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Biomedical subjects

Y Yanagihara

Publications and source records attributed to Y Yanagihara.

At least 253 records · Page 14Linked to original sources

[Immunopharmacological actions of 6-amidino-2-naphthyl-4-guanidinobenzoate (FUT-175). 2. Effect of FUT-175 on immunological reactions in man].

FUT-175 is a new anti-complemental drug which strongly inhibits complement-mediated allergic reactions in animals. It was reported that FUT-175 does not affect both antibody formation and host defense to bacterial infection in mice. The present study was undertaken to examine the effects of FUT-175 on various immunological reactions in humans. FUT-175 dose-dependently decreased the antigen-induced anaphylactic histamine release from leukocytes of atopic patients. However, i.d. treatment of FUT-175 neither inhibited antigen- or compound 48/80-induced immediate type skin reactions in atopic patients nor antigen-induced early, late or delayed type skin reactions in Candida-sensitive patients. FUT-175 also did not inhibit the PPD-mediated delayed type skin reaction in healthy subjects. FUT-175 at a dose of 10(-4)M but not at 10(-8) to 10(-5)M significantly decreased the proliferation of human atopic peripheral blood lymphocytes (PBL) caused by mite antigen, concanavalin A or pokeweed mitogen. 51Cr release from human PBL was slightly enhanced by FUT-175 at a dose range of 10(-6) to 10(-4)M. FUT-175 did not change the number of SIg receptors or C3 receptors on human B cells. FUT-175 hardly affected the nitroblue tetrazolium reduction test and Escherichia coli-mediated chemotaxis in human neutrophils. These results strongly suggest that FUT-175 does not affect immunological functions and host defense in humans.

Benzamidines↗

[Immunopharmacological actions of 6-amidino-2-naphthyl-4-guanidinobenzoate (FUT-175). 1. Effect of FUT-175 on immune response and host defense in mice].

FUT-175 is a new synthetic protease inhibitor which strongly inhibits complement-mediated hemolysis via the classical and alternative pathways. The present study was undertaken to examine the effects of FUT-175 on antibody formation and host defense in mice since the complement system participates in both immunological responses and host defense against bacterial infection. FUT-175 did not suppress the primary IgM and IgG antibody responses to sheep red blood cells, although FUT-175 was given at 10 to 100 mg/kg/day p.o. for 3 days before or after immunization. On the other hand, the primary anti-DNP IgE antibody response to DNP-conjugated ovalbumin was slightly suppressed only by post-administration of FUT-175 in a dose of 100 mg/kg/day p.o. for 5 days. However, the results of the adoptive transfer experiments indicate that FUT-175 did not affect either T cells or B cells participating in the secondary anti-DNP IgE antibody formation. FUT-175 in a dose of 10(-4)M but not at 10(-6) to 10(-5)M significantly decreased the proliferation of spleen cells caused by concanavalin A, lipopolysaccharide or the one-way mixed lymphocytes culture reaction using 1000 R-irradiated spleen cells from BDF1 mice as stimulator cells and those from C57BL/6 mice as responder cells. FUT-175 had an inhibitory rather than an enhancing effect on host defense to infection with Escherichia coli when administered at 10 to 100 mg/kg/day p.o. for 3 days before or after infection. These results strongly suggest that FUT-175 does not affect antibody formation and host defense in mice.

Animals↗

Isolation and chemical properties of a haptenic substance from buckwheat dialysate.

A haptenic substance was isolated from the dialysate of the aqueous extract of buckwheat. This substance, BWD II 22-3, which was composed of Asp(1), Thr(1), Ser(1), Gly(1), Gly(4), Ala(1), Val(1), Leu(1), Orn(2), Lys(1), Arg(1), Cys(1) and glucose was demonstrated to be homogeneous by gel filtration and paper electrophoretic analyses. The molecular weight was estimated to be 1600 by gel filtration on Sephadex G-50. The haptenic substance apparently has-SH group determinant caused about 50% inhibition at a concentration of 100 micrograms/disc in the RAST procedure using human serum sensitive to buckwheat. An active component, BWD II 22-3, might prove effective in the hyposensitization therapy of buckwheat-sensitive patients.

Desensitization, Immunologic↗

Hemolytic activity of Leptospira interrogans serovar canicola cultured in protein-free medium.

Hemolytic activity of the culture supernatant of Leptospira interrogans serovar canicola strain Moulton grown in protein-free medium was demonstrated. The activity began to appear in the late logarithmic phase of growth of the organism and reached a plateau after 2 weeks of cultivation. It was inactivated by the addition of dipotassium ethylenediaminetetraacetate, but was effectively restored by Mg2+. Hemolysis by the culture supernatant was stimulated by "hot-cold" incubation. Sleep erythrocytes treated with the culture supernatant of the organism were transformed into spherocytes, in which invagination was observed. A hemolysis inhibitor in rabbit serum was found to be in the chloroform-methanol soluble fraction of the serum. The hemolysin of Leptospira may be phospholipase C.

Animals↗

Mitogenicity and adjuvanticity of a marine bacterium, Vibrio anguillarum, in mice.

The effects of whole cells of three different O serotypes of Vibrio anguillarum on the murine immune response were studied. The addition of different doses (1-100 microgram/ml) of V. anguillarum cells, as well as Salmonella typhimurium lipopolysaccharide, markedly increased the incorporation of [3H]thymidine into in vitro cultured spleen cells of C57BL/6 mice. All three serotype strains of V. anguillarum were able to induce the mitogenic effect at 10 microgram /ml and 100 microgram/ml, but serotype I strains were more potent than the others. Since pretreatment of spleen cells with rabbit anti-mouse thymocyte antiserum did not affect the mitogenic activity of V. anguillarum, Vibrio cells may be a B-lymphocyte mitogen. When sheep or horse erythrocytes and Vibrio cells were injected intraperitoneally into ddY mice, Vibrio cells exhibited an enhancing effect on antibody response in vivo, regardless of the different serotypes. Vibrio cells, when injected intraperitoneally into mice before the antigen, markedly suppressed the antibody response. Several days after the injection of Vibrio cells, these mice showed an enhanced carbon clearance activity. Acid phosphatase activity in their peritoneal cells was also augmented, suggesting that Vibrio cells activated macrophages in the mice.

Acid Phosphatase↗

Anti-mite IgE antibody production in vitro by peripheral blood lymphocytes from mite-sensitive atopic patients.

Anti-mite IgE antibody production in vitro was investigated using peripheral blood lymphocytes (PBL) from mite-sensitive patients with bronchial asthma. Preculture of PBL with the mite antigen, which induced the remarkable cell proliferation, resulted in a marked decrease of the IgE antibody production directed to mite but not to unrelated antigens. Anti-mite IgE antibody formation was not inhibited by autologous or allogeneic T cells stimulated with the mite antigen. The spontaneous production of IgE antibody was observed when fractionated B cells were cultured alone or with pokeweed mitogen (PWM), but was suppressed when they were precultured with the antigen. Coculture of autologous T cells with B cells showed a considerable augmentation of anti-mite IgE antibody formation. The enhancing activity of autologous T cells was not observed when B cells were irradiated at 1,000 rad. The spontaneous IgE antibody production by B cells alone was radioresistant. Both mitotic inhibitors and 1,000 to 2,000 rad of gama-irradiation did not significantly suppress the spontaneous anti-mite IgE antibody production by B cells.

Antigens↗

[Immunopharmacological actions of neurotropin. (1). Immunostimulating actions of neurotropin (author's transl)].

Neurotropin (NSP) is an extract isolated from vaccinia virus-inoculated and inflamed skin of rabbits. The present study was undertaken to examine the immunostimulating actions of NSP. NSP alone did not induce a proliferation of spleen cells from mice or human peripheral blood lymphocytes (PBL). However, NSP clearly enhanced concanavalin A (Con A)-induced proliferation of both spleen cells and human PBL, but slightly inhibited lipopolysaccharide (LPS)-induced proliferation of spleen cells. NSP reversed the decreases of Con A-induced proliferation of spleen cells pretreated with mitomycin C (MMC) in a dose of 5 microgram/ml or irradiated at 100 to 500 R, while NSP did not reverse the decreases of LPS-induced proliferation of spleen cells pretreated with MMC, in a dose of 5 to 50 microgram/ml, or irradiated at 100 to 1000 R. NSP enhanced in a dose-dependent fashion one-way mixed lymphocytes culture (MLC) reaction using MMC-treated spleen cells from BDF1 mice as stimulator cells and those from C57BL/6 mice as responder cells, respectively. NSP reversed the considerable decrease of MLC-mediated proliferation of responder cells pretreated with MMC, in a dose of 5 to 10 microgram/ml, or irradiated at 100 to 250 R. These results indicate that NSP activates T cell function participating in cell-mediated immunity.

Adjuvants, Immunologic↗

[Immunopharmacological actions of neurotropin (3): Anti-allergic actions of neurotropin (author's transl)].

Neurotropin (NSP) is an extract isolated from vaccinia virus-inoculated and inflamed skin of rabbits. The anti-allergic actions of NSP were studied in the present paper. Death from anaphylactic shock in BALB/c mice mediated by active systemic anaphylaxis (ASA) or heterologous passive systemic anaphylaxis (PSA) was completely prevented in one of five cases by NSP given 5000 micrograms/animal i.v.. However in mice, NSP at a dose of 10 to 1000 micrograms/animal i.v. did not have any preventive effect on death from anaphylactic shock induced by ASA, homologous PSA, or heterologous PSA. NSP slightly inhibited histamine release from rat mast cells mediated by mouse IgE antibody, calcium ionophore A23187, or compound 48/80, but this inhibition was not in a dose-dependent fashion. NSP did not behave synergistically with isoproterenol- or theophylline- induced inhibition of mouse IgE antibody-mediated histamine release from rat mast cells. NSP did not inhibit D2O-enhanced histamine release from sensitized rat mast cells. NSP clearly inhibited antigen-induced histamine release from leukocytes of mite-sensitive patients with or without asthmatic attack. Potent inhibition was observed when leukocytes taken from patients with asthmatic attack were used. These results suggest that the anti-allergic action of NSP is not responsible for elevation of cyclic AMP levels or disruption of microtubules in target cells.

Anaphylaxis↗

[Immunopharmacological actions of neurotropin. (2). Effect of neurotropin on graft-versus-host reaction (author's transl)].

It was reported that Neurotropin (NSP) is a new immunostimulating agent which reverses the decrease of proliferation of irradiated spleen cells from mice caused by concanavalin A or specific antigen. The present study was undertaken to examine the possibility that NSP prevents graft-versus-host reaction (GVHR) through host-versus-graft reaction (HVGR) in mice. Allogeneic (C3H/He) spleen cells were performed intravenously into 900 R-irradiated recipient mice (BALB/c). Systemic GVHR was clearly prevented by NSP as well as by cyclophosphamide or prednisolone administered intraperitoneally into irradiated recipient mice. In recipient mice irradiated with 1000 R, a more remarkably systemic GVHR was induced as compared to recipients irradiated at 250 to 500 R. NSP suppressed the proliferation of donor cells at the induction phase of GVHR, whereas NSP did not inhibit both systemic and local GVHRs induced by cell transfer at the effector phase. A decrease in hematopoietic function following irradiation or dosing with immunosuppressive drugs was also reversed by NSP. However, NSP had no effect on increases in hematopoietic function mediated by syngeneic bone marrow transplantation into 900 R-irradiated mice. These results strongly suggest that the inhibition of allogeneic GVHR by NSP is responsible for the suppression of donor cell proliferation by adequately restoring immunologic function in irradiated recipient mice, namely HVGR.

Adjuvants, Immunologic↗

Inhibition of homologous passive cutaneous anaphylaxis (PCA) by disodium cromoglycate-related compounds.

A study was conducted to examine the effect on homologous PCA in rats of 14 different, newly synthesized compounds, given orally, in relation to the chemical structure of DSCG, when given orally on homologous PCA in rats. The structure-activity relationship of these compounds was also discussed. Among the 7 compounds of the glycerol bischromenonyl ether derivatives, 1,3-bis (2-phenyl-4-chromenon-5-yl) oxypropane-2-ol (compound 1) showed the most potent inhibitory activity on PCA. The other compounds showed a moderate or no effect. Two compounds of glycerol bisphenyl ether derivatives had little effect. On the other hand, 1,3-bis (2-carboxy-3-hydroxyphenyl)oxypropane (compound 11) out of alkandiol bisphenyl ether derivatives significantly inhibited PCA, and the other 4 compounds showed a tendency toward inhibition of the reaction. The late inhibition, seen in the biphasic inhibitory pattern induced by compound 11, may be caused by a certain active substance transformed in the body.

Animals↗

[Immunopharmacological study of buckwheat hypersensitivity (author's transl)].

Effect of dialysate from buckwheat extract on immediate hypersensitivity reactions. To investigate the hypersensitivity reaction of buckwheat, the aqueous extract of buckwheat was separated into dialysate (BWD) and non-dialysate (BWND). BWD neither decreased a release of anaphylactic mediator from the chopped lung tissue nor inhibited Schultz-dale reaction in the ileum of guinea pig sensitized with BWND. Heterologous PCA mediated by rabbit anti-BWND serum in guinea pig and homologous PCA in rats using anti-BWND IgE serum were inhibited by i.d. or i.v. treatment of BWD. Radioallegosorbent test (RAST) and PK reaction were inhibited in a dose dependent fashion by BWD mixed with human serum sensitive to buckwheat, although BWD required approximately 10,000 times more than BWND to produce a RAST inhibition. RAST, however, was not affected when BWD was added to 125I-labelled anti-human IgE. Anti-buckwheat IgE antibody in sensitized animals and atopic patients was specifically absorbed with an insoluble copolymer of BWD-conjugated BSA. BWD did not form a precipitin line against anti-BWND IgG antibody in immunoelectrophoresis. Rat IgE serum-induced degranulation and histamine release from mast cells were inhibited in a dose dependent fashion by BWD and the inhibition was specific to anti-BWND IgE antibody. BWD may be useful as an hyposensitization agent in buckwheat hypersensitivity, since BWD is a haptenic substance capable of neutralizing specific IgE antibody on mast cells.

Anaphylaxis↗

[Immunopharmacological study of buckwheat hypersensitivity III. Effect of dialysate-conjugated T cell mitogen on IgE formation (author's transl)].

It has already been reported that dialysate (BWD) separated from the aqueous extract of buckwheat is a haptenic substance capable of neutralizing specific IgE antibody both on mast cells and on B cells in some species. The present work represents a study carried out to determine the effect of BWD conjugated with T cell mitogen such as phyothemagglutinin-P (PHA) and concanavalin A (Con A) on IgE formation in mice. Anti-buckwheat IgE formation was little affected by the pretreatment of these conjugates given i.v. 3 days before the immunization, but was effectively suppressed by the pretreatment of BWD-PHA or BWD-Con A given i.p. together with incomplete Freund's adjuvant 2 weeks before the immunization. BWD-PHA induced a more potent suppression of IgE formation as compared with BWD-Con A, Con A or PHA. The transfer of T cells obtained from spleen cells primed with BWD-PHA, which responded with buckwheat and exerted a slight helper function for adoptive anti-DNP IgE formation to DNP-buckwheat, suppressed anti-buckwheat IgE formation in recipients with no effect on the anti-KLH IgE response. Our findings suggest that suppressor T cells specific to buckwheat are induced in spleen cells of mice treated with BWD-PHA.

Animals↗

[Immunopharmacological study of buckwheat hypersensitivity (II). Effect of dialysate on antibody formation (author's transl)].

It was reported that dialysate (BWD) separated from the aqueous extract of buckwheat was a haptenic substance capable of neutralizing IgE antibody on mast cells and that the activity was specific to non-dialysate (BWND)-induced hypersensitivity reaction. The effect of BWD on antibody formation was investigated in the present paper. In rats, anti-buckwheat IgE formation was slightly depressed by the administration of BWD, but both anti-DNP IgE and IgG formations in rats immunized with DNP-BWND were unaffected. In mice, anti-buckwheat IgE formation was suppressed by BWD administration. A good correlation was noted between a decrease of surface IgE population on B cells and that of IgE titer in serum. However, the helper function of T cells for adoptive anti-DNP IgE formation was little affected by BWD treatment. Lymphocyte transformation to BWND and other non-specific mitogens using spleen cells obtained from sensitized mice was inhibited in a dose-dependent fashion by the addition of BWD. However, lymphocyte transformation using spleen cells pretreated with BWD was not affected by other non-specific mitogens except for BWND and pokeweed mitogen.

Animals↗