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Biomedical subjects

H Nakase

Publications and source records attributed to H Nakase.

At least 145 records · Page 8Linked to original sources
PubMed1989

A gene specifying subunit VIII of human cytochrome c oxidase is localized to chromosome 11 and is expressed in both muscle and non-muscle tissues.

Subunit VIII of mammalian cytochrome c oxidase (COX; EC 1.9.3.1) exists in at least two isoforms, because different but related polypeptides have been identified in COX isolated from liver and heart of both beef and pig. We have isolated a full length cDNA specifying subunit VIII of human COX from a human liver cDNA library. Sequences hybridizing to this cDNA are present at only one site, the COX8 locus, on human chromosome 11q12-q13. The deduced human polypeptide is 58% identical with COX VIII isolated from beef liver, but only 38% identical with COX VIII isolated from beef heart. Transcriptional analysis shows that an mRNA identical with the isolated cDNA is present in abundant amounts not only in human and monkey liver tissue, but in heart and skeletal muscle as well, tissues not known previously to contain this isoform. Since the only COX VIII subunit found in human heart agrees 100% with the polypeptide deduced from this coxVIII cDNA, it may well be that, in distinction to other mammals, only one form of COX VIII exists in primates.

Amino Acid Sequence↗
PubMed1989

Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome.

We investigated the correlations of deletions of mitochondrial DNA in skeletal muscle with clinical manifestations of mitochondrial myopathies, a group of disorders defined either by biochemical abnormalities of mitochondria or by morphologic changes causing a ragged red appearance of the muscle fibers histochemically. We performed genomic Southern blot analysis of muscle mitochondrial DNA from 123 patients with different mitochondrial myopathies or encephalomyopathies. Deletions were found in the mitochondrial DNA of 32 patients, all of whom had progressive external ophthalmoplegia. Some patients had only ocular myopathy, whereas others had Kearns-Sayre syndrome, a multisystem disorder characterized by ophthalmoplegia, pigmentary retinopathy, heart block, and cerebellar ataxia. The deletions ranged in size from 1.3 to 7.6 kilobases and were mapped to different sites in the mitochondrial DNA, but an identical 4.9-kilobase deletion was found in the same location in 11 patients. Biochemical analysis showed decreased activities of NADH dehydrogenase, rotenone-sensitive NADH-cytochrome c reductase, succinate-cytochrome c reductase, and cytochrome c oxidase, four enzymes of the mitochondrial respiratory chain containing subunits encoded by mitochondrial DNA. We conclude that deletions of muscle mitochondrial DNA are associated with ophthalmoplegia and may result in impaired mitochondrial function. However, the precise relation between clinical and biochemical phenotypes and deletions remains to be defined.

Blotting, Southern↗
PubMed1989

A direct repeat is a hotspot for large-scale deletion of human mitochondrial DNA.

Kearns-Sayre syndrome (KSS) and progressive external ophthalmoplegia (PEO) are related neuromuscular disorders characterized by ocular myopathy and ophthalmoplegia. Almost all patients with KSS and about half with PEO harbor large deletions in their mitochondrial genomes. The deletions differ in both size and location, except for one, 5 kilobases long, that is found in more than one-third of all patients examined. This common deletion was found to be flanked by a perfect 13-base pair direct repeat in the normal mitochondrial genome. This result suggests that homologous recombination deleting large regions of intervening mitochondrial DNA, which previously had been observed only in lower eukaryotes and plants, operates in mammalian mitochondrial genomes as well, and is at least one cause of the deletions found in these two related mitochondrial myopathies.

Base Composition↗
PubMed1989

Myoclonic epilepsy and ragged-red fibers with cytochrome oxidase deficiency: neuropathology, biochemistry, and molecular genetics.

A 36-year-old man with myoclonic epilepsy and ragged-red fibers (MERRF) died after more than 18 years of follow-up study. He was 1 of 3 affected siblings and the offspring of an affected mother, suggesting maternal transmission. At autopsy, there was neuronal loss and gliosis in the dentate nucleus of the cerebellum and in the inferior olivary nucleus. Skeletal muscle showed ragged-red fibers, and paracrystalline inclusions in mitochondria by electron microscopy. Biochemical analysis showed a generalized partial defect of cytochrome c oxidase (COX) in mitochondria isolated from all tissues, including brain, heart, skeletal muscle, kidney, and liver. The Michaelis constant (Km) for cytochrome c was abnormally low, suggesting a defect of the mitochondrially encoded subunit II of COX. Immunological studies (enzyme-linked immunosorbent assay, dot-blot, Western blot, and immunohistochemistry) showed that the holoenzyme was decreased but subunit II was decreased more than the holocomplex or the nuclearly encoded subunit IV. However, Northern and Southern blots showed that the gene for subunit II, as well as the genes for subunits I, III, IV, and VIII, were of normal size and were normally transcribed. A point mutation or a small deletion of mitochondrial DNA, probably affecting the COX-II gene, may be responsible for the COX deficiency in this case of MERRF.

Adolescent↗
PubMed1988

Subunit Va of human and bovine cytochrome c oxidase is highly conserved.

We have isolated a full-length cDNA clone specifying the nuclear-encoded subunit Va of the human mitochondrial respiratory enzyme cytochrome c oxidase (COX; EC 1.9.3.1.). The deduced sequence of the polypeptide is 95% identical to that of the corresponding subunit of bovine COX, which makes it the most conserved polypeptide among the known bovine/human pairs of COX subunits. This polypeptide contains an N-terminal presequence which is rich in basic and hydroxylated residues, but differs from the deduced presequences of all other previously isolated COX subunits in that it also contains a negatively charged residue. We find no evidence of tissue-specific isoforms of subunit Va, as Northern analysis showed a single, identically-sized transcript in RNA from human muscle, liver, and brain, while coxVa cDNAs isolated from both endothelial and fetal muscle cDNA libraries had identical nucleotide sequences.

Amino Acid Sequence↗
PubMed1988

Sequence of cDNAs encoding subunit Vb of human and bovine cytochrome c oxidase.

We have isolated a full-length human fetal muscle cDNA clone specifying the nuclear-encoded subunit Vb of the human mitochondrial respiratory chain enzyme, cytochrome c oxidase (COX; EC 1.9.3.1), and a partial-length brain cDNA clone specifying the analogous bovine subunit. The two cDNAs are 85% identical at the nucleotide level. Similar to other proteins imported into mitochondria, the deduced human COX Vb protein contains a presequence, 31 amino acids long, rich in basic residues. We find no evidence for tissue-specific transcripts for subunit Vb of human COX, as Northern analysis of total RNA from human muscle, liver, and brain showed a single, identically sized transcript in each cell type, while partial-length cDNA clones isolated from human muscle and endothelial cell cDNA libraries were identical in sequence to the fetal muscle cDNA.

Amino Acid Sequence↗
PubMed1988

Molecular defects in cytochrome oxidase in mitochondrial diseases.

Defects of cytochrome c oxidase (COX) show remarkable clinical, biochemical, and genetic heterogeneity. Clinically, there are two main groups of disorders, one dominated by muscle involvement, the other by brain dysfunction. Biochemically, the enzyme defect may be confined to one or a few tissues (reflecting the existence of tissue-specific isozymes) or affect all tissues. Immunologically reactive enzyme protein is decreased in some forms of COX deficiency but not in others. Because COX is encoded both by nuclear and by mitochondrial genes, COX deficiencies may be due to mutations of either genome and may offer useful models to study the communication between nuclei and mitochondria. We have isolated full-length cDNA clones encoding human COX subunits IV, Vb, and VIII and a partial-length clone for subunit Va. These clones are being used as probes to analyze the DNA and RNA of patients with COX deficiency.

Brain Diseases↗
PubMed1988

Deletions of mitochondrial DNA in Kearns-Sayre syndrome.

We have identified large-scale deletions in muscle mitochondrial DNA (mtDNA) in seven of seven patients with Kearns-Sayre syndrome (KSS). We found no detectable deletions in the mtDNA of ten non-KSS patients with other mitochondrial myopathies or encephalomyopathies, or three normal controls. The deletions ranged in size from 2.0 to 7.0 kb, and did not localize to any single region of the mitochondrial genome. The proportion of mutated genomes in each KSS patient ranged from 45% to 75% of total mtDNA. There was no correlation between the size or site of the deletion, biochemical abnormality of mitochondrial enzymes, or clinical severity. The data bolster arguments that KSS is a unique disorder and genetic in origin.

Adolescent↗
PubMed1988

Intraventricular arachnoid cyst. Report of two cases.

Two patients with intraventricular arachnoid cysts are reported and a brief review of the relevant literature is presented. Arachnoid cysts are usually extracerebral or extraventricular. Intraventricular arachnoid cysts are rare: including the two cases reported here, only five cases have been described. The following characteristics were noted in these five patients: all were young; headache was the initial symptom in four; the cyst was in the trigone of a lateral ventricle in four; and there was dilatation of the inferior horn in three.

Adult↗
PubMed1987

[An autopsy case of multicentric glioma of multiple histopathology].

An autopsy case is described of an 66-year-old man with multicentric glioma of multiple histopathology, i.e. protoplasmic astrocytoma and glioblastoma. Enhanced CT scan revealed three separate lesions in the right cerebral hemisphere, pons, and cerebellar vermis. Initial diagnosis by CT included metastatic and primary brain tumor, multiple abscess, fungal infection, parasites, tuberculoma, and so on. Biopsy of the right frontal mass revealed astrocytoma grade-2. An autopsy revealed gelatinous, clear marginal mass in the right frontal, parietooccipital and cerebellar vermis; an opaque marginal mass with necrosis in dorsal pons was found. At microscopic examination, the right frontal tumor exhibited continuity with both the paraventricular and the right parietooccipital tumor. The right cerebral hemisphere and cerebellar vermis tumors showed protoplasmic astrocytoma; the dorsal pons tumor showed glioblastoma. CSF examination revealed no tumor cells. Tumor invasion of the internal capsule and the meninges was also not found. Accordingly, we diagnosed as multicentric astrocytoma of multiple histopathology. Only 11 case reports of multicentric glioma were recorded in Japan; only one of which was of multiple histopathology. Worldwide, only 7 case reports of multicentric glioma of multiple histopathology were recorded; this is the first case of protoplasmic astrocytoma and glioblastoma. Seen in terms of pathogenesis of multicentric glioma, this case is thought to be very interesting.

Astrocytoma↗
PubMed1986

Effect of cilostazol on experimental cerebral infarction in rabbits.

The effects of 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3, 4-dihydro-2(1H)-quinolinone (cilostazol, OPC-13013), acetylsalicylic acid (ASA) and ifenprodil on experimentally induced cerebral infarction were studied in anesthetized rabbits. Cerebral infarction was induced by injecting arachidonic acid (AA) at a dose of 0.5 mg/kg into the unilateral intracarotid artery. After the injection of AA, the brain was perfused with Indian ink, and the degree of thrombus formation was determined by calculating the percentage of perfused area in the hemispheres. The intracarotid injection of AA produced a non-perfused area amounting to 84% of the hemisphere in the injected side and 41% of the hemisphere in the non-injected side. Intravenously administered cilostazol did not produce a definite reduction in carbon-deficient area at 0.1 mg/kg, but it did produce a 49% reduction in the injected side and a 55% reduction in the entire brain at 1 mg/kg. ASA produced a 60% reduction in the carbon-deficient area in the injected side and a 62% reduction in the entire brain at 1 mg/kg. Ifenprodil at 1 mg/kg produced only a 19% reduction in the carbon-deficient area in the injected side.

Animals↗