Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.9.3.1 (cytochrome oxidase)
8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A comparative histochemical analysis of the prevalence and cytochrome oxidase staining characteristics of ragged-red fibres in limb skeletal muscles was performed in 19 patients spanning four distinct mitochondrial syndromes: chronic progressive external ophthalmoplegia; myoclonus epilepsy with ragged-red fibres; mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes; and pure limb myopathy. The percentage occurrence of non-ragged red but cytochrome oxidase negative fibres was additionally noted. Ragged-red fibres and cytochrome oxidase-negative fibres were generally more prevalent in the chronic progressive external ophthalmoplegia syndrome than in myoclonus epilepsy ragged-red fibres syndrome or mitochondrial myopathy encephalopathy lactic acidosis and stroke-like episodes syndrome. Isolated cytochrome oxidase-negative fibres were a common finding in each phenotypic syndrome except pure limb myopathy and could involve any of the major fibre types non-specifically. Ragged-red fibres were devoid of cytochrome oxidase activity in chronic progressive external ophthalmoplegia, but commonly displayed activity in the other three syndromes providing a clue to syndromal differentiation on a histochemical basis.
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PMID:Contrasting histochemical features of various mitochondrial syndromes. 762 56

MELAS is a mitochondrial cytopathy characterized by encephalopathy with stroke-like episodes and lactic acidosis. Most patients exhibit an A-G transition mutation at np 3243 of mitochondrial DNA (tRNA(Leu)(UUR)). We present a family of four in which the mutation was discovered in blood and in muscle mt DNA. Two patients had the classic MELAS syndrome with multiple stroke-like episodes. Some episodes were precipitated by metabolic stress. The remaining two patients had an oligosymptomatic disease with mild chronic encephalopathy, small stature and hearing loss. MRI was followed over a period of 4-8 years, during which the MELAS patients showed progression from nonspecific multifocal signal change to typical extensive cortico-subcortical parieto-occipital lesions and progressive cerebral atrophy. MRI in the oligosymptomatic cases was normal, or showed non-progressive cerebellar atrophy. Biochemical findings were non-specific, indicating increased mitochondrial volume in all cases, and a relatively complex IV defect in one case. All patients were treated with coenzyme Q with varying clinical response. The percentage of mutant mt DNA in blood and muscle did not correlate with clinical severity. Pathogenetic theories based on molecular genetics, and the therapeutic regimen in terms of the underlying biochemical concepts are discussed.
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PMID:[MELAS syndrome. Clinical aspects, MRI, biochemistry and molecular genetics]. 801 33

The accepted beneficial effects of hyperbaric oxygen (HBO) include a greatly diminished carboxyhemoglobin (COHgb) half-life, enhanced tissue clearance of residual carbon monoxide (CO), reduced cerebral edema, and reversal of cytochrome oxidase inhibition, and prevention of central nervous system lipid peroxidation. Debate regarding the criteria for selection of HBO versus 100% normobaric oxygen therapy continues, and frequently is based solely on the level of COHgb saturation. Patients who manifest signs of serious CO intoxication (unconsciousness, neuropsychiatric symptoms, cardiac or hemodynamic instability) warrant immediate HBO therapy. An unresponsive 33-year-old woman was found in a closed garage, inside her automobile with the ignition on. Her husband admitted to seeing her 6 hours before discovery. 100% normobaric oxygen was administered in the prehospital and emergency department settings. The patient had an initial COHgb saturation of 46.7%, a Glasgow coma score of 3, and was transferred for HBO therapy. Before HBO therapy, the patient remained unresponsive and demonstrated decerebrate posturing and a positive doll's eyes (negative oculocephalic reflex). The electroencephalogram pattern suggested bilateral cerebral dysfunction consistent with a toxic metabolic or hypoxic encephalopathy. The patient underwent HBO therapy at 2.4 ATA for 90 minutes twice a day for 3 consecutive days. On day 7, the patient began to awaken, was weaned from ventilatory support, and was not soon verbalizing appropriately. A Folstein mental status examination showed a score of 26 of 30. Neurological examination demonstrated mild residual left upper extremity weakness and a normal gait. There was no evidence of significant neurological sequelae at 1 month follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coma reversal with cerebral dysfunction recovery after repetitive hyperbaric oxygen therapy for severe carbon monoxide poisoning. 817 65

The pathophysiological significance of the mitochondrial microangiopathy in MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) syndrome was evaluated in an autopsy study of a nearly 13-year-old girl who had suffered from multiple infarctlike lesions in the brain, a mitochondrial myopathy-cardiomyopathy, and a generalized mitochondrial microangiopathy. Cytochemically, defects of cytochrome c oxidase (complex IV) were visualized by light and electron microscopy in the skeletal and heart muscle and in the altered vessels, as well as in single bile duct cells, with the activity of the hepatocytes being diffusely reduced, whereas in the brain, the cytochemical activity was only slightly diminished. Biochemical studies revealed a 50% reduction of both NADH (the reduced from of nicotinamide-adenine dinucleotide) dehydrogenase (complex I) and complex IV in the skeletal muscle. In the brain, complex I was diminished to 20%, whereas complex IV was only slightly below the low-normal range. Immunohistochemical studies with the use of subunit-specific antiserum samples against cytochrome c oxidase showed a varying protein profile, with loss of both mitochondrially and nuclearly derived subunits being most pronounced in the heart muscle and lesser in the skeletal muscle. In the brain, liver, bile ducts, and especially the vessels, no loss of enzyme protein content was observed. The results illustrate heterogeneous tissue expression of respiratory chain defects in MELAS syndrome and indicate that vascular cytochrome c oxidase deficiency may be involved in the cerebral manifestation of the disease, whereas in other organs like the heart, a similar pathogenetic importance of the microangiopathy cannot be verified.
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PMID:Generalized mitochondrial microangiopathy and vascular cytochrome c oxidase deficiency. Occurrence in a case of MELAS syndrome with mitochondrial cardiomyopathy-myopathy and combined complex I/IV deficiency. 838 Dec 71

Cerebral hypoxia-ischemia causes encephalopathy and neurologic disabilities in newborns by unclear mechanisms. We tested the hypothesis that hypoxia-ischemia causes brain damage in newborns that is system-preferential and related to regional oxidative metabolism. One-week-old piglets were subjected to 30 minutes of hypoxia and then seven minutes of airway occlusion, producing asphyxic cardiac arrest, followed by cardiopulmonary resuscitation and four-day recovery. Brain injury in hypoxic-ischemia piglets (n = 6) compared to controls (n = 5) was analyzed by hematoxylin-eosin, Nissl, and silver staining, relationships between regional vulnerability and oxidative metabolism were evaluated by cytochrome oxidase histochemistry. Profile counting-based estimates showed that 13% and 27% of neurons in layers II/III and layers of somatosensory cortex had ischemic cytopathology, respectively; CA1 neuronal perikarya appeared undamaged, and < 10% of CA3 and CA4 neurons were injured; and neuronal damage was 79% in putamen, 17% in caudate, but nucleus accumbens was undamaged. Injury was found preferentially in primary sensory neocortices (particularly somatosensory cortex), basal ganglia (predominantly putamen, subthalamic nucleus, and substantia nigra reticulata), ventral thalamus, geniculate nuclei, and tectal nuclei. In sham piglets, vulnerable region generally had higher cytochrome oxidase levels than less vulnerable areas. Postischemic alterations in cytochrome oxidase were regional and laminar, with reductions (31-66%) occurring in vulnerable regions and increases (20%) in less vulnerable areas. We conclude that neonatal hypoxia-ischemia causes highly organized, system-preferential and topographic encephalopathy, targeting regions that function in sensorimotor integration and movement control. This distribution of neonatal encephalopathy is dictated possibly by regional function, mitochondrial activity, and connectivity.
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PMID:Primary sensory and forebrain motor systems in the newborn brain are preferentially damaged by hypoxia-ischemia. 898 85

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

Defects of the mitochondrial respiratory chain are associated with a great variety of clinical disorders. In addition to the well recognized syndromes, a significant number of patients present non-specific encephalopathic disorders. In consequence these types of mitochondrial disorder are very difficult to diagnose on clinical features alone. In this paper, we describe the clinical and the magnetic resonance findings of 2 patients with a neurological syndrome indistinguishable from multiple sclerosis (Poser). Muscle biochemistry revealed defect of complex IV of the respiratory chain. We think that these patients have a mitochondrial encephalomyopathy. We suggest that in patients presenting as atypical multiple sclerosis it could be necessary investigating mitocondrial encephalopathy.
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PMID:[Mitochondrial respiratory chain deficiency may present as multiple sclerosis]. 960 60

By studying a large series of 157 patients, we found that complex I (33%), complex IV (28%), and complex I+IV (28%) deficiencies were the most common causes of respiratory chain (RC) defects in childhood. Truncal hypotonia (36%), antenatal (20%) and postnatal (31%) growth retardation, cardiomyopathy (24%), encephalopathy (20%), and liver failure (20%) were the main clinical features in our series. No correlation between the type of RC defect and the clinical presentation was noted, but complex I and complex I+IV deficiencies were significantly more frequent in cases of cardiomyopathy (P<.01) and hepatic failure (P<.05), respectively. The sex ratio (male/female) in our entire series was mostly balanced but was skewed toward males being affected with complex I deficiency (sex ratio R=1.68). Interestingly, a high rate of parental consanguinity was observed in complex IV (20%) and complex I+IV (28%) deficiencies. When parental consanguinity was related to geographic origin, an even higher rate of inbreeding was observed in North African families (76%, P<.01). This study gives strong support to the view that an autosomal recessive mode of inheritance is involved in most cases of mitochondrial disorders in childhood, a feature that is particularly relevant to genetic counseling for this devastating condition.
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PMID:A high rate (20%-30%) of parental consanguinity in cytochrome-oxidase deficiency. 968 89

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

Hypoxic-ischaemic encephalopathy (HIE) was diagnosed in an infant with acidosis. At 7 weeks of age further investigations revealed abnormal neuroimaging (CT and MRI scans) and a raised plasma and CSF lactate. A skeletal-muscle biopsy at 2 months of age confirmed the diagnosis of cytochrome oxidase deficiency. The course of the patient's disorder has taken that of a static encephalopathy (cerebral palsy). Inborn disorders of the respiratory chain should be considered in the differential diagnosis of HIE.
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PMID:Cytochrome oxidase deficiency presenting as birth asphyxia. 1087 29


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