The erythrocytes from various types of psychiatric patients, their apparently normal family members and normal controls were incubated in synthetic serum containing lithium. The lithium concentration in erythrocytes-to-serum (Li index) was measured as an index of lithium transport. The following results were obtained.
1) No sex difference was present in the Li index within the psychiatric group, their family members or normal controls. Psychiatric patients showed a significant positive correlation between Li index and age, but such a relationship was not evident in either the family members or normal controls.
2) Li indices showed wide variations within the psychiatric population and within the normal group but appeared relatively constant within members of the same family. Thus, a genetic factor was suspected as operating in lithium permeability across the erythrocyte membrane.
3) In schizophrenic patients, a positive tendency was noted between a high intrafamilial morbidity and a higher Li index. Schizophrenic patients with particularly high hereditary load showed a significantly higher Li index than the control values. Female patients of this group indicated marked Li indices high above the range for normal individuals.
4) Schizophrenic patients in hyperkinetic states showed lower Li indices than those in hypokinetic states. Hospitalized manic-depressive psychotic patients showed a tendency for low Li indices, but during remission, these patients showed higher Li indices.
5) In the combined psychiatric population, an apparent inverse relationship was found between extremely high serum creatine phosphokinase (CPK), glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activity and a low Li index. Patients with CPK activities above 100 units had significantly lower Li indices compared with those with CPK activities of less than 60 units.
6) CPK and Li index reflect different measures and can not be treated on the same basis, but it can be presumed that lithium transport outside erythrocytes in more active when serum CPK activity is abnormally high. Thus, the possibility is suggested here that permeability across the erythrocyte membrane varies according to psychiatric states.
7) In schizophrenic patients, no significant correlation was found between the Li index and dosages of antipsychotic drugs excluding lithium, the duration of medication or the duration of illness.

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In our Department, various attempts have been made in order to elucidate the mechanism of carcinogenesis by azo dyes using tissue culture system. In the present experiments, a total of 28 Donryu rats were fed with 4-dimethyl-aminoazobenzene (DAB) or 3'-methyl-4-dimethyl-aminoazobenzene (3'-Me-DAB) for 5-62 days. Five cell lines have been established from the liver tissues of rats fed by either of the above substance. Subsequently, several experiments were made to investigate the histological characteristics of the established cell lines. The results are summarized as follows:
1) Morphological features differed in the cell lines derived from rats fed by DAB and those from rats fed by 3'-Me-DAB. The former exhibited polygonal shape and formed pavement-like sheets. On the other hand, the latter showed oval shape, but did not form pavement-like sheets.
2) In chromosome analysis, the cell lines derived from rats fed by DAB exhibited the diploid number in contrast to those from rats fed by 3'-Me-DAB.
3) In rotation culture, 5 cell lines formed aggregates. The aggregates of the cell lines derived from rats fed by 3'-Me-DAB were much larger in size than those from rats fed by DAB.
4) Concerning branched-chain amino acid transaminase, cultured cells derived from rats fed by 3'-Me-DAB contained the isozymes I and III, whereas cells from rats fed by DAB contained only the isozyme I.
5) With radioimmunoassay alpha-fetoprotein level in culture medium of 5 cell lines ranged between 5 to 50 ng/ml.
6) To examine tumor-producing capacity of 5 cell lines, the cells were inoculated into rats intraperitoneally or subcutaneously. All cell lines induced by 3'-Me-DAB gave rise to tumors, but 3 cell lines induced by DAB did not produce tumors. The recultured cells derived from ascites of rats that died of tumors were morphologically similar to the cells before inoculation.

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Authentic guanidinosuccinic acid was converted into dimethylpyrimidyl derivative by reaction with acetylacetone, the carboxyl group was esterified by butylalcohol, and this derivative was analysed by the GC/MS technique. Then guanidinosuccinic acid was identified in urine of arginine loaded rabbit by means of selected ion recording. On the other hand, aspartic acid and isomolar of arginine was loaded simultaneously to rabbit, and a higher level of guanidinosuccinic acid was detected in the urine of 2 or 3 days and one week after. This fact suggest that guanidinosuccinic acid could be produced by transamidination of aspartic acid, receiving amidine group of arginine.

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The transverse level of electrodes, A, C, E, I and M in Frank system vectorcardiography is important, since it affects the accuracy of the vectorcardiogram.
1. Using a Japanese male torso mode, the effects of shift in electrode position from the fifth to the fourth intercostal space level on lead vector were studied, and results were as follows.
The magnitude of elad vector decreased in lead Z and increased in lead Y with moving all electrodes downward from the level of artificial dipole.
2. The transverse level of the center of heart vector was determined in healthy Japanese males in supine position using three-step technique. Following results were obtained.
The level was upper than the fifth intercostal space, and in association with an increase in cardio-thoracic ratio, it shifted upward from the fifth intercostal space.

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Normal 45 males and 25 females less than 40 years, and 30 male and 25 female more than 40 years of age, were analyzed for mechanocardiogram both at rest and by hand grip exercise. The results revealed that Q-IIA and LVET showed a significant negative correlation, PEP showed no or a little, correlation and Q-I showed no correlation with heart rate. With different time constant, while the waveform did not change essentially waveform and a time lage on wave were observed, i.e., with time constant of 0.1 in comparison with 2.0 sec., RF/E-O ratio and RFT increased, and UT, Q-E, IRT and A/E-O ratio tended to decrease. In terms of different positions, left hemilateral position as compared with supine one prolonged PEP in all groups and in the LVET at tachycardia and the Q-IIA at bradycardia, a difference by position was found in female.
In the over 40 year old group, Q-IIA, LVET, PEP, PEP/LVET, A/E-O ratio and IRT tended to increase as compared with the below 40 year old group. In female compared to male, examination at rest showed a tendency to have a greater Q-IIA and LVET, and lesser PEP, PEP/LVET, Q-I, A/E-O ratio and RFT. Hand grip exercise increased Q-IIA, LVET, PEP, ICT, PEP/LVET and A/E-O ratio accompanied with an rise in blood pressure and heart rate.

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As compared with normal 30 males and 25 females as controls, 80 males and 53 females with essential hypertension were studied for mechanocardiogram by hand grip exercise.
At rest, the hypertensive group as against the normal group showed an increment of PEP, ICT, PEP/LVET and A/E-O ratio, and shortening of LVET without any significant difference.
Hand grip exercise augmented LVET and A/E-O ratio, and reduced in PEP/LVET with a rise in blood pressure and heart rate. The hypertensive group with severe ECG changes showed, at rest, shortening of LVET and increases in PEP, ICT, and PEP/LVET. No definite tendency was observed in A/E-O. As compared with the normal group, decrease in PEP, ICT and PEP/LVET and increase in LVET and A/E-O ratio were observed during the exercise, regardless of the degree of ECG changes. The more severe in ECG changes, the more increment in A/E-O ratio was seen during the exercise. The recovery of each index after the cessation of the exercise showed a tendency to delay further according to increased ECG changes. Such a different response to the exercise in the hypertensives may be ascribed significantly to the hyperreactivity to catecholamine of hypertensive patients with high plasma level of catecholamine and to the elevated left ventricular end-diastolic pressure due to left ventricular hypofunction in advanced hypertension.

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Transfer to gold fish of brominated hydrocarbons (1-2-dibromoethane, bromoform, 1-1-2-2-tetrabromoethane) from rearing water was examined. The concentration of brominated hydrocarbons in fish flesh reached the first steady state 5 hours after fish were placed in rearing water. The concentration factors (cont. in gold fish/cont. in rearing water at steady state) of brominated hydrocarbons for gold fish were in the decreasing order of: bromoform 1-1-2-2-tetrabromoethane 1-2-dibromoethane.

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Analytical sensitivity of urinary HA screening method by porcelain dish is similar to that of direct colorimetric method and good agreement with both methods was obtained. Namely, eighteen samples out of twenty measured by screening method coincide with that of direct colorimetric method. Data indicate that this method is very useful for screening method having an advantage in which rapid determination at on the urinary HA as an index of toluene exposure.

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Toluene and xylene are widely used as industrial solvents. Concentrations of toluene and xylene in the air were measured as time lapsis at the paint shop in the shipbuilding company using thinner. Air density of toluene and xylene were relative low in the place where the room has extremely high ceiling or opened. In contrast to this, the density were high in the room in which the ceiling was low. In the room where ceiling is opened, concentration of toluene and xylene markedly decreased after painting work, but in the case that the room is closed in which concentration is very slow.

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It has been well known that glycine conjugates metabolites of toluene or xylenes are excreted in the urine of workers using thinner.
Glycine conjugates were measured in the urine of three painting workers who were working in the same shop. The urine was taken three workers working in the same shop at morning (Am. 8:00), at noon (Pm. 0:00), at afternoon (Pm. 5:00) three times in the day during two weeks. Concentration of urinary metabolites taken was higher at noon or in the afternoon than those taken at morning.
Data indicated that the painting workers were exposed to organic solvents at noon or at afternoon. This phenomenon was recognized in all week days. From these results, the authors suggested that alkyl benzene was excreted relatively fast.

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Relation between air concentration of organic solvents in the factory using thinner and urinary glycine conjugates of volunteers exposed to thinner was examined. The results were obtained as follows.
Three volunteers were exposed to thinner containing major m-xylene for one hour in the room where ceiling was opened. One volunteer out of three ones used the gas mask, but the others did not use it. The urinary glycine conjugates at time lapsis measured of the volunteers urine.
Air density which averaged hourly air solvents concentration in the shop was mainly coinceid with air density which calculated from urine that excreated from two volunteers without gas mask, using the chart deveiced by Ogata et al.¹
The urinary glycine conjugates of volunteer with gas mask was not so exchange after exposure.
From these results, Ogata's report made by steady account of m-xylene applied to the shop where air density change and gas mask was high efficiency of trapping to work in the high concentration of organic solvents, in this instance.

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There has been few reports about the relation between asthmatic symptoms and MEFVC.
In this study, we performed MEFV maneuvers for asthmatic patients in order to clarify the relations between mild asthmatic symptoms and MEFV curves, and the relation between the effect of the inhalation provocation test and MEFV curves.
The results obtained were as follows;
1. There was a characteristic difference in flow rates at high lung volumes after peak flow rate level in MEFVC between symptom-free period and the day when wheezing was detected.
2. The MEFV pattern was compared with the effect of the inhalation provocation test by housedust extracts. Before the inhalation provocation test, the MEFVC showed a reduction in the flow rates at all the lung volumes, especially the flow rates at the lung volumes after the peak flow rate level suddenly fell down remarkably. After the inhalation provocation test, the MEFVC showed a reduction in the flow rates all the more at all the lung volumes and the MEFV pattern looked like squashed, and the FVC was also reduced.

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There has been few reports about the relation between persistent asthmatic symptoms and MEFVC.
In this study, we performed MEFV maneuvers for asthmatic patients in order to clarify the relations between asthmatic attacks and MEFV curves, especially, to clarify the relation between the attacks provoked by spirometry and MEFV curves.
The results obtained were as follows;
1. Maximal expiratory flow-volume curves (MEFVC) showed marked reductions in flow rates all over the lung volumes both in the persistent wheezing period and in the persistent mild attack period, but there was little difference in MEFVC between two periods.
2. In a case of the attack provoked, whatever the causes might be, i.e., common cold or exercise (spirometry), there was no difference in flow rates near the peak flow rate level between two MEFV patterns, but there were differences in FVC reduction and flow rate changes in low lung volumes between the two MEFV patterns. The MEFV patterns showed marked reductions in flow rates all over the lung volumes and showed themselves squashed between the two MEFV patterns.
3. In a case of the attack provoked by the MEFV maneuvers, the MEFVC showed a marked reduction in the flow rates all over the lung volumes, especially at the high lung volumes, and it looked like squashed.
4. The measurement of the MEFVC is effective in taking care of asthmatic patients.

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In order to clarify the biological toxities of nitrosamines, the effects of nitrosamines on the biological membrane, especially on the energy transfer reaction and on the K₊ compartmentation of mitochondria were examined.
The results obtained were as follows;
1) DPNA and DBNA uncoupled the oxidative phosphorylation of rat liver mitochondria at the low concentration (about 0.2 mM solution).
2) Uncoupling activities of DPNA and DBNA to the mitochondrial oxidative phosphorylation were increased in accordance with the increase in concentration and showed a remarkable increase within the concentration range from 0.1 mM to 0.2 mM solution.
3) The release of K⁺ from mitochondria was induced by treatment with DPNA or DBNA, especially was accelerated by DPNA. However, it could not be induced by treatment of 1mM DMNA or DENA.
4) The order of K⁺-release intensity induced by nitrosamines was corresponding to that of uncoupling activities of nitrosamines.
5) In conclusion, it was recognized that the functions of mitochondrial membrane were damaged by nitrosamines and their injurious effects were influenced by their chemical structures in the order of DPNA, DBNA, DENA and DMNA. This suggests that nitrosamines may have injurious effects on the function of the biological membrane, as well as their already recognized effects of carcinogenecity or liver injury (liver cirrhosis).

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Specific granules in the atrial muscle cells were examined in normal and treated rats with electron microscopy.
By the Epon-embedded section, the specific granules existed in sarcoplasm along the nucleus and in sarcoplasm between myofibrils or beneath the cell membrane, and distributed as the granules with the electron dense core.
By the freeze-etching techniques, there were many membrane-associated particles on PF-surfaces of the limiting membrane of the granules.
By the administration of acetylcholine the shape and the distribution of the granules didn't change. But after the administration of atropine the granules increased, and after the administration of eserine these decreased in number without showing morphological changes.
By the administration of monocrotaline, the specific granules of the right atrial cells increased in perinuclear after 13 days, and increased in all areas of the atrial muscle cells according to many days and much dose of the administration.
On the basis of these experimental results, the function of these granules was discussed.

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Well water was contaminated by oil components in three houses living in K town located in the rural district in the northern part of Okayama prefecture in February of 1977. Authors conducted epidemiological survey and analysis of the well water. The results were obtained as follows.
1) Oil layer was recongized in the well erupted oil. Quantitative determination of oil components of well water obtained from two wells located in the neighbourhood was conducted. Data indicated that trace or no oil was detected by n-hexane extractive method and 0.3 ppm and 0.1 ppm of oil was detected by nondispersion type ultrared spectrophotometry.
2) It was recognized that oil components contaminating well water were derived from mineral oil by ultrared spectrophotometry of erupting oil.
3) Source of contamination was not clear. However, mineral oil-tanks and relational equipments in buildings with boilers or gasoline stands located in the neighbourhood of houses with contaminated well were considered. And it was suggested that mineral oil leaked from these sources and contaminated well water through underground.
4) It was confirmed that environmental pollution with mineral oil in such case could occur in rural district. Discussion was made that these evidence could be new problem in the field of public health.

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Since the cessation of vaccination for whooping cough in Okayama Prefecture in 1973, the tendency of the outbreak of whooping cough-patients is being watched with keen interest in the field of public health. From the outbreak of patients in four monitering hospitals in Okayama Prefecture, the authors conducted analysis of the tendency of the outbreak of whooping cough-patients by analysis of time series. The results may be summarized as follows;
1. The tendency of the outbreak of whooping cough-patients by month analyzed by average monthly indicator in 1976 and 1977.
1) The outbreak of patients in O-Hospital located in the southeastern part of Okayama Prefecture increased gradually from January and reached a smaller peak in April and reached a larger peak from July to September and decreased later.
In comparing the outbreak of patients in each of other hospitals with that in O-Hospital, the distinctive features could be recognized as follows. In K-Hospital located in the southwestern part of Okayama Prefecture, a larger peak was observed in April and May, and a moderate peak was observed from August to October. In Y-Hospital located in the northwestern part, no peak was recognized in April, and a larger peak was recognized in November as well as from July to September. In T-Hospital located in the northeastern part, a moderate peak was recognized in December.
2) From January to June, the tendency of the outbreak of patients in southern part was earlier than that in northern part. From July to October, monthly indicators in both northern and southern parts were high. In November and December, monthly indicator in southern part dicreased below 1.0, but that in northern part did not dicrease below 1.0. Data indicate that differences in the tendency of the outbreak of patients by month between northern and southern parts of Okayama Prefecture were recognized.
2. The tendency of the outbreak of whooping cough-patients by year analyzed by average monthly number of patients in 1976 and 1977 and average monthly estimated number of patients in 1978.
1) The number of patients in each of four hospitals was greater in 1977 than in 1976.
2) Statistically, it is forecarsted that the number of patients in O-Hospital would decrease more remarkably, and that in K-Hospital and Y-Hospital would increase gradually, and that in T-Hospital would increase more remarkably in 1978 than in 1977. Data indicate that differences in the tendency of the outbreak of patients by year among four districts were recognized.
3. The estimated number of patients in 1978. The estimated number of patients in O-Hospital is calculated as 52.9, and that in K-Hospital is calculated as 312.6, and that in Y-Hospital is calculated as 91. 1. and that in T-Hospital is calculated as 336. 3.
4. Discussion in the field of public health.
1) The authors discussed in respect to the tendency of the outbreak of whooping coughpatients in all of Okayama Prefecture and methods to grasp it.
2) Data of the tendency of the outbreak of whooping cough-patients by analysis of time series will be an important factor for taking countermeasures in the field of public health.
3) It is necessary for the party concerned to conduct surveillance and take countermeasures for whooping cough in each district.
4) It is necessary for the party concerned to analyze epidemiological factors as well as to conduct surveillance of the outbreak of whooping cough-patients.

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The hemagglutination inhibition (HI) test was conducted with serial sera of 63 persons, collected annually in 1972, 1973 and 1974, using 4 strains of A Hong Kong and 5 strains of influenza B virus as antigen. It was proved that the incidence of influenza A was reduced by means of lower positive rates (of titers 64 or over) of HI titers than prior observation before epidemic. The fact that the incidence of influenza B was reduced is proved by the more lower positive rates. From the result that HI titers against B/Osaka/2/70 strain and B/Hong Kong/72 viruses differed according to age distribution, it is suggested that B/Osaka/2/70 strain must have been prevalent about 50 years ago and B/Hong Kong/72 viruses have been about 30 years ago.

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ホルマリン浸漬濾紙の皮下埋没によって形成される,ラットの肉芽組織のcyclic AMP含量に対するhistamineの効果を調べ,次のような成績を得た.
histamine注射(5 mg/kg, i. p.)後10-30分にわたって有意のcyclic AMPレベルの上昇が認められ, histamineの用量を50 mg/kgに増やすと効果は減弱した. histamine 5 mg/kgによるcyclic AMPの増加はburimamide 1 mg/kg, s. c. あるいはmepyramine 1 mg/kg, s. c. による前処置により抑制されたが, burimamideの方がmepyramineよりもより有効であった.これらの両拮抗剤の併用によってhistamineの効果は完全に遮断された.
burimamideとmepyramineは, 1 mg/kgの用量ではいずれもadrenaline 1 mg/kg, i. p. によるcyclic AMP増加を遮断しなかった.
propranolol. 1 mg/kg, s. c. によって, adrenalineの効果は逆転し, histamineの効果は部分的に抑制された.
試験管内実験で, 1mMおよびそれ以下の濃度のhistamineは,単独では,肉芽組織切片のcyclic AMPレベルに影響を与えなかった.しかし, histamine 1 mMはtheophylline 1 mMの共存下では, theophylline単独の場合に比べてcyclic AMPを有意に増加させた. theophylline単独でも,薬物を添加しない対照に比べると有意のcyclic AMP増加が起こった.
metiamide 1 mMは, theophylline 1 mM存在下でのhistamine 1 mMによるcyclic AMP増加を完全に遮断した.一方, mepyramine 1 mMは,このhistamine効果を部分的に抑制した.
以上の成績より,肉芽組織構成細胞にはH₂-受容体が存在していて,その刺激がhistamineによるcyclic AMP増加に主要な役割を演じるものと考えられる.また, H₁-受容体もcyclic AMP増加に或る程度関与しているものとみられる.

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A cardiovascular epidemiologic survey was performed in three different areas in Okayama prefecture since 1966 with follow-up until 1976 regarding to blood pressure and ECG (Minnesota Code).
A total of 1906 subjects, 789 male and 1117 female, with an age-range of 35-65 years were studied and the following results were obtained:
1) The blood pressure was well controled by adequate antihypertensive therapy, especially in diastolic pressure.
2) By the Minnesota Code classification, most individuals with Code 1-0 in the initial examination, especially with normal blood pressure, maintained the same ECG code, while a Code 3 subcategory alone in the initial examination changed frequently to other codes with-out direct relation to blood pressure.
3) Such alterations to other codes were rare in those who had shown Code 3 combined with Code 4 or 5 initially.
4) There were little or no changes in ECG code of individuals with an initial rating of Code 4.
5) Code 5 was found more frequently in female, and restoration of the code to normal ECG occurred in a considerable population during the follow-up.

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The relationship between blood pressure and ECG findings (Minnesota Code) were studied in 1906 subjects aged from 35 to 65 in 1966 in three districts of Okayama prefecture from 1966 to 1976.
Following results were obtained;
1. Comparison of the mean values of blood pressure (of 918 subjects, 307 male and 611 female) between the first half (1966-1970) and the second half (1971-1976) period showed that the blood pressure fell in the majority of patients with moderate or severe hypertension but elevated in 13-15% of subjects with mild hypertension (satisfying both the systolic blood pressure of 180 mmHg and the diastolic blood pressure 100 mmHg). Both improvement and aggravation in blood pressure were more frequent in male, while in female blood pressure level mostly remained unchanged.
Blood pressure in the plane district (Osahune-Cho) was the most favourable than that in other two districts.
2. Along with an elevation of blood pressure, Code 1-0 in ECG decreased and codes for left ventricular hypertrophy (combination of two or more subcategories of Code 3, or of Code 3 with Code 4 or 5) increased.
Code 1-0 decreased with aging, while prevalence rate of Code 4 or Code 5 was affected neither by aging nor by blood pressure.
3. The ECG code suggesting left ventricular hypertrophy closely related to systolic blood pressure.

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