Tumors of the nervous system were induced in rats of Donryu strain by a single injection of 50mg/kg.b.w. of ethylnitrosourea (ENU) through the mothers. A total of 126 tumors were produced in 92 of 117 treated offsprings. The survival time of animals with tumor development ranged from 53 to 607 days. The neural tumors amounted 104, comprising 82.5% of the total number of neoplasms. Besides grossly visible tumors, histological examination of the brain and spinal cord disclosed a total of 166 foci of glial cell hyperplasia or tumors of microscopic size. On histological sections 86 of these lesions measured less than lmm in diameter, 61 between 1 and 2mm, and 19 more than 2mm. The predominant cell type of the smaller lesions was either astrocytic or oligodendroglial. With increasing tumor size, a number of microtumors with a mixed cellular composition became frequent. Sites of predilection for such microtumors were the subcortical white matter of the brain, the hippocampus, the paraventricular areas, the basal ganglia, and the spinal cord. It would seem that grossly visible tumors are formed by expansion and fusion of these lesions of microscopic size and by development of anaplasia of constituent glial cells.
Light and electron microscopic studies were also made on the brain and the trigeminal nerve of rats treated transplacentally with ENU at intervals of 10, 35, 80, 120, 150, 200, 250, 300 and 400 days after birth. A total of 48 microtumors were found in the brain of rats which had survived over 120 days. Electron microscopy disclosed these lesions to be largely composed of cells with ultrastructural features of astrocyte and oligodendroglia. The presence of a large amount of extracellular matrix was considered in part to account for the honeycombed structure typical of oligodendroglial microtumors in light microscopy. Observations of the trigeminal nerve disclosed occasional foci of diffuse endoneurial cell proliferation which started to arise from the 80th day. At the ultrastructural level, the proliferating cells were found to retain a typical Schwann cell appearance and relationship to axon. The nerve fiber was often surrounded by numerous cell processes, forming onion bulb-like structure.
The third experiment was undertaken to investigate the acute cytotoxic effect of ENU on the nervous system. A single dose of 50 or 100mg ENU was given to rats perinatally and the nervous system was examined with light and electron microscopy at intervals from 6 to 48 hours after injection. A considerable proportion of cells constituting subependymal matrix layer of the lateral ventricle and extragranular layer of the cerebellum were found undergoing degeneration with disappearance of mitotic figures after 6 to 12 hours. Schwann cells in the trigeminal nerve and glial cells of the cerebral white matter were also found similarly involved. Neurons seemed to be less affected.
From these observations it was concluded that oligodendroglia, astrocytes and Schwann cells are the most susceptible targets in the brain and nerve to carcinogenic nitrosourea compounds.

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Hemodynamic changes similar to normal healthy subjects were observed in patients with implanted permanent pacemaker and fixed heart rate during the sustaincd hand-grip and bicycle ergometer exercise.
The sustained hand-grip exercise caused a slight but significant elevation of blood pressure as well as a slight but significant prolongation of left ventricular ejection time (LVET), while the cardiac index remained unchanged.
On the other hand, during ergometer exercise, the blood pressure, cardiac index and LVET were markedly increased, while the pre-ejection period (PEP), PEP/LVET, isovolumetric contraction time and total peripheral resistance were significantly decreased. So far as the pacing rate is concerned, the increment in cardiac index was slightly augumented and the recovery time of the hemodynamic changes following the exercise was shortened when the pacing rate was increased from 70 to 100, although the differences were not very marked.
The present results indicate that the hemodynamic adjustments to the exercise are appropriately maintained even in the patients with artificial pacemaker and fixed heart rate. The results also suggest that a higher pacing rate than in rutine use may be more appropriate for the exercise.

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The effect of ouabain on sinoatrial and atrioventricular conduction, and the time required to intoxication was studied in 10 dogs with intact autonomic state, 8 dogs with vagotomy, 4 dogs with sympathectomy and 5 dogs with autonomic blockade state (vagotomy+ sympathectomy). The sinoatrial conduction time was determinded by using the premature atrial stimulation method and was represented as antegrade plus retrograde conduction time (SACT_A+R). Ouabain (10μg/kg) was administrated intravenously at 10 minute intervals until toxic arrhythmias developed. At each time interval, SACT_A+R and His bundle EKG was recorded. In intact autonomic group, as the dose of ouabain was increased, SACT_A+R was prolonged and reached to the peak at 40-80% subtoxic dose. However, when the dose was further increased, the prolongation of SACT_A+R was decreased and the SACT_A+R shortened in some cases. In vagotomized group (P < 0.05) and autonomic blockade group (P < 0.025), the prolongation of SACT_A+R was less marked than in intact group. On the other hand, in sympathectomized group, the SACT_A+R was markedly prolonged (P < 0.005) and the prolongation remained unchanged until toxic dose was reached. We concluded that the prolongation of SACT_A+R following ouabain adminstration was mainly dependent on vagal nerve activity, while the later decrease of prolongation was dependent on sympathetic nerve activity.
The A-H time was prolonged as to the ouabain dose was increased. The prolongation of A-H time was most marked in sympathectomized group, while less marked in vagotomized group and autonomic blockade group than in intact group. The time required to ouabain intoxication tended to be longer in sympathectomized and autonomic blockade group.
These results indicate that the effect of ouabain on SACT_A+R, A-V conduction and ouabain intoxication was mainly dependent on autonomic influences. The consideration on autonomic state is necessary to evaluate the SACT and A-V conduction time in digitalized patients.

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In this communication we described about simple method for measuring adenylate cyclase activity of human thyroid plasma membrane using competitive protein assay for C-AMP and cold ATP as substrate for the enzyme. Technical details for preparing the plasma membrane were also described. In our assay system for thyroid stimulator, 44 immunoglobulins from patients with Graves' disease and 15 normal immunoglobulins showed no stimulating activity on human thyroid plasma membrane adenylate cyclase except one immunoglobulin from patients with Graves' disease.

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Intranuclear inclusions of the testicular Leydig cells were described in an autopsy case of synovial sarcoma. The inclusions were histologically identical to the intranuclear inclusions of Cowdry's type A. Histochemical analysis disclosed that they were mainly composed of protein. Inclusions were tentatively classified into 3 groups on the basis of their ultrastructural features. Type 1 inclusions consisted of irregular grouping of electron dense, floccular material. They were usually situated centrally within the nuclei, and there were prominent margination of the chromatin granules on the nuclear envelopes. Inclusions with mixed composition of fine filaments and floccular material, disignated as type 2, were evenly distributed in the karyoplasm. Type 3 inclusions consisted of numerous clusters of fibrillar structures randomly oriented to each other. The fibrins were composed of parallel rows of 4 or 5 dense fine filaments. The incidence of the type 3 inclusions is lower than that of the other two. In no instance were intranuclear inclusions and Reinke crystals encountered in the same cell.

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1) The distribution of blood group P₁ antigens in human organs was investigated. P1 antigen was found in blood group P₁ kidney. Both group P₁ and P₂ kidneys contained much P antigens and lung, spleen and heart contained small amount of P antigens.
2) The each fraction corresponding to globoside and CTH (ceramide trihexoside) isolated from kidney showed P and P^k activities respectively.
3) Treatment of the globoside fraction from kidney with human liver's crude enzyme preparation (contained ß-N-acetylgalactosaminidase) caused the loss of P specificity and the appearance of P^k specificity.
As the above results, it was confirmed that blood group P antigens in kidney were identical with those in erythrocytes.

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Pathologic changes, in particular the hemorrhage in organs, produced by intravenous injection of a lethal to sublethal dose of 100-pacer snake (Agkistroden acutus) venom and its purified proteolytic enzymes (Ac₁-, Ac₂-, and Ac₃-proteinase) were studied in mice. Death occurred within 24 hours after the injection, the lethal activity of Ac₁-proteinase was twice as powerfull as those of both Ac₂-, and Ac₃-proteinase. The pathologic changes in the animals injected with the venom and each of three proteinases were characterized by bleeding into various organs, the representative organs involved in the hemorrhage were the lung and heart with the venom, the kidny and stomach with Ac₁-proteinase, the stomach and small intestine with Ac₂-proteinase, and the lung with Ac₃-proteinase, respectively. Peculiar changes, seen only in mice injected with the proteinases, were glomerular hemorrhages with cystic lesion of the glomerular tuft, and multifocal hepatic hemorrhages resembling peliosis hepatis. The renal change characterized by segmental cystic dilatation of the glomerular tuft due. to mesangiolysis and bleeding into the Bowman's space was found in mice with each of three proteinases, but not with the venom. The hepatic lesion resembling peliosis hepatis was only investigated in some of mice with Ac₂-, and Ac₃-proteinase.

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