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)

Gangliosides of healthy and pathologic muscles (amyotropic lateral sclerosis and facio-scapulo-humeral muscular dystrophy) were studied. Total ganglioside content of the affected muscles was approximately 2 fold higher than the unaffected muscles. Our results showed that ALS muscle contained a ganglioside which was absent in the unaffected and FSH muscular dystrophic muscles. Based on the results of hydrolysis with Vibrio cholerae neuraminidase and subsequent reactivity of the asialo derivative towards anti-globotetraosylceramide, we propose that the ALS ganglioside is sialosylglobtetraosylceramide, NeuAc(alpha 2-3)Ga1NAc(beta 1-3)Ga1(alpha 1-4)Ga1(beta 1-4)G1c-Cer.
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PMID:Sialosylglobotetraosylceramide: a marker for amyotropic lateral sclerosis. 669 69

It has recently been shown that merosin, a laminin variant, is deficient in a proportion of patients with congenital muscular dystrophy. Merosin is a heterotrimer composed of the alpha 2, beta 1, and gamma 1 subunits, and further studies have shown that it is the alpha 2 subunit that is deficient in these patients. Because the alpha 2 subunit is also expressed in S-merosin, found in Schwann cells, we have investigated whether peripheral nerve function is also affected in these patients. Motor nerve conduction velocities and sensory distal latencies were examined in 25 cases of congenital muscular dystrophy and the results correlated with the merosin expression in their muscle biopsies. All but two of the 10 merosin-deficient cases had reduced motor nerve conduction, whereas all the merosin-positive cases had normal results. Analysis of the biopsies of these two cases showed that they produced merosin in reduced amounts, in contrast to all other merosin-deficient patients that produced no or only traces of merosin. Sensory nerve studies showed no difference between the two groups. These results indicate that a peripheral demyelinating neuropathy is a feature of merosin-deficient congenital muscular dystrophy. The fact that the alpha 2 subunits is also expressed in Schwann cells supports the idea that the alpha 2 gene, located on chromosome 6, is the candidate gene for merosin-deficient congenital muscular dystrophy.
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PMID:Demyelinating peripheral neuropathy in merosin-deficient congenital muscular dystrophy. 857 59

Dystoroglycan is encoded by a single gene and cleaved into two proteins, alpha and beta-dystroglycan, by posttranslational processing. The 120kDa peripheral nerve isoform of alpha-dystroglycan binds laminin-2 comprised of the alpha 2, beta 1, and gamma 1 chains. In congenital muscular dystrophy and dy mice deficient in laminin alpha 2 chain, peripheral myelination is disturbed, suggesting a role for the dystroglycan- laminin interaction in peripheral myelinogenesis. To begin to test this hypothesis, we have characterized the dystroglycan-laminin interaction in peripheral nerve. We demonstrate that (1) alpha-dystroglycan is an extracellular peripheral membrane glycoprotein that links beta-dystroglycan in the Schwann cell outer membrane with laminin-2 in the endoneurial basal lamina, and (2) dystrophin homologues Dp116 and utrophin are cytoskeletal proteins of the Schwann cell cytoplasm. We also present data that suggest a role for glycosylation of alpha-dystroglycan in the interaction with laminin.
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PMID:Characterization of dp6troglycan-laminin interaction in peripheral nerve. 862 7

Laminin (laminin-1; alpha 1-beta 1-gamma 1) is known to promote myoblast proliferation, fusion, and myotube formation. Merosin (laminin-2 and -4; alpha 2-beta 1/beta 2-gamma 1) is the predominant laminin variant in skeletal muscle basement membranes; genetic defects affecting its structure or expression are the causes of some types of congenital muscular dystrophy. However, the precise nature of the functions of merosin in muscle remain unknown. We have developed an in vitro system that exploits human RD and mouse C2C12 myoblastic cell lines and their clonal variants to study the roles of merosin and laminin in myogenesis. In the parental cells, which fuse efficiently to multinucleated myotubes, merosin expression is upregulated as a function of differentiation while laminin expression is downregulated. Cells from fusion-deficient clones do not express either protein, but laminin or merosin added to the culture medium induced their fusion. Clonal variants which fuse, but form unstable myotubes, express laminin but not merosin. Exogenous merosin converted these myotubes to a stable phenotype, while laminin had no effect. Myotube instability was corrected most efficiently by transfection of the merosin-deficient cells with the merosin alpha 2 chain cDNA. Finally, merosin appears to promote myotube stability by preventing apoptosis. Hence, these studies identify novel biological functions for merosin in myoblast fusion and muscle cell survival; furthermore, these explain some of the pathogenic events observed in congenital muscular dystrophy caused by merosin deficiency and provide in vitro models to further investigate the molecular mechanisms of this disease.
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PMID:Merosin and laminin in myogenesis; specific requirement for merosin in myotube stability and survival. 883 Jul 76

We found partial merosin deficiency in a boy presenting at 12 yr with marked limb weakness and a waddling gait. Magnetic resonance imaging (MRI) showed the characteristic white matter abnormalities of merosin-negative congenital muscular dystrophy. There were also peripheral demyelinating polyneuropathy and evoked potential abnormalities. Unlike classic merosin-negative congenital muscular dystrophy, however, our patient was less hypotonic and weak and was able to achieve independent walking. Both by immunohistochemistry and Western blot merosin was shown to be moderately reduced. By immunostaining the alpha 1 laminin chain was overexpressed and beta 1 laminin chain was reduced. A spectrum of clinical phenotypes is likely to become evident in merosin-deficient patients in relation to the discovery of a range of molecular defects in, and variable expression of, this protein.
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PMID:Mild clinical phenotype in a 12-year-old boy with partial merosin deficiency and central and peripheral nervous system abnormalities. 893 2

We report adhalin deficiency in 8 patients with clinically diagnosed muscular dystrophy, dystrophic histopathological features, high plasma creatine kinase levels, normal expression of dystrophin, and marked variability of symptoms. Although the distribution of hyposthenia was similar in all 8 patients and predominantly involved muscles in the pelvic girdle, age at onset and rate of disease progression were highly variable: In 2 patients onset, at ages 24 and 25, was later than has been previously observed. We found no apparent relation between disease severity and the quantity of adhalin expressed. Two kinds of myopathy with adhalin deficiency have been reported: one caused by a mutation in the adhalin gene on chromosome 17 (primary adhalinopathy) and the other linked to chromosome 13. The product of the gene on chromosome 13 is probably associated with adhalin and its deficiency results in secondary adhalinopathy. The severity of clinical phenotypes in these adhalinopathies seems to relate more to the kind and site of the mutations than to the residual amount of the protein. We also detected a variable reduction in the laminin beta 1 subunit by immunohistochemistry in most patients, confirming that this is commonly associated with adhalin deficiency.
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PMID:Clinical heterogeneity of adhalin deficiency. 896 51

One recently described form of congenital muscular dystrophy (CMD) is associated with deficiency of the alpha 2-chain of laminin, an extracellular matrix protein that is specifically located in the basement membrane of placental villi, Schwann cells and skeletal muscle in healthy humans. This laminin is also normally present in the skin, kidney and basement membrane of blood vessels of the CNS, though it is absent from the blood vessel walls in other tissues. In this immunohistochemical study, we have explored the presence of the alpha 1, alpha 2, beta 1 and gamma 1 chains of laminin in the normal human retina, which are all localized in the basement membrane of blood vessels. This study adds to the growing evidence that the alpha 2-chain of laminin is selectively expressed in certain tissues, and suggests that CMD associated with a lack of this protein may be a multisystem disorder, with possible direct involvement of the visual system.
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PMID:Localization of laminin chains in the human retina: possible implications for congenital muscular dystrophy associated with alpha 2-chain of laminin deficiency. 913 36

Merosin, also called laminin-2, is an isoform of laminin comprised of the alpha 2, beta 1 and gamma 1 chains. Deficiency of merosin alpha 2 chain was recently identified as the primary cause of the classical form of congenital muscular dystrophy (CMD), an autosomal recessive neuromuscular disorder characterised by muscular dystrophy and brain white matter abnormalities. Interestingly, merosin-deficient CMD and its animal model dy mouse are also accompanied by dysmyelination of peripheral motor nerves. In peripheral nerve, merosin is expressed in the endoneurium surrounding the Schwann cell/myelin sheath, while the putative merosin receptors dystroglycan and alpha 6 beta 4 integrin are expressed in the outer membrane of Schwann cell/myelin sheath. Together with the well known fact that the deposition of laminin in the basement membrane is essential for Schwann cell myelination, these findings indicate that the interaction of merosin with dystroglycan and/or alpha 6 beta 4 integrin plays an important role in peripheral myelinogenesis and that the disturbance of this interaction leads to peripheral dysmyelination in merosin deficiency. The clinical significance of peripheral dysmyelination in merosin deficiency is also discussed.
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PMID:Peripheral nerve involvement in merosin-deficient congenital muscular dystrophy and dy mouse. 913 44

We studied the immunohistochemical expression of laminin subunits alpha 2, alpha 1, beta 1 in muscle and skin biopsy samples from three patients with congenital muscular dystrophy (CMD), and from ten control patients investigated for various neuromuscular disorders. Merosin alpha 2 chain was not detectable in the basement membrane of muscle fibers, or in the nerve endings, cutaneous nerves, and corium in the skin of the CMD patients, whereas it was clearly expressed in the skin biopsy samples from control patients, especially in the nerve endings of the arrector pili muscles. Laminin alpha 1 chain was expressed in the corium, in the muscle fiber membranes of arrector pili muscles and in cutaneous nerve fibers, perineurium and blood vessels in controls and in CMD patients. Laminin beta 1 chain was faintly expressed in the corium, and a diffuse labeling was detected on arrector pili muscle with enhanced expression at nerve endings, intracutaneous nerves and capillaries, with similar findings in all biopsy specimens. For merosin-negative CMD patients, skin biopsy may provide a diagnostic alternative to muscle biopsy since merosin deficiency can be demonstrated in the skin neural structures, and in particular in the nerve endings of the arrector pili smooth muscles.
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PMID:Immunohistochemical study of merosin-negative congenital muscular dystrophy: laminin alpha 2 deficiency in skin biopsy. 925 83

Using specific monoclonal antibodies against different subunits of laminin, we studied the differential distribution pattern of several laminin chains in the central (CNS) and peripheral (PNS) nervous system. Laminin chains alpha 1, beta 1 and gamma 1, were found in the basement membrane (BM) of blood vessels in both CNS and PNS. In contrast, laminin alpha 2 though present in the BM of capillaries in the CNS, was completely absent from PNS capillaries. Laminins alpha 2, beta 1, gamma 1 could be detected in peripheral nerve, in the BM of Schwann cells, which did not contain Laminin alpha 1. The possible importance of laminin alpha 2 for myelination in the PNS as well as in the function of the blood-brain barrier in the CNS, and its potential relevance to the pathology of congenital muscular dystrophy associated with deficiency of this laminin chain, is discussed.
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PMID:Immunolocalization of several laminin chains in the normal human central and peripheral nervous system. 926 51


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