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Biomedical subjects

A B Kay

Publications and source records attributed to A B Kay.

At least 271 records · Page 15Linked to original sources
PubMed1987

A monocyte function test (complement receptor enhancement) to assess the extent of bronchial carcinoma.

A monocyte function test (complement receptor enhancement) was undertaken on 45 patients with suspected bronchial carcinoma in whom this diagnosis was subsequently substantiated. In 38 (84%) complement receptor enhancement was below a range of values previously established for monocytes from 48 healthy control subjects and from 12 patients with non-malignant respiratory diseases. It was found that all 38 patients with reduced complement receptor enhancement had either local or widespread metastases, as determined by the chest radiograph and a variable combination of chest tomography, liver, bone and brain scanning, computed tomography, fibreoptic bronchoscopy, bone marrow aspiration, liver function tests, mediastinoscopy, and surgical assessment, where appropriate. By contrast, at the time of presentation there was no clear relationship between abnormal values in several conventional screening haematological or biochemical tests and the stage of the tumour. These results suggest that complement receptor enhancement might serve as a useful pointer to the extent of the disease, since low values were associated with extension within the chest and very low values were found with widespread metastases.

Adult↗
PubMed1987

Allergen-induced recruitment of bronchoalveolar helper (OKT4) and suppressor (OKT8) T-cells in asthma. Relative increases in OKT8 cells in single early responders compared with those in late-phase responders.

We measured the numbers of helper (OKT4) and suppressor (OKT8) T-cells in blood and bronchoalveolar lavage (BAL) in 6 patients who developed single early reactions after allergen inhalational challenge and in 6 subjects who developed dual (early- and late-phase) responses. The asthmatics were lavaged twice. On the first occasion, they inhaled the diluent control (Dil) solution, and after an interval of at least 7 days, allergen (Ag) inhalational challenge was undertaken. Significant differences were observed in the single early responders (SER) only. For instance, when the results obtained on the Dil day were compared with those obtained on the Ag day, there was a significant (p less than 0.05) increase in the percentage of OKT4 cells in the blood of SER. Also in the BAL of SER there was a significant (p less than 0.05) decrease in the percentage of OKT4 and an increase (p less than 0.05) in the percentage and absolute numbers of OKT8 cells. Furthermore, the percentage of OKT4 was highly significantly (p less than 0.005) lower on the Ag day in the SER than on the Ag day in the late-phase responders (LPR). The OKT4/OKT8 ratio was significantly (p less than 0.05) lower on the Ag day than on the Dil day in BAL from SER and highly significantly decreased (p less than 0.001) when results on the Ag day in the SER were compared with those on the Ag day in the LPR. These findings raise the possibility that mobilization of suppressor T-cells into the lung after allergen-induced single early reactions in asthma might be associated with the prevention of a subsequent late-phase response.

Adult↗
PubMed1987

Neutrophil chemotactic activity in acute severe asthma (status asthmaticus).

Serum neutrophil chemotactic activity (NCA) was measured in patients with acute severe asthma (status asthmaticus) and compared with that in control subjects (mild asthma, stable chronic irreversible air-flow obstruction, allergic rhinitis, noninfective lung conditions, or asymptomatic). There were 9 subjects in each group. Statistically significant elevations (p less than 0.002) in NCA were detected in acute severe asthma when compared with each control group. Serial measurements of NCA were subsequently undertaken in 12 patients with acute asthma, at the time of admission to hospital, after 3 days of treatment, and on discharge after approximately 7 days. A highly significant (p less than 0.001) reduction in serum NCA activity on Day 7 compared with that on Day 0 was observed, and this correlated inversely with the improvement in lung function (PEFR). Gel filtration by fast protein liquid chromatography (FPLC) using Superose 6 prep grade (6PG) indicated that NCA in acute severe asthma was heterogeneous and consisted of at least 4 peaks of activity associated with proteins with molecular weights of approximately 800, 600, 150, and less than 20 kD. The 800- and 150-kD peaks were also observed in control subjects, but to a lesser degree. The 600- and less than 20-kD activities were virtually confined to the patients with acute severe asthma. FPLC chromatofocusing of the 600-MW peak from the acute asthmatics, using a Mono-P column and a pH gradient from 8.3 to 5.0, revealed considerable activity in fractions eluting between pH 6.0 and 7.0, which was not observed in the normal control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Provoked asthma and mast cells.

There is now very substantial evidence to implicate mediators in the pathogenesis of asthma during both the early- and late-phase response. It seems likely that mast cells are activated since histamine was detected in early- and late-phase allergen- and exercise-induced asthma. On the other hand, the origin of NCA is still in some doubt, and the possibility exists that it may be derived from other cell types. Furthermore, there is no firm evidence that the mast cell is directly involved in pathogenesis and some evidence that it may have a secondary or amplifying role. There is an urgent need for further details of other mast-cell-associated mediators such as prostaglandins and leukotrienes. Measurements in the blood have the obvious disadvantage of only indirectly reflecting events in the lung. It seems likely that more invasive procedures such as fiberoptic bronchoscopy will yield more critical information regarding mast cells and their mediators in early- and late-phase reactions, as well as the effects of selective drugs and the role of other cell types.

Asthma↗
PubMed1987

Cloned human T lymphocytes reactive with Dermatophagoides farinae (house dust mite): a comparison of T- and B-cell antigen recognition.

In this report, T-cell and B-cell recognition of the house dust mite Dermatophagoides farinae (D. far.) is compared. Nitrocellulose immunoblots of polyacrylamide gel electrophoresis (SDS-PAGE)-fractionated D. far. were added to proliferation assays to map the antigen specificity of cloned human helper T cells and a long-term line induced with D. far. T-cell recognition was of a polypeptide of molecular weight 9000-13,000, that migrates with the serologically defined allergen Der fII (12,500 MW). Since the cloned T cells, unlike the polyclonal response, failed to respond to Dermatophagoides pteronyssinus (D. pter.), this suggests that they recognize a species-specific epitope. In contrast, analysis of the B-cell response using Western blotting demonstrated that, in addition to Der fII, antibodies reactive with the major allergens Der fI (26,000 MW) and Der fIII (29,000 MW) were present in the serum. Similar specificities were seen in the antibody response to D. pter., and while it has been reported that the B-cell response to D. far. and D. pter. are predominantly cross-reactive, our observations suggest that species-specific CD4-positive T cells are present in the overall cellular response to D. far.

Adult↗
PubMed1987

Leukotriene B4 generation by human neutrophils following IgG-dependent stimulation.

It has previously been shown that human neutrophils generate substantial quantities of LTB4 when stimulated with the calcium ionophore, A23187, or with unopsonized zymosan. We now report that normal human neutrophils produced substantial quantities of LTB4 (measured by radioimmunoassay and validated by RP-HPLC) when incubated with large non-phagocytosable IgG-coated beads (Sepharose 4B). LTB4 was identified in both the extra and intracellular compartments. The production of LTB4 was dependent upon the number of IgG-coated particles and the concentration of IgG bound to the beads. Release was maximal after a 15-30 min incubation time and was enhanced by prior activation of the neutrophils with the synthetic bacterial product f-met-leu-phe. Comparable LTB4 production was also observed when neutrophils were incubated with antigen (Aspergillus fumigatus)-coated beads sensitized with purified IgG obtained from the sera of patients with allergic bronchopulmonary aspergillosis. These results suggest a further mechanism by which neutrophils may be activated to produce inflammatory mediators in the tissues.

Antigens, Fungal↗
PubMed1987

Chemotactic factor-induced low density neutrophils express enhanced complement (CR1 and CR3) receptors and increased complement-dependent cytotoxicity.

We have studied chemotactic factor-induced 'complement receptor enhancement' to determine whether changes in receptor expression and complement-dependent cytotoxicity were associated with alterations in cell density. Ficoll-Paque separated normal human neutrophils (greater than 90%), when further fractionated on discontinuous metrizamide (MTZ) gradients (18, 19, 20, 21, 22, 23% MTZ), consistently gave two major bands at the 20/21% and 21/22% interfaces. Incubation with the synthetic chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (fMLP (10(-8) M)), converted virtually all neutrophils to low density cells sedimenting on MTZ at the 18/19% and 19/20% interfaces. There was a time-dependent change of density after fMLP-stimulation which was maximal at 30 min, with cells reverting towards normal density by 60 min. Control unstimulated cells did not alter their density at any of the time points examined. Activated, low density neutrophils had increased expression of CR1 and CR3 (as shown by flow cytometry and the uptake of 125I-F(ab')2 monoclonal anti-CR1 antibody (E11)). These cells also showed enhanced cytotoxic capacity in vitro for helminthic targets (schistosomula of Schistosoma mansoni) opsonized with autologous complement. There were highly significant correlations between cell density and anti-CR1 uptake (P less than 0.001), and between schistosomular killing and change in density (P less than 0.001). Increased CR1 expression also correlated with enhanced helminthicidal capacity of neutrophils (P less than 0.001). Complement dependent cytotoxicity was partially reduced after treatment of cells with anti-human CR1 and/or CR3 antibodies, but only in the presence of a second antibody. These findings indicate that chemotactic factor-induced complement receptor enhancement of human neutrophils is associated with a decrease in cell density and increased complement-dependent cytotoxicity (CTX).

Animals↗
PubMed1987

Release of leukotrienes during rapid expulsion of Trichinella spiralis from immune rats.

Rapid expulsion of the nematode Trichinella spiralis from immune rats is associated with an increase in volume of intestinal exudate and the presence of large numbers of tissue mucosal mast cells (MMC) and eosinophils. We have measured the concentrations of leukotrienes (LT) C4 (LTC4) and B4 (LTB4) in gut perfusates and mucosal homogenates at 30 min, 1, 3, 6 and 20 hr after challenge with larvae. Leukotrienes were identified by radioimmunoassay (RIA) combined with reverse-phase high-pressure liquid chromatography (RP-HPLC). There were significant elevations at 30 min and 1 hr in the concentrations of LTC4 in the perfusates from the gut of challenged immune rats compared to controls (infected unchallenged and uninfected naive rats). Similar increases in immunoreactive LTC4 and LTB4 were observed in mucosal homogenates from the gut of immune challenged animals. A second peak of LTB4 was also observed at 20 hr in both immune and naive challenged rats. There were also elevations in serum concentration of the MMC-associated specific serine protease, rat mast cell protease II (RMCPII). Since LTC4 causes smooth muscle contraction, increased vascular permeability and stimulation of mucus hypersecretion, and LTB4 recruits and activates inflammatory cells, leukotrienes may participate in the process of rapid expulsion of T. spiralis.

Animals↗
PubMed1986

Enteral and systemic release of leukotrienes during anaphylaxis of Nippostrongylus brasiliensis-primed rats.

Rats with acquired immunity to the intestinal nematode Nippostrongylus brasiliensis develop anaphylaxis after i.v. challenge with an extract of worm antigen, with the small intestine being the primary shock organ. In the present study we have shown that these events were associated with significant elevations in intestinal and plasma concentrations of leukotrienes LTB4 and LTC4. The changes were observed in immune rats over 10-, 30-, and 60-min intervals after antigen challenge but were absent in control animals. These lipid mediators were identified both in the perfusate of the gut lumen, which contained large quantities of mucus, and in homogenates of intestinal tissue. In addition, significant elevations in the concentrations of plasma LTB4 and LTC4 were detected in immune challenged rats but not in controls. Leukotrienes were identified by radioimmunoassay and validated by reverse-phase high-performance liquid chromatography (RP-HPLC). RP-HPLC analysis of SRS-A leukotrienes in immune challenged rats indicated that LTC4 was the predominant sulfidopeptide leukotriene at 10 min, with almost complete biodegradation to LTD4 and LTE4 within 30 min. Infected rats also had significant increases in the numbers of intestinal mucosal mast cells (MMC) and eosinophils. Evidence of MMC activation during anaphylaxis was obtained by showing significant elevations of intestinal and systemic concentrations of their exclusive serine enzyme, rat mast cell proteinase II (RMCPII). Thus, the release of substantial amounts of leukotrienes in the gut and plasma of N. brasiliensis-primed rats after interaction with worm antigens suggests that these potent mediators may play an important role in allergic-type hypersensitivity known to occur during immune reactions against parasitic helminths.

Anaphylaxis↗
PubMed1986

Morphological and secretory properties of bronchoalveolar lavage mast cells in respiratory diseases.

We have studied various functional and morphological characteristics of mast cells obtained in bronchoalveolar lavage from fifty-two patients with several lung diseases. The percentage of mast cells ranged from 0.04 to 0.6% (bronchial carcinoma), 0.05-0.3% (sarcoidosis), 0.06-0.25% (asthma), 0.04-1.8% (miscellaneous) and 0.02-0.04% (normals). There were no significant differences in the mast cell counts between the disease groups. Lung mast cells exhibited heterogeneity of size, shape and intensity of staining. Cells from thirty-seven subjects were further studied for total histamine content and histamine release using various secretagogues. There was a significant correlation (P less than 0.001) between the histamine content of the total lavage cell population and mast cell counts. The calculated mean histamine content per mast cell was 6.35 pg. Histamine was released in a dose-dependent fashion after stimulation with anti-IgE, calcium ionophore and phorbol myristate acetate with a time course of histamine release characteristic of the mast cell. Unlike peripheral blood basophils, no release was observed following incubation with f-met-leu-phe (10(-6)-10(-8) M) and neither cell type released histamine following incubation with 48/80 (10 micrograms/ml). Inhibition of anti-IgE-induced histamine release was obtained following pre-incubation with salbutamol (10(-4)-10(-6) M). These studies indicate that bronchoalveolar lavage is a suitable model for the study of human lung mast cells.

Adult↗
PubMed1986

The requirements for transferrin-dependent adherence of human granulocytes to pollen grains.

Human granulocyte/pollen binding protein (GPBP), previously identified as serum transferrin, promoted prolonged firm adherence of neutrophils to Timothy grass pollen. Some characteristics of this adherence reaction are reported. GPBP-induced binding was time-, temperature- and concentration-dependent. Maximal adherence was observed by 2 h and was only slightly decreased at 18 h. The optimal temperature for adherence was 37 degrees C. Concentrations of GPBP as low as 1.25 microgram/ml gave significantly greater binding than the albumin or lactoferrin control. Eosinophils, monocytes and lymphocytes did not appear to participate in GPBP-induced pollen binding reactions at concentrations up to 300 micrograms/ml. In the presence of GPBP, neutrophils adhered to a range of grass, weed and tree pollens. These included timothy, meadow, false oat, rye, giant and short ragweed, plantain, silver birch and ash. GPBP did not facilitate the adherence of granulocytes to inert particles of similar size such as Sephadex beads and agarose. The adherence was Mg++- but not Ca++-dependent and was not inhibited by a monoclonal antibody to the transferrin receptor (OKT9). Transferrin/GPBP did not bind to either neutrophils or pollen grains. A purified commercial transferrin reacted in all respects like GPBP in these pollen binding studies. These observations indicate that GPBP/transferrin-induced adherence of granulocytes to pollen grains is a hitherto unrecognized property of transferrin which appears unrelated to iron transport or the conventional transferrin receptor.

Antibodies, Monoclonal↗
PubMed1986

Persistence of hemoglobin allergenicity and antigenicity during metamorphosis of Chironomidae (Insecta: Diptera).

Chironomid hemoglobins are potent allergens. The allergenic and antigenic activities of these hemoglobins are studied with the help of RAST, RAST inhibition and double immunodiffusion. Human as well as rabbit antisera were used. It was shown that hemoglobins are the main antigenic/allergenic components in extracts of Camptochironomus tentans larvae. Furthermore, immunological cross-reactivity among larvae, pupae and adult midges of this species are shown to be due to the existence of hemoglobin antigenic determinants in all developmental stages of this insect.

Animals↗
PubMed1986

Enhancement of leukocyte cytotoxicity after exercise-induced asthma.

We have previously shown that there were elevations of neutrophil chemotactic activity (NCA) and increases in the percentages of neutrophil and monocyte complement rosettes after exercise-induced asthma (EIA). These observations suggested that leukocyte activation may occur after EIA, possibly as a result of the release of mast-cell-associated mediators. In the present study, we have attempted to establish whether neutrophils and monocytes are functionally altered after EIA as assessed by changes in their cytotoxic capacity. Cytotoxicity was assessed by a direct visual killing assay using opsonized (complement-coated) schistosomula of Schistosoma mansoni as target organisms. Neutrophils and mononuclear cells obtained from 8 patients after exercise-induced asthma (EIA+ve) had increased cytotoxicity for opsonized schistosomula for as long as 60 min after exercise. These changes were preceded by elevations in the concentrations of serum high molecular weight NCA (which were maximal at 10 min after exercise). In asthmatic patients who did not develop exercise-induced asthma (EIA-ve), no significant increases in neutrophil or mononuclear cell killing of schistosomula, or serum NCA concentrations, were observed. There was a highly significant correlation (p less than 0.001) between the reduction in FEV1 and the increases in neutrophil cytotoxicity. In 5 EIA+ve patients, administration of disodium cromoglycate (cromolyn) prior to the exercise task inhibited both the enhancement in neutrophil and mononuclear cell cytotoxicity, as well as the elevations in circulating NCA and the reductions in FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Platelet-activating factor. A potent chemotactic and chemokinetic factor for human eosinophils.

Platelet-activating factor (PAF-acether), an inflammatory mediator with a wide range of biological activities including neutrophil aggregation and chemotaxis, was studied for its effect on human eosinophil locomotion (chemotaxis and chemokinesis). Human eosinophils (25-95% purity) were obtained from donors with a variety of diseases associated with hypereosinophilia. PAF-acether elicited directional locomotion of eosinophils, in a time- and dose-dependent fashion, at concentrations from 10(-5) to 10(-8) M; lyso-PAF had minimal activity over the same dose range. Compared with PAF-acether, the eosinophil locomotory responsiveness of leukotriene B4 (LTB4), histamine, and the valyl- and alanyl-eosinophil chemotactic factor of anaphylaxis (ECF-A) tetrapeptides was negligible. Conversely, neutrophil responsiveness to PAF-acether (optimum 10(-6) M) was comparable in effect to LTB4 (optimum dose 10(-8) M). It was shown that PAF-acether elicited both chemotaxis and chemokinesis of eosinophils. Comparison of normal density and light density eosinophils revealed no qualitative difference in the response to PAF-acether and the other chemoattractants, although the light density cells seemed to demonstrate a greater degree of locomotion to PAF-acether and LTB4. Thus, PAF-acether appears to be a potent eosinophilotactic agent which may play a role in inflammatory reactions characterized by eosinophil infiltration.

Cell Movement↗