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Biomedical subjects

A B Kay

Publications and source records attributed to A B Kay.

At least 325 records · Page 18Linked to original sources
PubMed1984

Sputum leukotrienes in obstructive airways diseases.

Sputum samples from patients with bronchial asthma, chronic bronchitis and cystic fibrosis were examined for the presence of leukotrienes B4, C4 and D4. Following ethanol extraction and purification on Amberlite XAD-8, leukotrienes were identified by high pressure liquid chromatography (HPLC) using the appropriate markers. Fractions from HLPC were also tested for biological activity using both the Boyden chemotaxis assay and FPL 55712 inhibitable contraction of the isolated guinea-pig ileum. LTB4 was detected in the HPLC fractionated sputa from bronchial asthma (seven of seven), chronic bronchitis (four of four) and cystic fibrosis (four of four). In contrast, bioassay on the guinea-pig ileum failed to detect LTC4 or LTD4 in 17 asthmatic sputa, although they were detected in one of five bronchitics and 16 of 25 patients with cystic fibrosis. The activity in eight of these cystic fibrosis sputa was further characterized by HPLC and shown to be LTC4 and/or LTD4. Sputum from 11 of 17 asthmatics, four of 25 patients with cystic fibrosis and two of five bronchitics contained an anaphylatoxin like substance. The majority of sputum samples containing LTB4 also possessed an activity with physical and biological characteristics of the 5(S), 12(S), 6-trans LTB4 isomer. These studies indicate that lipoxygenase products of arachidonic acid metabolism are present in the sputum in various forms of obstructive airways disease. The failure to detect the 'SRS-A' leukotrienes in sputum from bronchial asthma may be attributable to either losses during extraction, the insensitivity of the assay procedure or to more rapid catabolism of LTC4 and LTD4 by bronchial secretions in asthma than in cystic fibrosis.

Asthma↗
PubMed1984

Receptor associated defects of cultured monocytes in bronchial carcinoma.

Using peripheral blood monocytes from individuals with bronchial carcinoma (BC) we have measured changes, over an 8 day culture period, in monocyte/macrophage complement (C3b) and IgG (Fc) rosettes, chemotactic factor (CF)-induced enhancement of C3b and IgG (Fc) rosettes, and the phagocytic index (PI) for yeast particles. The same measurements were made on monocyte/macrophages from individuals with non-malignant respiratory diseases (NMRD) and healthy controls (HC). Following 8 days of culture there was a significant increase in C3b rosettes, IgG (Fc) rosettes and the PI in NMRD and HC. In contrast there was no significant increase in C3b rosettes in BC. The PI increased in BC, but on day 8 was still significantly less than control monocytes/macrophages. IgG (Fc) rosettes increased in BC following culture to a similar degree as that observed with NMRD and HC. In addition, there were no differences between BC and HC in CF-induced enhancement of IgG (Fc) rosettes at either day 0 or day 8 of culture whereas complement receptor enhancement in BC was impaired both at the beginning and end of the 8 day culture period. These results indicate that in advanced BC there is an abnormality in the expression of monocyte/macrophage complement receptors (which is not readily demonstrable for IgG [Fc]receptors) and that the defect persists following an 8 day culture period.

Adult↗
PubMed1983

Complement receptor enhancement as evidence of neutrophil activation after exercise-induced asthma.

To determine whether neutrophils are activated after exercise-induced asthma, increases in neutrophil complement receptor numbers (complement receptor enhancement) were measured by the rosette technique. In twelve asthmatic patients there was a time-dependent rise in complement receptor numbers for up to 60 min after treadmill exercise. This enhancement of complement receptors was preceded by a rise in plasma neutrophil chemotactic activity and a reduction in the peak expiratory flow rate. These changes could be inhibited by prior administration of disodium cromoglycate. The changes were not observed in seven asthmatic patients in whom asthma was not induced by an identical exercise task. Complement receptor enhancement was also observed in vitro when partially purified neutrophil chemotactic activity from a patient with exercise-induced asthma was incubated with normal neutrophils. These findings suggest that inflammatory cells are activated after exercise-induced asthma, possibly as a result of the release of neutrophil chemotactic activity and other mast-cell-associated mediators.

Asthma↗
PubMed1983

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↗
PubMed1983

The link between exercise, respiratory heat exchange, and the mast cell in bronchial asthma.

There are two apparently conflicting theories on the pathogenesis of exercise-induced asthma. One view is that exercise-induced asthma is directly related to respiratory heat exchange and that mast cells are not involved. The other theory explains exercise-induced asthma on the basis of a temperature-independent release of mast-cell mediators. A theory is put forward here that airway cooling in asthmatic subjects during exercise leads directly to mast-cell degranulation and that this explains the association between exercise, respiratory heat exchange, and mediator release.

Asthma↗
PubMed1983

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↗
PubMed1983

Immunologic release of neutrophil chemotactic activity from human lung tissue.

The release of heat-stable neutrophil chemotactic activity (NCA) has been detected after challenge of isolated human lung tissue with anti-IgE. The major NCA released (NCAL) had similar physicochemical properties to the NCA detected in the circulation of asthmatic subjects after bronchial challenge with specific antigen (NCAAG). NCAL and NCAAG (1) had molecular weights of approximately 600,000 daltons as estimated by Sephacryl S-300 gel-filtration chromatography; (2) both eluted from DEAE-Sephacel (pH 7.8) between 0.1 and 0.2 molar NaCl; (3) had isoelectric points of between 6.5 and 6.8 as determined by chromatofocusing on Polybuffer Exchanger 94. In contrast to NCAAG, lung-derived neutrophil chemotactic activity appeared to be more heterogeneous after gel-filtration and anion-exchange chromatography. The release of NCA was complete by 15 min and there was no evidence of further release up to 12 hr. These observations indicate that high-molecular-weight NCA released from human lung tissue has similar properties to NCAAG and would support the view that NCAAG originates from lung tissue after antigen bronchial challenge in asthmatic subjects.

Chemotactic Factors↗
PubMed1983

Immediate-type skin reactivity to extracts of the 'green nimitti' midge, (Cladotanytarsus lewisi), and other chironomids in asthmatic subjects in the Sudan and Egypt.

Skin 'prick' tests with an extract of the 'green nimitti' midge, Cladotanytarsus lewisi (Freeman), a potent airborne allergen associated with asthma and rhinitis in the Khartoum area, were undertaken on asthmatic subjects in several localities in the Sudan and Egypt in order to provide further information on the extent of this allergic problem. In the Sudan skin-test-positive individuals were identified in the Khartoum area, Kosti, Sennar, Wad Medani, Shendi and Atbara, and in Egypt at Aswan, Luxor and Qena. A number of asthmatic individuals giving a positive reaction to C. lewisi were also tested with extracts of seven sub-dominant species of Nilotic Chironomidae. There appeared to be a limited degree of cross-reactivity with these species, particularly Dicrotendipes fusconotatus (Kieffer), Procladius noctivagus (Kieffer) and Conchapelopia cygnus (Kieffer). The numbers of C. lewisi sensitive subjects giving positive skin-tests to these other species were ten out of 20, 12 out of 28 and 12 out of 29 respectively. In contrast, only five out of 31 reacted to Paracladopelma graminicolor (Kieffer), five out of 24 to Cladotanytarsus pseudomancus (Goetghebuer), three out of 32 to Nanocladius vitellinus (Kieffer) and two out of 28 to Cryptochironomus neonilicola (Freeman). These results indicate that Cladotanytarsus lewisi is a major source of chironomid allergen(s) in these asthmatic subjects and that hypersensitivity to C. lewisi is probably far more widespread than originally envisaged.

Animals↗
PubMed1983

Responses of human skin to intradermal injection of leukotrienes C4, D4 and B4.

The ability of intradermally injected leukotrienes C4 (LTC4), LTD4 and LTB4 to produce inflammatory changes in human skin alone and in combination with prostaglandin E2 (PGE2) has been investigated. LTC4 and D4 (0.012-0.38 nmol) caused dose-related erythema and wealing. No evidence of synergism between PGE2 and LTC4 or LTD4 was detected, although only single dose combinations were studied. LTB4 (0.15-1.5 nmol) caused areas of induration which persisted for more than 4 h and which showed perivascular neutrophil infiltrates on histological examination. Only slight synergism between PGE2 and LTB4 was found. It was concluded that these pro-inflammatory properties of LTC4, LTD4 and LTB4 are consistent with their proposed roles as mediators of inflammation in the skin and other tissues.

Adult↗
PubMed1983

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↗
PubMed1983

Defective chemotactic factor-induced monocyte complement receptor enhancement in lung cancer.

We have studied monocyte complement (C3b) rosettes, and chemotactic factor (CF)-induced enhancement of rosettes, in 37 patients with bronchial carcinoma (BC), and compared these findings to those obtained from nine age and sex matched patients with non-malignant respiratory disease (NMRD), and 38 normal healthy controls (HC). No differences in monocyte C3b rosettes were found when BC was compared with NMRD or HC. In contrast, there was a highly significant inhibition of CF-induced complement receptor enhancement (CRE) in monocytes from patients with extensive or metastatic BC compared to NMRD or HC. These differences increased with time of incubation and concentrations of CF, and occurred when either f-met-leu-phe, leukotriene B4 (LTB4) or casein were used as the enhancing agent. The defect in monocyte CRE was related to the stage of the disease (with the rank order, metastatic greater than confined to chest greater than localized tumour) but not to the pathohistological type. A similar impairment in CRE was observed when neutrophils from BC were compared to HC. These experiments suggest that, in patients with advanced bronchial carcinoma, monocyte and neutrophil C3b receptors have impaired responsiveness to chemotactic factors.

Adult↗
PubMed1983

Enhancement of neutrophil- and eosinophil-mediated complement-dependent killing of schistosomula of Schistosoma mansoni in vitro by leukotriene B4.

We have studied the ability of leukotrienes and other lipoxygenase products of arachidonic acid (AA) to influence complement-dependent killing of schistosomula of Schistosoma mansoni in vitro by human neutrophils or eosinophils. These lipid mediators, which included LTB4, LTC4, LTD4, 5-HETE and 5-HPETE, had no apparent effect, by themselves, on schistosomular motility or viability. However, in the presence of granulocytes and fresh serum (as a source of complement) LTB4 (but not LTC4, LTD4, 5-HETE or 5-HPETE) enhanced neutrophil- and (to a much lesser extent) eosinophil mediated, complement-dependent killing. These effects varied with the concentration of LTB4, the dilution of complement and time of incubation. The percentage of LTB4-induced enhancement obtained with neutrophils was greater than that observed with eosinophils (although the latter were obtained from patients with helminthic parasitic disease). The synthetic bacterial analogue f-Met-Leu-Phe, also known to amplify complement associated granulocyte events, was comparable to LTB4 in its ability to enhance neutrophil- and eosinophil-mediated, complement-dependent killing of schistosomula. These results indicate that LTB4, which is released in mast cell associated reactions and promotes cell locomotion and enhancement of complement receptors in vitro, increases neutrophil- and eosinophil-mediated, complement-dependent damage of schistosomula, possibly through enhancement of C3b receptors and that this may be an important amplification mechanism in IgE related immunity to migrating helminthic larvae.

Arachidonic Acids↗
PubMed1983

Mediators of hypersensitivity in exercise-induced asthma.

Neutrophil chemotactic factor (NCF) is a slightly acidic macromolecule which is released into the circulation of asthmatic individuals following an exercise task. Its appearance was basophil-independent, accompanied the development of airflow obstruction and its release could be inhibited by administration of disodium cromoglycate. There was no elaboration of NCF after isocapnic hyperventilation with cold air, although the same asthmatics produced NCF following treadmill exercise. Finally, NCF was also released during exercise-induced late asthmatic reactions, as in antigen-induced late responses.

Asthma↗