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Biomedical subjects

A S Nelson

Publications and source records attributed to A S Nelson.

6 recordsLinked to original sources
PubMed2004

Directed evolution of enzymes for biocatalysis and the life sciences.

Engineering the specificity and properties of enzymes and proteins within rapid time frames has become feasible with the advent of directed evolution. In the absence of detailed structural and mechanistic information, new functions can be engineered by introducing and recombining mutations, followed by subsequent testing of each variant for the desired new function. A range of methods are available for mutagenesis, and these can be used to introduce mutations at single sites, targeted regions within a gene or randomly throughout the entire gene. In addition, a number of different methods are available to allow recombination of point mutations or blocks of sequence space with little or no homology. Currently, enzyme engineers are still learning which combinations of selection methods and techniques for mutagenesis and DNA recombination are most efficient. Moreover, deciding where to introduce mutations or where to allow recombination is actively being investigated by combining experimental and computational methods. These techniques are already being successfully used for the creation of novel proteins for biocatalysis and the life sciences.

Catalysis↗
PubMed1998

Modulation of nitric oxide improves cyclosporin A-induced hypertension in rats and primates.

Cyclosporin-induced hypertension is a major complication of immunosuppression in transplant recipients but its pathophysiology is only partly understood. Cyclosporin reduces endothelium-dependent vasodilation and increases endothelin synthesis and release, which may contribute to this hypertension. We examined the effects of: (1) nitric oxide enhancement with L-arginine administration and antagonism with N-nitro-L-arginine; and (2) chronic endothelin receptor blockade with the non-peptide endothelin receptor antagonist, bosentan, in two animal models of cyclosporin-induced hypertension. Cyclosporin, administered daily to female Wistar rats (10 mg/kg per day for 30 days, s.c.) and to marmosets (30 mg/kg per day for 20 days, p.o.) significantly elevated tail cuff systolic blood pressure (BP). L-arginine (250 mg/kg, in saline, i.p.), N-nitro-L-arginine (25 mg/kg, in saline, i.p.), bosentan (100 mg/kg, in arabic gum, p.o.) or vehicle were given daily to the rats during the last week of cyclosporin treatment. Marmosets received L-arginine (300 mg/kg, in water, p.o.), bosentan (100 mg/kg/day in arabic gum, p.o.) or vehicle for the last 7 days of cyclosporin treatment. L-arginine, but not saline alone significantly lowered BP in the cyclosporin-hypertensive rats from 129 +/- 2 mm Hg to 122 +/- 3 mm Hg (P < 0.05), and cyclosporin-hypertensive marmosets from 156 +/- 2 mm Hg to 139 +/- 4 mm Hg (P < 0.01). NOLA significantly increased systolic BP in cyclosporin-treated (from 133 +/- 2 mm Hg at week 3 to 142 +/- 3 mm Hg, P < 0.05) and control rats (from 124.0 +/- 2 mm Hg to 134 +/- 2 mm Hg, P < 0.05) indicating that nitric oxide synthesis in cyclosporin-hypertensive rats could be further antagonised. Bosentan, but not arabic gum alone, also lowered BP in the cyclosporin-hypertensive rats from 134 +/- 1 mm Hg to 122 +/- 3 mm Hg (P < 0.01), and cyclosporin-hypertensive marmosets from 156 +/- 2 mm Hg to 139 +/- 4 mm Hg (P < 0.01). These results support the roles of both increased endothelin synthesis and decreased nitric oxide activity in the pathogenesis of cyclosporin A-induced hypertension.

Animals↗
PubMed1996

Bosentan ameliorates cyclosporin A-induced hypertension in rats and primates.

Cyclosporine-induced hypertension is a major problem in transplant therapy. The pathophysiology of this disease is unclear. Cyclosporine increases endothelin synthesis and release, which may contribute to this hypertension. We examined the effects of chronic endothelin receptor blockade with the novel nonpeptide endothelin receptor antagonist bosentan in two animal models of cyclosporine-induced hypertension. Cyclosporine was administered daily to female Wistar rats (10 mg/kg per day SC for 30 days) and marmosets (30 mg/kg per day PO for 20 days). Control rats received vehicle. Tail-cuff systolic pressure was significantly elevated in the cyclosporine-treated animals before the last week of treatment. Bosentan (100 mg/kg) in arabic gum or arabic gum alone was given daily to the rats by gavage during the last 5 days of cyclosporine treatment and to the marmosets for the last 7 days of cyclosporine treatment. Tail-cuff systolic pressure was measured daily during bosentan treatment. Bosentan but not gum alone significantly lowered blood pressure in the cyclosporine-hypertensive rats from 134 +/- l to 122 +/- 3 mm Hg (P<.Ol) and in the cyclosporine-hypertensive marmosets from 156 +/- 2 to 139+/- 4 mm Hg (P<.Ol). There were no differential effects on plasma creatinine concentration, endothelin concentration, or end-organ weights. Bosentan had no effect in the vehicle-treated rats. These data provide further evidence to support a role for endothelin in cyclosporine-induced hypertension and demonstrate the effectiveness of endothelin receptor antagonism as a novel treatment in cyclosporine-induced hypertension.

Animals↗
PubMedDate not supplied

Techniques in evaluating nursing expert systems: A case study.

This study addresses the problems in evaluating nursing diagnostic artificial intelligence (AI) expert systems. Two separate experiments (N = 49) were conducted using a computer expert system. The first experiment, the "white box" experiment (n = 9), compared the diagnostic techniques applied by experience RNs against the programmed techniques used by the expert system. The second experiment, the "black box" experiment (n = 40), compared diagnostic results of beginning nurses against the computer expert systems results. In some cases the computer outperformed the nurses and vice versa. The evaluation techniques, as applied in both experiments, enhance the ability of nurses to evaluate and select AI expert systems to be used in computer-assisted diagnosis of nursing problems.

Clinical Competence↗