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Biomedical subjects

J Morley

Publications and source records attributed to J Morley.

At least 127 records · Page 7Linked to original sources
PubMed1985

Accumulation of inflammatory cells in response to intracutaneous platelet activating factor (Paf-acether) in man.

Platelet activating factor (Paf-acether, AGEPC) is a family of ether-linked phospholipids known to be released from a range of inflammatory cell types. In vitro and in experimental animals, it seems to be a mediator of inflammation, and intradermal injection of Paf-acether in man elicits a biphasic inflammatory response, reminiscent of the dual response to allergen in sensitized individuals. In the present study, cutaneous histology was assessed in sequential skin biopsies from six normal volunteers after intradermal injection of 200 or 800 pmol Paf-acether. Paf-acether (200 pmol) induced intravascular accumulation of neutrophils, accompanied by a perivascular mixed cellular infiltrate which was composed predominantly of neutrophils at 4 and 12 hours, and lymphocytes and histiocytes at 24 hours. Control injections of lyso-Paf and normal saline induced no noteworthy histological changes. Paf-acether (800 pmol) resulted in vessel destruction, gross endothelial swelling and a perivascular infiltrate of mononuclear cells and neutrophils, accompanied by occasional evidence of leucocytoclasis. By virtue of its ability to induce inflammatory cell accumulation in human skin, Paf-acether should be considered as a potential mediator of inflammatory disorders such as psoriasis.

Adult↗
PubMed1985

Inflammatory cell accumulation in response to intracutaneous Paf-acether: a mediator of acute and persistent inflammation?

The ether-linked phospholipid, Paf-acether (AGEPC) is released from a variety of inflammatory cell types and has properties consistent with those of a mediator of inflammation. We have examined the effects of locally administered Paf-acether on cellular accumulation in the skin of experimental animals and man by histological evaluation of sequential skin biopsies and quantification of accumulation of radiolabelled blood elements. In guinea-pig skin, immediate extravasation of plasma protein and intravascular accumulation of platelets and neutrophils was succeeded by a persistent mixed cellular infiltrate predominantly of neutrophils but also containing lymphocytes and histiocytes. Radiolabelling studies were consistent with these observations. Intradermal Paf-acether elicited persistent clinical and histopathological responses in human skin. The finding that Paf-acether is able to initiate cutaneous cellular accumulation may be important in the pathogenesis of inflammatory dermatoses.

Acute Disease↗
PubMed1985

Effects of serum albumin, indomethacin and histamine H1-antagonists on Paf-acether-induced inflammatory responses in the skin of experimental animals and man.

Cutaneous responses to synthetic platelet activating factor (Paf-acether) have been studied in guinea-pig and human skin. Intradermal injection of Paf-acether elicited an acute inflammatory response in guinea-pig skin (assessed by means of radioisotopic techniques) and acute oedema formation in human skin (assessed by means of weal volume and flare area). Acute inflammatory responses in guinea-pig and human skin are potentiated by the presence of serum albumin, a phospholipid carrier. Acute inflammatory responses induced by Paf-acether in guinea-pig and human skin are not significantly affected by concomitant administration of the cyclo-oxygenase inhibitor, indomethacin. Acute inflammatory responses induced by Paf-acether in guinea-pig and human skin are not significantly affected by concomitant administration of the cyclo-oxygenase inhibitor, indomethacin. Acute inflammatory responses induced by Paf-acether in guinea-pig and human skin are slightly modified by the H1-receptor antagonists, mepyramine and chlorpheniramine. These results indicate that the acute inflammatory response induced by Paf-acether is independent of cyclo-oxygenase products of arachidonic acid and that histamine release has a minor contribution to the inflammatory response induced by Paf-acether.

Adult↗
PubMed1985

Pharmacology of the late response to allergen and its relevance to asthma prophylaxis.

Inhalation of allergen by sensitised asthmatics results in an acute increase of airways resistance that, in some individuals, is succeeded by a response of late-onset. Late-onset responses are associated with an increased airway reactivity to constrictor stimuli that lasts for several days and hence may be akin to exacerbation of clinical asthma. For this reason, much attention has been given to inhibition of late-onset reactions by glucocorticosteroids or by cromoglycate. Such effects have been cited as evidence of anti-asthma efficacy for these drugs and also for ketotifen, as might be anticipated from prophylactic efficacy in clinical asthma. More recently, a similar inhibitory effect has been demonstrated for theophylline, which is in marked contrast to beta-adrenoceptor agonists, which have long been known not to inhibit expression of late-onset reactions. The profile of drug sensitivity observed for late-onset reactions precludes mast cell stabilisation as an adequate explanation, since late-onset reactions are unaffected by beta-adrenoceptor agonists, notwithstanding the potency of such drugs as inhibitors of mast cell secretion; furthermore, late-onset reactions can be inhibited by nonsteroidal anti-inflammatory drugs, even though such drugs can enhance mast cell secretion. Rather, present evidence favours platelet-activating factor (PAF, Paf-acether, AGEPC) as a primary determinant of late-onset reactions, especially since responses to this material can be inhibited by cromoglycate, glucocorticosteroids, ketotifen and theophylline, and since there is substantial evidence that PAF has properties that could account for exacerbation of asthma.

Airway Resistance↗
PubMed1985

Adrenoceptor function in atopic dermatitis: in vitro and in vivo observations.

Impaired beta-adrenergic and enhanced alpha-adrenergic reactivity have been implicated in the pathogenesis of atopic dermatitis. We have measured the elevation of cyclic AMP in peripheral blood leukocytes in response to isoprenaline, histamine and prostaglandin E2, in the presence and absence of a phosphodiesterase inhibitor. An impaired response to beta-adrenergic stimulation was demonstrated in subjects with atopic dermatitis but impaired responses were also observed with histamine and prostaglandin E2. In vivo, both noradrenaline and salbutamol caused significant inhibition of the histamine-induced weal response in atopic and normal subjects. However, there was no significant difference between the two groups when alpha- and beta-adrenoceptor responses were compared.

Adrenergic alpha-Agonists↗
PubMed1985

Inflammatory characteristics of PAF-acether in the skin of experimental animals and man.

PAF-acether (AGEPC) is released from a range of inflammatory cell types and has properties consistent with those of a mediator of inflammation. Intradermal injection of PAF-acether in experimental animals causes immediate extravasation of plasma protein, accompanied by intravascular accumulation of platelets and neutrophils; this is followed by persistent extravascular accumulation of neutrophils and mononuclear cells. We have studied the inflammatory characteristics of intradermally injected PAF-acether in human skin. An early (weal and flare) response is succeeded, in 60% of subjects, by a late-onset area of erythema at the site of the resolved weal, reminiscent of the dual response to allergen in sensitized individuals. The time course and dose-response relationship of the early response was determined and a synergistic interaction between PAF-acether and prostaglandin E2 established. The weal response to PAF-acether was not inhibited by concurrent administration of chlorpheniramine. Histopathological examination of serial elliptical biopsies revealed accumulation of both neutrophils and mononuclear cells in response to intracutaneous PAF-acether. We would suggest that PAF-acether is likely to be a mediator of both acute and persistent inflammation.

Animals↗
PubMed1984

Inhibition by heparin of platelet accumulation in vivo.

In vivo platelet aggregation has been studied using a novel, minimally invasive technique. No aggregatory effects of heparin were observed on normal circulating platelets nor was there enhancement of aggregation of platelets during activation by intravenous injection of ADP, collagen, PAF acether or thrombin. On the contrary, high doses of heparin were found to inhibit platelet accumulation induced by ADP, collagen or PAF-acether. Inhibition of these responses necessitated doses of heparin in excess of those required for anti-coagulant effects. The present experiments do not establish a mechanism for such inhibition. Extension to other species, including man, is needed before attributing clinical relevance to the present observations.

Animals↗