Medical Sciences Commons^™

Cholesterol-Mediated Dysfunction Of Surfactant Effects Of Surfactant Protein-A And Diet-Induced Hypercholesterolemia, Joshua Qua Hiansen

Electronic Thesis and Dissertation Repository

This thesis explored the effects of cholesterol and SP-A on surfactant function in vitro, and lung function in vivo. In the first experiment, we determined whether SP-A could mitigate cholesterol-mediated surfactant dysfunction. We hypothesized that SP-A can mitigate the surfactant inhibition caused by high cholesterol. In the second experiment, we tested the contribution of diet-induced serum hypercholesterolemia to surfactant composition and the development of lung injury in rats. We hypothesized that serum hypercholesterolemia would increase the amount of cholesterol in surfactant and would cause rats to develop more severe lung injury. Our results indicate that SP-A mitigates cholesterol-mediated surfactant …

Adjustment Of Pulmonary O2 Uptake, Muscle Deoxygenation And Metabolism During Moderate-Intensity Exercise Transitions Initiated From Low And Elevated Baseline Metabolic Rates, Joshua P. Nederveen

Electronic Thesis and Dissertation Repository

When instantaneous step-wise transitions within the moderate intensity domain are initiated from elevated metabolic rates, the rate of pulmonary oxygen uptake (V̇O_2p) adjustment is slowed, and the V̇O_2p gain (ΔV̇O_2p /ΔWR) is greater. This study sought to determine the relationship between V̇O_2p kinetics and metabolic activity and energy status during step transitions from low and elevated metabolic rates within the moderate intensity domain. Ten young men completed six double-step constant load cycling bouts, consisting of step-wise transitions from 20 W to 45% θ_L and 45% θ_L [lower step (LS)] to 90% θ_{L …}

Delayed Thrombus Resolution And Fibroproliferative Vascular Wound Healing From Deficiency Of Type Iii Collagen: A Paradoxical Mechanism For Tissue Fragility, Amy J. Reid

Dissertations & Theses (Open Access)

Vascular Ehlers-Danlos syndrome is a heritable disease of connective tissue caused by mutations in COL3A1, conferring a tissue deficiency of type III collagen. Cutaneous wounds heal poorly in these patients, and they are susceptible to spontaneous and catastrophic rupture of expansible hollow organs like the gut, uterus, and medium-sized to large arteries, which leads to premature death. Although the predisposition for organ rupture is often attributed to inherent tissue fragility, investigation of arteries from a haploinsufficient Col3a1 mouse model (Col3a1^+/-) demonstrates that mutant arteries withstand even supraphysiologic pressures comparably to wild-type vessels. We hypothesize that injury …

Characterizing Stomatin-Like Protein 2 And Its Role In Neuron Survival, Lisa A. Foris

Electronic Thesis and Dissertation Repository

Stomatin-like Protein 2 (SLP-2) has been identified as a stress-inducible transcript and has been shown to interact with and stabilize mitochondrial proteins. Since mitochondria are critical for neuronal function, we hypothesized that SLP-2 regulates neuron survival in response to stressful stimuli. A conditional SLP-2 knockout mouse (deletion) and the SN56 cell line (upregulation) were employed to study the role of SLP-2 in mitochondrial dynamics and neuron survival. SLP-2 deficient primary cortical neurons displayed significantly decreased levels of various mitochondrial respiratory chain proteins, indicating SLP-2 contributes to maintenance of mitochondrial membrane integrity. SLP-2 was up-regulated in response to oxidative stress and …

Improving Cardiac Repair By Stem Cell Factor Post-Myocardial Infarction, Fuli Xiang

Electronic Thesis and Dissertation Repository

Myocardial infarction (MI) occurs due to the complete occlusion of a coronary artery and is a leading cause of death, and a huge social and economic burden worldwide. Despite advances in treatment, patients still have a poor prognosis and there is a pressing need for strategies to improve cardiac repair post-MI. Stem cell factor (SCF), expressed by many cells and tissues including the myocardium, binds to its receptor, c-kit, and regulates the activity of c-kit-expressing cells. SCF has two isoforms: a soluble (S-SCF), and a membrane-associated isoform (M-SCF). M-SCF is more potent in supporting cell adhesion and survival. …

The Effects Of Hydrostatic Pressure On Early Endothelial Tubulogenic Processes, Ryan M. Underwood

Theses and Dissertations--Biomedical Engineering

The effects of mechanical forces on endothelial cell function and behavior are well documented, but have not been fully characterized. Specifically, fluid pressure has been shown to elicit physical and chemical responses known to be involved in the initiation and progression of endothelial cell-mediated vascularization. Central to the process of vascularization is the formation of tube-like structures. This process—tubulogenesis—is essential to both the physiological and pathological growth of tissues. Given the known effects of pressure on endothelial cells and its ubiquitous presence in the vasculature, we investigated pressure as a magnitude-dependent parameter for the regulation of endothelial tubulogenic activity. To …

Defining The Role Of Reactive Oxygen Species, Nitric Oxide, And Sphingolipid Signaling In Tumor Necrosis Factor - Induced Skeletal Muscle Weakness, Shawn Stasko

Theses and Dissertations--Physiology

In many chronic inflammatory diseases, patients suffer from skeletal muscle weakness, exacerbating their symptoms. Serum levels of tumor necrosis factor-alpha (TNF) and sphingomyelinase are increased, suggesting their possible role in the progression of this weakness. This dissertation focuses on the role that reactive oxygen species (ROS) and nitric oxide (NO) play in mediating TNF-induced skeletal muscle weakness and to what extent sphingolipid signaling mediates cellular response to TNF.

The first aim of this work was to identify which endogenous oxidant species stimulated by TNF contributes to skeletal muscle weakness. In C57BL/6 mice (n=38), intraperitoneal injection of TNF elicited a 25% …