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Biomedical subjects

A Koda

Publications and source records attributed to A Koda.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effects of nicotine and exposure to cigarette smoke on suppression of local graft-versus-host reaction induced by immobilization stress in mice.

To study the effects of emotional stress on immunological activities and modification of these effects by nicotine or cigarette smoke, we evaluated the effects of immobilization stress on local graft-versus-host (GVH) reaction, a cell-mediated immune response, and the effects of nicotine and cigarette smoke on them. The effects of immobilization stress on GVH reaction and the effects of nicotine and cigarette smoke on them were evaluated in two experiments: in Experiment 1 by applying the stimulations before and immediately after spleen cell transplantation, and in Experiment 2, by applying stimulations after transplantation. Spleen cells of BALB/C mice were injected into the footpad of CBF1 mice, and GVH reaction was examined after 7 days by weighing the popliteal lymph nodes. Immobilization, nicotine administration and inhalation of cigarette smoke were performed either for 5 days before and immediately after the transplantation (Experiment 1) or for 5 days after transplantation (Experiment 2). The weight of the lymph nodes was markedly increased in the control group, indicating GVH reaction, but the reaction was suppressed by immobilization in both experiments. This suppression of GVH reaction by immobilization was antagonized by nicotine administration and exposure to cigarette smoke in Experiment 1 but not in Experiment 2. These findings suggest that nicotine and cigarette smoke induce recovery of immune response suppressed by immobilization stress, especially by increasing the competence of antigen recognition.

Animals↗
PubMed1995

A similarity and a difference between two models of late eosinophil accumulation into the airway induced by antigen exposure in actively sensitized brown Norway (BN) rats.

1. Exposure of sensitized Brown Norway (BN) rats to ovalbumin aerosol induced a remarkable and a sustained accumulation of eosinophils into broncho-alveolar lavage (BAL) fluid. 2. When male BN rats, sensitized by i.m. injection of ovalbumin and i.p. injection of killed Bordetella pertussis, were exposed to the antigen on day 14, eosinophils accumulated into BAL fluid, maximal 48 hr after antigen exposure. This accumulation of eosinophils was inhibited completely by administration of cyclosporin A (Cs A, 50 mg/kg/day) during induction phase, whereas it was inhibited slightly by administration of CsA (50 mg/kg) during the effector phase. 3. When BN rats were sensitized by weekly exposure of ovalbumin, eosinophils accumulated into BAL fluid, maximal 48 hr after the third exposure of antigen. The accumulation of eosinophils by this method was observed only in female rats and was inhibited completely by administration of CsA (50 mg/kg) during induction phase, whereas it was inhibited slightly by administration of CsA (50 mg/kg) during effector phase. 4. The present study demonstrates similarities and differences between two models of eosinophilia and also suggests increased function of T cells in BN rats.

Aerosols↗
PubMed1995

Principle of the bark of Phellodendron amurense to suppress the cellular immune response: effect of phellodendrine on cellular and humoral immune responses.

Previously we have isolated the quaternary base alkaloids, magnoflorine and phellodendrine, from Phellodendri Cortex (cortex of Phellodendron amurense Rupr., Rutaceae) as the biologically active principles to suppress local graft-versus-host (GvH) reactions in mice. In this paper, we focus on phellodendrine. Phellodendrine suppressed local semisyngeneic GvH reactions and systemic allogeneic GvH reactions in X-ray irradiated recipient mice. Phellodendrine also suppressed the induction phase of sheep red blood cell (SRBC)-induced delayed type hypersensitivity in mice and tuberculin-induced delayed type hypersensitivity in guinea pigs, but did not suppress the effector phase of these reactions. Surprisingly, phellodendrine, unlike prednisolone and cyclophosphamide, did not affect antibody production in mice to SRBC. Phellodendrine was expected to be a valuable new type of immunosuppressor against the cellular immune response.

Animals↗
PubMed1995

Suppressive effects of tranilast on pulmonary fibrosis and activation of alveolar macrophages in mice treated with bleomycin: role of alveolar macrophages in the fibrosis.

We have reported that tranilast, an anti-allergic drug that inhibits chemical mediator release from mast cells, suppresses bleomycin (BLM)-induced pulmonary fibrosis in mice through mechanisms other than inhibiting chemical mediator release from mast cells. The purpose of this paper is to examine the effect of tranilast on alveolar macrophage (AM) activation and on the development of fibrosis in ICR mice instilled with BLM intratracheally. Twenty eight days after the BLM instillation (0.01 mg/mouse), AM often migrated into alveolar spaces surrounding the fibrotic areas. Flow cytometry analysis for the size and density of AM (MAC-1 positive cells) suggested that AM were activated not only in the earlier acute inflammatory phase, but also in the later chronic phase. The p.o. administration of tranilast suppressed an increase of AM activity to produce reactive oxygen species in BLM-instilled mice, and it inhibited the subsequent development of pulmonary fibrosis. In vitro treatment with tranilast suppressed the reactive oxygen species production from murine peritoneal macrophages. However, several different anti-oxidants failed to inhibit the development of fibrosis. These results suggest that the activation of AM plays an important role in the development of fibrosis, and it is likely that tranilast suppresses fibrosis by inhibiting AM activation but not by scavenging reactive oxygen species.

Administration, Oral↗
PubMed1994

Novel lowly immunosuppressive antitumor fluorouridine derivative, UK-21: antitumor activity and effect on humoral immune response in mice.

Our previous studies indicated that a newly synthesized 5-fluorouridine derivative, 2',3',5'-tris-O-[N-(2-n-propyl-n-pentanoyl)glycyl]-5-fluorouridine (UK-21), revealed its antitumor activity by being converted to 5-fluorouridine (5-FUR) and showed a low level of immunological side effects. However, the bioavailability of UK-21 given orally did not seem to be good. In the present study, we focused on the antitumor and immunosuppressive activities of UK-21 given i.p. to mice. UK-21 suppressed the growth of L-1210, P388 and EL4 leukemias inoculated i.v. into corresponding syngeneic mice and both the growth of Lewis lung carcinoma transplanted s.c. and its subsequent metastasis to the lung. UK-21 showed antitumor activity at doses almost 10 times lower than those of 5-fluorouracil (5-FU). The side effects of UK-21, especially on immune functions, were examined in comparison with those of 5-FUR, 5-FU, and cyclophosphamide (CY) at doses producing comparable antitumor activity. The suppressive effect of UK-21 on IgM and IgG antibody formation in mice immunized with ovalbumin was clearly weaker than that of 5-FUR, 5-FU, and CY. The suppressive effect of UK-21 on thymus weight was markedly weaker than that of 5-FU and CY. The reduction of WBC counts induced by UK-21 was also lower than that produced by any other agent. The results reported herein suggest the strong possibility of UK-21 being developed as a novel anticancer drug with cytotoxic mechanisms different from those of 5-FU. Our study also points to the chemical modification of 5-FUR as a feasible way of developing new anticancer drugs.

Analysis of Variance↗
PubMed1994

Potentiation of antigen-induced histamine release from rat peritoneal mast cells through a direct interaction between mast cells and non-mast cells.

Rat peritoneal mast cells, which had been sensitized two days earlier by an intraperitoneal injection of rat monoclonal IgE antibodies, were purified by density gradient centrifugation with 60% Percoll (cell purity > 95%). Histamine release from the purified mast cells (PMC) was then compared to that of a non-purified preparation (peritoneal exudate cells; PEC). Both PEC and PMC released similar amounts of histamine upon stimulation with calcium ionophore A23187 and compound 48/80. In contrast, antigen-induced histamine release from PMC was very low compared to that of PEC. PEC released up to 30% of total histamine upon challenge with 1 microgram/ml of antigen, whereas histamine release from PMC was only one third or less than that of PEC. When PEC was suspended in 60% Percoll and treated for a period needed for purification, the reduction of antigen-induced histamine release was negligible. Mast cells purified by centrifugation on a metrizamide gradient released only small amount of histamine similar to Percoll-purified mast cells. Non-mast cells (NMC) recovered from the interface of the 60% Percoll potentiated the antigen-induced histamine release from PMC concentration- and time-dependently. The supernatant of the NMC suspension which was incubated at 37 degrees C for 60 min, however, failed to potentiate histamine release in PMC. We concluded therefore that separation media such as Percoll and metrizamide do not cause the low antigen-induced histamine release in PMC, but that the separation of mast cells from other cells present in the peritoneal cavity itself causes it. Antigen-induced mast cell histamine release is potentiated through a direct interaction between mast cells and NMC, and some cell surface molecules also seem to be involved.

Animals↗
PubMed1994

Principle of the bark of Phellodendron amurense to suppress the cellular immune response.

We previously reported that Wen-Qing-Yin (Unsei-in), a traditional Chinese blended medicine, inhibited the induction phase of various kinds of delayed type hypersensitivity (DTH) and local graft-versus-host (GvH) reactions, but did not affect humoral immune responses or the effector phase of DTH in experimental animals. In another report, we demonstrated that Phellodendri Cortex (bark of Phellodendron amurense Rupr. Rutaceae) was a component having the most potent suppressive effect on the cellular immune response among the 8 medical plants composing Unsei-in. In the present study, we isolated OB-1 and OB-5 from Phellodendri Cortex as the biologically active principles to suppress local GvH reactions in mice. OB-1 and OB-5 are quaternary base alkaloids known as magnoflorine and phellodendrine, respectively. They suppressed the local GvH reaction, when given i.p. to the host mice at 5-20 mg/kg for 8 consecutive days from the day of spleen cell transfer to cause the reaction. Both OB-1 and OB-5 suppressed picryl chloride-induced delayed type hypersensitivity (PC-DTH) when given i.p. to mice at 10 and 20 mg/kg for 5 consecutive days from the day of the sensitization, but did not suppress it when given at the time of the challenge. These results suggest that OB-1 and OB-5 suppress the induction phase but not the effector phase of the cellular immune response. They are expected to have a value as a new type of immunosuppressor.

Analysis of Variance↗
PubMed1994

Mechanism for macrophage activation against Corynebacterium parvum--participation of T cells and its lymphokines.

It is well known that Corynebacterium parvum activates macrophages to produce tumor necrosis factor (TNF). It is suspected that the activation of macrophages by C. parvum requires T-cell participation. The purpose of this study was to confirm that T cells participate in the activation of macrophages by C. parvum. TNF production in vitro from the spleen cells of BALB/c(-)+/+ mice was abrogated completely by the pre-treatment of spleen cells with anti-Ia antiserum and complement, indicating that Ia+ cells are the source of TNF. TNF production was not elicited at all in BALB/c-nu/nu mice. However, there was an increase in the number of Ia+ cells as well as an increase in the weight of spleen and liver. Supernatant from a culture of spleen cells stimulated with phytohemagglutinin-P (a PHA-induced lymphokine) made it possible for BALB/c-nu/nu mice to produce TNF, associated with an induction of Lyt-1+ cells and Lyt-2+ cells. However, treatment with the lymphokine did not augment the increases of Ia+ cells or liver and spleen weights. These results suggest that increasing the number of Ia+ cells is not sufficient to bring about TNF production; Ia+ cells must also be stimulated by T cells or T-cell lymphokines in order to produce TNF. These results suggest that T cells play an essential role in the activation of Ia+ cells against C. parvum.

Animals↗
PubMed1993

Priming with murine recombinant interleukin-5 resulted in the augmentation of PAF-induced airway hyperresponsiveness to histamine in guinea pigs.

The effects of pretreatment with murine recombinant interleukin 5 (mrIL-5) on platelet activating factor (PAF)-induced bronchoconstriction and airway hyperreactivity were investigated in guinea pigs. The intratracheal administration of mrIL-5 (2.5-10 micrograms) augmented platelet activating factor (PAF; 50 ng/kg)-induced bronchoconstriction in guinea pigs. When IL-5 (2.5 micrograms) was injected intratracheally, PAF (25 ng/kg)-induced bronchoconstriction was not affected, but PAF-induced airway hyperresponsiveness to histamine was exacerbated. Airway inflammation, in terms of increased capillary permeability and the accumulation of leukocytes in bronchoalveolar lavage fluid, was not produced by pretreatment with PAF (25 ng/kg), mrIL-5 (2.5 micrograms), or by a combination of these agents. This mrIL-5-induced augmentation of airway hyperreactivity by PAF was clearly inhibited by the phosphodiesterase-type III inhibitors, SDZ-MKS-492 and AH 21-132, but not by aminophylline.

Aminophylline↗
PubMed1993

Effect of TYB-2285 on histamine release from human basophils in the presence/absence of IL-3.

1. The present study was carried out to investigate the effect of TYB-2285 (3,5-bis(acetoxyacetylamino)-4-chlorobenzonitrile) on histamine release from human basophils upon stimulation with anti-IgE in the presence/absence of recombinant interleukin 3 (rIL-3). 2. Histamine release was enhanced by the pretreatment of basophils with rIL-3 (0.3-10 U/ml) in 18 out of 22 subjects. 3. Histamine release in the presence of rIL-3 was inhibited by TYB-2285 and disodium cromoglycate (DSCG) in a dose-dependent manner (1-100 microM). 4. Histamine release in the absence of rIL-3 was not inhibited by TYB-2285 or DSCG at concentrations less than 1 mM. 5. From these results, it is suggested that TYB-2285 and DSCG might regulate allergic inflammation by the suppression of mediator release enhanced by IL-3.

Antibodies, Anti-Idiotypic↗
PubMed1993

Effect of TYB-2285 on antigen-induced histamine release from mouse bone marrow-derived persisting cells (P-cells) primed with interleukin-3-containing conditioned medium (IL3-CM).

1. The present study was carried out to investigate the effect of TYB-2285 [3,5-bis(acetoxyacethylamino)-4-chlorobenzonitrile] on histamine release from persisting cells (P-cells) primed with interleukin-3-containing conditioned medium (IL3-CM). 2. IL3-CM enhanced antigen-induced histamine release from P-cells, although IL3-CM did not affect spontaneous histamine release. 3. TYB-2285 inhibited antigen-induced histamine release in the presence of IL3-CM, although it did not inhibit histamine release in the absence of IL3-CM. 4. The enhancement of histamine release by IL3-CM was reproduced by recombinant IL-3 (1-100 U/ml). 5. These results demonstrate that TYB-2285 inhibits the histamine release primed with IL-3 and also suggests that TYB-2285 might regulate allergic inflammation in vivo by the suppression of mediator release primed with IL-3.

Animals↗
PubMed1993

Pharmacological model for airway hypersensitivity produced by propranolol and reserpine in guinea pigs.

Combined treatment with propranolol and reserpine enhanced acetylcholine-induced dose-response curves for bronchoconstriction in guinea pigs in vivo. This airway hyperreactivity model was investigated pharmacologically. (1) Increased capillary permeability and increases in leukocytes in bronchoalveolar lavage fluid (BALF) were not observed after this combined treatment. (2) The increased airway sensitivity to acetylcholine produced by propranolol and reserpine was inhibited by ketotifen and theophylline, reported in clinical studies to inhibit airway hyperreactivity. (3) Two leukotriene (LT) receptor antagonists, MCI-826 and FPL-55712, clearly inhibited this increased airway reactivity. (4) A thromboxane A2 (TXA2) receptor antagonist, ONO-3708, and TXA2 synthetase inhibitor, OKY-046, also inhibited this increased airway reactivity. These results suggest that the airway hyperreactivity model produced by propranolol and reserpine in guinea pigs is a valuable pharmacological tool for investigating a remedy and LT and TXA2 may be involved in the onset of this airway hyperreactivity.

Acetylcholine↗
PubMed1993

The effect of a novel thromboxane A2 (TXA2) receptor antagonist (S-1452) on the antigen-induced bronchoconstriction and airway hyperresponsiveness in guinea pigs.

The effect of a novel thromboxane A2 (TXA2) receptor antagonist (S-1452) on antigen-induced bronchoconstriction and airway hyperresponsiveness in guinea pigs was studied. Ketotifen was used as a reference drug. S-1452 at doses of 1 and 3 mg/kg (per oral administration, 1 h before the injection of U-46619) clearly inhibited U-46619-induced pulmonary pressure increase. Ketotifen at a dose of 10 mg/kg did not affect U-46619-induced bronchoconstriction. S-1452 at doses of 3 and 10 mg/kg and ketotifen at a dose of 10 mg/kg inhibited the antigen-induced bronchoconstriction in guinea pigs which had been passively sensitized with guinea pig IgE antibody. S-1452 at a dose of 10 mg/kg inhibited repeated antigen provocation-induced airway hyperresponsiveness in guinea pigs. The accumulation of inflammatory cells by antigen provocation in bronchial alveolar lavage fluid (BALF) was inhibited by ketotifen but not by S-1452. These results indicate the efficacy of S-1452 on antigen-induced bronchoconstriction and antigen-induced airway hyperresponsiveness in guinea pigs.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Effect of murine recombinant interleukin-5 on bronchial reactivity in guinea-pigs.

We have reported that an intratracheal injection of murine recombinant interleukin-5 (mrIL-5, 15 micrograms/0.25 ml/animal) induces the increased number of inflammatory leucocytes and epithelial cells in bronchoalveolar lavage fluid (BALF) 24 hr after administration of mrIL-5 in guinea-pigs [1]. In this paper, we have examined the effects of mrIL-5 on bronchial reactivity in guinea-pigs. An intratracheal injection of mrIL-5 (15 micrograms/0.25 ml/animal) induced airway hyperresponsiveness to acetylcholine (ACh) which was accompanied with eosinophilia and neutrophilia in blood at 24 hr in guinea-pigs. Bovine serum albumin (BSA, 15 micrograms/0.25 ml/animal) used as a reference material did not cause airway hyperresponsiveness, blood eosinophilia and neutrophilia. Prednisolone (20 mg/kg, i.p.) inhibited mrIL-5-induced airway hyperresponsiveness, eosinophilia and neutrophilia. Ketotifen (2 mg/kg, i.p.) also reduced this airway hyperresponsiveness and neutrophilia but not eosinophilia. In contrast, the injection of 2% disodium cromoglycate (DSCG) into the trachea showed the tendency of inhibitory effects against mrIL-5-induced airway hyperresponsiveness, eosinophilia and neutrophilia. The present data indicate that mrIL-5 induces airway hyperresponsiveness, blood eosinophilia and neutrophilia in guinea-pigs and that prednisolone and ketotifen inhibit mrIL-5-induced airway hyperresponsiveness accompanied with reduction of the increased number of leucocytes, suggesting that eosinophils and neutrophilia in blood may be important for the onset of bronchial hyperresponsiveness caused by mrIL-5 in guinea-pigs.

Animals↗
PubMed1993

Effects of NZ-107 on airway inflammation and cell activation in guinea-pigs.

The effects of NZ-107 on some airway inflammation models and the generation of superoxide anion (O2-) were studied in guinea-pigs. Airway inflammation was caused by intra-tracheal injection of murine recombinant interleukin-5 (mrIL-5, 15 micrograms/animal), inhalation of platelet-activating factor (PAF, 0.003%) and intra-tracheal injection of leukotriene B4 (LTB4, 10 micrograms/animal). NZ-107 (4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone) at a dose of 50 mg kg-1, intraperitoneally reduced mrIL-5- and PAF-induced eosinophilia. This compound at a dose of 25 and 50 mg kg-1 also suppressed LTB4-induced eosinophilia and neutrophilia in bronchoalveolar lavage fluid (BALF). On the other hand, prednisolone at a dose of 20 mg kg-1, i.p., prevented the increased number of macrophages, eosinophils and neutrophils induced by mrIL-5, the increased number of eosinophils induced by PAF and the increased number of eosinophils and neutrophils induced by LTB4 in BALF. Furthermore, both drugs reduced mrIL-5- or PAF-induced increase in the number of airway epithelial cells in BALF. The generation of O2- was measured by the method of cytochrome C reduction. NZ-107 (10-100 micrograms mL-1) attenuated PAF- and FMLP-induced O2- production from macrophages and reduced PAF-induced O2- generation by eosinophils but had no effect on that from neutrophils. These results indicate that NZ-107 prevents the increased number of pulmonary eosinophils and airway epithelial cells and the activation of macrophages and eosinophils, suggesting that NZ-107 may be useful as a remedy for airway inflammatory diseases such as bronchial asthma.

Animals↗
PubMed1993

Pharmacological modulation of antigen-induced airway hyperresponsiveness by thromboxane A2 inhibitors in guinea pigs.

The effects of OKY-046 (thromboxane A2 (TXA2) synthetase inhibitor) and ONO-3708 (TXA2 receptor antagonist) on antigen-induced airway hyperreactivity in guinea pigs were investigated. Ketotifen was used as a reference drug. Seven inhalations of an antigen into actively sensitized animals resulted in an increase in airway reactivity to acetylcholine. Twenty-four hours after the final inhalation, the number of leukocytes (macrophages, neutrophils, eosinophils and lymphocytes) and the quantity of mediators (thromboxane B2, leukotriene D4 and histamine) in bronchoalveolar lavage fluid increased. All examined drugs inhibited the antigen-induced airway hyperreactivity to acetylcholine. Whereas ketotifen inhibited an accumulation of inflammatory cells (eosinophils and neutrophils) in bronchoalveolar lavage fluid, OKY-046 and ONO-3708 had no effect on the accumulation of inflammatory cells. OKY-046, but not ketotifen and ONO-3708, inhibited an increase of thromboxane B2 in the bronchoalveolar lavage fluid after antigen provocation. These results suggest the participation of TXA2 in the onset of antigen-induced airway hyperresponsiveness in guinea pigs, and the efficacy of TXA2 inhibitors, without affecting the accumulation of inflammatory cells in bronchoalveolar lavage fluid.

Acetylcholine↗
PubMed1993

Novel low immunosuppressive derivatives of the antitumor drug fluoropyrimidine, UK-21 and UK-25: effect on delayed type hypersensitivity and tumor immunity.

Previously, we reported that two novel 5-fluoropyrimidine derivatives, 2',3',5'-tris-O-[N-(2-n-propyl-n-pentanoyl)glycyl]-5-fluorouridine (UK-21) and 1-(6-[N-(2-n-propyl-n-pentanoyl)glycyl]amino-n-hexylcarbamoyl)- 5-fluorouracil (UK-25), show potent antitumor activity with low immunotoxicological effects. The purpose of this paper was to evaluate the effect of these drugs on delayed type hypersensitivity (DTH). Not only UK-21 and UK-25 but also tegafur (FT-207) and 5-fluorouracil (5-FU) produced no suppression of picryl chloride (PC)-induced DTH in mice but rather enhanced it. It is known that variation of the sensitizing antigen dose alters the effect of drugs on the immune response. Because it was difficult to control the antigen dose in PC-DTH, the sheep erythrocyte (SRBC)-induced response was used to examine the effect of drugs on delayed type hypersensitivity in the succeeding experiments. Either a therapeutic dose or an over-dose of the respective drug was given to mice sensitized with 5 x 10(5) or 5 x 10(7) SRBC. The suppressive effects of UK-21 and UK-25 on the DTH were lower than those of FT-207 and 5-FU. UK-21 and UK-25 enhanced Meth A tumor-specific DTH in BALB/c mice, but FT-207 and 5-FU did not. UK-21, UK-25 and FT-207 showed a tendency to enhance or restore the Meth A tumor neutralizing activity of spleen cells in mice bearing the tumor, but carmofur (HCFU) did not. These results indicated that the suppressive effects of UK-21 and UK-25 on the tumor immune response were also low.

Animals↗