in vivo cross-linking techniques to analyze the sarcoglycan complex in cultured mouse myotubes. We demonstrate that the interaction between beta- and delta-sarcoglycan is resistant to high concentrations of SDS and alpha-sarcoglycan is less tightly associated with other members of the complex. Cross-linking experiments show that beta-, gamma-, and delta-sarcoglycan are in close proximity to one another and that delta-sarcoglycan can be cross-linked to the dystroglycan complex. In addition, three of the sarcoglycans (beta, gamma, and delta) are shown to form intramolecular disulfide bonds. These studies further our knowledge of the structure of the sarcoglycan complex. Our proposed model of their interactions helps to explain some of the emerging data on the consequences of mutations in the individual sarcoglycans, their effect on the complex, and potentially the clinical course of muscular dystrophies.
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PMID:Molecular organization of sarcoglycan complex in mouse myotubes in culture. 986 73


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