Synthesis of optically active N-(2-pyridyloxiran-2-ylmethyl) benzenesulfonamide derivatives and their herbicidal activity.

Novel herbicidally active sulfonamide compounds having a 2-arylsubstituted oxiranylmethyl structure are racemates due to a chiral carbon in the oxirane moiety. To clarify the stereochemical structure-activity relationship, we synthesized each enantiomer of 4-chloro-N-[2-(6-chloropyridin-2-yl)-2-oxiran-2-ylmethyl]-3,N-dimethylbenzenesulfonamide and N-[2-(6-chloropyridin-2-yl)-2-oxiran-2-ylmethyl]-N-methyl-5,6,7,8-tetrahydronaphthalene-2-sulfonamide by chemical methods including Sharpless asymmetric chlorohydroxylation. The results of herbicidal tests indicated that the (S)-isomers were the active forms.

Coffee consumption and serum aminotransferases in middle-aged Japanese men.

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.

Practical asymmetric synthesis of (S)-MA20565, a wide-spectrum agricultural fungicide.

A practical asymmetric synthesis of a wide-spectrum agricultural fungicide, (S)-MA20565 (1), is described. The convergent synthesis was achieved starting from commercially available 3-(trifluoromethyl)aniline (7) in 44% overall yield through five steps and 2-bromobenzaldehyde (9) in 48% overall yield through four steps, respectively. (S)-O-[1-(3-Trifluoromethylphenyl)ethyl]hydroxylamine (2), a key intermediate of 1, was prepared via ruthenium(II)-catalyzed asymmetric transfer hydrogenation of 1-(3-trifluoromethylphenyl)ethanone (6) followed by chlorination using methanesulfonyl chloride and oxyamination using potassium acetohydroxamate with high level of stereocontrol.

Coffee drinking and serum gamma-glutamyltransferase: an extended study of Self-Defense Officials of Japan.

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.

Relationship of cigarette smoking, alcohol use, recreational exercise and obesity with serum lipid atherogenicity: a study of self-defense officials in Japan.

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.

Anticipation of job loss or job change and cardiovascular risk factors: a study of retiring self-defense officials in Japan.

Self-defense officials in Japan are to retire at the age of early 50s. This unique situation prompted the authors to investigate whether preexisting morbid conditions cause any difficulty in finding a post-retirement job and whether anticipation of job loss or job change, as measured by the status of post-retirement job and months remaining until retirement, was related to biological cardiovascular risk factors. The subjects were 2,228 male self-defense officials who received a preretirement health examination at three Self-Defense Forces Hospitals from 1991 to 1992; the period in time remaining until retirement ranged from 1-40 months (median 12 months), and 62% had one year or less until the retirement. The defined preexisting illnesses included a wide range of chronic, non-communicable diseases. Overall, the preexisting illness was unrelated to the determination of a post-retirement job. In men having 6 months or less until retirement, however, the security of post-retirement job was less frequent when they had the preexisting illness, especially cardiovascular diseases. In 1,839 men excluding those with the preexisting illness, the period until retirement was not adversely related to obesity, blood pressure, serum lipids, serum uric acid, or glucose intolerance whether the post-retirement job had been secured or not. The findings suggest that the preexisting illness decreases the chance of obtaining a post-retirement job, but do not provide any evidence that anticipation of job loss or job change due to early retirement exerts an adverse effect on biological cardiovascular risk factors.

Relation of total and beverage-specific alcohol intake to body mass index and waist-to-hip ratio: a study of self-defense officials in Japan.

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.

Relation of green tea consumption to serum lipids and lipoproteins in Japanese men.

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.

Changes in rat plasma-free fatty acid composition under oxidative stress induced by carbon tetrachloride: decrease of polyunsaturated fatty acids and increase of palmitoleic acid.

In order to measure the changes in antioxidant levels and the composition of plasma-free fatty acids resulting from oxidative stress, male Fisher rats were given a twice weekly subcutaneous injection of a 50% solution of carbon tetrachloride (CCl4) in corn oil for a period of 2 to 13 weeks. The dosage was 1.3 ml/kg of body weight. This treatment significantly suppressed the gain of body weight compared with control rats receiving the same dosage of corn oil. Liver weight of the two groups was similar while necrosis and hyperplasia of hepatocytes and liver fibrosis were observed in CCl4 treated rats. Increased levels of plasma glutamate-oxalacetate transaminase and glutamate-pyruvate transaminase were indicative that hepatocyte necrosis was induced by CCl4. Increased oxidative stress in CCl4 treated rats was indicated by a significant decrease of liver ascorbate and a decrease in the plasma ratio of polyunsaturated fatty acids (PUFA) to total free fatty acids. Interestingly, a significant increase of palmitoleic acid was observed in CCl4 treated rats, which may compensate for the loss of PUFA. The possibility of using the plasma composition of PUFA and palmitoleic acid as a marker of oxidative stress is discussed.

The relation of smoking, alcohol use and obesity to risk of sigmoid colon and rectal adenomas.

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.

Relationship of cigarette smoking, alcohol use, and dietary habits with sigmoid colon adenomas.

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.

Relation of waist-hip ratio to glucose tolerance, blood pressure, and serum lipids in middle-aged Japanese males.

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.

Gallstone disease among Japanese men in relation to obesity, glucose intolerance, exercise, alcohol use, and smoking.

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.

Fatherhood and distal adenomas of the large bowel: a study of male self-defense officials in Japan.

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.

Obesity and adenomatous polyps of the sigmoid colon.

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.

Prognostic significance of long ventricular pauses in athletes.

The long-term prognosis of athletes with long ventricular pauses has been unknown. In this study, thirty highly-trained cross-country skiers and 24 age-matched controls underwent 24 h Holter monitoring to detect the duration of the longest ventricular pause (LVP), and we followed the athletes for more than 3 years to evaluate prognostic significance of prolonged LVP. The LVPs of the athletes averaged 2.2 +/- 0.6 sec (range 1.3-3.4), which were significantly longer than those, 1.6 +/- 0.3 sec, of the controls. In the athletes, 20 cases (66.7%) had LVPs more than 2 sec, and 5 (16.7%) showed LVPs longer than 3 sec. During 3 years follow-up, no athletes had symptoms of near syncope, syncope or death under continued heavy training. Our study suggested that athlete with prolonged ventricular pause, even of 3 sec or more, did not have a different clinical risk than those without long pauses.

[A case of schwannoma of intrathoracic right phrenic nerve].

A 22-year old man was admitted because of an abnormal shadow on his chest X-ray film. Radiographic findings revealed that the tumor was located in the right middle mediastinum. At operation a smooth round tumor was found arising from the right phrenic nerve. The tumor was removed with phrenic nerve. Pathohistological examination revealed this tumor was benign schwannoma. Intrathoracic schwannoma usually arise from intercostal and sympathetic nerve and that arising from phrenic nerve is very rare. We removed the tumor by means of cutting his right phrenic nerve because of complete resection. Postoperatively he did well without any respiratory distress. And his respiratory function studies recovered normal 9 months after the operation. We think that schwannoma arising from phrenic nerve should be removed completely and in such a case cutting of the one side phrenic nerve is at ease if the patient have normal respiratory function.