1. It was found that picrotoxine has an effect to arrest the sexual cycle on mature female rats for the period of 8 to 15 days, with the picture of diestrus. During the arrest of the sexual cycle the uterus presented a picture of luteohormone action, and the ovaries showed that of vigorous activity of the lutein body and the growth of ovarian follicles was inhibited and on about the seventh day of the reststadium the ovarian follicles began to develop and the luteinbody under-went retrogressive metamorphosis.
2. When luminal, a brain-stem narcotics, was concurrently used, there could be seen no such effects of picrotoxine just mentioned nor any noteworthy findings of the uterus and ovaries while in the case of concurrent use of urethan the effect of picrotoxine was rather potentiated.
3. The combined use of atropine or yohimbine had practically no influence on the effect of picrotoxine.
4. It seems that picrotoxine attacks the sexual function regulating center in the diencephalon, especially its inhibitory center of the sympathetic nervous system. In this instance, since the duration of the arrest of the sexual cycle and the findings of both organs coincide with those of pseudopregnancy, as reported by Long et al., the excitation of the central nervous system induces the pseudopregnancy phenomenon and the cerebral cortex plays a role of inhibitor and the resultant paralysis enhances the excitation of this center.

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While there are many basic and clinical studies on strychnine, reports on its derivatives are rare, except for a few reports by Koizumi and Chiyoda of our laboratory. They conducted general pharmacological studies on ethylstrychnine I, II, iodoethylstrychnine and strychnic acid ethylbetaine, new derivatives of strychnine. As a link in the series of such studies the author carried out some inverstigations on the effects of these three derivatives on blood clotting. and briefly presents the main results of the inverstigation.
1. Both ethylstrychnine I and II as well as iodoethylstrychnine, like their mother substance, strychnine, were found to shorten the blood clotting time of rabbits, and to enhance the blood coagulating elements. This effect was predominant in ethylstrychnine II followed by iodoethylstrychnine. The order of this potency coincides with that of the minimal lethal dose as found by Koizumi.
2. It was difficult to demonstrate this effect in vitro. Consequently, it is reasonable to assume that this effect to accelerate the blood clotting time is not due to a direct action of the drug on blood itself but is due to the bioreaction.
3. This accelerating effect on the blood clotting is almost completely inhibited by luminal, a brain-stem narcotics, but it is not affected by the premedication with yohimbine nor by the resection of bilateral, subdiaphragmatic splanchnic nerves.
4. It seems that this accelerating action is of a central nature and probably it is induced by an increase of coagulating elements such as fibrinogen and thrombin, resulting from the stimulating effect of the drug on the so-called blood coagulation-accelerative center in the diencephalon. In this instance, it appears that the splanchnic nerves are not involved in the transmission of excitation from the above metioned center to the peripheral region, but in this experiment it was impossible to demonstrate any evidence proving that the transmission of such stimuli is conducted via sympathetic accelerative fibers.

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Concering the relationship between the sexual cycle in albino rats and the autonomic nervous system, opinions are divided among workers. The principal reason for this difference in the opinions seems to lie especially in the methods employed in the application of autonomic drugs. Thus far most of investigators have administered autonomic drugs daily over a long period, but in the belief that for the solution of this problem it would seem to be more effectiv to administer repeatedly an adequate dose of these drugs for a short period of time, the author studied by this method the effect of pilocarpine on the sexual cycle of albino rats and reported that stimulation or tonic increase of the parasympathetic nervous system inhibited the development of ovarian follicles. In the present experiment for the purpose to verify this contention, the author used esmodil which is a chemical analogue of acetylcholine and has several pharmacological effects similar to the latter but whose effect on the sexual cycle remains obscure. As the results the following data were obtained.
1. The injection of esmodil in the dose of 0.1-0.15 mg repeated three times a day for 4 days beginning from proestrus arrested the sexual cycle for 6 to 14 days. In addition, there could be observed the findings in the ovary and uterus which corresponded such a suppression.
2. When esmodil was used concurrently with atropine, such a suppressing effect was practically all inhibited.
3. Consequently, these findings support considerably the author's contention that the stimulation or the tonic increase of the parasympathetic nervous system inhibits the development of the ovarian follicles.

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1. A certain dose of apomorphine and caffeine inhibits the sexual cycle in the albino rat.
2. Atropine administered in a certain dose has no influence on the inhibitory effect of either one of these two drugs, but luminal and urethan suppress almost completely the inhibitory action of these drugs, especially it has a reversal effect on the action of caffeine.
3. This prolongation of the sexual cycle seems to be due to the primary excitation of the cerebral cortex and subsequently that of the diencephalone, and aside from its inhibitory action caffeine has an accelerating effect and under normal conditions the former effect seems to predominate the latter.
4. It is to be concluded that the cerebral cortex is intimately related to the sexual cycle in the albino rat and its excitation inhibits the sexual cycle.

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1. A droplet application of adrenaline, ephedrine and adrenalone in the concentrations of 0.01%, 0.5% and 1% respectively applied to the pupil of normal rabbits brought about mydriasis of a similar degree in every case. Consequently, the potency of these drugs on bringing about mydriasis was in the order of 100:2:1. This finding coincides well with that of Kinoshita and Tani of our labaratory in which they found that ephedrine and adrenalone hardly affected the accelerative fibers of the sympathetic nervous system but these drugs strongly influenced the inhibitory fibers. The fact that the mydriatic action of ephedrine and adrenalone is far less potent than that of adrenaline seems to be explained by the fact that the dilatator muscles of the pupil are innervated with the accelerative fibers.
2. In the rabbit given a monolateral resection of the superior cervical ganglion the pupil on the resected side responded much more sensitively to these three drugs than that on the normal side. In such instances, there can be observed the so called “Paradoxe Pupillenerweiterung” phenomenon.
3. The administration of yohimbine alone has hardly any effect on the pupil of both normal and monolaterally resected rabbits, but in the rabbits previously treated with yohimbine, the mydriatic effect of adrenaline is clearly diminished. This fact further supports the contention that the accelerative fibers of the sympathetic nervous system are the principal controller of the dilatator muscles.
4. Urethan is found to enhance the mydriatic effet of adrenaline in both normal and rabbits monolaterally resected of superior cervical ganglion, but a similar phenomenon can also be observed in the rabbits given adrenalectomy. Therefore, it seems that the enhancement of adrenaline mydriasis induced by urethan is not due to the increase in the adrenaline secretion but rather due to the paralysis of the cerebral cortex.

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A histochemical study of ATPase activity in the experimentally intoxicated liver has been conducted and the following results were obtained.
1. ATPase was found to be mostly distributed at the sinusoid and bile capillary regions.
2. When the liver was damaged acutely or chronically with carbon tetrachloride, necrosis of the liver cells developed. At the site of necrosis, the capillary vessels were dilated and ran irregularly and often underwent cystic transformation which were caused by the necrotic degeneration of the hepatic cells. At the intercellular spaces around the necrotic resions, a high ATPase activity was demonstrated. These changes were considered to be resulted from the compression of bile capillary vessels with hepatic cells which underwent vacuolar degeneration.
3. No significant changes in ATPase activity at the bile capillary vessels was observed in the liver which received partial resection.
4. The distribution of ATPase in the liver after theα-naphthyl isothiocyanate administration or the ligation of the bile duct suggested the presence of marked biliary obstruction. In the former, ATPase activity was found at the perilobulular regions and increased towards the periphery. On the other hand, in the latter case a marked dilatation of the capillary vessels was observed and ATPase activity was more pronoucedly increased at the cholestasis.
5. ATPase activity in the sinusoid wall appeared to be lowered at the regions where vacuolar degeneration occurred but markedly increased where the hepatic cells underwent necrosis. This tendency was particulary apparent in Kupffer's cells. ATPase activity in the sinusoid seemed to be increased slightly when the liver underwent partial resection. ATPase activity of the sinusoid markedly increased at the perilobulular regions when intoxicated with α-naphthyl isothiocyanate and increased with the lapse of time in the case of hepatic duct ligation. These changes in ATPase activity under various experimental conditions suggest that this enzyme is involved in many aspects of hepatic functions particularly in the excretion and retention of the bile. The increase of ATPase activity in Kupffer's cells is also interpreted to indicate their intimate association to their functions.
6. The increase of ATPase in Glisson's capsule at the time of chronic hepatic disorders and high ATPase activity in the fibers developed at the border plate after theα-naphthyl isothiocyanate administration strongly suggest that this enzyme plays an important role in the formation of the fibers.

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Effects of anticoagulants on patency of venous graft were studied on dogs.
The following results were obtained.
1. A portion of superior vena cava was replaced with synthetic graft in 32 dogs, of which 20 were given Heparin and/or Warfarin postoperatively. The patency rate of graft was 77% in anticoagulant group compared to 50% in control group. However, there were 7 early deaths (35%) due to bleeding in the former group.
2. A portion of femoral vein was replaced with tetron graft (6mm in diameter) in 14 dogs and anticoagulants were given post-operatively. All grafts except one, were thrombosed within one week. Effects of anticoagulant on graft patency were not observed.
3. Patancy rate of patch graft with synthetic material for reconstruction of femoral and external carotid vein was ranging in from 50 to 60%. No effects of anticoagulants were observed.
4. Synthetic graft is not applicable to reconstruction of small vein and auto-vein graft or patch graft are suitable. Anticoagulants are not helpful in that case.
5. Anticoagulants should be given during operation in venous reconstraction, continued at least two weeks post-operatiovely and then gradually discarded.
Anticoagulant therapy was performed on 37 patients with thromboembolism and cases who underwent vascular surgery between Oct. 1962 and Dec. 1964.
The following conclusion was obtained.
1. Generally, results of anticoagulant therapy were satisfactory.
2. Heparin 1 mg per kilogram of body weight was given as an initial dosis and proper dosis was followed intermittently at 4 hours interval to keep coagulation time 2 or 3 times as normal.
Warfarin, 15.5mg on an average, was given as an initial dosis, then half as the second, and then 3.6mg (0.06 mg/kg in male adult, 0.09 mg/kg in the aged) as an maintanance. Prothrombin time was kept in 10 to 25%, and thrombotest in 5 to 15% during treatment.
3. Anticoagulant therapy should be continued as long as possible in patients with chronic arterial occlusive disease as Buerger's disease and arteriosclerosis obliterans.
It should be used until symptoms subside in patients with venous thrombosis and thrombophleditis.
It is preferable to continue anticoagulant therapy through life in patients with valvular heart disease who developed embolism unless radical operation is applicable.
It is not recommended for possible bleepings after aortic surgery, though it is preferable to use anticoagulants as long as possible after grafing for peripheral artery or vein.
4. Serious side effects are not acompanied to anticoagulant therapy provided it is used with meticulous care.

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Chemotherapy of malignant neoplasms by isolation perfusion using heart-lung machine was investigated for the purpose of increasing the effectiveness and prevention of side-effect of anticancer agent, in conbination with Survinal, Ipsilon (ε-Aminocapronic acid) and Bromelain which were not tumoricidal agents, under fundamental experiment and clinical use.
1) Effect of combination therapy on the solid tumor of mice MH 134 implanted intradermally
In case of Mitomycin C and Sarvinal in combination the tumor growth was. notably innibited as compared with control group, such as Mitomycin C alone or Sarvinal alone. In casd of Mitomycin C and Ipsilon, and in Mitomycin C and Bromelain the tumor effects were not more than in control group.
2) Effect of combination therapy in use of isolation perfurion perfusion technique on the Brown-Pearce tumor implanted into hind limb of rabbits
In case of isolation perfusion the combination therapy showed no valuable effect on the inhibition of tumor growth, though, histological investigation revealed that adequate doses of Mitomycin C and Sarvial in combination had a slight increase in destruction of tumor cells, and in case of Mitomycin C and Ipsilon the illeffects on the normal tissue of perfused area were considerably decreased. But in case of Mitomvcin C and Bromelain the effect was similar to control group.
3) Clinical use of the combination therapy in isolation perfusion
The combination therapy was used clinically following the acohe-described fundamental investigation. Those cases were malignant melanoma, fibrosarcomas, osteoma, metastatic carcinoma of scapula, rectal carcinoma and amelanotic melanoma. Ill-effect of combination theeapy by isolation perfusion was mostly negligible, and the tumor effect was greater than in case of using Mitomycin C alone.

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1) An acute experimental trial on bicuspidization of the aortic valve by direct suture of commissure between non coronary and right coronary cusp leaflet was attempted. The experiment was performed under direct vision utilizing retrograde coronary perfusion in combination with a bubble type pnmp-oxygenator.
2) The experiments were performed on sixteen dogs. Duration of cardio-pulmonary bypass ranged in from twenty-six to fifty-five minutes, Periods of aortic cross-clamping were twelve to twenty-three minutes.
3) Seven of 16 animals survived the acute experiments. However, they died half an hour to 21 hours postoperatively. Haemorrhage (haemothorax), traumatically produced aortic insufficiency and myocardial factors were considered to be responsible for their deaths.
4) Of 9 animals which tolerated direct commissural suturing procedures, six developed severe aortic insufficiency due to tearing of the valve leaflets. This fact limits the applicability of the direct suture method to the normal paper-thin valve leaflets.
5) Three animals were presented in which bicuspidization by direct suturing of one valve commissure was successfully produced. These animals were evaluated haemodynamically in terms of preoperative and postoperative aortic pulse patterns by ventricular and aortic pressure determinations. No evidences of aortic stenosis nor aortic insufficiency were demonstrated. In autopsies of these 3 animals, the valves remained bicuspid showing no tearing of the leaflets nor regurgitation.
6) The applicability of this technique in the treatment of clinical aortic insufficiency was discussed.

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In the electron microscopic observation on adenovirus type 12 infected cells, abundant virus particles can always be recognized in the nucleus, although in some rare instances virus particles are found in the cytoplasm. Therefore, it is difficult to consider the virus formation to take place aside from the nucleus and it seems that the nucleus is really the essential site of virus multiplication.
The fact that there are two different arrangements of virus particles presents a problem. It appears that usually crystalline arrayed virus particles come into being, and then they take noncrystalline arrangement, but this sequence does not necessarilly take place. The crystalline arranged virus particles and noncrystalline arranged ones often appear simultaneously and independently of each other,
At the early stage of infection, the electron dense masses are seen in the nucleus. These masses are the matrix of virus particles, because the arrangement of virus particles in crystalline or noncrystalline array are seen with these electron dense masses.

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