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Biomedical subjects

T Nagakura

Publications and source records attributed to T Nagakura.

At least 55 records · Page 3Linked to original sources

Disodium cromoglycate inhibits activation of human inflammatory cells in vitro.

Recent clinical studies indicate that disodium cromoglycate (DSCG) may have a direct effect on inflammatory cells because the drug reversed various changes in leukocyte function, such as increased membrane-receptor expression and enhanced cytotoxic capacity observed in peripheral white blood cells from subjects with asthma undergoing allergen-inhalation challenge. In the present study, we have demonstrated that DSCG, at low concentrations (a concentration of drug required to produce 50% inhibition, approximately 10(-8) mol/L) and in a time-dependent fashion, directly inhibited the activation in vitro of human neutrophils, eosinophils, and monocytes. Peripheral blood leukocytes were incubated with the synthetic chemoattractant, formyl-methionyl-leucyl-phenylalanine (at an optimal concentration of 10(-8) mol/L), and activation was assessed by measuring increases in the percentages of complement and IgG (Fc) rosettes as well as the enhanced capacity of these cells to kill target organisms (schistosomula of Schistosoma mansoni). DSCG at a concentration of 10(-7) mol/L totally inhibited both the formyl-methionyl-leucyl-phenylalanine-induced enhancement of complement and IgG rosettes, as well as increased schistosomular killing. These observations indicate that DSCG directly inhibits the secretory properties of inflammatory cells and that in turn might have important implications in modulating mechanisms contributing to the inflammatory component of asthma and allergic disease. It may also help to explain why compounds with considerably greater mast cell stabilizing properties than DSCG have been so disappointing when they are evaluated clinically.

Cromolyn Sodium↗

Mediator release from basophilic cells derived from cultured cord blood cells.

Mononuclear cells from human umbilical cord blood were separately cultured either in the presence of phorbol ester-phytohemagglutin-leukocyte-conditioned medium (PE-PHA-LCM) or PHA-LCM. Cells cultured in PE-PHA-LCM released histamine following calcium ionophore and compound 48/80 challenge. However, there was a similar histamine release from cells cultured in the presence of PHA-LCM following calcium ionophore but not following compound 48/80 challenge. Neutrophil chemotactic activity (NCA), recognized to be one of the markers for mast cell activation, was detected following calcium ionophore and anti-IgE challenge from the supernatant of cells cultured in the presence of PHA-LCM, suggesting unique features in the cells studied.

Basophils↗

Factors predisposing to exercise-induced late asthmatic responses.

Seventeen children developed reproducible early and late asthmatic responses (dual reactions) after cycle ergometer exercise. There was a significant correlation between the magnitude of their early and late reactions, emphasizing the direct relationship of these events. No significant differences were observed in the clinical severity of asthma, diurnal variations in FEV1, and extent of the early reaction after exercise between children with dual responses and 19 children with single reactions. These findings suggest that the occurrence of late reactions after exercise is not determined by differences in severity of disease or baseline airway reactivity in the asthmatic subjects. This view is supported by the finding that there was no significant difference in the dose of acetylcholine necessary to elicit a 20% decrease in FEV1 between eight children with dual response and seven children with single early response after exercise. The rate of spontaneous recovery from early reactions was slower in children with dual responses, suggesting that this variable may predict development of late-phase reactions in exercise-induced asthma.

Acetylcholine↗

Mediators in exercise-induced asthma.

Circulating concentrations of the mast cell-associated mediators, histamine and neutrophil chemotactic factor (NCF) of high molecular weight, were measured in atopic and nonatopic asthmatics after treadmill exercise. Elevations in the concentrations of both mediators accompanied the development of exercise-induced asthma (EIA). Normal individuals did not release mediators or develop bronchoconstriction after an identical exercise. The elaboration of mediators was not due to the onset of airflow obstruction, the postexercise basophilia, or the exercise task per se. A treadmill exercise undertaken while inhaling fully conditioned air inhibited EIA and NCF release; in contrast the same exercise undertaken while breathing cold, dry air elicited EIA and the production of mediators. This suggests that the stimulus for EIA and mediator release may be identical. Late-phase asthmatic reactions occur 3 to 9 hr after exercise in some asthmatics and are accompanied by the appearance of circulating NCF, as previously reported in allergen-induced late responses. In addition to the contribution of mediators to the spasmogenic reaction in EIA, mediators may contribute to bronchial inflammation by activating circulating leukocytes. There was a kinetic increase in the expression of neutrophil C3b receptors in EIA (+) asthmatics for up to 60 min after treadmill exercise. The enhancement of C3b receptors, as evidence of neutrophil activation, was preceded by release of NCF and reductions in peak expiratory flow rates. The prior administration of cromolyn inhibited EIA, NCF release, and enhancement of C3b receptors. These changes were not observed in EIA (-) asthmatics after an identical exercise task. These findings support the view that mediators are released in EIA and may play an important role in its pathogenesis.

Asthma↗

Neutrophil chemotactic activity and histamine in atopic and nonatopic subjects after exercise-induced asthma.

Seven atopic and 6 nonatopic asthmatics with exercise-induced asthma were subjected to a treadmill exercise task. After this procedure, both groups had elevations in the concentrations of plasma histamine and serum high molecular weight neutrophil chemotactic activity (as assessed by Sephadex G-200 chromatography). These findings support the view that the release of mast-cell-associated mediators can be independent of the atopic state.

Adolescent↗