Fumio Sakauchi

Serum phytoestrogens and prostate cancer risk in a nested case‐control study among Japanese men

The purpose of this study was to examine whether a high serum concentration of phytoestrogens reduces the risk of prostate cancer in a case‐control study nested in a community‐based cohort in Japan (Japan Collaborative Cohort (JACC) Study). Information on lifestyles and sera of the subjects were collected in 1988–90, and they were followed up to 1999. Incident and dead cases of prostate cancer and controls were matched for study area and age. Phytoestrogens and sex hormones in sera stored at −80°C were measured in 2002. Of 14,105 male subjects of the cohort who donated their sera, 52 cases and 151 controls were identified. Three datasets were analyzed; 1) all subjects, 2) 40 cases and 101 controls after excluding subjects with low testosterone levels who were suspected of having had medical intervention, and 3) 28 cases and 69 controls with prostate specific antigen level of ∼10.0 ng/ml. The odds ratio (OR) for the highest level to the lowest was 0.38 (95% confidence interval (CI); 0.13, 1.13) for genistein, 0.41 (0.15, 1.11) for daidzein, and 0.34 (0.11, 1.10) for equol for the second dataset. Genistein and daidzein showed similar findings in the third one. Equol and equol/daidzein ratio showed consistent findings in all three datasets (OR=0.39, 95% CI; 0.13, 0.89, trend P=0.02 for the first dataset). Their effects seemed to be independent of serum sex hormones. In conclusion, serum genistein, daidzein, and equol seemed to dose‐dependently reduce prostate cancer risk. (Cancer Sci 2004; 95: 65–71)

Diabetes mellitus and kidney cancer risk: The results of Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study)

Background:  Diabetes mellitus (DM) is reported as being a risk factor associated with kidney cancer in Western countries. The incidence of both kidney cancer and DM is lower in Japan than the other developed countries, albeit on the rise.

Dietary Habits and Risk of Urothelial Cancer Death in a Large-Scale Cohort Study (JACC Study) in Japan

Abstract: The Japan Collaborative Cohort (JACC) Study was established in 1988–1990 and consisted of 46,465 men and 64,327 women observed until the end of 2003. A self-administered food frequency questionnaire was used as a baseline survey, and associations of dietary habits with the risk of ovarian cancer death were evaluated, taking into consideration age, menstrual and reproductive, anthropometric, and lifestyle factors. During the observation period, 77 women died of ovarian cancer. Hazard ratios for dietary factors were calculated by Coxs proportional hazards model. Being adjusted only for age, high intakes of dried or salted fish and Chinese cabbage were positively associated with the risk of ovarian cancer death, and the risk increased dose-dependently. In contrast, intake of soybean curd (tofu) was inversely associated with the risk. After being adjusted for age and potential confounding factors, the results regarding the intakes of dried or salted fish and Chinese cabbage did not change. However, the significance relating to the intake of soybean curd (tofu) was attenuated. From the results of this cohort study, it was suggested that high intakes of dried or salted fish and Chinese cabbage were potential risk factors of ovarian cancer death. In contrast, however, a high intake of soy bean curd (tofu) might have preventive effects against the risk.

Effect of Physical Activity on Breast Cancer Risk: Findings of the Japan Collaborative Cohort Study

Purpose: This study aimed to examine prospectively the association between physical activity and breast cancer risk in a non-Western population. Methods: We analyzed data from the Japan Collaborative Cohort Study, which included 30,157 women, ages 40 to 69 years at baseline (1988-1990), who reported no previous history of breast cancer, and provided information on their walking and exercise habits. The subjects were followed prospectively from enrollment until 2001 (median follow-up period, 12.4 years). Breast cancer incidence during this period was confirmed using records held at population-based cancer registries. The Cox proportional hazards model was used to estimate the hazard ratio (HR) for the association of breast cancer incidence with physical activity. Results: During the 340,055 person-years of follow-up, we identified 207 incident cases of breast cancer. The most physically active group (who walked for ≥1 hour per day and exercised for ≥1 hour per week) had a lower risk of breast cancer (HR, 0.45; 95% confidence interval, 0.25-0.78) compared with the least active group after adjusting for potential confounding factors. The inverse association of exercise on breast cancer was stronger among those who walked for ≥1 hour per day than those who walked for <1 hour per day (P = 0.042). These results were not significantly modified by menopausal status or body mass index (BMI). Conclusions: Our analysis provided evidence that physical activity decreased the risk of breast cancer. Walking for 1 hour per day and undertaking additional weekly exercise both seemed to be protective against breast cancer, regardless of menopausal status or BMI. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3396–401)

Antimitochondrial antibody negative primary biliary cirrhosis in Japan: utilization of clinical data when patients applied to receive public financial aid.

BACKGROUND We examined patients who showed laboratory and histological evidence of primary biliary cirrhosis (PBC) in the absence of antimitochondrial antibody (AMA) to elucidate the characteristics of AMA negative PBC. METHODS From a total of 5,805 patients with symptomatic PBC, 2,419 cases (41.7%) were selected in the present study, who were diagnosed using the following criterion; chronic non-suppurative destructive cholangitis was histologically observed and laboratory data did not contradict PBC. The information collected from records included sex, age, symptoms, physical findings, and complicated autoimmune diseases. We then evaluated these data according to the positivity of AMA. RESULTS Of the total subjects, 470 cases (19.4%) were found to be negative for AMA. The proportion of female patients was higher among the AMA negative group than among the AMA positive one. Pruritus was found less frequently among patients with AMA negative PBC than among those with AMA positive PBC. Levels of alkaline phosphatase, γ-glutamyl transpeptidase, and IgM were significantly lower among patients with AMA negative PBC than among those with AMA positive PBC. Complications such as Sjögren’s syndrome, rheumatoid arthritis, and scleroderma, including CREST syndrome, were found with significantly higher frequency among patients with AMA negative PBC than among those with AMA positive PBC. CONCLUSION Considering serum level of IgM and frequencies of complicated autoimmune diseases, it is possible that Japanese patients with AMA negative PBC are consistent with the disease entity of autoimmune cholangitis reported in western countries.

Effects of colchicine on the hepatocellular transport of indocyanine green in the rat

SummaryThe effects of colchicine on plasma elimination and biliary excretion of indocyanine green (ICG) and sulfobromophthalein (BSP) in rats were examined. Elimination of two different doses of ICG (6 mg and 20 mg/kg body weight) from plasma was significantly delayed when rats were treated with colchicine (3 mg/kg body weight) 3 h prior to the administration of the dye. On the other hand, disappearance of BSP (100 mg/kg) from plasma was not influenced by colchicine. The fact that the difference in the ICG elimination from plasma between colchicine-treated and salinetreated rats was minimal in the early period (i.e., 2 min after administration of the dye), but evident after its half-life (i.e., 10 min, when 6 mg/kg body weight of ICG was given), suggested that colchicine mainly affected the hepatocellular transport of ICG rather than the uptake of the dye by hepatocytes. Colchicine also significantly reduced the excretion of ICG (6 mg and 20 mg/kg) into bile but did not alter that of BSP (100 mg and 200 mg/ kg). On the other hand, the same amount of lumicolchicine (3 mg/kg) did not have any effect on the biliary excretion of ICG. These results suggested that ICG is transported through hepatocytes into bile with the aid of the cytoplasmic microtubular system, whereas BSP is handled by hepatocytes in a different way.

Traditional Japanese diet and prostate cancer.

The traditional Japanese diet has been suggested by some researchers to be associated with a decreased risk of prostate cancer (PCa). In this paper, we assumed the following three characteristics of the traditional Japanese diet high in soybean products, high in fish, and low in red meat. Isoflavones, polyunsaturated long chain (n - 3) fatty acids, and saturated fatty acids were thought to be micronutrients in biological etiology relevant to soybean products, fish, and red meat, respectively. Analytical epidemiological studies on the risk of PCa were identified using the MEDLINE database from 1998 to 2007. Some published studies showed a negative association of soybean products and isoflavones to PCa risk, an inverse association for fish or polyunsaturated long chain (n - 3) fatty acids such as eicosapentaenic acid (EPA) and docosahexaenoic acid (DHA) with PCa risk, and a positive association of red meat or saturated fatty acids with PCa risk, respectively. In conclusion, although it is possible that the traditional Japanese diet may reduce the risk of PCa through a combination of characteristics such as being high in soybean products, high in fish, and low in red meat, further well-designed epidemiological studies such as nested case-control studies with nutritional analyses of blood samples are needed to confirm this association.

Ultrastructural, immunohistochemical and biochemical studies on amylase and ACTH producing lung cancer

Tumour tissue from a lung cancer patient who showed elevated serum amylase and adrenocorticotropin (ACTH) was studied ultrastructurally, immunohistochemically and biochemically. Histologically the tumour was a small cell carcinoma. On electron microscopic examination the tumour cells contained large zymogen-like granules within the cytoplasm. Furthermore, cells which possessed many small dense core granules of the endocrine type were also observed. It was of interest that the large zymogen-like granule-containing tumour cells had microvilli at the apical border, connected by desmosomes and forming lumina showing adenocarcinomatous differentiation. Electrophoretic analysis of the serum revealed that the major elevated amylase was of the salivary type with minor components. Immunostaining clearly demonstrated that most of the tumour cells possessed immunoreactive ACTH, whereas salivary amylase was only found in occasional clusters of the tumour cells. The results seem to indicate that the tumour showed both endocrine and exocrine characteristics - an amphicrine carcinoma, expressing amylase and ACTH simultaneously.

Relationship of hobby activities with mortality and frailty among community-dwelling elderly adults: results of a follow-up study in Japan.

Background The proportion of Japanese adults aged 65 years or older is predicted to increase; thus, it is becoming more important to identify factors that influence health status among elderly adults in Japan. We conducted a follow-up study of community-dwelling elderly adults to assess the relationship of hobby activities with mortality and incident frailty. Methods We randomly selected 3583 individuals aged 65 to 84 years from the residential registries of 7 study areas in Hokkaido, Japan in August 2007. Among them, 1955 (54.6%) returned completed questionnaires with written informed consent by mail. The baseline assessment questionnaire comprised questions on current and past involvement in hobby activities, self-perceived health status, smoking and drinking habits, and body height and weight. Questions on hobby activities were from 4 categories: solitary physical, group physical, solitary cultural, and group cultural activities. We later conducted a follow-up survey of the participants to ascertain all-cause mortality and incident frailty. A Cox proportional hazards model was used for analysis of data from September 2007 to May 2010. Results After adjusting for potential confounders, the risk of incident frailty among respondents participating in solitary physical activities was significantly lower than in those who did not participate in such activities (hazard ratio = 0.57; 95% CI 0.33, 0.99). Furthermore, the risk of incident frailty among respondents taking part in group cultural activities was significantly lower than in those who did not participate in such activities (0.41; 0.19, 0.87). Conclusions These findings may be important for programs that seek to promote good health among elderly adults.

Levels of blood and urine chemicals associated with longer duration of having arsenicosis in Bangladesh

Arsenicosis is presently one of the significant public health problems in Bangladesh. Employing household screening of over 3.6 million people living in 6 arsenic-affected Upzilas of Bangladesh, 1,503 arsenicosis patients were identified at first and then blood and urine were collected from some of them and analyzed through laboratory techniques. As the relation between blood and urine chemicals with duration of having arsenicosis (DHA) is not clear, this study presented all findings by shorter versus longer DHA. Complications namely chronic bronchitis, conjunctivitis/congestions, weakness, and wasting were common, with relatively higher rates in longer group. Logistic regression analysis – adjusted for age, sex, education, smoking, duration of drinking tube-well water, and whether any arsenicosis patients were in the family – indicated higher odds ratio (OR) of longer DHA (LDHA) in 3rd tertile with respect to GOT (OR = 2.12; 95%CI: 1.09 – 4.13), and blood glucose (OR = 2.00; 95%CI: 1.07 – 3.72) than 1st tertile. The OR of LDHA was significantly lower (OR = 0.48; 95%CI: 0.25 – 0.93) in 3rd tertile for triglycerides compared with 1st tertile. Albumin/globulin (A/G) ratio of 2nd tertile showed significantly lower OR of LDHA (OR = 0.51; 95%CI: 0.28 – 0.95) than 1st tertile. Further epidemiological investigations based on a large sample, through cohort or case – control studies, may be useful for validating and generalizing the results in Bangladesh.