Search PubMed⌕ Search

Biomedical subjects

K Konno

Publications and source records attributed to K Konno.

At least 163 records · Page 9Linked to original sources
PubMed1995

Effect of TJ-96, an anti-allergic herbal medicine, on tracheal transepithelial potential difference in vivo.

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, P < 0.001) 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.

Amiloride↗
PubMed1995

[Utility of polymerase chain reaction for diagnosis of tuberculous pleural effusion].

Polymerase chain reaction (PCR) assay to detect Mycobacterium tuberculosis was done on 14 pleural fluid samples. Eight samples were from patients with pleural effusions suspected to be tuberculous that were smear-negative and culture-negative for acid-fast bacilli, and six samples were from patients with malignant effusions. The DNA extracted from samples was amplified with two different pairs of primers of the 123-bp and the 383-bp target DNAs of the bacilli. Mycobacterial DNA was detected in all eight samples of effusions suspected to be tuberculous, but it was not detected in any malignant effusions. We conclude that PCR assay may be useful for the rapid diagnosis of tuberculous pleural effusions that are smear-negative and culture-negative.

Base Sequence↗
PubMed1995

[Clinical evaluation of cefpodoxime proxetil, a new oral cephem, in the treatment of respiratory tract infections with the special reference to community-acquired Streptococcus Pneumoniae infections].

The clinical usefulness of cefpodoxime proxetil (CPDX-PR) was investigated in the treatment of pneumonia and chronic airway infections occurring in patients first visiting our outpatient clinic or those being treated at the outpatient clinic. CPDX-PR was orally administered twice a day after meals at a dose of 100-200 mg for acute respiratory tract infections and at a dose of 200 mg for chronic respiratory tract infections. Excellent, good, fair, and poor responses were observed in 20, 33, 10, and 3 of 66 patients (4 with acute bronchitis, 27 with pneumonia, and 35 with acute exacerbation of chronic airway infection), respectively, demonstrating an 80.3% efficacy rate (53/66). Causative organisms, including Streptococcus pneumoniae, were all eradicated from the patients whose causative organisms were examined over time, although 2 of the patients were superinfected with Pseudomonas aeruginosa. There were no serious adverse reactions or abnormal changes in laboratory test results. It was concluded that CPDX-PR could be used as a first-choice drug for the treatment of respiratory tract infections at an outpatient clinic, and that this drug should acquire greater importance in particular consideration of recent increases in infections with S. pneumoniae.

Adult↗
PubMed1995

Stimulation of opioid mu-receptors potentiates beta adrenoceptor-mediated relaxation of canine airway smooth muscle.

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.

Amino Acid Sequence↗
PubMed1995

Clear cell variants of intracranial tumors: meningioma and ependymoma.

We report two cases of rare histological types of intracranial clear cell tumor. Case 1: The tumor, on the left frontal convexity in a 64-year-old woman, consisted largely of polygonal cells with clear cytoplasm which were divided into lobules of uneven size by abundant fibrous connective tissue. Most of the tumor cells were immunopositive for epithelial membrane antigen and vimentin. Ultrastructurally, the tumor cells showed conspicuous interdigitations of their plasma membranes with frequent junctional complexes, and contained numerous glycogen granules in the cytoplasm and its processes. Occasionally, amianthoid collagen fibers were found in the fibrous stroma. Our diagnosis of this tumor was clear cell meningioma. Case 2: The tumor, in the right cerebellar hemisphere in a 64-year-old woman, consisted of round, clear cells with a honeycomb-like pattern. The tumor cells were positive for glial fibrillary acidic protein, vimentin and S-100 protein. Ultrastructurally, the tumor was composed of round cells arranged in a cell-to-cell pattern, and the adjacent cells often formed microrosettes containing microvilli in their lumina. There were scattered cells with accumulatios of glycogen granules in their cytoplasm. Our diagnosis of this tumor was clear cell ependymoma. From the light microscopic features of these tumors, it does not necessarily seem easy to discriminate them from other intracranial tumors composed of similar clear cells, such as oligodendroglioma, central neurocytoma, hemangioblastoma and metastic renal cell carcinoma. Ultrastructural examination is crucial in the identification of the clear cell variants of meningioma and ependymoma.

Brain Neoplasms↗
PubMed1994

Biological activities of 24-fluoro-1 alpha,25-dihydroxyvitamin D-2 and its 24-epimer.

Biological activities of two epimeric 24-fluorinated vitamin D-2 analogs, 24-fluoro-1 alpha,25-dihydroxyvitamin D-2 [24-F-1,25-(OH)2D2] and its 24-epimer [24-epi-24-F-1,25-(OH)2D2], were studied and compared with 1 alpha,25-dihydroxyvitamin D-3 [1,25-(OH)2D3] and 1 alpha,25-dihydroxyvitamin D-2 [1,25-(OH)2D2]. 24-F-1,25-(OH)2D2 was nearly as active as 1,25-(OH)2D3 and 1,25-(OH)2D2 both in regulating calcium metabolism in vivo including bone mineral mobilization and intestinal calcium transport and in inducing differentiation of HL-60 cells. While 24-epi-24-F-1,25-(OH)2D2 showed distinct properties in these two types of the actions. Though the 24-epimer was nearly as potent as 1,25-(OH)2D3 in inducing differentiation of HL-60 cells, it showed little activity in regulating calcium metabolism in vivo. The fluorine atom introduced at the 24-position of either 1,25-(OH)2D2 or its 24-epimer had no potentiating effect. This is in sharp contrast with the cases of 24- and 26,27-multifluorinated analogs of active vitamin D-3.

Animals↗
PubMed1994

Effect of menthol on cytosolic Ca2+ levels in canine airway epithelium in culture.

Intracellular Ca2+ concentration ([Ca2+]i) in canine cultured tracheal epithelium in response to cyclic alcohols was measured by a fura-2 method. Menthol rapidly increased [Ca2+]i in a concentration-dependent fashion, the maximal increase from the baseline levels and the concentration of menthol required to produce a half-maximal effect (EC50) being 148 +/- 23 nM (mean +/- SE, p < 0.001) and 0.3 mM, respectively, whereas other cyclic alcohols including menthone and cyclohexanol had no effect. The menthol-induced increase in [Ca2+]i was not affected by verapamil but partially inhibited by low Ca2+ medium in the presence of EGTA. These results indicate that menthol specifically increases cytosolic Ca2+ in airway epithelium, which may be derived from intracellular Ca2+ stores.

Animals↗
PubMed1994

Transient neutropenia after intravenous injection of vindesine in patients with lung cancer.

We have found transient circulating neutropenia and pulmonary sequestration of neutrophils after the intravenous injection of vindesine, a microtubule disruptor. Experiment 1 Ten patients with lung cancer were given a bolus intravenous injection of 3 mg.m-2 vindesine (Fildesine(r)). In all patients, total leukocyte and neutrophil counts in the venous blood fell to 65% and 47% of baseline values respectively within 30 min, and returned to baseline values within 6 h. In contrast, the lymphocyte count was stable. Experiment 2 Male Wistar rats were given saline or 0.08 mg.kg-1 vindesine intravenously and were sacrificed after 30 min. Vindesine produced a 58% reduction in the neutrophil count in the systemic circulation and a threefold increase in the neutrophil/erythrocyte ratio in the pulmonary microvasculature. Experiment 3 We studied the effects of vindesine in vitro on neutrophils and lymphocytes isolated from the venous blood of healthy volunteers. Vindesine (10(-5)-10(-8) mol.l-1) reduced neutrophil deformability (filterability) and induced neutrophil polarization, with reversibility of both effects after washout. These effects of vindesine were completely inhibited by cytochalasin B, an actin filament disrupter. Vindesine did not stimulate the neutrophil functions of adherence to polystyrene tubes, chemotaxis, or superoxide anion generation. The filterability and morphology of lymphocytes were not altered by vindesine. Thus, we conclude that a bolus injection of vindesine produces pulmonary sequestration of neutrophils, which produces circulatory neutropenia, and that it is primarily mediated by a decrease in neutrophil deformability that occurs without activation of the cells.

Animals↗
PubMed1994

Role of K+ channel opening and Na(+)-K+ ATPase activity in airway relaxation induced by salbutamol.

To determine the role of K+ channel opening and Na(+)-K+ ATPase activity in the beta-adrenoceptor-mediated relaxation of airway smooth muscle, we studied canine bronchial segments under isometric conditions in vitro. Relaxant responses to salbutamol were not altered by glibenclamide or apamin but inhibited by charybdotoxin, where significant inhibition was observed only at salbutamol concentrations of less than 10(-6) M. In contrast, only the relaxations induced by salbutamol at 3 x 10(-6) M and greater were sensitive to ouabain. Relaxations produced by low and high concentrations of salbutamol were selectively attenuated by charybdotoxin and ouabain, respectively, in a concentration-dependent manner. These results suggest that both Ca(2+)-activated K+ channel and Na(+)-K+ ATPase may be operative in the airway relaxation induced by low and high concentrations of the beta-adrenergic agonist, respectively.

Albuterol↗
PubMed1994

Pertussis toxin-sensitive airway beta-adrenergic dysfunction by somatostatin.

To elucidate the effect of somatostatin and its mechanism of action on airway beta-adrenergic function, we studied canine bronchial smooth muscle under isometric conditions in vitro. Somatostatin (10(-6) M) inhibited the salbutamol-induced relaxation, so that the salbutamol concentration-response curves were displaced to higher concentrations (P < 0.01). This inhibition was dose dependent, the concentration of somatostatin required to produce a half-maximal effect being 10(-8) M. The relaxant responses to forskolin were likewise inhibited by somatostatin, but those to dibutyryl 3',5'--adenosine cyclic monophosphate (DB-cAMP), verapamil and nitroprusside were not. Somatostatin inhibited the salbutamol-induced accumulation of intracellular cAMP. These effects were abolished by the somatostatin antagonist cyclo [7-aminoheptanoyl-Phe-D-Trp-Lys-Thr (Bz)] or pertussis toxin. These observations suggest that somatostatin down-regulates beta-adrenergic function of airway smooth muscle through activation of an inhibitory guanine nucleotide (GTP)-binding regulatory protein, Gi, coupled to adenylate cyclase.

Adenylate Cyclase Toxin↗
PubMed1994

A sensitive assay system screening antiviral compounds against herpes simplex virus type 1 and type 2.

A highly sensitive and accurate assay system was developed for in vitro evaluation of anti-herpes simplex virus (anti-HSV) agents using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and human embryonic lung fibroblast (MRC-5) cells. This assay system was found to be highly sensitive for both HSV-1 and -2. Confluent MRC-5 cells were infected with either HSV-1 KOS strain or HSV-2 G strain of 25 TCID50 in the presence of various concentrations of test compounds. The optical density of formazan was used to determine cell viability. The EC50 values of acyclovir and several other anti-HSV agents were found to be similar to those obtained by the plaque reduction method. These results indicate that this MTT assay is useful for screening anti-HSV-1 and -2 agents.

Acyclovir↗
PubMed1994

MTT colorimetric assay system for the screening of anti-orthomyxo- and anti-paramyxoviral agents.

A rapid and sensitive method was developed for screening potential antiviral agents against orthomyxo- and paramyxoviruses, using the MTT method with cell culture suspensions. The cell lines used for the assay were as follows: MDCK cells for the influenza A virus (Fluv. A), HeLa cells for the respiratory syncytial virus (RSV), and Vero cells for the measles virus (MSV). Test compounds were diluted and plated in 96-well round-bottomed microtiter plates. Trypsinized cell suspensions and viruses were added to each well, the plates were then centrifuged (700 x g, 5 min, room temperature), and incubated for several days. The MTT assay was carried out after the degeneration of virus-infected cells became evident. The optical density (OD) of formazan was determined using a computer-controlled microplate reader. With this assay system, the EC50 values of Ribavirin (used as the reference compound) were 3.7 micrograms/ml for Fluv. A, 4.5 micrograms/ml for RSV, and 12.3 micrograms/ml for MSV, respectively. These EC50 values were equivalent to those obtained using the plaque reduction assay. The confluent cell culture system was inadequate for antiviral assays against RSV and MSV when the MTT method was used, because the inhibition of formazan formation was not observed in viral-infected cells. Moreover, the suspension method is more sensitive to the cytotoxicity of antiviral agents than the confluent cell culture system.

Amides↗
PubMed1994

Stimulation by menthol of Cl secretion via a Ca(2+)-dependent mechanism in canine airway epithelium.

1. To investigate the effect of menthol on airway epithelial ion transport function, we studied the bioelectrical properties of canine cultured tracheal epithelium by Ussing's short-circuit technique in vitro. 2. Addition of menthol (10(-3) M) to the mucosal but not the submucosal solution increased the short-circuit current (Isc) from 6.2 +/- 0.9 to 14.0 +/- 2.2 microA cm-2 (P < 0.001), and this effect was accompanied by increases in transepithelial potential difference and conductance. The response was dose-dependent, with the maximal increase from the baseline value and the concentration required to produce a half-maximal effect (EC50) being 6.4 +/- 0.9 microA cm-2 (P < 0.001) and 40 microM, respectively. 3. Other cyclic alcohols, including menthone and cyclohexanol, had no effect on the electrical properties. 4. The menthol-induced increase in Isc was not altered by pretreatment of the cells with amiloride, indomethacin, or propranolol but was abolished by diphenylamine-2-carboxylate, furosemide or substitution of Cl with iodide in the medium. 5. Menthol (10(-3) M) increased cytosolic levels of free calcium ([Ca2+]i) from 98 +/- 12 to 340 +/- 49 nM (P < 0.01) in fura-2-loaded tracheal epithelium but did not affect the intracellular adenosine 3',5'-cyclic monophosphate content. 6. These results suggest that menthol stimulates Cl secretion across airway epithelium, probably through a Ca(2+)-dependent mechanism, and might thus influence mucociliary transport in the respiratory tract.

Animals↗
PubMed1994

Effect of long term treatment with oxitropium bromide on airway secretion in chronic bronchitis and diffuse panbronchiolitis.

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.

Adult↗
PubMed1994

Angiotensin II 1 receptor-mediated contraction of pulmonary artery and its modulation by prolylcarboxypeptidase.

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.

Angiotensin II↗
PubMed1994

Effects of prostacyclin and beraprost on ciliary motility of rabbit airway epithelium.

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.

Animals↗
PubMed1994

Interleukin-1 beta inhibits airway smooth muscle contraction via epithelium-dependent mechanism.

To determine whether the cytokine interleukin (IL)-1 beta directly affects airway smooth muscle functions and, if so, what the mechanism of action is, we studied canine isolated bronchial segments under isometric conditions in vitro. Incubation of tissues with human recombinant IL-1 beta (10 ng/ml) for 150 min decreased the contractile responses to acetylcholine, histamine, and KCl. The inhibitory effect of IL-1 beta on the acetylcholine (10(-3) M)-induced contraction was concentration-dependent, the maximal decrease from the baseline contraction being 52 +/- 8% (mean +/- SD, p < 0.001) observed with 10 ng/ml IL-1 beta. Intracellular levels of cyclic AMP and cyclic GMP were not significantly altered by IL-1 beta. The IL-1 beta-induced inhibition of the contractile responses was not affected by pretreatment of tissues with indomethacin or propranolol, but it was greatly attenuated by mechanical removal of epithelium. These results suggest that IL-1 beta may play a protective role against bronchoconstrictor responses via epithelium-dependent mechanism such as the release of epithelium-derived relaxing factor.

Acetylcholine↗