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Biomedical subjects

M Orita

Publications and source records attributed to M Orita.

8 recordsLinked to original sources

Resistance to ketosis in moderately obese patients: influence of fatty liver.

To elucidate whether the presence of fatty liver influences ketogenesis in obesity, the metabolic and hormonal changes in basal and low-dose epinephrine (EPI)-stimulated states were studied in 12 obese patients (OB) with normal glucose tolerance, consisting of 6 without fatty liver (OBN) and 6 with fatty liver (OBF). In the basal state, the total ketone body (TKB) concentration and the TKB to free fatty acid (FFA) ratio were significantly (p < 0.01) lower in the OBF than in the OBN group, despite elevated, but comparable, FFA levels in both groups. The basal FFA level and the TKB/FFA ratio correlated with the degree of fatty liver (p < 0.05-0.01). EPI infusion resulted in accelerated lipolysis and diminished FFA-induced ketogenesis, similar to the findings of the basal data. These results suggest that fatty liver per se is related to diminished FFA-induced ketogenesis, leading to resistance to ketosis in obesity.

3-Hydroxybutyric Acid

Effects of calcium antagonists on the erythrocyte membrane.

The effects of dihydropyridine compounds nimodipine, nicardipine and NB818 (isopropyl methyl-6-carbamoyloxymethyl-4-(2,3-dichlorophenyl)-1,4-dihydro-2-methyl- 3,5- pyridine-dicarboxylate) on erythrocyte membranes have been studied. These compounds showed protective effects against hypotonic haemolysis, but not against heat-induced haemolysis. An increase in deformability of erythrocytes by these calcium antagonists was observed using a capillary tube centrifugal method. The erythrocytes showed slight stomatocytosis after 30 min of incubation with calcium antagonists, but did not show significant changes in mean corpuscular volume and ATP levels.

Animals

Age-related changes of erythrocyte membrane in the senescence-accelerated mouse.

Age-related changes in erythrocytes in senescence-accelerated mice (SAM-P) and control mice with normal aging characteristics (SAM-R) were examined. A significant decrease in the number of erythrocytes and significant increases in MCV and ATP levels were observed with aging in SAM-P, while no significant changes were seen in SAM-R. Erythrocytes in aged SAM-P were less fragile than those in aged SAM-R. The contents of cholesterol and phospholipids in erythrocyte membranes increased significantly in aged SAM-P, but the molar ratio of cholesterol/phospholipid decreased. The plasma cholesterol level of SAM-P decreased with aging. Changes such as those observed in SAM-P were not seen in SAM-R during the period of observation.

Aging

DNA sequence polymorphisms in Alu repeats.

We have developed an efficient method for detection of sequence differences in genomic DNA based on a new principle (M. Orita et al., 1989, Genomics 5: 874-879). Using this method, we show here that approximately half the Alu repeats interspersed in the human genome are significantly polymorphic. Analysis of Alu repeat polymorphism should be useful in construction of a high-resolution map and also in identifying genotypes of individuals for clinical and other purposes because the repeats are ubiquitous and the technique for their detection is simple.

Base Sequence

A new RFLP in intron 1 of the human c-Ha-ras1 gene and its close relationship with the variable tandem repeats in the region 3' to the gene.

Based on restriction fragment length polymorphism (RFLP) analysis of BamHI or MspI fragments, the human c-Ha-ras1 alleles could be divided into two major groups, one having about 80 copies of a 28 base pair (bp) sequence in the variable tandem repeat (VTR) region 1.4-kilobase pairs (kb) downstream from the end of the coding exon and the other having 40 copies of the sequence. We found a second RFLP in intron 1 of the c-Ha-ras1 gene at a position about 80 bp upstream from the 5'-end of exon 1. The size of the PstI fragments carrying this region is either 371 or 359 bp depending on the numbers of a hexanucleotide sequence, GGGCCT. In larger fragments, the unit sequence was repeated four times, while in smaller fragments it was repeated twice. Unexpectedly, we found that the alleles with 80 copies of the 28 bp sequence in the VTR region all carried two repeats of GGGCCT in intron 1, while alleles with 40 copies all had four repeats of the GGGCCT sequence.

Base Sequence

Detection of ras gene mutations in human lung cancers by single-strand conformation polymorphism analysis of polymerase chain reaction products.

A simple, sensitive method of DNA analysis of nucleotide substitutions, namely, single-strand conformation polymorphism analysis of polymerase chain reaction products (PCR-SSCP analysis), was used for detection of mutated ras genes in surgical specimens of human lung cancer. Of a total of 129 tumors analysed, 22 contained a mutated ras gene. Of the 66 adenocarcinomas analysed, 14 contained an activated c-Ki-ras2 gene (the mutations in codon 12 in 6, in codon 13 in 4, in codon 18 in one, and in codon 61 in 3), one contained a c-Ha-ras1 gene with a mutation in codon 61 and 3 contained N-ras genes with mutations (in codon 12 in one and in codon 61 in 2). Mutated rats genes were also found in 2 of 36 squamous cell carcinomas (c-Ha-ras1 genes with mutations in codon 61) and 2 of 14 large cell carcinomas (c-Ki-ras2 genes with mutations in codon 12). No mutation of the ras gene was detected in 8 small cell carcinomas and 5 adenosquamous cell carcinomas. These results indicate that activation of the ras gene was not frequent (17%) in human lung cancers, that among these lung cancers mutation of the ras gene was most frequent in adenocarcinomas (27%) and 73% of the point mutations were in the c-Ki-ras2 gene in codon 12, 13, 18 or 61.

Base Sequence