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Biomedical subjects

M Muto

Publications and source records attributed to M Muto.

At least 145 records · Page 8Linked to original sources

Analysis of transforming genes in indirectly induced radiogenic thymomas in mice.

The expression of oncogenes was studied in 12 types of 178 mouse tumors induced by radiations and chemicals. DNA was analyzed in tumors in which the overexpression of oncogenes was noted. Amplification of the myc oncogene was found in chemically induced sarcomas, but not in sarcomas induced by radiation. Activation of oncogenes by small mutations and the inactivation of tumor suppressor genes has to be taken in account in the radiation induction of mouse tumors. We therefore made further analyses of radiogenic thymomas. Loss of heterozygocity was revealed in directly induced thymomas by the deletions of allele specific minisatellite bands. Analysis of a hypervariable minisatellite locus also revealed that these thymoma cells suffered high recombinogenic activity during tumorigenesis. In addition, transfection of cellular DNA to normal Golden hamster cells identified the activated K-ras oncogene in the directly induced radiogenic thymomas. Indirectly induced radiogenic thymomas were tested similarly. Transformed cells from secondary transfection experiment were positive for the mouse-specific repetitious sequences, but devoid of mouse ras oncogenes. Indirectly induced radiogenic thymomas originate from unirradiated normal thymus cells transplanted in irradiated hosts. The spontaneous activation of oncogenes yet to be identified may therefore be involved in the development of this tumor.

Animals↗

Phenotypic characterization of thymic prelymphoma cells of B10 mice treated with split-dose irradiation.

Using an intrathymic injection assay on B10 Thy-1 congenic mice, it was demonstrated that thymic prelymphoma cells first developed within the thymuses from 4 to 8 days after split-dose irradiation and were detected in more than 63% of the test donor thymuses when examined at 21 and 31 days after irradiation. Moreover, some mice (25%) at 2 mo after split-dose irradiation had already developed thymic lymphomas in their thymuses. To characterize these thymic prelymphoma cells, the thymocytes from B10 Thy-1.1 mice 1 mo after irradiation were stained with anti-CD4 and anti-CD8 mAb and were sorted into four subpopulations. These fractionated cells were injected into the recipient thymuses to examine which subpopulation contained thymic prelymphoma cells. The results indicated that thymic prelymphoma cells existed mainly in CD4- CD8- and CD4- CD8+ thymocyte subpopulations and also in CD4+ CD8+ subpopulation. T cell lymphomas derived from CD4- CD8- prelymphoma cells had mainly CD4- CD8- or CD4- CD8+ phenotypes. T cell lymphomas developed from CD4- CD8+ prelymphoma cells mainly expressed CD4- CD8+ or CD4+ CD8+ phenotype. T cell lymphomas originating from CD4+ CD8+ prelymphoma cells were mainly CD4+ CD8+ but some CD4- CD8+ or CD4+ CD8- cells were also present. These thymic prelymphoma cells were further characterized phenotypically in relation to their expression of the marker defined by the mAb against J11d marker and TL-2 (thymus-leukemia) Ag, which is not expressed on normal thymocytes of B10.Thy-1.2 or B10.Thy-1.1 strain, but appears on the thymocytes of lymphomagenic irradiated mice. The results indicated that the prelymphoma cells existed in J11d+, TL-2+ cells.

Animals↗

Structure of polysaccharide-peptidoglycan complex from the cell wall of Lactobacillus casei YIT9018.

The isolation and analysis of the polysaccharide-peptidoglycan complexes of Lactobacillus casei YIT9018 are presented. Two polysaccharide-peptidoglycan complexes, PS-PG1 and PS-PG2, were solubilized from the heat-killed cell by treatment with N-acetylmuramidase. PS-PG1 was composed of glucose, rhamnose, and small amount of galactose and glucosamine. PS-PG2 was composed of glucose, rhamnose, galactosamine, and glucosamine. The ratio by weight of these fractions was about 1:8. PS-PG2 was analyzed in detail. Smith degradation and deamination of this complex yielded oligosaccharide units. The results of methylation analysis of these units and intact PS-PG2 led to the most probable structure of PS-PG2: (formula; see text)

Carbohydrate Conformation↗

Experimental studies on the oxygen tension in the myocardium and changes of cardiac function in hypoxia.

Using adult mongrel dogs, experiments were performed to elucidate the relationship between the changes in the myocardial oxygen tension (PmO2) in anoxia and disturbances of cardiac function. Dogs, forced to inspire 100% N2, suffered from a respiratory arrest after 5 min, and developed acute anoxia. However, by 100% O2 inhalation 2 min after the onset of the respiratory arrest, the anoxia rapidly resolved. The arterial oxygen tension (PaO2), left intra ventricular oxygen tension (PLVO2) and PmO2 showed the most pronounced fall 2 min after the respiratory arrest induced by N2 inhalation. The arterial carbon deoxide tension (PaCO2) decreased until the respiratory arrest, after which it started to rise. When inhalation of 100% O2 was initiated at the anoxia, the PaO2, PLVO2 and PmO2 recovered within 1 min followed by a rise beyond the baseline value. Left ventricular end-diastolic pressure (LVEDP), left atrial mean pressure (LAm), left ventricular systolic pressure (LVSP), aortic mean pressure (Aom), maximum rate of force development by left ventricle (LVmax.dp/dt), total peripheral resistance (TPR), cardiac output (CO) and heart rate (HR) were measured. At the onset of anoxia, these parameters decreased sharply. When inhalation of 100% O2 was initiated within 2 min of the respiratory arrest, these disturbances of cardiac function recovered rapidly. The fall of PmO2 plays an important role in the impairment of cardiac function.

Administration, Inhalation↗

Experimental studies of the load reducing effects of nitroglycerin in heart failure.

The load-reducing effect of nitroglycerin (NTG), a vasodilator, was studied in dogs with heart failure. The chordae tendineae of the mitral valve were transected to induce acute mitral regurgitation (MR) for hemodynamic evaluation. By such surgical treatment, preload indices such as left ventricular end-diastolic pressure (LVEDP) and left atrial pressure (LAP) increased significantly, and subsequent cardiac dysfunction and heart failure were indicated by another decrease in stroke volume, myocardial contractility, forward flow, and myocardial oxygen consumption. To dogs with artificially established acute MR, 3 micrograms/kg/min of NTG was administered intra-arterially by means of a continuous infusion, that resulted in decrease of LVEDP, LAP and central venous pressure (CVP). Thus, a reduction of preload was determined. Simultaneously, afterload indices such as aortic systolic pressure (Aos), aortic mean pressure (Aom) and total peripheral resistance (TPR) decreased remarkably. Afterload reduction depended on the amount of venous return; therefore, an extra-corporeal circulation system was applied in order to supply a constant venous return before NTG administration. This caused a significant decrease in aortic diastolic pressure (Aod), Aos, Aom, left ventricular systolic pressure (LVSP) and TPR, and an increase in myocardial contractility and cardiac output. This suggested that afterload reduction might be realized by the vasodilatory effect of NTG on the resistance vessels.

Animals↗

Studies on the changes in myocardial oxygen tension.

An arterial oxygen tension (PO2) sensor was used to measure the myocardial PO2 at three sites in the left ventricle supplied by the paraconal interventricular branch of the left coronary artery, cranial descending coronary artery (CDCA): a subendocardial site, a subepicardial site and an intermediate point in the left ventricular wall. At first, the PO2 sensor had been compared with the values from a blood gas analyzer. The regression equation Y = 1.4X-4.9 with a correlation coefficient of 0.993 indicated a high correlation between these two measurements. The PO2 of the arterial blood in the left ventricular cavity was assigned an index value of 100%. The PO2 was about 70% in the subendocardial myocardium, about 15% in the mid-ventricular wall myocardium and 9% in the subepicardial myocardium, demonstrating a decreasing PO2 gradient from the endocardial to the epicardial surface. A transient occlusion of the CDCA confirmed the pathway of myocardial oxygen supply. In the mid-ventricular and subepicardial myocardium, marked hypoxia occurred after occlusion of the CDCA. Release of the occlusion resulted in a rapid return to the normal PO2 level. The oxygen supply to these sites is strongly influenced by coronary artery blood flow. The PO2 in the subendocardial myocardium was not dependent on the cranial descending coronary artery. Oxygen appears to be probably supplied through arterial blood in the left ventricle via the endocardium.

Animals↗

[Continuous subcutaneous infusion of peplomycin in oral squamous carcinoma].

To determine the effect of continuous subcutaneous infusion of peplomycin on both antitumor activity and pulmonary toxicity, thirty-two patients with previously untreated oral squamous carcinoma were given peplomycin via osmotic microinfusion pump (SP-5, Nipro Co., Ltd.) at a daily dose of 5.0 mg subcutaneously. The mean dosage of peplomycin given was 79.8 mg. An overall response rate of 62.5% was achieved, with 21.9% complete response, and 40.6% partial response. The maximum reduction of tumor volume for responder could be generally observed when peplomycin was given at about 60 mg continuously. The most frequently encountered toxicity was a mucocutaneous reaction, manifested by stomatitis (34.4%) and skin eruption (18.8%), but they were mild and tolerable. A local skin reaction also occurred at the site of drug injection, and an ulcer formation developed in 12.5% of patients. Monitoring of pulmonary function by means of PaO2 revealed that 32.0% of patients had a decrease over 10% after peplomycin administration. However, interstitial pneumonitis eventually occurred in only one patient (3.1%). In conclusion, the regimen of continuous infusion of peplomycin is a useful method to administer peplomycin safely without reducing the antitumor effect compared to conventional intermittent injection.

Adult↗

Structure of 6-deoxytalose-containing polysaccharide from the cell wall of Bifidobacterium adolescentis.

The isolation and analysis of the cell wall and the polysaccharide-glycopeptide complexes of Bifidobacterium adolescentis YIT4011 are presented. Polysaccharide-glycopeptide complexes, PS-GP1 and PS-GP2, were solubilized from the cell wall by treatment with N-acetylmuramidase. PS-GP1 and PS-GP2 were found to be composed of glucose, 6-deoxytalose and a small amount of glycopeptide. The products of Smith degradation of the PS-GPs had no glucose-containing fraction, but were composed of 1,2/1,3-linked 6-deoxytalose. Furthermore, a second Smith degradation of this fraction yielded trisaccharide-glyceraldehyde. These results and methylation analysis led to the conclusion that PS-GP1 or 2 has a repeating unit of----3)6dTal(beta 1----3)6dTal(beta 1----3)6dTal(beta 1----2)-6dTal(alpha 1----2)6dTal(alpha 1----2)6dTal(alpha 1-, and that glucose residues are linked to position C-3 of the 2-O-substituted 6-deoxytalose residues.

Bifidobacterium↗

Development of prelymphoma cells committed to thymic lymphomas during radiation-induced thymic lymphomagenesis in B10 mice.

Intrathymic (i.t.) as well as i.p. injection of thymus cells from B10.Thy-1.1 mice manifesting overt thymic lymphomas, 4 months after split-dose irradiation, into B10.Thy-1.2 recipient mice resulted in the development of donor-type T-cell lymphomas, indicating that they contained "autonomous" lymphoma cells. In contrast, injection of thymus cells from apparently nonleukemic mice 1 month after split-dose irradiation resulted in the development of donor-type tumors only when they were injected i.t., suggesting that thymus cells from these mice contained "preneoplastic" cells that will eventually develop into thymic lymphomas under the influence of thymic microenvironment. These "thymus-dependent" preneoplastic cells were termed "thymic prelymphoma cells." With the use of i.t. injection assay, it was shown that these thymic prelymphoma cells were detected in 26.1% (6 of 23) of the test donor thymuses when examined at 14 days and in more than 63% (15 of 24 and 14 of 22) when examined at 21 and 31 days after irradiation. To examine the possibility that thymic prelymphoma cells might appear first in the bone marrow before they become detectable within the thymuses of the split-dose-irradiated mice, bone marrow cells from B10.Thy-1.1 donors recovered at 8, 14, 21, and 33 days after split-dose irradiation were also injected i.t. into B10.Thy-1.2-recipient mice. The results indicated that none of these recipients developed donor-type T-cell lymphomas, suggesting that bone marrow is not the first site of the appearance of thymic prelymphoma cells.

Animals↗

HLA-linked nonresponsiveness to Cryptomeria japonica pollen antigen. I. Nonresponsiveness is mediated by antigen-specific suppressor T cell.

The objective of this study was to elucidate the cellular mechanism of IgE nonresponse to the Cryptomeria japonica (Japanese cedar) pollen antigen (CPAg), which was shown in our previous study to be HLA-linked (1). We established an assay system for the measurement of small amounts of anti-CPAg IgE antibody, both in an antigen-specific and isotype-specific manner, and a culture system to induce antigen-driven IgE antibody synthesis in vitro. By using these methods, we clarified that the function of the HLA-DR molecule in the CPAg-driven IgE response is similar to that of I-A or I-E molecule in mice, namely the product of immune response genes (Ir-genes), because anti-HLA-DR monoclonal antibody blocked the response, and the interaction between monocyte and monocyte-depleted peripheral blood lymphocytes (PBL) to respond to CPAg was restricted by HLA-DR. Furthermore, PBL from nonresponders revealed a specific IgE response to CPAg when the Leu-2+3- T cell fraction was depleted, thereby suggesting that even nonresponders have Leu-2-3+ T cell and B cell clones specific for CPAg, and they apparently show no response due to the presence of CPAg-specific Leu-2+3- suppressor T cells. This suppressor T cell fraction abolished the IgE response of the autologous B + monocyte + Leu-2-3+ T cell in a CPAg-specific manner. The current cellular analysis together with our previous genetic analysis strongly suggest that the HLA-linked IgE nonresponse to CPAg is mediated by CPAg-specific suppressor T cells. The HLA-linked gene controlling the nonresponsiveness to CPAg is thus designated as the immune suppression gene for CPAg (Is-CPAg). Mapping of Is-CPAg within HLA-DQ subregion is discussed.

Antibody Specificity↗

Antitumor effect of formalin-fixed Toxoplasma gondii organisms on EL4 lymphoma in Toxoplasma-infected mice.

The antitumor effect of formalin-fixed Toxoplasma organisms (f-Tp) as an immunostimulant on EL4 lymphoma was examined in Toxoplasma-infected syngeneic female C57B1/6 mice. A potent antitumor effect, a marked suppression of tumor growth, as well as a prolongation of lifespan, was induced by an injection with 10(7) f-Tp in a mixture of 2.5 X 10(5) EL4 cells. The antitumor effect of f-Tp could be observed regardless of the time, route, or dose of infection. The peritoneal exudate cells induced by f-Tp in Toxoplasma-infected mice showed an antitumor activity when the cells were implanted with tumor cells in normal mice, indicating that the cells activated by f-Tp caused the antitumor effect of f-Tp. The effect of f-Tp on EL4 in Toxoplasma-infected mice was significantly stronger than that of 10(7) live bacillus Calmette-Guerin organisms (BCG) in BCG-sensitized mice.

Adjuvants, Immunologic↗