With the purpose of studying the influences of sulfonamides on the leucopoietic function of bone marrow, the bone marrow tissue culture (cover-slip method) of the rabbit was conducted.
Sulfonamides were added to the tissue culture medium at various concentrations, and the effects of these drugs on the tissue growth were observed; and the following results were obtained.
1. Sulfonamides such as sulfanilamide, sulfapyridine, sulfathiazole, sulfisoxazole, sulfisomidine and carbutamide, at the concentration equivalent to the therapeutic blood level (1-20 mg/dl), exerted no appreciable effect on the tissue growth of bone marrow.
2. These sulfonamides showed slight inhibitory action on the tissue growth of bone marrow at the higher concentration than 20 mg/dl.

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With the purpose of studying the influences of sulfonamides on the function of pseudoeosinophils of the rabbit bone marrow, the bone-marrow tissue culture (cover-slip method) was conducted.
Sulfonamides were added to the tissue culture medium at various concentrations, the effects of these drugs on the wandering velocity and carbon-particle phagocytosis of pseudoeosinophils were observed; and the following results were obtained.
1. Sulfonamides such as sulfanilamide, sulfapyridine, sulfathiazole, sulfisoxazole, sulfisomidine and carbutamide, at the concentration equivalent to the therapeutic blood level (1-20 mg/dl), slightly suppressed the wandering velocity and carbon-particle phagocytosis of pseudoeosinophils.
2. These sulfonamides showed a greater inhibitory action on the wandering velocity and carbon-particle phagocytosis of pseudoeosinophils at the concentration of more than 20 mg/dl.

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With the purpose of studying the influences of sulfonamides on the erythropoietic function of bone marrow, the cell suspension culture of the rabbit bone marrow was conducted.
Sulfonamides were added previously to the fluid medium of the bone-marrow tissue culture at various concentrations, and the effects of these drugs on the increasing rate of hemoglobin, erythrocytes and reticulocytes were studied; and the following results were obtained.
1. Sulfonamides such as sulfanilamide, sulfapyridine, sulfathiazole, sulfisoxazole, sulfisomidine and carbutamide, at the concentration equivalent to the therapeutic blood level (1-20 mg/dl), exerted a slight inhibitory action on the increasing rate of erythrocytes and reticulocytes but almost no effect on the increase of hemoglobin.
2. These sulfonamides, at the higher concentration than 20 mg/dl in the medium, slightly suppressed the increase of hemoglobin.

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植え込み電極を施しに慢性猫を用いて,正常脳波,インシュリン低血糖状態およびそれに対する中枢神経刺戟, 2, 3のアミノ酸と中枢神経抑制物質の影響を観察した.その結果は次の如くである.
1) 覚醒時に認められる低振巾速波は,猫が眠りに傾くと特徴的な12c/s前後のsleep spindleに変り,更に深睡眠では皮質および皮質下諸核に高電位徐波が出現する.
2) インシュリン低血糖状態は一般状態,血糖値,脳波を基準として,嗜眠期,痙攣前期,痙攣期,昏睡期とに分け得た.嗜眠期には正常猫で認められた深睡眠に至るまでのあらゆる脳波が認められた.痙攣前期は自律神経系の嵐と大徐波のburstを特徴とし,痙攣期は棘・鋭波を盛んに認め,ミオクロヌス攣縮・全身痙攣が起る.昏睡期にはあらゆる刺戟に応ぜず,脳波では1c/s以下の大徐波を認め,更に低血糖状態を続けると電位を減ずる.
3) インシュリン昏睡に対する中枢神経賦活剤およびアミノ酸の覚醒効果を葡萄糖を基準として検討すると,
i) 中枢神経刺戟
電気刺戟,メトラゾール,メジマイドを用いたが,全身てんかん様痙攣発作を起した時のみ血糖上昇と脳波および一般状態の覚醒を認めた.葡萄糖に較べその効果は一過性不確実であつた.
ii) アミノ酸
グルタミン酸ソーダは葡萄糖に次いで血糖上昇作用と覚醒作用を持ち,脳波を完全に覚醒パターンに置換しうるが,糖ほど迅速,且持続時間が長くない.この効果はグルタミン酸の投与が多いほど確実であるが,あまり大量を急速に投与すると危険である(全身痙攣を誘発).
GABAにも一過性の血糖上昇作用と脳波上の覚醒効果を認めたが,一般状態には変化がない.
GABOBを痙攣期に用いたが,確かな抑制作用は認められなかつた.
4) 更にインシュリン低血糖状態に神経抑制物質を加重して検討すると,
i) Nembutal
痙攣期にNembutalを静注すると,脳波上の棘波・鋭波を消失せしめ,特有な紡錘形の高振巾速波群を生ぜしめ,攣縮及び痙攣を完全に抑制したまま低血糖を進行させる.
深昏睡期にはNembutalの影響はない.
ii) Chlorpromazine
痙攣前期以後に適当量のCpを適用すると, Nembutalほどではないが,低血糖を静かに進行せしめる.大量のCpを急激に痙攣期の猫に静注すると,痙攣を誘発し易く,その後に糖水を補給しても覚醒しにくい事があるので注意を要する.
稿を終るに臨み,御懇篤な御指導と御校閲を賜わつた奥村教授に深く感謝します.更に植え込み手術,血糖定量,組織標本作製に際して御協力を載いた高坂助教授を始め教室の諸先生と技術員諸君に心から感謝します.

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Using the Ehrlich ascites tumor cells, the activities of the diphosphopyridine nucleotide diaphorase (DPNase), triphosphopyridine nucleotide diaphorase (TPNase), succinic dehydrogenase (SD) and α-gylcerophosphate dehydrogenase (α-GD) were cytochemically examined, and all of the cytochemical specimens were observed with the phase contrast microscope and formazanhaematoxylin counter staining. Several variations of their activities being caused by the differences of the cytochemical methods were also studied.
The results were summarized as follows.
1. In the smear method, in which the ascites is smeared and dried on the object glass, thereafter reacted with the modified Wattenberg's reagents, all cells reveal relatively intense reaction but the differences of the staining intensity of each cell are scarcely noticed.
2. In the suspension method, in which ascites tumor cells are suspended and reacted with the modified Wattenberg's reagents, all cells reveal relatively weak reaction, but the marked differences of the staining intensity of each cell are observed.
3. In order to clarify the relationship between the permeability of the cell membrane and the intensity of the cytochemical reaction, the cells are treated with the benzalkonium chloride solution. This method is called the permeability increasing suspension method, which reveals a intermediate intensity of the staining between the smear method and the suspension method. Each cell shows a definite difference of the staining.
4. No significant difference is observed between the staining intensity of the suspension method and that of the ascites suspension method in which the ascites supernatant is used as the cytochemical reaction medium instead of the inorganic salts solution.
5. The cells treated with the suspension, permeability increasing suspension and ascites suspension method are able to be successively transplanted into the same strain mouse. Therefore, it may be reasonably assumed that in these three methods the cells are cytochemically reacted in the living condition. However, it is impossible to transplant the cells treated with the smear method.
6. By the observation of the staining patterns of these four methods, it may be assumed that these dehydrogenases in the cells are not always activated and the intensities of their enzymatic activities change according to their life cycle.
(a) The DPNase activity remarkably increases in the end of the interphase and abruptly decreases to the lowest level at the metaphase. Then the activity gradually increases, keeping low level throughout the first half of the interphase. This enzyme is localized in the granulations of the cytoplasm and also a little in the cytoplasms of the cells with the high activity.
(b) In general, the TPNase activity is slightly lower than that of the DPNase, and shows the same mode of the activity and localization as the latter.
(c) The SD activity decreases to the lowest level at the metaphase and remains almost constantly low in the other phases, localizing in the mitochondria.
(d) The α-GD activity is generally lower than that of the SD and nearly negative, but shows the same changes of the activity and localization as the latter.
7. When the enzymatic activity of Ehrlich ascites tumor cells is compared with that of the normal ascites cells, the DPNase and TPNase activity are remarkably high, while the SD and α-GD activity are low.

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The isolated human rectus abdominis muscle and the pectoralis major muscle were used, and these muscles were mounted in constant-temperature bath containing oxygenated Tyrode's solution, and resting potential, action potential and electrical constants of the muscle fiber membrane were measured.
1. These muscles are considered to be suitable for the examination of human skeletal muscle fibers in vitro.
2. Resting potentials of the rectus abdominis muscle and the pectoralis major muscle are 77.2±7.8 mV and 73.9±9.7 mV repectively, and action potentials of these muscles are 93.9±9.7 mV and 87.2 8.0 mV respectively. These figures are in the same range of any other reported data of the mammalian muscle fiber, but distributions are little wider.
3. Durations of action potentials are about 1.9 msec. in both muscles.
4. Electrical constants of these muscles are as follows:
τm(msec) ρ(μ) Rm (cm) Cm (μF/cm²) λ(mm)
M. pectoralis major 7.25±2.14 33±5 1080±325 9.1±4.1 1.39±0.47
M. rectus abdominis 8.60±2.22 27±5 1228±187 6.1±2.3 1.15±0.23

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Muscles of the rectus abdominis, the pectoralis major, the gastrocunemius and the tibialis anterior of the human being were stained with Sudan Black B in order to differentiate red and pale muscle fibers.
1. In the rectus abdominis, the ratio of red muscle fibers and pale muscle fibers is almost constant, and there is no relation between Rohrer's index and the ratio. Diameters of fibers vary with each muscle, but red muscle fibers are thinner than pale ones in average.
2. In the pectoralis major muscle, red muscle fibers are a little more than pale ones, but not significant. Diameters of red muscle fibers and that of pale ones are almost the same.
3. In the tibialis anterior muscle, red muscle fibers are more than pale ones, on the contrary in the gastrocunemius muscle, only 50 % of muscle fibers are red. In both muscles red muscle fibers are a little thicker than pale ones in average.
4. Direct electrical stimulation on muscle does not change the stainability of the muscle to Sudan Bla k B.
5. The anterior tibialis muscle of the patient of dystrophia musculorus progressiva was exam ned by Sudan Black B staining.

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The conduction velocity of action potential of isolated human skeletal muscle was examined in oxygenated Tyrode's solution.
1. The velocity is distributed mainly between 3 and 4 m/sec, being neither more than 4.5 m/sec, nor less than 2.3 m/sec.
2. In the pectoralis major muscle and the rectus abdominis the conduction velocity does not distribute uniformly, but has two peaks. One peak is between 3 and 3.6 m/sec, and the other is between 3.6 and 4.2 m/sec.
3. When current I is applied intracellulary across the fiber membrane, the membrane potential is changed as much as V in terminal value. Then muscle fibers can be divided into two groups by V/I value and the conduction velocity. In one group V/I is in inverse proportion to the 3 power of the velocity. This means, if resistance of membrane and capacitance of membrane are constant in a group, the conduction velocity is in the proportion to the root of the fiber diameter, which is rational to the cable theory. The difference of two groups may depend upon the difference of capacitance of membrane.

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The PH-value of B.T.B. PH-paper is not exact but that of P.R. (Phenol Red) PH-paper is exact in inorganic salt solution or synthetic liquid media, which contains more than 2000 μg/ml Streptomycin. Because, B.T.B. binds to Streptomycin in existence of the trace inorganic salt, and forms insoluble salt and cannot become to express the PH-changes. P.R. does not bind to Streptomycin.

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194 patients with carcinoma of the stomach being admitted in our surgical department from September 1959 to December 1960 is studied. They are divided into two groups; the treated group with blood and fluid-transfusion and the untreated.
Six anti-cancer agents are administered to each group and their side effects are observed.
In the administration of one anti-cancer agent, the transfusion treatments are the most effective to the complaints; thirst, vertigo, headache, more effective to the loss of appetite, nausea and bleeding tendency and also effective to the generalized malaise. Also these treatments are the most effective to the hypochromia, hypoproteinemia and accelerated erythrocyte sedimentation rate, more effective to the erythrocytopenia, reduced hematocrit, prolongation of the bleeding and coagulation time, and somewhat effective to the leucopenia and thrombocytopenia.
The transfusion treatments are the most effective to the subjective complaints caused by the administration of Thio-TEPA and Carzinophilin, more to Mitomycin C and Toyomycin, in less degree to Sarkomycin and 8-Azaguanine, and the most effective to the objective symptoms by Thio-TEPA, more to Sarkomycin, 8-Azaguanine and Toyomycin and also somewhat effective to Mitomycin C and Carzinophilin.
In the administration of two anti-cancer agents, the transfnsion treatments are the most effective to the complaints; thirst and headache, more the generalized malaise and also to the loss of appetite and nausea. Also these treatments are the most effective to the erythrocytopenia, hypochromia and accelerated erythrocyte sedimentation rate, more to the leucopenia and reduced hematocrit, in less degree to the prolongation of the bleeding time and the hypoproteinemia.
The transfusion treatments are the most effective to the subjective complaints caused by the administration of Carzinophilin + Thio-TEPA, more to Mitomycin C + 8-Azaguanine and also somewhat to Sarkomycin + Thio TEPA and Mitomycin C + Thio TEPA, and the most effective to the objective symptoms by Mitomycin C + Thio TEPA, more to Sarkomycin + Thio-TEPA and also somewhat to Carzinophilin + Thio-TEPA and Mitomycin C + 8-Azaguanine.
It is confirmed that the side effects caused by the anti-cancer agents are seen in less degree in the combined medication of two different agents and their furthermore relieves are noticed by the transfusion treatment.

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The serum iron level and the symptoms of the patients with the carcinoma of the stomach with or without Mitomycin C are studied from the Ist pre-operative day to the 25th postoperative day and compared with the normal individual, whose serum iron level is 110.6γ% in male, 109.0γ% in female and 110.0γ% of average. The serum iron level of the former is lower than the latter.
In the gastrectomy cases, the serum iron level is revealed the lowest value on the 5 th post-operative day and has progressively increased to the highest level being kept under the normal range until the 15 th to 20 th post-operative day, following to be on the decrease during the following 5 days; whereas the progressive decrement is observed throughout the entire post-operative course in the cases of the explorative laparotomy.
In the cases with the Mitomycin C treatment, the serum iron level is revealed as same tendency as in the gastrectomy cases and approached more closely to the normal value than that of not administered cases. The same observation is obtained in the cases with the explorative laparotomy combined with Mitomycin C treatment. The more remarkable improvement of the symptoms is noticed in the combined therapy of the surgicad operation and the Mitomycin C administration than in the surgical operation alone.
It is assumed that there is a certain relationship between serum iron level and symptomes, and therefore, the determination of the serum iron level is useful for the decision of the effectiveness of anti-cancer agents.

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The effectiveness of the Mitomycin C on the reticuloendotherial system is studied in using normal rats and rats with Yoshida-Sarcoma. The serum iron colloid by labelled ⁵⁹Fe (S. ⁵⁹Fe. C.) administered intravenously is gradually decreased in the circulating blood, being almost disappeared 12 or 24 hours after administration, followed to be gradually increased later on again.
It has been assumed that the diminition of the ⁵⁹Fe from the circulating blood results from the colloid phagocytizing function of the reticuloendothelial system and the succeeding increase of the ⁵⁹Fe does from the Hb incorporation. But there is no significant difference in the colloid phagocytizing function of the intravenously injected S. Fe. C., but in the Hb incorporation between normal and treated rats with the Mitomycin C or with the Yoshida-Sarcoma; the Hb incorporation is delayed or inhibitted in the treated rats, while rather improved by the administration of the Mitomycin C to the rats with the tumor.
Of the distribution of the administered ⁵⁹Fe, which is increased in the spleen, and decreased in the bone in the normal rats with Mitomycin C and decreased in the liver in less degree and in the bone in some degree in the rats with the Yoshida-Sarcoma, compared with the normal rats. Whereas the ⁵⁹Fe is decreased in the liver and spleen, and increased in the bone and neoplastic tissue by the administration of the Mitomycin C to the rats with the Yoshida-Sarcoma, compared with the rats with Yoshida-Sarcoma alone.
The ratio of Ferritin/Hemosiderin is decreased in the normal rats given Mitomycin C or inplanted Yoshida-Sarcoma, compared with the normal rats, while this ratio rather approached to the normal range in the rats with the Yoshida-Sarcoma given Mitomycin C, compared with the Yoshida-Sarcoma alone.
The development of the neoplastic tissue of the rats with Yoshida-Sarcoma has been only temporarily inhibitted with the administration of the Mitomycin C 200 mcg/kg daily for 4 days. However, gradual but steady inhibition is noted with the dosis of 500 mcg/kg per day for 4 days.

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As mentioned above, the significant inhibition of the development of the neoplastic tissue and the improvement of the reticuloendothelial function has been noted with the administration of the Mitomycin C 500 mcg/kg daily for 4 days.
In the Mitomycin C treatment, the effectiveness of the various drugs; pantothenic acid, essential amino acid, Vitamine B₁₂, Vitamine K, to the endothelial system is studied, using serum iron colloid by labelled ⁵⁹Fe as an indicator.
The phagocytosis of the reticuloendotherial system and the Hb incorporation of the ⁵⁹Fe are accelerated in all cases with these drugs, especially in the pantothenic acid and Vitamine B₁₂. In the combined therapy of the Mitomycin C and these drugs, the distribution of ⁵⁹Fe is decreased in the liver and neoplastic tissue and increased in the spleen, kidney, bone and muscle.
The development of the neoplastic tissue is furthermore inhibitted in these combined treatments, especially in the pantothenic acid.

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Various dosages of glutamic acid, asparagine, GABA (γ-aminobutyric acid), GABOB (γ-amino-β-hydroxybutyric acid) and diphenylhydantoin each were given to the ep mouse once a day for 3 weeks and their effects on the convulsive seizure were compared.
1. Three week successive administration of various dosages, each of glutamic acid, asparagine, GABA and GABOB, could not inhibit convulsive seizure in the ep mouse.
2. In contrast, diphenylydantoin revealed to inhibit the convulsion: an absolute abolishment of the seizure was obtained a week, three days and 8 hours after the administration of 40-60, 80 and 100 mg/kg/ day of diphenylhydantoin respectively.
3. The convulsive seizure in the ep mouse was found to recur within 6 days after the abstention of diphenylhydantoin administration.

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Daily dosage of 100 mg/kg of diphenylhydantoin was administered on the ep-mouse for 3 weeks and cholinesterase activity, water, Na, K, glutamic acid, GABA (γ-aminobutyric acid) and glutamic decarboxylase activity in cerebrum were followed during the course.
1. The ChE activity of the ep-mouse at rest appeared to be lower than that of the normal mouse. Diphenylhydantoin manifested an increment of the ChE activity at the end of the first week and, in contrast, a decrement at the end of of the 3rd week of its administration course in both groups. It is, however, interesting to note that the variation of both directions was found to be greater in the ep mouse than in the normal mouse.
2. The content of total water in the ep-mouse was more than that in the normal mouse. Diphenylhydantoin did not make any change in the water coutent in either groups.
3. The total Na and K contents were greater in the ep-mouse than in the normal mouse. The administration of diphenylhydantoin did not affect their contents in the normal mouse, but showed a decrement in both contents down to the normal level in the ep mouse.
4. The cerebrum of the ep-mouse contained more glutamic acid and, in contrast, less GABA than that of the normal mouse. After the diphenylhydantoin administration, glutamic acid was found to be decreased and GABA to be increased in both mice. It is to be noted that the difference in the contents of glutamic acid and GABA between the ep-mouse and the normal mouse was approaching each other in the course of the administration.
5. Glutamic decarboxylase activity was lower in the ep-mouse than in the normal mouse. In the course of diphenylhydantoin administration, the activity was found to be increased beyond the level of the normal mouse at the end of the first week and to be decreased down to the normal level at the end of the 3 rd week in both mice.

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Parabiosis was attempted between ep-mice and normal pedigree mice.
1. Parabiosis between two ep mice could not affect the convulsive seizure in both animals regardless the passage of time after parabicsis.
2. In the possible four pairs of parabiosis between the ep-mice and normal mice, consisted of a male and female each or visa versa, it was found that in every pair the convulsive seizure in every ep-mouse was suppressed in 6 days after the parabiosis and thereafter, and after 100 days convulsive seizure was completely inhibited.
3. In an isotope ⁹⁰Y utilization and also in morphological observation, circulatory communication was established between the parabiosed mice after convulsion ceased to occur.
4. When the parabiosis was cut off in two different stages, the ep-mouse convulsive seizure persisted if the separation was done before the abolishment of convulsion, but the seizure occurred again 2 or 3 days later in the case separated after cessation of convulsive seizure.
5. In the case of the parabiosis between a 7 week-old ep-mouse given periodical postural stimulation but shown not a single convulsive seizure and a normal pedigree mouse of the same age, there could be observed not any convulsive seizure from the very beginning and as long as they survived.

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An attempt was made to study the influence of unilateral or bilateral adrenectomy of the ep-mouse, exchange transplantation of a pair of adrenal glands between the ep-mouse and the normal mouse followed by the successive administration of the adrenal gland emulsion and castration, on the convulsion of the ep-mouse. The recipients were all females. Transplanted glands were histologically verified.
1. The unilateral adrenectomy did not at all affect the convlusion.
2. No convulsion could be elicited in the bilaterally adrenectomized ep-mouse until the death. It is, of course, to be noted that all of them were found in characteristic tetanized extension posture at death as in the case of bilaterally adrenectomized normal mice.
3. Convulsion was inhibited in all of the ep-mice after exchange transplantation of adrenal glands of the normal mice followed by successive administration of the emulsion, and no convulsion occurred in the normal mice after transplantation of adrenal glands of the ep-mouse.
4. Castration was performed on two groups of the ep-mice: the one, adults and the other, 5 weeks old showing not any convulsive seizure in spite of a regular postural stimulation in its life. No change was found in convulsion of either groups.

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