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Biomedical subjects

M K Church

Publications and source records attributed to M K Church.

At least 199 records · Page 11Linked to original sources
PubMed1983

Human tonsillar mast cells. Characteristics of histamine secretion and methods of dispersion.

Mast cells can be dispersed from human tonsils by a mechanical procedure or by the use of proteolytic enzymes. The latter procedure does not always increase cell yield and may adversely affect the mast cell response to secretory stimuli. Mechanically dispersed tonsillar mast cells secrete histamine in response to stimulation with anti-IgE and calcium ionophore A23187 by a calcium-dependent and energy-dependent mechanism. With compound 48/80 and basic polyamines, histamine release only occurs at cytotoxic concentrations. Functionally, human tonsillar mast cells are similar to adenoidal and lung mast cells.

Calcimycin↗
PubMed1982

The role of basophils in asthma. I. Sodium cromoglycate on histamine release and content.

The increased plasma-histamine levels observed after provocation of asthmatic subjects with antigen or exercise may result from the release of this granule-associated mediator from either mast cells or basophil leucocytes. In this preliminary study, designed to ilucidate the source and role of mediators in asthma, the effects of sodium cromoglycate on basophil-histamine release has been assessed. Basophil histamine-release in vitro was not inhibited by 0.01-100 microgram/ml sodium cromoglycate. When administered by inhalation at a dose of 20 mg every 8 hr to six subjects, the drug did not modify the ability of basophils to synthesize and store histamine or to release histamine on incubation with antigen. As sodium cromoglycate reduces IgE-dependent histamine release from human mast-cells, these results suggest that lung mast-cells, rather than circulating basophils, are source of mediators in exacerbations of asthma and following exercise or antigen bronchial-provocation in asthmatic subjects.

Antibodies, Anti-Idiotypic↗
PubMed1981

Immunoglobulin E decapeptide-induced 5-hydroxytryptamine release from rat peritoneal mast cells. Comparison with corticotropin-(1-24)-peptide, polyarginine, polylysine and antigen.

A synthetic basic decapeptide from the C4 domain of human immunoglobulin E, corticotropin-(1-24)-peptide, polyarginine and polylysine stimulated up to 90% net release of 5-hydroxytryptamine from mast cells in rat peritoneal-cell suspensions. Concentration-response curves to all four polypeptides were parallel. Polyarginine and polylysine (EC50 congruent to 0.05 microM) were approximately 100-fold more potent than immunoglobulin E decapeptide and corticotropin-(1-24)-peptide (EC50 congruent to 5 microM). Polypeptide-induced release was complete within 5-10s. Immunoglobulin-E-decapeptide-induced 5-hydroxytryptamine release was additive to that induced by low concentrations of polyarginine, but non-additive to that induced by high concentrations of polyarginine. In contrast, release induced by antigen was additive along the whole length of the concentration-response curve to polyarginine. Benzalkonium chloride inhibited immunoglobulin-E-decapeptide- and polyarginine-induced 5-hydroxytryptamine release but enhanced release induced by immunological stimulation.

Animals↗
PubMed1980

Oxatomide: inhibition and stimulation of histamine release from human lung and leucocytes in vitro.

Oxatomide is a very potent inhibitor of histamine release induced by anti-1gE and Timothy pollen extract in passively sensitized human lung fragments and that induced by anti-1gE from human leucocytes. Its spectrum of activity is different from sodium cromoglycate-like drugs. In high concentrations oxatomide, like other antihistamines and related structures, induced histamine release from both lung and leucocytes. However, oxatomide induced histamine release far more effectively from sensitized lung than non-sensitized lung. Inhibition of immunologically induced histamine releast by oxatomide may play a part in its action as an anti-hay fever and, possibly, an anti-asthmatic drug.

Histamine H1 Antagonists↗
PubMed1980

Inhibition of histamine release from human lung in vitro by antihistamines and related drugs.

1 A series of cationic, lipophilic histamine H1-receptor antagonists, neuroleptics, antidepressants and monoamine oxidase inhibitors were tested for their effects on anti-IgE-induced histamine release from human lung fragments in vitro. 2 They had a biphasic effect: at low concentrations a dose-related inhibition of histamine release was observed whereas, at higher concentrations, the drugs liberated histamine even in the absence of antigen. 3 Mepyramine, a much less lipophilic drug than the others tested, was only weakly active on mast cells at pharmacological concentrations. 4 The potency of the drugs as release inhibitors was not related quantitatively to their histamine liberating potency. 5 There was no; correlation between activity on mast cells and histamine H1-receptor antagonism. 6 Mast cell stabilization may play a part in the activity of these drugs as anti-allergic agents.

Chlorpheniramine↗
PubMed1980

The activity of sodium cromoglycate analogues in human lung in vitro: a comparison with rat passive cutaneous anaphylaxis and clinical efficacy.

1 Eleven analogues of sodium cromoglycate have been tested for their ability to suppress histamine release induced by anti-IgE from passively sensitized human lung fragments in vitro. 2 With the exception of WY 16922, which released histamine at high concentrations, all inhibited histamine release in a linear dose-related manner. 3 The analogues were 30 to 1500 times more potent than sodium cromoglycate. However, their regression slopes of activity upon log-concentration were only one-third as steep as that for sodium cromoglycate, indicating a possible difference in their mechanism of action. 4 In comparison with sodium cromoglycate, the analogues were more potent in human lung than in rat passive cutaneous anaphylaxis (PCA); there was no quantitative correlation between potencies in the two tests. 5 The human lung model is not predictive of anti-asthmatic activity in man as the six analogues tested clinically are less effective than sodium cromoglycate. 6 These results throw doubt on the use of models of mast cell degranulation in the search for anti-allergic drugs and, possibly, on the relative importance of mast cell degranulation in the pathogenesis of asthma.

Animals↗
PubMed1978

Time courses of the anti-anaphylactic and anti-inflammatory effects of dexamethasone in the rat and mouse.

1 The time course of the activity of dexamethasone has been studied in a variety of anaphylactic and inflammatory reactions in the rat and the mouse. 2 The times of peak activity of dexamethasone, expressed as time between oral dosage and induction of response, and the approximate ED50 values (mg/kg) found were: anaphylactic bronchoconstriction in rats, 12-24 h, ED50 1.8; passive cutaneous anaphylaxis in rats, 6 h, ED50 0.04; cutaneous reactions to histamine in rats, 4 h, ED50 0.01; carrageenin-induced paw oedema in rats, 4 h, ED50 0.03; pinnal anaphylaxis in mice, 6 h, ED50 0.82; histamine-induced pinnal reactions in mice, 6 h, ED50 0.05. 3 In rats, the characteristics of the inhibitory effects of dexamethasone indicate a differential activity against anaphylactic and inflammatory reactions and between different types of inflammatory reactions. Possible reasons for these differences are discussed. 4 In mice there was little difference between the inhibition by dexamethasone of cutaneous allergic and histamine-induced reactions. 5 Pinnal anaphylaxis in mice was potentiated by dexamethasone given 1-2 h before challenge.

Anaphylaxis↗
PubMed1978

Hyperalgesia after treatment of mice with prostaglandins and arachidonic acid and its antagonism by anti-inflammatory-analgesic compounds.

Prostaglandin E1 (PGE1), prostaglandin E2 (PGE2) and arachidonic acid have been demonstrated to potentiate the peritoneal writhing response in the mouse induced by benzoquinone. The resultant dose-response relationships were bell shaped with a maximum activity of 10 ng/kg i.p. of potentiating agent. Floctafenine, indometacin and acetylsalicylic acid (ASA) blocked the potentiation induced by arachidonic acid but not that induced by PGE2. This suggests that it is prostaglandin that causes the potentiation and that the mechanism of action of ASA-like drugs against hyperalgesia associated with inflammation is blockade of prostaglandin synthesis. Morphine reduced the potentiation by PGE2 and arachidonic acid but the bell shaped hyperalgesia was still evident using both agonists. These results indicate that morphine does not inhibit prostaglandin synthetase but may modify the effect of prostaglandin. This method may be useful to distinguish between ASA-like and morphine-like analgesic compounds using a pain response in vivo.

Animals↗
PubMed1976

Sequential release of histamine and 5-hydroxytryptamine during pinnal anaphylaxis in the mouse.

Histamine and 5-HT have been demonstrated to be involved in pinnal anaphylaxis in mice. Each predominates at different stages during the 30-min development of the reaction. The main mediator of the early stage of the reaction (0-10 min) is histamine, that of the middle stage (10-20 min) is 5-HT, and that of the final 20- to 30-min stage is, again, histamine. The source and mechanism of release of the 5-HT and the late histamine are, as yet, unknown but under investigation.

Anaphylaxis↗
PubMed1976

Pinnal anaphylaxis in the mouse. Mediating antibodies and rhythmic variations in the response.

The anaphylactic reaction in the pinna of a mouse actively sensitized to horse serum is mediated by IgG1 and IgE antibodies. Anaphylactic sensitivity is subject to diurnal variation, peak sensitivity occurring at 16.00 hours and minimum sensitivity at 10.00 hours. Anaphylactic sensitivity also varied with the season of the year, being lower during June and July than in the rest of the year, when the reaction was fairly constant.

Anaphylaxis↗
PubMed1975

Response of rat lung to humoral mediators of anaphylaxis and its modification by drugs and sensitization.

1 The effects of humoral mediators of anaphylaxis on the bronchial function of the pithed rat have been assessed and compared with their effects in the guinea-pig and man. 2 5-Hydroxtryptamine, acetylcholine and bradykinin were bronchoconstrictor. Slow reacting substance in anaphylaxis and prostaglandin F2a caused only slight constriction at high doses and histamine was not active. 3 Bradykinin was less active in the rat than in the guinea-pig and its effects were not antagonized by anti-inflammatory analgesic drugs. 4 beta-Adrenoceptor blockade potentiated the activity of bradykinin but not that of 5-hydroxytryptamine or acetylcholine. 5 Dexamethasone reduced the activity of bradykinin but not that of 5-hydroxytryptamine or acetylcholine. 6 Sensitization with Nippostrogylus brasiliensis did not increase the sensitivity of the rat lung to the effects of mediators.

Acetylcholine↗
PubMed1975

Correlation of anaphylactic bronchoconstriction with circulating reaginic antibody level and active cutaneous anaphylaxis in the rat.

The interrelationships of anaphylactic bronchoconstriction, active cutaneous anaphylaxis and circulating reaginic antibody level in rats sensitized with Nippostrongylus brasiliensis have been studied. The mean rise in bronchial reactivity during the 5-week sensitization period was correlated with the rise in circulating reaginic antibody level in groups of rats, although weak bronchial reactivity was observed before circulating reagin was demonstrable. In individual animals bronchial reactivity did not significantly correlate with circulating reaginic antibody level or cutaneous reactivity. Bronchial and cutaneous reactivity on challenge may be transferred to non-sensitized rats by passive sensitization with reaginic serum. It is concluded that the ability of a tissue to respond to antigen challenge is multifactorial and may not be reliably predicted from a knowledge of circulating reaginic antibody level or the response of another tissue in the same animal.

Anaphylaxis↗