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Employing The Enzyme Cofactor Function Of Ascorbic Acid To Affect Oncogenic Pathways In Human Melanoma: Modulating Hypoxia Inducible Factor-1Α And Dna Demethylation To Reduce Malignant Potential, Adam Patrick Fischer

Theses, Dissertations and Capstones

Dioxygenase enzymes such as the HIF hydroxylases (PHD1-3, FIH) and the Ten-eleven translocation (TET1-3) enzymes regulate the activity of the hypoxia inducible factor-1_a (HIF1_a) transcription factor and the DNA methylation status of cells, respectively. Aberrant accumulation and activation of HIF-1_a can allow malignant cells to acquire attributes that promote progression, chemotherapy resistance, and survival, while aberrant hypermethylation of gene promoters can silence the expression of tumor suppressor genes essential to preventing tumorigenesis. Inadequate levels of intracellular ascorbic acid (AA), a necessary cofactor for optimal dioxygenase enzyme function, could potentiate these tumorigenic conditions. In fact, plasma levels …

The Role Of N-Myc Downstream Regulated Gene 1 In Breast Cancer Lipid Metabolism, Christopher James Sevinsky

Legacy Theses & Dissertations (2009 - 2024)

Altered carbohydrate and lipid metabolism are increasingly well characterized hallmarks of aggressive breast cancers. While aerobic glycolysis, or “the Warburg effect”, is a well-established metabolic adaptation exploited by tumor cells, the understanding of unique aspects of cancer lipid metabolism lags behind. This is especially true regarding the coordination of complex lipid synthesis and trafficking pathways, which remains poorly understood. N-Myc Downstream Regulated Gene1 (NDRG1) is overexpressed in many solid tumors, but its function is unclear. The importance of NDRG1 is best exemplified by the effect of null mutations on human physiology: inactivating mutations give rise to the severe autosomal recessive …

Mechanisms Of Hormonal Regulation Of Invasiveness And Metastasis Of Luminal Breast Cancer, Thomas Mcfall

Wayne State University Dissertations

ABSTRACT

MECHANISMS OF HORMONAL REGULATION OF INVASIVENESS AND METASTASIS OF LUMINAL BREAST CANCER

By

THOMAS MCFALL

December 2017

Advisor: Dr. Manohar Ratnam

Major: Cancer Biology

Degree: Doctor of Philosophy

Over 20% of breast cancer cases present with distal metastasis and they are predominantly of luminal subtypes. As luminal breast cancer is relatively indolent, it is believed that progression to metastasis must occur over many years, generally well into post-menopausal years. Unfortunately, very little is known about the mechanisms by which these hormone receptor positive tumors metastasize, likely in part due to their slow metastatic rates in animal model systems as …

A Mathematical Investigation On Tumor-Immune Dynamics: The Impact Of Vaccines On The Immune Response, Jonathan Quinonez, Neethi Dasu, Mahboob Qureshi

College of Osteopathic Medicine (TUN) Publications and Research

Mathematical models analyzing tumor-immune interactions provide a framework by which to address specific scenarios in regard to tumor-immune dynamics. Important aspects of tumor-immune surveillance to consider is the elimination of tumor cells from a host’s cell-mediated immunity as well as the implications of vaccines derived from synthetic antigen. In present studies, our mathematical model examined the role of synthetic antigen to the strength of the immune system. The constructed model takes into account accepted knowledge of immune function as well as prior work done by de Pillis et al. All equations describing tumor-immune growth, antigen presentation, immune response, and interaction …

Vitamin K2 (Menaquinone) Supplementation And Its Benefits In Cardiovascular Disease, Osteoporosis, And Cancer, Grant S. Buchanan, Md, Thomas Melvin, Brandon Merritt, Charles Bishop, Md, Franklin D. Shuler, Md, Phd

Marshall Journal of Medicine

Vitamin K is known to play an essential role in the coagulation cascade; however, a growing body of research has found that a subtype of this vitamin, vitamin K₂ (menaquinone) may have a beneficial effect in osteoporosis, cardiovascular disease, and cancer. This purpose of this article is to provide a comprehensive review of recent literature regarding menaquinone and its role in human health. This review discusses the physiology of menaquinone, its clinical benefits in cardiovascular disease, osteoporosis, and cancer, and how it may interact with certain medications. The authors conclude that menaquinone supplementation has been shown to improve carboxylation …

Revealing The Quality Of Movement: A Meta-Analysis Review To Quantify The Thresholds To Pathological Variability During Standing And Walking, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

Neuromotor processes are inherently noisy, which results in variability during movement and fluctu-ations in motor control. Although controversial, low levels of variability are traditionally considered healthy, while increased levels are thought to be pathological. This systematic review and meta-analysisof the literature investigates the thresholds between healthy and pathological task variability.

After examining 13,195 publications, 109 studies were included. Results from over 3000 healthy sub-jects and 2775 patients revealed an overall positive effect size of pathology on variability of 0.59 forwalking and 0.80 for sway. For the coefficient of variation of stride time (ST) and sway area (SA), upperthresholds of 2.6% …

Cooling Effectiveness Of Modified Cold-Water Immersion Method Following Exercise-Induced Hyperthermia, Katherine Elizabeth Luhring

Graduate Theses and Dissertations

Context: Recommended treatment of exertional heat stroke (EHS) includes whole body cold-water immersion (CWI); however, remote locations, spatial or monetary restrictions challenge CWI feasibility. Thus, the development of a modified, portable CWI method would allow for optimal treatment of EHS when restrictions apply. Objective: Determine cooling efficacy of modified CWI (tarp assisted cooling with oscillation; TACO) following exertional hyperthermia. Design: Randomized, crossover controlled trial. Setting: Environmental chamber (33.4 ± 0.8°C, 55.7 ± 1.9% relative humidity). Patients or Other Participants: Sixteen (9 males, 7 females) volunteers (26 ± 4.7y, 1.76 ± 0.09m, 72.5 ± 9.0kg, 20.7 ± 7.1%body fat) with no …

1st Place Contest Entry: The Effectiveness Of Yoga Therapy On An Adult, Post-Stroke Population: A Systematic Review, Baylor E. Hogan

Kevin and Tam Ross Undergraduate Research Prize

This is Baylor Hogan's submission for the 2016 Kevin and Tam Ross Undergraduate Research Prize, which won first place. She wrote about the effects of yoga therapy on the physical and mental wellbeing of stroke patients. You can read the final essay that came out of her research here.

Baylor is a senior at Chapman University, majoring in Kinesiology. Her faculty mentor is Dr. Elizabeth DeBaets.

Examination Of Reticulocytosis Among Chronically Transfused Children With Sickle Cell Anemia., Megha Kaushal, Colleen Byrnes, Zarir Khademian, Natalie Duncan, Naomi L. Luban, Jeffery L Miller, Ross Fasano, Emily R. Meier

Pediatrics Faculty Publications

Sickle cell anemia (SCA) is an inherited hemolytic anemia with compensatory reticulocytosis. Recent studies have shown that increased levels of reticulocytosis during infancy are associated with increased hospitalizations for SCA sequelae as well as cerebrovascular pathologies. In this study, absolute reticulocyte counts (ARC) measured prior to transfusion were analysed among a cohort of 29 pediatric SCA patients receiving chronic transfusion therapy (CTT) for primary and secondary stroke prevention. A cross-sectional flow cytometric analysis of the reticulocyte phenotype was also performed. Mean duration of CTT was 3.1 ± 2.6 years. Fifteen subjects with magnetic resonance angiography (MRA) -vasculopathy had significantly higher …

Examination Of Reticulocytosis Among Chronically Transfused Children With Sickle Cell Anemia., Megha Kaushal, Colleen Byrnes, Zarir Khademian, Natalie Duncan, Naomi L.C. Luban, Jeffery L Miller, Ross M. Fasano, Emily Riehm Meier

Pediatrics Faculty Publications

Sickle cell anemia (SCA) is an inherited hemolytic anemia with compensatory reticulocytosis. Recent studies have shown that increased levels of reticulocytosis during infancy are associated with increased hospitalizations for SCA sequelae as well as cerebrovascular pathologies. In this study, absolute reticulocyte counts (ARC) measured prior to transfusion were analysed among a cohort of 29 pediatric SCA patients receiving chronic transfusion therapy (CTT) for primary and secondary stroke prevention. A cross-sectional flow cytometric analysis of the reticulocyte phenotype was also performed. Mean duration of CTT was 3.1 ± 2.6 years. Fifteen subjects with magnetic resonance angiography (MRA) -vasculopathy had significantly higher …

Integrating Meal And Exercise Into Personalized Glucoregulation Models: Metabolic Dynamics And Diabetic Athletes, Sofie Schunk

Master's Theses (2009 -)

Diabetes affects nearly 26 million Americans, according to the American Diabetes Association, with as many as three million Americans who have Type 1 Diabetes (ADA, 2015). Type 1 Diabetes (T1D) is autoimmune and characterized by little to no insulin production whereas Type 2 Diabetes (T2D) concerns insulin resistance and inability to use produced insulin. Factors contributing to current diabetes management and regulation include exercise type, daily movement activities, and distinct tissue compartment metabolism, each challenging to model in a robust and comprehensive manner. Past models are highly limited in regard to exercise and varying glucose fluctuations dependent on type, intensity, …

Pleiotropic Effects Of Bitter Taste Receptors On [Ca2+]I Mobilization, Hyperpolarization, And Relaxation Of Human Airway Smooth Muscle Cells., Blanca Camoretti-Mercado, Susan H Pauer, Hwan Mee Yong, Dan'elle C Smith, Deepak A. Deshpande, Phd, Steven S An, Stephen B Liggett

Center for Translational Medicine Faculty Papers

Asthma is characterized by airway inflammation and airflow obstruction from human airway smooth muscle (HASM) constriction due to increased local bronchoconstrictive substances. We have recently found bitter taste receptors (TAS2Rs) on HASM, which increase [Ca2+]i and relax the muscle. We report here that some, but not all, TAS2R agonists decrease [Ca2+]i and relax HASM contracted by G-protein coupled receptors (GPCRs) that stimulate [Ca2+]i. This suggests both a second pathway by which TAS2Rs relax, and, a heterogeneity of the response phenotype. We utilized eight TAS2R agonists and five procontractile GPCR agonists in cultured HASM cells. We find that heterogeneity in the …

Understanding And Treating Emergence Delirium, Peter Currie

Nurse Anesthesia MSNA Student Capstones

This paper examines our current understanding of the phenomena of emergence delirium, which can occur following general anesthesia. Much research has been conducted to elucidate the causative factors of this condition, with findings ranging from anxiety to volatile agents and the neurodevelopment of the brain (Aono, Ueda, & Mamiya, 1997; Kain et al., 2004; McLott, Jurecic, Hemphill, & Dunn, 2013). While much of our understanding of emergence delirium has come from studying children, who are more prone to this condition, we can attempt to learn even more by examining the increased incidence of emergence delirium that occurs in those with …

Short-Wavelength Enrichment Of Polychromatic Light Enhances Human Melatonin Suppression Potency., George Brainard, John P. Hanifin, Benjamin Warfield, Marielle K. Stone, Mary E. James, Melissa Ayers, Alan Kubey, Brenda Byrne, Mark Rollag

Department of Neurology Faculty Papers

The basic goal of this research is to determine the best combination of light wavelengths for use as a lighting countermeasure for circadian and sleep disruption during space exploration, as well as for individuals living on Earth. Action spectra employing monochromatic light and selected monochromatic wavelength comparisons have shown that short-wavelength visible light in the blue-appearing portion of the spectrum is most potent for neuroendocrine, circadian, and neurobehavioral regulation. The studies presented here tested the hypothesis that broad spectrum, polychromatic fluorescent light enriched in the short-wavelength portion of the visible spectrum is more potent for pineal melatonin suppression in healthy …

Bioactive Lipid Coating Of Bone Allografts Direct Engraftment And Fate Determination Of Bone Marrow-Derived Cells In Rat Gfp Chimeras, Anusuya Das, Claire E. Segar, Yihsuan Chu, Tiffany W. Wang, Yon Lin, Chunxi Yang, Roy C. Ogle

School of Medical Diagnostics & Translational Sciences Publications

Bone grafting procedures are performed to treat wounds incurred during wartime trauma, accidents, and tumor resections. Endogenous mechanisms of repair are often insufficient to ensure integration between host and donor bone and subsequent restoration of function. We investigated the role that bone marrow-derived cells play in bone regeneration and sought to increase their contributions by functionalizing bone allografts with bioactive lipid coatings. Polymer-coated allografts were used to locally deliver the immunomodulatory small molecule FTY720 in tibial defects created in rat bone marrow chimeras containing genetically-labeled bone marrow for monitoring cell origin and fate. Donor bone marrow contributed significantly to both …

Development Of A Heart Rate Variability Measurement System Using Embedded Electronics, Naresh Kumar Velmurugan

Graduate Theses and Dissertations

Recent advances in embedded electronics have a remarkable influence on the health care system. One of the most important applications is to monitor the health care of the patients at anytime and anyplace. In the last two decades, many researchers have focused mainly on heart rate variability (HRV) measurements. Patient's heart rate variability should be continuously monitored to help them in case of emergency. Under these circumstances, patients are required to have a HRV measuring kit for a constant observation.

The proposed project focuses on the development of a heart rate variability measurement system with the use of embedded electronics. …

Development Of A Fatal Noncompressible Truncal Hemorrhage Model With Combined Hepatic And Portal Venous Injury In Normothermic Normovolemic Swine, Ujwal R. Yanala, Jason M. Johanning, Iraklis I. Pipinos, Gustavo F. Larsen, William H. Velander, Mark A. Carlson

William H. Velander Publications

Noncompressible truncal hemorrhage and brain injury currently account for most early mortality of warfighters on the battlefield. There is no effective treatment for noncompressible truncal hemorrhage, other than rapid evacuation to a surgical facility. The availability of an effective field treatment for noncompressible truncal hemorrhage could increase the number of warfighters salvaged from this frequently-lethal scenario. Our intent was to develop a porcine model of noncompressible truncal hemorrhage with a ,50% one-hour mortality so that we could develop new treatments for this difficult problem. Normovolemic normothermic domestic swine (barrows, 3 months old, 34–36 kg) underwent one of three injury types …

Serum Metabolomic Response Of Myasthenia Gravis Patients To Chronic Prednisone Treatment, Manjistha Sengupta, Amrita Cheema, Henry J. Kaminski, Linda Louise Kusner

Neurology Faculty Publications

Prednisone is often used for the treatment of autoimmune and inflammatory diseases but they suffer from variable therapeutic responses and significant adverse effects. Serum biological markers that are modulated by chronic corticosteroid use have not been identified. Myasthenia gravis is an autoimmune neuromuscular disorder caused by antibodies directed against proteins present at the post-synaptic surface of neuromuscular junction resulting in weakness. The patients with myasthenia gravis are primarily treated with prednisone. We analyzed the metabolomic profile of serum collected from patients prior to and after 12 weeks of prednisone treatment during a clinical trial. Our aim was to identify metabolites …

Iso-66, A Novel Inhibitor Of Macrophage Migration Inhibitory Factor, Shows Efficacy In Melanoma And Colon Cancer Models, K. Ioannou, K. F. Cheng, G. V. Crichlow, A. I. Birmpilis, E. J. Lolis, O. E. Tsitsilonis, Y. Al-Abed

Journal Articles

Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine, which possesses a contributing role in cancer progression and metastasis and, thus, is now considered a promising anticancer drug target. Many MIF-inactivating strategies have proven successful in delaying cancer growth. Here, we report on the synthesis of ISO-66, a novel, highly stable, small-molecule MIF inhibitor, an analog of ISO-1 with improved characteristics. The MIF:ISO-66 co-crystal structure demonstrated that ISO-66 ligates the tautomerase active site of MIF, which has previously been shown to play an important role in its biological functions. In vitro, ISO-66 enhanced specific and non-specific anticancer immune responses, …

Adolescence And Human Sexuality, Donald E. Greydanus, Hatim A. Omar

Pediatrics Faculty Publications

Human sexuality is a complex phenomenon involving the interaction of biology, sex, core gender identity, and gender role behavior. Successful completion of normal stages of sexuality development is important for children and adolescents to allow for optimal life as an adult. Controversies arise for clinicians as they work with their pediatric patients regarding health care sexuality issues. It is important that clinicians help these patients in an unbiased and neutral manner. As adults, these children and adolescents will function in a number of sexuality roles, whether heterosexual, homosexual, or bisexual. This chapter reviews many of these complex and critical issues …

Cochlear Development And Auditory Function In The Absence Of Thyroid Hormone Transporters Mct8 And Oatp1c1, Richard Sinn

All Graduate Theses, Dissertations, and Other Capstone Projects

Thyroid hormone (TH) is essential for the development and maturation of the nervous system. The thyroid gland secretes an active form of TH, triiodothyronine, and a prohormone, thyroxine, into the blood. TH is charged, which prevents it from passively diffusing across cell membranes and thus requires cell membrane transporters to facilitate its movement into and out of cells. However, whether TH transporters are required for TH-mediated developmental events, including the auditory system, is largely unknown.

The purpose of the present study was to investigate two specific TH transporters, monocarboxylate transporter 8 (Mct8) and organic anion transporting polypeptide 1c1 (Oatp1c1), and …

Differential Effects Of Fatigue On Movement Variability, N. Cortes, J. Onate, S. Morrison

Rehabilitation Sciences Faculty Publications

When individuals perform purposeful actions to fatigue, there is typically a general decline in their movement performance. This study was designed to investigate the effects exercise-induced fatigue has on lower limb kinetics and kinematics during a side-step cutting task. In particular, it was of interest to determine what changes could be seen in mean amplitude and all metrics of signal variability with fatigue. The results of the study revealed that post-fatigue there was an overall decrease in absolute force production as reflected by a decline in mean amplitude and variability (SD) of the ground reaction forces (GRF_V and GRF …

Hot Topics In Education, Michael Hartman

Faculty Works: AHS (2004-2023)

Presented at Society of Diagnostic Medical Sonography Annual Conference (2013) in Las Vegas, NV

The Identification And Classification Of Flow Disruptions In The Operating Room During Laparoscopic Cholecystectomy And Open Hernia Repair Procedures, Sacha N. Duff

Doctoral Dissertations and Master's Theses

The operating room is one of the most complex work environments in healthcare; it is estimated that at least 7% of adverse events due to medical error occur in the operating room. Flow disruptions are events that cause a "break" in the primary surgical task, or the loss of any team member's situational awareness. An empirical link between flow disruptions and surgical errors in the OR has been established; therefore, identifying and classifying the specific flow disruptions present during different types of procedures should facilitate the development of evidence-based interventions. The goal of this study was to identify and classify …

Holobiont Nutrition: Considering The Role Of The Gastrointestinal Microbiota In The Health Benefits Of Whole Grains, Jens Walter, Ines Martinez, Devin J. Rose

Food for Health: Publications

Intake of whole grains and other food products high in dietary fiber have long been linked to the prevention of chronic diseases associated with inflammation. A contribution of the gastrointestinal microbiota to these effects has been suggested, but little is known on how whole grains interact with gut bacteria. We have recently published the first human trial that made use of next-generation sequencing to determine the effect of whole grains (whole grain barley, brown rice or a mixture of the two) on fecal microbiota structure and tested for associations between the gut microbiota and blood markers of inflammation, glucose and …

Molecular Mechanisms Related To Endotoxemia In Primary Human Cardiomyocytes In Culture, Atijah J. Collins

PCOM Biomedical Studies Student Scholarship

Cardiovascular disease (CVD) is the leading cause of death in the United States and has been for the past 80 years. Development of novel therapeutic agents to address the large number of CVD deaths requires an in depth understanding of the structural and functional properties of human cardiomyocytes. Over the last few years we have been developing an in vitro paradigm to assess molecular cardiodynamics in Primary Human Cardiomyocyte in culture (PHCC). We tested the hypothesis whether endotoxemia would exhibit a marked decrease in contractile proteins and cause apoptosis in PHCC. In the current series of experiments, we induced endotoxemia …

Doxorubicin-Induced, Tnf-Α-Mediated Brain Oxidative Stress, Neurochemical Alterations, And Cognitive Decline: Insights Into Mechanisms Of Chemotherapy Induced Cognitive Impairment And Its Prevention, Jeriel T. Keeney

Theses and Dissertations--Chemistry

The works presented in this dissertation provide insights into the mechanisms of chemotherapy-induced cognitive impairment (CICI or “ChemoBrain”) and take steps toward outlining a preventive strategy. CICI is now widely recognized as a complication of cancer chemotherapy experienced by a large percentage of cancer survivors. Approximately fifty percent of existing FDA-approved anti-cancer drugs generate reactive oxygen species (ROS). Doxorubicin (Dox), a prototypical ROS-generating chemotherapeutic agent, produces the reactive superoxide radical anion (O₂^-•) in vivo. Dox treatment results in oxidation of plasma proteins, including ApoA-I, leading to TNF-α-mediated oxidative stress in plasma and brain. TNF-α elevation in brain …

The Effects Of Energy Beverages In Counteracting The Symptoms Of Mild Hypoxia At Legal General Aviation Altitudes, Daniel Mark Bull

Doctoral Dissertations and Master's Theses

The purpose of this thesis was to conduct preliminary research, in the form of a pilot study, concerning the natural effects of hypoxia compared to the effects of hypoxia experienced after the consumption of an energy beverage. The study evaluated the effects of hypoxia on FAA certificated pilots at a simulated legal general aviation altitude, utilizing the normobaric High Altitude Lab (HAL) located at Embry Riddle Aeronautical University, Daytona Beach, Florida. The researcher tested 11 subjects, who completed three simulated flight tasks within the HAL using the Frasca International Mentor Advanced Aviation Training Device (AATD). The flight tasks were …

Transfusion Of Cxcr4-Primed Endothelial Progenitor Cells Reduces Cerebral Ischemic Damage And Promotes Repair In Db/Db Diabetic Mice, Ji Chen, Jianying Chen, Shuzhen Chen, Cheng Zhang, Liangqing Zhang, Xiang Xiao, Avik Das, Yuhui Zhao, Bin Yuan, Mariana Morris, Bin Zhao, Yanfang Chen

Pharmacology and Toxicology Faculty Publications

This study investigated the role of stromal cell-derived factor-1α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) axis in brain and endothelial progenitor cells (EPCs), and explored the efficacy of CXCR4 primed EPCs in treating ischemic stroke in diabetes. The db/db diabetic and db/+ mice were used in this study. Levels of plasma SDF-1α and circulating CD34+CXCR4+ cells were measured. Brain SDF-1α and CXCR4 expression were quantified at basal and after middle cerebral artery occlusion (MCAO). In in vitro study, EPCs were transfected with adenovirus carrying null (Ad-null) or CXCR4 (Ad-CXCR4) followed with high glucose (HG) treatment for 4 days. For pathway block …

Sarcopenia, Obesity, And Natural Killer Cell Immune Senescence In Aging: Altered Cytokine Levels As A Common Mechanism, Charles T. Lutz, Lebris S. Quinn

Pathology and Laboratory Medicine Faculty Publications

Human aging is characterized by both physical and physiological frailty. A key feature of frailty, sarcopenia is the age-associated decline in skeletal muscle mass, strength, and endurance that characterize even the healthy elderly. Increases in adiposity, particularly in visceral adipose tissue, are almost universal in aging individuals and can contribute to sarcopenia and insulin resistance by increasing levels of inflammatory cytokines known collectively as adipokines. Aging also is associated with declines in adaptive and innate immunity, known as immune senescence, which are risk factors for cancer and all-cause mortality. The cytokine interleukin-15 (IL-15) is highly expressed in skeletal muscle tissue …