[The history of compensation system for workers with pneumoconiosis-related lung cancer].

OBJECTIVE: To review the historical aspects of compensation system for workers with pneumoconiosis who developed lung cancer. METHODS: Materials and papers published on the compensation system as discussed in administrative meetings were utilized. RESULTS: Legal claims for compensation for lung cancer among individuals with pneumoconiosis increased during the period of rapid economic growth in Japan. A possible causal relationship between pneumoconiosis and lung cancer in workers has been discussed by committees of specialists. The Expert Committee on Pneumoconiosis and Lung Cancer in 1978 did not find a causal relationship between them. However, a survey of physicians specializing in pneumoconiosis revealed medical disadvantages among individuals diagnosed with pneumoconiosis who developed lung cancer. The Ministry of Labour announced the risk of work-related lung cancer in patients with advanced pneumoconiosis (class IV or equivalent severity). Since then, numerous lung cancer patients with pneumoconiosis have been adjudicated. In 1997, the International Agency for Research on Cancer (IARC) re-evaluated the carcinogenicity of silica and declared it to be a Group I carcinogen in humans. The Expert Committee on Compensation of Lung Cancer Cases Developing from Pneumoconiosis discussed the IARC evaluation but did not accept this classification. However, the Committee of Occupational Exposure Limits in the Japan Society of Occupational Health upheld the IARC evaluation of silica as a Group I carcinogen. Because the Expert Committee of Medical Disadvantage of Lung Cancer Patients with Pneumoconiosis accepted the increased risk of lung cancer in patients with class III or equivalent severity pneumoconiosis, the Ministry of Labour announced worker compensation for such patients. The Expert Committee of Health Control of Pneumoconiosis Complicated with Lung Cancer reported in 2002 that a meta-analysis revealed no increased risk of lung cancer among workers exposed to crystalline silica; however, there was an increased risk of lung cancer in patients with pneumoconiosis. The Ministry of Labour has added lung cancer to the list of complications from pneumoconiosis and, if necessary, regular medical checkups for lung cancer. After Leaving dust work, the Health Care System provides for workers who are diagnosed With class II or higher pneumoconiosis. Therefore, if an individual with pneumoconiosis develops class II or higher lung cancer, that individual becomes eligible for workers' compensation. CONCLUSIONS: The conclusion of the Expert Committee in 2002 and the decision of the Ministry of Labour to add lung cancer to its list of complications of pneumoconiosis are evaluated to be appropriate.

IL-6-Mediated Upregulated miRNAs in Extracellular Vesicles Derived from Lund Human Mesencephalic (LUHMES) Cells: Effects on Astrocytes and Microglia.

Psychological stress plays a major role in depression, and interleukin-6 (IL-6) is elevated during depression and psychological stress. MicroRNAs (miRNAs) in extracellular vesicles (EVs), including exosomes and microvesicles, suppress mRNA expression in other cells when endocytosed. In this study, we analyzed the effect of IL-6 on EVs secreted by neural precursor cells. Cells from the human immortalized neural precursor cell line LUHMES were treated with IL-6. EVs were collected using a nanofiltration method. We then analyzed the uptake of LUHMES-derived EVs by astrocytes (ACs) and microglia (MG). Microarray analysis of miRNAs was performed using EV-incorporated RNA and intracellular RNA from ACs and MG to search for increased numbers of miRNAs. We applied the miRNAs to ACs and MG, and examined the cells for suppressed mRNAs. IL-6 increased several miRNAs in the EVs. Three of these miRNAs were originally low in ACs and MG (hsa-miR-135a-3p, hsa-miR-6790-3p, and hsa-miR-11399). In ACs and MG, hsa-miR-6790-3p and hsa-miR-11399 suppressed four mRNAs involved in nerve regeneration (NREP, KCTD12, LLPH, and CTNND1). IL-6 altered the types of miRNAs in EVs derived from neural precursor cells, by which mRNAs involved in nerve regeneration were decreased in ACs and MG. These findings provide new insights into the involvement of IL-6 in stress and depression.

Estimation of the global burden of mesothelioma deaths from incomplete national mortality data.

BACKGROUND: Mesothelioma is increasingly recognised as a global health issue and the assessment of its global burden is warranted. OBJECTIVES: To descriptively analyse national mortality data and to use reported and estimated data to calculate the global burden of mesothelioma deaths. METHODS: For the study period of 1994 to 2014, we grouped 230 countries into 59 countries with quality mesothelioma mortality data suitable to be used for reference rates, 45 countries with poor quality data and 126 countries with no data, based on the availability of data in the WHO Mortality Database. To estimate global deaths, we extrapolated the gender-specific and age-specific mortality rates of the countries with quality data to all other countries. RESULTS: The global numbers and rates of mesothelioma deaths have increased over time. The 59 countries with quality data recorded 15 011 mesothelioma deaths per year over the 3 most recent years with available data (equivalent to 9.9 deaths per million per year). From these reference data, we extrapolated the global mesothelioma deaths to be 38 400 per year, based on extrapolations for asbestos use. CONCLUSIONS: Although the validity of our extrapolation method depends on the adequate identification of quality mesothelioma data and appropriate adjustment for other variables, our estimates can be updated, refined and verified because they are based on commonly accessible data and are derived using a straightforward algorithm. Our estimates are within the range of previously reported values but higher than the most recently reported values.

The combination of strong immunohistochemical mtTFA expression and a high survivin index predicts a shorter disease-specific survival in pancreatic ductal adenocarcinoma.

Mitochondrial transcription factor A (mtTFA) plays a crucial role in both the transcription and maintenance of mitochondrial DNA. A high expression of mtTFA has been demonstrated in several solid tumors, and is closely associated with cancer cell survival/apoptosis and growth. However, its expression pattern in pancreatic ductal adenocarcinoma (PAC) remains to be elucidated. Additionally, our groups have recently revealed that a subset of apoptosis-related genes is strongly regulated by mtTFA, and that two putative mtTFA binding sites are present in the promoter region of the survivin gene, which is a member of the inhibitor-of-apoptosis protein family. We therefore investigated the correlation of the immunohistochemical mtTFA expression and the survivin index with various clinicopathological variables and the prognosis, using 70 paraffin-embedded tumor samples from patients with surgically-resected PAC. The mtTFA expression or survivin index was considered to be strong or high when ≥30% or 10% of the PAC cells showed positive staining, respectively. Strong mtTFA expression and/or a high survivin index was revealed to have a significant relationship to a pathologically high tumor grading and advanced tumor stage. Moreover, mtTFA showed significantly high co-expression with survivin. Univariate and multivariate analyses demonstrated that both the strong mtTFA expression and high survivin index groups had significantly shorter survival rates, especially within the first two years postoperatively. The combination of strong mtTFA expression and a high survivin index may predict a poor prognosis in patients with PAC, and these new biomarkers might offer useful information for the early clinical management.

The combination of a nuclear HMGB1-positive and HMGB2-negative expression is potentially associated with a shortened survival in patients with pancreatic ductal adenocarcinoma.

High-mobility group box (HMGB) proteins are ubiquitous, abundant nuclear non-histone chromosomal proteins that play a critical role in binding to distorted DNA structures and subsequently regulating DNA transcription, replication, repair, and recombination. Both HMGB1 and HMGB2 exhibit a high expression in several human cancers and are closely associated with tumor progression and a poor prognosis. However, the expression patterns of these molecules in pancreatic ductal adenocarcinoma (PDAC) remain to be elucidated. As most cases of postoperative relapse of PDAC occur within the first 2 years, the clinical significance of accurate biomarkers is needed. Therefore, we investigated the correlation between the immunohistochemical HMGB1 and HMGB2 expression and the clinicopathological characteristics and prognosis using 62 paraffin-embedded tumor samples obtained from patients with surgically resected PDAC. The HMGB1/2 expression was considered to be positive when 10 % or more of the cancer cells showed positive nuclear, not merely cytoplasmic, staining. Consequently, the expression of HMGB1/2 was observed in 54 (87.1 %) and 31 (50.0 %) patients, respectively. Unexpectedly, a positive HMGB1 expression was found to have a significantly close relationship with a negative HMGB2 expression. The univariate and multivariate analyses demonstrated that the patients with a HMGB1+ and HMGB2- status had markedly lower disease-specific survival rates, especially within the first 2 years postoperatively, whereas those with a HMGB1+ status alone did not. Therefore, the combination of a HMGB1+ and HMGB2- expression potentially predicts a poor prognosis in patients with PDAC, and these new biomarkers may be useful parameters for clinical management in the early postoperative phase.

Urinary 1-hydroxypyrene and 8-hydroxydeoxyguanosine levels among coke-oven workers for 2 consecutive days.

OBJECTIVES: This study evaluated the levels of exposure to polycyclic aromatic hydrocarbons (PAHs) and their relationship with oxidative DNA damage among Vietnamese coke-oven workers. METHODS: We collected urine from 36 coke-oven workers (exposed group) at the beginning and end of the shift on 2 consecutive days. We also collected urine from 78 medical staff (control group). Information was collected by questionnaire about smoking status, drinking habit, and working position. Urinary 1-hydroxypyrene (1-OHP) and 8-hydroxydeoxyguanosine (8-OH-dG) were measured using HPLC. All statistical analyses were performed with SPSS version 19. RESULTS: Urinary 1-OHP was significantly higher in the coke-oven workers than in the control group (p<0.05). Top-oven workers had the highest levels of internal exposure to PAHs, followed by side-oven and then bottom-oven workers (5.41, 4.41 and 1.35 ng/mg creatinine, respectively, at the end of the shift on day 2). Urinary 8-OH-dG was significantly higher in top- and side-oven workers at the end of the shift on day 2 (4.63 and 5.88 ng/mg creatinine, respectively) than in the control group (3.85 ng/mg creatinine). Based on a multi-regression analysis, smoking status had a significant effect on urinary 8-OH-dG (p=0.049). Urinary 1-OHP tended to have a positive correlation with urinary 8-OH-dG (p=0.070). CONCLUSIONS: Vietnamese coke-oven workers were exposed to PAHs during their work shift. Urinary 1-OHP exceeded the recommended limit, and elevated oxidative DNA damage occurred in top- and side-oven workers on the second day of work. A tendency for positive correlation was found between urinary 1-OHP and urinary 8-OH-dG.

Urinary 1-hydroxypyrene levels among office workers living in industrial areas.

We examined exposure to polycyclic aromatic hydrocarbons (PAHs) among non-smoking office workers in 2 countries living in the vicinity of a coke-oven factory by measuring their levels of urinary 1-OHP, a known metabolite of PAHs. Subjects included 10 non-smoking office workers in Kitakyushu city (Japan) and 20 workers in Thai Nguyen city (Vietnam). Measurement was optimized by using the high-performance liquid chromatography (HPLC) method developed by Jongeneelen et al. This method required only a small amount of urine and had a short incubation time, and its detection limit was very low (0.00448 ng/ml), which was practical and highly sensitive.The median urinary 1-OHP concentration in the Vietnamese subjects (0.417 ng/mg creatinine) was six times as high as that in the Japanese subjects (0.069 ng/mg creatinine) (P < 0.001). However, both concentrations were significantly below the guideline level, below which there is no genotoxic effect, implying a low probability of any adverse health effects.Our measurements from both countries showed higher urinary 1-OHP concentrations than in previous studies from locations without factories, indicating that ambient air pollution from industrial emissions is an important source of PAH exposure. Finally, the urinary 1-OHP concentrations did not correlate with gender or lifestyle factors.

Expression of heme oxygenase-1 in the lungs of rats exposed to potassium octatitanate whiskers.

OBJECTIVES: Oxidative stress is thought to be the pathogenesis of pulmonary fibrosis induced by asbestos, and heme oxygenase-1 (HO-1) protects lung tissue against oxidative stress. We hypothesized that HO-1 is also associated with oxidative lung injury caused by exposure to potassium octatitanate whiskers (PT1), which is one of the asbestos substitutes. METHODS: Male Wistar rats were administered 1 mg or 2 mg PT1 suspended in saline by a single intratracheal instillation and were sacrificed after recovery for 3 days, 1 wk, 1 mo, 3 mo or 6 mo. Gene expression of HO-1 protein and mRNA and immunostaining were investigated in rat lungs. RESULTS: HO-1 protein expression was increased from 3 days to 1 mo and at 6 mo in the 1 or 2 mg PT1-exposed groups, and the gene expression of HO-1 mRNA was also increased at 3 days and from 1 mo to 6 mo. HO-1-positive cells were mainly found in the alveolar macrophages and the bronchial epithelial cells in immunostaining. CONCLUSIONS: These findings suggest that HO-1 is involved in lung damage caused by PT1.

Prediction of myocardial infarction using coronary risk scores among Japanese male workers: 3M Study.

BACKGROUND: It remains unclear how much coronary risk factors contribute to the prediction of myocardial infarction among Japanese populations. METHODS AND RESULTS: A nested case-control study of Japanese male workers aged 35 to 65 years was conducted between 1997 and 2000 in the Morbidity of Myocardial Infarction Multicenter Study in Japan (3M Study). Two hundred four myocardial infarctions were identified and two controls per case were selected by matching for age. We calculated odds ratios using a conditional logistic regression model, and constructed risk predictive models for the risk of myocardial infarction using coronary risk factors. The multivariable odds ratios (95 percent confidence intervals) of myocardial infarction were 2.02 (1.29-3.16) for high blood pressure, 2.33 (1.51-3.59) for high LDL-cholesterol, 4.16 (2.36-7.33) for low HDL-cholesterol, 1.49 (0.94-2.35) for high triglycerides, 1.46 (0.89-2.39) for high glucose, and 2.95 (1.90-4.59) for current smoking. A large reduction of the predictive value for myocardial infarction was shown after exclusion of high LDL-cholesterol (reduction of predictive value was -3.4%), further exclusion of low HDL-cholesterol (-7.1%), and further exclusion of current smoking (-16.4%). CONCLUSIONS: High LDL-cholesterol and low HDL-cholesterol as well as current smoking had high predictive values for myocardial infarction among Japanese middle-aged male workers.

Heat exposure control using non-refrigerated water in Brazilian steel factory workers.

To test an economically reasonable method to reduce thermal stress, we performed an alternated intervention-control study on 2 groups of 8 male steel workers performing the same jobs, using 2 l of water at ambient temperature (23.5 degrees C +/- 1.4), poured on the head and hands. Each group participated for 2 d as control and 2 d as intervention during 4 consecutive summer days in Brazil, 5 h per shift per day. Testing was done by: 1) recording of temperature by thermistors placed on the external ear canal through earplug, skin (chest, upper arm, inner thigh, outer calf) and clothes; 2) recording of heart rate; and 3) Wet Bulb Globe Temperature recording. The intervention was held hourly, when body weight and water intake were evaluated. Symptoms and subjective sensations were evaluated in the beginning and at the end of each shift. No differences were observed in external ear canal and skin temperatures. Subjective thermal sensation (p = 0.018), sweat perception (p = 0.043), and tiredness (p = 0.028) presented positive statistically significant results when comparing intervention to control measurements. In conclusion, our results could not provide evidence that the proposed method cools the analyzed temperatures, although the subjective evaluation suggests a decrease in the head skin temperature, which could be a useful comfort measure.

Screening for sleep-disordered breathing at workplaces.

Sleep-disordered breathing (SDB) is a condition of repetitive episodes of decreased or arrested respiratory airflow during sleep. Many workers over the world remain undiagnosed and untreated for SDB, and leaving themselves at the high risk for accidents and cardiovascular disease. Since, the Japanese Ministry of Land, Infrastructure and Transport distributed the sleep apnea syndrome manual together with sending an official notice to relevant bodies in all over Japan in March, 2003, employees and employers are expected to co-operate to prevent SDB-related accidents at work. We have conducted several surveys using the pulse-oximetry to detect SDB in working populations and found the high prevalence of SDB among workers in Japan, as many as in the US and EU countries. The proper use of the result from the screening for SDB seems to be beneficial both to workers and employers by maintaining occupational safety and by preventing future development of cardiovascular disease.

Broccoli consumption and chronic atrophic gastritis among Japanese males: an epidemiological investigation.

Previous in vitro and animal experiments have shown that sulforaphane, which is abundant in broccoli, inhibits Helicobacter pylori (H. pylori) infection and blocks gastric tumor formation. This suggests that broccoli consumption prevents chronic atrophic gastritis (CAG) introduced by H. pylori infection and, therefore, gastric cancer. For an epidemiological investigation of the relationship between the broccoli consumption and CAG, a cross-sectional study of 438 male employees, aged 39 to 60 years, of a Japanese steel company was conducted. CAG was serologically determined with serum cut-off values set at pepsinogen I < or = 70 ng/ml and a ratio of serum pepsinogen I/pepsinogen II < or = 3.0. Broccoli consumption (weekly frequency) and diet were monitored by using a 31-item food frequency questionnaire. The prevalence of CAG among men who ate broccoli once or more weekly was twice as high as that among men who consumed a negligible amount (P < 0.05). Multiple logistic regression analysis indicated that broccoli consumption once or more weekly significantly increased the risk for CAG (odds ratio, 3.06; 95% confidence interval, 1.12-8.38; P < 0.05), after controlling for age, education, cigarette smoking, and alcohol consumption. The present study failed to show an expected association between frequent broccoli consumption and a low prevalence of CAG.

Effect of dilution of sports drink on water balance and beverage preference of heat-exposed steel workers.

Eight skilled workers engaged in heat-exposed work in front of a blast furnace in a steel factory were asked to drink a sports drink or one of its dilutions of x 2, x 3, or x 5 during a regular daytime shift in the summer of 1999. A regular lunch was taken and the examined beverage was iced and was allowed to be consumed ad libitum. The beverage was changed each day during four days of the experiment without informing the dilution ratio. The non-diluted beverage contained 21 mEq/l of Na+, 5 mEq/l of K+, 6.7 g/dl of carbohydrate. In average, the body temperature measured in the ear canal was elevated by 0.34 degree C, the loss of body weight was 1.77 kg, total beverage intake was 1,875 g, total amount of urine was 291 g, and the total water loss was 3,732 g (1,350-5,810 g) during a single shift. Twenty out of 24 cases experienced more than 1.5% of weight reduction during morning work without noticing any subjective symptoms of dehydration. The amount of weight loss during morning work was significantly smaller when x 2 or x 3 dilution was taken compared to a non-diluted beverage. The mean value of urinary Na+ concentration was decreased after 8 hours of work; however, the difference was not significant. The urinary K+ concentration was significantly increased. When the total amount of urinary sodium excretion in stored urine was calculated, the x 3 dilution recorded the largest amount. Regarding palatability, the x 2 dilution received the best evaluation, whereas all subjects felt the original beverage as too condensed. We did not observe any adverse effect from diluting the sports drink for x 2 or x 3, when supplying them as water and electrolyte replacements for dehydrated steel workers.