Search PubMed⌕ Search

Biomedical subjects

M Yamaya

Publications and source records attributed to M Yamaya.

At least 19 recordsLinked to original sources
PubMed2006

Carbocisteine inhibits rhinovirus infection in human tracheal epithelial cells.

The aim of the study was to examine the effects of a mucolytic drug, carbocisteine, on rhinovirus (RV) infection in the airways. Human tracheal epithelial cells were infected with a major-group RV, RV14. RV14 infection increased virus titres and the cytokine content of supernatants. Carbocisteine reduced supernatant virus titres, the amount of RV14 RNA in cells, cell susceptibility to RV infection and supernatant cytokine concentrations, including interleukin (IL)-6 and IL-8, after RV14 infection. Carbocisteine reduced the expression of mRNA encoding intercellular adhesion molecule (ICAM)-1, the receptor for the major group of RVs. It also reduced the supernatant concentration of a soluble form of ICAM-1, the number and fluorescence intensity of acidic endosomes in the cells before RV infection, and nuclear factor-kappaB activation by RV14. Carbocisteine also reduced the supernatant virus titres of the minor group RV, RV2, although carbocisteine did not reduce the expression of mRNA encoding a low density lipoprotein receptor, the receptor for RV2. These results suggest that carbocisteine inhibits rhinovirus 2 infection by blocking rhinovirus RNA entry into the endosomes, and inhibits rhinovirus 14 infection by the same mechanism as well as by reducing intercellular adhesion molecule-1 levels. Carbocisteine may modulate airway inflammation by reducing the production of cytokines in rhinovirus infection.

Aged↗
PubMed2006

Association of susceptibility to the development of pneumonia in the older Japanese population with haem oxygenase-1 gene promoter polymorphism.

BACKGROUND: Oxidative stresses including cigarette smoking are implicated in the pathogenesis of cerebrovascular diseases, which are associated with pneumonia because of frequent aspiration. Haem oxygenase-1 (HO-1) acts in cytoprotection against oxidants, provides anti-inflammatory effects, and inhibits atherogenesis. A (GT)(n) dinucleotide repeat in the human HO-1 promoter modulates HO-1 gene expression and shows length polymorphism, which is grouped into three classes: class S (<27 repeats), class M (> or = 27, <33 repeats), and class L (> or = 33 repeats) alleles. OBJECTIVE: To investigate the correlation between the HO-1 gene polymorphism and development of pneumonia in elderly Japanese. METHODS: The length of the (GT)n repeats was analysed in 200 elderly patients with pneumonia and 200 control subjects. The association of the HO-1 gene polymorphism with risk of pneumonia was estimated by logistic regression. RESULTS: The proportion of allele frequencies in class L, and the proportion of genotypic frequencies in the L-allele carriers (L/L, L/M, and L/S), was significantly higher in patients with pneumonia than in controls (20% v 10% in class L, and 34% v 18% in L-allele carriers). After adjustment for potentially confounding factors, both cerebrovascular disorders and HO-1 gene L-allele carriers were significant and independent risk factors for pneumonia. The adjusted odds ratio for L-allele carriers v non-L-allele carrier was 2.1 (95% confidence interval, 1.2 to 3.6). CONCLUSIONS: The large size of a (GT)n repeat in the HO-1 gene promoter may be associated with susceptibility to pneumonia in the older Japanese population.

Aged↗
PubMed2004

Human airway submucosal glands augment eosinophil chemotaxis during rhinovirus infection.

BACKGROUND: Asthma exacerbations are frequently associated with rhinovirus (RV) infections. However, the contribution of airway submucosal gland (SMG) to exacerbations of asthma in RV respiratory infection has not been studied. OBJECTIVE: This study was undertaken to examine whether RV-infected human respiratory SMG cells produce pro-inflammatory cytokines and chemokines for eosinophils, and augment eosinophil transmigration across human airway epithelium. METHODS: We infected cultured human tracheal SMG cells with RV14, collected culture media at 1, 3, and 5 days after infection, and measured the chemotactic activity for eosinophils in the culture supernatant using a 48-well microchemotaxis chamber and a (51)Cr-labelled eosinophil transmigration assay. RESULTS: Exposing a confluent human tracheal SMG cell monolayer to RV14 consistently led to infection. Human SMG cells with RV infection secreted soluble factors activating human eosinophil chemotaxis into the culture supernatant in a time-dependent manner, and the culture supernatant significantly augmented the transmigration of (51)Cr-labelled eosinophils through human airway epithelial cell layers from the basal to mucosal side. These effects were completely abolished by a mixture of a monoclonal antibody regulated on activation, normal T cells expressed and secreted (RANTES) and an antibody to granulocyte macrophage-colony stimulating factor (GM-CSF). CONCLUSION: These results suggest that human respiratory SMG cells may augment eosinophil transmigration across the airway epithelium through the secretion of RANTES and GM-CSF after RV infection, and may contribute to exacerbations of asthma.

Adult↗
PubMed2002

Neurochemical regulation of cough response to capsaicin in guinea-pigs.

1. Although monumental efforts have been made to define the action sites of cough, the importance of neurotransmitter systems in the cough reflex has received limited attention. We studied the roles for four major neurotransmitters [acetylcholine, histamine, serotonin (5-hydroxytryptamine, 5-HT) and dopamine] in the modulation of the cough reflex. 2. Atropine (muscarinic cholinergic blocking agent), pyrilamine maleate (PM, histamine H1 blocker), cimetidine (histamine H2 blocker), 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT, specific 5-HT1A receptor agonist) and SCH-23390 (selective dopamine D1 receptor antagonist) were examined on the cough response to inhaled capsaicin in conscious guinea-pigs. 3. All the drugs significantly decreased the number of capsaicin-induced coughs in a dose-dependent manner. To compare the sensitivity of these drugs on cough response, we calculated the effective doses for 50% inhibition of cough (ED50) when the animals were exposed to 3 x 10-4 m capsaicin. The ED50 values were 0.03 microm kg-1 for atropine, 0.2 microm kg-1 for 8-OH-DPAT, 6.2 microm kg-1 for SCH-23390, 8.5 microm kg-1 for PM and 13.9 microm kg-1 for cimetidine. 4. These findings indicated that all these four neurotransmitters may be involved in the regulation of the cough reflex. Multiple changes of these neurotransmitters in disorders of the central nervous system might synergically affect the cough reflex.

Animals↗
PubMed2002

Increased blood carboxyhaemoglobin concentrations in inflammatory pulmonary diseases.

BACKGROUND: Exhaled carbon monoxide has been reported to increase in inflammatory pulmonary diseases and to be correlated with blood carboxyhaemoglobin (Hb-CO) concentration. A study was undertaken to determine whether arterial blood Hb-CO increases in patients with inflammatory pulmonary diseases. METHODS: The Hb-CO concentration in arterial blood was measured with a spectrophotometer in 34 normal control subjects, 24 patients with bronchial asthma, 52 patients with pneumonia, and 21 patients with idiopathic pulmonary fibrosis (IPF). RESULTS: The mean (SE) Hb-CO concentrations in patients with bronchial asthma during exacerbations (n=24, 1.05 (0.05)%), with pneumonia at the onset of illness (n=52, 1.08 (0.06)%), and with IPF (n=21, 1.03 (0.09)%) were significantly higher than those in control subjects (n=34, 0.60 (0.07)%) (mean difference 0.45% (95% confidence interval (CI) 0.23 to 0.67), p<0.01 in patients with bronchial asthma, mean difference 0.48% (95% CI 0.35 to 0.60), p<0.0001 in patients with pneumonia, and mean difference 0.43% (95% CI 0.26 to 0.61) p<0.001 in patients with IPF). In 20 patients with bronchial asthma the Hb-CO concentration decreased after 3 weeks of treatment with oral glucocorticoids (p<0.001). In 20 patients with pneumonia the Hb-CO concentration had decreased after 3 weeks when patients showed evidence of clinical improvement (p<0.001). The values of C-reactive protein (CRP), an acute phase protein, correlated with Hb-CO concentrations in patients with pneumonia (r=0.74, p<0.0001) and in those with IPF (r=0.46, p<0.01). In patients with bronchial asthma changes in Hb-CO concentrations were significantly correlated with those in forced expiratory volume in 1 second (FEV(1)) after 3 weeks (r=0.67, p<0.01). Exhaled carbon monoxide (CO) concentrations were correlated with Hb-CO concentrations (n=33, r=0.80, p<0.0001). CONCLUSIONS: Hb-CO concentrations are increased in inflammatory pulmonary diseases including bronchial asthma, pneumonia, and IPF. Measurement of arterial Hb-CO may be a useful means of monitoring pulmonary inflammation.

Aged↗
PubMed2001

Relation between exhaled carbon monoxide levels and clinical severity of asthma.

Carbon monoxide (CO) can be detected in exhaled air and is increased in asthmatic patients not treated with corticosteroids. However, it is uncertain whether exhaled CO is related to severity of asthma. To study whether exhaled CO is related to severity of asthma in clinical courses, exhaled CO concentrations were measured on a CO monitor by vital capacity manoeuvre in 20 mild asthmatics treated with inhaled beta2-agonists alone, 20 moderate asthmatics treated with inhaled corticosteroids, and 15 stable asthmatics treated with high dose inhaled corticosteroids and oral corticosteroids once a month over 1 years. Exhaled CO concentrations were also measured in 16 unstable severe asthmatics who visited the hospital every 7 or 14 days for treatment with high dose inhaled corticosteroids and oral corticosteroids. The mean values of exhaled CO in severe asthma over 1 year were 6.7 +/- 9.5 p.p.m. (n = 31, mean +/- SD) and significantly higher than those of non-smoking control subjects (1.2 +/- 0.9 p.p.m., n = 20, P < 0.01). Exhaled CO concentrations in unstable severe asthmatics were significantly higher than those in stable severe asthmatics. However, exhaled CO concentrations in mild and moderate asthmatics did not differ significantly from those in non-smoking control subjects (P > 0.20). There was a significant relationship between the exhaled CO concentrations and forced expiratory volume in one second in all asthmatic patients. These findings suggest that exhaled CO concentrations may relate to the severity of asthma and measurements of exhaled CO concentrations may be a useful means of monitoring airway inflammation in asthma.

Adult↗
PubMed2001

Interventions to prevent pneumonia among older adults.

Pneumonia is a common cause of death in older people. Antimicrobial drugs do not prevent pneumonia and, because of increasingly resistant organisms, their value in curing infection will become more limited. Establishing new strategies to prevent pneumonia through consideration of the mechanisms of this devastating illness is essential. The purpose of this review is to discuss how pneumonia develops in older people and to suggest preventive strategies that may reduce the incidence of pneumonia among older adults. Aspiration of oropharyngeal bacterial pathogens to the lower respiratory tract is one of the most important risk factors for pneumonia; impairments in swallowing and cough reflexes among older adults, e.g., related to cerebrovascular disease, increase the risk for the development of pneumonia. Thus, strategies to reduce the volumes and pathogenicity of aspirated material should be pursued. For example, since both swallowing and cough reflexes are mediated by endogenous substance P, pharmacologic therapy using angiotensin-converting enzyme inhibitors, which decrease substance P catabolism, may improve both reflexes and result in the lowering of the risk of pneumonia. Similarly, since the production of substance P is regulated by dopaminergic neurons in the cerebral basal ganglia, treatment with dopamine analogs or potentiating drugs such as amantadine (and, of course, prevention of cerebral vascular disease, which can result in basal ganglia strokes) should affect the incidence of pneumonia. The purpose of this review is to consider promising pharmacologic treatments as methods of preventing pneumonia in older adults and to review other proven strategies, e.g., infection control and cerebrovascular disease prevention that will lessen the incidence of pneumonia.

Aged↗
PubMed2001

Type 2 rhinovirus infection of cultured human tracheal epithelial cells: role of LDL receptor.

To examine the role of the low-density lipoprotein (LDL) receptor on minor group human rhinovirus (RV) infection, primary cultures of human tracheal epithelial cells were infected with a minor group (RV2) or a major group (RV14) RV. Viral infection was confirmed by showing with PCR that viral titers in supernatants and lysates from infected cells increased with time. RV2 and RV14 increased expression of mRNA and protein of the LDL receptor on the cells and the cytokine production. RV2 induced activation of transcription factors SP1 and nuclear factor-kappaB (NF-kappaB). An antibody to the LDL receptor inhibited RV2 infection and RV2-induced cytokine production without an effect on RV14 infection and RV14-induced cytokine production. These findings imply that RV2 upregulates LDL receptor expression on airway epithelial cells, thereby increasing susceptibility to minor group RV infection. LDL receptor expression and cytokine production may be mediated, in part, via activation of transcription factors by RV2. These events may be important in airway inflammation after minor group RV infection in asthma.

Aged↗
PubMed2001

Bafilomycin A(1) inhibits rhinovirus infection in human airway epithelium: effects on endosome and ICAM-1.

To examine the effects of bafilomycin A(1), a blocker of vacuolar H(+)-ATPase, on rhinovirus (RV) infection in the airway epithelium, primary cultures of human tracheal epithelial cells were infected with RV14. Viral infection was confirmed by showing that viral RNA in the infected cells and the viral titers in the supernatants of infected cells increased with time. RV14 infection upregulated the production of cytokines and mRNA of intercellular adhesion molecule (ICAM)-1 in epithelial cells. Bafilomycin A(1) reduced the viral titers of RV14 and inhibited the production of cytokines and ICAM-1 before and after RV14 infection. Bafilomycin A(1) reduced susceptibility of epithelial cells to RV14 infection. RV14 increased activated nuclear factor-kappaB in the cells, and bafilomycin A(1) reduced the activated nuclear factor-kappaB. Bafilomycin A(1) decreased the number of acidic endosomes in the epithelial cells. These results suggest that bafilomycin A(1) may inhibit infection by RV14 by not only blocking RV RNA entry into the endosomes but also reducing ICAM-1 expression in the epithelial cells. Bafilomycin A(1) may therefore modulate airway inflammation after RV infection.

Amiloride↗
PubMed2001

Acid exposure stimulates the adherence of Streptococcus pneumoniae to cultured human airway epithelial cells: effects on platelet-activating factor receptor expression.

To examine the effects of acid exposure on the adherence of Streptococcus pneumoniae to cultured human tracheal epithelial cells, cells were exposed to acid at various pH levels, and various concentrations of S. pneumoniae were added to the culture medium. The number of S. pneumoniae adhering to cultured human tracheal epithelial cells increased after acid exposure. Y-24180, a specific inhibitor of the receptor for the platelet-activating factor (PAF) and PAF itself decreased the number of S. pneumoniae adhering to cultured human tracheal epithelial cells after acid exposure. Acid exposure increased the activation of transcription factor nuclear factor (NF)-kappa B and the expression of protein and messenger RNA (mRNA) of the PAF receptor. The pyrrolidine derivative of dithiocarbamate (PDTC), an inhibitor of NF-kappa B, also decreased the number of S. pneumoniae adhering to the cultured human tracheal epithelial cells after acid exposure. Acid exposure increased the content of interleukin (IL)-1 alpha and IL-1 beta in the culture supernatants, but monoclonal antibodies to IL-1 alpha and IL-1 beta failed to inhibit the increased number of S. pneumoniae adhering to cultured human tracheal epithelial cells after acid exposure. These findings suggest that acid exposure stimulates the adherence of S. pneumoniae to the airway epithelial cells via increases in PAF receptors. Increases in PAF receptor expression may be, in part, mediated via activation of transcription factors and subsequent PAF receptor mRNA expression by acid exposure. Increased adherence of S. pneumoniae may be one of the reasons why pneumonia develops after gastric juice aspiration.

Aged↗
PubMed2001

"Haemoxygenase-1 induction and exhaled markers of oxidative stress in lung diseases", summary of the ERS Research Seminar in Budapest, Hungary, September, 1999.

In recent years, there has been increasing interest in noninvasive monitoring of airway inflammation and oxidative stress. Several volatile and nonvolatile substances can be measured in exhaled breath and have been suggested as potential biomarkers of these events. Exhaled gases, including carbon monoxide (CO), alkanes (ethane, pentane), and substances measured in breath condensate, such as hydrogen peroxide (H2O2) and isoprostanes were all suggested as potential markers of oxidative stress in the lung. A European Respiratory Society (ERS) International Research Seminar entitled "Haemoxygenase-1 induction and exhaled markers of oxidative stress in lung diseases" was organized by the Airway Regulation and Provocation Group of the Clinical Allergy and Immunology Assembly in Budapest, Hungary in September, 1999 to integrate the latest knowledge on these issues and accelerate further improvement in this area. During this 2-day event several issues were raised about: the use and standardization of measurements in exhaled breath; problems of measuring expired H2O2 and other mediators in breath condensate; role and regulation of haemoxygenase (HO)-1 in the lung; and conditions and factors influencing exhaled CO. This report is a summary of the main presentations at the seminar, together with the current areas of research in this rapidly expanding field.

Antioxidants↗
PubMed2001

Erythromycin and common cold in COPD.

STUDY OBJECTIVES: To investigate whether erythromycin therapy lowers the frequency of the common cold and subsequent exacerbation in patients with COPD. DESIGN: Prospective, randomized, controlled, but not blinded, trial. PATIENTS: One hundred nine patients with COPD were enrolled into the study. Patients were randomly assigned to erythromycin therapy or to no active treatment in September 1997. Patients then were observed for 12 months, starting in October, during which time the risk and frequency of catching common colds and COPD exacerbations were investigated. Fifty-five patients received erythromycin at study entry (erythromycin group). The remaining 54 patients received no active treatment (control group). MEASUREMENTS AND RESULTS: The mean (+/- SE) number of common colds for 12 months was significantly lower in the erythromycin group than in the control group (1.24 +/- 0.07 vs 4.54 +/- 0.02, respectively, per person; p = 0.0002). Forty-one patients (76%) in the control group experienced common colds more than once, compared to 7 patients (13%) in the erythromycin group. The relative risk of developing two or more common colds in the control group compared with that in the erythromycin group was 9.26 (95% confidence interval [CI], 3.92 to 31.74; p = 0.0001). Thirty patients (56%) in the control group and 6 patients (11%) in the erythromycin group had one or more exacerbations. The relative risk of experiencing an exacerbation in the control group compared with that in the erythromycin group was 4.71 (95% CI, 1.53 to 14.5; p = 0.007). Significantly more patients were hospitalized due to exacerbations in the control group than in the erythromycin group (p = 0.0007). CONCLUSION: Erythromycin therapy has beneficial effects on the prevention of exacerbations in COPD patients.

Aged↗