Shoji Tokunaga

Relation between green tea consumption and the severity of coronary atherosclerosis among Japanese men and women

PURPOSE To examine the relation between green tea consumption and arteriographically determined coronary atherosclerosis. METHODS Study subjects were 512 patients (302 men and 210 women) aged 30 years or older who underwent coronary arteriography for the first time at four hospitals in Fukuoka City or one hospital in an adjacent city between September 1996 and August 1997. Lifestyle characteristics including green tea consumption were ascertained before arteriography by a questionnaire supported with interview. RESULTS 117 men (38.7%) and 50 women (23.8%) had significant stenosis of one or more coronary arteries. Green tea consumption tended to be inversely associated with coronary atherosclerosis in men, but not in women. An evident, protective association between green tea and coronary atherosclerosis was observed in a subgroup of 262 men excluding those under dietary or drug treatment for diabetes mellitus. In this subgroup, after adjustment for traditional coronary risk factors and coffee, odds ratios of significant stenosis for consumption of 2-3 cups and 4 or more cups per day were 0.5 (95% confidence interval 0.2-1.2) and 0.4 (0.2-0.9), respectively, as compared with a consumption of one cup per day or less. CONCLUSIONS The results indicate that green tea may be protective against coronary atherosclerosis at least in men.

Green Tea Consumption and Serum Lipids and Lipoproteins in a Population of Healthy Workers in Japan

PURPOSE To examine the relation between green tea consumption and serum lipids and lipoproteins. METHODS The subjects were 13,916 workers (8476 men and 5440 women) aged 40-69 years at over 1000 workplaces in Nagano prefecture, central Japan. They underwent health screening offered by a single medical institute between April 1995 and March 1996 and did not have morbid conditions affecting serum cholesterol levels. Serum concentrations of total cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides were measured at the screening. The consumption of green tea and other life-style characteristics were ascertained by a questionnaire. The data were analyzed with multivariate linear model. RESULTS Daily consumption of green tea was reported by 86.7% of subjects. Green tea consumption was, statistically, significantly associated with lower levels of serum total cholesterol in both men and women while its associations with serum triglycerides and HDL cholesterol were not statistically significant. The inverse association of serum total cholesterol with green tea consumption appeared to level off at the consumption of more than 10 cups/day. Excluding the outlying subjects drinking more than 10 cups/day (0.4%), the regression analysis adjusting for age, body mass index, ethanol intake, smoking habit, coffee intake, and type of work showed that daily consumption of one cup of green tea was associated with a reduction in serum total cholesterol by 0.015 mmol/L (95% confidence interval 0.006 to 0.024, p < 0.001) in men and 0.015 mmol/L (0.004 to 0.025, p < 0.01) in women. After additional adjustment for selected dietary factors, the inverse association remained statistically significant; one cup of green tea per day was associated with a reduction in serum total cholesterol by 0.010 mmol/L (0.001 to 0.019, p = 0.03) in men and 0.012 mmol/L (0.001 to 0.022, p = 0.03) in women. CONCLUSION Consumption of green tea was associated with lower serum concentration of total cholesterol in Japanese healthy workers age 40-69 years; however, green tea consumption was unrelated to serum HDL-cholesterol and triglycerides.

Intraductal Papillary Mucinous Neoplasms of the Pancreas With Distinct Pancreatic Ductal Adenocarcinomas Are Frequently of Gastric Subtype

Objective:To identify a high-risk group of patients with pancreatic ductal adenocarcinoma (PDAC), independently arising in the pancreas with intraductal papillary mucinous neoplasm (IPMN), using histopathologic subtypes. Background:Pathologic features of IPMN with distinct PDAC, including histopathologic subtypes of IPMN and PDAC phenotypes, have not been well characterized. Mucin expression patterns and the mutational status of GNAS and KRAS are useful to explore the relationship between these 2 lesion types. Methods:Clinicopathologic data of 179 resected IPMNs and 180 resected PDACs without IPMNs as a control group were reviewed. IPMNs were classified into 4 grades (low-grade, intermediate-grade, high-grade dysplasia, and an associated invasive carcinoma) and 4 subtypes (gastric, intestinal, pancreatobiliary, and oncocytic). The expression of MUC1, MUC2, MUC5AC, MUC6, and CDX2 was investigated by immunohistochemistry in IPMNs and PDACs with and without IPMNs. The mutational status of GNAS and KRAS was evaluated by cycle sequencing in PDACs and pre-/coexisting IPMNs. Results:Twenty-six synchronous or metachronous PDACs were identified in 20 patients (11.2%) with IPMNs. Occurrence of concomitant PDACs was more frequently observed in gastric-type IPMNs (18/110, 16.4%) compared with intestinal (1/49, 2.0%), pancreatobiliary (1/17, 5.9%), or oncocytic-type (0/3, 0%) (P = 0.047). Both PDACs with and without IPMNs were frequently positive for MUC1, MUC5AC, and MUC6 expression, as assessed by immunohistochemistry, but were negative for MUC2 and CDX2. The mucin-staining patterns were similar to those of invasive tubular adenocarcinoma arising from gastric-type IPMNs. Mutation of GNAS within codon 201 was not detected in PDACs and gastric-type IPMNs, whereas most of these exhibited KRAS mutations. However, the R201H GNAS mutation was detected in 1 intestinal-type IPMN with distinct PDAC. Conclusions:Mucin expression patterns demonstrate that PDAC without GNAS mutations of an aggressive phenotype frequently arise in the pancreas with benign gastric-type IPMN in the absence of GNAS mutations.

Leanness, Smoking, and Enhanced Oxidative DNA Damage

An increased risk of some forms of cancer, including lung cancer, among lean individuals has been consistent; however, there is a paucity of biological evidence supporting this relation. Subjects analyzed were 177 healthy Japanese workers who participated in a lifestyle intervention study. The levels of urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, were measured using an automated high-pressure liquid chromatography and urinary creatinine levels were adjusted for before statistical analysis. A clear inverse association was found between body mass index (BMI) and 8-OHdG levels among smokers [Pearson correlation coefficient (r) = −0.48], and the association did not materially change after adjustment for potential confounding factors. In contrast, no apparent relation was observed between BMI and 8-OHdG levels among nonsmokers (r = −0.12), although lean nonsmokers had a slightly higher mean of 8-OHdG levels compared with nonlean nonsmokers. The interaction of smoking and BMI reached statistical significance (P = 0.04). Leanness may enhance oxidative DNA damage induced by smoking and thus serve as a marker of host susceptibility to smoking-related cancers. (Cancer Epidemiol Biomarkers Prev 2006;15(3):582–5)

Long-term effects of polychlorinated biphenyls and dioxins on pregnancy outcomes in women affected by the Yusho incident.

Background Maternal exposure to polychlorinated biphenyls (PCBs) is associated with increased proportions of spontaneous abortion and stillbirth in animal studies. In Japan in 1968, accidental human exposure to rice oil contaminated with PCBs and other dioxin-related compounds, such as polychlorinated dibenzofurans (PCDFs), led to the development of what was later referred to as Yusho oil disease. Objective The aim of this study was to investigate the association of maternal PCB and dioxin exposure with adverse pregnancy outcomes in Yusho women. Methods In 2004, we interviewed 214 Yusho women (512 pregnancies) about their pregnancy outcomes over the past 36 years. Pregnancy outcomes included induced abortion, spontaneous abortion, preterm delivery, and pregnancy loss. Results In pregnancy years 1968–1977 (within the first 10 years after exposure), the proportions of induced abortion [odds ratio adjusted for age at delivery (ORadj) = 5.93; 95% confidence interval (CI), 2.21–15.91; two-tailed p < 0.001) and preterm delivery (ORadj = 5.70; 95% CI, 1.17–27.79; p = 0.03) were significantly increased compared with the proportions in pregnancy years 1958–1967 (10 years before the incident). Spontaneous abortion (ORadj = 2.09; 95% CI, 0.84–5.18), and pregnancy loss (ORadj = 2.11; 95% CI, 0.92–4.87) were more frequent (OR = 2.18; 95% CI, 1.02–4.66), but these were not significant (p = 0.11 and p = 0.08, respectively) in pregnancy years 1968–1977. We found no significant increases in the proportions of these adverse pregnancy outcomes in pregnancies occurring during 1978–1987 or 1988–2003 compared with those in pregnancies before 1968. Conclusion High levels of PCB/PCDF exposure had some adverse effects on pregnancy outcome in Yusho women.

Body mass index and oxidative DNA damage: A longitudinal study

Leanness has been shown to be related to an increased risk of some cancer forms, including lung cancer. However, biological evidence supporting a causal link between leanness and carcinogenesis is limited. The authors investigated longitudinally the association between body mass index (BMI) and levels of urinary 8‐hydroxydeoxyguanosine (8‐OHdG), a marker of oxidative DNA damage, using data from 174 healthy employees who participated in a lifestyle intervention study. 8‐OHdG levels were measured using automated high‐performance liquid chromatography and adjusted for urinary creatinine levels. Analysis of repeated measurements using a random effects model detected a statistically significant inverse association between BMI and 8‐OHdG levels (P = 0.003); one unit decrease in BMI was associated with a 2.7% (95% confidence interval 0.9–4.4) increase in 8‐OHdG levels. The association was pronounced among men consuming less than 20 cigarettes per day (8.8% increase per unit decrease in BMI) and among non‐smoking men (3.7% increase). The results based on a longitudinal observation suggest that weight loss is associated with increased oxidative DNA damage, a state presumably related to an increased risk of cancer. (Cancer Sci 2007; 98: 1254–1258)

Somatic symptoms most often associated with depression in an urban hospital medical setting in Japan

Somatic symptoms are known to be the major manifestation in patients with depression. The aim of the present study was to investigate the major somatic and psychiatric symptoms associated with depression in each sex. Patients with a DSM-IV diagnosis of depressive disorders (n=335) and comparison patients without depression (n=425) among new outpatients in an urban hospital medical setting were eligible for study. The relationship between the three most distressing subjective symptoms at the first visit, confirmed by the patients description on a health questionnaire and the admitting physicians interview, and depression was investigated in each sex. Most (77.4%) of the complaints in patients with depression were somatic. In a simple logistic regression analysis, diarrhea, excessive sweating and psychomotor retardation in men, and headache, depressed mood and grief in women were associated with depression. In multiple logistic regression analysis, diarrhea, excessive sweating and weight loss in men, and headache, dysesthesia and grief in women, as well as sleep disturbance, loss of appetite, general fatigue, loss of interest and agitation in both sexes, were statistically significantly associated with depression. Fever in men was also associated with depression by Fishers exact test.

N-myc downstream regulated gene-1/Cap43 may play an important role in malignant progression of prostate cancer, in its close association with E-cadherin

N-myc downstream regulated gene-1 (NDRG1)/Cap43 plays an important role in tumor progression and metastases in many kinds of cancers. Recently, it was reported that NDRG1/Cap43 is involved in the aggressiveness of prostate cancer and also that its expression is associated with the expression of E-cadherin in prostate carcinoma cell lines. In the current study, to elucidate the functional and pathologic roles of NDRG1/Cap43 in prostate cancer, we investigated whether the expression of NDRG1/Cap43 is associated with the clinicopathologic parameters of prostate cancer or E-cadherin expression. NDRG1/Cap43 expression and E-cadherin expression were examined immunohistochemically in 148 patients with prostate cancer. We investigated the correlation between membranous or cytoplasmic expression of NDRG1/Cap43 and E-cadherin and evaluated the prognostic or clinicopathologic significance of the expression of NDRG1/Cap43. The patients with decreased NDRG1/Cap43 membranous expression showed significantly lower disease-free survival rates compared with the patients with preserved NDRG1/Cap43 membranous expression. Decreased membranous and high cytoplasmic NDRG1/Cap43 expression was also correlated with a higher Gleason score. A significant correlation was observed between NDRG1/Cap43 membranous expression and E-cadherin membranous expression (r = 0.7130; P < .0001) and between NDRG1/Cap43 cytoplasmic expression and E-cadherin cytoplasmic expression (r = 0.5847; P < .0001). Decreased NDRG1/Cap43 membranous expression had a significant impact on patient disease-free survival in multivariate analysis (P = .0175). NDRG1/Cap43 could be a novel marker for malignant progression and poor prognosis in prostate cancer, plausibly in its close association with the down-regulation of E-cadherin expression.

Analysis of hospital charges for cerebral infarction stroke inpatients in Beijing, People's Republic of China

OBJECTIVE Stroke is a heavy economic burden on the individuals, society and health services in China, where health expenditure is rising rapidly. The purpose of the present study is to examine health services and demographic factors associated with inpatient charges for cerebral infarction in China, focusing on hospital charges of insured and uninsured patients. METHODS The study subjects were 545 patients with a principal diagnosis of cerebral infarction stroke who were discharged from the China-Japan Friendship Hospital from January 1, 1997 through December 31, 1998. Demographic, clinical and administrative data were retrospectively collected from the medical record and financial database. The influence of social and medical factors on total charges was analyzed with stepwise multiple regression model. RESULTS Of 545 subjects, 429 (79%) were the insured patients and 116 (21%) were the uninsured patients. Length of hospital stay (LOHS) for the insured patients (median, 32 days) was significantly longer (P<0.001) than that for the uninsured (median, 23 days). The hospital charges per discharge for the insured was significantly higher (geometric mean, 10407 yuan) (P<0.0001) than that for the uninsured patients (geometric mean, 5857 yuan). With stepwise multiple regression, factors associated independently with the hospital charge were: longer hospital stay, insurance status, increased number of head magnetic resonance imaging (MRI) and computerized tomography (CT), infection in hospital stay, and more severe condition of stroke. CONCLUSIONS Inpatient charge for cerebral infarction stroke was positively associated with being the insured. The findings suggest an overuse of health care resources in insured patients and limited use of resources by those who are not.

Temperature-Dependent Sex Determination in Gekko japonicus (Gekkonidae, Reptilia)

The effects of temperature on sexual differentiation in early development of the gekkonid lizard, Gekko japonicus were studied. The eggs were collected within 24 hr after the oviposition and were incubated at 20, 24, 28 and 32°C. The number of eggs hatched was 14 at 24°C, 20 at 28°C and 21 at 32°C. Hatching never occurred at 20°C. The hatched lizards without Müllerian ducts were judged as males. The sex of all lizards with Müllerian ducts were identified histologically. The sex ratios, male/(male+female), were 0.07 at 24°C, 0.75 at 28°C and 0.24 at 32°C. The disparities of the sex ratio from 1/2 were statistically significant and differences in the sex ratio with various incubation temperatures were also significant. These sex ratios can probably be best interpreted by a temperature‐dependent sex determination. The different sex ratios do not seem to be related to a predetermination of sex with a differential mortality.