検索

Rats were depleted of skin histamine by more than 80 % by intraperitoneal injections of sinomenine with daily increasing doses for 6 days. In these rats, egg-white edema induced in the hind paws was inhibited by 68 % of control. The weight of the wall of granuloma pouch made by croton oil was also evidently smaller in the rat treated similarly with sinomenine than that of control. This suggests an important role of histamine participating in the inflammation. It has been observed that a variety of non-steroidal anti-inflammatory drugs inhibited both degranulation and histamine release induced by compound 48/80 of mast cells isolated from rat peritoneal fluid. The degranulation inhibiting actions of anti-inflammatory drugs were markedly decreased in the presence of glucose as in cases of dinitrophenol, dicumarol and warfarin which are known uncouplers of oxidative phosphorylation. Also, prevention of edema provoked by anti-rat serum is roughly correlated to a potency of degranulation inhibiting effect of anti-inflammatory agents. These observations suggest that there is a common mechanism between these two phenomena, and the prevention of mast cell degranulation by the anti-inflammatory agents is, at least, partially due to their uncoupling effects. A working hypothesis explaining the process of edema formation at the inflammatory site has. been made based on the data of the present experiment and other ob3ervations: a leakage of plasma into the tissue space from the gap between two adjacent endothelial cells which are contracted by released histamine may activate a kinin-forming system in the plasma, and kinin(s) may further aggravate a leakage. The mechanism of action of anti-inflammatory agents, which interfere with the histamine effect in inflammation, should be understood in twofold: one is prevention of histamine release from the tissue, mainly by inhibiting mast-cell degranulation, and the other is prevention of the contraction of endothial cells by their uncoupling activities.

MC-induced sarcomas produced under the skin on the back between　scapulas of C3H mice were transplanted　successively to the mice of the　same strain. Using the first and the second generation tumors, viable　tumor cells were prepared and with these tumor cells C3H mice were　inoculated. From these sensitized mice regional lymph　nodes were taken　out at certain intervals and lymph-node cells were prepared. These tumor　cells were mixed with regional lymph-node cells in the ratio of 1 : 10, and the mixed cells were transplanted subcutaneously on the back of C3H　mice, and the development and growth of tumors were observed at intervals.　As a result it was found that the inhibitory effect of these regional　lymph-node cells on the tumor growth was strong one to two weeks after　the transplantation, but beyond 3, or 4 weeks no inhibition　was observable.　In connection with the present in vivo experiments, some comments　were made on the available literature, and it has been demonstrated that　even in the cancer-bearing animal destined to die of tumors, at certain stage of cancer there is seen an inhibitory effect of the host on the tumor　growth by way of the lymphoid system and that such a response of the　host in vivo seems to be　correlated well with in vitro reaction.

1. To have a rapid isolation of oligomycin-sensitive ATPase particles (OSA particles), 0.1 mg DOC per mg of protein and 72 g potassium chlo. ride per I were added to mitochondria suspended in a tris.sucrose-histidine solution, which was followed by addition of 2-fold volume of chilled water, and fractionated by a discontinuous sucrose density gradient centrifugation. As a result, it was possible to reveal the OSA particle structure, composed of the head piece, stalk and thread-like structure of a superficial portion of the base pieces, stripped off from the mitochondrial inner membrane, in a layer of density.l.lO. This fraction exhibited a remarkable activity of ATPase sensitive to oligomycin, approximately 15 ,lJ.moles Pi released per mg of protein per minute at pH 8.6 at 37° in a non-ATP regenerating assay system, and contained almost no cytochromes. 2. When the OSA particles thus isolated were heated in water bath at 65° for 2 minutes, the head pieces were detached with a concomitant loss of oligomycin-sensitivity and were purified from the supernatant by precipitation with ammonium sulfate. 3. Trypsin in low concentration slightly induced a rise in the ATPase activity of OSA particles but in higher concentration it inhibited the activity. 4. OSA particles were resistant to the treatment of urea, and it was difficult to detach the head pieces by this treatment. 5. The some fraction obtained by solubilization of thc crude OSA particles with cholate and fractionation with ammonium sulfate exhibited ATPase activity in a masked form, and the ATPase activity with oligomycin. sensitivity was restored on addition of phospholipid. 6. A discussion was made on the mode of assembly of the head pieces and associated components and biochemical properties of OSA particles.

For the purpo3e to determine exactly what stage of cell specialization the DNA level of erythroid cell nuclei begins to decline, the author observed the DNA level of erythroblasts in mitosis by microspectrophotometry and the DNA synthesis by flash labeling with H3-thymidine. The cell samples were obtained from the bone marrow of normal, blood-depleted and phenylhydrazine-treated animals, and the anemic animals received a mass red cell transfusion, all the animals being injected with colchicine 4 hours before obtaining the bone marrow sample. DNA level was measured on the smeared cells stained by Feulgen reaction and DNA synthesis by autoradiography on the smeared cells. Besides these, chromosome number was observed on the anemic rat erythroblasts at metaphase by air dry method. The observations indicated that the DNA level begins to decrease at polychromatic stage being accompanied by a decrease in TDH3-incorporation into DNA, reaching minimum level at orthochromatic cell both in DNA contents and synthesis. Chromosome numbers of erythroblasts of rat were irregular being distri buted between 42 to 20. The data have suggested that the DNA level of erythroblasts decreases only in the later stages of cell specialization, and at polychromatic stage the chromosome number may also decrease in rabbit at polychromatic stage by the cell division with an incomplete DNA replication. The high DNA level of the erythroblasts of rabbit, in severe anemia where most of the cells are denucleated at polychromatic and late basophilic stages, has been discussed from the view point of the insufficient DNA replication at polychromatic stages.

The body wall of the cercaria of Schistosoma japonicum is covered with a thin integument which is connected to epithel cells located under the uscle layer. On the outer and the basal surfaces of the integument are seen thin limiting membranes. In the matrix of the integument are distributed numerous dense granules, vacuoles and spines. The rootlet of the spine is attached to the basement membrane of the integument. The circular and longitudinal muscle layers, both underlying the integument, have smooth muscle fibers composed of thick and thin myofilaments. The cercaria possesses five pairs of secretion gland cells which are divided into two groups of three anterior and two posterior pairs. Both gland cells are filled with secretion balls. The tail of cercaria is likewise covered with a thin integumen t, whose structure is identically the same as the body integument. Beneath the integument are located thin circular and longitudinal muscle layers. The circular muscle cells have smooth muscle fibers, but the longitudinal muscle cells have striated muscle fibers. These muscle cells contain many large mitochondria. On observing the cross-sections of the tail at the flame cell level the arrangement of these muscle can be divided into four muscle groups and each muscle group reveals four or five muscle cells. The excretory system is well developed and has flame cells, excretory canal and bladder.

To obtain some information of the biological action of Kankohso 101dinicotinate and Kankohso 301-nicotinate, observations were made on the binding mode of these substances with protein, chondroitin sulfate and nucleic acids and the following results were obtained; 1. Kankohso 10 I-dinicotinate binds reversively with bovine serum albumin or serum r-globulin, resulting in metachromasia. By binding with proteins the absorption maximum of the dye shifts toward the long wave length side and the absorbance decreased distinctly. The data show that there are more than one kind of binding sites and the binding with bovine serum albumin is weak in acidic solution and strong in alkaline solution. 2. Kankohso 10 I-dinicotinate produces strong metachromasia with sodium chondroitin sulfate and the color of the solution changes from violet blue to reddish violet. The absorption maximum at 592 mp. decreases without shifting its wave length ,and the shoulder appears at 555 mp. be. comes distinct peak. The strongest metachromatical changes occurs at the concentration of the chondroitinsulfate whose sulfonate radicals is equal to the molecules of Kankohso 10 I-dinicotinate. 3. Kankohso IOI-dinicotinate produces metachromasia with nucleic acid, where absorption spectrum is shifted toward long wave length and absorbance is decreased at a certain concentration. 4. Kankohso 301.nicotinate binds weakly with bovine serum albumin, the binding of which is reversible and the maximum binding number is 1.1 per molecule of albumin. Metachromasia cannot be produced by binding. Kankohso 30I.nicotinate does not bind with bovine serum γ-globulin. This compund does not produce metachromasia with sodium chondroitin sulfate but produces weak metachromasia with nucleic acid, indicating some affinity to nucleic acid.

Transformation of Japanese encephalitis antibody from IgM to IgG in the sera of the experimental infected chicks with Japanese encephalitis virus and transmission of IgM or IgG from hen to chicks were examined by the gel filtration on Sephadex G-200 column. The following results were obtained. 1. Titer of hemoagglutination inhibiting antibody rose on seven days after inoculation of mouse brain homogenate infected with Japanese encephalitis, and that increased rapidly after the second inoculation of Japanese encephalitis. The maximum peak of antibody titer attained on 35 days after the first inoculation, on 7 days after the second inoculation and it maintained for a period of 2 months then decreased. Viremia was detected till 6 hours after the first inoculation. 2. IgM antibody by gel filtration appeared on 7 days after the first inoculation, kept on rising, reached the peak on 35 days after the first inoculation, then decreased, and disappeared on 120 days. IgG antibody appeared about 2 weeks after the IgM antibody appearance, and the titer of IgG antibody became higher than that of IgM antibody on 35 days after the first inoculation, then decreased gradually, and showed 1 : 16 of titer of peak on 150 days by gel filtration. 3. We could obtain the chicks by fertilization from experimentally infected hen, having IgM and IgG of hemoagglutination inhibiting antibody of Japanese encephalitis. And the localization of antibodies in the sera of its chicks was determined by Sephadex G-200 gel filtration. And IgG antibody was detected in chick serum, though IgM antibody was not detected by this method.

1. Mitochondria isolated from hamster tumors induced by adenovirus type 12 possessed circular DNA fibers. 2. The mean value of the length of the highest frequency group of the circular DNA molecules was 4.92 ±0.38 μ. 3. Catenated dimer DNA molecules and small (less than 2 μ in length) circular DNA molecules were observed.

As to trial toward the elimination of Japanese encephalitis virus in natural surroundings, pigs received inoculation of inactivated Japanese encephalitis vaccine supplemented with complete Freund's adjuvant twice at one-week interval. Effect of adjuvant supplement on the magnitude of antibody and also prevention of viremia caused by natural infection by antibody induced with vaccine were investigated. The results of this study are summarized as follows. 1. In the group of pigs inoculated with vaccine containing adjuvant, titer of hemoagglutination inhibiting and neutralizing antibodies was higher than those inoculated with vaccine alone and their high titer persisted. 2. With respect to natural infection of pigs, on August 22 when the pigs were thought to have been infected, there was observed a rise in antibody titers. And on antibody formed in those pigs inoculated with vaccine with or without adjuvant proved to be all 2-ME resistant type, whereas the antibodies produced in control group were 2-ME sensitive antibody. 3. Viremia was detected in the blood of pigs naturally infected, but it was not demonstrated pigs inoculated with vaccine supplemented with adjuvant or without adjuvant. The virus of pig blood which was inoculated into suckling mouse brain and was separated after low suckling passage mouse was supposed to be JaGAr strain from optimum hydrogen ion concentration of its hemoagglutination reaction. 4. Effect of vaccination on antibody response of pigs having maternal antibody was not recognized.

Morphological comparison at colonial level was made on a series of established liver cell lines derived from rats fed 4-dimethylaminoazo-benzene (DAB) for various periods of days for the purpose of elucidating more accurately the differences in morphology and growth patterns among these cell lines. Colonies of each cell line produced by the single cell plating technique were compared with regard to colony size, density and piling-up of cells, atypism and pleomorphism of cells, and the migration of cells from colonies. Plating efficiency of each cell line was also compared. The cultured rat liver cells obtained from those rats fed DAB for a longer period of days showed higher plating efficiency, and increased the incidence of large-sized, dense, and piled-up colonies, of colonies consisted of cells having nuclear atypism and pleomorphism, and of irregularly margined colonies with migrating cells. The correlation between the present results and the process of DABcarcinogenesis is discussed.

We applied unidirectional MLC test to skin allografts in dogs, and examined the correlation between the strength of the MLC reaction and the survival time of skin allografts. As a result it was found that the skin allografts was rejected within 10 days when the rate of blastformation was more than 18 %. In contrast, the skin graft survived over 13 days when the rate was less than 15 %. The rate of blastformation was inversely correlated with the median survival time of skin allograft.

Epidemiological study on the prevalence of SMON III Ibara City, Yoshii Town and Yubara Town in Okayama Prefecture was conducted and the following results were obtained. "Epidemization precession" (Die Prazession der Durchseuchung), described by Rudder which shows that ages common to this disease is shifting to younger generation as incidence rate increases, in the endemic regions was recognized in Ibara City and Yubara Town. The mode of the distribution of the interval between the primary and secondary patients in a family suggests that it corresponds to the incubation period. Distribution of the patients to the size of family is not adaptable to binomial model, but adaptable to chain binomial model, and the intra-household transmitted rate is 5 per cent, and the true intra-household transmitted rate is about two times as high as extra-household transmitted rate by the modified chain binomial model. Intra-hospital incidence among SMON patients and non-SMON patients as well as medical workers were observed at the time when the number of new patients increased in a hospital. In SMON patients, the rate of appendectomized ones was higher than that of non-SMON patients, suggesting that gastrointestinal tract has some relationship to the development of SMON disease.

A non.specific esterase activity was demonstrated III the jejunum of rats by an azoindoxyl method. 1) Microvilli of the jejunal epithelial cells were remarkably stained in non-frozen specimens and feebly in frozen specimens. 2) The other cytoplasmic structures, i. e. mitochondria, endoplasmic reticulum, nuclear envelope, plasma membrane and multivesicular body showed a positive reaction product in frozen sections but not in non-frozen blocks.

A human fetal fibroblast strain, belonging to a group resistant to SV40 transformation, was transformed by SV40 through a multiple inoculation procedure. Two independently transformed cells were described in comparison with each other. The proportions of cells with the nuclei possessing V antigen were 2.9% at the 5th passage in one strain and 1.1 % at the 4th passage in another, and they declined gradually as frequent passages were repeated. The percentages of the transformed cells with V antigen-positive nuclei were, in both strains, quantitatively compatible with those of the cells with the nuclei full of virus particles in crystalline arrays, which were demonstrated by immunofluorescent studies and electron microscopy.

An electron microscopic observation was made on the DNA's extracted from purified HeLa cell nuclei, mitochondria, and the whole cell, and fractionated by ethidium bromide-cesium chloride density gradient method or sucrose density gradient method. Nuclear DNA presents mainly long linear DNA derived from fragmented chromosomal DNA. In addition to this, the existence of small circular DNA molecules measuring 0.32 -1.78 μ, was confirmed. Mitochondrial DNA was mainly circular DNA, which measured 4.87 μ in the mean value of the contour lengths in the highest frequency group, and small circular DNA molecules, measuring 0.3-1.01 μ in contour length, were also found in an extremely low frequency.

By assuming a three-compartment model, kinetic analysis of peripheral hyroxine distributions in various organs was represented by the alues calculated on the basis of the disappearance curve of 131I-T4 radioactivity in the serum, time　dependent curve of radioactivity over the liver　and urinary excretion of 131I-T4 in attempts to clarify the kinetic distribution　of the thyroxine and the time　dependent pool size of thyroxine in each　compartment such as serum pool, liver pool, and the other pool,　As a result it has been demonstrated that pool size3 of tyroxine, in the serum, liver and the other pool are enlarged in　hyperthyroidism, while　they are decreased in　hypothyroidism in respective pools.　We have recognized the reduction in the values of the liver pool size　of 131I-thyroxine and 131I-thyroxine excretion into the bile, while the increase　of 131I-thyroxine excretion into the urine in the cases of chronic hepatitis　and cirrhosis of the liver, but the thyroxine concentration in the serum to remain within the normal level in liver diseases. As a result of the reduction　in the liver pool size of 131I-thyroxine and in its uptake into the liver,　the other pool size enlarges to compensate the reduction and the function of the other pool is elevated.

As a step in the elucidation of immunity of human cancer from the standpoint of homotransplantation immunity, we conducted mixed cultures of regional lymph node cells from C3H mouse isotransplanted with methylcholanthrene-induced sarcoma (MC-tumor) together with the primary culture MC-tumor cells, and observed the behaviors of these lymph node cells to the MC-tumor cells and compared the effects of these lymph node cells with lhose of normal mouse lymph node cells by counting the growth number of tumor cells and also by cinematography. As a result, it has been demonstrated that the regional lymph node cells from the mouse isotransplanted with the MC-tumor (2mm3 in size) acquire a strong antitumor activity by 14 days after the transplantation, but such antitumor activity diminishes and disappears in the terminal stage of cancer. When the number of these lymphocytes is increased, there can be observed some dosage effect, but no complete inhibition of the tumor growth can be attained. The cinematographic observations of these regional lymph node cells in the mixed culture with tumor cells reveal that lymphocytes of small to intermediate size aggregate onto the tumor cells and inhibit the movement of the latter.

The present report describes the findings on the infectivity of DNA partially purified from SV-40 which was propagated in the monkey kidney cells (BSC-1) in vitro and the importance of nucleic acids as oncogenic factors, particularly the induction of tumor by DNA in newborn hamsters. 593 newborn hamsters in total were used in the present experiments, and cannibalism among them posed as a serious problem. On 30 days postinoculation, very remarkable changes occurred in the liver, lung and subcutaneous areas. Cellular responses of the perivascular cells were predominant. and they were distributed in the interstitial tissues of the liver (liver cirrhosis in primates) and lung. Three hamsters of those subcutaneously inoculated with nucleic acids developed tumors and two tumors appeared in the subcutaneous tissues on 130 days postinoculation, which were identified to be the ones induced by intact SV-40 virus. Other tumors appeared in the liver, lung, intestinal ducts and abdominal surface at 126 days after subcutaneous injection. The cytological observations revealed multiple hemangiosarcoma combined with proliferation of the perivascular cells. On the other hand, cellular responses to nucleic acids were more marked by inoculation of the cell-free filtrate of BSC-1 infected by DNA than of DNA, and essential histologic findings were similar to the respo.nse to infectious DNA. Thirty-nine hamsters (30 per cent) developed tumor within about 200 days postinoculation of the filtrates. Sarcomas were common and they were confined to the subcutaneous tissues in 35 hamsters and to the peritoneum in two others by subcutaneous inoculation of the filtrates. The intestinal gland-cell carcinomas, however, could be induced at 37 and 59 days postinoculation in two hamsters of one litter (7 newborn hamsters) and in the other three newborn hamsters subcutaneous sarcomas were induced by inoculation of the same agent. These results suggest that the observation on the oncogenic capacity of nucleic acids would give us a clue to resolve the course of cancer from the view point of the infectious nucleic acid.

The distribution and activities of five hydrolytic and eight oxidative enzymes were histochemically studied in 60 different tumors of the human intestines. Benign polyp showed similar activities of most enzymes as those in normal crypt cells of large intestine with exception of higher activity of succinic dehydrogenase in benign polyp than in crypt cells. Malignant polyp had higher activities of most oxidative enzymes. Reticulo-sarcoma had weak activities of all enzymes. Carcinoid had strong activities of glucose-6-phosphate dehydrogenase and isocitric dehydrogenase while very weak of succinic dehydrogenase. Carcinoma showed varying degrees of the activity of all enzymes. Alkaline phosphatase and aminopeptidase were almost negative in all cells but in the stromal elements their weak activities were sporadically observed. Most enzymes were decreased in the central area of the carcinoma cell nestle, while in the infiltrating area or in the margin of cell nestle they were not decreased and sometimes increased.

1. Isovaleric acid-1-C14, -4-C14, or C14-CaC03 with or without non-isotopic isovaleric acid was orally administered to rats and the incorporation of these isotopes into liver cholesterol, fatty acid, or urinary isovalthine was examined. 2. Isopropyl group of isovaleric acid was more efficiently utilized for cholesterol synthesis than carboxyl group, and also for cholesterol synthesis than for fatty acid. These results indicate that isovaleric acid is cleaved into two fragments before it is utilized for cholesterol synthesis. 3. Carbon dioxide was used for the synthesis of liver cholesterol and of liver fatty acid. Isovaleric acid seems to enhance the incorporation of carbon dioxide into cholesterol. 4. All the experimental rats received isotopic or non-isotopic isovaleric acid excreted isovalthine, but no radioactivity was found in it. Thus, isovaleric acid residue of urinary isovalthine molecule is not derived from isovaleric acid administered, and carbon dioxide is not the carbon source of urinary isovalthine. 5. Suspicious metabolism of isovaleric acid or of carbon dioxide was discussed. 6. Isotopic isovalthine which was synthesized from (± ) α-bromoisovaleric acid-4-C14 is administered to rat and it was found that the isotope did not incorporate into cholesterol or fatty acid of liver and of brain. About 15% of isotopic isovalthine was recovered in urine up to the next day after injection. The large part of isovalthine was missing.