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Full-Text Articles in Medicine and Health Sciences

The Role Of Glutaminase And Extracellular Vesicles In Macrophages And Microglia, Beiqing Wu Aug 2016

The Role Of Glutaminase And Extracellular Vesicles In Macrophages And Microglia, Beiqing Wu

Theses & Dissertations

Glutamate serves as a crucial excitatory neurotransmitter that is essential for the proper functioning of the brain. However, excess levels of glutamate are neurotoxic and contribute to the pathogenesis of various neurodegenerative diseases, inducing HIV-1 associated neurocognitive disorders (HAND). Glutaminase 1 (GLS1) is an important mitochondrial enzyme responsible for producing glutamate from glutamine. GLS1 is upregulated during HAND and released from mitochondria to cytosol and extracellular space. However, why and how GLS1 is released remains unknown. In chapter II, we demonstrated that extracellular vesicles (EVs) carry GLS1 as cargos from cytosol to extracellular space during HIV infection and innate immune …


Changes To Echocardiography-Derived Left Ventricular Filling Pressures And Cardiac Output In Response To Fluid Boluses In Elderly Patients With Left Ventricular Diastolic Dysfunction Undergoing Vascular Surgery, Sasha K. Shillcutt Aug 2016

Changes To Echocardiography-Derived Left Ventricular Filling Pressures And Cardiac Output In Response To Fluid Boluses In Elderly Patients With Left Ventricular Diastolic Dysfunction Undergoing Vascular Surgery, Sasha K. Shillcutt

Theses & Dissertations

Left ventricular diastolic dysfunction (LVDD) of the heart is a condition where the heart does not relax properly. This condition is important during times of stress, as LVDD is associated with significant morbidity of elderly surgical patients. LVDD is often asymptomatic and unrecognized as many of these patients have normal ejection fractions. However, LVDD may lead to heart failure in patients with preserved systolic function, with the incidence being as high as 50% in hospitalized elderly patients. The diagnosis of LVDD is an independent risk factor for postoperative major adverse cardiac events (MACE) and negatively impacts post-surgery readmission rates. Anesthesiologists …


Mutations Affecting Epigenetic Regulators And Their Role In Peripheral T-Cell Lymphomas, Chao Wang Aug 2016

Mutations Affecting Epigenetic Regulators And Their Role In Peripheral T-Cell Lymphomas, Chao Wang

Theses & Dissertations

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of generally aggressive lymphoid malignancies, accounting for 10-15% of all non-Hodgkin lymphomas. Angioimmunoblastic T-cell lymphoma (AITL) represents approximately 20% of all PTCLs and is recognized as a distinct entity. Accurate diagnosis and classification of PTCL remain challenging. With the exception of ALK+ ALCL, patients with PTCL generally have a poor prognosis with standard chemotherapy and even with the availability of many novel drugs, including HDAC inhibitor (romidepsin and belinostat), gemcitabine, and bortezomib. Therefore, deciphering the pathogenesis of this group of diseases is needed to identify novel treatable targets for better therapeutic intervention. …


Ehd1 As A Positive Regulator Of Macrophage Colony-Stimulating Factor-1 Receptor, Luke R. Cypher Aug 2016

Ehd1 As A Positive Regulator Of Macrophage Colony-Stimulating Factor-1 Receptor, Luke R. Cypher

Theses & Dissertations

The master regulator of the macrophage development, differentiation, proliferation, survival, phagocytosis, cytokine secretion, motility, adhesion, migration, and spreading is the receptor tyrosine kinase (RTK) colony stimulating factor-1 receptor (CSF-1R). Aberrant CSF-1R signaling is present amongst a variety of highly prevalent and devastating human diseases in the United States such as atherosclerosis, cancer, inflammatory bowel disease, arthritis, and neuro-demyelination/neuro-degeneration. A better understanding of basic mechanisms that govern macrophage development and function is of vital importance in treating patients afflicted with these conditions/diseases. CSF-1R presentation on the macrophage cell surface is a required precursor for CSF1- induced RTK dimerization (activation) and downstream …


Modifiable Barriers To Optimal Outcomes In Gout Management, Brian W. Coburn May 2016

Modifiable Barriers To Optimal Outcomes In Gout Management, Brian W. Coburn

Theses & Dissertations

Improving patient outcomes in chronic disease is of critical importance to the future of health care. Gout, affecting 4% of the US population, is a highly treatable chronic disease from which patients experience unnecessarily suboptimal outcomes. In this dissertation, I demonstrate how interrelated patient and provider factors affect patient outcomes in gout. First, I describe how only 14% of gout patients know their serum urate (SU) goal for urate lowering therapy (ULT) despite otherwise being knowledgeable about gout and its treatment. I then demonstrate the importance of multiple patient and provider factors in achieving SU goal. Specifically, I demonstrate that …


Factors And Outcomes Associated With Potentially Inappropriate Medication Use In Rural Community-Dwelling Older Adults, Marcia Y. Shade May 2016

Factors And Outcomes Associated With Potentially Inappropriate Medication Use In Rural Community-Dwelling Older Adults, Marcia Y. Shade

Theses & Dissertations

Potentially inappropriate medications (PIMs) use in older adults is a significant public health concern. The use of PIMs to avoid may lead to negative outcomes such as adverse drug events. Prior conceptual analysis of PIMs use and observation of health-related factors in rural adults led to the design of this dissertation study. A sample was recruited from a population of rural community-dwelling older adults to examine the following specific aims: 1) Describe the use of PIMs to avoid, 2) Explore individual demographic characteristics (age, gender, income, education, and rural home location), health experience (comorbidity, number of medications and health providers), …


Recurrent Mutations Of T-Cell Receptor And Co-Stimulatory Signaling Proteins In Peripheral T-Cell Lymphomas, Joseph Rohr May 2016

Recurrent Mutations Of T-Cell Receptor And Co-Stimulatory Signaling Proteins In Peripheral T-Cell Lymphomas, Joseph Rohr

Theses & Dissertations

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T-cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation, through many signaling molecules including VAV1. This thesis identifies recurrent mutations in CD28 in PTCLs, as well as mutations in VAV1. Two residues of CD28 – D124 and T195 – were recurrently mutated in 11.3% …