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The effect of pyridoxine treatment of a homocystinuric patient on the urinary excretion of some sulfur-containing amino acids was studied and the following results were obtained. As a result of pyridoxine treatment, urinary homocystine decreased to a fairly great extent, and its unusual metabolites S.(3-hydroxy-3-carboxyn- propylthio) homocysteine (HCPTHC) and S-C8-carboxyethylthio homocysteine (j3-CETHC) increased to some extent. But its oxidation product (homocysteic acid) showed a tendency to decrease slightly. Urinary methionine and cystine increased to some extent, but cysteinehomocysteine mixed disulfide showed no remarkable change.

The mode of lymph flow from the breast to the regional lymph node was studied using 1llSAu colloid, to ascertain the concept of lymph node of Groups 1, 2, and 3. Lymph flow through the internal mammary nodes was found to be abundant. Especially so when 1llSAu colloid was injected into the lower half of the breast, there was observed more abundant flow than that to axillary lymph nodes. Therefore, it was concluded that regardless of the site of occupation of a tumor, internal mammary nodes should be con· sidered to be of Group 1. Lymph flow through the subclavian nodes proved to be always less than that to the axillary nodes or internal mammary nodes. The rate of the lymph flow appearance on the scintigram was about 20%. Whether the subclavian nodes should be classified as Group 1 or 2 should be further studied. The rate of supraclavicular node visualization was below 3%. Therefore, the supraclavicular nodes should be considered to be Group 2. When these results are applied to the current rule of handling of breast cancer, discrepancy occurs in the Stage number and R-numer.

In order to study the viral etiology of human brain tumors, attempts were made to isolate cytopathogenic agents from human brain tumors by the tissue culture of tumor tissues and by the mixed culture of tumor tissues with HeLa cells. Five glioblastomas, a mixed form of glioblastoma and fibrosarcoma, two astrocytomas, two ependymomas, two meningiomas, an oligodendroglioma, a spongioblastoma polare and a choroid plexus papilloma were studied. In the tissue culture, besides the cells which appeared to be the tumor parenchymal cells, varying amounts of fibroblastic cells appeared in all the tumors tested and they increased with the prolongation of the culture period. In any of the tumors tested, no cytopathogenic agents were detected by either the culture of tumor tissues or the mixed culture of tumor tissues with HeLa cells. From the virological point of view, the significance of these negative results was discussed.

To obtain a useful rat liver cell line for in vitro carcinogenesis, two rat diploid epithelial cell lines were established from a 7-day-old male rat by the repeated colonial clone method. More than 80% of cells from each cell line have maintained normal diploid karyotype for over 30 months in vitro. The diploid cells were identi. fied as normal diploid karyotype by conventional Giemsa and trypsin. Giemsa techniques. They showed little difference in morphology and growth rate between early and late passages. Without cloning, they tended to be heterogenous in cell morphology, became heteroploid in chromosome and showed increased growth potential with time. Highly heteroploid cells which were derived from one of the lines produced ascites and solid tumors when inoculated into syngeneic rats intraperitoneally. Histologically, the tumors were diagnosed as poorly differentiated hepatocarcinomas. One of these diploid epithelial cell lines in early passage contained some activity of tyrosine transaminase and liver type aldolase and .glycokinase. Therefore, it is suggested that these epithelial cell lines represent liver parenchymal cells.

The establishment of a hamster lymphoma cell line was attempted. Simple mincing and trypsinization of lymphoma tissue resulted in a high degree of cell degeneration. The ascitic tumor cells produced by intraperitoneal transplantation of lymphoma tissue gave a better result. These ascitic cells grew and were cultured successively in medium consisting of RPMI 1640 and 20% fetal calf serum. Cells were round and grew in suspension. Accelerated cell growth was observed one month after starting the culture. In the stained preparations, cells were lymphoblastic. Cells were transplantable into new-born hamsters and produced tumors, but not in young adult hamsters.

We detected an antibody to HCV envelope protein (E1) in sera of patients with HCV-related chronic liver diseases (20 patients with chronic hepatitis and 5 patients with liver cirrhosis) by Western blotting using the fusion protein of E1 envelope protein and beta-galactosidase as an antigen. The antibody to HCV E1 (anti-HCV E1) was detected in 8 (42%) of 19 patients positive for HCV-RNA (16 were positive and 3 were negative for antibody to C100-3) and in 1 (17%) of 6 patients negative for HCV-RNA but positive for antibody to C100-3. HCV-RNA was detected in 8 (89%) of 9 anti-HCV E1 positive sera. The value of alanine aminotransferase was significantly higher in patients positive for anti-HCV E1 than in patients negative for the antibody. Although an antibody to the envelope protein of HCV is suspected to be one of the candidates of virus-neutralizing antibodies, our results suggest this hypothesis appears to be unlikely.

We performed pulmonary artery angioplasty in 19 patients with lung cancer. The procedure consists of segmental or wedge resrection of the infiltrated pulmonary artery stem followed by reconstruction to avoid pneumonectomy and preserve pulmonary function. Among these cases "double sleeve resection" was performed in 10 cases. The 5-year survival of the angioplasty patients was poor at a rate of 11％, but not significantly different from the survival rates for those patients who underwent bronchoplasy alone or pneumonectomy. A promising prognosis may be expected in cases with N0 and N1 lymph node metastasis. However, this procedure may not replace pneumonectmy in patients with intact pulmonary function.

A single subcutaneous injection of 20-methylcholanthrene into newborn AKR mice less than 24 hours old resulted in the acceleration of the development of lymphocytic leukemia, and induction of subcutaneous sarcomas and multiple-lung adenomas. Morphological descriptions of the respective tumors were given. It is suggested that the lungs of newborn mice of strain AKR may prove to be a sensitive organ to evaluate carcinogenicity of certain carcinogenic compounds.

1. When chicken sarcoma virus is serially inoculated on the mouse brain, it loses its carcinogenecity, but when it is inoculated on young chicken, granuloma develops in the liver and lung. When this granuloma is transplanted on adult chicken, a transplantable fibrosarcoma is obtained. 2. According to literature, the originaltumor of the Brown-Pearce cancer is a basal cell cancer, but that imported to Japan in 1953 presented a histological picture of carcinosarcoma. The metastasized tumor of the eye presents a purely cancer tissue, but when this is inoculated on the testis, carcinosarcoma is reproduced. It is therefore considered that the mother cell of the sarcoma is of host origin. 3. MY sarcoma is not a sarcoma, but is a spindle cell cancer. It might be a sarcoma which transformed into a cancer during serial transplantation, but perhaps it was originally a cancer but had been erroneously diagnosed as sarcoma. 4. The tumors we obtained by means of the feeding tests of Yoshida tumor all developed at organs other than those of the digestive tract. They are chiefly reticulo-sarcoma, but others which develop are malignant granuloma in the liver and lung, malignant adenoma in the kidney, papilloma of pelvis, and ependymoma in the cerebral ventricle. Since the discovery of the Yoshida tumor in 1943, serial transplantation has been conducted for 19 years with this tumor not only in Japan but also in foreign countries, but there has been no report to this date that a transformed strain has developed by cell transplantation. It therefore must be considered that the carcinogenesis observed in our feeding tests is a carcinogenesis due to a mechanism completely unlike that of cell transplantation. It has been confirmed by electron microscopy that in the early stage of transplantation of this tumor into the abdominal cavity there was an additional tumor growth due to the anaplastic proliferation of serous cells. 5. During the serial transplantation of viral tumors and/or virus dependent tumors, the tumor sometimes undergoes a morphological change. Though the cause of this is not yet sufficiently elucidated, it is suspected that there is some relationship with virus in the wide sense.

Spontaneous C3Hf lymphatic leukemia maintained in an ascites form was transplanted into newborn Wistar rats less than 24 hours old. Single subcutaneous or intraperitoneal inoculation of the neoplastic cells resulted in progressive tumor growth fatal to the heterologous hosts. Limited serial passage through newborn rats was performed. The intraperitoneally heterografted leukemia grew as massive lymphosarcoma predominantly in the adipose and connective tissue compartments with invasion of the neighboring organs but without leukemic manifestations. The characteristic behavior and histopathologic features of the transplanted disease are presented in comparison with the results of similar experiments reported in the literature.

Man bestimmte die Gerinnungszeit einer Mischung von 0.1 ml des frischen Zitratplasmas, 0.1 ml einer Epsilon-Aminokapronsäure-Lösung in Konzentrationen von 0, 02, 0.5, 2.5, 10, 20, 50 und 100 gamma, 0.1 ml CaCl² Lösung und 0.1 ml Michaelis' Puffer. Die erwähnten EACA-Konzentrationen hatten keinen charakteristischen Einfluss auf die Rekalzifikationszeit des frischen und des gelösten lyophilisierten Plasmas.

It has been indicated that, when fatty acid iron is administered orally, the iron compound is split into iron and fatty acid and absorbed by different mechanisms.

The growth inhibitory effect of the fatty acids (OX) from the liver of X-irradiated rabbits on the solid type of Ehrlich ascites tumors has been observed both in gross and histologic observations. OX substance, a fraction of fatty acids extracted from the liver of X-irradiated rabbits has actually been found to inhibit the tumor growth by the local injection, resulting in the disappearance of the tumor after 12 injections for onemonth period, 2.4 ml of 2.5% emulsion in total dosage. Histologic observations reveal degeneration and necrosis of tumor cells, whereas in the control animals always active proliferation of tumor cells can be observed.

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.

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.

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.

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.