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)

Disruption of the development program of myosin gene expression has been reported in chicken muscular dystrophy. In the present report, the relationship between muscular dystrophy and the ability of muscle to respond to an increased work load with a transition in the myosin phenotype has been investigated. Hypertrophy of slow tonic anterior latissimus dorsi (ALD) and fast twitch patagialis (PAT) muscles was induced by overloading for 35 days and myosin expression was analyzed by electrophoresis and immunocytochemistry. Normal and dystrophic chicken ALD muscles have nearly identical proportions of SM-1 and SM-2 isomyosins and both exhibit an age-related repression of the SM-1 isomyosin which is enhanced and accelerated by overloading. Immunocytochemistry with anti-myosin heavy chain (MHC) antibodies demonstrates the appearance of nascent myofibers in overloaded ALD muscles from both normal and dystrophic chickens. A minor fast twitch fiber population is also identified which doubles in number with overloading in normal ALD muscles. There are only half as many fast twitch fibers in control dystrophic ALD muscles and this number does not increase with overloading. In contrast to ALD muscles, the isomyosin profile of normal and dystrophic PAT muscles is quite different. There is significantly more FM-3 and significantly less FM-1 isomyosin in the dystrophic PAT muscle. However, both normal and dystrophic PAT muscles exhibit an overload-induced accumulation of the FM-3 isomyosin. Immunocytochemistry reveals that, unlike the normal PAT muscle, the dystrophic PAT muscle contains a population of myofibers which express slow MHCs. As in the ALD muscle, overload-induced hypertrophy is associated with a repression of the SM-1 MHC in these fibers. Nascent myofiber formation does not occur in either normal or dystrophic overloaded PAT muscles.
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PMID:Myosin expression in hypertrophied fast twitch and slow tonic muscles of normal and dystrophic chickens. 182 96

The expression of fast myosin heavy chain (MHC) isoforms was examined in developing bicep brachii, lateral gastrocnemius, and posterior latissimus dorsi (PLD) muscles of inbred normal White Leghorn chickens (Line 03) and genetically related inbred dystrophic White Leghorn chickens (Line 433). Utilizing a highly characterized monoclonal antibody library we employed ELISA, Western blot, immunocytochemical, and MHC epitope mapping techniques to determine which MHCs were present in the fibers of these muscles at different stages of development. The developmental pattern of MHC expression in the normal bicep brachii was uniform with all fibers initially accumulating embryonic MHC similar to that of the pectoralis muscle. At hatching the neonatal isoform was expressed in all fibers; however, unlike in the pectoralis muscle the embryonic MHC isoform did not disappear. With increasing age the neonatal MHC was repressed leaving the embryonic MHC as the only detectable isoform present in the adult bicep brachii muscle. While initially expressing embryonic MHC in ovo, the post-hatch normal gastrocnemius expressed both embryonic and neonatal MHCs. However, unlike the bicep brachii muscle, this pattern of expression continued in the adult muscle. The adult normal gastrocnemius stained heterogeneously with anti-embryonic and anti-neonatal antibodies indicating that mature fibers could contain either isoform or both. Neither the bicep brachii muscle nor the lateral gastrocnemius muscle reacted with the adult specific antibody at any stage of development. In the developing posterior latissimus dorsi muscle (PLD), embryonic, neonatal, and adult isoforms sequentially appeared; however, expression of the embryonic isoform continued throughout development. In the adult PLD, both embryonic and adult MHCs were expressed, with most fibers expressing both isoforms. In dystrophic neonates and adults virtually all fibers of the bicep brachii, gastrocnemius, and PLD muscles were identical and contained embryonic and neonatal MHCs. These results corroborate previous observations that there are alternative programs of fast MHC expression to that found in the pectoralis muscle of the chicken (M.T. Crow and F.E. Stockdale, 1986, Dev. Biol. 118, 333-342), and that diversification into fibers containing specific MHCs fails to occur in the fast muscle fibers of the dystrophic chicken. These results are consistent with the hypothesis that avian muscular dystrophy is a developmental disorder that is associated with alterations in isoform switching during muscle maturation.
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PMID:Diversity of fast myosin heavy chain expression during development of gastrocnemius, bicep brachii, and posterior latissimus dorsi muscles in normal and dystrophic chickens. 246 Mar 89

We have previously demonstrated, based on comparison of homologous amino acid sequences and of two-dimensional CNBr peptide gel patterns, that the myosin heavy chain in pectoralis muscles of Storrs, Connecticut dystrophic chickens is different from that of their normal controls (Huszar, G., Vigue, L., De-Lucia, J. Elzinga, M., and Haines, J. (1985) J. Biol. Chem. 260, 7429-7434). Others have shown, however, that genomic banks and mRNA complements of the control and dystrophic birds are not different. In the present studies, we have examined the hypothesis that the "dystrophic" myosin heavy chain is not a novel gene product, but is a developmental isozyme which is expressed in pectoralis muscles of adult chickens due to the dystrophic process. Two-dimensional maps of myosin heavy chain CNBr peptides were prepared from breast muscles of 17-day in ovo (embryonic), 25-day posthatch (neonatal), and adult birds of the Storrs dystrophic and of two control strains. Also, myosin and actomyosin ATPase enzymatic activities of the various preparations were determined in the pH range of 5.5 to 9.0. Analysis of the peptide maps demonstrates that the embyronic, neonatal, and control adult myosin heavy chain isozymes are distinctly different gene products with only minute variations between the respective developmental isozymes in dystrophic and control muscles. However, the pectoralis myosin heavy chain of adult dystrophic birds, which is a homogeneous isozyme population by amino acid sequences and gel patterns, corresponds to that of the neonatal-type myosin heavy chain. The ATPase properties of the embryonic, neonatal, or adult pectoralis myosins and actomyosins were not different, whether the level of specific activity or the pattern of pH activation is considered. Since the mobility of neonatal chicks (primarily neonatal-type isozymes) is not restricted, the differences in myosin heavy chain structures are part of the syndrome, but not the cause of avian muscular dystrophy.
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PMID:Myosin heavy chain in avian muscular dystrophy corresponds to the neonatal isozyme. 316 Jul 8

The expression of myosin heavy chain isoforms was examined in normal and dystrophic chicken muscle with a monoclonal antibody specific for neonatal myosin. Adult dystrophic muscle continued to contain neonatal myosin long after it disappeared from adult normal muscle. A new technique involving western blotting and peptide mapping demonstrated that the immunoreactive myosin in adult dystrophic muscle was identical to that found in neonatal normal muscle. Immunocytochemistry revealed that all fibers in the dystrophic muscle failed to repress neonatal myosin heavy chain. These studies suggest that muscular dystrophy inhibits the myosin gene switching that normally occurs during muscle maturation.
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PMID:Continued expression of neonatal myosin heavy chain in adult dystrophic skeletal muscle. 396 67

We have studied the structure of myosin heavy chain (MHC) in the pectoralis muscle of genetically dystrophic (Connecticut Strain) and White Leghorn chicks. MHC was alkylated with N-ethylmaleimide, purified by Sepharose-4B chromatography, and cleaved with cyanogen bromide. The MHC CNBr peptides were analyzed by one-dimensional and two-dimensional isoelectric focusing/sodium dodecyl sulfate gradient gels and by amino acid sequencing. Specific changes were detected in the gel patterns which could be correlated with the loss of muscle function as measured by the exhaustion score (the ability of chicks to rise from a reclining position) in three experimental groups (exhaustion scores: less than 3, 10-20, greater than 30). We have also examined the amino acid sequence of a 3-methyl-histidine-containing peptide which originates from the 20-kDa fragment of pectoralis muscle MHC in dystrophic chicks: Val-Leu-Asn-Ala-Ser-Ala-Ile-Pro-Glu-Gly-*Gln-Phe-*Ile-Asp-Ser-Lys-Lys- Ala-Ser-Leu-Gln-Lys-Leu-Gly-Ser-Ile-Asp-Val-(Asp, 3-methylhistidine, Gln). Comparison of the homologous MHC sequences shows two positions at which MHC from dystrophic chicks differs from that of the White Leghorn chicks *(Glu----Gln and Met----Ile). Thus, both the peptide map and sequence analyses demonstrate that in avian muscular dystrophy an abnormal pectoralis MHC is synthesized. It is not yet clear whether the "dystrophic" MHC is a variant MHC or if it arises from the abnormal expression of an earlier developmental form (embryonic or neonatal) of pectoralis muscle MHC.
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PMID:Structure of myosin heavy chain in avian muscular dystrophy. 399 78

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

Avian muscular dystrophy is characterized by the degeneration of fast white skeletal muscle fibers, with onset during development. Using a one-dimensional peptide mapping technique, we have detected two forms of the myosin heavy chain in the fast white fibers of adult domestic chickens, one form characteristic of birds homozygous for muscular dystrophy, the other of their normal controls. Four dystrophic strains carrying the same gene for muscular dystrophy were examined. No differences were detected in the embryonic heavy chain peptide maps of normal and dystrophic chickens, consistent with the developmental onset of the condition. Differences were also absent from the peptide maps of heavy chains from slow red fibers, which are unaffected in dystrophy. No dystrophy-specific peptide map differences were detected in the three light chains. Analysis of peptide maps of rod and the heavy chain component of subfragment-1 from normal and dystrophic heavy chains indicates the presence of amino acid sequence differences in the two proteins.
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PMID:Abnormal myosin heavy chain variant associated with avian muscular dystrophy. 681 70

Morphological, morphometrical, histoenzymological, immunocytochemical and biochemical analysis were performed on muscle biopsies taken from patients suffering from tunisian autosomal recessive Duchenne-like muscular dystrophy (TDLMD) selected both by Duchenne-like clinical criteria and by the presence of normal dystrophin. Data were compared to that obtained from DMD biopsies characterized by the absence of dystrophin. The distribution of myosin heavy chain isoforms, desmin, vimentin and titin were determined in type I and type II muscle fibers. The protein pattern appeared to be less affected in TDLMD than in DMD biopsies. The regenerating fibers were mainly but not exclusively type IIC; a noticeable percentage of both type I and type II fibers coexpressed fast and slow MHC isoforms in TDLMD. This percentage was lower than in DMD. The expression of embryonic, fetal, and fast/slow myosin isoforms in type IIC fibers in TDLMD and DMD suggest different fiber type transformations in these two diseases.
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PMID:Expression of myosin isoforms and of desmin, vimentin and titin in Tunisian Duchenne-like autosomal recessive muscular dystrophy. 806 3

The expression of fast myosin heavy chain (MyHC) genes was examined in vivo during fast skeletal muscle development in the inbred White Leghorn chicken (line 03) and in adult muscles from the genetically related dystrophic White Leghorn chicken (line 433). RNA dotblot and northern hybridization was employed to monitor MyHC transcript levels utilizing specific oligonucleotide probes. The developmental pattern of MyHC gene expression in the pectoralis major (PM) and the gastrocnemius muscles was similar during embryonic development with three embryonic MyHC isoform genes, Cemb1, Cemb2, and Cemb3, sequentially expressed. Following hatching, MyHC expression patterns in each muscle differed. The expression of MyHC genes was also studied in muscle cell cultures derived from 12-day embryonic pectoralis muscles. In vitro, Cvent, Cemb1, and Cemb2 MyHC genes were expressed; however, little if any Cemb3 MyHC gene expression could be detected, even though Cemb3 was the predominant MyHC gene expressed during late embryonic development in vivo. In most adult muscles other than the PM and anterior latissimus dorsi (ALD), the Cemb3 MyHC gene was the major adult MyHC isoform. In addition, two general patterns of expression were identified in fast muscle. The fast muscles of the leg expressed neonatal (Cneo) and Cemb3 MyHC genes, while other fast muscles expressed adult (Cadult) and Cemb3 MyHC genes. MyHC gene expression in adult dystrophic muscles was found to reflect the expression patterns found in corresponding normal muscles during the neonatal or early post-hatch developmental period, providing additional evidence that avian muscular dystrophy inhibits muscle maturation.
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PMID:Expression of fast myosin heavy chain transcripts in developing and dystrophic chicken skeletal muscle. 909 21

The absence of dystrophin at the muscle membrane leads to Duchenne muscular dystrophy (DMD), a severe muscle-wasting disease that is inevitably fatal in early adulthood. In contrast, dystrophin-deficient mdx mice appear physically normal despite their underlying muscle pathology. We describe mice deficient for both dystrophin and the dystrophin-related protein utrophin. These mice show many signs typical of DMD in humans: they show severe progressive muscular dystrophy that results in premature death, they have ultrastructural neuromuscular and myotendinous junction abnormalities, and they aberrantly coexpress myosin heavy chain isoforms within a fiber. The data suggest that utrophin and dystrophin have complementing roles in normal functional or developmental pathways in muscle. Detailed study of these mice should provide novel insights into the pathogenesis of DMD and provide an improved model for rapid evaluation of gene therapy strategies.
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PMID:Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy. 928 51


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