Hazardous environmental factors enhance impairment of liver function in HBV and HCV hepatitis.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) often cause chronic liver disease. We hypothesized that environmental factors adversely impact the liver function in workers with these types of hepatitis. We used liver function tests including aspartate aminotransferase, alanine aminotransferase, and g -glutamyltransferase to evaluate whether hazardous work conditions increase the incidence of chronic liver disease among HBV and HCV infected workers. Organic solvent, night work, visual display terminals, dust, lead, vibrations, and ionizing radiation all led to increased impairment of liver function in patients with hepatitis as compared to the control group that were not exposed to such agents. Therefore, hazardous working conditions have to be carefully considered in the progress of chronic liver disease in workers infected with HBV and HCV.

Methods and rationale for keeping records of hepatitis virus testing in Japanese workplaces.

In Japan, the Ministry of Health, Labour and Welfare issued corporate guidance that employers should recommend their employees to have tests for hepatitis B virus and hepatitis C virus (HV) at least once in their lifetime. However, employers should treat this information as confidential, even though the testing is carried out along with the health examination designated by the Industrial Safety and Health Law. Therefore, the records of HV tests should not be kept by employers, even though records of medical examinations designated by the law must be. This study aimed to clarify the present method for keeping records of HV infection and the rationale in Japanese workplaces. Questionnaires about viral hepatitis were sent to 118 occupational health physicians, and 81 physicians from 100 workplaces responded. The HV test for employees was conducted in 58 workplaces (75.8% of large, 60.4% of bigger medium-sized and 16.7% of smaller medium-sized enterprises). These workplaces were the types of industries where the risk of infecting other persons was low. Subjects of the HV tests were workers who were suspected to have hepatitis virus, and workers who were applicants. Occupational health physicians from most workplaces answered that records of medical examinations designated by law and records of HV tests were not kept separately and shouldn't be. The opinion that the two types of records should not be kept separately appeared to be more from the workplaces where employers or health insurance covered the cost of the HV test. In these cases, the purpose of conducting HV tests at the workplaces was thought to be both promoting welfare of employees and occupational considerations for workers. Occupational health physicians from about 60% of workplaces had misgivings about employees who had hepatitis virus being discriminated against at the workplace if the HV test was included with the required medical examination. Among occupational health physicians from workplaces where occupational health professionals were in charge of the records, there was no standardized rationale for keeping records. However, most workplaces took into consideration the workers' privacy by getting employees' consent before divulging information to their employers. This relied not only on the occupational health professional's or health/safety officer's ethics, but also the necessity of reviewing the purpose and methods of keeping records of HV testing of employees, based on official notices or the Act on the Protection of Personal Information.

A pilot study on subacute ethanol treatment of ALDH2 KO mice.

Aldh (aldehyde dehydrogenase ) 2 knockout (KO) mice have been generated in our laboratory. We evaluated the effects of subacute ethanol treatment on the survival rate, expression of Aldh1, Aldh2, Cytochrome P450 (Cyp) 1A1, Cyp2e1 and Cyp4b1 in wild (Aldh2+/+) mice (C57BL/6) and Aldh2 knock out (Aldh2-/-) mice. Physiological saline (0.3 mL/day) was administered to 4 Aldh2+/+ and 4 Aldh2-/- mice for 8 days as a control. Forty percent ethanol (0.3 mL/day; ethanol 2 g/kg/day) was then administered to 5 Aldh2+/+ and 9 Aldh2-/- mice for 8 days. Three mice of the ethanol administered Aldh2+/+ group and eight mice of the ethanol administered Aldh2-/- group died during the 8 days. The weights of mice were decreased by ethanol exposure to 85% and 74% in Aldh2+/+ and Aldh2-/- group, respectively. The survival rates of the ethanol administered Aldh2+/+ and Aldh2-/- group were 40 and 11%. Liver and pancreas disorder was revealed in the ethanol administered Aldh2+/+ and Aldh2-/- group in the results of serum chemical examination, immunohistochemical staining and western blot analysis. Cyp2e1 is more inducible to ethanol toxicity in Aldh2-/- mice compared with Aldh2+/+ mice when ethanol is administered according to the results of quantitative PCR.

HBV- and HCV- infected workers in the Japanese workplace.

Around three million Japanese are persistently infected with HBV or HCV. Though most of them work in various industries, little is known about the actual conditions in their workplaces. To clarify the workplace conditions of workers with hepatitis, three kinds of questionnaire surveys, answered by occupational health physicians and workers with hepatitis, were carried out. The rates of workers recognized as workers with hepatitis B or C by occupational health physicians were 0.82% and 0.48% of 130,092 workers, respectively. About 30% of workers with hepatitis were engaged in "hazardous work". The percentage of workers engaged in various types of hazardous work among workers with hepatitis was nearly the same as that among all Japanese workers. About 30% of occupational health physicians witnessed exacerbation of hepatitis in the workers at their workplaces, and 22% of workers with hepatitis experienced exacerbation of hepatitis. The rate of workers with hepatitis who had experienced exacerbation was not significantly different between workers with and without hazardous work. Workers with hepatitis have strong concerns about the relationship between work and exacerbation. As causes of exacerbation, occupational health physicians cited "unknown", "drinking" and "quit treatment" while workers with hepatitis answered "work-related causes", besides "unknown" and "drinking."

Evidence-based prevention (EBP): A review of cytochrome P450 expression in the bronchial epithelium and new approach to lung cancer prevention.

The number of fatalities in Japan attributable to lung cancer exceeded 50000 in 2001. It is socially desirable that various markers, which can be utilized for the prevention of lung cancer, be established. We believe that smoking or exposure to carcinogens in air induces mutations in bronchial and alveolar epithelia, leading to the development of lung cancer. It would be useful to have markers of individual differences in susceptibility to chemical carcinogen-induced lung cancer 1) to identify genetic polymorphisms of enzymes metabolizing chemical carcinogens and 2) to investigate the expression of enzymes metabolizing chemical carcinogens. In this paper, we review CYP expression in the bronchial epithelium. CYP1, CYP2 and CYP3 are expressed in the bronchial epithelium. We also show the relationship between the genetic polymorphisms of cytochrome P450 (CYP) and a person's susceptibility to chemical carcinogen-induced lung cancer. We demonstrate the relationship between cigarette consumption and the CYP expression profile in the bronchial epithelium. To maintain and promote public health, we must apply evidence, such as CYP polymorphisms and CYP profiles to disease prevention and also to aggressively advance evidence-based prevention (EBP) of lung cancer.

Y-box-binding protein-1 expression is not correlated with p53 expression but with proliferating cell nuclear antigen expression in non-small cell lung cancer.

Transcription factor Y-box-binding protein 1 (YB-1), which binds to the inverted CCAAT box, is not only involved in the transcription of various genes, but also in cell proliferation and DNA repair. The aim of this study was to detect YB-1 and p53 expression and their relationship to proliferating cell nuclear antigen (PCNA) in non-small cell lung cancer (NSCLC) using immunohistochemical (IHC) staining, and to evaluate the relationship between their expression levels and the prognosis of patients with NSCLC. Positive expressions of YB-1, p53 and PCNA were detected in NSCLC cells in 43 (45.7%), 33 (35.0%) and 45 (47.9%) out of 94 patients, respectively. No significant differences were observed between YB-1 expression and the patients' gender, age at surgery, pathological stage, pathological T status, pathological N status, or pathological M status. The mean PCNA-labelling index (LI) for cells was 40.7+/-2.6. Also, a significant correlation between YB-1 and PCNA-LI was found (p<0.01), but none was found between p53 expression and PCNA. The positive expression of YB-1 was associated with squamous cell carcinoma and large cell carcinoma, compared with adenocarcinomas (p<0.01), and higher levels of PCNA-LI were associated with large cell carcinoma compared with adenocarcinomas and squamous cell carcinoma (p<0.01). These results suggest that YB-1 expression is correlated with PCNA expression in NSCLC. In addition, the DNA repair pathway and tumor proliferation mediated by YB-1 linking to PCNA may be responsible for controlling the growth of NSCLC.

Expression of cytochrome P450 in tumor tissues and its association with cancer development.

CYPs (cytochrome P450s) catalyze the conversion of numerous numbers of xenobiotics including carcinogens and drugs. CYPs can be involved in metabolic pathways of activation of procarcinogens and/or inactivation of carcinogens during the tumorigenic processes. Recently, increasing number of cancer tissues as well as normal tissues have been found to express a variety of CYPs. The local expression of CYPs in tumors appears to be very important for the management of cancers since CYPs expressed in tumors may be involved in activation and/or inactivation of anticancer drugs. The expression of CYPs in tumors may also convert endogenous substrates to metabolites that facilitate cancer development. In this review, we summarize the association of CYP expression in cancer tissues with carcinogenesis and cancer treatment.

Pleomorphic carcinoma: report of a case with massive pleural effusion and asbestos particles.

Pleomorphic (spindle/giant cell) carcinoma (PC) is one subset of large cell carcinoma. It is well known that PC patients have a poor survival rate. This report describes a 68-year-old man with PC. The patient's tumor had a massive pleural effusion. A left lower lobectomy and partial resection of the left diaphragm, peritoneum, and parietal pleura were performed to remove the tumor. Numerous asbestos particles were found in the left lower lobe. This is the first reported case of PC which may have been caused by asbestos particles. Further investigation is needed into whether asbestos exposure causes PC.