Different changes of quantity due to aging in the psoas major and quadriceps femoris muscles in women.

Bone fractures cause disabilities that leave the elderly bedridden and strengthening the muscles of the lower limbs, especially the quadriceps femoris, is the main kinematical method of preventing falls. Recently, however, it has become clear that the psoas major is critical for walking ability. We examined changes due to aging in the size of the psoas major compared with changes in the quadriceps femoris. Bone fractures are more frequent in women than in men; our participants (n=210) were therefore exclusively women ranging in age from 20 to 79 and divided into 6 age groups (n=35 each) in 10-year increments. Cross-sectional areas of the two muscles were measured by an MR scanner for a comparative estimation of muscle size. The psoas major showed the greatest quantity in subjects in their 20s, after which it declined steadily until the 60s and dramatically in the 70s, while the area of the quadriceps femoris was preserved until the 40s and showed no dramatic later decline. Exercise beyond regular daily activities is recommended to prevent the psoas major from decreasing in volume. We also recommend the development of a method of maintaining its muscle volume which would target women younger than 40 and older than 60.

Effects of selenium on gallbladder carcinogenesis induced by an intracholecystic 3-methylcholanthrene beeswax pellet in female Syrian golden hamsters.

This study represents the first report of the effects of selenium (Se) on chemically induced gallbladder carcinogenesis in hamsters. A total of 100 female Syrian golden hamsters was randomly assigned to four groups, which groups of 25 hamsters were given ad libitum drinking water containing either 0.0, 0.5, 2.0 or 4.0 ppm Se (as sodium selenite) for 24 weeks. Initiation was performed at week 4 by the insertion of a Beeswax pellet containing 3-methylcholanthrene (3-MC) into the gallbladder. The incidence of total malignant tumors at the end of the study (24 weeks) was 88, 75, 81 and 82% in the 0.0, 0.5, 2.0 and 4.0 ppm Se groups, respectively. All the cases of carcinoma but two were considered to develop through the sequence from dysplasia to carcinoma in situ (CIS) and from CIS to adenocarcinoma of invasive type. The incidence of CIS was significantly lower in hamsters treated without Se than in those treated with Se (P < 0.05). On the other hand, the incidence of invasive adenocarcinoma was significantly higher in the former than in the latter (P < 0.05). These results were summarized that Se might retard the progression of hamster gallbladder carcinogenesis induced by a 3-MC beeswax pellet.

Determination of free fatty acids in human bile by high-performance liquid chromatography.

We developed a high-performance liquid chromatography (HPLC) method for free fatty acids (FFAs) analysis in bile. In this method, FFAs were extracted from bile in a single step using an Isolute ODS cartridge, derivatized with 9-anthryldiazomethane (ADAM). ADAM was chosen because of its high reactivity with carboxylic acid at room temperature. Then, HPLC was used for separating and quantifying FFAs. This method proved to be simple and time-saving. The mean recovery of FFA added to human gallbladder bile was 97.6%, and the detection limit was 100-250 pg. Using this method, we determined FFA concentrations in the gallbladder bile of 11 gallstone patients. The mean concentration of total FFA was 0.61 (SD = 0.41) mmol/L, and there was wide variation in the individual FFAs.

Co-mutagenicity of glyco- and tauro-deoxycholic acids in the Ames test.

Mutagenicity and co-mutagenicity of glyco- and tauro-deoxycholic acids (GDCA and TDCA), which are abundant in human bile, were examined by the Ames test. The two chemicals were not mutagenic for themselves to Salmonella typhimurium TA98 and TA100, with and without S9 mix. They enhanced, however, the mutagenic activities of the pro-mutagens, 2-aminoanthracene (2AA) and benzo[a]pyrene (BaP), for both TA98 and TA100 with S9 mix. They were more co-mutagenic for the pro-mutagens on TA98 than on TA100. On TA98, the mutagenic activities of 2AA with GDCA (5 mumol/plate) and with TDCA (5 mumol/plate) were 9.7-fold and 11.8-fold as high as that of the corresponding control (2AA only), respectively. BaP with GDCA (2.5 mumol/plate) and with TDCA (2.5 mumol/plate) showed 2.8-fold and 3.0-fold increases over the corresponding control level (BaP only), respectively. It is hence concluded that GDCA and TDCA may enhance the activity of some mutagens existing in bile.

Mutagenicity of 24-hour duplicate of Japanese diet.

In order to elucidate the genotoxicological characteristics of the Japanese diet, the mutagenicity of 24-h duplicate of the diet samples were investigated. The mutagenicity of blue rayon extract was examined in the Ames Salmonella/microsome assay. Thirty-two (91.4%) of 35 samples revealed mutagenicity toward Salmonella typhimurium TA98 in the presence of S9 mix. The mutagenic activities showed significant correlations with the consumption rates of broiled fish (r = 0.517, p = 0.0021) and broiled meat (r = 0.494, p = 0.0036). In other test conditions, 6 (17.1%), 5 (14.3%) and 8 (22.9%) samples were mutagenic to Salmonella typhimurium TA98 without S9 mix, TA100 with S9 mix and TA100 without S9 mix, respectively. Findings in the present study suggest that high consumption of broiled fish and broiled meat are important as the source of mutagens/carcinogens in the Japanese diet. In the present study, however, biological inference of these findings could not be made in relation to the occurrence of cancers, especially of the gastric cancer, which is the most prevalent form of cancer in Japan.

Comparison of mutagenic activity of bile between Chilean and Japanese female patients having cholelithiasis.

The mutagenic activity of bile was compared between Chilean and Japanese female patients having cholelithiasis by the Ames assay using Salmonella typhimurium tester strain TA98 in the presence of S9 mix with blue rayon adsorption technique. A reason for conducting the present investigation is that Chile and Japan have the highest mortality rates for the gallbladder cancer (GBC) in the world. Of 24 bile samples collected in Chile, 20 (83.3%) samples showed mutagenicity. In the case of Japanese bile, 21 (80.8%) of 26 and 5 (19.2%) of 26 cases were mutagenic in samples from high- and low-risk areas for GBC, respectively. Therefore, both the Chilean and the Japanese samples collected in high-risk areas showed higher mutagenic rates than the Japanese ones in a low-risk area, with a statistical significance (p < 0.001), chi-square test). The average number of revertant colonies were 128 +/- 92 (mean +/- SD), 62 +/- 14 and 66 +/- 13, respectively, when the blue rayon extracts of 200 microliters bile were applied to the Ames test. Thus, Chilean bile had a tendency to show a higher mutagenic activity than Japanese.

Distribution of selenium and molybdenum and cancer mortality in Niigata, Japan.

Selenium and molybdenum have inhibitory effects on gastrointestinal carcinogenesis. We investigated the levels of selenium and molybdenum in sediments and mortality from cancers at specific sites in 19 areas of Niigata Prefecture, Japan, and compared these factors. The average concentrations of selenium and molybdenum were 0.44 +/- 0.19 ppm (micrograms/g dry weight; mean +/- standard deviation) and 3.82 +/- 1.03 ppm, respectively. Selenium was not associated significantly with cancer mortality. There were inverse correlations between molybdenum levels and female mortality from cancers of the esophagus (r = -.446, .05 < p < .1) and rectum (r = -.529, p < .05). Molybdenum was correlated positively with female mortality from cancer of the pancreas (r = .603, p < .01). Further investigations are needed for causal interpretation of these results.

[Ecological correlation studies on standardized incidence ratios of malignant neoplasms contracted from different sources of drinking water supply].

Ecological correlation analysis was made between the source of drinking water and standardized incidence ratios (SIRs) of malignant neoplasms registered in Niigata, Japan. The purpose of this study was to find out some clues for generating a working hypothesis that the contamination of drinking water with environmental chemicals especially of endocrine disrupting chemicals in big rivers may be related to the occurrence of cancers. Sources of drinking water in the year 1974 were classified into two categories; one from the Shinano and Agano and their down-stream rivers, and the other from small rivers flowing into these big rivers, rivers originating from the mountain areas, underground and reservoirs (The other group). After excluding registered cases under 20 years of age, the registry data (1992-94) were sub-divided into two categories according to the source of drinking water. The SIRs were calculated by using two different standard populations; Niigata total and "The other group". All of the sites were examined in the former standard. In the latter case, however, 12 and 9 sites in males and females, respectively were selected based on the assumption that the expected numbers in each age group totaled 5 or over when there were more than 200 registered patients as a total. Concerning the judgment for the significant association in the former standard, we considered the presence of positive associations when both of the SIRs in the two categories were significantly different from the Niigata total population (p < 0.05 by chi 2 test). Of the 33 sites in males, the following sites were correlated with the source of drinking water; tongue, colon, rectum, gallbladder, etc., prostate, kidney, etc. and all sites. Of 35 sites in females, those were the colon, gallbladder, etc., bronchus and lung, breast, corpus uteri, thyroid and all sites. Of the 12 and 9 respective sites subjected to the second analysis, positive associations were observed in the following: esophagus, colon, rectum, liver, gallbladder, etc., bronchus and lung, prostate, bladder and all sites in males, and colon, rectum, gallbladder, etc., bronchus and lung, breast and all sites in females. Final conclusion, however, should be waived until the consistency of association can be confirmed by using more reliable incidence data, because the difference in the death certificates only (DCO) rate between the two groups might have played as a bias. The use of mortality data may be an alternative way to evaluate the present findings in terms of the consistency of association.

[Risk factors for gallbladder cancer in Chilean females].

A case-control study of gallbladder cancer was conducted with 90 Chilean cases registered at one hospital in Santiago city, Chile from January, 1992 to August, 1994. Controls were selected among outpatients of the hospital who received abdominal echography. Each case was assigned 2 age- and sex-matched controls; either with or without gallstone(s). Study subjects were all directly interviewed by well-trained medical students. The present study focused on 74 female pairs and the following findings were obtained: 1) Odds Ratio(OR)s were significantly high for education years less than or equal to 6, body mass index greater than or equal to 24.0, constipation, and consumption of egg, fried meals, green and red chili. Chili pepper consumption of both types in cases showed significantly elevated risks with higher frequency. 2) While high ORs were observed, biliary symptoms such as dyspepsia and past history of cholelithiasis were strongly involved with present gallstone(s) and may not be independent factors for gallbladder cancer. 3) Significantly low ORs were seen for past history of intestinal parasitosis and surgical operation, hormone therapy, all industrial workers and workers in clothes & textile industry. However results may be influenced by more years of education or recall bias. 4) When a conditional logistic model was applied and controls with gallstone(s) were taken as reference, those with the habit of constipation showed a significantly high risk of 2.10 (95% CI: 1.01-4.38), and the consumers of red chili with a frequency > or = 1 time/day had elevated risks of 2.16 (1.27-3.66) vs those < 1 time/day and 4.66 (1.63-13.40) vs non-consumers, respectively. From the above results, the occurrence of gallbladder cancer in Chilean females may be related to constipation and chili pepper consumption, based on the presence of gallstone(s). Further investigations are needed to elucidate whether these are actual risk factors or whether only a false association was detected.

[Biliary tract cancer].

The proportion of mortalities from biliary tract cancer, which includes gallbladder and extrahepatic bile duct cancers, is only 5% of all deaths from malignant neoplasms in Japan. Epidemiologists, however, are concerned about the cancer due to its peculiar geographic distribution. In addition, they have also noted the recent decreasing trends in mortality rates, especially among females. The most probable explanation is either a change in the effects of risk factors or the development of abdominal ultrasound sonography and laparoscopic cholecystectomy, or both. Further research should be directed towards an analysis of the causes of this decreasing trend.

Geographic clustering patterns in mortality from biliary tract cancer in Japan.

We calculated the standardized mortality ratios (SMRs) of biliary tract cancer (BTC) in Japan from 1981 to 1990 and statistically analyzed the results according to 333 Secondary Areas of Medical Care, as well as sex and subsite [gallbladder cancer (GBC) and extrahepatic bile duct cancer (BDC)], in order to examine geographic clustering patterns of BTC. In GBC in both sexes, the Secondary Areas of Medical Care with high SMRs were clustered in the eastern part of Japan. In BDC in both sexes, the Areas with high SMRs were clustered between the northern and eastern parts of Japan. In comparison with GBC, this clustering favored the northern part of Japan. In males, the clustering pattern in mortality from BTC was mainly due to the occurrence of BDC. In females, the clustering pattern in mortality from BTC reflected that of GBC. The clustering of BTC, especially GBC, seems to be related to the distribution of plains, basins, and rivers.

Mutagenicity of activated carbon adsorbate of drinking water in the Ames assay.

Mutagenicity of activated carbon adsorbate from drinking water collected in Niigata City was assayed by the Ames assay. Adsorbate was extracted from activated carbon with benzene, and then with ethanol. Although the benzene extract was not mutagenic, the ethanol one showed the mutagenic activity for Salmonella typhimurium strains TA98 and TA100 with and without S9 mix. The ethanol extract was much more mutagenic on TA100 than TA98 both with and without S9 mix. The mutagenic activity per liter of water was found to be the strongest in winter and the weakest in summer.

Acute toxicity of tri-n-butyltin chloride (TBTC) in the Syrian golden hamster.

The effects of tri-n-butyltin chloride (TBTC) on Syrian golden hamsters were studied. TBTC in single doses of 0, 29.6, 44.4, 66.7, 100 or 150 mg/kg were given to 10 male hamsters in each group and the mortality rates were determined two weeks thereafter. They were 0% (0/10), 0% (0/10), 10% (1/10), 10% (1/10), 30% (3/10) and 70% (7/10) for 0, 29.6, 44.4, 66.7, 100 and 150 mg/kg groups, respectively. In the case of females, seven groups consisting of 10 animals each were given TBTC at doses of 0, 29.6, 44.4, 66.7, 100, 150, or 225 mg/kg. The mortality rates determined two weeks after the TBTC treatment were 0% (0/10), 10% (1/10), 10% (1/10), 0% (0/10), 40% (4/10), 30% (3/10) and 90% (9/10) for 0, 29.6, 44.4, 66.7, 100, and 225 mg/kg groups, respectively. Based on these mortality data, the LD50s via oral administration were determined as 146.9 mg/kg (95% C.I. 111.8-193.3 mg/kg) for the male and 172 mg/kg (95% C.I. 127.2-233.4 mg/kg) for the female. Regarding pathological changes, animals experienced lesions in the bile duct, such as the dilatation of the common bile duct and cholestasis, and/or adhesion of the bile duct to the liver, gallbladder, pancreas and duodenum. In a separate experiment, a single dose of 44.4 mg/kg TBTC was administered orally to 12 male hamsters, then the concentrations of TBTC and its metabolite, di-n-butyltin chloride (DBTC), in the liver were analyzed by means of gas chromatography for 14 days after the treatment. The maximum concentrations of TBTC and DBTC appeared one day after the administration, and decreased rapidly thereafter. The concentration of DBTC was found to be higher than that of TBTC throughout the experimental period.

Increases in body mass index and waist circumference as outcomes of working overtime.

This epidemiologic study was undertaken to determine whether working overtime is associated with anthropometric indices and serum lipids, risk factors for obesity, in white-collar workers. Non-management white-collar male workers were eligible. Body weight and height, waist circumference, skinfold thickness, serum total cholesterol and triglycerides were measured. Weight, height and waist circumference data obtained 3 years previously were also used. Lifestyle information was obtained by means of a self-administered questionnaire. Overtime hours correlated significantly with the 3-year change in body mass index (r = 0.206, p < 0.0017) and waist circumference (r = 0.218, p = 0.0091), but not with either the most recent anthropometric indices or serum lipids. Overtime hours were also intercorrelated (r = 0.436, p < 0.0001) with dinner time. The present study suggested that working overtime is associated with the increases in BMI and waist circumference over a 3-year period although the associations were weak. Additionally, eating habits of those with working overtime might reflect an intervening effect on the anthropometric changes.

Evaluation of complex activities in daily living of elderly Japanese with visual impairment.

This study was conducted to determine whether elderly subjects with visual impairment differ in the performance of complex activities in daily living from those without visual impairment. The study subjects were residents in two homes for the aged in Japan, and consisted of 37 elderly people with visual impairment, and 42 elderly people, serving as controls; ages ranged from 64 to 95 years. Complex activities of the subjects were ascertained by interview using a 46-item questionnaire. The visually impaired elderly had lower performance levels for telephone use (p = 0.007), shopping (p = 0.049), cleaning up one's room (p = 0.001), and utilization of medical facilities (p = 0.001) in instrumental ADL (IADL); for interest in TV or radio (p = 0.004) and religious faith (p = 0.042) in "enriching activities"; and for visiting behaviors (p < 0.05) in "social role". The performances of complex activities by the elderly with visual impairment were diminished in specific categories, but not overall, and this may be attributable to poor mobility and/or more passive attitudes in their daily activities.

Selenium contents in human gallbladder bile.

The selenium contents in human gallbladder bile were analyzed. Thirty-seven subjects were studied; 22 patients with cholelithiasis in Niigata Prefecture and 15 patients (13 with cholelithiasis and 2 with gallbladder polypus) in Kochi Prefecture. Five ml of bile was withdrawn with a syringe from the gallbladder during the operation and stored at -20 degrees C until analysis. For the analysis by gas chromatograph with an electron-capture detector, 0.2 ml of sample was used. The mean selenium contents in bile were 269 +/- 39.0 (mean +/- S.D.) ng/ml for the subjects in Niigata and 285 +/- 84.4 ng/ml in Kochi; without significant difference. Of 37 samples analyzed, the mean content was 276 +/- 61.0 ng/ml.

Cytogenetic analysis of human bile for mutagenicity and co-mutagenicity.

Cytogenetic analysis was used to test whether or not human bile induced chromosome abnormalities in lymphocytes grown in culture. Bile was obtained from gallbladders resected for various reasons such as cholecystitis, cholelithiasis, polypus and cancers of the biliary tract, stomach and pancreas. After adding human bile to a final concentration of 25 microliters/ml or 12.5 microliters/ml, the culture medium was incubated at 37 degrees C for 72 hr. Air-dried slides were stained with conventional Giemsa and the numerical and structural chromosome abnormalities were scored. Positive and negative controls in terms of chromosome abnormalities were established by using 0.03 micrograms/ml mitomycin C (MMC) and 0.9% normal saline, respectively. Cytogenetic analysis was successfully performed in 6 out of 10 bile samples (60.0%). Bile alone did not induce numerical or structural chromosome abnormalities. Structural abnormalities increased significantly in the 25 microliters/ml bile + 0.03 micrograms/ml MMC group, compared with the 0.03 micrograms/ml MMC group: 36.0% vs. 20.7% in the chromatid-type gaps and breaks, 27.8% vs. 22.7% in the chromosome-type gaps and breaks, and 8.3% vs. 3.2% in the exchange-type abnormalities. It is likely that the interaction between bile and MMC is synergistic rather than additive.

Shift work and risk factors for coronary heart disease in Japanese blue-collar workers: serum lipids and anthropometric characteristics.

This study was conducted to determine if there is an association between shift work and risk factors for coronary heart disease (CHD) in Japanese male blue-collar shift workers. Health check-up data on serum lipid concentration and anthropometric indices of 33 three-shift workers and 27 two-shift workers were compared with those of day workers. The average years in age of the shift workers and day workers were 34.5 (SD = 7.1) and 32.7 (SD = 7.6), respectively. Serum total cholesterol levels of three-shift, two-shift and day workers were 5.70 (SD = 1.19) mmol/l, 4.81 (SD = 1.01) mmol/l, 4.98 (SD = 0.95) mmol/l, respectively, and the cholesterol levels of three-shift workers were significantly higher than the other workers (p < 0.05). In addition, the abdominal to hip circumference ratios were 0.905 (SD = 0.060) for three-shift workers and 0.877 (SD = 0.054) for day workers, with a significant difference (p < 0.05). In the present Japanese population, three-shift workers had higher risks of CHD than day workers, which was characterized by higher levels of serum total cholesterol and tendency to central obesity. These findings held when lifestyle factors were taken into account.