17- (2-Dimethylaminoethoxyimino) -5α一androstan-3β-01はラット血漿cholestcrol値を低下させ同時にdesmostcro1の蓄積を来す.従つて, その作用は1- [4 (diethylaminocthoxy) phenyl] -1- (p-tolyl) -2- (p-ch-lorophenyl) -ethanol (MER-29) と同じくΔ²⁴-sterolreductaseを阻害してcholestcrolの生合成を阻害するものと考えられる.この化合物は肝cholcsterol値も低下させる.長期間投与すると血漿cholesterolのみならずphospholipidも低下し, 又, 副腎重量は増加する.然し, 他の組織重量は変化を受けないが体重の増加度は対照群よりも低い.この化合物は経口投与では活性が発現しないが誘導体の一つである3- (2-dim-ethylaminoethoxy) -17- (2-dimethylaminoethoxyimino) -estra-1, 3, 5 (10) -trieneは経口投与でも活性が認められる.20種の誘導体について検討した結果, 皮下注射で活性が発現する為には少くとも17位に2-dimethylaminoethoxyimino基が存在するか又は3位に2-dimethylaminoethoxy基が必要であり, 17- (2-dim-ethylaminoethoxyimino) -steroidの場合には末端Nがtrimethylamino誘導体 (4級アミン) になるか3位がoxo-誘導体になると活性は消失する.5α-Androstane誘導体は5β-誘導体よりも活性が高い.17位側鎖の炭素数を-つ長くすると活性は減弱する.3-Desoxy誘導体は活性が一般に強くなり特に3α-Cl置換体は活性が高い.

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Variation of urinary gonadotropin output was studied under various conditions in the gynecological area, such as oophorectomy, adrenalectomy, the administration of steroid hormones, clomiphene or triiodothyronine (T3).
Urinary gonadotropin was extracted by the modified Bradbury's kaolin adsorption method and determined with the method of weighing mouse uterus. The experimental results are summarized as follows.
The output of urinary gonadotropin was markedly increased in both postmenopausal and castrated women. There are, however, few cases which have shown low excretion value or daily variation. Moreover, in the postmenopausal women it tended to be higher in the sixth decade in general, but showed lower value with the increase of age.
Urinary gonadotropin was not significantly increased in the premenopausal women with unilateral oophorecomy.
On adrenalectomy in the patients who had advanced or recurrent breast cancer, the output of urinary gonadotropin was increased markedly after an adrenalectomy in post-menopause, but not marked in pre-menopausal women.
On administering the steroid hormones in castreted women, the following results were obtained : Urinary excretion of gonadotropin was slightly decreased in 2 out of 4 cases who had received 100γ of mestranol for 8 days, while it was decreased markedly in the group which received 20 mg of norethindrone for 14 days. The suppression of output of urinary gonadotropin was more emphasized, in effect. on administering the mixed preparation of both compounds.
The administration of a new ovulation-promoting agent, clomiphene, increased the urinary gonadotropin, but the synthetic thyoid hormone, T3. failed to affect the gona-dotropin noticeably.
On administering ACTH (a total of 40 I.U. in 4 days) in castrated women, the output of urinary gonadotropin tended to be decreased.
The effect of administration of predonisolone (30 mg for 5 days), in castrated women, was not apparent. On the other hand, a slight increase of urinary gonadotropin was obtained with administering dexamethasone (1.5 mg for 5 days).
Thus, even in the postmenopausal or castrated women, urinary excretion of gonadotropin is thought to be closely related to the adrenal cortex. Therefore, a certain feed-back mechanism has been suggested between the gonadotropic activity of the anterior pituitary and the adrenal cortex, and its leading role is assumed to be accomplished by the adrenal steroids, especially so-called extragonadal estrogen.

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合成黄体ホルモン剤であるchlormadinone acetate (GMA) をwistar系妊娠ラットの妊娠後期に1日8mg連続7日間経口投与し, 出生仔肛門一外性器間距離 (AGD), 性成熟, 交尾能などに対する影響をnorethisterone (NET, 1日2mg投与) と比較検討し次のごとき結果を得た. (1).CMA投与群雄AGDは対照に比し短縮即ち女性化 (fcminization) を示した.NET群では雌AGDの伸長即ち男性化 (masculinization) が認められた.この変化は胚仔発育とは特に関係なく肛門一外性器部位に独立した変化である. (2) CMAによりfeminizationを生じた雄ラットAGDは短縮したまま生長を続け, 離乳時でも出生時の対照との差がそのまま出現した.これに対しNETにより生じた雌ラットAGDの伸長は生後10日で正常に回復した. (3).外性器発育を指標とした性成熟過程は, CMA群, NET群共に雄ラットの性成熟が対照に比し遅延傾向を示した.雌ラットの性成熟は両群共対照と差が認められなかつた.なお外性器の形態異常は雌雄ラット共にみられなかつた. (4) Sister-brothermatingにより交尾能を検討したところ, CMA群の雌雄ラット及びNET群の雌ラットの交尾率は対照に比し著明に低下していた.このことは胎生期に受けたsteroidの影響が生後の性機能に出現する可能性を示すものであり, その作用機序と共に今後の検討を要する問題と考える.

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This study was made to clarify clinico-pathological character of malignant goiter. The materials used in this study comprise 1006 cases of thyroid diseases containing 78 malignant goiter which were removed by operation and 550 thyroids containing 6 malignant goiters which were obtained by autopsy. The following result were obtained.
1) On the histological classification of 84 malignant goiters, papillary adenocarcinoma occupied a greater part of them (58 cases, 69.2%). Of the 84 cases conclusive diagnosis of malignant goiter, only 36 (42.9%) had been clinically diagnosed as malignant from the initiation, and the remaining cases had been diagnosed as other diseases containing 32 cases of simple nodular goiter (38.1%).
2) Analysis of the duration of suffering and postoperative survaival rate of patients with malignant goiter was made. Patients with papillary adenocarcinoma showed a benign clinical course among the patients with malignant goiter. On the other hand, patients with non-papillary carcinoma, especially with anaplastic carcinoma showed the same malignant clinical course as those with cancer of the other organs.
3) In some cases that had been diagnosed clinically as simple nodular goiter, coexistence of carcinoma tissue and colloid follicular tissue was found histologically. The malignant goiter arises as a result of the malignant transformation of the tissue of a pre-existing nodular goiter, was suggested.
4) Study of distributions according to the age of the patient with malignant goiter revealed following result.
Malignant goiter was found most frequently in the middle age group, and also found frequently in the young age group under 20 years old. Nonpapillary carcinoma, especially anaplastic carcinoma was frequently found in the aged group over 60 years old.
5) Nodular goiter (including malignant goiter) appered with greatest frequency among patients in the middle age. But the rate of incidence of malignant goiter in the nodular goiter, was remakably low among the patients of middle age group, and high among senile and juvenile age group.
From this, it was considersds that nodular goiter of senile and juvenile age have a more malignant character than those of middle age.
6) Further, from the observation of duration of malignant goiter in senila and juvenile age, it was suggested that this might be carcinoma from the beginning without amy relationship with simple nodular goiter.

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Electron microscopic observations of the thyroid gland, especially with bening adenoma and papillary adenocarcinoma were made, and the following findings were obtained.
1) In papillary adenocarcinoma, the nuclear membrane of cells serpentined irregularly and invaginated deeply. The nucleus showed the largest as compared with others in other various diseases of the thyroid gland. The nucleoplasm with moderate electron density seemed to be crowded with spots beside the nuclear membrane in general. The nuclei showed good development and the nucleolonema was demonstrated distinctly. The mitochondria in cytoplasm showed incomplete appearance as well as swelling. The mitochondriale cristae were fairly destructive. In intracelluar space, microvilli-like projections with finger-like shape were observed abundantly.
In the basal parts of cancer cells, structures whcih correspond to the basal membrane were distinctly constituted from tripel-layer. The connective tissue fibres without cell components, on which there were about 640Å of stripes, were obtained. And the fibres seemed to be adjoined to the basal parts or the basal membrane of cancer cells through the interstitial connective tissue which developed into callositas-like structures.
From these observations, isolation or decampment of cells in papillary adenocarcinoma may be difficult on the their basal parts. It is postulated that papillary adenocarcinoma in the thyroid gland has a benign clinical course from these electron microscopic findings.
2) Tubular adenoma in thyroid tumor was observed to be in regular arrangement in adenoma cells. The nuclei were rounded in general the nuclear membranes had a smooth appearance. And the nucleoplasm was distributed homogeneously.
The mitochondria showed a moderate swelling and remarkable development, simultan-eously, in cytoplasm.
The basal membrane developed widely similar to the belt at the basal parts of cells. The findings of capillary vessels were varied in same electron microscopic fields and observed to have poor development or deficient compared with normal findings.
In some cells composed of identical follicles, epithelial cells were seen to have a dense nucleus or atrophy of the cell itself.
These changes seemed to be caused by the disturbance with absorption or excretion of produced follicle substance influenced by disorder of blood stream. Consequently, cystic degeneration occurs in nodular goiter may be concluded from these findings that.

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In this experiment, the author used nine kinds of vitamins and the normal or alloxan diabetic, male or nonpregnant female Wistar strain rats, weighing over 120 g, to find out if there was a hypoglycemic action without any side effect among those drugs.
The blood sugar content was measured by the method of Somogyi-Nelson's blood sugar determination (micro-micro method).
1) Individual doses of 100 mg/kg of thiamine, 50 mg/kg of nicotinamide, 100 mg/kg of pyridoxine, 100 mg/kg of anthranilic acid, 100 mg/kg of folic acid, 400 γ/kg of cyanocobalamin, 400 γ/kg of hydroxobalamin, 5000 mg/kg of ascorbic acid or 50 mg/kg of hesperidin were administered intravenously in normal rats which had not been fed for 18 hours, with the following results :
a) A potent activity of blood sugar lowering effect was observed in the case of folic acid, cyanocobalamin and hydroxocobalamin.
The maximal hypoglycemic reduction ratio of the blood sugar level in folic acid was 45% one hour after the administration, but was of transient duration. In cyanocobalamin, the reduction ratio was 55% one hour after the administration, but the duration was also transient. In hydroxocobalamin, the reduction ratio was 46% 4 hours after the administration, and its action continued over 8 hours.
b) No hypoglycemic effect was observed in thiamine, nicotinamide, pyridoxine, anthranilic acid, ascorbic acid or hesperidin.
2) Individual doses of 400 mg/kg of folic acid, 1500 γ/kg of cyanocobalamin or 1500 γ/kg of hydroxocobalamin were administered orally via stomach tube in normal rats, which had not been fed for 18 hours, and the blood sugar lowering effect was observed in all of them. The maximal hypoglycemic reduction ratio of blood sugar level in folic acid was found to be 41% one hour after the administration, but it was of transient duration. In cyanocobalamin, the reduction ratio was 51% one hour after the administration and its duration was also transient. In hydroxocobalamin, the reduction ratio was 57% 6 hours after the administration and was of long duration.
3) Individual doses of 400 mg/kg of folic acid, 1500 r/kg of cyanocobalamin or 1500 r/kg of hydroxocobalamin were administered orally via stomach tube in alloxan diabetic rats, and a blood sugar lowering effect of much longer duration was observed in all of them.
The maximal hypoglycemic reduction ratio of boold sugar level in the case of folic acid was found to be 69% 5 hours after the administration. and in the case of cyanocobalamin it was 66% 5 hours after the administration. In both of these cases the rats had not been fed for 18 hours. With rats that had been fed normally, the maximal reduction ratio of the blood sugar level was found to be 43% 3 hours after the administration of cyanocobalamin and 54% 6 hours after the administration of hydroxocobalamin.
4) The administration of folic acid via stomach in normal rats, at a dose rate of 400 mg/kg/day or of cyanocobalamin at a dose rate of 1500 γ/kg/day for a month revealed no histological change in the various organs, including Langerhans' islet.
5) In an experiment involving intravenous administration of folic acid at a dose of 100 mg/kg and of cyanocobalamin at a dose of 400 γ/kg in normal rats, the blood sugar levels were measured under the interruption treatment of the blood supply in the pancreas, and the situation of β-granules in Langerhans' islets was observed after the rats had been killed when they had almost reached the maximal hypoglycemic state.
The results obtained were as follows :
a) With or without interruption of the pancreatic blood supply, no change was found in blood sugar levels in the case of folic acid, cyanocobalamin or hydroxocobalamin.
b) There was no histological change in the β-granules of Langerhans' islets of the pancreas in all cases.
These three kinds of vitamins (folic acid, cyanocobalamin and hydroxocobalamin), therefore,

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