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)

The arginine requirement of young, female rabbits was reassessed using body weight gain, serum arginine concentration and expired 14CO2 following administration of 14C arginine as criteria of adequacy. With a diet that provided the indispensable amino acids at the previously estimated requirement level the arginine requirement was estimated at or near 0.6% of diet by all three of the criteria studied. When an amino acid pattern based on isolated soy protein was fed, a significantly lower serum arginine level was observed with 0.6% dietary arginine corroborating that the arginine requirement may be higher when this pattern is fed than when the requirement pattern is fed. Liver arginase and kidney transamidinase levels were normal and were not influenced by dietary arginine levels over the range used. Serum creatine phosphokinase, which has been studied in other species in relation to muscular dystrophy, showed a significant increase with increasing dietary level of arginine. No signs of this disorder however, were observed. Adult male rabbits maintained body weight and showed no change in serum arginine concentration when both arginine and glycine were completely omitted from the diet.
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PMID:Further studies on the arginine requirement of the rabbit. 94 64

We report cystinuria and symptoms of cerebellar atrophy in a 45-year-old man. His parents were first cousins, and many members of his family had stones of urinary tract or gait impairment. Neurological examination disclosed cerebellar signs resembling those of spinocerebellar degeneration. Urinalysis disclosed high cystine, lysine, ornitine and arginine output. Cystine was 1153.8 micro mol/day (normal range, 22-170); lysine, 3443.9 (normal range, 44-1000); ornitine, 283.8 (normal range, 7-40); and arginine, 154.0 (normal range, 9-50). Neurological complications reported to be associated with cystinuria include mental retardation, muscular dystrophy, hypotonia and dwarfism, mongolism, paroxysmal dyskinesia, myopathy, migraine, spastic paraplegia, multiple sclerosis, subacute combined degeneration and cranial polyneuropathy. Cerebellar signs have been reported in only two cases, and to our knowledge, this is the first case of cystinuria with cerebellar atrophy ever reported. Some common metabolic errors may have caused both disorders, although they also may have developed independently.
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PMID:[Cystinuria with symptoms of cerebellar atrophy--a case report]. 189 74

Plasma GH responses to human GHRH, arginine, L-dopa, and insulin-induced hypoglycemia were determined in seven myotonic dystrophy (MD) patients. An iv bolus injection of GHRH-(1-44)-NH2 (1 microgram/kg BW) only slightly increased plasma GH concentrations in MD patients. The mean peak plasma GH level after GHRH injection [4.2 +/- 0.8 (+/- SE) micrograms/L] was significantly lower than that in 10 age-matched normal subjects (26.7 +/- 4.3 micrograms/L) or that in 6 patients with progressive muscular dystrophy (22.8 +/- 6.6 micrograms/L) whose nutritional status was similar to that of the MD patients. Even with a larger dose of GHRH (3 micrograms/kg BW), the plasma GH rises were minimal in the MD patients (mean peak, 5.9 +/- 1.8 micrograms/L). The plasma GH responses to a 30-min iv infusion of arginine (0.5 g/kg BW) and oral ingestion of L-dopa (0.5 g) were attenuated to a similar extent, whereas insulin-induced hypoglycemia caused a significant increase in plasma GH in all seven MD patients [mean peak, 17.4 +/- 4.1 (+/- SE) microgram/L]. The plasma TSH responses to TRH and plasma insulin-like growth factor I levels were similar in the MD patients and normal subjects. These findings suggest that 1) the impaired GH release after GHRH, arginine, and L-dopa administration in MD patients is not due to somatotroph deficiency, since the GH response to hypoglycemia is well preserved; and 2) insulin-induced hypoglycemia may stimulate GH release at least in part via inhibition of somatostatin release.
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PMID:Discordance between growth hormone (GH) responses after GH-releasing hormone and insulin hypoglycemia in myotonic dystrophy. 314 49

Preclinical alterations of protease activities in skeletal muscles from 10-day-old dystrophic mouse, C57BL/10-mdx, were examined by using 10 fluorogenic peptide substrates. Among the activities tested, only Boc-Val-Pro-Arg-MCA-hydrolyzing enzyme of the muscle microsomes showed an about 6-fold higher level of activity in mdx mouse. The increase in activity was not observed in tissues other than skeletal muscle. The enzyme had a pH optimum between 8.5 and 11.0, and was inhibited with DFP and variety of trypsin inhibitors. The enzymatic activity transiently increased at 1-2 weeks of age, the preclinical or very early stage of the disease. These results imply that the increased level of a trypsin-like protease possibly present in muscle microsomes may be closely related to the manifestation of muscular dystrophy.
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PMID:Preclinical increase in activity of muscle microsomal trypsin-like protease in murine muscular dystrophy, C57BL/10-mdx. 351 21

Interactins between skeletal muscle protein and amino acid metabolism were investigated using C57BL and 129ReJ mice with hereditary muscular dystrophy. On incubation, hind limb muscle preparations from dystrophic mice released large quantities of amino acids, particularly alanine and glutamine which were increased 70% and 40% compared to muscles from carrier or control mice. The increased alanine release did not result from altered alanine oxidation to CO2 or reincorporation into protein. Alanine and glutamine formation from added amino acids were equal with dystrophic and control muscles. Incorporation in vitro of leucine, alanine, and glutamate into proteins of dystrophic muscle was 3- to 7-fold greater than control muscle, and the incorporation in vivo of [3H]- or [14C]arginine into muscle proteins was greater in extent and earlier in time with dystrophic as compared to control muscle. Proteins were also labeled in vivo using [guanido-14C]arginine. On incubation of these muscles in vitro, a 100% greater loss of label from protein was observed with dystrophic as compared to control preparations, and the appearance of label in the media was correspondingly increased. Sodium dodecyl sulfate-gel electrophoresis of dystrophic skeletal muscle showed numerous protein bands to be reduced in density, but autoradiographic studies demonstrated that these same bands were more highly labeled in vitro by [35S]methionine in dystrophic than in control muscle. Although insulin stimulation of glucose uptake was markedly blunted in dystrophic muscle, insulin inhibited alanine and glutamine release equally from both control and dystrophic muscle. These data indicate that alanine and glutamine formation and release are increased in hereditary mouse muscular dystrophy. An accelerated degradation and an increased resynthesis of many muscle proteins were also observed in dystrophic compared to control animals. This increased proteolysis may account for the increased alanine and glutamine formation in dystrophic muscle.
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PMID:Skeletal muscle protein and amino acid metabolism in hereditary mouse muscular dystrophy. Accelerated protein turnover and increased alanine and glutamine formation and release. 689 25

We have reported adhalin gene mutations in 4 patients from 3 families with malignant limb-girdle muscular dystrophy (MLGMD), and summarized the clinical features in adhalin-deficient muscular dystrophy (ADMD) reported as severe childhood autosomal recessive muscular dystrophy (SCARMD) in the English literatures. Adhalin cDNA amplified from RNA by reverse transcription polymerase chain reaction (RT-PCR) was sequenced in 3 patients from 2 consanguinous families (Wa. and Ta.) with MLGMD who showed immunohistochemically a complete deficiency of adhalin in the skeletal muscle, and adhalin genomic DNA amplified by PCR was sequenced in 1 patient from a non-consanguinous family (Ma.). In one patient from family Wa., a cytosine to thymine substitution at nt. 229 was identified in the adhalin gene, resulting in the replacement of Arg by Cys at codon 77. In two patients from family Ta., an adenine to guanine substitution at nt. 410 and an insertion of 15 bases between nt. 408 and 409 were identified, resulting in Glu to Gly replacement at codon 137 and insertion of a peptide with 5 amino acids. In one patient from family Ma., a deletion of adenine at nt. 404 or nt. 405 and a thymidine to cytosine substitution at nt. 470 were identified. These amino acid replacements are expected to change the secondary and tertiary structure, which may affect the interaction of adhalin with other dystrophin-associated glycoproteins and basal lamina, and may subsequently cause the degeneration of muscle fibers. Sixty-six cases from 49 families with ADMD have been reported in the literature. Compared with patients with Duchenne muscular dystrophy (DMD), patients with ADMD were older in age at the time of onset or loss of ambulation. Mental retardation and cardiac dysfunction were rarely observed in ADMD patients. On muscle histology, the number of necrotic fibers, opaque fibers and regenerative fibers was less in ADMD. ADMD was classified into two groups; complete and incomplete adhalin-deficient. There was no essential difference between the two groups in clinical features and muscle histology, but the former was characterized by more severe clinical features than the latter. ADMD can be caused by various types of mutations in the adhalin gene.
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PMID:[Adhalin gene mutations in malignant limb-girdle muscular dystrophy and clinical features in adhalin-deficient muscular dystrophy]. 874 43

Malignant limb-girdle muscular dystrophy (MLGMD) was proposed by Miyoshi et al. in 1966 as a clinical and genetic entity of muscular dystrophy, with clinical features similar to Duchenne muscular dystrophy but showing autosomal recessive inheritance. Recently, deficiency of alpha-sarcoglycan (adhalin), which is one of the components of dystrophin-glycoprotein complex, in the skeletal muscle has been found in several patients with MLGMD or severe childhood autosomal recessive muscular dystrophy. To investigate alpha-sarcoglycan gene mutations in patients with MLGMD, we analyzed cDNA prepared from skeletal muscle by reverse transcription polymerase chain reaction (RT-PCR), or genomic DNA prepared from peripheral blood leukocytes by PCR, using single-strand conformation polymorphism (SSCP). When products amplified by RT-PCR or PCR showed aberrant conformers on SSCP analysis, these products were sequenced by the fluorescence-based dideoxy termination method. We found missense mutations, insertions or deletions in the alpha-sarcoglycan gene in 6 families with MLGMD. In the literature, alpha-sarcoglycan gene mutations have been identified in 21 families with MLGMD/SCARMD including our 6 families. Half of the families have the cytosine to thymidine substitution at nt.229, resulting in the replacement of Arg by Cys at codon 77, and most of the mutations have been found in the region coding extracellular domain of alpha-sarcoglycan. Analysis of the alpha-sarcoglycan gene is indispensable for diagnosis, assessment of prognosis, genetic counseling, and future gene therapy in patients with autosomal recessive childhood-onset muscular dystrophy.
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PMID:[Gene analysis in patients with muscular dystrophy: alpha-sarcoglycan (adhalin) gene mutations in patients with malignant limb-girdle muscular dystrophy]. 912 Sep 97

Four of the currently recognized autosomal recessive limb-girdle muscular dystrophies (LGMD type 2C-F) are caused by mutations in the genes encoding components of the sarcoglycan complex. LGMD 2C, caused by mutations in gamma-sarcoglycan, is prevalent in northern Africa, especially in Tunisia, where this type of muscular dystrophy was originally described. Although the disease initially was assumed to be genetically homogeneous in this region, linkage to the alpha-sarcoglycan locus (LGMD 2D) has also been found. We have now identified the first Tunisian family with beta-sarcoglycanopathy (LGMD 2E), further adding to the genetic heterogeneity of autosomal recessive LGMD in this population. Direct sequencing of the beta-sarcoglycan gene revealed a homozygous mutation (G272-->T, Arg91Leu) in exon 3. This change affects the same arginine residue in the immediate extracellular domain of the protein that was mutated to a proline (G272-->C, Arg91Pro) in a Brazilian family with a severe form of the disease. Immunohistochemical analysis for the sarcoglycan complex demonstrates absence of the known components of the complex in both of these families. We postulate that the immediate extracellular domain of beta-sarcoglycan may be important for the assembly and/or maintenance of this complex, potentially mediated by disulfide-bond formation to another sarcoglycan via the single cysteine residue in that domain.
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PMID:LGMD 2E in Tunisia is caused by a homozygous missense mutation in beta-sarcoglycan exon 3. 963 1

Linkage studies have confirmed the existence of clinical an genetic heterogeneity among the muscular dystrophies due to adhalin deficiency. We present the clinical, histological and genetic characteristics in a case of primary adhalinopathy (deficiency of the 50 kD subunit or alpha-sarcoglycan). It was a 19 years-old woman, born of non consanguineous parents, who shows a long evolution myopathy with onset before age 7, a severe evolution and becoming wheelchair bound at 10 years. She showed evident calf pseudohypertrophy and serum creatinkinase (CK) levels were elevated (40-180 times the standard level). The histological pattern showed a destructed fascicular architecture in agreement with severe muscular dystrophy, normal staining with anti-dystrophin monoclonal antibodies and abnormal staining pattern with anti-adhalin antibodies. The molecular study evidenced an homozygous point mutation (Arg-->Cys) at position 77 of exon 3 of the gene coding for the 50 kD subunit of the alpha-sarcoglycan complex localised in chromosome 17. In the light of this case, we suggest a revision of the diagnostic orientation in the muscular dystrophies and we review the new taxonomy of the limb-girdle muscular dystrophies, remarking the clinical signs which could indicate a given genetic locus.
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PMID:[Muscular dystrophy due to a mutation in the gene of alpha-sarcoglycan subunit of dystrophin associated protein complex]. 964 69

Limb girdle muscular dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM), a distal muscular dystrophy, are both caused by mutations in the recently cloned gene dysferlin, gene symbol DYSF. Two large pedigrees have been described which have both types of patient in the same families. Moreover, in both pedigrees LGMD2B and MM patients are homozygous for haplotypes of the critical region. This suggested that the same mutation in the same gene would lead to both LGMD2B or MM in these families and that additional factors were needed to explain the development of the different clinical phenotypes. In the present paper we show that in one of these families Pro791 of dysferlin is changed to an Arg residue. Both the LGMD2B and MM patients in this kindred are homozygous for this mutation, as are four additional patients from two previously unpublished families. Haplotype analyses suggest a common origin of the mutation in all the patients. On western blots of muscle, LGMD2B and MM patients show a similar abundance in dysferlin staining of 15 and 11%, respectively. Normal tissue sections show that dysferlin localizes to the sarcolemma while tissue sections from MM and LGMD patients show minimal staining which is indistinguishable between the two types. These findings emphasize the role for the dysferlin gene as being responsible for both LGMD2B and MM, but that the distinction between these two clinical phenotypes requires the identification of additional factor(s), such as modifier gene(s).
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PMID:Identical mutation in patients with limb girdle muscular dystrophy type 2B or Miyoshi myopathy suggests a role for modifier gene(s). 1019 77


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