検索

Les urines humaines normales inactivent immédiatement la thrombine ajoutée quand leur pH est acide ou au moindre degré quand leur pH est a1calin. Quand le pH d'urine est neutral ou légerement alcalin l'inactivation de thrombine est faible ou s'annule. Après une incubation de 10 et 20 minutes de l'urine avec la thrombine l'inactivation ne subit pas de changements essentiaux. Les résultats obtenus in vitro démontrent que l'alcalinisation d'urine a l'aide d'une diète appropriés ou des remèdes pharmacologiques peuvent favorablement influencer les hémorragies imminentes ou déja existantes du systeme urinaire.

1. Addition of nicotinamide (l0-2M) into the culture medium brings about an increase of the NAD content and the inhibition of the growth of L cells in culture. This rise of NAD brought about by nicotinamide lasts for 2 to 3 days, and thereafter gradually subsiding, it returns to normal level. 2. When L cells are cultured for several days in the same medium without addition of nicotinamide, there occurs a slow-down of mitosis with lapse of cultivation time but it has been found that this is in no way connected with the intracellular content of NAD. 3. By the addition of isonicotinic acid hydrazide (l0-2M) into the culture medium, there can be recognized a decrease of NAD content in L cell and the inhibition of cell growth. 4. In the case when 3-acetylpyridine (l0-2M) is added, a decrease of intracellular content of NAD in L cells and a marked inhibition of the cell growth can be observed. In the groups cultured in the media, containing 3-AP at the concentration of l0-3M or l0-4M can be seen neither inhibition nor acceleration of the cell growth. The oxygen uptake of the cells cultured in the medium containing 3-AP (l0-2M) hardly differs from that of the control group cultured in the medium not containing 3-AP. 5. On the basis of these results discussion has been made on the relation ship between mitosis and NAD content in the cell.

As has been well established, reticulocytes (RC) synthesize the species specific protein, globin, actively for about 24 hours or more till the time of their complete maturation1,2,3. This will be possible only in the presence of messenger RNA (m-RNA)4,5. Since the splendid hypothesis of m-RNA proposed by JACOB and MONOD6 for explaining the mechanism of the transfer of genetic information from nucleus to cytoplasm, it has largely been accepted through the numerous observations that followed7,8,9,10. However, the m-RNA hypothesis, which has been deduced by observing the protein synthesis in E. Coli, includes the meaning of labile RNA which is incessantly decomposed and newly synthesized to compensate the rapid degradation. As m-RNA cannot be synthesized in RC which have no detectable DNA, it has been supposed that the m-RNA of RC should be considerably stablell,12,13. Even in the denucleated cells, however, the RNA synthesis might be possible because Borsook reported the positive RNA synthesis of RC14, and this result has recently been reconfirmed by BURNY15.

Cytochemical observation of the activities of diphosphopyridine nucleotide diaphorase (DPNH-D), triphosphopyridine nucleotide diaphorase (TPNH-D), succinic dehydrogenase (SDH) and a-glycerophosphate dehydrogenase (α-GDH) of Ehrlich ascites carcinoma cells were made and following results were obtained. The smeared cells showed moderate reactions and no marked difference in the intensity among the individual cells. The free floating cells were stained relatively faint but showed the differences in the staining intensity in individual cells. In the presence of benzalkonium, the reaction intensity proved to be intermediate between the smeared cells and free floating cells without benzalkonium and the differences in the staining intensity in individual cells were more marked. Observations revealed that the reaction intensity changes closely corelated with the stage of mitotic cycle of each cell. Namely, DPNH-D activity of the tumor cells, which generally hihger than that of leucocytes, increased remarkably in the end stage of interphase and decreases abruptly in mitotic stage reaching the lowest level in metaphase. After the metaphse the activity increased slightly and it is kept at almost the same level during the first half of interphase. This enzyme is localized mainly in the granules of the eytoplasm. The activity of TPNH-D showed the similar localizations as those of DPNH-D, though the reaction intensity is lower than that of DPNH-D. The activity of SDH of the tmnor cells is lower than that of leucocytes and its diformazan granules are localized in mitochondria. Its activity decreases in the mitotic stage the lowest level in metaphase and in the followed interphase it is kept in a almost constant low level. α-GDH activity of the tumor is lower than that of SDH but show the similar localizations as the latter.

Based on our original concept, a fibroblast-inhibiting agent, chloroquine, was used against various animal tumors. Among transplanted animal tumors, the drug was most effective on relatively connective tissue-rich Bashford and Brown-Pearce tumors, as reflected by prolongation of life span, inhibition of tumor growth, inhibition of lowering of liver catalase activity, improvement of iron metabolism, increase of tumor necrosis, inhibition of connective tissue formation, and decrease of acid mucopolysaccharide. On the other hand, it was of little advantage in Ehrlich, Yoshida and MH134 tumors which contain little connective tissue, except for a decrease of the amount of ascites and ascites tumor cells in the former two tumors. These results indicate that chloroquine suppress the growth of the tumors relatively rich in connective tissue. This effect of chloroquine appears to be due to the primary attack of the stromal connective tissue of tumors being followed by the degeneration of tumor cells, though its probable anti-tumor activity by the indirect effects through its anti-inflammatory and systemic humoral activities should be taken into consideration.

The effects of chloroquine on the growth and morphology of fibroblasts in tissue culture, and in vivo granulomas were investigated. As the result, the drug was shown to have a potent action to inhibit fibroblast growth, which has led to a possibility of its clinical use to patients with malignant tumors.

1. Attempts have been made to confirm how the formazan formation is affected in the presence of oxygen gas when the cells are incubated with neotetrazolium salt and the subsrtates for the enzymes to be tested. 2. In the cases of succinoxidase formazan formation is minimized under pure O2tension, it increases with decrease in O2 tension, and reaches its maximum value under N2gas. 3. This relationship between the oxygen tension and the diformazan formmation can likewise be observed even after pretreatment of the system with KCN. 4. In measuring enzyme activity of the DPN-diaphorase system with L-glutamate and DPN as substrate and NT as hydrogen acceptor, the same relationships between the oxygen tension and the NT-reduction can be seen as in succinoxidase system. 5. In the determination of enzyme activity of the cytochrome-c-cytochrome oxidase system with p-phenylene-diamine as substrate and NT as hydrogen acceptor, likewise the diformazan formation is markedly affected by oxygen tension and increased with the reduced oxygen tension but under pure Ns gas the value is reduced. When the systen is pretreated with KCN, however, the diformazan formation reveals its maximum value under pure nitrogen gas, the values of which correspond to those values of endogenous reaction without substrate. 6. The above results show that the neotetrazolium salt can compete with O2 as hydrogen acceptor, and less values of formazan formation may be obtained under higher oxygen tension and the higher values under lower oxygen tension independently from the true activity of the enzyme.

Since the classic work of Ranvier, it is well known that the mammalian striated muscle is composed of two types of muscle fibers, i. e., the red and white muscle fibers. In the previous paper1 it has been reported that the limb muscle fibers of mammals can be divided into three types from their activities of the histochemically demonstrable oxidative enzymes. Namely, the small red muscle fibers had a higher activity of oxidative enzymes, the large white muscle fibers a lower activity and the third type of muscle fibers being called "medium fiber" or "intermediate fiber" showed an intermediate activity between those of the red and white muscle fibers.

For the purpose to clarify the causes of X-ray disturbances a series of experiments have been conducted on biological and biochemical properties of compound lipids extracted from normal and X-ray irradiated rabbit organs with a special reference to the P³²-labeled compound lipids uptake, inhibitory action to L cell proliferation and uncoupling of oxidative phosphorylation, and the following results have been obtained. The compound lipids (lysophosphatide rich fraction) isolated from the X-ray irradiated rabbit organ have been found to possess a strong hemolytic action and also an action to inhibit the cell proliferation as well as to accelerate the respiration of the mitochondria in the rabbit liver and spleen. It has also been proven that they act as to induce a marked swelling of mitochondria, to impede the formation of high energy phosphate as well as to act as an uncoupler of oxidative phosphorylation in vivo. In the test to see the uptake of P³²-labeled compound lipids by various organs, a marked uptake has been observed in spleen, bone marrow, and liver of both irradiated and non-irradiated groups. Further, the uptake of P³²-labeled compound lipids in the rabbits given intravenous injections of compound lipid fraction for 30 consecutive days previously has been found to be greatest in pancreas followed by bone marrow, spleen, liver in the order mentioned in male group, whereas it is greatest in spleen, followed by liver and bone marrow in the female group. With these results the discussion was conducted concerning the relation between the lipid metabolism and X-ray disturbances.

As described in the foregoing, a certain degree of desirable effect can be recognized in every instance of the present trials. However, in order to apply these methods in clinics it is necessary to carry out further studies on the mechanism that operates in bringing about such an effect, but this paper is presented as a preliminary report.

A case of paroxysmal bundle branch block, two to one right bundle branch block followed by intermittent right bundle branch block, which is associated with chronic cor pulmonale secondary to active, far advanced pulmonary tuberculosis, is presented. The incidence and mechanism of the paroxysmal bundle branch block have been discussed.

A granuloma pouch was formed on the back of rats by the original method of SELYE. Seven days when granuloma tissue reached its maximum, 35S labeled ChS, 59Fe labeled ChS-Fe, labeled ferric ammoninum citrate and colloidal 198Au were injected into the pouch and their absorption and organ distribution examined and compared with the results in the case where 59Fe labeled ferric ammoninum citrate and colloidal 198Au were injected into the gluteal muscle. 1. When 35S labeled ChS was injected into the granuloma pouch, radioactivity of the organs per gram tissue was high in the kidney, liver, bone marrow and spleen, in descending order. The maximum activity was seen 12 to 24 hours after injection, which is slow compared to the results obtained by KISHIDA in intraperitoneal and oral administration. 2. The absorption of Ch S-Fe by pouch where the iron is enveloped by the large ChS molecule, is slower than that of ferric ammonium citrate, an inorganic compound. 3. The uptake of Fe from the blood by bone marrow is larger when the increase of blood Fe ion concentration is slow, rater than when the increase is rapid. 4. When conoidal 198Au is injected into the pouch and injected into the" gluteal muscle, the 198Au is phargocytozed by the reticuloendothelial system organs, the liver showing the largest uptake among all organs. 5. In the intramuscular injection of colloidal 198Au and 59Fe labeled ferric ammonium citrate, radioactivity of pouch fluid is lower than that of blood. However, the difference between the two is less in the case of colloidal 198Au. 6. In the granuloma ponch, radioactivity of the abdominal wall proves to be greater than that of the dorsal wall.

1. Rat liver mitochondria are swollen by inorganic phosphate in the medium of slightly hypotonic sucrose solution containing respiratory substrate and the mitochondrial swelling is inhibited or turned to shrink by ADP, respiratory inhibitor, anaerobiosis and uncoupler of oxidative phosphorylation. This mitochondrial swelling is not inhibited by the inhibitor of phosphorylating respiration such as oligomycin and tributyltin chloride. 2. Rat liver mitochondria are swollen by ATP in the presence of antimycin A, inorganic phosphate and 0.1 mM of CaCl2 and such a swelling is inhibited by oligomycin. 3. Accumulation of a small amont of P³² in acid soluble Pi fraction of rat liver mitochondria proceeds even in the medium containing neither ATP nor Ca++ but is inhibited by respiratory inhibitor, ATP, ADP and uncoupler of oxidative phosphorylation. The accumulation of P³² in mitochondria, however, is not inhibited by oligomycin. 4. The accumulation of P³² is induced by ATP in the presence of antimycin A and Ca++(O.l mM) and such an accumulation of P³² is inhibited by oligomycin. 5. It is suggested that the Pi-induced swelling of mitochondria is correlated to the accumulation of inorganic phosphate and both of them are tightly coupled to the initial step in the process of oxidative phosphoryaltion.

With the purpose to elucidate the cause and difference of blood fluidity in sudden death and natural one, we have observed the fibrinolysis of the blood in medico-legal and pathological autopsies by means of Fibrin Plate Method, a routine method devised in our laboratory. As the result it has been found that in the blood serum of sudden death and in some of natural deaths from tumors, leukemias, etc., the decrease in fibrinolytic activity is equivalent to the amount of proactivator that combined with the SK-like substance liberated into blood. On the other hand, in the blood of most of natural deaths, and in that bled from vessels and stored in body cavities, no natural fibrinolysis is observable and the same fibrinolytic activity with SK as normal one is demonstrated. Thus it is concluded that the cause of blood fluidity in sudden death is due to the fibrinolysis.

Some bile acids (dehydrocholic, cholic, chenodeoxycholic, ursodeoxycholic, and deoxycholic acids), and some hypocholesterolemic agents (22, 25 diazacholestanol, 20,25-diazacholesterol, triparanol, and SKF 525-A) are the inducers of isovalthinuria in guinea pig. Administration of methionine appears to increase the pool of sulfur compound which participates in the formation of isovalthine. Cholesterol appears to have no enhancing effect on the induction activity of isovalthinuria inducers. The mechanism of isovalthine formation and the role of sulfur amino acids in lowering blood cholesterol are discussed.

Using the method given by GOLDSTEIN (1961)9 for the determination of serum beta-glucuronidase activity, this value was determined in both normal and patients with epilepsy, neuroses, psychoses and multiple sclerosis. Of the patient groups examined, the group of those suffering from epilepsy is the only one showing any difference of statistical significance for all four methods of determination. The group of patients suffering from neuroses differs significantly from the normal group as regards the results got by the method of heat coagulation for removal of the proteins. The material is however too small to provide any explanation of the results, but it appears to show that a determination of serum glucuronidase activity may be of interest in groups of diseases other than malignant tumors.

A case of intramural pure pigment gallstones, which were fortuitously found in post-mortem examination, is presented. The incidence, mechanism of formation of the stones and roentgenological diagnosis of the intramural gallstones, porcelain gall bladder, are mentioned.

1. With strain L cells in culture the biological effects of oxygen rich environment have been observed with special reference to the cell growth, glycolysis, respiration, incorporation of P³² into Δ10 P and DNA synthesis. 2. Oxygen rich environment produces an increase in the vital activity of the cells at the initial stage of culture, i. e. increased activity of succinoxidase system, low glucose consumption and active cell growth, but in the later stage the activity of the cells is lowered likewise the activity of succinoxidase with the decreased oxidative phosphorylation, and an increase in the uptake of glucose and the enhanced lactic acid production. 3. The most adequate atmosphere for cell proliferation is found to be air though the reason for this remains unsolved. 4. Suppressed cell growth in the later stage of cell culture under the oxygen rich environment is accompanied by the increase of the cells containing smaller amount of DNA, but it is uncertain whether or not the decreased rate in DNA synthesis is responsible for the depressed cell growth.

Following Fibrin Plate Method of SZOLLOSY and RENGEI² , and ASTRUP and MULLERTZ³, the author conducted a series of experiments in an attempt to identify human blood by detecting the proactivator believed to be one of the enzyme proteins contained abundantly in human blood. As the results it has been found that with 0.1 mg. % SK-solution human blood alone responds to the reaction, showing almost absolute species-specificity within 4 hours but not with blood of monkey. In addition, the sensitivity is so high that it responds positively up to the dilution of 1: 8,000 to 1: 10,000 (human blood: physiological saline solution). By means of this method using 0.1 mg% SK-solution it has been clearly demonstated that the identification of human blood is possible in a variety of conditions and states as may be encountered in practical legal medicine such as with blood stains in cloth, wood, stone, leaves of tree even with a trace of blood stain, old human blood stain left standing for 20 to 30 years, old blood mixed with iron rust, blood stains soaked in various oils, and even the blood stained cloth washed thoroughly and left standing in room temperature for 6 months. Therefore, this Fibrin Plate Method seems to be the excellent one for the identification of human blood.