Medicine and Health Sciences Commons^™

Interactions Between Human Neutrophils And Mycobacterium Smegmatis : A Comparative General Analysis., Irina Miralda

College of Arts & Sciences Senior Theses

Mycobacteria smegmatis is an abundant soil and water inhabitant with which humans are continuously in contact. Despite the fact that it is typically considered non-­‐pathogenic, a few rare cases of M. smegmatis-­‐caused infections have been reported and it has been shown that M. smegmatis is able to modulate inflammatory responses in macrophages. Neutrophils are the innate immune system’s first line of centralized defense against invading microbes, especially the frequently encountered M. smegmatis. However, very little information is known of the mechanism by which neutrophils eliminate environmental bacteria. In this study, the hypothesis that M. smegmatis regulates neutrophil functional responses, and …

Cyclic Nucleotide-Dependent Phosphorylation Regulates Bk-Ca Channel Activity In Human Coronary Artery Smooth Muscle Cells, Raeonda Williams

PCOM Biomedical Studies Student Scholarship

Cardiovascular diseases (CVD) can induce dysfunction in organ systems by attenuating normal blood flow. Gonadal steroids are vasoactive hormones, but their role in contributing to cardiovascular function remains controversial. We have demonstrated that gonadal steroids can relax coronary arteries by opening the large-conductance, calcium- and voltage-activated potassium (BKca) channel in smooth muscle cells by increasing cyclic nucleotide levels; however, the signaling pathways involved remain to be elucidated. The purpose of this study was to identify how phosphorylation (via cAMP- and cGMP-dependent protein kinases) I dephosphorylation (via phosphoprotein phosphatase 2A, PP2A) regulates BKca channel activity in human coronary artery smooth muscle …

Development And Evaluation Of An Opioid Monitoring Clinic, Richard Luna Talusan

UNLV Theses, Dissertations, Professional Papers, and Capstones

An APRN-led Opioid Monitoring Clinic was developed and implemented in the primary care setting of Las Vegas' Department of Veterans Affairs in July 2013 to assist primary care providers (PCP) in the management of high risk patients on chronic opioid

therapy for chronic noncancer pain. The clinic assisted in monitoring patients for abuse and misuse of opioids and referred patients for treatment when abuse and misuse were discovered. A study to evaluate the OMC was undertaken from November 22, 2013

through February 23, 2014 to assess the effectiveness of the OMC in meeting its objectives. A total of 61 patients …

Life History Tradeoffs And The Costs Of Reproduction In Arizona Bark Scorpions (Centruroides Sculpturatus), Michael Marie Webber

UNLV Theses, Dissertations, Professional Papers, and Capstones

Tradeoffs in life history evolution result from conflicts in the time and energy that can be simultaneously invested in activities such as growth, reproduction, and survival. Reproduction is an energetically costly activity for organisms, and is known to elicit alterations in the daily activity patterns of individuals. I investigated reproductive tradeoffs in the Arizona Bark Scorpion,Centruroides sculpturatus. To better understand the nature of tradeoffs in this species, I examined the influence of reproductive state on the predatory efficiency and thermal preference of reproductive females. Further, I examined the influence of reproductive activities (i.e. gestation) on the ability of reproductive females …

The Grass Shrimp, Palaemonetes, Pugio: Hypoxic Influences On Embryonic Development, Christensen C. Javier

UNLV Theses, Dissertations, Professional Papers, and Capstones

Grass shrimp,Palaemonetes pugio, can survive in brackish waters and estuarine ecosystems despite the frequent oscillations and fluctuations in salinity, temperature and oxygen. AdultP. pugiohave the ability to osmoregulate (Romney and Reiber 2011), change cardiac parameters to tolerate temperatures (not yet published, Mika and Reiber) and oxyregulate (Guadagnoli and Reiber 2013). Manipulation of cardiac parameters allows for these methods of regulation. However, cardiac contraction and internal convection of oxygen do not occur until later stages of embryonic development. Studies focused on these morphological and physiological advantages may provide further understanding of the regulatory mechanisms within grass shrimp embryos, larvae and adults. …

Measuring The Effects Of Ctrp3 And Metformin On H4iie Hepatocyte Metabolism Using Seahorse Extracellular Flux Analyzer, Forrest J. Longway

Undergraduate Honors Theses

Non-alcoholic fatty liver disease (NAFLD) results from an unequal uptake/storage and export/oxidation of lipids within the liver and is often a secondary disease to type II diabetes (22). NAFLD causes this imbalance of lipids by altering glucose and lipid metabolism, which corresponds to a decrease in mitochondrial function leading to failure of the liver. One established treatment for type II diabetes and NAFLD is the drug metformin, which has similar properties to the newly discovered CTRP 3 protein which is part of a group of bioactive molecules secreted by adipose tissue, collectively termed adipokines (2-4). Both have similar effects on …

Modulated Functions Of The Fanconi Anemia Core Complex, Yaling Huang

Dissertations and Theses (Open Access)

Cells derived from Fanconi anemia (FA) patients are characterized by hypersensitivity to DNA interstrand crosslinks (ICLs), suggesting that FA genes play a role in ICL repair. Fanconi anemia core complex (including A, B, C, E, F, G, L, FAAP20, and FAAP100) activates the Fanconi pathway by providing the essential E3 ligase activity for FANCD2 mono-ubiquitination. Previous studies suggested the existence of three protein-protein interaction groups. However, the functions of most FA core complex protein are still limited to their presence in the complex. How the spatially-defined FANCD2 ubiquitination is accomplished by the core complex remains unknown.

To elucidate the roles …

Availability Of Dental Anomaly Phenotype In Individuals With Familial Adenomatous Polyposis, Andrea M. Lewis

Dissertations and Theses (Open Access)

Background: Mutations in the APC gene cause familial adenomatous polyposis (FAP), an autosomal dominant colorectal cancer predisposition associated with the development of hundreds to thousands of adenomatous colorectal polyps beginning in childhood or adolescence. Both malignant and non-malignant extracolonic manifestations are associated with APC gene mutations, including approximately 17% of individuals with various dental anomalies. The availability of dental anomaly information in the medical record remains to be evaluated.

Methods: Medical records were reviewed for documentation of dental anomalies. Dental questionnaires were mailed to 271 individuals with FAP at The University of Texas M. D. Anderson Cancer Center (UTMDACC) to …

Molecular Characterization Of Glioblastoma Cancer Stem Cells, Jo Meagan Garner

Theses and Dissertations (ETD)

Malignant gliomas are locally aggressive, highly vascular tumors that have an overall survival time less than 14 months, and current therapies provide little improvement in the disease course and outcome. While glioblastoma multiforme (GBM) patients present uniform histological phenotypes, the molecular determinants of the disease vary considerably between individual cases resulting in complicated prognosis. The heterogeneity, aggressiveness and rapid tumor relapse of GBM is believed to be sustained by cancer stem-like cell populations that are able to initiate and maintain tumors. Although CSCs represent only a small fraction of cells within a tumor, their high tumor-initiating capacity and therapeutic resistance …

Preliminary Study On How Tumor Suppressor Nf2 Inhibits Transcriptional Coactivators Yap/Taz In The Developing Mouse Brain, Yu He

Theses and Dissertations (ETD)

Normal brain development requires precise coordination of neural progenitor proliferation and differentiation, the mechanism of which is not well known. Recently the tumor suppressor neurofibromatosis 2 (Nf2) was shown to regulate the balance of neural progenitor proliferation and differentiation in the developing mouse brain through the Hippo pathway effectors, transcriptional coactivators Yap/Taz. The molecular mechanism of how Nf2 regulates Yap/Taz is not understood. Here I showed that Nf2 regulated the Yap/Taz activity by decreasing the stability of Yap/Taz. The regulation was independent of Yap-S366 phosphorylation, which is required for Yap degradation. I also showed that Nf2 did not regulate Lats1/2 …

Persistant Gata2 Expression Promotes Self-Renewal Of Myeloid Progenitors And Blocks Lymphoid Differentiation., Satish Kumar Nandakumar

Theses and Dissertations (ETD)

The transcription factor GATA2 is highly expressed in hematopoietic stem cells (HSCs) and is downregulated during differentiation. Overexpression of GATA2 is frequently observed in acute myeloid leukemia. In previous studies, enforced expression of GATA2 using a MSCV GATA2 retroviral vector blocked differentiation of HSC and progenitors without inducing leukemia. We hypothesized that a lower dose of GATA2 can relieve the HSC block and eventually transform myeloid progenitors into leukemia stem cells. To test this hypothesis we generated a MSCV GATA2-ERT vector in which nuclear concentration of GATA2 can be regulated by Tamoxifen (TAM). The GATA2-ERT protein was confirmed to leak …

Characterization Of Cre Mouse Models To Target Cns Barriers For Generating Conditional Knockouts Of Abc Transporters, Rachel L. Scheib

Theses and Dissertations (ETD)

The central nervous system (CNS) includes the brain and spinal cord, where both possess a blood to brain and a blood to cerebrospinal fluid (CSF) barrier. The blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) regulate the passage of many molecules to maintain and protect these sensitive organs from harmful xenobiotics (i.e. drugs, pollutants, etc.) or physiologic changes (i.e. glucose, ion, or water composition). These barriers also express ABC transporters, including P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP), which are known to contribute to efflux of endogenous toxins and therapeutics from the CNS. Pgp and BCRP expression and activity are …

Assessing The Relationship Between The Blood-Air Partition Coefficient And Fractional Uptake Of Inspired Halothane, Acetone, And Ethanol Vapors In The Airways Of The C57bl/6j Mouse, Joshua Baruch Baldino

Honors Scholar Theses

The following series of studies investigates the elimination and uptake trends of halothane, acetone, and ethanol vapors in the airways of C57BL/6J mice. These vapors were chosen because they span a wide range of solubilities, as indicated by their blood-air partition coefficients, and are not associated with any significant airway metabolism or reactivity with tissue substrates in vivo. Mice were exposed to a homogeneous vapor mixture containing a 1:1:1 ratio of halothane, acetone, and ethanol at relative concentrations of approximately 10 ppm. Exposure studies were performed with mice in two states, conscious and deceased, in order to provide control …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Follicular Dendritic Cell Sarcoma: A Rare Entity With Variable Pathologic Features And Prognosis, Sharif A. Ali Md, Miriam L. Enriquez Md, Shereen M. Gheith Md

Department of Pathology & Laboratory Medicine

No abstract provided.

Characterization Of T-Bet And Eomes In Peripheral Human Immune Cells., James J. Knox, Gabriela L. Cosma, Michael R. Betts, Laura M. Mclane

Department of Microbiology and Immunology Faculty Papers

The T-box transcription factors T-bet and Eomesodermin (Eomes) have been well defined as key drivers of immune cell development and cytolytic function. While the majority of studies have defined the roles of these factors in the context of murine T-cells, recent results have revealed that T-bet, and possibly Eomes, are expressed in other immune cell subsets. To date, the expression patterns of these factors in subsets of human peripheral blood mononuclear cells beyond T-cells remain relatively uncharacterized. In this study, we used multiparametric flow cytometry to characterize T-bet and Eomes expression in major human blood cell subsets, including total CD4(+) …

The Mi-2 Homolog Mit1 Actively Positions Nucleosomes Within Heterochromatin To Suppress Transcription, Kevin M. Creamer

Theses and Dissertations (ETD)

Eukaryotic DNA is packaged into the nucleus in complex with proteins that regulate access and utilization of the genetic material. These DNA and protein complexes form a dynamic structure known as chromatin. Nucleosomes are the repeating unit of chromatin, and consist of DNA wrapped around an octamer of histone proteins. Nucleosomes can then be modified and spatially arranged to facilitate processes such as transcription, DNA replication, and repair. A special transcriptionally repressive chromatin structure assembles onto gene-poor, repetitive regions of the genome known as constitutive heterochromatin. Mit1 is the putative chromatin remodeling subunit of the fission yeast Snf2/HDAC repressor complex …

Propagation Of Oligomeric Α-Synuclein And Amyloid-Β: Implications For Parkinson's And Alzheimer's Diseases, Matthew Stephen Planchard

Master's Theses

The aggregation of amyloidogenic proteins is a critical event in the pathology of a variety of neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). The proteins α-synuclein (αS) and amyloid-β (Aβ) are involved in the formation of amyloid lesions observed in PD and AD, respectively. Both PD and AD exhibit a significant amount of co-pathology in clinical settings, and the αS and Aβ proteins have been shown to interact in vitro. Recent experimental consensus has shown oligomeric species to be significant, if not primary, sources of toxicity in these diseases. …

Epigenetic Remodeling In An Imr-32 Cell Line And Transgenic Mouse Model Of Alzheimer's Disease, Matthew S. Baker

Senior Honors Theses

The pathological features of Alzheimer’s disease (AD) have been researched and documented extensively, however the causes of these features are still unknown. The following studies sought to determine if epigenetic methylation alterations contribute to AD. Two studies were sequentially carried out, first using an IMR-32 model and then using a transgenic mouse model overexpressing beta-amyloid. A few assay and confirmation methods were carried out to determine the promoter regions in disease state models undergoing drastic change, and the genes linked to these promoter regions were analyzed to determine significant gene ontology being altered by this epigenetic modification. This data was …

Tethered Il-15 To Augment The Therapeutic Potential Of T Cells Expressing Chimeric Antigen Receptor: Maintaining Memory Potential, Persistence, And Antitumor Activity, Lenka Hurton

Dissertations and Theses (Open Access)

Tethered IL-15 to augment the therapeutic potential of T cells expressing chimeric antigen receptor: Maintaining memory potential, persistence, and antitumor activity

Adoptive immunotherapy can retarget T cells to CD19, a tumor-associated antigen (TAA) expressed on B-cell malignancies, by the expression of a chimeric antigen receptor (CAR). Infusion of CAR-modified T cells for the treatment B-cell malignancies has demonstrated promise in preclinical and clinical trials. These data highlight the ability of infused CD19-specific T cells to be synchronously activated by large burdens of CD19⁺ leukemia and lymphoma. This can lead to dramatic antitumor effects, but also exposes the recipient to …

Differential Regulation Of Iress In The Aurora A Mrna By Bfgf Through The Mtor Complex To Rc2 Modulates Aurora A Kinase Expression, Roy L. Voice Iii

Dissertations and Theses (Open Access)

Identifying the mechanisms that contribute to tumorigenesis is a major area of focus in our fight against cancer. Epithelial malignant tumors, such as breast, colon, ovarian and pancreatic cancers have been shown to overexpress proteins that control cell mitosis, growth, and proliferation. One of those proteins is the Aurora A kinase. Aurora A kinase is a member of a small family of kinases that contribute to mitotic events such as centrosome duplication, separation, and maturation. Aurora A overexpression leads to genomic instability, which can contribute to tumorigenesis, on the other hand, inhibiting Aurora A expression leads to apoptosis, making it …

Development Of A Multi-Purpose Automated Synthesis Module For Production Of Novel Pet Radiopharmaceuticals, I Hong Shih

Dissertations and Theses (Open Access)

Among radiopharmaceuticals of positron emission tomography (PET), ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) made from commercialized automated synthesis module is the most frequently used in tumor diagnoses. But the false positive findings, such as infectious tissues and post-operative surgical conditions, show strong uptake of ¹⁸F-FDG in PET scans which requires extra clinical procedures to confirm the results. Moreover, the false negative findings, such as low glycolytic activity tumors, reduce the accuracy of PET scans. Therefore, there will be new PET radiopharmaceuticals to redeem the defects of ¹⁸FDG-PET applications.

Current commercialized automated synthesis modules are suitable for clinical use, but …

Eye-Tracking Measures Of Attentional Bias In Cocaine Dependent Subjects, Nadeeka Dias

Dissertations and Theses (Open Access)

Cocaine-dependent (CD) subjects show evidence of attentional bias toward cocaine-related cues, and this measure of cue-reactivity is predictive of craving and relapse. In previous work, cue-reactivity and attentional bias have been assessed by models that present drug-relevant stimuli (e.g., cocaine-specific Stroop task) and measure physiological and behavioral reactivity (e.g., heart rate, reaction times). Studies have indicated competition between the higher-order cortical processes (frontal eye-fields, DLPFC) in voluntary eye control (i.e., anti-saccades) and more reflexive saccades driven by involuntary midbrain (superior colliculus) perceptual input (i.e., pro-saccades). In addition, neuroimaging studies in patients with cocaine dependence have shown activation in frontal regions …

Performance Evaluation Of Material Decomposition Using Rapid Kvp-Switching Dual-Energy Ct For Assessing Bone Mineral Density, John M. Wait

Dissertations and Theses (Open Access)

Osteoporosis is diagnosed by assessing the bone mineral density (BMD) of the trabecular bone, and has previously been characterized with dual-energy x-ray absorptiometry (DXA) or single-energy computed tomography (SECT). Dual-energy computed tomography (DECT) is able to create two three-dimensional sets of images representing the densities of two materials in a given basis pair. DECT is theoretically capable of providing a true density measurement of trabecular bone material with the proper material basis pair.

Using the rapid kVp-switching GE HD750 scanner, the concentrations of various solutes were assessed in two-material syringe-phantoms in different experimental conditions with DECT material density images, SECT …

Evaluation Of Current Clinical Criteria For Li-Fraumeni Syndrome In A Diverse Sample Of Tp53 Mutation Carriers, Emily A. Parham

Dissertations and Theses (Open Access)

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome caused by heterozyogous germline mutations in the TP53 gene and characterized by an excess of early-onset cancers, high lifetime risk of cancer, and a wide range of tumor types. Recent studies suggesting a benefit in comprehensive screening protocols for both children and adults make the timely identification of individuals with LFS increasingly important.

A number of criteria have been proposed to identify patients with LFS. The National Comprehensive Cancer Network (NCCN) combines several in its Clinical Practice Guidelines for TP53 genetic testing. Prior studies have shown that the cumulative sensitivity of …

Cancers Associated With Brca1 And Brca2 Mutations Other Than Breast And Ovarian, Jacqueline Mersch

Dissertations and Theses (Open Access)

Mutations in BRCA1 and BRCA2 cause tumor development in Hereditary Breast and Ovarian Cancer syndrome (HBOC) through accumulation of unrepaired DNA damage. Extensive research of BRCA1 and BRCA2 mutations has led to well-defined breast and ovarian cancer risks in individuals with HBOC. Previous studies have reported additional cancers associated with BRCA mutations; however, the type of cancer, magnitude of risk, and differences between sexes remains to be clarified. Ultimately, a consensus of additional cancer risks can aid in better recommendations for genetic testing and more effective screening and prevention guidelines.

A retrospective chart review of MD Anderson Cancer Center patients …

Latinas And The Traditional Genetic Counseling Model: A Qualitative Study, Stephanie Thompson

Dissertations and Theses (Open Access)

The traditional genetic counseling model reflects an individualized counseling session that includes the presentation of information about genes, chromosomes, personalized risk assessment, and genetic testing and screening options. Counselors are challenged to balance providing educational information with discussion of implications of this information in an allotted amount of time. The aim of this study was to explore the perceptions of pregnant Latinas on the benefits and limitations of the traditional prenatal genetic counseling model and to determine the specific preferences for receiving prenatal genetic counseling. Data were collected through focus groups and one-on-one, semi-structured interviews of twenty-five Spanish speaking Latinas …

Effects Of Creosote-Contaminated Sediment Extracts On Mouse Macrophage Physiology And Function, Rayna Silva

All Theses

The southern branch of the Elizabeth River, at Portsmouth Virginia is one of the most polluted systems in North America. This harbor estuary system is also home to the Atlantic Wood Superfund site, which is heavily contaminated with creosote from the Atlantic Wood (AW) preservative company that ceased production in the later 1990s. Creosote is a mixture of polyaromatic hydrocarbons (PAHs), metals, and numerous aliphatic hydrocarbons, and well known to be carcinogenic. The toxicity of sediments and pore waters from the AW site has been studied extensively using Fundulus heteroclitus, also known as the mummichog, or Atlantic killifish. Most adult …

Extracellular Ubiquitin: Role In Cardiac Myocyte Apoptosis And Myocardial Remodeling, Christopher Ray Daniels

Electronic Theses and Dissertations

Activation of sympathetic nervous system is a key component of myocardial remodeling that generally occurs following ischemia/reperfusion (I/R) injury and myocardial infarction. It induces cardiac myocyte apoptosis and myocardial fibrosis, leading to myocardial dysfunction. Intracellular ubiquitin (UB) regulates protein turnover by the UB-proteosome pathway. The biological functions of extracellular UB in the heart remain largely unexplored. Previously, our lab has shown that β-adrenergic receptor (β-AR) stimulation increases extracellular UB levels, and extracellular UB inhibits β-AR-stimulated apoptosis in adult rat ventricular myocytes (ARVMs). This study explores the role of extracellular UB in myocyte apoptosis, fibroblast phenotype and function, and myocardial remodeling …

Novel Therapeutic Approaches For Ischemic Heart And Brain Injury: Modulation Of Toll-Like Receptor-Mediated Signaling Pathways And Pi3k/Akt Signaling, Chen Lu

Electronic Theses and Dissertations

Innate immune and inflammatory responses contribute to myocardial and cerebral ischemia/reperfusion (I/R) injury. Toll-like receptors (TLRs) play a critical role in the induction of innate immune and inflammatory responses via activation of nuclear factor kappa B (NF-κB). We have shown that activation of NF-κB contributes to myocardial and cerebral I/R injury. Indeed, inhibition of TLR4-mediated NF-κB activation significantly decreased myocardial and cerebral I/R injury via activation of PI3K/Akt signaling. PI3K/Akt signaling is an important pathway in regulating cellular survival and inflammatory responses. Therefore, an important question is how to differentially modulate PI3K/Akt signaling and TLR/NF-κB-mediated signaling pathway during I/R injury? …