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Biomedical subjects

P Jolicoeur

Publications and source records attributed to P Jolicoeur.

At least 37 records · Page 2Linked to original sources
PubMed2000

Visual encoding of patterns is subject to dual-task interference.

Two stimuli were presented at varying stimulus onset asynchronies (SOAs), with each stimulus associated with a distinct task. The first stimulus was a tone at one of either two or three frequencies. In two conditions, the task associated with a tone was either a speeded two-alternative discrimination (2AD), or a speeded three-alternative discrimination (3AD) based on the pitch of the tone. In a third condition, subjects were told to ignore the tone. The second stimulus was a briefly exposed study matrix of red and black squares followed by a mask. After a fixed delay, the mask was replaced by a test matrix that was either the same or different from the study matrix. The task associated with the matrices was to indicate, with no speed pressure, whether the study matrix and the test matrix were the same or different. Results from each speeded AD condition showed that subject's accuracy in the matrix task decreased as the SOA between the tone and the study matrix decreased. This effect was larger for the 3AD tone task than with a 2AD tone task. In addition, within each speeded AD condition, longer RTs in the tone task were associated with lower accuracy in the matrix task. None of these effects was evident when the subjects were told to ignore the tone. These results suggest that encoding visual information can be subject to significant capacity limitations imposed by cross-modal multitasking.

Adult↗
PubMed2000

Selective influence of second target exposure duration and task-1 load effects in the attentional blink phenomenon.

The purpose of the experiments was to constrain the locus of interference in the attentional blink (AB) paradigm. Two visual stimuli, T1 and T2, were shown 300 msec apart, and each was followed by a mask. T1 was an "H," an "S," an "&," or a blank field; T2 consisted of five letters. In Task1, blank fields and & characters could be ignored, whereas Hs and Ss had to be identified and reported. Task2 was always to report as many letters as possible from T2. Task2 performance was lower when T1 had to be reported, as expected from the attentional blink phenomenon (AB). The exposure duration of T2 was also manipulated. More letters could be reported as exposure duration was increased. However, this effect was additive with manipulations of Task1 processing load that produced the AB effect. Log-linear analyses assuming that effects of T2 exposure duration and Task1 load effects occur at functionally distinct stages of processing provided satisfactory fits to the results, suggesting that none of the AB effect occurs as early as those of T2 exposure duration. The results suggest that the locus of the AB effect is later than the stage(s) of processing affected by exposure duration.

Adult↗
PubMed1999

Involvement of Notch1 in the development of mouse mammary tumors.

The MMTV/neu transgenic (Tg) mice spontaneously develop mammary tumors stochastically after a long latent period, suggesting that the c-neu/erbB2 oncogene is not sufficient for tumor formation. To identify putative collaborator(s) of the c-neu/erbB2, we used the provirus insertional mutagenesis approach with mammary tumors arising in MMTV/neu Tg mice infected with the mouse mammary tumor virus (MMTV). The Notch1 gene was identified as a novel target for MMTV provirus insertional activation. In Notch1-rearranged tumors, the Notch1 gene was interrupted by the MMTV provirus insertion upstream of the exons coding for the TM domain. These insertions led to overexpression of novel 5' truncated approximately 7 kb RNA coding for 280 kDa mutant protein harboring only the Notch1 ectodomain, N(EC)mut. These may be involved in tumor formation. Another consequence of these insertions was the expression of truncated 3' Notch1 transcripts (3.5 - 4.5 kb) and proteins (86 - 110 kDa) deleted of most of the extracellular sequences (Notch1intra). We found that 3' truncated Notch1intra can transform HC11 mouse mammary epithelial cells in vitro. Deletion analysis revealed that the ankyrin-repeats and the domain 1 (aa 1751 - 1821) are required, while a signal peptide, the two conserved cysteines (C1652 and C1685) and the OPA and PEST sequences are dispensable for transformation. These results indicate that the N-terminally truncated Notch1intra protein behaves as an oncogene in this system.

Animals↗
PubMed1999

Dose-dependent reduction of apoptosis in nutrient-limited cultures of NS/0 myeloma cells transfected with the E1B-19K adenoviral gene.

It is now well documented that apoptosis represents the prevalent mode of death in lymphoid cultures and occurs spontaneously in late-exponential phase of batch cultures following nutrient exhaustion. In an attempt to enhance the cell survival of these cell lines, we have initially engineered nonproducing NS/0 myeloma cells with a vector expressing the adenoviral E1B-19K protein. NS/0 cells transfected with E1B-19K were found to be more resistant to apoptosis occurring in the late phase of batch culture and under stressful conditions such as cultivation in glutamine-free medium or following heat shock. In this study, we have characterised a number of NS/0 subclones constitutively expressing different levels of E1B-19K, as well as several subclones in which the expression of E1B-19K was regulated by a tetracycline-controllable gene switch. We have found that a threshold E1B-19K level was required in order to achieve protection against apoptosis. The extent of resistance against cell death induced by nutrient deprivation in glutamine-free medium and in the late phase of batch cultures correlated with the level of E1B-19K expression up to an optimal level where further increases in E1B-19K levels did not result in significant additional protection. To assess the effects of E1B-19K on antibody productivity, an apoptosis-resistant NS/0 clone was then transfected with a chimeric antibody construct. Despite their improved viability, the antibody productivity of E1B-19K clones in batch culture was not significantly improved. Moreover, while the use of E1B-19K considerably delayed cell death, cells eventually died by apoptosis. Surprisingly, E1B-19K had no beneficial effect on the efficiency of fusion of NS/0 myelomas and splenocytes for the generation of hybridoma cells. Furthermore, the resulting hybridomas, although expressing E1B-19K at levels comparable to the myeloma parent, were no longer resistant to apoptosis. This indicates that the ability of E1B-19K to prevent apoptosis is not only dose-dependent but also seems to be cell-type dependent.

Adenovirus E1B Proteins↗
PubMed1999

Elevated frequency of loss of heterozygosity in mammary tumors arising in mouse mammary tumor virus/neu transgenic mice.

Loss of heterozygosity (LOH) analysis was performed on 62 mammary tumors that were induced in (BALB/c x C57BL/6)F1 mouse mammary tumor virus/neu transgenic mice. Eighty-six simple sequence length polymorphism markers were used to cover all of the somatic chromosomes. Frequency of LOH was observed to be significant for chromosomes 4 (50%), 19 (32%), and 8 (21%). On chromosome 4, at least three distinct regions of allelic deletions could be identified: one proximal to 22 cM; the second close to the p16INK4a/p15INK4b locus, which is commonly deleted in various tumors; and the third one in the proximity of Mom1. The frequency of LOH on chromosome 19 was the same for the four markers used. Our data suggested the presence of two distinct LOH loci, one proximal to 47 cM and the other at the distal region. On chromosome 8, possibly two distinct LOH loci could be recognized, one around 52 cM and the other one at 67 cM or distal to it. These regions map close to E-cadherin (Cdh1) and M-cadherin (Cdh15) loci, respectively. Because LOH sites are thought to harbor tumor suppressor genes, this allelotype screening has allowed the mapping of putative tumor suppressor genes that may be implicated, in collaboration with the erbB-2/neu oncogene, in the development of mammary tumors in these transgenic mice.

Acyltransferases↗
PubMed1999

2,3-Diarylcyclopentenones as orally active, highly selective cyclooxygenase-2 inhibitors.

Cyclopentenones containing a 4-(methylsulfonyl)phenyl group in the 3-position and a phenyl ring in the 2-position are selective inhibitors of cyclooxygenase-2 (COX-2). The selectivity for COX-2 over COX-1 is dramatically improved by substituting the 2-phenyl group with halogens in the meta position or by replacing the phenyl ring with a 2- or 3-pyridyl ring. Thus the 3,5-difluorophenyl derivative 7 (L-776,967) and the 3-pyridyl derivative 13 (L-784,506) are particularly interesting as potential antiinflammatory agents with reduced side-effect profiles. Both exhibit good oral bioavailability and are potent in standard models of pain, fever, and inflammation yet have a much reduced effect on the GI integrity of rats compared to standard nonsteroidal antiflammatory drugs.

Analgesics, Non-Narcotic↗
PubMed1999

Convex hull test of the linear separability hypothesis in visual search.

Visual search for a colour target in distractors of two other colours is dramatically affected by the configuration of the colours in CIE (x, y) space. To a first approximation, search is difficult when a target's chromaticity falls directly between (i.e. is not linearly separable from) two distractor chromaticities, otherwise search is easy (D'Zmura [1991, Vision Research, 31, 951-966]; Bauer, Jolicoeur, & Cowan [1996a, Vision Research, 36, 1439-1466]; Bauer, Jolicoeur, & Cowan [1996b, Perception, 25, 1282-1294]). In this paper, we demonstrate that the linear separability effect transcends the two distractor case. Placing a target colour inside the convex hull defined by a set of distractors hindered search performance compared with a target placed outside the convex hull. This is true whether the target was linearly separable in chromaticity only (Experiments 1 and 2), or in a combination of luminance and chromaticity (Experiments 3 and 4).

Adult↗
PubMed1999

Attentional blink for color.

Colored letters were presented by means of rapid serial visual presentation (RSVP). Two letters (T1 and T2) were targets that required a speeded (T1) or delayed (T2) response. T1 was shown on half of the trials. Two tasks were performed in the experimental conditions. Task 1 required a discrimination between 2 letters (when T1 was shown) or an indication that T1 was absent. In Experiment 1, Task 2 was to detect the presence of a unique color in the RSVP stream (e.g., green in a stream of alternating red and gray). In Experiment 2, Task 2 was to report the color of the first colored letter to appear in the RSVP stream. The lag between T1 and T2 in the RSVP stream was manipulated. Accuracy of color reports in Task 2 was poor at shorter lags and improved as the lag was lengthened in both experiments, demonstrating an attentional blink for chromatic information. Theoretical implications of the results are discussed.

Adult↗
PubMed1999

Stimulus-determined discrimination mechanisms for color search.

Visual attention can be goal driven, stimulus driven, or a combination of the two. Here we report evidence for an unexpectedly stimulus-driven component of visual search for a target defined by color. Observers demonstrated a surprisingly cost-free ability to incorporate multiple classifiers in search for a target of one color from among distractors of other colors. A target color was presented among distractors that could change from trial to trial (intermixed presentation) or that remained constant across all trials in a block (blocked presentation). For blocked presentation, a single search classifier (a mechanism that segregates the target from distractors in color space) could be adopted, whereas for intermixed presentation different classifiers had to be used when the distractor colors changed. The benefit of blocked presentation was very small, suggesting that the appropriate classifier was determined very quickly in trials for which the classifier changed. The results suggest that the stimulus-driven activation of an appropriate stimulus classifier can be very efficient.

Adult↗
PubMed1999

Restricted attentional capacity between sensory modalities.

The purpose of the experiments was to demonstrate an attentional-blink (AB) effect in a visual second task following the processing of a simple auditory signal. Subjects monitored a stream of letters presented at the middle of a computer screen using rapid serial visual presentation for the presence of a visual target (an X or a Y). In experimental trials, the visual target followed a pure tone that required an immediate speeded-choice response. When the tone had to be processed, accuracy in the visual-encoding task suffered a marked and prolonged deficit that was timelocked to the onset of the tone. When the tone could be ignored or when no tone was presented, no deficit was observed in the visual task. The results demonstrate a cross-modal AB effect produced by a simple two-choice auditory discrimination task. The results are consistent with the view that at least part of the AB effect has a central, amodal, postperceptual locus.

Adolescent↗
PubMed1999

The effect of prior experience on recognition thresholds for plane-disoriented pictures of familiar objects.

We investigated plane rotation effects on the minimum presentation duration that is required in order to recognize pictures of familiar objects, using the method of ascending limits. Subjects made unspeeded verification responses, selecting from 126 written alternatives. Replicating similar identification studies in which brief, masked pictures (Lawson & Jolicoeur, 1998) were presented, disorientation reduced the efficiency of recognition. Mirroring the findings in speeded picture naming studies (e.g., Jolicoeur, 1985; Jolicoeur & Milliken, 1989), but in contrast to those of Lawson and Jolicoeur (1998), orientation effects were found over a wide range of views and were attenuated but not eliminated with experience with a given object. The results bridge the findings from unspeeded verification and speeded naming tasks. They suggest that the same orientation-sensitive processes are tapped in both cases, and that practice effects on these processes are object specific.

Adult↗
PubMed1998

Nef harbors a major determinant of pathogenicity for an AIDS-like disease induced by HIV-1 in transgenic mice.

Transgenic (Tg) mice expressing the complete coding sequences of HIV-1 in CD4+ T cells and in cells of the macrophage/dendritic lineages develop severe AIDS-like pathologies: failure to thrive/weight loss, diarrhea, wasting, premature death, thymus atrophy, loss of CD4+ T cells, interstitial pneumonitis, and tubulo-interstitial nephritis. The generation of Tg mice expressing selected HIV-1 gene(s) revealed that nef harbors a major disease determinant. The latency and progression (fast/slow) of the disease were strongly correlated with the levels of Tg expression. Nef-expressing Tg thymocytes were activated and alpha-CD3 hyperresponsive with respect to tyrosine phosphorylation of several substrates, including LAT and MAPK. The similarity of this mouse model to human AIDS, particularly pediatric AIDS, suggests that Nef may play a critical role in human AIDS, independently of its role in virus replication.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Transcription factor SCL is required for c-kit expression and c-Kit function in hemopoietic cells.

In normal hemopoietic cells that are dependent on specific growth factors for cell survival, the expression of the basic helix-loop-helix transcription factor SCL/Tal1 correlates with that of c-Kit, the receptor for Steel factor (SF) or stem cell factor. To address the possibility that SCL may function upstream of c-kit, we sought to modulate endogenous SCL function in the CD34(+) hemopoietic cell line TF-1, which requires SF, granulocyte/macrophage colony-stimulating factor, or interleukin 3 for survival. Ectopic expression of an antisense SCL cDNA (as-SCL) or a dominant negative SCL (dn-SCL) in these cells impaired SCL DNA binding activity, and prevented the suppression of apoptosis by SF only, indicating that SCL is required for c-Kit-dependent cell survival. Consistent with the lack of response to SF, the level of c-kit mRNA and c-Kit protein was significantly and specifically reduced in as-SCL- or dn-SCL- expressing cells. c-kit mRNA, c-kit promoter activity, and the response to SF were rescued by SCL overexpression in the antisense or dn-SCL transfectants. Furthermore, ectopic c-kit expression in as-SCL transfectants is sufficient to restore cell survival in response to SF. Finally, enforced SCL in the pro-B cell line Ba/F3, which is both SCL and c-kit negative is sufficient to induce c-Kit and SF responsiveness. Together, these results indicate that c-kit, a gene that is essential for the survival of primitive hemopoietic cells, is a downstream target of the transcription factor SCL.

Basic Helix-Loop-Helix Proteins↗
PubMed1998

Establishment of MAIDS-defective virus-infected B cell lines and their characterization.

Mice inoculated with the murine AIDS (MAIDS)-defective virus develop severe B and T cell dysfunctions. The primary event in the development of this disease is the infection and polyclonal expansion of the target cells of this defective virus, which have been reported to belong to the B cell lineage. To further study the central role that these cells play in the development of MAIDS, we attempted to establish MAIDS-defective virus-infected B cell lines in vitro. We succeeded in establishing two cell lines, SD1 and CSTB5, from the enlarged organs of C57BL/6 mice inoculated with helper-free stocks of the MAIDS-defective virus. Both cell lines are not transplantable in syngeneic C57BL/6 mice or in nude or CD8-/- mice and are apparently not malignant. They both belong to the B lineage, as their immunoglobulin (Ig) genes, but not the T cell receptor (TcR) beta locus, are rearranged, suggesting that they are relatively mature B cells. However, analysis of cell surface marker expression by FACS revealed a surface phenotype similar to that of pre-B cells (MHC I+, MHC II+, B7.2+, sIgM-, sIgG-, kappa-, B220-, CD5-, Thy1.2-, TcR-, CD3-, CD4-, CD8-, Mac-1-, 33D1-). Additionally, the CSTB5 cells express CD40 and the SD1 cells express CD43. Both cell lines contain the MAIDS-defective provirus and express the expected 4.2-kb viral RNA and the corresponding Pr60gag protein. The CSTB5 cells are nonproducer, while the SD1 cell line produces what appears to be an endogenous MuLV. The phenotype of these cell lines is very similar to what is known about the target B cells of this virus in vivo. These new established cell lines are likely to be useful in elucidating the mechanism(s) by which the MAIDS-defective virus causes its target B cells to proliferate and induce T cell anergy in infected animals.

Animals↗
PubMed1998

A full-length Notch1 allele is dispensable for transformation associated with a provirally activated truncated Notch1 allele in Moloney MuLV-infected MMTV(D)/myc transgenic mice.

The Notch1 gene was previously found to be targetted by provirus insertion in a high proportion of T-cell lymphomas arising in Moloney MuLV-inoculated MMTV(D)/myc transgenic mice. Proviral activation of Notch1 was associated with overexpression of truncated Notch1, deleted of the sequences coding for the extracellular domain. The high levels of truncated Notch1 RNA and proteins in these tumors are thought to be involved in the oncogenic transformation. However, in addition to these truncated RNA and proteins, high level expression of full-length Notch1 RNA and proteins was also observed in several tumors, suggesting that they could also contribute to the transformation process. To test this hypothesis, we used a genetic approach and studied MMTV(D)/myc transgenic mice in which one of the Notch1 alleles was mutated by targeted mutagenesis (Notch1+/- mice). Heterozygote (Notch1+/-) and wild-type (Notch1+/+) transgenic mice were inoculated with Moloney MuLV and the frequency of Notch1 rearrangements was compared between both groups. Notch1 was rearranged at similar frequencies in both groups, indicating that the full-length Notch1 allele is dispensable in tumors harboring an activated Notch1 allele.

Alleles↗
PubMed1998

The demonstration of short-term consolidation.

In a dual-task paradigm, a visual display (T1) containing characters (letters or symbols) was presented first, followed by an auditory signal (T2) at various stimulus-onset asynchronies (SOAs). A speeded response to T2 was required. When the information in T1 had to be recalled later, response times to T2 (RT2) were elevated at short SOAs and decreased as SOA was increased. The effects on RT2 were larger when there were more items to be remembered. We interpreted the results as evidence that encoding information into short-term memory (STM) involves a distinct process, which we call short-term consolidation (STC). The results suggested that STC has limited capacity and that it requires central processing mechanisms. Additional evidence suggested that no memory for T1 was formed in STM when STC was not engaged.

Adult↗
PubMed1998

Transgenic mice expressing human immunodeficiency virus type 1 in immune cells develop a severe AIDS-like disease.

We have constructed transgenic (Tg) mice expressing the entire human immunodeficiency virus type 1 (HIV-1) coding sequences in cells targeted by HIV-1 infection in humans. These Tg mice developed a severe AIDS-like disease leading to early death (< 1 month). They developed muscle wasting, severe atrophy and fibrosis of lymphoid organs, tubulointerstitial nephritis, and lymphoid interstitial pneumonitis. In addition the expression of RANTES was increased in various tissues of these Tg mice relative to that in the normal controls. Disease appearance was correlated with the levels of transgene expression. The numerous pathologies observed in these mice are remarkably similar to those observed in human AIDS and, more specifically, in pediatric AIDS.

Acquired Immunodeficiency Syndrome↗