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Biomedical subjects

M Kurosawa

Publications and source records attributed to M Kurosawa.

At least 163 records · Page 9Linked to original sources

Effects of azelastine on superoxide anion generation from gamma interferon treated human monoblast cell line U937 measured by chemiluminescence method.

U937 cells are established human monoblast cell line originally isolated from a patient with diffuse histiocytic lymphoma. In the present study, superoxide anion (O2-) generation from U937 cells were measured by 2-methyl-6-[p-methoxyphenyl]-3,7- dihydroimidazo[1,2-a]pyrazin-3-one (MCLA)-dependent luminescence. Addition of 0.5 mumol/l MCLA and a stimulatory agent, such as N-formyl-methionyl-leucyl- phenylalanine (fMLP) and phorbol myristate acetate (PMA), to a suspension of the cells treated with gamma interferon (IFN gamma) caused a marked luminescence which was inhibited by 0.5 mumol/l superoxide dismutase (SOD). On the other hand, the cells which were not treated with IFN gamma caused no significant luminescence by the stimulation with either fMLP or PMA. The adherent IFN gamma-treated cells generated more O2- than the nonadherent IFN gamma-treated cells by the stimulation with fMLP. The maximal luminescence intensity from the adherent IFN gamma-treated U937 cells stimulated by fMLP was dependent upon the number of the cells. Azelastine (A-5610, CAS 58581-89-8) significantly inhibited the O2- generation from the adherent IFN gamma-treated U937 cells stimulated by fMLP or PMA in a dose-dependent manner.

Cell Adhesion↗

Effects of antiallergic drugs on superoxide anion generation from activated human alveolar macrophages measured by chemiluminescence method.

Human alveolar macrophages were recovered by bronchoalveolar lavage and superoxide anion (O2-) generation from the macrophages were measured by 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo[1,2-a]pyrazin++ +-3-one (MCLA)-dependent luminescence. Addition of 0.5 mumol/l MCLA and a stimulatory agent, such as phorbol myristate acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP), to a suspension of the cells caused a marked luminescence which was inhibited by 0.5 mumol/l superoxide dismutase (SOD). The maximal luminescence intensity was dependent upon the number of the cells. Azelastine (A-5610, CAS 58581-89-8) significantly inhibited the O2- generation from the activated macrophages in a dose-dependent manner. However, the other antiallergic drugs, such as ketotifen, disodium cromoglycate and others showed little effects on the O2- generation from the activated human alveolar macrophages.

Bronchoalveolar Lavage Fluid↗

[Naturally occurring aliphatic polyamines-induced histamine release from rat peritoneal mast cells].

Rat peritoneal mast cells obtained by Percoll gradient were incubated with different concentrations of naturally occurring aliphatic polyamines, spermine and spermidine, at 0.1-10 mM and the amount of histamine release into the supernatant solutions was measured. The addition of each polyamine to the suspensions of the mast cells caused a histamine release in a dose-dependent manner. The histamine release from the cells incubated with each polyamine was rapid and the amount of the histamine release into the supernatant solutions reached maximum at one minute with the incubations.

Animals↗

[Effect of phospholipase A2 inhibitor on substance P-induced histamine release from rat peritoneal mast cells].

Rat peritoneal mast cells purified on a Percoll gradient were challenged with substance P and effect of phospholipase A2 inhibitor ONO-RS-082 on substance P-induced histamine release from the cells were investigated. Substance P at the concentration of 10(-5) M caused a significant histamine release and the amount of histamine release reached to its submaximum at 1 min after the challenge and then slowly increased. ONO-RS-082 inhibited the substance P-induced histamine release in a concentration-dependent manner at the concentration from 10(-6) to 10(-4) M, suggesting that phospholipase A2 may play some roles in the process of substance P-induced histamine release from rat peritoneal mast cells.

Aminobenzoates↗

[Changes in respiratory resistance and dynamic compliance induced by histamine in the guinea pig].

Respiratory resistance and dynamic compliance in guinea pigs were measured by pulmonary mechanics analyzer Buxco Model 6. Changes induced by intravenous injection of histamine were studied. Administration of histamine caused dose-dependent increase in respiratory resistance and decrease in dynamic compliance in guinea pigs. The increase in respiratory resistance by repeated injections of the same dose of histamine was maintained at the same level 5 hours after the first injection. However, the decrease in dynamic compliance by histamine administration decreased significantly from 1 to 4 hours after the first injection. The baseline resistance increased from 1 to 5 hours after the first injection of histamine. The baseline compliance decreased from 1 to 5 hours after the first injection.

Airway Resistance↗

A new model of focal brain ischemia based on the intracerebral injection of endothelin-1.

Endothelin-1 and its receptors are widely distributed in the brain of rodents and humans. In view of its potent and long-lasting vasoconstrictor activity, a role of endothelin-1 has been proposed in brain ischemia. In the present paper, the local injection of endothelin-1 was utilized to induce ischemia in rat striatum. An evaluation of the rostrocaudal extension of the lesion is reported. By using intracerebral microdialysis, a marked increase of lactate and dopamine, but not glutamate, was observed in this region upon endothelin-1 administration. Moreover, preliminary data reported show a protective effect of ganglioside treatment on endothelin-1 lesion of rat striatum. The characteristics of the present model of brain ischemia are discussed in comparison with well characterized models, such as the Pulsinelli's four vessel occlusion and the middle cerebral artery occlusion.

Animals↗

[Hypodense eosinophils are much labeled with 32P than normodense eosinophils].

Peripheral blood eosinophils from the patients with atopic dermatitis were isolated on a Percoll gradient and incubated with H3(32)PO4. After stopping the reaction, SDS/PAG electrophoresis was performed and autoradiographs were prepared to determine the incorporation of 32P into proteins. Eosinophils developed at least 14 protein bands below 66.2 K by SDS/PAG electrophoresis and the differences of the staining patterns between hypodense and normodense eosinophils were observed. In the autoradiographs 5 distinct radioactive bands were observed below 31 K. 32P incorporation into the bands of hypodense eosinophils were stronger than that of normodense eosinophils, suggesting possible involvement of protein phosphorylation in the activation process of eosinophils.

Adult↗

[Bronchial hyperresponsiveness to histamine induced by intravenous administration of thromboxane A2 (TXA2) in guinea-pigs].

Thromboxane A2 (TXA2) has been suggested to play an important role in the pathogenesis of bronchial asthma. In this study the effects of intravenous administration of TXA2 on bronchial smooth muscle in guinea-pigs were investigated by measuring dynamic compliance and dynamic respiratory resistance, using a formula to exclude the effects of differences in airway wall thickness. Using this formula, the ratio of bronchial smooth muscle constriction by histamine can be estimated as an index of bronchial hyperresponsiveness. Administration of TXA2 did not induce airway wall edema. The ratio of bronchial smooth muscle constriction by histamine was significantly (p less than 0.01) enhanced by the administration of TXA2. Moreover, TXA2 antagonists, ONO-NT-126 and ONO-8809, inhibited the effect of TXA2 administration. These results suggest that TXA2 is an important mediator affecting bronchial hyperresponsiveness.

Airway Resistance↗

[The expression of IgE Fc receptors on peripheral blood monocytes in asthmatic patients].

We measured the expression of the IgE Fc receptor, Fc epsilon RII, on peripheral blood monocytes isolated from asthmatic patients and normal subjects by laser flow cytometry. After peripheral blood mononuclear cells were incubated with monoclonal antibodies, H107, which recognize Fc epsilon RII, FITC-labeled second antibodies were reacted with them. The cells were then incubated with PE-labeled Leu M3 monoclonal antibodies and the ratios of H107 positive monocytes were measured by two color analysis. The ratio of H107 positive monocytes in atopic asthmatic patients was significantly greater than the ratio in normal subjects. But the ratio was not higher in 9 out of the 14 atopic asthmatic patients. This indicated that atopic asthmatic patients are divided into two groups by the expression of Fc epsilon RII on monocytes. Total serum IgE level was not related to the ratio of H107 positive monocytes.

Adult↗

[Bronchial hyperresponsiveness to histamine following antigen challenges in actively sensitized guinea pigs].

Guinea pigs were actively sensitized by intraperitoneally administered ovalbumin and challenged by intravenous injections of ovalbumin. Respiratory resistance and dynamic compliance were measured by pulmonary mechanics analyzer Buxco Model 6. Changes in resistance (delta R) and compliance (delta C) induced by intravenously administered histamine were investigated before and after the challenge. Responses to the histamine in sensitized guinea pigs were also compared with those in naive guinea pigs. The following results were obtained. 1) A significant increase in delta R by histamine administration was observed following the antigen challenge. delta C by histamine administration showed a tendency to increase after the challenge. 2) A significant increase of delta R by 7.2 micrograms/kg histamine administration was observed in actively sensitized guinea pigs. However, delta C by the histamine administration did not change in the sensitized animals.

Airway Resistance↗

[Therapeutic effect of ranimustine(MCNU) on myeloproliferative disorder and chronic myelomonocytic leukemia].

Seventeen patients with myeloproliferative disorders and one patient with chronic myelomonocytic leukemia (CMMoL) were treated with ranimustine++ (MCNU), and the efficacy was evaluated. MCNU was given intravenously by drip infusion at an usual dose of 100 approximately 150 mg with intervals arranged according to the counts of peripheral blood cells. A complete remission was achieved in all 10 patients with chronic myelogenous leukemia (CML) in chronic phase. In three of patients with polycythemia vera (PV) the excellent effects were obtained, and the other 2 cases showed moderate effect. An excellent effect was obtained in both 2 patients with essential thrombocythemia (ET). A patient with CMMoL revealed partial remission. The overall efficacy rate was 100%. The cases with CML needed more long term and much more dose of the drug in order to get remission compared with PV and ET. After remission in both PV and ET, well controlled states were maintained for a relatively long period with no additional administration. In CMMoL, MCNU combined with 6-mercaptopurine also showed remarkable anti-tumor effects. It suggests that MCNU may be one of the useful drugs for the treatment of CMMoL. The side effects observed with MCNU were a slight degree of nausea and vomiting (28%), however they showed no trouble on carrying out the therapy.

Adult↗

Polyamines stimulate the phosphorylation of phosphatidylinositol in rat mast cell granules.

Rat mast cell granules were obtained by homogenization of highly purified rat mast cells and isolated in a Percoll gradient. Diphosphoinositide (DPI) synthesis in rat mast cell granules was assayed by measuring the incorporation of 32P from [gamma 32P] ATP into DPI in the absence of exogenous phosphatidylinositol (PI). Lipids were isolated with methanol/chloroform/HCl and were separated by thin-layer chromatography on oxalic acid impregnated silica gel plates. DPI areas were identified by staining with iodine, scraped and measured for 32P radioactivity. The addition of polyamines, spermine and spermidine, to the granules caused an increase of DPI synthesis, which can be catalyzed by PI kinase. This effect of polyamines in the DPI synthesis was in a dose-dependent manner and maximal effects were observed at 1 mM spermine and 10 mM spermidine, respectively.

Animals↗

Rat mast cell granules reacting with a mouse monoclonal antibody M6764 which recognizes the same epitope of a mouse monoclonal antibody HNK-1.

Rat mast cell granules and plasma membrane fractions were obtained by homogenization of highly purified rat mast cells and isolation in a Percoll gradient and a sucrose gradient, respectively. Immunostaining of rat mast cells, granules and plasma membrane fractions was performed with mouse monoclonal antibody M6764 which was produced against the crude membrane fractions of the neural tubes. Rat mast cells and granules were immunostained with the monoclonal antibody, but not the plasma membrane fractions. The granules fixed with glutaraldehyde-paraformaldehyde showed ring-like forms. Chloroform-methanol treatment did not effect the staining of rat mast cells and granules with the monoclonal antibody. Western blotting analysis of rat mast cells and granules with the monoclonal antibody showed broad protein bands ranging from 100 to 250 kD.

Animals↗

Plasma prostaglandin levels from bronchial asthmatic patients assayed by 9-anthryldiazomethane-HPLC method.

Plasma prostaglandin (PG) and thromboxane (Tx) levels from bronchial asthmatic patients were assayed by 9-anthryldiazomethane reversed-phase high-performance liquid chromatography method. TxB2 levels from stable bronchial asthmatic patients were significantly higher than those from normal healthy subjects. PGF2 alpha levels were significantly elevated in atopic patients compared with nonatopic ones. PG patterns differed between asthmatic and nonasthmatic conditions in the same patients. PGF2 alpha levels were significantly elevated in the patients with spontaneous attacks compared with those without attacks and 6-keto PGF1 alpha levels were significantly lower in bronchial asthmatic patients having attacks than in the patients without attacks. There were no significant differences of PG levels between mild and moderate asthmatic subjects. Aminophylline injection in patients with mild spontaneous attacks had no significant effects on PG levels which were compared before and after injection.

Adult↗

[Anemia in the elderly].

We measured red blood cell counts, hemoglobin levels, hematocrit values, serum iron levels, total iron binding capacity, transferrin saturation, and serum ferritin levels in 364 elderly subjects in the eighth decade, who consisted of 283 subjects (171 males, 112 females) living in their own homes and 81 subjects (28 males, 53 females) living in an old-age home. The mean values of RBC, Hb, Ht, SI, s-Ft in both male and female subjects living in their own homes were 469 X 10(4)/microliters vs 439 X 10(4)/microliters, 14.6 g/dl vs 13.3 g/dl 44.3% vs 40.6%, 95.6 micrograms/dl vs 84.8 micrograms/dl, 50.2 ng/ml vs 42.6 ng/ml, respectively. On the other hand, the mean values of RBC, Hb, Ht, SI, s-Ft in both male and female subjects living in an old-age home were 421 X 10(4)/microliters vs 390 X 10(4)/microliters, 13.8 g/dl vs 12.6 g/dl, 39.9% vs 36.7%, 74.2 micrograms/dl vs 58.6 micrograms/dl, 98.8 ng/ml vs 69.1 ng/ml, respectively. All erythrocyte parameters were significantly lower in females than in males in both groups, and significantly lower in subjects living in an old-age home than in subjects living in their own homes. The erythrocyte parameters of subjects living in their own homes showed little difference compared with those of normal young adults. These results suggest that a sedentary lifestyle in the elderly people contribute to the tendency to have anemia and this is considered to relate to age-associated pathology such as inflammation. As anemia in elderly people often follows a underlying illness, we must always give attention to the factors which cause anemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Antigen-induced histamine release from peripheral leukocytes of "Konnyaku asthmatic patients".

Histamine release from peripheral leukocytes of "Konnyaku asthmatic patients," patients with a unique occupational bronchial asthma in Japan, was measured after challenge with the antigen. There was an antigen concentration-dependent response with highly significant correlations between the maximal histamine release and the ratio of the radioallergosorbent test (RAST) of the antigen to human serum albumin. These results suggest that the histamine release test from peripheral leukocytes as well as RAST can be a useful diagnostic test in patients with bronchial asthma.

Adult↗