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Biomedical subjects

F Taki

Publications and source records attributed to F Taki.

At least 19 recordsLinked to original sources

Higher concentrations of matrix metalloproteinases in bronchoalveolar lavage fluid of patients with adult respiratory distress syndrome.

This study was designed to investigate possible involvement of type IV collagenolytic matrix metalloproteinases (MMPs; 72-kDa type IV collagenase [MMP-2], 92-kDa type IV collagenase [MMP-9]), and the respective specific tissue inhibitors of these MMPs (TIMP-2 and TIMP-1) in the development of adult respiratory distress syndrome (ARDS). We determined the concentrations of these enzymes in the bronchoalveolar lavage fluid (BALF) from patients with ARDS using newly developed sensitive one-step sandwich enzyme immunoassay methods. BALF obtained from the 17 patients and eight healthy volunteer control subjects were also used for the analysis of the number of the cellular component. Concentrations of the 7S portion of type IV collagen and laminin in the BALF were measured as markers of basement membrane disruption. In the BALF from the ARDS patients, the concentrations of MMP-2 (66.7 +/- 57.0 ng/ml versus < 7.0 ng/ml for controls, p < 0.01) and MMP-9 (118.0 +/- 309.3 ng/ml versus 9.0 +/- 9.5 ng/ml for controls, p < 0.05), and the specific inhibitor of MMP-9 (TIMP-1) (161.0 +/- 145.0 ng/ml versus < 50 ng/ml for controls, p < 0.01) were significantly higher compared with those for healthy control subjects. In the ARDS patients, the concentrations of MMP-2 correlated both with those of 7S collagen and laminin; MMP-9 with the concentration of 7S collagen and the number of neutrophils. These findings suggest that the increased concentration of collagenolytic MMPs in lung plays a role in the pathogenesis of ARDS.

Adult↗

[Effect of dosing schedule on efficacy of corticosteroid inhalation in chronic asthma].

A randomized study was conducted for 4 weeks to evaluate the effect of twice daily inhalation of beclomethasone dipropionate (BDP) inhalation (group A) as compared to four times a day inhalation (group B) in chronic asthma. Patients were randomly allocated to receive BDP at a dosage of eight puffs twice daily (800 micrograms/day, group A) or four puffs four times daily (800 micrograms/day, group B). Forty four patients entered the study but eleven were excluded because of their insufficient records or unfitness to eligibility criteria. There was no significant difference in patients' characteristics such as types, and severity of diseases between the two groups. Daily keeping of symptom scores, twice daily measurement of morning and night peak expiratory flow (PEF) and checking of the drug consumption were performed throughout the study. There was no significant difference in the mean %PEF either at 2 and 4 weeks at the study between the two groups. Symptom scores, asthmatic scores, bronchial hyperresponsiveness, pulmonary function tests (FVC, FEV1, FEV1%) and serum cortisol levels also showed no significant difference between the two groups. These results indicate that twice daily inhalation of BDP (800 micrograms/day) for four weeks caused the same effects on the patients with chronic bronchial asthma as 4 times daily inhalation did. Therefore, twice daily inhalation therapy with BDP is recommended for chronic bronchial asthma patients.

Administration, Inhalation↗

Serum levels of soluble IL-2R, IL-4, and soluble Fc epsilon RII in adult bronchial asthma.

Examination was made of the serum levels of interleukin 4 (IL-4), soluble Fc epsilon RII (sFc epsilon RII), and soluble interleukin 2 receptor (sIL-2R) in 77 adult patients with bronchial asthma. All the patients had mild to moderate asthma and their symptoms were well controlled. The results were compared with values for 75 control subjects to clarify the involvement of these factors in the pathogenesis of bronchial asthma. Serum sIL-2R was elevated in asthmatics compared with control subjects (459.0 +/- 30.4 U/ml vs 251.5 +/- 10.0 U/ml; p < 0.001). The IL-4 and sFc epsilon RII levels were also elevated beyond those in the controls (IL-4: 1.89 +/- 0.13 pg/ml vs 1.08 +/- 0.15 pg/ml; p < 0.001) (sFc epsilon RII: 313.2 +/- 18.8 U/ml vs 228.8 +/- 6.7 U/ml, p < 0.001). A weak but significant correlation was observed between sIL-2R and sFc epsilon RII (r = 0.46, p < 0.001). Correlation among other parameters was not found. The patients were divided into atopic and nonatopic groups, based on the presence or absence of positive reaction to skin prick tests using extracts of common aeroallergens and positive specific IgE against house dust mite (Dermatophagoides pteronyssinus [Dp]). Mean IL-4 in the atopic group, with positive skin reaction and > 0.7 kU/L specific IgE against Dp was significantly elevated compared with the nonatopic group (2.35 +/- 0.26 pg/ml vs 1.56 +/- 0.12 pg/ml; p < 0.005). Such differences could not be detected in sIL-2R, sFc epsilon RII levels among the two groups. No significant correlation could be found among IL-4, sFc epsilon RII, and total IgE level. The activation of T cells and B cells would thus appear essential to the pathogenesis of bronchial asthma and the hypothesis that atopic status is associated with the preferential activation of TH2 cells which selectively produce IL-4 could be supported. The regulatory mechanism of IgE synthesis would not appear to be the only responsible factor.

Adult↗

Reduction of the severity of bronchial hyperresponsiveness by the novel leukotriene antagonist 4-oxo-8-[4-(4-phenyl-butoxy)benzoylamino]-2- (tetrazol-5-yl)-4H-1-benzopyran hemihydrate.

There is much evidence that the cysteinyl-leukotrienes (C-LTs) are important in the pathogenesis of asthma. The clinical effect of a new leukotriene antagonist, ONO 1078 (4-oxo-8-[4-phenylbutoxy)benzoylamino]-2-(tetrazol-5-yl)-4H- 1-benzopyran hemihydrate, CAS 103177-37-3) on symptoms, pulmonary lung function and bronchial hyperresponsiveness was evaluated in patients with bronchial asthma. Eleven patients were treated for 24 weeks with 450 mg of ONO 1078 twice daily. The score of asthma symptom severity and the number of inhaled procaterol were significantly reduced after 2 weeks of ONO 1078 treatment and remained decreased for another 22 weeks. Their FEV1 and PC20 to histamine significantly improved 12 and 24 weeks after ONO 1078 treatment. The effectiveness of ONO 1078 suggests that the C-LTs play an important role in the pathogenesis of asthma. ONO 1078 might help to favorably modify the pathophysiologic condition in patients with bronchial asthma.

Adult↗

[A case of interstitial pneumonia antedating rheumatoid arthritis--differentiation from idiopathic BOOP].

A 49-year-old female presented with productive cough, fever and chest pain, and was admitted to Nagoya University Hospital. Her chest X-rays, taken previously and on admission, showed infiltrative shadows in both upper lung fields and left-sided pleural effusion. Rheumatoid factors were positive in serum and the pleural effusion. Antibiotics were ineffective. Transbronchial lung biopsy revealed intraalveolar fibrosis as well as interstitial inflammation. Idiopathic BOOP was suspected on the basis of clinical findings together with the histological features. However, open lung biopsy revealed lymphoid hyperplasia with germinal center formation. The patient was diagnosed as having lung involvement antedating rheumatoid arthritis, despite the absence of joint symptoms at present.

Arthritis, Rheumatoid↗

[Platelet activating factor and tumor necrosis factor-alpha in bronchoalveolar lavage fluid of patients with ARDS].

Platelet activating factor (PAF) and tumor necrosis factor alpha (TNF-alpha) were examined in the bronchoalveolar lavage fluid (BALF) of 21 ARDS patients to clarify the role of these factors in ARDS. Neutrophil percentages and albumin concentrations in the BALF of the ARDS group were markedly elevated compared with those in the control group (p < 0.01), showing a significant correlation (r = 0.596, p < 0.01). PAF was detected in 14 of 19 ARDS patients (237.5 +/- 86.0 pg/ml) and TNF-alpha was detected in 7 of 16 ARDS patients (24.9 +/- 13.6 pg/ml), whereas these factors were not detected in control subjects. Neither PAF nor TNF-alpha showed a significant correlation with neutrophil percentage, neutrophil number or albumin concentration. They do not seem to be contributing factors to the prognosis of ARDS patients. However the existence of PAF and TNF-alpha in the BALF of some ARDS patients suggests that they might play a role in the pathogenesis of ARDS.

Adolescent↗

[A case of drug induced pneumonitis caused by oral etoposide].

We report a case of drug induced pneumonitis caused by oral etoposide. A 63-year-old man was admitted to our hospital in August 1991 because of low grade fever and dyspnea. He underwent right upper lobectomy on Nov. 27th, 1990 for lung cancer (squamous cell carcinoma), and courses of adjuvant chemotherapy (CBDCA, IFX, etoposide) during the following admission period. He was discharged on Feb. 14th, 1991, and as an outpatient, oral etoposide (25 mg/day) was administered for about 7 months (6,125 mg in total). Chest X-ray film on admission showed reticulonodular shadows in bilateral lung fields, and computed tomography showed diffuse interstitial shadows. Blood gas analysis showed marked hypoxemia (PaO2 breathing room air was 48.4 Torr). Transbronchial lung biopsy revealed edema of the alveolar walls and marked proliferation of type II alveolar epithelial cells, suggesting cytotoxic reaction. After termination of etoposide administration and following steroid pulse therapy, both clinical symptoms and hypoxemia were ameliorated. To our knowledge, this is the first report of etoposide-induced pneumonitis.

Administration, Oral↗

[A case of bronchiolitis obliterans organizing pneumonia associated with ulcerative colitis].

A 53-year-old male was admitted to our hospital with fever and chest pain. A chest X-ray film showed infiltrative shadows in the right upper and middle lung field. In spite of administration of antibiotics, the chest X-ray film revealed gradually increasing infiltrates and a new shadow appeared in the left upper lung field. The open lung biopsy specimen showed bronchiolitis obliterans organizing pneumonia (BOOP). There was marked roentgenographic improvement in response to steroid therapy. Very few cases of BOOP associated with ulcerative colitis have been reported.

Bronchiolitis Obliterans↗

Direct activation of phospholipase A2 by GTP-binding protein in human peripheral polymorphonuclear leukocytes.

In human peripheral polymorphonuclear leukocyte (PMN), 10% of PLA2 activity was found in the particulate fraction. In the particulate fraction, the activity of phospholipase A2 was enhanced 270% by 100 microM guanosine 5'-[gamma-thio]triphosphate, a hydrolysis-resistant analog of GTP. In the soluble fraction, such enhancement was not observed. Guanosine 5'-[beta-thio]diphosphate (2 mM), which irreversibly inactivates GTP-binding protein, blocked the enhancement in the particulate fraction. Membrane-binding phospholipase A2 activity of PMN would thus appear to be regulated directly by GTP-binding protein.

Enzyme Activation↗

Platelet-activating factor in bronchoalveolar lavage fluid of patients with adult respiratory distress syndrome.

1. To clarify the role of platelet-activating factor (PAF) in the development of adult respiratory distress syndrome (ARDS), we performed bronchoalveolar lavage (BAL) in 19 patients with ARDS and examined cell populations, albumin concentrations and PAF levels. PAF levels were measured by a newly developed radioimmunoassay. 2. In the BAL fluid of ARDS patients, neutrophil percentages and albumin concentrations markedly increased compared with control subjects. 3. PAF was detected in 14 of 19 patients with ARDS, whereas it did not exist in the control subjects. 4. Furthermore, we investigated the priming effect of recombinant human tumour necrosis factor-alpha (TNF alpha), which is known to be one of the most important mediators in the development of ARDS, on PAF production induced by the calcium ionophore in neutrophils. 5. Pre-incubation with TNF alpha dose-dependently increased both extracellular and intracellular PAF production in neutrophils. 6. These results suggest that PAF might play an important role in the development of ARDS.

Adolescent↗

7S collagen in bronchoalveolar lavage fluid of patients with adult respiratory distress syndrome.

To evaluate the disruption of the basement membrane in the pathogenesis of adult respiratory distress syndrome (ARDS), we measured the level of 7S collagen in the bronchoalveolar lavage (BAL) fluid of patients with ARDS and normal control subjects by using a radioimmunoassay method. Twelve of 14 patients with ARDS had evidence of 7S collagen in the BAL fluid, but no 7S collagen was detected in the BAL fluid of the controls. The mean 7S collagen concentration of the BAL fluid in patients with ARDS was 19.6 +/- 9.4 ng/ml. In patients with ARDS, the BAL levels of 7S collagen correlated strongly with neutrophil counts (r = 0.813; p less than 0.01) and with elastase-complex (r = 0.914; p less than 0.01). We conclude that 7S collagen may be an index of leukocyte-mediated lung injury in patients with ARDS, and detection of 7S collagen in BAL fluid is useful for evaluating the disruption of basement membrane.

Adult↗

[Effects of cepharanthin on leukopenia and thrombocytopenia induced by chemotherapy in lung cancer patients].

We studied the effects of Cepharanthin (CEP) on bone marrow suppression induced by chemotherapy in 18 primary lung cancer patients (14 NSCLC, 4 SCLC). NSCLC patients received IP (IFM+CDDP) therapy and SCLC patients received ION (IFM+VCR+ACNU) therapy. For the control, we chose the first course and we administered CEP (1 mg/kg) during the second course. The rate of leukopenia and neutropenia was significantly lower during the CEP course than during the control (p less than 0.01). The recovery rate (at 3 weeks) of leukopenia and neutropenia was significantly higher during the CEP course than during the control (p less than 0.05). But, obvious effects of CEP for lymphopenia and thrombocytopenia were not obtained. Side effects by CEP were not observed in this study. These data suggest that the large dose of CEP contributes to the prevention of leukopenia, especially neutropenia, in patients who receive a sufficient amount of anticancer drugs.

Adult↗

[A clinical study of combined therapy of aspoxicillin and ceftazidime on intractable respiratory infections].

Both aspoxicillin (ASPC) and ceftazidime (CAZ) were administered together to 55 patients with intractable respiratory tract infections. ASPC and CAZ were administered at daily doses of 4 g and 2 to 4 g, respectively. Clinical effects were excellent in 11 cases, good in 33, fair in 7 and poor in 4, thus the efficacy rate was 80.0%. Bacteriologically, identified organisms were eradicated in 14 cases out of 21, decreased in 3, exchanged in 2 and unchanged in 2. The eradication rate was 76.2%. As a side effect, diarrhea was found in only one case, and abnormal laboratory test values were observed in 4 cases. However, these adverse reactions were not severe, therefore it was possible to continue the chemotherapy. These results indicate that the combination antimicrobial chemotherapy of ASPC and CAZ is effective against intractable respiratory tract infections.

Adult↗

[A case of bronchiolitis obliterans organizing pneumonia in a patient with rheumatoid arthritis who responded to corticosteroid and immunosupressant therapy].

A 56-year-old man with rheumatoid arthritis was admitted to our hospital with dyspnea on exertion, fever and right chest pain. Chest X-ray showed bilateral, predominantly lower interstitial shadows and right pleural effusion. Open lung biopsy specimen showed bronchiolitis obliterans organizing pneumonia (BOOP) with prominent alveolitis, and corticosteroid therapy was introduced. Because the patient showed little response to corticosteroids, an immunosupressant (cyclophosphamide) was added. There was marked clinical, physiological and roentgenographic improvement in response to combined therapy. The therapeutic response of some BOOP patients seems to vary according to its pathogenesis and pathological findings, and these should be taken into consideration in the selection of therapeutic strategies.

Adrenal Cortex Hormones↗

Erythromycin reduces the severity of bronchial hyperresponsiveness in asthma.

It has been demonstrated that bronchial hyperresponsiveness is a characteristic feature of bronchial asthma, and airway inflammation plays an important role in bronchial hyperresponsiveness. Erythromycin is an antibiotic extensively used worldwide which is also reported to have anti-inflammatory action. This study was designed to clarify whether erythromycin could favorably alter bronchial responsiveness in patients with bronchial asthma. To estimate bronchial responsiveness, histamine challenge was performed in 23 patients with bronchial asthma (atopic type, 11; nonatopic type, 12). All patients were treated for ten weeks with erythromycin, 200 mg three times daily, orally. After ten weeks' treatment, PC20, an index of bronchial sensitivity, was increased significantly. There was no difference between atopic and nonatopic patients in the improvement of PC20. It was concluded that erythromycin reduces the severity of bronchial responsiveness in patients with bronchial asthma.

Adult↗

Effect of erythromycin on bronchial hyperresponsiveness in patients with bronchial asthma.

The effects of erythromycin (erythromycin stearate, Erythromycin; CAS 643-22-1) on the bronchial hyperresponsiveness and the functions of lymphocytes and neutrophils were evaluated. Administration of erythromycin to asthmatic patients in a dosage of 600 mg/d for 10 weeks reduced the bronchial hyperresponsiveness measured by histamine inhalation test. Furthermore, incubation with erythromycin for 96 h inhibited the mixed lymphocyte reaction at the concentration of more than 10 mumol/l in a dose-dependent manner, and the value of IC50 was about 30 mumol/l. 2-h incubation with erythromycin showed a weak inhibition to n-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced superoxide production of polymorphonuclear neutrophils (PMNs) at the concentration of more than 30 mumol/l in a dose-dependent manner. 1-h incubation with 1 mumol/l and 100 mumol/l of erythromycin inhibited FMLP-induced chemotaxis of PMNs. The rates of inhibition at the concentration of 1 mumol/l and 100 mumol/l were 29.7% and 41.7%, respectively. Erythromycin thus showed a beneficial effect on bronchial hyperresponsiveness. This effect might be due to the regulation of the inflammatory cells.

Adult↗

[The effect of azelastine on the down-regulation of beta-adrenoceptors].

The effect of azelastine, a new on the down-regulation of beta-receptor agonist was investigated. Male Hartley guinea pigs received injections of saline or terbutaline (T.) and/or azelastine (A.) for successive 7 days. The radioligand binding assays for beta-adrenoceptors in the lung membranes of the guinea pigs were performed. The results showed the differences of numbers of maximal binding sites (Bmax) among four groups were significant. The Bmax of beta-adrenoceptor in T. group was less than that in control group (P less than 0.02). The Bmax in A. group was more than that in control group (P less than 0.05). The Bmax in T. plus A. was more than that in T. group, and there was no significant difference between Bmax in T. group and in T. plus A. group (P greater than 0.1). The differences of affinity (Kd) of beta-adrenoceptor among four groups were not significant. Azelastine increased the density of beta-adrenoceptors and partially prevented the down-regulation of beta-adrenoceptor caused by terbutaline.

Animals↗

Effect of azelastine on the down regulation of beta-adrenoceptors in guinea pig lung.

The new antiallergic drug azelastine (E-0659, Azeptin; CAS 58581-89-8) is used in the treatment of rhinitis and bronchial asthma. In the present study, the effect of azelastine on the regulation of the beta-adrenoceptors and the down regulation of beta-adrenoceptors by terbutaline, a beta-agonist, was investigated using guinea pig lungs. Guinea pigs were divided into four groups; (1) the control (saline-treated) group, (2) the terbutaline-treated group, (3) the azelastine-treated group, (4) terbutaline plus azelastine-treated group. Guinea pigs intramuscularly injected with each agent three times a day for successive 7 days. In the terbutaline-treated group, a 26% reduction in the number of beta-adrenoceptors compared with those of the control group was observed. In the azelastine-treated group, the number of beta-adrenoceptors increased by 24% compared with those of the control group. The number of the beta-adrenoceptors in the terbutaline plus azelastine-treated group was significantly increased compared with that of the terbutaline-treated group. These results suggest that azelastine may prevent the down regulation observed during beta-agonist administration by increasing the number of beta-adrenoceptors.

Animals↗