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Biomedical subjects

J Duncan

Publications and source records attributed to J Duncan.

At least 19 recordsLinked to original sources
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Epidemic hepatitis E in Pakistan: patterns of serologic response and evidence that antibody to hepatitis E virus protects against disease.

IgM and IgG anti-hepatitis E virus (HEV) patterns were determined in sera collected during a hepatitis outbreak in Pakistan. HEV infection was detected serologically in 122 patients. IgM anti-HEV was detected in specimens collected up to 2 weeks before and 5-7 weeks after hospitalization in 91% and 100%, respectively, of 122 HEV-infected patients. IgG followed a similar pattern. Peak antibody titers appeared 2-4 weeks after hospitalization. At 20 months after hospitalization, IgM anti-HEV was not detected in any of 33 patients; IgG was found in all. IgG anti-HEV appeared to be protective in contracts of patients. This study confirms HEV as the cause of the outbreak, quantifies IgM and IgG anti-HEV responses, provides evidence that IgG anti-HEV protects against hepatitis E, and demonstrates that IgG anti-HEV persists, but at diminished titer, after infection. Hepatitis E in young adults is the result of primary infection with HEV and, if reinfection occurs, it does not commonly cause serious illness.

Antibodies, Viral↗
PubMed1994

Preliminary study using species-specific oligonucleotide probe for rRNA of Bilophila wadsworthia.

Portions of the 16S RNA from a urease-positive Bilophila wadsworthia strain were sequenced, and a probe was constructed. The probe was end labeled with [32P]ATP and polynucleotide kinase and hybridized on a nylon filter (by dot blot hybridization) to the immobilized rRNA of 12 B. wadsworthia strains and eight other anaerobic isolates. The probe efficiently hybridized only to the Bilophila strains. Cross-reactivity at high RNA levels (2,000 ng) was observed with one strain of Bacteroides thetaiotamicron and one strain of Bacteroides fragilis (with 10x SET buffer [20x SET buffer is 0.5 M NaCl, 0.03 M Tris, and 2 mM EDTA]) but was not seen at lower RNA levels or with 5x SET buffer. When tested against mixed cultures of aerobic and anaerobic isolates representative of appendiceal abscess flora, the probe did not react with mixed cultures containing no Bilophila cells and could detect > or = 10(5) Bilophila CFU/ml when the mixture was seeded with Bilophila cells. This probe is of potential use in the rapid identification of pure isolates and in the direct identification of B. wadsworthia in clinical specimens.

Base Sequence↗
PubMed1993

A neural basis for visual search in inferior temporal cortex.

We often search for a face in a crowd or for a particular object in a cluttered environment. In this type of visual search, memory interacts with attention: the mediating neural mechanisms should include a stored representation of the object and a means for selecting that object from among others in the scene. Here we test whether neurons in inferior temporal cortex, an area known to be important for high-level visual processing, might provide these components. Monkeys were presented with a complex picture (the cue) to hold in memory during a delay period. The cue initiated activity that persisted through the delay among the neurons that were tuned to its features. The monkeys were then given 2-5 choice pictures and were required to make an eye movement to the one (the target) that matched the cue. About 90-120 milliseconds before the onset of the eye movement to the target, responses to non-targets were suppressed and the neuronal response was dominated by the target. The results suggest that inferior temporal cortex is involved in selecting the objects to which we attend and foveate.

Animals↗
PubMed1993

Novel assay for the detection of immunoglobulin G antihuman immunodeficiency virus in untreated saliva and urine.

Epidemiological evidence and laboratory studies indicate that human immunodeficiency virus type 1 (HIV 1) is rarely, if ever, transmitted in saliva or urine. In that both specimens are easy to collect, each may be a useful alternative to serum specimens for anti-HIV screening. A rapid, simple, and robust IgG-capture enzyme-linked immunosorbent assay (GACELISA) suitable for the detection of anti-HIV 1 and 2 in saliva and urine was developed. Following optimisation of the assay, 177 salivary and 568 urine specimens collected from individuals of known serostatus were investigated. The assay was 100% sensitive on 50 salivary (median OD/CO = 8.9) and 126 urinary (median OD/CO = 8.6) specimens collected from anti-HIV-positive patients. The specificity was 100% on 127 salivary specimens (median OD/CO = 0.37) and 422 urinary specimens (median OD/CO = 0.39) collected from anti-HIV-negative individuals. These findings demonstrate that GACELISA HIV 1 + 2 tests on saliva or on urine are an accurate alternative to a conventional anti-HIV test of blood. This assay is satisfactory for surveillance purposes and, with appropriate precautions, could be used clinically.

Enzyme-Linked Immunosorbent Assay↗