Koichi Miyaki

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

Effects of Sarin on the Nervous System of Subway Workers Seven Years after the Tokyo Subway Sarin Attack: Koichi Miyaki, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—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(Tokyo Eidan subway) to assess the 7 yr after effects on the nervous system, and merged previous data including unpublished data to enhance statistical power.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.

RBC velocities in single capillaries of mouse and rat brains are the same, despite 10-fold difference in body size

Employing high-speed camera laser-scanning confocal microscopy with RBC-tracking software, we previously showed that RBC velocities in intraparenchymal capillaries of rat cerebral cortex are distributed over a wide range. In the present work, we measured RBC velocities in mice, whose body weights are less than one-tenth of that of rats. In an isoflurane-anesthetized mouse, a cranial window was opened in the left temporo-parietal region. Intravenously administered FITC-labeled RBCs were automatically recognized and tracked frame-by-frame at 500fps, and the velocities of all RBCs recognized were calculated with our Matlab-domain software, KEIO-IS2. Among 15241 RBCs detected in the ROI in 21 mice, 1655 were identified as flowing in capillaries. The velocities of these RBCs ranged from 0.15 to 8.6mm/s, with a mean of 2.03+/-1.42mm/s. A frequency distribution plot showed that RBC velocities were clustered at around 1.0mm/s, tailing up to 8.6mm/s, and 59% of the RBCs in capillaries showed velocities within the range of 0.5 to 2.0mm/s. Unexpectedly, these characteristics of RBC velocities in mice were very similar to those of rats, despite differences in RBC diameter (6.0 vs. 6.5microm), body size (25 vs. 327g), heart rate (461 vs. 319bpm) and arterial blood pressure (86 vs. 84mmHg). We speculate that physical factors relating to oxygen exchange may constrain general RBC velocity in capillaries to a certain range for optimum oxygen exchange, regardless of species.

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

AbstractThis 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) μmol/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.

Biological monitoring of indium by means of graphite furnace atomic absorption spectrophotometry in workers exposed to particles of indium compounds.

Since the rapid expansion of III-V semiconductor and liquid crystal display production, the consumption of indium (In) has been increasing. From the mid-1990s, animal experiments have shown that the inhalation or intratracheal instillation of In compounds causes severe lung inflammation and mild adverse reproductive effects. Although the health effects of In on workers’ respiratory and reproductive systems have been unclear to date, assessing the exposure-effect relationships in Inexposed workers is a serious concern, but no information is available on the exposure-effect relationships in workers. This study attempted to estimate the In concentration in biological specimens of In-exposed workers, and to clarify the relationships among them.

Genetic polymorphisms in homocysteine metabolism and response to folate intake: a comprehensive strategy to elucidate useful genetic information.

Homocysteine is a risk factor for atherosclerosis, and the level of homocysteine in plasma is known to be strongly influenced by genetic factors—not only rare variants, but also common polymorphisms. This report describes a comprehensive postgenomic strategy for elucidating useful genetic information about homocysteine metabolism. The standard method for gathering such information is the candidate gene approach, which is an effective method based on known biological information. After collecting evidence from independent research projects, a critical epidemiological review permits a determination as to whether a putative association is true or not. A genome-wide association study (GWAS), which requires no biological information, can identify new candidates and confirm associations suggested by the candidate gene approach. The importance of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, which was shown in a randomized controlled trial conducted by the present author, and in other studies, was independently confirmed by a large-scale GWAS. GWASs have also identified new candidate genes, but these must be confirmed by independent studies. In homocysteine metabolism, the classical candidate gene approach was sufficiently robust to detect the true association. However, candidate markers newly discovered by GWAS need to be confirmed by well-designed epidemiological studies to determine their significance. International statements, such as CONSORT and STREGA, provide useful principles for conducting such research.

Surgical site infection surveillance after open gastrectomy and risk factors for surgical site infection

Surgical site infection (SSI) surveillance was examined in gastric cancer patients who had undergone an open gastrectomy between 1997 and 2003 at Keio University Hospital in Tokyo, Japan. National Nosocomial Infections Surveillance (NNIS) reports and several studies have discussed SSI risk factors, but only open gastrectomy was analyzed by regression analysis. The purpose of this study was to examine these issues by performing a regression analysis for the prediction of SSI. SSI was defined by the surgical patient component according to the NNIS system (1999) produced by the Centers for Disease Control and Prevention. Patients undergoing an open gastrectomy were followed up and monitored for SSIs. Risk factors for SSI, after all factors were considered, were studied using single and multivariate analysis. The study enrolled 984 patients who had undergoing an open gastrectomy. Using multivariate and logistic regression analysis, the duration of the operation was identified as a [corrected] risk factor for SSI at open gastrectomy. Although numerous potential risk factors in surgical patients were examined, the duration of the operation was the only significant risk factor for SSIs after open gastrectomy.

Periodontal disease and atherosclerosis from the viewpoint of the relationship between community periodontal index of treatment needs and brachial-ankle pulse wave velocity

BackgroundIt has been suggested that periodontal disease may be an independent risk factor for the development of atherosclerosis. However, the relationship between periodontal disease and atherosclerosis has not been fully elucidated. This study aimed to assess the effects of periodontal disease on atherosclerosis.MethodsThe study design was a cross-sectional study. Subjects were 291 healthy male workers in Japan. We used the Community Periodontal Index of Treatment Needs (CPITN) score, average probing depth and gingival bleeding index (rate of bleeding gums) to assess the severity of periodontal disease. We also used the Brachial-Ankle Pulse Wave Velocity (baPWV) as the index for the development of atherosclerosis.ResultsThe unadjusted odds ratio (OR) of atherosclerosis in relation to the CPITN score was 1.41 [95% CI: 1.16–1.73]. However, after adjustment for age, systolic blood pressure and smoking, the CPITN score had no relationship with atherosclerosis (adjusted OR: 0.91 [0.68–1.20]).ConclusionOur results show no relationship between mild periodontal disease and atherosclerosis after appropriate adjustments.

The combined impact of 12 common variants on hypertension in Japanese men, considering GWAS results

Genome-wide association studies have identified several polymorphisms that appear to be on hypertension-susceptible regions. We performed the current replication study in order to evaluate the association of these loci with hypertension in healthy Japanese males and then examined the combined effect of 12 independent variants. Overall, 735 Japanese men from two independent cohorts were recruited. Association with hypertension was assessed in 16 polymorphisms on 12 genes and 12 were chosen to evaluate the combined impact. Polymorphisms on the COMT, ATP2B1, CYP11A1 and the CSK genes were confirmed to be associated with hypertension and blood pressure (BP). Current findings also replicated previous results for the CYP11B2 and PTGIS genes. Although there were no significant associations found for other variants, our results suggested there was a combined impact for 12 loci. Individuals carrying more risk alleles had a higher risk of hypertension (P for the slope=0.002). Blood pressures also increased in conjunction with an increasing risk allele score (P for trend=7.84 × 10−6 and 1.85 × 10−5 for SBP and DBP, respectively). Our results confirmed the associations between hypertension or blood pressure and four gene variants. We also found a significant combined effect of the 12 gene loci.

Two New Criteria of the Metabolic Syndrome: Prevalence and the Association with Brachial-Ankle Pulse Wave Velocity in Japanese Male Workers

Two New Criteria of the Metabolic Syndrome: Prevalence and the Association with Brachial‐Ankle Pulse Wave Velocity in Japanese Male Workers: Koichi Miyaki, et al. Department of Preventive Medicine and Public Health, School of Medicine, Keio University—In 1998 and 2001, The World Health Organization and the National Cholesterol Education Program Adult Treatment Panel III proposed working criteria for the metabolic syndrome (MS), but they are not perfect for use in diverse ethnicities. In 2005, the International Diabetes Federation (IDF) and eight societies in Japan respectively proposed new criteria. However, there has been no report regarding the application of these new criteria in Japanese workplaces. We conducted a cross‐sectional study of 377 healthy Japanese men aged 20–64 yr who worked in a chemical factory in Kanagawa, Japan. Participants completed a self‐reported questionnaire, underwent a physical examination including waist measurements and brachial‐ankle pulse wave velocity (baPWV), and provided overnight fasting blood samples. The prevalence of MS in Japanese men was 17.0% and 13.5% according to the new IDF and Japanese criteria respectively. In both of the new criteria, baPWV was significantly higher in those with MS than those without MS (1,563 ± 264.2 vs 1,362 ± 204.6 cm/sec, p<0.001 in the new IDF criterion; 1,574 ± 265.2 vs 1,368 ± 209.1 cm/sec, p<0.001 in the Japanese criterion). In the analysis of the 5 or 6 subgroups stratified according to the number of MS components, baPWV increased significantly with increasing number of MS components (p for trend<0.01 in both criteria). The new IDF and Japanese criterion are both good for diagnosing MS among Japanese because a linear increase in baPWV occurred with increasing MS components after adjustment for potential confounding factors. Further studies are expected using these new criteria.

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

AbstractSingle 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.