McGill University

About: McGill University is a education organization based out in Montreal, Quebec, Canada. It is known for research contribution in the topics: Population & Poison control. The organization has 72688 authors who have published 162565 publications receiving 6966523 citations. The organization is also known as: Royal institution of advanced learning & University of McGill College.

Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma

Abstract: Glioblastoma multiforme (GBM) is a lethal brain tumour in adults and children. However, DNA copy number and gene expression signatures indicate differences between adult and paediatric cases. To explore the genetic events underlying this distinction, we sequenced the exomes of 48 paediatric GBM samples. Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway were identified in 44% of tumours (21/48). Recurrent mutations in H3F3A, which encodes the replication-independent histone 3 variant H3.3, were observed in 31% of tumours, and led to amino acid substitutions at two critical positions within the histone tail (K27M, G34R/G34V) involved in key regulatory post-translational modifications. Mutations in ATRX (α-thalassaemia/mental retardation syndrome X-linked) and DAXX (death-domain associated protein), encoding two subunits of a chromatin remodelling complex required for H3.3 incorporation at pericentric heterochromatin and telomeres, were identified in 31% of samples overall, and in 100% of tumours harbouring a G34R or G34V H3.3 mutation. Somatic TP53 mutations were identified in 54% of all cases, and in 86% of samples with H3F3A and/or ATRX mutations. Screening of a large cohort of gliomas of various grades and histologies (n = 784) showed H3F3A mutations to be specific to GBM and highly prevalent in children and young adults. Furthermore, the presence of H3F3A/ATRX-DAXX/TP53 mutations was strongly associated with alternative lengthening of telomeres and specific gene expression profiles. This is, to our knowledge, the first report to highlight recurrent mutations in a regulatory histone in humans, and our data suggest that defects of the chromatin architecture underlie paediatric and young adult GBM pathogenesis.

The Mindful Body: A Prolegomenon to Future Work in Medical Anthropology

Abstract: Conceptions of the body are central not only to substantive work in medical anthropology, but also to the philosophical underpinnings of the entire discipline of anthropology, where Western assumptions about the mind and body, the individual and society, affect both theoretical viewpoints and research paradigms. These same conceptions also influence ways in which health care is planned and delivered in Western societies. In this article we advocate the deconstruction of received concepts about the body and begin this process by examining three perspectives from which the body may be viewed: (1) as a phenomenally experienced individual body-self; (2) as a social body, a natural symbol for thinking about relationships among nature, society, and culture; and (3) as a body politic, an artifact of social and political control. After discussing ways in which anthropologists, other social scientists, and people from various cultures have conceptualized the body, we propose the study of emotions as an area of inquiry that holds promise for providing a new approach to the subject.

Equipoise and the ethics of clinical research.

Abstract: The ethics of clinical research requires equipoise--a state of genuine uncertainty on the part of the clinical investigator regarding the comparative therapeutic merits of each arm in a trial. Should the investigator discover that one treatment is of superior therapeutic merit, he or she is ethically obliged to offer that treatment. The current understanding of this requirement, which entails that the investigator have no "treatment preference" throughout the course of the trial, presents nearly insuperable obstacles to the ethical commencement or completion of a controlled trial and may also contribute to the termination of trials because of the failure to enroll enough patients. I suggest an alternative concept of equipoise, which would be based on present or imminent controversy in the clinical community over the preferred treatment. According to this concept of "clinical equipoise," the requirement is satisfied if there is genuine uncertainty within the expert medical community--not necessarily on the part of the individual investigator--about the preferred treatment.

Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group

Abstract: The monoclonal gammopathies are a group of disorders associated with monoclonal proliferation of plasma cells. The characterization of specific entities is an area of difficulty in clinical practice. The International Myeloma Working Group has reviewed the criteria for diagnosis and classification with the aim of producing simple, easily used definitions based on routinely available investigations. In monoclonal gammopathy of undetermined significance (MGUS) or monoclonal gammopathy, unattributed/unassociated (MG[u]), the monoclonal protein is < 30 g/l and the bone marrow clonal cells < 10% with no evidence of multiple myeloma, other B-cell proliferative disorders or amyloidosis. In asymptomatic (smouldering) myeloma the M-protein is greater than or equal to 30 g/l and/or bone marrow clonal cells greater than or equal to 10% but no related organ or tissue impairment (ROTI)(end-organ damage), which is typically manifested by increased calcium, renal insufficiency, anaemia, or bone lesions (CRAB) attributed to the plasma cell proliferative process. Symptomatic myeloma requires evidence of ROTI. Non-secretory myeloma is characterized by the absence of an M-protein in the serum and urine, bone marrow plasmacytosis and ROTI. Solitary plasmacytoma of bone, extramedullary plasmacytoma and multiple solitary plasmacytomas (+/- recurrent) are also defined as distinct entities. The use of these criteria will facilitate comparison of therapeutic trial data. Evaluation of currently available prognostic factors may allow better definition of prognosis in multiple myeloma.

Some Studies of the Protein-Binding of Steroids and Their Application to the Routine Micro and Ultramicro Measurement of Various Steroids in Body Fluids by Competitive Protein-Binding Radioassay

Abstract: A method utilizing the steroid-binding properties of corticosteroid-binding globulin (CBG, transcortin) was described in 1963 for the routine determination of corticoids in 1 ml of plasma (J Clin Endocr 23: 293, 1963) and later modified to reduce the time required (J Clin Endocr 24: 919, 1964). A 100-fold increase in sensitivity has now been achieved by using tritiated steroids in place of 14C-labeled steroids, by utilizing the CBG's of species other than man, and by using adsorption in place of dialysis or gel filtration. The use of several insoluble adsorbing agents (Fuller's earth, Florisil, coated charcoal) to separate protein-bound and unbound steroids was investigated and their effects on specificity were studied. The use of these techniques in plasma, urine and cerebrospinal fluid was vindicated. With these methods, cortisol can be measured routinely in 0.01 ml of plasma or 0.1 ml of cerebrospinal fluid, and progesterone in 0.3 ml of plasma. Compound S (11-desoxycortisol), corticosterone, ...