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Biomedical subjects

T Ogihara

Publications and source records attributed to T Ogihara.

At least 379 records · Page 21Linked to original sources
PubMed1996

Calcitonin prevents CCl4-induced hydroperoxide generation and cytotoxicity possibly through C1b receptor in rat hepatocytes.

The effects of calcitonin (CT) on oxyradical generation and cellular damage induced by carbon tetrachloride (CCl4) were investigated in rat hepatocytes. Addition of CCl4 to the cells concentration dependently increased intracellular production of hydroperoxides and release of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The hepatocytes expressed mRNA for a CT receptor, C1b. Coaddition of CT to the cells concentration dependently suppressed the CCl4-induced increase in hydroperoxide production and also decreased the release of AST and ALT. The suppressive effect of CT on hydroperoxide production was reversed by further addition of H7 or by pretreatment with phorbol 12-myristate 13-acetate for 24 h. These results suggest that CT prevents CCl4-induced oxyradical production and cellular damage through activation of protein kinase C in hepatocytes.

Animals↗
PubMed1996

Association of Trp64Arg mutation of the beta3-adrenergic-receptor with NIDDM and body weight gain.

A possible pathogenic mutation in the beta 3-adrenergic-receptor gene (Trp64Arg) has been reported to be associated with an earlier age of onset of non-insulin-dependent diabetes mellitus (NIDDM) and clinical features of the insulin resistance syndrome in Pima Indian, Finnish and French subjects. Since marked heterogeneity has been reported in the association of mutations of candidate genes with NIDDM between Japanese and other ethnic groups, we investigated the association of Trp64Arg with NIDDM in Japanese subjects. The allele frequency of the mutation (Arg) was slightly, but not significantly, higher in NIDDM than in control subjects (70 out of 342 alleles [20.5%] vs 40 out of 248 [16.1%], respectively, p > 0.2). When our data were combined with those of Pima Indian and Finnish subjects, however, the Arg/Arg genotype was significantly associated with NIDDM as compared with the other two genotypes (p < 0.005, relative risk [RR] 2.13, 95% confidence interval [CI] 1.28-3.55). The Arg allele was also associated with NIDDM (p < 0.05, RR 1.27, 95% CI 1.06-1.52). Japanese subjects homozygous for the mutation had a significantly higher body mass index (mean +/- SD: 25.5 +/- 3.9 kg/m2) than heterozygotes (22.6 +/- 4.1, p < 0.05) and normal homozygotes (22.8 +/- 3.8, p < 0.05). NIDDM patients homozygous for the mutation tended to have an earlier age of onset of NIDDM than those with other genotypes. These data suggest that the Trp64Arg mutation not only contributes to weight gain and age-at-onset of NIDDM but is also associated with susceptibility to NIDDM.

Age of Onset↗
PubMed1996

Association of CTG repeats and the 1-kb Alu insertion/deletion polymorphism at the myotonin protein kinase gene in the Japanese population suggests a common Eurasian origin of the myotonic dystrophy mutation.

We have studied linkage disequilibrium between CTG repeats and an Alu insertion/deletion polymorphism at the myotonin protein kinase gene (DMPK) in 102 Japanese families, of which 93 were affected with myotonic dystrophy (DM). All of the affected chromosomes are in complete linkage disequilibrium with the Alu insertion allele. Among the normal chromosomes, alleles of CTG repeats 5 and > or = 17 are exclusively associated with the insertion allele. On the other hand, intermediate alleles of 11-16 repeats show a significantly greater association with the deletion allele. A strikingly similar pattern of linkage disequilibrium observed in European populations suggests a common origin of the DM mutation in the Japanese and European populations.

Asian People↗
PubMed1996

Identification of genes regulated by glucose in a pancreatic beta-cell line by a new method for subtraction of mRNA.

Various genes are differentially expressed in cells during cell differentiation, development, aging, and in pathological conditions. To identify and isolate the genes that are specifically and differentially expressed in cells, we established a ligation-mediated polymerase chain reaction (PCR)-based method for cDNA subtraction. As this method is PCR-based, when target genes are expressed at high levels relative to the driver (a control pool for subtraction), even a small amount of target genes can be amplified. By this newly developed PCR-based subtraction method, a set of genes regulated by glucose were identified in a mouse insulinoma cell line. This PCR-based and non-radioactive subtraction method will be a powerful tool for identification of novel genes, specifically and differentially expressed in cells.

Animals↗
PubMed1996

A novel microsatellite polymorphism in the human OB gene: a highly polymorphic marker for linkage analysis.

The mouse ob gene and its human homologue OB have recently been cloned. The mutations in the ob gene are known to be associated with extreme obesity. The relationship between the human OB gene and disease, however, is largely unknown due to the lack of suitable markers within or adjacent to the OB gene. To obtain informative markers, we searched for simple tandem repeat polymorphisms in the genomic sequence of the human OB gene and identified a novel tetranucleotide repeat in the 3' flanking region. Fifteen alleles were detected in this marker with a heterozygosity of 0.85 and polymorphism information content of 0.83, indicating a highly informative nature of this marker. Two-point linkage mapping in two Centre Etude Polymorphisme Humaine (CEPH) reference families suggested that this marker is located in the interval between D7S514 and D7S530, the same interval where the OB gene is located (recombination fractions with D7S514 and D7S530 were 0.026 and 0.034, respectively). Although allele frequency distributions of this marker did not differ between 84 control subjects and 69 NIDDM patients, there was a tendency to higher body weight in control subjects with class I/class I genotype than in those without this genotype (68.8 +/- 11.1 vs 60.8 +/- 10.3 kg, p = 0.05). The highly polymorphic nature of this marker and its location in the OB gene makes this marker useful for linkage studies of the OB gene with a number of phenotypes, such as obesity, non-insulin-dependent diabetes mellitus, hypertension and the insulin resistance syndrome.

Alleles↗
PubMed1996

Role of HLA class II alleles in Korean patients with IDDM.

MHC associations with IDDM in the Korean population were studied to investigate genetic susceptibility to this disorder. The frequencies of HLA-DR3, -DR4 and -DR9 were significantly higher in diabetic patients. However, the frequency of DR2 was significantly decreased in diabetic patients. DQA1*0301 and DQA1*0501 were positively and DQA1*0102 and DQA1*0201 negatively associated with IDDM. DQB1*0301 and DQB1*0601 were negatively associated with IDDM. Heterodimers DQA1*0301-DQB1*0201, DQA1*0501-DQB1*0201 and DQA1*0501-DQB1*0302 were positively associated with DQA1*0102-DQB1*0601 negatively associated with IDDM. The frequencies of DR3-DQA1*0301-DQB1*0201 and -DQA1*0501-DQB1*0201 were significantly higher in diabetic patients. The frequencies of DR4-DQA1*0301-DQB1*0201 and DR9-DQA1*0301-DQB1*0303 were significantly higher in diabetic patients. The presence of non-aspartic acid at position 57 of the DQ beta-chain was not associated with susceptibility to IDDM. However, the frequency of Arg 52 homozygotes was significantly higher in diabetic patients. These results suggest a role of the MHC molecule and also suggest racial differences in susceptibility to IDDM even within the Asian populations.

Adult↗
PubMed1996

Do reduced insulin sensitivity and dyslipidemia exist in borderline hypertensive patients?

To evaluate the relationship between insulin resistance, dyslipidemia, and blood pressure (BP), we measured BP, blood glucose, plasma insulin (INS) levels, total cholesterol (T-ch), and triglyceride after an overnight fast in 454 Japanese young, nonobese, nondiabetic factory workers, including 226 normotensive (NT), 120 borderline hypertensive (BHT), and 108 essential hypertensive (EHT) subjects. Age and body mass index were strictly matched among the three groups. Fasting INS and T-ch were greater in BHT > EHT > NT (BHT v NT, P < .05; EHT v NT, P < .05). We also recognized significantly positive correlations between T-ch and mean BP (R = 0.39, P = .021), and between fasting INS and mean BP (r = 0.56, P = .013). These results suggest that insulin resistance and dyslipidemia are associated with hypertension in its early stage.

Adult↗
PubMed1996

Mechanisms mediating postprandial blood pressure reduction in young and elderly subjects.

The objective of this study was to clarify potential differences in hormonal, neurogenic and hemodynamic mechanisms mediating postprandial blood pressure (BP) reduction. In 12 age- and body mass index-matched young normotensive (NT) subjects, 21 elderly NT, 17 young hypertensive (EH) patients, and 32 elderly EH, we measured BP, blood glucose, plasma insulin (IRI), and norepinephrine (NE) levels before and every 30 min for 3 h after a 75 g oral glucose solution ingestion. Cardiac output (CO) and total systemic resistance (TSR) were also measured before and 1 h after oral glucose ingestion. Postprandial BP reduction, defined as 10% or more decline in mean BP was recognized in 3/12 (25%) young NT, 9/21 (43%) elderly NT, 5/17 (29%) young EH, and 20/32 (63%) elderly EH. The most consistent finding was that the IRI response to glucose was high in all subjects with postprandial BP reduction regardless of age or level of BP, although changes in blood glucose levels showed no major differences. The NE level was low in young and elderly NT with postprandial BP reduction, but in EH the level was not different. Increases in CO in elderly subjects with postprandial BP reduction was significantly less than that in subjects without postprandial BP reduction. In addition, the decrease in TSR in young subjects with postprandial BP reduction was significantly greater than that in subjects without postprandial BP reduction, while the decrease in elderly subjects was not different between the subjects with and without postprandial BP reduction. In conclusion, postprandial BP reduction in elderly EH appears to be associated with hyperinsulinemia independent of age and BP status. The vasodilator effects of insulin may contribute to postprandial BP reduction. A second conclusion is that impairment of sympathetic nervous system responses to insulin may also contribute to altered postprandial hemodynamic responses especially in EH, suggesting multiple mechanisms in origin of postprandial BP reduction.

Adult↗
PubMed1996

Changes in frequency of orthostatic hypotension in elderly hypertensive patients under medications.

To evaluate changes in frequency of orthostatic blood pressure (BP) reduction (orthostatic hypotension; OH) in elderly hypertensive patients (HT) before and after treatment for hypertension, we measured BP after supine for 10 min and standing position for 2 min, before and after treatment for 2 years by five kinds of antihypertensive drugs in 50 elderly normotensive subjects (NT) and each of 50 HT in double-blind study. Orthostatic hypotension was defined as 10% or more decline of supine mean BP, and the frequency of OH was in 27% of HT following BP reduction by any kinds of antihypertensive drugs. In conclusion, the reducing or normalized BP by treatment for hypertension in elderly HT decreases the prevalence of orthostatic hypotension.

Aged↗
PubMed1996

Predominance of nocturnal sympathetic nervous activity in salt-sensitive normotensive subjects.

To assess the relation between salt sensitivity and autonomic nervous function by power spectral analysis of heart rate variability in normotensive subjects, low and high salt diets were given to 13 normotensive men (aged 25 to 39 years) for 4 days each. Autonomic function was assessed by power spectral analysis of R-R intervals based on an autoregressive algorithm from 24-h Holter electrocardiogram. Subjects whose mean blood pressure was increased more than 3 mm Hg by high salt diet were defined as salt sensitive (SS, n = 5), and the remainder as salt resistant (SR, n = 8). Using the low frequency (LF, 0.1 Hz) and high frequency (HF, 0.25 Hz) components, the LF to total power ratio (%LF) was used as a marker of sympathetic activity, and the HF to total power ratio (%HF) as a marker of parasympathetic activity. Compared to the daytime, SR revealed a decrease in %LF and an increase in %HF during the night on both diets. In SS, these circadian changes were observed only during low-salt diet. During the night, SS showed a higher %LF and a lower %HF than SR. Plasma catecholamines tended to be decreased by the high sodium diet in SR but not in SS subjects. These results suggest that the persistent nocturnal predominance of sympathetic nervous activity in a salt-sensitive men may contribute to the subsequent increase of blood pressure in these subjects.

Adult↗
PubMed1996

Differences in insulin and sympathetic responses to glucose ingestion due to family history of hypertension.

To evaluate the relationship of metabolic and neural factors in familial hypertension, we examined blood pressure (BP), blood glucose, and plasma insulin and norepinephrine (NE) levels before and every 30 min for 120 min after glucose ingestion in six groups with 20 subjects each: normotensive subjects (NT) with and without a family history of hypertension; borderline hypertensive patients (BHT) with and without a family history of hypertension; and established hypertensive patients (EH) with and without a family history of hypertension. The changes in blood glucose were similar in the six groups. In the subjects with a positive family history of hypertension regardless of BP levels, the basal levels and changes in insulin levels after glucose ingestion were significantly greater than those in the subjects without a family history of hypertension (F = 13.32, P = .0001). In BHT and EH subjects, regardless of family history, changes in insulin were greater than in NT (F = 16.00, P = .0001). Basal levels and changes in plasma NE were higher in BHT and EH (F = 26.55, P = .0001) than NT and changes in plasma NE were greater in subjects with a family history than those in subjects without a family history (F = 18.32, P = .0001). Thus, abnormal insulin and NE responses to glucose appear to aggregate in subjects with a history of familial hypertension, regardless of the level of BP. Furthermore, the ratio of delta NE/ delta insulin (changes from basal to peak) in NT and BHT, and in subjects with a family history were significantly greater than in EH and in subjects without a family history. Thus, we demonstrated that concomitant abnormalities in the glucose-insulin regulatory system and the sympathetic nervous system characterize the early phase in the development of hypertension and these abnormalities have an apparent genetic basis.

Adult↗
PubMed1996

Impaired endothelial function with essential hypertension assessed by ultrasonography.

The objective of this investigation was to evaluate the role of hypertension in endothelial function, changes in which are known to be an early event of atherosclerosis. We assessed endothelial function in 13 subjects with normal blood pressure and 13 subjects with essential hypertension who had never been treated for hypertension or hyperlipidemia and who had no history of smoking or coronary or cerebrovascular disease. B-mode ultrasonography was used to measure the diameter of the brachial artery. Endothelium-dependent dilatation was assessed as the change in diameter of the artery during reactive hyperemia. Endothelium-independent dilatation was evoked, as a control, by sublingual administration of isosorbide dinitrate. Despite similar ages and lipid and glucose levels in the study groups, endothelium-dependent dilatation was less in patients with hypertension (13.1% +/- 1.6%) than in subjects with normal blood pressure (18.5% +/- 1.9%) (p < 0.05), whereas isosorbide dinitrate-induced changes were similar. Systolic and diastolic blood pressure were significantly correlated with endothelium-dependent vasodilatation (r = -0.57 and r = -0.53, respectively) but not with the change by isosorbide dinitrate. These results suggest that endothelial dysfunction exists in patients with hypertension and precedes overt atherosclerotic disease.

Adult↗