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Biomedical subjects

Ikuo Saito

Publications and source records attributed to Ikuo Saito.

At least 19 recordsLinked to original sources
PubMed2007

Effects of nighttime alcohol intake on evening and next morning home blood pressure in Japanese normotensives.

Home blood pressure (HBP) is usually measured in the morning and evening, but the evening HBP tends to be influenced by an individual's behavior pattern, such as bathing and drinking, which are often seen in the Japanese. In this study, in order to elucidate the influence of nighttime drinking on the evening and next morning HBP and heart rate (HR), HBP measurement was performed in Japanese normotensives under conditions in which the influence of bathing was minimized. Among 700 registered volunteers, 245 normotensives (189 male, 56 female, mean age; 35.8 +/- 0.5 years old) whose data consisted of a combination of drinking and non-drinking on workdays were selected. A semi-automatic device was lent to all participants, and they were asked to perform triplicate morning and evening measurements on seven consecutive days between October 16, 2002, and November 13, 2002. The differences in evening HBP and HR between the drinking and non-drinking days were calculated, as were the differences in the next morning HBP and HR. Only data of evening HBP measured at least 30 min after bathing were accepted. Evening SBP and DBP on drinking days were significantly lower (2.5 +/- 0.5 mmHg, 3.1 +/- 0.5 mmHg) than those on non-drinking days. On the other hand, evening HR on drinking days was significantly higher (7.7 +/- 0.8 b.p.m.) than that on non-drinking days. Although there was no difference in morning SBP after days with and without drinking, morning DBP the day after drinking was slightly (0.8 +/- 0.3 mmHg) but significantly lower than that the day after non-drinking. Morning HR the day after drinking was significantly higher (2.4 +/- 0.4 b.p.m.) than that after non-drinking. Because nighttime drinking influenced the evening HBP even in normotensives, it was suggested that morning HBP could give more stable values than evening HBP in Japanese people.

Adult↗
PubMed2006

Coactivation of the N-terminal transactivation of mineralocorticoid receptor by Ubc9.

Molecular mechanisms underlying mineralocorticoid receptor (MR)-mediated gene expression are not fully understood. Various transcription factors are post-translationally modified by small ubiquitin-related modifier-1 (SUMO-1). We investigated the role of the SUMO-1-conjugating enzyme Ubc9 in MR transactivation. Yeast two-hybrid, GST-pulldown, and coimmunoprecipitation assays showed that Ubc9 interacted with N-terminal MR-(1-670). Endogenous Ubc9 is associated with stably expressing MR in 293-MR cells. Transient transfection assays in COS-1 cells showed that Ubc9 increased MR transactivation of reporter constructs containing MRE, ENaC, or MMTV promoter in a hormone-sensitive manner. Moreover, reduction of Ubc9 protein levels by small interfering RNA attenuated hormonal activation of a reporter construct as well as an endogenous target gene by MR. A sumoylation-inactive mutant Ubc9(C93S) similarly interacted with MR and potentiated aldosterone-dependent MR transactivation. An MR mutant in which four lysine residues within sumoylation motifs were mutated into arginine (K89R/K399R/K494R/K953R) failed to be sumoylated, but Ubc9 similarly enhanced transactivation by the mutant MR, indicating that sumoylation activity is dispensable for coactivation capacity of Ubc9. Coexpression of Ubc9 and steroid receptor coactivator-1 (SRC-1) synergistically enhanced MR-mediated transactivation in transient transfection assays. Indeed, chromatin immunoprecipitation assays demonstrated that endogenous MR, Ubc9, and SRC-1 were recruited to an endogenous ENaC gene promoter in a largely aldosterone-dependent manner. Coimmunoprecipitation assays showed a complex of MR, Ubc9, and SRC-1 in mammalian cells, and the endogenous proteins were colocalized in the nuclei of the mouse collecting duct cells. These findings support a physiological role of Ubc9 as a transcriptional MR coactivator, beyond the known SUMO E2-conjugating enzyme.

Aldosterone↗
PubMed2006

G501C polymorphism of oxidized LDL receptor gene (OLR1) and ischemic stroke.

The human lectin-like oxidized low-density lipoprotein receptor 1 (OLR1/LOX-1) is the major endothelial scavenger receptor against oxidized low-density lipoprotein (Ox-LDL), which has been implicated in the pathogenesis of atherosclerosis. We investigated the G501C mutation in the OLR1 gene in 235 Japanese patients with ischemic cerebrovascular disease (CVD) and 274 age- and sex-matched healthy controls using single nucleotide primer extension analysis (SNuPe). There was no significant difference in the polymorphism between patients with ischemic CVD and controls (GC+CC versus GG, p=0.48). The C allele was not significantly different between the patients and controls (C versus G, p=0.91). Our results show that the OLR1 gene polymorphism has little effect on an increased risk for ischemic CVD in the Japanese population.

Brain Ischemia↗
PubMed2006

Coronary artery disease and a functional polymorphism of hTERT.

Genetic variation, a -1327T/C polymorphism, of human telomerase reverse transcriptase (hTERT) is associated with leukocyte telomere length in healthy subjects, but clinical significances of this functional polymorphism are not clear. Recently, the relationship between the telomere system and coronary artery disease (CAD) was reported. We investigated the association between the -1327T/C polymorphism and (a) susceptibility to CAD and (b) telomere length in CAD patients. In a case-control study, 104 patients confirmed by coronary angiography and 115 age- and sex-matched controls were enrolled. There was a higher frequency of the -1327C/C genotype in CAD patients (51.9%) compared with controls (36.5%, p = 0.0218). Among the 104 CAD patients, leukocyte telomere length in the -1327C/C genotype (7.62+/-2.19 kb, mean+/-SD) was shorter than that in the -1327T/C and -1327T/T genotypes (8.74+/-2.92, p = 0.0287). These findings suggest that the -1327C/C genotype is a genetic risk factor for CAD and relates to shorter telomere length among CAD patients.

Case-Control Studies↗
PubMed2006

A561C polymorphism of E-selectin is associated with ischemic cerebrovascular disease in the Japanese population without diabetes mellitus and hypercholesterolemia.

E-selectin, which is a member of the selectin superfamily of adhesion molecules, contributes to the leukocyte-endothelial cell attachments and is involved in the pathogenesis of thrombovascular diseases as a consequence. We investigated the A561C mutation in the E-selectin gene in 235 Japanese patients with ischemic cerebrovascular disease (CVD) and 301 age- and sex-matched healthy controls. Excluding the subjects with diabetes mellitus and hypercholesterolemia, the AC genotype frequencies of patients with ischemic CVD were higher than those of controls: 12.7% vs. 5.8% (P=0.04). Our results show that E-selectin gene polymorphisms represent an increased risk for ischemic CVD in the Japanese population without diabetes mellitus and hypercholesterolemia.

Aged↗
PubMed2006

Improvement of hypertension and vascular dysfunction by hydroxyhydroquinone-free coffee in a genetic model of hypertension.

Chlorogenic acid, a polyphenol found in coffee, has antihypertensive actions, but epidemiologic data on the effects of coffee on blood pressure are controversial. Specific coffee components that inhibit the hypotensive effect of chlorogenic acid and the physiologic mechanisms underlying the effects of coffee without these components were investigated. One component, hydroxyhydroquinone (HHQ), inhibited the hypotensive effects of chlorogenic acid in spontaneously hypertensive rats (SHR). The attenuation of hypertension by HHQ-free coffee was associated with nitric oxide, the suppression of mRNA expression of NAD(P)H oxidase, and the improvement in endothelium-dependent vasodilation in the aorta. Thus, HHQ-free coffee might regulate vascular tone by improving the bioavailability of nitric oxide in SHR.

Animals↗
PubMed2006

Telomere length of normal leukocytes is affected by a functional polymorphism of hTERT.

Transcriptional regulation of human telomerase reverse transcriptase (hTERT), a catalytic subunit of telomerase, is essential for telomerase activity associated with telomere length. In this study, we investigated the effects of a (-1327)T/C polymorphism within the hTERT promoter region on the hTERT promoter activity and leukocyte telomere length in normal individuals. The promoter activity in the (-1327)T-sequence was significantly higher than that in the (-1327)C-sequence (p = 0.0004). For leukocyte telomere length, the (-1327)T-allele carriers had significantly longer than the (-1327)T-allele non-carriers (p = 0.0007). Also, there was no age-related shortening in leukocyte telomere length in the (-1327)T/T (p = 0.6633) and (-1327)T/C subjects (p = 0.1691), whereas there was clear age-related telomere shortening in the (-1327)C/C subjects (p = 0.0117). These findings suggest that the functional (-1327)T/C polymorphism of hTERT is associated with leukocyte telomere length in normal individuals.

Base Sequence↗
PubMed2006

The blood pressure-lowering effect and safety of chlorogenic acid from green coffee bean extract in essential hypertension.

Chlorogenic acids (CGA) in green coffee bean extract (GCE) reduce blood pressure in spontaneously hypertensive rats and humans. The authors examined the blood pressure-lowering effect and safety of CGA in patients with mild hypertension through a placebo-controlled, randomized clinical trial. Subjects (n = 28) were randomized to receive treatment with CGA (140 mg/day) from GCE or placebo. Blood pressure, pulse rate, body mass index, routine blood test, hematochemistry, urinalysis, and subjective symptoms were recorded throughout the study. In the CGA group, but not the placebo group, blood pressure (systolic and diastolic) decreased significantly during the ingestion period. There was no difference in body mass index and pulse rate between groups, nor were there any apparent side effects. Thus, CGA from GCE is effective in decreasing blood pressure and safe for patients with mild hypertension.

Adult↗
PubMed2006

Chlorogenic acid attenuates hypertension and improves endothelial function in spontaneously hypertensive rats.

BACKGROUND AND OBJECTIVES: Epidemiologic studies indicate that ingestion of vegetables and fruit inhibits the development of cardiovascular disease. Chlorogenic acids are abundant phenolic compounds contained in vegetables and fruits, but the impact of dietary chlorogenic acids on vascular function in hypertension is not known. We therefore examined the effects of 5-caffeoylquinic acid (CQA), a representative chlorogenic acid, on blood pressure and vascular function in age-matched normotensive Wistar-Kyoto rats and spontaneously hypertensive rats. METHODS AND RESULTS: A single ingestion of CQA (30-600 mg/kg) reduced blood pressure in spontaneously hypertensive rats, an effect that was blocked by administration of a nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester. When spontaneously hypertensive rats were fed diets containing 0.5% CQA for 8 weeks (approximately 300 mg/kg per day), the development of hypertension was inhibited compared with the control diet group. CQA ingestion increased urinary excretion of nitric oxide metabolites and decreased urinary excretion of hydrogen peroxide; decreased NADPH-dependent superoxide anion production in the aorta, suggesting that dietary CQA inhibited vascular NADPH oxidase activity; significantly improved acetylcholine-induced endothelium-dependent vasodilation in the aorta; and markedly reduced the degree of immunohistochemical staining for nitrotyrosine and media hypertrophy in aorta sections. In contrast, CQA had no effects in Wistar-Kyoto rats. CONCLUSIONS: Dietary CQA reduces oxidative stress and improves nitric oxide bioavailability by inhibiting excessive production of reactive oxygen species in the vasculature, and leads to the attenuation of endothelial dysfunction, vascular hypertrophy, and hypertension in spontaneously hypertensive rats.

Animals↗
PubMed2006

Influence of nighttime bathing on evening home blood pressure measurements: how long should the interval be after bathing?

The Japanese Society of Hypertension has recommended that evening home blood pressure measurement be taken just before bedtime. In this study, to elucidate the influence of nighttime bathing on evening home blood pressure and heart rate, measurements were performed for 7 days using volunteers who were employees of a single company and who had no alcohol intake during the study period. We used data obtained from 158 subjects (78 males and 80 females; mean age, 41.6 years) whose evening data consisted of a combination of pre-bathing and post-bathing measurements. We divided the subjects into four groups according to the time interval from bathing: blood pressure was measured at 30 min after bathing in group I (n=40), at 31-60 min after bathing in group II (n=89), at 61-120 min after bathing in group III (n=74) and at more than 121 min after bathing in group IV (n=53). We evaluated the changes after bathing in each group. For all subjects combined, the evening home blood pressure measured after bathing (114.0+/-17.1/69.4+/-10.9 mmHg) was significantly lower than the value before bathing (116.3+/-17.1/70.7+/-11.2 mmHg). However, there was no difference in heart rate. Both systolic and diastolic blood pressure after bathing in group I (109.1+/-15.2/66.3+/-10.8 mmHg) and II (112.0+/-15.2/66.5+/-10.1 mmHg) were significantly lower than those before bathing (group I: 113.2+/-15.8/70.2+/-10.6 mmHg; group II: 115.2+/-15.8/69.3+/-10.3 mmHg), but these differences disappeared in group III and IV. On the other hand, there was no difference in heart rate after bathing in group I, II, or III, but group IV showed a slight but significant decrease after bathing (67.7+/-10.0 --> 65.8+/-10.7 beats/min). In conclusion, if evening home blood pressure is to be measured after bathing, subjects should be instructed to wait more than 60 min after bathing before performing the measurement in order to eliminate the depressor effect of bathing.

Adult↗
PubMed2006

An inverse association between serum gamma glutamyl transpeptidase activity and Breslow's Lifestyle Index; its practical application for screening of subjects with unhealthy lifestyles.

We examined whether serum gammaGTP activity (gammaGTP) is associated with Breslow's lifestyle index and whether it could be used as a tool to detect subjects with unhealthy lifestyles. To that effect, 724 male Japanese workers excluding patients suffering from hepatitis virus infection, autoimmune liver diseases and apparently active bile duct diseases were cross-sectionally examined. gammaGTP was inversely associated with the total score of Breslow's index for all subjects (lambda=30.643) and in subjects aged 40 or more (lambda=37.073). The association was consistent even after adjustments of subjects' ages and levels of triglycerides, total cholesterol and uric acid (p=0.0001). Among the seven lifestyle factors comprising Breslow's index, improper habits of drinking (p<0.0001), smoking (p=0.0204), exercise (p=0.0189) and body weight control (p<0.0001), were associated with increased gammaGTP. Even in a survey in which subjects who had proper habits of drinking and body weight control were selectively examined, improper habits of smoking and exercise still tended to be associated with increased gammaGTP. Receiver operating characteristic curves indicated that gammaGTP was beneficial for detecting subjects who scored two or less on Breslow's index, at least in subjects aged 40 or more. gammaGTP was associated with insulin resistance level estimated by the homeostasis model assessment (p<0.0001), which was inversely associated with Breslow's index (p=0.0040). gammaGTP could be used as an objective substitute of Breslow's index, allowing us to identify subjects with low scores on Breslow's index, at least after sorting subjects properly. Such screening would enable interventions to correct subjects' unhealthy lifestyles, helping to solve lifestyle-related disease issues.

Adult↗
PubMed2005

T280M and V249I polymorphisms of fractalkine receptor CX3CR1 and ischemic cerebrovascular disease.

The contribution to atherosclerosis of two CX3CR1 single nucleotide polymorphisms, V249I and T280M has been recently reported. The atherosclerosis of intracranial vessels is thought to be the major pathological mechanism of ischemic stroke. In this study, we investigated the risk of ischemic stroke associated with fractalkine receptor CX3CR1 polymorphisms. We investigated the T280M and V249I mutations in the CX3CR1 gene in 235 Japanese patients with ischemic cerebrovascular disease (CVD) and 306 age- and sex-matched healthy controls. Polymerase chain reaction and restriction fragment length polymorphism were used for genotyping. There was no significant difference in both polymorphisms between patients with ischemic CVD and controls (VV versus II+VI, p=0.83; TT versus MM+TM, p=0.66). The I and M allele frequencies were not significantly different between CVD patients and controls: odds ratio (OR)=0.89 (95% confidence interval (CI)=0.50-1.60, p=0.70) and OR=1.19 (95% CI=0.71-2.00, p=0.51), respectively. We found eight of nine possible combined genotypes, including a new haplotype V249-M280, in Japanese. Our results show that these CX3CR1 gene polymorphisms are not associated with an increased risk for ischemic CVD in the Japanese population.

CX3C Chemokine Receptor 1↗
PubMed2005

GPR40 gene Arg211His polymorphism may contribute to the variation of insulin secretory capacity in Japanese men.

GPR40 is a member of the G-protein-coupled receptors. Recent studies suggest that GPR40 is highly expressed in pancreatic beta cells and insulin-secreting cell lines, and that fatty acids increase intracellular calcium concentration and amplify glucose-stimulated insulin secretion by activating GPR40. Despite identification of the Arg211His polymorphism in the GPR40 gene, there have been no clinical studies concerning this polymorphism. The present study was performed to investigate the effects of the GPR40 gene Arg211His polymorphism on clinical and metabolic parameters, including serum insulin level, in 327 healthy Japanese men, using the TaqMan polymerase chain reaction method. Serum insulin level, homeostasis model of insulin resistance (HOMA-IR), and beta-cell function (HOMA-beta were significantly different (P = .0075, .0152, and .0039, respectively) and were lowest in Arg/Arg homozygotes and highest in His/His homozygotes, although plasma glucose and serum lipids were not significantly different. Multiple regression analyses showed that serum insulin level, HOMA-IR, and HOMA- beta were significantly correlated with this polymorphism after adjusting for age and body mass index. After Bonferroni's correction for multiple comparisons was made, only HOMA- beta was significantly different among the 3 genotypes. These results suggest that the Arg211His polymorphism in the GPR40 gene may contribute to the variation of insulin secretory capacity in Japanese men.

Adult↗
PubMed2005

Cellular insulin resistance in Epstein-Barr virus-transformed lymphoblasts from young insulin-resistant Japanese men.

The metabolic syndrome is characterized by a blunted insulin-mediated glucose uptake in various cell types. We compared the glucose uptake characteristics of Epstein-Barr virus (EBV)-transformed lymphoblasts obtained from young men with vs without metabolic and cardiovascular evidence of metabolic syndrome. From a population of 218 men, 20- to 25-year-old, 10 men with a systolic blood pressure (BP) > or =130 mm Hg and family history of hypertension were assigned to a high BP (HBP) group, and 10 with a BP < or =110 mm Hg, and no family history of hypertension was assigned to a low BP (LBP) group. Multiple clinical and metabolic characteristics were examined in both groups and compared. Peripheral lymphocytes from HBP and LBP subjects were EBV-transformed, and the glucose transporter (Glut)-mediated glucose uptake from each group was compared in lymphoblasts. Body mass index, fasting glucose, immunoreactive insulin, insulin resistance index based on a homeostasis model assessment (HOMA-R), and total and low-density lipoprotein cholesterol were significantly higher in the HBP than the LBP subgroup (whole-body insulin resistance). Baseline Glut-mediated and Glut-mediated insulin-stimulated glucose uptake by lymphoblasts from the HBP group were significantly lower than by lymphoblasts from the LBP group (cellular insulin resistance). The net increment in Glut-mediated glucose uptake by insulin was inversely correlated with HOMA-R. In conclusion, cellular insulin resistance in EBV-transformed lymphoblasts is associated with young Japanese subjects with HBP. The net increment in Glut-mediated glucose uptake by insulin in lymphoblasts may be a useful intermediate phenotype to study genetic aspects of the metabolic syndrome.

Adult↗