Browsing by Subject "Fusion"
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Item Experimental discovery of surgical guidelines for cervical disc augmentation(2012-05) Mehta, Hitesh PrathivirajIntervertebral disc degeneration of the cervical spine affects over one half of all individuals over the age of 40 years and the last decade has seen an alarming increase in cervical disc degenerative disease related surgeries. In spite of newer technological advancements in devices for disc degeneration disease, spinal disc replacement and fusion, revision surgery rates have remained unchanged. 90% of the disc replacement revisions and 50% of fusion related revision can be attributed to improper device selection. Therefore, the objective of this research is to evaluate disc arthroplasty (replacement) and arthrodesis (fusion) devices and identify optimal implant size (height) selection criteria for biomechanical competence in force transmission, motion, and neurologic tissue protection. Eleven osteo-ligamentous human cadaver cervical spines were biomechanically evaluated after surgical augmentation with different sized implants for both arthroplasty and arthrodesis. The biomechanical outcomes measured were range of motion, neutral zone, stiffness, articular pillar strains, facet forces and intervertebral foramen area. Increased disc distraction was found to increase lordosis of the spine, increase compressive strains in articular pillars and increase in intervertebral foramen area. The kinematics outcomes were surgery type and implant size dependent where fusion lead to decreased range of motion, while arthroplasty maintained the range of motion with differential outcomes based upon the size of the implant. The integration of these biomechanical data demonstrate an implant size /spacer height relationship with direct clinical importance and the ability to guide clinical decision making so as to reduce revision surgery due to deviant biomechanical function.Item Side Population Cells in the Adult Heart(2018-06) Yellamilli, AmrithaThe clinical outcomes for heart failure remain poor because current therapies do not address a critical feature of heart failure – loss of functional cardiomyocytes. To decrease the morbidity and mortality of patients with heart failure, multiple strategies are being developed to replace dead cardiomyocytes with new, functional ones. Adult stem cell transplantation studies have had modest clinical benefits primarily attributed to paracrine effects on several endogenous processes including cardiac regeneration. Many cardiac progenitor cell populations have been isolated from the adult mammalian heart and studied in cell culture or after transplantation; however, their roles in endogenous cardiac regeneration are highly contested. In the thesis work presented here, we used the side population phenotype as an unbiased approach to determine whether an endogenous progenitor cell population exists in the adult mammalian heart. We generated a new Abcg2-driven, lineage-tracing mouse model that efficiently labels side population cells in multiple tissues throughout the body, including the heart. With this mouse model, we first showed that the side population phenotype enriches for endogenous stem cells in the bone marrow and small intestine under homeostatic conditions. In the adult heart, we showed that cardiac side population cells contribute to 21% of newly formed cardiomyocytes either through direct differentiation or fusion. Moreover, cardiac side population cells are responsive to different forms of cardiac injury. Further characterization of cardiac side population cells will help us understand how they can be targeted in vivo for the development of new heart failure therapies.Item Synaptotagmin is an environmentally sensitive calcium ion sensor.(2010-09) Murphy, Jesse RayExocytosis of neurotransmitters into the presynaptic space is triggered by an influx of Ca2+. Synaptotagmin 1 (Syt1) mediates the fusion of the vesicular bilayer with the presynaptic bilayer through its interactions with Ca2+, phospholipid, and the fusion machinery. The exact mechanism for this information transduction, however, is not well understood. Syt1 contains two homologous binding domains, C2A and C2B, which are tethered to a neurotransmitter containing vesicle by a flexible linker region. We hypothesize that the entire Syt1 C2A domain (linker + C2A) is necessary to translate this binding information into a fusion response. To understand the cooperativity of binding in Syt1 C2A, we studied two commonly utilized C2A constructs. The short construct is simply the structural C2A domain (amino acids 140-265). The second construct possesses more of the flexible linker (amino acids 96-265). To thermodynamically compare the binding behavior between the two constructs, we studied the Ca2+ and phospholipid binding using steady state fluorescence and Ca2+ binding using ITC. The results were modeled by binding partition functions. The data are consistent with diminished linkage among the binding sites in the short construct. We conclude that the flexible linker domain serves more of an important biological function than tethering the C2 domains to the membrane.