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The effect of a lymphotoxin-like substance, OH-1, released by human acute lymphatic leukemia BALL-1 cells, on metastatic tumor proliferation was investigated in BDF1 mice with transplanted Lewis lung carcinoma cells. Mitomycin-C, cyclophosphamide and adriamycin were used as control agents. The effect of OH-1 on metastases, as determined by comparison of the numbers of pulmonary nodules and by 3H-thymidine labeling indices, was significant. Also, investigation of the effect of OH-1 on host immunity showed that, while the control preparations had considerable side effects, immunodepression and emaciation were not noted with OH-1. As to direct cytotoxicity, OH-1 is principally cytostatic in activity and effects cell progression delay in both the G1 and G2 phases.

The distribution of ferritin has been studied in many tissues, but has not yet been established on the cellular level. We investigated the cellular distribution of ferritin in the liver, spleen and bone marrow using the immunoperoxidase method, and compared it with that of hemosiderin. We also examined changes in the distribution of these proteins after phlebotomy and iron overload. In normal rats, ferritin was seen in centrilobular hepatocytes, Kupffer cells, macrophages in the red and white pulp of the spleen and central macrophages in bone marrow. Hemosiderin was observed almost exclusively in the red pulp and partly in tangible body macrophages of the white pulp. After phlebotomy, neither ferritin nor hemosiderin were detectable in these cells except for ferritin-positive cells in the white pulp, which showed little change after either phlebotomy or iron overload. In iron overloaded rats, both ferritin and hemosiderin increased in hepatocytes and reticulo-endothelial (RE) cells. Ferritin-positive cells in the liver were mainly located in the periportal area. These results indicated that hepatocytes and RE cells except for those in the white pulp may play an important role in iron storage, and that ferritin-positive cells in the white pulp may have a function other than iron reserve. They also suggested that the zonal distribution of ferritin-positive hepatocytes may be due to microcirculation in the hepatic lobules.

Co-cultivation of human thymus and spleen lymphocytes, which were obtained from 26-week and 27-week fetuses, with a lethally-irradiated human cord T-cell line harboring human T-cell leukemia virus type Ι(HTLV-Ι) resultes in the establishment of T-cell lines positive for adult T-cell leukemia-associated antigens and producing HTLV-Ι. These cell lines had the phenotype of a helper/inducer subset of peripheral T-cells as evidenced by the reactivity with monoclonal antibodies to human T-cells.

The extent of homology between two protein fractions was compared by simple electrophoretic analysis. Nuclear proteins of several rodent cells of different origins were fractionated into acid-soluble and acid-insoluble fractions. The two protein fractions were subjected to polyacrylamide gel electrophoresis in separate gel systems, and protein bands with identical mobilities were sought either in all possible combinational pairs of cell types or in all cell types. The paired and overall homology indices calculated from these data and chi-square testing of the results indicated that acid-soluble nuclear nonhistone proteins are more homologous than acid-insoluble nuclear proteins. Several factors which might have affected the results were discussed.

The anti-tumor effect of immunization with heat-killed Mycobacterium tuberculosis (Tbc) and Tuberculin (PPD)-coupled syngeneic tumor cells was examined in vivo. Three tumor cell lines were employed. Immunization of Tbc-primed BALB/c mice with PPD-coupled syngeneic Meth-A tumor cells displayed a potent anti-tumor effect on viable Meth-A cells inoculated subcutaneously. Neither PPD-coupled LLC (Lewis Lung Carcinoma) cells nor sonicated PPD-coupled Meth-A cells were capable of immunizing these mice. PPD-coupled syngeneic whole tumor cells were indispensable for induction of this tumor-specific resistance. Immunization of Tbc-primed C3H/He mice with PPD-coupled syngeneic MH134 tumor cells did not elicit anti-tumor activity against MH134, but additional pretreatment of mice with cyclophosphamide brought on an anti-tumor effect. Antimetastatic reactivity was investigated in C57BL/6 mice bearing LLC, with a reduction in metastases noted. This antimetastatic effect was observed even when the mice were immunized with PPD-coupled LLC cells three days after removal of the initial tumor. Immunization with Tbc and PPD-coupled Meth-A cells together with intraperitoneal administration of murine or rat interleukin 2 (IL 2) further augmented anti-Meth-A resistance. Murine IL 2 further inhibited tumor growth during the early stage, while rat IL 2 showed an anti-tumor effect throughout the course of tumor growth.

Glial fibrillary acidic protein (GFAP) was purified from human spinal cord and cerebral white matter. GFAP was localized by an immuno-peroxidase method in normal adult and fetal human brains, rat brains, and 152 central nervous system (CNS) tumors. GFAP was found in reactive and normal astrocytes, immature cells of fetal brain at the 18th to 21st gestational weeks, and normal rat astrocytes. This GFAP staining was quite specific for glial tumors, including astrocytomas, glioblastomas, astroblastomas, and ependymomas. GFAP-positive cells were also found in oligodendrogliomas and choroid plexus papillomas, and they were interpreted as being astroglial or ependymal differentiations. Stromal cells in cerebellar hemangioblastomas were negative. However, engulfed astrocytes were found at the periphery of such tumors and often adjacent to the proliferate blood vessels. In meningiomas, neurinomas, metastatic carcinomas, pituitary adenomas and other non-glial tumors, GFAP-positive cells were not identified.

Basophil histamine release induced by allergens (house dust and Candida albicans) and anti-IgE was examined in 31 patients with bronchial asthma in relation to patient age, age at onset of the disease and serum IgE levels. Basophils from patients under 40 years of age generally released a significantly large amount of histamine by stimulation with house dust and anti-IgE. On the other hand, histamine release from patients over 41 years of age was generally not marked when the cells were incubated with house dust and anti-IgE, although, in some cases, the release induced by C. albicans was fairly marked. Basophils from patients under 30 years of age at onset were reactive to house dust and anti-IgE, while the cells from patients over 41 years of age at onset tended to be reactive only to C. albicans. Basophils from patients with low serum IgE levels were less reactive than the cells from patients with high levels of IgE to house dust and anti-IgE. C. albicans-induced release of histamine did not correlate with serum IgE levels.

Red blood cell and plasma polyamines in umbilical and maternal blood at delivery were measured using high performance liquid chromatography. The concentration of each polyamine in red blood cells and plasma of umbilical blood was significantly higher than in maternal blood. Spermidine and spermine concentrations in fetal red blood cells decreased markedly with the progress of pregnancy. In addition, younger red blood cells contained more polyamines than older cells. Red blood cell polyamines are closely associated with the cell membrane. Plasma polyamine in umbilical blood reflect active fetal metabolism, whereas red blood cell polyamines mainly reflect alterations in erythropoiesis in bone marrow and may indicate the proliferation of the bone marrow.

Cells from methylcholanthrene-induced tumor (MC-tumor), Ehrlich ascites cancer or mouse ascites hepatoma (MH-134) were subcutaneously implanted in dorsal area of mice to examine the specific cell mediated immunity following implantation. The migration index (MI) of lymphocytes was determined at various time periods after cell transplantation. The MI-activity increased under all three implantations, reached maximum at a certain period, decreased gradually and disappeared. The maximum MI-activity coincided with the proliferation period of the implanted tumor cells. This peak occurred on the tenth postimplantation day with MC-tumors, on the fifth day with Ehrlich ascites cancer and on the sixth day with MH-134 cancer. In lymphoid tissues of animals with MC-tumor and Ehrlich ascites cancer, strong MI-activity appeared early in the regional axillary lymph nodes, while weak activity was observed consistently in the distant mesenterial lymph nodes. The MI-activity of the splenic lymphoid cells resembled the axillary lymph nodes cell activity. The MI-activity of venous blood lymphoid cells was parallel to the average value of lymphoid cells of the spleen and axillary and mesenterial lymph nodes.

Hepatitis B core antigen (HBc Ag) and hepatitis B surface antigen (HBs Ag) were detected in the liver tissue of a patient with chronic aggressive hepatitis by the immunofluorescent complement technique. The presence of anti-HBc was examined by the same method in 67 human sera previously tested for HBs Ag, anti-HBs and s-GPT levels. HBc Ag was localized mainly in the nucleus and sometimes in the cytoplasm of the hepatic cells. HBs Ag was found only in the cytoplasm. The focal area of HBc Ag positive hepatic cells seemed to correspond to the HBs Ag positive cells. Double staining demonstrated the simultaneous presence of HBs Ag and HBc Ag in individual cells. Anti-HBc positive serum was found in 46 (68.7%) cases. Forty-eight (71.6%) indicated a combination of HBs Ag and anti-HBc.

Human adenovirus type 12 (Ad 12) was inoculated through subtentorial route into inbred newborn mice (C3H/BifB/Ki), and sequential changes of the brain and tumor induction were examined by histological and immunofluorescent methods. Two days after virus inoculation, Ad 12 specific tumor antigen (fluorescent T-antigen) appeared in the cells of ependymal and subventricular matrix layers, choroid plexuses and leptomeninges in the subtentorial as well as the supratentorial brains. After 10 days, these fluorescent positive cells decreased gradually in number but still remained focally beneath the ependyma. Sixty days later, early tumor nodules were detected in the same regions in which remained the fluorescent cells. After 107 days, neurological signs and well-developed tumors were noted in 25 of 63 (30.1%) mice examined. In the cerebellum, both of T-antigens and tumors were limited around the IVth ventricle, but not in the granular layers. Histomorphologically, the tumors were of primitive neuroectodermal origin and consisted of the cells resembling immature matrix cells in the subventricular zone. These findings strongly suggest that the virus has a selective affinity to the remaining matrix cells, but not to cerebellar granular cells, at least, in newborn mice.

Heterokaryon formation and Rous sarcoma virus (RSV)-induction were studied by fusion of RSV-transformed human embryonic cells with chick embryo fibroblasts in the presence of lysolecithin. Heterokaryon formation was observed by autoradiography. RSV-induction was identified by focus formation, electron microscopy and density gradient centrifugation of 3H-uridine-labeled particles. The most effective concentration of lysolecithin for virus induction was 10 mug/10(6) cells/0.1 ml. Efficiency of lysolecithin in virus induction was not less than that of ultraviolet-inactivated Sendai virus (UV-HVJ).

A cell line (HGC-27) was established by culture of the metastatic lymph node from a gastric cancer patient diagnosed histologically as undifferentiated carcinoma. HGC-27 cells were polygonal or short spindle-shaped and adhered to glass surfaces as a monolayer. The cells were probably derived from gastric cancer cells, as their origin from mesenchymal tissues can be excluded morphologically and enzyme-histochemically. Enzyme activities were generally negative or low, except for adenosine triphosphatase, lactic dehydrogenase and leucine aminopeptidase. These scanty findings might reflect the undifferentiated character of the original tumor cells. The cloning efficiency was 5.3% in liquid medium and 1.0% in soft agar. The doubling time was about 17 hr. Chromosomal analysis revealed a mode of 109 and 110 chromosomes.

The surface structure of myeloma cells was examined by scanning electron microscopy. The cells were collected from the pleural effusion of a multiple myeloma patient and purified by Conray-Ficoll gradient sedimentation. The cell size ranged from 8 mu to 12 mu in diameter and the microvilli were from 0.8 mu to 1.2 mu in length. The surfaces of the majority of the observed myeloma cells were more villous than lymphocytes.

The macrophage migration inhibition activity [MI activity) was stable in sensitized lymphocyte-to-marcophage ratios of 1:5 to 1:20 in mice. Antigen protein concentrations under 100 mug/ml did not induce nonspecific macrophage migration inhibition. Inhibition of tumor proliferation and survival was observed after a combined injection of BCG and MH-134 cells. After a single injection of MH-134 tumor cells, MI activity was reinforced and prolonged, demonstrating the clear effects of BCG as adjuvant. In DDS mice MI activity was weakened in the regional lymph node after a subcutaneous injection of just above or below 10(5) Ehrlich cancer cells previously treated with mitomycin C. This finding suggests the presence of an optimal tumor antigen concentration.

"Smoldering acute leukemia", a variant of acute myelogenous leukemia, has been recognized with frequent incidence in recent years. This is chracterized by benign clinical course, poor physical findings, leukopenia and mild anemia in the peripheral blood, and apparent infiltration of abnormal myeloblasts in the bone marrow. Immunological studies of the host defence mechanism were made, because the pathogenesis of its "smoldering" course has never been well understood. Nine cases, seen during last 2 years, were investigated for immunological profile, especially the cellular immunity. Purified protein derivative (PPD) skin test, i.e., tuberculin test, was found to be positive in 8 of 9 cases (88.9%). Dinitrochlorobenzene (DNCB) sensitization test showed to be positive in 4 of 6 cases examined (66.9%). Peripheral lymphocyte balstogenesis by stimulating with phytohemagglutinin (PHA) was evaluated using the smear counting method. The blastoid lymphocyte ratio was 55% at the median value (range: 31-68%), compared with 63% in normal young control (age: 25-32) and 41% in normal aged control (age: 60-75). In this report, the cellular immunity in smoldering acute leukemia was proved to be preserved at the normal level and to be more competent than that in aged group. The preserved cellular immunity is considered to explain the phenomenon of "smoldering", in other words, the exacerbating proliferation of leukemic cells is suppressed by immuno-surveillance system.

For the purpose to reveal whether or not the liver and the cell organellae are responsible for the abnormal metabolism of polysaccharides found in cancer bearing individuals, the author analyzed the liver and ascites with tumor cells of AH 130 hepatoma bearing rats biochemically with some histochemical observations. A quantitative increase in polysaccharides accompanied by the production of unusual polysaccharides is found in the supernatant of liver from cancer bearing rats, but not from mitochondrial or microsomal fractions. Tumor cells themselves and ascites fluid do not contain the abnormal polysaccharides found in the liver supernatant.

The author studied the distribution of polysaccharides and the amino-acid composition of cytoplasmic organellae, the problems that have come to call a great interest in the field of studies on cancer bearing animals. And also biochemical and electron microscopic observations were carried out to study the influences of cytoplasmic organellae in the cancer cells (AH 130), the livers of cancer bearing animals, and normal liver on the catalase activity of the liver. The results obtained are as follows : Cytoplasmic organellae of various cells do not affect so markedly the hexose metabolism of the liver. As for the amino-acid pattern of cytoplasmic organellae of various cells studied by paperchromatography, it is interesting to note that the pattern of the liver of cancer bearing animals, shows lack in histidine, while in can~er tissue and in the liver of cancer bearing animals an increase in phenylalanine can be observed. The decrease in the liver catalase activity is caused by the primary factor of cancer cells, especially their microsomes, and also by the secondary factor of the liver mitochondria in cancer bearing animals. On the other hand, the mitochondria of cancer cells, instead of reducing the catalase activity in the liver, markedly increases the catalase activity. By the morphological changes observed with light microscope and electron microscope, liver cells revealed marked morphological differences, proving that the microsomes of hepatoma cell induce considerably marked changes in the liver, while the mitochondria of hepatoma cell, on the contrary, induce the hypertrophy of liver cells. Sirriilarly in the electron microscopic observations the mitochondria of mouse liver injected with cancer mitochondria are enlarged, but no destruction of cellular structures such as cristae can be recognized. Also microbodies and the growing process of mitochondria can be observed, but no marked changes in endoplasmic reticulum.

1. Clinical and histological evaluation of so-called chorioepithelioma malignum and hydatidiform mole has been made on the cases treated at the Department of Obstetrics and Gynecology, Okayama University Hospital during the 20year period friom 1939 to 1958. 2. CC has been confirmed to be a poor risk in the treatment than CA and SE. 3. The two-year cure rate and the five-year cure rate yield an approximate value in each of CC, CA and SE, so that the two-year survival would be an ideal index for determination of the prognosis. 4. It may be pointed out that CC would indicate a tendency of a higher gonadotropin content suggestive of the poor prognosis, provided the disease contain a greater number of La-cells comparing to Sy-cells. 5. Metastasis of CA is not so infrequent as has been formerly believed, and there were two cases, which proved to be a typical SE and had metastasis to the vaginal wall. 6. Concerning the last labor preceding the chorioepithelioma, it has been clarified that the disease occurs more frequently following spontaneous abortion rather than after artificial abortion. 7. It is noted that the mole showing a marked proliferation of the trophoblasts entailed CC. However, in order to evaluate a correlation of the histological findings of the mole with chance occurrence of the subsquent CC, further study on the cases is required.