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The regional lymph node cells of the mice sensitized with Ehrlich ascites tumor cells is known to possess a substance that shows antitumor activity on target cells (JTC-II cells). For the purpose to clarify the localization of this substance the regional lymph node cells from such sensitized mice were treated with trypsin solution of different concentrations (1.0 %, 0.2 %, and 0.01 %), and the tissue culture was carried out with JTC.II cells. As a result it was found that these lymph node cells lost antitumor activity. Next, by the differential contrifugation of these sensitized lymphocytes we obtained F1 fraction (700 g, sediment), F2 (8,500 g sediment), F3 (100,000 g sediment) and F4 (100,000 g supernatant). In the presence of each of these fractions tissue culture was conducted with JTC-II cells as target cells, and it was found that the substance with antitumor activity is contained abundantly in F2 fraction (8,500 g sediment) and F4 fraction (100,000 g supernatant). After giving due consideration to the results of these two experiments and also to the available data in the literature, we assume that the substance with antitumor activity is contained in the cell membrane component.

In the mixed tissue culture of mouse lymphocytes with addition of PHA the rate of the appearance of large and intermediate cells increases markedly, but which side of the two cell groups have reacted stronger remains obscure. In order to solve this problem, mixed cultures were conducted in such a way that only one cell group of the two would react. Namely, one cell group was exposed to C0 6).irradiation (Table 2) prior to the culture and cultured with another viable cell group (FJ test group, Table 2) to see the percentage of the appearance of large and intermediate cells. Simultaneously, the skin homograft from respective donor mouse was transplanted to each other and the survival days of each skin graft were compared. As a result it has been shown that the percentage of blastformation and the survival time of the skin transplant in each group prove to be in an inverse relation. The results of these mixed cultures indicate that the extent of blast. formation reflects significantly the difference in B-2 histocompatibility antigens.

In this review of the chemistry, biochemistry and chemical pathology of the bile pigments I am well aware that I shall ask many more questions than I am able to answer. It seems appropriate that the subject should be considered under the five headings: -Chemistry; Formation from Haem Proteins; Transport in the Blood; Conjugation and Transport to the Bile; and Changes in the Gut. I shall conclude with a brief account of the early labelled bilirubin. Because investigation of the pathological significance of the chemical changes undergone in the body is possible only if the chemical structures of the bile pigments are accurately known, my department in London has been very much concerned during the last 15 years with the chemistry of the bile pigments. The work I shall describe has been carried out in collaboration with Dr. NICHOLSON, Dr. KULCZYCKA, Dr. COLE, Dr. PETRYKA and more recently by Mr. STOLL and Miss LEMMON.

Die Autoren berichten uber die guten Behandlungsmoglichkeiten in der Praxis bei verschiedenen peripheren venosen Durchblutungsstorungen bei Erkrankungen der Bewegungsapparate, bei leichteren Fallen von arteriellen DurchblutungsstOrungen und bei einigen Fallen von Hirnblutungen mit Vasotonin und Vasotonin-forte und auch in vitro-Blutgerinnungsuntersuchungen. Bei den erwahnten Fallen kann man die therapeutische Wirkung noch mit Vasotonin-forte-Salbe gut unterstutzen. Die Autoren konnen nachweisen, daB Extr. Arnicae insbesonder in dem Vasotonin-forte die hamodynamische und die blutgerinnungshemmende Wirkung von extr. Aesculi Hippercastani gut verstairkt.

Die physikalischen Grundlagen eines Kernreaktors werden beschrieben. Als spezielles Beispiel wird Aufbau, Kontrolle und Betrieb des Siemens-Unterrichtsreaktors SUR 100 beschrieben. Dieser homogene polyathylenmoderierte Nullleistungsreaktor hat eine Leistung von nur 100 mW. Trotzdem-oder gerade deswegen-ist dieser Reaktor fur Ausbildungszwecke und als Ubungsmoglichkeit auf dem Gebiet der Reaktortheorie und der Kernenergie sehr gut geeignet, denn die Leistungsbeschrankung erlaubt eine einfache Installierung und Betriebsweise des Reaktors. Neben seiner Verwendung als Ausbildungsinstrument kann dieser Reaktor aber auch als Strahlenquelle benutzt werden. Hiermit wurden verschiedene medizinische Praparate, die auch im Strahlenschutz Verwendung finden, bestrahlt, und anschlieBend ihre Dosisrate bestimmt. AuBerdem werden noch weitere Anwendungsmoglichkeiten des Siemens-Unterrichtsreaktors SUR 100 deschrieben.

For the purpose to clarify further the residual catalase in the blood cell ghost, the ghost has been applied to Cyanogum and starch block electrophoresis and the results are briefly summarized as follows. 1. It has been demonstrated that after Cyanogum electrophoresis of the ghost after several washings, bubbling due to enzymatic reaction of catalase occurs near the points of origin, when the plate is immersed in hydrogen peroxide solution and also it has been proved the presence of catalase so firmly bound to the ghost that it is hardly moved by the electro phoresis. Even with the ghost of hypocatlasemia there can be detected catalase which is likewise hardly eluted from the ghost. 2. In the estimation of catalase activities of each fraction from red cell ghost by starch block electrophoresis there can be detected catalase near the point of origin, that is not eluted by the electrophoresis, and the activity of which corresponds to about 0.1 % of the total red cell catalase activity.

The present investigation was carried out to see effects of muscle cornin, an alcoholic fiaction of boiling-water extract from rabbit skeletal muscle, on the nucleic acid synthesis in the early development of Pseudocentrotus depressus. In this study, the author used the assay method of our own device by which we can estimate the incorporation into whole cell simultaneously that into nucleic acid fraction, with one and the same specimen. The results of the observations are briefly summarized as follows. 1) Cornin accelerated the incorporation of 3H-uridine into whole cell by 10-20 %. 3H-thymine, 3H-thymidine and 3H-uracil all inhibited such incorporation. 2) As to the incorporation into the RNA, it was retarded in the course of phosphorylation at the synthetic stage. 3) In the incorporation into DNA, since the incorporation is inhibited by about 2/3 at the synthetic stage, it seems that the polymerization is inhibited. 4) This inhibition of the DNA synthesis was also substantiated by the autoradiography with tritiated thymidine. Some coments were made on the operation of the nucleic acid synthesis, the specific protein structure during the early development of sea urchin egg, and effects of cornin on these as well as on the other intrinsic substances.

Compound 48/80, sinomenine, tween 20 and polyvinylpyrrolidone (PVP) were injected intravenously to dogs, in doses producing similar degree of profound hypotension, and changes in the plasma histamine content and coagulation time were followed on the blood from the femoral artery. After the injection of 48/80 or sinomenine plasma histamine rose rapidly and markedly, attaining its maximum within 2 minutes, but the increase was rather of a short duration. In contrast, after the injection of tween 20 or PVP a less marked increase in plasma histamine developed more slowly, but lasted longer. The blood coagulation time was prolonged in all the cases injected with 48/80, and occasionally with sinomenine. Both beginning and recovery of the prolongation of blood coagulation time were sluggish as compared with the changes of plasma histamine. Tween 20 and PVP did not induce any detectable change of the blood coagulation time. These data were discussed with reference to the sites of action of different histamine releasers.

1. For the settlement of carbon origin of urinary isovalthine, acetic acid-2-C14, valine-U-C14 or leucine-U-C14 was administered to rats together with isovaleric acid as an isovalthinuria inducer, and urinary isovalthine excreted was tested by autoradiography. As the results of which, it was found that these isotopic compounds were not the precursor of urinary isovalthine. Although the isovalthinuria inducing effect of isovaleric acid was fairly diminished by these isotopic compounds, urinary isovalthine was detected by paper electrophoresis. 2. Some metabolic products of these isotopic compounds were also inquired in urine and some tissues. The results were as follows: a) Acetic acid incorporated into urea, aspartate, serine, glutamate, proline, glycine, alanine, ornithine, ethanolamine, r-amino-buthyric acid (brain only), cholesterol and fatty acids. b) Valine incorporated into urinary glutamate and glycine, and tissue cholesterol and fatty acids. Valine was rapidly excreted in urine and found in a very small amount in liver digest. c) Leucine incorporated into urinary aspartate, serine, glutamate and glycine, and tissue cholesterol and fatty acids. 3. Several important problems of isovalthine studies to be elucidated were discussed.

1. It has been found that mouse lymph.node cells, even destroyed by sonication with 20 KC supersonicator, maintain sufficient antigenicity both in vitro and in vivo. 2. When such sonicated cell homogenate is cultured with live lymph-node cells, there can be observed blastformation and the peak of the rate of the blastformation is seen at culture hour 48. 3. When PHA (phytohemagglutinin)-M is added to such mixed cultures, the blastformation is enhanced. 4. When mixed cultures of mouse lymph-node cells are conducted by using such one-way stimulation method in various combinations, the rate of blastformation can tell quite accurately the differences in H-2 antigens of mice. 5. In the experiment using F1 hybrid mice and the parents, it has been demonstrated that the rate of blastformation in mixed cultures of the present experiments shows a direct correlation to the rate of blast formation in mixed cultures of live lymph node cells, whlie it is an inverse proportion to the survival time of the skin transplant. 6. Differences in the transplanation antigens said to be located on sex chromosomes cannot be distinguished by this one.way stimulation method.

Cb strain female mice were exposed to 800 p.p.m. of carbon tetrachloride for 3 hours by the use of newly devised gas chamber via constant current of gas. Contents of ATP, triglyceride and total lipid in the liver were measured at appropriate intervals after inhalation of carbon tetrachloride and compared to non-treated controls. And P : 0 ratio of the liver mitochondria was measured by oxymeter and morphological changes of liver mitochondria were observed by electron microscopy. The following results were obtained. 1. ATP conten t in the liver decreased slightly immediately after inhalation, rapidly decreased until 4 hours after inhalation and gradually decreased until 20 hours after inhalation. 2. Contents of total lipids increased slightly immediately after the exposure and increased gradually until 20 hours later. Contents of triglyceride in the liver increased at almost constant rate during and after the exposure. 3. P : 0 ratio of liver mitochondria did not change immediately after the exposure and gradually increased after the exposure, keeping parallel relation to decrease in ATP content in the liver. Decrease in ATP content in the liver after inhalation of carbon tetrachloride seems to be mainly due to uncoupling of oxidative phosphorylation of liver mitochondria. 4. Morphological changes of liver mitochondria were observed at 4 hours after the exposure by electron microscopy. 5. Decrease in ATP levels of the liver suggested to have a close relation to accumulation of lipid in the liver after the inhalation of carbon tetrachloride.

1. Mitochondria isolated from human liver, hepatoma and gastric cancer contain DNA. The DNA content per mitochondrial protein is about ten times as much in cancer as in normal liver. 2. Human liver, hepatoma and gastric cancer contain circular DNA molecules in their mitochondria. Circular DNAs from normal liver and cancer mitochondria are mostly about 5 μ long, and the frequency of circular DNAs of multiple or shorter length is higher in cancer mitochondrial DNA. The outline of the present paper was presented at the 26th Congress of Japanese Cancer Association (1967) (52, 53).

Five (21 per cent) out of 24 mongrel dogs were found to be refractory to compound 48/80 and also to sinomenine (cross-tolerance). These nonreactor dogs responded normally to PVP and tween 20 and showed normal sensitivity to histamine. The incidence was similar in both sexes. Mechanisms of this type refractoriness were discussed.

As a step towards the elimination of Japanese encephalitis virus in natural surroundings, we inoculated pigs, rabbits and chicks with inactivated Japanese encephalitis vaccine supplemented with complete or incomplete Freund's adjuvant twice at one-week interval. Subsequently, we compared HI antibody titers of the groups inoculated with vaccine containing complete Freund's adjuvant (pigs, rabbits, chicks), of the group inoculated with vaccine containing incomplete adjuvant (rabbits), ar;d of the groups inoculated with vaccine containing no adjuvant (pigs, rabbits, chicks), and also observations on changes in the antibody titers due to natural infection. In a certain portion of these animals neutralizing antibody titers were also determined. The results of this study are briefly summarized as follows. 1. In the groups of pigs and rabbits inoculated with vaccine containing complete Freund's adjuvant, titers of HI antibody and neutralizing antibody were higher than those inoculated with vaccine containing no adjuvant and their high titers persisted. Further, in the group of chicks inoculated with inactivated Japanese encephalitis vaccine containing complete Freund's adjuvant, HI antibody titers were higher and persistent as compared with the antibody titers in the chicks inoculated with inactivated Japanese encephalitis vaccine alone. 2. In the rabbits inoculated with inactivated Japanese encephalitis vaccine contammg incomplete adjuvant, HI antibody titers were lower than in those receiving the vaccine with complete adjuvant, but it has been demonstrated clearly that vaccination of inactivated Japanese encephalitis vaccine supplemented with incomplete adjuvant brings about less sideeffects. Hence such a method of vaccination can be applied as the vaccination with least side-effects. 3. With respect to natural infection of swine, on August 27 when the pigs were thought to have been infected, there was observed a rise in antibody titers. And on being infected with Japanese encephalitis, the antibodies formed in those pigs inoculated with inactivated Japanese ence- phalitis vaccine with or without complete adjuvant proved to be all 2-ME resistant type, whereas the antibodies produced in the control groups not receiving such a vaccination were 2-ME sensitive antibody.

The amygdalofugal fibers were studied III the cat with the silver method of NAUTA-GYGAX. 1. The amygdalofugal fibers are distributed by way of the stria terminalis, the longitudinal association bundle, the inferior thalamic peduncle, and the medial forebrain bundle. 2. The amygdalofugal fibers running through the longitudinal association bundle arise in the lateral principal, intermediate principal nuclei and the lateral and possibly intermediate parts of the periamygdaloid cortex, and terminate in the lateral preoptic nucleus, the bed nucleus of the anterior commissure, the olfactory tubercle, the nucleus of the diagonal band of Broca, the nucleus accumbens, the medial and posterior septal nuclei and the basal part of the head of the caudate nucleus. In addition, there are scattered fibers coursing along the longitudinal association bundle proper. These fibers may have a widespread origin from the amygdaloid complex. The longitudinal association bundle contributes no fibers to the medial forebrain bundle. 3. The fibers, originating from the lateral principal, intermediate principal and medial principal nuclei, join the medial forebrain bundle to distribute widely in the lateral hypothalamic nucleus. A few fibers are seen to reach the ventromedial hypothalamic nucleus, and are considered to arise in the medial principal nucleus. 4. By way of the inferior thalamic peduncle some fibers from the amygdaloid complex course dorsally into the medial part of the dorsomedial thalamic nucleus at its caudal levels. They may arise widely from the amygdaloid complex. A few of them extend farther dorsally to reach the lateral habenular nucleus and the parataenial nucleus. They probably originate from the lateral principal nucleus. 5. The fibers forming the stria terminalis originate from the medial principal nucleus, the medial nucleus, the periamygdaloid cortex and the cortical nucleus, and are distributed in the bed nucleus of the stria terminalis and the lateral preoptic nucleus (preoptic component), as well as the medial preoptic nucleus, the anterior hypothalamic nucleus and the ventromedial hypothalamic nucleus (supracommissural component). The cortical nucleus, particularly its caudal part, and possibly the medial part of the periamygdaloid cortex are regarded as the main sources of the stria terminalis fibers ending in the hypothalamic region. The intermediate principal and lateral principal nuclei do not appear to contribute fibers to the stria terminalis. 6. The ventromedial hypothalamic nucleus receives amygdalofugal fibers both from the medial principal nucleus by way of the medial forebrain bundle, and from the cortical nucleus via the stria terminalis. 7. In addition to intrinsic internuclear fibers within the amygdaloid complex, some of the fibers from the complex are distributed to the ventralmost part of the putamen, the medial part of the claustrum, the periamygdaloid cortex, the prepiriform area and the anterior amygdaloid area, but do not reach the hippocampus.

A series of experiments was conducted to study the base composition of DNA in AVl2-induced tumor and host cells by paper chromatography, and it was found that DNA per cent. guanine-cystosine contents were around 42 % in both of them. The base composition of DNA of AV12 itself differs considerably from that of AVl2-induced tumor cells, while the DNA of tumor cells shows the property similar to that of host cell DNA. The genetical relationship among virus, host cells and tumor cells was discussed.

l) The submitochondrial particle system can synthesize ATP in the early phase (220 seconds after the accition of ADP) in the presence of sodium succinate and Pi, in spite of the absence of the hexokinase-glucose system, and this phosphorylation is inhibited by oligomycin. 2) The submitochondrial particle system can synthesize ATP by the base-acid transition (proton pulse) only in the presence of ADP and Pi, in spite of the absence of oxidizing substrates and the hexokinase-glucose system, and this phosphorylation is dependent on the span of pH change, and is inhibited by oligomycin and 2, 4-dinitrophenol. 3) The role of the proton vector in the oxidative phosphorylation and the proton ejection was discussed from the stand point of a new hypothesis.

Among various photosensitizing dyes, 4, 4'-dimethyl 3, 3'-di-n-heptyl-8- {2-(4-methyl-3-n-heptylthiazole) }-2, 2'-dicarbocyanin diiodide (abb. NK19), even in an extremely low concentration, is known to inhibit the proliferation of bacteria and tissue culture cells (1, 2, 3). With respect to the mechanism of such inhibitory action no other property of this NKl9 is known except that it has a marked adsorptive property to protein (4). As a step toward the elucidation of the mode of biological effect, the author studied the effect of NK19 on the energy transfer reaction of Irat liver mitochondria, followed by comparison with the mode of actions of various other inhibitors of the oxidative phosphorylation (5). NK19. NKl9 can be prepared by letting 2, 4-dimethylthiazole heptyliodide react with ethylorthoformate in anhydrous acetic acid. We used NKI9, a product of Nihon Kanko Shikiso Research Laboratories. The molecular structure is as in the following and in its MeOH state it has maximum absorbancy at 590 m,a. For the use in experiment it was made into 1 mg/ml of MeOH and was stored in the dark until used.

1. For the purpose to obtain parabiotic rats having well maintained humoral circulation, the author observed parabionts having coerio-anastomosis and vascular anastomosis. 2. In the parabiotic rats having coerio-auastomosis when one of the parabionts was prevented from taking food and water by mouth sealing, the animals died within 5 to 6 days just as the control animals subjected to complete starvation, indicating that in coerio-anastomosis no appreciable humoral exchange was established between the two parabionts. 3. In vascular parabiosis having cross anastomosis of the aortas with polyethylene tubules, the animals died about 24 hours after the operation because of blocking thrombosis formed in the polyethylene tubules. 4. In the vascular parabiosis having cross anastomosis of the aortas by the homologous thoracic aorta animals did not survive through the operation but those having parallel anastomosis of the aortas survived after the operation for 3 weeks at largest and they seem to serve as useful tool for the parabiosis experiment.

In vitro and in vivo experiments were conducted for the purpose to determine whether or not the antitumor factor found in the regional lymph node cells of the mouse sensitized with Ehrlich tumor cells would transfer its antitumor activity to normal lymph node cells. In in vivo experiments normal lymph node cells incubated at 5°C for 60 minutes in the supernatant containing the antitumor activity have shown the antitumor activity against JTC-11 cells in mixed culture. Namely, it hs been demonstrated that the antitumor activity in the supernatant can be transferred directly to normal lymph node cells in vitro. In the in vitro experiments, the same results as in in vivo experiments were obtained. The antitumor activity against JTC-11 cells has been detected in the lymph node cells obtained on 4, 7 and 9 days after subcutaneous and intraperitoneal injections of the supernatant having antitumor activity. Next, we tried DNase and RNase treatments of the sensitized supernant to observe the transfer factor-like snbstance. The results indicate that, while the passive transfer is possible with the supernatant treated with DNase, it is not with the RNase-treated supernatant. From these findings it is assumed that the factor (in the sensitized supernatant) capable of conferring the antitumor activity is an RNA-dependent substance (or a substance closely associated with RNA) and is probably different from the antitumor factor reported in Parts 1 and 2.