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Biomedical subjects

J Nakata

Publications and source records attributed to J Nakata.

At least 19 recordsLinked to original sources

A Novel real-time dosimetry technique based on radiation-induced surface activation.

A novel real-time dosimetry technique based on radiation-induced surface activation (RISA) phenomenon has been proposed that is similar to ultraviolet surface activation known typically in anatase-type titanium dioxide. It has been found that the RISA phenomenon occurs on the surface of an oxidised semiconductor or oxidised metal film by radiation incidence. The RISA dosemeter has the following advantageous characteristics: (1) output of the RISA dosemeter is proportional to the dose equivalent rate in harsh environments, (2) fluctuation of output of the RISA dosemeter irradiated by (60)Co gamma-rays is <2.5% beyond the total dose equivalent of 1.8 MSv, (3) the transient current observed in simple insulators for a few seconds or more after onset of irradiation was not detected in the RISA dosemeter and (4) this dosemeter worked well even at high temperatures.

Computer Systems↗

Validity and safety of sputum induction by inhaled uridine 5'-triphosphate.

UNLABELLED: Inhalation of hypertonic saline during sputum induction causes bronchoconstriction. We studied the validity and safety of sputum induction by uridine 5'-triphosphate (UTP). Sputum was induced by a 5-min inhalation of hypertonic saline (3%) on Day 1 and UTP (5 mg/ml in 0.9% saline) on Days 8 and 15 in 16 healthy subjects and 16 patients with mild-to-moderate asthma. Inhaled UTP produced twofold greater amounts of sputum than did hypertonic saline. There were significant differences in oxygen desaturation and bronchoconstriction during the procedure between the two methods: the maximal fall in Sa(O(2)), the AUC of the Sa(O(2))-time response, and the fall in PEF were less in the subjects who received UTP than in those who received hypertonic saline. Sputum total cell and differential cell counts, with a high proportion of eosinophils in asthmatics, were similar between specimens obtained by hypertonic saline and UTP. When we compared two consecutive measurements on the UTP-induced sputum samples, the reproducibility calculated by the intraclass correlation coefficient was high for the proportion of eosinophils, neutrophils, and macrophages. Therefore, inhalation of UTP aerosols may provide an effective, relatively noninvasive, valid, and reproducible method of sputum induction for the assessment of airway inflammation in asthma. KEYWORDS: uridine triphosphate; induced sputum; airway inflammation; bronchoconstriction; asthma

Administration, Inhalation↗

Effect of suplatast tosilate, a Th2 cytokine inhibitor, on steroid-dependent asthma: a double-blind randomised study. Tokyo Joshi-Idai Asthma Research Group.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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. INTERPRETATION: 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.

Administration, Inhalation↗

Ginsenoside-induced relaxation of human bronchial smooth muscle via release of nitric oxide.

Ginsenoside, an extract of Panax ginseng, is an essential constituent of anti-asthmatic Chinese herbal medicine. To elucidate whether ginsenoside affects airway smooth muscle tone and, if so, what the mechanism of action is, we studied relaxant responses of human bronchial strips under isometric condition in vitro, and directly measured the release of nitric oxide (NO) by an amperometric sensor for this molecule. Addition of ginsenoside relaxed the tissues precontracted with acetylcholine in a dose-dependent manner, the maximal relaxation and the ginsenoside concentration required to produce 50% relaxation being 67+/-8% and 210+/-29 microg ml(-1), respectively. The relaxant responses to ginsenoside were inhibited by N(G)-nitro-L-arginine methylester (L-NAME) and removal of the epithelium, but not by N(G)-nitro-D-arginine methylester (D-NAME) or tetrodotoxin. This inhibitory effect of L-NAME was reversed by L-arginine but not by D-arginine. Addition of ginsenoside to the medium containing bronchial tissues dose-dependently increased NO-selective electrical current, and this effect was greatly attenuated by the epithelial removal or Ca(2+)-free medium. Ginsenoside also increased tissue cyclic GMP contents, an effect that was abolished in the presence of L-NAME. It is concluded that ginsenoside induces relaxation of human bronchial smooth muscle via stimulation of NO generation predominantly from airway epithelium and cyclic GMP synthesis. This action might account for the anti-asthmatic effect of Panax ginseng.

Bronchi↗

Effect of inhaled indomethacin in asthmatic patients taking high doses of inhaled corticosteroids.

BACKGROUND: Cyclooxygenase products of arachidonic acid may play a part in bronchoconstriction and airway inflammation in asthma. OBJECTIVE: We sought to determine the effect of inhaled indomethacin on asthma control and asthma exacerbations during reduction of inhaled corticosteroids in patients with moderate-to-severe steroid-dependent asthma. METHODS: We conducted a double-blind, randomized, parallel-group, multicenter study in 38 patients with asthma taking high doses (> or =1500 microg/d) of beclomethasone dipropionate (BDP). After a run-in period, patients were assigned inhaled indomethacin (50 mg/d) or placebo for 6 weeks, during which the daily doses of BDP were reduced to half at week 2 and then to one third of the baseline dose at week 4. RESULTS: Data were available from 34 patients. After the reduction of BDP doses, FEV(1), peak expiratory flow, asthma symptoms, and exhaled nitric oxide concentrations deteriorated in both treatment groups, but these effects were less pronounced in the indomethacin group compared with the placebo group. During the 6-week treatment period, 89% of the patients receiving placebo had relapse of asthma, whereas only 38% of those receiving inhaled indomethacin did so (P =.003). CONCLUSION: Inhalation of indomethacin can reduce asthma exacerbations induced by reduction of high-dose inhaled corticosteroid in steroid-dependent asthma.

Administration, Inhalation↗

Impairment of airway mucociliary transport in patients with sinobronchial syndrome: role of nitric oxide.

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.

Adult↗

Effect of a thromboxane A(2) antagonist on sputum production and its physicochemical properties in patients with mild to moderate asthma.

STUDY OBJECTIVE: To determine the effects of a specific thromboxane A(2) (TxA(2)) receptor antagonist, seratrodast, on asthma control and airway secretions. DESIGN: Multicenter, double-blind, randomized, placebo-controlled study. PATIENTS: Forty-five patients with mild to moderate asthma who had been continuously expectorating sputum of > 20 g/d. Patients with a current pulmonary infection or taking oral corticosteroids, antibiotics, or mucolytic agents were excluded from the trial. INTERVENTIONS: Following a 2-week run-in period, while pulmonary function, sputum production, and mucociliary function were assessed, patients were assigned to receive seratrodast, 40 mg/d, or placebo for 6 weeks. MEASUREMENTS AND RESULTS: During the treatment period, the changes in FEV(1) and peak expiratory flow (PEF) were not different between the two patient groups, but there were significant reductions in diurnal variation of PEF (p = 0.034), frequency of daytime asthma symptoms (p = 0.030), and daytime supplemental use of beta(2)-agonist (p = 0.032) in the seratrodast group. For sputum analysis, seratrodast treatment decreased the amount of sputum (p = 0.005), dynamic viscosity (p = 0. 007), and albumin concentration (p = 0.028), whereas it had no effect on elastic modulus or fucose concentration. Nasal clearance time of a saccharin particle was shortened in the seratrodast group at week 4 (p = 0.031) and week 6 (p = 0.025), compared with the placebo group. CONCLUSION: Blockade of TxA(2) receptor has minimal effects on pulmonary function, but may cause an improvement in mucociliary clearance by decreasing the viscosity of airway secretions.

Adult↗

[An automated electronic anesthesia record using a hospital LAN (local area network)].

We have developed an automated electronic anesthesia record system using a hospital LAN. As the number of monitors we can use in the operating room is increasing, it is impossible to record all physiologic parameters in a handwritten anesthesia record. Physiologic parameters are recorded every 10 seconds from the anesthesia monitor. An operation ordering system by a hospital LAN has been completed and the patient's data are stored in a host computer, and we can use its data for the automated electronic anesthesia record preoperatively. The advantages of the automated electronic anesthesia record are continuous high quality, more data collection than the handwritten anesthesia record, and the electronic database. During a critical period, the anesthesiologist is too busy to plot physiologic parameters but the automated electronic anesthesia record is reliable and accurate. Disadvantage of the automated electronic anesthesia record is some practice required to input clinical events such as drug administration. The handwritten anesthesia record is easy to use and economical. Ergonomic problems still remain to be solved for wider acceptance of the automated electronic anesthesia record in clinical practice. At the end of the operation, intraoperative data are sent to a host computer and the anesthesia record is printed. We can use this database for clinical research and retrospective case reviews. The implementation of the automated electronic anesthesia record in anesthesia practice will improve quality of patient care.

Anesthesia↗

[Role of nitric oxide in airway mucociliary dysfunction in diffuse panbronchiolitis].

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 (p < 0.05), prolonged NCT (p < 0.01), and a higher Cl concentration in the sputum (p < 0.05). Among these variables, exhaled NO concentration was negatively correlated with NCT (p < 0.01) and sputum Cl concentration (p < 0.05). 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.

Breath Tests↗

Effect of azelastine on platelet-activating factor-induced microvascular leakage in rat airways.

To determine the effect of the antiallergic drug azelastine on airway mucosal inflammation, we studied airway microvascular permeability in response to platelet-activating factor (PAF) in pathogen-free rats. Vascular permeability and neutrophil accumulation were assessed by the percent area occupied by Monastral blue-labeled blood vessels and by myeloperoxidase-containing granulocytes, respectively, in whole mounts of the trachea and main bronchus. Intravenous PAF caused dose-dependent increases in the area density of Monastral blue-labeled vessels and neutrophil influx, and the former effect was inhibited by depletion of circulating neutrophils by cyclophosphamide or treatment with the neutrophil elastase inhibitor ONO-5046. Pretreatment with azelastine inhibited PAF-induced vascular leakage without affecting neutrophil accumulation. This inhibitory effect of azelastine was not seen in neutropenic rats and ONO-5046-treated rats. PAF increased neutrophil elastase contents in bronchoalveolar lavage fluid, an effect that was inhibited by azelastine. Therefore, azelastine attenuates PAF-induced airway mucosal microvascular leakage, probably involving inhibition of the release of neutrophil elastase from activated neutrophils.

Animals↗

Effect of cromolyn on adenosine-induced airway microvascular leakage in sensitized rats.

Inhalation of adenosine causes bronchoconstriction in asthmatic subjects, but the effect of this purine nucleotide on airway vascular permeability is unknown. In order to determine whether adenosine produces airway microvascular leakage and, if so, to examine the effect of cromolyn (sodium cromoglycate (SCG)) on this extravasation of Evans blue was measured in the airways of ovalbumin-sensitized Brown Norway rats. Inhaled adenosine caused microvascular leakage in sensitized but not in non-sensitized rats, and the response was abolished by capsaicin pretreatment or the tachykinin neurokinin-1 receptor antagonist FK888. Adenosine-induced vascular leakage became apparent in nonsensitized rats when treated with phosphoramidon, and airway neutral endopeptidase activity was lower in sensitized than in non-sensitized animals. The extravasation induced by adenosine in sensitized rats was dose dependently inhibited by SCG aerosols, SCG likewise inhibited microvascular responses to substance P, but had no effect on those to platelet-activating factor. These results suggest that: 1) adenosine induces airway microvascular leakage in sensitized rats through stimulation of neurokinin-1 receptors; 2) this effect is associated with a sensitization-induced decrease in neutral endopeptidase activity; and 3) sodium cromoglycate inhibits adenosine-induced extravasation, presumably via functional antagonism of tachykinins.

Adenosine↗

[Risk factor of liver disorders caused by flutamide--statistical analysis using multivariate logistic regression analysis].

The antiandrogenic drug, flutamide (Odyne), is widely used in the treatment of carcinoma of prostate. It is well known that flutamide has adverse effects of liver disorders. To ascertain the risk of liver disorders before administering this drug, past history and lifestyle preferences were resurveyed in 123 patients who had been treated with flutamide. The results obtained were assessed in relation to the occurrence of liver disorders by multivariate logistic regression analysis. The incidence of liver disorders was 26% (33/123), with 64% of the disorders occurring within 9 months. The chi-square test for dependent variables revealed that three variables, i.e., body mass index, past history of liver disorders and elevated glutamic-pyruvic transaminase levels were significantly related to the incidence of liver disorders (p > 0.05). Multivariate analysis indicated that a history of liver disorders and elevated alanine aminotransferase (ALT) levels were related to a higher incidence of liver disorders. Elevated ALT levels were associated with a higher incidence of liver disorders and smoking was related to a lower incidence of the liver disorders.

Alanine Transaminase↗

[High-dose chemotherapy with autologous peripheral blood stem cell transfusion in the treatment of advanced testis cancer].

Four patients with advanced testis cancer were treated by high-dose chemotherapy supporting by autologous peripheral blood stem cell transplantation. High-dose chemotherapy (carboplatin 250 mg/m2 or nedaplatin 200 mg/m2, etoposide 1,500 mg/m2, ifosphamide 7.5 g/m2 was given and peripheral blood stem cell transfusion was performed 72 hours after the last dose of chemotherapy. High-dose chemotherapy. was given followed by 1 or 2 cycles of pre high-dose therapy consisting of cisplatin 100 mg/m2 or carboplatin 500 mg/m2, etoposide 450 mg/m2, ifosphamide 6 g/m2. All 4 patients were evaluable. Three patients obtained a complete response and one showed a partial response. The partial responder was given RPLND. The RPLND specimen showed necrotic tissue.

Adult↗

[Effect of heparin on airway goblet cell secretion in sensitized guinea pigs].

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 (p < 0.001), 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.

Animals↗

Histamine H2 receptor-mediated airway goblet cell secretion and its modulation by histamine-degrading enzymes.

BACKGROUND: Airway goblet cell hypersecretion may contribute to the pathophysiology of asthma. However, it is unknown whether histamine affects goblet cell secretion and, if so, which subtype of histamine receptor is involved and whether endogenous histamine-degrading enzymes modulate these actions. METHODS: We morphometrically assessed goblet cell secretion in the guinea pig trachea stained with alcian blue and periodic acid Schiff stains by measuring the mucus score, which was inversely related to the degree of mucus glycoprotein discharge. RESULTS: Inhalation of histamine caused a dose-dependent decrease in mucus score, an effect that was inhibited by pretreatment with the H2-receptor antagonist cimetidine but not with the H1-receptor antagonist mepyramine or the H3-receptor antagonist thioperamide. Inhaled Dimaprit, a selective H2-receptor agonist, likewise decreased mucus score; whereas stimulation of H1- and H3-receptors with 2-methylhistamine and (R)-alpha-methylhistamine, respectively, had no effect. Pretreatment with the histamine N-methyltransferase inhibitor SKF 91488, but not the diamine oxidase inhibitor aminoguanidine, potentiated the dose-dependent effect of histamine on goblet cell secretion, causing a decrease in the concentration of inhaled histamine required to produce a half-maximal effect from 0.80 +/- 0.12 to 0.48 +/- 0.09 mg/ml (p < 0.01). The histamine methyltransferase activity in the tracheal mucosa was 29 times higher than diamine oxidase activity. CONCLUSION: These findings suggest that histamine stimulates airway goblet cell secretion through H2-receptors and that this effect may be modulated principally by endogenous histamine methyltransferase through a degradation of histamine.

Amine Oxidase (Copper-Containing)↗

Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. The Tokyo Joshi-Idai Asthma Research Group.

To test whether the leukotriene antagonist ONO-1078 (pranlukast) prevents asthma exacerbations during reduction of high-dose inhaled corticosteroid, we conducted a randomized, double-blind, placebo-controlled study in 79 asthma patients requiring high doses (1,500 microg/d or more) of inhaled beclomethasone dipropionate (BDI) for clinical control (duration of asthma, 11.0 +/- 3.1 yr; duration of BDI treatment, 0.5 +/- 0.3 yr; FEV1 percentage of predicted, 80.7 +/- 2.0%). After a 2-wk run-in period, the doses of BDI were halved, while the patients were assigned to receive orally ONO-1078, 450 mg twice daily, or placebo. In the placebo group FEV1 decreased by 0.33 +/- 0.20 L after 6 wk (p < 0.001). Likewise, morning and evening PEF decreased by 46 +/- 7 L/min and 18 +/- 6 L/min, respectively. By contrast these variables were sustained above baseline in the ONO-1078 group. The number of daytime and nighttime asthma symptoms and the use of beta2-agonist increased in the placebo group, whereas they remained unchanged in the ONO-1078 group. In the placebo group concentrations of serum eosinophil cationic protein and exhaled nitric oxide increased (p = 0.007 and p = 0.025, respectively), compared with no change in the ONO-1078 group. Therefore, the leukotriene antagonist ONO-1078 prevents the asthma deterioration provoked by a 6-wk reduction of the dose of inhaled BDI into half.

Administration, Inhalation↗