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

The literature contains sporadic accounts of neurologic complications occurring in patients with Crohn's Disease (CD). The pathogenesis of these is unknown and little has been reported about their incidence. Our review of the medical records of 253 patients with confirmed CD showed that neurologic and neuropsychiatric complications were evident in 84 of the patients, an incidence of 33.2%. In some the association could be casual, but in others the incidence of such complications was higher than that in the general population, suggesting a direct relationship with CD in 19.3%. Our study revealed a variety of neurologic and neuropsychologic events, such as seizure disorder, cerebrovascular accident, headache, peripheral neuropathy, myopathy, and major depression. We believe that an autoimmune phenomenon affecting the small vessels of the central and peripheral nerves may cause the most common neurologic complications of CD.
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PMID:Neurologic and neuropsychiatric complications of Crohn's disease. 919 36

We report a short-term double-blind, crossover study of CoQ10 in 8 patients with mitochondrial encephalomyopathies. Four patients had myoclonus epilepsy with ragged-red fibers syndrome, 3 had mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome, and 1 had chronic progressive external ophthalmoplegia with myopathy. A trend of effectiveness of CoQ10 in several parameters was noted. Fatigability of daily activities was alleviated. The endurance to muscle exercise was augmented. Global muscle strength scored by Medical Research Council scale was increased. The extent of elevation in serum lactate and pyruvate levels after exercise was decreased. However, only the global MRC index score had a statistical significance (p < 0.05). There were no side effects during therapy. The serum CoQ10 levels were significantly lower in patients than in normal controls before CoQ10 treatment and increased significantly after treatment.
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PMID:Coenzyme Q10 treatment in mitochondrial encephalomyopathies. Short-term double-blind, crossover study. 920 60

Single base substitutions of the mitochondrial genome are associated with a variety of metabolic disorders. The myopathy, encephalopathy, lactic acidosis, stroke-like episodes syndrome, most frequently associated with an A to G transition mutation at position 3243 of the mitochondrial tRNALeu(UUR) gene, is characterized by biochemical and structural alterations of mitochondria. To investigate the pathophysiology of the mutation, we established distinct Epstein-Barr virus-transformed B-cell lines for analyses that harbored 30-70% of the mutated genome. Interestingly, neither an alteration of the processing of primary transcripts nor a general impairment of individual mitochondrial protein subunit synthesis rates could be observed. Nevertheless a marked decrease of cytochrome-c oxidase activity and reduced content of mitochondrial encoded subunits in the assembled respiratory complex IV was recorded on the cell line harboring 70% mutated mtDNA. Quantitative analysis of incorporation rates of the amino acid leucine into newly synthesized mitochondrial proteins, representing the functionality of the tRNALeu(UUR) in protein biosynthesis, revealed a specific decrease of this amino acid in distinct mitochondrial translation products. This observation was supported by a variation in the proteolytic fingerprint pattern. Our results suggest that the malfunctioning mitochondrial tRNALeu(UUR) leads to an alteration of amino acid incorporation into the mitochondrially synthesized subunits of the oxidative phosphorylation system, thus altering it's structure and function.
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PMID:Pathophysiology of the MELAS 3243 transition mutation. 934 Nov 62

Atrial fibrillation (AF) is a common arrhythmia in patients with hypertensive heart disease. In addition, the presence of hypertension in patients with AF constitutes an important risk factor for the development of thromboembolic events and probably also selects out those individuals who may be resistant to drug therapy. AF in patients with hypertensive heart disease may lead to a number of serious clinical sequelae including stroke, left atrial myopathy, left ventricular dysfunction, and congestive heart failure. This needs to be treated aggressively since many patients may become quite symptomatic when AF develops in the setting of diastolic and systolic dysfunction, regular features of hypertensive heart disease. There are several treatment approaches that may be considered in such patients ranging from interventions to prevent thromboembolic events, drugs and procedures for control of the ventricular response, and drug and non-pharmacologic therapy specifically designed to prevent AF or to restore normal sinus rhythm. This review article will cover each of these components of therapy of AF and will attempt to focus on those therapies that might be best suited for patients with hypertensive heart disease.
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PMID:Management of atrial fibrillation in patients with hypertension. 941 79

We report a 31-year-old woman who developed myopathy and neuropathy during pregnancy. She was diagnosed as having mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). A T-to-C transition mutation at nucleotide position 3271 was detected in the mitochondrial gene. Her symptoms subsided spontaneously and she delivered a male infant at 38 weeks of gestation. Prior reports on mitochondrial diseases with pregnancy are very rare, probably because of the early onset of the disease. The metabolic changes during pregnancy increase the stress on the mitochondrial function, particularly in patients with impaired mitochondrial function. Therefore pregnancy can aggravate mitochondrial diseases.
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PMID:Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes with deterioration during pregnancy. 980 89

The serum pyruvate and lactate levels were studied after exercise on a bicycle ergometer in a family of diabetes mellitus (DM) associated with a mutation at nucleotide 3243 in the mitochondrial gene. A 56-year-old Japanese woman with the mutation at a percentage of 5% in the blood had insulin-dependent DM and sensory hearing loss without muscle symptoms. Her serum lactate and pyruvate levels increased markedly during and after exercise on a bicycle ergometer. Two of her sons were found to have the same mutation at a percentage of 17% and 18%, respectively. Her 26-year-old son was found to have borderline DM after oral glucose loading, although he showed no abnormalities of the metabolism of pyruvate and lactate. Her 31-year-old son showed no abnormalities after oral glucose loading and after exercise on a bicycle ergometer. Although the same mutation causes more severe MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes), little is known about whether these diabetic patients are subclinically involved with myopathy. The noninvasive ergometer exercise with determination of serum pyruvate and lactate may be useful in evaluating the severity of myopathy in these patients.
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PMID:[Exercises on a bicycle ergometer in a family of diabetes mellitus associated with a mutation of mitochondrial DNA]. 986 17

The transcript levels of nuclear and mitochondrial genes involved in oxidative phosphorylation were quantified in human myoblasts and myotubes cultured from biopsies of patients harboring either heteroplasmic point mutation or deletion of mitochondrial DNA. The transcript patterns were determined by two different methodologies, competitive reverse-transcription polymerase chain reaction and classical Northern blot analysis, both referred to the mitochondrial to nuclear DNA ratio. In myoblasts from the patients with MELAS (myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) and KSS (Kearns-Sayre) syndromes, both methodologies revealed an increase of mtDNA transcript levels. A higher level of the nuclear ATP synthase beta transcript was observed in the MELAS patient cells and could be the consequence of a feedback effect of the mitochondrial DNA mutation. Moreover, the nuclear and mitochondrial transcript accumulation is more pronounced after myoblast differentiation. Thus, the OXPHOS expression is specifically altered in patients with mitochondrial diseases. The competitive RT-PCR, a rapid and sensitive technique, could be applied to investigation of mitochondrial myopathies.
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PMID:Quantification of OXPHOS gene transcripts during muscle cell differentiation in patients with mitochondrial myopathies. 988 18

Mutations in the tRNA genes of mitochondrial DNA (mtDNA) cause the debilitating MELAS (mitochondrial, myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and MERRF (myoclonic epilepsy and ragged-red fibres) syndromes. These mtDNA mutations affect respiratory chain function, apparently without decreasing cellular ATP concentration [Moudy et al. (1995) PNAS, 92, 729-733]. To address this issue, we investigated the role of mitochondrial ATP synthesis in fibroblasts from MELAS and MERRF patients. The maximum rate of mitochondrial ATP synthesis was decreased by 60-88%, as a consequence of the decrease in the proton electrochemical potential gradient of MELAS and MERRF mitochondria. However, in quiescent fibroblasts neither ATP concentration or the ATP/ADP ratio was affected by the lowered rate of ATP synthesis. We hypothesized that the low ATP demand of quiescent fibroblasts masked the mitochondrial ATP synthesis defect and that this defect might become apparent during higher ATP use. To test this we simulated high energy demand by titrating cells with gramicidin, an ionophore that stimulates ATP hydrolysis by the plasma membrane Na+/K+-ATPase. We found a threshold gramicidin concentration in control cells at which both the ATP/ADP ratio and the plasma membrane potential decreased dramatically, due to ATP demand by the Na+/K+-ATPase outstripping mitochondrial ATP synthesis. In MELAS and MERRF fibroblasts the corresponding threshold concentrations of gramicidin were 2-20-fold lower than those for control cells. This is the first demonstration that cells containing mtDNA mutations are particularly sensitive to increased ATP demand and this has several implications for how mitochondrial dysfunction contributes to disease pathophysiology. In particular, the increased susceptibility to plasma membrane depolarization will render neurons with dysfunctional mitochondria susceptible to excitotoxic cell death.
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PMID:Decreased ATP synthesis is phenotypically expressed during increased energy demand in fibroblasts containing mitochondrial tRNA mutations. 991 28

Out of 90 Portuguese patients with mitochondrial cytopathy, six harbored the A3243G mutation in the mtDNA tRNA(Leu(UUR)) gene ('MELAS mutation'). They had heterogeneous clinical features, including myopathy with stroke-like episodes, progressive external ophthalmoparesis, diabetes mellitus, and subacute encephalopathy. Histochemical and biochemical analyses of muscle biopsies showed abundant ragged-red fibers reacting positively with the cytochrome oxidase stain, and decreased respiratory chain enzyme activities. On average, the proportion of mutated mtDNA was 67% (20-88%) in tissues from patients and 21% (0-49%) in blood from 20 maternal relatives. The proportion of mutated mitochondrial genomes in muscle did not correlate with clinical presentation or duration of disease. This study, the first in Portuguese patients, confirms the frequent occurrence of the A3243G mutation in patients with mitochondrial diseases, and emphasises the usefulness of genetic testing in reaching a correct diagnosis.
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PMID:The mitochondrial DNA A3243G mutation in Portugal: clinical and molecular studies in 5 families. 1037 Oct 79

The mitochondrial mutation A-->G at nucleotide position 3243 is associated with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and other mitochondrial encephalomyopathies. We found this mutation in a 61-year-old patient who developed at the age of 54 a myopathy with painful muscle stiffness as the predominant symptom. Additionally hypacusis, a mild hemisensory syndrome and impaired glucose tolerance were present. Muscle histopathology showed few ragged red fibers. The mutation was detected heteroplasmatically in DNA from muscle and blood. So far painful muscle stiffness has not been a known phenotype of the 3243 mutation.
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PMID:Mitochondrial 3243 A-->G mutation (MELAS mutation) associated with painful muscle stiffness. 1040 50


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