Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemopexin, a serum glycoprotein that binds free heme and transports it to hepatic parenchymal cells, has been measured by radial immunodiffusion. We have confirmed elevation of serum hemopexin concentration in Duchenne's muscular dystrophy patients and carries, and demonstrated elevations in dermatomyositis/polymyositis and myasthenia gravis, but not in amyotrophic lateral sclerosis. In monkeys, elevations of hemopexin levels were specifically induced by hematin injections, muscle-crush, or myoglobin injections. Myoglobin leakage is the likely explanation of hemopexin level elevation in Duchenne's dystrophy patients and carriers and in dermatomyositis/polymyositis. In myasthenia gravis there might be a slight myoglobin leakage not heretofore suspected; or, the elevation of hemopexin levels might be a new reflection of a dysimmune state in myasthenia gravis, and perhaps as such is a further incrementing factor in dermatomyositis/polymyositis. Hemopexin, presumably as a longer-phase reactant, is sometimes an index of neuromuscular disease when other data are negative or equivocal.
 ...
PMID:Elevations of hemopexin levels in neuromuscular disease. 9 25

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.
 ...
PMID:[Erythrocyte membrane proteins]. 14 51

A fraction of erythrocyte Band 3 (Mr, 93,000) glycoprotein that demonstrates decreased autophosphorylation in membranes from myotonic muscular dystrophy patients is demonstrated. Sequential affinity chromatography of Triton X-100 solubilized erythrocyte membrane proteins separated three specifically retained glycoprotein fractions on a Ricin Communis I-Sepharose 4B column. One fraction contains a portion of the major sialoglycoprotein (apparent Mr, 78,000) and is specifically eluted from the column by 10 mM NaCl and 100 mM D-galactose (10/100). The two other glycoprotein fractions are eluted by 100 mM NaCl, 10 mM D-galactose (100/10) and 100 mM NaCl, 100 mM D-galactose (100/100). The composition of both fractions contains greater than 95% Band 3 (apparent Mr, 93,000 glycoprotein. The quantities of glycoprotein in each fraction obtained from erythrocytes of myotonic dystrophy patients did not differ from the quantities obtained from control erythrocytes. Following endogenous protein kinase incubations of ghosts with [gamma-32P]ATP, the specific [32P] phosphorylation of the 10/100 and 100/10 fractions are identical. The 100/100 fraction, which makes up approximately 3% of the total erythrocyte membrane protein, demonstrates a different pattern for myotonic dystrophy patients; specific phosphorylation was reduced by 50% relative to activity in control experiments. These findings are consistent with previous experiments that demonstrated decreased autophosphorylation of the glycoprotein portion of Band 3 (Roses & Appel, 1975, J. Membrane Biol 20:51) and are consistent with the autosomal dominant mode of inheritance in this disease.
 ...
PMID:Isolation of an abnormally phosphorylated erythrocyte membrane band 3 glycoprotein from patients with myotonic muscular dystrophy. 44 24

Lectin binding sites in skeletal muscle from normal and dystrophic (dy/dy) C57 BL/6J mice were demonstrated by use of histochemistry and electrophoresis combined with electron microscopy. The following lectins were used: Canavalia ensiformis Con A, Triticum vulgaris (WGA), Glycine max (SBA), Griffonia simplicifolia (GS II), Arachis hypogaea (PNA), Pisum sativum (PSA) and Lens culinaris (LCA). After incubation of frozen sections with Con A, WGA, GS II, PSA and LCA a sarcoplasmic staining was observed in both normal and dystrophic muscle. The most consistent light microscopic observations in the dystrophic muscles were a decreased staining intensity of the sarcoplasm after incubation with Con A, WGA, PSA and LCA, but not with GS II, and a strong staining of the interfiber connective tissue. Supernatants, deprived of organelles and membranes, were prepared from normal and dystrophic muscle by high speed centrifugation. Lectin stained Western blots of the supernatant from dystrophic muscle showed two bands (120 and 67 K) with high affinities to avidin. Further this supernatant contained two glycoprotein bands (180 and 140 K) with affinities to Con A and a number of glycoprotein bands with apparent molecular weights below 67 K showing affinities to LCA and PSA. None of these glycoprotein bands could be detected in the supernatant from normal muscle. These changes of the muscle carbohydrate components might be involved in the expression of the dystrophic syndrome This seems to be the first report on changes of soluble glycoproteins in muscular dystrophy.
 ...
PMID:Changes of soluble glycoproteins in dystrophic (dy/dy) mouse muscle shown by lectin binding. 129 May 87

X-linked recessive Duchenne muscular dystrophy (DMD) is caused by the absence of dystrophin, a membrane cytoskeletal protein. Dystrophin is associated with a large oligomeric complex of sarcolemmal glycoprotein. The dystrophin-glycoprotein complex has been proposed to span the sarcolemma to provide a link between the subsarcolemmal cytoskeleton and the extracellular matrix component, laminin. In DMD, the absence of dystrophin leads to a large reduction in all of the dystrophin-associated protein. We have investigated the possibility that a deficiency of a dystrophin-associated protein could be the cause of severe childhood autosomal recessive muscular dystrophy (SCARMD) with a DMD-like phenotype. Here we report the specific deficiency of the 50K dystrophin-associated glycoprotein (M(r) 50,000) in sarcolemma of SCARMD patients. Therefore, the loss of this glycoprotein is a common denominator of the pathological process leading to muscle cell necrosis in two forms of muscular dystrophy, DMD and SCARMD.
 ...
PMID:Deficiency of the 50K dystrophin-associated glycoprotein in severe childhood autosomal recessive muscular dystrophy. 140 35

Dystrophin, the protein encoded by the Duchenne muscular dystrophy (DMD) gene, exists in a large oligomeric complex. We show here that four glycoproteins are integral components of the dystrophin complex and that the concentration of one of these is greatly reduced in DMD patients. Thus, the absence of dystrophin may lead to the loss of a dystrophin-associated glycoprotein, and the reduction in this glycoprotein may be one of the first stages of the molecular pathogenesis of muscular dystrophy.
 ...
PMID:Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle. 218 35

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.
 ...
PMID:[Dystrophin, dystrophin-associated protein and dystrophinopathy]. 758 23

In various neuromuscular diseases, the most significant muscle degeneration is muscle fiber necrosis as seen in Duchenne muscular dystrophy (DMD). A certain membrane instability is probably responsible for muscle fiber necrosis, because defects in membrane proteins have been proposed to associate with progressive muscular dystrophies including dystrophin in DMD, a 50 KD subunit of dystrophin associated glycoprotein (DAG) in severe childhood autosomal recessive muscular dystrophy (SCARMD), and subunit M of laminin (merosin) in congenital muscular dystrophy and dy mouse. The vulnerable muscle surface membrane may permit extracellular calcium influx into the sarcoplasm resulting in focal myofibrillar hypercontraction (opaque fiber) and activation of proteases such as calpain and cathepsins. The muscle fiber then undergoes necrosis and allows macrophage invasion, followed by muscle fiber regeneration. Focal myofibrillar degeneration involving rimmed vacuole (RV) formation is an another striking muscle fiber degeneration seen in various neuromuscular diseases including inclusion body myositis (IBM) and distal myopathy with rimmed vacuole formation (DMRV). Abnormal accumulation of ubiquitin, beta-amyloid protein precursor and tau protein has been described in IBM by Askanas et al. The similar findings are also recognizable in DMRV and in an experimentally induced myopathy after long-term chloroquin administration to rat. Therefore, if we clarify the pathomechanism of degenerative process involved in the rimmed vacuole formation, the results may provide some insights into the understanding the process involved in amyloid plaque formation in Alzheimer's disease.
 ...
PMID:[Muscle pathologic diagnosis--mechanism in muscle fiber degeneration]. 777 35

New observations demonstrate that several childhood forms of muscular dystrophy share a common pathogenesis. In muscle, dystrophin occurs as part of a membrane complex (dystrophin-glycoprotein) linking the cytoskeleton to the basal lamina. In Duchenne muscular dystrophy, dystrophin deficiency disrupts the linkage of the integral glycoproteins of the sarcolemma and leads to muscle fiber necrosis. In severe childhood autosomal recessive muscular dystrophy, a selective deficiency of adhalin (50-kd glycoprotein) also causes dysfunction of the dystrophin-glycoprotein complex. Most recently, a form of congenital muscular dystrophy demonstrates deficiency of laminin M (merosin) further demonstrating that sarcolemmal instability results from defects in structural proteins of the basal lamina. Animal models have been identified also demonstrating defects in specific proteins linking the subsarcolemmal cytoskeleton to the extracellular matrix. The mdx mouse has a defect in the gene encoding dystrophin. The cardiomyopathic hamster shows a specific deficiency of adhalin in skeletal muscle. The dy/dy mouse has been found deficient in merosin. These animal models will help researchers to understand their human counterparts and provide a system for testing therapeutic strategies.
 ...
PMID:The childhood muscular dystrophies: diseases sharing a common pathogenesis of membrane instability. 778 8

Mutations in the dystrophin gene cause the X chromosome-linked, recessive Duchenne and Becker muscular dystrophies. Dystrophin, a large cytoskeletal protein, copurifies with a complex of dystrophin-associated proteins which serve to anchor dystrophin to the sarcolemma. One of these associated proteins, adhalin, has been implicated as a candidate for severe childhood autosomal recessive muscular dystrophy (SCARMD) due to absence of anti-adhalin staining in muscle biopsy samples taken from SCARMD patients. Furthermore, the Duchenne-like dystrophic phenotype seen in the SCARMD families was shown to be tightly linked to chromosome 13 markers. To determine the genetic mutation responsible for autosomal dystrophy, we characterized the human adhalin gene. Contrary to our expectation, human adhalin was mapped to chromosome 17q21, excluding adhalin as the gene causing chromosome 13-associated SCARMD. Additionally, a splice form of adhalin message was found that predicts a 35-kDa nontransmembrane adhalin. The expression of both adhalin splice forms is exclusively restricted to striated muscle, unlike other components of the dystrophin-glycoprotein complex.
 ...
PMID:Human adhalin is alternatively spliced and the gene is located on chromosome 17q21. 793 74


1 2 3 4 5 6 7 8 9 10 Next >>