Matching Items (3)
Description
The goal of the works presented in this volume is to develop a magnetic resonance imaging (MRI) probe for non-invasive detection of extracellular matrix (ECM) underlying fenestrated endothelia. The ECM is the scaffold that supports tissue structure in all organs. In fenestrated structures the such as the kidney glomerulus and the hepatic sinusoid the ECM serves a unique role in blood filtration and is directly exposed to blood plasma. An assessment of the ECM in fenestrated organs such as the kidney and liver reports on the organ's ability to filter blood - a process critical to maintaining homeostasis. Unfortunately, clinical assessment of the ECM in most organs requires biopsy, which is focal and invasive. This work will focus on visualizing the ECM underlying fenestrated endothelia with natural nanoparticles and MRI. The superparamagnetic ferritin protein has been proposed as a useful naturally-derived, MRI-detectable nanoparticle due to its biocompatibility, ease of functionalization, and modifiable metallic core. We will show that cationized ferritin (CF) specifically binds to the anionic proteoglycans of the ECM underlying fenestrated endothelia and that its accumulation is MRI-detectable. We will then demonstrate the use of CF and MRI in identifying and measuring all glomeruli in the kidney. We will also explore the toxicity of intravenously injected CF and consider other avenues for its application, including detection of microstructural changes in the liver due to chronic liver disease. This work will show that CF is useful in detected fenestrated microstructures in small animals and humans alike, indicating that CF may find broad application in detecting and monitoring disease in both preclinical and clinical settings.
ContributorsBeeman, Scott (Author) / Bennett, Kevin M (Thesis advisor) / Kodibagkar, Vikram D (Committee member) / Fayad, Zahi A (Committee member) / Pizziconi, Vincent B (Committee member) / Pipe, James G (Committee member) / Arizona State University (Publisher)
Created2012
Description
In 1984, President Ronald Reagan passed the National Organ Transplant Act (NOTA) to create an organ national registry and prohibit the purchase and selling of specific organs. Despite the enactment, the kidney shortage remains. This leaves 13 people on the waiting list dying prematurely every day while waiting for a kidney donation. This revision of the amendment permits the selling and purchase of kidneys in order to decrease kidney organ trafficking and help alleviate the kidney shortage. An argument on why this amendment should be considered is explained through statistics, ethics, socioeconomic, market fundamentalism, and legislative history. These sections find ample support for amending the National Organ Transplant Act of 1984 to include the sale and purchase of kidneys.
ContributorsStarrs, Kaelyn (Author) / O'Flaherty, Kathleen (Thesis director) / Weins, William (Committee member) / Barrett, The Honors College (Contributor) / School of Criminology and Criminal Justice (Contributor) / School of Social Work (Contributor) / Historical, Philosophical & Religious Studies, Sch (Contributor)
Created2023-05
Description
The need of organs for transplantation has become an increasing medical need due to a limited donor organ supply. Many organs fail within 10 years due to acute and chronic rejection. Acute or antibody mediated rejection leads to decreased long term graft survival and increases the need for a repeat transplant. In prior work, reducing endothelial heparan sulfation and blockade of chemokine-glycosaminoglycan (GAG) interaction with Myxomavirus-derived protein, M-T7, reduced aortic and renal graft vascular inflammation and rejection. Conditional endothelial Ndst1 deficiency and inhibition of chemokine-GAG interaction reduces early allograft damage and suggest new therapeutic options for graft rejection. Here acute renal rejection was examined in grafts with conditional endothelial N-deacetylase-N-sulfotransferase-1 knockout (Ndst1-/-) and in wildtype (WT) C57Bl6/J grafts treated with saline, M-T7, antisense oligonucleotides (ASO) for Ndst1 or a scrambled ASO control. Viruses have a highly adaptive ability to evade hosts defense and immune response. The immunomodulatory proteins derived from viruses provide potential therapeutic uses to alleviate this need for organs. The Myxoma virus derived protein M-T7 is a promising therapeutic for reducing kidney transplant rejection. Orthotopic transplantations in mice are extremely difficult and costly because they require a highly trained microsurgeon. This kidney to kidney subcapsular and subcutaneous transplant model is a practical and simpler method that requires fewer mice, one kidney can be used for transplants in 6 or more mice and there is much lower morbidity, pain and mortality. Heterotopic transplantation of allografts is a simple model for preliminary testing of treatments for early inflammation, ischemia, and graft rejection. Subcapsular kidney transplantation provides a first step approach to test virus-derived proteins as potential treatments to reduce transplant rejection and inflammation. This project reports on a broadly applicable platform on which to rapidly and conveniently test new treatments for transplant rejection. This finding will significantly lower the barrier to entry for labs which are interested in translating their laboratory findings to animal models of organ transplantation which is a complex surgical procedure, and thus accelerate the bench-to-bedside translation of novel, putative treatments for transplant rejection as an initial screening tool.
ContributorsBurgin, Michelle A (Author) / McFadden, Douglas (Thesis advisor) / Lucas, Alexandra R (Thesis advisor) / Yaron, Jordan R (Committee member) / Lim, Efrem S. (Committee member) / Hogue, Brenda G (Committee member) / Arizona State University (Publisher)
Created2020