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Biomedical subjects

F Taki

Publications and source records attributed to F Taki.

At least 37 records · Page 2Linked to original sources
PubMed1991

[ARDS and leukotoxin].

It is well known that pulmonary influx of neutrophils is involved in lung injury in patients with adult respiratory distress syndrome (ARDS). Neutrophils are major contributors to the self-defence mechanism, however, adverse effects of neutrophils have also been recognized. Recently, we found that a highly toxic substance, 9, 10-epoxy-12-octadecenoate (leukotoxin) is biosynthesized by human neutrophils. This study was designed to investigate whether or not leukotoxin participates in lung injury in ARDS and coagulation abnormality which is often associated with ARDS. Intravenous injection of leukotoxin (100 mumol/kg) caused acute edematous lung injury, which was evidenced by increased lung weight, albumin concentrations, and angiotensin converting enzyme activities in lung lavages. Pulmonary capillary endothelial damage and pulmonary edema were observed by electron microscopy. Moreover, considerable amounts of leukotoxin were detected in lung lavage fluid of rats exposed to pure oxygen for 60 h and patients with ARDS. An increased number of neutrophils and albumin concentrations were also observed in these lavage fluids. Intravenous injection of leukotoxin (100 mumol/kg) induced coagulation abnormalities such as disseminated intravascular coagulation. Increased levels of plasma leukotoxin were detected in ARDS patients with coagulation abnormalities. These results suggest that leukotoxin biosynthesized by neutrophils is an important contributor to lung injury in ARDS and associated coagulation abnormalities.

Albumins↗
PubMed1991

[Tumor necrosis factor in sputa of patients with bronchial asthma on exacerbation].

TNF is a cytokine recently implicated as an important inflammatory mediator. TNF concentrations in sputa from 13 patients with bronchial asthma on exacerbation and 12 patients with chronic obstructive pulmonary disease were measured. After sonication, the sputa were centrifuged. The supernatants were assayed for the presence of TNF by use of an enzyme-linked immunosorbent assay. TNF was detected in all patients with bronchial asthma (1783 +/- 420 pg/ml), while low values of TNF were detected in only 5 of the 12 COPD patients. It is suggested that TNF is involved in airway inflammation in bronchial asthma.

Acute Disease↗
PubMed1991

Inhibitory effect of dietary administration of eicosapentaenoic acid on the contractions of guinea-pig tracheal smooth muscle induced by leukotriene C4 and D4.

The changes in fatty acid composition in phospholipids of guinea-pig lung parenchymal strips and trachea induced by dietary administration of eicosapentaenoic acid (EPA) were investigated as well as the resultant changes in leukotriene (LT) C4- and D4-induced contractions of guinea-pig tracheal smooth muscle. EPA levels in both parenchymal strips and trachea were significantly increased depending on the administered dose of EPA, but on the other hand, arachidonic acid levels in those preparations were not changed. Both the contractions of guinea-pig tracheal smooth muscle induced by LTC4 and D4 were significantly reduced in the EPA-treated group compared with the control group at all 3 concentrations, 10(-9), 3 x 10(-9) and 10(-8) mol/l, in the presence of 5 x 10(-5) mol/l indometacin, a cyclooxygenase inhibitor. But this significant reduction of the contraction was not recognized between these 2 groups in the presence of 10(-5) mol/l 2-(12-hydroxydodeca-5, 10-diynyl)-3,5,6-trimethyl-1,4-benzoquinone (AA861), a 5-lipoxygenase inhibitor, or in the combined presence of 5 x 10(-5) mol/l indometacin and 10(-5) mol/l of AA861. These results suggest that: 1. a 5-lipoxygenase pathway is partly involved in the contractions of guinea-pig tracheal smooth muscle induced by LTC4 and D4 and; 2. EPA suppresses LTC4- and D4-induced contractions of guinea-pig tracheal smooth muscle through a 5-lipoxygenase pathway.

Animals↗
PubMed1990

Emphysematous change in chronic asthma in relation to cigarette smoking. Assessment by computed tomography.

To evaluate the occurrence and the degree of emphysema in chronic asthma in relation to the effect of cigarette smoking, we examined 35 subjects with irreversible airway obstruction (17 nonsmokers and 18 smokers). We performed pulmonary function testing and CT scans on all subjects. The ES was assessed by a visual scoring system on CT scans. Between nonsmokers and smokers, there was a significant difference in the ES (p less than 0.05), but not in the FEV1, TLC, and Dsb/VA (expressed as percent predicted values). The ES was 2.3 +/- 4.7 percent (mean +/- SD) in nonsmoking subjects and 13.7 +/- 16.7 percent in smoking subjects. In all subjects the ES showed significant correlations with Dsb/VA (p less than 0.001) and pack-years of cigarette consumption (p less than 0.001) but did not show correlations with FEV1 and with TLC. We concluded that emphysema can occur in smoking asthmatic subjects because of the effect of cigarette smoking, and CT scans are useful for detecting this emphysematous change.

Asthma↗
PubMed1990

[Desquamative interstitial pneumonia-like changes in idiopathic pulmonary fibrosis].

A 61-year-old man was admitted to our hospital with fever, cough and dyspnea on exertion. The chest X-ray showed diffuse reticulo-granular infiltrates. Deterioration of clinical features and remarkable elevation of BALF lymphocytes (64.3%) suggested active interstitial pneumonia. The open lung biopsy specimen showed chronic interstitial pneumonia with DIP-like pathologic change. There was a remarkable clinical, physiological and roentgenographic improvement associated with decrease of BALF lymphocytes in response to steroid therapy. BAL is useful for monitoring disease activity and tapering steroids in patients with interstitial pneumonia who respond to steroid therapy.

Bronchoalveolar Lavage Fluid↗
PubMed1989

Effect of azelastine, an antiasthmatic drug, on bronchial responsiveness in patients with bronchial asthma.

This study was designed to clarify whether azelastine, an antiasthmatic drug, could favorably alter bronchial responsiveness in patients with bronchial asthma. To estimate bronchial responsiveness, methacholine challenge was performed in 21 patients with bronchial asthma. After the first examination, all patients were treated for eight weeks with azelastine, 2 mg twice daily. After four and eight weeks' treatment, methacholine challenge was repeated. After eight weeks' treatment, Dmin, an index of bronchial sensitivity, was increased significantly, and after four weeks an insignificant increase was observed. The RrsC, SGrs/GrsC, indices of respiratory resistance and bronchial reactivity, respectively, did not change significantly during eight weeks' treatment. Recently various chemical transmitters, especially leukotrienes, were shown to be closely related to the genesis of bronchial asthma. Accordingly, the effect of azelastine observed here might be ascribed to its antagonizing action on leukotriene. Since bronchial hyperresponsiveness is a critical etiologic factor in bronchial asthma, long-term administration of azelastine might help to modify the disease's basic pathophysiologic conditions.

Adult↗
PubMed1989

[Increased neutrophils in bronchoalveolar lavage fluid from a patient with developing adult respiratory distress syndrome].

A 16-year-old, 28-week pregnant woman was admitted to our hospital with multiple bone fractures caused by a traffic accident. She had massive blood transfusion because of anemia in her laboratory findings and ritodrine hydrochloride was administered because of the fear of threatened abortion. She developed a cough with bloody sputum on the 4th day after admission, and developed pulmonary insufficiency with PaO2 41.0 torr and presented bilateral diffuse infiltrates on chest roentgenograms on the next day. Swan-Ganz catheterization revealed normal pulmonary capillary wedge pressure and analysis of the lavage fluid from the patient showed an increase in the percentage of neutrophils (40.0%) and the existence of leukotriene B4 which is known to be the most potent chemokinetic and chemotactic agent for neutrophils. Her condition was considered to be permeability edema developing adult respiratory distress syndrome (ARDS) and 1 g/day of methylprednisolone was administered intravenously for 3 days, which brought about remarkable improvement of her respiratory failure. This report suggests that analysis of the lavage fluid may provide useful information for the early diagnosis of ARDS and the indications of corticosteroid treatment.

Adolescent↗
PubMed1988

Neutrophil microsomes biosynthesize linoleate epoxide (9,10-epoxy-12-octadecenoate), a biological active substance.

We demonstrated that linoleate epoxide (9,10-epoxy-12-octadecenoate) exists in human burned skin and in lung lavages in patients with adult respiratory distress syndrome. This epoxide shows a highly toxic effect on cellular function. Thus, it was given the name leukotoxin. In this communication, we reveal that neutrophils from various sources such as guinea-pig peritonea and canine or human blood biosynthesize linoleate epoxide from linoleate as a substrate. From the reaction mixture of neutrophils with linoleate, a leukotoxin isomer, 12,13-epoxy-9-octadecenoate, and a 'non-toxic' hydroxy derivative of linoleate, 9-hydroxy-12-octadecenoate, were detected. Biosynthesis of leukotoxin by neutrophils was substantially enhanced by osmotic activation or by a calcium-ionophore, A23187. Microsomes prepared from neutrophils could oxygenate linoleate to leukotoxin in the presence of NADPH. In liver or kidney microsomal reaction mixture, leukotoxin could be detected only in the presence of an epoxide hydrolase inhibitor, epoxytrichloropropane. As biosynthesis of leukotoxin was sensitive to carbon monooxide, it was concluded that cytochrome P-450 dependent monooxygenase is responsible for the biosynthesis. Elucidation of the biosynthesis pathway of leukotoxin might contribute to the treatment of diseases associated with neutrophil recruitment.

Animals↗
PubMed1988

Effect of the calcium antagonist, diltiazem, on beta-agonist-induced reduction of beta-adrenergic responsiveness in the guinea pig lung.

This study was designed to clarify the mechanism of tolerance that occurs during prolonged administration of a beta-agonist in relation to membrane phospholipid degradation and to elucidate the effect of diltiazem, a calcium antagonist. Guinea pigs were divided into 3 groups: (1) control--physiological saline (0.5 ml) was injected once a day for 7 successive days: (2) metaproterenol (Mp)--Mp was injected intraperitoneally (10 mg/kg/day) for 7 successive days: (3) Mp + diltiazem--diltiazem was injected intraperitoneally (20 mg/kg/day) 30 min before Mp injection for 7 successive days. The number of beta-adrenoceptors and the 10(5)M (-)-isoproterenol-stimulated adenylate cyclase activity were significantly decreased in the metaproterenol group. Diltiazem reduced these decreases. Phospholipase activity was increased and phosphatidylcholine and phosphatidylethanolamine levels were decreased in the metaproterenol group. Diltiazem also reduced these changes. These results suggest that the degradation of membrane phospholipids by phospholipase may be involved in a decrease in beta-adrenergic response caused by successive administration of metaproterenol. Diltiazem protects membrane phospholipids from phospholipase attack, which in turn maintains beta-adrenergic responsiveness.

Adenylyl Cyclases↗
PubMed1988

Neutrophil-derived epoxide, 9,10-epoxy-12-octadecenoate, induces pulmonary edema.

We have observed that neutrophils biosynthesize linoleate epoxide, 9,10-epoxy-12-octadecenoate, and have named it leukotoxin because of its cytotoxic effect. In this experiment, the effect of leukotoxin on the lung was investigated. Acute effect of leukotoxin: Using Wistar rats, leukotoxin (100 mumol/kg) was injected intravenously for the leukotoxin group, and linoleate (100 mumol/kg) for the linoleate group. Physiological saline was injected as the control. Ten min after injection, rats were divided into 3 groups: (1) lungs were isolated, and lung wet weight, and dry weight were measured; (2) lung lavages were performed, and albumin concentration and activity of angiotensin converting enzyme (ACE) were measured; (3) morphological changes were studied by light and electron microscope. After administration of leukotoxin, lung wet weight/body weight ratios and dry weight/wet weight ratios were increased. Albumin concentration and ACE activity in lung lavages were also increased. Pulmonary edema was also confirmed by light microscopic findings. Alveolar epithelial cell damage and endothelium damage were also observed. Linoleate had no significant effect on these biochemical parameters and morphological findings. Subacute effect of leukotoxin: Twelve hr after administration of leukotoxin (50 mumol/kg) or linoleate (50 mumol/kg), the same studies were performed as in the acute experiments. Immediately after administration of leukotoxin, no significant effect was observed. However, 12 hr later similar changes were observed as in the acute experiments. Linoleate did not show any significant effect 12 hr after injection. These results indicate that leukotoxin biosynthesized by neutrophils might be closely related to the genesis of inflammatory edema.

Animals↗
PubMed1988

Mechanism responsible for alterations in numbers of autonomic nerve receptors in experimental asthma.

This study was designed to elucidate the mechanism responsible for alterations in the numbers of autonomic nerve receptors in experimental asthma. In the in vivo experiment, guinea pigs sensitized by exposure to aerosol of 2% ovalbumin for 7-8 min for 10 successive days were used as the experimental asthma group. The control group was exposed to saline. Beta-, alpha-1-adrenergic and muscarinic acetylcholine receptors in lung membranes were studied by direct binding techniques using l-3H-dihydroalprenolol, 3H-bunazosin and l-3H-quinuclidinyl benzilate, respectively. The experimental asthma group showed a 33% decrease in the number of beta-adrenergic receptors, a 37% increase in the number of alpha-1-adrenergic receptors and no change in the number of muscarinic acetylcholine receptors compared with the control group. The endogenous phospholipase activity was determined by high-performance liquid chromatography using tridecanoyl phosphatidylcholine as a substrate. The phospholipase activity in lung membranes in the experimental asthma group was elevated by 50% compared with that in the control group. Lung membrane phospholipid composition was analyzed by thin-layer chromatography with a flame ionization detector. In the experimental asthma group, the amounts of phosphatidylcholine and phosphatidylethanolamine decreased significantly compared with those in the control group. In the in vitro experiment after pretreatment of lung membranes with phospholipase A2, a decreased number of beta-adrenergic receptors, an increased number of alpha-1-adrenergic receptors and no change in the number of muscarinic acetylcholine receptors were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Concerning the assays for autonomic nerve receptors. Effects of incubation temperature and time on alterations in the number of receptors.

Alterations in autonomic nerve receptors play an important role in various pathological conditions, including bronchial asthma. Nevertheless, receptor assay conditions such as incubation temperature and incubation time are not consistent among various investigators. This study was designed to clarify the effects of incubation temperature and time on alterations in the number of autonomic nerve receptors. Guinea pig lung membranes were divided into five groups which were incubated under different incubation temperatures and over different incubation times. After incubation, the following experiments were performed. Beta-, alpha-1-adrenergic, and muscarinic acetylcholine receptor assays were performed by direct binding technique using L-3H-dihydroalprenolol, 3H-bunazosin, and L-3H-quinuclidinyl benzilate, respectively. Elevation of incubation temperature and prolongation of incubation time caused a significant decrease in the number of beta-adrenergic receptors and an increase in the number of alpha-1-adrenergic receptors. The number of muscarinic acetylcholine receptors did not change significantly in spite of changes in incubation temperature and time. Adenylate cyclase activity was measured by following the synthesis of cyclic adenosine monophosphate from nonradioactive adenosine triphosphate. Isoproterenol-stimulated adenylate cyclase activity decreased significantly in correspondence with the elevation of incubation temperature and prolongation of the incubation time. Contents of free fatty acids in lung membranes were measured by high-performance liquid chromatography. Free fatty acid contents increased significantly in accordance with elevation of incubation temperature and prolongation of incubation time which reflected on the degradation of membrane phospholipids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1988

Existence of leukotoxin 9,10-epoxy-12-octadecenoate in lung lavages from rats breathing pure oxygen and from patients with the adult respiratory distress syndrome.

Pulmonary influxed neutrophils have been suggested to be involved in the development of hyperoxia-induced lung injury. We recently revealed that a highly toxic substance, 9,10-epoxy-12-octadecenoate, is biosynthesized by human neutrophils, thus it was named leukotoxin. Because hyperoxia-induced lung injury is a model of adult respiratory distress syndrome (ARDS), this study was designed to investigate whether or not leukotoxin is involved in the genesis of pulmonary oxygen toxicity and ARDS. After exposure to hyperoxia for 60 h, rats showed acute pulmonary edema, which was evidenced by increased lung weight, albumin concentrations, and angiotensin-converting enzyme (ACE) activities in lung lavages. These changes were correlated with an increased number of neutrophils. We detected leukotoxin in lung lavages of rats after exposure to hyperoxia for 60 h by high performance liquid chromatography and gas-chromatography/mass spectrometry. After intravenous injection of leukotoxin (100 mumol/kg) to rats, acute edematous lung injury occurred showing increases in lung weight, lung lavage albumin concentrations, and lung lavage ACE activities. In the lung lavages obtained from 5 patients with ARDS, significant increases in albumin concentrations and ACE activities were observed compared with those from subjects without pulmonary disease. Moreover, considerable amounts of leukotoxin, 38.5 +/- 21.9 nmol/lung lavage, were observed in the lavages from patients with ARDS. These findings suggest that leukotoxin plays an important role in the genesis of acute edematous lung damage in pulmonary oxygen toxicity, and that leukotoxin also links with the development of lung injury observed in patients with ARDS.

Animals↗
PubMed1988

Effect of nipradilol, a new beta-blocker, on leukotriene D4-induced contraction in guinea pig tracheal smooth muscle.

The relaxant effect on smooth muscle of nitro compounds is suggested to be linked with the increase in the tissue level of cyclic GMP by activating guanylate cyclase. In this study, we investigated the effects of nipradilol, a new beta-blocker, which has NO2 residue in the molecular structure, and isosorbide dinitrate (ISDN) on guinea pig tracheal smooth muscle in comparison with the effect of propranolol. Nipradilol and ISDN showed dose-dependent relaxant effects on leukotriene (LT) D4-induced contraction of tracheal smooth muscle, though propranolol had no effect. 8-Bromo-cyclic GMP also showed a relaxant effect dose dependently. Nipradilol and ISDN elevated cyclic GMP levels in tracheal tissue dose dependently; however, propranolol caused no change in cyclic GMP levels. From these results, it is suggested that nipradilol relaxes LTD4-induced contraction of tracheal smooth muscle by increasing the tissue level of cyclic GMP.

Adrenergic beta-Antagonists↗
PubMed1988

Migration of neutrophils in experimental asthma.

Ovalbumin (OA) aerosol exposure caused an increase in phospholipase (PLase) activity in guinea pig lung membranes and in leukotriene B4 (LTB4) in lung lavages with subsequent neutrophil influx into lung lavages. These results suggest that activation of PLase after exposure to OA aerosol triggers an increase in LTB4 synthesis resulting in neutrophil influx into the airways.

Animals↗
PubMed1988

Cytotoxic activity of leukotoxin, a neutrophil-derived fatty acid epoxide, on cultured human cells.

Leukotoxin (LX: 9,10-epoxy-12-octadecenoate) which was previously found to be biosynthesized by neutrophils, exhibited a dominant cytotoxic activity toward human tumor cells as well as toward normal cells. At the concentration of 50-100 micrograms LX/ml cell culture medium, LX completely blocked the growth of the cells of several transformed cell lines (HeLa, Hep-2, MG-63, Chang liver, Wish, FL-Amnion) as well as the normal (Flow 2000 and Flow 13000). From the results, a part of inhibition of tumor growth by neutrophils can be attributed to LX.

Cytotoxicity, Immunologic↗