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Biomedical subjects

Stephen J Wilson

Publications and source records attributed to Stephen J Wilson.

29 records · Page 2Linked to original sources
PubMed2004

Synthesis of a glucuronic acid and glucose conjugate library and evaluation of effects on endothelial cell growth.

Compounds that alter endothelial cell growth are of interest in the development of angiogenesis modulators. A structurally diverse series of saccharide derivatives (glycosylamide conjugates) have been synthesized and evaluated for their effects on bovine aortic endothelial cell (BAEC) growth. Heparin-albumin (HA) reduced BAEC growth by 32% at 10 microg/mL and a number of the novel saccharide conjugates from the library were found to mimic the effect of HA as they also inhibit endothelial cell survival under identical conditions. Two thiophene conjugates, thioglucamide (24% inhibition at 35 microM) and a related glucuronide (26% inhibition at 33 microM) were the most potent inhibitors of BAEC growth, as determined using a methylthiazol tetrazolium (MTT) assay. The effects of thioglucamide and HA on absolute cell number were also studied using cell counting experiments; thioglucamide (47% after 24 h) was more potent than indicated by the MTT assay and initially reduced the BAEC number to a greater extent than HA (30% after 24 h); however, its actions were over more rapidly than were HA's as cell growth had returned to levels of the control after 72 h where HA still caused 25% inhibition. The binding of the monosaccharide conjugates to fibroblast growth factor (FGF-2) in competition with heparin-albumin by ELISA was investigated to establish the possible mechanism by which glycoconjugates could alter growth but there was no general correlation between reduction in viable cell population and binding to FGF-2. No glycoconjugate reduced the proliferation of mouse mammary epithelial cells, nor did any alter gross cell morphology, supporting a proposal that the reduction in BAEC survival by monosaccharide conjugates such as thioglucamide is a result of the inhibition of cell proliferation rather than being an induction of cytotoxicity. These studies indicate that cell biological studies to determine the mechanism of action of the simple monosaccharide conjugates may be worthwhile.

Animals↗
PubMed2004

Prefrontal responses to drug cues: a neurocognitive analysis.

The construct of craving has been central to addiction research for more than 50 years. Only recently have investigators begun to apply functional neuroimaging techniques to the study of drug cue reactivity, and a small but growing number of studies implicate a distributed system of brain regions in the pathogenesis of craving. The internal consistency of this burgeoning literature has thus far been disappointing, however, leaving open the question of which brain regions contribute to craving. Here we review neuroimaging studies of cue-elicited craving in the context of a framework drawn from behavioral research indicating that perceived drug use opportunity significantly affects responses to the presentation of drug cues. Using this framework provides a way to reconcile discrepant findings among brain-imaging studies of cue-elicited craving.

Amygdala↗
PubMed2004

Direct costs of multidrug-resistant Acinetobacter baumannii in the burn unit of a public teaching hospital.

We conducted a case-control study to determine the attributable direct costs of multidrug-resistant Acinetobacter baumannii (MDRAB) in the burn unit of a public teaching hospital. The mean total hospital cost of patients who acquired MDRAB was 98,575 dollars higher than that of control patients who had identical burn severity of illness indices ( P <.01). These data should help infection control practitioners and others determine the cost-effectiveness of specific interventions designed to control this emerging nosocomial pathogen.

Acinetobacter Infections↗
PubMed2003

Brain activity during automatic semantic priming revealed by event-related functional magnetic resonance imaging.

Semantic priming occurs when a subject is faster in recognising a target word when it is preceded by a related word compared to an unrelated word. The effect is attributed to automatic or controlled processing mechanisms elicited by short or long interstimulus intervals (ISIs) between primes and targets. We employed event-related functional magnetic resonance imaging (fMRI) to investigate blood oxygen level dependent (BOLD) responses associated with automatic semantic priming using an experimental design identical to that used in standard behavioural priming tasks. Prime-target semantic strength was manipulated by using lexical ambiguity primes (e.g., bank) and target words related to dominant or subordinate meaning of the ambiguity. Subjects made speeded lexical decisions (word/nonword) on dominant related, subordinate related, and unrelated word pairs presented randomly with a short ISI. The major finding was a pattern of reduced activity in middle temporal and inferior prefrontal regions for dominant versus unrelated and subordinate versus unrelated comparisons, respectively. These findings are consistent with both a dual process model of semantic priming and recent repetition priming data that suggest that reductions in BOLD responses represent neural priming associated with automatic semantic activation and implicate the left middle temporal cortex and inferior prefrontal cortex in more automatic aspects of semantic processing.

Adult↗
PubMed2003

Role of hemin in the modulation of H2O2-mediated endothelial cell injury.

Heme oxygenase (HO) has been primarily regarded as the rate-limiting enzyme in the degradation of heme. However it has recently been proposed that the inducible isoform, HO-1 (EC 1.14.99.3), functions as a stress-responsive antioxidant enzyme, with the capacity to protect against oxidant-mediated vascular injury. This study used an in vitro model of endothelial permeability to determine the effects of the HO-1-inducing agent hemin on noncytotoxic endothelial injury mediated by acute oxidant stress. Effects of hemin on oxidant-mediated cytotoxicity in a number of endothelial cell types were also investigated. A 20-min exposure of human umbilical vein endothelial cell (HUVEC) monolayers to H(2)O(2) resulted in a significant concentration-dependent increase in permeability, which was reversible 48 h later. Pretreatment of monolayers with hemin for 2 h followed by 18 h in complete medium resulted in HO-1 induction and the attenuation of H(2)O(2)-mediated increases in endothelial permeability, and significantly improved the restoration of endothelial barrier function 48 h later. In HUVEC and in the human microvascular endothelial cell line HMEC-1, hemin treatment as above resulted in protection against cytotoxicity, but not in bovine aortic endothelial cells (BAECs), where such toxicity was potentiated. This potentiation was inhibited by incubation with the HO inhibitor tin protoporphyrin IX, supporting a role for HO-1 in the potentiation of the cytotoxic response. When the exposure time of BAEC to hemin was extended to 24 h, H(2)O(2)-mediated cytotoxicity was attenuated. We conclude that hemin treatment is cytoprotective against noncytotoxic endothelial injury in vitro, under conditions that may not offer global protection against cytotoxic injury to vascular endothelium. This would indicate that HO-1 induction associated with cytotoxic injury in vivo is not always beneficial and therefore that the use of hemin as a therapeutic agent to offset oxidant injury in vascular endothelium should be undertaken with caution.

Animals↗
PubMed2003

Elevated preoperative fasting serum glucose levels increase the risk of postoperative mediastinitis in patients undergoing open heart surgery.

We conducted a case-control study to investigate the relationship between preoperative fasting serum glucose and postoperative mediastinitis in patients undergoing open heart surgery. Multivariate analysis revealed that a glucose level of 126 mg/dL or greater was associated with a significantly increased risk of mediastinitis (OR, 5.25; P = .002).

Blood Glucose↗
PubMed2003

Pulmonary cryptococcosis after initiation of anti-tumor necrosis factor-alpha therapy.

Many patients with rheumatoid arthritis are being treated with immunosuppressive regimens that include an agent directed at blocking tumor necrosis factor (TNF)-alpha. Although reportedly safe, tuberculous and fungal infections have emerged as significant complications of therapy. We report a case of pulmonary cryptococcosis soon after the initiation of therapy with the anti-TNF-alpha antibody, infliximab. A diagnosis was made early in the disease course, and the patient responded quickly to antifungal therapy. This case should alert clinicians to the increased incidence of pulmonary mycoses in patients receiving anti-TNF-alpha therapy.

Antibodies, Monoclonal↗
PubMed2002

Identification of novel inhibitors of fibroblast growth factor (FGF-2) binding to heparin and endothelial cell survival from a structurally diverse carbohybrid library.

Inhibitors of FGF-2 binding to a heparin-albumin conjugate were identified by ELISA from a library of glucuronic acid derivatives. These compounds were also inhibitors of endothelial cell survival that is dependant on FGF-2 and heparin or heparan sulfate proteoglycans. The results indicate that these bioactive compounds may prove useful as lead structures for the further development of pharmaceutical agents capable of modulating biological activity of FGF-2.

Angiogenesis Inhibitors↗
PubMed2002

Orthographic/phonological facilitation of naming responses in the picture-word task: an event-related fMRI study using overt vocal responding.

In the picture-word interference task, naming responses are facilitated when a distractor word is orthographically and phonologically related to the depicted object as compared to an unrelated word. We used event-related functional magnetic resonance imaging (fMRI) to investigate the cerebral hemodynamic responses associated with this priming effect. Serial (or independent-stage) and interactive models of word production that explicitly account for picture-word interference effects assume that the locus of the effect is at the level of retrieving phonological codes, a role attributed recently to the left posterior superior temporal cortex (Wernicke's area). This assumption was tested by randomly presenting participants with trials from orthographically related and unrelated distractor conditions and acquiring image volumes coincident with the estimated peak hemodynamic response for each trial. Overt naming responses occurred in the absence of scanner noise, allowing reaction time data to be recorded. Analysis of this data confirmed the priming effect. Analysis of the fMRI data revealed blood oxygen level-dependent signal decreases in Wernicke's area and the right anterior temporal cortex, whereas signal increases were observed in the anterior cingulate, the right orbitomedial prefrontal, somatosensory, and inferior parietal cortices, and the occipital lobe. The results are interpreted as supporting the locus for the facilitation effect as assumed by both classes of theoretical model of word production. In addition, our results raise the possibilities that, counterintuitively, picture-word interference might be increased by the presentation of orthographically related distractors, due to competition introduced by activation of phonologically related word forms, and that this competition requires inhibitory processes to be resolved. The priming effect is therefore viewed as being sufficient to offset the increased interference. We conclude that information from functional imaging studies might be useful for constraining theoretical models of word production.

Adult↗
PubMed2002

Effects of perceived disability on persuasiveness of computer-synthesized speech.

Are perceptions of computer-synthesized speech altered by the belief that the person using this technology is disabled? In a 2 x 2 factorial design, participants completed an attitude pretest and were randomly assigned to watch an actor deliver a persuasive appeal under 1 of the following 4 conditions: disabled or nondisabled using normal speech and disabled or nondisabled using computer-synthesized speech. Participants then completed a posttest survey and a series of questionnaires assessing perceptions of voice, speaker, and message. Natural speech was perceived more favorably and was more persuasive than computer-synthesized speech. When the speaker was perceived to be speech-disabled, however, this difference diminished. This finding suggests that negatively viewed assistive technologies will be perceived more favorably when used by people with disabilities.

Adult↗