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Biomedical subjects

T Ohrui

Publications and source records attributed to T Ohrui.

At least 19 recordsLinked to original sources
PubMed1999

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↗
PubMed1998

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↗
PubMed1998

Dopamine D1 receptor antagonist inhibits swallowing reflex in guinea pigs.

To determine whether dopamine D1 receptor antagonist impairs the swallowing reflex and reduces substance P (SP) in the peripheral organs, the swallowing reflex in terms of the number of swallows elicited by injections of three different volumes (0.2, 0.4, and 0.6 ml) of distilled water into the pharynx through a catheter was examined in anesthetized guinea pigs pretreated with Sch-23390. Animals were pretreated with either subcutaneous Sch-23390 (200 micrograms/kg) or a vehicle of Sch-23390 every 12 h for 7 days. The number of swallows was counted by submental electromyographic activity and visual observation of characteristic laryngeal movement. Injections of distilled water caused a volume-dependent increase in the number of swallows in animals without Sch-23390 treatment. Sch-23390 significantly decreased and exogenously administered SP increased the number of swallows elicited by all volumes of distilled water. FK-888 (10(-5) M, 1 ml), a specific inhibitor of the NK1 receptor, reduced the number of swallows to a greater degree than Sch-23390. Sch-23390 significantly reduced SP content in the laryngeal and pharyngeal mucosa compared with control. These results suggest that inhibition of the dopamine D1 receptor may impair the swallowing reflex and reduce SP content in the peripheral organs.

Animals↗
PubMed1998

Effects of rhinovirus infection on hydrogen peroxide- induced alterations of barrier function in the cultured human tracheal epithelium.

To investigate whether rhinovirus infection impairs epithelial barrier functions, human rhinovirus 14 (HRV-14) was infected to primary cultures of human tracheal epithelial cells and experiments were performed on Day 2 after HRV-14 infection. Hydrogen peroxide (H2O2; 3 x 10(-)4 M) increased electrical conductance (G) across the epithelial cell sheet measured with Ussing's chamber methods. Exposure of the epithelial cells to HRV-14 had no effect on H2O2-induced increases in G and [3H]mannitol flux through the cultured epithelium in the control condition, but it markedly potentiated H2O2- induced increases in both parameters in IL-1beta (100 U/ml) pretreated condition. However, pretreatment with TNF-alpha (100 U/ml) was without effect. IL-1beta enhanced the intercellular adhesion molecule-1 (ICAM-1) expression assessed by immunohistochemical analysis and susceptibility of epithelial cells to HRV-14 infection. An antibody to ICAM-1 inhibited HRV-14 infection of epithelial cells and abolished H2O2-induced increases in G and [3H]mannitol flux in IL-1beta-pretreated epithelial cells with HRV-14 infection. These results suggest that rhinovirus infection may reduce barrier functions in the airway epithelium in association with upregulation of ICAM-1 expression.

Antibodies, Monoclonal↗
PubMed1998

Effects of air pollution and smoking on chronic obstructive pulmonary disease and bronchial asthma.

Although both tobacco smoking and air pollution are believed to be environmental factors affecting the prevalence of chronic obstructive pulmonary disease (COPD) and bronchial asthma, the mechanisms by which they induce/aggravate these diseases are still not known in detail. While smoking has been demonstrated to cause and aggravate COPD and bronchial asthma, the influence of air pollution, suspected to have hazardous environmental effects since the historical episodes of severe air pollution such as the London Smog, on the prevalence of airway diseases remains unclear. This is due, in part, to changes over time in the nature of the air pollutants concerned. There have been no consistent findings on the effects on airway diseases of air pollutants at levels currently observed in developed countries. It is believed that cessation of smoking is the most important factor in preventing the development of COPD.

Air Pollutants↗
PubMed1997

Rhinovirus infection of primary cultures of human tracheal epithelium: role of ICAM-1 and IL-1beta.

Exacerbations of asthma are often associated with respiratory infection caused by rhinoviruses. To study the effects of rhinovirus infection on respiratory epithelium, a primary target for respiratory viruses, human rhinovirus (HRV)-2 and HRV-14 were infected to primary cultures of human tracheal epithelial cells. Viral infection was confirmed by showing that viral titers of supernatants and lysates from infected cells increased with time and by polymerase chain reaction. HRV-2 and HRV-14 infections upregulated the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA, the major rhinovirus receptor, on epithelial cells, and they increased the production of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha in supernatants. Antibodies to ICAM-1 inhibited HRV-14 infection of epithelial cells and decreased the production of cytokines after HRV-14 infection, but they did not alter HRV-2 infection-induced production ofcytokines. IL-1beta upregulated ICAM-1 mRNA expression and increased susceptibility to HRV-14 infection, whereas other cytokines failed to alter ICAM-1 mRNA expression. Furthermore, a neutralizing antibody to IL-1beta significantly decreased viral titers of supernatants and ICAM-1 mRNA expression after HRV-14 infection, but a neutralizing antibody to TNF-alpha was without effect. Immunohistochemical studies revealed that both HRV-14 infection and IL-1beta increased ICAM-1 expression on cultured epithelial cells. These findings imply that HRV-14 infection upregulated ICAM-1 expression on epithelial cells through increased production of IL-1beta, thereby increasing susceptibility to infection. These events may be important for amplification of airway inflammation after viral infection in asthma.

Antibodies↗
PubMed1997

Increased carbon monoxide in exhaled air of asthmatic patients.

Exhaled carbon monoxide (CO) concentrations were measured on a CO monitor by vital capacity maneuvers in asthmatic patients receiving or not receiving inhaled corticosteroids and in nonsmoking and smoking 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 (5.6+/-0.6 ppm, p < 0.001) and similar in asthmatic patients receiving inhaled corticosteroids (1.7+/-0.1 ppm) compared with those in nonsmoking healthy control subjects (1.5+/-0.1 ppm). Smoking healthy control subjects had the highest levels of exhaled CO concentration among the groups (21.6+/-2.8 ppm, p < 0.001). To examine whether inhaling corticosteroids reduce exhaled CO concentration in a given asthmatic patient, 12 patients with symptomatic asthma who were being treated by inhaled beta2-agonists alone underwent measurements of exhaled CO concentration before and 4 wk after the initiation of inhaled corticosteroid treatment. All patients had reductions in exhaled CO concentration (p < 0.001) and eosinophil cell counts in sputum (p < 0.01) that were accompanied by an improvement in airway obstruction. Changes in exhaled CO concentration were significantly related to those in the eosinophil cell counts in sputum (p < 0.001). The present study shows an elevation of exhaled CO in asthmatic patients that decreases with corticosteroid therapy. Increases in the exhaled CO levels therefore may reflect inflammation in the asthmatic lung.

Administration, Inhalation↗
PubMed1997

Mechanisms of gastric juice-induced hyperpermeability of the cultured human tracheal epithelium.

PURPOSE: The respiratory aspiration of the stomach contents causes severe lung damage called aspiration pneumonia. The present study was undertaken to elucidate whether mucosal exposure of gastric juice causes hyperpermeability of the human airway epithelium and to determine the mechanisms responsible for gastric juice-induced airway epithelial damage. MATERIALS AND METHODS: Gastric juice was collected from 46 normal adults via gastroscope and samples were analyzed for pH, osmolarity, and concentration of pepsin and trypsin. Tracheal surface epithelial cells were obtained from 16 autopsies, cultured onto porous filters, and mounted in the Ussing chamber. Electrical conductance (G) was measured before and after exposure of cells to gastric juice or Krebs-Henseleit solution with pH at 1.8, 2.8, 4.0, or 7.4 in the presence or absence of pepsin. D-[3H] mannitol flux study across the epithelial layer and histologic observations using an inverted microscope were also performed after exposure of cells to gastric juice. RESULTS: Exposure of cultured human tracheal epithelium to gastric juice caused increases in G in a time- and pH-dependent fashion. A pepsin inhibitor (pepstatin A) inhibited gastric juice-induced increases in G at a pH of 2.8, and the addition of pepsin augmented increases in G induced by the Krebs-Henseleit solution at a pH of 1.8 and 2.8. Lowering the osmolarity of the solution to levels similar to gastric juice also potentiated increases in G induced by acid and pepsin. Gastric juice caused increases in D-[3H] mannitol flux across the epithelial layer bidirectionally, and microscopic observation revealed separation of the intercellular space and cell detachment from culture vessels after exposure of cells to gastric juice. CONCLUSION: Gastric juice causes hyperpermeability across human airway epithelium probably through the additive effects of gastric acid, pepsin activity, and lower osmolarity.

Adult↗
PubMed1997

New strategies for aspiration pneumonia.

Aspiration pneumonia is associated with decreases in both swallowing and cough reflexes and is the most common cause of death in the elderly. Basal ganglia strokes might predispose these patients to develop pneumonia owing to reductions of both reflexes, resulting in frequent aspiration during sleep. An impairment of dopamine metabolism in the basal ganglia is observed in these patients and levodopa administration improves the impaired swallowing reflex. Both swallowing and cough reflexes are mediated by endogenous substance P (SP) released from vagal sensory nerves in the pharynx and upper airways. The addition of a low dose of capsaicin to liquid or food, which stimulates the release of SP, may help prevent aspiration pneumonia. Angiotensin-converting enzyme inhibitor decreases SP catabolism resulting in improvements in both reflexes. Oral care and the sitting position after meals may decrease aspiration pneumonia in the elderly.

Aged↗
PubMed1996

Effects of adrenomedullin and calcitonin gene-related peptide on airway and pulmonary vascular smooth muscle in guinea-pigs.

1. The airway and pulmonary vascular effects of adrenomedullin were studied in the guinea-pig isolated trachea, main bronchi and pulmonary artery in vitro and compared to the effects of calcitonin gene-related peptide (CGRP). 2. In tracheal rings, CGRP (1 nM to 1 microM) potentiated the cholinergic contractions induced by electrical field stimulation (EFS) at 5 Hz in a concentration-dependent manner. At a concentration of 1 microM, CGRP slightly decreased the responses to log EFS frequency, producing 50% of the maximum contraction from a control value of 0.77 +/- 0.10 Hz to 0.54 +/- 0.05 Hz without a significant effect on the concentration-response curves to acetylcholine (ACh). In contrast, adrenomedullin (1 nM to 1 microM) did not alter either EFS-induced cholinergic or ACh-induced contractions. 3. In bronchial strips, CGRP (1 nM to 1 microM) slightly reduced both the non-adrenergic non-cholinergic (NANC) contraction induced by EFS at 10 Hz and the substance P (1 microM)-induced contraction in a concentration-dependent manner, whereas adrenomedullin (1 nM to 1 microM) was without effect. 4. Neither CGRP (1 microM) nor adrenomedullin (1 microM) altered NANC relaxation induced by EFS at 5 Hz in tracheal rings precontracted with histamine (10 microM). 5. Adrenomedullin (1 nM to 1 microM) and CGRP (1 nM to 1 microM) induced a concentration-dependent relaxation of the histamine (10 microM)- and prostaglandin F2 alpha (10 microM)-precontracted pulmonary arterial rings with intact endothelium with a similar potency. 6. Neither removal of the endothelium nor NG-nitro-L-arginine methyl ester (100 microM) altered the vasorelaxant effects of adrenomedullin (1 nM to 1 microM) and CGRP (1 nM to 1 microM). 7. The putative CGRP receptor antagonist, CGRP8-37 (1 microM to 10 microM) concentration-dependently attenuated the CGRP (3 nM to 30 nM)-induced vasorelaxant actions, whereas it had no effect on the relaxation of vessel rings induced by adrenomedullin (3 nM to 30 nM). 8. These results suggest that adrenomedullin is a potent vasodilator of the pulmonary artery without any bronchomotor effect in the guinea-pig lung, and that the vasorelaxant actions of adrenomedullin are not mediated via the activation of CGRP1 receptors.

Adrenomedullin↗
PubMed1996

P2u-purinoceptor regulation of chloride secretion in cultured human tracheal submucosal glands.

We examined the purinergic regulation of chloride secretion and intracellular calcium ion concentration ([Ca2+]i) in the cultured epithelial cells passaged from human tracheal submucosal glands. Adenosine, AMP, ADP, ATP, and UTP induced transient short-circuit current (Isc) responses in a concentration-dependent fashion. The rank order of peak Isc responses at 10 microM concentrations was UTP = ATP > ADP > AMP = adenosine. Diphenylamine-2-carboxylic acid (1 mM) and 4,4'- diisothiocyano-2,2'-stilbene disulfonate (0.5 mM), and quinidine (1 mM) inhibited Isc responses induced by extracellular nucleotides. However, amiloride (10 microM) was without effect. Theophylline (1 mM) did not alter ATP (10 microM)-induced Isc response. Increases in Isc induced by ATP and UTP were significantly larger than those by alpha, beta-methylene ATP, beta, gamma-methylene ATP, or 2-methylthio ATP. Extracellular nucleotides caused increases in [Ca2+]i, and the rank order of [Ca2+]i responses was same as that of Isc responses. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxy-methyl ester (50 microM) inhibited increases in Isc and [Ca2+]i induced by extracellular nucleotides. These results suggest that extracellular nucleotides induce chloride secretion across cultured human tracheal glands via a P2u-purinoceptor, and this chloride secretion appears to be dependent on increases in [Ca2+]i and activation of Ca-dependent K channels.

Adenosine Triphosphate↗