Institution
Sunnybrook Health Sciences Centre
Healthcare•Toronto, Ontario, Canada•
About: Sunnybrook Health Sciences Centre is a healthcare organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Breast cancer. The organization has 7689 authors who have published 15236 publications receiving 523019 citations. The organization is also known as: Sunnybrook.
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TL;DR: The adhesive phenotype and cell surface protein profile of S. aureus can be modified by V8 protease activity, and a limited number of other high-molecular-weight cell surface proteins were also sensitive to V 8 protease.
Abstract: The amount of cell surface fibronectin (Fn)-binding protein (FnBP) adhesin expressed by Staphylococcus aureus is maximal during exponential growth but disappears rapidly as the culture progresses into stationary phase. To identify factors responsible for the loss of cell surface FnBP, a culture of S. aureus L170, which shows high levels of Fn binding, was supplemented at the time of inoculation with concentrated stationary-phase supernatant from S. aureus L530, a strain which binds Fn poorly. The resulting exponential-phase cells were devoid of FnBP. The factor responsible for this activity was purified from the culture supernatant and identified as V8 protease. When cultured with 375 ng of exogenous V8 protease ml(-1), exponential-phase cells of S. aureus L170 were devoid of cell surface FnBP, and concentrations as low as 23 ng x ml(-1) resulted in reduced amounts of FnBP. Addition of the protease inhibitor alpha2-macroglobulin to the culture medium prevented the growth-phase-dependent loss of cell surface FnBP, whereas growth with exogenous V8 protease resulted in reduced adherence to the solid-phase N-terminal fragment of Fn and to the extracellular matrix synthesized by fetal rabbit lung fibroblasts. Although FnBP was extremely sensitive to V8 protease, exogenous protease did not exert a significant influence on the amount of cell surface protein A. However, a limited number of other high-molecular-weight cell surface proteins were also sensitive to V8 protease. Therefore, both the adhesive phenotype and cell surface protein profile of S. aureus can be modified by V8 protease activity.
168 citations
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TL;DR: The possibility of using antiadhesive agents to reverse multicellular-dependent Taxol resistance in certain circumstances as a potential means of increasing the initial efficiency of Taxol therapy against ovarian carcinoma is raised.
Abstract: Tumor cells grown as multicellular spheroids are known to be intrinsically more resistant to a large and diverse array of anticancer chemotherapeutic drugs compared to the same cells grown as dispersed monolayer cell cultures. Some drugs, however, seem relatively insensitive to this multicellular drug resistance, e.g., cisplatinum. Whether the cytotoxic effects of Taxol, an anticancer drug of growing importance in the treatment of breast and ovarian carcinomas, are diminished by multicellular growth conditions is unknown. To study this question, we examined the relative sensitivity of a panel of four different human ovarian carcinoma cell lines to either Taxol or cisplatinum. Upon exposure to Taxol, all the cell lines manifested a relative drug-resistant phenotype when grown as multicellular tumor spheroids, compared to the same cells grown as sparse monolayer cultures. This multicellular-dependent drug-resistant phenotype was not observed when the same cells were exposed to cisplatinum for an equivalent length of time. Monolayer but not spheroid cultures exposed to Taxol demonstrated an accumulation of cells at G2-M and a sub-G1 apoptotic region. In addition, Taxol-induced apoptosis was detected in monolayer conditions but not in the spheroid cultures. The relative sensitivity of the monolayer cell cultures was associated with a decrease in bcl-X(L) protein levels after Taxol exposure, an effect not observed in drug-exposed spheroids. Taken together, these results suggest that some aspects of intrinsic Taxol resistance in ovarian carcinoma may be due to multicellular-dependent or -associated mechanisms. This raises the possibility of using antiadhesive agents to reverse multicellular-dependent Taxol resistance in certain circumstances as a potential means of increasing the initial efficiency of Taxol therapy against ovarian carcinoma.
168 citations
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TL;DR: The three-variable NRF model is preferred because of its relative simplicity and the ability to separate patients into three prognostic groups and to predict their survival was similar using both SPS and NRF methods.
Abstract: Purpose To derive and validate a simple predictive model for survival of patients with metastatic cancer attending a palliative radiotherapy clinic. Patients and Methods We described previously a model predicting survival of patients referred for palliative radiotherapy using six prognostic factors: primary cancer site, site of metastases, Karnofsky performance score (KPS), and the fatigue, appetite, and shortness of breath subscales from the Edmonton Symptom Assessment Scale. Here we simplified the model to include only three factors: primary cancer site, site of metastases, and KPS. Each factor was assigned a value proportional to its prognostic weight, and the weighted scores for each patient were summed to obtain a survival prediction score (SPS). Patients were also grouped according to their number of risk factors (NRF): nonbreast cancer, metastases other than bone, and KPS ≤ 60. The three- and six- variable models were evaluated for their ability to predict survival in patients referred during a dif...
168 citations
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TL;DR: It is concluded that the exoproteins identified herein likely account in part for the success of CA‐MRSA as a human pathogen.
Abstract: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a threat to human health worldwide. Although progress has been made, mechanisms of CA-MRSA pathogenesis are poorly understood and a comprehensive analysis of CA-MRSA exoproteins has not been conducted. To address that deficiency, we used proteomics to identify exoproteins made by MW2 (USA400) and LAC (USA300) during growth in vitro. Two hundred and fifty unique exoproteins were identified by 2-dimensional gel electrophoresis coupled with automated direct infusion-tandem mass spectrometry (ADI-MS/MS) analysis. Eleven known virulence-related exoproteins differed in abundance between the strains, including alpha-haemolysin (Hla), collagen adhesin (Cna), staphylokinase (Sak), coagulase (Coa), lipase (Lip), enterotoxin C3 (Sec3), enterotoxin Q (Seq), V8 protease (SspA) and cysteine protease (SspB). Mice infected with MW2 or LAC produced antibodies specific for known or putative virulence factors, such as autolysin (Atl), Cna, Ear, ferritin (Ftn), Lip, 1-phosphatidylinositol phosphodiesterase (Plc), Sak, Sec3 and SspB, indicating the exoproteins are made during infection in vivo. We used confocal microscopy to demonstrate aureolysin (Aur), Hla, SspA and SspB are produced following phagocytosis by human neutrophils, thereby linking exoprotein production in vitro with that during host–pathogen interaction. We conclude that the exoproteins identified herein likely account in part for the success of CA-MRSA as a human pathogen.
168 citations
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Montreal General Hospital1, McGill University2, Heart and Stroke Foundation of Canada3, University of Western Ontario4, University of Alberta5, Dalhousie University6, Valley Regional Hospital7, McMaster University8, Kelowna General Hospital9, University of British Columbia10, Université de Montréal11, University of Toronto12, Thunder Bay Regional Health Sciences Centre13, University of Ottawa14, University of Manitoba15, Boston Children's Hospital16, Population Health Research Institute17, Sunnybrook Health Sciences Centre18
TL;DR: The 2017 update of The Canadian Stroke Best Practice Recommendations for the Secondary Prevention of Stroke is a collection of current evidence-based recommendations intended for use by clinicians across a wide range of settings to provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors.
Abstract: The 2017 update of The Canadian Stroke Best Practice Recommendations for the Secondary Prevention of Stroke is a collection of current evidence-based recommendations intended for use by clinicians across a wide range of settings. The goal is to provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors. Recommendations include those related to diagnostic testing, diet and lifestyle, smoking, hypertension, hyperlipidemia, diabetes, antiplatelet and anticoagulant therapies, carotid artery disease, atrial fibrillation, and other cardiac conditions. Notable changes in this sixth edition include the development of core elements for delivering secondary stroke prevention services, the addition of a section on cervical artery dissection, new recommendations regarding the management of patent foramen ovale, and the removal of the recommendations on management of sleep apnea. The Canadian Stroke Best Practice Recommendations include a range of supporting materials such as implementation resources to facilitate the adoption of evidence to practice, and related performance measures to enable monitoring of uptake and effectiveness of the recommendations. The guidelines further emphasize the need for a systems approach to stroke care, involving an interprofessional team, with access to specialists regardless of patient location, and the need to overcome geographic barriers to ensure equity in access within a universal health care system.
168 citations
Authors
Showing all 7765 results
Name | H-index | Papers | Citations |
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Gordon B. Mills | 187 | 1273 | 186451 |
David A. Bennett | 167 | 1142 | 109844 |
Bruce R. Rosen | 148 | 684 | 97507 |
Robert Tibshirani | 147 | 593 | 326580 |
Steven A. Narod | 134 | 970 | 84638 |
Peter Palese | 132 | 526 | 57882 |
Gideon Koren | 129 | 1994 | 81718 |
John B. Holcomb | 120 | 733 | 53760 |
Julie A. Schneider | 118 | 492 | 56843 |
Patrick Maisonneuve | 118 | 582 | 53363 |
Mitch Dowsett | 114 | 478 | 62453 |
Ian D. Graham | 113 | 700 | 87848 |
Peter C. Austin | 112 | 657 | 60156 |
Sandra E. Black | 104 | 681 | 51755 |
Michael B. Yaffe | 102 | 379 | 41663 |