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Biomedical subjects

M Vickers

Publications and source records attributed to M Vickers.

29 records · Page 2Linked to original sources

Induction of CYP1A1 gene expression in H4-II-E rat hepatoma cells by benzo[e]pyrene.

In the rat, expression of the CYP1A1 gene is closely associated with arylhydrocarbon hydroxylase (AHH) enzyme activity. AHH is an inducile enzyme activity known to play an important role in the bioactivation of polycyclic aromatic hydrocarbons (PAHs) to mutagenic and carcinogenic metabolites. PAH-induced expression of the CYP1A1 gene appears to be regulated by several trans-acting factors, including the Ah receptor and the 4S PAH-binding protein. In this study, we used the PAH isomers benzo[a]pyrene (BaP) and benzo[e]pyrene (BeP) to further evaluate the role of the 4S PAH-binding protein in induction of the CYP1A1 gene in H4-II-E rat hepatoma cells. Although BaP is believed to bind to both the Ah receptor and the 4S protein, BeP has been reported to bind exclusively to the 4S protein. The results of the study presented here indicate that BaP and BeP induce the expression of the CYP1A1 gene, as measured by ethoxyresorufin O-deethylase (EROD) activity, in a concentration-dependent manner. However, BaP is about 25 times as potent as BeP in inducing EROD activity in these cells. Slot-blot analysis of total RNA isolated from these cells indicated that BeP, BaP, and 3-methylcholanthrene increased the level of CYP1A1 mRNA expression. Sucrose-gradient analysis of BeP binding activity indicated that BeP bound with high affinity to the 4S PAH-binding protein, but not to the Ah receptor. These results suggest that the 4S protein may play a role in the PAH-induced expression of the CYP1A1 gene in rat H4-II-E cells.

Animals

Effects of a fish oil supplement on platelet function, haemostatic variables and albuminuria in insulin-dependent diabetics.

A randomised trial of the effects of 15 gm per day of a fish oil supplement (MaxEPA) on blood lipids, haemostatic variables (including platelet function) and albuminuria was undertaken in 41 insulin dependent diabetics. Compared with the control group there was a significant reduction in thromboxane production by platelets stimulated by collagen in vitro in the group who took the fish oil supplement. The extent of platelet aggregation was not altered but the lag phase before aggregation was prolonged. There were also statistically significant increases in plasma LDL cholesterol, fibrinogen and clotting factor X in the group who took the fish oil supplement. No other significant differences were noted.

Administration, Oral

Effect on blood lipids and haemostasis of a supplement of cod-liver oil, rich in eicosapentaenoic and docosahexaenoic acids, in healthy young men.

1. Twelve healthy male subjects took a daily supplement of 20 ml of cod-liver oil for 6 weeks. This provided 1.8 g of eicosapentaenoic acid (20:5 omega 3) and 2.2 g of docosahexaenoic acid (22:6 omega 3). The effects of the supplement on blood lipids, haemostatic variables, bleeding time and plasma vitamin A and carotene were studied. In seven subjects platelet aggregation induced by adenosine 5'-pyrophosphate (ADP) was also studied. 2. The proportions of 20: 5 omega 3 and 22: 6 omega 3 in platelet and erythrocyte phosphoglycerides were substantially increased by the supplement mainly at the expense of omega 6 polyunsaturated fatty acids. 3. Mean plasma triglyceride concentrations were reduced and those of high-density-lipoprotein (HDL) cholesterol were increased by the supplement. 4. The mean bleeding time was significantly prolonged after 3 weeks of taking the supplement, but had returned to the presupplementation value 5 weeks after withdrawal of the supplement. 5. The maximum estimated response to platelet aggregation induced by ADP was increased by the supplement. 6. The mean levels of antithrombin III (immunological) and blood pressure were lower at the end of the period of supplementation and remained so 5 weeks after withdrawal of the supplement. No significant changes in other variables were noted.

Adult

Effect of treatment of hyperlipidaemia on haemostatic variables.

The haemostatic function of 11 men with hyperlipidaemia was measured before and after they were treated with a carbohydrate-reduced, fat-modified diet. After treatment, which significantly reduced serum triglyceride and cholesterol concentrations, they showed a significant fall in mean levels of clotting factors VII, VIII, and X and a rise in fibrinolytic activity. These findings suggest that haemostatic function may be important in the pathogenesis of ischaemic heart disease.

Adult

Automation of two-stage factor VIII assay.

Two automated methods for two-stage factor VIII assays have been compared with one another, and evaluated in practice. The Depex method records the clotting time when an electric circuit is completed by the formation of a fibrin thread across a hook-type electrode; the Electra method is based on an optical density technique of clot detection. The two methods gave comparable results for measured levels of factor VIII when haemophilic or "normal" plasmas were assayed. Results from the two methods in practice also suggest that both are valid at low and "normal" factor VIII levels. The Electra method is also probably suitable for assays of concentrates; however, the Depex method appears to give falsely high values in these circumstances, and experimental findings suggest that the reason may be that increased viscosity due to the high fibrinogen levels in factor VIII concentrates causes premature closure of the circuit between the two ends of the Depex electrode. The main advantage of the Depex method is that, provided 3 or 4 machines are available, a given number of assays can be completed more quickly than on Electra. The main advantages of Electra are that it is probably subject to less laboratory error than Depex, and that it is suitable for assaying concentrates as well as haemophilic and "normal" plasmas.

Automation

An assessment of one year of computer-assisted microbiology reporting at Charing Cross Hospital.

The pilot scheme began in August 1972 after three months of running parallel with a conventional system. In October 1972 the system was moved from Fulham Hospital into the new Charing Cross Hospital. Sixty thousand routine bacteriology requests have been processed satisfactorily by the computer system, about 70% of the total received. The cost for a computer-printed report is 32p compared with 6p for a typed one.

Bacteriological Techniques