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We previously reported that the intracutaneous injection of DNA vaccines encoding Helicobacter pylori heat shock proteins elicited specific immune responses, and led to reduced infection in mice. In this study, we constructed DNA vaccine encoding H. pylori-catalase (pcDNA3.1-kat) and investigated the immune responses to intranasal and intracutaneous administration of pcDNA3.1-kat. C57/BL6 mice were immunized intracutaneously with 10 microg of pcDNA3.1-kat or intranasally with 50 microg of pcDNA3.1-kat. Catalase-specific IgG antibody was detected in the sera of intranasal and intracutaneous immunized mice. Both intranasal and intracutaneous immunized mice were significantly protected from colonization by H. pylori and had significantly reduced degrees of gastritis. These results demonstrate that DNA vaccine encoding H. pylori-catalase can induce an immune response against H. pylori, and that intranasal immunization works as well as intracutaneous immunization.

Background/aim: Results of epidemiological studies concerning the association between smoking and alcohol use and gallstone risk are inconsistent. We examined the relation of smoking and alcohol use to gallstone disease in Japanese men., Methods: We investigated 174 cases having gallstones as determined by ultrasonography, 104 cases of postcholecystectomy state, and 6,906 controls having a normal gallbladder in the consecutive series of 7,637 men aged 48-59 years receiving a retirement health examination at four hospitals of the Self-Defense Forces from 1986 to 1994. Fifty men had been aware of having gallstones. Known gallstones and postcholecystectomy state were combined as known gallstone disease. Smoking and drinking habits were ascertained by a self-administered questionnaire. Statistical adjustment was made for body mass index, glucose tolerance status, Self-Defense Forces rank, hospital, and either cigarette smoking or alcohol use., Results: Cigarette smoking was not measurably associated with either prevalent gallstones or postcholecystectomy state, nor with either newly diagnosed gallstones or known gallstone disease. Alcohol use was related to a significant decrease in the prevalence odds of both gallstones and postcholecystectomy state, and the decrease was slightly more profound for known gallstone disease., Conclusions: Cigarette smoking is probably unrelated to the gallstone risk, and alcohol consumption seems to confer protection against gallstone formation., (Copyright 2002 S. Karger AG, Basel)

We investigated the relation between coffee drinking and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) concentrations among 7313 Japanese men receiving a health examination, excluding former alcohol drinkers and men with a history of chronic liver disease. Serum AST > 40 and/or ALT > 40 U/L was defined as liver inflammation. Adjustment was made for alcohol use, smoking, body mass index, serum marker for hepatitis virus infection, and other possible confounders. Adjusted odds ratios of liver inflammation were 1.00 (reference), 0.80, 0.69, and 0.61 for men drinking < 1, 1-2, 3-4, and > or = 5 cups of coffee daily, respectively. Among 6898 men without liver inflammation, serum AST and ALT were inversely associated with coffee consumption, and alcohol-related rise in AST was attenuated with coffee drinking. These findings suggest coffee may have an effect of suppressing the rise of serum aminotransferase, partly by inhibiting the alcohol-related elevation. Studies regarding biological mechanism are warranted.

Objective: At present, H. pylori homogenates, extracts and recombinant proteins are used as antigens in immunoassays, but significant false positive and negative results are obtained. We attempted to develop an ELISA system using immobilized whole intact H. pylori cells as a solid phase antigen (WIC-ELISA) which specifically recognizes surface antigens., Methods: Intact H. pylori cells were immobilized on ELISA plates by centrifugation (150 g for 10 min). HRP-labeled antihuman IgG was used as the second antibody. H. pylori-infections were investigated with WIC-ELISA and a conventional method in which H. pylori-extracts were used as antigen in 117 patients., Results: WIC-ELISA showed better characteristics than conventional ELISA in regards to sensitivity (98.9 vs. 90.4%), specificity (95.7 vs. 95.7%), positive predictive value (98.9 vs. 98.8%), negative predictive value (95.7 vs. 71.0%) and accuracy (98.3 vs. 91.5%)., Conclusions: WIC-ELISA is useful for quantification of antibodies against H. pylori surface antigens and as a clinical screening test.

Alcohol drinking as well as cigarette smoking has been associated with development of colorectal polyps, Asians such, as Japanese, Chinese and Korean have high frequency of genetic polymorphism in low Km aldehyde dehydrogenase (ALDH2) gene which greatly regulates alcohol intake. In the present study, we investigated associations of this polymorphism and lifestyles with colorectal polyps in self-defense forces personnels in Japan. All subjects received colonoscopy at a retirement health examination. The ALDH2 genotype was determined using polymerase chain reaction and restriction fragment length polymorphism method. Frequency of the ALDH2 genotype was not different between those with colorectal polyps (n=69) and those without the polyps (n=131). Smoking was associated with development of colorectal polyps (OR=4.7, 95% confidence interval=1.9-11.5) in the ALDH2 proficient genotype. The association appeared to be enhanced by drinking alcohol since a synergistic effect of smoking and alcohol drinking (> or =60 ml/day) was indicated (OR=9.9, 95% confidence interval=2.9-34.1) by logistic regression analysis. In the ALDH2 deficient genotype, however, we could not evaluate interactions of smoking and alcohol drinking on colorectal polyp development because of the small sample size of heavy alcohol drinkers. The genotype analysis would be useful in evaluating effects of environmental factors on outcomes for each genetically defined subpopulation.

We investigated the effect of DNA vaccines encoding H. pylori-heat shock protein A and B (pcDNA3.1-hspA and -hspB) on inducing immune responses against H. pylori in mice. C57BL/six mice aged 5 weeks were immunized by single injection of 10 microg of pcDNA3.1-hspA and pcDNA3.1-hspB into intracutaneous tissue. Plasmid DNA lacking the inserted hsp were injected as a control. Three months after vaccination, significant specific antibodies against H. pylori were detected by ELISA in the sera of vaccinated mice. Antibody isotypes were predominantly IgG2a (Th1-like) with pcDNA3.1-hspA and mixed IgG1/IgG2a (Th0-like) with pcDNA3.1-hspB. DNA vaccination dramatically suppressed colonies of bacteria in stomach of vaccinated mice (28,400 +/- 21,600/mm(2) for pcDNA3.1-hspA and 6800 +/- 3470/mm(2) for pcDNA3.1-hspB) compared to control mice (128,000 +/- 42,200/mm(2)). Histological analysis of the gastric mucosa demonstrated that the degree of gastritis was significantly lower in the vaccinated mice than in control mice. These results demonstrated that DNA vaccines encoding H. pylori-Hsp induce significant immune response against H. pylori to decrease gastric mucosal inflammation, indicating that a DNA vaccine can be a new approach against H. pylori in humans., (Copyright 2000 Academic Press.)

Subjective health and alcohol intake are important predictors of mortality. There have been few epidemiological studies, however, of the relationship between alcohol consumption and subjective health among the Japanese. The purpose of this study is to investigate the association between alcohol consumption and subjective health. The study subjects were 2,020 Japanese male employees, who were free from serious disease conditions. The data on subjective health and alcohol consumption were obtained by means of self-reported questionnaire. The subjects who responded "poor health" in the answer to the question about the subjective health status were considered to be in ill-health. Ethanol intake per day was calculated by multiplying the frequency of drinking by the ethanol intake per drinking occasion and summing up for each alcoholic beverage. Age, smoking status, physical activity, and sleeping hours were treated as confounding factors. As a result, subjects who consumed 25-36 or 49 g ethanol or more per day had a significantly lower risk of self-rated ill-health compared with those who had never drunk, and a significantly inverse trend was found independent of age, smoking status, physical activity, and sleeping hours. In conclusion, moderate drinkers have a lower risk of self-rated ill-health among Japanese male employees investigated.

Consumption of caffeine-rich beverages, which have diuretic properties, may decrease serum uric acid concentrations. We examined cross-sectionally the relationship of coffee and green tea consumption to serum uric acid concentrations in 2240 male self-defence officials who received a pre-retirement health examination at four hospitals of the Self-Defence Forces between 1993 and 1994. The mean levels of coffee and green tea consumption were 2.3 and 3.1 cups/d respectively. There was a clear inverse relationship between coffee consumption and serum uric acid concentration. When adjusted for hospital only, those consuming less than one cup of coffee daily had a mean serum uric acid concentration of 60 mg/l, while that of those drinking five or more cups of coffee daily was 56 mg/l (P < 0.0001). No such relationship was observed for green tea, another major dietary source of caffeine in Japan. The relationship between coffee consumption and serum uric acid concentration was independent of age, rank in the Self-Defence Forces, BMI, systolic blood pressure, serum creatinine, serum total cholesterol and serum HDL-cholesterol concentrations, smoking status, alcohol use, beer consumption and intake of dairy products. These findings suggest that coffee drinking may be associated with lower concentrations of serum uric acid, and further studies are needed to confirm the association.

Purpose: To examine the effect of coffee drinking on serum gamma-glutamyltransferase (GGT) level in relation to alcohol drinking, smoking, and degree of obesity in middle-aged Japanese men., Methods: From 1986 to 1994, a total of 7,637 male officials of the Self-Defense Forces of Japan aged 48-59 years received a preretirement health examination. Coffee drinking was ascertained by a self-administered questionnaire, and serum GGT level was measured. After excluding 1,360 men with a possible pathologic condition influencing liver enzyme levels and 182 former alcohol drinkers, effect of coffee drinking on serum GGT was examined by a multiple linear regression model and analysis of variance adjusting for alcohol drinking, smoking, and body mass index (BMI)., Results: The adjusted percentage of difference in serum GGT was -4.3 (95% CI = -5.0; -3.5) per cup of coffee. The inverse coffee-GGT relation was most prominent among men drinking > or = 30 ml of ethanol and smoking > or = 15 cigarettes daily; and positive associations of alcohol and smoking with GGT were attenuated by coffee drinking, more clearly among men with BMI > or = 25.00 kg/m2. Adjusted percentages of difference in serum GGT were -2.6% (p = 0.0003) per cup of brewed coffee, and -5.1% (p = 0.0001) per cup of instant coffee, independently of each other., Conclusions: The present study suggests that coffee consumption may weaken GGT-induction by alcohol, and possibly by smoking. These effect modifications by coffee may differ according to the degree of obesity.

Few studies have investigated the relation between glucose tolerance status and ultrasonographically determined gallstone disease. Using a 75-g oral glucose tolerance test, we examined the association of impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) with gallstone disease in Japanese men. Subjects were men aged 48 to 59 of the Japan Self-Defense Forces who received a preretirement health examination between October 1986 to December 1994. After exclusion of 12 men under insulin treatment in the consecutive series of 7637 men, 174 were found to have gallstones; 103 were at the state of postcholecystectomy, and 6899 had normal gallbladder. IGT and NIDDM were associated with a modestly increased risk of gallstone disease; adjusted odds ratios were 1.3 (95% confidence interval [CI]: 0.9-1.8) for IGT and 1.3 (95% CI: 0.8-2.0) for NIDDM after adjustment for hospital, rank, smoking, alcohol use, and body mass index. Adjusted odds ratio for IGT and NIDDM combined was 1.3 (95% CI: 1.0-1.7, p=0.08). When prevalent gallstones and postcholecystectomy were considered separately, NIDDM showed a significant, positive association with postcholecystectomy, but not with prevalent gallstones. The findings add to evidence that glucose intolerance is associated with a modest increase in the risk of gallstone disease.

Objective: To examine the relation of body mass index (BMI) and waist-to-hip ratio (WHR) to gallstones and postcholecystectomy risk in middle-aged Japanese men., Design: Cross-sectional study., Subjects: We used 174 men with prevalent gallstones, 104 with postcholecystectomy and 6909 with normal gallbladder in the consecutive series of 7637 men aged 48-59y receiving a preretirement health examination at four hospitals of the Japan Self-Defense Forces between 1986 and 1994., Measurements: Gallbladder status was assessed by abdominal ultrasonography after an overnight fast. BMI was calculated as weight in kilogram divided by height in square meters, and WHR was used as a measure of central obesity. Analysis of the WHR was limited to a subset of data for the period 1991-1994 (gallstones 113, postcholecystectomy 66 and normal gallbladder 4410)., Results: After adjustment for hospital, rank in the Self-Defense Forces, cigarette smoking, alcohol use and glucose tolerance, BMI was significantly associated with an increased risk of both prevalent gallstones and postcholecystectomy. WHR also showed a significant positive association with each of the two conditions. When BMI and WHR were mutually adjusted for, both of the obesity indices tended to be associated positively with prevalent gallstones and postcholecystectomy., Conclusion: These findings indicate that obesity is associated with increased gallstone risk in men.

Objective: The relationship between cholecystectomy and the occurrence of subsequent colon cancer has been controversial. Using data collected as part of an incident case-control study of colon cancer conducted in northern California, Minnesota, and Utah, we evaluated this association., Methods: Participants were between 30 and 79 yr of age and had a first primary colon cancer diagnosed between October 1, 1991 and September 30, 1994. Analyses were adjusted for age, gender, family history of colorectal cancer, body mass index, dietary energy and fiber intake, use of aspirin or nonsteroidal antiinflammatory drugs, and long-term leisure-time vigorous physical activity., Results: A weak positive association between cholecystectomy and proximal colon cancer (odds ratio [OR] and 95% confidence interval [CI] 1.3 [1.0-1.6]) was observed. This was counterbalanced by a weak, nonsignificant negative association (OR 0.8, 95% CI 0.6-1.1) with distal colon cancer leading to no overall association (OR 1.0, 95% CI 0.9-1.2). The association between colon cancer and cholecystectomy did not differ by gender or race, but it did differ by study area, with most of the increased association being attributed to the Minnesota population. The elevated risk of proximal colon cancer increased after cholecystectomy but disappeared after 14 years., Conclusions: Our results suggest that cholecystectomy or the underlying gallstone disease that prompts it may be related weakly to the risk of subsequent proximal colon cancer. However, the association may differ by geographic area of the country, and may be artifactual at least in part.

The study aims to examine the relationship between habitual coffee consumption and blood pressure. The subjects were 3336 male self-defense officials aged 48-56 years, who received a preretirement health examination at the Self-Defense Forces Fukuoka Hospital between October 1986 and December 1992. Average coffee intake in the past year was ascertained by a self-administered questionnaire. A significant inverse relation between habitual coffee consumption and blood pressure was found with and without adjustment for alcohol use, cigarette smoking, body mass index, glucose tolerance, and green tea intake. Green tea, another major source of caffeine intake in Japanese, was unrelated to blood pressure. The adjusted mean differences per cup of coffee consumed per day were -0.6 mmHg (95% confident interval [CI]: -0.9 to -0.3, p = 0.0001) in systolic blood pressure and -0.4 mmHg (95% CI: -0.5 to -0.2, p = 0.0002) in diastolic blood pressure. Habitual coffee drinkers had lower blood pressure than non-drinkers at any levels of alcohol use, cigarette smoking, obesity, and glucose intolerance. Our findings consolidate the previous observation that habitual coffee consumption was associated with lower blood pressure.

We investigated the relationship of cigarette smoking, alcohol use, recreational exercise and obesity with serum lipid atherogenicity because of paucity of epidemiological studies. The subjects were 2,228 male officials of the Self-Defense Forces in Japan, who were aged 49-55 years and received a preretirement health examination in the period from 1991 to 1992. A self-administered questionnaire was used to ascertain cigarette smoking, alcohol use and recreational exercise. Serum total cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C) were increased with increasing levels of body mass index (BMI) and waist-to-hip ratio (WHR), and decreased with increasing levels of cigarette smoking and alcohol use. Serum high-density-lipoprotein cholesterol (HDL-C) was positively associated with alcohol use and recreational exercise, and negatively associated with cigarette smoking, BMI and WHR. BMI and alcohol use were most strongly associated with both LDL-C/HDL-C and TC/HDL-C ratios with BMI in an atherogenic direction and alcohol use in an antiatherogenic direction. Recreational exercise was weakly associated with less atherogenic lipid profile. BMI was the strongest determinant of serum lipid atherogenicity whereas alcohol use was most antiatherogenic. WHR was less important than BMI in the determination of serum lipid atherogenicity in Japanese men.

Objectives: The purpose was to investigate the relation between glucose tolerance and risk of sigmoid colon adenomas, a well-established precancerous lesion, in Japanese men., Methods: In the consecutive series of 7,637 men aged 48 to 59 years who received a preretirement health examination at four hospitals of the Self Defense Forces (SDF) in Japan from 1986 to 1994, we identified 821 cases of sigmoid colon adenomas and 4,372 controls with normal sigmoidoscopy or colonoscopy at 60 cm or more from the anus. Glucose tolerance status was classified as normal, impaired glucose tolerance (IGT), newly diagnosed non-insulin dependent diabetes mellitus (NIDDM), or diabetes mellitus under treatment, based on a 75g oral glucose tolerance test and medical history. Statistical adjustment was made for body mass index (wt/ht2), cigarette smoking, alcohol use, rank of the SDF, and hospital., Results: Modest increases in adenoma risk were observed for newly diagnosed NIDDM and diabetes mellitus under treatment while there was no association between IGT and adenoma risk. When small (< 5 mm in diameter) and large (5+ mm) adenomas were analyzed separately, increased risk associated with newly diagnosed NIDDM was more pronounced for small adenomas, and diabetes mellitus under treatment showed a slightly stronger association with large adenomas., Conclusions: The findings suggest that NIDDM is associated with modestly increased risk of sigmoid colon adenomas, and add to evidence that hyperinsulinemia increases colon cancer risk.

We investigated the independent associations of total and beverage-specific ethanol consumption with body mass index (BMI) and waist-to-hip ratio (WHR) in middle-aged Japanese males, because of the scarcity of epidemiologic data in Japan. The subjects were 2227 male self-defense officials who received a pre-retirement health examination at the Self-Defense Forces Fukuoka, Kumamoto, and Sapporo Hospitals. Data on alcohol intake, smoking, physical activity, and past medical history were obtained from a self-reported questionnaire. Height, weight, and waist and hip girth measurements were obtained at the examination. Multiple linear regression analysis was employed. Alcohol intake was positively and strongly associated with WHR (p = 0.0001), but not associated with BMI after adjustment for lifestyle variables, including either BMI or WHR. Subjects who consumed 15 ml per day or more of shochu ethanol showed a larger WHR than never drinkers, and a dose-response relationship was found. Dose-response relationships to other beverages were not found. Dose-response relationships to other beverages were not found. These findings suggest that alcohol intake is strongly and independently associated with WHR, but not with BMI. Abdominal obesity was positively associated with shochu ethanol, but not with other types of alcohol.

Objective: To investigate the independent effect of weight change in young adulthood on the risk of prevalent NIDDM among middle-aged Japanese men., Research Design and Methods: A case-control study was carried out in 895 male employees aged > or = 30 years of a railway company located in the vicinity of Tokyo. Adjusted odds ratios (ORs) were calculated for prevalent diabetes in each category of weight change (obtained from subjects' medical records) in young adulthood and adulthood. Adjustment for current age, initial BMI, and weight change in each age stratum was performed by the Mantel-Haenszel method or multiple logistic regression analysis., Results: Weight change between 20 years of age and the age at maximum weight was not associated with the risk of NIDDM. Weight gain between 20 and 25 years of age was significantly and positively associated with the risk of NIDDM (OR 3.87 for gains > or = 10.0 kg, 2.53 for gains of 5.0-9.9%, and 3.73 for gains > or = 10.0%). On the other hand, moderate weight gain after 30 years of age was significantly inversely associated with NIDDM (OR 0.44 for gains of 5.0-9.9 kg, 0.15 for gains of 10.0-19.9%, and 0.38 for gains of 20.0-29.9%)., Conclusions: Extreme weight gain between 20 and 25 years of age is a significant predictor of NIDDM, independent of current age, BMI at 20 years of age, and weight change within other age strata.

Animal experiments have shown a hypocholesterolemic effect of green tea extracts. Only few epidemiological studies have addressed the relation between green tea consumption and serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C). This paper examined the relation of green tea consumption to serum lipids and lipoproteins in 2,062 male self-defense officials in Japan, aged 49-55 years, who received a preretirement health examination at three hospitals of the Self-Defense Forces in 1991-1992. A self-administered questionnaire queried the consumption of green tea and a limited number of other dietary items as well as lifestyle characteristics. After adjustment for body mass index, waist-hip ratio, smoking, alcohol use, exercise, rank, and hospital, green tea consumption was inversely associated with serum levels of TC and LDL-C, but not with either high density lipoprotein cholesterol or triglycerides. Rice consumption was positively correlated with green tea consumption, and also was associated independently with lower levels of TC and LDL-C. Additional adjustment for rice, however, did not change the results. Daily drinking of 10 cups of green tea was associated with differences of 6.2 mg/dl in TC (95% confidence interval [CI] 0.4-12.1) and 6.2 mg/dl in LDL-C (95% CI 0.7-11.7). These findings of association of green tea with blood cholesterol hint at a possible causal relationship, which requires confirmation by further studies in humans using different methods.

The relationship between cigarette smoking, alcohol use, and dietary factors and the risk of adenomas of the sigmoid colon was examined in male self-defense officials who received a preretirement health examination at three Self-Defense Forces hospitals in Japan. In the comparison between 228 patients with sigmoid adenomas and 1484 control subjects with normal colonoscopy findings (> or = 60 cm from the anus), a clear dose-response relationship was observed between cigarette smoking and risk of adenoma. After adjustment for rank, body mass index, alcohol use, and physical activity as well as for hospital and survey season, the odds ratios (and 95% confidence intervals (CIs)) for the categories of 0, 1 to 399, 400 to 799, and 800 or more cigarette-years were 1.0, 2.1 (1.2 to 3.5), 2.8 (1.8 to 4.3), and 3.5 (2.1 to 5.8), respectively. Current alcohol drinkers tended to have an increased risk, but without a dose-response relation. Among four types of alcoholic beverages (shochu, sake, beer, and whiskey), only whiskey showed a weak association with risk of adenoma. None of the 13 dietary items studied (including meat and rice consumption) was measurably associated with adenoma risk. The present findings provide additional evidence that cigarette smoking is a risk factor for colon adenomas. It is inconclusive regarding alcohol intake's association with adenoma risk.

We conducted a case-control study, using 429 cases with histologically confirmed sigmoid adenoma, 75 cases with rectal adenoma, and 3101 controls showing normal colonoscopy at least up to 60 cm from the anus. The subjects were male Self-Defense Forces personnel aged 48-56 who received a retirement health examination including a routine sigmoid- or colonoscopy. Lifestyle characteristics were ascertained by a self-administered questionnaire. Smoking in the recent past (< or = 10 years preceding the colonoscopy) and smoking in the remote past (> 10 years before the colonoscopy) were both significantly associated with risk of sigmoid adenoma but not with rectal adenoma as a whole. After reciprocal adjustment for smoking in the two periods, only smoking in the recent past was associated with both sigmoid colon and rectal adenomas. Odds ratios (OR) of sigmoid adenoma (and 95% confidence interval) for the categories of 0, 1-150, 151-250 and > or = 251 cigarette-years were 1.0 (reference), 1.9 (1.3-2.8), 2.1 (1.4-3.0) and 3.0 (1.9-4.7), respectively (P for trend < 0.01), and those for rectal adenoma were 1.0 (reference), 1.2 (0.4 3.2), 3.5 (1.4-8.5) and 2.0 (0.6 6.7), respectively (P for trend = 0.03). Alcohol use was significantly positively associated with sigmoid adenoma, and insignificantly associated with rectal adenoma. Body mass index was significantly positively associated with sigmoid adenoma, especially large ones. No such association was found for rectal adenoma. These findings suggest that smoking, especially in the recent past, and alcohol use are common risk factors for sigmoid colon and rectal adenomas while obesity may be exclusively related to the growth of sigmoid adenoma.

Objective: To investigate whether waist-hip ratio (WHR) influences glucose tolerance, blood pressure, and serum lipids independently of body mass index (BMI)., Design: Cross-sectional study., Subjects: 2,228 male self-defense officials aged 49-55 years in Japan., Measurements: BMI, WHR, serum lipids, systolic and diastolic blood pressure, and glucose tolerance status according to World Health Organization (WHO) criteria., Results: Adjustment was made for smoking, alcohol use, physical activity, and inter-hospital variation in statistical analysis. Adjusted odds ratios of non-insulin-dependent diabetes mellitus (NIDDM) were progressively increased with increasing levels of WHR, but not BMI. Both BMI and WHR were independently positively associated with impaired glucose tolerance to almost the same degree. Adjusted means of blood pressure, total cholesterol, and triglycerides were almost linearly increased with increasing levels of both BMI and WHR, and high-density lipoprotein cholesterol was progressively decreased. Although the associations of BMI and WHR with blood pressure and serum lipids attenuated after mutual adjustment for each, BMI was less influenced by WHR than vice versa, except for triglycerides., Conclusion: WHR is an important contributor not only to NIDDM but also to impaired glucose tolerance, blood pressure, and serum lipids, although the associations of WHR with blood pressure and serum lipids were generally weaker than those of BMI, except for triglycerides.

Background: Risk factors for gallstones are not fully understood, especially in men. Obesity and other risk factors for gallstone disease were investigated in Japanese men based on gallbladder ultrasonography., Methods: Forty-one men with gallstones, 31 with postcholecystectomy state, and 2044 with a normal gallbladder were identified among 2228 men aged 49-55 years who received a retirement health examination at three hospitals of the Japan Self-Defense Forces between 1991 and 1992. Glucose tolerance was determined with a 75-g oral glucose tolerance test., Results: Body mass index was not associated with gallstones, although it was significantly, positively related to postcholecystectomy. Waist to hip circumference ratio tended to be weakly associated with gallstones. Diabetes mellitus was associated only with postcholecystectomy. Smoking, alcohol intake, and physical activity were not measurably related to either gallstones or postcholecystectomy., Conclusions: The present study failed to substantiate an association of gallstone risk with either obesity or any other risk factor. Further observation is needed in view of the limited study power.

Parity has been studied extensively as a risk factor for colorectal cancer but has not been definitively shown to be associated with altered risk. In a few studies, risk of colorectal cancer in childless men has been compared to risk in men with children, but results have not been consistent. We analyzed the association of fatherhood with risk of colorectal adenomas in male self-defense officials (ages 49-55) in Japan. The study participants received a preretirement health examination including flexible sigmoidoscopy at Self-Defense Forces hospitals in Japan from January 1991 through December 1992. The examinations identified 265 cases with rectal or sigmoid adenomas and 1480 controls with normal examinations up to 60 cm from the anus. Data on marital status, number of children, long-term work assignment away from wife and children, and other lifestyle variables were obtained by means of a self-administered questionnaire prior to physical examination. Multiple logistic regression analysis assessed the risk of adenomas in relation to number of children, marital status, long-term work assignment away from family, and military rank, with adjustment for cigarette smoking, alcohol intake, dietary variables, body mass index, and recreational physical activity. In this relatively homogeneous group, more than 98% of both cases and controls were currently married, and more than 93% had children. The adjusted odds ratio for the association of adenomas with fatherhood was 0.4 (95% confidence interval, 0.2-0.8). Marital status and work assignment away from the family were not associated with adenoma risk. These findings suggest that colorectal adenomas and perhaps cancer risk may be associated with childlessness in men.

The relationship of smoking, alcohol use, body mass index, and physical activity to glucose tolerance was studied in 2407 male self-defense officials aged 49-56 years who received a health examination before retirement at the Self-Defense Forces Fukuoka Hospital from October 1986 to December 1990. Body mass index (BMI) was significantly, positively related to impaired glucose tolerance (IGT) and noninsulin-dependent diabetes mellitus (NIDDM); after adjustment for rank of the Self-Defense Forces, smoking, alcohol use, prior diagnosis of diabetes mellitus, and parental history of the disease, odds ratios (ORs) of IGT and NIDDM for the highest (> or = 25.5 kg/m2) versus lowest (< 21.6 kg/m2) quintile of BMI were 4.2 [95% confidence interval (CI) 2.6-6.8] and 4.6 (95% CI 2.3-9.3), respectively. Cigarette smoking was weakly, positively associated with IGT and strongly so with NIDDM; adjusted ORs of IGT and NIDDM for 800 cigarette-years or more versus never smoking were 1.6 (95% CI 1.1-2.5) and 4.1 (95% CI 1.8-9.3), respectively. The prevalence of IGT and NIDDM tended to be decreased among men with high physical activity as measured by the time spent for vigorous exercise in leisure time. There was virtually no association between alcohol consumption and either IGT or NIDDM. The findings suggest that obesity and cigarette smoking are important factors in the development of glucose intolerance in middle-aged Japanese men.

Background: In Japan epidemiological data on correlates of serum uric acid are sparse., Methods: Behavioural and biological correlates of serum uric acid were investigated in 2487 men who received a retirement health examination at the Self-Defence Forces Fukuoka Hospital from October 1986 through 1990, excluding those under medication for hyperuricaemia, hypertension or hyperlipidaemia., Results: Multiple regression analysis demonstrated that serum creatinine was the strongest correlate followed by serum triglycerides, body mass index and diastolic blood pressure; these four variables accounted for 16% of the overall variation in serum uric acid. Serum total cholesterol, alcohol intake and past smoking were positively associated with serum uric acid levels while diabetes mellitus and serum high density lipoprotein (HDL) cholesterol were negatively related to serum uric acid; these five variables additionally explained 2% of the variation. Although an independent impact was minimal, beer consumption was significantly associated with an elevated level of serum uric acid after allowing for the previously mentioned correlates., Conclusions: Serum creatinine and triglycerides are major correlates of serum uric acid in Japanese men. Our data add to the body of evidence suggesting that weight control, avoiding excessive drinking and adequate control of hypertension are beneficial in the prevention of hyperuricaemia.

The relation between obesity and adenomatous polyps of the sigmoid colon was investigated in male self-defense officials who received a retirement health examination at three hospitals of the Self-Defense Forces in Japan between January 1991 and December 1992. Body mass index (BMI) and waist-hip circumference ratio (WHR) were used as indices of obesity. A total of 228 adenoma cases and 1484 controls with normal sigmoidoscopy were identified in 2228 men: cases having small adenomas (< 5 mm in diameter) and those with large adenomas (5 mm or greater) numbered 115 and 102, respectively. Smoking, alcohol use, physical activity, rank, and hospital were controlled for by multiple logistic regression analysis. BMI and WHR were classified into four levels using the 30th, 60th, and 90th percentiles of each distribution in the control as cut-off points. There was a significant two-fold elevation in the overall adenoma risk among men at the highest BMI level (> or = 26.95) compared with those at the lowest level (< 22.48), but the risk did not linearly increase: a similar increase was also noted for large adenomas. While WHR was only weakly related to the overall adenoma risk, the risk of large adenomas progressively increased with increasing levels of WHR; odds ratio (OR) 2.9 (95% confidence interval (CI) 1.4-5.9) for the highest (> or = 0.958) versus lowest (< 0.878) levels. BMI was not materially associated with adenoma risk after additional adjustment for WHR, but a positive association between WHR and large adenomas was independent of BMI: OR 3.4 (95% CI 1.5-7.6) for the highest versus lowest levels. These findings suggest that obesity is associated with an increased risk of colon adenomas, probably with adenoma growth.

The relation of coffee drinking and other behavioral factors to serum gamma-glutamyltransferase (GGT) was examined in 2,494 male self-defense officials aged 48-56 years, who received a retirement health examination at the Self-Defense Forces Fukuoka Hospital between October 1986 and December 1990. Coffee, but not green tea, consumption was inversely related to serum GGT independently of body mass index, alcohol use, and smoking. All of the latter variables were also independently and positively associated with serum GGT. Lower levels of serum GGT associated with coffee drinking were more evident among heavier alcohol drinkers and also among heavier smokers. The findings suggest that coffee may inhibit the inducing effects of alcohol and possibly of smoking upon GGT in the liver.

Effect of azelastine on the induction of Dermatophagoides farinae (Df)-antigen specific IL-2 responsiveness of the lymphocytes was examined. Azelastine suppressed the induction of IL-2 responsiveness induced by Df antigen in peripheral blood mononuclear cells from patients with bronchial asthma in a dose dependent manner. Azelastine suppressed antigen presenting adherent cells but not non-adherent responder cells (T cell rich fraction). The antigen specific IL-2 responsiveness induced by purified protein derivative (PPD) in healthy adults was also suppressed by this drug, but not by concanavalin A (Con A). These data suggest that Azelastine suppresses the antigen specific lymphocyte reactions, and that these effects are based on the weak suppressive effect on antigen presenting and/or processing pathway.