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J St-Pierre

Publications and source records attributed to J St-Pierre.

At least 19 recordsLinked to original sources
PubMed2002

The pleiotropic expression of the myotonic dystrophy protein kinase gene illustrates the complex relationships between genetic, biological and clinical covariates of male aging.

Aging is a complex process modulated by multiple interactions between environmental and genetic factors. Myotonic dystrophy (DM1) is an autosomal dominant disorder caused by an unstable (CTG)n repeat expansion in the DM1 protein kinase (DMPK) gene. The affected male patients' life expectancy at birth (53.2 years) is more than two decades below that observed in most occidental populations. The DMPK gene expression is pleiotropic and includes the premature expression of several age-related signs, symptoms and metabolic disturbances including hormonal dysfunctions, progressive decrease in muscular mass, presenile cataracts, alopecia, reduced alertness, insulin resistance, dyslipidemia, erectile dysfunction and hypogonadism. The aim of this study was to analyze the relationship between aging covariates and the severity of DM1 expression in 136 DM1 male subjects. DM1 clinical expression was assessed on a validated neuromuscular disability rating scale and was correlated with plasma total testosterone (rs = -0.31, p < 0.001), luteinizing hormone (LH) (rs = 0.52, p < 0.001) and follicle stimulating hormone (FSH) (rs = 0.54, p < 0.001) levels. Following LH releasing hormone stimulation, FSH and LH concentrations increased as a function of DM1 severity (p < 0.05). Muscular disability in DM1 was also positively associated with fasting plasma insulin and triglyceride concentrations (p < 0.05). The association of plasma apolipoprotein B and low-density lipoprotein cholesterol levels with DM1 was not linear across their distribution and tended to reflect cell membrane damage progression. These results suggest that DM1, a simple Mendelian trait, can represent a valuable model to illustrate the complex relationships between variables associated with male aging.

Adolescent↗
PubMed2001

Glycerol: a neglected variable in metabolic processes?

Glycerol is a small and simple molecule produced in the breakdown of glucose, proteins, pyruvate, triacylglycerols and other glycerolipid, as well as release from dietary fats. An increasing number of observations show that glycerol is probably involved in a surprising variety of physiopathologic mechanisms. Glycerol has long been known to play fundamental roles in several vital physiological processes, in prokaryotes and eukaryotes, and is an important intermediate of energy metabolism. Despite some differences in the details of their operation, many of these mechanisms have been preserved throughout evolution, demonstrating their fundamental importance. In particular, glycerol can control osmotic activity and crystal formation and then act as a cryoprotective agent. Furthermore, its properties make it useful in numerous industrial, therapeutic and diagnostic applications. Few studies have focussed directly on glycerol, however, and while its metabolism is increasingly well documented, much of the details remain unknown. Considering the importance of glycerol in multiple vital physiological processes, its study could help unlock important physiopathological mechanisms.

Amino Acid Sequence↗
PubMed2001

A sequence variation in the mitochondrial glycerol-3-phosphate dehydrogenase gene is associated with increased plasma glycerol and free fatty acid concentrations among French Canadians.

FAD-dependent glycerol-3-phosphate dehydrogenase (mGPD) enzyme is located in the mitochondrial inner membrane where it catalyzes irreversible oxidation reactions. Type 2 diabetes mellitus (DM) is a multifactorial disorder associated with physiological abnormalities in the glycerol and free fatty acids (FFA) metabolic pathways. In the present study, we have evaluated the association among the mGPD H264R sequence variation and postabsorptive plasma FFA and glycerol concentrations in a sample of French Canadians with and without type 2 DM. A sample of 81 recently diagnosed type 2 DM and 318 nondiabetic, nonobese, normotriglyceridemic French Canadians were screened for the presence of the mGPD H264R genetic variant using a PCR-RFLP-based method. The 318 nondiabetic subjects were free of known type 2 DM covariates (fasting glucose <7.0 mmol/L, body mass index <29 kg/m(2), fasting glycerol <2.0 mmol/L and absence of the N288D sequence variation in the glycerol kinase gene, fasting triglyceride <2.5 mmol/L). The association of mGPD H264R sequence variation with plasma FFA and glycerol concentrations was assessed in different regression models. Among non-DM individuals, the R allele (HR and RR genotypes) was associated with increased plasma FFA and glycerol concentrations (P < 0.05). However, the mean plasma FFA and glycerol concentrations were not affected by the H264R genotype in the type 2 DM sample. Overall, mean plasma FFA concentrations in non-DM RR homozygotes reached values that were similar to those achieved in patients with type 2 diabetes (0.87 +/- 0.63 vs 0.90 +/- 0.48 mmol/L). After controlling for age, gender, body mass index, fasting glucose, and fasting triglyceride concentrations, the relative odds of having fasting plasma FFA levels above the 90th percentile (0.9 mmol/L) in the absence of DM was increased by twofold in H264R heterozygotes (P = 0.04) and fourfold among R264 homozygotes (P = 0.009) compared to noncarriers. In the absence of DM, the mGPD R allele was also associated with higher plasma glycerol concentrations (P < 0.05). Results in non-DM individuals suggest that the mGPD R allele is associated with DM intermediate phenotypes. The absence of a relation between mGPD genotype and DM is in accordance with the view that DM is a complex phenotype in which increased plasma FFA or glycerol concentrations result from metabolic alterations which might obscure the effect of the mGPD polymorphism.

Adult↗
PubMed2000

AMP decreases the efficiency of skeletal-muscle mitochondria.

Mitochondrial proton leak in rat muscle is responsible for approx. 15% of the standard metabolic rate, so its modulation could be important in regulating metabolic efficiency. We report in the present paper that physiological concentrations of AMP (K(0.5)=80 microM) increase the resting respiration rate and double the proton conductance of rat skeletal-muscle mitochondria. This effect is specific for AMP. AMP also doubles proton conductance in skeletal-muscle mitochondria from an ectotherm (the frog Rana temporaria), suggesting that AMP activation is not primarily for thermogenesis. AMP activation in rat muscle mitochondria is unchanged when uncoupling protein-3 is doubled by starvation, indicating that this protein is not involved in the AMP effect. AMP activation is, however, abolished by inhibitors and substrates of the adenine nucleotide translocase (ANT), suggesting that this carrier (possibly the ANT1 isoform) mediates AMP activation. AMP activation of ANT could be important for physiological regulation of metabolic rate.

Adenosine Monophosphate↗
PubMed2000

Mitochondria as ATP consumers: cellular treason in anoxia.

In anoxia, mitochondria change from being ATP producers to potentially powerful ATP consumers. This change occurs, because the mitochondrial F(1)F(0)-ATPase begins to hydrolyze ATP to avoid the collapse of the proton motive force. Species that can survive prolonged periods of O(2) lack must limit such ATP use; otherwise, this process would dominate glycolytic metabolism and threaten ATP delivery to essential ATP-consuming processes of the cell (e.g., ion-motive ATPases). There are two ways to limit ATP hydrolysis by the F(1)F(0)-ATPase, namely (i) reduction of the proton conductance of the mitochondrial inner membrane and (ii) inhibition of the enzyme. We assessed these two possibilities by using intact mitochondria isolated from the skeletal muscle of anoxia-tolerant frogs. Our results show that proton conductance is unaltered between normoxia and anoxia. However, ATP use by the F(1)F(0)-ATPase is limited in anoxia by a profound inhibition of the enzyme. Even so, ATP use by the F(1)F(0)-ATPase might account for approximately 9% of the ATP turnover in anoxic frog skeletal muscle.

Adenosine Triphosphate↗
PubMed2000

Glycerol as a correlate of impaired glucose tolerance: dissection of a complex system by use of a simple genetic trait.

Glycerol kinase (GK) represents the primary entry of glycerol into glucose and triglyceride metabolism. Impaired glucose tolerance (IGT) and hypertriglyceridemia are associated with an increased risk of diabetes mellitus and cardiovascular disease. The relationship between glycerol and the risk of IGT, however, is poorly understood. We therefore undertook the study of fasting plasma glycerol levels in a cohort of 1,056 unrelated men and women of French-Canadian descent. Family screening in the initial cohort identified 18 men from five families with severe hyperglycerolemia (values above 2.0 mmol/liter) and demonstrated an X-linked pattern of inheritance. Linkage analysis of the data from 12 microsatellite markers surrounding the Xp21.3 GK gene resulted in a peak LOD score of 3.46, centered around marker DXS8039. In addition, since all of the families originated in a population with a proven founder effect-the Saguenay Lac-St.-Jean region of Quebec-a common disease haplotype was sought. Indeed, a six-marker haplotype extending over a region of 5.5 cM was observed in all families. Resequencing of the GK gene in family members led to the discovery of a N288D missense mutation in exon 10, which resulted in the substitution of a highly conserved asparagine residue by a negatively charged aspartic acid. Although patients with the N288D mutation suffered from severe hyperglycerolemia, they were apparently otherwise healthy. The phenotypic analysis of the family members, however, showed that glycerol levels correlated with impaired glucose metabolism and body-fat distribution. We subsequently noted a substantial variation in glycerolemia in subjects of the initial cohort with normal plasma glycerol levels and demonstrated that this variance showed significant family resemblance. These results suggest a potentially important genetic connection between fasting glycerolemia and glucose homeostasis, not only in this X-linked deficiency but, potentially, in individuals within the "normal" range of plasma glycerol concentrations.

Adult↗
PubMed2000

Surviving hypoxia without really dying.

In cases of severe O(2) limitation, most excitable cells of mammals cannot continue to meet the energy demands of active ion transporting systems, leading to catastrophic membrane failure and cell death. However, in certain lower vertebrates, hypoxia-induced membrane destabilisation of the kind seen in mammals is either slow to develop or does not occur at all owing to adaptive decreases in membrane permeability (i.e. ion 'channel arrest'), that dramatically reduce the energetic costs of ion-balancing ATPases. Mammalian cells do, however, exhibit a whole host of adaptive responses to less severe shortages of oxygen, which include energy-balanced metabolic suppression, ionic-induced activation of O(2) receptors and the upregulation of certain genes, all of which enhance the systemic delivery of oxygen and promote energy conservation. Accumulating evidence suggests that the mechanisms underlying these protective effects are orchestrated into action by putative members of an O(2)-sensing pathway that most if not all cells share in common. In this review we address three major questions: (i) how do cells detect shortages of oxygen and subsequently set in motion adaptive mechanisms of either energy production or energy conservation; (ii) how do these mechanisms restructure cellular pathways of ATP supply and demand to ensure that ion-motive ATPases are given priority over other cell functions to preserve membrane integrity in energy-limited states; and (iii) what mechanisms of molecular and metabolic defence against acute and long-term shortages of oxygen set hypoxia-tolerant systems apart from their hypoxia-sensitive counterparts?

Adenosine Triphosphate↗
PubMed2000

Metabolic depression and enhanced O(2) affinity of mitochondria in hypoxic hypometabolism.

This study examined whether the steady-state hypometabolism seen in overwintering frogs (Rana temporaria) is reflected at the mitochondrial level either by a reduction in their resting (state 4) and active (state 3) respiration rates and/or by increases in O(2) affinity. We isolated mitochondria from the skeletal muscle of cold-submerged frogs at different stages during their hibernation in normoxic and hypoxic water. A modest metabolic depression at the whole animal level (normoxic submergence) was not associated with a reduction in mitochondrial state 4 and state 3 respiration rates. However, mitochondria isolated from frogs that were submerged for 1 mo manifested an increase in their O(2) affinity compared with controls and with animals submerged for 4 mo. Hypometabolism was more pronounced at the whole animal level during hypoxic submergence and was accompanied by 1) a reduction in mitochondrial state 4 and state 3 rates and 2) an increase in the O(2) affinity of mitochondria. These findings demonstrate that metabolic depression can be reflected at all levels of biological organization in hypoxia-tolerant animals.

Animals↗
PubMed2000

The effect of metabolic depression on proton leak rate in mitochondria from hibernating frogs.

Futile cycling of protons across the mitochondrial inner membrane accounts for 20 % or more of the total standard metabolic rate of a rat. Approximately 15 % of this total is due to proton leakage inside the skeletal muscle alone. This study examined whether the rate of proton leak is down-regulated as a part of a coordinated response to energy conservation during metabolic depression in cold-submerged frogs. We compared the proton leak rate of skeletal muscle mitochondria isolated from frogs at different stages of hibernation (control, 1 month and 4 months of submergence in normoxia and hypoxia). The kinetics of mitochondrial proton leak rate was unaltered throughout normoxic and hypoxic submergence. The state 4 respiration rates did not differ between control animals and frogs hibernating in normoxia. In contrast, the state 4 respiration rates obtained from frogs submerged in hypoxic water for 4 months were half those of control animals. This 50 % reduction in respiration rate in hypoxic hibernation was due to a reduction in electron transport chain activity and consequent decrease in mitochondrial membrane potential. We conclude that proton leak rate is reduced during metabolic depression as a secondary result of a decrease in electron transport chain activity, but that the proton conductance is unchanged. In addition, we show that the rate of proton leakage and the activity of the electron transport chain are lower in frogs than in rats, strengthening the observation that mitochondria from ectotherms have a lower proton conductance than mitochondria from endotherms.

Animals↗
PubMed2000

The distinct HERG missense mutation L564P causes long QT syndrome in one French Canadian family.

BACKGROUND: Long QT syndrome is a congenital abnormality of cardiac repolarization causing syncope and sudden death from ventricular tachyarrhythmias known as torsades de pointes. This hereditary cardiac disorder often shows an increase of the value of the QT interval corrected for heart rate over 0.45 s in a 12-lead electrocardiogram. OBJECTIVE: To find and identify pertinent mutations occurring in French Canadians by extracting genomic DNA from blood samples and performing a combination of polymerase chain reaction (PCR), single-strand conformational polymorphism and DNA sequencing. RESULTS: A novel mutation was identified in the S5 region of the HERG potassium channel. In codon 564 CTA, T was replaced by C, resulting in a leucine to proline substitution. Two family members had the mutation in two distinct generations. A new restriction site was created at this position and therefore enabled the development of a rapid diagnostic test using PCR. HERG wild type and mutant potassium channel mRNAs were then expressed in Xenopus laevis oocytes. CONCLUSION: This electrophysiological study suggests that coexpression of HERG wild type and mutant L564P results in a dominant negative effect of the mutation.

Adult↗
PubMed1998

Massive gastrointestinal hemorrhage after transoesophageal echocardiography probe insertion.

PURPOSE: To describe a case of a massive gastric bleeding following emergency coronary artery bypass surgery associated with transoesophageal echocardiographic (TEE) examination. CLINICAL FEATURES: A 50-yr-old man was referred for an acute myocardial infarction and pulmonary edema (Killip class 3). Twelve hours after his myocardial infarction, he was still having chest pain despite an i.v. heparin infusion. Coronary angiography revealed severe three-vessel disease with multifocal stenosis of the left anterior descending, circumflex and total occlusion of the right coronary artery. The patient was transferred to the operating room for emergency coronary artery bypass graft surgery. After total systemic heparinization (3 mg.kg-1) was obtained for cardiopulmonary bypass, a multiplane TEE probe was inserted without difficulty to monitor myocardial contractility during weaning from CPB. During sternal closure, the TEE probe was removed and an orogastric tube was inserted with immediate drainage of 1,200 ml red blood. Endoscopic examination demonstrated a mucosal tear near the gastro-oesophageal junction and multiple erosions were seen in the oesophagus. These lesions were successfully treated with submucosal epinephrine injections and the patient was discharged from the hospital eight days after surgery. CONCLUSION: This is a report of severe gastrointestinal hemorrhage following TEE examination in a fully heparinized patient. This incident suggest that, if the use of TEE is expected, the probe should preferably be inserted before the administration of heparin and the beginning of CPB.

Anticoagulants↗
PubMed1996

Cellular and mediator responses twenty-four hours after local endobronchial allergen challenge of asthmatic airways.

The effects of acute allergen exposure on bronchoalveolar lavage cells and mediators and mucosal inflammatory cells were evaluated in 10 subjects with atopic asthma who underwent lavage and biopsy 24 hours after segmental endobronchial allergen challenge. Increased numbers of bronchoalveolar lavage eosinophils were retrieved from the allergen-challenged sites compared with the saline-challenged sites (mean 21.4 vs 1.5 x 10(3) cells/ml; p < 0.02). Numbers of neutrophils and proportions of CD4+, CD8+, CD25+, and HLA-DR+ T cells were similar at the saline- and allergen-challenged sites. In contrast to the bronchoalveolar lavage findings, eosinophil numbers were not increased in the bronchial submucosa or epithelium. There was also no significant difference in neutrophils, mast cells, CD3+, CD4+, or CD8+ T cells in the submucosa after allergen challenge, but the number of activated (CD25+) T lymphocytes in the mucosa did increase after allergen challenge. Allergen challenge did not induce any significant change in endothelial expression of P-selectin, E-selectin, intercellular adhesion molecule-1, or vascular cell adhesion molecule-1. CD11a+ and very late antigen-4+ cell numbers were similar in the saline- and allergen-challenged sites. This study suggests that in patients with very mild asthma, local allergen challenge induces persistent bronchoalveolar lavage eosinophilia, but the recruitment process seems to have diminished or ceased by 24 hours.

Adult↗
PubMed1996

Dexamethasone and cyclosporin A modulation of cytokine expression and specific antibody synthesis in an allergic bronchopulmonary aspergillosis murine model.

We previously demonstrated that, in C57B1/6 mice, cyclosporin A enhanced and dexamethasone inhibited the Aspergillus fumigatus-induced pulmonary eosinophilia and total IgE levels. To evaluate whether these effects were related to the modulation of T-lymphocyte recruitment and activation and cytokine expression, we performed immunohistochemical staining for T-cell surface marker CD3 and CD4, cell activation marker CD25, and cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4) and interleukin-5 (IL-5) on lung tissue sections from mice exposed to Aspergillus fumigatus and treated or not with dexamethasone or cyclosporin A. Dexamethasone significantly inhibited Aspergillus fumigatus-induced increased number of activated T cells and cytokine-expressing cells in parallel with a decrease in pulmonary eosinophils. In contrast, cyclosporin A did not decrease these immunological events but enhanced the lung eosinophil recruitment. Moreover, dexamethasone prevented the production of immunoglobulins against 76 and 36 kD antigen proteins and cyclosporin A against 76 and 18 kD antigen proteins. These results indicate that dexamethasone down-regulates and cyclosporin A up-regulates lung eosinophil recruitment and total IgE production, probably via the modulation of T-lymphocyte activation and GM-CSF, IL-4 and IL-5 expression. Both drugs inhibit Aspergillus fumigatus-specific antibody synthesis, but their suppressive actions are selective to different antigenic components.

Animals↗
PubMed1996

Haemodynamic interaction of high-dose fentanyl and increasing doses of vecuronium in patients undergoing myocardial revascularization.

BACKGROUND: Bradyarrhythmia has been reported with vecuronium when given with high dose narcotics. We hypothesized that if the bradycardic response is dependent on a vagal reaction mediated by narcotics, it should be independent of the vecuronium dose. A dose-related response of vecuronium on heart rate (HR) would be in favour of a chronotropic action of this agent. METHODS: We examined three induction techniques using high doses of fentanyl in which vecuronium was given in increasing doses. In addition, a reference group received a low dose of atracurium. Forty patients scheduled for elective CABG surgery were anaesthetized with fentanyl (50 mu g/kg) given over 5 min, and were randomly assigned to receive either 0.056, 0.14, 0.28 mg/kg of vecuronium or 0.28 mg/kg of atracurium. Haemodynamic measurements were obtained at the following intervals: before induction (time 0), after the administration of fentanyl (at 5 min), and 1, 2 and 5 min after tracheal intubation (at 10, 11 and 15 min). RESULTS: In vecuronium-treated groups, there were significant decreases in HR, mean arterial pressure, and cardiac output (P<0.05). There were no differences between the three vecuronium groups. Although the atracurium-treated group displayed no significant haemodynamic changes, 2 patients of this group developed HR < 40 bpm. CONCLUSIONS: Over the range of vecuronium doses studied, we observed a reduction in HR during induction for CABG surgery with high doses of fentanyl and vecuronium. This effect was not dose dependent and is likely related to a direct effect of a high-dose narcotic technique and/or due to a vagal stimulation regarding the airway procedure.

Adult↗
PubMed1994

Effects of 6-dimethylaminopurine on the length of the cell cycle and on the state of phosphorylation of putative intermediate filament proteins in sea urchin embryos.

The effects of 6-dimethylaminopurine (6-DMAP) on the length of the cell cycle and on the state of phosphorylation of a putative intermediate filament protein, p117, have been studied in sea urchin embryos. Embryos were transferred into sea water containing 600 microM 6-DMAP at 0.5, 2 or 5 min after insemination, and incubated for 30 or 90 min. The effects of 6-DMAP on cell cycle length were studied by determining the time required for completion of mitosis upon return of the embryos in normal sea water. In all instances, except for the embryos transferred 0.5 min after insemination (AI) and incubated for 30 min, the duration of the M phase was shortened compared to controls, being faster in the embryos incubated for 90 minutes compared to the 30 min incubation period. However, embryos transferred 0.5 min AI have a longer M-phase than those transferred 2 minutes or later after fertilization, suggesting that between 0.5 and 2 min after fertilization, critical phosphorylating events occur which affect the commitment of the cells to enter M-phase. To study the pattern of p117 phosphorylation during the cell cycle, the eggs were transferred 2 minutes after fertilization in presence of 600 microM 6-DMAP and with 200 microCi/ml of 32P-orthophosphate. Analyses of 32P-labelled proteins after exposure of SDS-PAGE gels and their corresponding blots suggested that phosphorylation of p117 greatly increases at the time of pronuclear fusion, and then declines slightly at prophase-metaphase. This decrease is markedly enhanced when the cells are treated with 6-DMAP during metaphase in order to induce a premature breakdown of the mitotic apparatus. A causal link is suggested between the level of phosphorylation of p117 and its state of assembly.

Adenine↗
PubMed1991

Effects of 6-dimethylaminopurine on microtubules and putative intermediate filaments in sea urchin embryos.

The effects of 6-dimethylaminopurine (6-DMAP) (a putative phosphorylation inhibitor) on the state of assembly of microtubules and intermediate filaments have been studied during the first cell cycle of the sea urchin Strongylocentrotus droebachiensis. Changes in the spatial organization of cytoskeletal structures were studied by indirect immunofluorescence with anti-tubulin and anti-IFa antibodies. The rates and patterns of protein phosphorylation in control and treated eggs were also investigated. The transfer of fertilized eggs to 600 microM 6-DMAP within 4 min following insemination inhibits pronuclear migration and syngamy. This also prevents male pronuclear decondensation, while chromatin condensation and nuclear envelope breakdown do not occur in the female pronucleus. Immunolabeling with anti-tubulin antibodies reveals the presence of cortical microtubules as early as 15 min after fertilization in both control and treated eggs. However, no sperm astral microtubules could be detected in the treated eggs. At later stages, from syngamy (40 min) up to nuclear envelope breakdown (90 min), 6-DMAP affects neither cortical microtubule organization nor the state of chromatin condensation but it precludes nuclear envelope breakdown and entry into mitosis. Treatment of the fertilized eggs after nuclear envelope breakdown induces permanent chromosome decondensation and premature disappearance of the mitotic apparatus. This last event involves disruption of the spatial organization of both microtubules and putative intermediate filaments. Quantitative measurements of protein phosphorylation show that 6-DMAP efficiently and reversibly inhibits 32P incorporation into proteins. Qualitative analysis of the autoradiograms of 32P-labeled proteins separated by SDS-PAGE reveals that a major protein band, migrating with an apparent molecular weight of 31 x 10(3)Mr, is specifically dephosphorylated in eggs treated with 6-DMAP. This study suggests that protein phosphorylation is required for sperm aster microtubule growth and migration, but not for cortical microtubule polymerization. It also strengthens the hypothesis that, in sea urchin eggs, putative intermediate filaments are tightly associated with spindle microtubules. Finally, it confirms that inhibiting protein phosphorylation before nuclear envelope breakdown reversibly prevents the entry into mitosis.

Adenine↗
PubMed1981

[Not Available].

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Canada↗