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Biomedical subjects

A B Kay

Publications and source records attributed to A B Kay.

At least 397 records · Page 22Linked to original sources

Human eosinophils, acidic tetrapeptides (ECF-A) and histamine. Interactions in vitro and in vivo.

The ECF-A acidic tetrapeptides Val-Gly-Ser-Glu, Ala-Gly-Ser-Glu and the analogue Val-Gly-Asp-Glu were selectively chemotactic for human eosinophils over a narrow dose range although eosinophils from different individuals varied in their dose-response pattern. Histamine abrogated the chemotactic properties of the individual tetrapeptides. When Val-Gly-Ser-Glu and Ala-Gly-Ser-Glu were combined in various concentrations the resultant chemotaxis was either negligible or no greater than that produced when each peptide was tested separately. Val-Gly-Ser-Glu and Ala-Gly-Ser-Glu both promoted eosinophil accumulation when applied to the abraded skin of man or i.d. to the marmoset. Biopsies of marmoset skin revealed that peptide-induced eosinophilia was not associated with mast-cell degranulation. Histamine, which was chemotactic in vitro, did not lead to appreciable eosinophil accumulation in vivo, and combinations of histamine and the acidic tetrapeptides evoked little or no cutaneous eosinophil infiltration either in man or the marmoset. These studies suggest that there is a complex interaction between histamine and the ECF-A tetrapeptides; however, the tetrapeptides alone can promote the recruitment and localization of eosinophils by a mechanism apparently independent of mast-cell degranulation.

Animals↗

Leucocyte function in a case of chronic benign neutropenia of infancy associated with circulating leucoagglutinins.

A case of chronic benign neutropenia is described in association with circulating leucoagglutinins. IgG and IgM leucoagglutinins demonstrated by Sephadex G-200 chromatography agglutinated neutrophils and monocyte enriched leucocyte preparations. Total IgG, IgA, IgM and IgE, total haemolytic complement, C3 and C4 complement components were all within normal limits. Lymphocyte populations and transformation were normal apart from a relative increase in the number of B lymphocytes. In vitro studies showed that the patient's monocytes responded in chemotaxis, phagocytosis and intracellular killing of S. aureus in a comparable fashion to that of control neutrophils. Although the patient's serum also agglutinated monocytes these findings do not exclude the possibility that leucoagglutinins may have aetiological significance in this disease. The study also emphasizes the versatility of the monocyte in benign neutropenia.

Agglutinins↗

Chemotaxis for human monocytes by fibrinogen-derived peptides.

Chemotactic activity for human peripheral blood monocytes was generated by the action of thrombin on human fibrinogen, a reaction known to release low molecular fibrinopeptides. Supernatants prepared by incubating Contortrix venom with fibrinogen, which cleaves the B peptide, were also chemotactic, whereas no activity was present in supernatants from Arvin venom, which cleaves peptides A, AP and AY. Thus fibrinopeptide B was chemotactic for the monocyte in addition to the neutrophil, as previously reported. Monocyte chemotactic activity was also generated by the action of plasmin on human fibrinogen and shown to be associated with the D and E fragments but not with a mixture of fragments X and Y. When plasmin digestion was stopped at time intervals up to 24 h, monocyte chemotactic activity corresponded with the appearance of the D and E fragments. The monocyte chemotactic activity, contained in a 24 h digest, eluted from Sephadex G-75 at VO, corresponding to the expected position of the D and E fragments whereas neutrophil chemotactic activity eluted with molecules of molecular size of approximately 30 000 daltons. Thus fragments D and E derived from plasmin digestion of fibrinogen attract the monocyte whereas only the small uncharacterized peptides were chemotactic for the neutrophil. These different profiles of chemotactic activity for the neutrophil and the monocyte in terms of plasmin digestion products of fibrinogen may be of significance in the events leading to the accumulation of these cells in vivo during fibrin deposition.

Chemotaxis↗

The effect of transfer factor on neutrophil function in chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis with hypoparathyroidism in a 6-year-old-boy is described. In addition to defects of in vivo and in vitro correlates of delayed-type hypersensitivity to Candida albicans the child also had abnormalities of neutrophil function in terms of their capacity to respond by chemotaxis to a known attractant and to kill suspensions of C. albicans. Dialysable transfer factor was given on six occasions at intervals of between 26 and 45 days. Neutrophil chemotaxis (optimal conditions) was restored following each of the six injections, neutrophil chemotaxis (sub-optimal conditions) following five of the six injections and candidicidal capacity following four of the six injections. The effects of transfer factor were transient requiring repeated injections. The Candida delayed-type hypersensitivity skin test was restored to normal but lymphocyte transformation to Candida extract was not consistently positive following treatment. There was a slight clinical improvement following therapy. These abnormalities of neutrophil and lymphocyte function point to the complexity of chronic mucocutaneous candidiasis. The improvement in neutrophil chemotaxis and candidicidal capacity following treatment suggests that transfer factor may be a heterogeneous group of molecules, some of which affect granulocytes and restore defects in their function.

B-Lymphocytes↗

Immunoglobulins and complement in pleural effusions associated with bronchogenic carcinoma.

Levels of IgG, IgA, IgM, the total haemolytic complement (CH50), and the individual components C1q, C3, C4, C6, and C7 were measured in 29 pleural effusions. Of these, 18 were associated with carcinoma of the bronchus and 11 were non-malignant effusions including empyemas. The level of IgG was significantly lower in the malignant group when compared with non-malignant effusions. The usefulness of measurements of IgG with respect to malignant effusions associated with carcinoma of the bronchus requires an expanded study to show whether it has any real diagnostic value. There were no significant differences in other immunoglobulins, the CH50, and individual complement components between the two groups. The identification of total haemolytic activity in the majority of effusions in both groups indicates that all nine components of the classical pathway of complement, including macromolecules such as C1, can be present in pleural fluids.

Carcinoma, Bronchogenic↗

Complement components and IgE in patients with asthma and aspirin idiosyncrasy.

Levels of circulating IgE, total haemolytic complement, and components C4 and C3 were measured in 16 asthmatics with aspirin idiosyncrasy and in control subjects. IgE levels were mostly within normal limits. No differences were found between the complement profiles-in particular the C4 levels-in the two groups. As low levels of C4 have been found in patients with intrinsic asthma, these results would suggest a fundamental difference between asthmatics with aspirin idiosyncrasy and others with intrinsic asthma.

Aspirin↗

Slow reacting substance as a preformed mediator from human lung.

Homogenates from human lung contained a preformed slow reacting substance (pSRS). The pattern of contraction on the guinea-pig ileum by pSRS was indistinguishable from that of SRS-A. The activity of pSRS could not be attributed to the presence of K+, Na+, Ca2+ and Mg2+ ions, or any prostaglandin including PGF2 or its 15-oxo derivative. As with SRS-A, pSRS could be absorbed onto Amberlite XAD-2 and silicic acid. Both were eluted from the former with 80 per cent ethanol and from the latter with a mixture of ethanol, ammonia and water. Both pSRS and SRS-A were resistant to the action of NaOH whereas their activities were destroyed by boiling in HCl. Arylsulphatase II B destroyed the activities of both pSRS and SRS-A. An antagonist of SRS-A, FPL55712, inhibited the action of pSRS at comparable concentrations to that of SRS-A. These experiments suggest that pSRS and SRS-A are identical. Thus SRS joins histamine and ECF-A as a preformed mediator. Although SRS was present in a preformed state the amount of material extractable was more than doubled by the anaphylactic reaction. The extraction of slow reacting substance from human lung without apparent requirement for antigen or antibody points to a possible role of this mediator in inflammatory reactions evoked by mechanisms independent of IgE and other tissue-sensitizing antibodies.

Antigens↗

Tissue inactivation of slow reacting substance of anaphylaxis.

The release of slow reacting substance of anaphylaxis (SRS-A) from sensitized guinea-pig lung challenged with antigen was followed by a fall in the activity of this mediator in the diffusate when the incubations were continued for 3 h. The inactivating principle was also present in normal lung in addition to other normal guinea-pig tissues such as the liver, kidney, spleen, ileum and skin. No acitivity was found in muscle. Evidence is provided that some of this SRS-A-inactivating activity was due to tissue arylsulphatases. These were measured by hydrolysis of p-nitrophenyl sulphate (p-NPS) and p-nitrocatechol sulphate (p-NCS), which reflect activities of arylsulphatase II A and II B respectively. Hydrolytic activity for p-NCS was present in all tissues with SRS-A-inactivating properties, whereas only lung, liver and skin tissue hydrolysed p-NCS and p-NPS. Following passage of a cell-free lung homogenate through a column of Sephadex G-200 the p-NCS hydrolysing and SRS-Z-inactivating activities eluted together, with molecules having a molecular size of approximately 150,000 Daltons, p-NPS hydrolysing activity being destroyed during the preparation of the homogenate. The release of arylsulphatase from sensitized tissue was not dependent on the presence of specific antigen. These experiments suggest that inactivation of SRS-A is related to tissue arylsulphatase and that these enzymes may play a role in the expression of the effective levels of this mediator within the tissues.

Animals↗

Eosinophil chemotaxis of supernatants from cultured Hodgkin's lymph node cells.

Cultured lymph node cell supernatants from five out of six cases of Hodgkin's disease were relatively more chemotactic for peripheral blood eosinophils than neutrophils. In contrast, supernatants from two cases of lymphocytic lymphoma and four nodes showing reactive hyperplasia were chemotactic for neutrophils but had little eosinophil chemotactic activity. In most instances the dgree of eosinophil infiltration observed histologically in the Hodgkin's lymph node correlated with elaboration of eosinophil chemotactic activity from the cultured cells. Following gel-filtration of three of the Hodgkin's lymphnode supernatants, four peaks of eosinophil chemotactic activity were demonstrated in each case. One of these corresponded in molecular size to th previously described eosinophil chemotactic factor of anaphylaxis (ECF-A). It is suggested that the eosinophil chemotactic activity of cultured lymph node cell supernatants may be on value in the diagnosis and classification of Hodgkin's disease.

Anaphylaxis↗

Activation of the classical and alternate pathways of complement by Corynebacterium parvum.

The immunological adjuvant Corynebacterium parvum has been to activate the alternate pathway of complement in human and guinea-pig serum. Human serum in addition contains anti-C. parvum antibodies leading to activation of the classical complement pathway. The possible role of a C. parvum derived polysaccharide in this activation is considered in relation to the biological effects of the micro-organism.

Agglutination Tests↗

The effect of enzyme digestions on the activity of eosinophil chemotactic factor of anaphylaxis (EFC-A).

Preparations of ECF-A derived from anaphylactic guinea-pig lung diffusates were subjected to a variety of enzymatic degradations. The enzymes employed had specificityonly for their appropiate subtstates. No effect was found following treatmentwith relatively high doses of trypsin, alpha-chymotrypsin, pronase, alkaline phosphataseand sialidase. In contrast a loss of activity was demonstated in a dose-dependent fashion following incubation with tyrosinase, aryl sulphatase and leucine aminopeptidase, suggesting that ECF-A contains a phenolic hydroxyl group, a sulphate ester anda peptide linkage with a free alpha-amino group.

Alkaline Phosphatase↗