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)

Glycine is an excitatory amino acid, a neurotransmitter for the brain. A recent experimental study by a 9.3T laboratory spectrometer identified the peak of pure glycine at 3.52 ppm, and in a clinical case this peak was demonstrated at 3.50 ppm by a 1.5 T clinical scanner. This study was undertaken to investigate the brain diseases having the glycine peak. An experiment with a 1.5 T clinical MRI unit was performed. Two grams of pure glycine was dissolved in 200 cc of distilled water and the solution was frozen, and proton MR spectroscopy (TR=1500 ms, TE=20 ms) was obtained. Nine patients with various diseases studied by two-dimensional chemical shift spectroscopy (hybrid CSI) with TR=1500 ms, and TE=40 ms are included in the study. Ten normal cases were available for comparison. In the experiment with the clinical MRI unit, the glycine peak was centered at 3.50 ppm. The disease processes associated with distinct glycine peaks at 3.50 ppm included infarction, high-grade astrocytoma, megalencephalic leukoencephalopathy with cysts, Leigh's disease, adrenoleukodystrophy, congenital muscular dystrophy, Rasmussen's encephalitis, gliosis in neuronal migrational disorder, and hamartoma in tuberous sclerosis. None of the control cases displayed a glycine peak. In conclusion, glycine has a peak centered at 3.50 ppm in in vivo environments. It is distinct from the myoinositol peak. Detection of glycine in a wide variety of brain diseases ranging from infarction, tumor, leukoencephalopathies, infection to gliosis likely reflects presence of excitotoxic brain damage or a disturbance of neurotransmitting mechanisms in these conditions.
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PMID:The glycine peak in brain diseases. 1263 15

Lactic acidosis has been associated with a variety of clinical conditions and can be due to mutation in nuclear or mitochondrial genes. We performed mutations screening of all mitochondrial tRNA genes in 44 patients who referred as hyperlactic acidosis. Patients showed heterogeneous phenotypes including Leigh disease in four, MELAS in six, unclassified mitochondrial myopathy in 10, cardiomyopathy in five, MERRF in one, pure lactic acidosis in six, and others in 12 including facio-scaplo-femoral muscular dystrophy (FSFD), familial cerebellar ataxia, recurrent Reye syndrome, cerebral palsy with mental retardation. We measured enzymatic activities of pyruvate dehydrogenase complex, and respiratory chain enzymes. All mitochondrial tRNA genes and known mutation of ATPase 6 were studied by single strand conformation polymorphism (SSCP), automated DNA sequence and PCR-RFLP methods. We have found one patient with PDHC deficiency and six patients with Complex I+IV deficiency, though the most of the patients showed subnormal to deficient state of respiratory chain enzyme activities. We have identified one of the nucleotide changes in 29 patients. Single nucleotide changes in mitochondrial tRNA genes are found in 27 patients and one in ATPase 6 gene in two patients. One of four pathogenic point mutations (A3243G, C3303T, A8348G, and T8993G) was identified in 12 patients who showed the phenotype of Leigh syndrome, MELAS, cardimyopathy and cerebral palsy with epilepsy. Seventeen patients have one of the normal polymorphisms in the mitochondrial tRNA gene reported before. SSCP and PCR-RFLP could detect the heteroplasmic condition when the percentage of mutant up to 5, however, it cannot be observed by direct sequencing method. It is important to screen the mtDNA mutation not only by direct sequence but also by PCR-RFLP and the other sensitive methods to detect the heroplasmy when lactic acidosis has been documented in the patients who are not fulfilled the criteria of mitochondrial disorders.
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PMID:Mitochondrial tRNA gene mutations in patients having mitochondrial disease with lactic acidosis. 1633 22

Mutations in COL6A1, COL6A2 and COL6A3, the genes which encode the extra-cellular matrix component collagen VI, lead to Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD). Although the Col6a1(-/-) null mouse has an extremely mild neuromuscular phenotype, a mitochondrial defect has been demonstrated, linked to dysregulation of the mitochondrial permeability transition pore (PTP) opening. This finding has been replicated in UCMD muscle cells in culture, providing justification for a clinical trial using cyclosporine A, an inhibitor of PTP opening. We investigated whether PTP dysregulation could be detected in UCMD fibroblasts (the predominant source of muscle collagen VI), in myoblast cells from patients with other diseases and its response to rescue agents other than collagen VI. Although we confirm the presence of PTP dysregulation in muscle-derived cultures from two UCMD patients, fibroblasts from the same patients and the majority of fibroblasts from other well-characterized UCMD patients behave normally. PTP dysregulation is found in limb girdle muscular dystrophy (LGMD) type 2B myoblasts but not in myoblasts from patients with Bethlem myopathy, merosin-deficient congenital muscular dystrophy, LGMD2A, Duchenne muscular dystrophy and Leigh syndrome. In addition to rescue by cyclosporine A and collagen VI, this cellular phenotype was also rescued by other extra-cellular matrix constituents (laminin and collagen I). As the muscle derived cultures demonstrating PTP dysregulation shared poor growth in culture and lack of desmin labelling, we believe that PTP dysregulation may be a particular characteristic of the state of these cells in culture and is not specific to the collagen VI defect, and can in any case be rescued by a range of extra-cellular matrix components. Further work is needed on the relationship of PTP dysregulation with UCMD pathology.
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PMID:Cyclosporine A treatment for Ullrich congenital muscular dystrophy: a cellular study of mitochondrial dysfunction and its rescue. 1929 42