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Nguyen B.N.,Departement de Pathologie du CHUM | Elleil M.S.,Luniversite Of Montreal | Meloche S.,Luniversite Of Montreal
Gastroenterology | Year: 2012

Development of fibrosis is part of the pathophysiologic process of chronic liver disease. Although it is considered deleterious, it also represents a form of tissue repair. Deposition of extracellular matrix changes the cellular environment of the liver; we investigated whether it increases resistance to noxious stimuli and the role of changes in intracellular signaling to hepatocytes in mediating this effect. Primary cultures of mouse hepatocytes were exposed to type I collagen (COL1); cell injury was assessed by morphologic and biochemical criteria. The expression of Bcl-2 family members was evaluated by immunoblot analyses. Activation of extracellular signalregulated kinase (ERK) was assessed using phospho-specific antibodies. Liver fibrosis was induced by repeated administration of thioacetamide or carbon tetrachloride to mice; mice were then exposed to Fas antibodies. Hepatocytes exposed to COL1 were more resistant to a variety of hepatotoxins, in a dose-dependent manner, and had lower levels of Bad, Bid, and Bax proapoptotic proteins compared with control hepatocytes. Activation of ERK1/2 was stronger and quicker in hepatocytes exposed to COL1. The MEK1/2 inhibitors U0126 and PD98059 reversed the protective effects of COL1 and the decrease in proapoptotic proteins. Hepatocytes isolated from ERK1 -/- mice were insensitive to the protective effect of COL1. Fibrotic livers from wild-type mice had high levels of phospho-ERK1 and were resistant to Fas-induced cell death. ERK1 -/- mice lost this effect. Production of COL1 during liver fibrosis induces a hepatoprotective response that is mediated by activation of ERK1 signaling. © 2012 AGA Institute.


Brass S.D.,University of California at Davis | Duquette P.,Luniversite Of Montreal | Proulx-Therrien J.,Luniversite Of Montreal | Auerbach S.,Boston University
Sleep Medicine Reviews | Year: 2010

Patients with multiple sclerosis (MS) often have unrecognized sleep disorders at higher frequency than the general population. Sleep disorders such as sleep disordered breathing, insomnia, REM sleep behavior disorder, narcolepsy and restless legs syndrome have all been reported in the MS population. Notably, the most common symptom of MS is "fatigue," which itself has been correlated with sleep disturbances. Sleep disorders may impact the quality of life of the MS patient population. This paper reviews the association of sleep disorders with MS, and discusses the association of sleep disruption with MS fatigue. © 2009 Elsevier Ltd. All rights reserved.


Donadi E.A.,University of Sao Paulo | Castelli E.C.,University of Sao Paulo | Arnaiz-Villena A.,Complutense University of Madrid | Roger M.,Luniversite Of Montreal | And 2 more authors.
Cellular and Molecular Life Sciences | Year: 2011

The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system. Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and 3′ untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas, in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized approach for the future use of HLA-G for therapeutic purposes. © 2010 The Author(s).


Beavis P.A.,Peter MacCallum Cancer Center | Stagg J.,Luniversite Of Montreal | Darcy P.K.,Peter MacCallum Cancer Center | Darcy P.K.,University of Melbourne | And 2 more authors.
Trends in Immunology | Year: 2012

Tumors use several strategies to evade immunosurveillance. One such mechanism is the generation of adenosine within the tumor microenvironment, which potently suppresses antitumor T cell responses. Adenosine within the tumor is generated by CD73, a membrane-bound nucleotidase that is expressed by tumor cells, suppressive immune subsets such as T regulatory cells (Tregs) and myeloid-derived suppressor cells and endothelial cells. Recent evidence suggests that targeted inhibition of CD73 has the potential to reduce tumorigenesis and metastasis, as well as enhancing the potency of T-cell-directed therapies. This review outlines the impact of adenosine on suppressing the antitumor response and the evidence supporting the rationale for CD73 targeting in the treatment of cancer. © 2012 Elsevier Ltd.


Duerr C.U.,McGill University | Mccarthy C.D.A.,McGill University | Mindt B.C.,McGill University | Rubio M.,Luniversite Of Montreal | And 14 more authors.
Nature Immunology | Year: 2016

Viral respiratory tract infections are the main causative agents of the onset of infection-induced asthma and asthma exacerbations that remain mechanistically unexplained. Here we found that deficiency in signaling via type I interferon receptor led to deregulated activation of group 2 innate lymphoid cells (ILC2 cells) and infection-associated type 2 immunopathology. Type I interferons directly and negatively regulated mouse and human ILC2 cells in a manner dependent on the transcriptional activator ISGF3 that led to altered cytokine production, cell proliferation and increased cell death. In addition, interferon-γ (IFN-γ) and interleukin 27 (IL-27) altered ILC2 function dependent on the transcription factor STAT1. These results demonstrate that type I and type II interferons, together with IL-27, regulate ILC2 cells to restrict type 2 immunopathology. © 2016 Nature America, Inc.


Shareck M.,University of Montréal | Shareck M.,Luniversite Of Montreal | Ellaway A.,Medical Research Council Social and Public Health science Unit
BMC Public Health | Year: 2011

Background: Smoking is a major public health problem worldwide. Research has shown that neighbourhood of residence is independently associated with the likelihood of individuals' smoking. However, a fine comprehension of which neighbourhood characteristics are involved and how remains limited. In this study we examine the relative contribution of objective (police-recorded) and subjective (resident-perceived) measures of neighbourhood crime on residents' smoking behaviours. Methods. Data from 2,418 men and women participating in the 2007/8 sweep of the West of Scotland Twenty-07 Study were analyzed. Smoking status and perceived crime were collected through face-to-face interviews with participants. Police-recorded crime rates were obtained from the Scottish Neighbourhood Statistics website at the datazone scale. Adjusted odds ratios and 95% confidence intervals were estimated for the likelihood of current smoking using logistic regression models. Adjusted mean daily amount smoked and F statistics were calculated using general linear models. Analyses were conducted for all respondents and stratified by sex and age cohort. Results: Compared to individuals living in low crime areas, those residing in an area characterized by high police-recorded crime rates or those perceiving high crime in their neighbourhood were more likely to be current smokers, after controlling for individual characteristics. The association with smoking was somewhat stronger for police-recorded crime than for perceived crime. Associations were only slightly attenuated when adjusting for either the objective or subjective crime measures, suggesting that these indicators may exert an independent influence on the risk of smoking. Stronger effects were observed for women compared to men. Police-recorded crime rates were more strongly related to smoking status among older respondents than among the younger cohort, whereas the strongest effect for perceived crime was observed among younger participants. Conclusions: Our findings highlight the relevance of paying attention to both objective and perceived neighbourhood crime measures when aiming to prevent smoking. © 2011 Shareck and Ellaway; licensee BioMed Central Ltd.


Pirkle C.M.,Laval University | De Albuquerque Sousa A.C.P.,Federal University of Rio Grande do Norte | Alvarado B.,Queen's University | Zunzunegui M.-V.,Luniversite Of Montreal
BMC Public Health | Year: 2014

Background: Early maternal age at first birth and elevated parity may have long-term consequences for the health of women as they age. Both are known risk factors for obstetrical complications with lifelong associated morbidities. They may also be related to diabetes and cardiovascular disease development. Methods. We examine the relationship between early maternal age at first birth, defined as ≤18 years of age, multiparity (>2 births), and poor physical performance (Short Physical Performance Battery ≤8) in community samples of women between 65 and 74 years of age from Canada, Albania, Colombia, and Brazil (N = 1040). Data were collected in 2012 to provide a baseline assessment for a longitudinal cohort called the International Mobility in Aging Study. We used logistic regression and general linear models to analyse the data. Results: Early maternal age at first birth is significantly associated with diabetes, chronic lung disease, high blood pressure, and poor physical performance in women at older ages. Parity was not independently associated with chronic conditions and physical performance in older age. After adjustment for study site, age, education, childhood economic adversity and lifetime births, women who gave birth at a young age had 1.75 (95% CI: 1.17 - 2.64) the odds of poor SPPB compared to women who gave birth > 18 years of age. Adjustment for chronic diseases attenuated the association between early first birth and physical performance. Results were weaker in Colombia and Brazil, than Canada and Albania. Conclusions: This study provides evidence that adolescent childbirth may increase the risk of developing chronic diseases and physical limitations in older age. Results likely reflect both the biological and social consequences of early childbearing and if the observed relationship is causal, it reinforces the importance of providing contraception and sex education to young women, as the consequences of early pregnancy may be life-long. © 2014 Pirkle et al.; licensee BioMed Central Ltd.


Boucher V.J.,University of Montréal | Ayad T.,Luniversite Of Montreal
Journal of Voice | Year: 2010

The lack of a physiological definition of "vocal fatigue" is a central problem in prevention research that seeks to identify effects of voice effort and acoustic signs of potential vocal fold lesions. This report presents a three-part synthesis of electromyographic (EMG) and acoustic observations from a study that served to define physiological features of vocal fatigue. The study used a technique of EMG to show that, contrary to views that laryngeal tissues are largely nonfatiguable, voice effort induces spectral compression in the contraction potentials of glottal adductors typically associated with muscle fatigue. In subsequent analyses, these observable attributes served to identify, in seven subjects with widely differing profiles, consistent signs of voice tremor and effects of vocal loading on the voice apparatus. Given the novel character of this criterion-based approach, the first part (section "The Rationale of Electromyographic Observations of Fatigue") describes the EMG technique and its usefulness in observing in vivo effects of vocal loading. The second part (section "Acoustic Signs of Fatigue in Muscles Involved in Voicing") summarizes the results of a test that served to determine whether the identified signs of tremor reflect muscle fatigue induced by voice effort or by "general fatigue" associated with waking hours. The third part (section "Compensatory Stabilization of Tremor and Effects of 'Critical Fatigue'") presents the results of analyses of compensatory effects in three laryngeal muscles by reference to EMG observations of one subject in conditions of vocal loading. Taken together, the results illustrate the benefits of an approach based on objective criterion changes in muscle fatigue and show that valid tremor signs may, nonetheless, be sporadic, given the varying compensatory behavior of muscles in fatiguing conditions. © 2010 The Voice Foundation.


Cohade C.,Luniversite Of Montreal
Seminars in Nuclear Medicine | Year: 2010

18F-fluorodeoxyglucose (FDG) is the radiotracer used in the vast majority of positron emission tomography (PET) cancer studies. FDG is a powerful radiotracer that provides valuable data in many cancer types. Normal FDG biodistribution is easily identified. In the PET-only era, physiological uptake provided important anatomical landmarks. However, the normal biodistribution of FDG is often variable and can be altered by intrinsic or iatrogenic factors. Recognizing these patterns of altered biodistribution is important for optimal FDG-PET interpretation. Altered FDG uptake in muscles, brown adipose tissue, bone marrow, the urinary tract, and the bowel is demonstrated in a significant proportion of patients, which can hide underlying malignant foci or mimic malignant lesions. The introduction of PET/computed tomography revolutionized PET imaging, bringing much-needed anatomical information. This modality allowed better characterization of some types of uptake, particularly brown adipose tissue FDG uptake. Different approaches to minimize interference from altered FDG biodistribution should be considered when performing PET scans. Otherwise, careful review and correlation of metabolic (FDG-PET) and anatomical (computed tomography) data should be performed to accurately characterize the foci of increased FDG uptake. © 2010 Elsevier Inc. All rights reserved.


Doucet P.,Luniversite Of Montreal
Santé mentale au Québec | Year: 2015

The author is the witness of a historic period of the psychiatry in the province of Quebec in Canada, widely francophone. He describes the context, the training in psychiatry, and the care. In Quebec, in the 1950s, the psychiatry did not exist as such as speciality. There was however a discipline: the neuropsychiatry. It was managed by the neurologists who agreed to take care of cases of psychiatry, which few doctors wanted to treat at this moment. The religious and rural society in Quebec of the 1950s got ready for the "Revolution tranquille". The latter finally burst after 1960. But the artistic environment was already in full excitement, and from 1948, it showed its opposition to the values which were current with the publication of the Refus global. Among the signatories of the latter, we find Bruno Cormier as medical student who will become, after 1950, a psychiatrist and a psychoanalyst. To become a psychiatrist, it was necessary to be trained as an intern in a residency program in the USA, UK or in France. The residency in the United States in the 1950s represented a great adventure for the young doctors of Quebec, especially for the French speakers. At the end of 1950s, the pharmacology emerged. However, he described his own experience as an observer or an actor with ECT, Sakel cure and about the lobotomy.

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