Biomedical subjects

S Côté

Publications and source records attributed to S Côté.

At least 19 recordsLinked to original sources

PubMed2005

Human metapneumovirus infection in adults with community-acquired pneumonia and exacerbation of chronic obstructive pulmonary disease.

We tested nasopharyngeal aspirate specimens by real-time polymerase chain reaction assays and paired serum samples by enzyme-linked immunosorbent assays. Acute human metapneumovirus infections were identified in 6 (4.1%) of 145 adult patients who presented to the emergency department for pneumonia or acute exacerbation of chronic obstructive pulmonary disease during 2 winter/spring seasons in Quebec, Canada.

Adult↗

PubMed2004

Very high concentrations of n-3 fatty acids in peri- and postmenopausal Inuit women from Greenland.

OBJECTIVES: The objectives of this study were to examine the profile of relative concentrations in plasma phospholipids of n-3 fatty acids among peri- and postmenopausal Inuit women living in Greenland and to verify their relationships with ischemic heart disease risk factors and more particularly, with concentrations of plasma triacylglycerols. STUDY DESIGN: This study was part of a survey conducted in 2000, which aimed to assess the prevalence of osteoporosis and the associated risk factors among peri- and postmenopausal Greenland Inuit women. METHODS: The study population consisted of 153 women aged 49-69 years (mean +/- SD: 55.3 +/- 4.4 y) randomly selected. Data were obtained through an interview (questionnaire on lifestyle habits, medical history etc) and a clinical session (physiologic and anthropologic measurements). Plasma samples were used to measure the fatty acid composition of plasma phospholipids. RESULTS: The mean body mass index of women was 27.9 +/- 6.1. Seventy-five percent were smokers and 9% were currently on hormone replacement therapy. Relative concentrations of total n-3 fatty acids were very high (13.8%, 95% CI: 13.1-14.6), with docosahexanoic and eicosapentanoic acids accounting for 4.7% and 7.2%, respectively. The ratio of n-3:n-6 fatty acids was 0.67. n-3 fatty acids were inversely correlated to triacylglycerols. CONCLUSION: These data show that peri- and post-menopausal Greenland Inuit women have very high plasma concentrations of n-3 fatty acids that protect them from ischemic heart disease.

Aged↗

PubMed2003

Glutathione depletion overcomes resistance to arsenic trioxide in arsenic-resistant cell lines.

Arsenic trioxide (As(2)O(3)) is an effective treatment for acute promyelocytic leukemia (APL), but is less effective against other leukemias. Although the response of APL cells to As(2)O(3) has been linked to degradation of the PML/RARalpha fusion oncoprotein, there is evidence that PML/RARalpha expression is not the only mediator of arsenic sensitivity. Indeed, we found that exogenous expression of PML/RARalpha did not sensitize a non-APL leukemic line to As(2)O(3). To evaluate possible other determinants of sensitivity of leukemic cells to As(2)O(3), we derived two arsenic-resistant NB4 subclones. Despite being approximately 10-fold more resistant to arsenic than their parental cell line, PML/RARalpha protein was still degraded by As(2)O(3) in these cells, providing further evidence that loss of expression of the oncoprotein does not confer arsenic sensitivity. Both arsenic-resistant clones contained high glutathione (GSH) levels, however, and we found that GSH depletion coupled with As(2)O(3) treatment dramatically inhibited their growth. Annexin V-staining and TUNEL analysis confirmed a synergistic induction of apoptosis. In addition, these cells failed to accumulate ROS in response to arsenic treatment, in contrast to their arsenic-sensitive parental cells, unless cotreated with buthionine sulfoximine. While other malignant cells did not show a good correlation between arsenic sensitivity and GSH content, GSH depletion nevertheless sensitized all cell lines examined, regardless of their initial response to arsenic alone. These findings suggest that PML/RARalpha expression is not a determinant of arsenic sensitivity, and further support the coupling of GSH depletion and arsenic treatment as a novel treatment for human malignancies that are unresponsive to arsenic alone.

Annexin A5↗

PubMed2001

Urea substitutes toxic formamide as destabilizing agent in nucleic acid hybridizations with RNA probes.

Since their introduction some three decades ago, methods for hybridization analysis of nucleic acids immobilized on solid supports have evolved to improve the sensitivity, speed, and convenience of their application. However, in many cases these methods still require the use of solutions containing formamide, a recognized hazardous solvent with potential toxicity. Here, we have compared the efficiency of urea to that of formamide as denaturing agent in nucleic acid hybridization with RNA probes. We show that urea at concentrations of 2-4 molar in solution performs as good as 50% formamide to reduce heterologous background hybridization in Northern blotting experiments realized at 68 degrees C. Presence of urea at higher concentrations resulted in reduced hybridization sensitivity, possibly due to increased viscosity. When tested in Southern blot analysis of genomic DNA, our results revealed that the use of urea in hybridization solution is also suitable to carry out single-copy gene detection. Together, these findings show that urea can efficiently and safely replace formamide in solutions.

Animals↗

PubMed2001

Predicting girls' conduct disorder in adolescence from childhood trajectories of disruptive behaviors.

OBJECTIVE: To examine girls' developmental trajectories of disruptive behaviors during the elementary school years and to predict conduct disorder symptoms and diagnosis in adolescence with trajectories of these behaviors. METHOD: The sample was 820 girls from the province of Quebec followed over 10 years (1986-1996). A semiparametric mixture model was used to describe girls' developmental trajectories of teacher-rated disruptive behaviors between the ages of 6 and 12 years. The trajectories were used to predict conduct disorder symptoms and diagnosis when the girls were on average 15.7 years. RESULTS: Four groups of girls following trajectories with distinct levels of disruptive behaviors were identified: a low, medium, medium-high, and high trajectory. Prediction with the trajectories indicated that girls on the medium, medium-high, and high trajectories reported a significantly higher number of conduct disorder symptoms in adolescence. However, only the girls on the medium-high and high trajectories were at significantly higher risk to meet DSM-III-R criteria for conduct disorder, compared with girls in the low group (odds ratio: 4.46). More than two thirds of the girls with conduct disorder were in the medium or higher-level trajectories. CONCLUSION: The results suggest that there is an early-onset type of conduct disorder in girls.

Adolescent↗

PubMed2000

Altered ligand binding and transcriptional regulation by mutations in the PML/RARalpha ligand-binding domain arising in retinoic acid-resistant patients with acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is characterized by a specific translocation, t(15;17), that fuses the promyelocytic leukemia (PML) gene with the RA receptor RARalpha. Pharmacologic doses of retinoic acid (RA) induce differentiation in human APL cells and complete clinical remissions. Unfortunately, APL cells develop resistance to RA in vitro and in vivo. Recently, mutations in PML/RARalpha have been described in APL cells from patients clinically resistant to RA therapy. The mutations cluster in 2 regions that are involved in forming the binding pocket for RA. These mutant PML/RARalpha proteins have been expressed in vitro, which shows that they cause a diversity of alterations in binding to ligand and to nuclear coregulators of transcription, leading to varying degrees of inhibition of retinoid-induced transcription. This contrasts with the nearly complete dominant negative activity of mutations in PML/RARalpha previously characterized in cell lines developing RA resistance in vitro. Current data from this study provide additional insight into the molecular mechanisms of resistance to RA and suggest that alterations in the ability of mutants to interact with coregulators can be determinant in the molecular mechanism of resistance to RA. In particular, ligand-induced binding to the coactivator ACTR correlated better with transcriptional activation of RA response elements than the ligand-induced release of the corepressor SMRT. The diversity of effects that are seen in patient-derived mutations may help explain the partial success to date of attempts to overcome this mechanism of resistance in patients by the clinical use of histone deacetylase inhibitors.

Amino Acid Substitution↗

PubMed2000

Combinatorial activity of pair-rule proteins on the Drosophila gooseberry early enhancer.

The early expression of the Drosophila segment polarity gene gooseberry (gsb) is under the control of the pair-rule genes. We have identified a 514-bp enhancer which reproduces the early gsb expression pattern in transgenic flies. The transcription factor Paired (Prd) is the main activator of this enhancer in all parasegments of the embryo. It binds to paired- and homeodomain-binding sites, which are segregated on the enhancer. Using site-directed mutagenesis, we have identified sites critical for Prd activity. Negative regulation of this enhancer is mediated by the Even-skipped protein (Eve) in the odd-numbered parasegments and by the combination of Fushi-tarazu (Ftz) and Odd-skipped proteins in the even-numbered parasegments. The organisation of the Prd-binding sites, as well as the necessity for intact DNA binding sites for both paired- and homeodomains, suggests a molecular model whereby the two DNA-binding domains of the Prd protein cooperate in transcriptional activation of gsb. This positive activity appears to be in competition with Eve and Ftz on Prd homeodomain-binding sites.

Animals↗

PubMed2000

Efficacy of brief coping skills interventions that match different personality profiles of female substance abusers.

Female substance abusers recruited from the community were randomly assigned to receive 1 of 3 brief interventions that differentially targeted their personality and reasons for drug use. The 90-min interventions were: (a) a motivation-matched intervention involving personality-specific motivational and coping skills training, (b) a motivational control intervention involving a motivational film and a supportive discussion with a therapist, and (c) a motivation-mismatched intervention targeting a theoretically different personality profile. Assessment 6 months later (N = 198) indicated that only the matched intervention proved to be more effective than the motivational control intervention in reducing frequency and severity of problematic alcohol and drug use and preventing use of multiple medical services. These findings indicate promise for a client-treatment matching strategy that focuses on personality-specific motives for substance abuse.

Adaptation, Psychological↗

PubMed2000

Pancreatic inflammation, apoptosis, and growth: sequential events after partial pancreatectomy in pigs.

Positive signs of pancreas regeneration were observed in rats after induced pancreatitis and partial pancreatectomy (1,2). Although the human pancreas did not regenerate after partial anatomic resection (3), the pig pancreas exhibited growth responses to bombesin after partial pancreatectomy (4). This study was undertaken to establish the time course of pancreatic inflammation, apoptosis, and hypertrophy and/or hyperplasia after partial pancreatectomy in pigs.

Animals↗

PubMed2000

Multiple signaling pathways mediate interleukin-4-induced 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase type 1 gene expression in human breast cancer cells.

The 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase (3beta-HSD) isoenzymes catalyze an essential step in the formation of all classes of active steroid hormones. We have recently shown that 3beta-HSD type 1 gene expression is specifically induced by interleukin (IL)-4 and IL-13 in breast human cancer cell lines and in normal human mammary epithelial cells in primary culture. There is evidence that IL-4 stimulates bifurcating signaling pathways in which the signal transducer and activator of transcription-6 (Stat6)-signal pathway is involved in differentiation and gene regulation, whereas insulin receptor substrate (IRS) proteins mediate the mitogenic action of IL-4. In fact, we have shown that Stat6 was activated by IL-4 in all cell lines studied where IL-4 induced 3beta-HSD expression, but not in those that failed to respond to IL-4. The present study was designed to investigate the potential contribution of IRS proteins and their downstream targets to IL-4-induced 3beta-HSD type 1 gene expression. IL-4 rapidly induced IRS-1 and IRS-2 phosphorylation in ZR-75-1 human breast cancer cell lines. Moreover, insulin-like growth factor (IGF)-I and insulin, which are well known to cause IRS-1 and IRS-2 phosphorylation, increased the stimulatory effect of IL-4 on 3beta-HSD activity. IRS-1 and IRS-2 are adapter molecules that provide docking sites for different SH2-domain-containing proteins such as the phosphatidylinositol (PI) 3-kinase. In this light, the inhibition of IL-4-induced 3beta-HSD expression by wortmannin and LY294002, two potent PI 3-kinase inhibitors, indicates the probable involvement of the PI 3-kinase signaling molecules in this response to IL-4. Furthermore, it has been suggested that the IRS proteins are part of the signaling complexes that lead to activation of the mitogen-activated protein (MAP) kinase by insulin; thus we investigated the potential role of the MAP kinase (MAPK) cascade in the IL-4 action. In ZR-75-1 cells, both the activation of MAPK by IL-4 and the IL-4-induced 3beta-HSD activity were completely blocked by PD98059, an inhibitor of MAPK activation. Wortmannin also blocked MAPK activation by IL-4, IGF-I, and insulin, suggesting that the MAPK cascade acts as a downstream effector of PI 3-kinases. To further understand the cross-talk between signaling pathways involved in IL-4 action, we investigated the possible involvement of protein kinase C (PKC). The potential role of PKC was suggested by the observation that the well known PKC activator phorbol-12-myristate-13-acetate (PMA) potentiated the IL-4-induced 3beta-HSD activity. Taken together, these findings suggest the existence of a novel mechanism of gene regulation by IL-4. This mechanism would involved the phosphorylation of IRS-1 and IRS-2, which transduce the IL-4 signal through a PI 3-kinase- and MAPK-dependent signaling pathway. The inability of IGF-I, insulin, and PMA to stimulate 3beta-HSD expression by themselves in the absence of IL-4 makes obvious the absolute requirement of an IL-4-specific signaling molecule. Our findings thus suggest that the multiple pathways downstream of IRS-1 and IRS-2 must act in cooperation with the IL-4-specific transcription factor Stat6 to mediate the induction of 31beta-HSD type 1 gene expression in ZR-75-1 human breast cancer cells.

Androstadienes↗

PubMed1999

Characterization and distribution of Hxt1, a Na(+)/Cl(-)-dependent orphan transporter, in the human brain.

Rxt1, a transporter-like protein structurally related to the large family of Na(+)/Cl(-)-dependent carriers, was isolated from the rat brain. In the present study, Hxt1, the homologue of Rxt1, was isolated from human cortex cDNA. Comparison of their respective nucleotidic sequences revealed a 96% conservation between Hxt1 and Rxt1. Genetic mapping with human genome radiation hybrids allowed the location of the gene coding for Hxt1 between 323ya5 and 084xb3 AFM markers, on a portion of chromosome 1p which spans over 7 cM or 118 cRay. Northern blot analyses demonstrated that Hxt1 mRNA ( approximately 7.5 Kb) is expressed in the human brain but not in peripheral tissues. The immunodistribution of Hxt1 was determined with antibodies raised against the C-terminus of Rxt1. Hxt1 is concentrated in the cerebral cortex, caudate-putamen, substantia nigra, hippocampus, and cerebellum, appearing as a diffuse or a punctate labeling at the light microscope level. This regional and cellular distribution suggests that Hxt1, as its rat homologue, could be present in axon terminals of glutamatergic neurons. The high pressure of selection exerted upon this protein, its strategic anatomical and subcellular distributions suggest that this orphan transporter could be involved in critical functions in the central nervous system.

Amino Acid Sequence↗

PubMed1999

Dependency, self-criticism, interpersonal behaviour and affect: evolutionary perspectives.

Evolutionary accounts of vulnerability to depression have focussed either on the attachment system (Bowlby, 1980) or the social rank system (Gilbert, 1992; Price, 1972). According to a two-factor evolutionary model, depression-prone dependent and self-critical individuals suffer from insecurities regarding both attachment and social rank, but they differ in their strategies for dealing with those insecurities. Event-contingent recording was used to assess agentic (dominant-submissive) and communal (agreeable-quarrelsome) interpersonal behaviour as well as affect in 119 employed adults over 20 days. Participants also completed questionnaire measures of agency and communion. Self-criticism predicted low levels of agency and low levels of communion. In the sample as a whole, agentic and communal behaviours were associated with pleasant affect, but highly self-critical participants experienced relatively less pleasant affect when they acted communally or agentically. Individuals with high levels of immature dependency (neediness) were low in agency, whereas those with high levels of mature dependency (connectedness) were high in communion. Implications for evolutionary theories of vulnerability to depression were discussed, and interpersonal processes that may contribute to vulnerability were identified.

Adult↗

PubMed1998

On the dynamic covariation between interpersonal behavior and affect: prediction from neuroticism, extraversion, and agreeableness.

It was posited that the traits of Neuroticism, Extraversion, and Agreeableness are predictors of dynamic intraindividual processes involving interpersonal behavior and affect. Hypotheses derived from the behavioral concordance model that individuals with high scores on a trait would experience more positively valenced affect when engaging in behavior concordant with that trait than individuals with low scores on the trait were tested. Participants completed a questionnaire measure of the traits and reported on behavior and affect during interpersonal interactions using event-contingent sampling forms approximately 6 times a day for 20 days. Trait scores were related to indexes of the association between each dimension of interpersonal behavior and affect calculated for each individual. Previous findings concerning the trait of Agreeableness were replicated, and results strongly supported the behavioral concordance model for the trait of Neuroticism. Thus, at least some traits can provide information about intraindividual processes that vary over time.

Adult↗

PubMed1998

Demethylation by 5-aza-2'-deoxycytidine of specific 5-methylcytosine sites in the promoter region of the retinoic acid receptor beta gene in human colon carcinoma cells.

The role of retinoic acid receptor beta(RARbeta), a putative tumor suppressor gene, in the development of colon malignancy still remains to be clarified. We reported previously that the expression of RARbeta in DLD-1 human colon adenocarcinoma cells was silenced by DNA methylation at the level of the promoter region (Anti-Cancer Drugs 1997; 8: 56). In addition, we observed that RARbeta expression could be activated by the hypomethylating action of 5-aza-2'-deoxycytidine (5-Aza-CdR). In this report we have identified, by sequencing of bisulfite-modified DNA of DLD-1 colon tumor cells, the specific 5-methylcytosine positions in the region of -46 to +251 bp from the transcription start site of RARbeta2. We observed that 5-Aza-CdR treatment demethylated these specific sites. Based on this sequence data, specific primers for the methylation-specific PCR (MSP) assay were designed to discriminate methylated from unmethylated CpG sites in the promoter region of RARbeta. This assay confirmed the changes in the methylation status of the RARbeta gene in DLD-1 colon tumor cells before and after treatment with 5-Aza-CdR. The methylation status of the promoter region of the RARbeta gene was also examined in primary human colon adenocarcinomas using the MSP assay. Six of the 14 colon tumor samples showed signs of hypermethylation of this gene. The MSP assay for RARbeta may be a useful tool to clarify the role of DNA methylation for this gene in colon tumorigenesis.

5-Methylcytosine↗

PubMed1997

Propofol or midazolam for sedation and early extubation following cardiac surgery.

PURPOSE: The purpose of this randomized, double-blind study was to evaluate the efficacy of midazolam and propofol for postoperative sedation and early extubation following cardiac surgery. METHODS: ASA physical status II-III patients scheduled to undergo elective first-time cardiac surgery with an ejection fraction > 45% were eligible. All patients received a standardized sufentanil/isoflurane anaesthesia. During cardiopulmonary bypass 100 micrograms.kg-1.min-1 propofol was substituted for isoflurane. Upon arrival in the Intensive Care Unit (ICU), patients were randomized to either 10 micrograms.kg-1.min-1 propofol (n = 21) or 0.25 microgram.kg-1.min-1 midazolam (n = 20). Infusion rates were adjusted to maintain sedation within a predetermined range (Ramsay 2-4). The infusion was terminated after four hours. Patients were weaned from mechanical ventilation and their tracheas extubated when Haemodynamic stability, haemostasis, normothermia and mental orientation were confirmed. Haemodynamic measurements, arterial blood gas tensions and pulmonary function tests were recorded at specified times. RESULTS: There were no differences between the two groups for the time spent at each level of sedation, number of infusion rate adjustments, amount of analgesic and vasoactive drugs, times to awakening and extubation. The costs of propofol were higher than those of midazolam. There were no differences in haemodynamic values, arterial blood gas tensions and pulmonary function. CONCLUSION: We conclude that midazolam and propofol are safe and effective sedative agents permitting early extubation in this selected cardiac patient population but propofol costs were higher.

Adolescent↗

PubMed1997

Pharmacological approach for optimization of the dose schedule of 5-Aza-2'-deoxycytidine (Decitabine) for the therapy of leukemia.

5-Aza-2'-deoxycytidine (5-Aza-CdR; Decitabine) is an active antineoplastic agent in patients with leukemia. Since 5-Aza-CdR is an S phase specific agent and has a short plasma half-life, its antileukemic activity is dose schedule-dependent. Leukemia patients who are candidates for 5-Aza-CdR therapy following relapse after therapy with cytosine arabinoside are at greater risk for the problem of drug resistance since these cytosine nucleoside analogues are metabolized by the same enzymes. Due to its unique mechanism of action of demethylating DNA, 5-Aza-CdR has the potential to activate tumor (growth) suppressor and differentiation genes that have been accidentally silenced by DNA methylation in leukemic cells. All these factors should be taken into account in the design of the optimal dose schedule of this analogue. The optimal dose schedule of 5-Aza-CdR should be based on the kinetic parameters of deoxycytidine kinase, its pharmacokinetics, its effects on DNA methylation and the cell cycle parameters of the leukemic cells and the normal hematopoietic stem cells. Since granulocytopenia is the major toxic effect produced by 5-Aza-CdR, the use of hematopoietic growth factors to shorten the duration of leukopenia should be investigated. Another approach which we are investigating is to use the methods of gene therapy to insert the cytidine deaminase gene into normal hematopoietic progenitor cells so as to make them drug resistant to 5-Aza-CdR. The use of other agents that can induce the differentiation of leukemic cells in combination with 5-Aza-CdR may have the potential to increase the clinical effectiveness of this analogue for the therapy of leukemia.

Antimetabolites, Antineoplastic↗

PubMed1997

Activation of the retinoic acid receptor beta gene by 5-aza-2'-deoxycytidine in human DLD-1 colon carcinoma cells.

We previously reported that 5-aza-2'-deoxycytidine (5-Aza-CdR) in combination with all-trans retinoic acid (ATRA) produced a synergistic antineoplastic effect on DLD-1 colon carcinoma cells. We also observed that 5-Aza-CdR, a potent inhibitor of DNA methylation, increased the expression of retinoic acid receptor (RAR)-beta. Methylation of cytosine in the promoter-first exon region of genes has been reported to silence their expression. In an attempt to clarify the mechanism responsible for the activation of the RAR-beta gene by 5-Aza-CdR in DLD-1 colon carcinoma cells, we investigated its methylation state by Southern blotting. Our results indicate that DNA hypermethylation of the RAR-beta gene, a putative tumor suppressor gene, may be the mechanism of silencing its expression in these tumor cells. We also reported that a different schedule of 5-Aza-CdR and ATRA produced a synergistic antineoplastic effect on the colon carcinoma cells.

Adenocarcinoma↗

PubMed1997

Pharmacological approach for optimization of the dose schedule of 5-Aza-2'-deoxycytidine (Decitabine) for the therapy of leukemia.

Animals↗