日本人男性海外勤務者の精神的健康度と職業関連要因との関係

目的：海外勤務者の精神的健康度と職業関連要因の関係と日本国内勤務者の精神的健康度の違いを明らかにすることである。方法：同一の金属製品製造業に勤務する男性海外勤務者450名と男性日本国内勤務者683名を対象に自記式質問紙調査を行った。精神的健康度は日本版気分プロフィール検査を用いて評価した。 結果：日本国内と海外勤務者の精神的健康度の比較では、34－39歳において海外勤務者が日本国内より低く、40代と50代では海外勤務者が日本国内より高かった。 　ロジスティック重回帰分析の結果、精神的健康度の不良に関連していたものは、ヨーロッパに対して東アジア（e.g. オッズ比 : 7.548, 95%信頼区間［以下CI］: 2.912－22.293［抑うつ－落込み〔以下D〕］）、東南・南アジア（e.g. オッズ比 : 4.675, 95% CI : 1.679－14.433［D］）、北米（e.g. オッズ比 : 3.997, 95% CI : 1.495－11.895［D］）。管理職に対してエンジニア（e.g. OR : 2.328, 95% CI : 1.168－4.679［緊張－不安〔以下T－A〕］）と生産管理（OR: 5.268, 95% CI : 1.520－18.013［T－A］）。労働時間10－11時間未満に対して12－13時間未満（e.g. OR : 2.063, 95% CI : 1.007－4.283［D］）、13時間以上（e.g. OR : 2.651, 95% CI :1.227－5.814［D］）。休日日数 8 日以上に対して 5 日未満（e.g. OR : 2.285, 95% CI : 1.276－4.129［疲労〔以下F〕］）、5－7日以下（e.g. OR : 2.219, 95% CI: 1.246－4.000［F］）であった。結論：海外勤務者の精神保健対策は、地域別ではアジア圏特に東アジア、職種ではエンジニアや生産管理を中心に取り組んでいく必要がある。また実労働時間が12時間を超える者や休日日数が7日以下の者には、就労時間の制限や休日日数を 8 日以上確保することも対策として考えられた。Objectives : The aim of this study was to clarify the relationship between the mental-health status of overseas employees and work-related factors, and also to determine the difference between the mental-health status of these employees and their counterparts in Japan. Method : Four hundred and fifty male overseas employees and 683 male employees in Japan were surveyed using a self-assessment questionnaire, namely the Japanese version of the Profile of Mood States, which is used to assess mental-health status. Result: The mental-health status of overseas employees in the age range 34－39 years was worse, and that for those in their forties and fifties better, than those o employees in Japan. A multiple logistic regression analysis showed that employees in East Asia Southeast & South Asia and North America were positively associated with poor ental-health status compared with employees in Europe (e.g. odd ratio [OR] : 7.548, 95% confidence interval [CI] : 2.912－22.293, OR : 4.675, 95% CI : 1.679－14.433 and OR: 3.997, 95% CI : 1.495－11.895 in depression/dejection, respectively). Engineers and production controllers were positively associated with poor mental-health status compared with those in managerial posts (e.g. OR : 2.328, 95% CI : 1.168－4.679 and OR : 5.268, 95% CI : 1.520－18.013 in tension/anxiety, respectively). As regards average daily working hours, those employees working for between 12 and less than 13 hours and 13 hours or more were positively associated with poor mentalhealth status compared with those working for between 10 and less than 11 hours (e.g. OR : 2.063, 95% CI : 1.007－4.283 and OR : 2.651, 95% CI : 1.227－5.814 in depression/dejection, respectively). In terms of number of days’ holiday in the last month, those employees who had taken less than five days and between five days and seven days were positively associated with poor mental-health status comparison with those who had taken eight days or more (e.g. OR : 2.285, 95% CI : 1.276－4.129 and OR : 2.219, 95% CI : 1.246－4.000 in fatigue, respectively). Conclusion : Mental-health protection measures in overseas bases need to focus on Asia, especially East Asia and employees who work as engineers or production controllers. Furthermore, average daily working hours should be shortened as much as possible and employees should take at least eight days’ holiday per month

A potent chemotherapeutic strategy in prostate cancer: S-(methoxytrityl)-L-cysteine, a novel Eg5 inhibitor

Docetaxel-based combination chemotherapy remains the predominant treatment for castration-resistant prostate cancer. However, taxane-related drug resistance and neurotoxicity have prompted us to develop substitute treatment strategies. Eg5 (kinesin spindle protein), which is crucial for bipolar spindle formation and duplicated chromosome separation during the early phase of mitosis, has emerged as an attractive target for cancer chemotherapy. The aim of this study was to investigate the anticancer efficacy of S-(methoxytrityl)-ℒ-cysteine (S(MeO)TLC), a novel Eg5 inhibitor in prostate cancer. Eg5 expression was examined in human prostate cancer cell lines and tissue microarrays were constructed from clinical specimens. Antiproliferative activity of S(MeO)TLC in prostate cancer cells was assessed by a cell viability assay. The anticancer effect and inhibitory mechanism of S(MeO)TLC in prostate cancer cells was further explored by Hoechst staining, flow cytometry and immunofluorescence. In addition, the antitumor effect of S(MeO)TLC on subcutaneous xenograft models was assessed. Eg5 expression was identified in PC3, DU145 and LNCaP cells. More than half of prostate cancer clinical specimens displayed Eg5 expression. S(MeO)TLC exhibited more powerful anticancer activity in prostate cancer cells compared with the other four Eg5 inhibitors tested. S(MeO)TLC induced cell death after arresting dividing cells at mitosis with distinct monopolar spindle formation. S(MeO)TLC exhibited its significant inhibitory activity (P<0.05) on subcutaneous xenograft models also through induction of mitotic arrest. We conclude that Eg5 is a good target for prostate cancer chemotherapy, and S(MeO)TLC is a potent promising anticancer agent in prostate cancer

Age dependency of hepatic response to gamma-rays in B6C3F1 mice.

Background: With a rapid increase in the frequency of medical radiation exposure, radiation effects on the children have become a great concern in recent years. Therefore, firm evidences are required for radiation protection for medical exposure. It has been reported that neonatal B6C3F1 mice had high sensitivity of radiation-induction of liver tumors and life shortening compared with adult mice. However, little is known about the underlying mechanism of its high susceptibility. We hypothesize here that the unique characteristic response of neonatal hepatocytes to radiation may contribute to high susceptibility to radiation hepatocarcinogenesis. In this study, we aimed to investigate the normal development, focusing on proliferative activity of fetal, neonatal and adult livers histologically, and then to analyze the hepatocyte response to radiation in terms of cell cycle arrest and apoptosis. \nMaterials and Methods: For investigation of normal development of liver in B6C3F1 mice, the livers of mice at various ages, from 13-days post-conception (fetus) up to 10-week of age (adult), were analyzed histologically. For investigation of the age dependence of hepatocyte response to radiation, 17 days post-conception, 1-week-old (neonatal), and 7-week-old mice were whole-body irradiated with 4 Gy at a dose rate of gamma-rays from 137Cs. Subsequently, mice were killed at 0 (unirradiated), 1, 3, 6, 12, 24 and 48 hours. Then immunohistochemical analyses, using antibody against p53, Ki67, active caspase3, PCNA, and gamma-H2AX, were performed. BrdU and TUNEL analyses were also performed at 3 to 48h after irradiation.\nResults and Discussion: The liver proliferative status was dramatically changed during development from fetus to adult stage. There were many active proliferaive hepatic cells as well as hematopoietic cells in the fetal livers. Immature bile ducts and hepatic cords were formed at 1 week of age. At 7 weeks of age, matured hepatic cells were morphologically fully developed. We here found that radiation responses, in terms of cell cycle arrest and induction of apoptosis, were different among fetus, neonatal and adult hepatocytes. In fetal hepatocytes, p53 was accumulated soon after irradiation, which was followed by cell cycle arrest and apoptosis. In adult hepatocytes, which are rarely proliferating, there showed few apoptotosis after irradiation. In great contrast, the neonatal hepatocytes showed, surprisingly, the few apoptotosis after irradiation and continued proliferation. The resistance to apoptosis and continued proliferation may contribute to the accumulation of damaged cells, which may lead to high susceptibility to radiation tumorigenesis.The 3rd JCA-AACR Special Joint Conferenc

Functional Analysis of Novel Mammary Cancer-Related Genes

Keystone Symposia　Integration of Developmental Signaling Pathway

Radiation exposure enhances hepatocyte proliferation in neonatal mice but not in adult mice

Intuitively, irradiation of an infant organ before it undergoes development-related expansion would be expected to confer greater cancer risk than irradiation of a fully-developed adult tissue, and this is generally observed. However, if tissues also vary in their initial responses to radiation depending on age, the interplay between tissue- and age-dependent risk would potentially be quite complex. We have previously shown opposing age-dependent induction of apoptosis for the intestinal epithelium and hematopoietic cells in mice, but such data are not yet available for the liver. Here, we have examined markers of DNA damage, initiation of DNA damage responses, cell cycle arrest, apoptosis and proliferation, as well as gene expression, in the B6C3F1 mouse liver over the hours and days following irradiation of mice at 1 or 7 weeks of age. We found that induction and resolution of radiation-induced DNA damage is not accompanied by significant changes in these cellular endpoints in the adult liver, while in infant hepatocytes modest induction of p53 accumulation and p21-mediated cell cycle arrest in a small fraction of damaged cells was overshadowed by a further stimulation of proliferation over the relatively high levels already found in the neonatal liver. We observed distinct expression of genes which regulate cell division between the ages which may contribute to the differential responses. These data suggest that the growth factor signaling environment of the infant liver may mediate radiation-induced proliferation and increased liver cancer risk following irradiation during early life