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Biomedical subjects

A Davies

Publications and source records attributed to A Davies.

At least 217 records · Page 12Linked to original sources
PubMed1990

Heterogeneity of the glucose transporter in malignant and suppressed hybrid cells.

Previous work has demonstrated unequivocally that the kinetics of glucose transport of tumorigenic and suppressed hybrid cells show a consistent difference. This lies in an increased affinity for glucose in the tumorigenic cell lines (i.e., a reduced Km). Evidence has also been presented that the degree of glycosylation of the transporter may affect the Km. When a suitable antiserum to the transporter present in these cells became available, it was of interest to examine the patterns of binding to immunoblots of extracts of the hybrid cell pairs. It became apparent that there was a clear difference between the two parental cell lines and that this difference was reflected in the hybrid cells. Both the tumorigenic parent and the tumorigenic hybrid cell presented a much more heterogeneous distribution of apparent molecular weights than the nontumorigenic parent or suppressed cell line. That this was probably due to differences in glycosylation was indicated by the effect of tunicamycin on the cells; this gave rise to a more homogeneous band of lower molecular weight. The significance of these differences is discussed in relation to results obtained with other tumorigenic cell lines and to the published structure of the human erythrocyte glucose transporter.

1-Deoxynojirimycin↗
PubMed1990

Reduced tumour growth of the human colonic cancer cell lines COLO-320 and HT-29 in vivo by dietary n-3 lipids.

Seventy-five nude mice received subcutaneous inoculation with 1 X 10(7) cells of the human colonic cancer cell lines COLO-320 or HT-29. Tumour growth was assessed over 4 weeks in animals given one of three iso-caloric diets; standard diet, high saturated fat (20% coconut) diet and high n-3 fat (20% Maxepa fish oil) diet. The n-3 diet produced significant tumour growth reduction compared to the other diets for COLO-320 at 3 to 4 weeks (P less than 0.05 at least) and similarly for HT-29 at 4 weeks (P less than 0.05). Significant incorporation of n-3 fatty acids occurred in red cell membranes, adipose tissue and both neutral lipid and phospholipid fractions of tumour lipids in animals fed Maxepa (P less than 0.01 at least). This was accompanied by reduction of linoleic acid and arachidonic acid in these tissues (P less than 0.01 at least) but was most marked in the metabolically labile phospholipid fraction. There was high mitotic activity in the tumours from all the groups but there was no difference according to diet.

Animals↗
PubMed1990

Effects of intravenous enoximone following coronary artery bypass surgery.

The effects of intravenous enoximone were investigated in patients with reduced left ventricular ejection fraction following coronary artery bypass graft surgery. Pulmonary capillary wedge pressure was maintained at its original level during therapy. Results showed an improvement in cardiac index of approximately 35% and a reduction of systemic vascular resistance of approximately 30% in 10 out of 16 patients. In an attempt to explain the failure of 6 patients to respond to enoximone therapy, preliminary studies revealed that a repeat dose of enoximone may elicit a response. It is further suggested that postsurgical trauma may change the behaviour of the heart in response to this agent, perhaps due to a reduction in high-energy phosphate levels.

Cardiotonic Agents↗
PubMed1990

Human protectin (CD59), an 18,000-20,000 MW complement lysis restricting factor, inhibits C5b-8 catalysed insertion of C9 into lipid bilayers.

Human cells are relatively resistant to lysis by the homologous complement system. Here we describe the mechanism of action of a recently discovered and widely distributed 18,000-20,000 molecular weight (MW) membrane glycoprotein (CD59), which appears to act as a major protective element against complement-mediated lysis (hence called protectin). When incorporated into heterologous erythrocyte membranes, protectin efficiently prevented cell lysis by human serum. Neutralization with antibody of the naturally occurring protectin on human erythrocytes or on nucleated K562 cells increased their susceptibility to lysis by homologous complement. During complement activation, protectin became incorporated into the membrane attack complex (MAC). By interacting with newly exposed regions in the C5b-8 complex and in aggregating C9 it limited the number of C9 molecules associating with the C5b-8 complex to a C8:C9 ratio of 1:1.5 instead of a normal average of 1:3.5. The results demonstrate directly that protectin is a powerful inhibitor of complement cytolysis and acts by inhibiting the C5b-8 catalysed insertion of C9 into the lipid bilayer.

Antigens, Differentiation↗
PubMed1990

New antibiotics.

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Anti-Bacterial Agents↗
PubMed1990

Role of the sympathetic nervous system in the pathogenesis of chronic stable angina. Implications for the mechanism of action of beta-blockers.

Thirteen patients with chronic stable effort angina underwent continuous ambulatory electrocardiographic and intra-arterial blood pressure monitoring during normal unrestricted daily activity. Each patient underwent two studies, the first while on no treatment and the second while on beta-blocker therapy. During the control period, we recorded 182 episodes of transient ST-segment depression, of which only 30 were associated with angina, and 43 (24%) were apparently caused by increased myocardial oxygen demand. Although the majority of ischemic events (139) were not preceded by an increase in either heart rate or systolic arterial pressure, most occurred during the daytime when the levels of the rate-pressure product were higher. Throughout the day, beta-blockade significantly decreased the levels of heart rate and blood pressure and reduced the number of ischemic attacks by 56%, particularly if such attacks were not caused by increased myocardial demand. The diurnal distribution of ischemic events was not significantly affected by beta-blockade, and again, the majority were observed during the day, in coincidence with high resting levels of rate-pressure product. Whatever the behavior of heart rate and blood pressure before ischemia, ST-segment depression was invariably associated with a parallel increase in these parameters, highly suggestive of cardiac sympathetic nerve activation. We conclude that: 1) The majority of ischemic events that occurred in patients with stable angina during normal daily activity were apparently not precipitated by an excessive increase in myocardial oxygen demand but rather by transient impairment of regional myocardial perfusion. 2) The observation that most ischemic events occur when the levels of sympathetic nerve activity are high suggests that the sympathetic nervous system may play a key pathophysiological role in this syndrome, as cardiac sympathetic nerve activation can both increase metabolic demand and impair myocardial perfusion. 3) beta-Blockers significantly reduced episodes of transient myocardial ischemia in these patients, primarily by reducing cardiac metabolic requirements. The possibility that sympathetically mediated coronary vasoconstriction may also be affected by these drugs needs further investigation.

Adrenergic beta-Antagonists↗
PubMed1989

Anatomical mapping of glucose transporter protein and pyruvate dehydrogenase in rat brain: an immunogold study.

The regional and cellular distributions of glucose transporter protein (GT) and pyruvate dehydrogenase (PDH) have been studied with an enhanced immunogold method. The results showed significant amounts of GT in neuropil within regions known to exhibit high demands for glucose whilst neuronal perikarya showed little immunostaining. In contrast PDH immunostaining was most intense in neuronal perikarya. The distributions of these proteins were compared and discussed in relation to existing data on local cerebral glucose utilization and the distribution of other important metabolic enzymes. The results suggest that glucose is transported and metabolised in neuropil and that metabolic products such as pyruvate are transported into the neuronal cell body to undergo further metabolism.

Animals↗
PubMed1989

CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells.

A novel cell surface antigen has been identified on a wide range of lymphoid cells and erythrocytes. A mAb YTH 53.1 (CD59) against this antigen enhanced the lysis of human red cells and lymphocytes by homologous complement. Studies of reactive lysis using different species of C56, and of whole serum used as a source of C7-9, indicated that the inhibitory activity of the CD59 antigen is directed towards the homologous membrane attack complex. CD59 antigen was purified from human urine and erythrocyte stroma by affinity chromatography using the mAb YTH 53.1 immobilized on Sepharose, and, following transient expression of a human T cell cDNA library in COS cells, the corresponding cDNA also identified using the antibody. It was found that the CD59 antigen is a small protein (approximately 20 kD as judged by SDS-PAGE, 11.5 kD predicted from the isolated cDNA) sometimes associated with larger components (45 and 80 kD) in urine. The sequence of CD59 antigen is unlike that of other complement components or regulatory proteins, but shows 26% identity with that of the murine LY-6 antigen. CD59 antigen was released from the surface of transfected COS cells by phosphatidylinositol-specific phospholipase C, demonstrating that it is attached to the cell membrane by means of a glycolipid anchor; it is therefore likely to be absent from the surface of affected erythrocytes in the disease paroxysmal nocturnal hemoglobinuria.

Antibodies, Monoclonal↗
PubMed1989

Immunocytochemical localization of the glucose-transport protein in mammalian brain capillaries.

The endothelial cells of mammalian brain capillaries, which form the anatomical basis of the blood-brain barrier, have been investigated by immunocytochemical methods to determine the distribution of the glucose-transport protein. A monoclonal antibody raised against the intact human erythrocyte glucose-transport protein and polyclonal antibodies raised against a synthetic peptide corresponding to the C-terminal sequence of the human erythrocyte glucose-transport protein were used for immunofluorescent staining of isolated human and bovine cerebral cortex microvessels. The pattern of fluorescence with both antibodies demonstrated the antigen to be distributed throughout the plasma membrane of the capillary endothelial cells. These results provide further evidence for the homology between the human erythrocyte and brain capillary glucose-transport protein, and confirm its abundance in brain capillaries.

Animals↗
PubMed1989

Transfer of Tn1545 and Tn916 to Clostridium acetobutylicum.

Tn1545, a conjugative transposon originally discovered in Streptococcus pneumoniae, has been transferred from Enterococcus faecalis and Bacillus subtilis to Clostridium acetobutylicum NCIB 8052. Transfer between different strains of C. acetobutylicum has also been observed. Insertion of Tn1545 into the C. acetobutylicum chromosome occurred at multiple sites, as shown by Southern hybridization. Although ermAM (erythromycin-resistance) was the most satisfactory marker for primary selection of transconjugants, all three Tn1545-encoded antibiotic resistance genes (aphA-3, ermAM, and tetM) were apparently expressed in C. acetobutylicum. Our results indicate that Tn1545 is potentially useful for undertaking mutagenesis and mutational cloning in this industrially important organism. Transfer of another conjugative transposon, Tn916, from E. faecalis to C. acetobutylicum NCIB 8052 was also apparently detected. Circumstantial evidence suggests that there may be a hot spot for Tn916 insertion in the C. acetobutylicum NCIB 8052 chromosome.

Bacillus subtilis↗
PubMed1989

Uptake of 14C-chlorhexidine diacetate to Escherichia coli and Pseudomonas aeruginosa and its release by azolectin.

Uptake of 14C-labelled chlorhexidine diacetate (14C-CHA) by wild-type and envelope mutant strains of Escherichia coli and Pseudomonas aeruginosa was very rapid. Maximum uptake was observed within a contact time of 20 s with no additional binding on increased contact, and was concentration-dependent. In contrast to this rapid binding of 14C-CHA, bactericidal studies revealed that the lethal activity of low concentrations of unlabelled CHA was slow, although higher concentrations had a rapid effect. Comparison of a wild-type strain with its envelope mutants indicated that there was little difference in 14C-CHA uptake, in minimal inhibitory concentrations or in bactericidal activity. Azolectin was found to be an effective neutralising agent of biguanide action, but in in vitro agar tests and in reducing or removing the amount of 14C-CHA taken up by the cells.

Chlorhexidine↗
PubMed1989

Comparative effects of azapropazone on cellular events at inflamed sites. Influence on joint pathology in arthritic rats, leucocyte superoxide and eicosanoid production, platelet aggregation, synthesis of cartilage proteoglycans, synovial production and actions of interleukin-1 in cartilage resorption correlated with drug uptake into cartilage in-vitro.

Azapropazone (APZ) has been compared with standard NSAIDs in title systems to establish aspects of its mode of action on cellular events at inflamed sites. APZ (150 mg kg-1 day-1) given for 10-13 days exhibited a reduction in joint pathology in established adjuvant arthritis in rats comparable with that of indomethacin (2 mg kg-1 day-1) and clobuzarit (20 mg kg-1 day-1). APZ was shown to be a potent inhibitor of the production of leucocyte superoxide and synovial interleukin-1 (IL-1)-like activity and stimulated articular cartilage proteoglycan synthesis, but was ineffective as an inhibitor of platelet aggregation or IL-1 induced cartilage degradation in-vitro. These in-vitro effects may have relevance to the mode of action of this weak inhibitor of prostaglandin synthesis.

Animals↗