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Biomedical subjects

K Minoguchi

Publications and source records attributed to K Minoguchi.

At least 19 recordsLinked to original sources
PubMed2003

Cough receptor sensitivity to capsaicin does not change after allergen bronchoprovocation in allergic asthma.

BACKGROUND: The relationship between cough receptor sensitivity and eosinophilic inflammation of the airway in patients with asthma remains unclear. METHODS: Eighteen patients with asthma sensitised to house dust mite (HDM) were enrolled in a randomised parallel group study. Patients with asthma whose main symptom was cough were not enrolled in the study. Half the patients were randomly assigned to inhale saline and the other half to inhale HDM allergen. Cough receptor sensitivity to capsaicin, airway responsiveness to histamine, and sputum eosinophils analysed with hypertonic saline inhalation were investigated before and 24 hours after saline or HDM allergen bronchoprovocation. RESULTS: Patients inhaling saline showed no significant changes in sputum eosinophils (from 7.87% (95% confidence interval (CI) 5.08 to 12.19) to 8.60% (95% CI 3.03 to 14.18); p=0.97), airway responsiveness to histamine (from 726.68 micro g/ml (95% CI 251.90 to 2096.36) to 773.01 micro g/ml (95% CI 251.36 to 2377.23); p=0.96), or capsaicin sensitivity (from 7.23 micro M (95% CI 2.45 to 21.31) to 7.24 micro M (95% CI 2.46 to 21.31); p=0.96). Early asthmatic response was induced in all patients, and late asthmatic response was observed in six of nine patients inhaling HDM allergen. Although there were significant increases in sputum eosinophils (from 9.83% (95% CI 6.78 to 14.27) to 21.00% (95% CI 13.85 to 28.15); p<0.01) and airway responsiveness to histamine (from 784.16 micro g/ml (95% CI 318.24 to 1932.24) to 377.81 micro g/ml (95% CI 118.43 to 1205.24); p<0.05) 24 hours after HDM allergen inhalation compared with baseline levels, capsaicin sensitivity did not change significantly (from 5.75 micro M (95% CI 1.91 to 17.30) to 6.20 micro M (95% CI 2.21 to 17.38); p=0.77). CONCLUSIONS: These findings suggest that cough receptor sensitivity to capsaicin is not associated with eosinophilic inflammation of the airway in patients with allergic asthma whose main symptoms are wheezing and dyspnoea but not cough.

Adult↗
PubMed2002

Suplatast tosilate inhibits thymus- and activation-regulated chemokine production by antigen-specific human Th2 cells.

BACKGROUND: Suplatast tosilate is an anti-allergic agent that suppresses cytokine production by human Th2 cells. OBJECTIVE: We investigated the effects of suplatast tosilate on the production of thymus- and activation-regulated chemokine (TARC) by T cells from allergic patients with asthma. METHODS: Purified protein derivative (PPD)-specific Th1 cell lines and Dermatophagoides farinae (Der f)-specific Th2 cell lines were established from nine patients with house dust mite-allergic asthma. The effects of suplatast tosilate on mRNA expression of TARC and protein production of TARC from antigen-specific Th1 or Th2 cell lines were investigated after stimulation with relevant antigens or phytohemagglutinin (PHA). In addition, the effects of IL-4, IL-10, and IFN-gamma on TARC production by Der f-specific Th2 cell lines in the presence or absence of suplatast tosilate were studied. RESULTS: Although PPD-specific Th1 cell lines did not produce TARC after stimulation with PPD antigen or PHA, stimulation of Der f-specific Th2 cell lines with Der f antigen or PHA increased production of TARC. Suplatast tosilate significantly and dose-dependently inhibited production of TARC by Der f-specific Th2 cell lines stimulated with either Der f antigen (76.5% inhibition at 100 microg/mL, P < 0.01) or PHA (81.9% inhibition at 100 microg/mL, P < 0.01). TARC production by Der f-specific Th2 cell lines was significantly increased only by activation with IL-4 but not with IL-10 or IFN-gamma; this increase in TARC production was significantly inhibited by suplatast tosilate (97.5% inhibition at 100 microg/mL, P < 0.01). CONCLUSION: Suplatast tosilate inhibits TARC production by human Th2 cells. Therefore, this agent inhibits both Th2 cytokine and Th2 chemokine and may be a useful anti-allergic agent.

Adult↗
PubMed2001

Analysis of IL-12 receptor beta 2 chain expression of circulating T lymphocytes in patients with atopic asthma.

Th2 cell predominance relative to Th1 cells contributes to pathological immune responses in patients with atopic asthma. IL-12 is a key cytokine in the induction of Th1 cells, and downregulation of IL-12 production is reported in these patients. However, IL-12 receptor expression of their T lymphocytes has not been clarified. In this study, expression of IL-12 receptor beta 2 on T cells and secretion of cytokines which affect IL-12 receptor beta 2 expression by their PBMC were examined. We found that IL-12 receptor beta 2 expression of the T cells is reduced. This is partly due to the diminished production of IL-12 and enhanced secretion of IL-4 by their PBMC. IL-18 production is not significantly modulated in these patients. Furthermore, intrinsic defects of the CD4(+) T cells, which reduce their IL-12 receptor beta 2 expression in response to IL-12 and/or IL-18 stimulation, are evident and are importantly involved in the Th1/Th2 imbalance of patients with atopic asthma.

Adolescent↗
PubMed2001

Interleukin-10 relieves the inhibitory effects of interferon-gamma on normal human lung fibroblasts.

Interleukin-10 (IL-10) is an important cytokine that suppresses the production of cytokines and chemokines by immune cells. IL-10 has been suggested to be involved in chronic inflammatory responses including the remodeling process in the lung. We investigated the effects of IL-10 on proliferation, extracellular matrix and cytokine production in normal human lung fibroblasts (NHLF). Human IL-10 (hIL-10) complementary DNA (cDNA) was transfected into NHLF using an adenoviral vector. No significant changes were observed in proliferation, fibronectin or procollagen type I production in the NHLF transfected with hIL-10 cDNA. Interferon (IFN)-gamma significantly inhibited cell proliferation and extracellular matrix production in a dose-dependent manner. Transfection of hIL-10 cDNA significantly relieved the suppressive effects of IFN-gamma in NHLF. Transforming growth factor (TGF)-beta production was not significantly affected by either transfection of hIL-10 cDNA or the addition of IFN-gamma. The relief of the suppressive function of IFN-gamma by IL-10 suggested that IL-10 is indirectly involved in the remodeling process in the lung interstitium.

Adenoviridae↗
PubMed2001

[Leukotriene modifiers].

Cysteinyl leukotriene (CysLT) C4, D4, and E4 play key roles in asthma. CysLTs are newly generated after cellular activation and are produced by eosinophils, mast cells, alveolar macrophages, and neutrophils. Pharmacological actions of CysLTs include potent bronchoconstriction, increased microvascular leakage and mucus secretion, chemoattraction of eosinophils, acceleration of eosinophil apoptosis, and proliferation of human airway smooth muscle. Recent studies demonstrated that CysLT1 receptors are distributed on CD34+ stem cells, eosinophils, monocytes, macrophages, basophils, and B cells in addition to airway smooth muscle. Because of these wide variety of distribution, Cys LTs may have another important roles in airway inflammation. CysLT1 receptor antagonist is widely used and found to be beneficial for the chronic management of asthma especially to symptomatic patients who had already been treated with moderate to high doses of inhaled corticosteroids and also to mild to moderate steroid-naive asthmatic patients.

Acetates↗
PubMed2001

[Thromboxane A2 synthase inhibitor and receptor antagonist].

Thromboxane A2 (TxA2) plays an important role in asthma. TxA2 are newly generated after cellular activation and are produced by not only platelets but also eosinophils, basophils, alveolar macrophages, and neutrophils. Pharmacological actions of TxA2 include potent bronchoconstriction, increased microvascular leakage, impairment of mucociliary clearance, and induction of airway hyperresponsiveness. Recent study demonstrated that TxA2 receptor antagonist decreased the number of eosinophils in bronchial biopsy specimens, suggesting that this type of agent possesses anti-inflammatory actions in asthma. Furthermore, addition of TxA2 synthase inhibitor significantly increased the PEF values in the persistent asthmatic patients despite the treatment with moderate-dose of inhaled corticosteroids. Therefore, these results suggest that TxA2 synthase inhibitor and receptor antagonist are useful for the treatment with symptomatic patients who had already been treated with inhaled corticosteroids.

Asthma↗
PubMed1999

Effect of suplatast tosilate (IPD-1151T) on cytokine production by allergen-specific human Th1 and Th2 cell lines.

Suplatast tosilate (IPD-1151T) is an antiallergic agent that suppresses airway eosinophil infiltration in asthma. We investigated the effects of IPD-1151T on proliferative response and cytokine production by human antigen-specific T cell lines. Purified protein derivatives (PPD)-specific T helper 1 (Th1) cell lines and Dermatophagoides farinae (Der f)-specific T helper 2 (Th2) cell lines were established from patients with asthma sensitized with house dust mite. Stimulation of PPD-specific and Der f-specific T cell lines with relevant antigens resulted in production of mostly interferon (IFN)-gamma and of interleukin (IL)-4 and IL-5, respectively. IPD-1151T did not inhibit the proliferative responses of either the Th1 or Th2 cell line to antigens. Although IPD-1151T did not inhibit IFN-gamma production by PPD-specific Th1 cell lines, it did inhibit IL-4 and IL-5 production by antigen-stimulated Der f-specific Th2 cell lines in a dose-dependent manner. IPD-1151T directly inhibited cytokine production by Der f-specific Th2 cell lines stimulated with immobilized anti-CD3 antibodies. Although IPD-1151T did not inhibit the clonal expansion of memory T cells among PBMCs into PPD-specific Th1 and Th2 cell lines, it did inhibit IL-4 and IL-5 production by Der f-specific Th2 cell lines but not IFN-gamma production by PPD-specific Th1 cell lines. These results suggest that IPD-1151T selectively inhibits Th2-type cytokine production.

Allergens↗
PubMed1999

Protein tyrosine phosphorylation: A possible common signaling pathway in human Th1 and Th2 cell clones.

BACKGROUND: It has been reported that protein tyrosine phosphorylation is essential for cytokine production in mouse Th1 cells but not in Th2 cells. However, little is known about the difference of signal transduction between human antigen-specific Th1 and Th2 cell clones. METHODS: Purified protein derivative-specific Th1 and Dermatophagoides farinae-specific Th2 cell clones were established. T cell clones were stimulated with anti-CD3 Abs and further treated with goat antimouse immunoglobulin Abs for cross-linking of TCR/CD3 complex. RESULTS: In contrast to murine Th2 clones, tyrosine phosphorylation including both ZAP-70 and phospholipase-C-Al was necessary for cell activation in both types of human T cell clones. This was further supported by the observation that genistein (protein tyrosine kinase inhibitor) inhibits IFN-A production for Th1 and IL-4 for Th2 in a dose-dependent manner. CONCLUSION: Protein tyrosine phosphorylation is thus an essential component in transducing the activation signal from TCR-CD3 complex both in human Th1 and Th2 cells.

Clone Cells↗
PubMed1999

Correlation between respiratory function and airway inflammation in asthma.

BACKGROUND: Eosinophilic airway inflammation is thought to be associated with airflow limitation and airway hyperresponsiveness. METHODS: Spirometry, peak expiratory flow (PEF) measurement, histamine challenge test, and sputum induction with hypertonic saline inhalation were performed in 70 asymptomatic patients with asthma who were treated with bronchodilators or an inhaled corticosteroid (beclomethasone dipropionate, 400-800 microg/day) or both for more than 2 months. The relationships between the sputum eosinophils, respiratory function, and airway responsiveness to histamine were investigated. RESULTS: Induced sputum was obtained from 53 patients. Although significant correlations between sputum eosinophils and forced expiratory volume in 1 s/forced vital capacity x 100% (FEV1%) or maximum expiratory flow at 25% of the forced vital capacity (V25) divided by height (V25/Ht) were observed, no significant correlations were found between sputum eosinophils and percent predicted PEF (%PEF) or airway responsiveness to histamine. Furthermore, airway responsiveness to histamine was not correlated with FEV1%, V25/Ht or %PEF. CONCLUSION: Single-point measurements of FEV1% and V25/Ht but not PEF or airway responsiveness to histamine correlate with the degree of airway inflammation evaluated indirectly with induced sputum.

Adult↗
PubMed1998

Long-term analysis of allergen-specific T cell clones from patients with asthma treated with allergen rush immunotherapy.

Rush immunotherapy (RI), a modified allergen-specific immunotherapeutic procedure, is an effective treatment for extrinsic (atopic) asthma, although the precise mechanism of its action is unclear. We have thus investigated the effect of RI on T cell response in seven mite-allergen-sensitive asthmatic patients who were successfully treated with RI. The proliferative response to mite allergen profoundly decreased after 3 months of therapy compared to the response before therapy; the response, however, recovered 18 months after RI. Regarding cytokine production patterns of mite-specific T cells, RI brought about a shift in cytokine profiles from Th2 to Th0 or Th1 in mite-specific T cell clones. The data indicate that the efficacy of RI is due to modification of T cell responses to mite antigens. Allergen RI results in the conversion of Th2 to Th1 and Th0 cells and/or selection of Th1 and Th0 cells over Th2 cells and thus may improve both clinical symptoms and airway inflammation in asthmatics.

Adolescent↗
PubMed1998

Effect of rush immunotherapy on airway inflammation and airway hyperresponsiveness after bronchoprovocation with allergen in asthma.

BACKGROUND: Rush immunotherapy (RIT) has been shown to be effective in allergic asthma. OBJECTIVE: We investigated the mechanisms of RIT on the basis of cytokine production by T-cell lines and airway inflammation and responsiveness. METHODS: Subjects were 8 patients with house dust mite-allergic asthma treated with dust mite extract RIT for 6 months and 6 RIT-untreated control patients. IL-5 production by Dermatophagoides farinae -specific T-cell lines, eosinophil percentages, and eosinophil cationic protein (ECP) in induced sputum and airway responsiveness to allergen and histamine were evaluated before and after treatment. Changes in eosinophil percentages and ECP in induced sputum and responsiveness to histamine 24 hours after allergen inhalation were also studied. RESULTS: After 6 months of RIT, percentages of total eosinophils (43. 0% +/- 6.90% to 16.8% +/- 2.48%; P <.01), percentages of EG2(+ ) eosinophils (32.6% +/- 6.39% to 19.7% +/- 4.68%; P <.01) and ECP (362.7 +/- 125.3 ng/mL to 26.2 +/- 5.15 ng/mL; P <.05) decreased in induced sputum, and IL-5 production by T-cell lines decreased (617 +/- 93.2 pg/mL to 200.0 +/- 34.1 pg/mL; P <.01). RIT decreased both early- and late-phase bronchoconstriction (early phase: 33.2% +/- 3. 46% to 25.4% +/- 1.42%; P <.03; late phase: 16.2% +/- 3.52% to 6.2% +/- 1.96%; P <.03) and suppressed increases in the percentages of total (61.8% +/- 4.89% to 42.0% +/- 4.67%; P <.01) and EG2-positive eosinophils (55.54% +/- 7.21% to 36.5% +/- 6.43%; P <.01) and ECP (685.6 +/- 217.0 ng/mL to 85.4 +/- 23.4 ng/mL; P <.05) in induced sputum after allergen inhalation. RIT also decreased airway responsiveness to dust mite (1:303.7 +/- 123.7 wt/vol to 1:65.0 +/- 13.2 wt/vol; P <.03) and to histamine before (397.1 +/- 206.9 microgra/mL to 1391.3 +/- 283.3 microgram/mL; P <.03) and after allergen inhalation (139.2 +/- 36.5 microgram/mL to 629.1 +/- 196.3 microgram/mL; P <.03). CONCLUSION: RIT decreases airway inflammation and airway hyperresponsiveness before and after bronchial provocation with allergen, possibly by inhibiting both allergen-specific T-cell- and mast cell-dependent pathways. RIT is an effective antiinflammatory treatment in allergic asthma.

Adult↗
PubMed1998

Effect of theophylline withdrawal on airway inflammation in asthma.

Theophylline has been used as a bronchodilator in acute and chronic asthma management, although there is accumulating evidence that it may have anti-inflammatory effects. We have investigated the effect of theophylline withdrawal for 6 weeks in asthmatic subjects whose peak expiratory flow (PEF) readings were more than 80% of the predicted value and its variability was less than 20% (Green Zone) by treatment with both a moderate dose of inhaled corticosteroids (BDP), 400-800 microg/day) and low dose theophylline (400 mg/day) for more than 3 months. In 38 asthmatic subjects, changes in clinical symptoms, respiratory function and airway inflammation detected with hypertonic saline induced sputum, and airway reactivity to histamine were investigated. One half of the patients were randomly withdrawn from theophylline, while the other half continued to take the same dose of theophylline for a period of 6 weeks. Mean steady state plasma theophylline concentrations when receiving treatment with theophylline were 8.08 microg/mL in the theophylline withdrawal group and 7.64 microg/mL in the control theophylline group, respectively. Although a significant increase in asthma symptoms emerged in the theophylline group, there were no significant changes in the theophylline administration group. In the theophylline withdrawal group, there were small but significant falls in PEF in the morning, FEV1 and V50 at the end of the study period. Analysis of induced sputum showed that there was also a significant increase in the percentage of total and activated (EG2+) eosinophils only in those patients who withdrew from theophylline. These results indicate that chronic treatment with low dose theophylline exerts an anti-inflammatory effect and that the additional use of theophylline with inhaled corticosteroids provides an effective treatment for moderate asthma. Taken together, we conclude that theophylline has long-term beneficial effects on the chronic asthma management.

Administration, Oral↗
PubMed1998

[Effect of slow-release theophylline on airway inflammation in bronchial asthma].

Theophylline has been used as a bronchodilator in acute and chronic asthma management but recent evidences suggest that it has anti-inflammatory effects. Therefore, we investigated the therapeutic effect of slow-release theophylline in mild to moderate asthmatic patients. Symptomatic 19 patients with mild asthma who were treated with inhaled beta 2-agonist alone, and 17 subjects with moderate asthma who were treated with moderate dose of inhaled corticosteroid (beclomethasone dipropionate, BDP, 400-800 micrograms/day) were enrolled to the present study. After two-week run-in period, slow-release theophylline was administered for six to eight weeks and asthma symptoms, respiratory function, airway inflammation evaluated by the inhalation of hypertonic saline, and airway reactivity to histamine were investigated during observation period and after treatment. Asthma symptom score was significantly improved after theophylline treatment in both groups. Morning peak expiratory flow was significantly elevated but FEV1 was not significantly improved by the additional treatment with slow-release theophylline in both groups. Significant decreases in the percentages of total and EG2 + eosinophils in induced sputum demonstrated that slow-release theophylline has anti-inflammatory effect in patients with asthma despite the treatment with inhaled corticosteroid. Because recent reports suggest that theophylline may act as an anti-inflammatory drug even in low dose concentration, we also investigated the effect of plasma theophylline concentration on the airway inflammation. Patients were divided into two groups by the plasma concentration of theophylline, more than 10 micrograms/mL which is necessary to dilate airway and below 10 micrograms/mL, referred to as low dose concentration of theophylline. The results suggest that the administration of slow-release theophylline significantly decreased the percentages of both total and EG2 + eosinophils in induced sputum in both concentration groups. However, airway reactivity to histamine did not significantly change by the treatment. Taken together, we conclude that low dose treatment of slow-release theophylline has an anti-inflammatory effect and treatment with slow-release theophylline alone or the additional use with inhaled corticosteroid is an effective therapy for the management of mild to moderate asthma.

Adult↗
PubMed1997

[The prevalence of orthostatic dysregulation complicated with bronchial asthma].

Orthostatic dysregulation (OD) has been reported to be complicated with childhood bronchial asthma. 42 patients (28 females and 14 males) with adult-onset bronchial asthma were selected randomly to investigate the prevalence of OD. OD was diagnosed by both questionnaire for subjective symptoms and tilting test (Schellong test and upright ECG). Our results revealed that 64.3% (both 64.3% in females and males) of the patients were complicated with OD. There was no significant difference in the duration of asthma, FEV0.1, %FEV1.0, serum IgE level, and severity of asthma between patients with OD and without OD. Furthermore, no significant difference in the results of tilting test were observed. In serum level of theophylline we couldn't detect any subjective difference between the two groups, however there was significant difference between positive patients and negative patients in tilting test. In conclusion, OD is frequently complicated with adult-onset asthma and we should be careful of the subjective symptoms concerned with OD.

Adult↗
PubMed1995

A 77-kDa protein associates with pp125FAK in mast cells and becomes tyrosine-phosphorylated by high affinity IgE receptor aggregation.

The focal adhesion kinase, pp125FAK, is a novel non-receptor protein tyrosine kinase expressed in different cells including mast cells. Here we report that a 77-kDa protein associates with pp125FAK in the mast cell analog, rat basophilic leukemia (RBL-2H3) cells. When pp125FAK immunoprecipitates were subjected to an in vitro kinase assay, there was prominent phosphorylation on tyrosine of pp125FAK and of a 77-kDa protein. By V8 protease digestion mapping and by immunoblotting with two different anti-pp125FAK antibodies, the 77-kDa protein was distinct from pp125FAK. This Fak Associated Protein or FAP was detected in RBL-2H3 cells but not in fibroblasts. The aggregation of the high affinity IgE receptor, Fc epsilon RI, induced the in vivo tyrosine phosphorylation of FAP. However, there was a marked decrease in the in vitro phosphorylation of FAP in the immunoprecipitates from Fc epsilon RI aggregated cells. Both of these Fc epsilon RI-mediated effects were enhanced by cell adhesion. There was strong association of FAP with non-tyrosine-phosphorylated pp125FAK. Thus this interaction does not appear to be mediated by the Src homology 2 domain. Together the data indicate that FAP associates with pp125FAK and suggest that FAP may play a role in Fc epsilon RI signaling.

3T3 Cells↗
PubMed1994

The aggregation of the high affinity IgE receptor induces tyrosine phosphorylation of paxillin, a focal adhesion protein.

Tyrosine phosphorylation of proteins is an essential component of high affinity IgE receptor (Fc epsilon RI) signaling and secretion. This signaling and secretion is also dependent on the organization of the cytoskeleton. Here we report that the aggregation of Fc epsilon RI on rat basophilic leukemia cells results in tyrosine phosphorylation of the cytoskeletal protein, paxillin. Tyrosine phosphorylation of paxillin is a relatively late event after Fc epsilon RI aggregation. Both the direct increase in intracellular Ca2+ with calcium ionophore and the activation of protein kinase C (PKC) with PMA induced tyrosine phosphorylation of paxillin. The optimal tyrosine phosphorylation of paxillin by Fc epsilon RI aggregation required PKC and extracellular Ca2+. However, there was also Fc epsilon RI-mediated tyrosine phosphorylation of paxillin independent of Ca2+ influx or PKC activation. By fluorescent microscopy, cell stimulation induced a redistribution of paxillin toward the periphery of the cells. Although Fc epsilon RI aggregation induced tyrosine phosphorylation of paxillin in nonadherent cells, adherence markedly enhanced this phosphorylation. Together, the data suggest a role for paxillin in Fc epsilon RI signaling.

Animals↗