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)

We report, for the first time, muscle immunocytochemical studies in sporadic, adult onset myotubular myopathy (SAOMM), which show intramyofibrillar central, perinuclear desmin and vimentin. This pattern was absent in a normal control and in myofibers with increased internal nuclei associated with denervation and myotonic muscular dystrophy (MyD). These findings resemble those reported in 8- to 15-week-old human fetal myotubes and myofibers of infantile MM, implying a possible regression of intermediate filaments of adult myofibers to an early developmental phase in SAOMM.
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PMID:Abnormal distribution of desmin and vimentin in myofibers in adult onset myotubular myopathy. 128 2

Desmin and vimentin are two intermediate filaments, abundant in fetal skeletal muscle, almost undetectable in mature skeletal muscle which increase in regenerating and partially damaged skeletal muscle fibers. To determine their content in neuromuscular disorders immunohistochemical studies of desmin and vimentin were performed on 53 human muscle specimens. The labelled streptavidin biotin technique (DAKO, LSAB Kit, alkaline phosphatase) was used. Strong staining intensity was seen in regenerating and partially damaged fibers of inflammatory myopathies and muscular dystrophy. Necrotic fibers lost their reactivity for both filaments. Type II glycogenosis showed an increased reactivity for desmin and vimentin. A mild increase in desmin and vimentin staining intensity was observed in the atrophic cells of spinal muscular atrophy, but not in the atrophic fibers from other disease entities. Weaker reactivity for desmin was noted in atrophic cells of myotonic dystrophy. The immunohistochemical study of desmin and vimentin in neuromuscular disorders is helpful in detecting degeneration, or regeneration changes, of muscle fibers and may provide clues to the pathogenesis of various muscular disorders.
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PMID:Immunocytochemical studies on desmin and vimentin in neuromuscular disorders. 774 34

Morphological, morphometrical, histoenzymological, immunocytochemical and biochemical analysis were performed on muscle biopsies taken from patients suffering from tunisian autosomal recessive Duchenne-like muscular dystrophy (TDLMD) selected both by Duchenne-like clinical criteria and by the presence of normal dystrophin. Data were compared to that obtained from DMD biopsies characterized by the absence of dystrophin. The distribution of myosin heavy chain isoforms, desmin, vimentin and titin were determined in type I and type II muscle fibers. The protein pattern appeared to be less affected in TDLMD than in DMD biopsies. The regenerating fibers were mainly but not exclusively type IIC; a noticeable percentage of both type I and type II fibers coexpressed fast and slow MHC isoforms in TDLMD. This percentage was lower than in DMD. The expression of embryonic, fetal, and fast/slow myosin isoforms in type IIC fibers in TDLMD and DMD suggest different fiber type transformations in these two diseases.
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PMID:Expression of myosin isoforms and of desmin, vimentin and titin in Tunisian Duchenne-like autosomal recessive muscular dystrophy. 806 3

Histomorphological and histochemical variability was studied in muscle specimens from 30 patients with congenital muscular dystrophy (CMD). We found involvement of the central nervous system in 8 patients (Fukuyama CMD, F-CMD), involvement of the brain and the eyes in 5 patients (muscle, eye and brain disease, MEB-D) and hypodense white matter on the CT scans of 2 patients with (sub)normal intelligence (occidental-type cerebromuscular dystrophy, O-CMD). No morphological hallmarks were found to differentiate these subgroups. Only fat cell infiltration was found to be increased with increasing age in 'pure' CMD (pure-CMD). The morphological data did not appear to be correlated with the clinical severity or type of dystrophy (pure-CMD, F-CMD, MEB-D and O-CMD). Immunohistochemistry with dystrophin, vimentin and desmin antibodies in 14 patients (6 pure-CMD, 5 F-CMD, 2 MEB-D and 1 O-CMD) showed a normal expression pattern.
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PMID:Congenital muscular dystrophy. A study on the variability of morphological changes and dystrophin distribution in muscle biopsies. 825 90

Epidermolysis bullosa simplex with muscular dystrophy (MD-EBS) is a disease characterized by generalized blistering of the skin associated with muscular involvement. We report that the skin of three MD-EBS patients is not reactive with antibodies 6C6, 10F6, or 5B3 raised against the intermediate filament-associated protein plectin. Immunofluorescence and Western analysis of explanted MD-EBS keratinocytes confirmed a deficient expression of plectin, which, in involved skin, correlated with an impaired interaction of the keratin cytoskeleton with the hemidesmosomes. Consistent with lack of reactivity of MD-EBS skin to plectin antibodies, plectin was not detected in skeletal muscles of these patients. Impaired expression of plectin in muscle correlated with an altered labeling pattern of the muscle intermediate filament protein desmin. A deficient immunoreactivity was also observed with the monoclonal antibody HD121 raised against the hemidesmosomal protein HD1. Furthermore, immunofluorescence analysis showed that HD1 is expressed in Z-lines in normal skeletal muscle; whereas this expression is deficient in patient muscle. Colocalization of HD1 and plectin in normal skin and muscle, together with their impaired expression in MD-EBS tissues, strongly suggests that plectin and HD1 are closely related proteins. Our results therefore provide strong evidence that, in MD-EBS patients, the defective expression of plectin results in an aberrant anchorage of cytoskeletal structures in keratinocytes and muscular fibers leading to cell fragility.
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PMID:Defective expression of plectin/HD1 in epidermolysis bullosa simplex with muscular dystrophy. 863 9

Plectin is a widely expressed cytomatrix component involved in the attachment of the cytoskeleton to the plasma membrane. We have recently reported that the skin and muscles of three patients affected by epidermolysis bullosa simplex with muscular dystrophy (MD-EBS), a genetic disorder characterized by skin blistering associated with muscle involvement, are not reactive with antibodies specific to plectin. We demonstrated that in the skin, lack of plectin leads to failure of keratin filaments to connect to the plasma membrane via the hemidesmosomes, whereas in the muscle the deficient expression of the molecule correlates with an aberrant localization of desmin in the muscle fibers. In this study we demonstrate that in a MD-EBS kindred with two affected members, the disease results from a homozygous nonsense mutation in the plectin (PLEC1) gene leading to a premature stop codon (CGA to TGA) and decay of the aberrant plectin messenger RNA. The segregation of the mutated allele implicates the mutation in the pathology of the disorder. These results confirm the critical role of plectin in providing cell resistance to mechanical stresses both in the skin and the muscle.
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PMID:A homozygous nonsense mutation in the PLEC1 gene in patients with epidermolysis bullosa simplex with muscular dystrophy. 894 34

Plectin/HD1 is a high molecular weight protein (approximately 500 kDa) that has been proposed to act as an important and versatile cytoskeletal cross-linker molecule. Mutations of the human plectin gene have recently been associated with the autosomal recessive disorder epidermolysis bullosa simplex with muscular dystrophy. We studied the expression of plectin/HD1 in various neuromuscular disorders by indirect immunofluorescence. In cross sections of normal human muscle, plectin/HD1 showed a checkerboard-like distribution with moderate to intense cytoplasmic and sarcolemmal staining in type 1 fibers and a faint staining of the sarcolemma in type 2 fibers. In longitudinal sections of plectin/HD1-positive fibers a cross-striation staining pattern was noted. This fiber type-related expression was significantly altered in the group of dystrophinopathies, whereas it was maintained in all other myopathies and denervating disorders. In seven dystrophinopathies studied, a markedly increased plectin/HD1 immunoreactivity at the sarcolemmal level of type 2 fibers was observed. Confocal laser microscopy of normal skeletal muscle revealed a colocalization of desmin and plectin/HD1 at the level of the sarcolemma. This suggests that plectin/HD1- in analogy to its demonstrated involvement in cytokeratin-hemidesmosome linkage in epidermis-may mediate the anchorage of desmin to the sarcolemma (i.e. to costameres).
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PMID:Altered distribution of plectin/HD1 in dystrophinopathies. 935 21

An attempt was made to study the histological and histochemical changes as well as immunohistochemical changes in desmin expression occurring in four types of clinical myopathies e.g. Chronic ischaemic myopathy due to Buerger's disease (Group I), Carcinomatous myopathy (Group II), Metabolic myopathy (Group III) and Muscular dystrophy (Group IV). The number of cases studied were 16 cases, 15 cases, 4 cases and 5 cases respectively. The study revealed: (i) a combination of normal, degenerated, necrotic and regenerating fibres in different proportions in all the four groups having maximum number of degenerated fibres in Group I and Group IV, relatively more number of regenerating fibres in groups III and absence of necrotic fibres in Group I. (ii) Altered tinctorial property in most of the fibres indicating degenerated and regenerating fibres in all the groups with Masson's trichrome staining against inconstant staining with PTAH appear to be a good indicator for myopathy. (iii) The Desmin expression was week and irregular in most of the cases with most of the fibres probably due to reduction of desmin content probably indicating degenerated fibres, appear to be a good indicator for myopathy. (iv) Chronic ischaemic myopathy showed close resemblance with muscular dystrophy though no typical or distinct distinguishing feature could be identified in these four groups.
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PMID:Study of myopathies by histological and histochemical methods with special reference to staining for desmin expression. 935 4

Plectin is a versatile linker protein which is associated with various types of cytoskeletal components and/or filaments including intermediate filaments, and its deficiency causes the disruption of myofibrils, or muscular dystrophy. To better understand the functional role of plectin in skeletal muscle fibers, we have examined the topological and structural relationships of plectin to intermediate filaments and Z-discs in rat diaphragm muscles by confocal and immunoelectron microscopy. Immunofluorescence analysis revealed that plectin was colocalized with desmin at the periphery of Z-discs. This plectin localization around Z-discs was constantly maintained irrespective of the contracted or extended state of the muscle fibers, suggesting either direct or indirect association of plectin with Z-discs. Immunogold labeling in skinned muscle fibers clearly demonstrated that plectin-labeled fine threads linked desmin intermediate filaments to Z-discs and connected intermediate filaments to each other. These results indicate that through plectin threads desmin intermediate filaments form lateral linkages among adjacent Z-discs, preventing individual myofibrils from disruptive contraction and ensuring effective force generation.
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PMID:Plectin is a linker of intermediate filaments to Z-discs in skeletal muscle fibers. 1003 36

Plectin is a multifunctional cytoskeletal linker protein with an intermediate filament-binding site and sequence elements with high homology to actin-binding domains. Mutations of the human plectin gene as well as the targeted inactivation of its murine analog cause a generalized blistering skin disorder and muscular dystrophy, thus implying its essential role in cells that are exposed to mechanical stress. In the present study we report the characterization of two new domain-specific plectin antibodies as well as ultrastructural localization of plectin in normal human skeletal muscle. Using immunogold electron microscopy, we localized plectin at three prominent sites: 1) Plectin is found at regularly spaced intervals along the cytoplasmic face of the plasma membrane. 2) It is distinctly localized at filamentous bridges between Z-lines of peripheral myofibrils and the sarcolemma and 3) at structures forming the intermyofibrillar scaffold. At the latter two locations, plectin and desmin were found to colocalize. Our ultrastructural analysis suggests that plectin may have a central role in the structural and functional organization of the intermediate filament cytoskeleton in mature human skeletal muscle.
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PMID:Immunogold EM reveals a close association of plectin and the desmin cytoskeleton in human skeletal muscle. 1035 Feb 17


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