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Biomedical subjects

A W Murray

Publications and source records attributed to A W Murray.

At least 127 records · Page 7Linked to original sources
PubMed1990

Human tumour necrosis factor-alpha (TNF-alpha) directly stimulates arachidonic acid release in human neutrophils.

The ability of tumour necrosis factor-alpha (TNF-alpha) to directly stimulate phospholipid turnover from human neutrophils was studied. Stimulation with recombinant human (rH) TNF-alpha induced the release of significant amounts of radioactivity from [3H]arachidonic acid-labelled neutrophils. This stimulation was equipotent to that induced by the bacterial tripeptide formyl-methionyl-leucylphenylalanine (FMLP). The time of maximum stimulated release varied between donors, with the most common maximal stimulation being 45 min. Dose-response experiments indicated that 100-1000 U/ml rH TNF-alpha were required for the maximum stimulatory effect. High-performance liquid chromatography analysis of the supernatants revealed that the radioactivity was associated with arachidonic acid, but not with its metabolites, indicating that TNF-alpha stimulates the release of arachidonic acid from cellular phospholipids but does not stimulate its metabolism. A comparison of TNF-alpha with other cytokines indicated that stimulation of arachidonic acid release paralleled the 'priming' of neutrophils for enhanced superoxide production, raising the possibility that phospholipid turnover and priming of neutrophils are causally related.

Arachidonic Acids↗
PubMed1989

Dominoes and clocks: the union of two views of the cell cycle.

We review the recent advances in understanding transitions within the cell cycle. These have come from both genetic and biochemical approaches. We discuss the phylogenetic conservation of the mechanisms that induce mitosis and their implications for other transitions in the cell cycle.

Animals↗
PubMed1989

Phorbol esters stimulate a phospholipase D-catalysed reaction with both ester- and ether-linked phospholipids in HeLa cells.

The phorbol ester, 12-tetradecanoylphorbol-13-acetate (TPA), stimulated the accumulation of labelled phosphatidylethanol (PEth) in HeLa cells prelabelled with [3H]hexadecanol and incubated in the presence of ethanol. PEth formation involves a phospholipase D-catalysed phosphatidyl transferase reaction. [3H]Hexadecanol labelled both ester- and ether-derivatives of HeLa cell phospholipids and TPA stimulated the conversion of both classes of lipid to PEth.

Ethers↗
PubMed1989

Characterization of a novel membrane glycoprotein involved in platelet activation.

When platelets bind certain specific ligands they are induced to secrete the contents of their cytoplasmic granules and to aggregate. Studies of the molecular events accompanying this vital physiological response have led to a greater understanding of cell activation in general since the pathways involved are common to a number of cell types. By contrast most of the information about the cell surface molecules that initiate signal transduction has emerged from work on T lymphocyte activation, a process essential to the initiation of the immune response. We have described an activation antigen on T lymphocytes that is involved in the differentiation of these cells. In the present report it is demonstrated that the antigen is expressed on the platelet membrane with about 1,200 copies/platelet. A monoclonal antibody detecting this antigen stimulates platelet secretion and aggregation with a half-maximal response at approximately 10(-8) M. Characterization of the antigen, termed PTA1, reveals a glycoprotein of Mr 67,000 showing extensive N-linked carbohydrate, much of which appears to be heavily sialated. The amino-terminal sequence of PTA1, EEVLWHTSVPFAEXMSLEXVYPSM, indicates that the protein has not previously been characterized. Preliminary investigation of the mechanism by which PTA1 mediates platelet activation suggests involvement of protein kinase C and the 47-kDa protein of platelets is rapidly phosphorylated upon antibody-mediated activation. During this process PTA1 is also phosphorylated, as it is following platelet activation by the other agonists, collagen, thrombin, and 12-O-tetradecanoylphorbol 13-acetate. These results provide the first example of a cell surface glycoprotein that is directly involved in both platelet and T lymphocyte activation.

Amino Acid Sequence↗
PubMed1989

Inhibition of protein kinase C activity by the antirheumatic drug auranofin.

The Ca2+-activated, phospholipid-dependent protein kinase (protein kinase C; PKC) has a central role in the transmission of extracellular signals. The orally active anti-rheumatic drug, auranofin, has been shown to modulate PKC-mediated cell responses. In this study, we report that auranofin directly inhibits PKC in a dose-dependent manner; inhibition can be overcome by mercapto-ethanol. Proteolytically-activated PKC is also inhibited by auranofin excluding an effect of the drug on the regulatory domain of the enzyme. These data clearly show that auranofin inhibits the catalytic activity of PKC, probably by interacting with thiol groups.

Auranofin↗
PubMed1989

Phorbol ester induces differential membrane-association of protein kinase C subspecies in human platelets.

Human platelets contained proteins which cross-reacted with antisera specific for brain protein kinase C-alpha and -beta. When platelets were incubated with 12-O-tetradecanoylphorbol-13-acetate there was a rapid accumulation of protein kinase C-alpha in the particulate fraction associated with a loss of this subspecies from the soluble fraction. No particulate accumulation or soluble loss of protein kinase C-beta could be detected when platelets were incubated with the phorbol ester.

Blood Platelets↗
PubMed1989

Cyclin synthesis drives the early embryonic cell cycle.

We have produced extracts of frog eggs that can perform multiple cell cycles in vitro. Destruction of the endogenous messenger RNA arrests the extracts in interphase. The addition of exogenous cyclin mRNA is sufficient to produce multiple cell cycles. The newly synthesized cyclin protein accumulates during each interphase and is degraded at the end of each mitosis.

Animals↗
PubMed1989

Comparison of the cardiorespiratory effects of ketorolac and alfentanil during propofol anaesthesia.

The cardiorespiratory effects of a new nonopioid analgesic, ketorolac tromethamine, were compared with alfentanil as part of a balanced technique in which anaesthesia was maintained by a constant infusion of propofol. Twenty patients were allocated randomly to receive a single dose of either ketorolac 30 mg or alfentanil 0.5 mg. The study medication was given during the anaesthetic when the rate of ventilation had been stable (+/- 1 b.p.m.) for 5 min. Measurements of ventilatory rate, end-tidal carbon dioxide partial pressure, arterial oxygen saturation (SaO2), heart rate and systemic arterial pressure were made at 1-min intervals for 15 min following the test drug. Patients having alfentanil developed significant decreases in ventilatory rate, heart rate and mean arterial pressure. A significant increase in end-tidal carbon dioxide partial pressure occurred also. No changes occurred in any of the measured variables in the ketorolac group.

Alfentanil↗
PubMed1989

Opioid supplementation during propofol anaesthesia. The effects of fentanyl or alfentanil on propofol anaesthesia in daycase surgery.

Sixty patients of ASA grade 1 or 2 who presented for minor daycase gynaecological or urological procedures were randomly allocated to three groups. Group A received fentanyl 1 microgram/kg and Group B alfentanil 5 micrograms/kg prior to induction. Group C received no pre-induction opioid. anaesthesia was induced intravenously with propofol and maintained using nitrous oxide 67% in oxygen supplemented with 20-mg bolus doses of propofol as required. The pre-induction administration of fentanyl or alfentanil was not found significantly to affect either the doses of propofol required for induction or maintenance or the quality of anaesthesia compared with propofol alone. These results suggest that for minor outpatient procedures under general anaesthesia, the concomitant use of a short-acting opioid confers no benefits over propofol with oxide and oxygen alone.

Adjuvants, Anesthesia↗
PubMed1989

Cyclin synthesis and degradation and the embryonic cell cycle.

I discuss recent advances in the study of somatic and embryonic cell cycles. In the frog embryonic cell cycle, cyclin is the only newly synthesized protein required to activate maturation-promoting factor and induce mitosis. Diminishing the rate of cyclin synthesis increases the length of interphase. Cyclin degradation is required for the progression from mitosis to interphase. Comparison of the frog embryonic cell cycle to other cell cycles suggests that all cell cycles will rely on the same closely conserved set of components. However, the component that is rate-limiting for any step in the cell cycle will vary in different cell cycles.

Animals↗
PubMed1988

DNA-binding proteins in protein kinase C preparations.

Human DNA enriched in repetitive sequences specifically bound to a component(s) in purified preparations of rat brain protein kinase C (PKC). DNA which bound to protein was cloned in pUC-19 and one clone characterized as containing an approx. 140 bp insert. The band containing this insert (separated by acrylamide gel electrophoresis) was lost when the DNA was incubated with purified PKC preparations. Thus a protein in relatively pure PKC preparations is a sequence-selective DNA-binding protein. The results raise the possibility that PKC or a fragment of PKC binds selectively to specific DNA sequences.

Animals↗
PubMed1988

Characterization of two telomeric DNA processing reactions in Saccharomyces cerevisiae.

We have investigated two reactions that occur on telomeric sequences introduced into Saccharomyces cerevisiae cells by transformation. The elongation reaction added repeats of the yeast telomeric sequence C1-3A to telomeric sequences at the end of linear DNA molecules. The reaction worked on the Tetrahymena telomeric sequence C4A2 and also on the simple repeat CA. The reaction was orientation specific: it occurred only when the GT-rich strand ran 5' to 3' towards the end of the molecule. Telomere elongation occurred by non-template-directed DNA synthesis rather than any type of recombination with chromosomal telomeres, because C1-3A repeats could be added to unrelated DNA sequences between the CA-rich repeats and the terminus of the transforming DNA. The elongation reaction was very efficient, and we believe that it was responsible for maintaining an average telomere length despite incomplete replication by template-directed DNA polymerase. The resolution reaction processed a head-to-head inverted repeat of telomeric sequences into two new telomeres at a frequency of 10(-2) per cell division.

Animals↗