397 results on '"J, Tamaoki"'
Search Results
2. Histamine N-methyltransferase Modulates Human Bronchial Smooth Muscle Contraction
- Author
-
J. Tamaoki, A. Chiyotani, E. Tagaya, K. Isono, and K. Konno
- Subjects
Pathology ,RB1-214 - Abstract
To elucidate the modulatory role of histamine-degrading enzymes in airway constrictor responses, human bronchial strips were studied under isometric conditions in vitro. Pretreatment of tissues with the histamine N-methyltransferase (HMT) inhibitor SKF 91488 specifically potentiated the contractile responses to histamine, causing a leftward displacement of the concentration response curves, whereas the diamine oxidase inhibitor aminoguanidine had no effect. This potentiation was attenuated by mechanical removal of the epithelium. The HMT activity was detected in the human bronchi, which was less in the epithelium-denuded tissues than the epithelium-intact tissues. These results suggest that HMT localized to the airway epithelium may play a protective role against histamine-mediated bronchoconstriction in humans. more...
- Published
- 1994
- Full Text
- View/download PDF
Catalog
3. Heterogeneity of the roles of leukotriene and thromboxane A2receptor antagonists in the treatment of moderate to severe asthma
- Author
-
K. Isono, Atsushi Nagai, Y. Nagano, E. Tagaya, M. Taira, and J. Tamaoki
- Subjects
Moderate to severe ,Leukotriene ,Thesaurus (information retrieval) ,business.industry ,Immunology ,Immunology and Allergy ,Medicine ,Thromboxane A2 receptor ,business ,medicine.disease ,Asthma - Published
- 2001
- Full Text
- View/download PDF
4. Impairment of Airway Mucociliary Transport in Patients with Sinobronchial Syndrome: Role of Nitric Oxide
- Author
-
M Taira, K Nishimura, Junko Nakata, A Nagai, and J Tamaoki
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Pathology ,Mucociliary clearance ,Nitric Oxide ,Gastroenterology ,Nitric oxide ,chemistry.chemical_compound ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,Expiration ,Sinusitis ,Respiratory system ,Aged ,Analysis of Variance ,Bronchiectasis ,business.industry ,Respiratory disease ,Sputum ,Syndrome ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,chemistry ,Mucociliary Clearance ,Luminescent Measurements ,Female ,medicine.symptom ,business ,Ciliary Motility Disorders ,Respiratory tract - Abstract
Nitric oxide (NO) produced within the respiratory tract can stimulate ciliary motility of airway epithelial cells and hence mucociliary transport. In this study, to determine the role of NO in mucociliary dysfunction in sinobronchial syndrome (SBS), we measured NO concentrations in the exhaled air by chemiluminescence analyzer and nasal clearance time (NCT) by saccharin test. Exhaled NO concentrations in patients with SBS were 39% of those in healthy nonsmokers and 55% of those in healthy smokers. The patients also showed prolonged NCT compared with healthy subjects, and there was a significant negative correlation between exhaled NO concentrations and NCT. Furthermore, concentrations of chloride (Cl) in the sputum supernatant were higher in SBS patients than in healthy subjects, and there was a significant negative correlation between sputum Cl concentrations and exhaled NO concentrations. These results suggest that airway mucociliary clearance is impaired in patients with SBS and that this impairment might result from the reduced production of NO and the impaired availability of the molecule in the mucociliary apparatus. more...
- Published
- 2000
- Full Text
- View/download PDF
5. Regulation of adrenergic nerve-mediated contraction of canine pulmonary artery by K+ channels
- Author
-
E Tagaya, J Tamaoki, H Takemura, and A Nagai
- Subjects
Pulmonary and Respiratory Medicine - Abstract
The aim of the present study was to investigate the role of certain subtypes of K+ channels in nerve-evoked contractions of pulmonary artery in vitro. The lobar or segmental pulmonary arteries were dissected from dogs, cut into ring segments, and the contractile responses to electrical field stimulation (EFS) and noradrenaline were measured under isometric conditions. Addition of iberiotoxin, a big conductance Ca2+-activated K+ channel blocker, and apamin, a small conductance Ca2+-activated K+ channel blocker, did not change the resting tension but augmented the contractile responses to EFS, so that the electric stimulus frequency required to produce a half-maximal contraction (ES50) was decreased from 18.2+/-3.5 to 7.4+/-2.3 Hz (p more...
- Published
- 1998
- Full Text
- View/download PDF
6. 5-Hydroxytryptamine inhibits Na absorption and stimulates Cl secretion across canine tracheal epithelial sheets
- Author
-
J. TAMAOKI, A. CHIYOTANI, H. TAKEMURA, and K. KONNO
- Subjects
Immunology ,Immunology and Allergy - Published
- 1997
- Full Text
- View/download PDF
7. Role of nitric oxide in tachykinin-induced increase in potential difference of rabbit tracheal mucosa
- Author
-
M. Kondo, A. Sakai, H Takemura, K. Konno, and J. Tamaoki
- Subjects
Male ,Neurokinin B ,Physiology ,Neurokinin A ,Substance P ,Arginine ,Nitric Oxide ,Epithelium ,Membrane Potentials ,Nitric oxide ,Amiloride ,chemistry.chemical_compound ,In vivo ,Tachykinins ,medicine ,Animals ,Respiratory system ,Transepithelial potential difference ,Mucous Membrane ,Histocytochemistry ,NADPH Dehydrogenase ,Anatomy ,respiratory system ,Molecular biology ,Electrophysiology ,Trachea ,NG-Nitroarginine Methyl Ester ,chemistry ,Rabbits ,Research Article ,medicine.drug - Abstract
1. The effect of tachykinins on transepithelial potential difference (PD) of rabbit trachea and possible involvement of nitric oxide (NO) generation in vivo were investigated. 2. Perfusion of tracheal mucosa with neurokinin A (NKA) or substance P (SP) dose dependently increased PD in the presence of amiloride, with the potency being NKA > SP, but neurokinin B (NKB) had no effect. 3. Application of NG-nitro-L-arginine methylester (L-NAME, 10(-3) M) attenuated the NKA-induced increase in the amiloride-sensitive PD, causing a rightward displacement of the dose-response curve by approximately 1.0 log U, whereas NG-nitro-D-arginine methylester (D-NAME, 10(-3) M) did not. 4. The inhibitory effect of L-NAME was reversed by L-arginine (10(-2) M) but not by D-arginine (10(-2) M). 5. The release of NO was determined by a real-time measurement of NO concentration ([NO]) in the perfusate using specific amperometric sensors for this molecule. 6. NKA and SP increased [NO] in a dose-dependent manner, the maximal increase from the baseline value being 114 +/- 11 nM (mean +/- S.E.M., P < 0.001) and 54 +/- 6 nM (P < 0.01), respectively. 7. Histochemistry for NADPH diaphorase activity showed a strong staining within the epithelial cells. 8. We conclude firstly that tachykinins increase amiloride-sensitive PD in vivo, which probably reflects Cl- movement from the submucosa toward the respiratory lumen in tracheal mucosa, and secondly that NO generation by epithelial cells may be involved in this process. more...
- Published
- 1995
- Full Text
- View/download PDF
8. Effect of long term treatment with oxitropium bromide on airway secretion in chronic bronchitis and diffuse panbronchiolitis
- Author
-
Etsuko Tagaya, J. Tamaoki, Kimio Konno, Atsushi Chiyotani, and N Sakai
- Subjects
Pulmonary and Respiratory Medicine ,Chronic bronchitis ,Water transport ,business.industry ,medicine.drug_class ,medicine.disease ,Metered-dose inhaler ,respiratory tract diseases ,chemistry.chemical_compound ,chemistry ,Bronchodilator ,Anesthesia ,Medicine ,Sputum ,Bronchitis ,medicine.symptom ,business ,Diffuse panbronchiolitis ,Oxitropium bromide ,Research Article - Abstract
BACKGROUND--Anticholinergic bronchodilator drugs improve lung function in chronic bronchitis but less is known of their effects on the volume and physical properties of sputum in conditions associated with excessive airway secretions. This study examines the effects of the regular use of oxitropium bromide in such patients. METHODS--The study was conducted in a parallel, double blind, placebo controlled fashion. Patients were divided into two groups: the first group (n = 17) received oxitropium bromide from a metered dose inhaler (two puffs three times daily; 100 micrograms/puff) for eight weeks, and the second group (n = 16) received placebo. Lung function was measured as forced expiratory volume in one second (FEV1) and vital capacity. In evaluating airway secretion, daily amount of expectorated sputum, percentage solid composition, viscoelastic properties including elastic modulus and dynamic viscosity, and sputum microbiology were determined. RESULTS--Oxitropium bromide increased FEV1 and decreased the mean (SE) sputum production from 61(4) to 42(3) g/day after treatment, whereas placebo had no effect. Bacterial density and sputum flora were unchanged, but solid composition and elastic modulus increased from 2.52(0.43)% to 3.12(0.34)%, and 68(12) dyne/cm2, respectively, in the group taking oxitropium bromide. CONCLUSIONS--Regular treatment with oxitropium bromide not only improves airflow limitation but also reduces sputum production, probably through the inhibition of both mucus secretion and water transport, the latter component being predominant. more...
- Published
- 1994
- Full Text
- View/download PDF
9. Angiotensin II 1 receptor-mediated contraction of pulmonary artery and its modulation by prolylcarboxypeptidase
- Author
-
J. Tamaoki, K. Isono, Etsuko Tagaya, Atsushi Chiyotani, F. Sugimoto, and Konno K
- Subjects
Male ,medicine.medical_specialty ,Endothelium ,Pyridines ,Physiology ,medicine.drug_class ,Tetrazoles ,Carboxypeptidases ,In Vitro Techniques ,Pulmonary Artery ,Arginine ,Nitric Oxide ,Losartan ,Muscle, Smooth, Vascular ,Angiotensin Receptor Antagonists ,chemistry.chemical_compound ,Dogs ,Isometric Contraction ,Physiology (medical) ,Internal medicine ,Hypoxic pulmonary vasoconstriction ,Renin–angiotensin system ,medicine ,Animals ,Protease Inhibitors ,Receptor ,Receptors, Angiotensin ,Chemistry ,Angiotensin II ,Biphenyl Compounds ,Phosphoramidon ,Imidazoles ,Receptor antagonist ,NG-Nitroarginine Methyl Ester ,medicine.anatomical_structure ,Endocrinology ,cardiovascular system ,Endothelium, Vascular ,medicine.symptom ,Vasoconstriction - Abstract
To determine the subtype of angiotensin II (ANG II) receptor involved in the contraction of pulmonary artery and to elucidate its possible modulation by endogenous peptidases, we studied canine isolated pulmonary arterial rings under isometric conditions in vitro. Addition of ANG II caused a concentration-dependent contraction, an effect that was not altered by the ANG II 2 receptor antagonist EXP655 but was depressed by the ANG II 1 receptor antagonist DuP 753 so that the ANG II response curves were displaced to higher concentration by 1.5–2.0 log U (P < 0.001). Pretreatment of tissues with the prolylcarboxypeptidase (PCP) inhibitor p-methylphenyl sulfonyl-fluoride potentiated the ANG II-induced contraction, with the concentration required to produce a half-maximal effect of ANG II being decreased from 4.1 +/- 0.9 x 10(-9) to 3.8 +/- 0.5 x 10(-10) M (P < 0.001), whereas other peptidase inhibitors such as p-chloromercuriphenyl sulfonic acid, amastatin, and phosphoramidon had no effect. The p-methylphenyl sulfonylfluoride-induced potentiation was abolished by the removal of endothelium, but it was still observed in the presence of NG-nitro-L-arginine methyl ester in the endothelium-intact tissues. The PCP activity in the tissues was reduced by the removal of endothelium from 645 +/- 88 to 91 +/- 29 nmol.mg protein-1.h-1 (P < 0.001), and cultured endothelium had the activity of 404 +/- 39 nmol.mg protein-1.h-1. These results suggest that ANG II contracts pulmonary artery via ANG II 1 receptor and that PCP localized to the endothelium may have a modulatory role in the ANG II-induced pulmonary vasoconstriction. more...
- Published
- 1994
- Full Text
- View/download PDF
10. Effects of Prostacyclin and Beraprost on Ciliary Motilitγ of Rabbit Airway Epithelium
- Author
-
Kiyoshi Takeyama, Konno K, S Sakai, Etsuko Tagaya, Atsushi Chiyotani, and J. Tamaoki
- Subjects
Male ,medicine.medical_specialty ,Prostacyclin ,In Vitro Techniques ,Biology ,Epithelium ,Internal medicine ,Cyclic AMP ,medicine ,Animals ,Cilia ,Pharmacology ,Tracheal Epithelium ,Lagomorpha ,General Medicine ,biology.organism_classification ,Epoprostenol ,Beraprost ,Trachea ,Endocrinology ,medicine.anatomical_structure ,Respiratory epithelium ,Rabbits ,Intracellular ,medicine.drug ,Respiratory tract - Abstract
The effects of prostacyclin and its stable analog beraprost on ciliary beat frequency (CBF) of rabbit tracheal epithelium were studied by a microphoto-oscillation technique in vitro. Addition of these drugs increased CBF in a dose-dependent fashion: the maximal increase from the baseline value and the drug concentration required to produce a half-maximal effect were 13.3 +/- 2.0% (p < 0.05) and 1.8 +/- 0.4 x 10(-7) mol/l for prostacyclin and 30.8 +/- 3.4% (p < 0.001) and 1.6 +/- 0.5 x 10(-7) mol/l for beraprost. These effects were accompanied by the increase in intracellular cyclic AMP levels. Thus, prostacyclin and beraprost may stimulate ciliary motility and, hence, mucociliary transport through the production of cyclic AMP. more...
- Published
- 1994
- Full Text
- View/download PDF
11. Effect of azelastine on sulphur dioxide induced impairment of ciliary motility in airway epithelium
- Author
-
Kiyoshi Takeyama, Kimio Konno, N Sakai, Atsushi Chiyotani, and J. Tamaoki
- Subjects
Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Mucociliary clearance ,Bronchi ,Epithelium ,Photometry ,Internal medicine ,medicine ,Humans ,Sulfur Dioxide ,Cilia ,Respiratory system ,Cells, Cultured ,business.industry ,Cilium ,Epithelial Cells ,Azelastine ,Stimulation, Chemical ,Bronchodilator Agents ,Light intensity ,medicine.anatomical_structure ,Endocrinology ,Mucociliary Clearance ,Phthalazines ,Respiratory epithelium ,business ,Intracellular ,Research Article ,medicine.drug - Abstract
OBJECTIVE--The effect of azelastine on airway mucociliary transport function was studied by measuring ciliary motility of human bronchial epithelium in vitro with a photoelectric method. METHOD--Bronchial epithelial cells were obtained by fibreoptic bronchoscopy, mounted in a Rose chamber, and perfused with Krebs-Henseleit solution. The preparations were placed on a microscope stage equipped with an illuminator, and the variations of light intensity caused by ciliary beating were detected by a photometer. RESULTS--The addition of azelastine to the perfusate increased ciliary beat frequency (CBF) in a dose dependent manner without ciliary discoordination. The mean (SE) maximal increase from the baseline value and the concentration required to produce a half maximal effect were 27.0 (4.2)% and 9.2 x 10(-6) mol/l, respectively. Exposure of the cells to the perfusate containing 3 ppm sulphur dioxide rapidly decreased CBF by 59.2 (5.0)%, and was accompanied by a reduction in intracellular cyclic AMP levels from 38.1 (4.3) to 10.1 (2.4) pmol/mg protein. This effect was prevented by pretreatment of cells with azelastine in a dose dependent manner. CONCLUSIONS--Azelastine not only stimulates ciliary motility of airway epithelium and hence mucociliary transport function, but may also protect against sulphur dioxide induced ciliary dysfunction, probably by inhibiting intracellular cyclic AMP loss. more...
- Published
- 1993
- Full Text
- View/download PDF
12. Erythromycin inhibits Cl secretion across canine tracheal epithelial cells
- Author
-
J Tamaoki, K Isono, N Sakai, T Kanemura, and K Konno
- Subjects
Pulmonary and Respiratory Medicine - Abstract
We studied the effect of the macrolide antibiotic erythromycin on bioelectrical properties of canine cultured tracheal epithelium under short-circuit conditions in vitro. Addition of erythromycin to the submucosal but not to the mucosal side dose-dependently decreased short-circuit current (Isc), the maximal decrease from the baseline value and the concentration required to produce a half-maximal effect (IC50) being 5.6 +/- 1.0 microA.cm-2 (mean +/- SE, p less than 0.001) and 18 microM, respectively. In contrast, other antibiotics including ampicillin, cephazolin and tetracycline were without effect. The erythromycin-induced decrease in Isc was not altered by amiloride, but it was abolished by bumetanide, diphenylamine-2-carboxylate2, and substitution of Cl in the bathing medium with gluconate (p less than 0.001, in each case). The effect of erythromycin on epithelial Isc was attenuated by pretreatment of cells with indomethacin but not with AA-861 a lipoxygenase inhibitor. Incubation of cells with erythromycin inhibited the release of prostaglandins E2 and F2 alpha from tracheal epithelial cells. These results indicate that erythromycin may selectively inhibit Cl secretion across airway epithelium through the inhibition of prostaglandin synthesis and suggest that this action possibly reflects its clinical efficacy in the treatment of airway hypersecretion. more...
- Published
- 1992
- Full Text
- View/download PDF
13. Stimulation of Na Absorption by the Antiasthmatic Kampo Drug Saiboku-to in Cultured Airway Epithelium
- Author
-
J, Tamaoki, K, Takeyama, A, Chiyotani, N, Sakai, T, Takizawa, and K, Konno
- Subjects
Male ,Pharmacology ,Epithelium ,Trachea ,Dogs ,Cyclic AMP ,Histamine H1 Antagonists ,Potentiometry ,Animals ,Female ,Medicine, Kampo ,Sodium-Potassium-Exchanging ATPase ,Cells, Cultured ,Drugs, Chinese Herbal - Abstract
To study the effect of the Kampo drug Saiboku-to (TJ-96) on ion transport function of airway epithelial cells, we studied bioelectric properties of cultured tracheal epithelium from dogs under short-circuit conditions in vitro. Addition of TJ-96 (1 mg/ml) to the mucosal solution of the Ussing chamber increased the epithelial short-circuit current (SCC) from 6.5 +/- 0.7 to 11.4 +/- 1.6 microA/cm2 (P less than 0.001). This effect was dose-dependent, with the maximal increase from the baseline value and the concentration required to produce a half-maximal effect (EC50) being 70.5 +/- 12.6% (P less than 0.001) and 3 micrograms/ml, respectively; and there were corresponding increases in transepithelial potential difference and cell conductance. Submucosal addition of TJ-96 likewise increased SCC, although the magnitude of the response was smaller as compared with the response to the mucosal addition. The TJ-96-induced increase in SCC was not affected by diphenylamine-2-carboxylate or furosemide but abolished by amiloride. Intracellular cyclic AMP levels were dose-dependently increased by TJ-96. These results indicate that TJ-96 may selectively stimulate Na absorption across the tracheal epithelium, probably through intracellular accumulation of cyclic AMP. more...
- Published
- 1992
- Full Text
- View/download PDF
14. [Effect of endothelin on DNA synthesis in human bronchial epithelium: role of MAP kinase cascade]
- Author
-
K, Nishimura, J, Tamaoki, K, Isono, K, Aoshiba, and A, Nagai
- Subjects
Endothelins ,Humans ,Bronchi ,DNA ,Mitogen-Activated Protein Kinases ,Cell Division ,Epithelium - Abstract
To elucidate the effect of endothelin (ET) on airway epithelial cell proliferation, we measured intracellular DNA levels and assessed a possible contribution of mitogen activated protein kinase (MAPK) cascade to the ET action. Incubation of transformed human bronchial epithelial (16 HBE) cells with ET in the serum-free medium caused time-dependent increases in DNA synthesis and MTT reduction, an effect that was attenuated by the MAPK kinase inhibitor PD 98059 in a concentration-dependent manner. Western blot analysis showed that ET induced the expression of phosphorylated MAPK protein, indicating an activation of MAPK, and that this effect was inhibited in the presence of PD 98059 or the ETA receptor antagonist BQ-123. These results suggest that ET may stimulate the proliferation of human airway epithelium via ETA receptors and the concomitant activation of MAPK cascade. more...
- Published
- 2002
15. Adenosine A3 receptor-mediated airway microvascular leakage: role of mast cells and tachykinins
- Author
-
Y, Nagano, J, Tamaoki, K, Nishimura, I, Yamawaki, and A, Nagai
- Subjects
Male ,Adenosine ,Bronchoconstriction ,Receptor, Adenosine A3 ,Receptors, Purinergic P1 ,Rats ,Capillary Permeability ,Rats, Sprague-Dawley ,Piperidines ,Tachykinins ,Administration, Inhalation ,Prostaglandins ,Purinergic P1 Receptor Agonists ,Animals ,p-Methoxy-N-methylphenethylamine ,Mast Cells - Abstract
To determine whether adenosine A3 receptor stimulation produces airway inflammation and, if so, what the mechanism of action is, we studied microvascular permeability in the rat trachea. After intravenous injection of Evans blue dye, adenosine and various adenosine analogues were given by inhalation, and the tracheal microvascular permeability was determined by a photometric measurement of extravasated dye. N6-2-(4-aminophenyl)-ethyladenosine (APNEA), an adenosine A3 receptor agonist, dose dependently increased plasma protein extravasation, whereas adenosine, the A1-receptor agonist N6-(R-phenylisopropyl)-adenosine, or the A2-receptor agonist 5'-N-ethyl-carboxamidoadenosine had no effect. The effect of APNEA was not altered by the adenosine A1/A2 receptor antagonist 8-(p-sulphophenyl)-theophylline, but was reduced by depletion of mast cell-derived mediators with compound 48/80 or pretreatment with the tachykinin NK1 receptor antagonist CP99,994. These results suggest that activation of A3 receptor specifically increase airway microvascular permeability probably via mast cell-derived mediators and tachykinins. more...
- Published
- 2002
16. Role of Na(+)-K(+)-ATPase in sodium nitroprusside-induced relaxation of pulmonary artery under hypoxia
- Author
-
E, Tagaya, J, Tamaoki, K, Kawatani, and A, Nagai
- Subjects
Male ,Nitroprusside ,Vasodilation ,Dogs ,Animals ,Female ,In Vitro Techniques ,Pulmonary Artery ,Sodium-Potassium-Exchanging ATPase ,Hypoxia ,Muscle, Smooth, Vascular - Abstract
The sodium pump (Na(+)-K(+)-ATPase) plays a part in the regulation of smooth muscle contractility, and alterations of enzyme activity by hypoxia could contribute to the mechanism of hypoxic pulmonary vasoconstriction.To determine the role of Na(+)-K(+)-ATPase in the sodium nitroprusside (SNP)-induced relaxation of pulmonary artery in hypoxia.Using isolated canine pulmonary arterial rings, we measured the relaxant responses of KCI-contracted tissues to SNP under hyperoxic (95% O2, 5% O2) and hypoxic conditions (5% O2, 5% CO2, 90% N2 in vitro. Na(+)-K(+)-ATPase activity was assessed by measuring ouabain-sensitive (86)Rb uptake.The SNP-induced relaxation was reduced under hypoxia, so that the maximal relaxation decreased from 80.1 +/- 8.6 to 57.8 +/- 6.8% (p0.01) and the concentration of SNP required to produce 50% relaxation increased from 1.9 +/- 0.4 x 10(-6) to 2.6 +/- 0.6 x 10(-5) M (p0.01). Addition of ouabain, an Na(+)-K(+)-ATPase inhibitor, attenuated the relaxant response to SNP and this inhibition was still observed under hypoxia. Incubation of endothelium-denuded rings with SNP caused dose-dependent increases in intracellular cGMP levels and ouabain-sensitive (86)Rb uptake, and these effects were not significantly altered by hypoxia.These results suggest that sarcolemmal Na(+)-K(+)-ATPase activity may be implicated in the mechanism of nitrovasodilator-induced vasodilation of pulmonary artery and may still be functioning under hypoxia. more...
- Published
- 2001
17. Macrolide antibiotics as biological response modifiers
- Author
-
B K, Rubin and J, Tamaoki
- Subjects
Animals ,Humans ,Immunologic Factors ,Bacterial Infections ,Macrolides ,Anti-Bacterial Agents - Abstract
Erythromycin was first isolated in the 1950s from a Philippine soil sample, and the derivatives of erythromycin A, called the macrolide antibiotics, have been used as effective antibacterial agents ever since. It has long been suspected that the 14-membered macrolides have immunomodulatory activity as demonstrated by their early use as adjunctive therapy for asthma and their astounding effectiveness for the therapy of diffuse panbronchiolitis. It is now clear, that the macrolides and their cousins, the 15-membered azalides, and perhaps the ketolides, have a broad range of biological response modifying effects on inflammation, tumor cells, airway secretions and host defenses. This review highlights some exciting new data, as well as controversies related to understanding the mechanism of action for these diverse effects. more...
- Published
- 2001
18. Effect of suplatast tosilate, a Th2 cytokine inhibitor, on steroid-dependent asthma: a double-blind randomised study. Tokyo Joshi-Idai Asthma Research Group
- Author
-
J, Tamaoki, M, Kondo, N, Sakai, K, Aoshiba, E, Tagaya, J, Nakata, K, Isono, and A, Nagai
- Subjects
Male ,Beclomethasone ,Sulfonium Compounds ,Administration, Oral ,Peak Expiratory Flow Rate ,Middle Aged ,Asthma ,Circadian Rhythm ,Th2 Cells ,Double-Blind Method ,Forced Expiratory Volume ,Administration, Inhalation ,Anti-Allergic Agents ,Cytokines ,Humans ,Female ,Anti-Asthmatic Agents ,Arylsulfonates - Abstract
Th2 cytokines play an important part in the pathogenesis of asthma. Our aim was to study the effect of suplatast tosilate, a selective Th2 cytokine inhibitor, on asthma control and asthma exacerbations during reduction of inhaled corticosteroid dose in patients with steroid-dependent asthma.85 patients with moderate to severe asthma taking high doses (or = 1500 microg per day) of inhaled beclometasone dipropionate, were assigned suplatast tosilate (100 mg three times daily) or placebo for 8 weeks in a double-blind, randomised, parallel-group, multicentre trial. During the first 4 weeks, other medications remained unchanged (add-on phase); during the next 4 weeks, the doses of beclometasone were halved (steroid-reduction phase). Main outcome measures were pulmonary function, asthma symptoms, and use of beta2-agonists.Data were available from 77 patients. During the add-on phase, suplatast tosilate treatment, compared with placebo, was associated with higher forced expiratory volume in 1 s (mean difference between groups for changes from baseline at week 4, 0.20 L [95% CI 0.16-0.24], p=0.043), morning peak expiratory flow (18.6 L/min [14.1-23.1], p=0.037), and less diurnal variation in peak expiratory flow rate, asthma symptom scores (7.1 [6.6-7.6], p=0.029), and serum concentrations of eosinophil cationic protein and IgE. In the steroid-reduction phase, pulmonary function, asthma symptoms, and use of beta2-agonist deteriorated significantly more in the placebo group than in the suplatast group.Treatment with a Th2 cytokine inhibitor in steroid-dependent asthma improves pulmonary function and symptom control, and allows a decrease in dose of inhaled corticosteroid without significant side-effects. Some improvements in pharmacokinetics are, however, needed. more...
- Published
- 2000
19. [Role of nitric oxide in airway mucociliary dysfunction in diffuse panbronchiolitis]
- Author
-
M, Taira, J, Tamaoki, J, Nakata, M, Kondo, H, Takemura, and A, Nagai
- Subjects
Male ,Nasal Mucosa ,Breath Tests ,Mucociliary Clearance ,Sputum ,Bronchiolitis ,Humans ,Female ,Chlorine ,Middle Aged ,Nitric Oxide - Abstract
Nitric oxide (NO) stimulates the ciliary motility of the airway epithelium, thereby assisting in the regulation of mucociliary transport in the respiratory tract. In the present study, to elucidate a possible involvement of NO in mucociliary disturbance in diffuse panbronchiolitis (DPB), we measured nasal clearance time (NCT) using the saccharin test, NO concentration in the exhaled air with a chemiluminescence analyzer, and electrolyte concentration in the sputum. Compared with healthy nonsmokers and smokers, patients with DPB showed a lower NO concentration in the exhaled air (p0.05), prolonged NCT (p0.01), and a higher Cl concentration in the sputum (p0.05). Among these variables, exhaled NO concentration was negatively correlated with NCT (p0.01) and sputum Cl concentration (p0.05). These results suggest that the inhibition of NO generation associated with an elevated Cl concentration in the airway surface liquid may contribute to airway mucociliary dysfunction in DPB. more...
- Published
- 2000
20. Inhaled indomethacin in bronchorrhea in bronchioloalveolar carcinoma: role of cyclooxygenase
- Author
-
J, Tamaoki, K, Kohri, K, Isono, and A, Nagai
- Subjects
Lung Neoplasms ,Cyclooxygenase 2 Inhibitors ,Indomethacin ,Sputum ,Membrane Proteins ,Adenocarcinoma, Bronchiolo-Alveolar ,Isoenzymes ,Treatment Outcome ,Peroxidases ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,Administration, Inhalation ,Humans ,Cyclooxygenase Inhibitors ,RNA, Messenger ,DNA Primers - Published
- 2000
21. [Role of FK506-binding protein (FKBP) in Ca+ oscillation in bronchial epithelial cells]
- Author
-
S, Kano, M, Kondo, J, Tamaoki, K, Aoshiba, H, Kobayashi, and K, Motoyoshi
- Subjects
Tacrolimus Binding Proteins ,Animals ,Bronchi ,Calcium ,Cattle ,Epithelial Cells ,Immunophilins ,Peptidylprolyl Isomerase ,Cells, Cultured ,Tacrolimus - Published
- 2000
22. [Mechanism and management of airway hypersecretion in obstructive lung disease]
- Author
-
J, Tamaoki
- Subjects
Ion Transport ,Anti-Inflammatory Agents ,Mucins ,Uridine Triphosphate ,Respiratory Mucosa ,Autonomic Nervous System ,Anti-Bacterial Agents ,Mucociliary Clearance ,Chronic Disease ,Cytokines ,Humans ,Steroids ,Bronchitis ,Glycoproteins - Abstract
Airway hypersecretion is a characteristic feature of chronic bronchitis and influences progression and prognosis of the disease, but the underlying mechanism remains uncertain. The increase in intraluminal viscid mucus may lead to disturbance of airway mucociliary clearance and deterioration of obstructive impairment of pulmonary function. Airway surface fluid is composed of mucous glucoprotein released from submucosal glands and goblet cells and water from airway epithelial cells, and the secretory function can be regulated by autonomic nervous system and a variety of chemical mediators and cytokines. Although several drugs may alter secretory responses and physicochemical properties of the sputum, it seems important to select mucoregulating drugs after understanding the mechanisms of hypersecretion and impaired mucociliary transport under individual conditions. more...
- Published
- 1999
23. [Effect of heparin on airway goblet cell secretion in sensitized guinea pigs]
- Author
-
J, Nakata, J, Tamaoki, K, Takeyama, Y, Takeda, I, Yamawaki, M, Kondo, and A, Nagai
- Subjects
Male ,Mucus ,Dose-Response Relationship, Drug ,Heparin ,Ovalbumin ,Depression, Chemical ,Guinea Pigs ,Animals ,Receptors, Histamine H2 ,Goblet Cells ,Histamine Release ,Asthma - Abstract
Heparin and related proteoglycans are released from mast cells and possess anti-inflammatory and anti-complement activities. To elucidate whether heparin affects goblet cell secretion in asthmatic airways and, if so, what the mechanism of action is, we studied guinea pigs sensitized with ovalbumin (OVA) by determining the mucus score (MS) of tracheal goblet cells stained with Alcian blue and PAS. Inhalation of OVA caused a rapid decrease in MS in a dose-dependent manner, with the maximal decrease being from 545 +/- 26 to 192 +/- 35 (p0.001), indicating an increase in goblet cell mucus discharge. This effect was selectively inhibited by the histamine H2 receptor blockade with cimetidine. Prior inhalation of heparin inhibited OVA-induced goblet cell secretion in a dose-dependent fashion, but had no effect on histamine-induced goblet cell secretion. The OVA-induced histamine release from the tracheal tissue was likewise inhibited by heparin. These results suggest that allergic challenge stimulates airway goblet cell secretion mainly through the release of histamine and the concomitant activation of histamine H2 receptors on goblet cells, and that heparin protects against this effect by inhibiting the histamine release from mast cells. more...
- Published
- 1999
24. [Effect of salbutamol on proliferation of human bronchial epithelial cells: role of MAP kinase]
- Author
-
K, Nishimura, J, Tamaoki, K, Aoshiba, K, Isono, and A, Nagai
- Subjects
Calcium-Calmodulin-Dependent Protein Kinases ,Humans ,Albuterol ,Bronchi ,Epithelial Cells ,DNA ,Adrenergic beta-Agonists ,Phosphorylation ,Adrenergic beta-2 Receptor Agonists ,Cell Division ,Cells, Cultured - Abstract
To determine whether stimulation of beta-adrenoceptors affects proliferation of airway epithelial cells and, if so, whether activation of mitogen-activated protein kinase (MAPK) is involved, we studied cultured human bronchial epithelial (16-HBE) cells in vitro. The 16-HBE cells were grown to subconfluence in 96-well plates, and their growth was inhibited by incubation in serum-free medium for 72 h. The cells were ten incubated in the presence of saltbutamol (SAL, 10(-7) M), a specific beta(2)-adrenoceptor agonist. Proliferation of the cells was evaluated by MTT assay and total DNA content, and activation of MAPK was assessed by immunocytochemistry and Western blotting for phosphorylated MAPK (phospho-MAPK). Immunocytochemistry and immunoblots demonstrated that phospho-MAPK was expressed within minutes of SAL exposure. This effect of SAL was as potent as that of 10% serum, and was greatly inhibited by treatment with propranolol. These results suggest that SAL is a potent mitogen of airway epithelial cells and that its effect may be exerted by beta(2)-adrenocepter-mediated activation of MAPK. more...
- Published
- 1998
25. [Effect of adenosine and its analogues on microvascular leakage in the rat trachea]
- Author
-
I, Yamawaki, J, Tamaoki, Y, Takeda, and A, Nagai
- Subjects
Male ,Adenosine ,Dose-Response Relationship, Drug ,Vasodilator Agents ,Receptors, Purinergic P1 ,Adenosine-5'-(N-ethylcarboxamide) ,Substance P ,Rats ,Capillary Permeability ,Rats, Sprague-Dawley ,Trachea ,Tachykinins ,Purinergic P1 Receptor Agonists ,Animals ,Neurons, Afferent ,Capsaicin - Abstract
We examined the effects of adenosine and its analogues on vascular permeability in rat trachea using Evans blue dye as a marker for plasma leakage. Inhalation of N6-2-(4-aminophenyl) ethyladenosine (APNEA), a specific A 3 receptor agonist, increased microvascular leakage in a dose-dependent manner, but adenosine, [R]-N6-(1-Methyl-2-phenylethyl) adenosine (R-PIA), aspecific A 1 receptor agonist, and 5'-(N-ethyl-carboxamide) adenosine (NECA), a specific A 2 receptor agonist, had no effect. Inhalation of capsaicin increased vascular permeability in a dose-dependent manner. Pretreatment with NECA (10-1000 nmol/kg, i.v.) but not adenosine (100 nmol/kg i.v.), R-PIA (100 nmol/kg, i.v.) or APNEA (100 nmol/kg, i.v.) inhibited microvascular leakage produced by capsaicin aerosol (3 x 10(-5) M) in a dose-dependent manner. However, NECA (10-100 nmol/kg, i.v.) failed to inhibit substance P aerosol (10(-4) M)-induced extravasation of the dye. These findings suggest that stimulation of adenosine A 3 receptors produces airway vascular permeability, and that A 2 receptors inhibit neurogenic plasma extravasation, presumably by inhibiting the release of tachykinins from sensory nerves. more...
- Published
- 1998
26. [Regulation and pathophysiology of airway secretion]
- Author
-
J, Tamaoki
- Subjects
Ion Transport ,Anti-Inflammatory Agents, Non-Steroidal ,Respiratory Tract Diseases ,Bronchi ,Uridine Triphosphate ,Autonomic Nervous System ,Cholinergic Antagonists ,Anti-Bacterial Agents ,Mucus ,Mucociliary Clearance ,Humans ,Inflammation Mediators ,Ciliary Motility Disorders ,Glycoproteins - Abstract
Although excessive production of sputum is one of the characteristic features of acute and chronic respiratory infections, bronchiectasis, diffuse panbronchiolitis, chronic bronchitis and asthma, pathophysiological mechanisms underlying airway hypersecretion remain uncertain. The increase in intraluminal mucus may lead to impairment of airway mucociliary clearance and deterioration of bronchial obstruction. Airway surface fluid is composed of mucus glycoprotein released from submucosal glands and goblet cells and water from airway epithelial cells, and the secretory function can be regulated by autonomic nervous system and a variety of chemical mediators. It is thus important to select mucoregulating drugs after understanding the mechanisms of hypersecretion and impaired mucociliary transport under individual conditions. more...
- Published
- 1998
27. [Airway hypersecretion and mucociliary dysfunction in asthma]
- Author
-
J, Tamaoki
- Subjects
Mucus ,Mucociliary Clearance ,Animals ,Humans ,Bronchi ,Asthma - Abstract
Mucociliary transport function can be determined by ciliary motility of airway epithelial cells, the amount and physicochemical properties of airway surface fluid, and the airway integrity. Mucus glycoprotein is released from submucosal glands and goblet cells in response to a variety of stimuli and, on other hand, water is secreted by airway epithelial cells through the movement of electrolytes. Marked airway goblet cell hyperplasia has been found in patients who died of severe asthma, indicating that goblet cell hypersecretion may play a significant role in the formation of mucus plugs in the respiratory tract. Goblet cell secretion is regulated by autonomic nerves and various chemical mediators associated with asthma. Antigen challenge causes an increase in mucus discharge from goblet cells in ovalbumin-sensitized animals, and this effect can be greatly inhibited by an histamine H2-receptor antagonist. Similarly, histamine released by antigen challenge stimulates airway epithelial Cl secretion and, hence, water secretion toward the airway lumen. There is ample evidence that mucociliary clearance is impaired in patients with asthma, which results in deterioration of airflow limitation. The precise mechanism for this impairment remains uncertain, but bronchospasm and the increased mucus secretion induced by peptide leukotrienes may be involved. more...
- Published
- 1998
28. [A case of pulmonary eosinophilic granuloma undergoing spontaneous remission]
- Author
-
I, Yamawaki, K, Kawatani, H, Uno, J, Tamaoki, T, Kaburagi, T, Ohnuki, and A, Nagai
- Subjects
Adult ,Antigens, CD1 ,Eosinophilic Granuloma ,Lung Diseases ,Male ,Time Factors ,Remission, Spontaneous ,S100 Proteins ,Humans ,Biomarkers - Abstract
A case of pulmonary eosinophilic granuloma that underwent spontaneous remission is presented. A 23-year old man presented with dry cough and fever. Chest X-ray film revealed diffuse reticulo-nodular infiltrates in the middle and upper lung fields. Chest CT and HRCT showed multiple cystic lesions with thick walls and small nodules predominantly in the inner zone. Based on radiographic findings, pulmonary eosinophilic granuloma was suspected. Bronchoalveolar lavage cell data showed lymphocyte and eosinophil alveolitis with no increase of CD 1 lymphocytes. The symptoms and radiographic findings improved markedly within 4 months after the onset of symptoms without treatment and upon cessation of smoking. Chest CT and HRCT showed that the cystic walls were thinner and that the small nodules had decreased. Thoracoscopic lung biopsy revealed granulomatous lesions consisting of CD 1 and S-100 protein positive histiocytes with infiltration of eosinophils and fibrous lesions. Pulmonary eosinophilic granuloma was diagnosed. There has been no recurrence for 1 year. more...
- Published
- 1998
29. [Effects of macrolides on intracellular Ca2+ response by airway epithelium]
- Author
-
S, Kyo, J, Tamaoki, M, Kondo, K, Isono, and A, Nagai
- Subjects
Clarithromycin ,Cefazolin ,Animals ,Ampicillin ,Bronchi ,Calcium ,Cattle ,Epithelial Cells ,Penicillins ,In Vitro Techniques ,Anti-Bacterial Agents ,Cephalosporins ,Erythromycin - Published
- 1998
30. [Effects of macrolide antibiotics on iNOS gene expression and NO production by alveolar macrophages]
- Author
-
J, Tamaoki, H, Gunwa, M, Kondo, K, Isono, K, Nishimura, and A, Nagai
- Subjects
Rats, Sprague-Dawley ,Clarithromycin ,Macrophages, Alveolar ,Animals ,Gene Expression ,Josamycin ,Nitric Oxide Synthase ,Nitric Oxide ,Cells, Cultured ,Anti-Bacterial Agents ,Erythromycin ,Rats - Published
- 1998
31. Inhaled cromoglycate reduces airway neurogenic inflammation via tachykinin antagonism
- Author
-
I, Yamawaki, J, Tamaoki, Y, Takeda, and A, Nagai
- Subjects
Inflammation ,Male ,Saline Solution, Hypertonic ,Dose-Response Relationship, Drug ,Substance P ,Rats ,Specific Pathogen-Free Organisms ,Capillary Permeability ,Rats, Sprague-Dawley ,Trachea ,Tachykinins ,Administration, Inhalation ,Cromolyn Sodium ,Animals ,Anti-Asthmatic Agents ,Platelet Activating Factor - Abstract
To determine whether sodium cromoglycate (SCG) inhibits airway neurogenic inflammation and, if so, to elucidate the mechanism of its action, we studied plasma extravasation evoked by hypertonic saline in the rat trachea by measuring the amount of extravasated Evans blue dye. Inhalation of hypertonic saline (5-15% NaCl) produced microvascular leakage, an effect that was reduced by pretreatment with SCG in a dose-dependent manner. Inhaled SCG (10 mg/ml) for 2 min did not affect the basal vascular permeability, but significantly inhibited the 10% NaCl-induced plasma extravasation by 34%. SCG likewise inhibited the responses of microvascular leakage to substance P aerosols, whereas it was without effect on those to platelet activating factor aerosols. These results suggest that SCG inhibits airway neurogenic inflammation presumably via functional antagonism of tachykinins, and that this novel effect may be involved in the therapeutic efficacy of SCG in the treatment of airway inflammatory diseases including asthma. more...
- Published
- 1998
32. Role of the sarcolemmal sodium pump in nitroprusside-induced vasodilation of the pulmonary artery
- Author
-
E, Tagaya, J, Tamaoki, K, Nishimura, and A, Nagai
- Subjects
Nitroprusside ,Potassium Channels ,Muscle Relaxation ,Vasodilator Agents ,In Vitro Techniques ,Pulmonary Artery ,Rubidium ,Sensitivity and Specificity ,Muscle, Smooth, Vascular ,Vasodilation ,Dogs ,Sarcolemma ,Animals ,Sodium-Potassium-Exchanging ATPase ,Ouabain ,Rubidium Radioisotopes - Abstract
To elucidate the mechanism of nitrovasodilator-induced pulmonary vasodilation, we examined the role of sodium pump and K+ channels in the relaxant responses of canine pulmonary arterial rings to sodium nitroprusside (SNP) under isometric conditions in vitro. Pretreatment with the sodium pump inhibitor ouabain attenuated the SNP-induced vasodilation of KCI-contracted tissues, so that the maximal relaxation decreased from 90 +/- 7 to 62 +/- 6% (P0.01), and the negative logarithm of SNP concentration required to produce a half-maximal effect (pD2) decreased from 5.9 +/- 0.4 to 5.1 +/- 0.4 (P0.01). This effect was not altered by mechanical removal of the endothelium. In contrast, pretreatment with K+ channel blockers including iberiotoxin, apamin and glibenclamide did not change the relaxant responses to SNP. Incubation of endothelium-denuded rings with SNP increased ouabain-sensitive 86Rb uptake in a dose-dependent manner, an effect that was inhibited by KT 5823, a cGMP-dependent protein kinase inhibitor. These results suggest that activation of sarcolemmal sodium pump may be involved in the nitrovasodilator-induced cGMP-mediated pulmonary vasodilation, whereas K+ channels may play a less important role in this action. more...
- Published
- 1997
33. Stimulation of airway mucociliary transport and epithelial ciliary motility by the triazolopyridazin derivative TAK-225
- Author
-
J, Tamaoki, A, Chiyotani, H, Takemura, K, Konno, T, Matsumoto, and Y, Ashida
- Subjects
Pyridazines ,Trachea ,Mucous Membrane ,Dose-Response Relationship, Drug ,Anti-Allergic Agents ,Animals ,Rabbits ,Triazoles ,Epithelium ,Respiratory Transport - Abstract
To elucidate whether a newly developed antiallergic drug, the triazolopyridazin derivative TAK-225, alters airway mucociliary clearance and, if so, what the mechanism of action is, we measured mucociliary transport in the rabbit tracheal mucosa ex vivo and ciliary motility of the tracheal epithelium in vitro. Mucociliary transport function was determined by the transport rate of Evans blue dye that had been placed on the mucosal surface above the carina. Oral administration of TAK-225 (0.3-30 mg/kg) increased Evans blue transport toward the larynx in a dose-dependent manner. Addition of TAK-225 caused a rapid and sustained increase in the ciliary beat frequency of tracheal epithelium, as assessed by photoelectric method; the maximal increase from the base-line value was 25.1 +/- 4.6% (P.01), and the concentration required to produce a half-maximal effect (EC50) was 3.1 +/- 0.8 x 10(-7) M. This effect was greatly attenuated by pretreatment with the cAMP antagonist adenosine 3',5'-cyclic monophosphorothioate, but not by Ca++-free medium containing ethylene glycol-bis [3-aminoethyl ether] N,N,N',N'-tetraacetic acid and [1,2-bis(2)aminophenoxy]ethane N,N,N',N'-tetraacetic acid-acetomethoxy ester. Incubation of tracheal epithelium with TAK-225 increased intracellular cAMP contents in a concentration-dependent manner. These results suggest that TAK-225 enhances airway mucociliary clearance probably through cAMP-mediated stimulation of ciliary motility of airway epithelium. more...
- Published
- 1997
34. Role of Ca(2+)-activated K+ channel in epithelium-dependent relaxation of human bronchial smooth muscle
- Author
-
J, Tamaoki, E, Tagaya, K, Isono, M, Kondo, and K, Konno
- Subjects
Potassium Channels ,Muscle Relaxation ,Bronchi ,Muscle, Smooth ,respiratory system ,Nitric Oxide ,Acetylcholine ,Apamin ,Glyburide ,Papers ,Humans ,Hypoglycemic Agents ,Calcium ,Peptides ,Muscle Contraction - Abstract
1. To elucidate whether K+ channels play a role in the action of epithelium-dependent bronchodilatation, we studied responses in human bronchial strips in the presence of indomethacin and NG-nitro-L-arginine methylester under isometric conditions, in vitro. 2. Mechanical removal of the epithelium increased the contractile responses to acetylcholine; the pD2 values increased from 5.0 +/- 0.2 to 5.9 +/- 0.3 (P0.001). This potentiation was abolished by iberiotoxin but not by apamin or glibenclamide. 3. In cascade bioassay, application of the bathing medium from dispersed, bronchial epithelial cells to epithelium-denuded bronchial strips decreased acetylcholine-induced contraction by 44 +/- 6%. This effect was reduced to 10 +/- 3% (P0.01) when the epithelial cells were pretreated with iberiotoxin, and to 4 +/- 1% (P0.001) when the epithelial cells were incubated with Ca(2+)-free medium containing [1,2-bis(2) aminophenoxy] ethane N,N,N',N'-tetraacetic acid-acetomethoxy ester. 4. In contrast, the bronchodilator effect of the medium bathing epithelial cells was not altered by the direct addition of iberiotoxin to epithelium-denuded tissues. 5. These results suggest that the Ca(2+)-activated K+ channel may play a role in the synthesis and/or release of smooth muscle relaxing factor, which is neither nitric oxide nor a cyclo-oxygenase product, from airway epithelial cells. more...
- Published
- 1997
35. [Role of neutrophil elastase in allergen-induced airway microvascular leakage in sensitized guinea pigs]
- Author
-
Y, Takeda, J, Tamaoki, I, Yamawaki, M, Kondo, and A, Nagai
- Subjects
Capillary Permeability ,Hypersensitivity, Immediate ,Male ,Leukocyte Count ,Sulfonamides ,Dose-Response Relationship, Drug ,Ovalbumin ,Guinea Pigs ,Glycine ,Animals ,Humans ,Leukocyte Elastase ,Bronchoalveolar Lavage Fluid - Abstract
To determine the role of neutrophil elastase in allergen-induced airway microvascular leakage, we assessed vascular permeability of guinea pig trachea by measuring the extravasation of Evans blue dye in the circulating blood. Inhalation of ovalbumin (OA) to guinea pigs sensitized with OA caused Evans blue extravasation, indicating an increased microvascular permeability. Pretreatment with ONO-5046 a specific inhibitor of neutrophil elastase, inhibited OA-induced vascular leakage in a dose-dependent manner. Tracheal instillation of human neutrophil elastase likewise increased microvascular permeability, and this effect was almost completely abolished by ONO-5046. Challenge with OA increased the number of neutrophils and neutrophil elastase activity in the bronchoalveolar lavage fluid, and these effects were inhibited by ONO-5046. These results suggest that neutrophil accumulation into the airway and the subsequent release of neutrophil elastase may play a role in the airway microvascular leakage produced by antigen challenge. more...
- Published
- 1997
36. Effect of adenosine on adrenergic neurotransmission and modulation by endothelium in canine pulmonary artery
- Author
-
J. Tamaoki, H. Takemura, K. Konno, A. Nagai, E. Tagaya, T. Onuki, Atsushi Chiyotani, and S. Nitta
- Subjects
Male ,medicine.medical_specialty ,Adenosine ,Physiology ,In Vitro Techniques ,Pulmonary Artery ,Synaptic Transmission ,Muscle, Smooth, Vascular ,chemistry.chemical_compound ,Adenosine A1 receptor ,Norepinephrine ,Adenosine deaminase ,Dogs ,Physiology (medical) ,Internal medicine ,Isometric Contraction ,medicine ,Animals ,biology ,Chemistry ,Biological Transport ,Dipyridamole ,Purinergic signalling ,Adenosine A3 receptor ,Adenosine receptor ,Electric Stimulation ,Kinetics ,Endocrinology ,CCPA ,biology.protein ,Female ,Endothelium, Vascular ,Cardiology and Cardiovascular Medicine ,Adenosine Deaminase Inhibitor ,Pentostatin ,medicine.drug - Abstract
To determine the effect of adenosine on adrenergic neurotransmission in pulmonary vasculature and its modulation by endothelial cells, we studied canine pulmonary arteries under isometric conditions in vitro. Adenosine decreased the contractile responses to electrical field stimulation but had no effect on those to norepinephrine. This inhibitory effect was concentration dependent, with a rank order of potency of NECA > 2-chloroadenosine > adenosine >> APNEA (an A3-adenosine-receptor agonist) > CGS-21680 (an A2a agonist) > CCPA (an A1 agonist). Adenosine reduced the electrical field stimulation-evoked 3H overflow in superfused pulmonary artery previously soaked in [3H]norepinephrine. Pretreatment with the adenosine uptake blocker dipyridamole or the adenosine deaminase inhibitor deoxycoformycin enhanced the adenosine action, and this enhancement was not observed in the endothelium-denuded tissues. Adenosine deaminase activity was found in endothelial cells. Therefore, adenosine inhibits norepinephrine release via an A2b-receptor mechanism, an effect that may be modulated by uptake and metabolism by endothelial cells. more...
- Published
- 1997
37. [Effects of erythromycin and roxithromycin on airway goblet cell secretion]
- Author
-
J, Nakada, J, Tamaoki, R, Takeyama, E, Tagaya, M, Kondo, and K, Kaneno
- Subjects
Male ,Mucus ,Roxithromycin ,Guinea Pigs ,Interleukin-8 ,Respiratory System ,Animals ,Anti-Bacterial Agents ,Erythromycin - Published
- 1997
38. [Effect of heparin on the increase in intracellular calcium caused by inositol 1,4,5-triphosphate in airway epithelial cells]
- Author
-
M, Kondo, J, Tamaoki, K, Isono, S, Kanoh, and K, Konno
- Subjects
Trachea ,Adenosine Triphosphate ,Heparin ,Animals ,Calcium ,Cattle ,Epithelial Cells ,Inositol 1,4,5-Trisphosphate ,Cells, Cultured ,Epithelium - Abstract
We studied the effect of heparin on the inositol 1,4,5-triphosphate (IP3)-dependent increase in intracellular calcium (Ca2+) caused by ATP. The Ca2+ concentration ([Ca2+]i) in cultured epithelial cells from cow tracheas was measured by the fura-2 method. ATP (10(-4) M) stimulated IP3 production and caused a biphasic increase in [Ca2+]i a transient response and a subsequent sustained response. Heparin (l 100 U/ml) dose-dependently inhibited the ATP-induced increase in [Ca2+]i but had no effect on IP3 production. Dextran sulfate, a polysaccharide with negative charge density, had a similar inhibitory effect on the ATP-induced increase in [Ca2+]i. These data suggest that heparin inhibits intracellular Ca2+ mobilization by acting at a site "distal to" IP3 production, and that the mechanism of action of heparin may be related to its negative charge. more...
- Published
- 1997
39. [Six patients with pneumonitis related to blended Chinese traditional medicines]
- Author
-
I, Yamawaki, H, Katsura, M, Taira, C, Kadoriku, I, Hashimoto, A, Chiyotani, M, Kondo, J, Tamaoki, A, Nagai, and K, Konno
- Subjects
Male ,CD4-CD8 Ratio ,Humans ,Female ,Medicine, Kampo ,Middle Aged ,Lung Diseases, Interstitial ,Lymphocyte Activation ,Aged ,Drugs, Chinese Herbal - Abstract
We encountered six patients with pneumonitis related to blended chinese traditional medicine (Kampo). The duration of treatment with kampo ranged from 14 to 110 days (mean: 38 days). The most common complaints were dyspnea, fever, and dry coughing. Fine crackles were heard at the bases of both lungs. Abnormal laboratory findings included high values of C-reactive protein and glutamic-oxaloacetic transaminase in all patients, lactate dehydrogenase in 5 patients, and eosinophil count in 1 patient. Chest X-ray films and CT films revealed diffuse reticulo-nodular interstitial shadows with consolidation in both lung fields in 3 patients and pleural effusion in 1 patient. Bronchoalveolar lavage was done in 4 patients; examination of the lavage fluid showed lymphocyte alveolitis, either pure or associated with neutrophilia and eosinophilia in 3 patients. Inverted CD4/CD8 lymphocyte ratios were found in 3 patients. Transbronchial lung biopsy was done in 4 patients and specimens from 3 of those 4 showed organizing pneumonitis with thickening of alveolar septa. Lymphocyte stimulation tests were positive in 4 patients. Discontinuation of the drug (2 patients) or administration of corticosteroids (4 patients) was followed by rapid improvement. Patients being treated with kampo preparations should be observed for signs and symptoms of drug-induced pneumonitis. more...
- Published
- 1996
40. Effects of K(+)-channel blockers on epithelium-derived relaxing factor (EpDRF)-mediated modulation of airway smooth muscle contractility
- Author
-
E, Tagaya, J, Tamaoki, Y, Takeda, H, Takemura, and K, Konno
- Subjects
Potassium Channels ,Muscle, Smooth ,In Vitro Techniques ,Nitric Oxide ,Acetylcholine ,Electric Stimulation ,Trachea ,Isometric Contraction ,Potassium Channel Blockers ,Animals ,Drug Interactions ,Endothelium ,Rabbits ,Muscle Contraction - Abstract
Airway epithelium plays a role in the regulation of bronchial smooth muscle tone releasing cyclooxygenase products and epithelium-derived relaxing factor (EpDRF). To test possible involvement of K+ channels in the action of EpDRF, we studied rabbit tracheal segments in the presence of indomethacin under isometric conditions in vitro. Mechanical removal of the epithelium increased the contractile responses to acetylcholine, so that negative logarithm of the concentration required to produce 50% of maximal effect (pD2) increased from 5.0 +/- 0.4 to 5.7 +/- 0.3 (P0.01). Addition of charybdotoxin per se caused a leftward shift of acetylcholine concentration-response curves in epithelium-intact tissues, but the subsequent removal of the epithelium did not further potentiated the contractile responses. In contrast, apamin or glibenclamide had no effect on the epithelium-removal-induced potentiation of the contraction. The responses to electrical field stimulation were likewise potentiated by epithelial removal, an effect that was abolished by charybdotoxin. These results suggest that Ca(2+)-activated K+ channels are involved in the EpDRF modulation of airway smooth muscle responsiveness. more...
- Published
- 1996
41. [Effect of sodium cromoglycate on airway vascular leakage caused by hypertonic saline in the rat trachea]
- Author
-
I, Yamawaki, J, Tamaoki, Y, Takeda, and K, Konno
- Subjects
Capillary Permeability ,Inflammation ,Male ,Rats, Sprague-Dawley ,Saline Solution, Hypertonic ,Tracheal Diseases ,Cromolyn Sodium ,Animals ,Anti-Asthmatic Agents ,Rats - Abstract
The action of the anti-asthmatic drug sodium cromoglycate (SCG) on airway inflammation remains uncertain. Using Evans blue dye as a maker of plasma leakage, we studied the effect of SCG on neurogenic vascular extravasation evoked by hypertonic saline (HTS) in the rat trachea. Inhalation of HTS (5-15%) caused a concentration-dependent increase in plasma leakage, but inhaled 0.9% NaCl had no effect. Inhalation of SCG did not affect the baseline level of vascular permeability, but it inhibited the effect of HTS in a dose-dependent manner: plasma extravasation induced by 10% NaCl was significantly reduced by 2 minutes of inhalation of SCG at concentrations of 10 and 50 mg/ml (p0.05 and p0.01, respectively). SCG (10 mg/ml), also inhibited the changes in microvascular permeability caused by aerosols of substance P (10(-4) M), whereas it did not affect the responses to aerosols of platelet-activating factor (3 x 10(-4) M). A similar dose of SCG did not significantly alter microvascular leakage caused by 5% NaCl. However, phosphoramidon, a selective inhibitor of neutral endopeptidase, potentiated the response to 5% NaCl, an effect that was inhibited by SCG (p0.05). These results suggest that SCG inhibits HTS-induced airway vascular permeability, presumably through a tachykinin-antagonist-like property, and that this inhibition is exaggerated when the activity of endogenous neutral endopeptidase is low. more...
- Published
- 1996
42. [T-kinin-induced increase in airway vascular permeability and its modulation by angiotensin-converting enzyme]
- Author
-
Y, Takeda, J, Tamaoki, I, Yamawaki, A, Chiyotani, and K, Konno
- Subjects
Capillary Permeability ,Male ,Rats, Sprague-Dawley ,Trachea ,Animals ,Bronchi ,Peptidyl-Dipeptidase A ,Bradykinin ,Rats - Abstract
We studied the effect of T-kinin on airway vascular permeability and its modulation by endogenous peptidases in anesthetized rats in vivo, Vascular permeability was assessed by photometric measurement of extravasated Evans blue dye after formamide extraction. Intravenous injection of T-kinin increased dye extravasation in the trachea and main bronchi in a dose-dependent manner. Plasma extravasation evoked by T-kinin was inhibited by Hoe 140, a B2 receptor but-not by des Arg9-Leu8-bradykinin, a B1 receptor antagonist. Treatment with captopril, an angiotensin-converting enzyme inhibitor, potentiated the T-kinin-induced plasma extravasation, whereas phosphoramidon, a neutral endopeptidase inhibitor, had no effect. These results suggest that T-kinin increases airway vascular permeability via stimulation of B2 receptors, and that this effect is modulated by endogenous angiotensin-converting enzyme. more...
- Published
- 1996
43. Effect of 5-hydroxytryptamine on bioelectric properties of airway epithelial cells in culture
- Author
-
J, Tamaoki, A, Chiyotani, H, Takemura, and K, Konno
- Subjects
Male ,Serotonin ,Sodium ,Cell Polarity ,Epithelial Cells ,Epithelium ,Sodium Channels ,Membrane Potentials ,Amiloride ,Bronchoconstrictor Agents ,Trachea ,Dogs ,Bucladesine ,Chlorides ,Electric Impedance ,Animals ,Calcium ,Female ,Egtazic Acid ,Cells, Cultured - Abstract
To elucidate whether 5-hydroxytryptamine (5-HT) affects airway epithelial electrolyte transport and, if so, what the mechanism of action is, we studied the bioelectric properties of canine cultured tracheal epithelium under short-circuit conditions in vitro. Mucosal addition of 5-HT dose-dependently increased short-circuit current (Isc), which was accompanied by increases in transepithelial potential difference and cell conductance. In contrast, 5-HT had no effect on bioelectric properties when it was added to the submucosal side. Pretreatment of cells with amiloride potentiated the increase in Isc produced by 5-HT. In the presence of diphenylamine-2-carboxylate or Cl-free medium, 5-HT decreased Isc from the baseline level. Incubation with BAPTA-AM but not dibutyryl cAMP greatly attenuated the 5-HT-induced increase in amiloride-insensitive portion of Isc. These results suggest that 5-HT inhibits Na absorption and stimulates Cl secretion across canine tracheal epithelium and that the Cl secretion may be associated with elevation of intracellular Ca2+ contents. more...
- Published
- 1996
44. Stimulation of opioid mu-receptors potentiates beta adrenoceptor-mediated relaxation of canine airway smooth muscle
- Author
-
E, Tagaya, J, Tamaoki, A, Chiyotani, and K, Konno
- Subjects
Male ,Muscle Relaxation ,Molecular Sequence Data ,Receptors, Opioid, mu ,Muscle, Smooth ,Enkephalins ,Enkephalin, Ala(2)-MePhe(4)-Gly(5) ,Trachea ,Dogs ,Receptors, Adrenergic, beta ,Cyclic AMP ,Animals ,Female ,Amino Acid Sequence ,Oligopeptides - Abstract
To elucidate the effect of an opioid on airway smooth muscle relaxant responses and its mechanism of action, we studied canine bronchial segments under isometric conditions in vitro. Addition of the opioid mu-receptor-specific agonist DAMGO (10(-5) M) or Tyr-D-Arg-phe-Lys-NH2 (10(-5) M) did not alter the resting tension or the contractile responses to Ach but augmented the relaxation induced by isoproterenol: the concentrations of isoproterenol required to produce a half-maximal effect were decreased from 1.9 +/- 0.6 x 10(-6) to 3.1 +/- 1.0 x 10(-7) M (P.01) by DAMGO and from 2.1 +/- 0.4 x 10(-6) M to 4.3 +/- 0.7 x 10(-7) M (P.01), by Tyr-D-Arg-phe-Lys-NH2. This effect of DAMGO was concentration-dependent and was abolished by naloxone or Cys2, Tyr3, Orn5, Pen7-amide, a mu-receptor antagonist. DAMGO likewise caused a leftward displacement of concentration-response curves for forskolin but was without effect on those for 3-isobutyl-3-methylxanthine and 8-bromo-cAMP. Also, DAMGO did not affect the relaxant responses to verapamil, nitroprusside or 8-bromo-cGMP. Incubation of bronchial smooth muscle with DAMGO (10(-5) M) potentiated the intracellular accumulation of cAMP induced by isoproterenol (10(-6) M) from 258 +/- 22 pmol/g tissue wt. to 420 +/- 27 pmol/g tissue wt. (P.01), an effect that was abolished by naloxone. These results suggest that stimulation of opioid mu-receptors specifically augments beta adrenoceptor-mediated bronchodilation probably by acting at the site proximal to adenylate cyclase in the cAMP-dependent pathway. more...
- Published
- 1995
45. [Airway epithelium and nitric oxide]
- Author
-
J, Tamaoki
- Subjects
Trachea ,Ion Transport ,Dose-Response Relationship, Drug ,Tachykinins ,Isoproterenol ,Animals ,Epithelial Cells ,Cilia ,Rabbits ,Chlorine ,Nitric Oxide ,Cells, Cultured ,Epithelium - Abstract
To measure the generation of nitric oxide (NO) by airway epithelial cells and to study the physiological role of NO in the regulation of epithelial functions, we studied ciliary motility of rabbit cultured tracheal epithelium in vitro and ion transport across tracheal mucosa in vivo. Isoproterenol dose-dependently increased ciliary beat frequency, as measured by photoelectric methods. Perfusion of tracheal mucosa with tachykinins increased the diffusion potential for chloride ions, as measured in the presence of amiloride under open-circuit conditions: the rank order of potency was neurokinin Asubstance Pneurokinin B. These responses to isoproterenol and to tachykinins were attenuated by pretreatment with NG-nitro-L-arginine methylester, and this attenuation was reversed by L-arginine. In contrast, NG-nitro-D-arginine methylester and D-arginine had no such effects. NO concentrations in the medium and perfusate were measured in realtime with an amperometric sensor specific to this molecule, and immersion of the electrode allowed detections of a polarographic current under unstimulated conditions. Addition of isoproterenol, neurokinin A, or substance P caused a rapid and dose-dependent increase in NO concentration. Histochemical examination for NADPH diaphorase activity in cultured epithelium showed strong staining within the cytoplasm. These results suggest that NO is spontaneously released from airway epithelial cells and that generation of this molecule may contribute to airway epithelial ciliary motility and chloride ion secretion mediated by beta-adrenoceptors and by tachyinin NK2 receptors. more...
- Published
- 1995
46. Isoproterenol increases Cl diffusion potential difference of rabbit trachea through nitric oxide generation
- Author
-
H, Takemura, J, Tamaoki, E, Tagaya, A, Chiyotani, and K, Konno
- Subjects
Diffusion ,Electrophysiology ,Male ,Trachea ,Chlorides ,Histocytochemistry ,Isoproterenol ,NADPH Dehydrogenase ,Animals ,Rabbits ,Nitric Oxide - Abstract
To determine whether nitric oxide (NO) formation is involved in Cl secretion across airway mucosa in response to beta adrenergic agonists, we studied the effect of isoproterenol (ISO) on the Cl diffusion potential difference of rabbit tracheal mucosa and measured NO formation by a highly specific electrode for this molecule in vivo. Perfusion of ISO on the tracheal mucosal surface increased the Cl diffusion potential difference, as determined in the presence of amiloride, in a dose-dependent fashion, the maximal increase from the base-line value being 12.1 +/- 1.7 mV (P.001). Application of NG-nitro-L-arginine methylester (10(-3) M) decreased the Cl diffusion potential difference by itself and attenuated the subsequent response to ISO, causing a rightward displacement of ISO concentration-response curves, whereas NG-nitro-D-arginine methylester had no effect. This inhibitory effect of NG-nitro-L-arginine methyl-ester was reversed by L-arginine but not by D-arginine. Addition of ISO dose-dependently increased polarographic current and, hence, NO concentration in the perfusate, the maximal increase from the base-line levels being 178 +/- 10 nM. Histochemistry for NADPH diaphorase activity showed a strong staining within epithelial cells. These results suggest that NO formation may play a role in the beta adrenoceptor-mediated Cl secretion by tracheal mucosa. more...
- Published
- 1995
47. [Role of nitric oxide in tachykinin-induced increase in Cl diffusion potential difference of rabbit tracheal mucosa]
- Author
-
H, Takemura, J, Tamaoki, E, Tagaya, A, Chiyotani, M, Kondo, and K, Konno
- Subjects
Diffusion ,Male ,Trachea ,Mucous Membrane ,Chlorides ,Tachykinins ,Animals ,Rabbits ,Nitric Oxide - Abstract
To examine the effect of tachykinins on Cl secretion across tracheal mucosa and the possible contribution of nitric oxide (NO) formation to their actions in vivo, we measured Cl diffusion potential difference (Cl-PD) with a high-impedance voltmeter in the presence of amiloride. Superfusion of each neurokinin A (NKA) and substance P (SP) increased Cl-PD in a concentration-dependent fashion, whereas neurokinin B (NKB) had no effect, with the rank order of potency being NKASPNKB. The tachykinin-induced increase in Cl-PD was inhibited by the NO synthase inhibitor NG-nitro-L-arginine methylester (L-NAME), an effect that was reversed by L-arginine but not by D-arginine. These results suggest that tachykinins increase Cl secretion across rabbit trachea from the submucosa toward the lumen via stimulation of NK2 receptors and that NO formation may be involved in at least part of this process. more...
- Published
- 1995
48. Effect of TJ-96, an anti-allergic herbal medicine, on tracheal transepithelial potential difference in vivo
- Author
-
J, Tamaoki, H, Takemura, M, Kondo, A, Chiyotani, A, Sakai, and K, Konno
- Subjects
Male ,Mucous Membrane ,Sodium ,Arginine ,Nitric Oxide ,Epithelium ,Membrane Potentials ,Amiloride ,Trachea ,NG-Nitroarginine Methyl Ester ,Histamine H1 Antagonists ,Hypersensitivity ,Animals ,Medicine, Kampo ,Rabbits ,Drugs, Chinese Herbal - Abstract
We studied the effect of Saiboku-to (TJ-96), an anti-allergic herbal medicine, on transepithelial potential difference of rabbit trachea and possible involvement of nitric oxide (NO) generation in vivo. Perfusion of TJ-96 on the tracheal mucosal surface increased PD in a concentration-dependent manner, the maximal increase from the baseline level and the concentration of TJ-96 required to produce a half-maximal effect (EC50) being 8.1 +/- 1.4 mV (mean +/- SE, P0.001) and 47 micrograms/ml. This effect was abolished by pretreatment with the Na channel blocker amiloride. NG-nitro-L-arginine methylester (L-NAME) but not NG-nitro-D-arginine methylester (D-NAME) inhibited TJ-96-induced increase in PD, and this inhibition was selectively reversed by L-arginine. These results suggest that TJ-96 stimulates Na absorption by airway epithelial cells probably through NO generation. more...
- Published
- 1995
49. [Continuous monitoring of nitric oxide release from airway mucosa]
- Author
-
J, Tamaoki, M, Kondo, H, Takemura, A, Chiyotani, E, Tagaya, and K, Konno
- Subjects
Male ,Trachea ,Mucous Membrane ,NG-Nitroarginine Methyl Ester ,Animals ,Rabbits ,Arginine ,Nitric Oxide - Abstract
There is increasing evidence that nitric oxide (NO) plays a role in the regulation of airway and vascular smooth muscle tone, pulmonary microvascular permeability, and host defense. However, it remains uncertain whether NO is actually released from airway mucosa. We therefore directly measured NO concentrations in the perfusate of rabbit tracheal mucosal surface, with an NO-selective electrode. The electrode was made of Pt/Ir alloy coated with a three-layered membrane that consisted of KCl, No-selective silicone resin, and a normal silicone membrane. Termination of tracheal perfusion with Krebs-Henseleit solution increased the electrical current derived from oxidation of NO at the electrode, and reperfusion rapidly decreased the current to the baseline value. Addition of L-NG-arginine methylester (L-NAME, 10(-3) M) to the perfusate decreased NO release, but D-NAME had no effect. Subsequent addition of L-arginine (10(-3) M) reversed the inhibition by L-NAME and greatly increased NO release above the baseline value. Histochemical staining to reveal NADPH diaphorase activity in the tracheal tissue showed a strong blue reaction mainly in the epithelial cells. These results suggest that NO is continuously released in the airway mucosal surface, probably from the epithelial cells rich in NO synthase. more...
- Published
- 1994
50. [Cell-to-cell interaction in airway mucosa--effect of eosinophils on airway epithelial ion transport]
- Author
-
M, Kondo, J, Tamaoki, and K, Konno
- Subjects
Eosinophils ,Male ,Trachea ,Ion Transport ,Mucous Membrane ,Guinea Pigs ,Animals ,Epithelial Cells ,Arachidonic Acids ,Cell Communication - Abstract
We examined the interaction between eosinophil-derived mediators and ion transport in airway epithelial cells. Eosinophils were obtained by peritoneal lavage from polymyxin B-treated guinea-pigs and were purified over discontinuous Percoll density gradients. The activated eosinophil supernatant was prepared with a two-stage method in the presence of A23187. The effects of eosinophil supernatant on the electric properties of cultured epithelial cells from cow trachea were examined in an Ussing chamber under short-circuit conditions. The eosinophil supernatant added to the serosal and mucosal sides increased the short-circuit current (Isc) in an eosinophil number-dependent manner (3 x 10(6), 10(7) eosinophils: delta Isc 9 +/- 1 microA/cm2, 18 +/- 3 microA/cm2). The response was inhibited by treatment of epithelial cells with diphenylamine-2-carboxylate but not by amiloride. The increase in Isc induced by the supermatant from eosinophils treated with indomethacin or the lipoxygenase inhibitor AA861 was significantly less than that induced by untreated eosinophils. These results indicate that activated eosinophils stimulate C1 secretion in airway epithelium via release of metabolites of arachidonic acid. more...
- Published
- 1994
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.