Medical Sciences Commons^™

Signaling Induced By Inflammatory Mediators In The Rodent Pulmonary Microvasculature, Rachel Escue Helms

Theses and Dissertations (ETD)

Acute lung inflammation (ALI), stemming from a disproportionate and detrimental immune response, may arise from or complicate other disease states, leading to the often-fatal acute respiratory distress syndrome (ARDS). Because of the many culpable factors and differing points of induction, pinning down the signaling mechanisms involved in the morbidity of this disorder as well as defining an effective treatment has proved problematic. However, the most detrimental characteristic of this condition is seen regardless of the development of the response: increased microvascular permeability. Because of the architecture and the size of the pulmonary microvascular network, the lungs have a resident, sequestered …

Targeting The Colchicine Binding Site On Tubulin To Overcome Multidrug Resistance And Anticancer Efficacy Of Selective Survivin Inhibitors, Kinsle E. Arnst

Theses and Dissertations (ETD)

Tubulin inhibitors are widely used as chemotherapeutic agents, and their successis attributed to their ability to target microtubule dynamics and disrupt critical cellular functions including cell signaling, motility, intracellular trafficking, and mitosis. Interference with microtubule dynamics consequently disrupts mitotic progression and ultimately leads to apoptosis, validating microtubule dynamics as an excellent target for anticancer agents. While this class of drug has proven to be effective against many cancer types, the clinical efficacy of current tubulin inhibitors is often limited by the development of multidrug resistance. The most common form of resistance to these agents arises from the overexpression of drug …

The Role Of Exosomal Transport Of Viral Agents In Persistent Hiv Pathogenesis, Benjamin J. Patters

Theses and Dissertations (ETD)

Human immunodeficiency virus (HIV) infection, despite great advances in antiretroviral therapy (ART), remains a lifelong affliction. Though current treatment regimens can effectively suppress viral load to undetectable levels and preserve healthy immune function, they cannot fully alleviate all symptoms caused by the presence of the virus, such as HIV-associated neurocognitive disorders (HAND). Exosomes are small vesicles that transport cellular proteins, RNA, and small molecules between cells as a mechanism of intercellular communication. Recent research has shown that HIV proteins and RNA can be packaged into exosomes and transported between cells, to pathogenic effect. This review summarizes the current knowledge on …

Roles Of Cytosolic Nucleic Acid Sensors In Cancer And Infection, Qifan Zhu

Theses and Dissertations (ETD)

Pattern recognition receptors are innate immune sensors that recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) with crucial roles in host defense against microbial infection, autoimmune diseases and cancer. Cytosolic nucleic acids including DNA and RNA originate from pathogens or self-cells, which form major groups of PAMPs and DAMPs. A range of nucleic acid sensors have evolved to sense various types of nucleic acids. How different DNA-sensing pathways regulate microbial infection and cancer is the focus of this dissertation.

Stimulator of IFN genes (STING) is a cytosolic innate immune sensor for cyclic dinucleotides that also serves a dual …

Assessing The Role Of Arsenite In Disrupting The Egfr Signaling Axis., Christine Kim

Electronic Theses and Dissertations

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase localized on the cell surface. Overexpression of EGFR has been used as biomarkers for many different types of cancers, including lung cancer. There is a strong association between arsenic and lung cancer development, although the mechanism is unclear. We hypothesize that chronic exposure of “a physiologically relevant” level of arsenite disrupts the EGFR endocytic trafficking. The goal of this project is to identify molecular mechanisms and roles of chronic arsenite-induced EGFR overexpression in lung cancer development. A non-malignant human bronchial epithelial cell line, Beas-2B cells were exposed to 100 …

The Migration And Developmental Remodeling Of Intrinsic Interneurons In Visual Thalamus And The Role Of Retinal Signaling., Naomi E. Charalambakis

Electronic Theses and Dissertations

The dorsal lateral geniculate nucleus (dLGN) of the mouse is a model system to study the development of thalamic circuitry. While most studies focus on relay neurons of dLGN, little is known about the factors regulating the development of the other principal cell type, intrinsic interneurons. To date, the targeting and migratory path of dLGN interneurons as well as their morphological development remains unclear. Here we examined whether the migration, structure, and function of interneurons relies on retinal signaling. We took a loss-of-function approach and crossed GAD67-GFP mice, which express green fluorescent protein (GFP) in dLGN interneurons, with math5 nulls …

Trna 3'-Amino-Tailing For Stable Amino Acid Attachment., Howard Gamper, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Amino acids are attached to the tRNA 3'-end as a prerequisite for entering the ribosome for protein synthesis. Amino acid attachment also gives tRNA access to nonribosomal cellular activities. However, the normal attachment is via an ester linkage between the carboxylic group of the amino acid and the 3'-hydroxyl of the terminal A76 ribose in tRNA. The instability of this ester linkage has severely hampered studies of aminoacyl-tRNAs. Although the use of 3'-amino-3'-deoxy A76 in a 3'-amino-tailed tRNA provides stable aminoacyl attachment via an amide linkage, there are multiple tailing protocols and the efficiency of each relative to the others …

Is Tpmt Testing A Predictor Of Duration Of Use Or Long-Term Benefit Of Thiopurine Agents?, Shatoya R. Wilson

Masters Theses

Background: Inflammatory Bowel Disease (IBD) affects as many as 1.3 million Americans and includes both ulcerative colitis (UC) and Crohn’s disease (CD). Recent practices have moved towards using immunomodulators early in the course of disease to prevent disease progression. Patients have shown improved outcomes on immunomodulators compared to aminosalicylates, and reduced risk for tachyphylaxis compared to corticosteroid treatment. Thiopurine agents such as azathioprine and 6-mercaptopurine are immunomodulators often used to treat IBD. Unfortunately, many patients experience cytotoxicity from thiopurine use. Recent studies have shown that patients deficient in thiopurine-S-methyltransferase (TMPT), produce an overabundance of the therapeutic end product, 6-thioguanine nucleotide …

The Role Of Non-Neuronal Acetylcholine In Urogenital Chlamydial Infection, Jessica R. Lockhart

Electronic Theses and Dissertations

Chlamydia trachomatiscauses a bacterial sexually transmitted infection, Chlamydia, that is often chronic and casues reproductive complications in women. We hypothesized that Chlamydia infection increases local acetylcholine (ACh) production, which regulates the host’s inflammatory response to the infection. Female mice infected with C. muridarumwere sacrificed at days 3, 9, 15, and 21 post-infection, genital tract tissues harvested, and immunohistochemistry performed to enumerate ACh-producing cells. Infection increased the number of ACh-producing cells in cervical tissue at days 3,15, and 21 post-infection (pi), uterine tissue at day 3 and 9 pi, and ovarian tissue day 3, 15, and 21 pi. These …

Genetic Predisposition To Necrotizing Enterocolitis In Premature Infants: Current Knowledge, Challenges, And Future Directions., Alain Cuna, Lovya George, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

The role of genetics in the pathogenesis of necrotizing enterocolitis (NEC) was initially informed by epidemiological data indicating differences in prevalence among different ethnic groups as well as concordance in twins. These early observations, together with major advances in genomic research, paved the way for studies that begin to reveal the contribution of genetics to NEC. Using the candidate gene or pathway approach, several potential pathogenic variants for NEC in premature infants have already been identified. More recently, genome-wide association studies and exome-sequencing based studies for NEC have been reported. These advances, however, are tempered by the lack of adequately …

Scientific Proceedings Of The Texas Children’S Hospital’S 16th Session Of The Advanced Quality Improvement And Patient Safety Program, Arjun M. Dangre Bds, Mph, Kelly Wallin Ms, Rn, Chse, Gertrude A. Leidich Mba, Rn, Angelo P. Giardino Md, Phd

Journal of Nursing & Interprofessional Leadership in Quality & Safety

The Texas Children’s Hospital’s Advanced Quality Improvement and Patient Safety (AQI) Program is a six month mixed didactic and experiential learning experience designed to improve patient care, lower costs, change the culture, and develop quality leaders. As a part of AQI program participants are grouped into teams and each team completes a healthcare related Quality Improvement (QI) project. Each project demonstrates use of various QI tools including process maps, fishbone diagrams, and key driver diagrams. The projects use the IHI ‘Model for Improvement’ as the primary QI methodology to achieve their aim. Three or more Plan-do-study-act (PDSA) cycles are required …

Efficacy And Renal Outcomes Of Sglt2 Inhibitors In Patients With Type 2 Diabetes And Chronic Kidney Disease, Michael S. Kelly, Jelena Lewis, Ashley M. Huntsberry, Lauren Dea, Ivan Portillo

Pharmacy Faculty Articles and Research

Objective: To review glucose-lowering efficacy and changes in renal function associated with sodium-glucose co-transporter 2 (SGLT2) inhibitors among patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM).

Data sources: A literature search of MEDLINE and Cochrane databases was performed from 2000 to August 2018 using search terms: SGLT2 inhibitors, sodium glucose co-transporter 2, canagliflozin, empagliflozin, dapagliflozin, ertugliflozin, and chronic kidney disease. References of identified articles were also reviewed.

Study selection and data extraction: English-language studies investigating glucose-lowering endpoints and/or changes in renal function with one of four U.S. approved SGLT2 inhibitors were included. A …

Research In Kinesiology Kin 691, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Concentrations Of Purine Metabolites Are Elevated In Human Fluids From Adults And Infants And In Livers From Mice Fed Diets Depleted Of Bovine Milk Exosomes And Their Rna Cargos, Ana Aguilar Lozano

Department of Nutrition and Health Sciences: Dissertations, Theses, and Student Research

Since miRNAs discovery, evidence keeps accumulating on their role in human physiology for homeostasis and implications during disease development. Upon the discovery that miRNAs could be encapsulated in exosomes and provide protection, evidence keeps accumulating on the possibility for miRNAs to be transferred between distant cells and elicit gene expression changes, and clinical trials are being developed to identify miRNAs in body fluids that could predict disease outcomes based on miRNA encapsulation in exosomes making them stable in body fluids. Recently, studies have shown that dietary miRNAs encapsulated in exosomes can be absorbed in mice and humans, and on the …

Non-Genomic Effects Of Glucocorticoids: An Updated View, Reynod A. Panettieri, Dedmer Schaafsma, Yassine Amrani, Cynthia Koziol-White, Rennolds S. Ostrom, Omar Tliba

Pharmacy Faculty Articles and Research

Glucocorticoid (GC) anti-inflammatory effects generally require a prolonged onset of action and involve genomic processes. Because of the rapidity of some of the GC effects, however, the concept that non-genomic actions may contribute to GC mechanisms of action has arisen. While the mechanisms have not been completely elucidated, the non-genomic effects may play a role in the management of inflammatory diseases. For instance, we recently reported that GCs ‘rapidly’ enhanced the effects of bronchodilators, agents used in the treatment of allergic asthma. In this review article, we discuss (i) the non-genomic effects of GCs on pathways relevant to the pathogenesis …

Mitochondrial Metabolism In Major Neurological Diseases, Zhengqiu Zhou, Grant L. Austin, Lyndsay E. A. Young, Lance A. Johnson, Ramon Sun

Molecular and Cellular Biochemistry Faculty Publications

Mitochondria are bilayer sub-cellular organelles that are an integral part of normal cellular physiology. They are responsible for producing the majority of a cell’s ATP, thus supplying energy for a variety of key cellular processes, especially in the brain. Although energy production is a key aspect of mitochondrial metabolism, its role extends far beyond energy production to cell signaling and epigenetic regulation–functions that contribute to cellular proliferation, differentiation, apoptosis, migration, and autophagy. Recent research on neurological disorders suggest a major metabolic component in disease pathophysiology, and mitochondria have been shown to be in the center of metabolic dysregulation and possibly …

Distinct White Matter Changes Associated With Cerebrospinal Fluid Amyloid-Β1-42 And Hypertension, Omar M. Al-Janabi, Christopher A. Brown, Ahmed A. Bahrani, Erin L. Abner, Justin M. Barber, Brian T. Gold, Larry B. Goldstein, Richard R. Murphy, Peter T. Nelson, Nathan F. Johnson, Leslie M. Shaw, Charles D. Smith, John Q. Trojanowski, Donna M. Wilcock, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Alzheimer's disease (AD) pathology and hypertension (HTN) are risk factors for development of white matter (WM) alterations and might be independently associated with these alterations in older adults.

OBJECTIVE: To evaluate the independent and synergistic effects of HTN and AD pathology on WM alterations.

METHODS: Clinical measures of cerebrovascular disease risk were collected from 62 participants in University of Kentucky Alzheimer's Disease Center studies who also had cerebrospinal fluid (CSF) sampling and MRI brain scans. CSF Aβ_1-42 levels were measured as a marker of AD, and fluid-attenuated inversion recovery imaging and diffusion tensor imaging were obtained to assess …

Radiofrequency Renal Denervation Attenuates Kidney Fibrosis In Spontaneously Hypertensive Rats (2267), Juan Gao, Ian Bart Denys, Luis Del Valle, Mihran V. Naljayan, Daniel R. Kapusta

School of Medicine Faculty Publications

No abstract provided.

Week Of November 19, 2018, New York Medical College

InTouch

• Center for Disaster Medicine Hosts "Mass Casualty Events and 'Stop the Bleeding'" Symposium
• School of Medicine Alumni Association Hosts Annual Reunion
• Department of Pediatrics and the Children's Health and Research Foundation Hosts Eighth Annual Assistant Professor Pediatric Research Symposium
• NYMC Helps Move the Needle Forward in Developing Anti-Chemical Warfare Drugs
• NYMC Hosts Fourth Annual Human Rights Institute for Middle School Student Leaders

H3k9 Methyltransferases And Demethylases Control Lung Tumor-Propagating Cells And Lung Cancer Progression, S. P. Rowbotham, F Li, A. F. M. Dost, S. M. Louie, B. P. Marsh, P. Pessina, C. R. Anbarasu, Christine Fillmore Brainson, S. J. Tuminello, A. Lieberman, S. Ryeom, T. M. Schlaeger, B. J. Aronow, H. Watanabe, K. K. Wong, C. F. Kim

Toxicology and Cancer Biology Faculty Publications

Epigenetic regulators are attractive anticancer targets, but the promise of therapeutic strategies inhibiting some of these factors has not been proven in vivo or taken into account tumor cell heterogeneity. Here we show that the histone methyltransferase G9a, reported to be a therapeutic target in many cancers, is a suppressor of aggressive lung tumor-propagating cells (TPCs). Inhibition of G9a drives lung adenocarcinoma cells towards the TPC phenotype by de-repressing genes which regulate the extracellular matrix. Depletion of G9a during tumorigenesis enriches tumors in TPCs and accelerates disease progression metastasis. Depleting histone demethylases represses G9a-regulated genes and TPC phenotypes. Demethylase inhibition …

Cyclophilin 40 As A Novel Disaggregase, Jeremy Dustin Baker

USF Tampa Graduate Theses and Dissertations

The negative health and economic impacts of neurodegenerative diseases on Americans is astounding and accelerating with an aging population. The Alzheimer’s Association reports that 5.7 million Americans suffer from Alzheimer’s disease (AD), a number which is expected to increase to 14 million by 2050. In economic terms, AD and other neurodegenerative disorders will cost the US over $275 billion in 2018, rising to over $1 trillion annually by 2050. AD causes gross brain atrophy and is most damaging throughout the cortex and the hippocampus, regions required for higher cognitive function and memory. AD presents as tangles within neurons composed of …

Shanghai, China: “Nontraditional” Traditional Chinese Medicine, Joshua Martin

Purdue Journal of Service-Learning and International Engagement

Joshua Martin is a second-year PharmD student in the Purdue University College of Pharmacy. Within the College of Pharmacy, he is the president-elect of the Industry Pharmacist Organization (IPhO), is on the Orientation Steering Committee for newly admitted PharmD students, and preforms nanoparticle research within the Industrial and Physical Pharmacy sector of the College. He hopes to pursue a career in the pharmaceutical industry where he can positively impact patients on a global scale. Josh comes from a family of Boilermakers and avidly supports the Black and Gold. In this article, he describes his experience studying at Shanghai University of …

Micu1 Interacts With The D-Ring Of The Mcu Pore To Control Its Ca2+ Flux And Sensitivity To Ru360, Melanie Paillard, György Csordás, Kai-Ting Huang, Peter Várnai, Suresh K. Joseph, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Proper control of the mitochondrial Ca²⁺ uniporter’s pore (MCU) is required to allow Ca²⁺ dependent activation of oxidative metabolism and to avoid mitochondrial Ca²⁺ overload and cell death. The MCU’s gatekeeping and cooperative activation is mediated by the Ca²⁺ sensing MICU1 protein, which has been proposed to form dimeric complexes anchored to the EMRE scaffold of MCU. We unexpectedly find that MICU1 suppresses inhibition of MCU by ruthenium red/Ru360, which bind to MCU’s DIME motif, the selectivity filter. This led us to recognize in MICU1’s sequence, a putative DIME Interacting Domain (DID) which is required for …

Proteolysis Of Cx3cl1 Impacts Cx3cr1 Signaling And Therapeutic Benefits In A Tauopathy Model, Dylan John Finneran

USF Tampa Graduate Theses and Dissertations

Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder and the most common form of dementia. The hallmark pathologies of AD are extracellular aggregates of amyloid-beta, intracellular aggregates of microtubule associated protein tau and increased neuroinflammation. Current therapeutics offer only symptomatic relief and clinical trials investigating therapeutic benefits of non-steroidal anti-inflammatory drugs have yielded no positive results. Therefore, recent work has focused on immunomodulators, such as CD200 and fractalkine, as potential therapeutic targets for AD.

Fractalkine (CX3CL1; FKN) is expressed as a transmembrane protein with an N-terminal chemokine domain followed by a long, mucin-like stalk. FKN can signal as a membrane-bound …

Comparison Of Calculated Energy Expenditure To Measured Energy Expenditure In Overweight And Obese Burn Patients In An Icu Setting: A Retrospective Study, Elle Maree Skinner, Deborah A. Cohen, Orrin B. Myers, Diana Gonzales-Pacheco

Individual, Family, and Community Education ETDs

Burns cause massive dermal wounds. Wound healing elicits a significant catabolic response and increase in energy expenditure, and thus, calorie needs. Overfeeding and/or underfeeding the overweight and obese critically ill patient can increase complications. Indirect Calorimetry (IC) is considered the ‘gold standard” for the measurement of Energy Expenditure (EE). Predictive equations are calculated to estimate EE instead. This study is a retrospective chart review. The difference between predictive energy expenditure (via Curreri formula) and measured IC were analyzed via non-parametric Wilcoxon signed rank match paired tests. Curreri equation prediction was analyzed on the ability to match IC (0% over or …

Platelet Cd36 Signaling Through Erk5 Promotes Caspase-Dependent Procoagulant Activity And Fibrin Deposition In Vivo, Moua Yang, Andaleb Kholmukhamedov, Marie L. Schulte, Brian C. Cooley, Na'il O. Scoggins, Jeremy P. Wood, Scott J. Cameron, Craig N. Morrell, Shawn M. Jobe, Roy L. Silverstein

Saha Cardiovascular Research Center Faculty Publications

Dyslipidemia is a risk factor for clinically significant thrombotic events. In this condition, scavenger receptor CD36 potentiates platelet reactivity through recognition of circulating oxidized lipids. CD36 promotes thrombosis by activating redox-sensitive signaling molecules, such as the MAPK extracellular signal-regulated kinase 5 (ERK5). However, the events downstream of platelet ERK5 are not clear. In this study, we report that oxidized low-density lipoprotein (oxLDL) promotes exposure of procoagulant phosphatidylserine (PSer) on platelet surfaces. Studies using pharmacologic inhibitors indicate that oxLDL-CD36 interaction–induced PSer exposure requires apoptotic caspases in addition to the downstream CD36-signaling molecules Src kinases, hydrogen peroxide, and ERK5. Caspases promote PSer …

Distinct Role Of Il-27 In Immature And Lps-Induced Mature Dendritic Cell-Mediated Development Of Cd4, Fang Zhou, Guang-Xian Zhang, A. M. Rostami

Department of Neurology Faculty Papers

Interleukin-27 (IL-27) plays an important role in regulation of anti-inflammatory responses and autoimmunity; however, the molecular mechanisms of IL-27 in modulation of immune tolerance and autoimmunity have not been fully elucidated. Dendritic cells (DCs) play a central role in regulating immune responses mediated by innate and adaptive immune systems, but regulatory mechanisms of DCs in CD4⁺ T cell-mediated immune responses have not yet been elucidated. Here we show that IL-27 treated mature DCs induced by LPS inhibit immune tolerance mediated by LPS-stimulated DCs. IL-27 treatment facilitates development of the CD4⁺ CD127⁺3G11⁺ regulatory T cell subset …

Who Did It?: A Review On The Possible Causes Of Multiple Sclerosis, Mia Difrancesco

D.U.Quark

Multiple Sclerosis (MS) is an incurable autoimmune disorder that attacks the myelin sheath surrounding nerve cells. Steady demyelination of these cells over time results in painful inflammation and reduced mobility. Genetic abnormalities could be responsible for the onset of this disease. Chromosomal mutations found in MS patients as well as environmental factors influencing the expression of certain genes will be analyzed in this review. Moreover, treatments regulating gene expression in MS patients will be discussed. Further genetic research would not only provide scientists and medical professionals with a deeper understanding of MS and other autoimmune disorders, but also lead to …

Week Of November 12, 2018, New York Medical College

InTouch

• GSBMS Launches New M.S. in Clinical Laboratory Sciences Program
• NYMC Takes Hard Hat Tour of Ellis Island
• HSL Hosts Special Presentation on "The Art of Observation"

Calibration And Analysis Of A Multimodal Micro-Ct And Structured Light Imaging System For The Evaluation Of Excised Breast Tissue., David M. Mcclatchy Iii, Elizabeth J. Rizzo, Jeff Meganck, Josh Kempner, Jared Vicory, Wendy A. Wells, Keith D. Paulsen, Brian W. Pogue

Dartmouth Scholarship

A multimodal micro-computed tomography (CT) and multi-spectral structured light imaging (SLI) system is introduced and systematically analyzed to test its feasibility to aid in margin delineation during breast conserving surgery (BCS). Phantom analysis of the micro-CT yielded a signal-to-noise ratio of 34, a contrast of 1.64, and a minimum detectable resolution of 240 ?m for a 1.2?min scan. The SLI system, spanning wavelengths 490?nm to 800?nm and spatial frequencies up to 1.37 , was evaluated with aqueous tissue simulating phantoms having variations in particle size distribution, scatter density, and blood volume fraction. The reduced scattering coefficient, and phase function …