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Biomedical subjects

A B Kay

Publications and source records attributed to A B Kay.

At least 307 records · Page 17Linked to original sources
PubMed1985

Influence of albuterol, cromolyn sodium and ipratropium bromide on the airway and circulating mediator responses to allergen bronchial provocation in asthma.

The effect of pharmacologic agents on mast cell mediator release was investigated in vivo. Eight atopic asthmatic subjects with airways relatively unreactive to nonspecific stimuli (geometric mean PC20 methacholine, 4.0 mg/ml) underwent single-concentration allergen challenge before (control) or after inhaling albuterol 200 micrograms, cromolyn sodium 20 mg, or 0.9% sodium chloride placebo. Six of the same subjects also underwent allergen challenge after pretreatment with ipratropium bromide, 1 mg. Airway responses to pharmacologic agents and bronchial challenge were measured by change in both specific airway conductance (SGaw) and FEV1. Mast cell mediator release was monitored by serial change in plasma histamine and, in addition, serum neutrophil chemotactic factor (NCF) on the placebo, albuterol, and cromolyn sodium challenge days. Control and placebo allergen challenges were associated with repeatable mean maximal falls in SGaw (48.5 versus 49.6%) and FEV1 (25.7 versus 25.5%). The mean increments in plasma histamine were not significantly different on the control (0.17 to 0.44 ng/ml) or placebo challenge days (0.18 to 0.64 ng/ml), with maximal levels occurring 5 min after challenge. A sustained increase in NCF was identified on the placebo challenge day (155.0% above baseline). Pretreatment with albuterol abolished any significant bronchoconstriction, with mean maximal falls in SGaw and FEV1 after challenge of 7.5 and 1.4%, respectively. These changes in airway caliber were not associated with any significant increment in mean plasma histamine (0.17 to 0.22 ng/ml) or serum NCF (4.1% increase). Cromolyn sodium pretreatment, while attenuating the airway response, was still associated with significant falls in SGaw (22.7%) and FEV1 (7.3%) and increases in plasma histamine (0.18 to 0.27 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Airways reversibility after prednisolone therapy in chronic asthma is associated with alterations in leukocyte function.

In 6 patients with chronic asthma, we studied the effects of orally administered prednisolone on monocyte and neutrophil membrane receptor expression for IgG (Fc) and complement, neutrophil locomotion, and calcium ionophore-induced leukotriene C4 production by granulocytes. Prior to treatment, monocyte IgG (Fc) and complement receptor expression, but not neutrophil IgG (Fc) or complement receptor expression, were increased when patients were compared with nonasthmatic control subjects (p less than 0.01 and p less than 0.01, respectively). After a 7-day course of orally administered prednisolone (30 mg/day daily), the increases in peak expiratory flow rate were accompanied by significant decreases from baseline in the percent of monocyte IgG (Fc) (Day 3, p less than 0.001; Day 7, p less than 0.001), monocyte complement (Day 3, p less than 0.001; Day 7, p less than 0.001), and neutrophil complement rosettes (Day 3, p less than 0.02; Day 7, p less than 0.02), but not neutrophil IgG (Fc) rosettes. Neutrophil locomotion in vitro, in response to casein, from the asthmatics was enhanced when compared with cells from control subjects, and was significantly depressed following prednisolone. Each of the 6 subjects had a peripheral blood eosinopenia in response to prednisolone that corresponded to a decrease in the amount of immunoreactive LTC4 generated from granulocyte suspensions challenged with the calcium ionophore A23187. These findings suggest that prednisolone suppresses monocyte and neutrophil activation in chronic asthma and that this is accompanied by an improvement in lung function.

Adult↗
PubMed1985

Eosinophils: role in asthma, allergy and parasite immunity.

The distinct features of the eosinophil include their content of large crystalloid granules which contain a number of unique basic proteins, and their capacity to selectively generate the SRS-A, sulphidopeptide leukotrienes. Eosinophil-derived products probably play an important role in the destruction of helminthic larvae but in some situations, for instance, chronic bronchial asthma and the hypereosinophilic syndrome, the cell might be responsible for considerable tissue damage. Eosinophils can be activated, in vitro, by a variety of agents which include factors associated with eosinophil maturation, mast cell products and other substances released during allergic tissue reactions and other inflammatory processes. At the present time there is growing interest in the fact that in many conditions associated with eosinophilia there is a population of light density "activated" cells which, in a variety of biological systems, respond more vigorously than normal ("normodense") eosinophils. Knowledge of eosinophils and eosinophil-associated events is growing rapidly and there is a need to modify continuously our views on the precise role(s) of the eosinophil in the light of these new findings.

Animals↗
PubMed1985

Enhancement of human neutrophil complement receptors: a comparison of the rosette technique with the uptake of radio-labelled anti-CR1 monoclonal antibody.

We have compared the rosette technique (using C3b-coated red cells) with the uptake of a 125I F(ab')2 anti-complement receptor type 1 (CR1) monoclonal antibody (E11) for studying the phenomenon of chemotactic factor (fMLP)-induced complement receptor enhancement (CRE) on human neutrophils. With both methods the dose responses of fMLP were similar with maximal CRE being observed at 10(-7) moles 1(-1). Conversely, the time course of CRE and the effects of disodium cromoglycate (DSCG) on inhibition of enhancement were discrepant. Maximal CRE with the rosette method was observed at 30 min, whereas increased uptake of anti-CR1 had still not reached a plateau after 1 h. DSCG inhibited fMLP-induced CRE, as assessed by the rosette technique, whereas this agent had no effect on increased binding of radio-labelled anti-CR1 antibody. These results suggest that in CRE the increased adherence of C3b-coated red cells to fMLP-stimulated neutrophils, as measured by the rosette technique, is not dependent exclusively on the increased numbers of CR1.

Antibodies, Monoclonal↗
PubMed1985

Enhancement of human eosinophil- and neutrophil-mediated killing of schistosomula of Schistosoma mansoni by reversed type (IgE-mediated) anaphylaxis, in vitro.

Using human peripheral blood leucocytes we have developed a model for studying the effect of in vitro anaphylaxis on granulocyte-mediated killing of helminthic larvae (schistosomula (Sch) of Schistosoma mansoni). Leucocytes were incubated with either an F(ab')2 rabbit anti-human IgE (alpha E) or a control F(ab')2 prepared from non-specific rabbit IgG (alpha Ec). A time-dependent enhancement of eosinophil- and neutrophil-mediated complement (C) or antibody- (Ab) dependent killing of Sch was observed following incubation with alpha E, but not alpha Ec. Optimal enhancement of granulocyte killing was dependent on the concentration of alpha E, pre-incubation of granulocytes with alpha E prior to addition to C coated Sch, as well as the granulocyte: Sch ratio. Baseline killing of Ab and/or C coated Sch by eosinophil rich cells was significantly greater than neutrophil rich suspensions and both were proportionally increased following incubation with alpha E. Enhanced eosinophil and neutrophil killing by alpha E required the presence of mononuclear cells containing basophils, whereas there was no difference in the killing of C or Ab coated Sch when eosinophils or neutrophils alone were incubated with alpha E or alpha Ec. This IgE and leucocyte-dependent model might facilitate the isolation and identification of the pharmacological mediator(s) of hypersensitivity which enhance eosinophil or neutrophil killing of appropriately opsonized helminthic larvae.

Anaphylaxis↗
PubMed1984

Leukocyte activation in allergen-induced late-phase asthmatic reactions.

Some patients with allergen-induced asthma have both an early and late reaction to allergen (dual asthmatic reactions). To investigate the role of leukocyte activation in dual asthmatic reactions, we measured neutrophil chemotactic activity, percentages of neutrophil and monocyte complement rosettes, and one-second forced expiratory volume (FEV1) in 11 patients with allergen-induced dual asthmatic reactions after a challenge with allergen. To control for the effects of bronchoconstriction, the same studies were done after a challenge with methacholine. In all subjects there was a biphasic increase in neutrophil chemotactic activity and the percentages of neutrophil and monocyte complement rosettes, accompanied by a reduction in the FEV1. After methacholine, there were no significant changes in neutrophil chemotactic activity or percentages of complement rosettes, despite bronchoconstriction. Six patients with single-phase allergen-induced asthma had similar responses, but they were monophasic. We conclude that allergen-induced early and late asthmatic reactions are accompanied by activation of leukocytes and that these alterations probably reflect the release of mediators from mast cells rather than an effect of bronchoconstriction.

Adult↗
PubMed1984

Bronchoalveolar lavage in asthma: the effect of disodium cromoglycate (cromolyn) on leukocyte counts, immunoglobulins, and complement.

In a double-blind, placebo-controlled study, we measured the effect of disodium cromoglycate (DSCG) on leukocyte counts, total IgE, IgG, IgA, IgM, house dust mite-specific IgE, C3, and C4 in bronchoalveolar lavage (BAL) fluid and peripheral blood in 36 atopic, perennial asthmatic subjects (DSCG 19; placebo 17). Differential cell counts on bronchial mucus were also performed. The percentage of eosinophils in bronchial mucus and BAL fluid was significantly less after DSCG. There was also a significant decrease in the concentration of total IgA (expressed as an IgA/albumin ratio) in BAL fluid after a 28-day treatment with DSCG. When the DSCG-treated patients were divided into responders and nonresponders on the basis of average daily symptom scores, the responders had significantly less bronchial mucus eosinophils, BAL eosinophils, and house dust mite-specific IgE (but not IgA) after DSCG. No significant differences in any of the measurements were observed in the nonresponders or the placebo group similarly subdivided on the basis of symptom scores. These results suggest that the efficacy of DSCG in bronchial asthma might be related to its ability to suppress the local accumulation of eosinophils and specific-IgE antibodies.

Adolescent↗
PubMed1984

Immunologic studies in allergen-induced late-phase asthmatic reactions.

We have measured plasma histamine, serum neutrophil chemotactic activity (NCA) and complement (C3 and C4) over a 24-hour period in patients experiencing either early- and late-phase (dual) or single early asthmatic reactions to inhaled allergens. There was a significant biphasic elevation in plasma histamine, which paralleled the fall in forced expiratory volume in 1 sec in 10 patients with dual responses, whereas in seven subjects with single early reactions, only a single early increase in histamine concentrations was observed. In general, in the individual subjects, the changes in plasma histamine paralleled both the elevations in serum NCA and the decreases in forced expiratory volume in 1 sec. By gel filtration on Sephacryl S-400, anion exchange chromatography on DEAE Sephacel, and chromatofocusing with Polybuffer Exchanger 94, the major NCA of both the early and the late reactions was associated with proteins having an estimated molecular size of 600,000 daltons, an elution from DEAE Sephacel at 0.15M to 0.30M of NaCl (pH 8.1), and a pI of approximately 6.5. There were no appreciable changes in serum C3 and C4 up to 24 hr after challenge in subjects with late-phase responses. The patterns of asthmatic response were not related to either the total or allergen-specific serum IgE or IgG4 concentrations. These results support the view that mediators of hypersensitivity participate in late-phase as well as early asthmatic reactions.

Adolescent↗
PubMed1984

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↗
PubMed1984

Partial characterization of allergens associated with hypersensitivity to the 'green nimitti' midge (Cladotanytarsus lewisi, Diptera: Chironomidae).

Allergens in extracts of the 'green nimitti' midge, Cladotanytarsus lewisi Freeman (Diptera: Chironomidae), a cause of widespread hypersensitivity in the Sudan, were isolated and partially characterized by assays which depend on the binding of 125I-anti-IgE to allergen-IgE complexes. These methods included RAST inhibition, crossed radioimmunoelectrophoresis (CRIE) and rocket radioimmunoelectrophoresis (RRIE). Following Sephadex G100 chromatography the 'major peak' of allergenicity as determined by RAST inhibition, RRIE and SDS-PAGE was associated with molecules of approximately 17 000 daltons. The peak eluting at Vo contained material of molecular weight 66 000 daltons which also bound 125I-anti-IgE, but had only 61% of the activity of the 'major peak' by RAST inhibition. By isoelectric focusing and RRIE of fractions obtained by chromatofocusing with polybuffer exchanger 94, the 'major peak' was associated with multiple bands with a pI range of 3.5-5.5. These results indicate that the major allergens from C. lewisi are a group of closely related acidic peptides.

Allergens↗
PubMed1984

Disodium cromoglycate relieves symptoms in symptomatic young smokers. A double blind placebo controlled trial.

We have undertaken a double blind placebo controlled study of disodium cromoglycate (DSCG) in 32 symptomatic young smokers. These individuals had regular morning cough and sputum with the sensation of wheeze, but were not asthmatics as determined by the usual criteria. No significant changes were observed in sputum or serum eosinophils, IgE, IgG or IgA, or sputum histamine concentrations following the administration, for 3 weeks, of either DSCG (20 mg) or placebo, thrice daily. However DSCG, but not placebo, was associated with significant improvements in the symptoms of cough (P less than 0.01) and wheezing (P less than 0.025). We suggest that these changes may be due to an effect of DSCG on the irritant receptor mediated reflex response to cigarette smoke rather than the involvement of mast cells.

Adolescent↗
PubMed1984

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↗
PubMed1984

Human granulocyte/pollen-binding protein. Recognition and identification as transferrin.

Normal human serum was found to contain a heat-stable protein which promoted the binding of granulocytes to timothy grass pollen (granulocyte/pollen-binding protein [GPBP]). GPBP was purified by gel filtration, anion exchange, and affinity chromatography. Virtually all of the granulocyte/pollen-binding activity was associated with a beta-1-protein having a molecular mass of approximately 77,000 D and an isoelectric point of between 5.5 and 6.1. By immunoelectrophoresis and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the protein was identified as transferrin. Monospecific antisera raised against either GPBP or transferrin removed biological activity from GPBP preparations, and GPBP and transferrin gave lines of identity with these two antisera. The apparent heterogeneity in the molecular size and charge of GPBP observed during progressive purification was minimal when GPBP was saturated with ferric ions before the separation procedures. These experiments indicate that granulocyte/pollen binding is a hitherto unrecognized property of transferrin which appears to be unrelated to iron transport and raises the possibility that transferrin might have a physiological role in the removal of certain organic matter.

Carrier Proteins↗
PubMed1984

Preferential generation of leukotriene C4 by human eosinophils.

The leukotriene generating capacities of ionophore stimulated human eosinophils and neutrophils were compared using specific radioimmunoassays for LTB4 and LTC4. Mixed granulocyte preparations (neutrophils and eosinophils) produced both LTB4 and LTC4 in a time-dependent fashion which was maximal at 10 and 15 min, respectively. Following the separation of eosinophils (greater than 75%) and neutrophils (greater than 90%) by metrizamide gradients, LTC4 production was predominantly from eosinophils, whereas neutrophils were the principal source of LTB4. The concentrations of leukotrienes produced by the eosinophil and neutrophil rich cell preparations were directly proportional to the concentration of ionophore. Following purification of eosinophil derived products by RP-HPLC the LTC4 immunoreactivity corresponded to the elution profile of a synthetic LTC4 marker. Furthermore, in 32 atopic subjects (21 bronchial asthmatics and 11 non-asthmatics) the amounts of LTC4 produced by unseparated leucocytes were directly proportional to the percentage of eosinophils in the total cell suspension. Preferential generation of LTB4 by neutrophils was also demonstrated by immunoreactivity of ionophore stimulated supernatants subjected to RP-HPLC, as well as by its characteristic u.v. absorbance and GC-MS profile and the ability to promote directional neutrophil locomotion (chemotaxis). These experiments support the concept that eosinophils accumulate in tissues partly as a result of the response to neutrophil derived LTB4, and that these cells contribute to the production of sulphidopeptide leukotrienes with subsequent amplification of the acute allergic response.

Adolescent↗
PubMed1984

Chemotactic factor-induced enhancement of the binding of human immunoglobulin classes and subclasses to neutrophils and eosinophils.

Sheep erythrocytes (E) coated with either human IgG1, IgG2, IgG3 or IgG4 myeloma proteins formed rosettes with human neutrophils and eosinophils. Prior incubation with the chemotactic agents f-met-leu-phe or leukotriene B4 enhanced neutrophil and eosinophil E-IgG1 rosettes in a time- and dose-dependent fashion. There were comparable increases in neutrophil and eosinophil f-met-leu-phe-induced rosettes with either E-IgG1, E-IgG2, E-IgG3 or E-IgG4 whereas this agent did not appear to influence E-IgA1, E-IgD, E-IgM or E-IgE binding to these granulocytes. These studies indicate that human neutrophil and eosinophil IgG (Fc) receptors are enhanced by chemotactic agents in a similar way to that previously described for complement receptors.

Eosinophils↗