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Biomedical subjects

K Onoue

Publications and source records attributed to K Onoue.

At least 37 records · Page 2Linked to original sources
PubMed1989

Requirement for delivery of signals by physical interaction and soluble factors from accessory cells in the induction of receptor-mediated T cell proliferation. Effectiveness of IFN-gamma modulation of accessory cells for physical interaction with T cells.

We analyzed the mechanism by which accessory cells support the induction of the proliferation of human peripheral blood T cells by a monoclonal anti-CD3 antibody, OKT3. Cross-linking of T cell receptor/CD3 complex by anti-CD3 coupled to latex beads and the addition of IL-1 are not enough to induce the IL-2 production and proliferation of T cells extensively depleted of accessory cells, while the addition of both the culture supernatant of macrophages or a monoblastic cell line, U937 cells, and the paraformaldehyde-fixed macrophages or U937 cells which had been precultured with interferon-gamma before fixation into the culture of the T cells with anti-CD3-latex did induce the T cell proliferation. Lack of the addition of either one of these did not induce the response. These results indicate that the signal(s) delivered by soluble factors released from the accessory cells and that delivered by the physical interaction between accessory cells and T cells are both required for the induction of IL 2 production and proliferation of T cells by anti-CD3-latex. Importantly, the macrophages or U937 cells had to be cultured with Con A-stimulated lymphocyte culture supernatant or IFN-gamma prior to fixation with paraformaldehyde, suggesting that a molecule(s) inducible on accessory cells surface by IFN-gamma or other lymphokine is necessary for the effective accessory cell-T cell interaction to induce the T cell response. It was further revealed that the activity of the culture supernatant of accessory cells may be mediated synergistically by IL 1 and a certain other factor(s) and was actually shown to be replaced by the combined addition of rIL-1 and rIL-6 but not by rIL-1 alone. The experimental system described here will be very useful for dissecting the accessory functions for T cell activation.

Adjuvants, Immunologic↗
PubMed1989

[An epidemiological study on dental caries of children in Fuji town. 1. Prevalence of dental caries].

An epidemiological investigation on dental caries was undertaken with 810 children of nursery school, kindergarten, elementary and junior high school age in the town of Fuji, saga prefecture which is a mountain village with less movement of the population. From this investigation the following results were obtained regarding the dental caries prevalence and the status of treatment: 1. As for the dental caries prevalence of deciduous teeth, the dft index was 8.8 at age 3, whereas it was 10.7 at age 5. 2. As for the dental caries prevalence of the permanent teeth, the DMFT value was 7.7 at age 12, whereas it was 9.9 at age 14. 3. As for differences based on set, concerning the deciduous teeth, none was not recognized except for the caries prevalence indices at age 11 for the dft index, at age 6 and 11 for the dfs index, and at age 11 for the ft index. 4. As for differences based on sex, concerning the permanent teeth, none was not recognized except for the caries prevalence indices at age 5 and 9 for the DFT and DFS indices, and at 7 for the FT and F tooth rate. 5. There was a tendency toward as significant increase in dental caries in the deciduous teeth. 6. There was a tendency toward as increase in dental caries in permanent teeth from the commencement of eruption and rapid aggravation approximately from the upper grades of elementary school. 7. In the status of treatment of dental caries in deciduous teeth, the ft index was 4.1 at age 6. 8. In the status of treatment of dental caries in permanent teeth, the FT index was 4.5 at age 14. 9. There was no statistically significant difference among kindergarten and nursery school children except for the dft and dfs indices at age 4.

Adolescent↗
PubMed1989

Signal delivery by physical interaction and soluble factors from accessory cells in the induction of receptor-mediated T-cell proliferation. Synergistic effect of BSF-2/IL-6 and IL-1.

Our recent study revealed that soluble factors derived from accessory cells (AC; monocytes) and physical interaction with T cells of the accessory cells are both required for the induction of the proliferation of human peripheral blood T cells by anti-CD3 antibody coupled on latex beads. The accessory cell-derived soluble factor could be replaced by IL-1 and IL-6, and the role of live macrophages for physical interaction with T cells was found to be replaceable with paraformaldehyde(PFA)-fixed macrophages, provided the macrophages were pretreated with interferon-gamma (IFN-gamma) before fixation. Quantitative analysis in the present study revealed that IL-1 and IL-6 act synergistically to induce T-cell proliferation in the above system but either one of the factors alone reveals only a marginal or weak activity. Furthermore, it was shown that the potentiating activity of the culture supernatants of monocytes was substantially inhibited by anti-IL-6 antibody. Taken together with our previous results that anti-IL-1 serum strongly inhibited the potentiating activity of the culture supernatant, these results indicate that the main responsible molecules in the culture supernatant are IL-1 and IL-6, although a presence of other effective factors is not excluded. The anti-CD3-induced thymidine uptake by T cells in the presence of IL-1 and IL-6 was significantly inhibited by anti-Tac antibody, suggesting that the proliferation of T cells in this system is mostly mediated by a IL-2-dependent pathway. Our study further showed that accessory cells seem to acquire cell surface properties necessary for the effective interaction with T cells during 6-24 hr of culture with IFN-gamma. Presumably, a certain molecule(s) required for the interaction is induced on the cell surface of the AC by IFN-gamma.

Antibodies, Monoclonal↗
PubMed1988

Effect of wheat germ agglutinin on T lymphocyte activation.

Wheat germ agglutinin (WGA) is low mitogenic or nonmitogenic for human T lymphocytes and inhibits phytohemagglutinin (PHA)-induced mitotic response of the lymphocytes. In this study, the effect of WGA was analyzed in terms of interleukin 2 (IL2) production, expression of IL2 receptor, and IL2 responsiveness of the T lymphocytes. WGA as well as PHA could induce IL2 mRNA and IL2 production and also elevate cytoplasmic free Ca2+ concentration. The IL2 production was reduced by inhibitors of calmodulin and protein kinase C. The IL2 receptor (Tac) expression was induced at about 20% of the lymphocytes by WGA and the expression induced by PHA was not blocked by the addition of WGA. The lymphocytes precultured with WGA for 3 days could proliferate by the addition of IL2 after removal of WGA. The IL2-dependent proliferation of PHA-blasts was blocked by the addition of WGA. These results indicate that WGA inhibits T lymphocyte proliferation by inhibiting the responsiveness of the lymphocytes to IL2 but not by interfering with IL2 production and IL2 receptor expression.

Calcium↗
PubMed1988

Arachidonic acid release is closely related to the Fc gamma receptor-mediated superoxide generation in macrophages.

Stimulation of macrophages with IgG2 immune complexes induced dose-dependently the O2- generation and the release of arachidonic acid and its metabolites. This Fc gamma R-mediated O2- generation was inhibited by a phospholipase A2 inhibitor, 4-p-bromophenacyl bromide (4-pBPB), in parallel to the dose-dependent inhibition of arachidonic acid release. The main arachidonic acid metabolites released were shown to be prostaglandin E2 and thromboxane B2 and blocking of the production of these metabolites by indomethacin did not inhibit the O2- generation. Inhibition of the Fc gamma R-mediated O2- generation and the arachidonic acid release by the C-kinase inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), was less intense than by 4-pBPB. These results support the previously proposed hypothesis that arachidonic acid acts as an intracellular activator of the Fc gamma R-mediated O2- generation in macrophages. Although the C-kinase activation may also contribute to the activation of the O2--generating system, arachidonic acid release appears to play a major role in Fc gamma R-mediated O2- generation. In contrast, activation of C-kinase seems to be contributing mainly in the induction of both the arachidonic acid release and O2- generation by 12-o-tetradecanoylphorbol 13-acetate (TPA). Furthermore, suboptimal concentrations of TPA and arachidonate were found to act synergistically to stimulate O2- generation and the inhibition study suggested a positive synergism between C-kinase and arachidonic acid release to induce O2- generation. This synergistic action may have general importance in receptor-mediated O2- generation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

Thymic accessory cells required for the increased responsiveness of thymocyte subpopulations to interleukin 1-like monokine in guinea pigs.

The proliferative response of guinea-pig thymocytes to co-mitogenic stimulation with phytohaemagglutinin and the guinea-pig interleukin 1 (IL-1)-like lymphocyte-activating monokine was lost by removing the cells that adhere to a Sephadex G-10 (G-10) column or the cells of low density in a Ficoll-Conray gradient. The diminished response in the G-10 non-adherent thymocyte or high-density thymocyte fraction was restored by the addition of a macrophage-depleted G-10 adherent thymocyte fraction or a low-density, Ia-positive thymocyte fraction but not by the addition of peritoneal macrophages. These results suggest that the accessory cells which mediate the increased responsiveness of thymocytes to the IL-1-like monokine existed in G-10 adherent cell fractions and the cells with this accessory function were not macrophages. The accessory cells were shown to be of low density, glass-non-adherent, G-10-adherent, Fc receptor-negative, and Ia-positive. These results also suggest that the G-10-non-adherent and high-density thymocyte subpopulation, which is unresponsive or responds very little to the IL-1-like monokine by itself, acquires responsiveness to the monokine and proliferates by stimulation with the IL-1-like monokine and lectin in the presence of the accessory cells.

Animals↗
PubMed1987

Calmodulin inhibitors, W-7 and TFP, block the calmodulin-independent activation of NADPH-oxidase by arachidonate in a cell-free system.

The calmodulin inhibitor, N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7), or trifluoperazine inhibited not only Fc gamma-receptor mediated cytosolic free Ca2+ increase and O2- generation in macrophages, but also an arachidonate-induced activation of NADPH-oxidase in a cell-free system. Although these results suggested the involvement of Ca2+-calmodulin system, the cell-free activation of NADPH-oxidase occurred in the presence of EGTA and addition of calmodulin had no effect. Furthermore W-7 shifted the optimal concentration of arachidonate required for the activation to a higher level, suggesting that W-7 may block the interaction between arachidonate and NADPH-oxidase system rather than inhibiting a Ca2+-calmodulin system.

Animals↗
PubMed1987

Arachidonic acid acts as an intracellular activator of NADPH-oxidase in Fc gamma receptor-mediated superoxide generation in macrophages.

A protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), inhibited phorbol ester (12-o-tetradecanoylphorbol 13-acetate)-induced and Fc gamma receptor-mediated superoxide anion (O2-) generations in guinea pig macrophages, but the inhibitory effect on Fc gamma receptor-mediated O2- generation was only partial. Both O2- generations were inhibited extensively by a phospholipase A2 inhibitor, 4-p-bromophenacyl bromide (4-pBPB). It was confirmed in control experiments that H-7 and 4-pBPB had no direct inhibitory effect on NADPH-oxidase activity. Dose-dependent stimulation of O2- generation was induced by arachidonate in macrophages, and the arachidonate-induced O2- generation was not inhibited by H-7. Arachidonate could also induce NADPH-oxidase activation in a post-nuclear fraction obtained from unstimulated macrophages and this activation was not inhibited by H-7, indicating that protein kinase C activation was not involved in this cellfree system. These results support the hypothesis that the O2- generation induced by Fc gamma receptor stimulation is mainly mediated by arachidonic acid which is released by the action of phospholipase A2 activated by receptor stimulation. Arachidonic acid seems to be acting rather directly in activating the NADPH-oxidase system of macrophage membrane. Protein kinase C may have a significant role in Fc gamma receptor-mediated O2- generation but it is not obligatory, and protein kinase C seems to activate NADPH-oxidase rather indirectly, probably by inducing the arachidonic acid release.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1987

Heterogeneity in response to interleukin 2 and interleukin 2-producing ability of adult T cell leukemic cells.

To examine the possibility of heterogeneous mechanisms in the proliferation of adult T cell leukemia (ATL) cells, leukemic cells from 13 patients, nine acute-type and four chronic-type ATL, were examined for the production of interleukin 2 (IL 2) with or without mitogenic stimulation and their response to recombinant IL 2 when exogeneously added. The leukemic cells were classified into four groups, as follows. Group 1 (two patients): Cells of this group produced IL 2 messenger RNA, secreted IL 2, and proliferated when cultured in mitogen-free medium. The spontaneous proliferation of the cells in mitogen-free medium was inhibited by anti-Tac/IL 2 receptor and anti-IL 2 monoclonal antibodies. Moreover, the thymidine incorporation by the cells was enhanced in response to exogeneously added recombinant IL 2 and IL 2 produced by themselves. These results indicate that the ATL cells of this group proliferate with autostimulation by IL 2. Group 2 (seven patients): Cells of this group did not secrete IL 2 when cultured in mitogen-free medium, but the cells showed response to exogeneously added recombinant IL 2 and proliferated in culture. These results indicate that the ATL cells of this group proliferate by a paracrine mechanism. Group 3 (one patient): Cells of this group secreted IL 2 in mitogen-free medium. However, the spontaneous proliferation of these cells in vitro was very low, and the response to recombinant IL 2 was also very low. Group 4 (three patients): Cells of this group did not secrete IL 2 in mitogen-free medium. Spontaneous proliferation and the response to recombinant IL 2 were also very low. The clinical feature of all patients of Groups 1 and 2 was acute-type, and that of Groups 3 and 4 was chronic-type. Thus, we conclude that heterogeneous mechanisms exist in the proliferation of leukemic cells, and that growth rate in mitogen-free medium and response to IL 2 of the cells may have a significant relationship to the clinical feature, acute- or chronic-type.

Adult↗
PubMed1987

Muramyl dipeptide induced augmentation of the proliferative response of thymocytes to phytohemagglutinin.

N-Acetylmuramyl-L-alanyl-D-isoglutamine (MDP) augmented the proliferative response of thymocytes to phytohemagglutinin (PHA). The augmenting effect of MDP disappeared by passage of glass-nonadherent thymocytes through Sephadex G-10 (G-10) column or by removal of low density cells by the Ficoll-Conray gradient centrifugation. The diminished augmenting effects of MDP on the proliferative response of glass-nonadherent-G-10 nonadherent thymocytes was restored by the addition of the G-10 adherent cells. When G-10 adherent cell fraction was extensively depleted of macrophages by glass adherence and EA-rosetting, it was found that neither the macrophage-depleted G-10 adherent cell fraction nor the macrophage fraction supported by itself the proliferative response of G-10 nonadherent thymocytes. However, addition of macrophage fraction together with the macrophage-depleted G-10 adherent cells did support the proliferation of G-10 nonadherent thymocytes. It was further shown that peritoneal exudate macrophages could be substituted for thymic macrophage fraction. These results suggested that both the G-10 adherent-glass nonadherent cells and macrophages were essential for the MDP-induced augmentation of the proliferative response of thymocytes to PHA and these cells exerted different accessory roles in this response.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Urethral metastasis from prostatic carcinoma as diagnosed by immunoperoxidase technique using prostate-specific antigen and prostate-specific acid phosphatase.

A rare case of urethral metastasis from prostatic adenocarcinoma is reported. Ordinary histological examination by hematoxylin and eosin staining could not determine whether the primary site was the prostate or the urethra. However, with an immunoperoxidase technique using prostate-specific acid phosphatase and prostate-specific antigen as markers for prostatic cells, we obtained a precise diagnosis of the primary sites. As a result, the patient could be successfully treated with hormonal therapy.

Acid Phosphatase↗
PubMed1986

The purification and biological activity of a macrophage-derived factor with interleukin 1-like activities from guinea pigs.

A macrophage-derived factor with interleukin 1-like activity was purified from culture supernatant of muramyl dipeptide-stimulated peritoneal exudate macrophages of guinea pigs. Starting with serum-free culture supernatant, the purification was carried out by gel permeation chromatography, affinity chromatography on procion red agarose, removal of carry-over serum proteins by Sepharose-coupled antibodies against bovine serum proteins, anion exchange chromatography and hydrophobic chromatography. The purified sample potentiated the phytohemagglutinin-induced thymidine uptake of thymocytes with a 50% effective concentration of 9.6 X 10(-11) M. The sample showed a single band in polyacrylamide gel electrophoresis, and a 65 kDa band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis by silver staining. A single peak of activity was detected by thymocyte assay at the position corresponding to the stained band in both of the electrophoretic analyses. The purified factor had activities to potentiate the antigenic activation of sensitized T cells for the production of a lymphokine, macrophage migration inhibitory factor, and also the proliferative response of sensitized T cells to antigen. Thus, the 65 kDa factor has activities to modulate various T cell responses in guinea pigs such as interleukin 1 does in other species. The molecular relationship of the 65 kDa macrophage factor to interleukin 1 remains to be determined.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1986

Induction and regulation of human interleukin 2 gene expression: significance of protein kinase C activation.

Phytohemagglutinin (PHA) and a tumor-promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) act synergistically to induce interleukin 2 (IL2) mRNA in human lymphocytes in vitro. The induction was inhibited by a potent inhibitor of protein kinase C (C-kinase), 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) at less than 10 microM. H-7 inhibited C-kinase activity itself in lymphocytes at the same range of the concentration but did not interfere with the translocation of C-kinase from the cytosol to the membrane fraction of the lymphocytes induced by TPA. H-7 is also known to inhibit cAMP-dependent protein kinase (A-kinase) and cGMP-dependent protein kinase (G-kinase). However, the lymphocytes cultured with dibutyryl cAMP or dibutyryl cGMP could not be activated to produce IL2 mRNA. These results show that activation of C-kinase but not A-kinase and G-kinase is necessary in signal transduction for IL2 gene expression. Prostaglandin E2, which is known to elevate intracellular cAMP level, also inhibited IL2 mRNA induction in the lymphocytes stimulated with PHA and TPA. Addition of alpha-methylornithine and methylglyoxal bis (guanyl hydrazone), which inhibit polyamine synthesis, did not affect the induction of IL2 mRNA in the lymphocytes stimulated with PHA and TPA, indicating that polyamine synthesis is not necessary for IL2 mRNA induction.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1986

Dissection of the role of macrophages in triggering T lymphocytes for interleukin 2 production by monoclonal antibody OKT3.

Unfractionated human peripheral blood mononuclear cells produce a small amount of interleukin 2 (IL 2) by stimulation with a monoclonal anti-T3 antibody (OKT3) in vitro. The IL 2 production could be greatly augmented by the addition of a phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA). In the presence of TPA, the T cell enriched fraction deprived of macrophages did not produce IL 2, but the T cells pulse-incubated with OKT3 and reconstituted with macrophages efficiently produced IL 2 in subsequent culture in the presence of TPA as did T cells reconstituted with OKT3-pulse-incubated macrophages. The stimulating effect of OKT3 in the presence of macrophages was inhibited dose-dependently by the addition of immunoglobulins, particularly by mouse IgG2a which is the same isotype as that of the OKT3 antibody, showing that it inhibits by blocking the binding of OKT3 to Fc receptors on macrophages. The same extent of IL 2 production was induced in T cells when paraformaldehyde-fixed macrophages were substituted for intact macrophages. Remarkable IL 2 production was also induced by OKT3 when latex beads coated with rabbit anti-mouse IgG2a antibody and TPA were added to the culture. It was confirmed that the production induced by these stimulations was due to an increase of IL 2 mRNA. These results show that effective signals for IL 2 production are generated by efficient crosslinking of T3 molecules which results from multi-interaction of T3 molecules on the T cell membrane and anti-T3 antibody molecules on macrophage membrane or on the surface of the latex particle.

Antibodies, Monoclonal↗
PubMed1986

Autocrine growth of interleukin 2-producing leukemic cells in a patient with adult T cell leukemia.

Leukemic cells in the peripheral blood of a patient with adult T cell leukemia (ATL), which expressed the Tac antigen/interleukin 2 (IL2) receptor, were investigated in vitro for autocrine growth by IL 2. The cells showed spontaneous proliferation in mitogen-free medium. The spontaneous proliferation of the cells was inhibited by monoclonal anti-IL 2 or anti-Tac antibody. These cells were found to produce messenger RNA for IL 2 and secrete IL 2 during short-term culture in the same medium. Recombinant IL 2 and IL 2 secreted by the cells enhanced the proliferation of the cells in a dose-dependent manner when added to the initial culture. These findings demonstrate that an autocrine mechanism by IL 2 is involved in the proliferation of ATL cells during short-term culture.

Cell Cycle↗