Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using RNase protection analysis, we found a novel C to G mutation at nucleotide position 3093 of mitochondrial DNA (mtDNA) in a previously reported 35-year-old woman exhibiting clinical features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome together with diabetes mellitus, hyperthyroidism and cardiomyopathy. The patient also had an A3243G mutation in the tRNA(Leu(UUR)) gene and a 260-base pair duplication in the D-loop of mtDNA. The fibroblasts of the patient were cultured and used for the construction of cybrids using cytoplasmic transfer of the patient's mtDNA to the mtDNA-less rho(0) cells. RNA isolated from the cybrids was subjected to RNase protection analysis, and a C3093G transversion at the 16S rRNA gene and a MELAS-associated A3243G mutation of mtDNA were detected. The novel C3093G mutation together with the A3243G transition were found in muscle biopsies, hair follicles and blood cells of this patient and also in her skin fibroblasts and cybrids. The proportion of the C3093G mutant mtDNA in muscle biopsies of the patient was 51%. In contrast, the mutation was not detected in three sons of the proband. To characterize the impact of the mtDNA mutation-associated defects on mitochondrial function, we determined the respiratory enzyme activities of the primary culture of fibroblasts established from the proband, her mother and her three sons. The proportions of mtDNA with the C3093G transversion and the A3243G transition in the fibroblasts of the proband were 45 and 58%, respectively. However, the fibroblasts of the proband's mother and children harbored lower levels of mtDNA with the A3243G mutation but did not contain the C3093G mutation. The complex I activity in the proband's fibroblasts was decreased to 47% of the control but those of the fibroblasts of the mother and three sons of the proband were not significantly changed. These findings suggest that the C3093G transversion together with the A3243G transition of mtDNA impaired the respiratory function of mitochondria and caused the atypical MELAS syndrome associated with diabetes mellitus, hyperthyroidism and cardiomyopathy in this patient.
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PMID:A novel mutation in the mitochondrial 16S rRNA gene in a patient with MELAS syndrome, diabetes mellitus, hyperthyroidism and cardiomyopathy. 1145 95

A 25-year-old man developed a stroke-like episode. He suffered from renal failure and became dialysis-dependent. His mother was also dialysis-dependent. A3243G point mutation of the mitochondrial tRNA(leu) gene was detected in both of them. The patient was diagnosed with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), and died of a recurrence of stroke-like episodes at the age of 30. Autopsy revealed numerous abnormal mitochondria in the kidneys, but no renal vascular changes. This is the first report of a MELAS case in which the presence of numerous abnormal mitochondria in podocytes and tubules was confirmed by electron microscopy.
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PMID:An autopsy case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome with chronic renal failure. 1150 92

Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episode (MELAS) and myoclonic epilepsy and ragged-red fibers (MERRF) are rare disorders caused by point mutation of the tRNA gene of the mitochondrial genome. To understand the pathogenetic mechanism of MELAS and MERRF, we studied four patients. Serially sectioned frozen muscle specimens with a battery of histochemical stains were reviewed under light microscope and ultrastructural changes were observed under electron microscope. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was performed and the tRNA genes were sequenced to confirm mutations. In two patients with MELAS, strongly succinyl dehydrogenase positive blood vessels (SSVs) and many cytochrome oxidase (COX) positive ragged-red fibers (RRFs) were observed, and A3243G mutations were found from the muscle samples. In two patients with MERRF, neither SSV nor COX positive RRFs were seen and A8344G mutations were found from both muscle and blood samples. In the two MERRF families, the identical mutation was observed among family members. The failure to detect the mutation in blood samples of the MELAS suggests a low mutant load in blood cells. The histochemical methods including COX stain are useful for the confirmation and differentiation of mitochondrial diseases. Also, molecular biological study using muscle sample seems essential for the confirmation of the mtDNA mutation.
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PMID:Histochemical and molecular genetic study of MELAS and MERRF in Korean patients. 1185 May 98

General principles of structure and function of the ribosome are surveyed, and the translating ribosome is regarded as a molecular conveying machine. Two coupled conveying processes, the passing of compact tRNA globules and the drawing of linear mRNA chain through intraribosomal channel, are considered driven by discrete acts of translocation during translation. Instead of mechanical transmission mechanisms and power-stroke 'motors', thermal motion and chemically induced changes in affinities of ribosomal binding sites for their ligands (tRNAs, mRNA, elongation factors) are proposed to underlie all the directional movements within the ribosomal complex. The GTP-dependent catalysis of conformational transitions by elongation factors during translation is also discussed.
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PMID:Ribosome as a molecular machine. 1190 72

We report an unusual case of encephalo-entero-myopathy associated with the A8344G mutation in the tRNA(Lys) gene of mitochondrial DNA (mtDNA). This patient had mitochondrial myopathy, multiple lipomatosis, mild hearing loss, stroke-like episodes, and paralytic ileus, but she lacked the canonical clinical features of MERRF, myoclonus, epilepsy, or ataxia. We conducted genetic, biochemical, histochemical, and immunohistochemical studies in skeletal muscle, brain, intestine, and lipoma tissue. The mutation was abundant in all tissues, and cytochrome c oxidase (COX) activity was selectively decreased in brain and small intestine. COX deficiency was also documented histochemically and immunohistochemically in the small intestine, suggesting that mitochondrial dysfunction played a role in the pathogenesis of paralytic ileus. This case illustrates an unusual and dramatic clinical phenotype of the A8344G mutation, characterized by stroke-like episodes and acute ileus.
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PMID:The A8344G mutation in mitochondrial DNA associated with stroke-like episodes and gastrointestinal dysfunction. 1247 64

We report on a unique patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) presenting optic atrophy, cardiomyopathy, and bilateral striatal necrosis before stoke-like episodes became apparent. Skeletal muscle total mitochondrial DNA analysis identified a heteroplasmic A to G point mutation in the tRNA(Lys) gene at position 8296. Skeletal muscle pathology revealed typical MELAS findings, including ragged-red fibers cytochrome c oxidase positive strongly succinate dehydrogenase-reactive blood vessels. Recent reports describe the 8296 mutation identified in patients with diabetes mellitus or myoclonus epilepsy with ragged-red fibers, not MELAS. We conclude that the 8296 mutation is likely to be pathogenic and that it may be not only a mutation responsible for diabetes mellitus or myoclonus epilepsy with ragged-red fibers but also for MELAS.
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PMID:Atypical MELAS associated with mitochondrial tRNA(Lys) gene A8296G mutation. 1250 10

We have taken advantage of the similarity between human and yeast (Saccharomyces cerevisiae) mitochondrial tRNA(Leu)(UUR), and of the possibility of transforming yeast mitochondria, to construct yeast mitochondrial mutations in the gene encoding tRNA(Leu)(UUR) equivalent to the human A3243G, C3256T and T3291C mutations that have been found in patients with the neurodegenerative disease MELAS (for mitochondrial 'myopathy, encephalopathy, lactic acidosis and stroke-like episodes'). The resulting yeast cells (bearing the equivalent mutations A14G, C26T and T69C) were defective for growth on respiratory substrates, exhibited an abnormal mitochondrial morphology, and accumulated mitochondrial DNA deletions at a very high rate, a trait characteristic of severe mitochondrial defects in protein synthesis. This effect was specific at least in the pathogenic mutation T69C, because when we introduced A or G instead of C, the respiratory defect was absent or very mild. All defective phenotypes returned to normal when the mutant cells were transformed by multicopy plasmids carrying the gene encoding the mitochondrial elongation factor EF-Tu. The ability to create and analyse such mutated strains and to select correcting genes should make yeast a good model for the study of tRNAs and their interacting partners and a practical tool for the study of pathological mutations and of tRNA sequence polymorphisms.
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PMID:The yeast counterparts of human 'MELAS' mutations cause mitochondrial dysfunction that can be rescued by overexpression of the mitochondrial translation factor EF-Tu. 1252 21

Accumulation of RNA 19 has been associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. We analyzed total RNA in muscle specimens from six patients who had one of three pathogenetic point mutations in the mitochondrial tRNA(Leu(UUR)) gene, including A3243G, T3271C, and T3303C. Mitochondrial processing intermediates were identified and quantitated by Northern blotting. The percentage of DNA with the mutation also was determined in each patient. The intermediate (RNA 19) was significantly increased in all patients. The proportion of mutation-carrying RNA in processing intermediates was always higher than in the DNA fraction, suggesting that these mutations may have dominant-negative effects on mitochondrial RNA processing events at the tRNA(Leu(UUR)) gene boundary.
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PMID:Increased mitochondrial processing intermediates associated with three tRNA(Leu(UUR)) gene mutations. 1260 8

We studied two patients with ragged-red fibers and combined defects of the mitochondrial respiratory chain in their muscle biopsy. One had mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, and harbored a T3258C transition in the tRNA(Leu(UUR)) gene. The other showed myopathy plus cardiomyopathy and had an A3280G mutation in the same gene. Both mutations were heteroplasmic, abundant in muscle of the patients, less abundant in blood, and still less abundant in blood from their maternal relatives. In both patients, single muscle fiber analysis revealed greater abundance of mutant genomes in ragged-red fibers than in normal fibers, supporting the pathogenicity of both mutations.
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PMID:Two pathogenic mutations in the mitochondrial DNA tRNA Leu(UUR) gene (T3258C and A3280G) resulting in variable clinical phenotypes. 1279 97

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) are usually associated with the common 3243A-->G mutation of mtDNA. Onset of stroke-like episodes usually occurs before age 30. We report a patient with late onset MELAS harboring a rare 3256C-->T mutation in the tRNA(Leu(UUR)) gene of mtDNA. The patient presented with a stroke-like episode at age 36. MRI showed a stroke-like lesion in the right parietooccipital brain region. Proton MR spectroscopy showed elevated lactate concentrations in the lesion (8.4 mmol/l), and in the mid-occipital region (2.3-3.2 mmol/l) that appeared normal on MRI. Further tests revealed evidence of a severe oxidative defect of muscle metabolism as well.
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PMID:Late onset of stroke-like episode associated with a 3256C-->T point mutation of mitochondrial DNA. 1297 83


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