Risk of bladder cancer in male Japanese workers exposed to ortho-toluidine and other aromatic amines.

PURPOSE: Nine bladder cancer (BCa) cases were reported among aromatic amine-exposed male workers at a factory manufacturing organic dye/pigment intermediates in Japan. We aimed to evaluate the characteristics of aromatic amine-exposed workers by cross-sectional observation, and the risk of BCa by assessing the standardized incidence ratio (SIR). METHODS: In the cross-sectional study, our subjects were: 9 BCa patients, 36 aromatic amine-exposed non-patients, and 79 non-exposed workers from 3 factories. We evaluated the subjects' medical history, urinalysis, qualitative determination of nuclear matrix protein 22, and urinary cytology. For SIR assessment, 98 aromatic amine-exposed workers from 1 factory were included, and the Japanese general male population was used as a referent population. Since no direct aromatic amine-exposure data were available, we calculated surrogate exposure levels using information on job sites, exposure potency, and duration. RESULTS: Coexistent aromatic amines were ortho-toluidine (OT), aniline, para-toluidine, ortho-anisidine, 2,4-xylidine, and ortho-chloroaniline. The prevalence rates of cystitis and bladder lesion-related symptoms in both BCa patients and aromatic amine-exposed non-patient workers were significantly higher than those of non-exposed workers. Overall, the SIR for BCa in OT-exposed workers was 56.8 (95% CI 27.7-104.3) and apparent dose-response relationships were revealed between the SIR and the surrogate exposure level in the 0-10-year lagged analyses. Overall, SIRs in other aromatic amine-exposed workers were also significantly high but no or unclear dose-response relationships were observed. CONCLUSIONS: We conclude that OT may be responsible for the increased risk of BCa. Regular monitoring of bladder lesion-related symptoms is essential for the early identification of BCa.

Changes of median nerve conduction velocity in rayon manufacturing workers: A 6-year cohort study.

OBJECTIVES: We conducted a 6-year cohort study to evaluate the relationship between carbon disulfide (CS2) exposure and reductions in the motor and sensory nerve conduction velocity (MCV and SCV) of the median nerve. METHODS: Study subjects at baseline included 432 exposed workers and 402 unexposed workers. Among the exposed workers, 145 workers terminated CS2 exposure during the follow-up period (ex-exposed workers). MCV and SCV were measured at baseline and followed up. CS2 personal exposure concentration was measured two times a year during a 6-year follow-up period and mean (range) CS2 exposure concentrations (ppm) were 5.96 (0.8-16.0) and 3.93 (0.6-9.9) in the exposed and ex-exposed workers, respectively. RESULTS: Reductions in MCV during the follow-up period did not differ among the exposed, ex-exposed, and unexposed workers. Reduction in SCV (m/s) of the exposed workers (-4.47±3.94) was significantly larger than that of the unexposed (-3.38±3.97) and ex-exposed workers (-3.26±3.79). For SCV reduction, a partial multiple regression coefficient of (ex-exposed workers) / (unexposed workers) was significantly positive (+0.915, p < 0.01) after adjustment for confounding variables. CONCLUSIONS: This cohort study showed that 6-year CS2 exposure around a mean level of 6 ppm did not affect MCV reduction but induced significant SCV reduction beyond the influence of aging. The effect of CS2 on SCV around a mean exposure level of 4 ppm may be reversible, since it disappeared in the ex-exposed workers after CS2 exposure cessation for a mean period of 4.1 years.

Five-year cohort study: emphysematous progression of indium-exposed workers.

BACKGROUND: Dose-dependent adverse lung effects due to indium exposure have been reported in a cross-sectional study. This is a 5-year longitudinal cohort study of indium-exposed and unexposed workers, assessing indium exposure levels and its clinical lung effects. METHODS: From 2008 to 2011, a 5-year follow-up study was conducted on 40 unexposed and 240 workers formerly or currently exposed to indium at 11 factories. Indium exposure was assessed by serum indium (In-S) (µg/L). Lung effects were assessed by subjective symptoms, serum biomarkers, spirometry, and chest high-resolution CT scan. Effect biomarkers used were Krebs von den Lungen and surfactant protein D. RESULTS: Mean values of In-S, Krebs von den Lungen, and surfactant protein D among the workers exposed to indium at baseline declined during the 5-year follow-up by 29.8%, 27.2%, and 27.5%, respectively. Of the exposed subjects with In-S levels > 20 µg/L, 26.3% experienced emphysematous progression on high-resolution CT scan. Ninety percent (18 of 20) of workers with emphysematous progression during follow-up were current smokers at baseline, and a trend of increasing incidence of emphysematous progression at higher In-S levels was observed among the smokers (P = .005). Emphysematous changes among subjects with In-S levels > 20 µg/L were likely to progress, after adjusting for age, mean duration since initial indium exposure, and smoking history (OR = 10.49, 95% CI = 1.54-71.36). CONCLUSIONS: Long-term adverse effects on emphysematous changes were observed. The results suggest workers exposed to indium with In-S levels > 20 µg/L should be immediately removed from exposure.

Higher serum dehydroepiandrosterone sulfate levels are protectively associated with depressive symptoms in men, but not in women: a community-based cohort study of older Japanese.

OBJECTIVE: Dehydroepiandrosterone sulfate (DHEAS) appears to have a protective effect against depression, but evidence from prospective cohort studies is sparse. Therefore, we examined the association between serum DHEAS levels and depressive symptoms in older community-dwelling Japanese. DESIGN: A community-based cohort study. SETTING: Kurabuchi Town, Gunma Prefecture, Japan. PARTICIPANTS: A total of 554 residents (248 men and 306 women) age 65 years or older without depressive symptoms at baseline. MEASUREMENTS: We performed a baseline examination of the subjects between 2005 and 2006 to determine serum DHEAS levels. The subjects were categorized into three groups based on age strata- and sex-specific tertiles of DHEAS. Depressive symptoms were assessed with the Geriatric Depression Scale 15-item version (GDS-15) in face-to-face home visit interviews carried out once in 2007 and once in 2008. The association of DHEAS with depressive symptoms (GDS-15 ≥ 6) was analyzed with the use of logistic regression models. RESULTS: The incidence of depressive symptoms was 12.1% in men and 19.6% in women. In men, the multiadjusted odds ratio of depressive symptoms was 0.24 (95% confidence interval: 0.06-0.94, Wald χ2 = 4.20, degrees of freedom = 1, p = 0.04) for the highest tertile compared with the lowest. The association observed for the highest versus the lowest remained significant even after adjustment for physical performance and cognitive function. In women, DHEAS was not associated with depressive symptoms. CONCLUSIONS: In this study, higher serum DHEAS levels were found to be protectively and independently associated with the risk of developing depressive symptoms in men, but not in women.

Causal relationship between indium compound inhalation and effects on the lungs.

BACKGROUND: Recent case reports and epidemiological studies suggest that inhalation of indium dust induces lung damage. OBJECTIVES: To elucidate the dose-dependent effects of indium on the lungs and to prove a causal relationship more clearly. METHODS: A baseline observation was conducted on 465 workers currently exposed to indium, 127 workers formerly exposed to indium and 169 workers without indium exposure in 12 factories and 1 research laboratory from 2003 to 2006. Indium in serum (In-S) was determined as an exposure parameter, and its effects on the lungs were examined. RESULTS: The means of In-S in the current, former and no exposure workers were 8.35, 9.63 and 0.56 ng/ml, respectively. The current and former exposure workers had significantly higher levels of KL-6, and showed significant dose-dependent increases in KL-6, SP-D, and SP-A. Current exposure workers with In-S of 3 ng/ml or above demonstrated a significant increase of KL-6 in both GM and prevalence exceeding the reference value. Approximately a quarter of the former exposure workers had interstitial changes as seen on chest HRCT. In-S of exposed workers who had been working before improvements of the working environment (Group Bef) and those who started working after improvements (Group Aft) were 12.29 and 0.81 ng/ml, respectively. Adjusted odds ratios indicated 87%, 71% and 44% reductions among Group Aft workers who exceeded the reference values of KL-6, SP-D and SP-A, respectively. CONCLUSION: Dose-dependent lung effects due to indium exposure were shown, and a decrease of indium exposure reduced the lung effects. An In-S value of 3 ng/ml may be a cut-off value which could be used to prevent early effects on the lungs.

Trichloroethylene liver toxicity in mouse and rat: microarray analysis reveals species differences in gene expression.

Trichloroethylene (TCE), an industrial organic solvent found in the environment, is a known carcinogen in laboratory animals and is believed to be carcinogenic in humans. Its carcinogenicity is subject to species-specific differences in biological activity, causing hepatocellular carcinoma in mouse and renal-cell carcinoma in rat. We have sought to better understand TCE's mode of action (MOA) by studying the alterations in gene expression profiles of liver in mice and rats that were administrated TCE by oral gavage either once or daily for 14 days. Microarray analysis revealed distinct transcriptional profiles and differences in biological pathways not only species-specific, but also pulse-dose effects within each species. For example, inhibition of the TGF-beta pathway and activation of MAPK signaling were specific to mice repeatedly exposed to TCE. A better understanding of the MOA in mice and rats will lead to better hypotheses of TCE's affect on humans.

Urinary excretion of an oxidative stress marker, 8-hydroxyguanine (8-OH-Gua), among nickel-cadmium battery workers.

The relationship between oxidative stress and carcinogenic metals including nickel and cadmium is a matter of interest. To assess the oxidative stress status of workers exposed to nickel and cadmium simultaneously, we determined urinary excretion of 8-hydroxyguanine (8-OH-Gua), a urinary oxidative stress marker. Our subjects were 66 (64 males and 2 females) nickel-cadmium battery workers. Spot urine and blood samples were collected. The levels of cadmium in blood (Cd-B) and nickel in urine (Ni-U) were determined by graphite furnace atomic absorption spectrophotometry. 8-OH-Gua in urine was analyzed using a high performance liquid chromatography-electrochemical detector (HPLC-ECD) system. Data on age, sex, duration of present work and smoking status were also obtained from each subject. Creatinine-adjusted 8-OH-Gua was significantly correlated with age, Ni-U and Cd-B in univariate analysis, while multivariate analysis revealed that Ni-U and Cd-B were significant independent variables and that these two biological exposure indices were positively correlated with 8-OH-Gua. The data were also analyzed in the context of mixture toxicity. The subjects were divided into groups based on median level of Ni-U and Cd-B (2.86 mug/g creatinine and 0.23 mug/dl, respectively). Workers with high Ni-U/high Cd-B (Group IV) had the highest levels of 8-OH-Gua levels (GM (GSD), 21.7(2.0)), followed by those with high Ni-U/low Cd-B (11.5(1.6) Group III), those with low Ni-U/high Cd-B (8.9(1.9) Group II), and those with low Ni-U/low Cd-B (8.5(1.5) Group I). The p values of Students' t-tests between Group I and Group II, III and IV were 0.847, 0.050 and <0.001, respectively. The combined effect of Cd and Ni on the urinary excretion of 8-OH-Gua departed from additivity.

Association of thoracic kyphosis with subjective poor health, functional activity and blood pressure in the community-dwelling elderly.

OBJECTIVES: The prevalence of thoracic kyphosis is considered to increase as the population is ageing in Japan. However, little is known about the clinical and preventive significance of kyphosis. The purpose of the study is to assess the association of kyphosis with subjective poor health and functional activity in the community-dwelling Japanese elderly. The relation of kyphosis with blood pressure, as a subclinical indicator of arteriosclerosis, is also examined. METHODS: The subjects consisted of 536 (male 241, female 295) elderly persons aged 65 years old and older. Trained examiners measured thoracic kyphosis using a flexicurve, and kyphosis index was calculated. Information on the subjects' subjective poor health and functional activity were collected through a face-to-face interview, and blood pressure was measured by a conventional method. RESULTS: In females, their kyphosis index increased with age increased, whereas in males, there was no clear age-related change. An increased kyphosis index was associated with subjective poor health only among females. Compared with the lowest kyphosis index tertile, adjusted odds ratios for being in poor health were 5.4 (95% confidence interval: 1.1-27.4) in the middle tertile, and 6.4 (95% confidence interval: 1.3-32.1) in the highest tertile. Kyphosis index did not seem to be associated with functional activity score and blood pressure both in males and females even after adjustment. CONCLUSIONS: Kyphosis is associated with subjective poor health in the community-dwelling female elderly in this study population, but not with functional activity and blood pressure both in males and females.

Full-length cDNA cloning of Toll-like receptor 4 in dogs and cats.

In the present study, full length of canine and feline Toll-like receptor 4 (TLR4) cDNAs were sequenced, and the expression of canine and feline TLR4 mRNAs in dog and cat tissues were investigated. The full-length cDNA of TLR4 of dog and cat was 2709 bp encoding 637 amino acids and 3113 bp encoding 833 amino acids, respectively. The similarity of canine and feline TLR4 were 83.6% at the nucleotide sequence level and 77.6% at the amino acid sequence level. At the amino acid sequence level, canine and feline TLR4 showed sequence similarities of approximately 62-78% with those of Homo sapiens, Mus musculus, Bos taurus and Equus caballus, respectively. Southern hybridization analyses with TLR4 cDNA probes gave one distinct band in BamHI, EcoRI and HindIII digests of genomic DNA from dogs and cats, respectively, indicating the likely presence of a single TLR4 gene in each species. By RT-PCR analysis, mRNA of canine TLR4 was expressed highly in peripheral blood leukocytes (PBL), moderately in spleen, stomach and small intestine, at low levels in liver, with no expression in kidney, large intestine and skin. On the other hand, mRNA of feline TLR4 was expressed highly in lung, bladder and PBL, moderately in kidney, liver, spleen and large intestine and at low levels in pancreas and small intestine.

Aspergillus niger pulmonary infection in a dog.

A 6-month-old male golden retriever was presented with fever, bloody-watery diarrhea and mild cough. Parvovirus and Isospora canis infection was confirmed and successfully treated. Two weeks later, the dog had severe cough and mucopurulent nasal discharge. Aspergillus niger was cultured from endotracheal washings on blood agar at 37 degrees C. Treatment with itraconazole for about 10 weeks resolved the clinical signs.