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The effect of murine sarcoma virus of Moloney strain on central nervous system was examined morphologically in Swiss mice of different age. A single intracranial inoculation of cell-free virus solution resulted in the induction of characteristic intracerebral granulomas in 82.8% of the newborn to 5 day-old group, in 71.4% of the 6 to 10 day-old group, and in 68.0% of the 11 to 20 day-old group. The mean latency periods to tumor recognition were 16.5, 21.1, and 33.5 days, respectively. The granuloma consisted of inflammatory cell infilrations, reactive gliosis, and richly developed blood vessels. The lesions consistently contained numerous characteristic large round cells. In cases of long-survival, the findings included reparative changes, such as extensive gliosis, withdrawal of inflammation, and a decrease in the numbers of large round cells and blood vessels. These lesions were tentatively designated as "large round cell granuloma." The early foci of the granoloma were composed of proliferating glial cells and large round cells at the subependymal regions. Electron microscopically these large round cells had abundant intracytoplasmic fibrils quite similar to gliofibrils. Numerous C-type virus particles were present in the intercellular nad perivascular spaces, and occasionally budded from cell membranes of the large round cells and vascular endothelia. The large round cells were considered to be reactive astrocytes activated by biral infection. It was conclided that MSV-M was not a sarcomogenic but a granulomogenic virus in mice. Control animals showed no pathological changes.

Forty-five patients with acute leukemia were compared on cellular immunity measures versus prognosis. The patients were treated according a multicombination therapy protocol. The purified protein derivative (PPD) test and dinitrochlorobenzene (DNCB) test on admission indicated low positive percentages. In acute non-lymphocytic leukemia (ANLL) patients, the 50% survival durations were 11 months in the PPD positive group and 6 months in the PPD negative group. In acute lymphocytic leukemia (ALL) patients, the 50% survival durations were 21 months in the PPD positive group and 13 months in the PPD negative group. Peripheral lymphocyte blastogenesis by phytohemagglutinin (PHA) stimulation was examined at various clinical stages. The stimulation indices were generally low, and no correlation was found between the PHA test and clinical stages. These cellular immunity measures appeared to reflect one aspect of the clinical condition in acute leukemia patients, and further studies are needed for predicting prognosis.

The relationship between alveolar macrophages and spheroid alveolar epithelial cells was studied with the electron microscope after injection of squid-ink solution into the trachea of the mouse. At 20 hours after injection of squid-ink solution slight degeneration was evident in alveolar macrophages with sepia-melanin particles being phagocytized with partial digestion by lysosmes. Furthermore, hardly any changes were seen in mitochondria and inclusion bodies of the spheroid alveolar epithelial cells. In contrast, at one week after injection of squid-ink solution, almost all alveolar macrophages were degenerated with destruction of the ectoplasm in which the ingested sepia-melanin particles were digested by lysosomes into fine particles, and the mitochondria of spheroid alveolar epithelial cells were degenerated and the inclusion bodies were hardly formed. At three weeks after injection of squid-ink solution, alveolar macrophages as well as speroid alveolar epithelial cells showed almost complete recovery of functional structure. As the phagocyte in the alveolar space, neutrophile leucocytes were also observed in addition to the so-called alveolar macrophage.

Tissue localization of a subcomponent of the first component of complement (CLq) was examined in one postmortem case of HBs antigen (HBs Ag) positive hepatocellular carcinoma and in six cases of chronic hepatitis from liver biopsy specimens. The direct immunofluorescent method was used after fixation with 2% para-formaldehyde in concentrated ammonium sulfate. CLq localization was found in collagen fibers and the cytoplasm of fibroblasts in the connective tissues of specimens examined. The localization was particularly marked in the region of the fundal glands of the gastric wall. Apart from collagen fibers, other sites of localization included the surface membrane of lymphocytes, especially those cells of the mesenteric lymph nodes. In HBs Ag positive specimens, immune deposit-like substances appeared localized intra-hepatically and in the renal glomeruli. Since C3 and C4 were identified concomitantly, it indicates that these substances were indeed immune diposits. Despite the finding that C3 and C4 were identified together in the hepatic cell cytoplasm, C1q itself was not demonstrated in all hepatic cell cytoplasms.

Further purification and characterization are reported on rat cytosol cornin (RLCC), an antimitotic substance. Fraction I (purified RLCC) was purified more than 10-fold from crude RLCC with Sephadex G-50 column chromatography and showed a remarkable inhibitory effect on division of inseminated sea urchin eggs and mouse fibroblast cells. Fraction I was observed as one spot, and the molecular weight was estimated to be about 25,000 by thin layer gel filtration. Fraction I contained protein (92%) and RNA (8%), but the antimitotic activity was scarcely affected by treatment by pancreatic RNase. The protein of Fraction I was separated into two bands by SDS-polyacrylamide gel electrophoresis, and the molecular weight was estimated as 10,000 and 15,000, respectively. The 50% inhibition dose of Fraction I on the first division of inseminated sea urchin eggs and on proliferation of mouse L cells was about 2.5 X 10(-5) g/ml and 5 X 10(-4) g/ml, respectively. The yield of fraction I was about 35 mg from 100 g rat liver.

The present study was conducted to investigate the usefulness of the direct leucocyte migration agarose method for studying cell-mediated immunity in vitro. Comparative studies of the purified protein derivative (PPD) skin test and the leucocyte migration inhibition test (LMIT) in which PPD was used as test antigen indicated a significant qualitative and a weak quantitative correlation between these two tests. Furthermore a positive correlation was found between the LMIT and the macrophage migration inhibition test (MIT) using ultrasonicated authochthonous tumor antigen. Comparative studies of the LMIT, MIT, PPD skin and DNCB tests on the same patients showed that cases responding positively to the the PPD skin and DNCB tests tended to respond positively to the LMIT and MIT. Patients with digestive organ cancers were examined by the LMIT. With the advance of cancer, decreased positive test test rates were found. After gastric cancer operations the LMIT findings were divided into two groups: one type changed from positive to negative, and the other type changed from negative to positive. The former response was suggestive of a successful operation, and the latter response was suggestive of a non-curative operation. These results indicated that the direct leucocyte migration inhibition agarose test was useful investigating cell-mediated immunity.

Twenty cases of suspected drug induced liver injury (16 cases of which satisfied the criteria for at least a query positive diagnosis as based on the Fourth Congress of "Drugs and the Liver" in Japan) were studied by the whole blood culture technique of lumphocyte blast transformation. The positive rate with this technique was 10%, and no more than 15% even with the addition of one query positive. One reason for the low positive rate was that there was not only an allergic mechanism at work in the study group but that liver injury due to direct cytotoxicity of the drug was involved also. For a drug such as chlorpromazine with strong cytotoxicity for lymphocytes, it was difficult to demonstrate a relationship between allergic mechanisms and the drug with this method.

1. Three cases of acute rejection were detected by macrophage migration inhibition tests (MIT) conducted directly on seven patients who had received renal allografts. The macrophage migration inhibitory factor (MIF) activity was positive in all cases 1-2 days before the appearance of acute rejection. 2. After the administration of a high dose of Solu-Medrol (1g/day for 3 days) to suppress the acute rejection, MIF activity recovered to its normal level 3 days later. These findings seem to indicate that MIT yields immunologically useful criteria for the early detection of an acute rejection.

Mice were trained in an avoidance learning task. The incorporation of 3H-leucine into the hippocampal regions of trained mice was higher than that of control mice. When mice were injected with cycloheximide, a strong inhibitor of protein synthesis, impairment was evident in acquisition of learning. Cycloheximide produced morphological changes in mitochondria and microtubules of some brain axons. It is suggested that the cycloheximide-induced learning impairment may be due to the blocking of the synthesis of the specific protein necessary of neutral conductivity.

Cell-mediated immunity was studied in 23 cases of advanced gastrointestinal cancer. The patients received levamisole at 150 mg/day for three consecutive days each week for four weeks. In cases at the terminal stage of gastrointestinal cancer, the blastformation rate of peripheral blood lymphocytes against phytohemagglutinin (PHA) after the administration of levamisole showed a slight increase, but cases with blastformation rates over 40% increased markedly three or four weeks after the initial administration of levamisole. The peripheral blood lymphocyte count showed little change in these cases.

The microfilaria of Brugia pahangi obtained from an experimentally infected dog were observed with the electron microscope. The sheath was composed of small granules and was covered with electron-dense particles on the outer surface and with small granules on the inner surface. The cuticle was composed of an outermost layer, a trilaminate membrane and an inner layer. The hypodermis was composed of four components as in the adult stage (two small ones on the lateral sides, two large ones on the dorsal and ventral sides). The muscle cells comprised a single layer under the hypodermis on the dorsal and ventral sides. On each side, two muscle cells usually appeared in a transverse section. The thick myofilament was surrounded with 8 to 12 thin myofilaments. Dense bodies were present around the cephalic space. In the cells of the nuclei column, the cytoplasm was very narrow, and the electron-dense nucleus close to each other. The cuticular central canal was connected to the buccal cavity and to the inner body. A sponge-like structure was seen at the junctional part of the canal and the inner body. The inner body showed a homogeneous granular appearance. Eight cephalic papillae were observed at the head tip. Two amphids, each having more than eight cilium-like structures, were connected with the nerve elements and open in the head part. Two phasmids, each having one ciliumlike structure, opened in the caudal part. Two types of neurosecretory granules were observed in the nerve ring and the dorsal and ventral longitudinal nerves were clear except in the anterior and the posterior part of the worm. The excretory and the anal vesicles had contacts with thin and thick cytoplasmic processes respectively, and these vesicles opened to the exterior. The nuclei of the G cell and R cells showed similar electron-density. Lamellate structures were present in the muscle and the hypodermis.

In vitro and in vivo testosterone metabolism was studied using rat skin. The in vitro stoichiometric studies strongly suggested the existence in the skin of 5a-reductase and other enzymes involved in testosterone metabolism. The predominant metabolites were 5adihydrotestosterone, androstandiol and 6.4-androstenedione. The rate of testosterone metabolism in vitro was higher in preputial skin than in dorsal skin. The main metabolites were androstandiol and 6 4-androstenedione in vivo whereas dihydrotestosterone and androstandiol were predominant in vitro. .6.4-Pathway is considered to be more active in vivo in adults than in newborns. The difference in the in vivo uptake increase of testosterone-3H after castration suggests the possible existence in the organs and skin areas of androgen pools of different sizes. The in vivo uptake and metabolism of testosterone were examined in the nuclei of newborn rats. Dihydrotestosterone and androstandiol detected in the nuclei of preputial skin, dorsal skin and liver were 42.8%, 24.3% and 27.8%, of total radioactivity incorporated into the respective organs. The liver incorporated only a small amount of radioactivity compared with the skin.

The intracellular localization of the avian myeloblastosis virus (AMV) genome was studied. Nuclear and mitochondrial DNAs from myeloblasts were examined by hybridization with 32P labeled AMV-RNA of high molecular weight for the presence of virus specific DNA sequences. Nuclear DNA (nDNA) from myeloblasts specifically hybridized with viral RNA, whereas purified closed circular mitochondrial DNA (mtDNA) did not hybridize with viral RNA. It was therefore concluded that viral genome was present in nuclear DNA and not in mitochondrial DNA. Likewise, in normal chick cells, nDNA but not mtDNA hybridized with viral RNA.

Deoxyuridine suppression tests have been performed by two different methods of six normoblastic and eight megaloblastic marrows. A good correlation was obtained between the results by the modified and the original methods. The simplified method was found to be applicable for a clinical purpose to diagnose megaloblastosis in the marrow. Uptake of 3H-deoxyuridine into DNA and effect of various concentrations of thymidine was studied on five normoblastic and six megaloblastic marrows. In megaloblastic marrows, a greater amount of thymidine was required to obtain the same rate of suppression of 3H-deoxyuridine incorporation into DNA than in normoblastic marrows. Impairment of thymidine incorporation into DNA in megaloblastic marrows was not revealed. Therefore, lower rate of suppression of 3H-deoxyuridine by thymidine in megaloblastic marrows may be due to impairment of the incorporation of deoxyuridine before the addition of thymidine.

Mitochondrial RNA (mtRNA) was synthesized from purine and pyrimidine nucleosides in coupling with oxidative phosphorylation using isolated mitochondria. The in vivo synthesized mtRNA was adenine-uracil rich and sedimented at about 20 S by sucrose density gradient centrifugation. A major part of the newly synthesized mtRNA was shown to be poly (A)-containing RNA by the resistance to the digestion with pancreatic RNase and RNase T1 and the affinity to poly (U)-Sepharose columns or Millipore filters.

Factors influencing the prognosis in gastric cancer treated by curative resection include lymph node metastasis and the extent of invasion of the gastric wall. Lymph node metastasis can be removed surgically, but the extent of invasion is not amenable to external measures. Of these two factors, the extent of wall invasion has the greatest influence on prognosis in cases undergoing curative resection. With lymph node removal of equal extent the prognosis worsens in proportion to the depth of invasion. Further, lymph node metastasis increases with increasing depth of invasion. Metastasis was seen in Group 2 and 3 nodes in more than 60% of cancer with invasion beyond the Tunica muscularis propria (pm), indicating that wide lymph node removal is essential in cancers with deep invasion of the wall. The effects of extended radical operation on the host as illustrated by the indices of total serum protein and albumin levels were no different from those of less extensive resections. It was confirmed that extensive radical resection did not delay postoperative recovery.

Twenty-five cases of paraplegia due to fracture-dislocations of the thoracic and lumbar vertebrae were treated using the halo-pelvic apparatus. Thirteen of them only needed the apparatus, two underwent laminectomy, and ten had posterior spinal fusion in addition. The advantages of this method are that gentle reduction can be achieved without severe complications, and that posterior spinal fusion can be performed with this apparatus on, thus enabling an early start to the subsequent exercise program and minimal absence from work.

Isolated hepatic cells from adult rats were prepared by perfusing the livers with trypsin. The highest yield of viable cells was obtained by perfusing the liver with 0.1% trypsin, pH 7.0, at 37 degrees C for 30 min. Following this treatment about 70% of cells excluded trypan blue. The isolated cells contained many binucleate cells. Between 60 and 70% of DNA present originally in the liver was recovered from the isolated hepatic cells, which had higher glucose 6-phosphatase activity than the liver. Thus the resulting cell population seems to be rich in hepatocytes. The isolated hepatic cells, however, lost some of their cellular proteins such as alanine and tyrosine amino-transferases. It was suggested that the membranes of isolated hepatic cells might be damaged by both enzymatic digestion and mechanical destruction.

A case of uterine adenomatoid tumor in a 47-year-old female was studied with both light and electron microscopes. The tumor was circumscribed, 2.5 cm in diameter, and located in the posterior wall of the uterus. In light microscopy, tumor cells showing "signet-ring" appearance arranged in cords or tubules. Hyaluronidase-sensitive acid mucopolysaccharide was present in the cells and luminal surfaces. Mucicarmine stain was negative and periodic acid-Schiff reaction was faintly positive. In electron microscopy, the tumor showed basal laminae, well-developed desmosomes and numerous microvilli. Intercellular spaces were present between adjacent cells. Small intercellular spaces were separated from the large lumens by desmosomes and tight junctions, while large spaces communicated with the tubular lumens. Forty-four reported cases of adenomatoid tumor in females were briefly reviewed.