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Biomedical subjects

P Jolicoeur

Publications and source records attributed to P Jolicoeur.

At least 55 records · Page 3Linked to original sources
PubMed1998

Inducible overexpression of a toxic protein by an adenovirus vector with a tetracycline-regulatable expression cassette.

We have constructed two new adenovirus expression cassettes that expand both the range of genes which can be expressed with adenovirus vectors (AdV) and the range of cells in which high-level expression can be attained. By inclusion of a tetracycline-regulated promoter in the transfer vector pAdTR5, it is now possible to generate recombinant adenoviruses expressing proteins that are either cytotoxic or that interfere with adenovirus replication. We have used this strategy to generate a recombinant adenovirus encoding a deletion in the R1 subunit [R1(delta2-357)] of the herpes simplex virus type 2 ribonucleotide reductase. Cell lines expressing the tetracycline-regulated transactivator (tTA) from an integrated vector or following infection with an AdV expressing tTA are able to produce deltaR1 protein at a level approaching 10% total cell protein (TCP) when infected with Ad5TR5 deltaR1 before they subsequently die. To our knowledge, this is the first report of the overexpression of a toxic gene product with AdV. We have also constructed a new constitutive adenovirus expression cassette based on an optimized cytomegalovirus immediate-early promoter-enhancer that allows the expression of recombinant proteins at a level greater than 20% TCP in nonpermissive cell lines. Together, these new expression cassettes significantly improve the utility of the adenovirus system for high-level expression of recombinant proteins in animal cells and will undoubtedly find useful applications in gene therapy.

Adenoviridae↗
PubMed1998

Modulation of the attentional blink by on-line response selection: evidence from speeded and unspeeded task1 decisions.

Two critical target stimuli (T1 and T2) were embedded in a stream of white letters shown on a black background, using a rapid serial visual presentation paradigm (RSVP, 100 msec/item). T1 was a red H or S; T2 was an X or a Y. Performance in a two-alternative discrimination on T2 was impaired when processing of T1 was required--a result often called an attentional blink (AB). In previous work, the response in Task1 has been an unspeeded and delayed response at the end of the trial. Three experiments compared performances in Task2 that depended on whether Task1 required an unspeeded delayed response or a speeded immediate response. A larger AB was found when a speeded response was required. Furthermore, in the speeded conditions, faster responses in Task1 were associated with a smaller and shorter AB effect than were slower responses. The results show that manipulations affecting a relatively late stage of processing--response selection--affect the magnitude and duration of the AB phenomenon. A new central inhibition theory is proposed to account for these results. According to this theory, the AB is similar to the psychological refractory period effect and is caused by central postponement of short-term consolidation of T2.

Adult↗
PubMed1998

The effects of plane rotation on the recognition of brief masked pictures of familiar objects.

Two experiments examined the effects of plane rotation on the recognition of briefly displayed pictures of familiar objects, using a picture-word verification task. Mirroring the results of earlier picture naming studies (Jolicoeur, 1985; Jolicoeur & Milliken, 1989), plane rotation away from a canonical upright orientation reduced the efficiency of recognition, although in contrast to the results from picture naming studies, the rotation effects were not reduced with experience with the stimuli. However, the rotation effects were influenced by the visual similarity of the distractor objects to the picture of the object presented, with greater orientation sensitivity being observed when visually similar distractors were presented. We suggest that subjects use orientation-sensitive representations to recognize objects in both the present unspeeded verification and in the earlier speeded naming tests of picture identification.

Adult↗
PubMed1998

The linear separability effect in color visual search: ruling out the additive color hypothesis.

Bauer, Jolicoeur, and Cowan (1996b, 1996c) demonstrated difficult visual search for color targets that were not linearly separable (in color space) from two distractor colors and easier search for linearly separable targets. This suggested that search is mediated by a chromatically linear discrimination mechanism (see D'Zmura, 1991). However, in those experiments, the targets that were not linearly separable fell midway between the distractor colors and thus corresponded to the admix of the distractor colors. An alternate interpretation of the results of Bauer et al. is that search was more difficult when the target corresponded to the distractor admix than when it did not. We tested this hypothesis in three experiments by contrasting conditions in which a target that was not linearly separable did or did not correspond to the admix of the distractor colors. In all cases, a target that was not linearly separable produced difficult search, demonstrating that linear separability determines search performance.

Color Perception↗
PubMed1998

Use of mouse mammary tumour virus (MMTV)/neu transgenic mice to identify genes collaborating with the c-erbB-2 oncogene in mammary tumour development.

Mouse mammary tumour virus (MMTV)/neu transgenic mice develop clonal or oligoclonal mammary tumours stochastically. The pathology of these tumours is very similar to that of human breast tumours. Moreover, these mouse tumours metastasize in the lungs. We present evidence that this mouse model of human breast tumours can be instrumental in identifying novel genes of two distinct classes (activated oncogenes or tumour suppressor genes) which may collaborate with the c-erbB-2/neu transgenic oncogene.

Animals↗
PubMed1997

Decision and Response in Dual-Task Interference

Experiments with two stimuli (S1 and S2) and two responses suggest the existence of a stage of processing that cannot be shared between two concurrent tasks. Widespread support has been found for the hypothesis that response selection for Task2 is postponed when the S1 to S2 stimulus onset asynchrony (SOA) is short (Pashler, 1994a). At short SOAs, manipulations which impact Task2 processing prior to response selection (e.g., degradation of stimulus quality) have little effect on Task2 response times (RTs). On the other hand, manipulations which are thought to impact response selection or execution (e.g., Stroop interference) always impact Task2 RTs. There is, however, one particularly compelling demonstration that appears to be inconsistent with the response selection bottleneck hypothesis: Karlin and Kestenbaum (1968) report that the RT difference between detection (i.e., 1-choice) and 2-choice discrimination dramatically decreases with decreasing SOA. Given that the primary difference between detection and discrimination is believed to be at response selection, their result may indicate a processing bottleneck at response execution (Keele, 1973). We fail to replicate the Karlin and Kestenbaum result in two substantive replications of Karlin and Kestenbaum's tasks and procedures. In the single experiment in which Karlin and Kestenbaum's result is replicated, a simple response execution bottleneck account is ruled out by the stability of the difference between 2-choice and 3-choice discrimination times across SOA. Two additional experiments demonstrate that response preparation and task strategy do not substantially contribute to the attenuation of response selection-level effects with decreasing SOA.

Journal Article↗
PubMed1997

Expression of the protein encoded by Epstein-Barr virus (EBV) BARF1 open reading frame from a recombinant adenovirus system.

Epstein-Barr virus (EBV) has been associated with human cancers of lymphocytic or epithelial origin, but viral functions implied in oncogenesis are not yet clear. We previously reported the oncogenic transformation of rodent fibroblast and human B lymphocyte cell lines by the BARF1 coding sequence from EBV. We more recently observed immortalizing effects of this gene on monkey kidney primary epithelial cells. Here we describe an efficient recombinant adenovirus expression system which allowed us to characterize BARF1 translation products, with the help of rabbit polyclonal antibodies raised to the entire protein. The present data demonstrate that BARF1 encodes a 31-33 kDa hydrophobic protein, linked to cell membranes though also recovered in the cytosol, and recognized by human sera from patients with various EBV-related pathologies.

Adenoviridae↗
PubMed1997

Repetition blindness for pseudoobject pictures.

In this study the nature of type activations that underlie repetition blindness (RB) was addressed. According to the token individuation hypothesis put forward to explain RB, both instances of a repeated stimulus make contact with the mental representation, or type, for that stimulus. In the resulting confusion only the first stimulus is encoded as an episodic instance or token. Type representations have traditionally been thought of as preexisting and are often linked within a network of nodes. The authors developed and tested a picture frequency task, which does not require stimulus naming, and used it to examine repetition performance for unfamiliar nonobject pictures. RB was found for these stimuli, despite the fact that they had no prior phonological or semantic representation. These results suggest that the reactivation of a newly formed visual type is sufficient to produce RB. Implications for the role of types in the token individuation hypothesis are discussed.

Adolescent↗
PubMed1997

The murine AIDS virus Gag precursor protein binds to the SH3 domain of c-Abl.

The Pr60gag protein of the murine AIDS (MAIDS) defective virus promotes the proliferation of the infected target B cells and is responsible for inducing a severe immunodeficiency disease. Using the yeast two-hybrid system, we identified the SH3 domain of c-Abl as interacting with the proline-rich p12 domain of Pr60gag. The two proteins were shown to associate in vitro and in vivo in MAIDS virus-infected B cells. Overexpression of Pr60(gag) in these cells led to a detectable increase of the levels of c-Abl protein and to its translocation at the membrane. These results suggest that this viral protein serves as a docking site for signaling molecules and that c-Abl may be involved in the proliferation of infected B cells.

Amino Acid Sequence↗
PubMed1997

Studies of the susceptibility of nude, CD4 knockout, and SCID mutant mice to the disease induced by the murine AIDS defective virus.

Murine AIDS (MAIDS) is induced by a defective retrovirus that infects lymphocyte cells of the B lineage. To determine whether functional T cells are required for the infection of B cells, T-cell-deficient mice (nude, CD4 knockout, and SCII)) were infected with helper-free stocks of the MAIDS defective virus. Infection of B cells was monitored by Northern blot analysis and in situ hybridization. The C57BL/6 nude mice contained clusters of infected B cells, but less so than did the euthymic mice. In contrast, the (C57BL/6 x BALB/c)F1 nude mice harbored more infected B cells than did their euthymic littermates when maintained in a pathogen-free environment. Clusters of infected B cells were also detected in the MAIDS virus-infected CD4-/- knockout mice despite the total absence of CD4+ T cells in these mice. However, infected cells were not detected in SCID mice (deficient in mature T and B cells) inoculated with the same virus, indicating that precursor B cells are not a target of the virus in the absence of mature CD4+ T cells. These data confirm that the primary event in the development of MAIDS is the infection of relatively mature peripheral B cells and that CD4+ T cells are required to promote the expansion of these infected B cells.

Animals↗
PubMed1997

Use of a dicistronic expression cassette encoding the green fluorescent protein for the screening and selection of cells expressing inducible gene products.

To facilitate the screening and selection of cells expressing inducible gene products, we have constructed a plasmid that, by the inclusion of a viral internal ribosome entry site, permits the synthesis of a dicistronic mRNA encoding both a gene of interest and the gene encoding the green fluorescent protein (GFP) from the jellyfish Aequorea victoria. This greatly simplifies the task of clone selection, since GFP fluorescence can be visualized non-obtrusively in live cells with a standard fluorescence microscope. We have applied this method to the tetracycline-regulated expression system in which the expression of a target gene, placed under the control of a promoter containing the tetracycline operator sequence (tetO), can be induced by a tetracycline-regulated trans-activator protein (tTA). Binding of the tTA to the tetO is inhibited in the presence of tetracycline. Optimal results with this system require two sequential rounds of transfection and screening. Obtaining a cell line expressing high levels of functional tTA is greatly simplified by transiently transfecting a plasmid encoding GFP into a pool of cells that has first been transfected with a tTA-expressor construct and selecting GFP-positive cells using a fluorescence-activated cell sorter. In the second step, the tTA cell line can then be stably transfected with a dicistronic expressor-GFP cassette. This method eliminates the task of characterizing cell lines by the standard method of examining levels of the exogenously expressed protein in cell extracts of individual clones.

Animals↗
PubMed1996

Expression of the calcium-binding protein S100A4 (p9Ka) in MMTV-neu transgenic mice induces metastasis of mammary tumours.

Increased levels of S100A4 (p9Ka) confer metastatic ability on a normally non-metastatic epithelial cell line. To find out whether S100A4 can induce metastasis in vivo, transgenic mice expressing high levels of S100A4, but which show no phenotypic effect, have been mated with MMTV-neu transgenic mice which succumb to stochastic mammary neoplasia related to expression of the MMTV-neu transgene. Resultant bitransgenic, multiparous, female progeny expressing both S100A4 and Neu have a slightly earlier incidence of palpable mammary tumours than the MMTV-neu offspring and specifically exhibit macroscopic metastatic lesions in the lungs. The S100A4 transgene is expressed in primary and secondary lesions of bitransgenic offspring and its expression is particularly associated with regions of invasion of primary lesions and metastases.

Animals↗
PubMed1996

Frequent provirus insertional mutagenesis of Notch1 in thymomas of MMTVD/myc transgenic mice suggests a collaboration of c-myc and Notch1 for oncogenesis.

The MMTVD/myc transgenic mice spontaneously develop oligoclonal CD4+CD8+ T-cell tumors. We used provirus insertional mutagenesis in these mice to identify putative collaborators of c-myc. We found that Notch1 was mutated in a high proportion (52%) of these tumors. Proviruses were inserted upstream of the exon coding for the transmembrane domain and in both transcriptional orientations. These mutations led to high expression of truncated Notch1 RNAs and proteins (86-110 kD). In addition, many Notch1-rearranged tumors showed elevated levels of full-length Notch1 transcripts, whereas nearly all showed increased levels of full-length (330-kD) or close to full-length (280-kD) Notch1 proteins. The 5' end of the truncated RNAs were determined for some tumors by use of RT-PCR and 5' RACE techniques. Depending on the orientation of the proviruses, viral LTR or cryptic promoters appeared to be utilized, and coding potential began in most cases in the transmembrane domain. Pulse-chase experiments revealed that the 330-kD Notch1 proteins were processed into 110- and 280-kD cleavage products. These results suggest that Notch1 can be a frequent collaborator of c-myc for oncogenesis. Furthermore, our data indicate that Notch1 alleles mutated by provirus insertion can lead to increased expression of truncated and full-length (330/280-kD) Notch1 proteins, both being produced in a cleaved and uncleaved form.

Animals↗
PubMed1996

Visual search for colour targets that are or are not linearly separable from distractors.

D'Zmura [(1991) Vision Research, 31, 951-966] reported qualitative differences in visual search rates for a target colour in a background of differently coloured distractors depending on their colour configuration in CIE(x,y) space. A target colour that was chromatically mid-way between the distractor colours resulted in steep search slopes. A target off the distractor-distractor line, "popped out". We replicated his finding in several loci, investigated several potential confounds, and discovered boundary conditions for the phenomenon: for a given target, the effect of collinearity dissipates with increasing distractor-distractor colour difference. Furthermore, within limits, performance was dependent on the target to distractor-line distance.

Adult↗
PubMed1996

Stimulus dimensionality effects in mental rotation.

Do 3-dimensional (3-D) figures require more time to rotate mentally than do 2-dimensional (2-D) figures? This question was examined in 2 experiments incorporating 15 2-D and 15 3-D stimuli. For 3-D stimuli, block figures were used of the type used by R. N. Shepard and J. Metzler in their classic studies. For 2-D stimuli, block figures were also used, but with all cubes in a single plane, resulting in 2-D and 3-D figures matched on surface features. Three-D figures elicited steeper slopes than did 2-D figures, supporting the view that the mental rotation of visual representations is sensitive to stimulus dimensionality. The authors summarize the results of several mental rotation studies that investigated stimulus dimensionality and suggest that the evidence across studies is consistent with the present finding. They discuss 2 plausible loci for the dimensionality effect in S. M. Kosslyn's (1980) theory of mental imagery.

Adolescent↗
PubMed1996

Vacuolar myelopathy in transgenic mice expressing human immunodeficiency virus type 1 proteins under the regulation of the myelin basic protein gene promoter.

Vacuolar myelopathy is a common neurological complication in AIDS patients. The pathogenesis of this spinal cord white matter disease remains unclear and it is still debated whether infection of spinal cord with the human immunodeficiency virus type 1 (HIV-1) is causing the disease. We have generated transgenic mice expressing the entire HIV-1 genome under the regulation of an oligodendrocyte-specific promoter. These mice develop spinal cord vacuolar lesions similar to those found in AIDS patients. This animal model provides in vivo evidence linking the expression of HIV-1 proteins in oligodendrocytes to the spinal cord damage found in vacuolar myelopathy.

Acquired Immunodeficiency Syndrome↗