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

We have examined the transcript levels of a variety of oxidative phosphorylation (OXPHOS) and associated bioenergetic genes in tissues of a patient carrying the myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) A3243G mitochondrial DNA (mtDNA) mutation and the skeletal muscles of 14 patients harboring other pathogenic mtDNA mutations. The patients' tissues, which harbored 88% or more mutant mtDNA, had increased levels of mtDNA transcripts, increased nuclear OXPHOS gene transcripts including the ATP synthase beta subunit and the heart-muscle isoform of the adenine nucleotide translocator, and increased ancillary gene transcripts including muscle mitochondrial creatine phosphokinase, muscle glycogen phosphorylase, hexokinase I, muscle phosphofructokinase, the E1alpha subunit of pyruvate dehydrogenase, and the ubiquinone oxidoreductase. A similar coordinate induction of bioenergetic genes was observed in the muscle biopsies of severe pathologic mtDNA mutations. The more significant coordinated expression was found in muscle from patients with the MELAS, myoclonic epilepsy with ragged red fibers, and chronic progressive external ophthalmoplegia deletion syndromes, with ragged red muscle fibers and mitochondrial paracrystalline inclusions. High levels of mutant mtDNAs were linked to a high induction of the mtDNA and nuclear OXPHOS genes and of several associated bioenergetic genes. These observations suggest that human tissues attempt to compensate for OXPHOS defects associated with mtDNA mutations by stimulating mitochondrial biogenesis, possibly mediated through redox-sensitive transcription factors.
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PMID:Coordinate induction of energy gene expression in tissues of mitochondrial disease patients. 1043 62

Several cases of hereditary glomerulopathy associated with an A to G transition at position 3243 in mitochondrial DNA, which is known to be associated with most cases of MELAS syndrome (myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), have been recently reported. These patients share the characteristics of hereditary progressive glomerular disease and hearing loss with Alport syndrome. We therefore screened 27 patients with kidney disease clinically mimicking Alport syndrome for the presence of the 3243 mitochondrial mutation, and found one girl with the mutation and a positive family history. Her clinical features were very similar to those of all cases reported to date. An absence of hematuria, severe kidney involvement in a female, pathological changes of focal segmental glomerulosclerosis with no basket-weave change of the glomerular capillary wall, and the frequent association of steroid-induced diabetes are the major features that distinguish this condition from Alport syndrome. Careful neurological examination may detect neuromuscular symptoms compatible with mitochondrial cytopathies. In conclusion, progressive glomerulopathy should be included in the broad spectrum of mitochondrial cytopathies, especially in cases of MELAS syndrome. This mutation should also be included in the etiologies of secondary focal segmental glomerulosclerosis and in the differential diagnosis of Alport syndrome.
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PMID:Hereditary glomerulopathy associated with a mitochondrial tRNA(Leu) gene mutation. 1045 73

Mutations in human mitochondrial tRNA genes are associated with a number of multisystemic disorders. Using an assay that combines tRNA oxidation and circularization we have determined the relative amounts and states of aminoacylation of mutant and wild-type tRNAs in tissue samples from patients with MELAS syndrome (mito- chondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) and MERRF syndrome (myoclonus epilepsy with ragged red fibers), respectively. In most, but not all, biopsies from MELAS patients carrying the A3243G substitution in the mitochondrial tRNA(Leu(UUR))gene, the mutant tRNA is under-represented among processed and/or aminoacylated tRNAs. In contrast, in biopsies from MERRF patients harboring the A8344G substitution in the tRNA(Lys)gene neither the relative abundance nor the aminoacylation of the mutated tRNA is affected. Thus, whereas the A3243G mutation may contribute to the pathogenesis of MELAS by reducing the amount of aminoacylated tRNA(Leu), the A8344G mutation does not affect tRNA(Lys)function in the same way.
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PMID:Decreased aminoacylation of mutant tRNAs in MELAS but not in MERRF patients. 1069 70

We applied the singular value decomposition (SVD) method to study single motor unit firing patterns. Two projects were carried out: (1) a computer simulation study to confirm the meanings of two SVD parameters, the eigenvalue corresponding to the positive-slope eigenvector (PEV) and that corresponding to the negative-slope eigenvector (NEV); and (2) a clinical study for which electromyographic (EMG) recordings were made from first dorsal interosseous muscle in patients with stroke, myopathies, or neuropathies and in healthy control subjects. Results of computer simulation reveal that the NEV reflects the amount of instantaneous firing variability, whereas the PEV/NEV (P/N) ratio exhibits the relative effect of a trend in the firing pattern. In human studies, the P/N ratio of stroke patients was significantly higher than that of the controls, whereas their NEV was comparable. By contrast, in the myopathy and neuropathy groups, the NEV increased significantly, whereas the P/N ratio did not. These results suggest that the SVD method decomposes the motor unit (MU) firing variation into two components and that the mechanism for increased firing variability is different for supraspinal and spinal-infraspinal lesions.
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PMID:Analysis of motor unit firing patterns in patients with central or peripheral lesions using singular-value decomposition. 1088

A mutation was found in an Italian child affecting the gene encoding the mitochondrial transfer RNA for leucine (codon UUR). This mutation (3291T-->C) had previously been reported in a single Japanese patient. In contrast with the original patient, who suffered from early-onset mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), our patient presented an apparently isolated mild myopathy. Mutational analysis in the proband and her family showed that the mutation was heteroplasmic, and that its relative amount was positively correlated with the severity of the phenotype. These findings lead to the definitive confirmation that the 3291T-->C is indeed pathogenic. As commonly found in mitochondrial-DNA related disorders, also for this mutation different clinical manifestations can be associated with the same genetic abnormality.
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PMID:Neuromuscular syndrome associated with the 3291T-->C mutation of mitochondrial DNA: a second case. 1089 47

In the past decade, maternally inherited disorders have been described manifesting as hypertrophic cardiomyopathy. These are primarily associated with defects in oxidative metabolism due to an alteration in mitochondrial DNA. Although the biochemistry and molecular biology is well-defined, there is little information regarding clinical presentation and course. Reported manifestations can be broad and can include myopathy, encephalopathy, stroke-like episodes, hearing loss, cardiomyopathy, multiorgan dysfunction and sudden death. Predominant or exclusive involvement of the heart is rare. We report the clinical presentations, investigations, pathologic findings, and clinical course in two families with two mitochondrial tRNA defects with exclusive cardiac involvement and demonstrable clinical heterogeneity based on the percentage of mutant tRNA.
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PMID:Maternally inherited hypertrophic cardiomyopathy: a manifestation of mitochondrial DNA mutations--clinical course in two families. 1112 21

The A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene (mt.3243A>G) is associated with both diabetes mellitus and myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). Recently, this mutation was found in three diabetic subjects with progressive kidney disease, suggesting that it may be a contributing factor in the development of kidney disease in patients with diabetes. The aim of this study was to evaluate the contribution of this mutation to the development of end stage renal disease (ESRD) in patients with diabetes. The study group consisted of 135 patients with diabetes and ESRD. The control group consisted of 92 non-diabetic subjects with ESRD who were receiving hemodialysis. The mt.3243A>G mutation was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We found the mt.3243A>G mutation in eight patients (8/135; 5.9%), all of whom were initially diagnosed with type II diabetes. Five of the eight patients were subsequently also diagnosed with MELAS. We did not find the mutation in any of the 92 nondiabetic subjects with ESRD. The prevalence of this mutation was 6.5-fold higher in patients with diabetes and ESRD than in those with diabetes alone (8/135 vs 5/550, respectively; chi2 = 13.704; P = 0.0002). The mt.3243A>G mutation may be a contributing genetic factor in the development of ESRD in Japanese patients with diabetes.
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PMID:Prevalence of A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene in Japanese patients with diabetes mellitus and end stage renal disease. 1139 36

The floppy mitral valve prolapses into the left atrium in such a dynamic manner that the prolapsing floppy mitral valve becomes a space-occupying lesion within the left atrium. A significant result of the floppy mitral valve prolapsing into the left atrium during left ventricular systole is the development of a "third chamber" located between the mitral annulus and the prolapsing mitral valve leaflets. Since the blood in the third chamber does not contribute to forward stroke volume, the third chamber may have significant effects on stroke volume and cardiac output. The floppy mitral valve/mitral valve prolapse dynamics also affect left ventricular papillary muscle tension and traction, altering the patterns of left ventricular contraction and relaxation, activating papillary muscle and left ventricular stretch receptors, and contributing to the production of cardiac arrhythmias. Floppy mitral valve innervation patterns with distinct nerve terminals provide a neural basis for brain-heart interactions, augmented by mechanical stimuli from the prolapsing floppy mitral valve. With the onset of mitral valvular regurgitation, and gradual progression of the mitral valve regurgitation from mild, to moderate, to severe, alterations in left atrial and left ventricular chamber size and performance occur, resulting in left atrial and left ventricular myopathy. As a connective tissue disorder, floppy mitral valve/mitral valve prolapse may be associated with abnormal structural and elastic properties of the aorta, with resultant changes in aortic function. Progression of mitral valve regurgitation and the aging process also affect aortic function indices in an adverse manner. The phenomena associated with floppy mitral valve dysfunction, with prolapse of the mitral valve into the left atrium and the unique, resultant forms of mitral valve regurgitation, are dynamic in nature. As the long-term natural history of these interrelated phenomena is being clarified, it is apparent that the floppy mitral valve/mitral valve prolapse/mitral valve regurgitation influences the circulation in a global fashion.
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PMID:Floppy mitral valve/mitral valve prolapse/mitral valvular regurgitation: effects on the circulation. 1143 20

With the aging of the population, death from coronary heart disease (CHD) and stroke has become more prevalent. Cardiovascular disease (CVD) risk factors, such as hypertension, obesity, and diabetes mellitus increase with age as well. Recent secondary-prevention studies have established the positive effect of statins in decreasing the risk of CHD mortality through the lowering of cholesterol. Statins have an excellent safety record, at least with users under age 65, and provide a cheaper alternative to more costly medical options. The most serious side effect associated with their use is myopathy, which is infrequent. Drug interactions have been found with drugs that compete for the same CYP450 isoenzymes as statins. Several drugs have been shown to significantly inhibit the CYP3A4 pathway; in combination with statins such as lovastatin, simvastatin, atorvastatin, and cerivastatin, they have been shown to elevate serum concentrations of these statins, or may increase the risk of myopathy. Alternatively, other drugs can inhibit the CYP2C9 pathway and may elevate serum concentration of fluvastatin. Due to the number of medications the elderly receive, an understanding of the various metabolic pathways is of vital importance to minimize the potential for drug interactions. The elderly population, while at high risk for CVD, is currently undertreated. Statins can effectively lower low-density lipoprotein cholesterol levels and lessen the risk of CVD for this population.
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PMID:Treatment of the elderly with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors: focus on drug interactions. 1158 28

The mitochondrial cytopathies are genetically and phenotypically heterogeneous group of disorders caused by structural and functional abnormalities in mitochondria. To the best of our knowledge, there are very few studies published from India till date. Selected and confirmed fourteen cases of neurological mitochondrial cytopathies with different clinical syndromes admitted between 1997 and 2000 are being reported. There were 8 male and 6 female patients. The mean age was 24.42+/-11.18 years (range 4-40 years). Twelve patients could be categorized into well-defined syndromes, while two belonged to undefined group. In the defined syndrome categories, three patients had MELAS (mitochondrial encephalopathy, lactic acidosis and stroke like episodes), three had MERRF (myoclonic epilepsy and ragged red fibre myopathy), three cases had KSS (Kearns-Sayre Syndrome) and three were diagnosed to be suffering from mitochondrial myopathy. In the uncategorized group, one case presented with paroxysmal kinesogenic dystonia and the other manifested with generalized chorea alone. Serum lactic acid level was significantly increased in all the patients (fasting 28.96+/-4.59 mg%, post exercise 41.02+/-4.93 mg%). Muscle biopsy was done in all cases. Succinic dehydrogenase staining of muscle tissue showed subsarcolemmal accumulation of mitochondria in 12 cases. Mitochondrial DNA study could be performed in one case only and it did not reveal any mutation at nucleotides 3243 and 8344. MRI brain showed multiple infarcts in MELAS, hyperintensities in putaminal areas in chorea and bilateral cerebellar atrophy in MERRF.
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PMID:Neurological mitochondrial cytopathies. 1213 80


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