Search PubMed⌕ Search

Biomedical subjects

J Duncan

Publications and source records attributed to J Duncan.

At least 73 records · Page 4Linked to original sources

Effect of leukotriene inhibitor on salicylate induced morphologic changes of isolated cochlear outer hair cells.

Our previous studies have shown that salicylate ototoxicity is associated with decreased levels of prostaglandins (PGs) and increased levels of leukotrienes (LTs) in the perilymph. Other studies have demonstrated that salicylate ototoxicity is associated with decreased cochlear blood flow, reversible changes in isolated cochlear outer hair cells (OHCs), and decreased otoacoustic emission. We have shown that pretreatment with an LT inhibitor prevents salicylate induced hearing loss, a decrease in cochlear blood flow and changes in otoacoustic emissions. The objectives of the current study were to determine the effect of exposure of salicylate and LTs on the morphology of isolated OHSc and to determine the effect of LT inhibitors on salicylate induced morphologic changes of isolated OHCs. Isolated OHCs from chinchilla cochlea were exposed to different test solutions. The groups included sodium salicylate (10 mM) with or without pretreatment with an LT inhibitor (L-663, 536, 30 microM), 0.1 or 1.0 microM solution of LTC4, LTD4, LTE4, and two control solutions, standard bathing solution (SBS) or leukotriene inhibitor alone. Osomolality of all solutions were kept at 305 +/- 5 mmolkg-1. The OHCs were observed under an inverted microscope. Images were stored onto a computer and analyzed later. OHCs exposed to the salicyalate developed a decrease in mean cell length. The exposure of OHCs to LTC4, LTD4, and LTE4 also demonstrated a similar decrease in mean cell length. Cells in the control SBS or LT inhibitor alone groups did not show any change. OHCs exposed to salicylate in the presence of the LT inhibitor did not exhibit morphologic changes. This study suggest that arachidonic acid metabolites, especially an increase in the concentration of LTs, seem to play an important role in the pathogenesis of salicylate ototoxicity.

Animals↗

Effects of similarity, difficulty, and nontarget presentation on the time course of visual attention.

Long-lasting interference from an initial visual target on a subsequent one has been measured in two paradigms: rapid serial presentation of targets and nontargets at a single location, and simple presentation of two spatially separated targets. We note that comparisons between these paradigms might be invalid, since interference in each paradigm can be attributed to a different source: demands on selective attention, or demands to switch locations. We use a novel target presentation that both minimizes selection demands and eliminates location switching, yet we still find long-lasting interference. We suggest that all three paradigms discussed tap a common attentional limit. We also examine effects of similarity between targets, and effects of discrimination difficulty on the initial target. We find that similarity effects are more pronounced when nontargets are present, and we find no effect of discrimination difficulty on subsequent interference.

Adult↗

Manipulating systemic and mucosal immune responses with skin-deliverable adjuvants.

Most medically important bacterial and viral pathogens gain entry into the body either via the skin or a mucosal surface. Vaccination provides a viable and cost-effective strategy for the prevention of such diseases and it has always been a principal aim with vaccinologists, to be able to promote simultaneously, protective immune responses both systemically and at mucosal surfaces. The paradigm that mucosal immunity is best stimulated by exposure to antigen via a mucosal route simply because inductive sites such as Peyer's patches and bronchial associated lymphoid tissues are located in the mucosal epithelium, has promoted a plethora of immunizing strategies aimed at delivering both antigen and adjuvant to mucosal surfaces. We have developed a novel adjuvant system capable of intradermal delivery of antigens complexed in an ISCOSOME delivery vehicle. This adjuvant, referred to as a skin and mucosal adjuvant or SAMA4, was efficacious in eliciting both systemic and mucosal IgG and IgA antibodies in sheep, pigs and mice. SAMA4 does not induce granulomatous lesions at the site of vaccine delivery and can be used to deliver adjuvanted antigens by other routes including intranasal, oral and intravaginal. Using ovalbumin as a test antigen, intradermally delivered ovalbumin-SAMA4 complexes was found to be very effective in promoting a cytotoxic T cell response. Attempts to dissect the mode of action of SAMA4 by flow cytometric analysis of lymphocyte populations from the spleen, lung, liver and thymus revealed an effect of route of vaccine delivery upon the composition of specific lymphocyte subsets in these various organ compartments. From this, it can be inferred that SAMA4 induced a route-dependent re-mobilization and alteration in lymphocyte trafficking patterns. Other mucosal adjuvants such as cholera toxin B and microspheres, when injected intradermally, tended to promote primarily, an IgG and not an IgA response against hte carrier antigen.

Animals↗

The Slow Time-Course of Visual Attention

Visual attention is often conceived as a high-speed serial system moving rapidly from one object to another at rates of a few dozen milliseconds per item. We present four experiments demonstrating that this high-speed model is incorrect. Subjects identify two objects, presented at separate times. We measure how long the first object continues to interfere with accuracy on the second, and hence the time-course of the first object's attentional demand. We find interference for a half-second or more-roughly 10 times longer than might be predicted from conventional visual search paradigms. In further experiments, we show that the time-course of interference depends upon the number of attended objects, not the number or complexity of responses. Even objects which require no response, such as nontargets in visual search, can still produce long lasting interference on subsequent identification. We suggest that visual attention is not a high-speed switching mechanism, but instead a sustained state during which representations of relevant objects become available to guide behavior.

Journal Article↗

Intelligence and the frontal lobe: the organization of goal-directed behavior.

Basic to the study of individual differences is the concept of 'general intelligence' or Spearman's g. In this article we suggest that g is largely a reflection of the control functions of the frontal lobe. A series of experiments investigates a phenomenon we call goal neglect: disregard of a task requirement event though it has been understood and remembered. Subjectively it is as though the neglected requirement "slips the subject's mind." Previously described in frontal patients, we show that goal neglect can also be seen in some members of the normal population. In line with conventional distinctions between controlled and automatic processing, eliciting conditions for goal neglect include novelty, weak error feedback, and multiple concurrent task requirements. Under these conditions neglect is linked closely to g and extremely common after frontal lesions. Following many other models, we suggest that behavior in any task is structured by a set of action constraints or requirements, derived in part from verbal instructions and specified at multiple levels of abstraction. A frontal process of constraint or requirement activation is fundamental to Spearman's g.

Adult↗

Young women with advanced aortoiliac occlusive disease: new insights.

We identified a group of 24 young (less than 50 years of age) women with isolated, premature atherosclerotic aortoiliac occlusive disease and attempted to identify distinguishing hemostatic characteristics. Most of these patients (62%) presented with acute thromboembolic events (blue toe syndrome, n = 6; macroemboli, n = 6; or aortoiliac thrombosis, n = 3). Aortoiliac reconstruction (aortoiliac endarterectomy, n = 10, aortobifurcation bypass grafts, n = 6; and percutaneous angioplasty, n = 4) was complicated by early thrombosis in 6 of 20 cases (30%), (1 of 10 endarterectomies, 4 of 6 bypass grafts, and 1 of 4 angioplasties). Fresh thrombus overlying an atherosclerotic plaque was a common finding at surgery. This observation and the relatively high incidence of thromboembolic events led us to hypothesize that a characteristic hemostatic profile might underlie the remarkably similar clinical presentations of these women. Levels of antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulant), plasminogen activator inhibitor-1, fibrinogen, antithrombin III, protein C, protein S, plasminogen, prothrombin fragment F1 + 2, and D-dimer were determined for these young women and for 21 age-matched white female control subjects without vascular disease and nine white male patients with aortoiliac occlusive disease (mean 61 years, range 43 to 74 years). The incidence of anticardiolipin antibodies was 42% (8 of 19) in the female patients, which was significantly elevated (p = 0.028). The female (62.5%) and male (100%) patients had significantly elevated D-dimer levels (p < 0.001). Deficiencies of antithrombin III, protein C, and protein S were rare. A unique pattern of premature aortoiliac atherosclerosis exists in some young women. Intra-arterial thromboembolic events are common at presentation and complicate surgical management. The role of antiphospholipid antibodies remains uncertain.

Adult↗

Naturally-occurring Wolbachia infection in Drosophila simulans that does not cause cytoplasmic incompatibility.

Microbes of the genus Wolbachia are transmitted by their hosts via the maternal parent and are responsible for cytoplasmic incompatibility among insect populations. This phenomenon can result in Wolbachia spreading through natural populations as previously demonstrated in Drosophila simulans. Here we describe another Wolbachia infection in D. simulans that does not cause cytoplasmic incompatibility. This is a property of the Wolbachia rather than the nuclear background. The infection occurs at a low frequency in natural populations from eastern Australia. The infection shows perfect maternal transmission in the field and does not cause any detectable deleterious effects on its host. These findings suggest that the Wolbachia infection behaves like a neutral variant in populations. The infection may represent an evolutionary outcome of interactions between Wolbachia infections and their hosts.

Animals↗

Sutterella wadsworthensis gen. nov., sp. nov., bile-resistant microaerophilic Campylobacter gracilis-like clinical isolates.

Campylobacter gracilis (formerly Bacteroides gracilis) is an asaccharolytic, nitrate-positive, urease-negative organism that requires formate and fumarate or hydrogen as a growth additive and may pit agar media. Clinical isolates that were obtained primarily from appendiceal and peritoneal fluid specimens and initially were identified in our laboratory as B. gracilis were later found to include "unusual" strains that could be distinguished by biochemical and genetic criteria. These unusual C. gracilis strains were bile resistant, could not reduce tetrazolium chloride under aerobic conditions if formate and fumarate were added to the medium, and could grow in the presence of 2 or 6% oxygen if no blood was added to the medium. C. gracilis, other campylobacters, and the unusual strains produced distinctive dehydrogenase patterns when gels were incubated anaerobically. A cellular fatty acid analysis revealed that the cluster formed by the unusual organisms was distinct from the (separate) clusters formed by C. gracilis, Bacteroides ureolyticus, and other Campylobacter species. 16S rRNA sequence data indicated that these organisms are not related phylogenetically to either C. gracilis or other Campylobacter species; the most closely related taxa as determined by rRNA sequence analysis were unrelated aerobes (members of the genera Bordetella, Alcaligenes, Rhodocyclus, and Comamonas). DNA homology data confirmed that these taxa are separate groups. Our data indicate that the unusual organisms are members of a new genus and new species, for which we propose the name Sutterella wadsworthensis. The type strain of S. wadsworthensis is strain WAL 9799 (= ATCC 51579).

Base Sequence↗

Objects and attributes in divided attention: surface and boundary systems.

A series of experiments investigated concurrent discriminations of surface and nonsurface attributes, including color, brightness, texture, length, location, and motion. In all cases but one, results matched those previously reported: Interference occurred when two discriminations concerned different objects, but not when they concerned the same one. In the two-object case, interference was the same whether discriminations were similar (e.g., two surface discriminations) or different (e.g., one surface, one boundary). Such results support a model of visual attention in which separate visual subsystems are coordinated, converging to work on surface and boundary properties of the same selected object. A partial exception is color: For reasons that are unclear, color escapes two-object interference except from other, concurrent surface discriminations.

Adult↗

Fluid intelligence after frontal lobe lesions.

Generally positive correlations between different ability tests provide the evidence for a factor of "general intelligence" or Spearman's g. Though a possible neural substrate for g is suggested by executive impairments following frontal lobe lesions, preserved IQs in some frontal patients have been taken as strong evidence against this interpretation. We show that such results depend on how g is measured. Patients with superior IQs on the most clinically popular test--the Wechsler Adult Intelligence Scale--show impairments of 20-60 points on conventionally measured fluid intelligence or novel problem solving. On psychometric grounds, it is fluid intelligence that is most closely related to Spearman's g. The data suggest that g may in large part be a reflection of frontal functions.

Adult↗

Veillonella myositis in an immunocompromised patient.

Infectious myositis is rather uncommon. When caused by anaerobic organisms, myositis is usually polymicrobial. Trauma, ischemia, or a contiguous focus of infection is often an antecedent of myositis. We report a case of monomicrobial veillonella myositis in an immunocompromised patient. The infection responded to debridement and therapy with metronidazole.

Anti-Bacterial Agents↗

Target and nontarget grouping in visual search.

The results of Driver et al. rule out strictly element-by-element approaches to the problem of easy conjunction search. Neither can they be explained by a simple bias toward mismatching display elements, at least as it is implemented in guided search. Such a bias is the only means of within-display interaction in many current models (Sagi & Julesz, 1984; Ullman, 1984). Instead, models (Sagi & Julesz, 1984; Ullman, 1984). Instead, the results suggest that perceptual grouping brings a bias toward common fate. For nontarget groups, this fate is rejection from further consideration; for target groups, complementarily, it is selection for further processing.

Attention↗

Non-spatial extinction following lesions of the parietal lobe in humans.

Efficient behaviour in the visual environment requires selection between stimuli competing for control of action. Many current models of selection are spatial: relevant objects are chosen by attending to their locations. The unilateral stimulus extinction observed following lesions of the parietal lobe provides evidence for spatial selection. Such patients may identify a single stimulus presented in their contralesional field, but can fail to detect the same stimulus when a competing stimulus is shown simultaneously on the ipsilesional side. Here we demonstrate that extinction need not be spatial in nature, but may be determined by characteristics of the objects to be selected. In two patients with parietal lobe lesions and poor spatial localization, pictures extinguished words and closed shapes extinguished open shapes. This object-based extinction indicates the existence of biases within non-spatial selection mechanisms which are independent of biases produced by spatial selection mechanisms. We suggest that selection of objects for action requires that the 'winners' produced by the independent competitive biases for selection are bound together within distinct neural areas concerned with object properties and space.

Brain Diseases↗

Direct measurement of attentional dwell time in human vision.

In vision, attentional limitations are reflected in interference or reduced accuracy when two objects must be identified at once in a brief display. In our experiments a brief temporal separation was introduced between the two objects to be identified. We measured how long the object continued to interfere with the second, and hence the time course of the first object's attentional demand. According to conventional serial models, attention is assigned rapidly to one object after another, with a dwell time of only a few dozen milliseconds per item. But we report here that interference lasts for several hundred milliseconds--an order of magnitude more than the prediction of conventional models. We suggest that visual attention is not a high-speed switching mechanism, but a sustained state during which relevant objects become available to influence behaviour. This conclusion is consistent with recent physiological results in the monkey.

Adult↗

Inhibition and sex specific induction of spawning by serotonergic ligands in the zebra mussel Dreissena polymorpha (Pallas).

Serotonin (5-hydroxytryptamine, 5-HT) stimulates spawning in the zebra mussel (Dreissena polymorpha), a macrofouling European bivalve that has recently invaded North America. To develop methods of controlling zebra mussel spawning, two vertebrate serotonin antagonists, methiothepin and metergoline, known to bind with high affinity to snail 5-HT receptors, were tested for their ability to block 5-HT-induced spawning in zebra mussels. Methiothepin inhibited 5-HT-induced spawning at concentrations as low as 10(-6) M. Metergoline (10(-4) M) inhibited 5-HT-induced spawning; however, at lower concentrations (10(-8) to 10(-5) M), metergoline by itself significantly induced spawning in male, but not female zebra mussels. Metergoline (10(-5) M)-induced male spawning was inhibited by 10(-5) M methiothepin. Thus, methiothepin is the most effective inhibitor and metergoline the most powerful inducer of spawning yet tested in zebra mussels.

Animals↗

Retinoblastoma protein monoclonal antibodies with novel characteristics.

We have developed a family of monoclonal antibodies directed against the retinoblastoma gene product (p110RB). One of these monoclonal antibodies, 3C8, binds p110RB near the C-terminal end of the protein (aa886-aa905). It was characterized by immunoblotting, ELISA, fluorescence-activated flow cytometry and immunohistostaining. It was shown to be useful for the detection of p110RB in formalin-fixed and paraffin-embedded tissue sections. Because 3C8 binds outside of regions shown to be involved in p110RB interactions with other cellular proteins, it may be an especially useful reagent for the reliable detection of p110RB in tumor cells, and for the isolation by affinity chromatography of p110RB complexes with other cellular proteins.

Animals↗