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Biomedical subjects

M Yamaya

Publications and source records attributed to M Yamaya.

At least 37 records · Page 2Linked to original sources

[Detection of exhaled CO as a simple non-invasive tool for monitoring acute exacerbations of asthma in the elderly].

Exhaled carbon monoxide (CO) concentrations were measured on a CO monitor by vital capacity maneuvers in asthmatic patients either receiving or not receiving inhaled corticosteroids, and in nonsmoking healthy control subjects. CO was detectable and measured reproducibly in the exhaled air of all subjects. The exhaled CO concentrations were higher in asthmatic patients not receiving inhaled corticosteroids and similar in asthmatic patients receiving inhaled corticosteroids and nonsmoking healthy control subjects (Am J Respir Crit Care Med 1997: 156: 1140-1143). All patients with inhaled corticosteroid treatment had reductions in exhaled CO concentration and eosinophil cell counts in sputum that were accompanied by an amelioration of airway obstruction. These results showed that detection of exhaled CO could be a simple non-invasive tool for monitoring airway inflammation and acute exacerbation of asthma.

Aged↗

[Difficulties in diagnosis and treatment of asthma in the elderly].

The cause of the high asthma mortality in the elderly is not exactly known. We measured intrabronchial pressures in elderly asthma patients who had long-standing asthma and compared them with those in newly-diagnosed asthma and young healthy volunteers. In elderly asthmatics, at baseline conditions, both central and peripheral airway resistances were significantly higher compared with those in the other groups, which may partly explain the high asthma mortality in the elderly. We report a case of severe acute asthma associated with disturbed consciousness, in which asthma-induced cerebral swelling was considered to be accompanied by neuronal damage, after examination of cerebrospinal fluid. Inhaled steroid is essential for the treatment of moderate to severe asthma. However, approximately 40% of the elderly patients in this category did not use inhaled steroid. Physicians should strongly recommend the use of inhaled steroid to prevent asthma death in elderly asthma patients.

Administration, Inhalation↗

Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema.

Cigarette smoke, containing reactive oxygen species, is the most important risk factor for chronic pulmonary emphysema (CPE). Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung. A (GT)n dinucleotide repeat in the 5'-flanking region of human HO-1 gene shows length polymorphism and could modulate the level of gene transcription. To investigate the correlation between the length of the (GT)n repeat and susceptibility to the development of CPE, we screened the frequencies of alleles with varying numbers of (GT)n repeats in the HO-1 gene in 101 smokers with CPE and in 100 smokers without CPE. Polymorphisms of the (GT)n repeat were grouped into three classes: class S alleles (<25 repeats), class M alleles (25-29 repeats), and class L alleles (>/=30 repeats). The proportion of allele frequencies in class L, as well as the proportion of genotypic frequencies in the group with class L alleles (L/L, L/M, and L/S), was significantly higher in the smokers with CPE than in smokers without CPE. Moreover, we analyzed the promoter activities of the HO-1 gene carrying different (GT)n repeats (n=16, 20, 29, and 38), by transient-transfection assay in cultured cell lines. H2O2 exposure up-regulated the transcriptional activity of the HO-1 promoter/luciferase fusion genes with (GT)16 or (GT)20 but did not do so with (GT)29 or (GT)38. These findings suggest that the large size of a (GT)n repeat in the HO-1 gene promoter may reduce HO-1 inducibility by reactive oxygen species in cigarette smoke, thereby resulting in the development of CPE.

Aged↗

Effects of dexamethasone on rhinovirus infection in cultured human tracheal epithelial cells.

To examine the effects of glucocorticoid on rhinovirus (RV) infection, primary cultures of human tracheal epithelial cells were infected with either RV2 or RV14. Viral infection was confirmed by demonstrating that viral RNA in infected cells and viral titers of supernatants and lysates from infected cells increased with time. RV14 infection upregulated the expression of mRNA and protein of intercellular adhesion molecule-1 (ICAM-1), the major RV receptor, on epithelial cells, and it increased the production of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor-alpha in supernatants. Dexamethasone reduced the viral titers of supernatants and cell lysates, viral RNA of infected cells, and susceptibility of RV14 infection in association with inhibition of cytokine production and ICAM-1 induction. In contrast to RV14 infection, dexamethasone did not alter RV2 infection, a minor group of RVs. These results suggest that dexamethasone may inhibit RV14 infection by reducing the surface expression of ICAM-1 in cultured human tracheal epithelial cells. Glucocorticoid may modulate airway inflammation via reducing the production of proinflammatory cytokines and ICAM-1 induced by rhinovirus infection.

Aged↗

[The pathogenesis and therapy of virus infection-induced senile bronchial asthma].

We investigated the pathogenesis and therapy of virus infection-induced senile bronchial asthma in vitro. To examine the effects of rhinovirus infection on the production of cytokines and intercellular adhesion molecule-1 (ICAM-1), human tracheal epithelial cells and submucosal gland cells were cultured, and infected with human rhinovirus. Rhinovirus upregulated the production of interleukin (IL)-1 beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha in supernatants of epithelial cells and submucosal-gland cells, and IL-1 alpha and granulocyte macrophage colony-stimulating factor (GM-CSF) in supernatants of submucosal gland cells. Rhinovirus upregulated the expression of ICAM-1 mRNA. Rhinovirus infection also increased epithelial permeability. These events may be important for the spread of airway inflammation after rhinovirus infection. Furthermore, we studied the effects of dexamethasone and erythromycin on the modulation of virus infection and induction of cytokines and ICAM-1 in tracheal epitherial cells. Both of them reduced viral titers of rhinovirus type 14, a major group rhinovirus, and cytokine production of supernatants, and ICAM-1 mRNA expression in the cells. Because it is known that acidic conditions by proton pumps are needed for rhinovirus entry into the cells, we studied the effects of H+ ATPase inhibitor bafilomycin A1. Bafilomycin A1 reduced the virus titers of both rhinovirus type 2 and 14 in supernatants. These findings in our in vitro study suggest that dexamethasone, erythromycin and bafilomycin A1 may inhibit rhinovirus infection and modulate airway inflammation induced by rhinovirus infection.

Aged↗

Prevention of severe premenstrual asthma attacks by leukotriene receptor antagonist.

BACKGROUND: The etiology and treatment of premenstrual exacerbations of asthma (PMA) remain uncertain. OBJECTIVE: We investigated the role of cellular mediators released from inflammatory cells in the airflow limitation during PMA. METHODS: Serum levels of leukotriene (LT) B(4), LTC(4), platelet- activating factor, histamine, IL-1beta, IL-4, IL-5, IL-6, and GM-CSF were measured at different time points, first just before or during menstruation when the peak expiratory flow rate (PEFR) began to decrease precipitously and second during the menstrual midcycle week (days 10-16) when the PEFR returned to baseline values in patients with PMA and in age-matched asthma patients without PMA at the same intervals. RESULTS: Serum levels of LTC(4) were significantly higher during exacerbations of asthma than after recovery (69.0 +/- 16.0 pg/mL vs 24.0 +/- 9.5 pg/mL, P <.05), whereas those of IL-1beta, IL-4, IL-5, IL-6, GM-CSF, histamine, LTB(4), and platelet-activating factor did not differ between 2 periods in 5 patients with PMA. In contrast, in 5 asthmatic patients without PMA serum levels of cellular mediators did not differ between corresponding periods. Oral administration of pranlukast, an LT receptor antagonist (225 mg twice daily), significantly reduced decreases in PEFR from the baseline values (110 +/- 21 L/min with pranlukast vs 233 +/- 20 L/min without pranlukast, P <.01) in association with an improvement of asthma symptom scores (6.5 +/- 1. 1 with pranlukast vs 9.8 +/- 0.7 without pranlukast, P <0.05) in 5 patients with PMA. CONCLUSION: LTs are partly involved in the pathogenesis of PMA, and LT receptor antagonists may be useful for preventing airflow obstruction in patients with PMA.

Adolescent↗

Kinin and histamine stimulate Cl- secretion in gerbil middle ear epithelium: connection to otitis media.

The effects of bradykinin (BK) and histamine on transepithelial ion transport in primary cultures of gerbil middle ear epithelium were investigated. Lysyl-bradykinin (lys-BK) elicited a transient increase in short-circuit current (I(sc)) when added to apical or basolateral surfaces. Lys-BK had a larger effect than BK or des-arg9-BK on both epithelial surfaces. Histamine induced a transient increase in I(sc) only when added to the basolateral surface. Mepyramine, an H1 histamine antagonist, greatly reduced the histamine-induced I(sc). The H2 and H3 histamine antagonists were both ineffective for inhibiting the I(sc) responses to histamine. Diphenylamine-2-carboxylate or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, Cl- channel blockers, significantly blocked the I(sc) responses to lys-BK or histamine. The Ca2+-mobilizing action of lys-BK and histamine was also investigated in single middle ear epithelial cells. BK and histamine induced an increase in the intracellular Ca2+ concentration. 1,2-Bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester, a calcium chelator, greatly reduced the increase in the I(sc) responses to lys-BK or histamine. These data indicate that BK and histamine activate intracellular Ca2+-dependent mechanisms, leading to apical Cl- secretion in the cultured gerbil middle ear epithelium via B2 BK receptors and H1 histamine receptors.

Animals↗

Exhaled carbon monoxide levels during treatment of acute asthma.

Carbon monoxide is known to be present in measurable quantities in the exhaled air of normal subjects and at higher concentrations in asthmatic patients not treated with glucocorticoids. To examine whether exhaled CO is useful in monitoring asthma control, time course changes in peak expiratory flow rate (PEFR) and exhaled CO concentration before and after treatment of acute asthma exacerbations were measured in 20 asthmatic patients. Exhaled CO was measured in triplicate by a portable CO analyser. Exhaled CO was reproducible at all time points. Asthma exacerbations caused a fall in PEFR and a rise in exhaled CO (towards an average of 3.3 parts per million (ppm)) in all patients, and treatment with oral glucocorticoids reversed these changes in both parameters. An improvement of PEFR was closely associated with a reduction of exhaled CO (to an average of 1.5 ppm) after treatment. The maximal exhaled CO concentration significantly correlated with recovery time of PEFR after treatment with oral glucocorticoids (p<0.01). The present study suggests that exhaled CO may be a useful noninvasive means of monitoring the control of asthma.

Administration, Inhalation↗

Effects of inhaled beclomethasone dipropionate on serum IgE levels and clinical symptoms in atopic asthma.

BACKGROUND: A high serum immunoglobulin (Ig)E level is considered a potent predictor for the development of asthma and IgE is targeted for treatment of asthma. Although inhaled corticosteroids are well established in the treatment of asthma, the effects of inhaled corticosteroids on serum IgE levels in asthma remain uncertain. METHODS: We therefore examined asthma symptoms, concentrations of total serum IgE and specific IgE antibodies to selected allergens, blood eosinophil counts and lung functions before and 3 months after treatment with either inhaled beclomethasone dipropionate (BDP; 800 microg/day) (n = 7) or inhaled beta2-agonists alone (n = 7) in patients with atopic asthma in a randomized, double-blind, parallel-group controlled trial. RESULTS: Inhaled BDP significantly improved asthma symptom scores and forced expiratory volume in 1 s, and decreased blood eosinophil counts, total serum IgE levels and specific IgE antibodies to house dust mite and cedar. Decreases in total serum IgE significantly correlated with an improvement in asthma symptom scores. In contrast, none of parameters altered in patients with atopic asthma treated with inhaled beta2-agonists alone. CONCLUSIONS: Inhaled corticosteroids may improve the subsequent clinical course of atopic asthma in association with a reduction of serum IgE levels.

Administration, Inhalation↗

Increased carbon monoxide in exhaled air of patients with seasonal allergic rhinitis.

BACKGROUND: Carbon monoxide (CO) can be detected in exhaled air and is increased in asthmatic patients. However, it is uncertain whether exhaled CO is increased in patients with allergic rhinitis. OBJECTIVE AND METHODS: To study whether exhaled CO is increased in patients with allergic rhinitis, exhaled CO concentrations were measured on a CO monitor by vital capacity manoeuvre in 86 patients with seasonal allergic rhinitis during and out of the cedar pollen season. RESULTS: During the season, exhaled CO concentrations were 3. 6 +/- 0.3 p.p.m. and decreased to 1.2 +/- 0.1 p.p.m. out of the season. The values of exhaled CO out of the season were similar to those in age-matched non-smoking healthy control subjects (1.2 +/- 0. 1 p.p.m.). Exhaled CO concentrations were significantly higher in patients with symptoms than in those without symptoms (P < 0.01). Exhaled CO concentrations in patients did not differ significantly among oral and nasal exhalation, and oral exhalation with an expiratory resistance (P > 0.20). CONCLUSION: These findings suggest that allergic rhinitis increases the concentration of CO in exhaled air and increases in exhaled CO may be derived from lower airways.

Adult↗

Infection of human respiratory submucosal glands with rhinovirus: effects on cytokine and ICAM-1 production.

To further understand the early biochemical events that occur in infected surface epithelium, we developed for the first time a model in which a respiratory submucosal gland cell population can be infected with rhinovirus (RV). Viral infection was confirmed by demonstrating with PCR that viral titers in supernatants and lysates from infected cells increased with time. Infection by RV14 upregulated the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA, the major RV receptor, on submucosal gland cells, and it increased production of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-8, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor in supernatants. Antibodies to ICAM-1 inhibited RV infection of submucosal gland cells and decreased the production of cytokines after RV infection. Both IL-1alpha and IL-1beta upregulated ICAM-1 mRNA expression and increased susceptibility to RV infection, whereas other cytokines failed to alter ICAM-1 mRNA expression. Furthermore, neutralizing antibodies to IL-1alpha and IL-1beta significantly decreased the viral titers in supernatants and ICAM-1 mRNA expression after RV infection, but a neutralizing antibody to tumor necrosis factor-alpha was without effect. These findings suggest that respiratory submucosal gland cells play an important role in the initial stages of inflammation and provide useful insights into the pathogenesis of RV infection.

Adult↗

Protective effects of heme oxygenase-1 against oxidant-induced injury in the cultured human tracheal epithelium.

To examine whether increases in heme oxygenase (HO)-1 activity have protective effects on the oxidant-induced injury of airway epithelial cells, human tracheal epithelial cells were cultured on a porous filter membrane, and electrical conductance (G) and mannitol flux across epithelial membrane were measured with Ussing's chamber methods and D-[(3)H]mannitol, respectively. Hydrogen peroxide (H(2)O(2); 1 mM) increased G with time from the baseline value of 6.0 +/- 0.6 to 17.8 +/- 0.9 mS/cm(2) at 6 h after administration (P < 0.001). Likewise, H(2)O(2) significantly increased mannitol flux through the cultured epithelium (P < 0.01). Pretreatment of cultured epithelial cells with hemin (10 microM; 8 h) or interleukin (IL)-1beta (10 ng/ml; 16 h) completely inhibited increases in G and mannitol flux induced by H(2)O(2). Tin protoporphyrin IX (50 micrometer) and zinc protoporphyrin IX (10 microM), inhibitors of HO-1, reduced hemin-induced and IL-1beta-induced inhibitory effects. Hemin treatment increased HO-1 messenger RNA expression, HO-1 protein production, and HO activity and bilirubin content as well as ferritin content in the cultured epithelial cells. Pretreatment with hemin and desferoxamine, which, like ferritin, can bind iron, inhibited H(2)O(2)-induced increases in G and mannitol permeability. Although exogenous bilirubin mimicked hemin-induced inhibitory effects, exogenous apoferritin failed to inhibit H(2)O(2)-induced effects on G and mannitol permeability. These findings suggest that HO-1 induction provides protection against H(2)O(2)-induced injury of the cultured human airway epithelial cells in part via the HO-bilirubin pathway.

Adult↗

Dipeptidase inhibitor and epithelial removal potentiate leukotriene D4-induced human tracheal smooth muscle contraction.

We investigated the role of epithelium in smooth muscle contraction induced by leukotriene D4 (LTD4) in isolated human trachea. The contractile response to LTD4 was potentiated by an inhibitor of dipeptidases L-cysteine and by removal of the epithelium. Both L-cysteine (3 x 10(-3) M) and removal of the epithelium shifted the concentration-response curves to LTD4, to lower concentrations by 0.7 and 0.6 log units, respectively. Incubation of cultured or isolated human tracheal epithelial cells with LTD4 resulted in the formation of LTE4, which was completely blocked by pretreatment with L-cysteine (3 x 10(-3) M). The isolated and cultured human tracheal epithelial cells contained microsomal dipeptidase (MDP) activity. Immunohistochemical study indicated MDP protein was present in the epithelium and endothelial cells of submucosal microvessels in the human trachea. These results suggest that the epithelium modulates the contractile response to LTD4 in human trachea by dipeptidases degrading LTD4.

Acetylcholine↗

Laminin inhibits Cl- -secretion across canine tracheal epithelium.

We examined the effect of laminin (a major component of the basement membrane) on potential difference (PD) and short circuit current (SCC) in both posterior epithelial membranes (native tissue) and cultured epithelial cell layers from canine trachea using an Ussing chamber. Although laminin itself did not alter the baseline values of SCC or PD, it significantly inhibited in a dose-dependent manner the isoproterenol induced SCC and PD rises of the epithelial membrane. In the cultured epithelial layer treated with amiloride, laminin did not alter the baseline values of SCC, PD or resistance (R) but it significantly inhibited the isoproterenol induced SCC rises. However, laminin did not significantly inhibit the bradykinin induced SCC rise in the cultured epithelial layer treated with amiloride. These findings indicate that laminin is a determinant in ion transport (mainly Cl- secretion) across canine tracheal epithelium, inhibiting the beta-agonist induced Cl- transport.

Adrenergic beta-Agonists↗