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)

Proteins are important constituents of the red blood cell plasma membrane. Several important breakthroughs have occurred in their analysis over the past few years. SDS-polyacrylamide gel electrophoresis lead to the separation of the major proteins and glycoproteins. Location of most of these proteins -- either on the external, the internal or both surfaces of the membrane -- was determined. The strenght of the binding of the protein to the membrane was established. Hydrophobicity of membrane proteins has so far hindered their purification. However, the major glycoprotein (glycophorin A) was isolated and recently sequenced. The description of several membrane-associated enzyme activities has been followed by some understanding of their specific role in the red blood cell physiology. Abnormalities of glycoproteins, Ca2+-ATPase and of membrane protein phosphorylation have been reported under various conditions: sickle cell disease, hereditary spherocytoses, progressive muscular dystrophy.
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PMID:[Erythrocyte membrane proteins]. 14 51

Nutritional muscular dystrophy in the chick results from the simultaneous deficiency of vitamin E and cystine. Being a biological antioxidant, vitamin E might be functional in maintaining a proper redox state of the sulfur-containing amino acid in the proteins. The analyses of protein-bound sulfhydryls and disulfides at onset of muscular dystrophy in young chicks were carried out. The ratio of disulfide to sulfhydryls increased two- to three-fold in dystrophic muscle as compared to that in the control muscle proteins. Dystrophic and normal muscle proteins also were subjected to SDS-gel electrophoresis. Proteins of low molecular weight, supposedly derived from proteolysis, were present in the gels of the dystrophic muscle and absent in those of normal muscle extracts. As a result of these studies, a chemical model has been proposed to explain the oxidative deterioration of proteins in nutritional muscular dystrophy due to vitamin E deficiency.
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PMID:Oxidative deterioration of the muscle proteins during nutritional muscular dystrophy in chicks. 90 23

A group of 44 monoclonal antibodies (mAbs) raised against the central helical rod (25 mAbs) and C-terminal (19 mAbs) regions of dystrophin were prepared using trpE recombinant fusion proteins as immunogens. Some mAbs cross-react with the structurally related proteins, alpha-actinin and utrophin. Epitope mapping revealed uneven distribution of mAb-binding sites, no mAbs being produced against the C-terminal end of the helical fragment or the cysteine-rich region of the C-terminal dystrophin fragment. The failure of these large regions of the recombinant immunogens to elicit anti-dystrophin antibodies may be because of their inability to fold into the correct dystrophin-like conformation. The mAbs were selected for their ability to recognize 427 kDa dystrophin on Western blots after SDS/PAGE, and/or for immunostaining of the membrane in frozen muscle sections. Although some mAbs obtained by Western-blot screening failed to bind native dystrophin in frozen muscle sections, successful binding could be obtained after SDS or urea treatment of the tissue section to expose the epitopes. This increases the range of mAbs available for detection of dystrophin deletions in muscular dystrophy and evaluation of myoblast therapy.
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PMID:Monoclonal antibodies for dystrophin analysis. Epitope mapping and improved binding to SDS-treated muscle sections. 128 10

Antibody-binding epitopes in the central helical region of the muscular dystrophy protein, dystrophin, have been mapped using a new strategy of transposon mutagenesis. Tn1000 transposons carrying translation termination codons were introduced randomly by bacterial mating into a large fragment of dystrophin cDNA in a pEX2 plasmid to produce a library of transformants expressing truncated dystrophin fusion proteins. Epitopes were progressively lost as the expressed sequences were shortened, enabling the epitopes recognised by 22 monoclonal antibodies to be placed in order along the dystrophin molecule without in vitro manipulation of DNA. The C-terminus of each truncated fusion protein was precisely located within the dystrophin sequence by direct sequencing of pEX2 transformants using transposon-specific primers. Sequences as short as 7 and 17 amino-acids have been identified as essential for antibody binding in this way. Nineteen of the 22 monoclonal antibodies had been selected for their ability to bind both native and SDS-denatured dystrophin and 15 of these bind to one sequence of 74 amino-acids (residues 1431-1505 of the 3684 residue sequence). This may be an area of high immunogenicity or of close structural similarity between native dystrophin and the SDS-treated recombinant fragment used for immunization.
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PMID:Rapid mapping by transposon mutagenesis of epitopes on the muscular dystrophy protein, dystrophin. 171 82

A subsynaptic protein of Mr approximately 300 kD is a major component of Torpedo electric organ postsynaptic membranes and copurifies with the AChR and the 43-kD subsynaptic protein. mAbs against this protein react with neuromuscular synapses in higher vertebrates, but not at synapses in dystrophic muscle. The Torpedo 300-kD protein comigrates in SDS-PAGE with murine dystrophin and reacts with antibodies against murine dystrophin. The sequence of a partial cDNA isolated by screening an expression library with mAbs against the Torpedo 300-kD protein shows striking homology to mammalian dystrophin, and in particular to the b isoform of dystrophin. These results indicate that dystrophin is a component of the postsynaptic membrane at neuromuscular synapses and raise the possibility that loss of dystrophin from synapses in dystrophic muscle may have consequences that contribute to muscular dystrophy.
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PMID:Dystrophin is a component of the subsynaptic membrane. 172 Jan 19

The distributions of plasma concentrations of complement proteins C3 and C4 were studied in sample populations of merino and Suffolk sheep. No differences between the breeds or the sexes were observed. The distribution for ovine C4 was polymodal and very disperse relative to that for C3. It was found, however, that C3 concentrations were elevated in specimens from 20 merino sheep bred as high responders to a Trichostrongylus vaccine. Significantly decreased plasma C4 concentrations were observed in representatives of both merino and merino X Border Leicester cross-bred sheep affected with congenital progressive ovine muscular dystrophy. Agarose gel electrophoretic variants of ovine C3 were not detected. Evidence for electrophoretic variants of ovine C4 in agarose gels was found although individual allotypes could not be reliably identified. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) did not reveal size heterogeneity for the alpha and beta chains of immunoprecipitated ovine C3. Analysis of reduced immunoprecipitated ovine C4 by SDS-PAGE revealed considerable size heterogeneity in the alpha chain consistent with isotypic and/or allotypic variability. The data presented strongly suggest the presence of two C4 loci in sheep, each of which exhibits polymorphism.
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PMID:Analysis of C3 and C4 in ovine plasma. 356 28

Skeletal muscle cells of genetically dystrophic mice (dy/dy) of the REJ-129 Bar Harbor strain exhibit reduced cytoplasmic levels of the enzyme creatine phosphokinase (CPK) when compared with normal (+/+) mice following SDS-gel electrophoresis of sarcoplasmic proteins. This observation has been thought to reflect "leakage" of CPK from dystrophic muscle cells through lesions in the sarcolemma. The present study has employed the freeze-fracture method to examine vast expanses of sarcolemma fracture face for determination of whether lesions do exist in the membrane or an alternate route is present for extravasation of CPK from dystrophic muscle cells. Most of the dystrophic cells examined in this study appeared intact and were therefore presumed viable. The intramembrane lipoprotein particles characteristic of PF-fracture face membrane were reduced in dystrophic as compared with normal murine skeletal muscle, and the plasmalemma possessed a greatly amplified population of caveolae as compared with nondiseased sarcolemma. No abnormal structural feature of these dystrophic muscle plasma membranes could be interpreted as a perforating focal "delta" lesion, such as the structures seen in thin plastic sections by other investigators. However, a second group of cells, generally few in number, that exhibited features indicative of necrosis (and loss of viability), were seen in both thin sections and platinum replicas. These moribund cells were usually embedded in dense sheaves of connective tissue along with other dystrophic cells that lacked signs of necrosis. The cytoplasm of the necrotic muscle cells was disorganized, as was the contractile machinery. The sarcolemma showed numerous perforations, through which CPK could escape into the tissue extracellular compartment. We conclude on the basis of our observations that the "focal lesions" reported by other investigators are not a structural feature of viable dystrophic muscle cell plasma membranes and are found only in necrotic or dying cells, and that the elevated serum levels of CPK associated with muscular dystrophy may result either from escape of the enzyme through lesions present in necrotic or dying cells or by extravasation along avenues provided by the hyperplastic mass of membrane caveolae present in dystrophic sarcolemma.
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PMID:The dystrophic murine skeletal muscle cell plasma membrane is structurally intact but "leaky" to creatine phosphokinase. A freeze-fracture analysis. 647 81

A single direct injection of a local anesthetic, 0.5% bupivacaine hydrochloride (BPVC) (Marcaine), into rat soleus and extensor digitorum longus (EDL) muscles produced massive fiber necrosis with extensive phagocytosis followed by rapid regeneration, predominantly in the soleus. Since the sarcoplasmic reticulum (SR) was functionally disturbed by BPVC administration as confirmed by an in vitro study, the sarcolemmal lysis seen in the early phase of degeneration was not assumed to simply result from direct damage to the plasma membrane caused by BPVC. The extracellular fluid containing a high concentration of calcium (Ca) ions then permeated into the sarcoplasm through the defective membrane resulting in hyper-contracted myofibrils. Selective damage to the Z-line, an early sign of muscle degeneration, was shown by electron microscopy and SDS gel electrophoresis (preferential loss of alpha-actinin). Administration of leupeptin, a thiol protease inhibitor, proved to be ineffective in inhibiting the necrotic process, because the BPVC induced muscle fiber breakdown was probably too acute and fulminant to demonstrate the inhibitory effect upon the degenerative process. Well preserved satellite cells, peripheral nerves, and acetylcholinesterase activity, and the absence of fibrous tissue proliferation in this system may be responsible for the extremely rapid regeneration with complete muscle fiber type differentiation. Since the sequence of fiber breakdown induced by BPVC administration was similar to that of progressive muscular dystrophy, this chemical will be one of the most useful tools for studying the pathophysiology of fiber necrosis and regeneration in diseased muscle.
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PMID:Pathophysiology of muscle fiber necrosis induced by bupivacaine hydrochloride (Marcaine). 661 29

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

To search for potentially mutant proteins, we have investigated erythrocyte ghost proteins from normal and dystrophic hamster by two-dimensional gel electrophoresis. No significant differences are observed between dystrophic and normal erythrocytes in their peptide patterns on SDS-polyacrylamide gel electrophoresis while on two-dimensional gels a protein spot of approximate Mr 20 000 with an approximate isoelectric point of 4.5 is found in erythrocytes from dystrophic animals and is consistently absent in normal erythrocytes. A large population of erythrocyte (60%) from dystrophic hamsters shows distorted shape as visualized by scanning electron microscopy. The nature of this protein and its relevance in hamster muscular dystrophy are at present not known.
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PMID:Analysis of erythrocyte membrane proteins from dystrophic hamsters. 685 49


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