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Biomedical subjects

T Nagakura

Publications and source records attributed to T Nagakura.

At least 73 records · Page 4Linked to original sources

Exercise-induced late asthmatic reactions with neutrophil chemotactic activity.

Two adults and 13 children with exercise-induced asthma had both immediate and late reductions in forced expiratory volume in one second (FEV1) after treadmill exercise. The late reactions developed 4 to 10 hours after exercise and in each instance were associated with wheezing or chest tightness (or both). Increases in neutrophil chemotactic activity, measured in the 2 adults and in 11 of the children, accompanied the reductions in FEV1 in all these subjects. In contrast, four other adults with only an immediate fall in FEV1 after exercise had only an initial elevation in neutrophil chemotactic activity, with no subsequent increase for the remaining 24-hour period. The agent responsible for the neutrophil chemotactic activity released during exercise-induced late reactions appeared to be identical to that released during immediate reactions. These observations suggest that some patients with exercise-induced asthma have late reactions that, as in the case of antigen-induced bronchoconstriction, are accompanied by the release of neutrophil chemotactic activity.

Adolescent↗

Neutrophil chemotactic activity in milk-induced asthma.

Four subjects with clinical histories of milk-induced asthma were studied (three allergic to cow's milk; one to soya milk). In each instance, skin prick tests, RAST (IgE and IgG4), the basophil histamine release, and serum precipitins, using appropriate milk extracts, were negative. After the ingestion of milk all the subjects developed a reproducible and dose-dependent increase in airflow limitation. Three patients (two allergic to cow's milk; one to soya milk) gave a characteristic immediate-type reaction, which was maximal at 30 min after challenge. The fourth individual developed an isolated late-phase response, with maximal airways obstruction 3 hr after ingesting milk. In the three subjects who gave an early reaction, wheezing was accompanied by an elevation in circulating neutrophil chemotactic activity (NCA). This was not observed in the individual with the isolated late reaction. By Sephacryl S-400 gel-filtration chromatography it was shown that NCA of the early reactions eluted with proteins having an estimated molecular weight of 600,000 daltons. The immediate asthmatic response in peak expiratory flow rate and the elevation in NCA were inhibited by the prior oral administration of either disodium cromoglycate (DSCG) or oral beclomethasone dipropionate (BDP). In contrast, DSCG had no effect on airways obstruction in the subject with the isolated late asthmatic response, although inhibition was achieved by BDP.

Adult↗

Serum dopamine beta-hydroxylase and free fatty acids in exercise-induced asthma.

Serum dopamine beta-hydroxylase activity, which is thought to reflect noradrenaline secretion, and free fatty acid level were measured in twenty atopic asthmatic children, of whom ten had exercise-induced asthma (EIA), after exercise on the treadmill. There was a significant decrease in the level of serum dopamine beta-hydroxylase activity in the asthmatics who developed EIA and this closely accompanied the onset of airflow obstruction. There was no change in the free fatty acid levels. In contrast, the asthmatics, who did not have EIA showed a significant rise in the levels of dopamine beta-hydroxylase activity and free fatty acids after the same exercise task. Our results suggest that the atopic children studied, who developed EIA, may have had an impaired noradrenaline response to exercise. It is further suggested that this impaired noradrenaline secretion may facilitate mediator release and contribute to the airflow obstruction in EIA.

Asthma↗

Neutrophil chemotactic factor in exercise- and hyperventilation-induced asthma.

Elevated levels of the mast-cell-associated serum neutrophil chemotactic factor (NCF) and an increase in blood basophil counts were observed in 6 atopic asthmatics during exercise-induced asthma (EIA). These changes were not found when the same degree of airways obstruction was elicited in the same subjects by isocapnic hyperventilation (ISH) with cold air. The NCF was unlikely to be related to the basophilia alone, because asthmatics without EIA who underwent the same exercise task, produced a similar basophilia but significantly less NCF. These findings suggest that mast-cell-associated (as opposed to basophil-associated) mediators of hypersensitivity are detectable in the bloodstream during the bronchoconstriction induced by exercise, but not by ISH.

Adolescent↗

Identification and partial characterization of an exercise-induced neutrophil chemotactic factor in bronchial asthma.

A heat-stable neutrophil chemotactic factor (NCF) has been identified in the serum of 13 atopic asthmatic subjects after treadmill exercise. Peak activity was detected at 10 min and returned to prechallenge values by 1 h. No NCF activity was detected in the sera of three nonasthmatic atopic or four normal nonatopic individuals performing the same task. NCF produced by exercise (NCFEX) had a similar time-course of release to NCF provoked by specific antigen (NCFAG). The appearance of circulating NCFEX and NCFAG closely paralleled the fall in peak expiratory flow rate/forced expiratory volume in 1 s (PEFR/FEV1). Histamine challenge in atopic asthmatics at concentrations giving a comparable change in PEFR/FEV1 to that evoked by exercise or inhaled antigen was not associated with the appearance of circulating NCF. In seven subjects NCFEX release was inhibited by prior administration of disodium cromoglycate. NCFEX and NCFAG eluted as single peaks of activity when applied separately to columns of Sephadex G-200, and both were an estimated 750,000 daltons. NCFEX and NCFAG also eluted as single peaks of activity, at between 0.15 and 0.30 M NaCl, following anion exchange chromatography on DEAE-Sephacel (pH 7.8). The isoelectric points of NCFEX and NCFAG were virtually identical (between pH 6.0 and 6.5) as determined by chromatofocusing on Polybuffer Exchanger 94. The activities of NCFEX and NCFAG were substantially reduced, in both a time- and dose-dependent fashion, after incubation with trypsin and chymotrypsin. Partially purified NCFEX and NCFAG promoted both stimulated random migration (chemokinesis) as well as directional migration (chemotaxis). These experiments indicate that NCFEX and NCFAG might be identical substances and raise the possibility that mediators by hypersensitivity are released during exercise-induced asthma in atopic subjects.

Adolescent↗