Biomedical subjects
Publications and source records attributed to D Stout.
83 participants thought about a white bear before or after trying to suppress the idea. There was no rebound effect (more expression of white-bear thoughts after than before suppression) for either introverts or extraverts.
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Farnesylation of Ras is required for its transforming activity in human cancer and the reaction is catalysed by the enzyme farnesyltransferase. Recently, we discovered a novel chemical series of potent farnesyl pyrophosphate (FPP) analogues which selectively inhibited farnesyltransferase. Our most potent compound to date in this series, A-176120, selectively inhibited farnesyltransferase activity (IC(50) 1.2+/-0.3 nM) over the closely related enzymes geranylgeranyltransferase I (GGTaseI) (IC(50) 423+/-1.8 nM), geranylgeranyltransferase II (GGTaseII) (IC(50) 3000 nM) and squalene synthase (SSase) (IC(50)>10000 nM). A-176120 inhibited ras processing in H-ras-transformed NIH3T3 cells and HCT116 K-ras-mutated cells (ED(50) 1.6 and 0.5 microM, respectively). The anti-angiogenic potential of A-176120 was demonstrated by a decrease in Ras processing, cell proliferation and capillary structure formation of human umbilical vein endothelial cells (HUVEC), and a decrease in the secretion of vascular endothelial growth factor (VEGF) from HCT116 cells. In vivo, A-176120 reduced H-ras NIH3T3 tumour growth and extended the lifespan of nude mice inoculated with H- or K-ras-transformed NIH3T3 cells. A-176120 also had an additive effect in combination with cyclophosphamide in nude mice inoculated with K-ras NIH3T3 transformed cells. Overall, our results demonstrate that A-176120 is a potent FPP mimetic with both antitumour and anti-angiogenic properties.
Dopamine reuptake transporter binding kinetics of 2beta-carbomethoxy-3beta-(4-[18F]fluoromethylphenyl)tropane (p-FWIN) and 2beta-carbomethoxy-3beta-(2-[18F]fluoromethylphenyl)tropane (o-FWIN) were determined in vervet monkeys using positron emission tomography (PET). Ligand localization was rapid and specific to the striatum with kinetic estimates comparable with those of 11C-labeled WIN 35,428 (CWIN). Binding was more specific with p-FWIN than with CWIN or o-FWIN. The relatively longer half-life of the 18F radiolabel enabled longer acquisition times with p-FWIN, resulting in less variability in the kinetic estimates.
Participants (N = 509) were tested for backward cued recall of concrete noun pairs illustrated with pictures. Recall was considerably higher when a picture showed an interactive relationship than when the two items were drawn separately. However, with separate pictures in which the stimulus drawing appeared in a color that bore a direct relationship to the response object or when both drawings shared a color that was not related to the response object, recall was higher than with uncolored drawings. Performance was even better when the shared color was associated with the response object, although it remained below that with uncolored interactive pictures. The positive effects of shared colors did not occur with interactive pictures, but recall improved further when the response color appeared either in the stimulus or response portions of the combined drawing. It is concluded that cued recall is mediated by common elements and that the effects are additive, at least with separate pictures.
Undergraduate university students (N = 103) participated in a study of the relationship between test anxiety and the variables of trait anxiety, self-esteem, locus of control, mental ability, and gender. Results indicated bivariate associations between total test anxiety and the other measures except for mental ability. Further analyses revealed independent relationships between the "worry" component of test anxiety and the variables of trait anxiety, internality, chance, and mental ability. We also found independent associations between the "emotionality" aspect of test anxiety and the measures of trait anxiety and chance.
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Over a 2-year period we observed three cases of unilateral suppression of the electroencephalogram (EEG) lasting from 45 s to 4 min following intracarotid injection of 60% iothalamate meglumine (Conray) for intraoperative carotid angiography postendarterectomy. As a result of these cases we undertook studies in 11 dogs anesthetized with isoflurane to examine causes of EEG suppression following intracarotid contrast medium injection. In group 1 (n = 6) cerebral blood flow (CBF), the cerebral metabolic rate for oxygen (CMRO2), EEG activity, and permeability of the blood-brain barrier (BBB) were determined. In group 2 (n = 5) cerebrospinal fluid (CSF) pressure, EEG activity, and BBB permeability were determined. Intracarotid injection of 5 ml of 60% Conray was associated with unilateral EEG suppression and increased BBB permeability in 1 of 11 dogs. Injection of contrast material caused no change in CBF or CMRO2 and caused a statistically significant but physiologically unimportant increase of CSF pressure (from 12 +/- 1 to 16 +/- 1 cm H2O, mean +/- SEM). It is concluded that EEG suppression following intracarotid injection of Conray is a rare event. It seems unlikely that EEG suppression resulted from cerebral ischemia or hypoxia, but rather was associated with increased BBB permeability. Increased BBB permeability likely was caused by the osmotic effect of Conray and not by hypoxic-ischemic microvascular injury or loss of autoregulation of CBF.
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Infiltrating ductal carcinoma of the breast occurred in a total of six men from two families. In one family specimens from three men who had prophylactic mastectomies revealed focal intraductal hyperplasia, suggesting a familial tendency toward proliferation of mammary-duct epithelium. In the other family, benign and malignant breast lesions also developed in several women. Preliminary data suggest elevated urinary oestrogen excretion in three men from these families, implicating a defect in oestrogen production or metabolism in the pathogenesis of male breast neoplasms.