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Biomedical subjects

R Anderson

Publications and source records attributed to R Anderson.

At least 433 records · Page 24Linked to original sources

Interactions of the oxygen-dependent antimicrobial system of the human neutrophil with difloxacin, ciprofloxacin, pefloxacin and fleroxacin in the intraphagocytic eradication of Staphylococcus aureus.

The effect of the O2-dependent antimicrobial systems of the human neutrophil on the intraphagocytic activity of difloxacin, ciprofloxacin, pefloxacin and fleroxacin was determined by use of a radioassay with Staphylococcus aureus as the test organism. The fluoroquinolones exhibited good intraphagocytic activity with normal neutrophils. However the intracellular bioactivities of the four antimicrobial agents were substantially less in tests with neutrophils from two patients with chronic granulomatous disease. These observations suggest a synergic interaction between fluoroquinolones and the O2-dependent antimicrobial systems of phagocytes in the eradication of intracellular microbial pathogens.

Anti-Infective Agents↗

The examination attainments of secondary school pupils who abuse solvents.

A sample of 105 adolescents who had abused solvents and an equal number of controls matched for school, school year and sex were identified by means of a two-stage screening procedure involving (a) administration of a self-completed questionnaire to approximately 5,000 third, fourth and fifth year pupils in 16 secondary schools, and (b) individually conducted interviews. These two groups were followed up at the end of their final year of compulsory education when details of their fifth year public examination entries and results were obtained from their schools. The examination attainments of the solvent abusers were generally lower than those of the controls. They were more likely to leave school at Easter of their fifth year and a much higher proportion of them were not entered for any examinations. Those who were entered for exams were less likely to pass at O level and, regardless of the type of exam, much less likely to obtain higher examination grades. Poor examination attainments among the solvent abusers were associated with adverse domestic circumstances, frequent self-reported behaviour problems and low scores on educational tests administered at the time of transfer from primary to secondary school. After controlling for these factors, the difference between groups in examination attainments was no longer statistically significant.

Absenteeism↗

Dissection of H-2Db-restricted cytotoxic T-lymphocyte epitopes on simian virus 40 T antigen by the use of synthetic peptides and H-2Dbm mutants.

Five distinct cytotoxic T-lymphocyte (CTL) recognition sites were identified in the simian virus 40 (SV40) T antigen by using H-2b cells that express the truncated T antigen or antigens carrying internal deletions of various sizes. Four of the CTL recognition determinants, designated sites I, II, III, and V, are H-2Db restricted, while site IV is H-2Kb restricted. The boundaries of CTL recognition sites I, II, and III, clustered in the amino-terminal half of the T antigen, were further defined by use of overlapping synthetic peptides containing amino acid sequences previously determined to be required for recognition by T-antigen site-specific CTL clones by using SV40 deletion mutants. CTL clone Y-1, which recognizes epitope I and whose reactivity is affected by deletion of residues 193 to 211 of the T antigen, responded positively to B6/PY cells preincubated with a synthetic peptide corresponding to T-antigen amino acids 205 to 219. CTL clones Y-2 and Y-3 lysed B6/PY cells preincubated with large-T peptide LT220-233. To distinguish further between epitopes II and III, Y-2 and Y-3 CTL clones were reacted with SV40-transformed cells bearing mutations in the major histocompatibility complex class I antigen. Y-2 CTL clones lysed SV40-transformed H-2Dbm13 cells (bm13SV) which carry several amino acid substitutions in the putative antigen-binding site in the alpha 2 domain of the H-2Db antigen but not bm14SV cells, which contain a single amino acid substitution in the alpha 1 domain. Y-3 CTL clones lysed both mutant transformants. Y-1 and Y-5 CTL clones failed to lyse bm13SV and bm14SV cells; however, these cells could present synthetic peptide LT205-219 to CTL clone Y-1 and peptide SV26(489-503) to CTL clone Y-5, suggesting that the endogenously processed T antigen yields fragments of sizes or sequences different from those of synthetic peptides LT205-219 and SV26(489-503).

Amino Acid Sequence↗

Energy expenditure during bicycling.

This study was designed to measure the O2 uptake (VO2) of cyclists while they rode outdoors at speeds from 32 to 40 km/h. Regression analyses of data from 92 trials using the same wheels, tires, and tire pressure with the cyclists riding in their preferred gear and in an aerodynamic position indicated the best equation (r = 0.84) to estimate VO2 in liters per minute VO2 = -4.50 + 0.17 rider speed + 0.052 wind speed + 0.022 rider weight where rider and wind speed are expressed in kilometers per hour and rider weight in kilograms. Following another rider closely, i.e., drafting, at 32 km/h reduced VO2 by 18 +/- 11%; the benefit of drafting a single rider at 37 and 40 km/h was greater (27 +/- 8%) than that at 32 km/h. Drafting one, two, or four riders in a line at 40 km/h resulted in the same reduction in VO2 (27 +/- 7%). Riding at 40 km/h at the back of a group of eight riders reduced VO2 by significantly more (39 +/- 6%) than drafting one, two, or four riders in a line; drafting a vehicle at 40 km/h resulted in the greatest decrease in VO2 (62 +/- 6%). VO2 was also 7 +/- 4% lower when the cyclists were riding an aerodynamic bicycle. An aerodynamic set of wheels with a reduced number of spokes and one set of disk wheels were the only wheels to reduce VO2 significantly while the cyclists were riding a conventional racing bicycle at 40 km/h.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Investigation of the effects of oral administration of vitamin E and beta-carotene on the chemiluminescence responses and the frequency of sister chromatid exchanges in circulating leukocytes from cigarette smokers.

Sixty asymptomatic cigarette smokers were randomly allocated into three treatment groups. Smokers in Group 1 received 900 international units of Vitamin E (VE) daily for 6 wk, whereas 40 mg of beta-carotene (BC) daily was administered to those in Group 2 for the same period. Subjects in Group 3 were treated with a matched placebo. Plasma levels of VE and BC as well as circulating leukocyte counts, sister chromatid exchanges (SCEs), and the luminol-enhanced chemiluminescence (LECL) responses of blood phagocytes activated with phorbol myristate acetate (PMA) and FMLP with cytochalasin B (FMLP/CB) were measured prior to the administration of the antioxidant/placebo after 4 and 6 wk of supplementation and 12 wk after cessation of treatment. SCEs and leukocyte counts remained unchanged throughout the trial in all three treatment groups. Administration of VE for 4 wk was accompanied by decreased FMLP/CB-activated (p less than 0.005) and PMA-activated (p less than 0.005) LECL responses. However, with PMA as stimulant, the inhibition of LECL was transient, with partial recovery observed after 6 wk despite continued administration of VE. Administration of BC was associated with progressive inhibition of both FMLP/CB-activated (p less than 0.05 and p less than 0.01 after 4 and 6 wk, respectively) and PMA-activated (p less than 0.025 after 6 wk) LECL. No alterations in LECL responses were observed in Group 3 (placebo). VE appeared to inhibit the generation of oxidants by activated phagocytes, whereas BC scavenged oxidants generated by the myeloperoxidase/H2O2/halide system.

Acridines↗

Competitive titration in living sea urchin embryos of regulatory factors required for expression of the CyIIIa actin gene.

Previous studies have located some twenty distinct sites within the 2.3 kb 5' regulatory domain of the sea urchin CyIIIa cytoskeletal actin gene, where there occur in vitro high-specificity interactions with nuclear DNA-binding proteins of the embryo. This gene is activated in late cleavage, exclusively in cells of the aboral ectoderm cell lineages. In this study, we investigate the functional importance in vivo of these sites of DNA-protein interaction. Sea urchin eggs were coinjected with a fusion gene construct in which the bacterial chloramphenicol acetyltransferase (CAT) reporter gene is under the control of the entire CyIIIa regulatory domain, together with molar excesses of one of ten nonoverlapping competitor subfragments of this domain, each of which contains one or a few specific site(s) of interaction. The exogenous excess binding sites competitively titrate the available regulatory factors away from the respective sites associated with the CyIIIa.CAT reporter gene. This provides a method for detecting in vivo sites within the regulatory domain that are required for normal levels of expression, without disturbing the structure of the regulatory domain. We thus identify five nonoverlapping regions of the regulatory DNA that apparently function as binding sites for positively acting transcriptional regulatory factors. Competition with a subfragment bearing an octamer site results in embryonic lethality. We find that three other sites display no quantitative competitive interference with CyIIIa.CAT expression, though as shown in the accompanying paper, two of these sites are required for control of spatial expression. We conclude that the complex CyIIIa regulatory domain must assess the state of many distinct and individually necessary interactions in order to properly regulate CyIIIa transcriptional activity in development.

Actins↗

Relation of hypesthesia to the outcome of glycerol rhizolysis for trigeminal neuralgia.

The effects of percutaneous retrogasserian glycerol rhizolysis were observed in a population of 58 cases of classical trigeminal neuralgia. The follow-up period ranged from 7 to 52 months postoperatively. It was noted that 84% of the patients had immediate relief of pain. The overall recurrence rate was 29%. Based on Kaplan-Meier survival curves, the overall half-life (T1/2) of this procedure was 16 months. Although none of the patients developed anesthesia dolorosa or corneal ulceration, one group of patients developed either a clinical or subclinical persistent "minimal hypesthesia." In these there was a statistically significant difference in the T1/2 associated with this procedure (p = 0.01). This finding suggests that, contrary to the general belief, persistent hypesthesia after glycerol rhizolysis is a negative indicator of long-term success.

Adult↗

The influence of structural modifications of dihydrophenazines on arachidonic acid mobilization and superoxide generation by human neutrophils.

In this study the effects of nine dihydrophenazine derivatives, relative to clofazimine (B663), on the N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) stimulated release of superoxide anion and on the spontaneous generation of arachidonic acid by human neutrophils were investigated. Previous findings that the pro-oxidative activity of the agents depended largely on the substitution in position 2 of the phenazine molecule and on chlorination in the paraposition of the phenyl and anilino rings were confirmed. Only riminophenazines, but not aposafranone derivatives or the imidazophenazine B621, could enhance superoxide release from activated neutrophils. The lack of chlorination of the phenyl and anilino rings could be compensated for by chlorine substitution in position 7 of the phenazine core. The priming effect of the agents on FMLP stimulated superoxide generation was completely prevented by the phospholipase A2 inhibitor 4-p-bromophenacyl bromide. Furthermore pro-oxidative activities correlated closely with a stimulatory effect of the agents on arachidonic acid release. It was therefore concluded that dihydrophenazine derivatives with pro-oxidative properties can prime neutrophils for FMLP-stimulated superoxide release by modulation of phospholipase A2 activity.

Arachidonic Acid↗

Investigation of the role of phagocytes and anti-oxidant nutrients in oxidant stress mediated by cigarette smoke.

In this study we have correlated the plasma levels of the anti-oxidant vitamins C and E, and beta-carotene with smoking histories, the release of reactive oxidants from circulating phagocytes and spirometry in asymptomatic cigarette smokers. Smoking histories, the generation of reactive oxidants by activated phagocytes and spirometric abnormalities were strongly inter-correlated. However, plasma levels of the anti-oxidant nutrients did not correlate with any of the other measured parameters. These findings indicate that plasma levels of vitamins C and E, and beta-carotene are apparently not predictive of predisposition to oxidant-mediated-spirometric abnormalities in cigarette smokers.

Antioxidants↗

Structure of a novel glucosamine-containing phosphoglycolipid from Deinococcus radiodurans.

The structure of a major novel lipid from Deinococcus radiodurans has been determined to be 2'-O-(1,2-diacyl-sn-glycero-3-phospho)-3'-O-(alpha-N-acetylglucosaminyl) -N- glyceroyl alkylamine. The lipid was shown to contain a phosphatidic acid backbone by digestion with phospholipase A2 and by hydrolysis with hydrofluoric acid. Using a combination of chemical and NMR spectroscopic techniques, the structure of this lipid was elucidated and compared with that of a similar phosphoglycolipid reported earlier (Anderson, R., and Hansen, K. (1985) J. Biol. Chem. 260, 12219-12223) in which galactose was found in place of N-acetylglucosamine. The fatty acid compositions of the two lipids were similar.

Acetylation↗

Generation of biologically active C-reactive protein peptides by a neutral protease on the membrane of phorbol myristate acetate-stimulated neutrophils.

The association of human C-reactive protein (CRP) with nonstimulated and PMA-stimulated human neutrophils and the concomitant degradation of CRP (monitored by TCA-soluble peptides and SDS-PAGE analysis) has been studied. Maximum association of 125I-labeled CRP with neutrophils and 125I-labeled CRP degradation during association with these cells was achieved by stimulating the neutrophils with PMA at 10 ng/ml; a concentration in which azurophil granule release was not significant. For PMA-stimulated neutrophils, the association of 125I-labeled CRP was 1.8 times higher and PMA-stimulated neutrophil-mediated degradation of the ligand was three times faster than that for nonstimulated cells. The neutrophil-associated 125I-labeled CRP in the absence and presence of PMA proved on SDS-PAGE analysis to be approximately 50% degraded. There was a positive correlation between the extent of CRP degradation and the association of 125I-labeled CRP with neutrophils. In addition to generation of neutrophil associated CRP intermediates, small soluble CRP peptides were generated during association of CRP with neutrophils. These peptides inhibited superoxide production from opsonized zymosan-activated neutrophils by approximately 40% at 10 micrograms/ml. 125I-labeled CRP degradation mediated by nonstimulated neutrophils, and neutrophil-conditioned medium (from both non-stimulated and PMA-stimulated cells) was inhibitable by alpha 1-antitrypsin and approximately seven times less at 1 h than that occurring during 125I-labeled CRP-association with PMA-stimulated neutrophils. The degradation of 125I-labeled CRP mediated by PMA-stimulated neutrophils was not fully inhibitable by alpha 1-antitrypsin. The data point to the involvement of a membrane-associated serine protease, which is maximally activated by PMA, in the degradation of 125I-labeled CRP during association with neutrophils. Our results indicate that at an inflammatory site CRP-derived peptides can be produced that inhibit the action of activated neutrophils.

C-Reactive Protein↗