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Biomedical subjects

R Robson

Publications and source records attributed to R Robson.

16 recordsLinked to original sources

Intranasal fluticasone propionate versus loratadine in the treatment of adolescent patients with seasonal allergic rhinitis.

Fluticasone propionate (FP) is a topical corticosteroid with minimal systemic activity. We examined safety and compared the efficacy of FP aqueous nasal spray, 200 micrograms every day with loratadine tablets, 10 mg by mouth every day in 240 adolescents with ragweed pollen-induced seasonal allergic rhinitis for 4 weeks in a randomized, double-blind, parallel-group study. Nasal and eye symptoms were recorded daily on a 4-point (0 to 3) scale. A higher percentage of symptom-free days was observed for nasal blockage on waking during treatment with FP (p < 0.0001). Significant results were also obtained for all other nasal symptoms when analyzed for both symptom-free days and symptom scores. No differences were found for eye irritation symptoms (p = 0.14). Morning and evening nasal peak inspiratory flow (PIF) was recorded daily by 57 subjects. FP treatment was associated wit significantly higher PIF values than loratadine both morning (p = 0.0051) and evening (p = 0.0036). A greater improvement over 4 weeks was observed for PIF morning values in the FP group (p = 0.008) but not for evening values (p = 0.358). Statistically significant correlations were found for nasal blockage and PIF in the morning (r = -0.54, p = 0.0001) and in the evening (r = -0.46, p = 0.008).

Administration, Intranasal

Dose proportionality of bisoprolol enantiomers in humans after oral administration of the racemate.

Dose proportionality of racemic bisoprolol and the stereoselectivity of its enantiomers were studied after single oral dosing of 5 to 40 mg of bisoprolol hemifumarate in eight healthy male volunteers in an open-label, randomized, four-way cross-over trial. There were dose-proportional increases in mean peak plasma concentration (Cmax) and area under the plasma concentration versus time curve (AUC) values for the racemate and the individual enantiomers. No statistically significant differences were detected between the mean half life (t 1/2), Cmax, and time to reach Cmax (tmax) of the R- and S-isomers at each of the four dose levels studied. These findings support dose proportionality and absence of stereoselective pharmacokinetics for bisoprolol in the dose range studied.

Administration, Oral

Immunochemical and catalytical characterization of the human liver NADPH-cytochrome P450 reductase.

1. The NADPH-cytochrome P450 reductases (EC 1.6.2.4) from human and rabbit liver have been purified to electrophoretic homogeneity. The human reductase had an apparent monomeric molecular weight of 77,500 and the rabbit enzyme of 76,500. 2. Both flavoproteins exhibited typical flavoprotein spectra and contained equimolar quantities of FAD and FMN. The two reductases were catalytically active in reducing cytochrome c, ferricyanide and dichlorophenolindophenol, and in supporting rabbit liver cytochrome P450 Form 4 metabolism of 2-acetylaminofluorene. 3. An antibody raised in the goat against the human enzyme formed a precipitin line with the human reductase in a double-diffusion assay, but did not react with the rabbit reductase. Similarly, an antibody raised in the goat against the rabbit reductase formed a precipitin line with the rabbit enzyme, but did not cross-react with the human reductase. 4. Both antibodies inhibited cytochrome c reduction by the two reductases suggesting some immunochemical recognition. 5. Immunochemical cross-reactivity was confirmed when both reductases were subjected to the more sensitive immunoblot technique using either anti-human or anti-rabbit reductase IgG. 6. The human and rabbit reductases are essentially similar in amino acid composition, except that the former has larger amounts of serine and glycine.

Amino Acids

Further analysis of nitrogen fixation (nif) genes in Azotobacter chroococcum: identification and expression in Klebsiella pneumoniae of nifS, nifV, nifM, and nifB genes and localization of nifE/N-, nifU-, nifA- and fixABC-like genes.

The results presented extend previous investigations on the genetics of nitrogen fixation in Azotobacter chroococcum and indicate that nif- and fix-like DNA is located in at least five different regions of the genome. Region I contains functional copies of nifS,V and M, as well as nifH, D and K, all of which complemented mutants of Klebsiella pneumoniae. In addition, nifE- and/or nifN-like and nifU-like DNA is located in this region. The organization of the nif cluster in region I closely resembles that of K. pneumoniae. though spread over 22 kb as compared with 14 kb. Region II contains a functional nifB gene, which complemented a K. pneumoniae nifB mutant, and seems to be adjacent to ap nifA-like gene. Region III harbours nifH*, encoding a second nitrogenase Fe-protein. Region IV contains a reiteration of nifE- on and/or nifN-like sequences, and DNA homologous to Rhizobium meliloti fixABC is present in region V. The apparent complexity of nifDNA in A. chroococcum is probably related to the two systems for N2-fixation pr present in this organism.

Azotobacter

Immunohistochemical localization and quantitation of NADPH-cytochrome P-450 reductase in human liver.

An antibody raised in a goat against the human liver NADPH-cytochrome P-450 reductase (EC 1.6.2.4.) enzyme has been used to: 1) immunoquantify the level of this enzyme in human liver microsomes, and 2) study the distribution of the reductase across the human liver acinus. Employing the Western blot procedure, anti-human reductase IgG recognized a single band in human liver microsomes which corresponded in molecular weight to the purified reductase. The content of the NADPH-cytochrome P-450 reductase in six normal human livers varied from 87 to 121 pmol/mg of microsomal protein. NADPH-cytochrome P-450 reductase activity of the same microsomes ranged from 107 to 222 nmol of cytochrome c reduced per min per mg of protein. The correlation between reductase content and activity (r = 0.54) was not statistically significant (p greater than 0.1). The total cytochrome P-450 content (cytochrome P-450 and P-420) of the same microsomes varied from 423 to 1413 pmol/mg of microsomal protein. The average ratio of cytochrome P-450 to NADPH-cytochrome P-450 reductase was 7.1:1 +/- 3.1 (mean +/- SD) in the human liver microsomal preparations studied. The reductase was found to be nonuniformly distributed across the human liver acinus. Although all hepatocytes stained positively for NADPH-cytochrome P-450 reductase, the staining intensity was highest in zone 3 and in some cases also in zone 1 hepatocytes. These results show that human liver contains a gross excess of cytochrome P-450 molecules to NADPH-cytochrome P-450 reductase molecules. Furthermore, the differential distribution of the reductase within the human liver acinus may lead to a better understanding of the mechanism underlining site-specific drug hepatotoxicity.

Cytochrome P-450 Enzyme System

Assessment of caffeine exposure: caffeine content of beverages, caffeine intake, and plasma concentrations of methylxanthines.

The caffeine content of all tea or coffee beverages consumed by 17 healthy adults over 24 hours was measured. Plasma caffeine, theophylline, theobromine, and paraxanthine concentrations were determined over the same 24 hours. The average caffeine content per drink was 60.4 +/- 21.8 mg for instant coffee (14-fold range), 80.1 +/- 19.2 mg for brewed coffee (2.8-fold range), and 28.8 +/- 13.7 mg for tea (5.5-fold range). The number of drinks of coffee and tea consumed was a poor index of actual caffeine intake (r2 = 0.42). Caffeine intake correlated poorly with the 24-hour average caffeine concentration (r2 = 0.41), but there was a very good correlation between a single plasma caffeine concentration measured at 5 PM and the 24-hour average concentration (r2 = 0.94). The same was true for paraxanthine (r2 = 0.86). Paraxanthine accounted for 67.3% of the total dimethylxanthines in plasma, while theobromine and theophylline accounted for 24.4% and 8.3%, respectively. Mean caffeine clearance was 1.2 +/- 0.3 ml/min/kg. Plasma caffeine concentration before the first drink in the morning correlated very poorly with caffeine clearance (r2 = 0.07), even when adjusted for caffeine intake (r2 = 0.21).

Adult

Cloning and organisation of some genes for nitrogen fixation from Azotobacter chroococcum and their expression in Klebsiella pneumoniae.

By DNA hybridisation, restriction fragments of genomic DNA from Azotobacter chroococcum and A. vinelandii bearing sequences homologous to Klebsiella pneumoniae nitrogenase structural genes were detected. These were different in the two species and inconsistent with the arrangement of the homologous sequences as a contiguous cluster of unique genes. The use of a DNA probe specific for nifH showed that in A. chroococcum two nifH-like sequences were present in the genome. From gene libraries for A. chroococcum, several recombinant cosmid clones bearing nif genes were identified and physically mapped. One copy of the nifH-like sequences was closely linked to nifD and K, the order of genes being as for K. pneumoniae. This cluster was sub-cloned into the broad host-range vector pKT230. The resultant plasmid complemented for C2H2-reduction but not growth in N2 several Nif- mutants of A. vinelandii and K. pneumoniae and also abolished growth in N2 in Nif+ parents. The inhibition was ascribed to a short region adjacent to nifH, which probably corresponds to the promoter as its inhibitory affects were alleviated by provision of K. pneumoniae nifA in multiple copies. 3 sizes of transcripts are produced from the region containing nifH and nifD of A. chroococcum in cultures derepressing for nif. A region bearing homology to a fragment of the K. pneumoniae nif cluster bearing nifV was identified 15 Kb away from nifHDK in A. chroococcum however the order of genes is probably similar to that of K. pneumoniae.

Azotobacter

Refusing treatment.

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Ethics, Nursing