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Biomedical subjects

Y Yazaki

Publications and source records attributed to Y Yazaki.

At least 37 records · Page 2Linked to original sources
PubMed2001

Successful prevention of recurrent ventricular fibrillation by intravenous isoproterenol in a patient with Brugada syndrome.

Intravenous administration of isoproterenol restored the ST-segment configuration to nearly normal in the right precordial leads and completely prevented spontaneous VF attacks in a patient with Brugada syndrome. The formation of a Brugada-type ECG has been attributed to the transmural dispersion of repolarization of the right ventricular epicardium and related to modulation of the autonomic nervous system. Our case may provide clues to the pathophysiological mechanism of this syndrome.

Adult↗
PubMed2001

Two cases of bronchial asthma after treatment with amiodarone.

Amiodarone is a highly effective antiarrhythmic agent for the prevention of life-threatening arrhythmias. Two cases are described of patients who developed bronchial asthma after treatment with amiodarone. The bronchial asthma resolved after the dose of amiodarone was decreased in both patients. To our knowledge, an association between amiodarone and severe bronchial asthma has previously been reported only once in the medical literature. Physicians should note that amiodarone may cause bronchospasm in susceptible patients.

Aged↗
PubMed2001

Association analysis of beta(2)-adrenergic receptor polymorphisms with hypertension in Japanese.

Significant evidence has been provided for the pathophysiological involvement of the beta(2)-adrenergic receptor (ADRB2) in hypertension. Among ADRB2 polymorphisms identified to date, 2 amino acid substitutions, Arg16Gly and Gln27Glu, and a promoter variant, T-47C, are considered functionally important. In particular, Arg16Gly was shown to be associated with hypertension in black and white subjects. To investigate the relevance of ADRB2 polymorphisms to hypertension, we undertook an extensive association study in a Japanese population. An association was tested in 2 ways. First, a case-control study was conducted in 842 hypertensive and 633 normotensive subjects. In addition to the overall comparison between case and control groups, each was stratified by body mass index and compared with an independent panel of 525 diabetic subjects. Second, ANOVA and multivariate analyses were performed to test the significance of an association between ADRB2 genotype and the level of blood pressure within the entire population except for 395 subjects who had been under treatment for hypertension. Although no significant association was observed for Arg16Gly and T-47C, 2 analytical methods indicated a marginal association (P:=0.01 to 0.04) between the Glu27 variant and lower blood pressure levels. Given such a normotensive propensity, the odds ratio for Glu27 versus Gln27 allele frequencies was estimated to be 0.74, with a wide confidence interval (95% CI, 0.55 to 0.99) reflecting the low Glu27-allele frequency (6% to 8%) in Japanese. There were no apparent confounding influences of obesity and diabetes on the postulated association. Our data suggest that 3 ADRB2 polymorphisms tested are unlikely to confer principal genetic susceptibility for hypertension in the Japanese population. However, further investigation is warranted to clarify the relevance of ADRB2 polymorphisms to blood pressure regulation.

Aged↗
PubMed2001

Biventricular hypertrophic cardiomyopathy with right ventricular outflow tract obstruction associated with Noonan syndrome in an adult.

This report describes an adult patient with Noonan syndrome accompanied by biventricular hypertrophic cardiomyopathy causing isolated right ventricular outflow tract obstruction. Biventricular hypertrophic cardiomyopathy causing right- and/or left-side outflow tract obstruction, as well as valvular pulmonary stenosis, is relatively common in infants with Noonan syndrome. However, this condition without a dysplastic pulmonary valve, or indeed any polyvalvular dysplasia, is rare in adults with Noonan syndrome. Treatment with a beta-adrenergic receptor blocking agent improved the patient's symptoms. Because neither the etiologic and prognostic relationship nor the genetic linkage between hypertrophic cardiomyopathy associated with Noonan syndrome and non-syndromic hypertrophic cardiomyopathy is clearly defined, clinicopathological findings and further follow-up may provide important evidence for the pathogenesis of hypertrophic cardiomyopathy.

Adult↗
PubMed2001

Two distinct mechanisms of angiotensin II-induced negative regulation of the mitogen-activated protein kinases in cultured cardiac myocytes.

Increasing evidence has suggested that mitogen-activated protein kinases (MAPKs) play important roles in the development of cardiac hypertrophy. We and others have reported that the activity of MAPKs is tightly regulated by angiotensin II (Ang II) in cardiac myocytes. In the present study, we determined the molecular mechanism of Ang II-induced inactivation of MAPKs in rat neonatal cardiac myocytes. Ang II increased MAPK phosphatase 1 (MKP-1) gene expressions within 10 min. Levels of MKP-1 transcripts peaked at 30 min and gradually decreased thereafter. The increase in MKP-1 mRNA levels was Ang II-concentration dependent. An Ang II type 1 receptor (AT1)-specific antagonist, CV-11974, completely suppressed the Ang II-induced increase in MKP-1 gene expression, while a type 2 receptor (AT2)-specific antagonist, PD-123319, had no significant effects. Induction of MKP-1 gene expressions by Ang II was inhibited by pretreatment with an intracellular Ca2+ chelator, BAPTA-AM, or with the protein kinase C inhibitors, H-7 and Calphostin C. Phorbol ester and Ca2+ ionophore both significantly increased MKP-1 mRNA levels and showed synergistic action. Overexpression of MKP-1 cDNA blocked the Ang II-induced increase in expressions of immediate early response genes. In addition, Ang II-induced MAPK activation was significantly inhibited by pretreatment with CV-11974, but significantly enhanced by pretreatment with PD-123319. Addition of the AT2 agonist, CGP42112A, reduced basal MAPK activities, and pretreatment with PD-123319 abolished MAPK inactivation by CGP42112A. In conclusion, these observations suggest that Ang II negatively regulates MAPKs through AT1 receptors by increasing MKP-1 mRNA levels and through AT2 receptors by unknown mechanisms.

Angiotensin II↗
PubMed2001

Evaluation of selected polymorphisms of the Mendelian hypertensive disease genes in the Japanese population.

It remains to be defined whether molecular variants of the genes underlying Mendelian forms of hypertension play some etiological role in essential hypertension. To pursue this issue, we focused on the following three genes: the epithelial sodium channel (ENaC), 11beta-hydroxysteroid dehydrogenase type 2, and mineralocorticoid receptor genes. Five sequence variations of these genes, which were either previously reported to show significant association with hypertension or identified as "mild" molecular variants, were chosen for our study. Each variation was screened in 247 severe hypertensive patients with early onset (<45 years) and any detectable variations were subsequently characterized in 291 older normotensive subjects (>60 years) for the case-control comparison. We also investigated the significance of association between the tested variants and biochemical parameters reflecting sodium-water homeostasis, such as plasma aldosterone concentration (PAC) and renin activity (PRA). Only the T663A variant (alpha-subunit of ENaC) turned out to be polymorphic in the Japanese population. In disagreement with positive associations previously reported in white and black subjects, we observed no significant association between T663A and hypertension, while allele frequencies of A663 were higher in Japanese (58-64%) compared with a reported prevalence of 29% in whites and 15% in blacks. T663A showed a borderline association (p=0.02) with the PAC/PRA ratio but not with PAC or PRA in the multivariate analysis. Our data did not support the association between Mendelian disease gene variants and essential hypertension in the Japanese. However, the present study did not definitively resolve this issue and further investigation is certainly warranted.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2001

[Calcineurin inhibitor attenuates the development and induces the regression of cardiac hypertrophy in rats with salt-sensitive hypertension].

BACKGROUND: It remains unclear how hemodynamic overload induces cardiac hypertrophy. Recently, activation of calcium-dependent phosphatase, calcineurin, has been elucidated to induce cardiac hypertrophy. In the present study, we examined the role of calcineurin in load-induced cardiac hypertrophy by using Dahl salt-sensitive (DS) rats, which develop both pressure and volume overload when fed a high salt diet. METHODS AND RESULTS: In the DS rat heart, the activity of calcineurin was increased and cardiac hypertrophy was induced by high salt diet. Treatment of DS rats with the calcineurin inhibitor FK506 (0.1 or 0.01 mg/kg every second day) from the age of 6 weeks to 12 weeks inhibited the activation of calcineurin in the heart in a dose-dependent manner and attenuated the development of load-induced cardiac hypertrophy and fibrosis without change of hemodynamic parameters. Additionally, treatment with 0.1 mg/kg every second day but not with 0.01 mg/kg every second day of FK506 from the age of 12 weeks to 16 weeks induced regression of cardiac hypertrophy in DS rats. Load-induced reprogramming of gene expression was also suppressed by the FK506 treatment. CONCLUSIONS: These results suggest that calcineurin is involved in the development of cardiac hypertrophy in rats with salt-sensitive hypertension and that inhibition of calcineurin could induce regression of cardiac hypertrophy.

Animals↗
PubMed2000

Targeted disruption of Na+/Ca2+ exchanger gene leads to cardiomyocyte apoptosis and defects in heartbeat.

Ca(2+), which enters cardiac myocytes through voltage-dependent Ca(2+) channels during excitation, is extruded from myocytes primarily by the Na(+)/Ca(2+) exchanger (NCX1) during relaxation. The increase in intracellular Ca(2+) concentration in myocytes by digitalis treatment and after ischemia/reperfusion is also thought to result from the reverse mode of the Na(+)/Ca(2+) exchange mechanism. However, the precise roles of the NCX1 are still unclear because of the lack of its specific inhibitors. We generated Ncx1-deficient mice by gene targeting to determine the in vivo function of the exchanger. Homozygous Ncx1-deficient mice died between embryonic days 9 and 10. Their hearts did not beat, and cardiac myocytes showed apoptosis. No forward mode or reverse mode of the Na(+)/Ca(2+) exchange activity was detected in null mutant hearts. The Na(+)-dependent Ca(2+) exchange activity as well as protein content of NCX1 were decreased by approximately 50% in the heart, kidney, aorta, and smooth muscle cells of the heterozygous mice, and tension development of the aortic ring in Na(+)-free solution was markedly impaired in heterozygous mice. These findings suggest that NCX1 is required for heartbeats and survival of cardiac myocytes in embryos and plays critical roles in Na(+)-dependent Ca(2+) handling in the heart and aorta.

Animals↗
PubMed2000

Functional analyses of three Csx/Nkx-2.5 mutations that cause human congenital heart disease.

A homeodomain-containing transcription factor Csx/Nkx-2.5 is an important regulator of cardiogenesis in mammals. Three different mutants, Gln170ter (designated A) and Thr178Met (designated B) in the helix 2 of the homeodomain and Gln198ter mutation (designated C) just after homeodomain, have been reported to cause atrial septal defect with atrial ventricular block. We here examined the functions of these three mutants of Csx/Nkx-2.5. The atrial natriuretic peptide (ANP) promoter was activated by wild type Csx/Nkx-2.5 (WT, approximately 8-fold), B ( approximately 2-fold), and C ( approximately 6-fold) but not by A. When A, B, or C was cotransfected into COS-7 cells with the same amount of WT, WT-induced activation of the ANP promoter was attenuated by A and B (A > B), whereas C further enhanced the activation. Immunocytochemical analysis using anti-Myc tag antibody indicated that transfected Myc-tagged WT, B, and C were localized in the nucleus of both COS-7 cells and cardiomyocytes of neonatal rats, whereas A was distributed diffusely in the cytoplasm and nucleus in COS-7 cells. Electrophoretic mobility shift assay showed that Csx/Nkx-2.5-binding sequences were bound strongly by WT and C, weakly by B, but not by A. Immunoprecipitation and GST pull-down assay revealed that WT and all mutants interacted with GATA-4. The synergistic activation of the ANP promoter by WT and GATA-4 was further enhanced by C but was inhibited by A and B. In the cultured cardiomyocytes, overexpression of C but not WT, A, or B, induced apoptosis. These results suggest that although the three mutants induce the same cardiac phenotype, transactivation ability and DNA binding ability are different among the three mutants and that apoptosis may be a cause for C-induced cardiac defect.

Animals↗