Medicine and Health Sciences Commons^™

Elevated Plasma Il-6 Associates With Increased Risk Of Advanced Fibrosis And Cholangiocarcinoma In Individuals Infected By Opisthorchis Viverrini, Banchob Sripa, Bandit Thinkhamrop, Eimorn Mairiang, Thewarach Laha, Sasithorn Kaewkes, Paiboon Sithithaworn, Maria V. Periago, Vajarabhongsa Bhudhisawasdi, Ponlapat Yonglitthipagon, Jason Mulvenna, Paul J. Brindley, Alex Loukas, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Opisthorchis viverrini is considered among the most important of the food-borne trematodes due to its strong association with advanced periductal fibrosis and bile duct cancer (cholangiocarcinoma). We investigated the relationship between plasma levels of Interleukin (IL)-6 and the risk of developing advanced fibrosis and bile duct cancer from chronic Opisthorchis infection. We show that IL-6 circulates in plasma at concentrations 58 times higher in individuals with advanced fibrosis than age, sex, and nearest-neighbor matched controls and 221 times higher in individuals with bile duct cancer than controls. We also observed a dose-response relationship between increasing levels of plasma IL-6 and …

Environmental Friendly Synthesis, Characterization Of Surface Modifiable Starch Encapsulated Gold Nanoparticles With Bactericidal And Catalytic Activity, Dillon Pender

Mahurin Honors College Capstone Experience/Thesis Projects

In the present study, we report the green synthesis of gold nanoparticles (GNPs), using potato starch as a reducing as well as a stabilizing agent in an aqueous buffer medium. The resulting starch-GNPs (St-GNPs) were near spherical in shape with an average diameter of 15 ± 5 nm. In this approach, St-GNPs were characterized and investigated for their antibacterial properties against both gram negative (Escherichia coli) and gram positive (Staphylococcus epidermidis) bacteria. These St-GNPs were found to possess significant dose dependent antibacterial activity against bacteria. Also, St-GNPs showed a significant catalytic activity and can easily be …

The Prevalence Of Essential Hypertension In Kasigau, Kenya, Lindsay Williams

Mahurin Honors College Capstone Experience/Thesis Projects

Hypertension is the leading cause of cardiovascular disease worldwide. Cardiovascular disease (CVD) is a widespread chronic non-communicable disease (NCD) which is on the rise in developing countries. Evidence based on extensive research studies on risk factors for NCDs suggests that they could be easily significantly decreased by simply controlling their risk factors. Although high blood pressure has been recognized as a leading risk factor for CVD, little research has been done to document the prevalence and incidence of essential hypertension (EH) in lower socioeconomic developing countries. One such country is Kenya. It was found in our research study that Kasigau …

Screening Mammograms In Alzheimer’S Disease Patients, George M. Yousef, Piyush Sovani, Sirisha Devabhaktuni, Lynne J. Goebel

Internal Medicine

Very little guidance exists to help clinicians and families decide whether mammograms are useful in elderly women with Alzheimer’s Disease (AD). We present a case of a patient with moderate AD who had a positive mammogram and discuss the dilemma faced by the family and clinician in deciding what was best to do for the patient. In this case, the family opted for breast conserving surgery (BCS) followed by palliative care which brought up the question of whether screening was appropriate with this treatment goal in mind. We reviewed the literature on AD and breast cancer screening and summarize these …

Genetic Ablation Of Cav1 Differentially Affects Melanoma Tumor Growth And Metastasis In Mice: Role Of Cav1 In Shh Heterotypic Signaling And Transendothelial Migration., Franco Capozza, Casey Trimmer, Remedios Castello-Cros, Sanjay Katiyar, Diana Whitaker-Menezes, Antonia Follenzi, Marco Crosariol, Gemma Llaverias, Federica Sotgia, Richard G Pestell, Michael P Lisanti

Department of Cancer Biology Faculty Papers

Both cell-autonomous and non-cell-autonomous factors contribute to tumor growth and metastasis of melanoma. The function of caveolin-1 (Cav1), a multifunctional scaffold protein known to modulate several biologic processes in both normal tissue and cancer, has been recently investigated in melanoma cancer cells, but its role in the melanoma microenvironment remains largely unexplored. Here, we show that orthotopic implantation of B16F10 melanoma cells in the skin of Cav1KO mice increases tumor growth, and co-injection of Cav1-deficient dermal fibroblasts with melanoma cells is sufficient to recapitulate the tumor phenotype observed in Cav1KO mice. Using indirect coculture experiments with fibroblasts and melanoma cells …

Uptake And Toxic Effects Of Surface Modified Nanomaterials In Freshwater Aquatic Organisms, Brandon Seda

All Dissertations

Nanomaterials are a class of materials with unique properties due to their size, and the association of these properties with the toxicity of nanomaterials is poorly understood. The present study assessed the toxic effects of stable aqueous colloidal suspensions of three distinctly different classes of nanomaterials in aquatic organisms. The fullerene, C70, was stabilized through non-covalent surface modification with gallic acid. Toxicity of C70-gallic acid was confirmed to exhibit similar toxic effects as C60-fullerene, including changes in antioxidative processes in Daphnia magna. Daphnia magna fecundity was significantly reduced in 21d bioassays at C70-gallic concentrations below quantifiable limits (0.03 mg/L C70). …

Racemization Of Amino Acids In Teeth For The Determination Of Age, Andrea Lee Toll

Masters Theses & Specialist Projects

Instrumental to forensic investigations is the ability to identify unknown human remains providing key evidence to criminal cases, resolution to missing persons, and assistance in mass or natural disasters. Identification of remains in an effort to determine age is an area of forensics that has received considerable attention. Traditional methods in age determination such as morphology are often biased, antiquated, and frequently result in a large margin of error. Conversely, the emergence of new forensic techniques provide promise to reduce the margin of error in determining age. One such technique has focused on relating the extent of amino acid racemization …

Effects Of Moderate Swim Exercise On Adiposity And Metabolic Function In Mice, Roberta L. Pohlman, Ana Carneiro, Vera Farah, Lynn K. Hartzler, Mariana Morris

Biological Sciences Faculty Publications

No abstract provided.

The Use Of Infliximab In Older Inflammatory Bowel Disease Patients, Stephanie M. Moleski, Christina C. Lindenmeyer, Patricia L. Kozuch

Department of Medicine Faculty Papers

Limited data suggest anti-tumor necrosis factor (TNF) antibodies have equal efficacy but higher morbidity and mortality in older compared to younger inflammatory bowel disease (IBD) patients(1).

Development Of A Microfluidic Device Coupled To Microdialysis Sampling For The Pre-Concentration Of Cytokines, Randy Francisco Espinal Cabrera

Graduate Theses and Dissertations

A proof-of-concept microfluidic device combined with heparin-immobilized magnetic beads was created to concentrate cytokine proteins collected from microdialysis samples. Cytokines are known to be related to several diseases such as cancer, and Parkinson's diseases, so to be able to develop more effective diseases treatments their interactions have to be well understood. Amine-functionalized polystyrene and carboxyl-functionalized magnetic microspheres of ~6.0 ìm in diameter were used to immobilize heparin. The amount of heparin immobilized on polystyrene beads was 5.82 x 10-8 ± 0.36 x 10-8 M per 1.0 x 106 beads and for magnetic beads was 0.64 x 10-8 ± 0.01 x …

Cns Penetration Of Tyrosine Kinase Inhibitors In Mouse Models, Mohamed Elmeliegy

Theses and Dissertations (ETD)

For the past three decades, advances in the treatment of central nervous system (CNS) tumors such as malignant glioma have only been modest. One particular challenge facing treatment of brain tumors is the delivery of therapeutically effective concentrations of anti-cancer agents to the target site in the brain. The sanctuary of the brain is protected by several barrier systems such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). These barriers restrict the passage of anti-cancer drugs into the brain via several protective mechanisms.

In the present study, we used cerebral microdialysis sampling, a technique for sampling unbound …

Isolation And Characterization Of A Novel Substrate For The Pro-Apoptotic Omi/Htra2 Protease, Nathan Ward

HIM 1990-2015

Omi, also known as HtrA2, is a mammalian pro-apoptotic mitochondrial protein and a member of the HtrA (high temperature requirement A) family of serine proteases. Omi promotes the caspase-dependent apoptotic pathway through cleavage of IAPs (inhibitor of apoptosis proteins); this cleavage inactivates IAPs and facilitates caspase activity. Omi's proteolytic activity is necessary and essential for its pro-apoptotic function. This study is aimed to further understand the role of Omi in the cytoplasm by using the yeast two-hybrid system to identify novel Omi interactors/substrates. A HeLa (cervical carcinoma cell line) cDNA library was screened using Omi as a "bait" protein. One …

Exercise-Induced Neuroprotection In A Hemiparkinsonian 6-Hydroxydopamine Rat Model, Merrill Russen Landers

UNLV Theses, Dissertations, Professional Papers, and Capstones

Outside of finding a cure, one of the preeminent goals of research in Parkinson's disease (PD) is finding a neuroprotective treatment that when applied prior to the onset of the disease will decrease the risk and severity of the subsequent disease. One such treatment that has potential as a neuroprotective agent in PD is exercise. Several studies have found forced exercise to be protective of Parkinson's disease in adult rodent models; however, few of these studies have used a design wherein voluntary exercise was evaluated. Moreover, no study has used a true neuroprotective design in which exercise was applied prior …

Effects Of Hyperthermia On Photochemical Internalization-Mediated Delivery Of Bleomycin, Christina Schlazer

UNLV Theses, Dissertations, Professional Papers, and Capstones

Standard treatment protocols for high-grade gliomas, such as glioblastoma multiforme (GBM), are highly ineffective due to their inability to eradicate infiltrating tumor cells. Improvements in overall survival are likely to be realized only with the development of more effective localized therapies capable of eradicating tumor cells in the surgical resection margin and beyond. Photochemical internalization (PCI) is a localized light-based therapeutic modality that enhances the efficacy of therapeutic macromolecules including chemotherapeutic agents such as bleomycin. A number of studies have shown that this photodynamic therapy (PDT) - based modality may prove effective in the treatment of high-grade gliomas.

Three-dimensional multicell …

Biomass Assisted Synthesis Of Antibacterial Gold Nanoparticles And Commentary On Its Future Potential And Applications In Medicine, Chad Willis

Mahurin Honors College Capstone Experience/Thesis Projects

Xylose is a natural monosaccharide found in biomass such as straw, pecan shells, cottonseed hulls, and corncobs. Using this monosaccharide, we report the green synthesis and characterization of biocompatible, biodegradable xylose encapsulated gold nanoparticles (Xyl-GNPs) with potential antibacterial activity. GNPs were synthesized using the bioreduction property of xylose on the chloroaurate anions in an aqueous solution at room temperature and at atmospheric pressure. The characterization of synthesized GNPs was examined by UV-vis spectroscopy; transmission electron microscopy (TEM), energy-dispersive x-ray spectroscopy (EDS) and fourier transform infrared spectroscopy (FTIR). Results indicate that the particles were stable; near spherical in shape with an …

Novel Napi-Iic Mutations Causing Hhrh And Idiopathic Hypercalciuria In Several Unrelated Families: Long-Term Follow-Up In One Kindred., Y Yu, S R. Sanderson, M Reyes, A Sharma, N Dunbar, Tarak Srivastava, H Jüppner, C Bergwitz

Manuscripts, Articles, Book Chapters and Other Papers

Homozygous and compound heterozygous mutations in SLC34A3, the gene encoding the sodium-dependent co-transporter NaPi-IIc, cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate-wasting resulting in hypophosphatemia, elevated 1,25(OH)(2) vitamin D levels, hypercalciuria, rickets/osteomalacia, and frequently kidney stones or nephrocalcinosis. Similar albeit less severe biochemical changes are also observed in heterozygous carriers, which are furthermore indistinguishable from those encountered in idiopathic hypercalciuria (IH). We now searched for SLC34A3 mutations (exons and introns) in two previously not reported HHRH kindreds, which resulted in the identification of three novel mutations. The affected members of kindred A were compound heterozygous …

Neocortical Layer 4 To Layer 2/3 Sensory Information Processing Investigated With Digital-Light-Projection Neuronal Photostimulation, Jason Paul Jerome

Theses and Dissertations (ETD)

The mammalian brain forms neuronal networks and microcircuits with cell-type- and anatomical-specific synaptic connections. Despite great advances in elucidating the cellular physiology of the nervous system, little is known about the computational processes occurring at the level of neuronal microcircuits. Much success has been reported in describing the synaptic input patterns of many brain regions and cell types using photostimulation systems; however, these systems are severely limited in their ability to study the integration of synaptic input from multiple synchronous or temporally correlated presynaptic locations. Here we describe a system that allows the generation of arbitrary 2-D stimulus patterns with …

Contribution Of The Unfolded Protein Response To Vegf Expression, Ethel Rose Pereira

Theses and Dissertations (ETD)

Tumor cells experience a limiting microenvironment due to inadequate vascularization that can affect the normal functioning of intracellular organelles. In the case of the endoplasmic reticulum, the limiting environment is further exacerbated by the high metabolic demands of the tumor cells, which together interfere with the proper maturation of nascent proteins synthesized there. The resultant accumulation of unfolded proteins activates a signal transduction pathway known as the Unfolded Protein Response, which serves primarily to protect the cell during stress and helps restore homeostasis to this organelle. As tumors expand resulting in regions that are a greater distance from functional blood …

Phenotypic And Electrophysiologic Characterization Of A Mouse Model Of Fragile X Syndrome, Snigdha Roy

Theses and Dissertations (ETD)

Fragile X syndrome (FXS) is the most common form of inherited mental retardation. It is caused by a mutation in the fragile X mental retardation (FMR1) gene on the X chromosome. Many children with FXS exhibit autistic behaviors and deficits in motor coordination including speech articulation deficits. The development of the FMR1 knockout (Fmr1 KO) mouse, in which the Fmr1 gene is inactivated, has provided an animal model that can be used to investigate underlying neuro-physiological mechanisms associated with FXS as well as to evaluate potential therapeutic treatments. In this study, quantitative behavioral assays were used, such as long term …

Hp Turns 17: T Helper 17 Cell Response During Hypersensitivity Pneumonitis (Hp) And Factors Controlling It, Hossam Abdelsamed

Theses and Dissertations (ETD)

Hypersensitivity Pneumonitis (HP) is an interstitial lung disease caused by repeated inhalation of a wide range of environmental antigens. It is characterized by alveolitis, granuloma formation, and fibrosis. Since HP is a T cell-mediated disease, it is important to determine the type of T cell response associated with granuloma formation and the factors that control this response. We hypothesized that HP is associated with a predominant Th17 cell response where both T-bet and TLRs 2 and 9 are controlling T cell response during HP. The results demonstrated a predominant Th17 response associated with granuloma formation in the lungs of C57BL/6J …

The Molecular Basis Of Fitness And Transmissibility Of Neuraminidase Inhibitor Resistant Influenza A Viruses, Susu Duan

Theses and Dissertations (ETD)

Neuraminidase (NA) inhibitors including oral oseltamivir and inhaled zanamivir are among the first line of defense against influenza virus infection. Development of resistance to NA inhibitors is a huge drawback for limited options for the control of influenza. During the first decade of NA inhibitor use, the detection rates of resistance to both NA inhibitors had remained low in circulating influenza viruses. However, the 2008~2009 season was marked by a radical increase of prevalence of oseltamvir resistance from <1% to >90% in worldwide surveillance in less than a year. The resistance was solely linked to NA H275Y variants of seasonal H1N1 viruses, …

Beta-2-Adrenergic Receptor Regulates Insulin Signaling To Reduce Cell Death In Müller Cells, Robert Jason Walker

Theses and Dissertations (ETD)

No abstract provided.

Management Of Sexual Disorders In Spinal Cord Injured Patients., Vafa Rahimi-Movaghar, Alexander R Vaccaro

Department of Neurosurgery Faculty Papers

Spinal cord injured (SCI) patients have sexual disorders including erectile dysfunction (ED), impotence, priapism, ejaculatory dysfunction and infertility. Treatments for erectile dysfunction include four steps. Step 1 involves smoking cessation, weight loss, and increasing physical activity. Step 2 is phosphodiesterase type 5 inhibitors (PDE5I) such as Sildenafil (Viagra), intracavernous injections of Papaverine or prostaglandins, and vacuum constriction devices. Step 3 is a penile prosthesis, and Step 4 is sacral neuromodulation (SNM). Priapism can be resolved spontaneously if there is no ischemia found on blood gas measurement or by Phenylephrine. For anejaculatory dysfunction, massage, vibrator, electrical stimulation and direct surgical biopsy …

Improved Techniques For Acquisition And Analysis Of Dynamic Contrast-Enhanced Magnetic Resonance Imaging For Detecting Vascular Permeability In The Central Nervous System, Cheukkai Hui

Dissertations and Theses (Open Access)

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive technique for quantitative assessment of the integrity of blood-brain barrier and blood-spinal cord barrier (BSCB) in the presence of central nervous system pathologies. However, the results of DCE-MRI show substantial variability. The high variability can be caused by a number of factors including inaccurate T1 estimation, insufficient temporal resolution and poor contrast-to-noise ratio. My thesis work is to develop improved methods to reduce the variability of DCE-MRI results. To obtain fast and accurate T1 map, the Look-Locker acquisition technique was implemented with a novel and truly centric k-space segmentation scheme. In …

Taz As A Regulator Of Mesenchymal Transformation And Clinical Aggressiveness In Gliomas, Katrina Salazar

Dissertations and Theses (Open Access)

Glioblastoma multiforme (GBM) is an aggressive, high grade brain tumor. Microarray studies have shown a subset of GBMs with a mesenchymal gene signature. This subset is associated with poor clinical outcome and resistance to treatment. To establish the molecular drivers of this mesenchymal transition, we correlated transcription factor expression to the mesenchymal signature and identified transcriptional co-activator with PDZ-binding motif (TAZ) to be highly associated with the mesenchymal shift. High TAZ expression correlated with worse clinical outcome and higher grade. These data led to the hypothesis that TAZ is critical to the mesenchymal transition and aggressive clinical behavior seen in …

Bim Mediates Imatinib-Induced Apoptosis Of Gastrointestinal Stromal Tumors: Translational Implications, David Reynoso

Dissertations and Theses (Open Access)

Gastrointestinal stromal tumors (GISTs) are oncogene-addicted cancers driven by activating mutations in the genes encoding receptor tyrosine kinases KIT and PDGFR-α. Imatinib mesylate, a specific inhibitor of KIT and PDGFR-α signaling, delays progression of GIST, but is incapable of achieving cure. Thus, most patients who initially respond to imatinib therapy eventually experience tumor progression, and have limited therapeutic options thereafter. To address imatinib-resistance and tumor progression, these studies sought to understand the molecular mechanisms that regulate apoptosis in GIST, and evaluate combination therapies that kill GISTs cells via complementary, but independent, mechanisms. BIM (Bcl-2 interacting mediator …

Metabolic Regulation Of Mtor Activation And Endoplasmic Reticulum Stress In The Heart, Shiraj Sen

Dissertations and Theses (Open Access)

When subjected to increased workload, the heart responds metabolically by increasing its reliance on glucose and structurally by increasing the size of myocytes. Whether changes in metabolism regulate the structural remodeling process is unknown. A likely candidate for a link between metabolism and growth in the heart is the mammalian target of rapamycin (mTOR), which couples energy and nutrient metabolism to cell growth. Recently, sustained mTOR activation has also been implicated in the development of endoplasmic reticulum (ER) stress. We explored possible mechanisms by which acute metabolic changes in the hemodynamically stressed heart regulate mTOR activation, ER stress and cardiac …

Cellular Trafficking Of Single And Multistage Vectors, Silvia Ferrati

Dissertations and Theses (Open Access)

Nanomedicine is an innovative field of science which has recently generated many drug delivery platforms with exciting results. The great potential of these strategies rely on the unique characteristics of the devices at the nano-scale in terms of long time circulation in the blood stream, selective accumulation at the lesions sites, increased solubility in aqueous solutions, etc.

Herein we report on a new drug delivery system known as a multistage system which is comprised of non-spherical, mesoporous silicon particles loaded with second stage nanoparticles. The rationally designed particle shape, the possibility to modulate the surface properties and the degree of …

Regulation Of Protein Degradation In The Heart By Amp-Activated Protein Kinase, Kedryn K. Baskin

Dissertations and Theses (Open Access)

The degradation of proteins by the ubiquitin proteasome system is essential for cellular homeostasis in the heart. An important regulator of metabolic homeostasis is AMP-activated protein kinase (AMPK). During nutrient deprivation, AMPK is activated and intracellular proteolysis is enhanced through the ubiquitin proteasome system (UPS). Whether AMPK plays a role in protein degradation through the UPS in the heart is not known. Here I present data in support of the hypothesis that AMPK transcriptionally regulates key players in the UPS, which, under extreme conditions can be detrimental to the heart. The ubiquitin ligases MAFbx /Atrogin-1 and MuRF1, key regulators of …

Predictors Of Contralateral Breast Cancer In Brca Negative Women, Ann E. Simmons

Dissertations and Theses (Open Access)

Breast cancer is the most common cancer diagnosis and second leading cause of death in women. Risk factors associated with breast cancer include: increased age, alcohol consumption, cigarette smoking, white race, physical inactivity, benign breast conditions, reproductive and hormonal factors, dietary factors, and family history. Hereditary breast and ovarian cancer syndrome (HBOC) is caused by mutations in the BRCA1 and BRCA2 genes. Women carrying a mutation in these genes are at an increased risk to develop a second breast cancer. Contralateral breast cancer is the most common second primary cancer in patients treated for a first breast cancer. Other risk …