A5042052621- Muscle Physiology and Disorders
- Respiratory Support and Mechanisms
- Virus-based gene therapy research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Neuroscience of respiration and sleep
- Exercise and Physiological Responses
- Adipose Tissue and Metabolism
- Neonatal Respiratory Health Research
- Intensive Care Unit Cognitive Disorders
- Obstructive Sleep Apnea Research
- Mitochondrial Function and Pathology
- Autophagy in Disease and Therapy
- Cystic Fibrosis Research Advances
- Neurogenetic and Muscular Disorders Research
- Viral Infectious Diseases and Gene Expression in Insects
- Cardiomyopathy and Myosin Studies
- Immune Response and Inflammation
- Congenital Diaphragmatic Hernia Studies
- Asthma and respiratory diseases
- RNA Interference and Gene Delivery
- Cardiac Arrest and Resuscitation
- Anesthesia and Neurotoxicity Research
- Cytomegalovirus and herpesvirus research
- Inflammation biomarkers and pathways
- Advanced Sensor and Energy Harvesting Materials
McGill University Health Centre
2016-2025
McGill University
2015-2025
Christie (Canada)
2012-2024
Christ University
2014-2020
KU Leuven
2019
Centre National de la Recherche Scientifique
2004-2015
Promega (United States)
2015
SynZyme Technologies (United States)
2015
Inserm
2004-2012
Hôpital Arnaud de Villeneuve
2012
The protein dystrophin, normally found on the cytoplasmic surface of skeletal muscle cell membranes, is absent in patients with Duchenne muscular dystrophy as well mdx (X-linked dystrophy) mice. Although its primary structure has been determined, precise functional role dystrophin remains subject speculation. In present study, we demonstrate that dystrophin-deficient fibers mouse exhibit an increased susceptibility to contraction-induced sarcolemmal rupture. level damage directly correlated...
Rationale: Diaphragmatic function is a major determinant of the ability to successfully wean patients from mechanical ventilation (MV). Paradoxically, MV itself results in rapid loss diaphragmatic strength animals. However, very little known about time course or mechanistic basis for such phenomenon humans.Objectives: To determine prospective fashion development weakness during MV; and relationship between duration injury atrophy, status candidate cellular pathways implicated these...
Dynamic hyperinflation and the development of intrinsic positive end-expiratory pressure (PEEPi) are commonly observed in patients with severe chronic obstructive pulmonary disease (COPD) acute respiratory failure. The presence PEEP acts as an inspiratory threshold load, contributes significantly to increase work oxygen cost breathing. present study examined effects continuous airway (CPAP) (at 5, 10, 15 cm H2O) its ability reduce mechanical load imposed by PEEPi on breathing pattern,...
Chronic inflammation and fibrosis characterize Duchenne muscular dystrophy (DMD). We show that pro-inflammatory macrophages are associated with in mouse human DMD muscle. DMD-derived Ly6Cpos exhibit a profibrotic activity by sustaining fibroblast production of collagen I. This is mediated the high latent-TGF-β1 due to higher expression LTBP4, for which polymorphisms progression patients. Skewing macrophage phenotype via AMPK activation decreases ltbp4 macrophages, blunts latent-TGF-β1,...
Inflammatory cell infiltration and afferent neuropathy have been shown in the upper airway (UA) mucosa of subjects with obstructive sleep apnea (OSA). We hypothesized that inflammatory denervation changes also involve muscular layer pharynx OSA. Morphometric analysis was performed on UA tissue from nonsnoring control (n = 7) patients OSA 11) following palatal surgery. As compared subjects, cells were increased OSA, CD4+ activated CD25+ T (both ∼ threefold) predominating. Inflammation present...
Controlled mechanical ventilation (CMV) results in atrophy of the human diaphragm. The autophagy-lysosome pathway (ALP) contributes to skeletal muscle proteolysis, but its contribution diaphragmatic protein degradation mechanically ventilated patients is unknown.To evaluate autophagy responses CMV diaphragm and limb muscles humans identify roles FOXO transcription factors these responses.Muscle biopsies were obtained from nine control subjects brain-dead organ donors. Subjects for 2 4 hours...
Increasing numbers of patients are surviving episodes prolonged mechanical ventilation or benefitting from the recent availability user-friendly noninvasive ventilators. Although many publications pertaining to specific aspects home (HMV) exist, very few comprehensive guidelines that bring together all current literature on at risk for using ventilatory support available. The Canadian Thoracic Society HMV Guideline Committee has reviewed available English topics related in adults, and...
Rationale: Mechanical ventilation (MV) is associated with adverse effects on the diaphragm, but cellular basis for this phenomenon, referred to as ventilator-induced diaphragmatic dysfunction (VIDD), poorly understood.Objectives: To determine whether mitochondrial function and energy status are disrupted in human diaphragms after MV, role of mitochondria-derived oxidative stress development VIDD.Methods: Diaphragm biceps specimens obtained from brain-dead organ donors who underwent MV...
Muscle fibers show great differences in their contractile and metabolic properties. This diversity enables skeletal muscles to fulfill adapt different tasks. In this report, we that the Six/Eya pathway is implicated establishment maintenance of fast-twitch muscle phenotype. We demonstrate MEF3/Six DNA binding element present aldolase A pM promoter mediates high level activation glycolytic (but not slow-twitch) fibers. also among Six Eya gene products expressed mouse muscle, Six1 Eya1...
Background Mitochondrial injury develops in skeletal muscles during the course of severe sepsis. Autophagy is a protein and organelle recycling pathway which functions to degrade or recycle unnecessary, redundant, inefficient cellular components. No information available regarding degree sepsis-induced mitochondrial autophagy ventilatory locomotor muscles. This study tests hypotheses that are more prone injury, depressed biogenesis induction compared with Methodology/Principal Findings Adult...
Significance Ventilator-induced diaphragmatic dysfunction (VIDD) refers to the diaphragm muscle weakness that follows prolonged controlled mechanical ventilation, impeding recovery from respiratory failure. The mechanisms underlying VIDD are still not fully understood. Using human samples and murine models of VIDD, we identify here a pathophysiological pathway involving structural functional impairment ryanodine receptor (RyR1), main sarcoplasmic reticulum (SR) Ca 2+ release channel. We...
PRINCIPAL AIMSThe role of the cytoskeletal protein dystrophin in providing protection against mechanical stress-induced cardiomyocyte damage and dysfunction has been investigated using an ex vivo perfused working heart preparation, together with approaches, to experimentally manipulate level stress imposed on hearts normal dystrophin-expressing dystrophin-deficient, X-linked muscular dystrophic (mdx) mice. We have addressed hypothesis that cardiac muscle cells lacking dystrophin, absence...
The X chromosome-linked muscular dystrophic (mdx) mouse lacks the subsarcolemmal protein dystrophin and thus represents a genetic homologue of human Duchenne dystrophy. present study examined alterations in diaphragm contractile properties myosin heavy chain (MHC) expression young (3-4 mo) old (22-24 control mdx mice. In mice, maximum isometric tension (Po) was reduced to 50% values. An increase fibers coexpressing types I (slow) IIa MHC as well regenerating expressing embryonic occurred,...
We have generated high-titer adenoviral recombinants (AVR) expressing a 6.3-kb partial dystrophin cDNA insert under the control of either Rous sarcoma virus (RSV) or cytomegalovirus (CMV) promoter. These AVR preparations were free both E1-containing and with nonfunctional expression cassette. With these optimal preparations, we obtained high degree short-term (10 days) truncated (approximately 200 kD) in dystrophin-deficient mdx muscles injected neonatal period; lesser was found young adult...
Intramuscular injection of plasmid is a potential alternative to viral vectors for the transfer therapeutic genes into skeletal muscle fibers. The low efficiency plasmid-based gene can be enhanced by electroporation (EP) coupled with intramuscular application hyaluronidase. We have investigated several factors that influence transfer. These include electrical parameters EP, optimal use hyaluronidase, age and strain host, size. Muscles very young mature normal, mdx, immunodeficient mice were...
Recent work has demonstrated the ability of continuous positive airway pressure (CPAP) to relieve dyspnea during exercise in patients with severe chronic obstructive pulmonary disease (COPD). The present study examined effects CPAP (7.5-10 cmH2O) on pattern respiratory muscle activation and its relationship constant load submaximal bicycle [20 +/- 4.8 (SE) W] eight COPD (forced expiratory volume 1 s = 25 3% predicted). Tidal volume, rate, minute ventilation, end-expiratory lung increased as...
Overproduction of nitric oxide (NO) with attendant oxidative and nitrosative stress has been implicated in sepsis-induced diaphragm dysfunction. Here we determined the impact controlled mechanical ventilation (MV) on rat sarcolemmal injury, inducible NO synthase (iNOS) expression, during endotoxemia. At 4 h after injection endotoxin, impaired integrity decreased force production by were observed spontaneously breathing rats. The use MV endotoxemia largely eliminated damage significantly...
Chemokines have been implicated in the promotion of leucocyte trafficking to diseased muscle. The purpose this study was determine whether a subset inflammatory chemokines are able directly drive myoblast proliferation, an essential early component muscle regeneration, manner which is entirely independent leucocytes. Cultured myoblasts (C2C12) were exposed monocyte chemoattractant protein-1 (MCP-1; CCL2), macrophage protein-1alpha (MIP-1alpha; CCL3) or MIP-1beta (CCL4). All induced...
Cystic fibrosis (CF) patients often have reduced mass and strength of skeletal muscles, including the diaphragm, primary muscle respiration. Here we show that lack CF transmembrane conductance regulator (CFTR) plays an intrinsic role in atrophy dysfunction. In normal murine human muscle, CFTR is expressed co-localized with sarcoplasmic reticulum-associated proteins. CFTR–deficient myotubes exhibit augmented levels intracellular calcium after KCl-induced depolarization, exposure to...