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Biomedical subjects

R Duckworth

Publications and source records attributed to R Duckworth.

At least 19 recordsLinked to original sources

Expression of a rat neurotensin receptor in Escherichia coli.

With the goal of obtaining sufficient quantities of seven-helix G-protein-coupled receptors for structural analysis, we have studied the functional expression of a rat neurotensin receptor cDNA in Escherichia coli with and without a signal sequence and as a fusion with the gene coding for maltose-binding protein. The addition of an N-terminal signal peptide resulted in increased expression levels. In vitro translation at a high level revealed that the codon usage of the rat neurotensin receptor cDNA was not critical for overproduction. Expression of neurotensin receptor cDNA fused to the 3' end of the gene encoding maltose-binding protein resulted in a 40-fold increase in neurotensin-binding sites. Binding of [3H]neurotensin to intact bacteria or E. coli membranes was saturable, with a dissociation constant, KD, of 0.23 nM (Bmax. = 450 sites/bacterium or 15 pmol/mg of crude membrane protein). The binding properties of all recombinant receptors presented in this study were similar and corresponded to those of the high-affinity binding sites in rat brain. For immunological detection and future purification of neurotensin receptor, a C-terminal pentahistidine/c-myc tail was introduced. Western-blot analysis revealed the association of neurotensin receptor with E. coli membranes.

ATP-Binding Cassette Transporters↗

Metabolic effects of low-dose dopamine infusion in normal volunteers.

1. Dopamine in 5% (w/v) D-glucose was infused into five healthy male volunteers at doses of 2, 5 and 10 micrograms min-1 kg-1 over three sequential periods of 45 min each. 2. Oxygen consumption, respiratory exchange ratio, blood glucose concentration and plasma levels of free fatty acids, glycerol, lactate, dopamine, adrenaline and noradrenaline were measured. The results were compared with values obtained during infusion over the same time period of the corresponding volumes of 5% (w/v) D-glucose alone. 3. Energy expenditure calculated from the oxygen consumption and the respiratory exchange ratio was higher than control values during infusion of dopamine (P less than 0.001, analysis of variance) specifically at a rate of 10 micrograms min-1 kg-1 (P less than 0.05) when it was 14% higher, but not at a rate 2 of or 5 micrograms min-1 kg-1. The plasma noradrenaline concentration was 74 and 230% and the blood glucose concentration was 21 and 36% higher than control values at 5 and 10 micrograms of dopamine min-1 kg-1, respectively (P less than 0.01). At 10 micrograms of dopamine min-1 kg-1 the plasma free fatty acid concentration was 70% and the plasma glycerol concentration was 80% higher than during the control infusion (P less than 0.01). The respiratory exchange ratio and the plasma lactate concentration were the same in the two groups and did not alter during the dopamine infusion. The plasma adrenaline concentration rose significantly (P less than 0.01), but only transiently, during dopamine infusion at a rate of 2 micrograms min-1 kg-1. 4. Dopamine at low doses has metabolic effects. It increases the blood glucose concentration and the circulating noradrenaline level at an infusion rate of 5 micrograms min-1 kg-1. It increases energy expenditure and circulating free fatty acid and glycerol levels at an infusion rate of 10 micrograms min-1 kg-1, presumably due to stimulation of lipolysis.

Adult↗

A follow-up study 3 years after metronidazole therapy for chronic periodontal disease.

In a previous study, a double-blind between subject comparison of the effects of metronidazole and placebo tablets was completed over 22 weeks in 45 subjects with chronic periodontal disease ranging in severity from moderate (PI = 2.0-3.9) to high (PI = 4.0-6.0). The results showed a significantly greater reduction in the mean probing depth of pockets with the use of metronidazole, but this reduction was apparent only in subjects with severe periodontal disease (PI = 4.0-6.0). 3 years later, 28 subjects attended. All groups still showed statistically significant improvements in all parameters when compared with those at the first visit. However, when compared with those at the end of the trial, there were statistically significant increases in gingival bleeding and calculus scores. An increase in plaque levels was also observed but this was not statistically significant. When subjects with moderate and severe periodontal disease were grouped together, there were no significant differences in any of the parameters between test and control groups. Moreover, the significantly greater reductions in mean probing depth of pockets, achieved with the use of metronidazole in the severe group at the end of the trial, had disappeared after 3 years. However, in subjects with mild disease, statistically significant reductions in pocket probing depth, not originally apparent, were observed 3 years later.

Chronic Disease↗

Effect of metronidazole on chronic periodontal disease in subjects using a topically applied chlorhexidine gel.

A double blind between subject comparison of the effect of metronidazole and placebo tablets was completed over 22 weeks in 45 subjects with chronic periodontal disease ranging in severity from moderate (PI = 2.0-3.9) to high (PI = 4.0-6.0). All subjects used a topically applied chlorhexidine gel for the first 10 weeks. Throughout the trial plaque, bleeding and calculus were assessed on the buccal, lingual, mesial and distal surfaces of teeth 16, 21, 24, 36, 41 and 44 and their supporting tissues. The pocket depths on the same 4 aspects of all teeth present were measured. The regime employed consisted of oral hygiene instruction (OHI) at the initial visit followed by scaling and further OHI at visits 1 and 2 weeks later. After the third visit 16 X 200 mg metronidazole or placebo tablets were issued with instructions to take 1 that evening and 3 per day at 5-h intervals for the next 5 days. 4 weeks later, scaling and OHI were carried out and the course of test or placebo tablets was repeated. The subjects returned for further scaling and OHI 4 weeks later and the chlorhexidine gel was withdrawn. Final assessments were made 12 weeks later. The results showed that metronidazole had no effect on plaque levels and gingival bleeding beyond the effect of OHI, scaling and chlorhexidine gel. On the other hand, significantly greater reductions in pocket depths were achieved with the use of metronidazole. A surprising and interesting finding was that these reductions were apparent only in the subjects with severe periodontal disease (PI = 4.0-6.0).

Administration, Topical↗