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Biomedical subjects

Robert Wilson

Publications and source records attributed to Robert Wilson.

12 recordsLinked to original sources

Isolation of proteins that interact with the signal transduction molecule Dof and identification of a functional domain conserved between Dof and vertebrate BCAP.

Dof is a large molecule essential for signal transduction by the two FGF receptors in Drosophila. It contains two ankyrin repeats and a coiled-coil region, but has no other recognisable structural motif. Dof shares these features with its closest vertebrate relatives, the B-cell signalling molecules BCAP and BANK. In addition, this family of proteins shares a region of homology upstream of the ankyrin repeats, which we call the Dof/BCAP/BANK (DBB) motif. We have identified 44 proteins that interact with Dof in a yeast two-hybrid screen. These include the Drosophila FGF-receptor Heartless and Dof itself. We show that the integrity of the DBB motif is required both for Dof and for BCAP to form dimers. Analysis of the interactions between a set of deletion constructs of Dof and the panel of interactors suggests that Dof may adopt different conformations, with a folded conformation stabilized by interactions between the DBB motif and the C-terminal part of the protein.

Adaptor Proteins, Signal Transducing↗

Electrochemiluminescence enzyme immunoassay for TNT.

Details of an electrochemiluminescence (ECL) enzyme immunoassay for TNT (2,4,6-trinitrotoluene) are reported. The design and construction of a computer controlled flow injection electrochemiluminometer in which the immunoassays are carried out is described. This system is used to select and pump solutions through a flow cell, which contains a gold working electrode as part of a three-electrode arrangement. The deposition of a re-usable immunosorbent dextran surface anchored to a gold surface in the flow cell by chemiadsorbed thiol groups is described. Antibodies are labeled with the enzyme glucose oxidase and used in competitive immunoassays in which the separation step is carried out by concentrating unbound antibodies on the immunosorbent surface. Hydrogen peroxide generated by the enzyme label when glucose is pumped through the flow cell is detected using luminol ECL. Light intensity was inversely proportional to the concentration of TNT in the sample in the range 0-100 ppb. The results are compared with colorimetric ELISA's carried out using the same reagents, and potential for developing a portable instrument for use in the field is discussed.

Enzyme-Linked Immunosorbent Assay↗

Assessment of lifetime participation in cognitively stimulating activities.

Cognitively stimulating experience is thought to contribute to cognitive reserve. We constructed a questionnaire consisting of 25 items about frequency of participation in cognitive activities across the life span and administered it to two groups of older persons. The total score on the scale had high internal consistency (coefficient alpha = 0.88) and temporal stability over a 4-week re-test interval (r = 0.79), and it was positively correlated with education. In analyses controlling for age, sex, and education, more frequent cognitive activity was related to better perceptual speed, visuospatial ability, and semantic memory but not to episodic memory or working memory. The results suggest that the scale provides a psychometrically sound measure of frequency of cognitive activity across the life span.

Aged↗

Interpreting the results of the amplified Mycobacterium tuberculosis direct test for detection of M. tuberculosis rRNA.

The Amplified Mycobacterium tuberculosis Direct (AMTD) test detects M. tuberculosis rRNA. By using culture of M. tuberculosis as a gold standard, a number of different diagnostic indices were examined in an attempt to determine the diagnostic performance of the AMTD test and demonstrate how it might usefully be interpreted during the early management of disease.

Data Interpretation, Statistical↗

Do oxidized fatty acids activate coagulation factor VII during post-prandial lipemia in women?

Factor VII is activated to VIIa within hours after dietary fat, irrespective of its fatty acid composition. Edible oils contain oxidized material (hydroxy fatty acids, HOFA). Twenty-five fasting women, aged 38 (10) years, consumed 30 g walnut oil containing 26 (6) mg HOFA. Blood was collected 2-hourly to measure plasma triglycerides and plasma lipid HOFA by gas chromatography/mass spectrometry. VII and sTF-dependent VIIa were quantified at 0, 6 and 24 h. Increased plasma triglycerides and HOFA (areas under the curve 0-8 h, AUC) were related r = 0.83, p < 0.001. VIIa increased from 2.6 (1.4) to 4.2 (1.9) ng/mL at 6 h (p < 0.001). Plasma VII remained constant. VIIa (6 h) was related to plasma triglycerides- and HOFA-AUC: r = 0.38 and 0.53, respectively (both p < 0.05). Plasma VIIa was also related to body weight, fasting triglycerides, HOFA and VII. Only HOFA-AUC and body weight related to VIIa (6 h) in stepwise regression analysis (p = 0.007 and 0.038, respectively). Oxidized, not normal, fat activates VII and could increase coronary risk in humans.

Adult↗

Structure theorems for game trees.

Kohlberg and Mertens [Kohlberg, E. & Mertens, J. (1986) Econometrica 54, 1003-1039] proved that the graph of the Nash equilibrium correspondence is homeomorphic to its domain when the domain is the space of payoffs in normal-form games. A counterexample disproves the analog for the equilibrium outcome correspondence over the space of payoffs in extensive-form games, but we prove an analog when the space of behavior strategies is perturbed so that every path in the game tree has nonzero probability. Without such perturbations, the graph is the closure of the union of a finite collection of its subsets, each diffeomorphic to a corresponding path-connected open subset of the space of payoffs. As an application, we construct an algorithm for computing equilibria of an extensive-form game with a perturbed strategy space, and thus approximate equilibria of the unperturbed game.

Journal Article↗

Dietary hydroxy fatty acids are absorbed in humans: implications for the measurement of 'oxidative stress' in vivo.

Lipid peroxidation products formed in vivo or originating from the diet may lead to atherosclerosis. However, little is known about the absorption of these products in man. We studied the absorption of fat (30 g) containing 14-15 mg [U-13C]-labeled hydroxy or dihydroxy triglycerides in two groups of six apparently healthy women aged 40 +/- 2 years. Post-prandial 13C-labeled hydroxy fatty acid concentration increased in a pattern somewhat different from that of plasma triglycerides, with peak levels being reached between 4 and 6 h. However, the amount of 13C-labeled oxidized fat absorbed (area under the curve of plasma concentrations from 0 to 8 h) was related to that of plasma triglycerides: 13C hydroxy vs TG (r = 0.88, p <.02), and 13C dihydroxy vs TG (r = 0.85, p <.05). 13C monohydroxy triglycerides appeared to be absorbed to a greater extent than those of 13C dihydroxy triglycerides. Although low levels of 13C hydroxy lipids could be detected in fasting plasma after 24 h, concentrations were very low. Dietary lipid oxidation products are absorbed. The measurement of hydroxy fatty acids in plasma total lipids may not be a valid marker of lipid peroxidation in vivo when subjects are not fasting.

Adult↗

A comparison of gemifloxacin and clarithromycin in acute exacerbations of chronic bronchitis and long-term clinical outcomes.

BACKGROUND: Gemifloxacin is an enhanced-affinity quinolone with potent activity against lower respiratory tract pathogens. OBJECTIVE: The efficacy and safety of a 5-day course of gemifloxacin were compared with those of a standard 7-day regimen of clarithromycin in patients with an acute exacerbation of chronic bronchitis (AECB). The impact of treatment on the long-term (26 weeks) clinical outcome was also assessed. METHODS: The acute phase of this randomized, double-blind study was performed in 93 centers in 7 countries. Adult patients (age >40 years) with a history of chronic bronchitis and an Anthonisen type 1 acute exacerbation (increased dyspnea, cough, and sputum purulence) were eligible. Patients receiving systemic steroids at a dose of >10 mg prednisone or the equivalent were excluded. Patients were randomized to receive gemifloxacin 320 mg once daily for 5 days or clarithromycin 500 mg twice daily for 7 days. Clinical and bacteriologic response rates were assessed at the end-of-therapy visit (days 8-12), the week 2-3 follow-up visit (days 13-24), and the week 4-5 follow-up visit (days 25-38). The long-term phase (26 weeks), which included US and Canadian participants only, evaluated the proportion of patients who remained free of a recurrence of AECB requiring additional antimicrobial therapy after resolution of the initial episode. RESULTS: Seven hundred twelve patients were randomized to treatment, 351 to gemifloxacin and 361 to clarithromycin. The long-term study included 438 patients, 214 receiving gemifloxacin and 224 receiving clarithromycin. Clinical success rates at the 2-3 week follow-up visit were 85.4% for gemifloxacin and 84.6% for clarithromycin. Bacteriologic success rates were 86.7% for gemifloxacin and 73.1% for clarithromycin. Significantly more patients receiving gemifloxacin than clarithromycin remained free of AECB recurrences (71.0% vs 58.5%, respectively; P = 0.016). Both treatments were well tolerated. CONCLUSIONS: In the acute treatment of Anthonisen type 1 AECB, a 5-day course of gemifloxacin was at least as effective as a 7-day regimen of clarithromycin. In this population, significantly more patients receiving gemifloxacin remained free of AECB recurrence after 26 weeks compared with those receiving clarithromycin.

Adult↗