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)

In our experience, more than half of muscular dystrophy patients show a primary dystrophinopathy. The underlying cause of muscular dystrophy in the vast majority of patients with normal dystrophin is unknown. Recently, a French family with 4 young siblings showing a muscular dystrophy of unknown progression was shown to have a primary deficiency of "adhalin," the 50-kd dystrophin-associated protein. Here we report the screening of the entire adhalin coding sequence in muscle biopsy specimens from 30 muscular dystrophy patients to (1) determine whether adhalin deficiency is restricted to the French population, (2) determine the incidence of adhalin deficiency in muscular dystrophy patients, and (3) characterize the clinical features and mutations in adhalin-deficient patients. We identified a single African-American girl with childhood-onset muscular dystrophy and adhalin gene mutations. We found her to be a compound heterozygote for two different mutations of the same amino acid (Arg98Cys; Arg98His), one of which was previously identified in the French family. Our results suggest that primary adhalin deficiency in patients with muscular dystrophy but normal dystrophin is relatively infrequent, and that adhalin-deficient patients are not restricted to the French population.
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PMID:Primary adhalin deficiency as a cause of muscular dystrophy in patients with normal dystrophin. 766 18

Following free vascularized normal muscle graft in mice, a study was made to determine whether dystrophin expression is possible in dystrophin-deficient muscles. In this study, dystrophic C57BL/10 ScSn-mdx mice were used as recipients and normal C57BL/10 ScSn mice as donors. A free vascularized quadriceps muscle 8.0 x 6.0 x 6.0 mm in size was orthotopically transplanted into a muscle defect produced in the recipient mouse. The diameter of the sutured vessels was about 0.4 mm. Transplantation was successful in 7 of 20 mice. At 12 weeks after the transplantation, the grafted muscle was examined by immunocytochemical stain using anti-dystrophin antibody. This study showed that dystrophin was expressed in the transplanted muscle but not in the adjacent recipient quadriceps muscle, suggesting that grafted donor cells with dystrophin failed to migrate into dystrophic muscle cells and fuse together. However, since the grafted normal skeletal muscle successfully survived and normal dystrophin was expressed in almost all the grafted muscle fibers, the possibility was suggested that the function of muscular dystrophy muscle can be compensated by complete replacement with a larger muscle.
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PMID:Experimental challenge for the treatment of Duchenne muscular dystrophy using a vascularized free muscle graft. 770 29

Dystrophin is normally localized in smooth muscle fibers of various organs in experimental animals, and it has been shown to be defective in the smooth muscle fibers of the mdx mouse, including the myoepithelial cell layer of the sweat glands. We investigated dystrophin localization, using three antisera raised against different domains of skeletal muscle type of dystrophin, in the smooth muscle structures of the skin, using immunohistochemical methods with monoclonal antibodies against dystrophin, in 24 patients with various neuromuscular diseases, and in a normal control. Skin biopsy showed a strong dystrophin reaction in the arrector pili muscles and in the myoepithelial cells of the sweat glands of patients with congenital muscular dystrophy, polymyositis, distal myopathy, putative Duchenne muscular dystrophy carriers, myoglobinuria, neurogenic atrophy and in a normal control. A faint positive dystrophin reaction was seen in four patients with Becker muscular dystrophy, whereas it was absent in 3 patients with Duchenne muscular dystrophy. As our data suggest that immunohistochemical dystrophin expression in smooth muscle structures of the skin is similar to that observed in striated muscle, skin biopsy may represent an alternative way to ascertain dystrophin deficiency.
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PMID:Dystrophin expression in skin biopsy immunohistochemical. Localisation of striated muscle type dystrophin. 775 41

In various neuromuscular diseases, the most significant muscle degeneration is muscle fiber necrosis as seen in Duchenne muscular dystrophy (DMD). A certain membrane instability is probably responsible for muscle fiber necrosis, because defects in membrane proteins have been proposed to associate with progressive muscular dystrophies including dystrophin in DMD, a 50 KD subunit of dystrophin associated glycoprotein (DAG) in severe childhood autosomal recessive muscular dystrophy (SCARMD), and subunit M of laminin (merosin) in congenital muscular dystrophy and dy mouse. The vulnerable muscle surface membrane may permit extracellular calcium influx into the sarcoplasm resulting in focal myofibrillar hypercontraction (opaque fiber) and activation of proteases such as calpain and cathepsins. The muscle fiber then undergoes necrosis and allows macrophage invasion, followed by muscle fiber regeneration. Focal myofibrillar degeneration involving rimmed vacuole (RV) formation is an another striking muscle fiber degeneration seen in various neuromuscular diseases including inclusion body myositis (IBM) and distal myopathy with rimmed vacuole formation (DMRV). Abnormal accumulation of ubiquitin, beta-amyloid protein precursor and tau protein has been described in IBM by Askanas et al. The similar findings are also recognizable in DMRV and in an experimentally induced myopathy after long-term chloroquin administration to rat. Therefore, if we clarify the pathomechanism of degenerative process involved in the rimmed vacuole formation, the results may provide some insights into the understanding the process involved in amyloid plaque formation in Alzheimer's disease.
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PMID:[Muscle pathologic diagnosis--mechanism in muscle fiber degeneration]. 777 35

Dystrophin is a 427-kDa protein localized adjacent to the sarcolemma in skeletal muscle. Its physiological role remains uncertain, although its absence is known to cause muscular dystrophy. In this study, the function of dystrophin was investigated using the dystrophin-deficient mdx mouse. Control and mdx animals at 2, 5, and 13 wk of age (n = 8-11/age) were compared to evaluate in situ gastrocnemius-plantaris-soleus muscle contractile, endurance, and excitability properties at nondegenerated, degenerated, and regenerated stages, respectively. Twitch and tetanic tensions expressed per gram of muscle mass were lower in mdx muscle only at 5 wk. Fatigue produced during successive contractions at 2, 10, and 20 Hz did not differ between the two groups at 2 and 5 wk but was lower in mdx muscle at 13 wk. This was not attributed to differences in mitochondria, since cytochrome-c oxidase activity was similar in mdx and control muscle. Contractile properties of control and mdx muscle became faster with age, and at 13 wk the time to peak twitch tension was shorter in mdx muscle relative to control, whereas the half-relaxation times did not differ. Mass action potential area (M wave), an index of muscle excitability, was not significantly different between mdx and control muscle at 2 or 5 wk but was greater in mdx muscle at 13 wk. Thus, in this weight-bearing muscle group, the lack of dystrophin has only a moderate impact in modifying muscle function relative to contractile properties, fatigability, or excitability.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Performance and excitability of mdx mouse muscle at 2, 5, and 13 wk of age. 777 42

New observations demonstrate that several childhood forms of muscular dystrophy share a common pathogenesis. In muscle, dystrophin occurs as part of a membrane complex (dystrophin-glycoprotein) linking the cytoskeleton to the basal lamina. In Duchenne muscular dystrophy, dystrophin deficiency disrupts the linkage of the integral glycoproteins of the sarcolemma and leads to muscle fiber necrosis. In severe childhood autosomal recessive muscular dystrophy, a selective deficiency of adhalin (50-kd glycoprotein) also causes dysfunction of the dystrophin-glycoprotein complex. Most recently, a form of congenital muscular dystrophy demonstrates deficiency of laminin M (merosin) further demonstrating that sarcolemmal instability results from defects in structural proteins of the basal lamina. Animal models have been identified also demonstrating defects in specific proteins linking the subsarcolemmal cytoskeleton to the extracellular matrix. The mdx mouse has a defect in the gene encoding dystrophin. The cardiomyopathic hamster shows a specific deficiency of adhalin in skeletal muscle. The dy/dy mouse has been found deficient in merosin. These animal models will help researchers to understand their human counterparts and provide a system for testing therapeutic strategies.
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PMID:The childhood muscular dystrophies: diseases sharing a common pathogenesis of membrane instability. 778 8

1. Attachment to extracellular matrix is thought to be particularly important for striated muscle cells, since skeletal and heart muscle have to withstand considerably strong forces. 2. We have recently shown that a defect in a protein of the muscle basement membrane, M-laminin, is correlated with muscular dystrophy in human and mouse. The disease associated with defects in M-laminin is thus analogous to that caused by defects in the cytoskeletal protein, dystrophin, the Duchenne/Becker muscular dystrophy. 3. One may propose the hypothesis that a pathway of interacting proteins is required to connect the cytoskeleton of the muscle fiber to the extracellular matrix, and that a defect in any protein in this chain would result in severe impairment of muscle cell attachment with resulting muscle damage upon use of the muscle. The existence of such chains of proteins may be expected from known mutations in muscle proteins in Drosophila and Caenorhabditis elegans. Some of these mutations cause phenotypes resembling muscular dystrophy in mammals. 4. It will be important to identify all the proteins that are participants in muscle cell attachment, including receptors for M-laminin and proteins associated with these receptors.
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PMID:Cell adhesion in muscle. 778 6

1. MDX mice derived from a colony of C57BL/10ScSn mice develop an X-linked recessive muscular dystrophy, thus providing an adequate model to study the pathogenesis of muscular dystrophy. 2. Skeletal myofibers of MDX mutant mice were heterogeneous, with disorganization of myofilaments and the absence of immunolabelling for dystrophin with monoclonal antibody DY4/6D3. 3. Marked deposition of reticulin, collagenic fiber (types, I, IV) and laminin (LN) were consistently present mostly around lesioned and necrotic myofibers associated with an intense inflammatory reaction, whereas strong immunolabelling for TIII-C, TIV-C and FN was often associated with regenerated fibers. 4. During the onset (3 weeks of postnatal life) of disease and height of myonecrosis (5-6 weeks of postnatal life), popliteal lymph nodes showed dense argyrophilic meshwork, intense immunolabelling for collagens types I and IV, FN, LN and enlargement of the hili which were packed with mononuclear cells. Such alterations, albeit less intense, were still observed in MDX mice with 20 weeks of postnatal life. 5. The results support the view that ECM components might be influencing the migration of inflammatory cells and the process of myonecrosis in the skeletal muscle of MDX dystrophic mice.
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PMID:Altered deposition of extracellular matrix components in the skeletal muscle and lymph node of the MDX dystrophic mouse. 778 7

We examined 19 muscle biopsies from 14 patients with autosomal recessive distal muscular dystrophy (DisMD) histochemically and immunohistochemically to characterize the histologic features of this disease and to determine whether dystrophin and dystrophin-associated proteins (DAPs) are normally present in the muscles of patients with this disorder. The common histologic features in DisMD were active muscle fiber necrosis and regeneration with variation in fiber size, predominantly in the gastrocnemius muscle. There were occasional disorganizations of the intermyofibrillar network such as moth-eaten appearance, lobulated, whorled and targetoid fibers. In one half of the patients, small angular fibers and scattered rimmed vacuoles were also found. On immunohistochemical examination, dystrophin, DAPs, spectrin and laminin were normally expressed along the surface membrane of muscle fibers, even in the advanced stages of the disease. In contrast, dystrophin was absent and DAPs reduced in the sarcolemma of Duchenne muscular dystrophy (DMD) muscles. The overall histochemical features in DisMD were similar to those seen in DMD, though dystrophin and DAPs were normally expressed even in severely affected gastrocnemius muscle. A defect in an as yet unidentified protein rather than in DAPs and dystrophin is probably responsible for the muscle fiber necrosis in DisMD.
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PMID:Autosomal recessive distal muscular dystrophy: normal expression of dystrophin, utrophin and dystrophin-associated proteins in muscle fibers. 783 50

All previous studies of the localization of utrophin (the dystrophin-related protein) in muscle and other tissues have been performed only with antibodies against the C-terminal region of the protein. Since several short forms of dystrophin, the apo-dystrophins, are produced from the 3' end of the dystrophin gene, there is a possibility that similar short forms of utrophin exist and that these could be responsible for some of the many different localizations of 'utrophin' in muscle. We have produced a new panel of 15 mAbs against the N-terminal region of utrophin and we have used it together with mAbs against the C-terminal region to show that full-length utrophin is present at neuromuscular junctions, in nerves, blood vessels and capillaries in normal muscle and in the sarcolemma of patients with muscular dystrophy and dermatomyositis. However, two of the 15 mAbs also recognised rat/mouse utrophin and both of these detected an additional 62 kDa protein on Western blots of rat C6 glioma cells. This potential 62 kDa 'apo-utrophin' was not detected in human cerebral cortex, in rat Schwannoma cells nor in any of the non-nerve cells and tissues tested.
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PMID:Full-length and short forms of utrophin, the dystrophin-related protein. 784 13


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