Publications by authors named "Pearce F"

The functional and histochemical properties of isolated mast cells from human skin, uterine myometrium and lung parenchyma were compared. The skin cell showed a marked difference in responsiveness to both secretagogues and anti-allergic compounds when compared to mast cells from the uterus and lung. The latter cell types responded more strongly to immunologically-directed ligands and calcium ionophores than the skin cell.

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Mast cells isolated from human gastric mucosa released histamine on challenge with IgE-directed ligands and calcium ionophores but were essentially unresponsive to a variety of non-immunological stimuli. Moreover, immunologically induced histamine secretion from these cells was inhibited by a number of anti-allergic agents including anti-asthmatic chromones, beta-adrenoceptor agonists and phosphodiesterase inhibitors. In total, these data indicate that mast cells from the human gastric mucosa are in many respects functionally similar to their lung and colonic counterparts.

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Sodium orthovanadate was found to be an effective histamine liberator from serosal mast cells of the rat and mouse. The release process was slow, non-cytotoxic and strongly dependent on pH and extracellular calcium. The effect was highly tissue and species specific and human basophil leucocytes, human lung mast cells and tissue mast cells of the rat and guinea pig were only weakly responsive or essentially unreactive.

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Routine epicardial two-dimensional echocardiography, Doppler, and Doppler color flow imaging studies were performed before and after cardiopulmonary bypass in 328 patients undergoing operations for congenital heart disease. Ages ranged from 1 day to 59 years (mean 5.9 years); the smallest patient was 1.

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The functional properties of enzymically dispersed mast cells from human lung parenchyma, colonic mucosa and colonic submucosa/muscle were compared. In general, the cells responded in a similar fashion to the histamine releasing action of a variety of immunological and non-immunological stimuli. However, some differences were observed in their responses to anti-allergic compounds.

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Bradykinin and a range of peptide analogues induced a dose-dependent release of histamine from rat peritoneal mast cells. The characteristics of the release were not consistent with the involvement of defined bradykinin receptors but indicated that the peptide acted through the putative mast cell polyamine receptor. Consistently, the effect of bradykinin was largely confined to serosal mast cells of the rat and hamster, while human histaminocytes were essentially unresponsive.

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Adenosine 5'-triphosphate (ATP) induced a non-cytotoxic, calcium-dependent release of histamine and prostaglandin D2 from rat serosal mast cells. The effect was tissue and species specific. In particular, tissue mast cells from the guinea pig and man were totally unresponsive.

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We have examined the effect of a range of histamine H1- and H2-receptor agonists and antagonists on rat peritoneal mast cells. Most of the compounds had a dual action: at low concentrations they inhibited the histamine release produced by immunologic activation of the cell whereas at higher concentrations they themselves induced a cytotoxic release of the amine. The test agents did not affect intracellular levels of cyclic AMP.

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The presence of left ventricular outflow tract obstruction (LVOTO) of either a resting or dynamic nature may have important therapeutic and prognostic implications in patients with hypertrophic cardiomyopathy (HCM). Doppler echocardiograms combined with amyl nitrite (Amyl) inhalation were performed in 333 consecutive patients referred for suspected HCM to diagnose and categorize the nature and severity of LVOTO. Hypertrophic cardiomyopathy was present by 2-D and M-mode criteria in 145/333 (44 percent) patients.

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Detection of the proximal left and right coronary arteries is possible by transesophageal echocardiography with rather high frequencies. The proximal left coronary artery can be detected in 86% of patients and the proximal right in 82%. Precise identification of obstructive disease is possible but is confounded by heart movement and as yet inadequate criteria for its presence to make this routinely clinically possible.

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1. The divalent cations calcium, strontium and barium--and in that order of decreasing effectiveness--were capable of supporting the stimulated release of histamine from rat peritoneal mast cells (RPMC). 2.

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Low concentrations of H1- and H2-receptor directed compounds inhibited the immunologic secretion of histamine from human lung mast cells and basophil leucocytes and protected human erythrocytes from hypotonic lysis. Higher concentrations induced a release of the amine from the histaminocytes. These results are discussed in terms of the possible membrane effects of the test compounds.

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Sodium orthovanadate induced a release of histamine from rat peritoneal mast cells. Other oxyanions of vanadium with the metal in the +V oxidation state also evoked histamine release but neither vanadyl sulphate (+IV oxidation state) nor the analogous orthophosphate anion were effective secretagogues. The release evoked by vanadate was selectively inhibited by the anion channel blocker SITS, and by theophylline and Bu2cAMP, but was unaffected by disodium cromoglycate and lanthanum ions.

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Peritoneal mast cells from specific pathogen-free rats that had been sensitized to the nematode Nippostrongylus brasiliensis released histamine in a dose-dependent fashion on challenge with antigen, anti-rat IgE, anti-rat IgG and concanavalin A. Cells from non-sensitized animals showed weak or insignificant responses to these agents. However, the two preparations did not obviously differ in their reactivity to a range of pharmacological agents including ATP, dextran, polyamines and calcium ionophores.

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The effect of a variety of non IgE-mediated stimuli on histamine release from mast cells from different locations is described. Sensory neuropeptides are shown to resemble other polycationic compounds in preferentially activating mast cells from the rat while having a limited effect on human mast cells, except possibly those from skin. Similar results were obtained with the putative non-adrenergic, non-cholinergic neurotransmitter ATP, thereby questioning the role of neuronal mast cell activation in allergy and inflammation.

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Nedocromil sodium and sodium cromoglycate inhibited histamine release from rat peritoneal mast cells. Tachyphylaxis was observed with both drugs. The 2 compounds were extremely selective in their action, being less active against peritoneal mast cells from the hamster and completely ineffective against mast cells from the mouse.

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A variety of basic, sensory neuropeptides induced the release of histamine from rat peritoneal mast cells. However, a wide range of other polycationic agents, such as compound 48/80, the mast-cell-degranulating peptide from bee venom and polylysine also activated this cell type. Histamine release induced by all of these agents had characteristic features in common.

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Sodium cromoglycate and nedocromil sodium produced a dose dependent inhibition of histamine secretion from human pulmonary mast cells obtained by bronchoalveolar lavage and by enzymatic dissociation of lung parenchyma. Both compounds were significantly more active against the lavage cells than against the dispersed lung cells, and nedocromil sodium was an order of magnitude more effective than sodium cromoglycate against both cell types. Tachyphylaxis was observed with the parenchymal cells but not with the lavage cells.

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The effects of a number of non-steroidal anti-inflammatory drugs (NSAID) on histamine secretion from tissue mast cells of the rat and the guinea pig have been examined. According to the experimental conditions and cell type, the drugs potentiated, inhibited or had no effect on histamine release. The possible mechanisms of these effects are discussed.

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In guinea pig (GP) and human heart and kidney cell or tissue preparations fixed with Carnoy's fluid (but not with formol-saline), mast cells (MC) were extremely well preserved and could be detected after staining with alcian blue (AB). Although histamine content and distribution in GP and human heart appeared to be different, morphological and histochemical studies of MC suggested a similarity between the two species and a clear distinction from rat peritoneal MC.

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Mast cells were isolated by the enzymic dissociation of lung tissue from the pig. The responses of these cells to a variety of histamine liberators and anti-allergic drugs were examined. On the basis of these findings, the possible use of porcine pulmonary mast cells in the study of immediate hypersensitivity reactions is discussed.

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Histamine release from isolated mast cells stimulated with somatostatin resembled that induced by other basic agents. The process was rapid, independent of added calcium or phospholipids, non-cytotoxic, species and tissue specific, not mediated through cell-fixed antibodies or glucoreceptors, and inhibited by antagonists of the polyamine receptor. Somatostatin and other polycations may then act through a common receptor or binding site on the mast cell membrane.

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The effects of calcium, serine phospholipids and the phorbol ester tetradecanoylphorbol acetate (TPA), a known activator of protein kinase C, have been examined on mastocytes from different sources. A complex and differential interaction between these agents and histamine secretion was observed in human basophil leucocytes and in peritoneal mast cells from the rat, mouse and hamster. On this basis, the possible role of kinase C in histamine release is discussed.

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