Search PubMed⌕ Search

Biomedical subjects

K Gomi

Publications and source records attributed to K Gomi.

At least 217 records · Page 12Linked to original sources

Influence of surgical removal and effect of levamisole on cytotoxic T-cell-mediated antitumor immunity in mice.

In BALB/c mice bearing syngeneic fibrosarcoma Meth 1 tumors, effects of surgical removal and levamisole (LMS) on the growth of reinoculated Meth 1 cells were investigated. The growth of secondary tumors in mice with surgical removal of primary tumors was significantly inhibited as compared with that of secondary tumors in primary tumor-bearing mice without surgical removal. LMS (2.5 mg/kg) augmented the growth inhibition of secondary tumors. Its effect was significant only in mice bearing primary tumors without surgical removal. Cytotoxicity, which was detected in the spleen cells of Meth 1-bearing mice, was mediated by tumor-specific cytotoxic T-cells and augmented after surgical removal of the tumors. LMS augmented the cytotoxicity when it was administered before surgical removal of the tumors but not after surgical removal. The spleen cells of Meth 1-bearing mice in the last stage of tumor development did not exhibit cytotoxicity, but rather exhibited suppressor activity on the in vitro generation of cytotoxicity. In this stage, effect of LMS was not detected. For the induction of cytotoxic T-cells in vitro, the cooperation of nylon wool-nonadherent cells and antigen-presenting cells appeared to be necessary. Nylon wool-adherent cells exhibited the suppressor activity. LMS stimulated the activity of nonadherent cells and partially modulated the suppressor activity of adherent cells. These effects of LMS were suggested to result in the augmentation of the cytotoxicity of the spleen cells and the growth inhibition of the secondary tumors in Meth 1-bearing mice.

Animals↗

Growth-inhibitory activity of recombinant human interferon-beta against cultured human cells.

The growth-inhibitory activity of recombinant human interferon-beta (ReIFN-beta) against cultured human cells was compared with that of natural human fibroblast interferon-beta (IFN-beta), and the influence of deficiency of carbohydrate on the anticellular activity was examined. The IC50 (concentration of drug required for 50% inhibition) of ReIFN-beta against 14 human cell lines was almost equivalent to that of IFN-beta, when the cells were cultured for 7 days and ReIFN-beta or IFN-beta was added on day 0 and exchanged every day from day 1 to day 6. The most sensitive cells (ICE less than 10 units/ml) were Daudi lymphoma cells and 3 melanoma cell lines, and the most insensitive cells (IC50 greater than 10(3) units/ml) were HeLa S3/IS cells (insensitive line) and CCRF-CEM leukemia cells. The other 8 cell lines were moderately sensitive to both interferons. As the intervals of exchange of ReIFN-beta or IFN-beta were extended, the growth-inhibitory activity of both interferons decreased. This phenomenon, which was more significant with ReIFN-beta than IFN-beta, was explicable in terms of the stability of both interferons incubated in the culture medium at 37 degrees. The species specificity of IFN-beta was not mediated by carbohydrate since the growth-inhibitory activity of ReIFN-beta against 2 mouse cell lines was almost equivalent to that of IFN-beta. These results indicate that the anticellular activity of ReIFN-beta was not essentially affected by deficiency of carbohydrate.

Animals↗

Cytotoxic T-cell-mediated antitumor effect of levamisole against murine syngeneic fibrosarcoma.

Growth of the secondary Meth 1 tumors, which had been inoculated s.c. in the abdomens of BALB/c mice bearing primary Meth 1 tumors in the flanks, was inhibited as compared with that of tumors in the normal mice, suggesting the development of concomitant antitumor immunity. When levamisole (LMS, 0.625 or 2.5 mg/kg) was administered i.p. to the Meth 1-bearing mice daily before or after secondary inoculation, growth inhibition of secondary tumors was augmented. This effect of LMS was suggested to be tumor specific as evidenced by no growth inhibition of secondary Meth A tumors in mice bearing primary Meth 1 tumors. The spleen cells of 11-day Meth 1-bearing mice exhibited growth-inhibitory activity against Meth 1 cells in the Winn assay. Administration of LMS augmented the growth-inhibitory activity. This effect of LMS was mediated by nonadherent spleen cells and completely lost by the preincubation with anti-Thy 1.2 antibody and complement. Cytotoxicity was detected in the spleen cells of Meth 1-bearing mice by 51Cr release assay after in vitro sensitization with mitomycin C-treated Meth 1 cells. In vivo administration of LMS augmented the cytotoxicity, which was tumor specific and completely lost by the preincubation of the spleen cells with anti-Thy 1.2 antibody and complement. These results suggest that the growth-inhibitory effect of LMS against secondary tumors was mediated by cytotoxic T-cells.

Animals↗

[Effects of levamisole on methylcholanthrene-induced tumor. II. Potentiation of cytotoxic T-cell activities].

1) Levamisole(LMS) augmented the ability to inhibit specifically the growth of secondary Meth 1 tumors in Meth 1-bearing BALB/c mice. 2) When spleen cells of Meth 1-bearing mice were restimulated in vitro with MMC-treated Meth 1 cells, cytotoxicity became detected by 51 Cr release assay. Such cytotoxicity was augmented by in vivo treatment with LMS. The cytotoxicity was tumor-specific and completely abrogated by incubation with anti-thy 1.2 antibody and complement before the assay. 3) Cytostatic activity of peritoneal macrophages induced by i. p. inoculation with MMC-treated Meth 1 cells was augmented by LMS treatment of Meth 1-bearing mice but such an activity was not Meth 1-specific. 4) LMS did not augment the natural killer cell activity of the spleen cells of BALB/c mice or BALB/c nude mice. These results suggested that the growth-inhibitory effect of LMS against secondary tumors was mediated by cytotoxic T-cells.

Adjuvants, Immunologic↗

[Effects of levamisole on methylcholanthrene-induced tumor. I. Its antitumor effect and immunological mechanism].

Malignancy and antigenicity of fibrosarcoma Meth 1 cells induced in a BALB/c mouse were compared with sarcoma Meth A cells. Furthermore, antitumor effect of levamisole (LMS) against Meth 1 cells and its immunological mechanism were studied. 1) The lifespan of BALB/c mice inoculated i.p. with 10(2) Meth 1 cells was prolonged by the treatment with LMS. 2) Growth of s.c. inoculated secondary tumors was tumor-specifically inhibited in solid Meth 1-bearing mice as compared with that in non-tumor-bearing mice. Administration of LMS (0.625 or 2.5 mg/kg) augmented the growth inhibition of these secondary tumors. 3) Spleen cells of Meth 1-bearing mice showed a growth-inhibitory activity against Meth 1 cells in Winn assay. LMS (0.625 or 2.5 mg/kg) augmented such a growth-inhibitory activity of spleen cells. The activity was attributed to non-adherent, thy 1-positive spleen cells.

Adjuvants, Immunologic↗

L-Alloisocitrate dehydrogenase and oxalosuccinate decarboxylase from a Pseudomonas sp. utilizing L-alloisocitrate.

Two novel enzymes, NAD+-linked L-alloisocitrate (erythro-Ls-isocitrate) dehydrogenase and oxalosuccinate decarboxylase, were found and purified from a strain of Pseudomonas isolated as an L-alloisocitrate utilizing bacterium. The former enzyme catalyzes a reversible oxidation-reduction between L-alloisocitrate and oxalosuccinate which favors oxalosuccinate reduction. The latter enzyme catalyzes rapid decarboxylation of oxalosuccinate to alpha-ketoglutarate and CO2. Both enzymes require no metals for their activities. Complete oxidative decarboxylation of L-alloisocitrate to alpha-ketoglutarate occurs as a result of the sequential reactions catalyzed by these two enzymes. L-Alloisocitrate induces both enzymes in the growing pseudomonad.

Alcohol Oxidoreductases↗

In vivo potentiation of concanavalin A-bound L1210 vaccine by antimacrophage agents.

Carrageenan potentiated in vivo the primary and secondary responses by concanavalin A (Con A)-bound L1210 murine leukemia vaccine and induced in histocompatible animals enhanced immune resistance to subsequent inoculations of live L1210 cells. This enhancement was critically dependent on the vaccine preparation and the administration timing of carrageenan. Carrageenan potentiated Con A-free vaccine to a much lesser extent if at all, than did Con A-bound vaccine, and it was effective only on the day of or one day after vaccine administration. This enhancement was L1210 specific as evidenced by the lethal growth of P388 leukemia cells in animals inoculated with Con A-bound L1210 vaccine and carrageenan. This is explicable by the increase of spleen but not peritoneal exudate effector cells as measured by suppression of in vitro L1210 cell growth. The following findings suggested that potentiation of Con A-bound vaccine by carrageenan was achieved by affecting suppressor macrophages. Silica and trypan blue, other antimacrophage agents, potentiated Con A-bound vaccine. The enhancement was nullified by the macrophage-stabilizing agent, poly-2-vinylpyridine N-oxide. This hypothesis was further evidenced by the following findings. Phagocytic peritoneal cells induced by Con A-bound vaccine and adhering to the plastic vessel suppressed in vitro spleen cell blastogenesis. Antimacrophage agents abrogated not only production but also activity of these suppressor cells. The combined administration of Con A-bound L1210 vaccine and carrageenan produced an enhanced antitumor immune response and prolonged the life span of tumor-bearing animals marginally but significantly.

Animals↗

Macro creatine kinase: a study on CK-linked immunoglobulin.

We describe three cases in which creatine kinase (CK, EC 2.7.3.2) was linked to immunoglobulin in serum. In this study, its prevalence was 0.8%. Enzyme-immunofixation electrophoresis revealed that the heavy chain of CK-linked immunoglobulins was of class alpha in all cases. The light-chain type was identified as lambda in two cases and as both lambda and kappa in one case. The complexes were dissociated at pH 3.4 and re-formed with CK isoenzymes MM and MB at pH 7.4. The complex fraction obtained by gel filtration was not inhibited by anti-CK-M antibodies. Treatment of the serum with urea after heating shows residual CK-MM activity; in contrast, normal CK activity disappeared entirely after this treatment. The present study suggests that CK-linked immunoglobulins may be one of the circulating immune complexes and must be distinguished from other macro-CK in the strict sense. The results obtained show that the presence of the complexes results in false-positive CK-B activity in the immuno-inhibition test, and they may provide interesting insights into the mode of binding of the CK-linked immunoglobulins.

Adult↗

Creatine kinase isoenzyme of high relative molecular mass in serum of a cancer patient.

We describe an atypical serum creatine kinase isoenzyme in the serum of a woman with cancer of the left breast. This isoenzyme migrated toward the cathode, closely following the MM isoenzyme on agarose gel electrophoresis. Its relative molecular mass was estimated to be about 325,000, fourfold that of normal creatine kinase. It is more heat-stable and is inhibited more by urea than the normal MM isoenzyme. Isoenzyme monomer B activity was observed to be 20 U/liter in the serum, as measured with use of an antibody against the M monomer. On anion-exchange column analysis, creatine kinase activity was observed only in the MM fraction, in spite of the fact that B activity was observed in the patient's serum. Results of the immunological investigation make it unlikely that the atypical isoenzyme is linked to immunoglobulin or beta-lipoprotein. It may have been present as the result of modification of normal creatine kinase by the therapeutic radiation the patient was receiving.

Breast Neoplasms↗

Ultrastructural, histochemical, and biochemical studies of two cases with amylase, ACTH, and beta-MSH producing tumor.

Two cases of intrathoracic tumor, different in histology and accompanied by hyperamylasemia, were studied ultrastructurally, histochemically, and biochemically. The ultrastructure of the tumor cell cytoplasm showed many zymogen granules in case 1 and smaller cored granules in addition to zymogen granules in case 2. Both tumors contained not only a large amount of amylase, which was electrophoretically of saliva type with three components, but also significant amounts of immunoreactive ACTH and beta-MSH. Starch film and immunofluorescence showed that the tumor cells stored amylase. It was concluded from these findings that the tumor cells ectopically producing amylase, which showed differentiation toward the cells with zymogen production, could differentiate toward the cells of ACTH-MSH system at the same time.

Adenocarcinoma↗