Biomedical subjects

Junichi Masuda

Publications and source records attributed to Junichi Masuda.

22 records · Page 2Linked to original sources

PubMed2002

Hyperosmotic stimuli inhibit VCAM-1 expression in cultured endothelial cells via effects on interferon regulatory factor-1 expression and activity.

Transcriptional up-regulation of the VCAM-1 gene, induced by proinflammatory cytokines such as IL-1beta and TNF-alpha, requires activation of not only NF-kappaB, but also involves interferon regulatory factor (IRF)-1. During a study of gene induction by mechanical stimuli in cultured human endothelial cells, we noted that medium hyperosmolarity appeared to influence cytokine-induced expression of VCAM-1. Indeed, addition of hyperosmotic, pathophysiologically relevant concentrations of NaCl effectively inhibited IL-1beta or TNF-alpha induction of VCAM-1, but not E-selectin, at the level of mRNA and cell surface protein. Because induction of both VCAM-1 and E-selectin by these cytokines is NF-kappaB dependent, we investigated whether the inhibitory effect of hyperosmotic medium might involve IRF-1. Electrophoretic mobility shift assays of the VCAM-1 promoter demonstrated that hyperosmotic medium suppressed IL-1beta- or TNF-alpha-activated binding activities of IRF-1, but not NF-kappaB, to their respective sites. Hyperosmotic medium also inhibited the expression of IRF-1 induced by TNF-alpha or IFN-gamma. Furthermore, hyperosmotic medium inhibited TNF-alpha or IFN-gamma induction of guanylate binding protein-1, another IRF-1-dependent gene. Taken together, hyperosmolarity selectively inhibits cytokine-induced VCAM-1 in endothelial cells, via an IRF-1-dependent mechanism. Thus, pathophysiological fluctuations in plasma osmolarity may influence certain endothelial-dependent components of the inflammatory response and host defense mechanisms.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2002

The genetic effect of the apoprotein AV gene on the serum triglyceride level in Japanese.

The newly identified apoprotein AV (apoAV) gene was suggested to have a significant effect on triglyceride (TG) metabolism in Caucasians. We studied the genetic effect of this gene on serum TG in a Japanese population. Participants (481 male and 412 female) were recruited at a health examination. A T/C single nucleotide polymorphism called SNP3 in the 5'-region of the apoAV gene was genotyped as described previously. The frequency of the C allele was much greater in Japanese than in Caucasians (0.34 vs. 0.08). The serum TG level in subjects with the TT genotype was significantly lower than the level in those with TC/CC (1.10, 1.25 and 1.21 mmol/l for TT, TC and CC, respectively, P=0.0003 by ANOVA), while there were no significant differences either in the serum total cholesterol or the low- and high-density lipoprotein cholesterol levels among the three genotypes. Multiple regression analysis indicated that SNP3 had a significant independent effect on the serum TG level in Japanese (P<0.0001). This result indicates that polymorphism in the apoAV gene influence serum TG in populations of different ethnicities.

Apolipoprotein A-V↗

PubMed2002

Association of G-33A polymorphism in the thrombomodulin gene with myocardial infarction in Koreans.

Thrombomodulin (TM), a thrombin receptor expressed on the endothelial surface, is known to play an important role in the anti-thrombogenic system in vivo. In this study, we examined the effects of 3 single-nucleotide polymorphisms (SNPs) in the TM gene (G-33A, C1418T and C1922T) on the development of myocardial infarction (MI) in Koreans. We found that G-33A was a common SNP (the minor allele frequency was 0.09) in Koreans. Eighty-five MI patients who had received coronary angiography were enrolled and were divided into 3 groups according to the number of coronary arteries in which stenosis was found angiographically (1-vessel disease (1VD) to 3-vessel disease (3VD)). The criterion of coronary stenosis was 50% or more stenosis on angiography. In addition, 102 controls (CONT) who had no significant stenosis were employed. The number of AA/GA genotypes of G-33A was found to be significantly greater in the 1VD than in the CONT (p=0.004 by chi2-test) while no significant difference was found between the multivessel disease (2-3VD) and the CONT. Multiple logistic analysis showed that G-33A was an independent risk factor for the 1VD with an odds ratio of 4.63 (95% confidence interval; 1.62-13.3). C1418T and C1922T were both in linkage disequilibrium with G-33A; however, they were not independent risks for either the 1VD or the 2-3VD. A reporter gene assay showed that G-33A had a significant effect on the TM promoter activity. These results indicated that G-33A polymorphism in TM might be a genetic risk factor for myocardial infarction.

Adult↗

PubMed2002

Fine linkage mapping of the blood pressure quantitative trait locus region on rat chromosome 1.

To narrow the area known to contain the blood pressure quantitative trait locus (QTL) on rat chromosome 1, we constructed a fine linkage map covering the blood pressure OTL region on the chromosome using 22 genetic markers informative for stroke-prone spontaneously hypertensive rats of the Izumo colony (SHRSP/Izm) and Wistar-Kyoto rats of the Izumo colony (WKY/Izm). Linkage mapping was done by genotyping 626 backcrossed rats from matings between SHRSP/Izm and WKY/Izm. Nineteen genetic markers informative for the two strains were selected from public databases. Two markers were newly isolated by screening a rat genomic library. One marker was mapped using a restriction endonuclease polymorphism. The region between DlWox29 and D1Smu11 was covered with 22 informative markers placed every 0.6 cM on average. In addition, 6 physiological candidates for a hypertension gene were mapped in this region either by linkage or by radiation hybrid (RH) mapping. This information should be essential for the construction and analysis of congenic strains for this QTL region.

Animals↗