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P Noguchi

Publications and source records attributed to P Noguchi.

25 records · Page 2Linked to original sources

Interleukin 2 production induced by chemically defined cell membrane modification.

We present evidence that murine spleen cells produce a T-cell growth-stimulating factor following oxidation by periodic acid (H5IO6). The identification of this factor as interleukin 2 (IL-2) is indicated by its ability to support the growth of the IL-2-dependent CT6 cell line. In addition, preliminary analysis shows that H5IO6-stimulated growth factor has biochemical properties similar to IL-2. The time course of H5IO6-induced IL-2-like production by spleen cells was determined. No growth-stimulating activity was detected after 1 h of culture. The peak of periodic acid-induced IL-2-like production was between 18 and 24 h, while the maximum 3H-thymidine incorporation in spleen cells occurred at 72 h. Flow cytometry of CT6 cells was used for cell cycle analysis and to demonstrate their stimulation by IL-2-containing supernatants. These results were in agreement with the 3H-thymidine incorporation data. Electron microscopy of CT6 cells stimulated by supernatants from concanavalin A- or H5IO6-treated spleen cells showed no differences in their morphology. Degradation of spleen cell sialic acid prior to periodic acid oxidation inhibited IL-2-like production by 84% and inhibited 3H-thymidine uptake by 80%.

Animals↗

Enhanced expression of surface tumor-associated antigens on human breast and colon tumor cells after recombinant human leukocyte alpha-interferon treatment.

Treatment of human breast or colon carcinoma cells with recombinantly derived human leukocyte (clone A) interferon (IFN-alpha A) increases the surface expression of specific tumor-associated antigens (TAAs) recognized by monoclonal antibodies (MAbs). The MAbs used, B1.1, B6.2, and B72.3, recognize three distinct TAAs, i.e., the Mr 180,000 carcinoembryonic antigen, a Mr 90,000, and a Mr 220,000 to 400,000 glycoprotein, respectively. The binding of the MAbs to the surface of tumor cells increased in a dose-dependent manner, with optimal levels of TAA enhancement at 100 to 1,000 units IFN-alpha A/ml. Higher concentrations of IFN-alpha A that were cytostatic or cytotoxic were also less effective in enhancing TAA expression. Human melanoma (A375) cells and normal fibroblasts (WI-38 and Flow 4000) do not express any of the three TAAs, either before or after interferon treatment. The ability of IFN-alpha A to increase the expression of TAAs on human carcinoma cells was also temporally dependent, with optimal enhancement occurring after 16 to 24 hr. The enhancement of specific TAAs at the surface of the carcinoma cells by IFN-alpha A was confirmed, using fluorescence-activated cell sorter analysis. These data demonstrate that the IFN-alpha A-mediated increase of surface antigen is a result of both an accumulation of more antigen per cell, and an increase in the percentage of cells expressing the antigen. The ability of recombinant interferon to enhance specific TAAs on human carcinoma cells may be exploited in designing protocols for the in situ detection and therapy of human carcinoma lesions by MAbs, as well as in further defining the role of specific TAAs in the expression of the transformed phenotype.

Antibodies, Monoclonal↗

Initiation of carcinogenesis dependence upon MNNG-induced release of the G1 block of density-inhibited Syrian hamster cells.

After N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment of density-inhibited postconfluent (DDIR) Syrian hamster embryo cell cultures, only a small population of the cells incorporate [3H]-thymidine within the next 10-20 h. The transformed colonies, observed subsequent to reseeding, are derived from the population incorporating [3H]-thymidine. This study demonstrates that MNNG-induced thymidine incorporation resulted from semiconservative DNA synthesis as analyzed by DNA density gradients. Furthermore, cell cycle distributions at selected times after treatment indicate that the MNNG-responsive population was released from the density-dependent G1 block, proceeded through S, and became blocked again at G2 or M. These results indicate that DNA synthesis is temporally related to an early step in carcinogenesis.

Animals↗

Characterization of the WIDR: a human colon carcinoma cell line.

We describe the establishment and characterization of WiDr, a cell line derived from a human colon carcinoma. It produces carcinoembryonic antigen in culture, and has a doubling time of 15 hr with plating efficiency of 51%. The HLA antigenic profile and the allozyme genetic signature (composed of eight gene-enzyme systems) of WiDr cells are different from those of HeLa cells. Furthermore, WiDr cells possess three marker chromosomes, again distinct from the HeLa marker chromosomes. Finally, it is highly tumorigenic in four different xenogeneic animal models. Based on these studies, WiDr represents a useful model cell line for tumor cell biology investigations.

Carcinoembryonic Antigen↗

Respiratory diseases in cyclophosphamide-treated mice. II. Decreased virulence of PR8 influenza virus.

Mice infected intranasally with the PR8 strain of influenza virus were treated with cyclophosphamide, a potent immunologic suppressor. During the first week of infection, mortality in the unmodified influenza infection averaged 65%, whereas in those animals also treated with cyclophosphamide it averaged 22.5%. After the first week, the mortality rate in the infected cyclophosphamide-treated animals rose to that seen during the first week in the animals only infected. This decreased mortality in the first week was found despite the fact that the cyclophosphamide-treated and infected animals had higher virus titers which persisted longer, decreased circulating antibody, and a decreased interferon response. This delayed mortality appeared to be related to the finding of decreased cellular infiltration in the lungs of infected cyclophosphamide-treated animals.

Administration, Intranasal↗