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Biomedical subjects

R Drew

Publications and source records attributed to R Drew.

At least 55 records · Page 3Linked to original sources

Complementation analysis of the aliphatic amidase genes of Pseudomonas aeruginosa.

A plasmid, pCL34, capable of autonomous replication in Escherichia coli and Pseudomonas aeruginosa has been constructed which carries the promoter and structural gene (amiE) for P. aeruginosa amidase, but not the regulator gene (amiR). Plasmid pCL34 has been mobilized from E. coli to P. aeruginosa using the broad host range plasmid RP4. Complementation studies were performed in P. aeruginosa strains carrying various amidase mutations. Measurements of amidase activity in the recipients under inducing, non-inducing and repressing conditions showed trans-complementation by the chromosomally located regulator gene product. These results confirmed the positive control model for amidase gene expression. Levels of amidase expression seen during these studies were approximately threefold higher than in the parental, amidase-positive strains.

Amidohydrolases↗

Asthma associated with a circulating IgG antibody to Calliphora maggots.

The case report of an angler with delayed onset asthma, following fishing with Calliphora (Blue Bottle) maggots, is presented. The investigations showed that the symptoms were associated with the presence of a circulating IgG antibody to a crude water soluble maggot extract. The patient progressed to develop symptoms suggestive of immune complex disease.

Adult↗

Properties of monoclonal antibodies to human immunoglobulin kappa and lambda chains.

Hybridomas have been produced from mice immunized with human IgG. Culture supernates were assayed for the presence of antibody-producing cells by passive haemagglutination. Hybridomas producing antibodies to human kappa (kappa) and lambda (lambda) light chains have been cloned and grown as ascitic tumours in BALB/c mice. The antigen-binding characteristics of the monoclonal antibodies, contained in the ascitic fluid, were assessed by haemagglutination inhibition, ELISA and radioimmunoassay systems and by the binding of radiolabelled antigen in analytical flat-bed iso-electric focussing gels. One monoclonal anti-kappa reacted better with free than with combined kappa chains; for another the reverse was true. Antibody fractions separated by DEAE chromatography of ascitic fluids were coupled to ox red cells with chromic chloride and compared with polyclonal antibodies for the detection of cell-surface immunoglobulins.

Animals↗

Cimetidine: a specific inhibitor of hepatic aryl hydrocarbon hydroxylase (AHH) in the rat.

Aryl hydrocarbon hydroxylase was selectively inhibited in hepatic microsomes prepared 2 hours after administration of cimetidine (150 mg/kg, i.p.) to male Wistar rats. Cytochrome P-450 content and other mixed function oxidase activities were not affected. In rats pretreated with phenobarbital or 3-methylcholanthrene, cimetidine caused a 50% and 90% reduction or aryl hydrocarbon hydroxylase activity respectively, compared to 70% inhibition in uninduced animals. Chronic administration of cimetidine (150 mg/kg, b.i.d. for 5 days) to uninduced rats resulted in 70% inhibition of aryl hydrocarbon hydroxylase but no change in other microsomal enzyme activities. Hexobarbital sleeping time was markedly prolonged 30 min after a single dose of cimetidine but had returned to control values after 24 hrs. Similar effects were observed with chronic dosing of cimetidine. It is concluded that in vivo administration of cimetidine is a relatively specific inhibitor of hepatic aryl hydrocarbon hydroxylase in the rat, and that cimetidine does not induce the microsomal mixed function oxidase system when administered chronically.

Aniline Hydroxylase↗

Effect of a specific 5HT uptake inhibitor (citalopram) on drug accumulation by rat lung slices.

Rat lung slices were used to examine the effects of citalopram, a compound reported to be a specific inhibitor of neuronal uptake of 5-hydroxytryptamine (5HT), on the pulmonary accumulation of 5HT, noradrenaline (NA), imipramine (IP) and paraquat (PQ). 5 X 10(-9) mol/l citalopram inhibited 5HT uptake by 30-40% but NA uptake was not affected at any of the concentrations of citalopram studied. At the highest concentrations of citalopram (10(-5) to 10(-4) mol/l) the accumulation of IP and PQ was reduced by25-30%. It is concluded that at low concentrations, citalopram is a specific and potent inhibitor of 5HT uptake by rat lung slices.

Animals↗

Hepatic cytochrome P-450-dependent metabolism and enzymatic conjugation of foreign compounds in vitamin A-deficient rats.

The temporal effects of vitamin A deficiency on hepatic cytochrome P-450-dependent and conjugation reactions were studied in the rat. Cytochrome P-450 levels and N-methyl-p-chloroaniline N-demethylase activity were significantly reduced in the deficient animals. No other changes in parameters dependent on cytochrome P-450 were observed in vitro. Decreases in hepatic cytochrome P-450 were accompanied by a prolongation in hexobarbital sleeping times in deficient animals. The p-aminobenzoic acid N-acetyltransferase activity was higher in the deficient animals at 8 weeks, but by 10 weeks the activity in fact was significantly lower as compared to controls. Activities of 'native' and UDP N-acetylglucosamine 'activated' UDP-glucuronyltransferase were reduced in vitamin A deficiency. In contrast to this general pattern of impaired drug metabolism in vitamin A deficiency, glutathione S-aryltransferase activity was markedly enhanced at all time points from 4 to 10 weeks. Activities of this enzyme were twice controls at 6 weeks, a time at which no other enzyme changes were observed.

Animals↗

Choleretic and cholestatic effects of infused bile salts in the rat.

In rats, at low infusion rates taurocholate (TC), taurochenodeoxycholate (TCDC) and taurodeoxycholate (TCD) each produced an increase in bile flow of 20-50%. However, at high infusion rates (5-20 mumoles min-1kg-1) the cholestatic effects of the bile salts were revealed and the relative toxicity of the bile salts was seen to be TDC greater than TCDC greater than TC.

Animals↗

Effect of chlorpromazine and erythromycin on bile salt-induced cholestasis in the rat.

The effects of subacute administration of chlorpromazine HCI (CPZ), erythromycine base and erythromycin estolate on the cholestatic response to intravenous taurolithocholate (TLC) and taurochenodeoxycholate (TCDC) in the rat were investigated. All three enhanced the recovery of bile flow after TCDC but not after TLC. Erythromycin base and estolate enhanced bile flow recovery after TCDC and potentiated the increase of plasma 5'-nucleotidase, as did CPZ. Neither erythromycin estolate nor CPZ precipitated a cholestatic response in rat maintained for 9-13 days on a diet supplemented with 0.05% lithocholic acid. It is concluded that the interaction of CPZ and erythromycins with bile salts is not based on the cholestatic properties of the drugs, and hence is not a practical way of distinguishing cholestatic from non-cholestatic drugs.

Alanine Transaminase↗