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Biomedical subjects

M Ennis

Publications and source records attributed to M Ennis.

At least 181 records · Page 10Linked to original sources
PubMed1984

Measurement of prostaglandin D2 and identification of metabolites in human plasma during intravenous infusion.

A stable isotope dilution assay has been developed for the quantification of prostaglandin D2 (PGD2) in plasma. Samples are analysed by capillary column gas chromatography/negative ion chemical ionisation mass spectrometry (GC/NICIMS). The method employs an internal standard of [2H6]PGD2, prepared biosynthetically by incubation of rat peritoneal mast cells with deuterated arachidonic acid. No PGD2 was detected in peripheral venous plasma samples obtained from 10 healthy male volunteers (detection limit = 5 pg ml-1). Following intravenous infusion of PGD2 at increasing incremental infusion rates ranging from 16-256 ng kg-1 min-1, a dose related increase in the plasma concentration of PGD2 was observed. Plasma levels at 128 ng kg-1 min-1 ranged from 724-1444 pg ml-1. The major circulating metabolites of PGD2, during infusion, were identified as 13,14-dihydro-15-oxo-PGF2 alpha and 15-oxo-PGF2 alpha.

Animals↗
PubMed1983

Mast cells isolated from guinea-pig lung: characterization and studies on histamine secretion.

A method has been developed for the dispersion of guinea-pig lung into its component cells using the proteolytic enzyme collagenase. The procedure typically yielded 5 X 10(6) mast cells per g of tissue with a recovery of histamine of ca. 20%. The mast cells comprised 2% of the total nucleated cells, had a histamine content of 1-2 pg per cell and exhibited a low spontaneous release of the amine (ca. 6%). In contrast to the rat peritoneal mast cell, guinea-pig lung mast cells were refractory to the action of compound 48/80, peptide 401 (MCD-peptide), dextran and Concanavalin A. However, the cells released histamine on antigenic challenge following active sensitization and dose-dependent histamine secretion was also produced by the ionophores A23187, ionomycin and Br-X537A. These results further emphasize the functional heterogeneity of mast cells obtained from different species and tissues.

Animals↗
PubMed1983

Calcium antagonists and histamine secretion from rat peritoneal mast cells.

The calcium antagonists verapamil and nifedipine inhibited histamine release induced from rat peritoneal mast cells by a number of secretory stimuli. However, the concentrations required were much higher than those active in smooth muscle preparations. The inhibition was unaffected by elevated levels of external calcium and the drugs prevented release in the absence of added calcium. The novel calcium antagonist, PY 108-068, had no effect on histamine secretion from mast cells. These results suggest that calcium channels in the mastocyte may differ from those in smooth muscle and that at concentrations required to inhibit secretion, verapamil and nifedipine may have non-specific stabilizing effects on the mast cell membrane.

Animals↗
PubMed1983

Action of 3-isobutyl-1-methylxanthine and prostaglandins D2 and E1 on histamine release from rat and guinea pig mast cells.

The action of three compounds reported to elevate intracellular cyclic adenosine monophosphate (cAMP) namely 3-isobutyl-1-methylxanthine (IBMX) and prostaglandins D2 and E1 (PGD2 and PGE1), on histamine release was examined. Three test systems were used: (i) the perfused ovalbumin-sensitized guinea pig lung and (ii) isolated cells from ovalbumin-sensitized guinea pig lung, both of which are IgG-mediated models of anaphylaxis, and (iii) an IgE model of anaphylaxis, using isolated rat peritoneal mast cells from sensitized rats. Both PGD2 and PGE1 were without effect at concentrations likely to be found during anaphylaxis. In contrast, the phosphodiesterase inhibitor, IBMX, was highly active in all three test systems. The role of raised intracellular cAMP levels in the inhibition of histamine release is discussed.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Analysis of picomolar concentrations of 6-oxo-prostaglandin F1 alpha in biological fluids.

A highly sensitive and specific assay for the quantitation of 6-oxo-prostaglandin F1 alpha, the stable hydrolysis product of prostacyclin, is described. The method involves the addition of [3,3',4,4'-2H4]-6-oxo-prostaglandin F1 alpha as internal standard, extraction from biological fluids using muBondapak C18 reversed-phase Sep-Paks, and preliminary purification by normal-phase chromatography. Following conversion to the methoxime, tris-trimethylsilyl, pentafluorobenzyl derivative, samples were analysed using combined capillary column gas chromatography negative ion chemical ionisation mass spectrometry. Fragments ions at m/z 614 (1H) and 618 (2H) [M-C7H2F5]- were monitored for quantitation. This method was used for the measurement of endogenous levels of 6-oxo-prostaglandin F1 alpha in human urine and for the determination of prostacyclin release from rat peritoneal mast cells and from rat aortic rings incubated in human plasma.

Animals↗
PubMed1982

Histamine release from human pulmonary mast cells.

The enzyme collagenase was used to disperse human lung into its component cells. The resulting cell suspensions contained circa 8% mast cells and were used for studies of mediator release without further purification. They exhibited a low (circa 7%) spontaneous release of histamine. They could be sensitized passively and released histamine upon challenge with anti-human IgE. They responded to concanavalin A but not to dextran. Phosphatidyl serine did not potentiate the release induced by these agents. The calcium ionophores, A23187 and ionomycin, both elicited histamine release. The cells were refractory to the action of the basic releasers 48/80 and peptide 401 (MCD-peptide). These results indicate marked differences between human pulmonary mast cells and the more widely used rat peritoneal mast cells.

Calcimycin↗
PubMed1982

Some characteristics of histamine secretion from mast cells treated with ionomycin.

The ionophorous antibiotic ionomycin released histamine from rat peritoneal mast cells in both the presence and absence of added calcium ions. The response under the latter conditions was potentiated by brief pretreatment of the cells with chelating agents. The interaction between the ionophore and exogenous calcium was complex. Supramaximal concentrations of calcium potentiated the release induced by low levels of ionomycin but markedly inhibited the secretion evoked by larger amounts of the compound. Dispersed mesenteric mast cells of the rat and guinea pig also responded to ionomycin but were less reactive than the peritoneal cells.

Animals↗
PubMed1981

Inhibition of histamine secretion from mast cells.

Histamine secretion from mast cells may be inhibited by elevated intracellular levels of cyclic AMP and by several anti-allergic drugs. These compounds are claimed to act directly on the calcium-gating mechanism activated by the anaphylactic reaction, preventing influx of Ca2+ from the external environment and so blocking exocytosis. To examine this hypothesis further, we have compared here the histamine secretion induced by immunoglobulin E-directed ligands in the presence and absence of added calcium and by the ionophore A23187. Exocytosis evoked by these former agents was originally considered to be almost totally dependent on extracellular calcium but recent studies have shown otherwise. In the absence of added cation, the agents act by mobilizing membrane-bound or intracellular stores of calcium. We show that here that a variety of anti-allergic drugs are potent inhibitors in the conditions used, suggesting that alternative explanations for their action must be sought.

Animals↗
PubMed1981

Role of intra- and extracellular calcium in histamine release from rat peritoneal mast cells.

The present study provides evidence for a number of calcium pools important in histamine secretion from the mast cell. Firstly, calcium loosely bound to the cell membrane, and in rapid equilibrium with the extracellular environment, may be utilized for histamine release induced by most secretagogues. Secondly, all inducers are able to mobilize deeply buried or internal stores of calcium to initiate exocytosis. Finally, calcium bound to regulatory sites in the membrane may modulate the secretory process. Removal of calcium from the latter sites by brief treatment with chelating agents markedly enhances the secretory response in the absence of extracellular calcium, probably by facilitating the mobilization of bound stores of the ion. Saturation of these sites in the presence of excess calcium inhibits the release process and may restrict influx of the cation.

Animals↗
PubMed1981

HLA antigens in adults negative for antibody to Epstein-Barr virus (EBV).

Evidence for a genetic component in susceptibility to Epstein-Barr virus (EBV) infection was sought by comparing HLA A and B phenotypes of EBV antibody-negative Scottish medical students and randomly chosen antibody-positive controls. No statistically significant differences were observed, but three antigens, (A10, A29 and B15), were relatively underrepresented in the EBV seronegative group; findings which agree with data previously reported from a similar study in Los Angeles. A strong association between the HLA A1/Blank phenotype and EBV seronegativity, evident in the Los Angeles population, was not confirmed in the present study.

Adult↗
PubMed1980

Differential reactivity of isolated mast cells from the rat and guinea pig.

The effects of various chemical histamine liberators on isolated rat peritoneal, rat mesenteric and guinea-pig mesenteric mast cells were examined. All three cell types responded, but to different degrees, to calcium ionophores and surface active agents. The rat mesenteric cells also reponded, but less effectively than the peritoneal cells, to compound 48/80, peptide 401 from bee venom and ATP. Rat mesenteric cells were essentially refractory to the action of dextran and guinea-pig cells were almost totally unresponsive to the named secretagogues. These results show that there are marked functional differences between the mast cells examined and suggest that isolated tissue cells may usefuly complement rat peritoneal cells in the study of anaphylactic and anaphylactoid reactions.

Adenosine Triphosphate↗
PubMed1980

Inhibition of histamine release induced by compound 48/80 and peptide 401 in the presence and absence of calcium. Implications for the mode of action of anti-allergic compounds.

Histamine may be released from rat peritoneal mast cells by compound 48/80 and peptide 401 in the presence and absence of extracellular calcium. The process is non-cytolytic and requires an intact cell metabolism. The release produced under both conditions is inhibited by disodium cromoglycate, theophylline, dibutyryl cyclic AMP and (at high concentrations) quercetin. The efficacy of the drugs in the absence of extracellular calcium cannot be explained in terms of their postulated effect on the calcium-gating mechanism operative in anaphylactic secretion. Alternative modes of action of the compounds are thus considered.

Animals↗
PubMed1980

Arrhythmias occurring during intravenous urography.

A low but significant fatality rate persists in intravenous urography. Fatalities are sudden and their cause is not understood. This trial assessed the arrhythmogenic effects of a common urographic contrast agent. Using standard bolus injection techniques, 12 patients out of 58 (20%) developed post-injection arrhythmias. Seven of these cases (12%) were considered to have significant or potentially serious arrhythmias. This group includes various paroxysmal tachycardias and a case of atrioventricular block. Arrhythmia post-injection was commoner in the male and in the older age groups. An abnormal control ECG was not found to be a predisposing factor to the development of arrhythmia. It is suggested that the findings reflect the high incidence of latent coronary heart disease in our older male population. No correlation was found with minor side-effects of contrast injection and the development of arrhythmia.

Adolescent↗
PubMed1980

Some studies on the release of histamine from mast cells stimulated with polylysine.

1 Polylysine is an extremely potent releaser of histamine from rat peritoneal mast cells. Isolated mesenteric mast cells of the rat also respond to the secretagogue but guinea-pig mesenteric cells are unreactive. 2 The release does not require the presence of extracellular calcium ions but shows some dependence on internal stores of the cation. 3 The effect of polylysine is blocked by extremes of temperature and by metabolic inhibitors. 4 The release is very rapid and is virtually complete within 10 s of adding the inducer. 5 The release is unaffected by the anti-allergic drug, doxantrazole, but is inhibited by theophylline and disodium cromoglycate. The latter compounds are effective in both the presence and absence of added calcium. This result is discussed in terms of the postulated effect of the drugs on calcium transport.

Animals↗
PubMed1980

Calcium pools involved in histamine release from rat mast cells.

Basic secretagogues, antigen, concanavalin A, the ionophore A23187 and, to a lesser extent, anti-rat IgE produce a significant release of histamine from rat peritoneal mast cells in the absence of extracellular calcium. This release is due to the mobilization of intracellular reservoirs of calcium. The release is abolished by prolonged exposure to chelating agents, but is potentiated by brief exposure to these substances. It is suggested that the latter treatment removes calcium from a superficial, regulatory site and thus facilitates the mobilization of more internal pools of the ion. By analogy with smooth muscle, these regulatory sites may also modulate calcium influx into the cell. On the basis of these and other results, the possible calcium pools important in histamine secretion are discussed.

Animals↗