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Biomedical subjects

J Duncan

Publications and source records attributed to J Duncan.

At least 19 recordsLinked to original sources

The herpes simplex virus type 1 immediate-early polypeptide ICP4 is required for expression of globin genes located in the viral genome.

We infected Vero cells with ICP4-deficient herpes simplex virus recombinants bearing the rabbit beta-globin and human alpha 2-globin genes under the control of their own promoters and found that globin gene expression occurred only when ICP4 was provided in trans. These results demonstrate that ICP4 is required for the activity of globin promoters located in the viral genome and support the hypothesis that these cellular promoters are functionally equivalent to HSV early regulatory regions.

Animals

Distinct hemagglutinin and neuraminidase epitopes involved in antigenic variation of recent human parainfluenza virus type 2 isolates.

A panel of fourteen neutralizing anti-HN monoclonal antibodies (mAbs) to the prototype Greer strain of human parainfluenza virus type 2 (PI2) was used to determine the extent of antigenic variation in recent virus isolates. Competitive binding analysis with the mAbs indicated the presence of at least five distinct antigenic sites (I to V) on the HN glycoprotein molecule. MAbs recognizing different antigenic sites were found to be associated with the hemagglutinin (sites I, IV and V), hemagglutinin and neuraminidase (site II), or neuraminidase (site III) activities. The location of two distinct epitopes identifying the neuraminidase sites (II and III) was further verified from the generation of escape mutants. Antibodies directed to sites I and III failed to show any detectable binding or neutralizing activity against a number of natural PI2 virus isolates collected in Texas between 1986 and 1987. Interestingly, these natural variants, unlike the prototype virus, did not show any detectable neuraminidase activity with fetuin as a substrate and the enzyme activity was only detected with N-acetylneuramin-lactose as an alternative substrate. Despite the observed variation in the antigenic sites, primary infection with the prototype virus or the natural variants generated a protective immune response against challenge infection with the other virus strains.

Animals

Beyond the search surface: visual search and attentional engagement.

Treisman (1991) described a series of visual search studies testing feature integration theory against an alternative (Duncan & Humphreys, 1989) in which feature and conjunction search are basically similar. Here the latter account is noted to have 2 distinct levels: (a) a summary of search findings in terms of stimulus similarities, and (b) a theory of how visual attention is brought to bear on relevant objects. Working at the 1st level, Treisman found that even when similarities were calibrated and controlled, conjunction search was much harder than feature search. The theory, however, can only really be tested at the 2nd level, because the 1st is an approximation. An account of the findings is developed at the 2nd level, based on the 2 processes of input-template matching and spreading suppression. New data show that, when both of these factors are controlled, feature and conjunction search are equally difficult. Possibilities for unification of the alternative views are considered.

Arousal

On the time course of perceptual information that results from a brief visual presentation.

A briefly presented visual stimulus engenders an available-information function that lags behind the physical stimulus. We report two experiments that focus on the iconic-decay portion of this function, which falls to 0 over a 200-300 ms period following stimulus offset. In each experiment, to-be-reported digit strings were shown for varying durations followed by a noise mask at varying poststimulus intervals. We found the shape of the performance curve relating digit-report probability to stimulus exposure duration to be independent of stimulus-mask interstimulus interval. This finding is consistent with the proposition that the iconic-decay function's shape is independent of stimulus duration and allows us to identify this shape. We rejected exponential iconic decay for 6 of 8 observers; however, all observers' decay functions could be adequately fit by gamma decay, a generalization of exponential decay.

Adult

Regulation of herpes simplex virus true late gene expression: sequences downstream from the US11 TATA box inhibit expression from an unreplicated template.

The true late genes of herpes simplex virus type 1 (HSV-1) are expressed only after the onset of viral DNA replication. Previous studies demonstrated that late promoters lack elements upstream of the TATA box and suggested that only a subset of TATA elements can function in the context of true late promoters. We determined which structural features of true late promoters are responsible for the stringent requirement for viral DNA replication by inserting a series of simple model constructs into the HSV-1 genome in place of one of the two promoters of the UL24 gene. An oligonucleotide consisting of 19 nucleotides spanning the TATA box of the HSV-1 true late US11 gene drove barely detectable levels of expression; by contrast, the corresponding regions of the Adenovirus type 2 major late promoter and the HSV-1 true late glycoprotein C promoter were much more active. Transcripts driven from all of these minimal TATA box promoters accumulated without viral DNA replication. The activity of the US11 TATA box was stimulated by adding upstream Sp1-binding sites or placing the US11 or rabbit beta-globin cap/leader region (-11 to +39) downstream. The Sp1-TATA and TATA-beta-globin cap/leader constructs remained replication independent, while the TATA-US11 cap/leader promoter displayed true late regulation. These results demonstrate that sequences located within the US11 cap/leader region impose a strict requirement for viral DNA replication on a minimal TATA box promoter.

Adenoviruses, Human

Sequence requirements for DNA rearrangements induced by the terminal repeat of herpes simplex virus type 1 KOS DNA.

We investigated the sequence requirements for the site-specific DNA cleavages and recombinational genome isomerization events driven by the terminal repeat or a sequence of herpes simplex virus type 1 KOS DNA by inserting a series of mutated a sequences into the thymidine kinase locus in the intact viral genome. Our results indicate that sequences located at both extremities of the a sequence contribute to these events. Deletions entering from the Ub side of the a sequence progressively reduced the frequency of DNA rearrangements, and further deletion of the internal DR2 repeat array had an additional inhibitory effect. This deletion series allowed us to map the pac1 site-specific DNA cleavage signal specifying the S-terminal cleavage to a sequence that is conserved among herpesvirus genomes. Constructs lacking this signal were unable to directly specify the S-terminal cleavage event but retained a reduced ability to give rise to S termini following recombination with intact a sequences. Deletions entering from the Uc side demonstrated that the copy of direct repeat 1 located adjacent to the Uc region plays an important role in the DNA rearrangements induced by the a sequence: mutants lacking this sequence displayed a reduced frequency of novel terminal and recombinational inversion fragments, and further deletions of the Uc region had a relatively minor additional effect. By using a construct in which site-specific cleavage was directed to heterologous DNA sequences, we found that the recombination events leading to genome segment inversion did not occur at the sites of DNA cleavage used by the cleavage-packaging machinery. This observation, coupled with the finding that completely nonoverlapping portions of the a sequence retained detectable recombinational activity, suggests that inter-a recombination does not occur by cleavage-ligation at a single specific site in herpes simplex virus type 1 strain KOS. The mutational sensitivity of the extremities of the a sequence leads us to hypothesize that the site-specific DNA breaks induced by the cleavage-packaging system stimulate the initiation of recombination.

Animals

Clinical assessment of a new breath-actuated inhaler.

Up to 50 per cent of patients cannot use a conventional metered-dose inhaler (MDI) efficiently and therefore obtain less than optimum benefit. Seventy adults with no previous experience of inhalers were asked to demonstrate their inhaler techniques after reading written instructions for an MDI and for a new breath-actuated inhaler. The breath-actuated inhaler was found to be easier to use and was preferred to the MDI.

Adult

Toxicity of IL-2 and Corynebacterium parvum following direct intracranial injection.

The toxicity of IL-2 and/or C. Parvum when injected directly into the mouse brain was examined by survival and histopathology using different numbers of injections, different doses of IL-2, different solvents for the IL-2, and different doses and routes of administration of C. Parvum. Two injections was found significantly to increase mortality (19%) over a single injection (4%). Mortality from two injections of 30,000 U (23%) or 60,000 U (20%) was higher than from two injections of 15,000 U (12%). The mortality from two injections with normal saline as solvent was much higher (29%) than from two injections with sterile water (19%) or D5W (9%). Two injections of IL-2 given simultaneously with C. Parvum showed a much higher mortality (26%) than other doses and routes of C. Parvum administration. Mice dying acutely (6-24 days) of toxicity showed an extensive mononuclear infiltrate at the site of injection. The brains of surviving mice (sacrificed at 30 days) showed a mild residual mononuclear cell infiltrate with the exception of mice which had received IL-2 and C. Parvum simultaneously. Brains from this latter group had an extensive residual mononuclear cell infiltrate.

Animals

Boundary conditions on parallel processing in human vision.

A new theory of visual search is tested experimentally with simple colour patches. The essential element of this new theory is that, whatever the search materials, efficiency increases continuously with (i) decreasing similarity between targets and nontargets, and (ii) increasing similarity between one nontarget and another. Control of 'attention' (access to visual short-term memory) is seen as a competitive interaction between display elements, and the theory shows how stimulus similarities influence the outcome of this competition. One alternative view is that parallel visual processes are limited to local mismatch detection. Search is parallel if the target forms a break in an otherwise homogeneous field, but is serial when absolute stimulus identification is required. It is shown, however, that even colour identification can be parallel, providing targets and nontargets are sufficiently dissimilar. A second alternative view is that search for simple features is parallel whereas search for conjunctions is serial. Conjunction search, however, has a characteristic similarity structure: different kinds of nontarget each share one relevant attribute with the target, but none with one another. When this structure is mimicked in search for colour patches, correspondingly poor performance is obtained.

Adult

Long-term storage of eggs of Simulium ornatum.

A method for the storage of non-diapausing eggs of Simulium ornatum Meigen has been developed. High survival rates for 5-6 months depend on the age of eggs when placed at reduced temperature. A period of precooling or conditioning is required for 28 days before storage of the eggs at 1 degree C with lowering of oxygen partial pressure. Induced quiescence does not appear to affect development from egg to adult.

Animals

The molluscicidal properties of Ambrosia maritima L. (Compositae). 4. Temporal and spatial distribution of Biomphalaria alexandrina in Egyptian village irrigation systems with reference to schistosomiasis transmission control.

Data on the temporal and spatial distribution of Biomphalaria alexandrina were collected throughout one year in two village irrigation systems near Alexandria, Egypt. Snails bearing Schistosoma mansoni cercariae were found from May to December but about 80% of annual transmission potential was confined from June to August. Although snail infection rates were generally 0-2%, higher rates were recorded and tended to be associated with smaller number snail collections. Infected snails were found in most canal and drain types and were judged to be present across most of the irrigated area of each village. In view of the dispersed nature of both infected snails and human-water contact in the area, it is suggested that schistosomiasis transmission is more widespread than focal. Effective transmission control using molluscicides should therefore require application to all village irrigation water-courses. The difficulties these various findings might impose on the use of commercial molluscicides are discussed and some possible advantages of the alternative plant molluscicide, Ambrosia maritima are noted.

Animals

Molluscicide resistance and a field test kit.

Molluscicide resistance literature is reviewed. Alterations in tolerance have been recorded in some laboratory experiments and field surveys but not others. Resistance, as the failure to control a natural snail population, has not been reported. A kit is described for measuring molluscicide susceptibility of snails. A microlitre delivery device is used to prepare molluscicide solutions. Trials have shown that the kit can be used successfully in the field.

Animals