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Biomedical subjects

J Morley

Publications and source records attributed to J Morley.

At least 19 recordsLinked to original sources
PubMed1992

Cyclosporin A in asthma therapy: a pharmacological rationale.

Lymphocytes play a central role in immunological reactions and control the mobilisation and recruitment into lung tissue of eosinophils and mast cells. Since cyclosporin A can profoundly influence lymphocyte activation, it is appropriate to consider this drug as a novel anti-asthma therapy. Inhalation of low doses of cyclosporin A strongly inhibits the influx of inflammatory cells into the airways during acute allergic reactions, even though associated bronchospasm and airway hyper-reactivity are undiminished. It is suggested that cyclosporin A will be an effective anti-asthma therapy with an anti-asthma profile resembling that of established glucocorticosteroids.

Animals↗
PubMed1992

Effects of a potassium channel opener (SDZ PCO 400) on guinea-pig and human pulmonary airways.

1. SDZ PCO 400 evoked dose-related relaxation of isolated airway smooth muscle. For human bronchus precontracted by endogenous tone or addition of carbachol (10(-5) M), IC50 values were 1.74 microM and 1.82 microM respectively. With guinea-pig trachea contracted by endogenous tone, a comparable IC50 (1.79 microM) was observed, but no IC50 (less than 100 microM) could be determined following contraction by carbachol (10(-6) M). 2. Airway obstruction induced by intravenous bombesin in the anaesthetized ventilated guinea-pig was diminished by intravenous injection of SDZ PCO 400 (ID50 54 micrograms kg-1) or by introduction into the duodenum (ID50 1.0 mg kg-1). Inhalation of nebulized SDZ PCO 400 (0.1 mg kg-1) diminished airway obstruction due to intravenous injection of histamine (3.2-5.6 micrograms kg-1) for up to 20 min. 3. Increased bronchoconstrictor responses to bombesin (180-240 ng kg-1) following intravenous infusion of platelet activating factor (PAF) or (+/-)-isoprenaline, or to histamine (1.0-3.2 micrograms kg-1) following intravenous injections of immune complexes, were suppressed following concomitant intravenous infusion of SDZ PCO 400 (ID50 0.3 mg kg-1 h-1, 1.0 mg kg-1 h-1 and 0.1 mg kg-1 h-1 respectively). 4. Intravenous injection of SDZ PCO 400 (0.1 mg kg-1) effected transient (less than 10 min) inhibition of histamine-induced bronchospasm, yet diminished, for prolonged periods [up to 40 min] the enhanced bronchoconstrictor responses to histamine that followed intravenous injections of immune complexes.The capacity of SDZ PCO 400 to resolve such established airway hyperreactivity was prevented by prior intraduodenal instillation of a potassium channel antagonist, glibenclamide (30 mg kg-').5. In sensitized guinea-pigs, SDZ PCO 400 inhaled as a dry powder (5.7 mg kg-') suppressed development of allergic airway hyperreactivity to histamine (1.8-3.2;pg kg-', i.v.), but failed to diminish accumulation of eosinophils or other inflammatory cells within the airway lumen 24 h after inhalation of ovalbumin.6. Preincubation (30 min) of isolated sensitized trachea of guinea-pig with SDZ PCO 400 (10-5-10-4M) did not influence contractile responses to ovalbumin. However in anaesthetized sensitized guinea-pigs,insufflation of SDZ PCO 400 (1.25 mg) as a powder substantially diminished airway obstruction that followed inhalation of ovalbumin. This effect was prevented by prior vagal section.7. It is concluded that SDZ PCO 400 reduces airway obstruction not only through direct actions on airway smooth muscle but also by impairing the expression of airway hyperreactivity, without directly influencing inflammatory events in the airways.

Airway Obstruction↗
PubMed1992

Effects of liposome encapsulated hemoglobin on the reticuloendothelial system.

The effects of different doses (4, 10, and 25%) of liposome encapsulated hemoglobin (LEH) were measured on the Reticuloendothelial System (RES) and Kupffer cells (KC) by i) colloidal carbon clearance in the rat in vivo and in the isolated perfused liver, ii) magnetometry, and iii) histological analysis. At the highest dose, in vivo carbon clearance rates (k) were half the rate as in controls at 2 and 12 hours post-treatment. By 24 hours post-treatment clearance rates were at control levels. Empty liposomes (LIP) caused a 2-fold decrease in k at 2 hours only. With both LEH and LIP, the effects were less severe when rats were given the lower doses. Magnetometric studies showed a decrease in KC phagosomal motion in the LEH-treated (25%) rats at 2 and 24 hours that returned to control levels at 2 weeks. Perfused livers from rats treated with a low dose of LEH cleared carbon at the same rate as LIP and Krebs Ringer Bicarbonate (KRB) controls. Histological examination showed minimal tissue damage in all test groups. Thus, LEH and LIP have some short-term deleterious effects on KC and the RES probably due to RES blockade rather than cellular damage.

Animals↗
PubMed1979

Prostaglandin and thromboxane production by human and guinea-pig macrophages and leucocytes.

The ability of partially purified human and guinea-pig haematogenous cell populations, when cultured in vitro, to metabolise arachidonic acid (AA) has been studied. Supernatants from 24 hour cell culture have been subjected to analysis for products of AA metabolism by gas chromatography with electron-capture detection. The cell types studied were human peripheral blood monocytes (both glass adherent and non-adherent), neutrophils, eosinophils and leukemia leucocytes; thoracic duct lymphocytes and lung alveolar macrophages. From the guinea-pig, induced and non-induced macrophage or neutrophil enriched peritoneal exudate populations, lymph node cells, peritoneal eosinophils and peripheral blood platelets were examined. Supernatants were assayed for the presence of PGE2, PGD2, PGF2 alpha, TXB2 and 6-keto-PGF1 alpha. In all types studied PGE2 and TXB2 were the major products formed. The identification of PGE2 and TXB2 was confirmed by GC/MS with multiple ion monitoring. The results have been compared with other reports and their possible significance discussed in relation to the proposed role of prostaglandins as mediators and modulators in immunopathology.

Animals↗
PubMed1978

Anti-inflammatory drug actions on allergic responses in guinea-pig skin.

Five non-steroidal anti-inflammatory drugs (indomethacin, naproxen, meclofenamic acid, feprazone and phenylbutazone: NSAIDs) and three glucocorticosteroids (dexamethasone, hydrocortisone and prednisolone) have been tested as local inhibitors of increased vascular permeability in guinea-pig skin. Lesions were induced by histamine or by antigen to evoke type I (passive cutaneous anaphylaxis), type III (reverse passive Arthus) and type IV (delayed hypersensitivity) allergic reactions. NSAIDs and glucocorticosteroids caused either weak, inconsistent inhibition or slight, high-dose inhibition of the response to histamine. None of the drugs tested showed significant inhibition of the type IV response. The NSAIDs caused dose-related inhibition of both type I and type III responses whereas glucocorticosteroids were ineffective. Maximum inhibition with the NSAIDs was never greater than 50--60% Feprazone, meclofenamic acid and indomethacin were the most potent inhibitors of histamine, PCA and Arthus responses respectively. The possible significance of the effects of these anti-inflammatory agents on vascular permeability is discussed.

Animals↗
PubMed1978

Prostaglandins as regulators in cellular immunity.

Guinea-pig peritoneal macrophages have been shown to generate substantial concentrations of E-type prostaglandins during culture in vitro. Partially purified lymphokine preparations stimulate PGE production by macrophages. Exogenous PGE1 and PGE2 are potent inhibitors of lymphocyte activation and secretion of lymphokines causing lymphocyte mitogenesis and macrophage migration inhibition. Also indomethacin augments the secretion of these lymphokines in vitro. It is therefore suggested that production of PGE by macrophages provides a physiological mechanism for the regulation of lymphocyte activation in reactions of delayed hypersensitivity.

Animals↗
PubMed1978

The effect of luteinizing hormone releasing hormone (LRH) on pituitary gonadotropins in male homosexuals.

Basal serum LH and FSH values were found to be within normal limits in 9 homosexual men. The mean LH and FSH responses following the intravenous administration of 100 microgram of LRH were not significantly different from that of heterosexual controls. In addition, the mean basal plasma serum testosterone was similar in the two groups. There is thus no definite implication of endocrine factors in the genesis of male homosexuality.

Adult↗
PubMed1978

Prostaglandins and lymphokines in inflammation.

It is suggested that the inflammatory process in rheumatoid arthritis (RA) results from activation of small lymphocytes to produce lymphokines, whose biological properties are appropriate to a mediator of chronic inflammation. Since prostaglandins (PGs) and allied products of arachidonic acid metabolism have properties pertinent to chronic inflammation, these compounds can also be regarded as potential mediators of chronic inflammation, a viewpoint supported by the capacity of steroids and non-steroidal anti-inflammatory drugs (NSAIDs) to suppress PG formation. Certain observations are inconsistent with PGs fulfilling this role. These anomalies may be resolved by considering PGE2 formation by macrophages to be a device for regulating lymphocyte activation. A defect of lymphocyte reactivity to PGE2 provides a basis for chronicity and has been demonstrated in multiple sclerosis (MS). Alternatively, should lymphocytes in lesions of RA be susceptible to PGE2 inhibition, one consequence of NSAID treatment may be exacerbation of joint destruction.

Animals↗
PubMed1978

Prostaglandin production in arthritis.

Inflammatory cell populations from synovial effusions or synovial villi in rheumatoid arthritis have been cultured in vitro. Prostaglandin productive capacity, measured by radioimmunoassay, showed the polymorphonuclear leucocyte rich populations from synovial effusions to be poor sources of PGE production whereas the synovial fragments produced substantial amounts of PGE activity. It is suggested that the macrophage is the major source of local prostaglandin formation both in gout and rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1978

A comparison of the hematogenous cell infiltrate evoked by lymphokine injection with that of delayed hypersensitivity reactions.

Lymphokine preparations of high potency obtained by in vitro assay were employed in vivo to determine whether they could produce inflammatory responses showing a cellular infiltrate that qualitatively or quantitatively resembled responses of delayed hypersensitivity. Hematogenous cell infiltrates in guinea pig skin were characterized in terms of the number and types of participating cells following intradermal injection of either lymphokines or an antigen (PPD) to which the animals exhibited delayed hypersensitivity. The dose of lymphokine or PPD per skin test site was selected on the basis of comparable ability to enhance vascular permeability. Delayed hypersensitivity responses showed, as expected, a persistent mononuclear cell exudate both in dermis and subcutis, but most notable in the dermis, during the 24 hours following antigen injection. In contrast, the response to lymphokine over the same period was characteristically neutrophilic and principally in the subcutis. There was no pronounced mononuclear cell infiltrate at any time throughout the reaction to lymphokine. It is concluded that preformed lymphokine produces a pattern of increased vascular permeability appropriate to a mediator of delayed hypersensitivity reactions, provided there is sustained secretion of this material. The ability of lymphokine to cause carbon labeling of dermal capillaries is also pertinent to a mediator of delayed hypersensitivity. The absence of significant mononuclear cell accumulation suggests that the in vitro chemotactic activity of lymphokine toward mononuclear cells may be more important for retention of mononuclear cells in the extravascular connective tissue space than for their selective accumulation.

Animals↗