Toshio Nakadate

Change in obstructive pulmonary function as a result of cumulative exposure to welding fumes as determined by magnetopneumography in Japanese arc welders.

OBJECTIVES: To examine the effect of chronic exposure to welding fumes on pulmonary function by a direct estimate of fumes accumulated in the lungs. METHODS: The strength of the residual magnetic field of externally magnetised lungs (LMF) was used as an estimate of fumes accumulated in the lungs. The results of forced spirometry manoeuvres obtained in 143 of 153 male welders in the original sample were cross sectionally evaluated according to LMF. Seven conventional forced spirogram indices and two time domain spirogram indices were used as pulmonary function indices, and height squared proportional correction was performed when necessary. RESULTS: The distribution of LMF values was considerably skewed towards positive. There was a weak but significant positive relation between age and log transformed LMF. Obstructive pulmonary function indices correlated well with LMF. After adjustment for age and smoking, however, a significant association with LMF was only found with percentage rate of forced expiratory volume in one second (FEV1%) divided by forced vital capacity (FVC) and mu, and average component of assumed time constant distribution of lung peripheral units. Neither FVC nor vital capacity (VC), as indices of restrictive disorders, showed a significant association with LMF. Based on the results of multiple regression analyses, a 0.6% decrease in FEV1% and 0.039 unit increase in mu were expected for each doubling of LMF. CONCLUSION: Obstructive changes in pulmonary function were found to be related to level of cumulative exposure to welding fume in male Japanese arc welders after controlling for age and smoking, assuming that LMF adequately reflects accumulation of welding fumes in the lungs.

A cross sectional study of the respiratory health of workers handling printing toner dust.

Background: Although recent case reports have suggested possible respiratory effects of solid toner dust inhalation, this hypothesis has not been verified by epidemiological studies. Objectives: To conduct a cross sectional study to evaluate the association between the biological indices of lung fibrosis and toner dust exposure in an occupational cohort handling solid toner dust in their work life. Methods: A total of 600 male toner workers and 212 control subjects were surveyed in terms of their subjective respiratory symptoms, pulmonary functions, and chest radiographic findings. In addition to the exposure history, the current working conditions and personal exposure levels to toner dust were also examined. Results: Although subjects handling toner for more than 20 years tended to show a higher prevalence of respiratory symptoms and minimal chest x ray abnormalities, there was no consistent relation between the exposure to toner dust and the biological responses of the respiratory system. Conclusion: Deterioration of respiratory health related to toner dust exposure is less likely to occur in current well controlled work environments, especially if the powdered toner is handled carefully. Nonetheless, it is important to collect further epidemiological evidence on the biological effects of toner dust inhalation, preferably using a longitudinal study design.

Four-year follow-up of effects of toluene diisocyanate exposure on the respiratory system in polyurethane foam manufacturing workers. II. Four-year changes in the effects on the respiratory system.

SummaryFifty-seven polyurethane foam manufacturing workers (PF workers) and 24 reference workers were followed for 4 years to clarify the effects on pulmonary function of working in PF factories with exposure to toluene diisocyanate (TDI). No significant differences in the average annual losses (AALs) of pulmonary function for 4 years were observed among the 28PF workers whose TDI exposure levels were very low (mean= 0.1 ppb, group L), the remaining 29 PF workers with mean TDI exposure of 5.7 ppb (group H), and the reference workers. However, 15 PF workers in group H who had experienced peak exposure excursions to 30 ppb or above with a mean concentration of 8.2 ppb showed significantly larger AALs in percentage maximal mid-expiratory flow, forced expiratory volume in 1 s ratio to vital capacity (FVC), and forced expiratory flow at 25% of FVC than expected, and significantly larger AALs in some obstructive pulmonary function indices than those of the 14 remaining PF workers in group H whose peak exposure excursion levels were 3-14 ppb with a mean time-weighted average (TWA) of 1.7 ppb, group L, and the reference workers. These findings suggest that the peak exposure excursion level of TDI might be important in inducing obstructive pulmonary function changes in the PF workers rather than the TWA exposure levels, though further comparative studies of the AAL in those who are exposed to different peak exposure excursion levels but the same mean exposure levels are necessary. From the standpoint of prevention, the proposition that peak exposure excursion levels exceeding 20 ppb should be avoided is reasonable.

Association between traffic-related air pollution and development of asthma in school children: Cohort study in Japan

Air pollution is widely understood to be capable of exacerbating asthma symptoms. Here we examined the association between traffic-related air pollution and development of asthma in school children. Subjects were 10,069 school children in their first through third years of compulsory education (6–9-year old). The main outcome was incidence of asthma as determined from the questionnaire. Follow-up surveys were conducted every year up to 4 years after the end of the study. To evaluate individual level of exposure to traffic-related air pollution, we used a simulation model that accounted for exposure level both at home and at school. As surrogates of traffic-related air pollution, the estimation target was the annual average individual exposure of automobile exhaust-originating nitrogen oxides (NOx) and elemental carbon (EC). Confounding factors were adjusted using a discrete-time logistic regression model. We found a positive association between exposure to EC and incidence of asthma. The odds ratio (OR) (95% confidence interval) for asthma incidence was 1.07 (1.01–1.14) for each 0.1 μg/m3 EC and 1.01 (0.99–1.03) for each 1 p.p.b. NOx. Traffic-related air pollution is associated with development of asthma in school children.

Survival Prognosis of Japanese With Severe Motor and Intellectual Disabilities Living in Public and Private Institutions Between 1961 and 2003

Background Although the prognosis for survival in people with severe functional disabilities is a serious concern for their families and health care practitioners, there have been few reports on survival rates for this population. Every year, the Japanese Association of Welfare for Persons with Severe Motor and Intellectual Disability collects anonymous records of individual registrations and deaths from all private and public institutions, excepting national institutions. We used these data to estimate the prognosis for survival. Methods We reviewed the records of 3221 people with severe motor and intellectual disabilities (SMID); all subjects had lived in one of 119 public or private institutions in Japan between 1961 and 2003. Kaplan–Meier survival estimates were calculated according to disability type and birth year range. Results Of the 3221 persons, 2645 were alive and 576 had died. The survival rate at the age of 20 for all subjects was 79% (95% confidence interval, 78%–81%). Among people who were unable to sit, those with lower intelligence quotients had lower survival rates. Conclusions The survival rate among people with SMID housed in public and private institutions in Japan was much worse than that of the general population, and has not improved since the 1960s.

Four-year follow-up of effects of toluene diisocyanate exposure on the respiratory system in polyurethane foam manufacturing workers. I. Study design and results of the first cross-sectional observation.

SummaryA 4-year cohort study was designed to assess the exposure-effect relationship of working in polyurethane foam (PF) manufacturing factories with exposure to toluene diisocyanate (TDI) and its effects on the respiratory system. This paper describes the results of the first cross-sectional observations. The study population included 90 male workers who had been working in PF factories for 0.5–25 years (mean 13.3 years) (PF workers) and 44 reference workers in the same factories. The mean exposure concentration of TDI calculated from 129 personal samples was 3.2 ppb. Peak exposure excursions above 20 ppb occurred in 16 of 129 samples. Pulmonary function and its change during the working day as assessed by examining the forced expiratory flow-volume curve, respiratory impedance, and airway resistance and specific airway conductance were not different in the PF workers from those in the reference workers. Chest X-radiographs did not show any noteworthy radiological changes. Prevalences of “phlegm in winter,” “nasal stuffiness or discharge in winter,” and “irritation of eye and throat mucous membranes” were significantly higher in the PF workers. The findings indicate that TDI exposure at levels around 3 ppb may not adversely affect the pulmonary function over many years of exposure of those who are not hypersensitive to TDI. The causal chemicals inducing some respiratory and irritative symptoms could not be specifically identified since the PF workers were exposed not only to TDI but also to other irritative agents in the PF manufacturing processes.

Associations between hazard indices of di-n-butylphthalateand di-2-ethylhexylphthalate exposure and serum reproductive hormone levels among occupationally exposed and unexposed Chinese men

The knowledge on the dose-response relationships between cumulative phthalate exposure and reproductive hormones in human are lacking. To assess the characteristics of the associations between hazard index (HI) of cumulative di-n-butylphthalate (DBP) and di-2-ethylhexylphthalate (DEHP) exposures and serum concentrations of free testosterone (fT), estradiol, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), we used restricted cubic spline function to characterize the dose-response curves between the HI values and reproductive hormones for 74 male workers occupationally exposed to high levels of DBP and DEHP, and 63 male construction workers as comparison group matched for age and smoking status. The median of HI value was 5.30 for exposed workers, 53.0-fold that of unexposed workers (0.10). 89.2% of exposed workers and 1.6% of unexposed workers have HI over 1.00. We observed a borderline significantly negative association between HI and fT in exposed workers (r=-0.195, p=0.096), but not in unexposed workers. The exposed workers showed inverted long-tailed J-shaped fT and FSH curves, and small changes in the LH curve, whereas unexposed workers had inverted and flattened-S-shaped fT and mirror-S-shaped LH and FSH curves. Both T production and hypothalamo-pituitary-testis (HPT) axis function were damaged in workers with high HI of phthalate exposures. HPT feedback function was activated in workers with both high and low HI, and plays an important role in preventing fT level from further decreasing with a rise in HI.

Involvement of annexin A8 in the properties of pancreatic cancer.

Although Annexin A8 (ANXA8), a member of a superfamily of calcium and phospholipid binding proteins, is physiologically expressed in a tissue‐specific manner, recent microarray studies reported that ANXA8 was also ectopically expressed in pancreatic cancers. We investigated the molecular mechanism of expression of ANXA8 in cancer cells and its functional role in pancreatic cancer cells. ANXA8 was diversely expressed in human cancer cell lines. Expression was enhanced by treatment with 5‐aza‐dC and butyrate, and correlated with methylation status at CpG in the promoter‐exon 1 region. Inhibition of ANXA8 using siRNA in BxPC‐3 cells which express ANXA8 at a high level elevated caspase‐3 and ‐7 activities. In in vitro invasion assay, inhibition of ANXA8 using siRNA in BxPC‐3 reduced the numbers of migrating cells, and down‐regulated HIF‐1α mRNA transcription. Overexpression of ANXA8 increased the number of viable cells and BrdU incorporation in PANC‐1 cells, which express ANXA8 at a low level. Expression of ANXA8 was induced under conditions of nutrient deprivation, and overexpression of ANXA8 showed resistance against serum starvation in PANC‐1 cells. In a promoter assay, co‐transfection with the expression vector of ANXA8 and the vector of a reporter gene containing the promoter of HIF‐1α enhanced HIF‐1α promoter activity. In contrast, this effect of ANXA8 was inhibited by administration of BAPTA‐AM, an intracellular Ca2+ chelator. These results suggest that ectopic ANXA8 expression in cancer cells might involve an epigenetic mechanism. ANXA8 might play an important role in calcium fluctuation‐mediated HIF‐1α transcriptional activation and cell viability.

Passive smoking is associated with lower serum HDL-C levels in school children.

Background:  In recent years, a number of studies have reported that exposure to environmental tobacco smoke (ETS) reduces high‐density lipoprotein cholesterol (HDL‐C) levels in children, as well as in adults. Further, a number of countries have indicated that passive smoking increases the risk of early arteriosclerosis onset. Here, to evaluate the effects of ETS exposure, we conducted a cross‐sectional epidemiological study on primary school children in Japan using answers from a questionnaire survey, as well as urine cotinine and lipid metabolism‐related variable measurements.

Three Occupationally Exposed Cases of Severe Methyl Bromide Poisoning : Accident Caused by a Gas Leak during the Fumigation of a Folklore Museum

Methyl bromide (CH 3 Br) is widely used as a plant quarantine fumigant and as a soil fumigant, but in 1992 it was designated by the Montreal Protocol on Substances that Deplete the Ozone Layer. According to the Montreal Protocol, its use is to be fully phased out by 2005 in developed countries and by 2015 in developing countries. However, its use is still currently being allowed after abolishment for such purposes as quarantine processing, shipping pretreatment, some essential uses, and emergency processing since an alternative substitute that is as easy to use as methyl bromide, has an equivalent effect, and is effective against a variety of pests, does not exist. For this reason, it continues to be used in Japan. It is still frequently used, and poisoning accidents caused by its use are still common. We herein report three cases of severe methyl bromide poisoning thought to have been caused by the presence of the victims in an adjoining room during the fumigation of a folklore museum.