Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the pathogenesis of Leigh encephalopathy, histologic, biochemical, and mitochondrial DNA analyses were performed on biopsied muscles from 33 patients with the clinical characteristics of this disorder. On muscle histochemistry, cytochrome c oxidase activity was decreased or absent in 7 patients (21%), although none had ragged-red fibers. In 2 patients with cytochrome c oxidase deficiency, staining for this enzyme was poor in the muscle fibers and fibroblasts but was normal in the arterial wall, indicating tissue-specific involvement. Ten patients (30%) had biochemical defects, including 2 with pyruvate dehydrogenase complex, 4 with cytochrome c oxidase, 1 with NADH-cytochrome c reductase (complex I), and 3 with multiple complex deficiencies. None of the 28 patients in whom muscle mitochondrial (mt)DNA was analyzed had DNA deletions or point mutation at nucleotide positions 3,243 or 8,344. These results indicate that the underlying defect in Leigh encephalopathy is heterogeneous because only 30% of patients had enzyme defects demonstrable in muscle biopsy material.
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PMID:Leigh encephalopathy: histologic and biochemical analyses of muscle biopsies. 132 89

To investigate the molecular abnormality in the mitochondria from various tissues of an autopsied patient exhibiting mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes, we have examined the enzymatic activity, iron-sulfur cluster, and subunit composition of the NADH-ubiquinone oxidoreductase (complex I). Rotenone-sensitive NADH-cytochrome c reductase activity was found to be decreased in all the tissues examined. A detailed study of the liver mitochondria has shown that NADH-ubiquinone oxidoreductase activity was greatly diminished. Analysis of the electron paramagnetic resonance spectra of the liver submitochondrial particles revealed a disproportionate deficiency of iron-sulfur clusters in the complex I segment of the respiratory chain. Signals from the clusters N-2 and N-3 diminished more drastically than those from clusters N-1b and N-4. Immunoblotting analysis showed that the 75-kD, 51-kD, and several other subunits were markedly diminished among multiple subunit polypeptides of complex I. These findings suggest that the underlying bases for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes are defects, at least, in the complex I subunits containing a flavin and/or iron-sulfur cluster(s), which resulted in deficiencies of some iron-sulfur clusters.
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PMID:Disproportionate deficiency of iron-sulfur clusters and subunits of complex I in mitochondrial encephalomyopathy. 249 47

A male with mitochondrial myopathy, encephalopathy, lactic acidemia, and strokelike episodes is reported. He had also recurrent episodes of ileus. Muscle biopsy revealed ragged-red fibres. The cytochemistry of cytochrome c oxidase (CCO) showed scattered nonstained fibres, while all muscle fibres were heavily stained by immunocytochemistry using CCO antibody. These findings suggest that partical CCO deficiency may be present in the skeletal muscles of the patient. NADH cytochrome c reductase in the patient's muscle mitochondria was low compared with normal controls (about 26%), although succinate cytochrome c reductase was normal. Coenzyme Q10 administration (90 mg/day) did not improve CSF lactate levels, but did decrease plasma lactate levels. His muscle weakness slightly improved.
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PMID:Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes with recurrent abdominal symptoms and coenzyme Q10 administration. 282 4

The electron transport system of muscle mitochondria was examined in a familial syndrome of lactacidemia, mitochondrial myopathy, and encephalopathy. The propositus, a 14-year-old female, and her 12-year-old sister had suffered from progressive muscle weakness, abnormal fatigability, and central nervous system dysfunction since early childhood. In the propositus, the state 3 respiratory rate of muscle mitochondria with NADH-linked substrates and with succinate was markedly reduced. The levels of cytochromes a + a3, b, and c + c1 were normal. The activities of complexes I, II, III, and IV of the electron transport chain were normal or increased. By contrast, the activities of complex I-III and of complex II-III, both of which need coenzyme Q10 (CoQ10), were abnormally low. On direct measurement, the mitochondrial CoQ10 content was 3.7% of the mean value observed in 10 controls. Serum and cultured fibroblasts of the propositus had normal CoQ10 contents. In the younger sister, the respiratory activities and CoQ10 level of muscle mitochondria were similar to those observed in the propositus. The findings establish CoQ10 deficiency as a cause of a familial mitochondrial cytopathy and suggest that the disease results from a tissue-specific defect of CoQ10 biosynthesis.
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PMID:Muscle coenzyme Q deficiency in familial mitochondrial encephalomyopathy. 292 37

Muscle biopsy specimens from two patients with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes) were studied biochemically. 14CO2 production rates from (1-14C)pyruvate, (U-14C)malate, and (1-14C)2-ketoglutarate were all decreased in intact mitochondria in both patients. Rotenone-sensitive NADH cytochrome c reductase activities were decreased to 8% (patient 1) and 6% (patient 2) of control values; succinate cytochrome c reductase and cytochrome c oxidase values were within normal limits. These results indicate that both patients have a defect of NADH-CoQ reductase of the respiratory chain and that MELAS can be brought about by a defect of NADH-CoQ reductase.
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PMID:Two cases of NADH-coenzyme Q reductase deficiency: relationship to MELAS syndrome. 310 Jul 53

We describe a 16-year-old Japanese girl with a mitochondrial encephalomyopathy who presented with progressive dementia, limb weakness and atrophy, episodic vomiting, generalized convulsions, myoclonic seizures, and hypertrophic cardiomyopathy. CT scan revealed transient focal low density areas in her occipital and parietal lobes, and cerebellar atrophy. The clinical features were consistent with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). Microscopically, most of muscle fibers in the skeletal muscles and heart were occupied by markedly increased mitochondria. Polarographic studies on mitochondria isolated from postmortem heart muscle showed severe impairment of oxidation of NADH-linked substrates in contrast to normal succinate oxidation. The rotenone-sensitive NADH-coenzyme Q reductase activity was markedly decreased in heart, skeletal muscle and liver mitochondria. The biochemical investigations have led to the identification of a defect of complex I in the respiratory chain. Reported cases of a defect of complex I have revealed pure myopathy, encephalopathy or encephalomyopathy. The reason for a varied clinical expression of a single defect remains to be clarified.
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PMID:A mitochondrial encephalomyopathy with cardiomyopathy. A case revealing a defect of complex I in the respiratory chain. 310 81

A mitochondrial defect was investigated in an infant with fatal congenital lactic acidosis (3-14 mM), high lactate-to-pyruvate ratio, hypotonia, and cardiomyopathy. His sister had died with a similar disorder. Resting oxygen consumption was 150% of controls. Pathological findings included increased numbers of skeletal muscle mitochondria (many with proliferated, concentric cristae), cardiomegaly, fatty infiltration of the viscera, and spongy encephalopathy. Mitochondria from liver and muscle biopsies oxidized NADH-linked substrates at rates 20-50% of controls, whereas succinate oxidation by muscle mitochondria was increased. Mitochondrial NADH dehydrogenase activity (complex I, assayed as rotenone-sensitive NADH oxidase, NADH-duroquinone reductase, and NADH-cytochrome c reductase) was 0-10% of controls, and NADH-ferricyanide reductase activity was 25-50% of controls in the mitochondria and in skin fibroblasts. Activities of other electron transport complexes and related enzymes were normal. Familial deficiency of a component of mitochondrial NADH dehydrogenase (complex I) proximal to the rotenone-sensitive site thus accounts for this disorder.
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PMID:Deficiency of the reduced nicotinamide adenine dinucleotide dehydrogenase component of complex I of mitochondrial electron transport. Fatal infantile lactic acidosis and hypermetabolism with skeletal-cardiac myopathy and encephalopathy. 311 Feb 16

Enzymic activities of the respiratory chain and content of immunochemically detectable subunits in NADH-ubiquinone oxidoreductase (Complex I) were measured in mitochondria from the skeletal muscles of 4 patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes (MELAS). The rotenone-sensitive NADH-cytochrome c reductase activity was extremely decreased, ranging from 0% to 27% of the control value. In all patients, the content of subunits of Complex I was also reduced in parallel with the rotenone-sensitive NADH-cytochrome c reductase activity. It is suggested that the variation in the degree of deficiency of Complex I subunits could explain the clinical heterogeneity of patients with MELAS.
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PMID:Deficiency of subunits of Complex I and mitochondrial encephalomyopathy. 313 77

The alpha-keto acid dehydrogenase complex and its component enzymes, lactate dehydrogenase, pyruvate carboxylase, cytochrome c oxidase, succinate-cytochrome c reductase, NADH-cytochrome c reductase, and the concentration of cytochromes and enzymes of beta-oxidation in muscle from a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes were studied and no specific defect was found. These results raise the possibility that the mitochondrial changes in the patient may be secondary.
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PMID:Biochemical studies in mitochondrial encephalomyopathy. 368 14

Oral administration of manganese chloride (25 mg/kg b. w. daily) to monkeys for a period of 18 months produced congestion and marked increase in weight of testis. Histopathologic examination revealed interstitial oedema and degeneration of seminiferous tubules. Activities of succinic dehydrogenase, glucose-6-phosphate dehydrogenase and acid phosphatase were significantly inhibited whereas NADH-diaphorase and alkaline phosphatase activities showed only slight inhibition in seminiferous tubules of treated monkeys. It was concluded that chronic exposure to manganese does not produce sever degenerative changes in the testis earlier than metal induced encephalopathy in primates.
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PMID:Manganese induced testicular changes in monkeys. 624 33


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