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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Of 50 patients with the clinical characteristics of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), 38 had a point mutation at nucleotide position (nt) 3243 in the tRNA(Leu(UUR)) region in mitochondrial DNA and 6 at nt 3271 in the same tRNA(Leu(UUR)) gene. Except for the later onset of the disease in the patients with the 3271 mutation, there were no clinical, biochemical and pathological differences between the two groups. Since the nt 3271 region is not located in the binding site for mitochondrial transcription termination (mTERM) factor, which has been proposed to be defective in the 3243 mutation, a functional defect in tRNA itself might be responsible for the enzyme defects in MELAS patients; however the mechanism by which the defective tRNA(Leu(UUR)) induces the stroke-like episodes remains to be clarified.
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PMID:Mitochondrial DNA mutations at nucleotide positions 3243 and 3271 in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes: a comparative study. 848 77

We analysed the distribution of mutant mitochondrial DNA (mtDNA) with A-to-G substitution mutation of tRNA(Leu)(UUR) in various autopsied tissues from a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). There was no significant difference in the proportion (76-86%) of mutant mtDNA in many tissues, except in the lung and spleen. Unequal partitioning of mtDNA in somatic cells appears less prominent than that in germ cells.
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PMID:Tissue distribution of mutant mitochondrial DNA in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). 848 99

Point mutations in the mitochondrial tRNA(leu(UUR)) gene have been recently reported in patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). To investigate the relationship between the degree of heteroplasmy and the organ damage, the ratio of mutant and wildtype genes was quantitated in 14 different organs obtained at an autopsy case of MELAS. The percentages of mitochondrial tRNA(leu(UUR)) gene carrying an A to G transition mutation at nucleotide 3243 were determined by the restriction enzyme digestion of the polymerase chain reaction products. The organs largely depending on oxidative phosphorylation for the sources of energy contained higher proportions of the mutant tRNA(leu(UUR)) gene than organs with a lower oxygen demand. However, the percentage of the mutant genes was similar in both symptomatic and asymptomatic organs with a higher oxygen demand.
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PMID:Organ distribution of mutant mitochondrial tRNA(leu(UUR)) gene in a MELAS patient. 849 68

The expression of nuclear and mitochondrial oxidative phosphorylation (OXPHOS) genes was examined in the skeletal muscle of patients with Kearns-Sayre syndrome (KSS), myoclonic epilepsy associated with ragged red fibers (MERRF), and myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and compared with controls. In KSS muscle, mtDNA transcripts outside the deletion were elevated, while those within the deletion were reduced according to the percentage of deleted mtDNA molecules. In MERRF and MELAS muscle, mitochondrial transcripts levels were increased, but the increase was greater in MERRF muscle. The processing of mtDNA transcripts was reduced in all pathogenic muscles. This was true for full-length heavy and light strand transcripts as well as for the 16 S rRNA + tRNA(Leu)+ND1 transcript. However, the tRNA(Lys) level was reduced in all three muscles. In MELAS muscle, our results are not consistent with an impairment of transcription termination at the end of the 16 S mitochondrial rRNA. Finally, the transcription of the nuclear ATPsyn.beta and ANT1 genes was induced in parallel with the high level of mtDNA transcripts in MERRF and MELAS muscle, but was repressed in KSS muscle. The results demonstrate that the expression of nuclear and cytoplasmic OXPHOS genes is coordinated and that OXPHOS gene expression increases to compensate for respiratory deficiency. The repression of nuclear genes in KSS muscle could be a consequence of the segmental distribution of deleted mtDNA molecules in muscle cells.
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PMID:Mitochondrial DNA expression in mitochondrial myopathies and coordinated expression of nuclear genes involved in ATP production. 850 36

We reviewed 10 patients (5 males, 5 females) with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes. The age of symptom onset ranged from 3 months to 12 years. All had lactic acidosis, multiple stroke-like events with secondary neurological deficits, radiological changes of progressive brain infarction, and muscle biopsy showing ragged-red fibers. In patients with earlier onset of symptoms (< 2 yr), involvement tended to be more diffuse, with failure to thrive and early onset of delayed development. Patients whose symptoms appeared later tended to have focal neurological deficits with migraine-like headache, and a rate of cognitive regression reflecting the rapidity of disease progression. Radiological changes included multiple areas of infarction with initial predilection for parietal occipital areas, progressing to generalized atrophy. Pathological findings in muscle biopsies included type 1 fiber predominance, ragged-red fibers, increased intermyofibrillar lipid deposition, and abnormal mitochondria. Four patients showed mitochondrial DNA tRNA mutation at position 3,243. No difference was noted in clinical, radiological, or pathological findings in patients with and without this mutation, suggesting that multiple sites of point mutation may give rise to mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes.
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PMID:Mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS): clinical, radiological, pathological, and genetic observations. 851 76

We describe a two-generation family with combined clinical features of myoclonic epilepsy, progressive external ophthalmoplegia (PEO), proximal myopathy, pigmentary retinopathy, progressive deafness, basal ganglia calcification, and ragged-red fibers in a muscle biopsy specimen. One family member died unexpectedly at age 22 years. The molecular tests revealed an A-to-G transition at nucleotide position 3243 of the mitochondrial tRNA(Leu(UUR)) gene. No one in this family had stroke-like episodes. Although the propositus (a 28-year-old woman) had a significant number of white hairs, the percentage of mutant mtDNA in white-hair roots was not different from that in the colored-hair roots. Our findings suggest that the 3243 mutation can be associated with mixed clinical features of myoclonic epilepsy with ragged-red fibers (MERRF) and PEO and that a preferential increase in the levels of the mutant mtDNA is not related to graying of hair, and hence to the hypothesized production of premature aging of cells.
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PMID:A MERRF/PEO overlap syndrome associated with the mitochondrial DNA 3243 mutation. 862 77

Mitochondrial encephalomyopathy is a hereditary syndrome showing impairment of muscle and the central nervous system. In this disorder, the following three syndromes have been identified on the basis of characteristic symptoms: Kearns-Sayre syndrome (KSS), mitochondrial encephalomyopathy with lactic acidosis, and stroke-like episodes (MELAS), and myotonic epilepsy with ragged-red fibers (MERRF). In this report, we describe a case of mitochondrial encephalomyopathy with renal disease. A 25-year-old man was referred to our hospital in May, 1992 for evaluation of long-standing proteinuria. He had a small stature, exotropia and no pretibial edema. No mental retardation was observed. Urinary protein excretion was 2.0 g/day and urine sugar was negative. Laboratory examination revealed a serum urea nitrogen 19 mg/dl, and a creatinine value of 1.5 mg/dl. Creatinine clearance was 45.8 ml/min. His serum and spinal fluid lactate value were elevated. Biopsied muscle showed an absence of ragged-red fibers, and the presence of an A-to-G point mutation at nucleotide pari 3243 in the mitochondrial tRNA(Leu(UUR)) in peripheral blood leucocytes. He was thought to have MELAS. On the renal biopsy specimens, light microscopic examinations showed minor glomerular abnormalities with two glomerular collapses and tubulo-interstitial damage. Electron microscopic examinations showed partial thickening of the glomerular basement membrane. We report here this rare case of MELAS with renal disease, and also review seventeen cases of mitochondrial encephalopathy associated with renal disease. The existence of a relationship between mitochondrial disorder and renal damage remains obscure.
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PMID:[A case of mitochondrial encephalomyopathy (MELAS)]. 871 14

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), a maternally inherited disorder, is usually associated with a point mutation in mitochondrial DNA (mtDNA) at position 3,243 in the tRNA Leu(UUR) gene. To further study the pathogenesis of MELAS, we analyzed tissues from 8 MELAS-3,243 patients. Southern blot analysis showed an increase in the ratio of mtDNA to nuclear DNA in almost all tissues examined, implying that mitochondrial proliferation is ubiquitous and is not confined to ragged-red fibers in muscle. By northern blot analysis, we demonstrated increased steady-state levels of RNA 19, a polycistronic transcript corresponding to the 16S rRNA + tRNA Leu(UUR) + ND1 genes (which are contiguous in the mtDNA) in heart, kidney, and muscle. These results provide further evidence that altered mitochondrial nucleic acid metabolism may have pathogenic significance in MELAS.
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PMID:Mitochondrial DNA and RNA processing in MELAS. 877 98

A number of human diseases are caused by inherited mitochondrial DNA mutations. Two of these diseases, MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF (myoclonic epilepsy and ragged-red fibres), are commonly caused by point mutations to tRNA genes encoded by mitochondrial DNA. Here we report on how these mutations affect mitochondrial function in primary fibroblast cultures established from a MELAS patient containing an A to G mutation at nucleotide 3243 in the tRNA(Leu(UUR) gene and a MERRF patient containing an A to G mutation at nucleotide 8344 in the tRNA(Lys) gene. Both mitochondrial membrane potential and respiration rate were significantly decreased in digitonin-permeabilized MELAS and MERRF fibroblasts respiring on glutamate/malate. A similar decrease in mitochondrial membrane potential was found in intact MELAS and MERRF fibroblasts. The mitochondrial content of these cells, estimated by stereological analysis of electron micrographs and from measurement of mitochondrial marker enzymes, was similar in control, MELAS and MERRF cells. Therefore, in cultured fibroblasts, mutation of mitochondrial tRNA genes leads to assembly of bioenergetically incompetent mitochondria, not to an alteration in their amount. However, the cell volume occupied by secondary lysosomes and residual bodies in the MELAS and MERRF cells was greater than in control cells, suggesting increased mitochondrial degradation in these cells. In addition, fibroblasts containing mitochondrial DNA mutations were 3-4-fold larger than control fibroblasts. The implications of these findings for the pathology of mitochondrial diseases are discussed.
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PMID:Altered mitochondrial function in fibroblasts containing MELAS or MERRF mitochondrial DNA mutations. 880 26

An A3243G point mutation of the mitochondrial tRNA(Leu(UUR)) gene was detected in a Caucasian family with maternal diabetes mellitus and signs of mitochondrial dysfunction such as muscular hypotonia, encephalopathy, lactic acidosis, stroke-like episodes (MELAS), neurosensory hearing loss, cardial pre-excitation, and short stature. Low levels (10 JDF) of islet cell antibodies (ICA) in insulin-treated diabetes of the mother and impaired glucose tolerance with high levels of ICA (80 JDF) in her older son indicated that mitochondrial diabetes mellitus may involve beta cell damage. Furthermore, exocrine pancreas cell damage may also occur since the stroke-like episodes of this son were combined with pancreatitis. In all family members HLA types and plasma antioxidants were determined. Normal concentrations of hydro- and lipophilic antioxidants (including ubiquinol-10) were found.
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PMID:Islet cell antibodies in diabetes mellitus associated with a mitochondrial tRNA(Leu(UUR)) gene mutation. 881 38


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