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1. In the present experiments, Ehrlich ascites carcinoma (K-tsrain), JTC-11, and C3H mouse mammary tumor (A-strain) were used to study the inhibitory effects of two kinds of comins, crude muscle cornin and crude intestine comin. 2. Daily intraperitoneal administrations of both comins had shown a marked inhibitory effect on the Ehrlich ascites carcinoma. 3. Intestine comin was more effective on the inhibition of the growth of the Ehrlich ascites carcinoma than muscle cornin when administered intraperitoneally. 4. Daily subcutaneous adminstrations of muscle comin had no effect, but doses of 10 mg/mouse/day or 20 mg/mouse/day of intestine cornin had a slight or moderate inhibitory effect on the Ehrlich ascites carcinoma. 5. Intestine comin had an inhibitory effect on the growth of JTC-ll cells in vitro, and made the tumor cells to undergo morphological changes during incubation. 6. Daily intraperitoneal administrations of muscle comin had hardly any effect on the C3H mouse mammary tumor, but intestine comin was evidently effective in male. 7. Intraperitoneal administrations of intestine comin proved to be hardly effective on the C3H mouse mammary tumor, but only in the dose of 30 mg/ mouse/day, it had a moderate inhibitory effect in female. 8. Daily subcutaneous administrations of muscle comin had no effect on the C3H mouse mammary tumor, but intestine comin had a slight effect in male. 9. Muscle cornin had a slight or moderate effect on the C3H mouse mammary tumor, but intestine cornin was hardly effective in female when administered subcutaneously. 10. Repeated intraperitoneal administrations in doses of 30 mg/mouse/day of muscle comin produced intoxication in the treated mice. 11. In general, it seems that intestine comin is more effective on the inhibition of tumor growth than muscle comin.

A case of malignant melanoma with metastases mainly to the liver and the right ilium was treated with a gluconeogenic diet. The carbohydrate content of the diet was finally reduced to 5∼10 g per day and the remaining calories were derived from protein and fat. Increased blood citrate and NEFA concentrations, increased ketone body formation and the maintenance of a reasonable level of blood sugar confirmed the attainment of a gluconeogenic metabolic state. Definite improvements in size of a hepatic tumor, serum alkaline phosphatase activity and the general condition were observed transient1y during the dietary therapy. Growth of the tumor resumed despite the continued gluconeogenic therapy, and the patient died of cardiac failure. Concentrations of gluconeogenic enzymes, fructose-1, 6-diphosphatase, glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, were all found to be very low in the tumor tissue as expected.

a) A modified procedure of the WIDNELL and TATA8 method yields rat liver nuclei manifesting a high degree of purity and activity. b) These nuclei contain a nucleoside-dependent phosphorylating activity that is readily released and apparently unrelated to either glycolysis or respiration. c) The main incorporation of the 32Pi is into ribose-I-phosphate; nucleoside phosphorylase activity satisfactorily accounts for the observed purine nucleoside stimulation of the nuclear phosphorus metabolism.

In the immunofluorescent study it has been revealed that rabbit sera immunized with transformed cells induced by SV-40 DNA, produce circulating antibody capable of re:lcting with intranuclear antigens synthesized by SV-40 complyte virus transforming process, In addition, the result confirmed that SV-40 DNA replicates DNA-containing viruses in the host cell and that also the genome coding for the synthesis of SV-40 tumor antigen is resposible for viral DNA.

For the purpose of revealing the molecular organization of the mitochondrial membrane the authors attempted to clarify the fine structure of reduced coenzyme Q-cytochrome c reductase and also studied how the CoQH2-cyt. c reductase is arranged in the mitochondrial membrane by systematic analyses of fractions from the purification process of CoQH2-cyt. c reductase. 1. Purified CoQH2-cyt. c reductase contained high concentration of cyt. b (9.5 mμmoles per mg protein) and cyt. Cl (4.5 mμmoles per mg protein), and was almost free from cyt. c, a, flavoproteins, primary dehydrogenases and ATPase. The enzyme complex also showed a high specific activity (48 μmoles of cyt. c reduced per mg protein per min at 30°). 2. CoQH2-cyt. c reductase was composed of particles of about 120 Å in diameter with irregular form, some time exhibiting electron opaque cores. In the loose aggregates of the particles, the size of each particle was about 95 Å in diameter. 3. An intimate correlation was observed between the particles of CoQH2cyt. c reductase and those on the surface of the NADH-cyt. c reductase fraction. 4. Regular arrays of uniform particles (about 82 Å in diameter with a center to center distance of about 100 Å) were observed on the surface of the submitochondrial membrane (brown membrane) obtained from beef heart mitochondria by treatment with deoxycholate (0.1 mg / mg protein) and KCl (72 g/l). The correlation between these particles and CoQH2-cyt. c reductase was discussed.

As a link in the series of studies on tumor specific immunity an attempt was made to clarify specificity if any, in aggregation of sensitized lymph-node cells on target cell in vitro. For this purpose sensitized regional lymph-node cells from isologous CsH mouse transplanted with A cells derived from CaH mouse mammary cancer were incubated with M cells derived from mammary cancer of homologous Cb mouse and HeLa-Ss cells as with A cells. The results are briefly summarized in the following. These sensitized regional lymph-node cells (A-L) inhibited the proliferation of A cells and M cells in tissue culture. When the interaction between the sensitized lymph-node cells and the terget cells was pursued over a long period by cinematography, these lymph-node cells became attached to the target cell by 6-to 12-hour culture in aggregation of rosette form, and by 30 hours some of the target cells were seen to undergo lysis. However, when these sensitized lymph-node cells were cultured with heterologous HeLa-S3 cells (derived from human uterine cancer), no such phenomena were observed. In the case with untreated normal lymph-node cells (control) there could be hardly observed any inhibitory effect on target cells. When the number of the target cells on which the lymph-node cells became attached was counted along with lapse of time, it was more numerous in the case of A and M cells but only a few in the case of HeLa-S3 cells. It seems that most of the sensitized lymph-node cells that inhibit the growth of the target cells become attached and aggregated fairly specifically onto the target cells.

A case of arteriosclerotic retinopathy associated with retinal venous thrombosis was treated with Anginin and the following results obtained: 1) Visual acuity was improved from 0.03 to 0.7. 2) Retinal hemorrhages were absorbed and pipe-stem sheathing of the branch of retinal artery decrease, with white sheathing remaining partially. 3) It was therefore considered that the pipe-stem sheathing was decreased because Anginin removed venous spasm and improved the blood stream of the branch of the artery, and that the organic changes already established on the arterial wall would remain as white sheathing. 4) Anginin could not prevent retinal veins from changing into white lines. 5) Consequently the authors considered that Anginin may be a drug effectively used for retinal arteriosclerosis and retinal venous thrombosis associated therewith.

The compositions of nitrogen pools of ox liver, bladder bile, kidney and lung were analyzed with an especial bearing on their minor components, and some distinctive features of these tissues were described. DCEC and CMC were found in ox liver and kidney. Liver was low in free arginine and lysine, but high in ornithine, ethanolamine, and glutathione. Glycine was only a predominant amino acid in ox bile. All amino acids were contained moderately in kidney, but glutathione content was low. The concentrations of arginine and lysine were relatively high in lung.

For the purpose of settling the specialization stage of erythroblast where the transcription for hemoglobin is initiated, the absorption of heme and the incorporation of tritiated uridine into RNA have been observed on the cells from the anemic rabbit after a mass red cell transfusion by which the DNA synthesis of large size precursors is suppressed and the early denucleation of erythroblasts is stimulated. In the erythroblasts obtained 24 to 72 hours after red cell transfusion a distinct absorption of heme appears first in the proerythroblast, followed by a progressive increase with the advance of the specialization. Hemoglobin synthesis is markedly stimulated after the denucleation. The incorporation of tritiated uridine into RNA is most marked in the proerythroblast and decreases with the advance of specialization stage suggesting that the mRNA synthesis for hemoglobin is initiated at the proerythroblast, continuing to the polychromatic erythroblast where. the synthesis is minimized. The volumetric observations indicate a possible denucleation at proerythroblast, but it has been revealed that the maximum RNA level of macrocytes is comparable to that of early basophilic erythroblast and its highest hemoglobin level is only that expected in the cells denucleated at late basophilic stage. From these observations it has been concluded that the transcription for hemoglobin is triggered at the initial step of erythroid cell specialization, proerythroblast, but it is insufficient for the synthesis of the expected amount of hemoglobin and is compensated or completed by the mRNA synthesis in more advanced stage of specialization.

Concentrations of ampholytes in the nitrogen pool of ox ocular tissues and nervous tissues were analyzed systematically by an automatic amino acid analyzer with a special reference to their minor components. DCEC was found in lens and also in nervous tissues. Ophthalmic acid was found in lens (highest), in retina (moderate), and in vitreous humor and spinal cord (trace). Glutathione content was extremely high in lens, and moderate in nervous tissues, retina and cornea. Carnosine content was moderate in cornea and in retina, but hemocarnosine may be rather high in nervous tissues. Anserine-like compound was found only in spinal cord, but free 1- and 3-methylhistidine were detected in most ocular tissues. Ethanolamine and γ-aminobutyric acid were high in retina and their concentrations were comparable to those of nervous tissues.

The contents of nucleic acids in rat liver and hepatoma mitochondria and the physico-chemical properties on DNA's isolated from these mitochondria were comparatively investigated. The results are briefly summarized as follows. 1. The contents of DNA and RNA per mg protein of the hepatoma cell mitochondria were about 10 and 2 to 4 times higher than those of rat liver mitochondria, respectively. 2. The λ max. and λmin. values of DNA isolated from the hepatoma mitochondria were 257 mμ and 231 mμ, respectively and those of DNA isolated from the nuclei were 259 mμ and 233 mμ, respectively, in saline-citrate, pH 7.0. 3. Three fractions of mitochondrial DNA were obtained by the sucrose density gradient and these DNA fractions corresponded, probably, to about 30 S, and 20 S and 14 S DNA's. 4. There was little difference in base compositions between nuclear and mitochondrial DNA's of the hepatoma cells. 5. The degree of hybridization between the nuclear and mitochondrial DNA's of the hepatoma cells was almost the same as that between the nuclear and nuclear DNA's of the hepatoma cells, and somewhat higher than that between the nuclear DNA of rat liver and the nuclear DNA of hepatoma cells. 6. "Highly twisted" circular, "open" circular and linear forms were observed in the DNA preparations of the hepatoma mitochondria. The average values of contour lengths of rat liver and the hepatoma DNA's observed at high frequency were 5.3 μ and 4.5 μ. 7. A discussion was made on the relation between the genetic informations of mitochondrial DNA and the formation of a mitochondrion in rat liver and the hepatoma cells.

As a link in a series of studies on the effects of blood constituents on the brain function by means of brain perfusion, we used four kinds of artificial blood; namely, the blood containing a low molecular dextran, one containing glutamic acid, one containing essential amino acid group and the one containing both essential amino acid group and glutamic acid. During the perfusion experiments we observed the effects of blood constituents on the function and metabolism of the perfused brain and obtained the following results. 1. When a low molecular dextran is used as the colloid osmotic pressure agent instead of hydrodextran, the amount of the blood flow in the brain is maintained roughly at a certain fixed level throughout the experiment, showing no gradual decreasing tendency. 2. When using the artificial blood supplemented with glutamic acid, EEG of the perfused brain shows an increase in the appearance rate of β32 and β33 bands, approaching closely to the pattern of EEG of unrestrained controls at arousal state. 3. In the case of the blood added with essential amino acids similar to the case using the blood with glutamic acid, EEG approaches towards the alert pattern of the controls. 4. When the perfusion is done with the artificial blood lacking in amino acids, about one hour after the start of the perfusion the amount of glutamic acid and its related compounds in the brain can no longer be maintained at normal level and the decrease, being so marked, brings about a marked decrease also in total amino acid content. 5. When the perfusion blood contains glutamic acid, essential amino acid group or both, the concentrations of amino acids of the brain glutamic acid group and the total amino acid can be maintained approximately at normal level for the duration of over one hour.

An electron microscopic study on the fine structural differences of motor endplates among the red, white and intermediate muscle fibers of the rat intercostal muscles was made and the following results were obtained. 1. In the motor endplate of the red fiber, the junctional folds were poorly developed and their number was small. 2. In the motor endplate of the white fiber, the junctional folds were well developed and their number was far more numerous than those in the red fiber. 3. The fine structure of the motor endplate of the intermediate fiber was of an intermediate character between the red and white fiber.

Since Hahn's observation of the postalimentary lipemia clearing actIvity following the injection of heparin, physiological, biochemical and clinical significances of the postheparin lipoprotein lipase have been well clarified. The presence of the endogenous lipoprotein lipase in human blood, which was at first doubted, has been repeatedly confirmed2∼8. Recent papers9,10 described elevated endogenous lipoprotein lipase activity in patients with essential hyperlipemia after ample fat uptake. In this preliminary report, changes of the lipoprotein lipase activity during oral glucose tolerance test is illustrated.

1. An oligomycin -sensitive ATPase was isolated and partially purified from beef heart mitochondria. The specific activity of ATPase sensitive to oligomycin of the fraction was five to eight times that of aged mitochondrial or of DNP-induced mitochondrial ATPase assayed under the same condition. 2. Electron micrographs of the partially purified oligomycin- sensitive ATPase reveal a structure in which headpieces are regularly attached by way of stalks to a thread-like structure derived from a superficial portion of base pieces. 3. A high concentration of the structured material coincided with a high activity of oligomycin-sensitive ATPase. When the headpieces were detached from the structure, the ATPase became insensitive to oligomycin. 4. The fraction of oligomycin -sensitive ATPase was essentially free of membrane structure and was contaminated with a small amount of cytochromes b and Cl but no cyt. a. Cytochrome concentrations of the preparations were indifferent to the activity of oligomycin sensitive ATPase. It follows that ATPase does not require cytochromes or membrane structure for its oligomycin sensitivity. 5. From these results it seems that the factor rendering ATPase sensitive to oligomycin should be contained in the stalks and/or the thread-like portion of basepieces of the structure. The structure is the simplest unit of oligomycinsensitive ATPase as yet obtained. 6. The structure was called "oligomycin-sensitive ATPase particles" (abbreviated as OSA particles). A unit of OSA particles consists of a headpiece attached by a stalk to a portion of base piece.

Non-hemin iron content in gastric juice was examined in 46 patients with various blood diseases, especially idiopathic hypochromic anemia and in 26 healthy controls. 1. The iron content in gastric juice was found to be 290 μg/ dl in healthy controls, a lower value of 110 μg/ dl in idiopathic hypochromic anemia and a higher value of 550 μg / dl in aplastic anemia. These values were in a close correlation with serum iron or sideroblasts. 2. In idiopathic hypochromic anemia there was also a close correlation between the iron content in gastric juice and hemoglobin. In the course of treating idiopathic hypochromic anemia (stage of recovery of anemia) the iron content in gastric juice showed a marked increase over the value in healthy controls as well as a transient increase after an intravenous iron tolerance test. This condition may be interpreted as an "iron-losing anemia". Iron excretion of gastric mucosa in various blood diseases and its changes in the course of treating idiopathic hypochromic anemia in relation to the cause of this anemia were discussed.

The site of localization of TCA cycle dehydrogenases in mitochondria has been investigated by observing the dehydrogenase activities and fine structure of the fractionated samples after freezing and thawing or sonication of beef heart and rat liver mitochondria. 1. In the sonicated mitochondria, activities of malic and isocitric dehydrogenases were highest in the supernatant fraction centrifuged at 198,000 x g for 60 minutes, while the specific activity of a-ketoglutaric dehydrogenase was higher in the fluffy or residue fraction. The distribution of the activity of pyruvic dehydrogenase was similar to that of a-ketoglutaric dehydrogenase. 2. In a sucrose density gradient fractionation of the fluffy fraction obtained by centifugation of sonicated mitochondria at 198, 000 x g for 60 minutes, the activities of malic and pyruvic dehydrogenase were observed in the top (or low density) layer in the form of fine particles, while that of a-ketoglutaric dehydrogenase was observed in the middle (or medium density) layers in the form of aggregates of fine particles and membranous fragments. 3. In the samples fractionated after freezing and thawing of mitochondria, which were considered to be a relatively mild disruption, the specific activity of a-ketoglutaric dehydrogenase was higher in the residue (submitochondria) fraction than that in the supernatant fraction (centrifuged at 144,000 x g, 30 minutes), and the activity of malic dehydrogenase still remained significantly high in the residue fraction. 4. It was deduced that the TCA cycle dehydrogenases could be localized in the matrix of the mitochondria by a loose binding to the inner membrane.

The results of our study may briefly be summarized as follows: 1) The irradiation with microrays (20∼30 watts) similar as 2,000 R and 5,000 R Gamma radiation did not substantially affect the activity of fibrinolysin (SK+SD). 2) By the irradiation method so far mentioned it has been demonstrated that the fibrinolytic activity of anticoagulant of the SK+SD preparation is preserved in all the clotting systems which we used. 3) Our findings indicate that it is possible to irradiate patients for therapeutical purpose with Radarmed (electromagneticrays) provided that there is produced some enhancing influence of the same blood clotting factors or systems. Together with earlier works in this field it appears that this method of the microirradiation could provide us with an important evidence on which we can base our further in vitro and in vivo radiohematologic studies; investigations with various preparations, types of radiation that are still underway9∼16.

With a certain fixed methods of analyses, we carried out the determination of flavins and cytochromes in the mitochondria (Mt) and electron transfer particles (ETP) of the heart and liver of rats and cows, and made a comparison of the data with one another. Our findings may briefly be summarized as follows. 1. The concentration of each component of the beef heart mitochondria proved to be 0.47 for acid extractable flavins; 0.22 for acid nonextractable flavin; O. 75 for cytochrome (cyt.) a; 0.58 for cyt. b; and O. 51 for cyt. C + Cl, all units being mμ mole per mg of protein. 2. In the beef liver mitochondria it was 0.46 for acid extractable flavins; 0.18 for acid non-extractable flavin; 0.092 for cyt. a; 0.089 for cyt. b; and 0.122 for cyt. C+Cll likewise all units in term of mμ mole per mg of protein. 3. In the case of rat heart mitochondria, it was found to be O. 42 for acid extractable flavins; 0.22 for acid non-extractable flavin; 0.88 for cyt. a; 0.41 for cyt. b; and 0.62 for cyt. C + Cll all in mμ mole per mg of protein. 4. In the rat liver mitochondria it was 0.56 for acid extractable flavins; 0.19 for acid non-extractable flavin; 0.20 for cyt. a; 0.14 for cyt. b; and 0.19 for cyt. C+Cl. 5. The concentration ratios of Fs, cyt. a and cyt. b of the mitochondria, what are considered to be intrinsic and fixed components of the mitochondrion. to those of the electron transfer particles were 1. 3 in both the beef heart and the rat heart, while 2.2 in the beef liver and 2.1 in the rat liver. 6. These findings were compared with the data reported by other workers, and also a discussion was made on the molecular organization of the mitochondrial inner membrane.

For the purpose to know whether the annual increase of leukemia incidence in Japan is due to some leukemogenic factors or due to the increased detection rate, the authors made some statistical survey of autopsy cases in which the diagnosis is reliable and not any type of leukemias escape the detection. The results showed that acute leukemias, which are found mostly in younger age, is actually increasing. In addition, it has been deduced that among the suspected factors the increase in ionizing radiation will be one of the most probable factors for the increase in leukemia incidence