Rabbits, guinea pigs and rats were adminstered with imidazol derivatives and methylthiouracil for months in continuance and subjected to morphological and biochemical examinations. The results obtained may be summarized as follows ;
1. When histidine or creatine was administered for 3 months and longer, the thyroid gland of rabbits and guinea pigs was found swollen, to a higher degree after creatine.
2. When histidine or creatine was administered for long duration to rabbits, their thyroid gland showed the microscopic figure of struma parenchymatosa diffusa microfollicularis.
3. When histidine or creatine was administered to guinea pigs for long time, their thyroid gland microscopically showed the figure of struma colloides.
4. When histidine or creatine was administered to rats for long time, no symptom of struma was forthcoming.
5. Administration of methyl-thiouracil to rabbits, guinea pigs and rats caused severe struma parencymatosa diffusa microfollicularis.
6. Histidine or creatine administration, unless continued long enough, induced neither macroscopic nor microscopic changes in the thyroid gland of any of the experimental animals.
7. Administration of methyl-thiouracil, even of short duration, caused evident morphological changes in the thyroid gland.
8. Following administration of histidine and creatine the I “' uptake rate and the I” ' conversion rate into organic iodine were found remaining within the normal ranges.
9. Following administration of methyl-thiouracil, the above rates were found fallen frankly below normal.
10. The PBI value of blood and the serum cholesterol level following histidine and creatine administration were generally within the normal range.
11. The blood PBI value was found markedly reduced and the serum cholesterol content risen after administration of methyl-thiouracil.
12. No marked change was observed in the pituitary gland after histidine or creatine administration.
13. Following methyl-thiouracil administration, however, basophil cells were proliferated and hypertrophied and thyroidectomy cells began to apper in the anterior lobe of the pituitary gland.
14. From the above findings, it is inferred that the effect of histidine and creatine of the thyroid gland is utterly different from that of thiouracil derivatives, and may be called a goitrogen-accelerating action.
This action has been confirmed as being due to the imidazol radical but not to a direct chemical combination of the imidazol derivatives with iodine.
Acknowlegement : The author is greatly indebted to Professor Shigeki Mori and assistant Professor Osamu Midorikawa for incessant kind guidance.

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Many experimental studies about the correlations between function of the thyroid and the hypothalamico-hypophyseal system have been recently executed.
But in spite of these efforts some points are not clear, so the morphological changes of neurosecretory pathways during 60 days after thyroidectomy in normal cats were observed to investigate the interactions of both organs.
The specimens from the hypothalamico-hypophsel system were mainly stained with A.-F method and C.H.P. method.
The diameters of the nuclei of neurosecretory cells were measured by an “Okular Schrauben Mikrometer” to know the condition of cells' functions.
The results obtained were as follows : The production and discharge of the Gomori positive materials of the paraventricular nucleus already began to increase from the 3rd day after thyroidectomy, and after two weeks this function reached a peak.
On the other hand, the supraoptic nucleus indicated slightly the state of hypofunction.
After 30 days both the paraventricular nucleus and supraoptic nucleus showed morphological change of atrophy, and decreased the Gomori positive materials.
From these findings, it may be surmised that the neurosecretory pathways were influenced by thyroidectomy ; especially the activity of the paraventricular nucleus increased markedly.
And thus, it seems likly that there are some close relationships between the function of the para. ventricular nucleus and TSH secretions.

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The Robinson-Power-Kepler test was originally used as one of tests for adrenocortical functions ; however, when applied to elderly people, the incidence of the positive result of the test was very frequent even though there, was no apparent adrenocortical insufficiency, furthermore, there was a parallelism between incidence and chronological age. This test may be applied as an index for the evaluation of the biological age of an individual.
In this report, the various elderly individuals in an assylum were subjected to the test, and to investigate the shift in the incidence of the positive result of the test as compared with the progress of chronological age, individuals from different age groups were studied. In order to elucidate the peculiarity of the positive results in elderly people, clinical tests pertaining to the functions of the kidney, adenohypophyseal aderenocortical system and neurohypophysis were evaluated and in addition the effects of the administrations of various hormones related to waterdiuresis on the results of the Robinson-Power-Kepler test also were observed.
1) The Robinsou-Power-Kepler test was give to 67 elderly subjects, 49 of whom were healthy and 18 were suffering from nephritic and or hypertensive disorders. The results of the first procedure showed positive result for 56 of the total number of subjects. The factors accounting for so many positive results in the first procedure of the test on these elderly subjects were the increase in the volume of urine excreted by each subjects during the night and the decrease in water diuresis.
Almost all the subjects, 63 out of 67 showed positive results in the second procedure of the test.These results may be attributed to the above-mentioned factors and in addition the retention by these elderly subjects of urea in the blood.
Finally, 10 subjects 20-30, 30-40, 40-50, 50-60 years of age respectively, were given to the first procedure of the Robinson-Power-Kepler test and an increase in the incidence of a positive results was observed with an increase in the subjects' chronological age.
2) Seven subjects were selected at random among the elderly subjects showing positive results to the test and the glomerular filtration rate, renal plasma flow, filtration fraction, reabsorption rate, urea clearance of thse patients' kidney functions were determined. The averages of the above indexes in these subjects were low but still within the range of the rejection limits of the averages of the indexes of the healthy adults in Japan, this fact indicating a slightly reduced renal function in aging. It may be stated that even slight decreases in kidney functions which usually accompany the aging processes may be more clearly revealed by the Robinson-Power-Kepler test than by ordinary renal function tests.
3) The activity of the adrenal cortex was evaluated by investigating the daily amounts to the total 17-hydroxycorticoids excreted, and the change in the amounts of the steroids after an intramuscular injection with ACTH Gel were observed in 12 subjects picked at random. The daily excretion of 17-hydroxycorticoids in the urine of the elderly subjects investigated was almost at the same level as that of healthy adults, while the increase of urinary 17-hydroxycorticoids, after the ACTH administration, was lower in the elderly subjects than in that of healthy adults. This indicated a reduced hormone researve in the adrenal cortex of elderly people : however, the reduction is assumed to be far less than in Addison's disease. Another index for adrenocortical activity, the urinary excretion of uropepsin, also suggested the same information on adrenocortical activity.
4) Eosinopenic responses to ACTH, insulin, and epinephrine, used as a criterion for the evaluating of the status of the diencephalo-pituitary adrenocortical system, were examined at random in 6 subjects. The eosinopenic response was normal to ACTH,

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Since ten years ago, problem of the hypothalamic control of ACTH secretion have been studied, but there is no agreement concerning of its localization in the hypothalamus. This experiment was planned to clarify this point in non-pregnant adult rabbits, and the results are shown as follows :
1) Preliminary experiments.
In unrestrained rabbits, bleeding procedures and anesthesia with nembutal did not evoke a lymphopenic response. On the other hand, restrained rabbits in the fixing box, showed the remarkable response and it could not be prevented by a certain amount of nembutal. The administration of ACTH or the exposure to the stress stimuli (subcutaneous electrical stimulation), did also evoke the lymphopenic response in the unrestrained rabbits.
2) Experiments of electrical stimulation and destruction in the hypothalamus.
This experiments were carried out by Kurotsu's method using the Kurotsu-Shimizu's apparatus.
In restrained rabbits without anesthesia, the decrease of the number of lymphocyte was statistically significant three hours after stimulation of nucl. ventromed., although this response was not constantly evoked by the stimulation of nucl. lat., probably because of the influence of restraint.
In the unrestrained rabbits anesthetised with nembutal, hypothalamic stimulation which was described above was carried out. The stimulation of nucl. ventromed. evoked the remarkable lymphopenic response, whereas the stimulation of nucl. lat. induced no significant change. These results seem to confirm the tendency of the former experiment.
Rabbits which were destructed their bilateral nucl. ventromed. did not show the lymphopenic response by the subcutaneous stimulation, whereas rabbits destructed their bilateral nucl. lat. still could respond by the same stimulation.
3) Experiments in hypophysectomized rabbits.
After the administration of ACTH to the hypophysectomized rabbits, lymphopenic response was evoked as in the normal rabbits. The subcutaneous electrical stimulation and the stimulation of the nucl. ventromed. instead of the administration of ACTH, could not evoke the lymphopenic response in these operated rabbits. From these results, it is supposed that the stress stimuli reaches anterior lobe of pituitary gland via b-sympathetic zone (Kurotsu) in the hypothalamus and activates ACTH secretion.

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The statistical study on albuminuria, hypertension, diabetic retinopathy and ECG abnormalities as the cardiovascular complications in 172 diabetic patients was performed. All patients were admitted to Kurokawa's Clinic of Tohoku University Hospital from 1955 through 1957. They were divided into several groups according to sex, diabetic type, decade of age and the duration of diabetes for the purpose of study.
Following results were obtained.
(1) The incidence of albuminuria was 30.4 per cent, and was 17.9 per cent when the cases with faint albuminuria were excluded. It was equally frequent in females and males, and more frequent in type II diabetics than in type I. This type of diabetes mellitus are clinical classification used in our Clinic. Type I indicates the mild diabetic case which can be controled by only the diet, and type II indicates the severe diabetic case which requires insulin besides diabetic diet.
(2) Hypertension was present in 38.2 per cent. It was also about equally frequent in both sexes, there was more frequent in type I than in type II.
(3) The occurrence of hypertension in the diabetic patients in this series was greater than in the nondiabetics in all decades. Significant difference was observed in only the 5th decade. It was not found, however, that the average systolic blood pressure of diabetic people in this series was higher than of normal Japanese people in both sexes, and the average diastolic too.
(4) Diabetic retinopathy was observed in 27.1 per cent, and there was no significant difference in the occurrence between both sexes.
(5) Kimmelstiel-Wilson syndrome was present in 9.3 per cent. There was no significant difference in the frequence of Kimmelstiel-Wilson syndrome between the both sexes, and between type I and type II also.
(6) The occurrence of ECG abnormalities was 38 per cent. There was no significant difference between both sexes, and between both types also.
(7) The incidence of the vascular complications shows a gradual increase from 1955 to 1957, and it was found that more than a half of the diabetics in last 2 years had at least one of the vascular complicatons.
(8) The frequency of hypertension and Kimmelstiel-Wilson syndrome increased with age of diabetic patient, while the frequency of albuminura, diabetic retinopathy and ECG abnormalities was not parallel to the age.
(9) It seems, however, that the frequency of albuminuria, diabetic retinopathy, Kimmelstiel-Wilson syndrome and ECG abnormalities, except hypertension, increase with the prologation of the duration of diabetes.

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Derangement in metabolism was studied on 59 slight cases of obese diabetics. Predominance of these cases is characteristic after the close of World War II. Metabolic observations were made on diurnal alteration and responsive changes to stress in these patients and the following results were obtained.
1) Concomitant retarded response in protein metabolism was observed with retardation in carbohydrate metabolism. Following the recovery in carbohydrate metabolism after two successive injection of insulin, normalization in protein metabolism was also observed. However, derangement in circulating eosinophils, serum iodic acid value, and water content of blood was still observed in spite of the blood sugar being regulated to the level characteristic for each individual.
2) Decrease in circulating eosinophils was observed in instances where the blood sugar level was heigh and in instances where blood sugar level was controlled, the circulating eosinophils tended to be increased gradually to normal levels.
3) In normal subjects, response to stress was observed to be stronger after injection of ACTH as compared with intravenous injection of glucose. In diabetics, this was observed to be visa versa. These results lead to the presumption that the adrenocortical system of diabetics is not in the hypo-functional state.

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