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Full-Text Articles in Medical Specialties

Role Of Cerebrovascular Abnormality In Neurodegenerative Disease And Subcortical Ischemic Disease: Ct Perfusion And Pet Imaging, Jun Yang Sep 2015

Role Of Cerebrovascular Abnormality In Neurodegenerative Disease And Subcortical Ischemic Disease: Ct Perfusion And Pet Imaging, Jun Yang

Electronic Thesis and Dissertation Repository

Clinical studies indicate that about 30% ~ 50% of patients have cognitive impairment after the first or recurrent stroke. Ischemic injury, particularly subcortical lesions, caused by stroke has been demonstrated to further exacerbate cognitive impairment of Alzheimer’s disease (AD) and vascular dementia. However, the mechanisms whereby cerebrovascular abnormalities contribute to neurodegeneration at early stage of disease and eventually to cognitive decline remain unclear. CT perfusion and positron emission tomography (PET) were used to investigate early mechanisms in a rat comorbid model of cerebral ischemia (CI) and β-amyloid (Aβ, a pathological hallmark of AD) toxicity, and in patients with small subcortical …


A Randomized Clinical Trial To Compare The Effect Of Non Operative Treatment With And Without Autologous Conditioned Plasma (Acp) On Healing And Function In Patients With Achilles Tendon Ruptures, Tyler M. Pratt Sep 2015

A Randomized Clinical Trial To Compare The Effect Of Non Operative Treatment With And Without Autologous Conditioned Plasma (Acp) On Healing And Function In Patients With Achilles Tendon Ruptures, Tyler M. Pratt

Electronic Thesis and Dissertation Repository

The purpose of this study was to determine whether there is evidence to support conducting a larger randomized control trial (RCT) to compare the non-operative treatment of Achilles tendon (AT) ruptures with or without Autologous Conditioned Plasma (ACP®). Twenty-four patients were randomized to receive an ACP® or saline injection within seven days and again at two weeks post-rupture. Tendon healing was longitudinally evaluated using ultrasound (US) and magnetic resonance imaging (MRI). Functional and patient-reported quality of life measures were also assessed. A small sample size limited our ability to detect statistically significant differences. The mean rankings of healing were slightly …


Interpretation Of Mutations, Expression, Copy Number In Somatic Breast Cancer: Implications For Metastasis And Chemotherapy, Stephanie Dorman Sep 2015

Interpretation Of Mutations, Expression, Copy Number In Somatic Breast Cancer: Implications For Metastasis And Chemotherapy, Stephanie Dorman

Electronic Thesis and Dissertation Repository

Breast cancer (BC) patient management has been transformed over the last two decades due to the development and application of genome-wide technologies. The vast amounts of data generated by these assays, however, create new challenges for accurate and comprehensive analysis and interpretation. This thesis describes novel methods for fluorescence in-situ hybridization (FISH), array comparative genomic hybridization (aCGH), and next generation DNA- and RNA-sequencing, to improve upon current approaches used for these technologies. An ab initio algorithm was implemented to identify genomic intervals of single copy and highly divergent repetitive sequences that were applied to FISH and aCGH probe design. FISH …


Characterization Of The Atsr/Atst Global Regulatory Pathway In Burkholderia Ceocepacia, Maryam Khodai-Kalaki Aug 2015

Characterization Of The Atsr/Atst Global Regulatory Pathway In Burkholderia Ceocepacia, Maryam Khodai-Kalaki

Electronic Thesis and Dissertation Repository

Phosphorylation cascades governed by two-component signal transduction systems provide key signalling mechanisms in bacteria, simple eukaryotes and higher plants, allowing them to translate signals into adaptive responses. These regulatory pathways consist of a transmembrane sensor protein that responds to an environmental cue leading to autophosphorylation, followed by the transfer of the phosphate to a cytoplasmic response regulator. Here, I study AtsR, a membrane-bound hybrid sensor kinase of Burkholderia cenocepacia, that negatively regulates quorum sensing related virulence factors such as biofilm, type 6-secretion and protease secretion. B. cenocepacia is a Gram-negative opportunistic pathogen which causes severe, chronic respiratory infections in …


A Clinically Relevant Relevant Post-Traumatic Osteoarthritis Mouse Model, Chantel P. Arce Aug 2015

A Clinically Relevant Relevant Post-Traumatic Osteoarthritis Mouse Model, Chantel P. Arce

Electronic Thesis and Dissertation Repository

Osteoarthritis affects 13-20% of Canadians with the majority being under 65years of age. Post-traumatic osteoarthritis (PTOA) is of great concern in young athletes following knee injury. Current research attempts at modeling the disease fall short. This study aimed to incorporate two important aspects of injury, the nature of the injury and the post-injury standard of care in humans, to a model of PTOA in mice. The study validated a non-invasive protocol to elicit an anterior cruciate ligament (ACL) injury at varying loading speeds addressing the closed capsule nature of an ACL injury that occurs in humans. Secondly, we proposed a …


Kidney Injury Molecule-1 Signalling In Ischemic Acute Kidney Injury And Phagocytosis, Ola Z. Ismail Aug 2015

Kidney Injury Molecule-1 Signalling In Ischemic Acute Kidney Injury And Phagocytosis, Ola Z. Ismail

Electronic Thesis and Dissertation Repository

Acute kidney injury (AKI) is defined by the rapid loss of kidney function due to tissue damage. It affects 10-30 % of hospitalized patients and is independently associated with increased morbidity and mortality. Ischemia-reperfusion injury (IRI) is the most common pathoetiological mechanism of AKI, whereby tissue injury is mediated by reactive oxygen species. Ischemic AKI leads to the rapid upregulation of a transmembrane protein, kidney injury molecule-1 (KIM-1) on the apical membrane of proximal tubular epithelial cells (TECs). Previous work from our group and others demonstrated that the extracellular domain of KIM-1 specifically binds to phosphatidylserine on apoptotic cells, thereby …


Development Of A Small Animal Conformal Irradiator With Dual Energy X-Ray Computed Tomography Imaging For Kilovoltage Dosimetry, Michael D. Jensen Aug 2015

Development Of A Small Animal Conformal Irradiator With Dual Energy X-Ray Computed Tomography Imaging For Kilovoltage Dosimetry, Michael D. Jensen

Electronic Thesis and Dissertation Repository

External beam radiotherapy has become technically sophisticated with image guided radiation therapy (IGRT) and intensity modulated radiation therapy (IMRT). These technologies allow for precise delivery of radiation to geometric targets in cancer patients. However, many questions remain on how to best define targets based on biological information, such as functional imaging, and how to combine radiation with other cancer therapies. To help answer these questions, small animal preclinical studies are needed to generate data to inform clinical trials. However, the precise radiation delivery capabilities of IGRT and IMRT have not been available in the preclinical labs. To enable translational experiments …


The Role Of Bone Sialoprotein In The Tendon-Bone Insertion, Ryan M. Marinovich Jul 2015

The Role Of Bone Sialoprotein In The Tendon-Bone Insertion, Ryan M. Marinovich

Electronic Thesis and Dissertation Repository

Tendons and ligaments insert into bone through a transitional tissue termed the enthesis which is susceptible to injury and difficult to repair. Entheses contain a region of calcified fibrocartilage (CFC), however mineral-associated proteins in this tissue remain poorly characterized. Bone sialoprotein (BSP) is a phosphoprotein associated with mineralizing tissues. In these studies BSP was identified in the CFC of entheses by immunohistochemistry. Analysis of the entheses of Bsp-/- mice indicate abnormalities in the CFC. Compared to controls, the CFC of the quadriceps tendon enthesis is 28% and 41 % longer in 15 week and 14 month old Bsp-/- …


Kiss1r Signaling Promotes Breast Cancer Drug Resistance, Alexandra J. Blake Jun 2015

Kiss1r Signaling Promotes Breast Cancer Drug Resistance, Alexandra J. Blake

Electronic Thesis and Dissertation Repository

Kisspeptins signal via the G-protein coupled receptor, KISS1R, and act as metastasis suppressors in numerous cancers. In estrogen receptor (ERα)-negative breast cancer cells, however, KISS1R signaling promotes cell invasion by activating the epidermal growth factor receptor (EGFR). Unfortunately, clinical success of anti-EGFR therapeutics has been limited, as patients often develop drug resistance. Recently, another receptor tyrosine kinase, AXL, has been shown to promote breast cancer drug resistance. We hypothesize that KISS1R promotes EGFR expression and induces breast cancer drug resistance. We demonstrated that KISS1R increases EGFR transcription, by increasing SP-1 binding to the EGFR promoter, as demonstrated by chromatin immunoprecipitation …


Investigating The Role Of Hydrogen Sulfide In The Survival, Growth And Angiogenic Potential Of Clear Cell Renal Cell Carcinoma Cell Lines And Xenografts, Eric Sonke Jun 2015

Investigating The Role Of Hydrogen Sulfide In The Survival, Growth And Angiogenic Potential Of Clear Cell Renal Cell Carcinoma Cell Lines And Xenografts, Eric Sonke

Electronic Thesis and Dissertation Repository

Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel-Lindau (VHL)-deficiency, resulting in pseudohypoxic, angiogenic and glycolytic tumours. Hydrogen sulfide (H2S) is an endogenously-produced gasotransmitter that accumulates under hypoxia and has been shown to be pro-angiogenic and cytoprotective in cancer. It was hypothesized that H2S levels are elevated in VHL-deficient ccRCC, contributing to survival, metabolism, and angiogenesis. Using H2S-specific probes, it was found that H2S levels were higher in VHL-deficient ccRCC cell lines compared to cells with wild-type VHL. Inhibition of H2S-producing enzymes could reduce the proliferation, metabolism …