Pathological Conditions, Signs and Symptoms Commons^™

Technical Adaptations For Cardiac Sodium Mri, Taylor L. Marcus

Electronic Thesis and Dissertation Repository

Cardiac sodium (Na⁺) MRI has the potential to unveil relationships between chronic kidney disease (CKD) and cardiovascular disease (CVD). Unfortunately, this modality requires many technical adaptations before it’s possible to extract and compare image data between individuals. This study investigated whether cardiac electrocardiogram (ECG) gating could improve image quality, and whether a uniform phantom could increase signal uniformity if a surface coil is used to acquire the image. Healthy participants were imaged with a custom-built surface coil and 3.0-T MR system. Cardiac gated images presented with a decreased signal-to-noise ratio (SNR), but intensity correction significantly increased image signal …

Characterizing The Cellular, Molecular, And Behavioural Pathology Of Repetitive Mtbi In A Human Tau Transgenic Mouse, Morgan A. Walker

Electronic Thesis and Dissertation Repository

After an episode of repetitive mild traumatic brain injury (rmTBI), many cellular and molecular cascades are initiated that result in the disruption of the structural and chemical integrity of the components in the brain, leading to the development of various cognitive deficits. The goal of this thesis was to evaluate a mouse model of concussion in order to study the relationship between rmTBI, GSK3β and tau phosphorylation, and behavioural outcomes in a transgenic mouse line expressing solely human tau. We found that there was increased phosphorylation of the two main regulatory sites on GSK3β, Tyr216 and Ser9, in the C57BL/6 …

Trna Regulation In Humans: The Cellular Effect Of A Pathological Hars Y454s Mutation, Rosan Kenana

Electronic Thesis and Dissertation Repository

tRNAs are the adapter molecules involved in translating the genetic code into functional protein in a living cell. tRNAs are charged with their cognate amino acids - by aminoacyl-tRNA synthetases (aaRS or ARS) - which are then transferred to a growing peptide in a process called mRNA translation. The efficiency of translation is dependent on the ratio of ARS enzymes to their cognate tRNAs and the availability of correctly amino acylated tRNAs. Disruptions of this process, caused by mutations in ARS genes, in particular, have been linked to complex inherited diseases. USH3B syndrome, a recessively inherited disorder among consanguineous families …

Determining The Relative Transmission Fitness Of Hiv-1 Subtypes A, B, C, And D, Spencer Yeung

Electronic Thesis and Dissertation Repository

There is in vivo evidence that suggests the genetic diversity of HIV-1 subtypes influence heterosexual transmission efficiency. To recapitulate sexual transmission in vitro, blocks of genital tissue were exposed to mixtures of genetically different subtype viruses. Migrating immune cells were collected and co-cultured with a CD4+ T-cell line permissive to HIV infection (PM1) to measure dendritic cell virus transfer; HIV-exposed tissues were cultured separately. Next generation sequencing (NGS) of HIV-1 DNA was used to quantify relative infection rates of the various challenge viruses, and to assess fitness differences in infection of the tissue vs. migratory/T cell co-cultures. Our results …

Effects Of Maternal Protein Restriction On The Pulmonary Surfactant System During The Early Life And Adulthood, Reza Khazaee

Electronic Thesis and Dissertation Repository

Fetal growth restriction (FGR) is defined by low birth weight and contributes to a variety of adult-onset diseases with different severities between males and females. However, the effects of FGR on the pulmonary surfactant are not fully elucidated. In this thesis, first, we investigated the FGR effects on the lung function and the surfactant system at the early postnatal life. It was hypothesized that FGR contributes to alterations of lung mechanics and the surfactant system during the neonatal period. Second, we assessed the FGR effects on the surfactant system in response to sepsis in adulthood. It was hypothesized that FGR …

The Epidemiology Of Infective Endocarditis Among People Who Inject Drugs In London, Ontario., Brian Hallam

Electronic Thesis and Dissertation Repository

Infective endocarditis is an infectious disease that affects the valves of the heart. Injection drug use is currently a leading risk factor among patients with endocarditis. We conducted a prospective study using data from hospital chart records among patients with endocarditis in London, Ontario, which has a relatively high prevalence of people who inject drugs to assess the severity of the issue and the major risk factors of mortality pertaining to this population. This study had a sample size of 353 and included a review of the incidence of admissions of endocarditis, as well as a survival analysis, using both …

Role Of Long Noncoding Rnas In Diabetic Complications, Anu Alice Thomas

Electronic Thesis and Dissertation Repository

LncRNAs, recently found to be pervasively transcribed in the genome, can play key roles in epigenetic modifications during gene transcription. Their role in diabetic complications are however not clear.

Using array analysis, we identified alterations of two lncRNAs in high glucose (25mM/L,HG) treated retinal endothelial cells (HRECs). ANRIL expressions were further measured with or without siRNA knockdown in ECs. ANRIL knockout (KO) mice with or without streptozotocin (STZ)-induced diabetes were also investigated for mRNA and protein expression of VEGF and ECM proteins FN and Col1α4. ANRIL knockdown prevented glucose-induced increased VEGF, FN and Col1α4 levels. Comparable results were observed in …

A Clinico-Pathological Study Of The Structural And Functional Changes In The Retina And Optic Nerve Following Diabetic Retinopathy Treatments, Richard Filek

Electronic Thesis and Dissertation Repository

Diabetic retinopathy (DR) is the result of microvascular changes in the retina due to hyperglycemia which alter the blood-retinal barrier (BRB). The increased permeability of BRB results in the accumulation of extracellular fluid, the development of diabetic macular edema (DME) and capillary occlusion. Capillary occlusion results in retinal ischemia which increases vascular endothelial growth factor (VEGF) levels, increases vascular permeability and results in neovascularization in proliferative diabetic retinopathy (PDR) patients. The treatments clinically used for DR are panretinal photocoagulation (PRP) for PDR and injectable vascular endothelial growth factor inhibitors (anti-VEGFs) for DME.

The safety of PRP and anti-VEGF therapy on …

Investigating The Mechanism Of Ectopic Mineralization In A Mouse Model Of Diffuse Idiopathic Skeletal Hyperostosis (Dish), Neil A. Tenn

Electronic Thesis and Dissertation Repository

Equilibrative nucleoside transporter 1 (ENT1) transfers adenosine across plasma membranes. Mice lacking ENT1 (ENT1^-/-) develop pathological calcification of spinal tissues resembling diffuse idiopathic skeletal hyperostosis (DISH) in humans. Our goal was to investigate the mechanism underlying ectopic mineralization in ENT1^-/- mice. We detected aberrant alkaline phosphatase (ALP, promoter of mineralization) activity in the annulus fibrosus (AF) of ENT1^-/- mice. In vitro, AF cells from ENT1^-/- mice exhibited greater ALP activity than cells from wild-type (WT) mice. Inhibition of ENT1 in the presence of extracellular adenosine modeled in WT cells the phenotype of ENT1 …