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Biomedical subjects

T Takishima

Publications and source records attributed to T Takishima.

At least 109 records · Page 6Linked to original sources
PubMed1993

Histamine N-methyltransferase modulates histamine- and antigen-induced bronchoconstriction in guinea pigs in vivo.

To examine whether histamine N-methyltransferase (HMT; EC 2.1.1.8) modulates the effects of allergic reaction in vivo, we studied the effects of aerosolized SKF 91488, a specific HMT inhibitor, on the responses to aerosolized histamine in unsensitized guinea pigs and to ovalbumin (OA) antigen inhalation in guinea pigs sensitized to OA. Airway responsiveness was assessed by determining provocation concentrations of histamine and OA aerosols that increased pulmonary resistance to twice the baseline values. SKF 94188 shifted, in a dose-dependent fashion, the dose-response curves to histamine and OA antigen to lower concentrations, and it significantly decreased provocation concentrations of both histamine and OA antigen (p < 0.01). In contrast of SKF 91488, aerosolized aminoguanidine, a specific inhibitor of diamine oxidase (10(-2) M, 90 breaths), did not alter the provocation concentration of histamine (p > 0.20). SKF 91488 (10(-2) M, 90 breaths) caused no significant changes in response to acetylcholine (p > 0.30). HMT activities were observed in the entire airways of the trachea, main bronchi, segmental bronchi and bronchioles, and parenchymal tissues. These findings suggest that HMT modulates the effects of exogenous histamine and endogenously released histamine by antigen challenge on bronchoconstrictor responses in guinea pigs in vivo.

Aerosols↗
PubMed1993

Involvement of superoxide in ozone-induced airway hyperresponsiveness in anesthetized cats.

To determine whether oxygen radical scavengers inhibit ozone-induced airway hyperresponsiveness, we examined the protective effect of polyethylene glycol-superoxide dismutase (PEG-SOD) and PEG-catalase (PEG-CAT) on ozone-induced airway hyperresponsiveness in cat airways. Twenty-five cats divided into five groups were anesthetized and mechanically ventilated. There was no difference between the groups in baseline airway responsiveness to inhaled acetylcholine (ACh). In the control group, AChPC, the concentration required to produce a doubling increase in baseline pulmonary resistance, was significantly reduced by ozone exposure (2.0 ppm for 2 h); the ratios of AChPC before ozone exposure to after ozone exposure (AChPC ratio) were 14.8 +/- 5.7 (p < 0.001) and 4.80 +/- 1.6 (p < 0.01) 30 and 120 min after exposure, respectively. Local administration of PEG-SOD (2,000 U/kg) into airways partially but significantly prevented ozone-induced airway hyperresponsiveness. The AChPC ratios were 6.2 +/- 1.4 and 1.5 +/- 0.2 30 and 120 min after exposure, respectively, which were significantly different from those of the control group (p < 0.05), whereas PEG-CAT pretreatment (6,000 U/kg) was without effect. Combined pretreatment with PEG-SOD and PEG-CAT had no additional protective effect compared with PEG-SOD alone. PEG-SOD had no direct effect on airway responsiveness to ACh. These results suggest that superoxide may be involved in ozone-induced airway hyperresponsiveness.

Acetylcholine↗
PubMed1993

Antiasthma drug, ibudilast, inhibits neurogenic plasma extravasation in guinea-pig airways.

We examined the effect of ibudilast, an antiasthma drug, on neurogenic microvascular leakage in guinea-pig airways by measuring extravasation of Evans blue dye. After intravenous pretreatment with atropine (1 mg/kg) and propranolol (1 mg/kg), bilateral vagal stimulation significantly increased nonadrenergic noncholinergic (NANC)-mediated leakage of dye in the trachea (Tr), the main bronchi (MB), and the central (cIPA) and peripheral (pIPA) intrapulmonary airways. Ibudilast (1.0 to 100 micrograms/kg given intravenously) did not affect basal leakage, but it significantly inhibited NANC-mediated plasma extravasation in a dose-dependent manner, with a maximal inhibition of 74.0% (Tr, p < 0.05), 89.1% (MB, p < 0.05), 91.4% (cIPA, p < 0.01), and 84.3% (pIPA, p < 0.05) at 100 micrograms/kg. Plasma extravasation induced by exogenous substance P (1 microgram/kg given intravenously) was not inhibited by ibudilast. Glibenclamide, an inhibitor of ATP-sensitive potassium channels, blocked the inhibitory effect of ibudilast. We conclude that ibudilast inhibits neurogenic leakage by prejunctional inhibition of neuropeptide release from airway sensory nerve terminals via an ATP-sensitive potassium channel.

Animals↗
PubMed1993

Morphometric analysis of airways in Sjögren's syndrome.

Sjögren's syndrome is characterized by a decrease in exocrine gland secretion and the destruction of secretory tissue and cells, that is, salivary and lacrimal glands. Although patients with Sjögren's syndrome have chronic cough and sometimes sputum, we have little knowledge concerning the morphology of their airways. We performed morphometric analysis of goblet cells and bronchial glands and compared them with intraluminal mucus volume by measuring the mucus-occupying ratio (MOR) in the airways of patients with Sjögren's syndrome. A total of 6 nonsmoking patients with Sjögren's syndrome who had no significant prolonged airway infections (Group SG) (6 women, 55 +/- 2 yr) were compared with four control patients with no pulmonary diseases (Group NL) (1 woman and 3 men, 64 +/- 2 yr) and five patients with chronic bronchitis (Group CB) (1 woman and 4 men, 52 +/- 5 yr). Autopsied lungs from 15 patients were used for morphometry by a digitalizing computer. Area proportion of bronchial glands (gland %) to bronchial wall, goblet cell-occupying ratio to total epithelial layer (goblet %), and MOR were measured in central (3-8 mm in diameter) and peripheral airways (2 mm or less in diameter). Gland % and goblet % in central and MOR in peripheral airways from Group SG were significantly larger than those from Group NL: 15 +/- 2 versus 6 +/- 1% (p < 0.01), 6 +/- 1 versus 2 +/- 1% (p < 0.05), and 9 +/- 2 versus 0.6 +/- 0.3% (p < 0.05), respectively. Further, these values from Group SG did not significantly differ from those from Group CB.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The effect of cytokines on the differentiation of an eosinophilic leukemia cell line (EoL-1) is associated with down regulation of c-myc gene expression.

In this study, we measured hydrogen peroxide (H2O2) release as one of the functions of mature eosinophils, and utilized it as a quantitative index. We demonstrated that 1) the human eosinophilic leukemia cell line, EoL-1, did not release H2O2 when stimulated with phorbol myristate acetate (PMA), but after culturing with tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) it acquired the ability to release H2O2; 2) the ability to release H2O2 was time dependent and reached a peak after 4 days of culture; 3) administration of TGF-beta or GM-CSF, with TNF and IFN-gamma enhanced the PMA-induced release of H2O2 from EoL-1. To examine the potential relationship between c-myc gene expression and induction of the ability to release H2O2, Northern analysis of c-myc gene expression in EoL-1 cocultured with TNF and IFN-gamma was performed. The results showed that the c-myc gene was spontaneously expressed in EoL-1, and the level of c-myc mRNA was markedly reduced after the cells were cocultured with TNF and IFN-gamma, suggesting that the decrease of the c-myc mRNA level is closely associated with induction of the ability to release H2O2.

Cell Differentiation↗
PubMed1993

Effects of a combination therapy of anticoagulant and vasodilator on the long-term prognosis of primary pulmonary hypertension.

A therapy consisting of a combination of an anticoagulant and a vasodilator was investigated to determine its effects on the long-term prognosis of primary pulmonary hypertension (PPH). Twenty patients with PPH who had undergone diagnostic catheterization in our hospital were studied. The mean follow-up period after the initial catheterization was 6 years, with the longest follow-up being 24.4 years. Seven patients were treated with warfarin as an anticoagulant, combined with either isoproterenol (3 patients) or nifedipine (4 patients) as a vasodilator (AV group). The remaining 13 patients were not treated (control group). Although there were no significant differences in the physical activity or hemodynamics between the groups, improvement was seen in 43% of the AV group and in only 7.6% of the controls. The 5 year survival rate was significantly higher in the AV group (57% vs 15%; P < 0.05). Hemodynamics were evaluated repeatedly in 8 patients and improvement was seen only in the AV group. These results suggest that a therapy consisting of a combination of an anticoagulant and a vasodilator may improve the long-term prognosis of PPH.

Adolescent↗
PubMed1993

Decrease in beta-adrenergic receptors of lymphocytes in spontaneously occurring acute asthma.

To clarify changes in beta-adrenergic receptor (BAR) density in spontaneously occurring acute asthma, BAR binding studies were performed on peripheral blood lymphocytes in eight asthmatic and ten normal subjects. Spirometry also was performed. Maximum binding capacity (Bmax) of BAR in acute asthma was significantly lower by 44.2 percent compared with that in stable asthma; FEV1/FVC ratio decreased by 23.9 percent. The Bmax for acute asthma also was significantly lower than that in normal subjects. The Bmax of BAR in all subjects was significantly correlated with FEV1/FVC ratio and percent FEV1. The percentage decrease in the FEV1/FVC ratio and FEV1 from the stable to acute state for each asthmatic subject did not correlate with corresponding percentage decrease in Bmax. These data demonstrate that BAR density of lymphocytes decreases substantially in acute asthma and, simultaneously, suggest that some factors other than the BAR mechanism contribute to the airway obstruction during acute asthma.

Acute Disease↗
PubMed1993

Effects of changes in afterload on regional wall motion in acute ischemic canine heart.

The aim of the present study was to examine effects of changes in afterload on regional myocardial motion in acute ischemia. Ischemic and non-ischemic segment lengths of the left ventricular free wall were measured by miniature ultrasonic gauges in eleven open chest dogs with the pericardium preserved. In a stable state after left anterior descending coronary artery occlusion, peak left ventricular pressure was varied by the infusion of angiotensin II (n = 8) and sodium nitroprusside (n = 8). To exclude effects of preload on the responses, end-diastolic lengths of the non-ischemic region before and during infusion of each drug were matched with vena caval occlusion. When peak left ventricular pressure elevated from 113 +/- 2 (mean +/- S.E.)mmHg to 145 +/- 6, in isovolumetric contraction phase, degree of active shortening in the non-ischemic region and that of paradoxical expansion of the ischemic region did not change. In ejection phase, active shortening of the non-ischemic region decreased from 1.38 +/- 0.11 mm to 1.06 +/- 0.10 but that of the ischemic region remained unchanged. Stroke volume decreased from 14.5 +/- 1.3 ml to 10.8 +/- 1.0. When peak left ventricular pressure decreased from 111 +/- 4 mmHg to 101 +/- 6, in isovolumetric contraction phase, active shortening of the non-ischemic region decreased from 0.90 +/- 0.13 mm to 0.76 +/- 0.15 and paradoxical expansion of the ischemic region reduced from -0.95 +/- 0.11 mm to -0.80 +/- 0.11. In ejection phase, shortening of the non-ischemic region increased from 1.05 +/- 0.13 mm to 1.31 +/- 0.15 but that of the ischemic region did not change. Stroke volume increased from 11.5 +/- 1.3 ml to 14.0 +/- 1.4. These results indicate that in acute ischemia, changes in isovolumetric shortening of the non-ischemic region and paradoxical expansion of ischemic region are related with each other in isovolumetric contraction phase when afterload is altered and suggest that stroke volume is affected by the shortening of ejection phase in the non-ischemic region.

Angiotensin II↗
PubMed1993

Small airway involvement in mixed connective tissue disease.

We studied pulmonary functions in 17 female patients with mixed connective tissue disease (MCTD) to detect early pulmonary involvement in this disease; in 8 of the 17 patients follow-up studies were also performed at 1.2- to 5.9-year intervals. In the first pulmonary function tests, decreases in vital capacity (VC) and diffusing capacity (DLCO) were observed in 6 (35%) and 8 (47%) patients, respectively. The ratio of forced expiratory volume in one second to VC was normal in all the patients, but pulmonary resistance and static compliance were abnormal in 6 (35%) and 10 (59%) patients, respectively. However, frequency dependence of dynamic compliance was found in all 16 patients tested. Moreover, 4 (24%) of the 17 patients had normal DLCO and DLCO-to-alveolar volume ratio (DLCO/VA). Reductions in DLCO and DLCO/VA were significantly correlated with the disease duration. These results suggest that small airway obstruction is an early and frequent indication of functional pulmonary impairment, and that impairment of alveolar gas exchange is progressive in patients with MCTD.

Adolescent↗
PubMed1993

[Effect of AS-35 aerosol on bronchoconstriction induced by specific antigens in macacus rhesus monkeys].

In a previous in vitro study, 9-[(4-acetyl-3-hydroxy-2-n-propylphenoxy) methyl]-3-(1H-tetrazol-5-yl)-4H- pyrido[1,2-a]pyrimidin-4-one (AS-35) was shown to have an inhibitory effect on antigen-induced mediator release and an antagonistic effect on leukotriene C4 and D4 receptors. In the present study, therefore, we investigated the effect of AS-35 aerosol on allergen-induced bronchoconstriction, using 6 female Macacus rhesus monkeys sensitized with DNP-Ascaris extracts (DNP-As). After treatment with an inactive placebo, inhalation challenge with DNP-As increased total lung resistance and decreased dynamic lung compliance dose-dependently 1 week after sensitization with DNP-As. Treatment with AS-35 aerosol, however, significantly inhibited allergen-induced bronchoconstriction dose-dependently 2 weeks after the sensitization. The inhibitory effect was about ten times more potent than that of DSCG. Because we confirmed that DNP-As evoked almost the same bronchoconstriction 1 and 2 weeks after sensitization and also that AS-35 did not inhibit histamine-induced bronchoconstriction at all, we inferred that AS-35 diminished allergen-induced bronchoconstriction by inhibiting allergen-induced mediator release from the cells in the airway.

Aerosols↗
PubMed1993

[Neurogenic inflammation].

Airway neurogenic inflammation is caused by neuropeptides released from airway sensory nerves, and may be involved in the pathogenesis of asthma. Airway sensory nerves are stimulated by chemical mediators such as bradykinin and leukotrienes, hyperventilation and cigarette smoke. Presynaptic modulation of airway sensory nerves by opioids, histamine H3-agonists, NPY, and potassium channel openers is effective in the control of neurogenic inflammation. Tachykinin receptor antagonists also inhibit airway neurogenic inflammation. Recently, we have demonstrated that pretreatment with a tachykinin receptor antagonist can protect against bradykinin-induced airway narrowing in asthmatic patients. This evidence indicates that endogenously released tachykinins have a functional role in the airways of asthmatics.

Asthma↗
PubMed1993

[Sleep-disordered breathing in Japan: an overview].

Questionnaires were answered by 3,243 presumably healthy subjects who underwent regular medical checkups in four cities. The prevalences of risk factors for sleep-disordered breathing (SDB) were as follows; habitual snoring was reported by 13-16%, excessive daytime sleepiness by 8-9%, insomnia by 7-13% and systemic hypertension by 5-13%. Polysomnographic studies performed on some possible SDB cases who were selected by the presence of risk factors estimated that the average prevalence of SDB in the present population would be in the range of 1.14-1.94%. Secondly, questionnaires were sent to the main hospitals and institutes involved in the management of patients with SDB, asking about diagnostic criteria, number of SDB patients, management, effectiveness of treatment, etc. The total number of patients registered at those hospitals was 2,751 in 1991. Of the 132 patients who were followed for more than six months, the efficacies of body weight loss, medications, nasal CPAP and UPPP were compared. Based on the analyses of the 279 patients examined some tentative vriteria for diagnosis and for treatment are proposed.

Female↗
PubMed1993

[Effects of nipradilol on the patients of angina pectoris: results from the study of the exercise electrocardiography using HR-ST loop method].

This study was performed to confirm the usefulness of 12 mg nipradilol, a beta-blocker with a vasodilator action similar to that of nitrate-type drugs, in the treatment of effort angina pectoris. It also discusses the mechanism of the action of this drug when using the exercise test heart rate-ST displacement analysis. The symptom threshold multistage graded exercise test was performed using nine patients with chronic stabilized effort angina pectoris after an observation period and an 8-week administration period and HR-ST analysis was performed simultaneously. The number of anginal attacks significantly decreased from the 2nd week, and the heart rate at rest decreased significantly in the prone position although blood pressure did not change. The maximum oxygen intake increased markedly from 13.7 +/- 1.1 ml/kg/min to 19.3 +/- 2.5 ml/kg/min, and the maximum ST decrease improved significantly from 1.72 +/- 0.45 mm to 1.17 +/- 0.19mm. In HR-ST analysis, delta ST/delta HR and delta ST/delta DP tended to improve slightly. Since monotherapy with a beta-blocker causes significant increase in delta ST/delta HR and delta ST/delta DP, it was assumed that a vasodilator action in addition to a beta-blocker action is involved in the improvement of maximum ST decrease brought about by nipradilol.

Adrenergic beta-Antagonists↗
PubMed1993

[Effect of thromboxane receptor antagonist, BAY u 3405 on the late phase pulmonary response in guinea pigs].

The effect of the specific thromboxane (Tx)A2 receptor antagonist, BAY u 3405 on the late asthmatic response (LAR) was investigated in guinea pigs which are sensitized actively with Ascaris suum antigen. Respiratory resistance (Rrs) of awake guinea pigs was measured by 30 Hz oscillation method for 6 hours after antigen challenge. %Rrs was calculated as the increase rate of Rrs to baseline Rrs (pre-challenge value). Ten mg/kg of BAY u 3405 or vehicle (0.5% methyl cellulose) was administered orally after the end of immediate asthmatic response, i.e., 2 hours after antigen challenge. %Rrs of the control group at 4 and 5 hours after antigen challenge were 101.4 +/- 27.5% and 77.5 +/- 19.9%, respectively. Those of the BAY group were 32.5 +/- 6.2% and 23.5 +/- 5.0%, respectively. %Rrs of the BAY group were significantly lower than those of the control group at both timings (p < 0.05). No significant difference was shown between the BAY group and the control group in the results of the bronchoalveolar lavage (BAL) 4 hours after challenge. Concerning the results of BAL at 6 hours after challenge, the total cell count and its segment, eosinophils count and lymphocytes count in the BAY group were 274.9 +/- 70.5, 62.5 +/- 13.1, 11.3 +/- 3.3 (x 10(5) cells), respectively, resulting in significantly smaller numbers (each p < 0.05) than those in the control group which were 491.9 +/- 55.1, 198.6 +/- 43.9, 32.1 +/- 7.3 (x 10(5) cells), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1992

Protection against bradykinin-induced bronchoconstriction in asthmatic patients by neurokinin receptor antagonist.

Axon reflex mechanisms may be involved in the pathogenesis of asthma, but there has been no direct evidence that endogenous tachykinins cause bronchoconstriction in asthmatic subjects. We have studied the effect of a tachykinin receptor antagonist (FK-224) on bronchoconstriction induced by inhalation of bradykinin in asthmatic patients. In a double-blind, placebo-controlled, crossover trial, ten subjects with stable asthma were given FK-224 (4 mg) or placebo by inhalation 20 min before challenge with bradykinin (0-1250 micrograms/ml, five breaths of each concentration) given with 5 min intervals. Bradykinin caused dose-dependent bronchoconstriction in all subjects. FK-224 significantly opposed the bronchoconstrictor effect; the geometric mean of the cumulative concentration required to elicit a 35% fall in specific airway conductance was 5.3 micrograms/ml after placebo and 40 micrograms/ml after FK-224 (p < 0.001). Inhalation of bradykinin caused coughing in three subjects, which was inhibited by FK-224 in all three. Antagonism of the tachykinin receptor by FK-224 greatly inhibited both bronchoconstriction and coughing induced by bradykinin in asthmatic patients, suggesting that tachykinin release from the airway sensory nerves is involved in responses to bradykinin. Tachykinin receptor antagonists may be useful in the treatment of asthma.

Administration, Inhalation↗
PubMed1992

Functional analysis of alternatively spliced transcripts of the human histidine decarboxylase gene and its expression in human tissues and basophilic leukemia cells.

L-Histidine decarboxylase (HisDC) is the enzyme catalyzing the formation of histamine from L-histidine. HisDC activity is expressed specifically in mast cells/basophils, endocrine cells in stomach, and histaminergic neurons in brain. As a first step in the analysis of the regulation of HisDC gene expression, we have cloned the cDNA coding for HisDC from a cDNA library of a human basophilic leukemia cell line, KU-812-F. We identified two types of HisDC cDNA, representing the 2.4-kb and 3.4-kb HisDC mRNA constitutively expressed in these cells. Sequence analysis of these cDNA revealed that the 3.4-kb mRNA contains the insert sequence of 824 bases and suggests that both 2.4-kb and 3.4-kb mRNA may represent the alternatively spliced transcripts of the HisDC gene. Using expression plasmids containing a cDNA for each HisDC mRNA, we analyzed the function of possible HisDC isoforms. We show that only the 2.4-kb mRNA encodes functional HisDC and is expressed in human brain and lung. However, we were unable to detect the 3.4-kb mRNA in these tissues. Thus, the 3.4-kb mRNA may be generated by KU-812-F cell-specific splicing of the HisDC gene transcripts. Furthermore, we demonstrated the increase in the level of 2.4-kb HisDC mRNA and HisDC activity in KU-812-F cells following treatment with phorbol 12-myristate 13-acetate.

Alternative Splicing↗