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We examined the influence of the A1330V variant in the low-density lipoprotein receptor-related protein 5 gene on blood pressure in a large cohort of Japanese workers. This study used analysis of covariance in a multivariate general linear model to adjust for other potential factors such as age, body mass index, blood chemistry and lifestyle. The target subjects were 1440 males and 1169 females selected from 3834 male and 2591 female workers in a single company. Hypertension was defined as systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg or the use of antihypertensive medications. Genotype distributions for A1330V in hypertensive males (AA = 139(54.5%), AV = 101(39.6%), VV = 15(5.9%)) and females (AA = 48(63.2%), AV = 24(31.6%), VV = 4(5.3%)) were not significantly different from normotensive males (AA = 594(50.1%), AV = 488(41.2%), VV = 103(8.7%)) and females (AA = 568(52.0%), AV = 441(40.3%), VV = 84(7.7%)). Allele distributions were not significantly different in either sex. In males, analysis of covariance showed that the VV genotype was associated with a 2.5 mm Hg lower diastolic blood pressure and a 2.3 mm Hg lower mean blood pressure than the AA genotype. This study indicates that the 1330V allele is an independent factor for lower diastolic and mean blood pressure in Japanese males.

Objectives: This study was undertaken to examine the association between sickness absence in Japanese employees and job demand/control and occupational class as psychosocial work characteristics. Methods: The study was cross-sectional in design with data collected from 20,464 male and 3,617 female employees, whose mean age was 40.9 years (SD ± 9.1 years) and 36.9 years (SD ± 10.8 years), respectively. The participants were asked to write the total number of sick leaves they had taken during the past year, and a comparison was made between the group with more than 6 days of sickness absence and the group with 0–6 days as a reference group. Job demands, job control, and worksite support from supervisors and colleagues were analyzed by the Job Content Questionnaire, and likewise by the Generic Job Stress Questionnaire of the National Institute for Occupational Safety and Health. Results: Both low job control and low support at the worksite were associated with a high frequency of sickness absence. But there was no clear relationship between job demands and sickness absence. The lowest sickness absence rate was found in male managers and the highest in male and female laborers. Conclusion: This is the first report of a large-scale survey of Japanese employees to show a high frequency of sickness absence associated with increased work stress and a socioeconomically low occupational class.

The influence of cadmium (Cd) body burden on mortality remains controversial. Excess mortality and the dose-response relationship between mortality and urinary cadmium excretion were investigated in this study among environmentally exposed subjects. A 15-year follow-up study was carried out on 3119 inhabitants (1403 men and 1716 women) of the Cd-polluted Kakehashi River basin, whose urinary Cd concentration was examined in a 1981-1982 health impact survey. The mortality risk of high urinary Cd (or = 10 microg/g Cr) subjects after adjustment for age using Cox's proportional hazard model was higher than that of moderate urinary Cd (10 microg/g Cr) subjects in both sexes. When the subjects were divided into five groups according to the amount of urinary Cd (3, 3-5, 5-10, 10-20,or = 20 microg/g Cr), the mortality risk was significantly increased among the subjects with urinary Cdor = 3 microg/g Cr in proportion to the increases in the amount of urinary Cd concentration after adjustment for age, especially in women. Furthermore, special causes of death among high and moderate urinary Cd were investigated, and mortality risk ratio for heart failure, which is a cause of death often diagnosed in cases with a gradual deterioration culminating in death, was significantly increased in both sexes, compared with the moderate urinary Cd subjects. Also, in women the mortality risk for renal diseases in the high urinary Cd subjects was significantly higher than that in the moderate urinary Cd subjects. These results suggest that a causal association between Cd body burden and mortality exists among inhabitants environmentally exposed to Cd but that no special disease may be induced except renal diseases.

We examined the influence of the Q89R variant in low-density lipoprotein receptor-related protein 5 on hypertension in a large Japanese cohort. We used multivariate logistic regression analysis to adjust for the effects of other factors known to influence hypertension such as age, body mass index, blood chemistry and lifestyle. Our cohort consisted of 1444 males and 1161 females selected from 3834 male and 2591 female workers in a single company. Hypertension was defined as systolic blood pressure 140 mmHg and/or diastolic blood pressure 90 mmHg or the use of antihypertensive medication. Because the RR genotype was so rare (three normotensive males and three normotensive females), they were excluded from analyses. Genotype distributions for Q89R in hypertensive females (QR = 14, QQ = 60) were significantly different (p = 0.033) from normotensive females (QR = 113, QQ = 971). In contrast, those in hypertensive males (QR = 26, QQ = 230) and in normotensive males (QR = 145, QQ = 1040) were similar. Allele distributions were not significantly different in either gender. In females, multivariate logistic regression showed that the QR genotype was associated with hypertension with odds ratio of 2.1 compared to the QQ genotype. This study indicates that the Q89R polymorphism is an independent factor for hypertension in Japanese females.

Yeast is often considered to be a model eukaryotic organism, in a manner analogous to E. coli as a model prokaryotic organism. Yeast has been extensively characterized and the genomes completely sequenced. Despite the small genome size, yeast displays most of features of higher eukaryotes. The facts that most of cellular machinery is conserved among different eukaryotes and that the powerful technologies of genetics and molecular biology are available have made yeast model eukaryotic cells in biological and biomedical sciences including virology. Cumulative data indicate that yeast can be a host for animal viruses. I briefly describe yeast gene expression and review viral replication in yeast. Great discovery include complete replication of animal viruses and production of virus-like particle vaccines in yeast. Current studies on yeast focus on identification of host factors and machinery used for viral replication. The studies are based on traditional yeast genetics and genome-wide identification using a complete set of yeast deletion strains.

The present study investigated the effects of job stress on cellular immune function, such as NK cell activity and NK cell subsets. The participants were 61 female nurses aged 23-59, who worked in a public psychiatric hospital in Ishikawa, Japan. Each subject completed the Nursing Job Stressor Scale (NJSS) and their NK cell activity and lymphocyte surface antigens (CD16+56+) were evaluated as immune system parameters. The NJSS has seven subscales: conflict with other nursing staff, nursing role conflict, conflict with physicians or autonomy, conflict with death or dying, quantitative work load, qualitative work load and conflict with patients. Factors influencing NK cell activity, and the proportion and cell counts of CD16+56+ lymphocytes were evaluated. Increase in quantitative work load significantly decreased NK cell activity. Conversely, no linear relationship was observed between qualitative work load and immunological variables, with the highest percentage of CD16+56+ lymphocytes observed among participants in the medium work load group. The other five NJSS subscales did not relate to immune parameters. In conclusion, the results suggest that perceived job strains, particularly quantitative work load, decreased NK cell function.

Information has been sparse on the comparison of 4 blood pressure (BP) indexes (systolic BP [SBP], diastolic BP [DBP], pulse pressure [PP], and mean BP [MBP]) in relation to long-term stroke incidence, especially in middle-aged and older Asian people. A prospective cohort study was performed in 4989 Japanese (1523 men and 3466 women) aged 35 to 79 at baseline with 10 years of follow-up. End points included stroke incidence (total, ischemic, and hemorrhagic). Multivariate-adjusted hazard ratios with a 1-SD higher value for each BP index were determined by Cox proportional hazard analyses; Wald χ 2 tests were used to compare the strength of relationships. Analyses were also done for each of 4 age-gender groups consisting of men and women aged 35 to 64 and 65 to 79 years. During follow-up, 132 participants developed stroke. Adjusted hazard ratios for all strokes were 1.68 for SBP, 1.72 for DBP, and 1.80 for MBP, which were higher than that for PP (1.34). SBP and DBP were related positively to stroke risk after adjustment of each other. PP was not the strongest predictor in any age-gender groups among 4 BP indexes. In men aged 65 to 79 years, SBP showed the strongest relationship to all stoke risk (hazard ratio 1.62) among 4 BP indexes. In women aged 65 to 79 years, hazard ratios for all strokes were 2.48 for MBP, 2.46 for DBP, 2.25 for SBP, and 1.57 for PP. The long-term incident stroke risk of high BP in Asians should be assessed by SBP and DBP together, or by MBP, not by PP.

Human immunodeficiency virus Gag protein self-assembles into spherical particles, and recent reports suggest the formation of assembly intermediates during the process. To understand the nature of such assembly intermediates along with the mechanism of Gag assembly, we employed expression in Escherichia coli and an in vitro assembly reaction. When E. coli expression was performed at 37 degrees C, Gag predominantly assembled to a high order of multimer, apparently equivalent to the virus-like particles obtained following Gag expression in eukaryotic cells, through the formation of low orders of multimer characterized with a discreet sedimentation value of 60 S. Electron microscopy confirmed the presence of spherical particles in the E. coli cells. In contrast, expression at 30 degrees C resulted in the production of only the 60 S form of Gag multimer, and crescent-shaped structures or small patches with double electron-dense layers were accumulated, but no complete particles. In vitro assembly reactions using purified Gag protein, when performed at 37 degrees C, also produced the high order of Gag multimers with some 60 S multimers, whereas the 30 degrees C reaction produced only the 60 S multimers. However, when the 60 S multimers were cross-linked so as not to allow conformational changes, in vitro assembly reactions at 37 degrees C did not produce any higher order of multimers. ATP depletion did not halt Gag assembly in the E. coli cells, and the addition of GroEL-GroES to in vitro reactions did not facilitate Gag assembly, indicating that conformational changes rather than protein refolding by chaperonins, induced at 37 degrees C, were solely responsible for the Gag assembly observed here. We suggest that Gag assembles to a capsid through the formation of the 60 S multimer, possibly a key intermediate of the assembly process, accompanied with conformational changes in Gag.

It has not been fully clarified whether exercise blood pressure (BP) in young adult men and women is useful to predict future BP, especially in Asian people. A long-term prospective study was conducted in graduates of a medical school in Japan; 138 men and 76 women whose mean age was 19.8 and 19.2, respectively, at baseline. A 5-min exercise tolerance test was performed at baseline, and BP immediately after exercise was measured. BP at 50% intensity exercise was also calculated. Multiple regression analysis was carried out to clarify the relationship of exercise BP at baseline to follow-up BP after an average of 12 years. In multivariate-adjusted models, the relationship of systolic blood pressure (SBP) at follow-up was stronger to SBP immediately after exercise (F=7.7, P=0.006) than to resting SBP (F=3.7, P=0.055) in men. The models in men showed that SBP immediately after exercise was a stronger predictor of follow-up SBP than SBP at 50% intensity exercise, and the results were similar for diastolic blood pressure (DBP) in men. For SBP in women, resting SBP was the strongest predictor of follow-up SBP (F=14.3, P

OBJECTIVE To examine the association between hypertension and the C825T polymorphism in the G-protein beta 3 subunit gene in Japanese workers. METHODS This study used logistic regression analysis and multiple regression analyses to investigate whether the C825T polymorphism was associated independently with hypertension or blood pressure when factors such as age, body mass index, blood chemistry and lifestyle were taken into consideration. The target subjects were 1452 male and 1169 female workers selected from 3834 male and 2591 female workers in a single company. Hypertension was defined as a systolic blood pressure > or = 140 mmHg and/or diastolic blood pressure > or = 90 mmHg, or taking antihypertensive medication. The power of the study was estimated as 83% for males and 41% for females based on allelic frequencies in Caucasians. RESULTS Genotype distributions for C825T in hypertensive males (CC = 58, CT = 135, TT = 63) and females (CC = 20, CT = 36, TT = 20) were not significantly different from normotensive males (CC = 300, CT = 614, TT = 282) or females (CC = 274, CT = 602, TT = 217), respectively. Allele distributions were not significantly different in either sex. Multiple logistic regression analysis showed that genotype was not associated significantly with hypertension, whereas there was a significant relationship between hypertension and age, family history of hypertension, body mass index, hematocrit, platelet count, gamma-glutamyl transpeptidase (gamma-GTP) and uric acid. Data analysis using one-way analysis of variance and multiple regression showed that the C825T allele had no significant influence on either systolic, diastolic or mean blood pressure. CONCLUSIONS This study indicates that the C825T polymorphism is not a significant factor for hypertension or blood pressures in Japanese people. Targeting of this polymorphism is therefore unlikely to be beneficial when attempting to prevent hypertension in the general Japanese population.

Background Detailed epidemiological investigations on the relationship of environmental factors, especially occupational and microbiological factors, to the development of idiopathic dilated cardiomyopathy (IDC) are scarce. Methods and Results A multi-hospital case - control study was conducted in 38 hospitals throughout Japan in order to survey IDC cases and age, sex-matched outpatient controls at each hospital. Crude and adjusted odds ratios (ORs) by various environmental factors were calculated in 135 pairs of cases and controls. Univariate analyses revealed significantly increased ORs for lower education, passive smoking in the workplace, cold and/or hot workplace, symptoms of fatigue and history of bacterial infection; in contrast, decreased ORs were associated with a history of rubella and gastroduodenal diseases. Based on multivariate adjusted analyses, lower education (OR 1.96, 95% confidence interval (CI) 1.13-3.40), cold or hot workplace (OR 1.84, 95%CI 1.08-3.12) and history of measles (OR 1.78, 95%CI 1.01-3.08) exhibited a significant positive relationship with IDC risk. History of rubella (OR 0.17, 95%CI 0.06-0.52) and gastroduodenal diseases (OR 0.14, 95%CI 0.07-0.29) were inversely related to the risk. Conclusions Some occupational and microbiological factors appear to relate independently to the development of IDC and further investigation is required to establish their respective mechanisms. (Circ J 2004; 68: 1011 - 1017)

The construct validity of the Maslach Burnout Inventory (MBI) has been a major point of focus for many studies. The validity of the MBI-General Survey (MBI-GS), a newly developed instrument intended for use outside the human services has not been sufficiently investigated. The aim of this present study is to investigate the validity of the MBI-GS. The Japanese language version of the MBI-GS was prepared for this research and it was administered to a sample of intermediate managers (n = 696) working for a manufacturing company in Japan. The total of 691 effective data were obtained. The exploratory factor analysis replicated the same three-factor structure (Exhaustion, Cynicism, and Professional Efficacy) as the original whereas inter-factor correlation between Exhaustion and Cynicism was moderate. Cronbach's alpha coefficients for all three subscales were above 0.80. The confirmatory factor analysis supported a three-factor model whereas Exhaustion and Cynicism were moderately related. To investigate the construct validity, three subscales of the MBI-GS were then related to selected work characteristics. Based on conservation of resources theory, differential patterns of effects were predicted among the correlates and the burnout subscales. A path analysis revealed that the expectations were largely supported, suggesting that the meaning of the three subscales is quite different with a path from Exhaustion to Cynicism. The study found support for the construct validity of the MBI-GS. Copyright © 2004 John Wiley & Sons, Ltd.

We examined the association of the G-protein beta3 subunit gene (GNB3) C825T polymorphism with overweight in Japanese workers. This cross-sectional study used multivariate analysis to investigate whether a polymorphism in the C825T polymorphism was associated independently with overweight when factors such as age and lifestyle were taken into account. The study in 1453 men and 1172 women involved identifying subjects with the C825T genotype using the polymerase chain reaction, followed by restriction fragment-length polymorphism analysis. Overweight was defined as a BMI > or = kg/m(2). Genotype distributions for C825T in overweight men (CC = 80, CT = 162, TT = 80) and women (CC = 52, CT = 91, TT = 40) were not significantly different from normal-weight men (CC = 278, CT = 588, TT = 265) and women (CC = 242, CT = 549, TT = 198). The allele distributions were also not significantly different between either sex. The power of the study was estimated as 98% in men and 81% in women based on the allelic frequencies reported in a previous positive study in Chinese subjects. Multiple logistic regression analysis showed that the genotype was not significantly associated with overweight. In conclusion, this study indicated that the GNB3 C825T polymorphism is not a significant factor for overweight in Japanese people.

Monitoring in Ishikawa Prefecture (mean population; 1,150,000), during the 20-year period from 1981 to 2000, involved monitoring the prevalence of congenital anomalies starting at gestational week 22. The main objectives of the present study were (1) to investigate the trend over the past 20 years in the prevalence of congenital anomalies, and (2) to investigate whether there is area accumulation in congenital anomalies or not. In addition, the prevalence of well-known risk factors such as smoking, drinking and family history among cases with congenital anomalies was analyzed to obtain clues to the background of such anomalies. During the 20 years, more than 200,000 births have been observed. Thirty-three selected congenital anomalies, consisting mainly of external anomalies, were analyzed in this study. The percentage of children born with congenital anomalies did not change markedly between the first and second halves of the monitoring period, remaining at approximately 4.5/1,000 births. There was also no significant change in annual trends in either Ishikawa Prefecture as a whole or in the three regions within Ishikawa. The prevalence of congenital anomalies by type showed a significant decrease in anencephaly and spina bifida. In contrast, Down syndrome and microcephaly increased significantly. The mean maternal age for Down syndrome increased significantly from the first-half period to the second-half period. The percentage of children with polydactyly whose mother smoked were relatively higher than that for the other congenital anomalies.

To evaluate the immunogenicity of human immunodeficiency virus (HIV) type 1 p55 gag virus-like particles (VLPs) released by budding from yeast spheroplasts, we have analyzed the effects of yeast VLPs on monocyte-derived dendritic cells (DCs). Yeast VLPs were efficiently incorporated into DCs via both macropinocytosis and endocytosis mediated by mannose-recognizing receptors, but not the mannose receptor. The uptake of yeast VLPs induced DC maturation and enhanced cytokine production, notably, interleukin-12 p70. We showed that yeast membrane components may contribute to DC maturation partly through Toll-like receptor 2 signaling. Thus, Gag particles encapsulated by yeast membrane may have an advantage in stimulating Gag-specific immune responses. We found that yeast VLPs, but not the control yeast membrane fraction, were able to activate both CD4 + and CD8 + T cells of HIV-infected individuals. We tested the effect of cross-presentation of VLP by DCs in two subjects recruited into a long-term nonprogressor-slow progressor cohort. When yeast VLP-loaded DCs of these patients were cocultured with peripheral blood mononuclear cells for 7 days, approximately one-third of the Gag-specific CD8 + T cells were activated and became perforin positive. However, some of the Gag-specific CD8 + T cells appeared to be lost during in vitro culture, especially in a patient with a high virus load. Our results suggest that DCs loaded with yeast VLPs can activate Gag-specific memory CD8 + T cells to become effector cells in chronically HIV-infected individuals, but there still remain unresponsive Gag-specific T-cell populations in these patients.

The aim of the present study was to ascertain the role of social support and individual styles of coping on employee well-being. The subjects were intermediate managers working for a zipper and sash manufacturing company in Japan. Measurements were made of the following: depression using the Self-rating Depression Scale (SDS), job demand, job control, social support using Karasek's Job Content Questionnaire, and of three coping styles: emotion-oriented coping, task-oriented coping and avoidance-oriented coping using the Coping Inventory for Stressful Situations (CISS). Data was analysed by structural equation modeling. Each coping style had a direct effect on depression. Emotion-oriented coping had a negative effect. On the other hand, task-oriented coping and avoidance-oriented coping had a positive effect. Moreover, there was an indirect effect that coping styles precede and determine the perception of social support as well as job demand and control. Social support showed a direct positive effect on depression. However, the overall impact on employee well-being was greater for individual coping styles as compared to social support from either supervisors or co-workers. The present study showed the effectiveness of coping strategies in the workplace. Copyright © 2003 John Wiley & Sons, Ltd.

Recent biochemical studies have identified high molecular complexes of the HIV Gag precursor in the cytosol of infected cells. Using immunoelectron microscopy we studied the time course of the synthesis and assembly of a HIV Gag precursor protein (pr55gag) in Sf9 cells infected with recombinant baculovirus expressing the HIV gag gene. We also immunolabeled for pr55gag human T4 cells acutely or chronically infected with HIV-1. In Sf9 cells, the time course study showed that the first Gag protein appeared in the cytoplasm at 28–30 h p.i. and that budding started 6–8 h later. Colloidal gold particles, used to visualize the Gag protein, were first scattered randomly throughout the cytoplasm, but soon clusters representing 100 to 1000 copies of pr55gag were also observed. By contrast, in cells with budding or released virus-like particles the cytoplasm was virtually free of gold particles while the released virus-like particles were heavily labeled. Statistical analysis showed that between 80 and 90% of the gold particles in the cytoplasm were seen as singles, as doublets, or in small groups of up to five particles probably representing small oligomers. Clusters of gold particles were also observed in acutely infected lymphocytes as well as in multinuclear cells of chronically infected cultures of T4 cells. In a few cases small aggregates of gold particles were found in the nuclei of T4 lymphocytes. These observations suggest that the Gag polyprotein forms small oligomers in the cytoplasm of expressing cells but that assembly into multimeric complexes takes place predominantly at the plasma membrane. Large accumulations of Gag protein in the cytoplasm may represent misfolded molecules destined for degradation.

HIV Gag assembly is the first and most essential step in the formation of virus particles. Following protein synthesis, Gag relocates from ribosomes and forms a virus particle at the plasma membrane, using host factors and machinery. Early studies focused on mapping the regions within Gag required for assembly and identified three distinct domains (M, I, and L), although their precise locations within the three-dimensional structure of Gag awaited later study. In this review, I summarize the mapping results in the light of recent progress on Gag structures made by nuclear magnetic resonance and X-ray crystallography as well as further functional analysis. These data are largely consistent and provide sufficient information for an understanding of the interactions and functions of the assembly domains at a macromolecular level. Current studies have moved on to the identification of the host factors and machinery used in the process of Gag assembly. Cumulative data suggest that the dynamics of Gag assembly and transport are achieved not by simply using, but rather by taking control of, cellular machinery. Key area in the process include interactions with TSG101, L domain receptor which normally functions in the endosomal sorting pathway and with lipid rafts, a type of M domain receptor, which has been suggested to be the sites for effective concentration of Gag. The review provides a summary of these data and discusses the likely direction of future studies.

Efficient transcription and replication of the influenza virus genome are dependent upon host-derived factors. Using an in vitro RNA synthesis system, we have purified and identified Hsp90 as one of the host factors that stimulate viral RNA polymerase activity. Hsp90 interacted with the PB2 subunit of the viral RNA polymerase through the amino-terminal chaperone domain and the middle region containing a highly acidic domain. The acidic middle region was also responsible for its stimulatory activity. We found that a portion of Hsp90 is re-localized to the cell nucleus after viral infection. A PB2 fragment containing a Hsp90 binding domain inhibited viral gene expression in a dominant-negative manner. These results suggest that Hsp90 is a host factor for the influenza virus RNA polymerase.

To investigate the association of calcium intake independently of other nutrients already known as predictors of hypertension, a cross-sectional study was carried out on the same population in Japan as used for the INTERSALT study. Dietary calcium intake was estimated from a 1-day 24-h recall. Sodium and potassium intakes were evaluated by 24-h urinary excretion. Data from 476 subjects aged 20-59 years, 230 men and 246 women, were analysed. The mean dietary calcium intake ranged from 557 to 608 mg/day among men, and from 528 to 639 mg/day among women. Among men, the pooled estimate of the regression coefficients of blood pressure (mm Hg) per 100 mg increase of calcium intake, adjusted for age and body mass index (BMI), were -0.42 mm Hg for systolic blood pressure (SBP) and -0.35 mm Hg for diastolic blood pressure (DBP), but there was no statistical significance. Among women, the pooled estimates of regression coefficients adjusted for age and BMI were -0.92 mm Hg for SBP and -0.83 mm Hg for DBP with statistical significance. After adjustment for age, BMI, alcohol intake and urinary excretion of sodium and potassium, the pooled estimate of calcium intake was -0.66 mm Hg for DBP with statistical significance and -0.70 mm Hg for SBP. A significant negative association of calcium intake with blood pressure was observed among the subjects in Osaka. Our study suggests that increased calcium intake may provide a benefit of lowering blood pressure independently of other minerals such as sodium and potassium.

The effects of dietary orotic acid on the metabolism of tryptophan to niacin in weaning rats was investigated. The rats were fed with a niacin-free, 20% casein diet containing 0% (control diet) or 1% orotic acid diet (test diet) for 29 d. Retardation of growth, development of fatty liver, and enlargement of liver were observed in the test group in comparison with the control group. The concentrations of NAD and NADP in liver significantly decreased, while these in blood did not decrease compared to the control group. The formation of the upper metabolites of tryptophan to niacin such as anthranilic acid, kynurenic acid, and 3-hydroxyanthranilic acid were not affected, but the quinolinic acid and beyond, such as nicotinamide, N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide, and N1-methyl-4-pyridone-3-carboxamide, were significantly reduced by the administration of orotic acid. Therefore, the conversion ratio of tryptophan to niacin significantly decreased in the test group in comparison with the control group.

Nationwide clinico-epidemiological surveys of cardiomyopathies in Japan were carried out. Disorders surveyed included idiopathic dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), arrhythmogenic right ventricular dysplasia (ARVD), mitochondrial disease, Fabry's disease of the heart and prolonged Q-T interval syndrome. The total number of patients was estimated at 17,700 for DCM, 21,900 for HCM, 300 for RCM, 520 for ARVD, 640 for mitochondrial disease, 150 for Fabry's disease of the heart, and 1,000 for prolonged Q-T interval syndrome. The prevalence of both DCM and HCM was higher in men than women: the male-to-female ratios were 2.6 and 2.3 for DCM and HCM, respectively. Detailed data on patients with DCM or HCM were collected by a follow-up survey. In 1 year more patients with DCM (5.6%) died than with HCM (2.8%): congestive heart failure (CHF) and arrhythmias were the leading causes of death for DCM and HCM, respectively. Angiotensin converting enzyme inhibitors (64.6%) and beta-adrenergic blockers (40.9%) are commonly used to treat the CHF complicating DCM and may be associated with the clinical improvement in a significant number of DCM patients. Thus, the nationwide surveys of Japanese patients have yielded important current epidemiological and clinical information on the characteristics of cardiomyopathies in Japan.

The aim of the present study was to evaluate the dose-effect relationship between urinary cadmium (U-Cd as an index of internal Cd exposure) and mortality in a cohort of the Japanese general population.A 19-year cohort study was conducted in 897 men and 1307 women who lived in two non-polluted areas in Japan. The subjects were categorized into four quartiles based on creatinine adjusted U-Cd (μg/g cre). Hazard ratio (HR) and 95% confidence interval (95%CI) of the quartiles of U-Cd for mortality was calculated using a proportional hazards regression. Forward stepwise model selection was applied to the potential covariates such as age, body mass index, mean arterial pressure, various lifestyle factors and present illness.The mortality rates per 1000 person years were 27.8 and 12.5 in men and women, respectively. In men, the fourth quartile of U-Cd (≥ 2.919 μg/g cre) showed a significant, positive HR (1.50, 95%CI: 1.11-2.02) for mortality compared to the first quartile (1.014). In women, the fourth quartile of U-Cd (≥ 3.943 μg/g cre) also showed a significant HR (1.50, 95%CI: 1.08-2.09) for mortality compared to the first quartile (1.140).The present study clarified that U-Cd was significantly associated with increased mortality, indicating the worsened life prognosis of the general population in Cd non-polluted areas in Japan. These results highlight the importance of further discussion of the health risk assessment of Cd exposure in the general population.

Background Previous studies have shown that a diet with a high-glycemic index is associated with good sleep quality. Therefore, we investigated the association of sleep quality with the intake of 3 common starchy foods with different glycemic indexes–rice, bread, and noodles–as well as the dietary glycemic index in a Japanese population. Methods The participants were 1,848 men and women between 20 and 60 years of age. Rice, bread, and noodle consumption was evaluated using a self-administered diet history questionnaire. Sleep quality was evaluated by using the Japanese version of the Pittsburgh Sleep Quality Index, and a global score >5.5 was considered to indicate poor sleep. Results Multivariate-adjusted odds ratios (95% confidence intervals) for poor sleep across the quintiles of rice consumption were 1.00 (reference), 0.68 (0.49–0.93), 0.61 (0.43–0.85), 0.59 (0.42–0.85), and 0.54 (0.37–0.81) (p for trend = 0.015); those for the quintiles of noodle consumption were 1.00 (reference), 1.25 (0.90–1.74), 1.05 (0.75–1.47), 1.31 (0.94–1.82), and 1.82 (1.31–2.51) (p for trend = 0.002). Bread intake was not associated with sleep quality. A higher dietary glycemic index was significantly associated with a lower risk of poor sleep (p for trend = 0.020). Conclusion A high dietary glycemic index and high rice consumption are significantly associated with good sleep in Japanese men and women, whereas bread intake is not associated with sleep quality and noodle consumption is associated with poor sleep. The different associations of these starchy foods with sleep quality might be attributable to the different glycemic index of each food.

The physiological significance of casein kinase II (CK-II) on the protease (PR) activity of recombinant HIV-1 PR (rPR) was biochemically investigated in vitro. We found that (i) the purified rPR (p11) functions as a phosphate acceptor of CK-II; (ii) the PR activity of rPR is stimulated approximately 2.9-fold after its full phosphorylation by recombinant human CK-II (rhCK-II) in a manner similar to that observed for recombinant HIV-1 reverse transcriptase (rRT); and (iii) this stimulation is completely inhibited by two polyphenol-containing anti-oxidant compounds [quercetin and epigallo-catechin gallate (EGCG)] at 0.1 microM or a glycyrrhetinic acid derivative (oGA) and catechin at 10 microM without significant effect on the PR activity of rPR. These results suggest that (i) CK-II may be a host mediator responsible for stimulation of PR and RT in HIV-1-infected cells; and (ii) the selective inhibition of the CK-II-mediated stimulation of HIV-1 PR and RT by potent CK-II inhibitors may be involved in their anti-HIV-1 effects at the cellular level.

Background and Purpose —Stroke mortality in Japan has significantly declined during recent decades. To determine the cause of this decrease, we studied the trends in stroke incidence and case fatality within 28 days after stroke in a rural area in Japan. Methods —We used a population-based registry during 1977–1991 in Oyabe, a rural area in the central part of Japan. The average population aged 25 years and older numbered 32 859 persons. Changes in age-standardized stroke incidence rate were calculated and compared between the 3 periods 1977–1981, 1982–1986, and 1987–1991. The 28-day case fatality rate was evaluated and also compared between the 3 periods by onset year. Results —The total number of strokes was 2068. The age-standardized incidence rate of all strokes decreased during the 15-year period, from 605 to 417 per 100 000 in men and from 476 to 329 per 100 000 in women. A marked decline was found during 1977–1986 but was not apparent during 1987–1991. Moreover, there was an increase in the group aged 75 years and older. The 28-day case fatality rates for all strokes improved from 18.0% to 14.2% in men and from 26.8% to 19.1% in women during the observation period. Conclusions —These data indicate that declines in the stroke incidence and the 28- day case fatality have been associated with a marked decrease in stroke-related mortality in Japan.

Human immunodeficiency virus type 1 Gag protein is cotranslationally myristoylated at the N terminus and targeted to the plasma membrane, where virus particle assembly occurs. Particle assembly requires the ordered multimerization of Gag proteins, yet there is little direct evidence of intermediates of the reaction or of the domains that lead to each stage of the oligomerization process. In this study, following the expression in insect cells of C-terminally truncated Gag proteins and their purification, both the multimeric nature of each Gag protein and the ability to form Gag virus-like particles (VLP) were analyzed. Our results show that (i) the matrix (MA) domain forms a trimer and contributes to a similar level of oligomerization of the assembly-competent Gag; (ii) the p2 domain, located at the capsid/nucleocapsid junction, is essential for a higher order of multimerization (>1,000 kDa); (iii) the latter multimerization is accompanied by a change in Gag assembly morphology from tubes to spheres and results in VLP production; and (iv) N-terminal myristoylation is not required for either of the multimerization stages but plays a key role in conversion of these multimers to Gag VLP. We suggest that the Gag trimer and the >1,000-kDa multimer are intermediates in the assembly reaction and form before Gag targeting to the plasma membrane. Our data identify a minimum of three stages for VLP development and suggest that each stage involves a separate domain, MA, p2, or N-terminal myristoylation, each of which contributes to HIV particle assembly.

Using the identical protocol of an Intersalt Study previously conducted, we undertook a new study (Intersalt-2) 8 years later. We measured changes in various factors affecting blood pressure (BP) including urinary sodium and potassium excretion in three districts of Japan: Osaka, Tochigi, and Toyama. Also we evaluated the trends in the relationships of those factors to BP. The Intersalt Study revealed that the average sodium excretion of all three study centres was high (particularly in Toyama) while potassium excretion was relatively low. The sodium/potassium ratio was therefore relatively high. The body mass index (BMI) was favourable, but the prevalence of heavy alcohol drinkers was high. Comparing the first to the second study reveals a decrease in sodium excretion in Toyama, although that area still had the highest value of the three study centres. The average potassium excretion increased only in Osaka. Sodium/potassium ratio decreased in all centres. BMI and the prevalence of heavy drinkers among the subjects of both studies were nearly the same. The trend of the relationship of sodium to BP in Osaka changed from negative to positive. In Toyama, it changed from positive to negative. It is thought that this negative relationship might occur in conjunction with a reduction in salt consumption in a population. In conclusion this study reveals that average sodium consumption in Japan remains high while potassium consumption is still low. As a factor in the prevention of hypertension, further efforts to reduce salt consumption and increase potassium intake are still needed.

Burnout and Related Factors among Hospital Nurses: Kazuyo HIGASHIGUCHI, et al. Department of Nursing, Kanazawa Medical University—The overall goal of this study is to examine the relationship between burnout in hospital nurses and three parameters: occupational factors, individual attributes, and workplace stressors. Two hundred and sixty-eight female nurses from two public general hospitals were surveyed. Three forms were used: first, a demographic data form to ascertain personal attributes; second, the Japanese version of the Maslach Burnout Inventory (MBI) to assess burnout; and third, the Japanese version of the Job Content Questionnaire (JCQ) to assess workplace stressors. The Japanese version of MBI consists of three subscales: Physical Exhaustion (PE), Emotional Exhaustion/ Depersonalization (EE+DP), and Personal Accomplishment (PA). The results were as follows: 1. There was a significant correlation between both PE and EE+DP and years of nursing experience, as well as the age of children. 2. There was a significant correlation between PE and the work schedule or workplace. 3. There was no significant correlation between the Japanese MBI subscales and job rank, marital status, or the number of children. 4. There was a significant correlation between the three subscales of Japanese MBI and the Japanese JCQ scales. These findings are discussed.

Retroviral Gag protein is sufficient to produce Gag virus-like particles when expressed in higher eukaryotic cells. Here we describe the in vitro assembly reaction of human immunodeficiency virus Gag protein, which consists of two sequential steps showing the optimal conditions for each reaction. Following expression and purification, Gag protein lacking only the C-terminal p6 domain was present as a monomer (50 kDa) by velocity sedimentation analysis. Initial assembly of the Gag protein to 60 S intermediates occurred by dialysis at 4 degrees C in low salt at neutral to alkaline pH. However, higher order of assembly required incubation at 37 degrees C and was facilitated by the addition of Mg(2+). Prolonged incubation under these conditions produced complete assembly (600 S), equivalent to Gag virus-like particles obtained from Gag-expressing cells. Neither form disassembled by treatment with nonionic detergent, suggesting that correct assembly might occur in vitro. Electron microscopic observation confirmed that the 600 S assembly products were spherical particles similar to authentic immature human immunodeficiency virus particles. The latter assembly stage but not the former was accelerated by the addition of RNA although not inhibited by RNaseA treatment. These results suggest that Gag protein alone assembles in vitro, but that additional RNA facilitates the assembly reaction.

Objectives This study investigated the possibility of a relationship between blood pressure level and rotating 3-shift work in a prospective follow-up of workers in a zipper and aluminum sash factory in Japan. Methods Altogether 1551 men aged 18-49 years were followed prospectively for 5 years, and the cumulative incidence of hypertension among 3-shift workers was compared with that of day workers. A multiple logistic analysis was used for adjusting for base-line characteristics such as age, body mass index, blood pressure, and drinking habit. Results In the younger age group, the relative risk of the rotating 3-shift workers during the observational period was increased compared with that of day workers after adjustment for the confounding factors. In the older group, the cumulative incidence of hypertension was not higher for workers who had continued shift work. However, a relatively high risk of hypertension was found for workers who converted from 3-shift work to day work when compared with those who remained on shift work and day work. Conclusion It is suggested that there is an association between 3-shift work and blood pressure.

In common with many aspects of the HIV life cycle, the assembly of the virus particle has been the subject of intense investigation over recent years. Study of the subject is facilitated by the fact that only a single gene product, the Pr55 Gag protein, is required for virus assembly. A combination of site directed mutagenesis, biochemical characterisation and structural studies have led to a picture of the overall architecture of the particle, the partial structure of Pr55, and the subdomains involved in oligomerisation. Copyright 1998 John Wiley & Sons, Ltd.

DNAJ/HSP40 is an evolutionarily conserved family of proteins bearing various functions. Historically, it has been emphasized that HSP40/DNAJ family proteins play a positive role in infection of various viruses. We identified DNAJ/HSP40B6 as a potential negative regulator of HIV-1 replication in our genetic screens. In this study, we investigated the functional interactions between HIV-1 and HSP40 family members.We took genetic and comparative virology approaches to expand the primary observation.Multiple HSP40/DNAJ proteins were tested for their ability to inhibit replication of adenovirus, herpes simplex virus type 1, HIV-1, and vaccinia virus. The mechanism of inhibition was investigated by using HSP40/DNAJ mutants and measuring the efficiencies of each viral replication steps.HSP40A1, B1, B6, and C5, but not C3, were found to be able to limit HIV-1 production. This effect was specific to HIV-1 for such effects were not detected in adenovirus, herpes simplex virus type 1, and vaccinia virus. Genetic analyses suggested that the conserved DNAJ domain was responsible for the inhibition of HIV-1 production through which HSP40 regulates HSP70 ATPase activity. Interestingly, HSP40s lowered the levels of steady-state viral messenger RNA. This was not attributed to the inhibition of Tat/long terminal repeat-driven transcription but the downregulation of Rev expression.This is the first report providing evidence that HSP70-HSP40 complex confers an innate resistance specific to HIV-1. For their interferon-inducible nature, HSP40 family members should account for the anti-HIV-1 function of interferon.

This study looked to identify determinants of exposure to dioxin in breast milk from breast-feeding women in a hot spot of dioxin exposure in Vietnam. Breast milk was collected from 140 mothers 1 month after delivery. The risk factors investigated included length of residency, drinking of well water and the frequency of animal food consumption. Cluster analysis was performed to identify dietary patterns of fish and meat portions, fish variety and egg variety. Residency, age and parity were clearly associated with increased dioxin levels. Drinking well water and the consumption of marine crab and shrimps were related to higher levels of furans in breast milk. The consumption of quail eggs also appeared to be associated with increased levels of some dioxin isomers in this area. Some mothers who ate no or less meat than fish and mothers who consumed more freshwater fish than marine fish had lower levels of dioxins in their breast milk. However, the type of water and the eating habits of mothers contributed only partly to the increased dioxin levels in their breast milk; the length of residency was the most important risk factor associated with increased dioxin body burdens of mothers.

The present cohort study investigated the relationship between participation in a secondary screening test for the frail elderly and the findings of this screening test, and the relationship between participation and new onset of the need for long-term care in the elderly.A primary screening survey was conducted on all 4,050 functionally independent elderly people agedor = 65 years living in Ishikawa Town, Japan. We included 3,150 subjects for analysis, dividing them into the following 3 groups: 1) non-frail elderly, 2) possible frail elderly who participated in the secondary screening test, and 3) possible frail elderly who did not participate in the secondary screening test. We used Cox's proportional hazards model to calculate the hazard ratios of new onset of the need for long-term care by the participating and non-participating groups as compared to the non-frail group over 2 years.The proportion of non-frail elderly and possible frail elderly was 72.7% (n=2,289) and 27.3% (n=861), respectively. The number of subjects who did not participate in the secondary screening test (n=582) were 2.1-fold greater than that of subjects who did (n=279). The prevalences of withdrawal and impaired instrumental activity of daily living were significantly higher in the non-participating group than in the participating group. During the 2-year follow-up period, 168 subjects developed the need for long-term care. The incidence of new onset of the need for long-term care for each group (/1,000 persons) was 24.0 in the non-frail group, 93.2 in the participating group, and 149.5 in the non-participating group. The hazard ratios of new onset of the need for long-term care were 2.55 (95% confidence interval, 1.59-4.10) for the participating group and 4.46 (3.15-6.32) for the non-participating group after adjustment for confounding factors, including sex, age, and type of household. The hazard ratios were 0.75 (0.41-1.37) for the participating group and 1.09 (0.65-1.82) for the non-participating group after additional adjustment for total points on the Kihon Checklist (a frailty checklist) for assessing the frail elderly.Compared to non-frail elderly, the possible frail elderly had an increased risk of developing the need for long-term care. Moreover, compared to the possible frail elderly who participated in the secondary screening test, the possible frail elderly who did not participate in the test had a further increased risk of developing the need for long-term care.

Given the lack of economic studies evaluating the outcomes of smoking cessation programs from the viewpoint of program sponsors, we conducted a case study to provide relevant information for worksites. The present study was carried out between 2006 and 2008 at a manufacturing factory in the Toyama Prefecture of Japan and included subjects who voluntarily entered a smoking cessation program. The program included face-to-face counselling followed by weekly contact to provide encouragement over six months using e-mail or inter-office mail. Nicotine patches were available if required. All 151 participants stopped smoking immediately. Over the 24-month study period, self-report showed 49.7% abstained continuously from smoking. The rate of 24-month consecutive abstinence was higher in participants with lower Fagerström Test scores for Nicotine Dependence at baseline than in those with higher scores (63.6% for 0-2 points vs. 46.5% for 3-6 points vs. 43.8% for 7-10 points; chi-square test p = 0.19). A logistic regression model showed a significant linear trend for the association between the score and abstinence status after adjustment for possible confounding factors (p = 0.03). The crude incremental cost for one individual to successfully quit smoking due to the support program was ¥46,379 (i.e., ¥100 = $1.28, £0.83, or €1.03 at foreign exchange rates). The corresponding costs for the three categories of the Fagerström Test score for Nicotine Dependence were ¥31,953, ¥47,450 and ¥64,956, respectively. When a sensitivity analysis was conducted based on the 95% confidence interval of the success rate, the variance in the corresponding costs was ¥25,514-45,034 for 0-2 points, ¥38,344-61,824 for 3-6 points, and ¥45,698-108,260 for 7-10 points. The degree of nicotine dependence may therefore be an important determinant of the cost-effectiveness of smoking cessation programs.

Myristoylation of human immunodeficiency virus (HIV) Gag protein is essential for virus particle budding. Two reactions are involved; activation of free myristate to myristoyl-CoA and transfer of the myristoyl residue to the Gag N-terminal glycine. We have investigated the effects of triacsin C, an inhibitor of long chain acyl-CoA synthetase, on release of HIV Gag virus-like particle (VLP) produced using the recombinant baculovirus system. First, inhibition of acyl-CoA formation by triacsin C was confirmed using the membrane fractions of insect Sf9 cells as an enzyme source. Second, when HIV Gag protein was expressed in the presence of triacsin C (0-48 microM), Gag myristoylation was inhibited in a dose-dependent manner. Budding of Gag VLP, however, did not follow similar inhibition kinetics but appeared unaffected up to 24 microM, yet was completely abolished at 48 microM when the myristoylation of Gag protein was also completely inhibited. The "all-or-none" inhibition of Gag VLP budding suggests that although inhibition of acyl-CoA synthetase blocks the production of myristoylated Gag protein, only complete inhibition of Gag myristoylation prevents VLP budding. Thus, relatively few myristoylated Gag molecules are sufficient for plasma membrane targeting and VLP budding.

Purpose: This cohort study investigated the association between sugar-sweetened beverage (SSB) and diet soda consumption and the incidence of type 2 diabetes in Japanese men. Methods: The participants were 2,037 employees of a factory in Japan. We measured consumption of SSB and diet soda using a self-administered diet history questionnaire. The incidence of diabetes was determined in annual medical examinations over a 7-year period. Hazard ratios (HRs) with 95% confidence intervals (CIs) for diabetes were estimated after adjusting for age, body mass index, family history, and dietary and other lifestyle factors. Results: During the study, 170 participants developed diabetes. The crude incidence rates (/1,000 person-years) across participants who were rare/never SSB consumers

The aim of this cross-sectional study was to examine whether occupational class inequalities existed in the behavioral and biological risk factors for cardiovascular disease among workers in medium- and small-scale enterprises. We asked 1,900 enterprises in the Ishikawa prefecture who were users of an external heath check-up facility to supply anonymous individual data in 2009. The 446 enterprises consented to the invitation. The study population was 12,625 individuals (8,104 males and 4,521 females) 16-59 yr of age. We compared indices among occupational classes. The indices of lipid and glucose metabolism were used only for subjects 40-59 yr of age. The results of this study revealed occupational class inequalities in the prevalence of current smoking, heavy drinking and hypertension in men. These inequalities were more prominent among men in the younger age group than in the older age group. In men, the most disadvantaged occupational class was transportation workers, followed by laborers. Occupational class inequalities in smoking were also found among female workers. However, the influences of occupational class on obesity and indices of lipid or glucose metabolism were inconsistent. A strategy for health promotion that targets the disadvantaged population is necessary for the prevention of cardiovascular disease.

We report single-point mutations that are located in the matrix protein domain of the gag gene of human immunodeficiency virus type 1 and that prevent Gag particle formation. We show that mutations of p17 that abolish human immunodeficiency virus particle assembly also prevent the dimerization of p17 protein, as measured directly by a protein-protein binding assay. In the three-dimensional structure of p17, mutations that abolish dimerization are located in a single alpha helix that forms part of a fingerlike projection from one side of the molecule. Peptides derived from this region of p17 also reduce the level of p17 dimer when they are added to p17-expressing cells and compete for p17 self-association when present in protein-protein binding assays. We propose that the dimerization of the Gag precursor that occurs by the interdigitation of alpha helices on adjacent matrix molecules is a key stage in virion assembly and that the prevention of such an interaction is the molecular basis of particle misassembly.

Aims/Introduction: This cohort study of middle-aged Japanese participants investigated the relationship between family history of diabetes, the incident risk of type 2 diabetes and the interaction of these variables with other factors. Materials and Methods: Study participants were 3,517 employees (2,037 men and 1,480 women) of a metal products factory in Japan. Baseline health examinations included questions about medical history, physical examination, anthropometric measurements, questions about lifestyle factors, such as smoking, alcohol consumption and habitual exercise, and a self-administered diet history questionnaire. Family history of diabetes was defined as having at least one-first-degree relative with diabetes. The incidence of diabetes was determined in annual medical examinations over a 7-year period. Hazard ratios (HRs) for type 2 diabetes were estimated by Cox proportional hazards analysis. Results: Of the 3,517 participants, 630 (18%) had a family history of diabetes mellitus. During the study, 228 participants developed diabetes. The age and sex-adjusted HR for type 2 diabetes in participants with a family history of diabetes was 1.82 (95% confidence interval 1.36-2.43) as compared with those without a family history of diabetes. HRs did not change after adjustment for body mass index and lifestyle factors. We found no interactions with body mass index, insulin resistance, pancreatic β-cell function or lifestyle factors. Conclusions: Family history of diabetes was associated with the incident risk of diabetes, and these associations were independent of other risk factors, such as obesity, insulin resistance, and lifestyle factors in Japanese men and women. © 2013 Asian Association for the Study of Diabetes and Wiley Publishing Asia Pty Ltd.

We conducted a longitudinal study to investigate whether increased serum gamma-glutamyltransferase independently predicts subsequent development of hyperuricemia. The study participants included 3 310 Japanese men without hyperuricemia, aged 20–54 years. The participants had annual heath examinations for 6 years to assess incident hyperuricemia (defined as serum uric acid>416.4 μmol/l and/or taking medication for hyperuricemia). The risk of incident hyperuricemia was compared in participants grouped according to their baseline serum gamma-glutamyltransferase level. During follow-up, there were 529 incident cases of hyperuricemia. A positive, dose-response relationship was observed between serum gamma-glutamyltransferase and the risk of incident hyperuricemia. The hazard ratios (95% confidence intervals) for hyperuricemia, compared with a serum gamma-glutamyltransferase level≤19 U/l, were 1.32 (1.05–1.67) for 20–39 U/l, 1.28 (0.90–1.83) for 40–59 U/l, 1.56 (0.98–2.47) for 60–79 U/l, and 1.57 (1.02–2.41) for ≥80 U/l after adjustment for baseline serum uric acid, creatinine, total cholesterol, and glycated hemoglobin levels, ln(serum alanine aminotransferase), age, systolic blood pressure, medications for hypertension, hypercholesterolemia, and diabetes, body mass index, and smoking and exercise habits. A similar positive relationship was observed regardless of the presence or absence of alcohol drinking, obesity, metabolic disorders (any combination of hypertension, hypercholesterolemia and/or diabetes), or clinically high serum aminotransferases, without evidence of a significant interaction between increased serum gamma-glutamyltransferase and risk factors for incident hyperuricemia. These findings indicate that increased serum gamma-glutamyltransferase is an independent predictor of subsequent development of hyperuricemia.

BACKGROUND Epidemiological studies have observed conflicting patterns as to whether overtime work increases blood pressure (BP), probably as a consequence of methodological issues. METHODS We conducted a prospective cohort study to investigate the relationship between overtime work hours and 1-year changes in BP in 1,235 normotensive Japanese male workers who carried out a variety of jobs in a manufacturing factory. Casual BP measurements were repeated at annual health examinations in 2004-2005, using an automatic manometer. An analysis of covariance that incorporated potential confounding factors including baseline age, body mass index (BMI), and lifestyle factors was used to calculate and compare the means of the 1-year change in systolic (SBP) and diastolic BP (DBP). The participants were grouped according to their average monthly overtime work hours obtained from timecard data between April and September 2004. RESULTS The multivariate-adjusted mean for 1-year change in DBP in 611 male assembly-line workers was 1.5 mm Hg (95% confidence interval (CI) 0.8-2.2) for

Several studies have suggested that the exposure to cadmium (Cd) increased mortalities from renal diseases, cardiovascular diseases and malignant neoplasm, including lung cancer and prostate cancer among inhabitants living in Cd-polluted areas and factory workers. This study aimed to assess the influence of environmental exposure to Cd on long term outcome of inhabitants living in an area polluted by Cd.A 22-year follow-up study was conducted with 3119 inhabitants (1403 men and 1716 women) living in the Cd polluted Kakehashi River basin in Japan. The subjects were divided into 4 groups according to the amount of urinary Cd level (3.0 µg/g creatinine (Cr), 3.0 - 4.9 µg/g Cr, 5.0 - 9.9 µg/g Cr, and ≥ 10.0 µg/g Cr). Mortality was calculated by the person-years method. Hazards ratios (HR) and 95% confidence intervals (CI) were assessed by the Cox's proportional hazard model.Compared with urinary Cd3.0 µg/g Cr group, the HR of 5.0 - 9.9 µg/g Cr and ≥ 10.0 µg/g Cr groups were significantly increased after adjustment for age in both sexes: 1.24 (95%CI 1.01 - 1.51) and 1.48 (95%CI 1.17 - 1.90) for men; 1.64 (95%CI 1.17 - 2.28) and 1.78 (95%CI 1.27 - 2.50) for women. The most frequent cause of death was malignant neoplasm in men and cardiovascular diseases in women. The significant increase in mortality risk for cardiovascular diseases was observed in the subjects with ≥ 10 µg/g Cr in both sexes: 1.79 for men (95%CI 1.02 - 3.12) and 2.38 for women (95%CI 1.11 - 5.07). When the subjects were divided into 2 categories (20 µg/g Cr and ≥ 20 µg/g Cr), the HR of the urinary Cd ≥ 20 µg/g Cr group for nephritis and nephrosis were 4.82 (95%CI 1.07 - 21.61) in men and 7.92 (95%CI 1.77 - 35.33) in women, respectively. The significant increase was not observed for malignant neoplasm.These results suggest a dose-response relationship between Cd body burden and mortality for cardiovascular diseases, cerebrovascular diseases and nephritis and nephrosis.

On the basis of the 1990 Chinese death notice data and 1990 Japanese populations vital statistical materials, the mortality patterns and proportions of individual causes of death in the two countries were compared. In both sexes, the mortality rates were the highest in almost all age groups in Chinese rural areas followed by urban areas and Japan. In Japan and in Chinese urban areas, malignant neoplasms cardiovascular diseases and cerebrovascular diseases were the major causes of death, with these three making up about 60% of the total. In Chinese rural areas, these three conditions were responsible for 43% of all deaths, a considerably lower figure as compared to those in the other two areas, and the mortality rates for infectious diseases and accident/suicide were higher than those in the other two areas. Of the three major adult diseases, cerebrovascular diseases were found to be especially frequent in both Chinese urban and rural areas. On the other hand, ischemic heart disease was found at comparable levels in Japan and China and the rate was lower than in other developed countries. Site-specific mortality rates for malignant neoplasms were characterized by high rates for lung, liver and esophageal cancers in China. The mortality rates for bronchitis in both Chinese urban and rural areas were markedly higher than those in Japan These differences in mortality rates and proportions of individual causes of death between China and Japan are thought to be attributable to the differences in medical services and the level of risk factors for each disease.

The global spread of highly pathogenic avian influenza A H5N1 viruses raises concerns about more widespread infection in the human population. Pre-pandemic vaccine for H5N1 clade 1 influenza viruses has been produced from the A/Viet Nam/1194/2004 strain (VN1194), but recent prevalent avian H5N1 viruses have been categorized into the clade 2 strains, which are antigenically distinct from the pre-pandemic vaccine. To understand the antigenicity of H5N1 hemagglutinin (HA), we produced a neutralizing monoclonal antibody (mAb12-1G6) using the pre-pandemic vaccine. Analysis with chimeric and point mutant HAs revealed that mAb12-1G6 bound to the loop (amino acid positions 140-145) corresponding to an antigenic site A in the H3 HA. mAb12-1G6 failed to bind to the mutant VN1194 HA when only 3 residues were substituted with the corresponding residues of the clade 2.1.3.2 A/Indonesia/5/05 strain (amino acid substitutions at positions Q142L, K144S, and S145P), suggesting that these amino acids are critical for binding of mAb12-1G6. Escape mutants of VN1194 selected with mAb12-1G6 carried a S145P mutation. Interestingly, mAb12-1G6 cross-neutralized clade 1 and clade 2.2.1 but not clade 2.1.3.2 or clade 2.3.4 of the H5N1 virus. We discuss the cross-reactivity, based on the amino acid sequence of the epitope.

Background RD-114 virus is a feline endogenous retrovirus and produced as infectious viruses in some feline cell lines. Recently, we reported the contamination of an infectious RD-114 virus in a proportion of live attenuated vaccines for dogs and cats. It is very difficult to completely knock out the RD-114 proviruses from cells, as endogenous retroviruses are usually integrated multiply into the host genome. However, it may be possible to reduce the risk of contamination of RD-114 virus by regulating the viral release from cells. Results In this study, to understand the molecular mechanism of RD-114 virus budding, we attempted to identify the viral and cellular requirements for RD-114 virus budding. Analyses of RD-114 L-domain mutants showed that the PPPY sequence in the pp15 region of Gag plays a critical role in RD-114 virus release as viral L-domain. Furthermore, we investigated the cellular factors required for RD-114 virus budding. We demonstrated that RD-114 virus release was inhibited by overexpression of dominant negative mutants of Vps4A, Vps4B, and WWP2. Conclusions These results strongly suggest that RD-114 budding utilizes the cellular multivesicular body sorting pathway similar to many other retroviruses.

Objectives: We investigated the effects of fatigue on NK cell function and lymphocyte subpopulations in nurses performing shift work using a longitudinal design. Methods: Fifty-seven female nurses engaged in shift work at a hospital in Japan were selected for our study cohort. The hospital used a counterclockwise rotating three-shift system. Night shifts followed day shifts after a seven-hour interval. Immune parameters measured at the beginning of the day shift through to the end of the night shift were compared between two groups stratified by their level of fatigue. Statistical differences were evaluated after adjusting for baseline immune values and other demographic features. Results: Subjective feelings of fatigue increased progressively from the beginning of day shifts to the end of night shifts. From the beginning of day shifts to the end of night shifts, NK cell activity and CD16+CD56+ lymphocytes decreased, while CD3+ and CD4+ lymphocytes increased. The group with the greater increase in fatigue showed a larger decrease in NK cell activity and a larger increase in CD4+lymphocytes when compared with the group reporting less fatigue. These findings did not change after adjusting for demographic factors and sleep hours. Conclusion: Our data suggest that shift work has deleterious effects on NK cell function and that the effects depend on the degree of fatigue. Proper management of shift work may lessen fatigue in workers and also ameliorate many health problems experienced by shift workers.