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Biomedical subjects

K Gomi

Publications and source records attributed to K Gomi.

At least 199 records · Page 11Linked to original sources
PubMed1985

Characteristics of antiviral and anticellular activities of human recombinant interferon-gamma.

The antiviral and anticellular activities of recombinant human interferon-gamma (Re-IFN-gamma) were compared with those of natural human interferon-gamma (IFN-gamma), natural human interferon-alpha (IFN-alpha), and recombinant human interferon-beta (ReIFN-beta). ReIFN-gamma and IFN-gamma induced the antiviral state in FL cells against Sindbis virus more rapidly than IFN-alpha or ReIFN-beta. The antiviral state induced by a short exposure time to IFN-gamma declined rapidly after the removal of IFN-gamma and the incubation of FL cells in fresh medium, whereas that induced by ReIFN-gamma was persistent. However, other characteristics of the antiviral activity of ReIFN-gamma were shown to be very similar to those of IFN-gamma (e.g., stability at 56 degrees or pH 2.0, and neutralization by anti-IFN serum). The anticellular spectrum of ReIFN-gamma or IFN-gamma against 26 human cell lines differed in some respects from that of IFN-alpha or ReIFN-beta, since ReIFN-gamma and IFN-gamma were more effective at inhibiting the growth of human carcinoma or sarcoma cell lines. The IC50 (IFN concentration required for 50% growth inhibition) values of ReIFN-gamma were several times smaller than those of IFN-gamma in all cell lines sensitive to both IFNs. ReIFN-gamma and IFN-gamma, but not IFN-alpha or ReIFN-beta, were cytotoxic against HeLa S3 cells. These cytotoxicities of both IFNs were inactivated by treatment at 56 degrees or pH 2.0 and by anti-ReIFN-gamma serum. These results indicate that the characteristics of antiviral and anticellular activities of ReIFN-gamma are somewhat different from those of other IFNs including IFN-gamma.

Animals↗
PubMed1985

The different effects of recombinant human interferon-gamma and recombinant human interferon-beta on the activation of natural killer cells.

Highly purified recombinant human interferon-gamma produced by Escherichia coli (ReIFN-gamma) was examined for ability to stimulate natural killer (NK) cell cytotoxic activity and antibody-dependent cell-mediated cytotoxicity in human peripheral blood lymphocytes (PBLs) in comparison with natural human interferon-gamma (IFN-gamma) and with recombinant human interferon-beta produced by E. coli (ReIFN-beta). The activity of ReIFN-gamma to stimulate NK cell cytotoxicity was about 10 times greater than that of ReIFN-beta and similar to that of IFN-gamma when PBLs were pretreated with each interferon for 16 hr. The effects of ReIFN-gamma were completely neutralized by a rabbit anti-ReIFN-gamma antibody, but not by a rabbit anti-ReIFN-beta. ReIFN-gamma did not show any significant NK-enhancing effect when it was added directly to the killing phase of standard 51Cr-release assay for 4 hr, while ReIFN-beta showed a marked effect. The time course study showed that the NK-activating effect of ReIFN-gamma was not expressed until 2 hr after the start of incubation, while that of ReIFN-beta was expressed rapidly and sufficiently within 15 min. This kinetic difference between ReIFN-gamma and ReIFN-beta was confirmed by an experiment using the Ca2+-pulse method, in which the killing rate in the Ca2+-dependent stage of NK cytolysis was increased by ReIFN-gamma, but only after 6 hr of preincubation, while the effect by ReIFN-beta was expressed rapidly at 30 min. These findings suggest that ReIFN-gamma and ReIFN-beta may stimulate NK cell cytotoxicity through different intracellular events after they bind to their receptors on the surface of NK cells.

Antibodies↗
PubMed1984

Effect of levamisole on cytotoxic T-cell-mediated immune resistance to L1210 murine leukemia in hyperimmune mice.

The effect of levamisole (LMS) on T-cell-mediated antitumor immunity was examined in adult and aged mice hyperimmune to L1210 leukemia. The immune resistance of aged mice was depressed compared with that of adult mice, which almost completely rejected 5 X 10(7) L1210 cells inoculated IP. A significant level of tumor-specific cytotoxicity was detected in the spleen cells of adult hyperimmune mice by the 51Cr-release assay after in vitro sensitization with mitomycin C-treated L1210 cells. This was mediated by cytotoxic T cells, since in vivo administration of antithymocyte serum or in vitro treatment of the spleen cells with anti-Thy 1.2 antibody and complement abrogated the cytotoxicity completely. In aged mice, however, cytotoxic T-cell activity was lower although the animals were immune to L1210. Administration of LMS (0.38 mg/kg) restored the depressed cytotoxicity of aged mice to the level seen in adult mice. Furthermore, in adult hyperimmune mice LMS augmented T-cell-mediated cytotoxic activity and restored the reduced cytotoxicity caused by in vivo administration of antithymocyte serum. These results indicate that LMS was effective in augmenting T-cell-mediated tumor immunity in immunologically competent or deficient hosts.

Aging↗
PubMed1984

Antitumor effect of human recombinant interferon-beta against human melanomas transplanted into nude mice.

The antitumor activity of recombinant human interferon-beta (ReIFN-beta) against 2 human melanomas, Mela3 and SK-MEL-26 cells, transplanted into nude mice was examined, comparing with that of natural interferon-beta (IFN-beta). The growth of Mela3 and SK-MEL-26 cells was inhibited significantly by the daily intravenous injection of 10(8) units(U)/kg of ReIFN-beta for 10 d starting from day 0. The effect of ReIFN-beta decreased when its administration was started from the established stage of tumor development. Intravenous injection of 10(7) U/kg of ReIFN-beta or IFN-beta did not significantly inhibit the growth of Mela3 cells. Mela3 cells, prepared from Mela3-bearing mice which had been injected 10(8) U/kg of ReIFN-beta intravenously for 10 d, showed the slight resistance to ReIFN-beta in vitro. Intratumoral injection of 10(7) U/kg of ReIFN-beta in the established stage of tumor development inhibited the growth of Mela3 and SK-MEL-26 cells significantly. This effect of ReIFN-beta was almost equivalent to that of IFN-beta. From the histological examination, these effects of intratumoral injection of ReIFN-beta or IFN-beta were suggested to be mediated by their direct anticellular activities, but not by immunological activities. These results indicate that the in vivo antitumor activity of ReIFN-beta was not essentially affected by the deficiency of carbohydrate.

Animals↗
PubMed1984

Pharmacokinetics of human recombinant interferon-beta in monkeys and rabbits.

The pharmacokinetics of human recombinant interferon-beta ( ReIFN -beta) was compared with that of natural human interferon-beta (IFN-beta) in monkeys and rabbits after intravenous or intramuscular injection. After intravenous injection of 10(6) units/kg of ReIFN -beta or IFN-beta into monkeys or rabbits, serum levels of both interferons declined biexponentially. No significant differences between ReIFN -beta and IFN-beta were detected in most pharmacokinetic parameters including T1/2-beta, though T1/2-alpha of ReIFN -beta was significantly shorter than that of IFN-beta. These results seemed to be in conflict with the observed difference of stability of the interferons in vitro since ReIFN -beta was less stable than IFN-beta in monkey and rabbit serum. When ReIFN -beta (10(7) units/kg) was injected intramuscularly into monkeys or rabbits, it remained detectable in the serum for 24 hr; an absorption phase and an elimination phase were seen. However, AUC (the area under the serum concentration curve) after the intramuscular injection of ReIFN -beta was about one-half and one-third of that after the intravenous injection in monkeys and rabbits, respectively. ReIFN -beta and IFN-beta (10(6) units/kg) were both detectable in the serum after intramuscular injection into rabbits, but the level of ReIFN -beta was lower than that of IFN-beta. These results indicate that the lack of carbohydrate in ReIFN -beta did not essentially affect the in vivo pharmacokinetics in monkeys and rabbits after intravenous injection, but this was not the case after intramuscular injection.

Absorption↗
PubMed1983

Tumor dependency of concanavalin A-induced potentiation of tumor cell immunogenicity.

The immunogenicity of concanavalin A (Con A)-treated tumor cells was examined in 4 histologically distinct tumors originated from 3 different strains of mice. In all of these tumors, Con A-treated tumor cells induced stronger tumor-specific immunity than Con A-free tumor cells as determined from the survival of sensitized mice after live tumor cell inoculation. However, Con A-induced potentiation of tumor cell immunogenicity was dependent on 2 experimental factors associated with the tumor cell vaccine preparation. One was the agent used for inhibiting in vivo transplantability of tumor cells and the other was the dose of tumor cell vaccine. In Meth A, Meth 1, and Lewis lung tumors, glutaraldehyde and Con A-treated cells, but not mitomycin C and Con A-treated cells, induced an enhanced immune resistance, whereas in L1210 leukemia, mitomycin C was more beneficial than glutaraldehyde. Higher doses of Con A-treated tumor cells (up to 10(7)) induced stronger immune resistance in Meth A and Meth 1 tumors, as was the case with L1210 tumor, whereas in Lewis lung tumor there existed an optimal vaccine dose. These results indicate a tumor species dependence of pretreatment agents and cell vaccine doses in inducing immune resistance, although Con A potentiated the immunogenicity of all the tumors tested.

Animals↗