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Biomedical subjects

Yasuyuki Nakamura

Publications and source records attributed to Yasuyuki Nakamura.

At least 19 recordsLinked to original sources

Relation of adult height with stroke mortality in Japan: NIPPON DATA80.

BACKGROUND AND PURPOSE: The age-adjusted stroke mortality rate in Japan was the highest in the world from 1950 to the 1970s, but it started to dramatically decrease after 1965. In addition to improved management of high blood pressure, the increase in average height might also contribute to this reduction. The present study investigates whether height is an independent risk for stroke mortality in Japan. METHODS: Among participants of the National Survey on Cardiovascular Diseases in 1980 who were randomly selected from the Japanese population, we followed up 3969 and 4955 Japanese men and women without prior cardiovascular disease for a maximum of 19 years and observed 158 and 132 stroke deaths. RESULTS: Height was inversely correlated with age and with crude stroke mortality. The relationship was attenuated in men when we adjusted for age or other possible confounders (multivariate adjusted relative hazards of a 5-cm increase of height for stroke mortality: 0.92, 95% CI: 0.79 to 1.08). For women, the inverse relationship (relative hazard: 0.77: 95% CI: 0.64 to 0.91) remained after multivariate adjustment. These relationships persisted when we stratified participants by age. CONCLUSIONS: Height is inversely related to stroke mortality and the relationship is statistically significant among Japanese women.

Adult↗

gamma-Glutamyltransferase predicts cardiovascular death among Japanese women.

The clinical importance of gamma-glutamyltransferase (GGT) has recently been debated. Although some studies have suggested that the relationship between GGT and cardiovascular disease (CVD) mortality is independent of alcohol consumption, to our knowledge no studies have reported the relationship between GGT and CVD mortality in never-drinker subgroups. Since Japanese women are known to have a lower prevalence of alcohol consumption, we examined whether GGT predicts CVD mortality in never-drinkers. We followed 2724 Japanese men and 4122 Japanese women without prior CVD or liver dysfunction for 9.6 years and observed 83 and 82 CVD deaths, respectively. Current alcohol drinkers comprised 59% of men and 7% of women. Among women, the multiple adjusted hazard ratio (HR) for CVD mortality compared with the reference group (GGT: 1-12 U/L) was 2.88 (95% confidence interval (CI), 1.14-7.28) for the elevated group (GGT>or=50 U/L). This positive relationship was unchanged in the never-drinkers subgroup (HR for log-transformed continuous GGT, 1.62 (95% CI, 1.11-2.37)). No significant relationships were observed in men. GGT displays a strong positive association with CVD mortality among Japanese women, for whom the prevalence of ever-drinkers is very low. Exploring the significance and biological mechanisms of GGT might provide useful insights into CVD prevention.

Biomarkers↗

Synthesis of brominated directly fused diporphyrins through gold(III)-mediated oxidation.

Highly efficient synthesis of meso,meso-dibromo doubly and triply fused diporphyrins has been achieved through a powerful oxidative coupling mediated by AuCl3-AgOTf combination. In addition, palladium-catalyzed debromination of meso-bromoporphyrins has been developed. This debromination protocol enables employment of bromine as a protecting group for the reactive meso-position of porphyrins.

Bromine↗

The potential role of DFNA5, a hearing impairment gene, in p53-mediated cellular response to DNA damage.

The tumor suppressor p53 plays a crucial role in the cellular response to DNA damage by transcriptional activation of numerous downstream genes. Although a considerable number of p53 target genes have been reported, the precise mechanism of p53-regulated tumor suppression still remains to be elucidated. Here, we report a novel role of the DFNA5 gene in p53-mediated etoposide-induced cell death. The DFNA5 gene has been previously reported to be responsible for autosomal-dominant, nonsyndromic hearing impairment. The expression of the DFNA5 gene was strongly induced by exogenous and endogenous p53. The chromatin immunoprecipitation assay indicated that a potential p53-binding sequence is located in intron 1 of the DFNA5 gene. Furthermore, the reporter gene assay revealed that the sequence displays p53-dependent transcriptional activity. The ectopic expression of DFNA5 enhanced etoposide-induced cell death in the presence of p53; however, it was inhibited in the absence of p53. Finally, the expression of DFNA5 mRNA was remarkably induced by gamma-ray irradiation in the colon of p53(+/+) mice but not in that of p53(-/-) mice. These results suggest that DFNA5 plays a role in the p53-regulated cellular response to genotoxic stress probably by cooperating with p53.

Animals↗

Alcohol consumption and coronary artery calcium in middle-aged Japanese men.

Epidemiologic studies have investigated the relation between alcohol intake and coronary calcification, with controversial results. Furthermore, the influence of heavy drinking has not been well elucidated. In the present study, a random sample of community-based Japanese men aged 40 to 49 years without a history of cardiovascular disease (n=245) were examined for coronary artery calcium (CAC) determined by electron-beam computed tomography and drinking status. There was a J-shaped association between alcohol intake and CAC. There was an increase of CAC in heavy drinkers (>or=46 g/day), and participants who were drinking>or=69 g/day showed a significant increase in CAC compared with never drinkers after adjusting for other cardiovascular risk factors.

Adult↗

The association between high-density lipoprotein cholesterol level and cholesteryl ester transfer protein TaqIB gene polymorphism is influenced by alcohol drinking in a population-based sample.

Cholesteryl ester transfer protein (CETP) is a key enzyme in high-density lipoprotein (HDL) cholesterol metabolism. We studied the association between CETP TaqIB polymorphism and the HDL cholesterol levels considering environmental factors in a population-based sample consisting of 1729 participants who did not use lipid-lowering agents (659 men and 1070 women). The CETP TaqIB genotypes were determined by PCR-RFLP analysis. The serum HDL cholesterol levels of female participants with the B2B2 genotype were significantly higher than those with other genotypes (p<0.001). Multiple regression analysis with covariates such as age, waist to hip (W/H) ratio, alcohol drinking, current smoking, non-HDL cholesterol, and logarithm of triglyceride revealed that the CETP TaqIB genotype was an independent determinant of HDL cholesterol levels in men (p=0.049) and women (p<0.001). Subgroup analysis revealed that an interaction was observed between the CETP TaqIB polymorphism and alcohol consumption in the regulation of HDL cholesterol levels in men (p=0.049) and women (p=0.022). No interactions were observed between the CETP TaqIB polymorphism and current smoking status, body mass index, or W/H ratio in the regulation of HDL cholesterol levels. The association between the CETP TaqIB polymorphism and HDL cholesterol levels was more evident in alcohol consumers than in non-drinkers.

Adult↗

A directly fused tetrameric porphyrin sheet and its anomalous electronic properties that arise from the planar cyclooctatetraene core.

Oxidation of a directly meso-meso linked cyclic porphyrin tetramer 2 gave a porphyrin sheet 3. The symmetric square structure of 3 is indicated by its simple 1H NMR spectrum that exhibits only two signals for the porphyrin beta-protons. The absorption spectrum of 3 displays characteristic Soret-like broad bands and weak Q-bands, and its magnetic circular dichroism (MCD) spectrum exhibits a negative Faraday A term at the 762 nm band as a rare case, indicating the absorption as a transition from a nondegenerate level to a degenerate level. A slightly longer S1-state (1.1 ps) and smaller TPA cross section (2750 GM) than a tetrameric linear porphyrin tape also indicate its unique electronic properties. The porphyrin sheet 3 forms stable 1:2 complexes with guest molecules G1 and G2, whose 1H NMR spectra exhibit remarkable downfield shifts for the guest protons that are located just above the cyclooctatetraene (COT) core of 3, whereas the imidazolyl protons bound to the zinc(II) porphyrin local cores are observed at slightly upfield positions. These results have been qualitatively accounted for in terms of the presence of a strong paratropic ring current around the COT core that propagates through the whole pi-electronic network of 3, hence competing with and cancelling the weak diatropic ring currents of the local zinc(II) porphyrins. This explanation was supported by DFT calculation performed at the GIAO-B3LYP/6-31G level, which indicated large positive NICS values within the COT core and small NICS values within the local zinc(II) porphyrins.

Journal Article↗

The relationship between serum total cholesterol and all-cause or cause-specific mortality in a 17.3-year study of a Japanese cohort.

No study has shown a positive relationship between hypercholesterolemia and all-cause mortality in the Japanese population. Therefore, a cohort study of 17.3 years' duration was conducted on 9216 participants aged 30 years or older, selected randomly from throughout Japan. In both the lowest (<4.14mmol/L, 160mg/dl) and highest (>or=6.71mmol/L, 260mg/dl) total cholesterol (TC) groups, there was a positive association between TC and risk of all-cause mortality (hazard ratio (HR) 1.19; 95% confidence interval (CI), 1.03-1.37 and 1.36 (95% CI, 1.05-1.77), respectively). The lowest TC group had an increased risk of liver disease (HR 3.03; 95% CI, 1.70-5.43), whereas the highest TC group had an increased risk of coronary heart disease (HR 3.81; 95% CI, 1.70-5.43). After exclusion of deaths due to liver disease during the entire follow-up period and all-cause deaths within the first 5 years of follow-up, the increased HR in the lowest TC group disappeared (HR 1.05; 95% CI, 0.89-1.24). Although the cut-off point seemed to be higher than that for Western populations, hypercholesterolemia was shown to be positively associated with all-cause mortality in Japan.

Adult↗

Higher levels of adiponectin in American than in Japanese men despite obesity.

Levels of adiponectin are inversely associated with obesity levels. We examined the levels of adiponectin in American (n = 98) and Japanese (n = 92) men aged 40 to 49 years. Contrary to our expectations, the American men had higher levels of adiponectin than the Japanese men (13.3 +/- 5.8 vs 7.3 +/- 4.2 (microg/mL) despite higher levels of obesity. Smaller areas of visceral adipose tissue in American than in Japanese men may have resulted in the higher levels of adiponectin.

Adiponectin↗

Egg consumption, serum total cholesterol concentrations and coronary heart disease incidence: Japan Public Health Center-based prospective study.

Limited egg consumption is often recommended to reduce serum cholesterol concentration for the prevention of CHD. We examined the association of egg consumption and total cholesterol concentration with the risk of CHD. A total of 90 735 subjects (19 856 men and 21 408 women, aged 40-59 years in cohort I; 23 463 men and 26 008 women, aged 40-69 years in cohort II) were followed from 1990-4 to the end of 2001 under the Japan Public Health Center-based prospective study. Total cholesterol was obtained in 36 % of the subjects. Men and women were combined for the analyses. The subjects were categorised into four groups according to egg consumption. Subjects with total cholesterol >or=2200 mg/l were less frequent in frequent egg consumption groups in both cohorts (trend P<0.0001). Subjects with <1 d/week of egg consumption were more likely to avoid a cholesterol-rich diet. Egg consumption was not associated with the risk of CHD, although total cholesterol was significantly related to the risk of CHD. The multivariate hazard ratio of CHD in subjects with total cholesterol >or=2400 v. <1800 mg/l was 2.17 (95 % CI 1.22, 3.85; trend P=0.0018). In conclusion, eating eggs more frequently, up to almost daily, was not associated with an increase in CHD incidence for middle-aged Japanese men and women. Subjects with hypercholesterolaemia were less frequently in frequent egg consumption groups, probably because they avoided eating eggs.

Adult↗

Identification of p53-46F as a super p53 with an enhanced ability to induce p53-dependent apoptosis.

More than half of human cancers contain mutations in the tumor suppressor protein p53, most of which accumulate in the DNA binding domain of the protein. Here we report the identification of a mutant p53, designated p53-46F, in which Ser-46 is replaced with phenylalanine. In vitro, adenovirus-mediated transduction of the p53-46F gene induced apoptosis more efficiently than wild-type p53 in a number of cancer cell lines, whereas Ser-15 phosphorylation of p53-46F was enhanced in all cancer cell lines examined. Moreover, the expression level of the cell cycle inhibitor p21/WAF1 was decreased in cell lines infected with adenovirus p53-46F (Ad-p53-46F). p53-46F caused a more enhanced level of transcriptional activation of several p53-target genes, including Noxa, p53AIP1 and p53RFP, compared with wild-type p53. In vivo, adenovirus-mediated gene transfer of p53-46F enhanced apoptosis, thus suppressing tumor growth of a lung cancer cell line more effectively than wild-type p53 or p53-121F, another p53 mutant. Collectively, our data suggest that p53-46F is an active version of p53 that demonstrates enhanced induction of p53-dependent apoptosis. This is probably mediated by upregulated transactivation of genes downstream of p53, increased Ser-15 phosphorylation and a decrease in p21/WAF1 levels. We propose p53-46F as an alternative candidate to wild-type p53 for use in developing new therapeutic strategies for the treatment of cancer.

Adenoviridae↗

Combined cardiovascular risk factors and outcome: NIPPON DATA80, 1980-1994.

BACKGROUND: To examine the prognostic significance of the high-risk group with combined cardiovascular risk factors in the Japanese, we analyzed the relationship between the high-risk group with combined risks and coronary heart disease (CHD) and stroke mortality using the NIPPON DATA80 database. METHODS AND RESULTS: At baseline in 1980, those of age>or=30 years were randomly selected and 4,144 men and 5,318 women without CHD and/or stroke at baseline were followed for 14 years. The cutoff values for risk components obtained heuristically by Cox analysis were hypertension (systolic>or=130, or diastolic>or=85 mmHg, or on antihypertensive drugs), hypercholesterolemia (total cholesterol>or=200 mg/dl), hyperglycemia (>or=130 mg/dl, or self-reported diabetes) and obesity (body mass index>or=27 kg/m2). Subjects were divided into 3 groups (0, 1-2 and 3-4 risks). Compared with those men in the risk 0 group, the hazard ratios in men in the risk 3-4 for CHD mortality was 8.04 (95% confidence interval: 1.03-62.6), and the stroke mortality was 5.06 (1.53-16.7). In women, no statistically significant difference was found due to a lesser number of events. CONCLUSION: The high-risk group with combined risk factors is important risk for Japanese men.

Adult↗

The determinants of plasma plasminogen activator inhibitor-1 levels differ for American and Japanese men aged 40-49.

BACKGROUND: Elevated plasma plasminogen activator inhibitor-1 (PAI-1) levels were associated with higher incidence of type II diabetes. Elucidating the determinants of PAI-1 in various ethnicities may help to understand the susceptibility to developing diabetes. The aim of our study was to compare PAI-1 levels between Americans and the Japanese in the post-war generation and to elucidate the determinants of the PAI-1 levels. METHODS: We conducted a cross-sectional study on a total of 198 men aged 40-49 in the US (Body mass index (BMI): 27.0+/-3.3 kg/m(2)) and Japan (BMI: 23.3+/-3.1 kg/m(2)). Examination included physique measurement (BMI and waist girth), blood analysis (lipid profiles, glucose, insulin, C-reactive protein, and PAI-1), and life-style assessment by self-administered questionnaires. RESULTS: PAI-1 levels were significantly lower in American than in Japanese men, even after adjustment for age, waist girth, cigarette smoking, habitual alcohol drinking, and other factors. In the Americans, waist girth, insulin, and cigarette smoking were significantly associated with PAI-1 levels, while waist girth and triglycerides were significantly associated with PAI-1 levels in the Japanese. CONCLUSIONS: PAI-1 levels were significantly lower in American than in Japanese men and the determinants of PAI-1 levels differ for American and Japanese men aged 40-49.

Adult↗

Directly meso-meso linked porphyrin rings: synthesis, characterization, and efficient excitation energy hopping.

Directly meso-meso linked porphyrin rings CZ4, CZ6, and CZ8 that respectively comprise four, six, and eight porphyrins have been synthesized in a stepwise manner from a 5,10-diaryl zinc(II) porphyrin building block. Symmetric cyclic structures have been indicated by their very simple (1)H NMR spectra that exhibit only a single set of porphyrin and their absorption spectra that display a characteristic broad nonsplit Soret band around 460 nm. Energy minimized structures calculated at the B3LYP/6-31G* level indicate that a dihedral angle between neighboring porphyrins decreases in order of CZ6 > CZ8 > CZ4, which is consistent with the (1)H NMR data. Photophysical properties of these molecules have been examined by the steady-state absorption, fluorescence, fluorescence lifetime, fluorescence anisotropy decay, and transient absorption measurements. Both the pump-power dependence on the femtosecond transient absorption and the transient absorption anisotropy decay profiles are directly related with the excitation energy migration processes within the porphyrin rings, where the exciton-exciton annihilation time and the polarization anisotropy rise time are well described in terms of the Forster-type incoherent energy hopping model. Consequently, the excitation energy hopping rates have been estimated for CZ4 (119 +/- 2 fs)(-)(1), CZ6 (342 +/- 59 fs)(-)(1), and CZ8 (236 +/- 31 fs)(-)(1), which reflect the magnitude of the electronic coupling between the neighboring porphyrins. Overall, these porphyrin rings serve as a well-defined wheel-shaped light harvesting antenna model in light of very efficient excitation energy hopping along the ring.

Journal Article↗

Association between fish consumption and all-cause and cause-specific mortality in Japan: NIPPON DATA80, 1980-99.

PURPOSE: Although high consumption of fish may be one of the contributing factors for Japanese longevity, no epidemiological study using Japanese data has tested this hypothesis. SUBJECTS AND METHODS: The relationship between fish consumption and all-cause as well as cause-specific mortality was analyzed using the database of NIPPON DATA80. At baseline in 1980, history, physical, and blood biochemical measurement and a nutritional survey by the food-frequency method were performed in randomly selected community-based subjects aged 30 years and over in Japan. After exclusion of subjects with significant comorbidities at baseline, we followed 3945 men and 4934 women for 19 years. Men and women were analyzed comprehensively. Age- and sex-adjusted and multivariate adjusted relative risk for all-cause or cause-specific mortality was calculated using a Cox proportional hazards model with delayed entry. RESULTS: During 19 years of followup, there were 1745 deaths. Subjects were divided into 5 groups according to fish consumption frequency. The multivariate Cox analyses showed that relative risks for subjects who ate fish more than twice daily compared with those of subjects who ate 1 to 2 times weekly were 0.99 (95% confidence intervals: 0.77-1.27) for all-cause, 1.26 (0.70-2.29) for stroke, 0.92 (0.20-4.23) for cerebral hemorrhage, 1.09 (0.48-2.43) for cerebral infarction, and 0.91 (0.35-2.35) for coronary heart disease mortality. CONCLUSION: Our results did not provide evidence in support of the fish hypothesis, perhaps because the majority of the Japanese subjects in the study ate fish more than the threshold level shown to be beneficial in the previous studies.

Adult↗

Incidence of acute myocardial infarction in Takashima, Shiga, Japan.

BACKGROUND: The incidence and mortality from ischemic heart disease (IHD) in Japan seem to be among the lowest of all the industrialized countries, but there are few reliable registers of acute myocardial infarction (AMI). METHODS AND RESULTS: To assess the incidence of AMI in Takashima County, Shiga, Japan, from 1988 to 1998 and compare the data with similar registers in the world, cases of AMI or sudden death presumed from myocardial ischemia were registered. The criteria of AMI were based on the WHO MONICA Projects. The medical records of all the hospitals inside as well as outside the county, the original death records in the health center, and the ambulance records in the county were investigated and 291 cases were registered (190 males, 101 females; average age (mean +/- SD), 69.5+/-12.2). The 28-day and 24-h case fatality was 38.1% and 33.0%, respectively. Age-adjusted annual incidence of AMI per 100,000 population aged between 25 and 74 years were 58.2 for men and 18.0 for women. The incidence of AMI showed a constant trend from 1988 to 1998. CONCLUSION: The results confirmed that Japan has the lowest incidence of AMI among the industrialized countries.

Adult↗

Combined analysis of polymorphisms in angiotensinogen and adducin genes and their effects on hypertension in a Japanese sample: The Shigaraki Study.

We examined the interactions between lifestyle and polymorphisms of salt-sensitive genes and their effects on hypertension in a general Japanese sample (The Shigaraki Study). The study group consisted of 2,902 subjects who underwent a medical examination in 1999 in Shigaraki, a suburban area in Shiga. Among 1,647 subjects not receiving antihypertensive medication, in a combined analysis of angiotensinogen (AGT) and adducin (ADD1) polymorphisms, double homozygosity of 235Thr or 460Trp was not found to be associated with hypertension. A multiple logistic regression analysis showed that age (odds ratio [OR]: 1.07, 95% confidence interval [95% CI]: 1.06-1.08), body mass index (BMI) (OR: 1.18, 95% CI: 1.13-1.23), alcohol consumption (OR: 1.39, 95% CI: 1.16-1.66), family history of hypertension (OR: 1.57, 95% CI: 1.18-2.07), and combined AGT M235T Thr/Thr and ADD1 Trp/Trp polymorphisms (OR: 1.37, 95% CI: 1.03-1.82) were associated with hypertension. However, there was no interaction between eating salty food and combined AGT and ADD1 polymorphisms. Furthermore, eating salty food was not associated with hypertension in a multivariate analysis. Therefore, a combination of the AGT and ADD1 polymorphisms appears to be associated with hypertension. However, a simple questionnaire regarding salt intake was not sufficient to confirm the relationship between salt intake and hypertension and/or salt-sensitive genes.

Adult↗