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

Extraocular muscle is uniquely spared from damage in merosin-deficient congenital muscular dystrophy. Using a murine model, we have tested the hypothesis that the maintenance of calcium homeostasis is mechanistic in extraocular muscle protection. Atomic absorption spectroscopy has demonstrated a strong correlation between the perturbation of calcium homeostasis in hindlimb muscle that is severely damaged and the absence of changes in calcium in extraocular muscle. If, as in other skeletal muscles, extraocular muscle fibers are destabilized by merosin deficiency, we would expect an increase in total muscle calcium coupled with an adaptive response in the high capacity/speed of the sarcoplasmic reticulum of the eye muscle. However, we have not observed the expected increases in total muscle calcium content, Ca2+-ATPase activity, Na+/Ca2+ exchanger content, or smooth ER Ca2+-ATPase content that are predicted by this model. Instead, these results indicate that the increased membrane permeability that characterizes, and is potentially mechanistic in, myofiber degeneration in muscular dystrophy does not occur in merosin-deficient extraocular muscle. Thus, the high-capacity calcium-scavenging systems are not primarily responsible for extraocular muscle protection in muscular dystrophy.
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PMID:Extraocular muscle in merosin-deficient muscular dystrophy: cation homeostasis is maintained but is not mechanistic in muscle sparing. 958 6

Merosin alpha 2 chain, an extracellular matrix protein, is deficient in a proportion of patients with classical congenital muscular dystrophy (CMD). A study of clinical, laboratory and histopathological features of 18 patients with CMD was performed in relation to the merosin expression in muscle biopsy. Immunohistochemistry study showed that merosin was deficient in 11 patients and present in 7. None of the 9 merosin-deficient patients evaluated achieved walking. In contrast, 4 of 7 merosin-positive patients achieved independent ambulation. Creatine kinase levels were higher in merosin-deficient patients, but this difference was not statistically significant. Motor nerve conduction study was carried out on 12 children. All 4 merosin-positive patients had normal exams whereas 2 out 8 merosin-deficient patients presented decreased motor nerve conduction velocity. Among 69 histopathological features studied, we did not find any significant difference between merosin-deficient and merosin-positive patients. These results suggest that merosin status evaluation is important in the determination of the prognostic, since merosin-positive patients can achieve independent walking. This study also suggests that there is no relation between absence of merosin and histopathological features.
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PMID:[Congenital muscular dystrophy and merosin deficiency]. 962 38

The evidence of severe structural brain abnormalities in association with severe mental retardation is characteristic in congenital muscular dystrophy (CMD) forms other than the 'classical' form. However, it seems that the nosology of CMD is not complete yet, as we have clinical, immunohistochemical and genetic data suggesting that there are other unclassified forms. Here we report two CMD siblings from a consanguineous family with partial merosin-deficiency in muscle biopsies, severe mental retardation and normal MRI of the brain. The disease was not linked to the LAMA2 gene (6q22-23) or to Fukuyama congenital muscular dystrophy (FCMD) (9q31-33). To our knowledge, such an association may constitute a new entity within the broad clinical spectrum of CMD.
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PMID:Merosin-deficient congenital muscular dystrophy with severe mental retardation and normal cranial MRI: a report of two siblings. 963 97

Muscles or muscle groups exhibiting responses to neuromuscular disease that are unlike those of other skeletal muscles may provide novel information about pathogenesis leading to improved treatment strategies. The author's laboratory studies the relationship between the unique phenotype of the extraocular muscles and their selective sparing or targeting in neuromuscular disease. This commentary evaluates the evidence for and against four hypotheses for the selective protection of extraocular muscle in Duchenne muscular dystrophy (DMD) and merosin-deficient congenital muscular dystrophy (CMD).
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PMID:Commentary: extraocular muscle sparing in muscular dystrophy: a critical evaluation of potential protective mechanisms. 963 2

Mutations in the gene coding for the alpha 2 chain of laminin-2 and -4 (merosin) cause a severe form of congenital muscular dystrophy in humans and mice. To establish a defined model for in vitro and in vivo studies of the role of laminin alpha 2/merosin in development and cell and tissue function, we generated several lines of mutant embryonic stem (ES) cell with disruption of the laminin alpha 2 chain gene. We find that homozygous mutant ES cells differentiate normally in vitro, giving rise to cardiomyocytes, myotubes, and smooth muscle cells in addition to many other cell types. However, the myotubes that are formed are unstable. They detach, collapse, and degenerate, a process which is initiated at the appearance of the mature, contractile phenotype of the cells. We propose that the detachment and death of contracting myotubes in vitro has its counterpart in vivo and that contraction-induced myofiber damage, along with the lack of survival cues provided by laminin alpha 2/merosin, is a significant contribution to muscle degeneration in merosin-deficient muscular dystrophy.
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PMID:Disruption of the lama2 gene in embryonic stem cells: laminin alpha 2 is necessary for sustenance of mature muscle cells. 963 19

Muscle biopsies of 13 congenital muscular dystrophy (CMD) patients were investigated for the expression of laminin-alpha2 (merosin), beta-dystroglycan, alpha-sarcoglycan (adhalin) and dystrophin. Expression of these proteins was normal in six out of eight patients with pure-CMD, in three non-Japanese patients clinically resembling Fukuyama-CMD (F-CMD), and in two patients with Walker-Warburg syndrome (WWS). The two 'pure'-CMD patients with white matter hypodensity showed severely decreased laminin-alpha2 expression and normal expression of the other proteins. Our findings in the non-Japanese patients, clinically resembling F-CMD, are different from those in Japanese cases with F-CMD in the literature. Consequently, our patients suffer from WWS or from another yet undetermined form of CMD.
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PMID:Laminin-alpha2 (merosin), beta-dystroglycan, alpha-sarcoglycan (adhalin), and dystrophin expression in congenital muscular dystrophies: an immunohistochemical study. 963 97

This study evaluates whether abnormalities of visual function are present in children with congenital muscular dystrophy and whether these, if present, are associated with merosin status or magnetic resonance imaging (MRI) findings. Twenty children (age range 5-17 years) with a diagnosis of classical congenital muscular dystrophy were assessed on visual acuity, stereopsis, and visual fields and the results compared with merosin status and MRI findings. Visual-evoked potential results were available for 14 of 20 children. All 20 children revealed normal results on all the clinical tests assessing visual function, irrespective of their merosin status or of MRI findings. Visual-evoked potentials were normal in the children with merosin-positive congenital muscular dystrophy but were abnormal in those with merosin deficiency. Unlike the other forms of congenital muscular dystrophy, which are associated with structural brain changes and eye involvement, visual function was always normal in the classical form of congenital muscular dystrophy. Interestingly, visual function was normal also in the group of children with merosin-deficient congenital muscular dystrophy who manifested white matter changes involving the occipital lobes on MRI and abnormal visual evoked potentials. Further studies are needed to specify the nature of the white matter changes observed with MRI and the reason for the dissociation between clinical and neurophysiologic findings.
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PMID:Visual function in children with merosin-deficient and merosin-positive congenital muscular dystrophy. 965 Jun 78

Merosin, the laminin alpha2 chain located on the surface of muscle fibers, has recently been shown to be absent in a subset of cases with the classical type of congenital muscular dystrophy (Cl-CMD). By immunocytochemistry and immunoblot analysis, using monoclonal antibodies to both the 80- and the 320-kDa fragments, the same protein was found to be only partially deficient in 3 of our cases. All these 3 patients were able to walk, with evidence of a mild to moderate muscle involvement, as opposed to the merosin-negative cases which are never ambulant because they are affected by severe muscular deficit. All of them also suffered from a late onset form of epilepsy, a clinical expression of brain involvement rarely described in cases with merosin-negative CMD. The 3 patients with CMD and partial merosin deficiency were investigated by brain MRI and pattern reversal visual evoked potentials (VEP) associated with electroretinography (ERG). The results were compared with those obtained by similar studies on 3 of our cases with complete merosin deficiency. In both types of patients, the neuroimaging evaluation showed supratentorial white matter changes, usually of moderate degree, irrespective of the amount of merosin detected in muscle. The VEP were normal in all the 3 cases with partial merosin deficiency, whereas they showed reduced amplitude or prolonged latency in all the 3 cases with the merosin-negative form. ERG was normal in all 6 cases. As a whole, our data indicate that leukoencephalopathy does not seem to distinguish between the two variants of Cl-CMD. On the other hand, a benign muscle involvement and normal VEP findings seem to distinguish CMD patients with partial merosin deficiency from those with complete deficiency of the same protein. Late onset epilepsy, evident in all our 3 cases with partial merosin deficiency, needs to be evaluated in a larger series of patients in order to be considered a characteristic of this variant of CMD.
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PMID:Congenital muscular dystrophy with partial merosin deficiency and late onset epilepsy. 969 31

Humans and mice with deficiency of the alpha2 subunit of the basement membrane protein laminin-2/merosin suffer from merosin-deficient congenital muscular dystrophy (MCMD). We have expressed a human laminin alpha2 chain transgene under the regulation of a muscle-specific creatine kinase promoter in mice with complete or partial deficiency of merosin. The transgene restores the synthesis and localization of merosin in skeletal muscle, and greatly improves muscle morphology and integrity and the health and longevity of the mice. However, the transgenic mice share with the nontransgenic dystrophic mice a progressive lameness of hind legs, suggestive of a nerve defect. These results indicate that the absence of merosin in tissues other than the muscle, such as nervous tissue, is a critical component of MCMD. Future gene therapies of human MCMD, and perhaps of other forms of muscular dystrophy, may require restoration of the defective gene product in multiple tissues.
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PMID:Merosin-deficient congenital muscular dystrophy. Partial genetic correction in two mouse models. 971 Apr 54

The alpha-dystroglycan binding properties of laminins extracted from fully differentiated skeletal muscle were characterized. We observed that the laminins expressed predominantly in normal adult rat or mouse skeletal muscle bound alpha-dystroglycan in a Ca2+-dependent, ionic strength-sensitive, but heparin-insensitive manner as we had observed previously with purified placental merosin (Pall, E. A., Bolton, K. M., and Ervasti, J. M. 1996 J. Biol. Chem. 271, 3817-3821). Rat skeletal muscle laminins partially purified by heparin-agarose affinity chromatography also bound alpha-dystroglycan without sensitivity to heparin. We also confirm previous studies of dystrophic dy/dy mouse skeletal muscle showing that the alpha2 chain of merosin is reduced markedly and that the laminin alpha1 chain is not up-regulated detectably. However, we further observed a quantitative decrease in the expression of laminin beta/gamma chain immunoreactivity in alpha2 chain-deficient dy/dy skeletal muscle and reduced alpha-dystroglycan binding activity in laminin extracts from dy/dy muscle. Most interestingly, the alpha-dystroglycan binding activity of residual laminins expressed in merosin-deficient dy/dy skeletal muscle was inhibited dramatically (69 +/- 19%) by heparin. These results identify a potentially important biochemical difference between the laminins expressed in normal and dy/dy skeletal muscle which may provide a molecular basis for the inability of other laminin variants to compensate fully for the deficiency of merosin in some forms of muscular dystrophy.
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PMID:Differential heparin sensitivity of alpha-dystroglycan binding to laminins expressed in normal and dy/dy mouse skeletal muscle. 972 35


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