Effect of carcinogens on chicken atherosclerosis.

Weekly i.m. injections of the polycyclic hydrocarbon carcinogens, 7,12-dimethylbenz(a,h)anthracene (DMBA; 25 mg/kg/injection) and benzo(a)pyrene (50 mg/kg/injection) were given for a period of up to 22 weeks to chickens (SC strain) beginning at age 4 weeks. Atherosclerotic lesions of the abdominal aorta occurred more frequently and were larger in the DMBA- and benzo(a)pyrene-treated birds than in controls. These lesions were proliferative in character as indicated by a higher [3H]thymidine autoradiographic labeling index compared to the underlying medial cells of the aorta. Measurements of serum cholesterol in DMBA-treated birds showed no differences from controls. Although both carcinogens accelerated the development of atherosclerotic plaques, DMBA was more potent than benzo(a)pyrene.

Enhancement of diethylnitrosamine hepatocarcinogenesis in rats by exposure to polychlorinated biphenyls or phenobarbital.

Diethylnitrosamine (DENA) hepatocarcinogenesis was enhanced by sequential exposure with polychlorinated biphenyls (PCBs) and with phenobarbital. This was shown by the earlier appearance of tumors and a significant increase in the number of tumors. However, there was no evidence suggesting an acceleration of tumor growth.

Enhancing effect of 2,3,4,7,8-pentachlorodibenzofuran and 1,2,3,4,7,8-hexachlorodibenzofuran on diethylnitrosamine hepatocarcinogenesis in rats.

Enhancement of diethylnitrosamine(DENA)-induced hepatic tumor production in rats was observed by sequential exposure to 2,3,4,7,8-pentachlorodibenzofuran (PenCDF) or 1,2,3,4,7,8-hexachlorodibenzofuran (HCDF). This effect was more evident in the group of rats treated with 2,3,4,7,8-PenCDF (80 micrograms/rat), in which approximately 43% of this compound administered was accumulated in the liver at 8 weeks after the last treatment.

Alcohol and mortality: a cohort study of male Japanese physicians.

The relationship between drinking habit surveyed in 1965 and cause-specific mortality over 19 years was investigated in 5135 male Japanese physicians taking into account smoking habit and separating ex-drinker from non-drinker. As compared with non-drinkers, daily drinkers with high consumption had a significantly increased mortality from all causes. Drinking was significantly related to the so-called alcohol-related causes of death; upper aerodigestive cancer, liver cancer and liver cirrhosis. Mortality from acute myocardial infarction was inversely related to drinking, whereas other coronary heart disease showed a somewhat higher mortality among men consuming a large amount of alcohol than among non-drinkers. There was a weak, but significant, association between stroke and drinking, and the relation did not differ between haemorrhagic stroke and other stroke. No obvious relationship with drinking was observed for cancers of the stomach, large bowel, pancreas and lung.

The relationship between alcohol and mortality among Japanese physicians.

Based on the survey in 1965 on smoking and drinking habits of physicians in western Japan, the mortality pattern among 5139 male Japanese physicians over 12.7 years was examined in terms of drinking habit. Among six groups with different drinking habits: ex-drinker, non-drinker, occasional drinker and daily drinker whose intake of alcohol was equivalent to below 1, 1-1.9 or 2 and more go of sake (1 go of sake congruent to 27 ml of alcohol), ex-drinkers had the highest risk of dying. Mortality from all causes among non-drinkers was higher than that among occasional drinkers or the lowest daily drinkers, but the differences were not significant. Among daily drinkers, total mortality was significantly increased with the amount of alcohol. As for cause-specific mortality, cancer and stroke showed a significant positive association with alcohol. No significant inverse relationship was noted for heart disease or coronary heart disease, although non-drinkers had higher mortality than occasional or daily drinkers. There was no obvious effect of alcohol on mortality from either liver cirrhosis or accidents, but deaths from these causes were few.

Smoking and mortalities from cancer, coronary heart disease and stroke in male Japanese physicians.

A cohort of 5,477 male Japanese physicians was studied to examine the relationship between smoking habits and mortalities from cancer, coronary heart disease (CHD) and stroke over 12.7 years. The logistic regression analysis based on proportional hazard models was used for statistical assessment. The risks of both lung cancer and CHD were strongly associated with smoking habits in terms of the number of cigarettes smoked per day, inhalation level and age at starting to smoke. These associations were not influenced by the effect of drinking habits. However, the risk increment of lung cancer due to cigarette smoking was fairly small as compared with the data from other studies of male Caucasians. A statistically significant association was observed between upper aerodigestive cancer and cigarette smoking. But this relationship became insignificant after adjustment for drinking habits, and the risk of heavy smokers was drastically reduced. No clear association was noted between smoking and mortalities from gastric cancer and stroke.

Alcohol and cancer in male Japanese physicians.

The relationship between alcohol and site-specific cancers was investigated in a follow-up study of 5,139 male Japanese physicians. Information on drinking habits was obtained by mail questionnaire in 1965, and cancer deaths over 12.7 years were analyzed with drinking habits classified into five categories; nondrinker, ex-drinker, occasional drinker, and daily drinker whose intake of alcohol was equivalent to less than 2 or 2 and more go of sake (1 go sake congruent to 27 ml alcohol). Both age and smoking habits were taken into account in the calculation of death rates based on man-years at risk. Logistic regression analysis was also performed on cummulative mortality data. Upper aerodigestive cancer was strongly associated with alcohol consumption, giving some confidence in the validity of the present study. Excluding ex-drinkers, the risk of stomach cancer and liver cancer was gradually increased from nondrinkers to daily drinkers with lower intake of alcohol, but no further increase was noted for daily drinkers with larger consumption. Logistic regression did not show any significant associations between drinking habits and these two cancers, but the number of deaths from liver cancer was still small. Not particular patterns were observed for cancers of the large bowel and lung.

Decreased skeletal muscle capillary density is related to higher serum levels of low-density lipoprotein cholesterol and apolipoprotein B in men.

The relationships between skeletal muscle morphology, particularly muscle fiber capillary density, and serum lipid profiles were evaluated in 25 non-obese men aged 18 to 36 years (body mass index [BMI], 22.7 +/- 2.5 kg/m2; body fat, 13.6% +/- 4.0%, maximal oxygen uptake [VO2max], 46.2 < or = 6.3 mL/kg/min). Skeletal muscle samples were taken from the vastus lateralis using the needle-biopsy method. The fiber types (I, IIa, and IIx) and their percent distribution, the indices of capillary density, and the diffusion index expressed as the cross-sectional area occupied by one capillary were determined. Blood samples were drawn from the antecubital vein after a 12-hour fast. Based on Pearson's correlation analysis, the number of capillaries around type IIx fiber correlated inversely with the serum level of low-density lipoprotein cholesterol ([LDL-C] r = -.50, P < .05). The number of capillaries per fiber (cap/fiber ratio), number of capillaries per area (cap/mm2), and capillaries around each fiber type correlated inversely with the serum level of apolipoprotein B ([apo B] r = -.40 to -.54, P < .05 to .01). Further, the diffusion index for each fiber type correlated positively with LDL-C and apo B (r = .42 to .50, P < .05 to .01). Among 14 subjects in whom high-density lipoprotein cholesterol (HDL-C) subfractions were analyzed, a positive correlation was found between cap/mm2 and HDL2-C (r = .64, P < .05). Partial correlation analysis showed that these correlations either remain or improve after adjusting for age, VO2max, and body fatness. These results indicate that skeletal muscle capillary density and diffusion capacity are related to lipid and apolipoprotein concentrations for both type I and type II fibers.

The relationships of testosterone, estradiol, dehydroepiandrosterone-sulfate and sex hormone-binding globulin to lipid and glucose metabolism in healthy men.

We investigated the relationships of plasma sex hormones (free testosterone; free T, estradiol; E2 dehydroepiandrosterone-sulfate; DHEA-S) and sex hormone-binding globulin (SHBG) levels to lipid and glucose metabolism cross-sectionally in 212 apparently healthy men aged from 18 to 59 years. A multiple linear regression analysis for lipid and glucose parameters with age, body mass index (BMI), percent body fat (%fat), waist to hip ratio (WHR), estimated maximal oxygen uptake (VO2max), alcohol and cigarette consumption, sex hormones, and SHBG, respectively, as independent variables, was performed. DHEA-S was indicated as one of the independent predictors of both high density lipoprotein cholesterol (HDL-C), with a positive relation, and of triglyceride and total cholesterol/HDL-C ratio, with a negative relation, while SHBG was one of the predictors of both HDL-C, with a positive relation, and of fasting insulin, with a negative relation. The E2 level was found to be negatively related to both low density lipoprotein cholesterol and fasting blood glucose. These findings thus suggest that the higher levels of SHBG, DHEA-S and E2 within physiological ranges in healthy men may partially help to maintain a desirable profile of the plasma lipid and glucose metabolism.

Impaired non-insulin mediated glucose uptake after downhill running in rats.

To evaluate the effects of a single bout of exercise on non-insulin mediated glucose uptake in rats, hyperglycemic clamp tests were performed either 12 h after the rats were subjected to downhill running (90 min, -16 degrees incline, n = 10) or without any prior exercise (n = 10). Somatostatin (1.0 microgram/kg/min) was infused during clamps to suppress insulin secretion, while the serum glucose was clamped at a level of 200 mg/dl for 100 min. The serum insulin levels during the hyperglycemic clamp was maintained at basal levels. The non-insulin mediated glucose disposal rate was significantly decreased during clamp performed after downhill running (5.45 +/- 0.61 mg/kg/min) compared to the control conditions (9.63 +/- 0.32 mg/kg/min, P < 0.01). The creatine kinase level after downhill running (561 +/- 206 IU/l) was significantly higher than the control conditions (118 +/- 20 IU/l, P < 0.01). These results thus suggest that the muscle damage caused by downhill exercise, which predominantly consists of eccentric type, may therefore decrease the non-insulin mediated glucose uptake.

Risk of developing hepatocellular carcinoma according to the titer of antibody to hepatitis C virus.

BACKGROUND/AIMS: Hepatitis C virus infection has been reported to be one of the main risk factor for developing hepatocellular carcinoma in Japan. The aim of the study was to examine the differences in the risk of developing hepatocellular carcinoma according to the titer of antibody to HCV. METHODOLOGY: A total of 13,173 inhabitants had their titers of anti-HCV examined based on a second generation passive hemagglutination assay, and we thus found 1,758 inhabitants whose anti-HCV titers were equal to or above 2(5). After carefully comparing our findings with the list of hepatocellular carcinoma in the Saga Prefectural Cancer Registry, we ascertained 45 cases of hepatocellular carcinoma (males 37, females 8). The logistic regression model was used to estimate the Odds ratio of risk factors for hepatocellular carcinoma. RESULTS: The risk of hepatocellular carcinoma in the subjects from 60-69 years of age was significantly higher than in the other age groups (Odds ratio = 3.88, P < 0.01). The risk of hepatocellular carcinoma in the males was also significantly higher than in the females (Odds ratio = 8.96, P < 0.001). The risk of hepatocellular carcinoma in the subjects with a titer of anti-HCV equal to or above 2(12) was significantly higher than in the subjects with a titer of less than 2(12) (Odds ratio = 33.46, P < 0.001). Furthermore, the age- and sex-adjusted risk for developing hepatocellular carcinoma for the subjects with a titer equal to or above 2(12) was significantly higher than that for subjects with a titer of less than 2(12) (Odds ratio = 32.56, P < 0.001). CONCLUSIONS: The risk of developing hepatocellular carcinoma was significantly high in the subjects with a titer equal to or above 2(12). To measure the titer of anti-HCV is thus considered to be useful for effectively detecting infection in a mass screening program.

[Effects of aerobic capacity and body fat accumulation on the insulin response after an oral glucose load].

The effects of aerobic capacity and body fat accumulation on the insulin response after an oral glucose load were investigated in 21 college students. The subjects were divided into three groups based on their insulin response after an oral glucose load: the first group showed a hyper and prolonged insulin response; HI (n = 6), the second group showed a lower insulin response; LI (n = 6), and the third group consisted of other subjects; MI (n = 9). The maximal oxygen consumption in the HI group (29.6 +/- 3.3 ml/kg/min) was significantly lower than that in the LI group (42.5 +/- 3.1 ml/kg/min, P < 0.05). Although no significant difference was observed in the body mass index between the HI (24.6 +/- 1.9) and LI groups (22.2 +/- 0.4, p > 0.05), the body fat and the waist-to-hip ratio were significantly higher in the HI group (25.3 +/- 3.1%, 0.87 +/- 0.03) than in the LI group (12.9 +/- 0.7%, 0.76 +/- 0.01, P < 0.05). All subjects in the LI group performed regular exercise, while none of the subjects in the HI group performed any regular exercise. These results suggest that an inactive life style, decreased aerobic capacity and increased body fat accumulation all appear to result in an increased insulin response after a glucose load.

[Bone mineral density of the calcaneus and related factors in men].

In this cross-sectional study, the bone mineral density of the calcaneus was investigated in healthy young (n = 35, 22-33 years) and middle-aged (n = 49, 45-59 years) men. The relationships among the bone mineral density, body fatness, physical fitness, physical activity in recent and past days, smoking, alcohol, and sex hormones (free testosterone, estradiol, and dehydroepiandrosterone-sulfate; DHEA-S) and sex hormone binding globulin were evaluated. The speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness were measured by ultrasonic measurement. There was no association between age and bone density in each group. In the young group, there was a positive correlation between the body mass index (BMI) and BUA and between the training time during junior high school and BUA, and an inverse correlation between alcohol consumption and SOS after adjustment for the confounding factors using partial correlation analysis. The level of DHEA-S was weakly but not significantly associated with BUA. In the middle-aged group, there was an inverse correlation between the waist to hip ratio and SOS, and between the height of jump and SOS after adjustment for the confounding factors using partial correlation analysis. These results suggest that different factors may affect bone density in the young and middle-aged men. In young men, the higher BMI and the longer training time during boyhood may have a positive effect, and heavy alcohol consumption may have a negative effect on bone density. In middle-aged men, abdominal fat accumulation has a negative effect and leg muscle power has a positive effect on bone density.

[Bone mineral density by ultrasonic measurement in pre- and postmenopausal women--relationship with sex hormones and nutritional states].

In this cross-sectional study we evaluated the relationships of the sex hormones, estradiol (E2), free testosterone (free T), dehydroepiandrosterone-sulfate (DHEA-S), sex hormone-binding globulin (SHBG) and nutritional status to bone density assessed by ultrasonic measurements. The subjects were 16 premenopausal (38-50 years) and 28 postmenopausal (47-86 years) women living in a rural area in Yamaguchi Prefecture in Japan. They were healthy and did not smoke or drink. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and the stiffness index (SI) were used as the indices to evaluate ultrasonic bone density (UBD) for the calcaneus. In premenopausal women, the concentration of free T was negatively associated with BUA. The DHEA-S concentration had a significant negative correlation with BUA after adjustments for age and body mass index (BMI). Daily intakes of fat, animal fat, animal protein, calcium (Ca) and vitamin B2 (Vit B2) were positively associated with UBD. In postmenopausal women, although DHEA-S positively correlated with SOS, BUA and SI, the significance disappeared after adjustments for age and BMI. The protein intake was positively associated with BUA. Multiple regression analysis for SOS, BUA and SI as dependent variables was performed. Independent variables were age, BMI, E2, free T, DHEA-S, SHBG and daily intakes of animal fat, animal protein, Vit B2 and Ca. In premenopausal women, the animal fat intake contributed significantly and positively to the variations of SOS and SI. The intake of Vit B2 had a significant positive correlation, and the level of DHEA-S had a significant negative correlation with BUA. In postmenopausal women, age and BMI contributed significantly to the variations of SOS, BUA and SI, while the nutritional variables and the sex hormones were not found to be significant. In conclusion, different factors predicting UBD were suggested for pre- and postmenopausal women. In premenopausal women, daily intakes of animal fat and Vit B2 might be effective to maintain higher bone density. Further investigations are still needed to clarify the relationship between DHEA-S and UBD.

[A survey of allergic diseases among elementary school children in Saga Prefecture. The first report. Prevalence and past history].

This study was carried out to determine the prevalence of several allergic diseases among elementary school children in Saga prefecture. A questionnaire was distributed to the parents of 2,795 children in 12 elementary schools located in urban, seaside and mountainous areas. The response rate was 92.8%. The prevalence rate of allergic diseases among school children was 24.6% (24.5% for boys and 21.5% for girls). The common types of allergic diseases among boys were allergic rhinitis (11.3%), atopic dermatitis (9.7%), and bronchial asthma (5.7%), and those among girls were atopic dermatitis (9.7%); allergic rhinitis (6.5%), and bronchial asthma (3.7%). Analysis by residential area of the children, showed that the prevalence rate of allergic diseases in total was increased in the order of mountainous (20.8%), seaside (24.1%) and urban area (28.7%). The most common type of allergic diseases was atopic dermatitis in urban and mountainous area, while allergic rhinitis was most common in seaside area.

[Carcinogenicity of 2,3,4,7,8-pentachlorodibenzofuran and 1,2,3,4,7,8-hexachlorodibenzofuran when given by gavage to rats].

Previous studies showed that 2,3,4,7,8-pentachlorodibenzofuran (PenCDF) and 1,2,3,4,7,8-hexachlorodibenzofuran (HCDF) could produce tumors in the liver and subcutaneous tissues of rats by subcutaneous administration. The present study has examined the carcinogenicity of the same compounds in rats by oral administration. Wistar strain male rats were sacrificed at two years after oral administration (0.2 mg/rat) of 2,3,4,7,8-PenCDF or 1,2,3,4,7,8-HCDF. Among rats given 2,3,4,7,8-PenCDF, a cholangiohepatoma and a osteosarcoma were revealed in a rat each. Moreover, a few hepatic nodules were found in two rats in each experimental group. These results suggest that these compounds of polychlorinated dibenzofurans have a tumorigenic potency by oral administration.

[Acute or subacute toxicity of 2,3,4,7,8-pentachlorodibenzofuran and 1,2,3,4,7,8-hexachlorodibenzofuran to rats in non-lethal dose].

Two isomers of polychlorinated dibenzofurans, 2,3,4,7,8-pentachlorodibenzofuran or 1,2,3,4,7,8-hexachlorodibenzofuran, both of which are present in the yusho patients, were subcutaneously administered to rats in a single non-lethal dose to examine acute or subacute toxicity. Maximal inhibition of increase in body weight and decrease in daily locomotor activity were observed in the rats treated with 370 micrograms/kg of these compounds at 3 to 4 weeks after treatment, especially with 2,3,4,7,8-pentachlorodibenzofuran. Histopathologically, hypertrophy of the liver and atrophy of the thymus were noted at 4 weeks after treatment with this dose, while bile duct hyperplasia in the liver was observed at 40 weeks after treatment with 250 micrograms/kg of these compounds.

Carcinogenicity of 2,3,4,7,8-pentachlorodibenzofuran and 1,2,3,4,7,8-hexachlorodibenzofuran in rats.

In order to examine the carcinogenicity of 2,3,4,7,8-pentachlorodibenzofuran and 1,2,3,4,7,8-hexachlorodibenzofuran, these two chemicals were subcutaneously administered to Wistar strain male rats at the dose of 80 micrograms, 40 micrograms or 4 micrograms per rat. At sacrifice in two years after the start of the experiment, tumors were observed in the subcutaneous tissue and the liver. Although the number of the rats used is small, the tumor occurrence showed some tendency to relate with the dose of the chemicals given.

[Effect of PCBs on insulin sensitivity in rats].

Insulin sensitivity was assessed by euglycemic insulin clamp method in the rats given Kanechlor (KC)-400 for 1 to 12 weeks. As a result, insulin sensitivity was depressed increasingly with period of administration of KC-400. Increases in total cholesterol, HDL-C, triglyceride, lipid peroxide and T3 in blood plasma were also observed in the experimental rats. Voluntary daily activity of rats given KC-400, especially in a later half of night-time, had been depressed since approximately 9 weeks after start of the experiment. It was concluded that depression of insulin sensitivity might be related to not only disturbance of glucose and lipid metabolism, but reduced daily activity in conjunction with disturbed thyroid function.

[Studies on mechanism of wasting syndrome in TCDD-intoxicated rats].

In order to examine a relevance of glucose metabolism and thyroid function in TCDD-induced wasting syndrome, an insulin sensitivity assessment with chemical analysis of blood plasma were carried out in male Wistar rats exposed orally to TCDD. Laboratory findings in plasma showed elevation of glutamic-oxalacetic transaminase (GOT) and lipid peroxide value, decrease in thyroxine (T4) with increase in triiodothyronine (T3) value, and slight but significant decrease in fasting blood glucose and basal insulin level. The glucose disposal rate in euglycemic insulin clamp test was significantly elevated. These data suggest that TCDD-induced wasting syndrome might relate to the disturbance of glucose metabolism of the main organ through insufficiency of caloric intake, T4 and insulin.