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

This study attempted to dispel the confusion that exists in the understanding of the origin of myoblasts during muscle regeneration. Regenerating hamster muscle explants from cultures were studied under the EM on 4 consecutive days, after incubation. Preincubation specimens served as controls. Revelations were that euchromatic myonuclei underwent dense granulation and activation after incubation. Presumptive myoblasts (PM) lying clearly within the myofibre increased in numbers with incubation time. Some myonuclei showed partial transformation towards a PM. This study concluded that myonuclei transformed into myoblasts during the process of muscle regeneration and that the PM, produced from a myonucleus, was a stage in the development of the satellite cell (SC) in regenerating muscle. These SC, myoblasts from myonuclear origin, proliferated, fused, and formed multinucleate myotubes that matured into myofibres which replaced damaged muscle. Findings of this study may have new implications for the proposed myoblast transplant or gene transfer therapy, both of which, whilst being possible answers for muscular dystrophy, depend on a sound knowledge of muscle regeneration mechanisms.
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PMID:EM investigation of myoblast origin in regenerating hamster skeletal muscle explants. 128 17

The purpose of this study was to use direct in vivo contractility measurements to assess muscle function in patients with myotonic muscular dystrophy (MMD). The tetanic and twitch responses and several time parameters of muscle contraction were obtained from nine MMD subjects and nine able-bodied, age-matched controls. After a routine nerve conduction study, in vivo contractility measurements were obtained by stimulating the ulnar nerve at the wrist and recording the isometric flexor function of the intrinsic muscles at the metacarpophalangeal joint of the index finger. A series of single stimuli, paired stimuli, and fused tetanic stimulations were generated during a 20-minute experimental protocol. A stable tetanus was produced at 50Hz for 1.2 seconds. M-wave and contractile data were recorded at 1,000Hz by digitization of the analog signal and storage by the microcomputer. The MMD patients were weaker than controls (p less than .05), as shown by the 39% reduction in tetanic tension and 57% reduction in twitch tension. The MMD patients also had a significant impairment in relaxing their muscles as shown by the 1,100% increase in half-relaxation time after contraction, even though there was no evidence of repetitive firing after cessation of stimulus. These data show that MMD patients exhibit failure of sarcolemmal activation, altered excitation-contraction coupling mechanisms, and failure of the contractile machinery. The myotonia is due in part, to some defect in the contractile machinery; it is not solely due to failure of sarcolemmal activation.
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PMID:In vivo quantification of muscle contractility in humans: healthy subjects and patients with myotonic muscular dystrophy. 154 25

In order to understand the mechanism of defective myofibrilogenesis in muscular dystrophy, we have used the genomic cloned DNA specific for myosin light chain 2A (MLC 2A) to check its expression. The fusion of a partial digest of lambda LC5, containing the upstream sequence of MLC 2A gene with the expression vector of PSVOCAT has already been reported. Using this CAT-fused recombinant containing 1.6 kb of MLC 2A gene, we were able to detect the promoter activity in normal heart cells, H9C2 cell line whereas a restricted expression of MLC 2A gene was noticed in muscular dystrophic muscle cells from heart and skeletal. We have also measured the transient transfection efficiency by contransfecting with the plasmid LacZ. Simultaneous assay of beta-galactosidase and CAT in the cell extract was performed. With beta-galactosidase as control, we confirmed that the promoter activity of MLC 2A gene is inhibited in muscular dystrophy though there is a normal rate of transfection occurred.
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PMID:Restricted expression of cardiac myosin light chain 2A gene in muscular dystrophic condition. 190 50

Chick embryo myoblasts in culture will respond to extracts of adult anterior latissimus dorsi muscle with an increase in cell number and an increase in total protein and in myosin heavy chain in fused myotubes. Extracts of adult pectoralis major and of posterior latissimus muscles are only marginally active. The active adult muscle extracts are fractionated by DEAE-cellulose column chromatography and transferrin is identified as the active component based on the following findings: (1) the active fractions are shown to contain an 80K protein that comigrates with chicken transferrin on SDS-PAGE, (2) the active extract from the anterior latissimus dorsi completely replaced embryo extract in the culture medium and supported normal myogenesis, (3) the active extract requires iron for its ability to support myogenesis, (4) the peptide map of the 80K protein is identical to a peptide map of transferrin. Under conditions where the 80K protein is detected in adult anterior latissimus dorsi muscles it is shown that the protein is nevertheless not synthesized in the muscle. These results support the idea that tissues of selective muscles in the adult chicken accumulate transferrin. An accompanying paper shows that transferrin also accumulates in early developmental stages of fast muscle tissue but that accumulation ceases after hatching in these muscles in normal chickens but not in animals of congenic strains with inherited muscular dystrophy.
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PMID:There is selective accumulation of a growth factor in chicken skeletal muscle. I. Transferrin accumulation in adult anterior latissimus dorsi. 672 29

Thirteen patients with Duchenne's muscular dystrophy underwent spinal fusion and Harrington instrumentation between 1967 and 1979. Curve progression was the most common indication for surgery. Cardiorespiratory evaluation was most important in the timing of surgery. After 12 months of immobilization, all spines fused. Major and minor complications occurred in eight of 13 patients. The major benefit of surgery was improved or maintained sitting balance. Surgery is not recommended for patients with symptomatic cardiomyopathy, vital capacity less than 40%, a nonfunctional cough, or rapidly progressive deterioration in muscle strength with a projected life span of less than two years.
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PMID:Spinal fusion in Duchenne's muscular dystrophy. 717 88

In soleus muscles of rats treated for 2 to 11 days with high doses of chloroquine or chlorphentermine, muscle fibres showed autophagocytosis followed by segmental contracture and necrosis. Vascuolar degeneration, "splitting", and internal nuclei were absent. At variance with findings in progressive muscular dystrophy, the incidence of intramembrane particles was unchanged and membrane defects in necrotizing fibres were absent. Autophagic vacuoles were formed by cup-shaped cisternae derived from tubules that often enclosed single mitochondria. Golgi complexes occurred in the centre of the fibres; dilated vesicles of the sarcoplasmic reticulum contained an electrondense substance, possibly lysosomal enzymes. Exocytosis of autophagic vacuoles and of almost undigested mitochondria was observed. The changes in the plasma membrane were as in other cells: a bulge was formed that was cleared of intramembrane particles; the membrane fused with the limiting membrane of the autophagic vacuole, the content of which was expelled through an orifice. Inside autophagic vacuoles, persisting phospholipids arranged themselves into protein-free lipid bilayers, that formed concentric membranes or single-layered vesicles. Both drugs are known to inhibit degradation of phospholipids; the findings indicate that the rate of autophagocytosis and exocytosis were enhanced as well. Fibre necrosis was probably due to the fact that fibres eventually became unable to maintain their integrity.
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PMID:The early changes in experimental myopathy induced by chloroquine and chlorphentermine. 735 73

EM study of cultured human skeletal muscle explants on 10 consecutive days after incubation made possible a record for the first time, the early events occurring during regeneration. After incubation, normal myonuclei underwent activation and dense granulation. Some myonuclei showed early transformation to presumptive myoblasts. The conclusion was that myonuclei transformed into myoblasts which developed into satellite cells (SC). These SC of myonuclear origin, proliferated, and fused forming myotubes that matured into myofibres, replacing damaged muscle. The findings have new implications for the current myoblast/cell transplant and gene transfer therapy research which may provide possible answers for muscular dystrophy in the future.
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PMID:EM evidence of myoblast origin in regenerating human skeletal muscle explants. 822 Mar 8

We have prepared two fragments of the human dystrophin rod domain, each containing eight spectrin-like repeating units, by expression in Escherichia coli. The first corresponds to the central portion of the rod, the other to three repeats from the N-terminal end, fused to five repeats from the C-terminal end. The latter makes up the entire mutant rod, found in a patient with mild (Becker-type) muscular dystrophy. Both fragments were found to possess an ordered, stable structure, and had the form of short rod-like particles in the electron microscope. Molecular weight determinations by sedimentation equilibrium revealed that both polypeptides were monomeric in solution, suggesting that the dystrophin rod domain is incapable of forming an antiparallel homodimer. This supports the inference from sequence analyses [Winder et al., 1995: FEBS Lett. 369:27-33, 1996: Biochem. Soc. Trans. 24:2805] that the dystrophin rod domain lacks the arrangement of sites required for lateral self-association, and that dystrophin, unlike the other known proteins of the spectrin superfamily, may thus exist as a monomer.
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PMID:Physical properties of dystrophin rod domain. 906 20

To monitor the presence of introduced genes and the distribution of the encoded proteins in host tissues after gene transfer, we combined fluorescence in situ hybridization (FISH) and immunohistochemistry in two separate gene therapy paradigms. In brain tissue sections from animals injected with pHSVlac vector, we localized nuclei containing vector DNA both in cells expressing and not expressing beta-galactosidase (beta-gal). This suggests that the efficiency of gene transfer is affected not only by gene delivery, but also by cellular controls on gene expression. In a second paradigm, following myoblast transplantation, we detected donor nuclei in the muscle of a patient with Duchenne's muscular dystrophy. The donor nuclei were either surrounded by host nuclei or apparently fused in the patient's muscle fiber producing dystrophin. The combined FISH and immunohistochemistry assay offers greater sensitivity and more information than currently used polymerase chain reaction and protein detection methods.
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PMID:A method to codetect introduced genes and their products in gene therapy protocols. 963 Oct 42

Absence of dystrophin, as found in Duchenne boys, mdx mice and HFMD cats, leads to destabilization of the sarcolemmal-associated protein complex. Gene and cell therapy strategies aim to restore the dystrophin-associated protein complex. In order to better understand the cellular events involved in such therapy in feline and human muscular dystrophy, we asked whether dystrophin-deficient myoblasts would fuse with myoblasts expressing normal dystrophin, and whether the complex would be restored after such a fusion. Cat and human myoblasts were isolated from skeletal muscle of normal subjects and of patients with dystrophin deficiency and proliferated well. After co-culture with normal myoblasts, they fused to form hybrid myotubes. These hybrid myotubes expressed dystrophin, utrophin and dystrophin- associated proteins. Expression of these proteins were restored also in the vicinity of nuclei from dystrophin-deficient donors. These results demonstrate that dystrophin can be expressed and handled normally by hybrid myotubes. They show that myoblasts with a normal dystrophin gene can restore dystrophin expression in dystrophin-deficient myoblasts.
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PMID:Restoration of dystrophin expression in cultured hybrid myotubes. 1236 21


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