We studied the role of S-adenosylmethionine (SAM) as a methyl group donor in the methylation of inorganic arsenic in mammalians.
The SAM and S-adenosylhomocysteine (SAH) levels in the livers of untreated hamsters were 74.3±8.2 and 40.0±6.4nmol/g, respectively. The SAM level was 63.9±6.5nmol/g following oral administration of 1.5mg/kg of arsenic trioxide, which was 14% lower than the control level (t-test, p<0.05). This fall of the SAM level in the liver presumably derived from the SAM having acted as a methyl group donor.
Oral administration of 1.5mg/kg of arsenic trioxide once only to hamsters pretreated intraperitoneally with 2.0mg/kg of SAM once only gave the following arsenic levels in the liver and urine. The dimethylated arsenic (DMA) levels in the livers of hamsters treated with SAM plus arsenic trioxide were significantly high, that is, 2 times as high as the control value at 6 hours, and 1.5 times as high as the control value at 24 hours after the administration of arsenic trioxide. The urinary DMA excretion rate in the hamsters treated with SAM plus arsenic trioxide during the first 24 hours after the administration was significantly higher, that is, higher by 36%, than the control value. The urinary DMA excretion rate following pretreatment with SAM was not dose-dependent. Pretreatment with methionine failed to exert any significant acceleratory effect on the methylation of arsenic trioxide.
The decreasing pattern of the SAM level in the liver following administration of arsenic trioxide and the DMA behavior in the liver and urine following administration of SAM and arsenic trioxide revealed that SAM accelerated the methylation of inorganic arsenic. In other words, it appeared that SAM could be a very potent methyl group donor to inorganic arsenic.

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A non-saturated mixed-gas dive to 180 meters depth was carried out at JAMSTEC, using diving simulator (hyperbaric chamber) facilities. Compression started at 10:00h with helium and oxygen and was carried out at a rate of 12m/min. Decompression started at 11:15h using the Comex Helox 180 Diving Manual. Decompression to 1 ATA required 49.2h.
A survey of subjective symptoms, sleep feelings and ball-bearing tests were performed. All night electrophysiological recording of subjects' sleep was performed and polygraphic analysis of nocturnal sleep was done with visual scoring.
The results were as follows:
Arriving at 180 meters, the complaint rate was 39.2% and fatigue was greater. The type of fatigue that was based on the composion ratio of symptoms was that of mental fatigue. During the decompression it was recovery.
The performance in the ball-bearing test decreased about 20% at a depth of 180 meters because of tremors and disturbance of attention as well as other factors showing symptoms of high-pressure nervous syndrome.
The sleep feelings were different in experimenced persons and nonexperimenced persons. The non-experienced persons had markedly decreased REM stages and slept badly all night.
Based on these results, fatigue and the performance of divers were discussed.

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The ion chromatographic method is a rapid and reliable technique for the simultaneous determination of inorganic anion concentrations in serum. We are investigating the effects of various diseases on the serum levels of the following inorganic anions: phosphate, bromide, nitrate, and sulphate.
In this paper, we tested the intra-and intermeasurement reproducibility of the ion chromatographic method using pooled normal human serum. We found a good intrameasurement reproducibility for all of the above inorganic anions. The intermeasurement reproducibility was good for three of the inorganic anions but not for nitrate.
We measured the serum levels of these inorganic anions in 241 inhabitants in one rural area. Using sera of normal inhabitants chosen from the above group, we used the mean value plus or minus two standard deviations as the normal range of each inorganic anion. Our values are in agreement with previously published reports.
We found that the serum levels of nitrate and sulphate tended to be increased in inhabitants with liver or kidney disfunction respectively.

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Four male Japanese were fed a semisynthetic diet including egg and soy powder as protein source for seven days (Basal-diet period), and in the following seven days 200g of polished rice, wheat flour and buckwheat flour added at the expense of part of the corn starch and sugar in the basal diets (Test-diet period). Urine and feces were collected throughout both periods and the contents of nitrogen, fat and energy in these excreta were determined. Digestibility of protein (N), fat and carbohydrate (by difference) was calculated.
The protein digestibilities of the polished rice (in the form of cooked grains), wheat flour (in the form of cooked powder) and buckwheat flour were 89.6±5.0%, 93.4±2.9% and 85.1±2.5%, respectively. The fat digestibilities of the polished rice, wheat flour and buckwheat flour were 93 .6±1.8%, 70.8±13.5% and 103.1±8.4%, respectively showing relatively large variation (This results may be caused by an errors in measurement). The carbohydrate digestibility was close to 100%. The net energy availabilities of the polished rice, wheat flour and buckwheat flour were 100.6±1.4%, 96.5±1.1% and 96.0±1.1%, respectively.

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The purpose of this study is to evaluate waist size as an indicator of health risk among subjects considered to have normal body construction based on height-weight obesity indices. For estimating standard waist sizes based on height, a regression equation was formulated from 46 male subjects who had no abnormal findings in their health checkups. The regression equation was as follows:
Standard waist size (cm)=0.8×height(cm)-57.7.
The ratio of measured waist size to standard waist size was defined as the “waist ratio”. The correlation coefficient between the waist ratio and the modified Broca's obesity index was 0.898 (N=207, p<0.01).
To clarify the meaning of the waist ratio, 95 male subjects were divided into three groups on the basis of the difference between their waist ratio and their obesity index. The group whose waist ratios were larger than their obesity indices had significantly worse findings than the group whose waist ratios were not in the following medical categories: systolic blood pressure, glutamic oxaloacetic transaminase levels, gamma glutamyl transpeptidase levels, uric acid levels, total bilirubin, electrocardiogram readings and optic funduscopic observation.
Accordingly, the waist ratio derived from waist size might be useful for assessing obesity-related health risks even for subjects judged to be normal from the height-weight obesity index.

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The effects of zirconium (Zr) on T cells and macrophages in mice were studied in vitro using the indexs of immunological reactions, mitogenesis of C3H/HeJ mouse thymocytes induced by PHA and the production of interleukin-1 of C3H/He mouse intraperitoneal macrophages (MIL-1).
The mitogenesis of thymocytes induced by PHA when stimulated with Zr solutions at various concentrations or culture supernatants of macrophages stimulated with LPS and Zr, or Zr alone, ware as shown below.
1. The mitogenesis of thymocytes by PHA was enhanced in the presence of Zr at 0.625-2.5μM, and suppressed in the presence of Zr at 5-10μM in culture
2. This reaction was enhanced by the addition of supernatants of macrophages stimulated with LPS and Zr. The most activation by LPS and Zr was shown at concentrations of 0.625-1.25μM in culture, and the degree activated corresponding to 12.5-25 I. U. of MIL-1.
3. On the other hand, this reaction was inhibited by addition of supernatants of macrophages stimulated with Zr alone.
From these results, it is suggested that Zr serves various functions such as an activator or inhibitor of T-cell mitogenesis by PHA, and that this may depend upon the Zr concentration in culture. In regard to the effect of Zr on MIL-1 production, Zr may activate this reaction by LPS, and Zr alone may induce MIL-1 production from macrophages.

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Scalp hair samples were collected by mail from 97 married couples who were living in several places in Okinawa-prefecture and supposedly had no specific exposure to mercury compounds. They were selectively analysed for organic and inorganic mercury content and the difference of hair mercury concentration between the sexes was discussed in relation to the frequency of fish intake, fish species, drinking habits and permanent-wave hair treatment. Results obtained were as follows;
1) The increase in hair levels of organic and inorganic mercury concentrations was roughly proportional to the dietary intake of fish in the range from none or low to moderate frequencies for both husbands and wives. However, this increase was not proportional to the dietary intake of fish in the range from moderate to high frequencies, showing almost the same level irrespective of the frequency of fish intake.
2) Though husbands and wives had dietary consumption patterns quite similar to each other, husbands were found to have higher hair organic mercury levels than wives, the average values being 6.40ppm with a standard deviation of 4.69ppm for husbands and 2.86ppm with a standard deviation of 1.97ppm for wives, respectively. The difference was statistically significant. No significant difference between the sexes was detected for inorganic mercury concentrations. However, a highly significant positive correlation coefficient for organic mercury and also a significant positive correlation coefficient for inorganic mercury were found between husbands and wives.
3) Hair without permanent-wave treatment showed higher levels of organic mercury concentrations than hair with permanent-wave treatment for both husbands and wives. Drinkers also had higher levels of hair mercury as compared to non-drinkers. However, the lower levels of organic mercury concentrations in women's hair than in men's hair were not fully explained by these factors.
4) Both men and women who showed higher hair levels of organic mercury had a preferance for highly predatory fish such as tuna and bonito, which probably contributed most to the human intake of mercury.

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In our previous study we reported that the secular change of the mean birth weight (MBW) of Okinawa was different from that of Japan as a whole, that is, the MBW of Okinawa was lower, but the annual increase rate of the MBW of Okinawa was larger than that of Japan as a whole. Through analyses using birth records of several obstetric facilities in Naha, we concluded that this phenomenon must be due to the remarkable improvement of the socioeconomical environment of Okinawa.
In this report we analyzed secular changes of mean birth weight (MBW) and mean gestational day (MGD) of 15, 847 singleton babies born at an obstetric clinic in the city of Naha for the 33 years from 1955 to 1987. To avoid fluctuations of annual changes in MBW and MGD caused by a small number of babies born in a single year, we also used the moving average of three years. In analyzing birth weight we stratified birth weight by sex, parity and the number of gestational weeks. It is considered that birth weight stratified by the number of gestational weeks reflects the intrauterine growth rate of infants.
According to our results, both the MBW of infants with 40 gestational weeks, which reflects the intrauterine growth rate, and the MGD increased during the period from the 1950s to the early 1970s in this clinic. On the basis of these results we concluded that the increase of birth weight in this clinic until the early 1970s was due to increases in both the intrauterine growth rate and the gestational period.
Our results also show that the mean height of mothers who delivered at this clinic also increased, which might reflect the development of the socioeconomical environment during their childhood. During the period when MBW increased, the economic growth rate of Okinawa was higher than that of other prefectures.
From these results we concluded that the MBW can be used as a community health indicator reflecting the total health condition in a given community.

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The distributions of erythrocyte values (red cell count, hemoglobin concentration, etc.) of healthy male workers working in a certain factory were studied in order to evaluate the usefulness of the variables as health indicators. In addition to the estimation of erythrocyte values, anamneses concerning chronic bleeding, smoking habit and alcohol consumption were questioned and serum Fe, Cu, TIBC, ferritin, plasma erythropoietin, and serum enzymes (GOT, GPT, γ-GTP) were measured. Two-dimensional frequency distributions with axes for the red cell count and hemoglobin concentration, and frequency distributions of the score calculated from principal component analysis, showed bimodal patterns. Using nonlinear curve fitting methods, the distributions of principal component scores were fitted to a mixture of two different Gaussian distributions. The workers were then divided into two groups corresponding to the Gaussian distribution he belongs. Then the frequencies of the items and mean values of the variates were compared between them. There were no differences in the incidences of diseases that caused iron deficiencies, but the mean serum ferritin level was significantly lower in one group than in the other, in other words the workers belonging to the group with low serum ferritin level had smaller iron stores than the other. The mean serum erythropoietin level and the mean serum copper level were higher in that group than in the other. As a result, this analysis gives a new evaluation of the health status of a man who belongs to the so-called healthy male group.

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In order to assess tissue blood flow quantitatively under various temperature conditions, we have developed a new blood-flow measurement apparatus based on the thermal diffusion method. This new method is hardly affected by environmental temperature, by means of using the thermal clearance curve with its baseline corrected before each measurement. Fundamental studies concerning the measurement of human skin blood flow were carried out in the finger. The results obtained were as follows.
1) The gradient of the thermal clearance curve did not show significant changes under various temperature conditions. This result indicated that the effects of environmental temperature on the thermal clearance curve were almost removed.
2) A highly positive correlation was obtained between the thermal conductivity of various materials similar to human skin in thermal conductivity and the gradient of the thermal clearance curve from a probe placed on a plate of each material.
3) There was linear relationship between the water flow and the gradient of the thermal clearance curve in various water flows of a micro-circulation model. The gradient of the thermal clearance curve obtained for each water flow had good reproducibility.
4) The gradient of the thermal clearance curve changed in parallel with the finger ischemia and hyperemia induced by inflation of a tourniquet. There was good reproducibility in continuous measurements.
5) A highly significant positive correlation was obtained between finger blood flow measured by the inhaled hydrogen clearance method and the gradient of the thermal clearance curve, indicating that it was possible to assess finger blood flow quantitatively by the gradient of the thermal clearance curve.
The weak point in the former thermal diffusion method, where the baseline was unstable as a result of environmental temperature, was removed. It was concluded that this new thermal diffusion method using the thermal clearance curve, which was calibrated previously by the hydrogen clearance method, enabled us to measure finger blood flow noninvasively at various temperatures. This method will be useful for diagnosis and research in various medical fields.

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In order to study the effects of static force such as a handgrip in detail, the peripheral circulatory function and the autonomic nervous function of workers who used chain-saws were examined in a handgrip test at 30% of maximum voluntary contraction (30% MVC). Workers using chain-saws were divided into three groups: group A without any symptoms, group B with numbness and/or pain but without Raynaud's phenomenon and group C with Raynaud's phenomenon.
The results obtained were as follows:
1. The finger blood flow (FBF) of all groups significantly decreased during the handgrip and significantly increased after the end of the handgrip as compared with the initial value. There was a tendency for the FBF decrease of group C to be less than that of group A.
2. The mean value of both maximum FBF decrease and maximum FBF increase during handgrip tests fell in alphabetical order (A, B, C). The maximum FBF increase of group C was significantly less than that of group A.
3. The finger skin temperature (FST) of each group significantly fell during the handgrip but there was no significant difference among the three groups. FST returned to the level of the initial value one minute after the end of the handgrip, and significantly rose two minutes and three minutes after the end of the handgrip as compared with the initial value.
4. Both the systolic blood pressure and the diastolic blood pressure of all groups significantly rose during the handgrip but there was no significant difference among the three groups. Concerning the maximum rise of diastolic blood pressure, which is an indicator of autonomic nervous function, there was no significant difference among the three groups.
It was concluded that observation of FBF, which is an indicator of peripheral circulatory function, in the handgrip test at 30% MVC was useful not only in the assessment of the peripheral circulatory function of workers with Raynaud's phenomenon in the period without attack of Raynaud's phenomenon but also for early diagnosis of peripheral circulatory disorders in workers without Raynaud's phenomenon.

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The present study, a follow-up study for 669 aged examinees of a health check performed in July 1983 in a rural area in Fukushima Prefecture, was conducted to clarify the relationship between relative weight and mortality among aged individuals living in a Japanese rural area. Using the standard body weights calculated from Japanese mean body weights by sex, age class (60-69 and 70 or more) and height cited from the data of the Ministry of Health and Welfare from 1966, mortalities during the five year follow-up were compared among four groups different in relative weight at baseline.
The results are as follows.
1) The mortalities in the group of ‘Relative weight≤-10%’, the leanest group among the four groups, were highest in both sexes, 52.8per 1000 person-years for males and 33.2per 1000 person-years for females. On the other hand, those in the group of ‘+10%≤Relative weight<+20%’ were lowest in both sexes, 23.1per 1000 person-years for males and 7.0per 1000 person-years for females. In females, the difference in the mortality between these two groups was statistically significant at the 0.05 level, provided age structures in both groups were taken into consideration.
2) In both sexes, the mortalities of cancer and cerebrovascular diseases in the group of ‘Relative weight≤-10%’ were highest among the four groups, whereas such mortalities in the group of ‘+10%≤ Relative weight<+20%’ were lowest. However, the differences controlled for age in the mortality of these diseases between the two groups were not significant at the 0.05 level in both sexes. The relation of relative weight to mortality for heart diseases was similar to that for cancer and cerebrovascular diseases in females, but the relationship between relative weight and heart disease mortality was not clear in males.
3) The prevalences of hypertension, heart diseases, cerebrovascular diseases, diabetes mellitus or other major chronic diseases in the group with a relative weight≤-10% were not high as compared with those in all other groups at baseline.
4) These results suggest that leanness without manifest chronic diseases should also be considered as an important health problem in aged individuals living in Japanese rural areas.

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This study was carried out to clarify the effects of methylmercury intoxication on the ethanolinduced sleeping time of mice. The mice were injected with methylmercury chloride (MMC) (10mgMMC/kg body weight) subcutaneously for 1, 5 and 10 successive days (1, 5 and 10inj.), and control mice received only saline. Twenty-four hours, after the last injection, these mice were treated with ethanol (4.5mgEtOH/kg body weight) intraperitoneally and subsequent sleeping time was observed. After 24 hours, mice were sacrificed to measure the concentration of MMC in various brain regions and liver. A similar experiment without ethanol treatment was also performed to assay the biogenic monoamines in various brain regions and alcohol dehydrogenase (ADH) activity in liver. The results can be summarized as follows:
1) Ethanol-induced sleeping time was 170min. in the 10inj. and it was significantly longer than saline, 1 and 5inj. However, other experimental groups showed no change when compared with saline.
2) Norepinephrine levels increased in white matter and pons + medulla after 1inj.
3) Dopamine levels increased only in white matter of the 10inj. when compared with saline. No changes were shown in the other groups.
4) Serotonin levels increased in all the regions after 1inj.
5) ADH activity in liver did not show any alteration during the experimental period when compared with saline.
6) MMC in brain and liver increased with time and finally reached 15-16ppm in the cerebrum and 11ppm in pons + medulla; however, we could not recognize paralysis of hind leg crossing in mice.
Thus, it may be suggested that changes in ethanol-induced sleeping time of the MMC-administered mice were dependent on the alteration of biogenic monoamines and the concentration of MMC in the brain.

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