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

The physiatrist can now be instrumental in prolonging the survival of individuals with neuromuscular disease by using respiratory muscle aids. As a result, morbidity and mortality from cardiomyopathy are likely to increase for patients with generalized myopathies. One hundred consecutive patients with dystrophin-deficient muscular dystrophy and a mean age of 17.2 yr (range, 5-41) satisfied criteria for having dilated cardiomyopathy (DCM) and received digitalis and diuretics. Nine of the 14 patients were symptom-free, despite left ventricular ejection fractions (LVEFs) of 25-40%. The five patients with symptomatic heart failure had severe ventricular dilatation, with LVEFs < 25%. Two of the five patients died of heart failure within 1 yr. For the remaining three patients, we evaluated the addition of the angiotensin-converting enzyme (ACE) inhibitor enalapril and, subsequently, the use of beta-blockers to the therapeutic regimen. Addition of these medications, never before attempted in the management of cardiomyopathy associated with generalized myopathic disease, complemented each other in relieving symptoms and reversing signs of congestive heart failure and DCM. We conclude that the combination of ACE inhibitor and beta-blocker deserves further exploration for inclusion in any management regimen for the treatment of muscular dystrophy-associated cardiomyopathy.
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PMID:A management trial for Duchenne cardiomyopathy. 757 10

It has recently been shown that merosin, an extracellular matrix protein linked to the dystrophin-associated glycoproteins, is deficient in a proportion of patients with classical congenital muscular dystrophy (CMD). We have undertaken a detailed study of the clinical features and brain imaging in 24 cases of CMD in relation to the merosin status. Immunocytochemistry showed that merosin was present in 13 cases and markedly deficient in 11. In the merosin-positive cases, the maximum motor achievement was independent walking in 11, walking with support in one and sitting unsupported in one (currently 18 months old). In contrast, none of the merosin-deficient cases achieved independent ambulation. Two achieved walking with support, nine standing with support. In addition, nine of the 11 merosin-deficient cases had a creatine kinase level greater than 2000 whereas only one merosin-positive case had this degree of elevation. Magnetic resonance imaging of the brain was carried out on 15 of the children. All eight merosin-positive cases had normal scans whereas all seven of the merosin-deficient cases had significant changes in the white matter. This study has demonstrated that children with merosin-deficient CMD have a more severe clinical phenotype and associated white matter changes on brain imaging.
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PMID:Clinical phenotype in congenital muscular dystrophy: correlation with expression of merosin in skeletal muscle. 758 Feb 43

Dystrophin is a protein product of the gene responsible for Duchenne muscular dystrophy (DMD), and is a long slender protein localized at the protoplasmic surface of sarcolemma. Dystrophin binds with actin filaments at its amino-terminal region, and with dystrophin-associated proteins (DAPs) at its carboxyl-terminal region. DAPs are composed of a glycoprotein complex and a syntrophin complex, a complex of proteins binding with dystrophin and located intracellularly. Glycoprotein complex is composed of dystroglycan complex and sarcoglycan complex, both of which are membrane-integrated. Dystrophin binds with dystroglycan complex which transverse through sarcolemma and then binds with laminin in the basal lamina, forming a long axis between action threads and the extracellular matrix. Sarcoglycan complex does not directly bind with dystrophin but binds with dystroglycan complex. Disruption of the axis results in dystrophic changes in one kind of congenital muscular dystrophy (CMD). Loss of the sarcoglycan complex gives rise to childhood severe autosomal recessive muscular dystrophy (SCARMD) which is clinically very similar to DMD. In DMD, the sarcoglycan complex is mostly lost, and the axis is for the most part defective. Therefore, it is likely that the causes of DMD and SCARMD may be similar and may be modified by the mechanism which gives rise to CMD.
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PMID:[Dystrophin, dystrophin-associated protein and dystrophinopathy]. 758 23

Aberrant expression of the dystrophin-associated protein complex is thought to underlie the pathogenesis of Duchenne dystrophy, Becker muscular dystrophy, and severe childhood autosomal recessive muscular dystrophy. Recently, our laboratory identified an agrin receptor from Torpedo electric organ postsynaptic membranes. It is a heteromer of 190- and 50-kDa subunits with similarity to two components of the dystrophin-associated protein complex of alpha- and beta-dystroglycan. We now confirm the relationship between the Torpedo agrin receptor and mammalian dystroglycans and provide further information about the structure of the alpha-dystroglycan-beta-dystroglycan complex. The sequences of three peptides from each Torpedo subunit were 69% identical to mammalian dystroglycans. An antiserum to mammalian beta-dystroglycan recognizes the Torpedo 50-kDa polypeptide. Additionally, like alpha-dystroglycan, the 190-kDa agrin receptor subunit binds laminin. Previous studies have indicated that alpha- and beta-dystroglycan arise by cleavage of a precursor protein. Tryptic peptide mapping of both subunits and amino-terminal sequencing of Torpedo beta-dystroglycan indicate a single cleavage site, corresponding to serine 654 of the mammalian dystroglycan precursor. Gel electrophoresis analysis indicates there is at least one intrachain disulfide bond in beta-dystroglycan. These results provide precise primary structures for alpha- and beta-dystroglycan.
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PMID:The alpha-dystroglycan-beta-dystroglycan complex. Membrane organization and relationship to an agrin receptor. 759 85

A patient with non-Fukuyama type merosin-positive congenital muscular dystrophy (nonFCMD) who had severe muscle weakness leading to early death was reported. He was the first product of epileptic mother who had been placed on phenobarbital and phenytoin. The patient had severe respiratory failure and muscle weakness at the neonatal period, and died at 4 months of age. Multiple joint contractures were also noted at birth. Serum creatine kinase was within normal limits (123 IU/l). Electromyography showed a myogenic pattern. Brain computed tomographic (CT) scan and magnetic resonance imaging (MRI) were normal without white matter lucency or pachygyria. Muscle biopsy revealed dystrophic changes and type 2C fiber predominance. Dystrophin, dystrophin-associated glycoproteins and merosin were all positively demonstrated. Although patients with merosin-positive nonFCMD have relatively mild clinical course, our patient had severe muscle weakness with fatal outcome. Defect in muscle fiber maturation and differentiation, such as an increase of undifferentiated type 2C fibers, may be a major factor to influence muscle symptoms in non FCMD.
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PMID:[Non-Fukuyama type merosin-positive congenital muscular dystrophy with delayed muscle fiber type differentiation: a case report]. 761 93

A calcium-dependent proteinase (calpain) has been suggested to play an important role in muscle degradation in Duchenne muscular dystrophy (DMD). In immunohistochemical studies, calpain and its endogenous inhibitor (calpastatin) were located exclusively in the cytoplasm in normal human muscles. The intensity of the staining was stronger in type 1 than in type 2 fibers. Quantitative immunohistochemical study showed an increase of calpain in biopsied muscles from the patients with DMD and Becker muscular dystrophy. Abnormal increases in calpain and calpastatin were demonstrated mainly in atrophic fibers, whereas necrotic fibers showed moderate or weak immunoreactions for the enzymes. Opaque fibers and hypertrophic fibers were negative. Not all dystrophin-deficient muscle fibers necessarily showed a strong reaction for calpain. We suggest that calpain may play an important role in muscle fiber degradation, especially in the early stage of muscle degradation in muscular dystrophy.
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PMID:Immunohistochemical study of calpain and its endogenous inhibitor in the skeletal muscle of muscular dystrophy. 761 37

Mutations in the dystrophin gene can lead to muscular dystrophy. The dystrophin-associated complex of proteins that was first characterized at the muscle cell membrane is now also being found in other cell types.
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PMID:Muscular dystrophy. Brain, as well as brawn? 762 42

In this report, we study the suitable conditions for myoblast cultures through analysis of myoblast growth and differentiation, and then try to develop a mouse model for myoblast transfer therapy (MTT). Recently, some research has indicated that Muscular Dystrophy Murine Mice (MDX) have an X-linked recessive dystrophin deficiency which is caused by dystrophin gene point mutation at the X chromosome. Therefore, MDX mice are usually used for MTT models of muscular dystrophy disease. Control mice, C57BL10/SCSN (B-10) were chosen as a source of normal myoblasts. Myoblasts isolated from the hindlimb muscle tissues of two- to three-day-old neonatal B-10 mice were cultured in vitro for one to seven days. Through our modifyied techniques of isolation and culturing conditions, a myoblast purity of 70% could be achieved, with fibroblast the only contaminating cell type. The proliferative capacity and the doubling time of myoblasts were counted from analysis of growth kinetics. While differentiative capacity was analyzed morphologically, we found the fusion of myoblasts was time-dependent. Immunostaining myoblasts of different stages with anti-dystrophin antibody showed that purified myoblasts with the capacity of fusion can express dystrophin and can be utilized as a donating source in MTT. In the MTT experiment, eight young MDX mice were injected with normal myoblasts at a concentration of 1 x 10(6) cells. All transplated mice received daily cyclosporine A injection for immunosuppression. Two to three months later, dystrophin was found in the myoblast-transferred muscles while staining immunocytochemically. The result suggests that we successfully transferred the normal dystrophin gene from the normal myoblasts into the MDX mice since their myoblast-injected muscle could express dystrophin.
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PMID:[Study of myoblast culture and myoblast transfer therapy in dystrophic mice]. 765 Jul 79

Homozygous adhalin gene mutations were found in three patients from two consanguineous families with autosomal recessive childhood onset muscular dystrophy. Muscle biopsies from patients in each family showed complete absence of adhalin. Sequencing of adhalin cDNA prepared from skeletal muscle by reverse transcription PCR demonstrated a cytosine to thymidine substitution at nt 229 in the patient in family 1 and an adenine to guanine substitution at nt 410 and a 15-base insertion between nt 408 and 409 in the two patients in family 2. Sequencing of genomic DNA prepared from peripheral blood leukocytes by PCR confirmed these mutations. The parents in each family were found to be heterozygous for the respective mutations. These adhalin gene mutations are presumed to be responsible for the absence of adhalin in the skeletal muscle. Adhalin deficiency likely causes disruption of the muscle cell membrane, resulting in dystrophic changes in the skeletal muscle similar to dystrophin deficiency in Duchenne muscular dystrophy.
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PMID:Adhalin gene mutations in patients with autosomal recessive childhood onset muscular dystrophy with adhalin deficiency. 765 92

Duchenne's dystrophy (DMD), a recessive chromosome X-related disease, is the most common and severe form of myopathy. The different theories (vascular, neurogenic, membraneous, calcic and auto-immune) formulated to account for this disease have not been swept away by the discovery of the DMD gene and the deficient protein, dystrophin, since the exact cellular role played by the latter is still unknown. Our work on skeletal muscle has demonstrated a mitochondrial deficiency of the calcium-specific protein, calmitine, in degenerating muscle of myopathic persons and animals. Considering its great affinity for calcium, this protein specific to skeletal muscle could be essential to mitochondrial calcium regulation and thus to the functioning of the entire muscle cell. Its deficiency in Duchenne's and Becker type muscular dystrophy could be due to a mitochondrial genome alteration solely accountable for muscular degeneration. This hypothesis challenges the supposedly essential but still undefined role that researchers have attributed to dystrophin.
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PMID:Muscular degeneration in Duchenne's dystrophy may be caused by a mitochondrial defect. 766 33


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