Search PubMed⌕ Search

Biomedical subjects

A Tsuji

Publications and source records attributed to A Tsuji.

At least 325 records · Page 18Linked to original sources

Characterization of hepsin, a membrane bound protease.

Hepsin is a membrane bound protease of 51 kDa present in mammalian cells. It contains a stretch of hydrophobic sequence of 27 amino acid residues in its N-terminal region. By employing fluorescent immunostaining of cells and western blot analysis of the various cell subfractions, the catalytic subunit (carboxyl terminal half) of hepsin is found at the cell surface. The hepsin gene is expressed in most tissues of a young adult baboon, particularly in the liver at high levels.

Animals↗

[The effect of a specific thromboxane A2 antagonist, AA-2414 on airway hyperresponsiveness induced by ozone exposure in dogs].

To determine whether thromboxane A2 (TxA2) is involved in airway hyperresponsiveness induced by ozone exposure, we studied the effect of a specific TxA2 antagonist, AA-2414 on ozone-induced airway hyperresponsiveness in seven dogs. Airway responsiveness to inhaled methacholine was determined by modified Astograph (7 Hz oscillation method), and numbers of neutrophils in the peripheral blood, neutrophil counts in bronchoalveolar lavage fluid (BALF), the levels of TxB2 and 6-keto-Prostaglandin F1 alpha (6-keto-PGF1 alpha) in BALF were measured before and after ozone exposure, and after ozone exposure with pretreated AA-2414. Ozone exposure was carried out for 2 hr at an ozone level of 3.06 +/- 0.06 ppm (mean +/- SE). Airway responsiveness to inhaled methacholine increased significantly after ozone exposure (p less than 0.01), and the hyperresponsiveness induced by ozone exposure was inhibited significantly by pretreated AA-2414 (p less than 0.01). Numbers of neutrophils in the peripheral blood and neutrophil counts in BALF increased after ozone exposure, and these increase were not inhibited by pretreated AA-2414. There was no apparent change in the levels of TxB2 in BALF after ozone exposure and after ozone exposure with pretreated AA-2414, however the levels of 6-keto-PGF1 alpha in BALF decreased after ozone exposure and after ozone exposure with pretreated AA-2414 (p less than 0.1). These results suggest that TxA2 plays an important role in the development of airway responsiveness after ozone exposure in dogs, and ozone-induced airway hyperresponsiveness may not be associated with the hyperproduction of TxA2 but with the relative increase of TxA2 due to the decrease of PGI2.

Animals↗

[The role of 5-lipoxygenase products in the development of airway responsiveness induced by platelet activating factor inhalation in dogs].

To determine whether 5-lipoxygenase products are involved in the development of airway responsiveness and in the infiltration of inflammatory cells into the airway after platelet activating factor (PAF) inhalation, we studied the effect of a selective 5-lipoxygenase inhibitor, AA-861 on PAF-induced airway hyperresponsiveness and on the increase of neutrophil and eosinophil counts in bronchoalveolar lavage fluid (BALF) after PAF inhalation in seven dogs. Airway responsiveness to inhaled methacholine was determined by modified Astograph (7Hz oscillation method). PAF (1000 mu/ml) was delivered as an aerosol, generated from a Devilbiss 646 nebulizer for ten minutes. Airway responsiveness to inhaled methacholine increased significantly 3 hr after PAF inhalation (p less than 0.01). After PAF inhalation, neutrophil and eosinophil counts in BALF increased significantly (p less than 0.01), and the levels of thromboxane (Tx)B2 in BALF also increased (p less than 0.05). Pretreated AA-861 significantly inhibited the increase of airway responsiveness after PAF inhalation (p less than 0.01). The increase of neutrophil and eosinophil counts in BALF after PAF inhalation was also inhibited significantly by pretreated AA-861 (p less than 0.01). The levels of TxB2 in BALF did not change after PAF inhalation following pretreatment with AA-861. These results suggest that 5-lipoxygenase products play important roles in the increase of airway responsiveness and in the infiltration of inflammatory cells into the airway after PAF inhalation in dogs. TxA2 released from inflammatory cells may be involved in the increase of airway responsiveness induced by PAF inhalation.

Animals↗

[In vivo and in vitro antifungal activity of fluconazole].

We examined in vivo efficacy and in vitro activity of fluconazole, a novel triazole antifungal agent, and obtained results which are summarized as follows: 1. Fluconazole showed a higher serum concentration than ketoconazole after oral administration to mice. The 50% effective dose of fluconazole administered orally to mice was similar to that of fluconazole injected to mice intraperitoneally in a systemic candidiasis model. 2. Prophylactic effects of fluconazole were excellent against systemic candidiasis, cryptococcosis and aspergillosis in mice in comparison with those of ketoconazole and miconazole. 3. The multiple administration of fluconazole effectively decreased the number of viable cells of Candida albicans colonized in kidneys of mice when the serum level of fluconazole was kept to exceed its IC99 values against the inoculated pathogen. Thus, a good correlation between the in vitro activity of fluconazole and its in vivo efficacy was confirmed. In vivo efficacies of ketoconazole and miconazole, however, failed to reflect their marked in vitro activities. 4. C. albicans No. 32 developed no drug-resistance to fluconazole during transfers in medium containing fluonazole at a concentration of 1 micrograms/ml.

Animals↗

[The effect of AH 21-132 on airway hyperresponsiveness induced by ozone exposure].

We examined the effect of AH 21-132, which has been reported to relax airway smooth muscle and inhibit platelet activating factor (PAF)-induced airway hyperreactivity, on ozone-induced airway hyperresponsiveness (AHR) with airway inflammation in dogs. Airway responsiveness (AR) to methacholine was measured by modified Astograph (7 Hz oscillation method) before and after ozone exposure, and the numbers of neutrophils in the peripheral blood and total cell counts, differential cell counts and TXB2 in BALF were measured before and after ozone exposure. Ozone exposure was carried out for 2 hr at an ozone level of 3.46 +/- 0.10 ppm (mean +/- SE). There was a significant increase in AR to methacholine after ozone exposure (p less than 0.01), and the numbers of neutrophils in the peripheral blood and the total cell and neutrophil counts in BALF increased significantly (p less than 0.05). Pretreatment with AH 21-132 at an oral dose of 20 mg/kg significantly prevented the ozone-induced AHR to methacholine (p less than 0.01), and also inhibited the increase of neutrophil counts in the peripheral blood, and the total cell counts and the neutrophil counts in BALF after ozone exposure. There was no significant change in the levels of TXB2 in BALF before and after ozone exposure. In dogs not exposed to ozone, AR to methacholine and respiratory resistance to methacholine significantly decreased after administration of AH 21-132 at an oral dose of 20 mg/kg (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗

Transport of monocarboxylic acids at the blood-brain barrier: studies with monolayers of primary cultured bovine brain capillary endothelial cells.

The kinetics and mechanism of the transport of monocarboxylic acids (MCAs) were studied by using primary cultured bovine brain capillary endothelial cells. Concentration-dependent uptake of acetic acid was observed, and the kinetic parameters were estimated as follows: the Michaelis constant, Kt, was 3.41 +/- 1.87 mM, the maximum uptake rate, Jmax, was 144.7 +/- 55.7 nmol/mg of protein/min and the nonsaturable first-order rate constant, Kd, was 6.66 +/- 1.98 microliters/mg of protein/min. At medium pH below 7.0, the uptake rate of [3H]acetic acid increased markedly with decreasing medium pH, whereas pH-independent uptake was observed in the presence of 10 mM acetic acid. An energy requirement for [3H]acetic acid uptake was also demonstrated, because metabolic inhibitors (2,4-dinitrophenol and rotenone) reduced significantly the uptake rate (P less than .05). Carbonylcyanide-p-trifluoro-methoxyphenylhydrazone, a protonophore, inhibited significantly the uptake of [3H]acetic acid at medium pH of 5.0 and 6.0, whereas 4,4'-diisothiocyanostilben-2,2'-disulfonic acid did not. Several MCAs inhibited significantly the uptake rate of [3H]acetic acid, whereas di- and tricarboxylic acids did not. The uptake of [3H]acetic acid was competitively inhibited by salicylic acid, with an inhibition constant, Ki, of 3.60 mM, suggesting a common transport system between acetic acid and salicylic acid. Moreover, at the medium pH of 7.4, salicylic acid and valproic acid inhibited significantly the uptake of [3H]acetic acid, demonstrating that the transport of MCA drugs could also be ascribed to the MCA transport system at the physiologic pH.(ABSTRACT TRUNCATED AT 250 WORDS)

3-O-Methylglucose↗

[The role of thromboxane A2 in the development of airway responsiveness after platelet activating factor inhalation in dogs].

To determine whether thromboxane A2 (TxA2) is involved in airway hyperresponsiveness after platelet activating factor (PAF) inhalation, we studied the effect of a specific TxA2 receptor antagonist, AA-2414 on the development of airway responsiveness induced by PAF inhalation in six dogs. Airway resistance and airway responsiveness to inhaled methacholine were determined by modified Astograph (7 Hz oscillation method). PAF inhalation (1000 micrograms/ml, ten minutes) caused a significant increase of airway resistance (p less than 0.01), and the increase of airway resistance was not inhibited by pretreated AA-2414. Airway responsiveness to inhaled methacholine increased significantly 3 hr after PAF inhalation (p less than 0.01). Pretreated AA-2414 inhibited the increase of airway responsiveness significantly (p less than 0.01), but the inhibition was partial. After PAF inhalation, total cell counts, neutrophil counts, eosinophil counts and the levels of TxB2 in bronchoalveolar lavage fluid increased significantly (p less than 0.05), and these increase were not affected by pretreated AA-2414. These results suggest that TxA2 is not involved in the bronchoconstriction induced by PAF inhalation, but TxA2 plays a partial role in the development of airway responsiveness after PAF inhalation in dogs.

Administration, Inhalation↗

Effect of low-frequency electric stimulation on in vivo release of cholecystokinin-like immunoreactivity in medial thalamus of conscious rat.

Release of cholecystokinin-like immunoreactivity (CCK-LI) in the medial thalamus of conscious rats was measured by brain dialysis and enzyme immunoassay. Analgesia caused by low-frequency electric stimulation of the tibial muscle, the tsusanli acupuncture point, was judged by change of pain threshold due to the stimulation. Medical thalamic CCK-LI released was increased by peripheral electric stimulations of both the acupuncture point and the non-acupuncture point. Results suggest that CCK acts as a neurotransmitter in the medial thalamus, a part of the analgesia inhibitory system.

Acupuncture Analgesia↗

Chemiluminescence high performance liquid chromatography of corticosteroids using lucigenin as post-column reagent.

A chemiluminescence high performance liquid chromatographic method for the determination of corticosteroids and tetrahydrocorticosteroids has been developed. Corticosteroids and their metabolites extracted from urine samples were separated using an ODS column and a mixture of methanol + water + 0.01 M sodium acetate solution (70:30:5) as eluent. The eluent from the column was mixed with the chemiluminescent solution containing lucigenin and Triton X-100 and a 0.28 M KOH solution by pumps and monitored by a chemiluminescence detector. No interference was encountered and the method is both precise and reproducible.

Acridines↗

Clinical assessment of specific enzyme immunoassay for the human cardiac myosin light chain II (MLC II) with use of monoclonal antibodies.

A highly specific enzyme-linked "sandwich" immunoassay was developed for determining cardiac myosin light chain II (MLC II) in serum by using an anticardiac MLC II monoclonal antibody and a solid phase consisting of glass rods coated with another monoclonal antibody. We can detect as little as 0.2 ng of cardiac MLC II per assay. The measurable range of cardiac MLC II concentration in serum is 1 to 30 micrograms/L. The assay demonstrated no cross-reactivity with a skeletal muscle MLC within the measurable range. The mean coefficients of variation were 6.1% within assay and 5.1% between assay. The concentration of cardiac MLC II in sera from healthy subjects ranged from 0 to 4.0 micrograms/L (mean 0.75 micrograms/L and median 0 micrograms/L). The concentrations of cardiac MLC II in serum of patients with skeletal muscle disease due to various causes (n = 15) and patients with effort angina (n = 25), in general, were not significantly elevated above normal. In all patients with myocardial infarction, the concentrations of cardiac MLC II were over 4.0 micrograms/L at 12 h after onset. The mean (+/- 1 SD) peak concentration of cardiac MLC II was 16.2 (+/- 4.4) micrograms/L at 90 h (mean) after onset. On the 5th day, the cardiac MLC II concentrations in all patients with myocardial infarction were significantly elevated above normal; none showed abnormal MB-creatine kinase (CK-MB) activity at this time. Thus, the measurement of cardiac MLC II concentration in serum may be useful to provide a specific and sensitive diagnosis of myocardial necrosis at any time period following myocardial infarction.

Adult↗

Vascular abnormalities in congenital cutis laxa--report of two cases.

Two cases of Japanese girls with congenital cutis laxa associated with cardiovascular abnormalities are described. Case 1: A 12-year-old girl has been under our observation from the age of 6 months. Cardioangiogram revealed dilatation of the ascending aorta, meandering of the descending aorta and the coronary arteries, coiling of the carotid and innominate (brachiocephalic) arteries, and hypoplasia of the pulmonary arteries. Case 2: A 2.8/12-year-old girl died after our follow-up from the age of 3 months. The cause of death was congestive heart failure secondary to peripheral stenosis of the pulmonary arteries. In both cases, skin biopsy revealed a decreased number of elastic fibers and an increased amount of acidic mucopolysaccharides. The same histological features were observed in the pulmonary arteries and other arteries as well. Electron microscopic findings were diffuse thinning of elastic fibers and reduced elastic content. The high blood level of elastase (167.8 micrograms/l) in case 1 may cast a light on the unknown etiology of the disease.

Abnormalities, Multiple↗