Biomedical subjects

Kazuyuki Omae

Publications and source records attributed to Kazuyuki Omae.

At least 19 recordsLinked to original sources

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

Identification of ADRA2A polymorphisms related to shear-mediated platelet function.

alpha2A adrenergic receptor (ADRA2A) on platelets interacts with epinephrine, which has a key role in regulating platelet functions. There is familial clustering of inter-individual variations in the epinephrine-induced platelet aggregation, the molecular basis of which, however, has not been fully understood. In this study, we screened the sequence variations in the transcriptional region of ADRA2A gene and analyzed the relationship between the two common polymorphisms and platelet function using epinephrine/collagen cartridge in the platelet function analyzer-100 system, in a healthy Japanese male population (n=211). Among the identified 16 sequence variations including five novel variations, 1780GG genotype was associated with longer closure time which represents low platelet function under high shear-stress conditions (p=0.0478). We also observed enhanced effect of the combination of 1780GG and 2372AA genotypes on longer closure time (p=0.0319). These findings suggest that 1780A/G and 2372A/G polymorphisms are associated with platelet function in interactions with collagen/epinephrine.

Asian People↗

PubMed2006

Historical and geographical aspects of the increasing perfluorooctanoate and perfluorooctane sulfonate contamination in human serum in Japan.

Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) have recently received attention due to their widespread contamination in the environment, as well as in wildlife and humans. We measured the PFOS and PFOA concentrations in historically recorded human serum samples at an age range between 20 and 59 years collected in Kyoto, 20 persons per each time point (n=100), and also the PFOS and PFOA concentrations in human serum samples at an age range between 20 and 59 years from 10 locations throughout Japan (n=200). The historical samples collected from 1983 to 1999 demonstrated that the PFOA concentrations in males and females from Kyoto have increased 4.4-fold and 4.3-fold at a rate of increase of 0.49 ng/ml/year and 0.42 ng/ml/year, respectively. In contrast, serum concentrations of PFOS reached a plateau in the late 1980s. There are also regional differences in both the PFOS and PFOA serum concentrations. The concentrations in serum [geometric mean (geometric standard deviation)] (ng/ml) in 2003-2004 ranged from 7.6(1.6) in the town of Matsuoka in Fukui prefecture to 27.8(1.6) in Kyoto city, and ranged from 2.3(1.5) in Matsuoka to 14.5(1.3) in Osaka city for PFOS and PFOA, respectively.

Adult↗

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

Gorog Thrombosis Test: analysis of factors influencing occlusive thrombus formation.

We used the Gorog Thrombosis Test to analyze the factors influencing the occlusion time, which represents platelet activation and subsequent occlusive thrombus formation, in 132 healthy Japanese volunteers (116 men, 16 women; mean age, 45.0 +/- 12.0 years). The Gorog Thrombosis Test was designed to evaluate platelet aggregation and thrombolytic activity under a high shear stress condition (175 dynes/cm) in a native blood sample in vitro. The mean +/- SD occlusion time was 154.8 +/- 64.7 s (men, 153.4 +/- 64.2 s and women, 165.4 +/- 56.5 s). The occlusion time was inversely correlated with von Willebrand factor ristocetin cofactor activity (VWF:Rco) (r = -0.242, P = 0.0055) and von Willebrand factor antigen (r = -0.230, P = 0.0080). The mean occlusion time in the group with VWF:Rco of at least 170% (137 s) was significantly shorter than that in the group with VWF:Rco less than 170% (156 s, P < 0.05). Platelet counts, other coagulation markers and smoking showed no significant correlations with occlusion time. Red blood cells (r = -0.177, P = 0.0365), hemoglobin (r = -0.191, P = 0.0245) and hematocrit (r = -0.182, P = 0.0329) also showed inverse correlations with the occlusion time. This report is the first to clearly demonstrate the role of von Willebrand factor in the formation of occlusive thrombi in the Gorog Thrombosis Test.

Adult↗

PubMed2005

Large-scale evaluation of the current level of polybrominated diphenyl ethers (PBDEs) in breast milk from 13 regions of Japan.

Polybrominated diphenyl ethers (PBDEs) were measured in 2004 in 105 breast milk samples collected from 13 regions of Japan (Hokkaido, Akita, Miyagi, Tokyo, Gifu, Fukui, Kyoto, Hyogo, Wakayama, Shimane, Yamaguchi, Kochi and Okinawa). Six congeners (BDE-28, BDE-47, BDE-99, BDE-100, BDE-153 and BDE-154) were determined by gas chromatography /mass spectrometry (GC/MS). Total PBDE levels ranged from 0.01 to 23.0 ng/g lipid (geometric mean (GM), 1.34 ng/g lipid). BDE-47 (GM, 0.66 ng/g lipid, 59% of sigmaPBDE) was the most abundant congener present in breast milk and was detected in 99% of the samples. Total PBDE levels were higher in northern Japan than in other regions. We analyzed the effects of occupation, age, smoking status, alcohol consumption and number of deliveries on total PBDE levels. None of these factors were significantly associated with the level of PBDEs. The present study revealed that the current level of exposure to PBDEs in Japan is lower than that in the USA or Sweden. GMs (ng/g lipid) (GSD, geometric standard deviation) and medians (ng/g lipid) of PBDE levels in each district are as follows: Hokkaido 2.70 (1.70), 2.74; Akita 4.49 (2.19), 5.44; Miyagi 1.77 (4.37), 1.11; Tokyo 1.39 (2.09), 1.63, Gifu 2.83 (4.79), 2.23; Fukui 1.05 (2.34), 1.18; Kyoto 1.31 (2.95), 1.33; Hyogo 1.02 (2.69), 0.88; Wakayama 1.33 (3.80), 1.70; Shimane 0.83 (2.51), 0.66; Yamaguchi 1.74 (2.82), 1.76; Kochi 0.50 (2.69), 0.74 and Okinawa 1.91 (2.75), 1.22. This is the first large-scale study of current PBDE levels in breast milk in Japan.

Environmental Exposure↗

PubMed2005

Assessment of tailor-made prevention of atherosclerosis with folic acid supplementation: randomized, double-blind, placebo-controlled trials in each MTHFR C677T genotype.

This study aimed at assessing the effect of folic acid supplementation quantitatively in each MTHFR C677T genotype and considered the efficiency of tailor-made prevention of atherosclerosis. Study design was genotype-stratified, randomized, double-blind, placebo-controlled trials. The setting was a Japanese company in the chemical industry. Subjects were 203 healthy men after exclusion of those who took folic acid or drugs known to effect folic acid metabolism. Intervention was folic acid 1 mg/day p.o. for 3 months. The primary endpoint was plasma total homocysteine level (tHcy). In all three genotypes, there were significant tHcy decreases. The greatest decrease was in the TT homozygote [6.61 (3.47-9.76) micromol/l] compared with other genotypes [CC: 2.59 (1.81-3.36), CT: 2.64 (2.16-3.13)], and there was a significant trend between the mutated allele number and the decrease. The tHcy were significantly lowered in all the genotypes, but the amount of the decrease differed significantly in each genotype, which was observed at both 1 and 3 months. Using these time-series data, the largest benefit obtained by the TT homozygote was appraised as 2.4 times compared with the CC homozygote. Taking into account the high allele frequency of this SNP, this quantitative assessment should be useful when considering tailor-made prevention of atherosclerosis with folic acid.

Alleles↗

PubMed2005

Assessment of human exposure to polychlorinated biphenyls and polybrominated diphenyl ethers in Japan using archived samples from the early 1980s and mid-1990s.

Persistent organic pollutants have been linked to various adverse effects on human health. We conducted a retrospective exposure assessment for 11polychlorinated biphenyl (PCB) congeners and 4 polybrominated diphenyl ether (PBDE) congeners. We analyzed paired samples of blood and food duplicate portions collected in the 1980s (1980 survey, N=40) and the mid-1990s (1995 survey, N=40) from females (five participants from each of eight sites per survey) living throughout Japan, from Hokkaido to Okinawa. The study populations in the 1980 and 1995 surveys were different but had lived in the same community. We measured PCBs and PBDEs in serum and PCBs in diet. Total serum PCBs (ng/g lipid) [geometric mean (geometric standard deviation)] were similar in the 1980 [163.0 (1.7)] and the 1995 [142.6 (2.0)] surveys. In contrast, dietary intake (ng/day) between 1980 and 1995 decreased significantly, from 522.8 (2.5) to 165.9 (3.3), respectively, (P<0.05). We classified the participants by birth year-before 1941 (older generation) and equal to or after 1941 (younger generation). Serum PCB levels decreased significantly in the younger generation, from 179.1 (1.8) in the 1980 survey to 115.4 (2.0) in the 1995 survey (P<0.05). However, in the older generation, serum levels (ng/g lipid) did not change: 150.4 (1.6) in the 1980 survey and 180 (1.8) in the 1995 survey. Total PBDE serum levels (ng/g lipid) increased significantly during the 15 years, from 0.5 (3.5) to 1.8 (3.7) (P<0.05). At the Shimane site, PBDE serum levels (ng/g lipid) increased 20-fold, from 1.3 (4.8) to 26.0 (5.0). The serum levels of PCBs decreased in the younger generation but not in the older, although levels in daily intakes decreased significantly. Exposure levels of PBDEs appear to be increasing in an area-specific manner.

Adult↗

PubMed2005

Salt intake affects the relation between hypertension and the T-786C polymorphism in the endothelial nitric oxide synthase gene.

BACKGROUND: Recent genetic studies have shown an association between the T-786C polymorphism in the endothelial NO synthase gene and coronary artery diseases, but any possible association with hypertension has been controversial. Other studies indicate the effect of restricting salt intake differ depending on individual salt-sensitivity, and the mixture of different sensitivity in study subjects may obscure the results. The objective of this study was to investigate the gene-environment interaction between the salt intake and this polymorphism. METHODS: We genotyped 281 healthy men after excluding 37 men on hypertensive therapy (mean age 44.8 +/- 11.9 years) for the mutation, and evaluated their daily salt intake using a validated food frequency questionnaire. RESULTS: A quartile classification of salt intake revealed that the blood pressure of subjects with the mutation was significantly higher than that of subjects without the mutation, but only in the 4th quartile (the highest intake group). A multiple logistic regression analysis also showed that the presence of this mutation increased the risk of hypertension only in the 4th quartile (adjusted odds ratio = 6.38, P = .025). CONCLUSIONS: The presence of this mutation alone does not significantly increase the risk of hypertension. However, high salt intake interacts with the mutation and leads to a significant increase in the risk of hypertension. The T-786C mutation warrants being considered a candidate for further study with the aim of tailor-made hypertension prevention.

Adult↗

PubMed2005

Secular trends and geographical variations in the dietary intake of polybrominated diphenyl ethers (PBDEs) using archived samples from the early 1980s and mid 1990s in Japan.

A retrospective exposure assessment among the general population for polybrominated diphenyl ethers (PBDEs) was conducted using dietary surveys. We analyzed samples of food duplicate portions collected in the early 1980s (1980 survey: N=40) and the mid 1990s (1995 survey: N=39) from female subjects (5 participants from each of 8 sites per survey except for one site) living throughout Japan, from the north (Hokkaido) to the south (Okinawa). The study populations in the 1980 and 1995 surveys were different, but lived in the same communities. We measured four PBDE congeners [2,2',4,4'-tetrabrominated diphenyl ether (tetraBDE): #47; 2,2',4,4',5-pentaBDE: #99; 2,2',4,4',6-pentaBDE: #100; and 2,2',4,4',5,5'-hexaBDE: #153] in the diet. #99 was the most abundant congener in the diet (49% of the total PBDEs), followed by #47 (33%), #100 (12%) and #153 (6%). Regional variations found in the 1980 survey decreased in the 1995 survey. The total daily intake of PBDEs (ng/d) [GM (GSD)] in the 1980 survey [91.4 (4.1)] was not significantly different from that in the 1995 survey [93.8 (3.4)] for the total population, nor did it differ among the sites including Shimane, in which a 20-fold increase in serum concentrations was observed in the same population1). In consideration of the significant increases in the serum concentration, inhalation may be more important than food ingestion as the route of human exposure to PBDEs.

Adult↗

PubMed2005

A 13-week toxicity study of bismuth in rats by intratracheal intermittent administration.

Although bismuth is widely used as a lead substitute in the industrial field, the toxicity of bismuth by inhalation is little known. We performed a 13-wk intratracheal intermittent bismuth dose toxicity study. Bismuth was administered at dose levels of 0, 0.8, 4, 20 mg/kg to male Crj:CD(SD)IGS rats (SPF) by intratracheal intermittent administration once a week for thirteen weeks to investigate its potential toxic effects; especially for specific adverse effects and changes related to pre-neoplastic lesions. Our results showed foreign body inflammation in the lungs, which was caused by intratracheal administration of bismuth, and physical changes related to pulmonary lesions; however, there were no serious changes in other organs. We concluded that dose-dependent, but not specific adverse effects, were attributable to bismuth inhalation in the rat.

Administration, Inhalation↗

PubMed2005

Oral toxicity of bismuth in rat: single and 28-day repeated administration studies.

The consumption and production of bismuth are increasing, however there is very little information about the direct toxic effect of bismuth. The present study aimed to characterize the potential toxic effects of bismuth through oral administration and observation for fourteen days following single dose of 0 and 2,000 mg/kg (acute oral toxicity study), and repeated oral administration for twenty-eight days at dose levels of 0, 40, 200, and 1,000 mg/kg daily (28-d repeated oral dose toxicity study) to male and female Crj:CD (SD) IGS rats (SPF). We found no deaths and no abnormalities in clinical signs, body weights, and necropsy findings for any of the animals in the acute oral toxicity study and no changes attributable to bismuth in either males or females in the dose group up to 1,000 mg/kg of the 28-d repeated-dose toxicity study. Therefore, we determined that the lethal dose with a 50% mortality rate (LD50) is greater than 2,000 mg/kg and the no-observed-adverse-effect level (NOAEL) of bismuth is 1,000 mg/kg in both sexes. We conclude that the adverse toxic effects of bismuth as a simple metal substance are low compared to lead toxicity under the conditions tested in our studies.

Administration, Oral↗

PubMed2005

Effects of sarin on the nervous system of subway workers seven years after the Tokyo subway sarin attack.

This study was designed to assess the after effects of sarin exposure on the nervous system in victims of the Tokyo Subway Sarin Attack, which occurred on 20 March, 1995. We performed a similar study 3 yr after the disaster. This time, we newly enrolled 36 staff of the Teito Rapid Transit Authority (Tokyo Eidan subway) to assess the 7 yr after effects on the nervous system, and merged previous data including unpublished data to enhance statistical power. New subjects consisted of 23 male exposed subjects and 13 referent subjects matched for age and working types. Neurobehavioral tests for psychomotor function and memory, stabilometry, and Benton visual retention test were performed. As reported previously, the exposed group performed significantly less well in the psychomotor function test (tapping) than the referent group (117.8 +/- 1.2 vs. 105.6 +/- 1.2 msec). Using merged data, this phenomenon was also observed in a dose-dependent manner and the exposed group performed significantly less well in the backward digit span test (4.47 +/- 1.17 vs. 5.11 +/- 1.65 digits). These results indicate that chronic decline of psychomotor function and memory function still exist 7 yr after the sarin exposure.

Adult↗

PubMed2005

[Effects of volcanic sulfur dioxide on reconstruction workers and residents returning to Miyake Island].

Four and half years have passed since Mt. Oyama in Miyake Island erupted. Ambient sulfur dioxide (SO2) is still above the environmental air standard in parts of the island, even though emission of the volcanic gas has diminished. Reconstruction of life-support infrastructure in the island and safety measures started in July 2002, and a short-term trial stay project for former residents was completed in April 2003 for the total rehabilitation of the island. We conducted health examinations, and questionnaires on clinical symptoms among the reconstruction workers in January 2003, as well as questionnaires on respiratory symptoms among former residents who joined the trial stay, in late fall of 2003. The peak expiratory flow rate and symptoms of the workers and the symptoms of the short-term residents were not correlated to SO2 concentrations. In addition, we investigated the medical histories of outpatients at Miyake-mura National Insurance Center Clinic. We could not recognize any cases directly connected with higher ambient SO2 concentration in the area of the island, but there was a male worker, in his thirties, who suffered an initial attack of bronchial asthma, which required intensive care and treatment. As a general rule, all the workers and the residents are asked to wear gas masks for SO2 when its concentration is above 2.0 ppm and to stay in the house with desulfuration facilities as a precautionary measure at night. The residents are now well informed about the risks of volcanic gas and preventive measures for adverse health effects. We could not evaluate correlations between SO2 exposure indices and health effects sufficiently due to the limitation of the field study, but this study presents useful pieces of information as a risk communication for reconstruction workers and former inhabitants to the island.

Adult↗

PubMed2005

Increased risk of obesity resulting from the interaction between high energy intake and the Trp64Arg polymorphism of the beta3-adrenergic receptor gene in healthy Japanese men.

BACKGROUND: Few studies have investigated the interaction between the Trp64Arg polymorphism of the beta3-adrenergic receptor gene (ADRB3) and environmental factors. This study aimed to investigate whether energy intake affects the relationship between this polymorphism and obesity. METHODS: Healthy Japanese men (n=295; age 46.1+/-11.5 years (mean +/-standard deviation); waist circumference 83.9+/-9.3 cm; body mass index (BMI) 23.3+/-3.3 kg/m2) recruited in a Japanese chemical industry firm were eligible for analysis. Daily energy intake, protein, fat, and carbohydrate (PFC) ratio and daily physical activity were assessed by self-reported questionnaires. Genotyping for the polymorphism was performed with written informed consent. RESULTS: When the subjects were classified into two groups according to presence of the polymorphism, the groups were not significantly different in waist circumference or BMI. Quartile classification of energy intake, however, demonstrated a significantly larger ratio of obese subjects to non-obese subjects in the group with the polymorphism in the highest 4th quartile alone. Multiple logistic regression analysis also revealed that the presence of the polymorphism increased the risk of obesity significantly in the 4th quartile alone (adjusted odds ratio=3.37, 95% confidence interval=1.12-10.2). CONCLUSION: Presence of the polymorphism alone does not significantly increase the risk of obesity. However, high energy intake interacts with the polymorphism and leads to a significant increase in risk of obesity. The Trp64Arg polymorphism of ADRB3 warrants consideration, along with other polymorphisms involved in the development of obesity, for tailor-made prevention of obesity.

Body Mass Index↗

PubMed2004

High throughput multiple combination extraction from large scale polymorphism data by exact tree method.

Single nucleotide polymorphisms (SNPs) are increasingly becoming important in clinical settings as useful genetic markers. For the evaluation of genetic risk factors of multifactorial diseases, it is not sufficient to focus on individual SNPs. It is preferable to evaluate combinations of multiple markers, because it allows us to examine the interactions between multiple factors. If all the combinations possible were evaluated round-robin, the number of calculations would rapidly explode as the number of markers analyzed increased. To overcome this limitation, we devised the exact tree method based on decision tree analysis and applied it to 14 SNP data from 68 Japanese stroke patients and 189 healthy controls. From the obtained tree models, we succeeded in extracting multiple statistically significant combinations that elevate the risk of stroke. From this result, we inferred that this method would work more efficiently in the whole genome study, which handles thousands of genetic markers. This exploratory data mining method will facilitate the extraction of combinations from large-scale genetic data and provide a good foothold for further verificatory research.

Adult↗

PubMed2004

[Intake and excretion of cadmium and iron balance and influence of dietary habits among young women].

OBJECTIVE: Absorption of cadmium is increased by deficiency of iron in animals, but it is uncertain that the same phenomenon occurs in humans. The purpose of this study is to investigate the relationship between cadmium and iron in the body and to evaluate the influence of dietary habits. METHODS: Twenty-five healthy women, aged 20-23 years, were selected by excluding those with renal disease and habitual constipation. They participated in the dietary intervention study to estimate tolerable weekly intake of Cd for 3 weeks in the same dormitory. At 3 months before, at 0 Day, at the 12th Day of the study and 9 months after the study, health check-ups were performed, and Cd in the blood and urine, hemoglobin (Hb), serum iron (iron) and serum ferritin (ferritin) were measured. RESULTS: Cd concentration in the blood (B-Cd) showed a significant correlation with Cd concentration in the urine (U-Cd), and inverse correlation with the body iron storage, such as Hb, iron and ferritin. A food frequency questionnaire showed that no subject showed insufficient dietary intake of iron. Subjects who had eaten grain, millet and brown rice showed higher levels of B-Cd and U-Cd and low levels of Hb, iron and ferritin. CONCLUSION: Absorption of Cd tended to increase according to a low level of body iron storage among healthy young women.

Adult↗

PubMed2003

Lack of relationship between occupational exposure to carbon disulfide and endocrine dysfunction: a six-year cohort study of the Japanese rayon workers.

OBJECTIVES: A six-year prospective cohort study was conducted to clarify whether the current carbon disulfide (CS2) exposure level is low enough to prevent subclinical health impairment and/or to ameliorate health effects due to previous high exposure. This paper describes the follow-up results, exposure assessment, and effects on the endocrine system. METHODS: The study subjects were 432 male workers exposed to CS2 at one of the 11 rayon factories in Japan and 402 referent workers from the same factories, all of whom were examined in 1992-93. 251 CS2-exposed, 140 former-exposed and 359 referent workers participated in the follow-up survey (follow-up rate 89.9%) in 1998-99. Urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) at the end of a shift as internal exposure index and the time-weighted average CS2 concentration as external exposure index were measured twice a year from 1992-1993. By using various blood indices, we evaluated effects on thyroid, hypophysis, and gonad function, as well as effects on glucose metabolism. Information on potential confounding factors, such as age, smoking and alcohol drinking, were collected and adjusted for. RESULTS: When the individual exposure level was represented by arithmetic mean for TTCA and CS2 concentration, geometric means (SD) of CS2 workers were 1.61 (1.91) mg/g.crea and 5.02 (1.84) ppm, respectively. There were no exposure-related differences in glucose metabolism or any of the endocrinological indices. CONCLUSIONS: No biologically significant effects of CS2 were found on endocrine function in Japanese rayon manufacturing workers when the average internal and external exposure levels were maintained below the current occupational exposure limit.

Adult↗