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Biomedical subjects

A B Kay

Publications and source records attributed to A B Kay.

At least 379 records · Page 21Linked to original sources
PubMed1979

Metabolic studies on the uptake of [14C]-histidine and [14C]-histamine and histamine synthesis by guinea-pig basophils, in vitro.

The uptake of [14C]-histidine and [14C]-histamine and the conversion of [14C]-histidine to [14C]-histamine was measured in suspensions of guinea-pig bone marrow cells rich in basophils. When comparable amounts of labelled histidine or histamine were added to equal numbers of basophils, the uptake of histidine was approximately forty-five times greater than that of histamine. Purified eosinophils, neutrophils and mononuclear cells incorporated only a small proportion of [14C]-histidine when compared to the basophil; [14C]-histamine uptake by all these cell types was virtually negligible. Histidine uptake and the amount of histamine formed de novo was directly related to the number of basophils, the time of incubation and the substrate concentration. Histidine uptake was decreased by agents which inhibit glycolysis, oxidative phosphorylation, Na + - K + -dependent ATPase, protein synthesis and RNA synthesis. Inhibition was demonstrable in a dose-dependent fashion and at concentrations which had no apparent effect on cell viability. Inhibitors of DNA synthesis, and of microtubule function, had no influence on histidine uptake. Cytochalasin B, an inhibitor of microfilament function, also decreased histidine uptake but only at concentrations previously showen to affect hexose transport. None of the agents tested affected the uptake of [14C]-histamine or the amounts of new histamine formed from the histidine that had been incorporated. These studies suggest that histidine is preferentially incorporated into the basophil; that the uptake depends on the integrity of a number of metabolic pathways, but that once the histidine is taken up these requirements do not apply to the formation of new histamine. In contrast, histamine appeared to diffuse passively, and in relatively small amounts, into all the cell types tested.

Animals↗
PubMed1979

Leucoattractants enhance complement receptors on human phagocytic cells.

The N-formyl-methionyl peptides, F-Met-Leu-Phe, F-Met-Met-Phe and F-Met-Phe, when tested at differing concentrations, proportionally increased both in vitro cell locomotion and the expression of surface receptors for C3b on human peripheral blood neutrophils and monocytes. In contrast, the unformylated peptides, Met-Leu-Phe and Me-Met-Phe, had no chemotactic or complement receptor-enhancing activity at comparable concentrations. Casein and supernatants from human lymphocytes (cultured either in the presence or absence of phytohaemagglutinin), also recognized as chemotactic agents for human neutrophils and monocytes, enhanced C3b receptors on these cells in a similar dose-dependent fashion. These data, taken together with our previous findings with the eosinophil, suggest that in addition to promoting cell locomotion a further biological function of leucoattractants may be their capacity to render complement receptors more freely available thereby increasing the magnitude of adhesion of phagocytic cells to opsonized particles.

Caseins↗
PubMed1978

Variations in chemical mediators of hypersensitivity in the sputum of chronic bronchitics: correlation with peak expiratory flow.

Histamine, slow reacting substance of anaphylaxis (S.R.S.-A), IgE, eosinophils, and an eosinophil-associated enzyme, arylsulphatase IIB, were measured in sputum from 11 chronic bronchitics at weekly intervals for 6 weeks. The agents were detected in all patients at some time and in the majority at all times throughout the study period although their concentrations varied. The variations in histamine, S.R.S.-A and IgE gave a highly significant negative correlation with the peak expiratory flow-rate, suggesting that chemical mediators of hypersensitivity may play some role in the pathogenesis of airways obstruction in this disease. Sputum eosinophilia correlated with the arylsulphatase IIB concentration but not with the peak expiratory flow-rate, IgE, histamine, or S.R.S.-A, a finding consistent with the view that eosinophils accumulate at the site of type I reactions after the peak of mediator release.

Bronchitis↗
PubMed1978

Widespread IgE-mediated hypersensitivity in Northern Sudan to the chironomid Cladotanytarsus lewisi ('green nimitti').

Hypersensitivity to Chironomidae (non-biting midges) has been a problem in Northern Sudan since about 1927 and is probably due to the working of dams which have produced lake-like conditions on parts of the Blue and main Niles where breeding has evidently increased. Studies were undertaken to determine whether this hypersensitivity is mediated by IgE. Sixteen Sudanese, with bronchial asthma associated with exposure to the chironomid, Cladotanytarsus lewisi ('green nimitti'), were investigated. All patients gave a positive immediate-type skin reaction to an extract of the midge and the majority had markedly elevated concentrations of circulating IgE. Serum from all patients passively sensitized human lung fragments in vitro for the release of histamine and slow-reacting substance of anaphylaxis by the 'nimitti' antigen. This tissue-sensitizing activity could be removed by immunoabsorption with an anti-IgE. These results indicate that this widespread and important hypersensitivity in the Sudan is IgE-mediated and thus may potentially be treated by desensitization.

Adolescent↗
PubMed1978

Treatment of Goodpasture's disease by plasma exchange and immunosuppression.

Three cases of Goodpasture's disease are described who were treated with intensive plasma exchange and immunosuppression. There was no improvement in renal function and the patients required chronic haemodialysis, but renal function did recover with treatment for recurrence of disease in a transplanted kidney. Anti-GBM antibody levels were not controlled and substantial reduction in fibrinogen and complement were only achieved with daily treatment. A controlled trial of this regime is urgently required.

Adult↗
PubMed1977

Mediators of immediate-type hypersensitivity in sputum from patients with chronic bronchitis and asthma.

Mediators of immediate-type hypersensitivity were studied in the sputum of patients with chronic bronchitis. The same mediators were also measured in early-onset, skin-test-positive asthmatics, in late-onset, skin-test-negative asthmatics, and in patients with bronchial carcinoma, bronchiectasis, and pneumonia. Sputum eosinophilia was a feature of bronchitics and asthmatics, whereas raised blood eosinophil levels were found only in the early-onset, skin-test-positive asthmatics. Histamine and IgE were present in considerable amounts in the sputum of bronchitics and early-onset, skin-test-positive asthmatics. Smaller amounts were found in the other groups. The sputum in all the groups contained material giving an "S.R.S (slow-reacting substance) like" induced contraction of the guinea pig ileum. "Classical" S.R.S.-A., determined by arylsulphatase IIB susceptibility, was present only in bronchitics and both types of asthmatics. Since the bronchitics were, in general, skin-test negative and had normal concentrations of circulating IgE and eosinophils, it is suggested that the findings in the sputum indicate an element of local immediate-type (type I) hypersensitivity in bronchitis although its significance for pathogenesis is not known.

Adult↗
PubMed1977

Human transfer factor prepared by dialysis, ultrafiltration and gel chromatography: biological activity in local transfer of skin sensitivity.

Human transfer factor (TF) was prepared by a variety of methods including dialysis using cellophane tubing, ultrafiltration through a membrane of known pore size. Sephadex G25 chromatography or combinations of some of these methods. In general the various preparations when injected locally into human skin gave greater delayed-type responses than antigen (PPD or Candida) alone. The combination of either vacuum dialysis, or ultrafiltration, with G-25 chromatography gave as good or better TF activity when compared with unchromatographed materials. Since ultrafiltration and concentration is rapid procedure and eliminates the need for freeze-drying, in contrast to vacuum dialysis against water, these results indicate that ultrafiltration and G-25 chromatography provide a convenient method for preparing large batches of relatively pure TF from leucocyte extracts.

Antigens, Fungal↗
PubMed1977

Monocyte chemotaxis in bronchial carcinoma and cigarette smokers.

Chemotaxis of blood monocytes was measured in 31 patients with bronchial carcinoma and 19 cigarette smokers. Thirteen patients with metastatic bronchial carcinoma had significantly less (P less than 0.005) chemotactic response than matched controls. Those with disease confined to the chest, or with recurrent or operable bronchial carcinoma, had no significant depression of monocyte chemotaxis. There was also no significant difference in monocyte chemotaxis between cigarette smokers and matched controls. These results support the concept that in human cancer there is a defect in monocyte chemotaxis, but in bronchial carcinoma significant depression was only apparent in those with advanced disease.

Aged↗
PubMed1977

Neutrophil accumulation in vivo following the administration of chemotactic factors.

Intravenously administered 51Cr-labelled homologous neutrophils accumulated at guinea-pig skin sites prepared by intradermal injection of factors derived from complement-activated serum, possessing in vitro chemotactic activity. There was a strong correlation between the in vitro potency of Sephadex G-100 fractions of the activated serum and their ability to evoke neutrophil accumulation in vivo. These experiments suggest that agents which are chemotactic for neutrophils in vitro also induce the localization of this cell in vivo.

Animals↗
PubMed1977

Cutaneous eosinophil accumulation in atopic and non-atopic individuals: the effect of an ECF-A tetrapeptide and histamine.

The numbers of eosinophils recruited locally to abraded human skin were measured in eight atopic and eight non-atopic volunteers, at time intervals over 24 hr, following the application of an ECF-A tetrapeptide (Val-Gly-Ser-Glu) or histamine. In all subjects the higher doses of the peptide (10(-4) and 10(-6) mol/l) or histamine (10(-3) and 10(-5) mol/l) produced significantly greater counts than the Tyrode's diluent alone. The counts produced with the lowest dose of peptide (10(-8) mol/l) or histamine (10(-7) mol/l) were not significantly different from the control. The peptide or histamine evoked a greater local eosinophilia in the atopics than the non-atopics. This effect was probably independent of the peripheral blood eosinophil counts since at the time of study the numbers of circulating eosinophils between the two groups were not significantly different. In the atopics, histamine in doses of 10(-3) and 10(-5) mol/l were required to give the same eosinophil response as that obtained with 10(-4) and 10(-6) mol/l of the peptide, respectively. It is suggested that the relative paucity of eosinophils recruited by locally applied ECF-A peptide or histamine, when compared to antigen-induced eosinophilia, is due either to an inability to mimic the events associated with the release of these mediators from mast-cells or the involvement of other pharmacological agents.

Chemotaxis, Leukocyte↗
PubMed1977

Chemotactic activity of guinea pig eosinophils for the ECF-A acidic tetrapeptides, histamine, histamine metabolites, and the effect of H1- and H2-receptor antagonists.

Histamine and one of its major metabolites, imidazoleacetic acid, were selectively chemotactic for guinea pig eosinophils, whereas L-histidine, 1,4-methylimidazoleacetic acid, 1,4-methylhistamine and N-acetylhistamine were inactive. The response to histamine was unaffected by concentrations of eosinophils of between 30 and greater than 90% but it was abrogated by preincubation of the cells with histamine prior to assay (self-deactivation). Eosinophilotaxis was also inhibited by H1-(mepyramine-) and H2-)burimamide)-receptor antagonists at high doses (10(-3)m), although at lower concentrations (10(-5) M) inhibition was principally associated with burimamide. The human tetrapeptide, alanine-glycine-serine-glutamic acid, and the analogue, valine-glycine-aspartic acid-glutamic acid, were inactive whereas alanine-glycine-serine-glutamic acid was chemotactic for the guinea pig eosinophil. These results support the concept that the tissue accumulation of eosinophils following anaphylaxis depends on a complex interaction of factors, which in part may be mediated by H2 receptors on the target cells. There may be species differences in the composition of ECF-A.

Alanine↗