Biomedical subjects

L G Cleland

Publications and source records attributed to L G Cleland.

At least 73 records · Page 4Linked to original sources

PubMed1991

Prevention of chronic erosive streptococcal cell wall-induced arthritis in rats by treatment with a monoclonal antibody against the T cell antigen receptor alpha beta.

Rats treated with an mAb (R73) against the TCR-alpha beta failed to develop chronic persistent arthritis after injection of streptococcal cell walls. Histologically, R73 mAb-treated rats had mild hyperplasia of synovial lining cells and minimal destruction of cartilage. In contrast, control-treated animals developed marked pannus formation, with pronounced infiltration of mononuclear cells and severe destruction of cartilage and subchondral bone. The preventive effect of R73 mAb on streptococcal cell wall-induced arthritis was associated with the marked depletion of alpha beta + T cells by R73 mAb. These results indicate that T cells play a crucial role in chronic erosive streptococcal cell wall-induced arthritis.

Animals↗

PubMed1991

Treatment of collagen-induced arthritis in rats with a monoclonal antibody against the alpha/beta T cell antigen receptor.

A monoclonal antibody (MAb) to the alpha/beta T cell receptor (TCR alpha/beta), R73 MAb, completely blocked the induction of collagen-induced arthritis (CIA) in rats when the MAb was administered at the time of immunization with type II collagen. When administered after CIA had begun, the progression of the arthritis was suppressed significantly by R73 MAb treatment. The preventive and suppressive effects of R73 MAb on CIA were associated with the depletion of peripheral blood alpha/beta-positive T cells. These results indicate that alpha/beta-positive T cells play a role in the progression of existing CIA as well as in its induction.

Animals↗

PubMed1991

Separation and quantification of PGE3 following derivatization with panacyl bromide by high pressure liquid chromatography with fluorometric detection.

Separation of prostaglandin E3 (PGE3) from prostaglandin E2 (PGE2) and prostaglandin E1 (PGE1) was achieved following derivatization with p-(9-anthroyloxy)phenacyl bromide (panacyl bromide). The eicosanoid esters were analysed by reverse phase high pressure liquid chromatography with fluorometric detection (excitation 360nm and emission 470nm). Human, rat and mouse adherent cells were incubated overnight and the culture medium extracted, derivatized and analysed for PG production. PGE2 was detected from biological samples of each species tested. PGE2 synthesis was reduced when cells were incubated overnight with 5 microM eicosapentaenoic acid. PGE3 was not detectable under these experimental conditions. Studies were also undertaken using adherent cells from mice, rats and human subjects given dietary fish oil supplements rich in EPA. PGE3 production by these cells was not detected although the dietary regimens yielded substantial incorporation of EPA into cell membranes and leukocyte LTB5 production was demonstrable.

Alprostadil↗

PubMed1991

The effect of adjuvant-induced arthritis on rat leukocyte membrane phospholipid fatty acid levels following fish oil feeding.

Inflamed rats with adjuvant-induced polyarthritis showed similar incorporation of dietary eicosapentaenoic acid (EPA) into peritoneal exudate cell (PEC) membrane phospholipids compared to pair fed non-inflamed control rats. Arachidonic acid (AA) content was similar in PEC phospholipids of inflamed and control rats whereas the linoleic acid content was consistently higher in inflamed rats.

Animals↗

PubMed1991

Strategies for increasing the antiinflammatory effect of fish oil.

While both animal and human studies have shown that fish oil can exert antiinflammatory actions, the effects are modest and require large doses. The effects may be amplified by modifying the intake of other dietary fats and by making use of favourable interactions between fish oil and drugs.

Animals↗

PubMed1991

Interaction between fish and vegetable oils in relation to rat leucocyte leukotriene production.

We examined the influence of mixtures of dietary fish oil and three vegetable oils (linseed, olive and sunflower) on the incorporation of dietary eicosapentaenoic acid (EPA) into rat leucocyte phospholipids and the subsequent metabolism of EPA and arachidonic acid by 5-lipoxygenase. Eicosapentaenoic acid in leucocyte phospholipids of fish oil-fed rats was decreased by the addition of each vegetable oil to the dietary fish oil, with sunflower oil, the oil highest in linoleate (LA), having the largest EPA-lowering effect (66% decrease). The rate of synthesis of leukotriene B4 (LTB4) was increased by the addition of each vegetable oil to the basic fish oil diet, with sunflower oil having a significant effect on LTB4 synthesis (145% increase). The effects of olive oil (enriched in oleate) were similar to those of linseed oil (enriched in alpha-linolenic acid) with regard to EPA incorporation (mean decrease = 30%) and LTB4 synthesis (mean increase = 72%). The level of arachidonic acid in leucocyte membranes and the rate of synthesis of LTB4 were proportional to the level of dietary LA added to the basic fish oil diet. The results indicate that olive or linseed oil ingested in combination with fish oil have less effect than does sunflower oil on leucocyte EPA content and LTB4 production. They further suggest that, when ingested with fish oil, dietary linoleic acid is more important than oleate or alpha-linolenic acid as a determinant of these variables.

Animals↗

PubMed1991

Inhibition of human endothelial prostacyclin synthesis by different aspirin formulations.

The availability of different formulations of low-dose aspirin for use as anti-thrombotic agents merits a comparison of their effects on vessel wall biochemistry. We compared the effect of ingestion of an enteric-coated slow-release aspirin (Astrix) with that of soluble aspirin (Cardiprin) on human endothelial prostacyclin synthesis. Patients undergoing varicose vein surgery (10 per group) ingested 100 mg aspirin per day as Astrix or Cardiprin for 7 days prior to surgery. A control group ingested no aspirin. Prostacyclin synthesis by the endothelial surface of the great saphenous vein was determined in vitro. Both aspirin formulations caused significant inhibition of endothelial prostacyclin synthesis compared with the control group. Using the median values, the enteric-coated slow-release aspirin caused 76% inhibition, whereas the soluble formulation caused significantly greater inhibition (95%). If differential inhibition of platelet thromboxane synthesis with 'sparing' of endothelial prostacyclin synthesis is necessary for an optimum anti-thrombotic effect of aspirin, the results suggest that a lower dose of soluble aspirin than enteric-coated slow-release aspirin may be preferred.

Aspirin↗

PubMed1991

Cryofibrinogenaemia: a case report.

A case of chronic acral ulceration is described in a 54-year-old man with cryofibrinogenaemia. Initial management with prednisolone and azathioprine was unsuccessful in controlling the disease. Introduction of a programme of plasmapheresis in addition to treatment with cyclophosphamide and prednisolone has brought about marked improvement.

Cryoglobulinemia↗

PubMed1990

IL-3 and granulocyte-macrophage colony-stimulating factor stimulate two distinct phases of adhesion in human monocytes.

IL-3 and granulocyte-macrophage CSF are hemopoietic growth factors involved in monocytopoiesis and functional stimulation of circulating blood monocytes. We demonstrate that both cytokines enhance the adhesion of purified human monocytes to cultured human umbilical vein endothelial cells and to plastic surfaces. The stimulation seen was biphasic: an early phase detectable by 10 min, and a late phase seen after 9 h of in vitro culture. IL-3- and granulocyte-macrophage-CSF-stimulated adhesion was seen at concentrations as low as 6 pM, with maximal monocyte adhesion of up to 60% seen at concentrations of 60 pM and above. Both phases of stimulated adhesion were partially inhibited by a monoclonal antibody to CD18, the common beta-chain of the leukocyte functional Ag family of adhesion molecules, but not by an antibody to CD11b, the alpha-chain of MAC-1. However, a difference in the mechanism by which the early and late phases of stimulated adhesion arise could be shown by the use of cycloheximide as an inhibitor of protein synthesis. Although the late phase was totally dependent on de novo protein synthesis, early phase adhesion was not inhibited by cycloheximide, suggesting receptor redistribution or conformational change as the mechanism mediating enhanced adhesion at this time. These findings may be relevant to the pathogenesis of inflammatory disease and may have implications for the clinical use of these cytokines.

Antibodies, Monoclonal↗

PubMed1990

Effect of dietary oils on the production of n-3 and n-6 metabolites of leukocyte 5-lipoxygenase in five rat strains.

We examined the influence of various dietary oils, including linseed and fish oil on the relative rates of leukotriene B4 (LTB4) and LTB5 production by rat peritoneal exudate cells in five rat strains. While there was an association between the membrane phospholipid levels of the fatty acid precursors (arachidonic acid (AA) and eicosapentaenoic acid (EPA)) and the rate of synthesis of their respective 5-lipoxygenase products (LTB4 and LTB5), the rate of LTB4 synthesis was a combined function of both AA and EPA levels. We observed a strong linear relationship (correlation coefficient = 0.99) between the ratio of EPA/AA in the cell membrane phospholipids and the ratio of LTB5/LTB4 produced by these cells in vitro; this association was independent of genetic (strain) variability and was independent of the source of EPA (dietary EPA or EPA endogenously synthesized from dietary alpha-linolenic acid).

Animals↗

PubMed1990

Auranofin stimulates LTA hydrolase and inhibits 5-lipoxygenase/LTA synthase activity of isolated human neutrophils.

The effect of auranofin on the 5-lipoxygenase pathway was studied in human neutrophils stimulated with either fMLP or A23187 (with or without arachidonic acid). The synthesis of leukotriene B4 (LTB4), 5-HETE and the all-trans isomers of LTB4 was measured by HPLC. At low concentrations (0.5-2.0 microM), auranofin stimulated LTB4 synthesis, but inhibited it at higher concentrations (100% inhibition at less than 10 microM). In contrast auranofin caused dose-dependent inhibition of the synthesis of 5-HETE and the all-trans isomers of LTB4. Similar observations were made with each agonist. The stimulation of LTB4 synthesis and inhibition of the trans isomer production suggests that auranofin at low concentrations stimulates LTA hydrolase--the enzyme that converts LTA4 to LTB4, whereas the inhibition of synthesis of all lipoxygenase products at higher auranofin concentrations, suggests inhibition of 5-lipoxygenase/LTA synthase.

Arachidonate 5-Lipoxygenase↗

PubMed1990

Comparison of cell membrane phospholipid fatty acids in five rat strains fed four test diets.

The fatty acid composition of phospholipids in peritoneal exudate cells and spleen cells was assessed in five rat strains fed four test diets of differing fatty acid composition. Distinctive patterns of fatty acids were seen in the total phospholipid preparations in both cell types in response to the diets which contained either olive, sunflower, linseed or fish oil. In general, similar fatty acid profiles were seen in each of the rat strains fed the same diet with the only evidence of possible genetic (strain) variation being a relative deficiency of delta 4 desaturase in Dark Agouti rats.

Animals↗

PubMed1990

The effect of dietary fish oil supplement upon the content of dihomo-gammalinolenic acid in human plasma phospholipids.

Patients (n = 23) with definite or classical rheumatoid arthritis were given 18 g/day fish oil in gelatin capsules which provided 3.2 g/day EPA and 2.0 g/day DHA. The treatment period was 12 weeks followed by a 4 week washout period. Fish oil supplementation to the diet resulted in a substantial increase in the content of EPA and DHA in each of the plasma fractions examined (PL, TG, and CE). Little change was seen in the AA level of the TG and CE fractions but a modest decrease in AA was seen in PL. However the intake of fish oil caused a significant depression in the content of DGLA in the PL (p less than 0.005) and CE (p less than 0.01) fractions relative to baseline values. All changes had reverted to near baseline levels 4 weeks after dietary intervention. Since DGLA is the precursor of PGE1, which has been shown to be anti-inflammatory, our findings suggest that the anti-inflammatory effects of fish oil consumption could be mitigated by an associated reduction in DGLA.

8,11,14-Eicosatrienoic Acid↗

PubMed1990

Intraarticular pressure and the relationship between synovial perfusion and metabolic demand.

We examined the influence of intraarticular pressure on products of synovial energy metabolism in patients with knee effusions. A range of intraarticular pressures was generated by controlled flexion. Pressures greater than or equal to 45 mm Hg were associated with increased synovial fluid lactate concentrations and pCO2, and decreased pH. Our results suggest that pressures greater than or equal to 45 mm Hg, which we also observed during standing and walking, can cause synovial ischemia and hypoxia manifest in a perfusion/metabolic demand mismatch. Monitoring changes in SF concentrations of uric acid did not provide consistent evidence for accelerated purine degradation following periods of inadequate perfusion. Overall, our results suggest that synovial blood flow can be compromised by modest elevations in intraarticular pressure in the range encountered during daily activity in patients with knee effusions.

Adult↗

PubMed1989

Recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor show common biological effects and binding characteristics on human monocytes.

Two human hemopoietic growth factors involved in monocytopoiesis, interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were studied for their ability to stimulate blood monocytes and to bind to the monocyte membrane. Both cytokines maintained monocyte/macrophage numbers during long-term culture and increased cell size as compared with controls. Effects on cell numbers were present at low cytokine concentrations (6 to 20 pmol/L), whereas enhanced 3H-thymidine incorporation was observed only at higher concentrations (greater than or equal to 60 pmol/L). Autoradiographic studies showed only 1% to 3% of stimulated monocytes with nuclear grains. These results suggest that the primary mechanism for IL-3 and GM-CSF-induced maintenance of monocyte/macrophage numbers in humans is through an effect on cell survival. Surface receptors for both IL-3 and GM-CSF were studied by using 125I-labeled recombinant human (rh) cytokines and performing Scatchard analyses. Both cytokines showed curvilinear Scatchard plots, and computer analyses favored a two-site binding model. High-affinity binding data for 125I rhIL-3 (Kd 7.7 to 38.2 pmol/L; receptor number/cell 95 to 580) and for 125I rhGM-CSF (Kd 4.7 to 38.9 pmol/L; receptor number/cell 8 to 67) show similar binding affinities for the two cytokines but a lower receptor number/cell for 125I rhGM-CSF. Low-affinity binding characteristics for 125I rhIL-3 (Kd 513 to 939 pmol/L; receptor number/cell 179 to 5,274) and for 125I rhGM-CSF (Kd 576 to 1,120 pmol/L; receptor number/cell 130 to 657) show a similar pattern for the two cytokines. Specificity of 125I rhIL-3 and 125I rhGM-CSF binding to monocytes was established by the ability of the homologous cytokine to inhibit binding and the inability of a range of other cytokines to compete at 100-fold excess molar concentration. It is important, however, that binding of 125I rhIL-3 was partially inhibited by rhGM-CSF and that rhIL-3 partially inhibited binding of 125I rhGM-CSF to the monocyte membrane under conditions shown to prevent receptor internalization. The degree of inhibition varied between 25% and 80% in different experiments, and quantitative inhibition experiments showed that 1,000-fold excess concentrations of competitor failed to inhibit binding of the heterologous ligand completely. These results demonstrate that human IL-3 and GM-CSF have similar effects on growth and survival of human monocytes in vitro and suggest that these and other common biological effects may be mediated either through a common receptor or through distinct receptors associated on the monocyte membrane.

Binding, Competitive↗

PubMed1989

Ischaemia reperfusion injury in pedicle skin flaps in the pig: lack of protective effect of SOD and allopurinol.

A model of ischaemia and reperfusion was established which consistently achieved a 50% reduction in viable length of random pattern pedicle skin flaps in pigs. Flaps were subjected to two periods of ischaemia and reperfusion. Superoxide dismutase (SOD) in a dose of 3000 mu/kg given intravenously and allopurinol 70 mg/kg/day orally had no effect on viable skin flap length, skin blood flow or histological characteristics of flaps. SOD polymers, which have been used in other species to delay SOD clearance, were found to cause anaphylactoid reactions in pigs.

Allopurinol↗

PubMed1989

The effects of hyaluronic acid on macrophage Fc receptor binding and phagocytosis are independent of the mode of depolymerization.

In order to determine whether exposure of hyaluronic acid to oxygen radicals caused an alteration in its properties, independent of the change in molecular weight induced, we examined its effect upon macrophage Fc receptor binding. High molecular weight hyaluronic acid (Healon-Pharmacia) caused a dose dependent inhibition of binding between the concentrations of 0.2-1 mg/ml. At a concentration of 0.3 mg/ml both oxygen radical depolymerized and enzymatically degraded hyaluronic acid caused an inhibition of Fc receptor binding at molecular weights of 1 x 10(6), 1.5 x 10(6) and 2 x 10(6). Oxygen radical degraded hyaluronic acid caused a stimulation of Fc receptor binding at molecular weights of 2 x 10(5) and 3.5 x 10(5), and enzyme degraded hyaluronic acid causes stimulation at a molecular weight of 2.5 x 10(6). Thus this "biological property" of hyaluronic acid is dependent upon molecular weight solely and not upon the mode of depolymerization.

Azure Stains↗

PubMed1988

Clinical and biochemical effects of dietary fish oil supplements in rheumatoid arthritis.

In a double blind noncrossover study, dietary supplementation with fish oil (18 g/day), was compared with an olive oil supplement over a 12-week period in patients with rheumatoid arthritis receiving established conventional therapies. An improvement in tender joint score and grip strength was seen at 12 weeks in the fish oil treated group but not in the olive oil treated group. The more subjective measures of mean duration of morning stiffness and analogue pain score improved to a similar extent in both groups, although statistical significance was only achieved in paired analyses in the olive oil treated group. Production of leukotriene B4 by isolated neutrophils stimulated in vitro was reduced by 30% in the fish oil treated group and unchanged in the olive oil treated group.

Adult↗