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Biomedical subjects

M Kurosawa

Publications and source records attributed to M Kurosawa.

At least 127 records · Page 7Linked to original sources
PubMed1993

Extracellular release of acetylcholine, noradrenaline and serotonin increases in the cerebral cortex during walking in conscious rats.

The effect of walking on the extracellular release of acetylcholine (ACh), noradrenaline (NA) and serotonin (5-HT) in the parietal lobe of the cerebral cortex was examined in conscious rats using the microdialysis technique. Walking at the speed of 2.3 m/min for 5 min produced significant increases in ACh, NA and 5-HT release in the cerebral cortical extracellular space. The increase in ACh release was the most prominent among the transmitters examined. It is suggested that the increased release of ACh in the cerebral cortex may contribute at least partly to the increases in the cerebral cortical blood flow during walking.

Acetylcholine↗
PubMed1993

Determination of a functional lysine residue of a plant cysteine synthase by site-directed mutagenesis, and the molecular evolutionary implications.

Comparison of seven deduced amino acid sequences of cysteine synthase (O-acetyl-L-serine (thiol)-lyase, EC 4.2.99.8) from plants and bacteria disclosed the presence of 12 conserved Lys residues, which can be candidates for a functional binding site for pyridoxal phosphate cofactor. These 12 conserved Lys residues in a cDNA clone encoding spinach cysteine synthase A were replaced with Gly by oligonucleotide-directed in vitro mutagenesis. These Lys-->Gly mutated cDNAs were transferred into Escherichia coli NK3, a cysteine auxotroph lacking both cysteine synthase loci, cysK and cysM. One mutant replaced at Lys-49 could not complement the cysteine requirement of NK3, whereas other mutants and wild-type clone could. No enzymatic activity of cysteine synthase A was detected either in the cell-free extracts of E. coli NK3 transformed with the Lys-49 mutant. These results indicated that Lys-49 is a functional residue for the catalytic activity of cysteine synthase. This Lys residue is conserved in other evolutionarily related amino acid-metabolizing enzymes catalyzing reactions involving the beta-carbon of amino acids.

Amino Acid Sequence↗
PubMed1993

Inhibition of 9 alpha,11 beta-prostaglandin F2-induced bronchial hyperresponsiveness by thromboxane A2 receptor antagonists in guinea pigs.

We studied the effect of intravenous administration of 9 alpha,11 beta-prostaglandin F2 on bronchial responsiveness to histamine and airway wall thickening in guinea pigs. The infusion of 9 alpha,11 beta-prostaglandin F2 induced an increase of the relative thickness of the airway wall in peripheral bronchi demonstrable by histological examination. Analysis of airway function showed that the infusion of 9 alpha,11 beta-prostaglandin F2 induced airway hyperresponsiveness to histamine with airway wall thickening. The thromboxane A2 receptor antagonists, ONO-NT-126 (5(Z)-6-[(1R,2R,3R,4S)-3-(n-4-bromobenzenesulfonyl-aminomethyl) bicyclo[2.2.1]heptane-2-yl]hex-5-enoic acid) and ONO-8809 (n-decyl(Z)-6-[(1S,2S,3R,4R)-3-(4-bromobenzenesulfonylaminomethyl) bicyclo[2.2.1]hept-2-yl]-5-hexenoate), inhibited these effects of 9 alpha,11 beta-prostaglandin F2 in a dose-dependent manner.

Airway Resistance↗
PubMed1993

Inhibitory effect of a thromboxane A2 synthetase inhibitor OKY-046 on bronchial hyperresponsiveness to histamine, but not on airway wall thickening, induced by intravenous administration of leukotriene C4 in guinea-pigs.

We studied the effect of i.v.administration of leukotriene (LT) C4 on bronchial responsiveness to histamine and airway wall thickening in guinea-pigs. The infusion of 3 micrograms/kg LTC4 for 1 h induced an increase of the relative thickness of the airway wall in peripheral bronchi, found by histological examination. In analysis of airway function, the infusion of 3 micrograms/kg LTC4 for 1 h induced airway wall thickening and airway hyperresponsiveness to histamine administered i.v.at doses of 1.8 and 3.6 micrograms/kg. Thromboxane A2 synthetase inhibitor OKY-046, which was administered perorally, inhibited the LTC4-induced airway hyperresponsiveness to histamine in a dose-dependent manner at doses from 30-100 mg/kg, but not the airway wall thickening induced by LTC4.

Airway Resistance↗
PubMed1993

Evidence that cyclosporine causes both intracellular migration and inappropriate urinary excretion of magnesium in rats.

We determined the effects of cyclosporine on calcium, magnesium, and potassium metabolism in rats. Thirty Sprague-Dawley rats were randomized into three groups of ten animals each--control rats given olive oil, rats given cyclosporine at a dosage of 5 mg/kg daily, and rats given 15 mg/kg daily for four weeks. Urinary excretion of calcium, magnesium, and potassium was determined before and after 2 and 4 weeks of cyclosporine therapy. All rats were sacrificed after 4 weeks of therapy, and calcium, magnesium, and potassium concentrations in serum and tissues were determined. Serum magnesium levels were significantly lower in the cyclosporine-treated groups than in the control group, but there was no significant difference between the control and either of the cyclosporine-treated groups with regard to total urinary excretion of magnesium after four weeks of treatment. Magnesium content in the kidney, muscle, and liver was significantly higher in the 15 mg/kg group than in the control group. Calcium content in the kidney and liver was significantly higher as well. Potassium content in any type of tissue was similar in the three groups. We conclude that the intracellular migration of magnesium plays an important role--as does impaired renal conservation of magnesium--in the pathogenesis of cyclosporine-induced hypomagnesemia and that there is a discrepancy between magnesium and potassium metabolism in cyclosporine-treated rats.

Animals↗
PubMed1993

Inhibition of bronchial hyperresponsiveness to histamine induced by intravenous administration of leukotriene C4 by novel thromboxane A2 receptor antagonists ONO-NT-126 and ONO-8809 in guinea-pigs.

We studied the effect of intravenous administration of leukotriene (LT) C4 on bronchial responsiveness to histamine and airway wall thickening in guinea-pigs. Guinea-pigs were killed and the lungs were fixed in formalin. Slides from paraffin-embedded sections of the lungs were stained and the airways that were cut in transverse sections were measured by tracing enlarged images using a digitizer. Moreover, airway resistance (Raw) was determined by a pulmonary mechanics analyser and we calculated two indices, an index of airway wall thickening and the one of airway hyperresponsiveness to histamine, from changes of baseline-Raw and peak-Raw following intravenous administration of histamine before and after the intravenous administration of LTC4. Intravenous administration of 3 microg/kg LTC4 for 1 hr induced an increase of the relative thickness of the airway wall in peripheral bronchi by the histological examination. In analysis of airway function, intravenous administration of 3 microg/kg LTC4 for 1 hr induced airway hyperresponsiveness to histamine with airway wall thickening. Thromboxane A2 receptor antagonists ONO-NT-126 and ONO-8809 inhibited the LTC4-induced airway hyperresponsiveness to histamine in a dose-dependent manner, but not the airway wall thickening induced by LTC4, suggesting that the effect of LTC4 on bronchial hyperresponsiveness is likely to be mediated through TXA2.

Airway Resistance↗
PubMed1993

Formation of phosphatidylinositol-4-phosphate in human peripheral blood eosinophils.

To evaluate the presence of phosphatidylinositol-4-phosphate in peripheral blood eosinophils, venous blood was drawn from normal healthy volunteers. The eosinophils were isolated on a Percoll gradient and were incubated with [gamma32P]ATP in the presence of Mg2+. After stopping the reaction, lipid extraction was performed with acidic medium and phospholipids were separated by thin-layer chromatography on 1% (w/v) oxalic acid- and potassium oxalate-impregnated silica gel plates. Considerable amounts of radioactivity were found to be incorporated into phosphatidylinositol-4-phosphate on both plates. This reaction requires ATP and Mg2+, and maximal response is seen at 10 microM ATP and 20 mM Mg2+. The reaction is dependent upon the time and temperature of the assay system. No significant superoxide anion generation from the eosinophils incubated with ATP at the concentrations used in the study was observed. These results suggest the possible presence of phosphatidylinositol kinase which catalyses the formation of phosphatidylinositol-4-phosphate from endogenous phosphatidylinositol in human peripheral blood eosinophils.

Adenosine Triphosphate↗
PubMed1993

Cu-Zn superoxide dismutase activities in platelets from stable bronchial asthmatic patients.

Cu-Zn superoxide dismutase (SOD) activities in platelets from stable bronchial asthmatic patients were measured using 2-methyl-6-[p-methoxyphenyl]-3,7- dihydroimidazo[1,2-a]pyrazin-3-one as a chemiluminescence probe. Cu-Zn SOD activities in platelets from the asthmatics were significantly higher than those from normal healthy subjects. Platelet Cu-Zn SOD activities were significantly higher in atopic than in non-atopic asthmatics. There were no significant differences in platelet Cu-Zn SOD activities between aspirin-sensitive and aspirin-tolerant patients. These results suggest that an oxidant-to-antioxidant imbalance may play a role in the inflammatory situations in the airways of asthmatics.

Adult↗
PubMed1993

BCR/ABL oncoprotein-targeted antitumor activity of antisense oligodeoxynucleotides complementary to bcr/abl mRNA and herbimycin A, an antagonist of protein tyrosine kinase: inhibitory effects on in vitro growth of Ph1-positive leukemia cells and BCR/ABL oncoprotein-associated transformed cells.

We investigated whether antisense oligodeoxynucleotides complementary to bcr/abl mRNA or protein kinase antagonists display antitumor activity on Ph1-positive leukemia cell lines. bcr/abl antisense oligomers showed inhibitory effects on the in vitro growth of Ph1-positive leukemia cell lines in liquid culture, and further displayed an inhibitory effect on transformed murine hematopoietic cells using transfection with a retroviral vector expressing P210bcr/abl oncoprotein. However, in vitro treatment with a bcr/abl antisense oligomer did not completely abolish the expression of bcr/abl mRNA and did not display the desired "killing effect" on Ph1-positive leukemia cells. On the other hand, investigation of the effect on Ph1-positive leukemia cells by various types of protein kinase antagonists revealed that herbimycin A, a protein tyrosine kinase antagonist, displays preferential and remarkable suppression of the growth of Ph1-positive leukemia cells and P210bcr/abl associated transformed cells by virtue of suppressing bcr/abl protein tyrosine kinase activity. These results may provide important future insights in developing a new category of antitumor therapy by targeting oncogene products.

Antibiotics, Antineoplastic↗
PubMed1993

[Protein phosphorylation in interleukin-5 (IL-5)-stimulated human peripheral blood eosinophils].

Peripheral blood eosinophils from normal healthy subjects were purified on a Percoll gradient and were incubated with H3(32)PO4. 32P-labeled eosinophils were stimulated by IL-5 under various conditions. After the reaction was stopped. SDS/PAGE and autoradiography were performed to determine the incorporation of 32P into proteins. 32P incorporation into the bands with molecular weights of 52 kDa and 65 kDa was obtained. 32P incorporation into the band of 52 kDa was presumed to be non-specific. 32P incorporation into the band of 65 kDa increased when it was incubated with 1-3 U/ml IL-5. IL-5-induced 32P incorporation into the band of 65 kDa was dependent on the temperature of the reaction system and the incubation time with IL-5. However, IL-5-stimulated eosinophils generated no significant superoxide anion as measured by MCLA-dependent chemiluminescence method.

Autoradiography↗
PubMed1993

[Possible presence of protein kinase in human peripheral blood eosinophils].

Peripheral blood eosinophils from normal subjects and patients with atopic dermatitis were isolated on a Percoll gradient and incubated with [gamma 32P] ATP in the presence of Mg2+. After the reaction was stopped, SDS/PAGE was performed and autoradiography was used to determine the incorporation of 32P into the proteins in the eosinophils. Both normodense and hypodense eosinophils showed 32P incorporation into the proteins at the molecular weights of 65 kDa & 66.2 kDa. These reactions were dependent upon Mg2+ concentration, and maximal response was observed at concentrations of 2-6 mM MgCl2. 32P incorporation into the bands was dependent upon the reaction time and temperature, and maximal response was observed at 20 degrees C. 32P incorporation into the proteins was inhibited by Ca2+ in a dose-dependent manner. Cyclic GMP at concentrations of 5 x 10(-8) to 5 x 10(-6) M enhanced the 32P incorporation. These data suggest the possible presence of protein kinase in human peripheral blood eosinophils.

Adenosine Triphosphate↗
PubMed1993

[Effects of different concentrations of an inhaled anesthetic agent, sevoflurane on sympatho-adrenal medullary functions in rats].

Effects of different inspiratory concentrations of an inhaled anesthetic agent, sevoflurane on efferent activities of the adrenal sympathetic nerve and adrenal catecholamine secretion were examined using rats either under the resting condition or during noxious mechanical stimulation of a hindpaw. Under the resting condition, an increase in the inspiratory concentration of sevoflurane from 2.1% to 4.2% caused a gradual decrease in the adrenal nerve activity and the catecholamine secretion. When noxious mechanical stimulation was applied to a hindpaw by pinching, both the adrenal nerve activity and adrenaline secretion increased, and the responses were attenuated dose-dependently by sevoflurane concentration of between 2.1% and 4.2%. Noradrenaline secretion was unchanged during the pinching stimulation throughout the administration of sevoflurane 2.1-4. 2%.

Adrenal Medulla↗
PubMed1993

[Effect of thromboxane A2 synthetase inhibitor (OKY-046) on leukotriene C4-induced airway hyperresponsiveness in guinea pigs].

In this study, we investigated the effects of peroral (p.o.) administration of a thromboxane A2 (TXA2) synthetase inhibitor, OKY-046, on the airway hyperresponsiveness (AHR) in guinea pigs induced by intravenous administration of leukotriene C4 (LTC4). A 3 micrograms/kg/hr LTC4 infusion induced airway wall thickening (AWT) and AHR to 1.8 and 3.6 micrograms/kg histamine bolus shot. OKY-046 100 mg/kg p.o. partially inhibited the AHR induced by LTC4 without inhibition of AWT. Previously, we have reported that LTC4-induced AHR was partially inhibited, to the same exert as by OKY-046, by TXA2 receptor antagonists, ONO-NT-126 and ONO-8809. These data suggest that intravenous administration of LTC4 generates TXA2, and TXA2 augments LTC4-induced AHR partially in guinea pigs.

Administration, Oral↗
PubMed1993

[Effect of Asthremedin on bronchial hyperresponsiveness (BHR) to histamine induced by intravenous administration of platelet activating factor (PAF) in guinea pigs].

Platelet activating factor (PAF) has been suggested to play an important role in the pathogenesis of bronchial asthma. In the present study, the effect of i.c. administration of asthremedin on bronchial hyperresponsiveness (BHR) induced by i.v. administration of PAF was investigated in guinea pigs. Changes of airway wall thickness and ratio of bronchial smooth muscle constriction by histamine were calculated from dynamic respiratory resistance. Administration of PAF induced airway wall thickening. The ratio of bronchial smooth muscle constriction by histamine was enhanced by administration of PAF. Asthremedin did not inhibit airway wall thickening by PAF, but inhibited BHR to histamine induced by PAF.

Adrenocorticotropic Hormone↗
PubMed1993

[Bronchial hyperresponsiveness to histamine induced by intravenous administration of 9 alpha,11 beta-prostaglandin F2 (9 alpha,11 beta-PGF2) in guinea pigs].

The effects of intravenous administration of 9 alpha,11 beta-PGF2, a stable metabolite of prostaglandin D2 (PGD2), on bronchial smooth muscle in guinea pigs were investigated by measurement of dynamic compliance and dynamic respiratory resistance using a formula to exclude the effects of differences in airway wall thickness. With this formula, the ratio of bronchial smooth muscle constriction by histamine can be estimated as an index of bronchial hyperresponsiveness to histamine. Administration of 9 alpha,11 beta-PGF2 induced airway wall edema. The ratio of bronchial smooth muscle constriction by histamine was significantly enhanced by the administration of 9 alpha,11 beta-PGF2a. TXA2 antagonists, ONO-NT-128 and ONO-8809, inhibited the effect of 9 alpha,11 beta-PGF2 administration. These results suggest that 9 alpha,11 beta-PGF2 act as important mediators affecting bronchial hyperresponsiveness, and TXA2 may play a role in 9 alpha,11 beta-PGF2-induced airway wall edema and bronchial hyperresponsiveness to histamine.

Animals↗
PubMed1993

[Effect of thromboxane A2 (TXA2) antagonists on bronchial hyperresponsiveness induced by intravenous administration of leukotriene C4 (LTC4) in guinea pigs].

Effects of TXA2 antagonists on bronchial hyperresponsiveness induced by intravenous administration of LTC4 in guinea pigs were investigated by measurement of dynamic compliance and dynamic respiratory resistance, using a formula to exclude the effects of changes in airway wall thickness. With the formula, the ratio of bronchial smooth muscle constriction by histamine can be estimated as an index of bronchial hyperresponsiveness to histamine. Administration of LTC4 induced airway wall edema. The ratio of bronchial smooth muscle constriction by histamine was enhanced by the administration of LTC4. TXA2 antagonists, ONO-NT-126 and ONO-8809, inhibited the increased ratio of bronchial smooth muscle constriction of LTC4. On the other hand, the antagonists showed no significant effects on airway wall edema by LTC4. These results suggest TXA2 may play a role in LTC4-induced bronchial hyperresponsiveness to histamine.

Animals↗
PubMed1992

Effect of herbimycin A, an antagonist of tyrosine kinase, on bcr/abl oncoprotein-associated cell proliferations: abrogative effect on the transformation of murine hematopoietic cells by transfection of a retroviral vector expressing oncoprotein P210bcr/abl and preferential inhibition on Ph1-positive leukemia cell growth.

Herbimycin A, a benzoquinoid ansamycin antibiotic, was demonstrated to decrease intracellular phosphorylation by protein tyrosine kinase (PTK). In Philadelphia chromosome (Ph1)-positive leukemias such as chronic myelogenous leukemia (CML) and Ph1-positive acute lymphoblastic leukemia (ALL), both of which express bcr-abl fused gene products (P210bcr-abl or P190bcr-abl protein kinase) with augmented tyrosine kinase activities, herbimycin A markedly inhibited the in vitro growth of the Ph1-positive ALL cells and the leukemic cells derived from CML blast crisis. However, the same dose of herbimycin A did not inhibit in vitro growth of a broad spectrum of Ph1-negative human leukemia cells, and several other protein kinase antagonists also displayed no preferential inhibition. Furthermore, we demonstrated that herbimycin A has an antagonizing effect on the growth of transformed cells by a transfection of retroviral amphotrophic vector expressing P210bcr/abl into a murine interleukin (IL)-3-dependent myeloid FDC-P2 cell line. This inhibition was abrogated by the addition of sulfhydryl compounds, similar to the reaction previously described for Rous sarcoma virus transformation. The inhibitory effect of herbimycin A on the growth of Ph1-positive cells was associated with decreased bcr/abl tyrosine kinase activity, but no decrease of bcr-abl mRNA and protein, suggesting that the inactivation of bcr-abl tyrosine kinase activity by herbimycin A may be induced by its binding to the bcr-abl protein portion that is rich with sulfhydryl groups. The present study indicates that herbimycin A is a beneficial agent for the investigation of the role of the bcr-abl gene in Ph1-positive leukemias and further suggests that the development of agents inhibiting the bcr-abl gene product may offer a new therapeutic potential for Ph1-positive leukemias.

Benzoquinones↗