Biomedical subjects

F Gagnon

Publications and source records attributed to F Gagnon.

At least 19 recordsLinked to original sources

PubMed2005

Quantitative founder-effect analysis of French Canadian families identifies specific loci contributing to metabolic phenotypes of hypertension.

The Saguenay-Lac St-Jean population of Quebec is relatively isolated and has genealogical records dating to the 17th-century French founders. In 120 extended families with at least one sib pair affected with early-onset hypertension and/or dyslipidemia, we analyzed the genetic determinants of hypertension and related cardiovascular and metabolic conditions. Variance-components linkage analysis revealed 46 loci after 100,000 permutations. The most prominent clusters of overlapping quantitative-trait loci were on chromosomes 1 and 3, a finding supported by principal-components and bivariate analyses. These genetic determinants were further tested by classifying families by use of LOD score density analysis for each measured phenotype at every 5 cM. Our study showed the founder effect over several generations and classes of living individuals. This quantitative genealogical approach supports the notion of the ancestral causality of traits uniquely present and inherited in distinct family classes. With the founder effect, traits determined within population subsets are measurably and quantitatively transmitted through generational lineage, with a precise component contributing to phenotypic variance. These methods should accelerate the uncovering of causal haplotypes in complex diseases such as hypertension and metabolic syndrome.

Adolescent↗

PubMed2004

New real-time PCR assay for rapid detection of methicillin-resistant Staphylococcus aureus directly from specimens containing a mixture of staphylococci.

Molecular methods for the rapid identification of methicillin-resistant Staphylococcus aureus (MRSA) are generally based on the detection of an S. aureus-specific gene target and the mecA gene. However, such methods cannot be applied for the direct detection of MRSA from nonsterile specimens such as nasal samples without the previous isolation, capture, or enrichment of MRSA because these samples often contain both coagulase-negative staphylococci (CoNS) and S. aureus, either of which can carry mecA. In this study, we describe a real-time multiplex PCR assay which allows the detection of MRSA directly from clinical specimens containing a mixture of staphylococci in <1 h. Five primers specific to the different staphylococcal cassette chromosome mec (SCCmec) right extremity sequences, including three new sequences, were used in combination with a primer and three molecular beacon probes specific to the S. aureus chromosomal orfX gene sequences located to the right of the SCCmec integration site. Of the 1,657 MRSA isolates tested, 1,636 (98.7%) were detected with the PCR assay, whereas 26 of 569 (4.6%) methicillin-susceptible S. aureus (MSSA) strains were misidentified as MRSA. None of the 62 nonstaphylococcal bacterial species or the 212 methicillin-resistant or 74 methicillin-susceptible CoNS strains (MRCoNS and MSCoNS, respectively) were detected by the assay. The amplification of MRSA was not inhibited in the presence of high copy numbers of MSSA, MRCoNS, or MSCoNS. The analytical sensitivity of the PCR assay, as evaluated with MRSA-negative nasal specimens containing a mixture of MSSA, MRCoNS, and MSCoNS spiked with MRSA, was approximately 25 CFU per nasal sample. This real-time PCR assay represents a rapid and powerful method which can be used for the detection of MRSA directly from specimens containing a mixture of staphylococci.

Bacterial Proteins↗

PubMed2001

The importance of connections: joining components of the Hutterite pedigree.

We analyzed a quantitative trait (serum IgE levels), and a binary trait (asthma), in four Hutterite sub-pedigrees. A genome screen for asthma was performed using GENEHUNTER, and interesting regions were followed up using extended pedigrees and the FASTLINK package. Markov chain Monte Carlo (MCMC) methods were used to assess haplotype sharing among affected individuals (MORGAN/AUTOZYG), and to perform a combined oligogenic segregation and linkage analysis (LOKI) for log10(IgE). We found evidence for at least two susceptibility loci for asthma on chromosome 5, and a QTL for log10(IgE) on chromosome 1. Our analyses demonstrate that using the most complete pedigree structure possible is advisable, with attention to the possibility of heterogeneity among subunits of a very large pedigree.

Adult↗

PubMed2000

Effects of propofol on cerebral oxygenation during cardiopulmonary bypass in children.

PURPOSE: Neurologic complications occur following cardiopulmonary bypass surgery. We conducted a randomized, controlled, single-blind study to determine the effect of propofol on the redox status of cytaa3, and to evaluate its potential for decreasing neurologic complications. METHODS AND MATERIALS: Twenty-four children (median age: 3.3 yr; median weight: 14.4 kg) scheduled for elective cardiopulmonary bypass surgery were assigned to either the experimental group (Group P, given sufficient propofol to eliminate brain electrical activity as measured on EEG (i.e. burst suppression)) or the control group (Group C, no propofol). Near infrared spectroscopy data were collected at one-second intervals throughout the surgical procedures. Pre- and postoperative neurologic examinations were completed by a physician blinded to the group to which the patient was assigned. Change in cytochrome aa3 data at 10-min intervals (10, 20, 30, 40 min) following start of bypass were compared between groups by repeated measures analysis of variance. RESULTS: The patterns of change in redox state of cytochrome were different between the two groups (P < 0.002). The pattern of change within Group P was similar to that in hypothermic patients in Group C. There were correlations between change in cytaa3 redox status and temperature in the control subjects. There were no gross neurologic complications in either group. CONCLUSIONS: Propofol appears to stabilize the energy supply/demand equilibrium of the brain during cardiopulmonary bypass surgery and thus theoretically could reduce the incidence or severity of neurologic complications.

Anesthetics, Intravenous↗

PubMed2000

Strategies used with intrusive thoughts: a comparison of OCD patients with anxious and community controls.

Models of intrusive thoughts attribute a key role to strategies used by people to cope with their unwanted cognitions. In an extension of previous work, the authors conducted structured interviews with 38 people with obsessive-compulsive disorder, 38 people with another anxiety disorder, and 19 healthy volunteers. The interview identified the repertoire of strategies used with the participant's most troubling thought. The 2 clinical groups reported significantly more strategies than the nonclinical group. The clinical groups also reported significantly greater intensity of the thought and their emotional response and lower efficacy for the strategies. People with OCD reported a significantly higher proportion of strategies that were specifically linked to the thought content (as distinct from nonspecific strategies that were only linked sequentially in time). The results identify both common and differential characteristics of intrusive cognition in anxiety disorders.

Adult↗

PubMed2000

Efficacy of a cognitive-behavioral treatment for generalized anxiety disorder: evaluation in a controlled clinical trial.

Recent advances in the understanding of worry have led to the development of treatments for generalized anxiety disorder (GAD). The present study tested a GAD treatment that targeted intolerance of uncertainty, erroneous beliefs about worry, poor problem orientation, and cognitive avoidance. Twenty-six primary GAD patients were randomly allocated to a treatment condition (n = 14) or a delayed treatment control condition (n = 12). Self-report, clinician, and significant other ratings assessed GAD and associated symptoms. The results show that the treatment led to statistically and clinically significant change at posttest and that gains were maintained at 6- and 12-month follow-ups. Furthermore, 20 of 26 participants (77%) no longer met GAD diagnostic criteria following treatment. With regard to the treatment's underlying model, the results show that intolerance of uncertainty significantly decreased over treatment and that gains were maintained at both follow-ups. Although nonspecific factors were not significant predictors of treatment outcome, their role in the treatment of GAD requires further investigation.

Adult↗

PubMed1999

Purinergic modulation of Na(+),K(+),Cl(-) cotransport and MAP kinases is limited to C11-MDCK cells resembling intercalated cells from collecting ducts.

We demonstrated recently that in renal epithelial cells from collecting ducts of Madin-Darby canine kidneys (MDCK), Na(+),K(+), Cl(-) cotransport is inhibited up to 50% by ATP via its interaction with P(2Y) purinoceptors (Biochim. Biophys. Acta 1998. 1369:233-239). In the present study we examined which type of renal epithelial cells possesses the highest sensitivity of Na(+),K(+),Cl(-) cotransport to purinergic regulation. We did not observe any effect of ATP on Na(+),K(+),Cl(-) cotransport in renal epithelial cells from proximal and distal tubules, whereas in renal epithelial cells from rabbit and rat collecting ducts ATP decreased the carrier's activity by approximately 30%. ATP did not affect Na(+),K(+),Cl(-) cotransport in C7 subtype MDCK cells possessing the properties of principal cells but led to approximately 85% inhibition of this carrier in C11-MDCK cells in which intercalated cells are highly abundant. Both C7- and C11-MDCK exhibited ATP-induced IP(3) and cAMP production and transient elevation of [Ca(2+)](i). In contrast to the above-listed signaling systems, ATP-induced phosphorylation of ERK and JNK MAP kinases was observed in C11-MDCK only. Thus, our results reveal that regulation of renal Na(+),K(+),Cl(-) cotransport by P(2Y) receptors is limited to intercalated cells from collecting ducts and indicate the involvement of the MAP kinase cascade in purinergic control of this ion carrier's activity.

Adenosine Triphosphate↗

PubMed1999

Heat stress preconditioning does not protect renal epithelial Na(+),K(+),Cl(-) and Na(+),P(i) cotransporters from their modulation by severe heat stress.

This study compares the effects of heat and osmotic stress on heat stress protein (HSP) production while examining the putative protective action of HSPs on modulation of Na(+),K(+),Cl(-) and Na(+),P(i) cotransporters in Madin-Darby canine kidney (MDCK) epithelial cells by severe heat stress (46 degrees C, 15 min). Preconditioning heat stress (43 degrees C, 20 min) followed by 4 h recovery at 37 degrees C led to a 35-fold increase of HSP70 mRNA expression measured by Northern blot analysis. The protein content of HSP70 and HSP27, assessed by Western blots, was augmented by 5- and 2-fold, respectively, after 6 h of recovery. In contrast to preconditioning heat stress, hyperosmotic stress (520 vs. 320 mosm) elevated HSP70 mRNA content only by 7-fold and did not significantly affect the protein content of HSP70 or HSP27. Neither cell survival, assessed as lactate dehydrogenase (LDH) release, nor the basal activities of the ion transporters and their modulation by protein kinase C, P(2)-purinoceptor and cell volume were altered by preconditioning heat stress. Severe heat stress increased extracellular LDH content from 3+/-2 to 23+/-5% and enhanced Na(+),K(+),Cl(-) and Na(+),P(i) cotransport activity by 2-3-fold. The volume- and protein kinase C-dependent regulation of these carriers was abolished by severe heat stress while regulation by P(2)-purinoceptors was preserved. Preconditioning heat stress diminished severe heat stress-induced LDH release to 11+/-4% but did not protect Na(+),K(+),Cl(-) and Na(+),P(i) cotransporters from activation by severe heat stress and did not prevent severe heat stress-induced inactivation of protein kinase C- and volume-dependent signaling pathways. These results show that in MDCK cells, preconditioning heat stress-induced HSPs are not involved in the regulation of Na(+),K(+),Cl(-) and Na(+),P(i) cotransporters and do not protect them from modulation by severe heat stress.

Animals↗

PubMed1999

ATP-induced inhibition of Na+, K+, Cl- cotransport in Madin-Darby canine kidney cells: lack of involvement of known purinoceptor-coupled signaling pathways.

P2U/2Y-receptors elicit multiple signaling in Madin-Darby canine kidney (MDCK) cells, including a transient increase of [Ca2+]i, activation of phospholipases C (PLC) and A2 (PLA2), protein kinase C (PKC) and mitogen-activated protein kinase (MAPK). This study examines the involvement of these signaling pathways in the inhibition of Na+,K+,Cl- cotransport in MDCK cells by ATP. The level of ATP-induced inhibition of this carrier ( approximately 50% of control values) was insensitive to cholera and pertussis toxins, to the PKC inhibitor calphostin C, to the cyclic nucleotide-dependent protein kinase inhibitors, H-89 and H-8 as well as to the inhibitor of serine-threonine type 1 and 2A phosphoprotein phosphatases okadaic acid. ATP led to a transient increase of [Ca2+]i that was abolished by a chelator of Ca2+i, BAPTA. However, neither BAPTA nor the Ca2+ ionophore A231287, or an inhibitor of endoplasmic reticulum Ca2+-pump, thapsigargin, modified ATP-induced inhibition of Na+,K+, Cl- cotransport. An inhibitor of PLC, U73122, and an inhibitor of MAPK kinase (MEK), PD98059, blocked ATP-induced inositol-1,4, 5-triphosphate production and MAPK phosphorylation, respectively. However, these compounds did not modify the effect of ATP on Na+,K+, Cl- cotransport activity. Inhibitors of PLA2 (AACOCF3), cycloxygenase (indomethacin) and lypoxygenase (NDGA) as well as exogenous arachidonic acid also did not affect ATP-induced inhibition of Na+,K+,Cl- cotransport. Inhibition of the carrier by ATP persisted in the presence of inhibitors of epithelial Na+ channels (amiloride), Cl- channels (NPPB) and Na+/H+ exchanger (EIPA) and was insensitive to cell volume modulation in anisosmotic media and to depletion of cells with monovalent ions, thus ruling out the role of other ion transporters in purinoceptor-induced inhibition of Na+,K+,Cl- cotransport. Our data demonstrate that none of the known purinoceptor-stimulated signaling pathways mediate ATP-induced inhibition of Na+,K+,Cl- cotransport and suggest the presence of a novel P2-receptor-coupled signaling mechanism.

Adenosine Triphosphate↗

PubMed1999

Na+,K+ pump and Na+-coupled ion carriers in isolated mammalian kidney epithelial cells: regulation by protein kinase C.

This review updates our current knowledge on the regulation of Na+/H+ exchanger, Na+,K+,Cl- cotransporter, Na+,Pi cotransporter, and Na+,K+ pump in isolated epithelial cells from mammalian kidney by protein kinase C (PKC). In cells derived from different tubule segments, an activator of PKC, 4beta-phorbol 12-myristate 13-acetate (PMA), inhibits apical Na+/H+ exchanger (NHE3), Na+,Pi cotransport, and basolateral Na+,K+ cotransport (NKCCl) and augments Na+,K+ pump. In PMA-treated proximal tubules, activation of Na+,K+ pump probably plays a major role in increased reabsorption of salt and osmotically obliged water. In Madin-Darby canine kidney (MDCK) cells, which are highly abundant with intercalated cells from the collecting duct, PMA completely blocks Na+,K+,Cl- cotransport and decreases the activity of Na+,Pi cotransport by 30-40%. In these cells, agonists of P2 purinoceptors inhibit Na+,K+,Cl- and Na+,Pi cotransport by 50-70% via a PKC-independent pathway. In contrast with MDCK cells, in epithelial cells derived from proximal and distal tubules of the rabbit kidney, Na+,K+,Cl- cotransport is inhibited by PMA but is insensitive to P2 receptor activation. In proximal tubules, PKC-induced inhibition of NHE3 and Na+,Pi cotransporter can be triggered by parathyroid hormone. Both PKC and cAMP signaling contribute to dopaminergic inhibition of NHE3 and Na+,K+ pump. The receptors triggering PKC-mediated activation of Na+,K+ pump remain unknown. Recent data suggest that the PKC signaling system is involved in abnormalities of dopaminergic regulation of renal ion transport in hypertension and in the development of diabetic complications. The physiological and pathophysiological implications of PKC-independent regulation of renal ion transporters by P2 purinoceptors has not yet been examined.

Adenosine Triphosphate↗

PubMed1998

Complete inhibition of Na+, K+, Cl- cotransport in Madin-Darby canine kidney cells by PMA-sensitive protein kinase.

This study examines the involvement of hormones and neuromediators in the regulation of Na+, K+, Cl- cotransport in renal epithelial cells using Madin-Darby canine kidney cells with low transepithelial electrical resistance (194+/-47 Omega/cm2). In this cell line, Na+, K+, Cl- cotransport measured as bumetanide-sensitive 86Rb influx was inhibited up to 50-60% with agonists of P2-purinoceptors (ATP approximately ADP>UTP>AMP), slightly (15-30%) increased by activators of cAMP signaling (forskolin, 8-Br-cAMP) and was insensitive to activators of cGMP signaling (8-Br-cGMP, nitroprusside), EGF, angiotensin II, bradykinin, methacholine, propranolol, vasopressin, adenosine, dopamine and histamine. Thirty min of preincubation of MDCK cells with 0.1 microM PMA completely blocked the activity of Na+, K+, Cl- cotransport whereas down-regulation of this enzyme by 24 h of preincubation with 1 microM PMA activated Na+, K+, Cl- cotransport by 60% and abolished the effect of short-term treatment with PMA. Regulation of Na+, K+, Cl- cotransport by ATP was insensitive to down-regulation of PMA-sensitive isoforms of protein kinase C. In addition, an inhibitor of protein kinase activity, staurosporine, abolished the effect of 0.1 microM PMA but did not change inhibition of this carrier by ATP. Thus, these results show for the first time that P2-purinoceptors and PMA-sensitive isoforms of protein kinase C play a key role in the regulation of Na+, K+, Cl- cotransport in MDCK cells. These results also show that neither PMA- nor staurosporine-sensitive forms of protein kinase are involved in the inhibition of Na+, K+, Cl- cotransport by activators of P2-purinoceptors.

Animals↗

PubMed1998

Is lipoprotein(a) an independent risk factor for ischemic heart disease in men? The Quebec Cardiovascular Study.

OBJECTIVES: This study was undertaken to determine whether lipoprotein(a) [Lp(a)] is an independent risk factor for ischemic heart disease (IHD) and to establish the relation of Lp(a) to the other lipid fractions. BACKGROUND: Several, but not all, studies have shown that elevated Lp(a) concentrations may be associated with IHD; very few have been prospective. METHODS: A 5-year prospective follow-up study was conducted in 2,156 French Canadian men 47 to 76 years old, without clinical evidence of IHD. Lipid measurements obtained at baseline included total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, apoprotein B and Lp(a). During the follow-up period, there were 116 first IHD events (myocardial infarction, angina, death). Adjusted proportional hazards models were used to estimate the relative risk for the different variables. The cohort was also classified according to Lp(a) levels and other lipid risk factor tertiles to evaluate the relation of elevated Lp(a) levels to these risk factors. A cutoff value of 30 mg/dl was used for Lp(a). Risk ratios were calculated using the group with low Lp(a) levels and the first tertile of lipid measures as a reference. RESULTS: Lp(a) was not an independent risk factor for IHD but seemed to increase the deleterious effects of mildly elevated LDL cholesterol and elevated total cholesterol and apoprotein B levels and seemed to counteract the beneficial effects associated with elevated HDL cholesterol levels. CONCLUSIONS: In this cohort, Lp(a) was not an independent risk factor for IHD but appeared to increase the risk associated with other lipid risk factors.

Adult↗

PubMed1998

Generalized anxiety disorder: a preliminary test of a conceptual model.

This study presents a preliminary test of a conceptual model of Generalized Anxiety Disorder (GAD) which is theoretically driven and has clear clinical implications. The model's main features are intolerance of uncertainty, beliefs about worry, poor problem orientation and cognitive avoidance, Subjects were 24 GAD patients and 20 non clinical control subjects. The results show that all main components of the model were highly related to the discriminant function and that intolerance of uncertainty was pivotal in distinguishing GAD patients from non clinical subjects. Further, the discriminant function derived from these four process variables was very effective for classifying GAD patients and non clinical subjects into their respective groups. Overall, 82% of subjects were correctly classified as 18 of 24 subjects in the GAD group and 18 of 20 subjects in the non clinical group were properly identified. The results are discussed in terms of the proposed model of GAD and its clinical implications.

Adult↗

PubMed1998

Risk of avascular necrosis following short term megadose methylprednisolone treatment.

We conducted a prospective cohort study to determine whether administration of large doses of the corticosteroid methylprednisolone following spinal cord injury as recommended in the National Acute Spinal Cord Injury Study-2 (NASCIS-2) protocol results in an increased incidence of avascular necrosis (AVN) of the femoral or humeral head. All subjects were patients treated by a spinal cord injury physician in an Acute Spinal Cord Injury Unit between 1989 and 1996 where some received the megadose steroids while others did not. Patients younger than 15 years and older than 75 years were excluded, as were those with any hip or shoulder disease, with pelvic fracture, or with a history of predisposition to AVN by hip dislocation, excessive alcohol consumption, previous high dose steroid use, or systemic lupus erythematosus. Screening for AVN of the femoral and humeral heads was performed at a minimum of 6 months following injury, using magnetic resonance imaging (MRI). The films were read by a radiologist blinded to the treatment protocol received by the individual subject. Among the 59 spinal cord injured patients who received steroids (age 15-64 years (mean 32 years)), five were female. Among the 32 spinal cord injured subjects who did not receive steroids (age 16 to 65 years (mean 34 years)), seven were female. There was no case of AVN found in either group. Using binomial distribution, we conclude that the true incidence of AVN among the methylprednisolone treated group is less than 5% (alpha < 0.05) and therefore continue to recommend short term (24 h) methylprednisolone therapy.

Adolescent↗

PubMed1997

Cognitive-behavioral treatment of obsessive thoughts: a controlled study.

Twenty-nine patients with obsessive-compulsive disorder as diagnosed in accordance with the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised; American Psychiatric Association, 1987) who did not have overt compulsive rituals were randomly assigned to treatment and waiting-list conditions. Patients in the treatment condition received cognitive-behavioral therapy consisting of a detailed explanation of the occurrence and maintenance of obsessive thoughts, exposure to obsessive thoughts, response prevention of all neutralizing strategies, cognitive restructuring, and relapse prevention. Compared with waiting-list patients, treated patients improved significantly on measures of severity of obsessions, current functioning, self-report obsessive-compulsive symptoms, and anxiety. When waiting-list patients were subsequently treated, the combined group improved on all outcome measures. Treatment gains were maintained at 6-month follow-up. Results indicate that cognitive-behavioral therapy is effective in the treatment of patients with obsessive thoughts, a group that has often been considered resistant to treatment.

Adult↗

PubMed1996

Antisense and sense poly(A)-RNAs from the Xenopus laevis pyruvate dehydrogenase gene loci are regulated with message production during embryogenesis.

The structure and temporal expression of two Xenopus cDNAs encoding the beta subunit of pyruvate dehydrogenase (XPdhE1 beta) have been determined. XPdhE1 beta was 88% homologous to mature human PdhE1 beta, but the putative N-terminal mitochondrial signal peptide was poorly conserved. Zygotic expression of XPdhE1 beta mRNA was detected at neural tube closure and increased until stage 40. RT-PCR cloning identified a short homology to a protein kinase open reading frame within the 3' non-coding sequence of the XPdhE1 beta cDNAs. This homology, which occurred on the antisense cDNA strand, was shown by strand specific RT-PCR to be transcribed in vivo as part of an antisense RNA. Northern analysis showed that this RNA formed part of an abundant and heterogeneous population of antisense and sense poly(A)-RNAs transcribed from the XPdhE1 beta loci and coordinately regulated with message production.

Amino Acid Sequence↗

PubMed1996

Obsessive-compulsive disorder. Diagnosis and management.

We present three diagnostic tools to identify overt compulsive rituals, obsessional thinking, and neutralizing behaviours in obsessive-compulsive disorder (OCD) and describe the most effective cognitive-behavioural technique for treating obsessional thinking without overt rituals. Basic dysfunctional beliefs that lead to OCD are explained and integrated in the treatment model. We suggest how combined therapy can be used to tread OCD.

Antidepressive Agents↗

PubMed1996

Dendritic cells prevent radiation-induced thymic lymphoma.

Thymic lymphomas develop in C57BL/Ka mice within 36 weeks after split-dose X-irradiation. Lymphoma development can be abrogated in such mice by the injection of syngeneic bone marrow from healthy donors. The abrogation mechanism is unknown, but since bone marrow supplies the thymus with precursors of thymocytes and of dendritic cells, we tested the ability of early thymocytes and of immortalized thymic dendritic cells to abrogate lymphomagenesis. Fifteen weeks after irradiation, mice which had received bone marrow or dendritic cells had an equally low incidence of lymphoma, whereas mice which had received thymocytes or which had been only irradiated developed equally high levels of lymphomas, indicating that thymic dendritic cells played a key role in the prevention of lymphoma development. When thymuses from 15-week survivors were tested for pre-lymphoma cells, those from dendritic cell-treated mice proved to be endowed with a level of lymphomagenic potential intermediate between that from bone marrow-treated mice (nonlymphomagenic) and that from untreated or thymocyte-treated mice (highly lymphomagenic). These data indicate that lymphoma abrogation by bone marrow cells involves the participation of marrow-derived thymic dendritic cells.

Animals↗