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Three inoperable patients with primary hepatoma could be placed on gluconeogenic diets (minimum carbohydrate-high fat diets) for one to three months. A transient inhibition or a marked retardation of the tumor growth was observed with these patients and their entire clinical courses were fairly good. These results confirmed our previous observation with a metastatic liver tumor patient.

By subcutaneous inoculation of N, N'-dimethylnitrosourea to adult male C3Hf/Bi mice once a week for 10 consecutive weeks the authors studied the correlation between immunological functions and histological changes in lymphatic tissues at the latent period of thymic lymphoma whose development is known to occur in 100 per cent. As a result, it was found that PFC of the spleen to sheep erythrocytes decreased to about one third the normal level by two weeks, and to one tenth by 8 weeks after initial inoculation of this compound. Hemolysin and hemagglutinin titers of the serum became less than 1 : 2 after 6 weeks and later. As for histological changes in the thymus, disappearance of lymphocytes became marked by 2 weeks, and there appeared tumor cells by 8 weeks. Also the peripheral lymphocytes as well as the total spleen cells decreased in number along with increase of the frequency of inoculation of N,N'-dimethylnitrosourea. These results seem to suggest that the immunosuppressive effect of carcinogen facilitates the development and proliferation of tumor cells possessing tumor specific antigenicity in the course of N, N'-dimethylnitrosourea- carcinogenesis.

As the first step to analyze the autoimmune disease of red cells the recognition mechanism of macrophage to red cells or erythrophagocytosis has been studied in vitro by using mouse peritoneal macrophage and homologous and cells and the following results were obtained: 1. In Hanks solution, the mouse macrophage hardly phagocytizes living red cells, both homologous and heterologous ones. But in the presence of mouse serum, the macrophage phagocytizes heterologous red cells selectively but does not phagocytize homologous ones. 2. The macrophage actively phagocytized homologous red cells prior to treatment with concanavalin A (Con A) at a concentration as low as 1.95 ltg/ml. 3. Red cell agglutination was clearly recognized in those treated with Con A at 62.5 lag/ml or more, but not at 1.95 ltg/ml. 4. The red cell agglutination by Con A was inhibited with D-glucose, D.mannose and a-methyl glucopyranoside at the concentration as low 1.5 mM, while the phagocytosis was suppressed only at a very high concentration of the sugars, 1, 000 mM. 5. Fragility test of the red cells treated with Con A showed a lower resistance of red cells to hypotonic solution than those treated with Con A at the concentration of 31.25 p.g/ml or more 6. Electron microscope observation revealed no membrane damage of red cells by treating with Con A at a concentration of 1.95 ,ag/ml, where erythrophagocytosis was observed. The membrane damage occur. red by treating with Con A at 31.25 ltg/ml or higher. 7. All the data indicate that the phagocytosis of homologous red cells by macrophage is induced by the adherence of a small amount of Con A, which induces no detectable changes of red cell surface and red cell membrane as revealed by agglutination test, fragility test, electron microscope observation and circular dichroism. On the basis of these observations a possible recognition error to homologous red cells by adsorbing a minute quantity of foreign substances on their surfaces has been discussed.

A method of intracranial transplantation of the tumor induced by adenovirus type 12 in syrian hamster has been described. The incidence of intracranial tumor development was 86 (90.5 %) out of 95 animals and the average survival time and tumor size at death were 15.1 days and 4.1 mm in diameter respectively. The consistency of the days of death after intracranial transplantation of the tumor was remarkable. The transplanted tumors developed preferentially at the site of implantation and tumor cell seeding and tumor growing took place rarely along the ventricular system. Glial or lymphoid cell response to the tumor was not observed at any stage after transplantation in surrounding cerebral tissues of the animals. Histomorphologically, no elementary differences were observed between intracranially transplanted tumors and serially transplanted subcutaneous tumors. These facts permit the system to be applied to an experimental brain tumor model as large-scale testing.

Newborn mice of C3Hf/Bi (Zb) strain were divided into three groups and injected, intracranially with adenovirus type 12 alone, subcutaneously with 20 mgjkg of N, N'-dimethylnitrosourea following intracranial inoculation of adenovirus type 12, and subcutaneously with 20 mgjkg of N, N'-dimethylnitrosourea alone at 10 days of age, respectively. With adenovirus type 12 alone, intracranial tumors were induced in 12 out of the 25 effective animals. With N, N'-dimethylnitrosourea following adenovirus type 12, intracranial tumors were produced in 19 out of the 21 effective animals and these tumors were virus-induced ones. With N, N'-dimethylnitrosourea alone, no intracranial tumors were induced. In control mice, administered subcutaneously with 20 mgjkg of N, N'.dimethylnitrosourea within 24 hr after birth, necrosis of the external granular cells and hypoplasia of the granular layer of the cerebellum was observed.

As a step in the elucidation of human cancer immunity we studied antitumor activity of lymphoid cells by conducting a series of cultures using the primary culture of cells from spontaneous mammary cancers from C3H and RIll mice mixed with autochthonous lymphoid cells, and obtained the following results. 1) With 24 mammary tumors obtained from 24 mammary cancer. bearing mice, we prepared 22 suspensions containing sufficient numbers of free tumor cells, and attempted primary culture with them. As a result we were able to attain satisfactory primary culture cells in 18 trials. 2) With each group of the 18 primary culture tumor cells we conducted mixed cultures with autochthonous lymphoid cells (mainly spleen cells) in proportion of 1 : 40, for 48 hours, and counted viable tumor cells after the culture. As a result it was found that in 11 trials the lymphoid cells showed antitumor activity. In the remaining 7 groups of lymphoid cells there could be observed no antitumor activity, but some of them showed tendency to slightly accelerate the growth of tumor cells. 3) On looking at the correlation between the antitumor activity of lymphoid cells and the ratio of tumor weight/body weight, it was revealed that the antitumor activity is greatest when the tumor is around 10% the body weight, and as the tumor grows larger, such antitumor activity disappears. From these results, it may be concluded that even in spontaneous mammary cancer of mouse, autochthonous lymphoid cells exhibit anti. tumor activity on indigenous tumor, and this seems to indicate that cell. mediated immunity has been established.

Circular DNA isolated from human kidney mitochondria was studied by electron microscopy. I. Mean contour length of monomers of the mitochondrial DNA was 4.96 ± SE 0.28 /μ 2. The complex molecules (oligomers) of mitochondrial DNA were observed in frequency of 6.2 per cent. Among them circular dimers accounted for two per cent of all circular DNA molecules. 3. Circular DNA fibers with an intermediate perimeter between the　monomer and dimer, and with a contour length shorter than 3 μ were occasionally observed. 4. Some discussions were made on the emergence of the circular dimer.

Electron microscopic observation of replicating SV 40 DNA has revealed the existence of two types of RF, e form and (1 form. The frequency of RF at 54 hours after infection was 8.9% for the e form and 4.3% for the (1 form. Morphological evidence exhibits that in (1 form RF the tails are, predominantly, shorter than the viral genome and double length SV-40 genomes are also capable of replication in SV-40 infected VERO cells.

The effect of 6.MPR on the antibody formation of rabbits challenged with bovine serum albumin has been studied in comparison with that of 6.MP. Observation revealed that the antibody formation is profoundly suppressed when the animal is treated with 6.MPR in an appropriate dose and period in relation with the introduction of antigen. Discussion was made of the possibility of 6.MPR as a superior therapeutic agent for autoimmune diseases.

Under in vivo conditions JTC-II cells derived from Ehrlich ascites　tumor are led to destruction by lymph node cells by two processes. The　one is the interaction of lymph node cells of the C57BL (♀) mouse sensitized with Ehrlich ascites tumor cells, and the other is the interaction of　normal C57BL (♀) mouse lymph node cells treated with PHA-M. In　these two reaction systems the following differences have become clear. The regional lymph node cells from the C57BL (♀) mouse sensitized　with Ehrlich ascites tumor cells show a marked inhibitory effect on the　growth oflTC-II cells by 10 days after sensitization.　In the observations under the phase contrast microscope these lymph node cells tend to adhere around the antigenic cells by culture hour 5-6, and by culture hour 24-48 they lead the latter to undergo cytolysis. The normal lymph node cells of C57BL (♀) mouse treated with PHA show anti-growth effect oflTC-II cells. PHA-M used proves to be effective in the concentration of 2% (v/v). Likewise after such normal lymph node cells are previously treated with 2% PHA-M for 12 hours, they also inhibit the growth of lTC-II cells when two cell groups are cultured together. In such intercellular reaction between the two cell groups there is no specificity. By observations under the phase contract microscopy, by culture hour 2-3 the adherence and aggregation of lymph node cells begin to occur, and by 18-24 hours of culture the target cells are led to undergo cytolysis. In this instance, lymph node cells are prone to adhere and aggregate on one side of the target cell.

Effects of propranolol on ischemic segmental function were studied in anesthetized open-chest dogs. Two segment-length gauges were used for measuring the regional myocardial function: one was sutured on to the left ventricular surface perfused by the anterior descending coronary artery (ischemic zone) and the other was on to that perfused by the circumflex coronary artery (normal zone). A bolus of propranolol (0.5 mg/kg) was injected into the right femoral vein. Five min later, the left anterior descending coronary artery (LAD) was completely occluded for one mine and thereafter released. Then a second coronary occlusion for 20 min was performed; an interval of 20 min was allowed between two occlusions. Propranolol, in the ischemic segment, apparently decreased the extent of paradoxical lengthening in the late systole following one min LAD occlusion, and facilitated improvement of segmental function after release of the occlusion. Moreover, the extent of abnormal stretching induced by 20 min occlusion during early systole, was also reduced by propranolol pretreatment. In contrast, compensatory increase in shortening by the normal segment was disturbed by propranolol. These results suggest that propranolol might exert a favourable influence on the segmental myocardial function during either transient or maintained myocardial ischemia.

The biological specificity of the endotoxin receptor on platelet membranes was examined. The binding indices of platelets in experimental endotoxemia which was induced by intravenous administration of endotoxin (Lipopolysaccharide of E. coli, Difco) to rabbits were found to be 30% of the control at 60 min after the injection. The result suggests that the endotoxin receptor of platelets was already occupied. The binding indices of human platelets were measured after pretreatment with pharmacologically active substances which were assumed to effect platelet activity. The binding of LPS to platelets showed competitive inhibition at pharmacologically effective doses, but other substances merely inhibited platelet activity. One interpretation is that there is a common receptor on platelet cell membranes for lipopolysaccharide of E. coli and endotoxin. The sensitivity to endotoxin in vivo and binding indices of platelets were examined in rabbits and guinea pigs since their response to endotoxin is almost opposite with regard to sensitivity. The binding indices of platelets from rabbits and guinea pigs showed a positive correlation with the endotoxin sensitivity. Those findings indicate that platelets play a key role in vivo in the clinical course of endotoxemia.

The intestinal mucosal barrier of rabbits was damaged by carrageenan-induced ulceration of the colon, superior mesenteric artery occlusion (SMAO) and hemorrhagic shock and the values of Endotoxin (lipopolysaccharide, LPS) were determined by radioimmunoassay and the concentration of lysozyme (LZM) by the turbidimetric method. As a result, endotoxemia was observed in 13 out of 15 carrageenan rabbits, and in all of the SMAO and hemorrhagic shocked rabbits. Serum LZM concentration rose with time in all cases. As to the correlation of LPS and LZM, they changed almost in parallel in carrageenan rabbits, SMAO and hemorrhagic shock. LPS value and LZM concentration in blood were also determined in LPS injected rabbits. It was confirmed that injected LPS increased the LZM concentration of blood. On the basis of these results, it can be concluded that destruction of intestinal mucosal barrier permits an invasion of LPS into blood and then releases LZM into the blood stream.,/p>

This research was performed to establish a cell line from experimental bladder tumor and to discuss the biological characteristics of the cell line so established. Tissue cultures of epithelial cells were derived from a rat bladder cancer induced by BBN. The cells showed loss of contact inhibition and the phenomenon of piling up after several subcultures. Colonial cloning was used. The population doubling time of the wild strain and the colonial clones was about 30 h. The chromosomal mode ranged from triploid to tetraploid to tetraploid. Plating efficiency was well below 20%. Intraperitoneal backtransplantation into newborn Wister rats resulted in tumors in all cases. These tumors, in some parts, resembled primary transitional cell carcinoma. The major tumor cell groups, however, showed marked keratinization and the picture of squamous cell carcinoma. The nucleus/cytoplasm ratio and the numbers of nuclei, free ribosomes and intracytoplasmic microfibrils were increased. Dense microvillus arrangements characterized the electron microscopic picture. During the mitotic phase, the cells became large and globular whereas the microvilli were relatively short and were gathered profusely over the whole surface. Cells in the gap 1-synthetic phase developed lamellipodia and pseudpodia-like cytoplasmic processes and were polygonal in shape. Microvilli were present in the central part containing the nucleus, but their numbers were somewhat decreased and their height increased (scanning electron microscopy).

A new instrument for visual field examination with binocular fixation is described. The binocular vision was dissociated with polarizing plates. Only the point of fixation was visible to both eyes while the testing chart (Amsler chart) was visible to one eye in the use of this apparatus. The examination was done with both the patient's eyes open. With the use of this apparatus, not only was the visual line fixed steadily in order to detect various changes of the central visual field due to maculopathy or optic neuropathy and these changes were detected accurately and quickly, but also suppression scotoma associated with amblyopia or squint could be detected quantitatively.

With the parameters of a flow-volume and a volume-time curve, the discriminant analysis of bronchial asthma is described. The subjects were classified into three groups (healthy adults, mild asthmatic patients and moderates ones). The difference of the mean vectors of the parameters of the three groups was made clear by the selection methods of the discriminant analysis between any two of the groups both with 6 parameters (%FVC, FEV1.0%, peak flow rate (PF), flow rate at 50% of FVC (V50), flow rate at 25% of FVC (V25), and V50/V25) and with 8 (6 parameters mentioned above and V75, V10). Forced expiratory volume in 1 second percent (FEV1.0%) or V50 was selected at the first step with 6 parameters, and V75 was selected at the first step with 8 parameters. Probabilities of misclassification with 8 parameters were lower than those with 6 ones and the probability of misclassification at the discriminant analysis between healthy adults and mild asthmatic patients with 8 parameters was 15.75% at the final step.

Enzyme deviations in injured livers were studied by analyzing isozyme patterns of phosphorylase using a newly developed electrophoretic method, which separates six molecular species of this enzyme, i.e. M,FM,F,L,L', and FL'. In hepatic injuries caused by CCl4 and galactosamine intoxications of rats, F appeared in early stages and L' (and FL') in later stages of the injuries with a concurrent decrease or loss of L, which is a sole isozyme component of adult liver. In injured livers of patients with hepatitis and cirrhosis of the liver, increases in FL' activity were also found. Appearance of F was found only in hepatocellular carcinoma. The results obtained with phosphorylase isozyme analysis support the idea that an undifferentiated gene expression takes place in the injured livers of non-malignant hepatic disorders.

Micromethods for estimation of bilirubin uridine diphosphate-glucuronyl and -xylosyl transferases in liver are described. With these methods, a liver specimen as small as 10 mg is sufficient for assay of either enzyme activity and 15 mg is sufficient for assay of both enzymes. Normal values for livers with minimal elevation of SGOT and minimal histological change were 0.260-0.400 U/g protein for glucuronyl transferase and 0.142-0.302 U/g protein for xylosyl transferase.

The case of a patient with repeated attacks of collapse induced by sublingual isosorbide dinitrate is reported. The patient was an 81 year-old female who was admitted to Yura Hospital because of attacks of precordial pain. Several minutes after the sublingual administration of isosorbide dinitrate (10 mg) for an anginal attack, she developed a sensation of general weakness, and thereafter because unconscious. Arterial blood pressure fell and became unmeasurable. Electrocardiograms recorded during the syncopal attack showed sinus tachycardia and significant elevation of ST-segment in right precordial leads. In response to a drip infusion of noradrenaline, arterial blood pressure returned to normal with recovery of consciousness. Two similar syncopal attacks induced by sublingual isosorbide dinitrate occurred in the next three days. These attacks were not due to augmentation of the vagal reflex. Decrease of venous return probably was the primary etiological factor.

Ninety-nine gastric cancer patients initially received levamisole at a daily dose of 150 mg for three consecutive days before operation. This therapy was repeated fortnightly (3-day administration followed by 11-day withdrawal period) for more than one month as long as possible and the survival rate up to 18 months was compared with thas of control patients. The 18 month survival rate of advanced Stage IV patients was significantly higher in patients receiving levamisole than that of control patients. The effects of levamisole in cases of advanced cancer have been discussed in relation to the literature available.