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Biomedical subjects

M Greaves

Publications and source records attributed to M Greaves.

At least 199 records · Page 11Linked to original sources
PubMed1985

Effects of dietary fish oil supplementation on the fatty acid composition of the human platelet membrane: demonstration of selectivity in the incorporation of eicosapentaenoic acid into membrane phospholipid pools.

The fatty acid composition of membrane phospholipids of stimulated and unstimulated platelets was studied in six normal volunteers given a daily dietary supplement of a fish oil rich in eicosapentaenoic acid (EPA) for 4 weeks. The supplement was equivalent to 1.8 g of EPA daily. Thromboxane synthesis and platelet aggregation responses to sodium arachidonate, thrombin and the ionophore A23187 were also investigated. A marked increase in the relative EPA content of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was noted after 2 and 4 weeks fish oil supplementation. However, there was no incorporation into phosphatidylinositol (PI) or phosphatidylserine (PS). The relative arachidonic acid (AA) content of PC and PE was significantly reduced at 2 and 4 weeks but that of PI and PS remained unchanged. Significant reductions in the relative linoleic acid content of total phospholipids, PC and PE were also noted. Stimulation of platelets obtained after 4 weeks fish oil supplementation by thrombin and A23187 was associated with a marked reduction in the AA content of PI and a minor reduction in that of PE. There was no change in the relative proportions of EPA in PI, PS, PC or PE after stimulation. Throughout the study there were no significant changes in platelet aggregation responses or in platelet thromboxane production. Our results indicate that the incorporation of EPA into the platelet membrane phospholipids is selective and that if PI is the major source of AA for platelet prostaglandin biosynthesis then the reported beneficial effects of EPA on haemostasis cannot be explained on the basis of its incorporation into and mobilization from the platelet membrane phospholipid pool.

Adult↗
PubMed1985

Hemolytic-uremic syndrome: demonstration of abnormalities of platelet reactivity and insensitivity to prostaglandin I2.

Platelet aggregation and thromboxane synthesis and platelet sensitivity to the antiaggregatory action of prostaglandin I2 were studied serially in a subject suffering from adult hemolytic-uremic syndrome. Platelet aggregation in vitro was defective during the acute phase of the disease and recovered during the convalescent phase. Defective aggregation was not associated with a failure of thromboxane synthesis although it was related to an intrinsic platelet defect rather than an inhibitor in the plasma. The platelets were insensitive to prostaglandin I2, even in the recovery phase of the disease. Furthermore, plasma from the patient rendered normal platelets insensitive to prostaglandin I2 and more sensitive to aggregating agents. It is concluded that the platelet abnormality in hemolytic-uremic syndrome is complex and it combines both an intrinsic platelet abnormality and a plasma component.

Acute Disease↗
PubMed1985

Thrombotic vascular disease.

Thrombovascular disease represents one of the most important causes of morbidity and mortality. Although coronary artery disease attracts most attention, other types of vascular disease also make a substantial contribution to the overall statistics. These include microangiopathy, particularly in relation to diabetes mellitus, and deep vein thrombosis and its associated complications of pulmonary embolus and postphlebitic syndrome.

Arteries↗
PubMed1984

Acute lymphoblastic leukemia supervening in a case of chronic lymphocytic leukemia after continuous 3-year treatment with chlorambucil.

A case is presented of a patient with classical chronic lymphatic leukemia (CLL) treated with continuous chlorambucil for 3 years who presented with a picture of acute leukemia. The peripheral blood still showed a prevalence of mature lymphocytes with a few blast cells, whereas the bone marrow showed a predominant population of blast cells possessing a null acute lymphoblastic leukemia phenotype. Karyotype analysis showed a prevalent hyperdiploid clone of 67 to 68 chromosomes with endoreduplication and marker chromosomes. The coexistence of a CLL-type population with the blastic, undifferentiated cell clone suggests a second malignancy superimposed on the previous leukemic process, and possibly brought about by the continuous chlorambucil treatment.

Aged↗
PubMed1984

Stanozolol-induced changes in fibrinolysis and coagulation in healthy adults.

The effect of orally-administered stanozolol, 5 mg b.d. on fibrinolysis, coagulation and on various haematological and biochemical parameters have been studied in 16 healthy adults, 8 males and 8 females. Statistically significant enhancement of extrinsic (tissue-type) plasminogen activator activity was detected in all subjects studied. This was associated with significant increases in plasma plasminogen and a concomitant reduction in histidine-rich glycoprotein. There were no changes in plasma urokinase activity. Changes in the coagulation system included significant reduction in plasma fibrinogen and elevation of protein C and antithrombin III. Changes in plasma lipids included significant reduction of HDL cholesterol associated with an increase in LDL triglycerides. No change occurred in total cholesterol. There were no major differences between the sexes, nor were there serious side effects. The effects of stanozolol on extrinsic (tissue-type) plasminogen activator activity, "free" plasminogen, protein C and antithrombin III, argue strongly in favour of its therapeutic potential.

Adult↗
PubMed1984

Beneficial effect of fish oil on blood viscosity in peripheral vascular disease.

Reports suggest that the low incidence of ischaemic heart disease in Greenlandic Eskimos is related to the effect of a diet rich in eicosapentaenoic acid on platelet reactivity and plasma lipid concentrations. A double blind randomised investigation was therefore conducted of the effects on blood viscosity of dietary supplementation with an oil rich in this fatty acid (1.8 g/day, given as fish oil) and an eicosapentaenoic acid poor oil (as corn/olive oil) in patients with peripheral arterial disease. A statistically significant reduction in whole blood viscosity was observed at seven weeks in those patients receiving the eicosapentaenoic acid rich oil. No changes in plasma viscosity, haemoglobin concentration, packed cell volume, or platelet count were seen. A significant fall in plasma triglyceride concentration was also noted only in the patients receiving oil rich in eicosapentaenoic acid; plasma concentrations of cholesterol and high density lipoprotein cholesterol were unchanged. It is concluded that rheological changes that result from a diet rich in eicosapentaenoic acid may contribute to the suggested protective effects of such a diet against arterial disease and that such changes are of potential therapeutic importance in established arterial disease.

Aged↗
PubMed1984

Characterization of the response of human thymocytes and blood lymphocytes to the synergistic mitogenicity of 12-O-tetradecanoylphorbol-13-acetate (TPA)-ionomycin.

The combination of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and the calcium ionophore ionomycin is synergistically mitogenic for human fetal and infant thymocytes as well as peripheral blood lymphocytes. Optimal mitogenic stimulation is achieved when TPA and ionomycin are used at doses of 0.5-1 ng/ml and 0.5-1 microgram/ml, respectively. Phenotypic analysis and cell sorting show that the thymocytes responsive to the mitogen have a mature or medullary phenotype (T1+, T3+, T11+, T6-, HLA-A,B++, [TdT]-); similarly in blood the T cell subsets (T11+, T4+ and T11+, T8+) are selectively responsive to TPA-ionomycin. Both activated lymphocytes and thymocytes express HLA-DR antigens as well as activation antigens such as T9, T10 and T cell activation antigen. T cells activated by TPA-ionomycin can be grown for periods of up to 50 days without addition of exogeneous interleukin 2. The observations may have implications for the membrane-associated signals involved in T cell growth and proliferation.

Cell Division↗
PubMed1984

Near-normal glycaemic control does not correct abnormal platelet reactivity in diabetes mellitus.

The effect of improved glycaemic control, effected by 16 weeks continuous subcutaneous insulin infusion (CSII), on platelet aggregation and platelet prostaglandin biosynthesis has been assessed in a group of 11 diabetic patients with painful peripheral neuropathy. Before CSII and compared with results obtained on samples from age- and sex-matched control subjects, there was enhanced reactivity of the platelets from diabetic patients to ADP, collagen and sodium arachidonate (NaAA). There was also increased thromboxane B2 (TXB2) production after platelet stimulation by NaAA. In contrast, collagen-induced thromboxane production by platelets from diabetic patients was significantly less than that of platelets from controls. Treatment by CSII resulted in a statistically significant improvement in glycaemic control and this was maintained for the 16 week period of the study. At 16 weeks and in the presence of near-normal glycaemic control, the enhanced platelet reactivity in response to collagen and NaAA persisted and that to ADP was further increased. Collagen-induced thromboxane production was, however, corrected by CSII.

Adenosine Diphosphate↗
PubMed1984

Production of intraepidermal microabscesses by topical application of leukotriene B4.

Leukotriene B4 is a highly potent leukocyte chemotactic compound. It has been identified in chamber fluid and scale from psoriatic skin lesions, in which epidermal neutrophil infiltration is reported to be one of the earliest pathologic events. The ability of leukotriene B4 to reproduce the inflammatory events of psoriasis, by topical application to the skin of normal human volunteers, was thus studied. Persistent visible inflammatory reactions were elicited by application of amounts of leukotriene B4 as low as 5 ng, and the maximum diameters of the reactions were dose-related up to at least 500 ng. The visible reactions appeared 12-24 h after initial application of leukotriene B4, and persisted for several days, leaving brownish pigmentation and scaling at 7 days. Histologic examination showed intraepidermal neutrophil microabscesses at 24 h, but these had resolved by 48 h. A mixed, perivascular neutrophil and mononuclear cell infiltrate was seen in the dermis at 24 h, becoming predominantly mononuclear after 24 h. Nonspecific chemical irritant contact dermatitis was excluded by the absence of reactions to high doses of two chemically similar metabolites of arachidonic acid which lack significant in vitro chemokinetic activity. These experiments provide further evidence for the role of leukotriene B4 in the pathogenesis of psoriasis, and may lead to the development of an experimental model of the inflammatory events in psoriasis, and of a simple in vivo test of neutrophil function.

Abscess↗
PubMed1984

The release of leukotriene B4-like material in biologically active amounts from the lesional skin of patients with psoriasis.

The 5,12-dihydroxy metabolite of arachidonic acid, leukotriene B4, is a highly potent neutrophil chemoattractant. In view of the characteristic epidermal neutrophil infiltrate in psoriasis, the presence of leukotriene B4 in samples from untreated lesional and uninvolved skin has been sought. Chambers were fixed to abraded skin and filled with phosphate-buffered saline (PBS). After 35 min, the fluid was removed, and acidic lipids were extracted and subjected to high-performance liquid chromatography (HPLC). Extracts were purified by both straight- and reversed-phase HPLC, and assay of evaporated fractions by an agarose microdroplet chemokinesis technique indicated the presence of leukotriene B4-like material. No significant leukotriene B4-like activity was found in samples from uninvolved skin. Subsequent experiments using a modification of the initial skin chamber method indicated that leukotriene B4 was being released from deeper layers of lesional skin and not only from superficial scale. Monohydroxy-eicosatetraenoic acid-like activity was also seen in lesional samples as determined by straight-phase HPLC and chemokinesis assay. These findings and the proinflammatory properties of these compounds in human skin suggest that they may play a role in the pathogenesis of the psoriatic neutrophil infiltrate.

Chemotaxis, Leukocyte↗
PubMed1983

Chromosome assignment of monoclonal antibody-defined determinants on human leukemic cells.

Hybrids formed between human acute lymphoblastic leukemia (ALL) cells and mouse myeloma have been used to determine the chromosomal location of genes required for the expression of several monoclonal antibody (mAb)-defined cell surface antigens on ALL cells. Cloned hybrids were tested for antibody binding, immunoprecipitation of the relevant protein, chromosome isoenzyme markers and karyotype. Two antigens of those studies could be definitively mapped, OKT10/p45 to chromosome 4 and BA-2/p24 to chromosome 12. mAb BA-2 reacts with the same protein as another mAb designated 609-29 (anti-teratocarcinoma). Reactivity with the latter mAb has been previously shown to segregate with chromosome 12.

Animals↗
PubMed1983

Isolation of cDNA clones for the human transferrin receptor.

A cDNA clone bank containing 30 000 clones was constructed from sucrose gradient-fractionated mRNA from human placenta. mRNA coding for transferrin receptor (TR) was enriched by polysome immuno-adsorbed chromatography with monospecific rabbit IgG and protein-A Sepharose. The library was screened for hybridisation to 32P-labelled cDNA synthesised from immunoselected TR mRNA and from poly(A)+ RNA of the polysome fraction that failed to bind to protein-A Sepharose. Plasmids isolated from colonies showing hybridisation only to the probe made from immunoselected mRNA were then subjected to hybrid selection. Two clones, pTR-48 and pTR-67, were able to hybridise the mRNA coding for the TR.

Cell Line↗