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Biomedical subjects

T Shida

Publications and source records attributed to T Shida.

At least 55 records · Page 3Linked to original sources
PubMed1988

Effect of deuterium oxide on leukotriene C4 generation in immunologically stimulated human leukocytes.

Addition of deuterium oxide (D2O), 6-36%, resulted in a dose-dependent increase in allergen- or anti-IgE-induced leukotriene C4 (LTC4) generation from human basophils. In the presence of 36% D2O, the enhancement was 260 +/- 135% for allergen stimulation and 480 +/- 152% for anti-IgE stimulation as compared with the control incubated in normal buffer. The increasing effect of D2O on LTC4 generation from basophils was completely reversed by washing the cells before incubation with allergen. Vinblastine as well as colchicine, at a concentration of 100 microM, counteracted the effect of D2O. The enhanced release of histamine and LTC4 from basophils challenged with allergen was suppressed by Dimaprit, a histamine H2 receptor agonist, at a concentration required to inhibit the release by 50% of 5 X 10(-5) M for histamine and 10(-5) M for LTC4. These observations suggest that microtubules may be involved in LTC4 generation from immunologically stimulated basophils.

Basophils↗
PubMed1988

Augmentation of leukotriene C4 production by gamma interferon in leukocytes challenged with an allergen.

Leukocytes from mite-sensitive asthmatic patients were challenged with an allergen and the supernatant assayed for histamine, immunoreactive leukotriene C4 (i-LTC4), and gamma-interferon (gamma-IFN). In addition, the concentration of gamma-IFN in the plasma of patients with bronchial asthma was assayed. Significantly higher concentrations (p less than 0.01) of gamma-IFN were detected in patients' plasma (0.27 +/- 0.32 U/ml, n = 61) than in that of healthy controls (0.04 +/- 0.06 U/ml, n = 19). The leukocytes produced 7.3 +/- 6.7 ng of i-LTC4/10(6) basophils (n = 32), and histamine release was 41.1 +/- 37.1% of total histamine. There was a significant correlation (p less than 0.01) between the capacity of leukocytes to release i-LTC4 and gamma-IFN. The capacity of leukocytes to release histamine and to produce gamma-IFN was not significantly correlated (r = 0.263). About twice as much i-LTC4 was generated from leukocytes pretreated for 24 h with 0.1-1.0 U/ml of recombinant human gamma-IFN, but histamine release was not changed. Another type of IFN, alpha-IFN, did not alter the capacity of leukocytes to release histamine as well as gamma-IFN upon preincubation for 24 h at 1-1,000 U/ml. Pretreatment with 1-10 U/ml of beta-IFN slightly enhanced the capacity upon challenge with 10 ng/ml of mite allergen. The enhancing effect of gamma-IFN on i-LTC4 generation was decreased by treatment with H-7, a nonspecific inhibitor of protein kinase C activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗
PubMed1988

[Antiallergic effects of mequitazine. 1. In vitro experiments].

The antiallergic effects of 10-(3-quinuclidinylmethyl)phenothiazine (mequitazine) were investigated in vitro. The results obtained were as follows: 1) In the isolated trachea and lung parenchyma of guinea pigs, mequitazine showed a fairly potent antagonistic action against contractions induced by both histamine (Hi) and acetylcholine (ACh). Mequitazine was much less potent in antihistaminic action and slightly more potent in anticholinergic action than ketotifen. The contractions of the preparation by leukotriene (LT) D4 were antagonized by mequitazine, although the potency was moderate, showing an IC50 value of 2.3 x 10(-5) g/ml in the trachea and 5.1 x 10(-5)g/ml in the lung parenchyma. Mequitazine had no effect on the contraction of the trachea by PGF2 alpha, but inhibited that of the lung parenchyma with pA2 = 7.0. 2) Mequitazine (10(-6) g/ml) slightly inhibited the Schultz-Dale reaction of the isolated guinea pig trachea, while ketotifen at the same concentration did not show any effect. 3) The contraction of the isolated guinea pig trachea by Ca2+ influx was slightly inhibited by mequitazine (10(-5) g/ml). 4) Mequitazine competitively inhibited the cyclic AMP-dependent phosphodiesterase activity from the rat lung with a potency of 10 times and 5 times more than those of ketotifen and theophylline, respectively. 5) Mequitazine (10(-6) to 10(-5) M) suppressed both the anaphylactic and phospholipase A2-induced histamine release from the peritoneal cells of rats. 6) Mequitazine (10(-5) g/ml) also inhibited the anaphylactic and Ca ionophore-induced histamine release from the leukocytes of the atopic patients and normal subjects. 7) The anaphylactic releases of histamine, LTB4 and peptide LT from the human lung fragments were dose-dependently inhibited by mequitazine (10(-7) approximately 10(-5) g/ml).

Acetylcholine↗
PubMed1988

[Antiallergic effects of mequitazine. 2. In vivo experiments].

Antiallergic effects of mequitazine were investigated in vivo and compared with those of ketotifen and disodium cromoglycate (DSCG). The results obtained were as follows: 1) Mequitazine in doses of 2 and 5 mg/kg given, p.o., 1 hr prior to antigen challenge inhibited dose-dependently the 48-hr passive cutaneous anaphylaxis in rats. Five mg/kg of mequitazine showed almost the same extent of inhibitory activity as that of 1 mg/kg of ketotifen. An i.v. administration of 1 mg/kg DSCG 1 min before antigen challenge also showed a marked inhibition. 2) The experimental asthma induced by challenge with an i.v. injection of antigen in passively sensitized guinea pigs was fairly inhibited by the pretreatment with 5 mg/kg of mequitazine administered p.o., although 2 mg/kg of this drug showed only a slight inhibition. 3) The experimental asthma induced by aerosolized antigen was also fairly inhibited by the pretreatment with 5 mg/kg of mequitazine given p.o.

Administration, Oral↗
PubMed1988

Immunopharmacological studies on TBX, a new antiallergic drug (2). Inhibitory effects on histamine release from peritoneal mast cells and lung fragments of rats.

The ability of 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one potassium salt (TBX) to inhibit histamine release from both peritoneal exudate cells (PEC) containing mast cells and lung fragments of rats was investigated in vitro. Low concentrations of TBX dose-dependently inhibited IgE-mediated histamine release from PEC of passively sensitized animals; its IC50 was 5.1 x 10(-9) g/ml. When TBX was added simultaneously with the antigen challenge, the highest inhibition was obtained. In contrast, extension of preincubation time with the agent resulted in a marked decrease in the inhibition of histamine release. The potent inhibition of histamine release by TBX was observed equally in glucose-free as well as complete Tyrode's solution, whereas TBX reduced its inhibitory action in Ca2+-free or D2O-supplemented medium. In addition, TBX inhibited compound 48/80- but not calcium ionophore A23187-induced histamine release from normal PEC. With regard to the intracellular cyclic AMP level in normal PEC, it was significantly enhanced by a high concentration of TBX (10(-3) g/ml). TBX also inhibited antigen-induced histamine release from lung fragments of actively immunized animals. Interestingly, TBX displayed non-competitive inhibition of cyclic AMP-dependent phosphodiesterase derived from lung homogenates; its K1 value was 8.70 x 10(-4) M.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1988

Immunopharmacological studies on TBX, a new antiallergic drug (1). Inhibitory effects on passive cutaneous anaphylaxis in rats and guinea pigs.

The effects of 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one potassium salt (TBX), a new antiallergic drug, on passive cutaneous anaphylaxis (PCA) mediated by homologous IgE or IgG antibody were investigated in rats and guinea pigs. TBX (i.v. and p.o.) clearly inhibited IgE- and IgGa-mediated homologous PCAs in rats, without showing any inhibition of the skin reactions caused by histamine, serotonin and bradykinin in contrast to the inhibition of prostaglandin E1-induced skin reaction. Neither adrenalectomy nor propranolol treatment modified TBX's inhibition of the former PCA. With regard to tachyphylaxis to TBX, it was demonstrable in IgE-mediated homologous PCA in rats when they were pretreated with TBX (0.5 mg/kg, i.v.), followed 60 min later by a second dose of the drug (0.05 mg/kg, i.v.). There was no cross-tachyphylaxis between disodium cromoglycate (DSCG) and TBX. Homologous PCA caused by guinea pig IgE was also inhibited in a dose-dependent fashion by i.v. and p.o. administrations of TBX, although higher doses of TBX were needed to inhibit guinea pig PCA than the rat one. Interestingly, TBX showed more potent inhibition of both rat and guinea pig homologous PCAs than DSCG or tranilast. The results obtained indicate that TBX is an orally effective antiallergic agent displaying no antagonistic actions on the chemical mediators released.

Animals↗
PubMed1988

Immunopharmacological actions of the new antiallergic drug butyl 3'-(1H-tetrazol-5-yl)oxanilate. 2nd communication: inhibitory effects on histamine release from rat mast cells and lung fragments.

The effects of butyl 3'-(1H-tetrazol-5-yl)oxanilate (WP-833), a new antiallergic drug, on its ability to inhibit histamine release from both peritoneal mast cells and lung fragments of rats were investigated. WP-833 inhibited in a dose-dependent fashion immunoglobulin E (IgE)-mediated histamine release from mast cells. Such potent inhibition was observed in glucose-free as well as complete Tyrode's solution but neither in Ca2+-free nor D2O-supplemented Tyrode's solution. In addition, WP-833 significantly increased intracellular cyclic adenosine monophosphate (AMP) levels in purified mast cells. On the other hand, WP-833 inhibited compound 48/80-but not calcium ionophore A23187-induced histamine release from normal mast cells. Also both IgE- and IgG-mediated histamine release from lung fragments were inhibited by WP-833. WP-833 showed non-competitive inhibition of cyclic AMP-dependent phosphodiesterase derived from lung preparations.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1988

Immunopharmacological actions of the new antiallergic drug butyl 3'-(1H-tetrazol-5-yl)oxanilate. 3rd communication: inhibitory effects on histamine release from lung fragments, Schultz-Dale reaction in isolated tracheal muscle and experimental asthma in guinea pigs.

The inhibitory effects of butyl 3'-(1H-tetrazol-5-yl) oxanilate (WP-833), a new antiallergic drug, on histamine release from lung fragments, Schultz-Dale (SD) reaction in isolated tracheal muscle and experimental asthma were investigated in guinea pigs passively sensitized with homologous immunoglobulin E (IgE) serum. WP-833 dose-dependently inhibited antigen-induced histamine release from lung fragments. In addition, synergism as to inhibition of histamine release was observed with a combination of WP-833 and isoprenaline but not with that of WP-833 and theophylline. WP-833 also inhibited antigen-mediated SD reaction of isolated tracheal muscle without showing antagonistic actions upon histamine- and leukotriene D4-induced contraction of normal tracheal muscle. Experimental asthma was clearly inhibited in a dose-dependent fashion by oral administration of WP-833.

Animals↗
PubMed1988

Immunopharmacological actions of the new antiallergic drug butyl 3'-(1H-tetrazol-5-yl)oxanilate. 4th communication: effects on histamine release from human leukocytes and from human and monkey lung fragments.

The effects of butyl 3'-(1H-tetrazol-5-yl)oxanilate (WP-833), a new antiallergic drug, on histamine release from human leukocytes and from human and monkey lung fragments were investigated. WP-833 showed no inhibition of antigen, anti-immunoglobulin E (IgE)- and calcium ionophore A23187-induced histamine release from leukocytes of atopic patients allergic to house dust mite. In addition, no influences of WP-833 on the levels of cyclic adenosine monophosphate and guanosine monophosphate in leukocytes from healthy subjects were observed. However, antigen- or anti-IgE-mediated histamine release from human and monkey lung fragments passively sensitized in vitro with human serum IgE sensitive to mite antigen was clearly inhibited by WP-833. Interestingly, prolonged pretreatment of lung fragments with WP-833 resulted in a decay in inhibition of anaphylactic histamine release. Spontaneous histamine release from human leukocytes and monkey lung fragments were not inhibited by WP-833.

Animals↗
PubMed1988

Immunopharmacological actions of the new antiallergic drug butyl 3'-(1H-tetrazol-5-yl)oxanilate. 1st communication: effects on type I to type IV allergic reactions in animal models.

The effects of butyl 3'-(1H-tetrazol-5-yl)oxanilate (WP-833), a new antiallergic drug, on type I to type IV allergic reactions were investigated by employing various animal models. WP-833 (i.v. and p.o.) dose-dependently inhibited homologous or heterologous passive cutaneous anaphylaxis (PCA) mediated by rat or mouse immunoglobulin E (IgE) in rats. Homologous PCA caused by guinea pig IgE was also inhibited by WP-833. In addition, WP-833 had inhibitory actions upon homologous PCA induced by rat or guinea pig IgG. However, WP-833 showed no inhibition of rat skin reactions caused by histamine, serotonin and bradykinin, contrasting with the inhibition of prostaglandin E1-induced skin reaction. Furthermore, both adrenalectomy and propranolol treatment exerted no influences on the inhibition of IgE-mediated homologous PCA in rats by WP-833. In contrast to above findings demonstrating that WP-833 clearly inhibited type I allergic reaction, systemic Forssman shock in guinea pigs and reversed cutaneous anaphylaxis in rats (type II), passive Arthus reaction in rats (type III), and contact dermatitis and tuberculin reaction in mice (type IV) were unaffected by WP-833 even in higher doses than in those capable of completely inhibiting type I allergic reaction.

Adrenalectomy↗
PubMed1988

Immunopharmacological actions of the new antiallergic drug butyl 3'-(1H-tetrazol-5-yl)oxanilate. 5th communication: effects on immunological reactions in mice and humans.

The effects of butyl 3'-(1H-tetrazol-5-yl)oxanilate (WP-833), a new antiallergic drug, on immunological reactions in mice and humans were studied in view of possible side effects. Hemagglutinin formation in mice immunized with sheep red blood cells was not suppressed by WP-833 administered i.p. or p.o. for 3 days either before or after immunization. In addition, the same treatments with WP-833 showed no suppression of hapten-specific immunoglobulin E (IgE) or immunoglobulin G (IgG) antibody formation in mice immunized with dinitrophenyl-conjugated ovalbumin mixed with alum. The proliferation of human peripheral blood lymphocytes induced by concanavalin A, phytohemagglutinin-P, pokeweed mitogen, protein A or Cowan I was not suppressed by WP-833. Nitroblue tetrazolium reduction test, phagocytosis and chemotaxis in human neutrophils were not inhibited by WP-833.

Animals↗
PubMed1987

Enhancement of IgE synthesis and histamine release by T cell factors derived from atopic patients with bronchial asthma.

Culture supernatants of unstimulated T cells (TCS) derived from normal donors or from atopic patients with bronchial asthma were tested for their ability to regulate the spontaneous IgE synthesis by B cells of normal and atopic subjects. The same TCS were also tested for their influence on the histamine release from leukocytes of house dust mites-sensitive patients. Addition of TCS to B cell cultures from allergic donors induced a dose-dependent increase of the spontaneous IgE production without affecting the synthesis of IgG, IgM, and IgA. The potentiating activity of TCS was observed only in B cell cultures spontaneously producing IgE; TCS were still active on irradiated B cells. The maximal IgE-enhancing activity was observed when TCS were added at the onset of B cell cultures. The supernatants of T cells lysed at day 0 did not contain IgE-potentiating factors. The antigen-induced but not the spontaneous histamine release from leukocytes of house dust mite-sensitive patients was enhanced by pretreatment with TCS from allergic donors. The enhancing activities of TCS on IgE synthesis and on histamine release could be removed by absorption with IgE-Sepharose and subsequently recovered by elution with glycine buffer. The results indicate that T cells of patients with asthma spontaneously release IgE-binding factors capable of increasing both the spontaneous IgE synthesis by B cells and the antigen-induced histamine release.

Asthma↗
PubMed1987

Modulation of IgE synthesis by IgE-binding factors released by T cells of asthmatic patients with elevated serum IgE.

The culture supernatants of unstimulated T cells (TCS) from asthmatic patients with elevated serum IgE were tested for IgE-binding factors (IgE-BFs) displaying the IgE-potentiating activity. The IgE-BFs were detected by their ability to inhibit the rosetting of RPMI 8866 cells with ox erythrocytes coupled with mouse monoclonal antibody (E-Mab) specific to Fc receptors for IgE (Fc epsilon R). TCS showing the rosette-inhibiting activity significantly enhanced the spontaneous IgE synthesis by B cells of allergic individuals. Interestingly, rosette-inhibiting factors could be removed by absorption with IgE-Sepharose from which they were subsequently eluated with acid buffer, indicating that the rosette inhibition was indeed mediated by IgE-BFs. In addition, such IgE-BFs had affinity for concanavalin A and lost their IgE-potentiating activity after treatment with trypsin and neuraminidase. In contrast, T cells treated with tunicamycin released IgE-suppressing factors capable of inhibiting the IgE-potentiating activity of TCS derived from untreated T cells. On the other hand, the culture supernatants from subpopulations depleted of Fc epsilon R+ T cells but not of Fc gamma R+ T cells contained neither rosette-inhibiting factors nor IgE-potentiating factors, suggesting that IgE-BFs were released by in vivo pre-activated Fc epsilon R+ T cells. With regard to circulating Fc epsilon R+ T cells determined by E-Mab, they were significantly higher in asthmatic patients with elevated serum IgE (0.77 +/- 0.15%) than in normal subjects (0.17 +/- 0.07%) in spite of a very small proportion of T cells bearing Fc epsilon R.

Asthma↗
PubMed1987

Effect of human interferon on different functions of human neutrophils and eosinophils.

The capacity of neutrophils treated with interferon to release peroxidase or superoxide anion was increased when the cells were stimulated with opsonized zymosan, while it was decreased in eosinophils. The effect of treatment with interferon was thought to be mediated by a change in expression of C3b receptors on the neutrophils or eosinophils. The production of a slow-reacting substance of anaphylaxis by eosinophils stimulated with opsonized zymosan or human IgG-coupled Sepharose 4B beads was markedly enhanced after incubation with interferon. Therefore it is suggested that interferon may play a role in the worsening of the condition in patients with bronchial asthma.

Asthma↗