Biomedical subjects

J Côté

Publications and source records attributed to J Côté.

At least 19 recordsLinked to original sources

PubMed2005

Prediction of adherence to antiretroviral therapy: a one-year longitudinal study.

The aim of this longitudinal study was to identify the determinants of adherence to antiretroviral therapy (ART) in HIV patients over a period of 12 months. A total of 376 individuals living with HIV treated with ART participated in the study. Data were collected at baseline and at three, six, nine and 12 months. Variables assessed were adherence, attitude, outcome expectancies, self-efficacy, patient satisfaction with the relationship with their physician, provision of social support, optimism, CD4 cell count, viral load and side effects. Predictors of adherence in the Generalized Estimated Equation (GEE) were: high perception of self-efficacy (OR=1.68; 95%CI 1.27-2.22), positive attitude towards taking medication (OR=1.56; 95%CI 1.18-2.06), not living alone (OR=1.47; 95%CI 1.04-2.08) and being a male (OR=2.81; 95%CI 1.47-5.34). Subsequent analysis showed that a positive attitude towards taking medication was associated with a high level of patient satisfaction with their physician, high perceived social support, being optimistic, living with HIV for five years or less and experiencing no side effects. Also, a strong sense of self-efficacy was associated with positive perception of social support, high level of patient satisfaction with their physician and not living alone. These results suggest that interventions aimed at improving adherence to ART should focus on reinforcing self-efficacy and developing a positive attitude towards taking medication.

Adult↗

PubMed2003

The MYST family of histone acetyltransferases.

Multiple chromatin modifying proteins and multisubunit complexes have been characterized in recent years. Histone acetyltransferase (HAT) activities have been the most thoroughly studied, both biochemically and functionally. This review sums up the current knowledge on a specific group of proteins that is extremely well conserved throughout evolution, the MYST family of histone acetyltransferases. These proteins play critical roles in various nuclear functions and the control of cell proliferation.

Acetyltransferases↗

PubMed2001

Identification of Sam68 arginine glycine-rich sequences capable of conferring nonspecific RNA binding to the GSG domain.

Sam68 is an RNA-binding protein that contains a heterogeneous nuclear ribonucleoprotein K homology domain embedded in a larger RNA binding domain called the GSG (GRP33, Sam68, GLD-1) domain. This family of proteins is often referred to as the STAR (signal transduction and activators of RNA metabolism) proteins. It is not known whether Sam68 is a general nonspecific RNA-binding protein or whether it recognizes specific response elements in mRNAs with high affinity. Sam68 has been shown to bind homopolymeric RNA and a synthetic RNA sequence called G8-5 that has a core UAAA motif. Here we performed a structure function analysis of Sam68 and identified two arginine glycine (RG)-rich regions that confer nonspecific RNA binding to the Sam68 GSG domain. In addition, by using chimeric proteins between Sam68 and QKI-7, we demonstrated that one of the Sam68 RG-rich sequences of 26 amino acids was sufficient to confer homopolymeric RNA binding to the GSG domain of QKI-7, another STAR protein. Furthermore, that minimal sequence can also give QKI-7 the ability (as Sam68) to functionally substitute for HIV-1 REV to facilitate the nuclear export of RNAs. Our studies suggest that neighboring RG-rich sequences may impose nonspecific RNA binding to GSG domains. Because the Sam68 RNA binding activity is negatively regulated by tyrosine phosphorylation, our data lead us to propose that Sam68 might be a specific RNA-binding protein when tyrosine phosphorylated.

Amino Acid Sequence↗

PubMed2001

The Candida glabrata Amt1 copper-sensing transcription factor requires Swi/Snf and Gcn5 at a critical step in copper detoxification.

The yeast Candida glabrata rapidly autoactivates transcription of the AMT1 gene in response to potentially toxic copper levels through the copper-inducible binding of the Amt1 transcription factor to a metal response element (MRE) within a positioned nucleosome. Our previous studies have characterized the role of a 16 bp homopolymeric dA:dT DNA structural element in facilitating rapid Amt1 access to the AMT1 promoter nucleosomal MRE. In this study, we have used the genetically more facile yeast Saccharomyces cerevisiae to identify additional cellular factors that are important for promoting rapid autoactivation of the AMT1 gene in response to toxic copper levels. We demonstrate that the Swi/Snf nucleosome remodelling complex and the histone acetyltransferase Gcn5 are both essential for AMT1 gene autoregulation, and that the requirement for these chromatin remodelling factors is target gene specific. Chromatin accessibility measurements performed in vitro and in vivo indicate that part of the absolute requirement for these factors is derived from their involvement in facilitating nucleosomal access to the AMT1 promoter MRE. Additionally, these data implicate the involvement of Swi/Snf and Gcn5 at multiple levels of AMT1 gene autoregulation.

Acetylation↗

PubMed2001

Role of an ING1 growth regulator in transcriptional activation and targeted histone acetylation by the NuA4 complex.

The yeast NuA4 complex is a histone H4 and H2A acetyltransferase involved in transcription regulation and essential for cell cycle progression. We identify here a novel subunit of the complex, Yng2p, a plant homeodomain (PHD)-finger protein homologous to human p33/ING1, which has tumor suppressor activity and is essential for p53 function. Mass spectrometry, immunoblotting, and immunoprecipitation experiments confirm the stable stoichiometric association of this protein with purified NuA4. Yeast cells harboring a deletion of the YNG2 gene show severe growth phenotype and have gene-specific transcription defects. NuA4 complex purified from the mutant strain is low in abundance and shows weak histone acetyltransferase activity. We demonstrate conservation of function by the requirement of Yng2p for p53 to function as a transcriptional activator in yeast. Accordingly, p53 interacts with NuA4 in vitro and in vivo, an interaction reminiscent of the p53-ING1 physical link in human cells. The growth defect of Delta yng2 cells can be rescued by the N-terminal part of the protein, lacking the PHD-finger. While Yng2 PHD-finger is not required for p53 interaction, it is necessary for full expression of the p53-responsive gene and other NuA4 target genes. Transcriptional activation by p53 in vivo is associated with targeted NuA4-dependent histone H4 hyperacetylation, while histone H3 acetylation levels remain unchanged. These results emphasize the essential role of the NuA4 complex in the control of cell proliferation through gene-specific transcription regulation. They also suggest that regulation of mammalian cell proliferation by p53-dependent transcriptional activation functions through recruitment of an ING1-containing histone acetyltransferase complex.

Acetylation↗

PubMed2001

An unusual case of hepatic abscess.

A case of recurring primary hepatic actinomycosis is reported. A 50-year-old man presented with fever, weight loss and multiple hepatic masses. A diagnosis was obtained by cytological examination of a biopsy sample taken from the largest hepatic mass, which revealed the presence of Actinomyces species. The patient was treated with penicillin for 12 months and did well. Seven years later, he presented with similar symptoms but with a single large liver mass and a pulmonary infiltrate in the right lower lobe. Liver biopsy showed an inflammatory pseudotumour, and lung biopsy showed the presence of Actinomyces species. Again, the patient was treated with penicillin. Five months later, the patient was doing well, and a follow-up computed tomography scan showed partial regression of the hepatic pseudotumour. This case indicates that hepatic actinomycosis can recur several years after an appropriate treatment and stresses the need for careful follow-up in such patients.

Actinomycosis↗

PubMed2001

Evaluation of two different educational interventions for adult patients consulting with an acute asthma exacerbation.

Asthma education decreases the number of emergency visits in specific subgroups of patients with asthma. However, it remains unknown whether this improvement is related only to the use of an action plan alone or to other components of the educational intervention. A total of 126 patients consulting urgently for an acute asthma exacerbation were recruited; 98 completed the study. The first 45 patients were assigned to Group C (control; usual treatment). Thereafter, patients were randomized to either Group LE (limited education; teaching of the inhaler technique plus self- action plan given by the on call physician) or Group SE (same as group LE plus a structured educational program emphasizing self-capacity to manage asthma exacerbations). At baseline, there was no difference between groups in asthma morbidity, medication needs, or pulmonary function. After 12 mo, only Group SE showed a significant improvement in knowledge, willingness to adjust medications, quality of life scores, and peak expiratory flows. In the last 6 mo, the number of unscheduled medical visits for asthma was significantly lower in Group SE in comparison with groups C and LE (p = 0.03). The number (%) of patients with unscheduled medical visits also decreased significantly in Group SE compared with Groups C and LE (p = 0.02). We conclude that a structured educational intervention emphasizing self-management improves patient outcomes significantly more than a limited intervention or conventional treatment.

Acute Disease↗

PubMed2000

Polypyrimidine track-binding protein binding downstream of caspase-2 alternative exon 9 represses its inclusion.

We have been using the caspase-2 pre-mRNA as a model system to study the importance of alternative splicing in the regulation of programmed cell death. Inclusion or skipping of a cassette-type exon in the 3' portion of this pre-mRNA leads to the production of isoforms with antagonistic activity in apoptosis. We previously identified a negative regulatory element (In100) located in the intron downstream of alternative exon 9. The upstream portion of this element harbors a decoy 3' acceptor site that engages in nonproductive commitment complex interactions with the 5' splice site of exon 9. This in turn confers a competitive advantage to the exon-skipping splicing pattern. Further characterization of the In100 element reveals a second, functionally distinct, domain located downstream from the decoy 3' acceptor site. This downstream domain harbors several polypyrimidine track-binding protein (PTB)-binding sites. We show that PTB binding to these sites correlates with the negative effect on exon 9 inclusion. Finally, we show that both domains of the In100 element can function independently to repress exon 9 inclusion, although PTB binding in the vicinity of the decoy 3' splice site can modulate its activity. Our results thus reveal a complex composite element that regulates caspase-2 exon 9 alternative splicing through a novel mechanism.

Alternative Splicing↗

PubMed2000

Differential remodeling of the HIV-1 nucleosome upon transcription activators and SWI/SNF complex binding.

Here we have examined HIV-1 nucleosome remodeling upon the binding of transcription factors and the SWI/SNF complex using a novel approach. The approach combines UV laser protein-DNA crosslinking, electrophoretic mobility-shift analysis and DNase I protection analysis with immunochemical techniques. It was found that single activator-bound HIV-1 nucleosomes exhibit very weak perturbation in histone NH(2) tail-DNA interactions. However, the simultaneous binding of the transcription activators Sp1, NF-kB1, LEF-1 and USF synergistically increased the release of histone NH(2) tails from nucleosomal DNA. In contrast, the binding of SWI/SNF complex to HIV-1 nucleosome disrupted structured histone domain-DNA contacts, but not histone NH(2) tail-DNA interactions. Stable remodeled nucleosomes, (obtained after detachment of SWI/SNF), displayed identical structural alterations with those bound to SWI/SNF. These results demonstrate a different in vitro remodeling of the HIV-1 nucleosome upon the binding of multiple transcription activators and of SWI/SNF complex.

DNA Footprinting↗

PubMed2000

A family of chromatin remodeling factors related to Williams syndrome transcription factor.

Chromatin remodeling complexes have been implicated in the disruption or reformation of nucleosomal arrays resulting in modulation of transcription, DNA replication, and DNA repair. Here we report the isolation of WCRF, a new chromatin-remodeling complex from HeLa cells. WCRF is composed of two subunits, WCRF135, the human homolog of Drosophila ISWI, and WCRF180, a protein related to the Williams syndrome transcription factor. WCRF180 is a member of a family of proteins sharing a putative heterochromatin localization domain, a PHD finger, and a bromodomain, prevalent in factors involved in regulation of chromatin structure.

Adenosine Triphosphatases↗

PubMed2000

Competitive recruitment of CBP and Rb-HDAC regulates UBF acetylation and ribosomal transcription.

RNA polymerase I (PolI) transcription is activated by the HMG box architectural factor UBF, which loops approximately 140 bp of DNA into the enhancesome, necessitating major chromatin remodeling. Here we show that the acetyltransferase CBP is recruited to and acetylates UBF both in vitro and in vivo. CBP activates PolI transcription in vivo through its acetyltransferase domain and acetylation of UBF facilitates transcription derepression and activation in vitro. CBP activation and Rb suppression of ribosomal transcription by recruitment to UBF are mutually exclusive, regulating in vivo PolI transcription through an acetylation-deacetylation "flip-flop." Thus, PolI transcription is regulated by protein acetylation, and the competitive recruitment of CBP and Rb.

3T3 Cells↗

PubMed2000

Multiple links between the NuA4 histone acetyltransferase complex and epigenetic control of transcription.

NuA4 is an essential histone H4/H2A acetyltransferase complex that interacts with activators and stimulates transcription in vitro. We have identified three novel NuA4 subunits: Act3/Arp4, an actin-related protein implicated in epigenetic control of transcription, Act1, and Epl1, a protein homologous to Drosophila Enhancer of Polycomb. Act3/Arp4 binds nucleosomes in vitro and is required for NuA4 integrity in vivo. Mutations in ACT3 and acetyltransferase-encoding ESA1 cause gene-specific transcription defects. Accordingly, NuA4 is localized in precise loci within the nucleus and does not overlap with the silent chromatin marker Sir3. These data along with the known epigenetic roles of Act3/Arp4 and homologs of Epl1 and Esa1 strongly support an essential role for chromatin structure modification by NuA4 in transcription regulation in vivo.

Acetyltransferases↗

PubMed2000

The relationship between coaching behaviours and sport anxiety in athletes.

Previous research has identified the relationship between athlete sport anxiety and various sport outcomes (e.g., performance and dropout). For the majority of athletes involved in sport, the coach is an influential element of the competitive experience. Two hundred and twenty-eight athletes from 15 sports, completed the Sport Anxiety Scale (SAS) and the Coaching Behavior Scale for Sport (CBS-S). The predictive ability of athletes' perceived frequency of seven coaching behaviours (physical training, mental preparation, goal setting, technical skills, competition strategies, personal rapport and negative personal rapport) on four forms of sport anxiety (total anxiety, somatic anxiety, concentration disruption and worry) was examined. Results indicate that negative personal rapport was a significant predictor of all measured forms of sport anxiety while competition strategies was a significant predictor for total anxiety, concentration disruption, and worry. Other behaviours were not significant. The findings suggest that negative rapport between coach and athlete is an important contributor to athlete anxiety. In addition, behaviours that the coach demonstrates relative to competition can be influential in reducing athlete anxiety.

Adolescent↗

PubMed2000

Mapping of the human upper arm muscle activity with an electrode matrix.

Surface electrode matrices allow measurement of muscle activity while avoiding certain hazardous risks and inconvenience associated with invasive techniques. Major challenges of such equipment involve optimizing spatial resolution, and designing simple acquisition systems able to record simultaneously many potentials over large anatomical areas. We present a surface electromyography acquisition system comprising of 3 x 8 Ag-AgCl electrodes mounted onto an elastic band, which can be adjusted to fit an entire human upper limb segment. Using this equipment, we acquired a simultaneous representation of muscular activity from a segment of the upper limb surface of 6 healthy subjects during isometric contractions at various intensities. We found that the location of regions of highest activity depended on elbow torque direction but also varied among subjects. Signals obtained with such equipment can be used to solve the inverse problem and help optimize the electrode configuration in volume conduction studies. The efficacy of decision algorithms of multi-functional myoelectric prostheses can be tested with the global muscle activity patterns gathered. The electrode cuff could also be used in the investigation of fatigue and injury mechanisms during occupational activities.

Action Potentials↗

PubMed1999

NuA4, an essential transcription adaptor/histone H4 acetyltransferase complex containing Esa1p and the ATM-related cofactor Tra1p.

Post-translational acetylation of histone H4 N-terminal tail in chromatin has been associated with several nuclear processes including transcription. We report the purification and characterization of a native multisubunit complex (NuA4) from yeast that acetylates nucleosomal histone H4. NuA4 has an apparent molecular mass of 1.3 MDa. All four conserved lysines of histone H4 can be acetylated by NuA4. We have identified the catalytic subunit of the complex as the product of ESA1, an essential gene required for cell cycle progression in yeast. Antibodies against Esa1p specifically immunoprecipitate NuA4 activity whereas the complex purified from a temperature-sensitive esa1 mutant loses its acetyltransferase activity at the restrictive temperature. Additionally, we have identified another subunit of the complex as the product of TRA1, an ATM-related essential gene homologous to human TRRAP, an essential cofactor for c-Myc- and E2F-mediated oncogenic transformation. Finally, the ability of NuA4 to stimulate GAL4-VP16-driven transcription from chromatin templates in vitro is also lost in the temperature-sensitive esa1 mutant. The function of the essential Esa1 protein as the HAT subunit of NuA4 and the presence of Tra1p, a putative transcription activator-interacting subunit, supports an essential link between nuclear H4 acetylation, transcriptional regulation and cell cycle control.

Acetylation↗

PubMed1999

An element in the 5' common exon of the NCAM alternative splicing unit interacts with SR proteins and modulates 5' splice site selection.

The neural cell adhesion molecule (NCAM) gene contains an 801 nt exon that is included preferentially in neuronal cells. We have set up an in vitro splicing system that mimics the neuro-specific alternative splicing profile of NCAM exon 18. Splicing regulation is observed using model pre-mRNAs that contain competing 5' or 3' splice sites, suggesting that distinct pathways regulate NCAM 5' and 3' splice site selection. While inclusion of exon 18 is the predom-inant choice in neuronal cells, an element in the 5' common exon 17 improves exon 17/exon 19 splicing in a neuronal cell line. A similar behavior is observed in vitro as the element can stimulate the 5' splice site of exon 17 or a heterologous 5' splice site. The minimal 32 nt sequence of the exon 17 enhancer consists of purine stretches and A/C motifs. Mutations in the purine stretches compromise the binding of SR proteins and decreases splicing stimulation in vitro. Mutations in the A/C motifs do not affect SR protein binding but reduce enhancing activity. Our results suggest that the assembly of an enhancer complex containing SR proteins in a 5' common exon ensures that NCAM mRNAs lacking exon 18 are made in neuronal cells.

Alternative Splicing↗

PubMed1999

Long-term followup of initial Ta grade 1 transitional cell carcinoma of the bladder.

PURPOSE: We evaluate the long-term outcome of initial Ta grade 1 transitional cell carcinoma. MATERIALS AND METHODS: A total of 152 patients with initial Ta grade 1 bladder tumor were followed for a mean of 76 months (range 6 to 241). Recurrence was defined as positive findings on cystoscopy or biopsy. Progression was defined as an increase in tumor grade or stage. RESULTS: Tumor recurrence in 83 of 152 patients (55%) was noted within 12 months of followup in 38 patients (46%), between 12 and 24 in 11 (13%), and between 24 and 60 in 22 (27%). A significant number of recurrences (12, 14%) were diagnosed more than 60 months after the first tumor. Of 83 patients with recurrence 31 (37%) had progression, including 21 to grade 2 and 2 to grade 3 disease. Carcinoma in situ was diagnosed in 3 patients and 5 had muscle invasive disease. Progression occurred more than 24 months after initial diagnosis in 20 patients and more than 60 months after first tumor event (2 had carcinoma in situ and 2 had muscle invasive disease) in 12. CONCLUSIONS: Ta grade 1 bladder transitional cell carcinomas have a high recurrence rate and progression is not uncommon. These findings warrant close long-term followup, even when in some settings the trend is to discontinue followup after 5 years without any abnormal findings.

Adult↗

PubMed1999

The SWI/SNF complex creates loop domains in DNA and polynucleosome arrays and can disrupt DNA-histone contacts within these domains.

To understand the mechanisms by which the chromatin-remodeling SWI/SNF complex interacts with DNA and alters nucleosome organization, we have imaged the SWI/SNF complex with both naked DNA and nucleosomal arrays by using energy-filtered microscopy. By making ATP-independent contacts with DNA at multiple sites on its surface, SWI/SNF creates loops, bringing otherwise-distant sites into close proximity. In the presence of ATP, SWI/SNF action leads to the disruption of nucleosomes within domains that appear to be topologically constrained by the complex. The data indicate that the action of one SWI/SNF complex on an array of nucleosomes can lead to the formation of a region where multiple nucleosomes are disrupted. Importantly, nucleosome disruption by SWI/SNF results in a loss of DNA content from the nucleosomes. This indicates a mechanism by which SWI/SNF unwraps part of the nucleosomal DNA.

Animals↗