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Biomedical subjects

J Morley

Publications and source records attributed to J Morley.

At least 145 records · Page 8Linked to original sources
PubMed1984

Cutaneous and pulmonary histopathological responses to platelet activating factor (Paf-acether) in the guinea-pig.

The effect of synthetic Paf-acether has been studied in guinea-pig skin, following intradermal injection, and in guinea-pig lung, following intravenous administration. Histopathological responses to Paf-acether were assessed by both light microscopy and electron microscopy. In addition, plasma protein extravasation and platelet accumulation were quantitatively assessed using radiolabelling techniques. Intradermal injection of Paf-acether, but not lyso-Paf, elicited acute increased vascular permeability, accompanied by intravascular accumulation of platelets and neutrophils. There was evidence, 2-8 h after intradermal injection of Paf-acether, of perivascular infiltration with neutrophils. At 24 h there was a mixed cellular infiltrate comprising mononuclear cells in addition to neutrophils. Following systemic administration of Paf-acether, aggregates of platelets in close association with neutrophils were evident within the pulmonary vasculature. Intravenous injection of Paf-acether, but not lyso-Paf, caused intrathoracic accumulation of radiolabelled platelets. These results suggest that Paf-acether has properties consistent with those of a mediator of inflammation.

Animals↗
PubMed1984

Effects of non-steroidal anti-inflammatory drugs on lymphocyte activation.

Guinea-pig lymph node lymphocytes were stimulated with mitogen (phytohaemagglutinin) in vitro and lymphocyte activation was measured by tritiated thymidine incorporation (DNA synthesis). Inclusion of non-steroidal anti-inflammatory drugs (NSAIDs) in the culture medium at therapeutic concentrations, frequently exerted an inhibitory effect. Such inhibition could not be attributed to the ability of these drugs to inhibit cyclo-oxygenase or lipoxygenase enzymes. Inhibition by salicylates was not associated with cytotoxic or cytopathic effects, since inhibition was only evident when the drugs were included in the early phase of culture. Other NSAIDs exhibited varying degrees of toxicity, which in some instances may account for observed inhibition. The effects on lymphocyte activation of selective inhibitors of pathways of arachidonic acid metabolism, do not support the proposition that the generation of prostaglandins, thromboxanes, leukotrienes or related compounds is an obligatory step during lymphocyte activation.

Animals↗
PubMed1984

Mononuclear cell accumulation and plasma protein extravasation (PPE) during induction, remission and re-challenge of experimental allergic encephalomyelitis in the rat.

Plasma protein extravasation (PPE) and cell accumulation have been studied in the CNS of rats during experimental allergic encephalomyelitis (EAE) using radioisotopic techniques. Use of such techniques makes it possible to study objectively and conveniently the rate of cell infiltration and PPE during the disease process in relation to clinical signs and time after immunization. The following observations have been made: After the first immunization, the number of rats showing increased PPE in the CNS correlated well with the severity of EAE. Mononuclear cell infiltration into brain and spinal cord during EAE did not parallel one another; infiltration being of earlier onset and shorter duration in the spinal cord, in comparison with brain. Animals re-challenged with encephalitogenic antigen showed considerably increased cellular infiltration into the brain but failed to exhibit comparable infiltration in the spinal cord. In this case infiltration of cells is not accompanied by increased PPE, in contrast to what is seen during primary disease. Increased infiltration into the brain of re-challenged animals appears, therefore, unrelated to gross damage of vascular endothelium.

Animals↗
PubMed1984

Synergistic interaction between prostaglandins and PAF-acether in experimental animals and man.

Platelet activating factor (PAF-acether) is released from a variety of inflammatory cell types and has properties appropriate to a mediator of allergy and inflammation. Here, we have examined the interaction between PAF-acether and the prostaglandins, PGE2 and ZK 36374 (a stable analogue of prostacyclin, PGI2) in the skin of guinea-pigs and human volunteers. PGE2 and ZK 36374 significantly potentiated increased plasma protein extravasation induced by PAF-acether in guinea-pigs, assessed by extravasation of I-125-HSA. In addition, PGE2 significantly potentiated the ability of PAF-acether to elicit acute wheal (volume) and flare responses in human skin. The inflammatory properties of PAF-acether should not be considered in isolation since this phospholipid interacts synergistically with prostaglandins which are recognised as modulators of inflammation.

Animals↗
PubMed1984

Modulation by cyclosporin-A of mononuclear cell distribution during experimental allergic encephalomyelitis.

The capacity of CS-A to modify some inflammatory aspects of a cell mediated disease process, has been studied. In the present work, CS-A was shown to be effective at two levels during the development of experimental allergic encephalomyelitis (EAE) in rats. If CS-A was given at the time of the induction of the disease it inhibited lymphocyte proliferation in vivo, lymphocyte trapping into the draining lymph nodes, and delayed the subsequent infiltration of cells into the CNS and other inflammatory sites. When given around the time of disease manifestation, CS-A also reduced the rate of cell accumulation into the CNS and foot, but was without effect in modifying lymphocyte trapping in the draining nodes, despite the fact that this was still an ongoing process. Clinical signs were similarly delayed or reduced by both regimen of CS-A treatment. Treatment with CS-A did not lead, however, to long lasting unresponsiveness, since both treated groups suffered a relapse of disease at various times after treatment had been discontinued.

Animals↗
PubMed1984

Mononuclear leukocyte cyclic adenosine monophosphate responses in psoriasis are normal.

It has been proposed that immune dysfunction in psoriasis is a consequence of aberrant cyclic nucleotide metabolism. We have examined cyclic AMP responses to isoprenaline, histamine, and prostaglandin E2 in peripheral blood mononuclear leukocytes from patients with psoriasis, in the presence and absence of a potent cyclic AMP phosphodiesterase inhibitor. Stimulated and basal cyclic AMP levels in mononuclear leukocytes from psoriatics did not differ from those observed in mononuclear leukocytes from normal subjects, irrespective of the stimulant employed, either in the presence or in the absence of the phosphodiesterase inhibitor. These findings do not support the hypothesis that psoriasis is associated with either impaired beta-adrenergic reactivity or a more generalized abnormality of mononuclear leukocyte cyclic nucleotide metabolism.

Adult↗
PubMed1984

Inflammatory characteristics of platelet activating factor (PAF-acether) in human skin.

The phospholipid PAF-acether is released from a range of inflammatory cell types and, in experimental animals, has properties appropriate to a mediator of inflammation. We have studied the inflammatory characteristics of intradermally injected PAF-acether in human skin. An early weal and flare response was succeeded, in a proportion of subjects, by an area of late-onset 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 has been determined and a synergistic interaction between PAF-acether and prostaglandin E2 established. PAF-acether should therefore be considered as a potential mediator of both acute and persisting inflammation in man.

Adult↗
PubMed1984

Platelet-activating factor: a possible mediator of the dual response to allergen?

Certain allergic asthmatic patients exhibit a dual response in the lung following bronchial challenge with the appropriate allergen. Often this is paralleled by a cutaneous dual response when the antigen is injected intradermally. The mechanisms underlying such phenomena are not established, but some evidence suggests that the late response is a consequence of the early response. Since platelet activation has been observed following antigen challenge in asthmatic subjects, we have studied the ability of platelet activating factor (PAF-acether, AGEPC) to induce cutaneous inflammatory responses in man. In a time course study over 24 hr, PAF-acether produced a biphasic response: an immediate weal and flare reaction, which resolved within 1-2 hr and was followed some 3-6 hr later by a delayed reaction in which erythema associated with hyperalgesia was evident. These observations suggest that PAF-acether should be considered in the context of allergic asthma as a possible mediator of the dual response to allergen.

Adult↗
PubMed1984

Autonomic regulation of mucociliary transport rate in the oesophagus of the frog, Rana temporaria.

Transport of lead particles along the mucosal surface of the frog oesophagus has been measured by direct observation with the aid of video recording. Electrical stimulation of the vagus nerve increased the rate of particle transport. This acceleration was suppressed by atropine or by hexamethonium. Acetylcholine and other parasympathomimetic agents accelerated particle transport rate. Such acceleration was abolished by atropine. Nicotine increased the rate of particle transport and this effect was suppressed by hexamethonium or by atropine. Atropine did not significantly alter basal particle transport rate. Neither basal particle transport rate nor the response to vagal nerve stimulation were affected by eserine. Adrenaline, noradrenaline or isoprenaline did not affect basal particle transport rate. Adrenaline or noradrenaline were without effect on the increased particle transport rate due to electrical stimulation of the vagus.

Animals↗
PubMed1984

Platelets and bronchospasm.

The intrathoracic accumulation of radiolabelled platelets and concomitant changes in airway resistance have been recorded continuously in anaesthetised guinea pigs. Platelet-activating factor (PAF-acether) and antigen (in sensitised animals) elicited dose-related intrathoracic accumulation of platelets that could be associated with an increase in airway resistance. Maximal increases in airway resistance preceded maximal increases in platelet accumulation. Low doses of antigen could elicit substantial platelet accumulation, without detectable changes in lung function. It is concluded that physical obstruction of the pulmonary vasculature is not the sole determinant of platelet-dependent bronchoconstriction.

Airway Resistance↗
PubMed1984

Beta-adrenoceptor agonist responses in the skin and lungs of asthmatic subjects.

Concomitant intradermal injection of salbutamol inhibits histamine-induced weal volume in the skin of atopic asthmatic subjects and the degree of this inhibition (index of beta-adrenergic effect in the skin) correlates with the bronchodilator effect of inhaled salbutamol in the same subjects (index of beta-adrenergic effect in the lung).

Adrenergic beta-Agonists↗
PubMed1984

Circulating beta-adrenoceptor blocking factors in asthma.

The hypothesis that a generalized defect in beta-adrenoceptor function characterized asthma and atopy has been proposed by Szentivanyi. Such a defect may be intrinsic to the beta-adrenoceptor mechanism or could be attributed to circulating factors which interfere with the binding of catecholamines to beta-adrenoceptors. This study shows that sera from a proportion of the asthmatic population studied contain beta-adrenoceptor blocking activity and that the degree of inhibition correlates with some of the clinical indices of asthma.

Adrenal Cortex Hormones↗
PubMed1983

Cyclosporin A--a pre-recruitment action in the cutaneous response?

Mononuclear cell accumulation in rat skin sites, over a 24 h period following intradermal injections of concanavalin A (Con A) and carrageenan, was quantitated using an isotopic technique. Cyclosporin A (CS-A) inhibited the accumulation of [51Cr]-labelled blood mononuclear cells into cutaneous reactions to Con A but not carrageenan reactions in the same animals. Conversely, indomethacin or cobra venom factor inhibited cell accumulation into carrageenan-induced lesion, whilst leaving infiltration into Con A reactions unimpaired. Since CS-A did not show a general anti-inflammatory effect, it is suggested that this compound reduces cell accumulation by inhibiting the local release of lymphokines in vivo.

Animals↗
PubMed1983

A comparative study of PGI2 and two analogues (FCE 21292 and FCE 21258) in vitro and in vivo.

Two analogues of PGI2, FCE 21258 (5E-13,14-didehydro-carboprostacyclin) and FCE 21292 (5E-13,14-didehydro-20-methyl-carboprostacyclin) have been evaluated in comparison with PGI2 in different in vitro and in vivo screening tests. The rank order of potency was PGI2 greater than FCE 21292 greater than FCE 21258 in the following tests: potentiation of bradykinin-induced increased plasma protein extravasation in the guinea pig skin, inhibition of guinea pig platelet aggregation in vivo where the duration of action of FCE 21292 was longer than that of PGI2, lowering of mean systemic arterial pressure in conscious normotensive and spontaneously hypertensive rats and inhibition of rabbit platelet aggregation in vitro. In the relaxation of bovine coronary artery in vitro the rank order of potency was FCE 21292 greater than PGI2 greater than FCE 21258.

Animals↗
PubMed1983

Impaired lymphocyte cyclic adenosine monophosphate responses in atopic eczema.

Peripheral blood lymphocyte cyclic AMP responses to isoprenaline, prostaglandin E2 and histamine were examined in patients with atopic eczema, in the presence and absence of a potent phosphodiesterase inhibitor (PDEI). Basal cyclic AMP levels were not significantly different in atopic and control groups. In the presence of the PDEI, there were impaired cyclic AMP responses to both isoprenaline and prostaglandin E2 in the atopic group. Differences between atopic and control cyclic AMP responses were exaggerated by the omission of the PDEI, when impaired responses to all agonists were observed in lymphocytes from atopic subjects. These results imply that, in atopic eczema, lymphocytes exhibit impaired responses not only at the beta-adrenoceptor site but at unrelated sites of adenylate cyclase activation, and these observations are consistent with increased leukocyte phosphodiesterase activity.

Adult↗