Search PubMed⌕ Search

Biomedical subjects

J Morley

Publications and source records attributed to J Morley.

At least 163 records · Page 9Linked to original sources
PubMed1983

Inflammatory actions of platelet activating factor (Pafacether) in guinea-pig skin.

Cutaneous responses to synthetic platelet activating factor (Paf-acether) have been studied in guinea-pigs by means of radioisotopic marker techniques. Intradermal injection of Paf-acether elicited increased plasma protein extravasation (IPPE) (0.2-200 pmol/site), platelet accumulation (PA) (20-200 pmol/site) and red blood cell accumulation (RBCA) (200 pmol/site), whereas lyso-Paf (up to 2 nmol/site) was inactive in all these respects. Following intradermal injection, the IPPE responses to Paf-acether (2 and 20 pmol/site) were complete within 15 and 30 min respectively, although in response to 200 pmol/site, IPPE was detectable up to 1.5 h. The PA and RBCA responses to Paf-acether (200 pmol/site) were complete within 1 h. IPPE induced by Paf-acether (3 pmol/site) was potentiated by concomitant intradermal injection of a cutaneous vasodilator prostaglandin E2 (PGE2, 1 nmol/site) and inhibited by the beta-adrenoceptor agonist, isoprenaline (4.5 nmol/site) or the alpha-adrenoceptor agonist, phenylephrine (6 nmol/site). Such observations are consistent with Paf-acether effecting increased vessel wall permeability. Intradermal injection of PGE1 (3 nmol/site) significantly reduced PA in response to Paf-acether (200 pmol/site), whilst significantly enhancing IPPE. This dissociation of increased vascular permeability from PA is consistent with Paf-acether eliciting IPPE via a platelet-independent mechanism. These results indicate that a direct effect on vessel wall permeability contributes to the inflammatory response to Paf-acether in guinea-pig skin. It is suggested that Paf-acether is a potential mediator of allergy and inflammation.

Alprostadil↗
PubMed1983

The late reaction following bronchial provocation with house dust mite allergen. Dependence on arachidonic acid metabolism.

The involvement of arachidonic acid metabolism in early and late bronchial reactions has been studied in four asthmatic subjects sensitive to Dermatophagoides pteronyssinus. Pre-treatment with either indomethacin (an inhibitor of the cyclo-oxygenase pathway) or benoxaprofen (an inhibitor of both cyclo-oxygenase and lipoxygenase pathways) failed to affect the amplitude, but did produce some foreshortening of the early response to allergen. If benoxaprofen is an effective inhibitor of SRS-A formation in vivo, then these observations question the role of SRS-A as a spasmogen in allergen-induced bronchospasm. Both drugs were effective inhibitors of the late reaction, implying involvement of cyclo-oxygenase products (endoperoxides, prostaglandins or thromboxanes) in the genesis of a late response to allergen.

Adolescent↗
PubMed1982

An in vivo model for studying platelet aggregation and disaggregation.

A simple minimally invasive technique has been developed for the continuous monitoring of 111-Indium labelled homologous platelets in the thoracic (C1) and abdominal (C2) regions of experimental animals. The effects of the aggregatory agents adenosine diphosphate (ADP), collagen and platelet activating factor (PAF) and the anti-aggregatory agent, prostacyclin (PGI2) have been studied in the guinea-pig. Administration of ADP, collagen or PAF produces an increase in counts in C1, a decrease in counts in C2, and hence an increase in the ratio C1/C2. The rise in C1/C2 is more protracted after collagen administration than after ADP or PAF. PGI2 (50-500 ng/kg) reduces the response to ADP. The present technique is both simple, reproducible and although the present experiments are in the presence of heparin, the technique remains functional in the presence of minimal heparin, thus making it a suitable method for studies of platelet function and the evaluation of anti-aggregatory agents in vivo.

Abdomen↗
PubMed1982

Evidence in man of synergistic interaction between putative mediators of acute inflammation and asthma.

The two-component hypothesis of acute inflammation postulates that the acute inflammatory response depends on both increased local blood flow and increased microvascular permeability: the validity of this concept has previously been established in animals and was tested here in man. A mixture of the mediators prostaglandin E2 and bradykinin produces a larger cutaneous wheal (volume) response than can be accounted for either by summation of the responses to the individual substances or by the slopes of their dose-response curves. This enhanced response is inhibited by noradrenaline (consistent with the vasoconstrictor property of noradrenaline) and by salbutamol (consistent with the anti-permeability property of salbutamol). These observations indicate that the two-component hypothesis of acute inflammation applies to man as well as animals; this finding is important in the evaluation of the role of putative mediators in the pathogenesis of asthma and other diseases in which inflammation plays a part.

Acute Disease↗
PubMed1982

Enhancement of lymphocyte activation by BW755C in vitro.

BW755C considerably enhances the increased DNA synthesis of lymphocytes responding to mitogen stimulation. This effect is evident at much lower concentrations of BW755C than are required to inhibit cyclooxygenase or lipoxygenase enzymes. This suggests that in vivo effects of BW755C may not solely depend upon modification of arachidonic acid metabolism.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1982

Cyclosporin-A inhibits accumulation of lymphocytes within lymph nodes.

The ability of cyclosporin-A (CS-A) to modify lymphocyte accumulation, seen in lymph nodes draining a site of antigen deposition, has been compared with the effect of other drugs known to affect lymphocytes and/or macrophages. CS-A markedly inhibited lymphocyte accumulation in a dose-related manner, whereas aspirin, BW755c (3 amino 1 [m (trifluoromethyl) phenyl] 2-pyrazoline) and hydrocortisone were without effect. Indomethacin produced inconclusive results. The time of CS-A administration was critical, the drug needing to be present before antigen inoculation, being ineffective if given 23 hr after antigen.

Animals↗
PubMed1981

Leucotrienes, SRS-A and the vascular manifestations of PCA.

In order to study possible mediators of the vascular manifestations of passive cutaneous anaphylaxis (PCA), several arachidonic acid metabolites were injected into guinea-pig skin. SRS-A, LTB4, LTC and LTD increased vascular permeability, responses to LTs being enhanced by PGE2. Mepyramine inhibited responses to histamine, but not those to SRS-A and LTs; the latter were inhibited by the SRS-A antagonist FPL-55712. Both mepyramine and FPL-55712 exert limited inhibitory effects on vascular permeability during PCA. Leukotrienes may contribute towards vascular permeability during PCA.

Animals↗