Digital Commons Network^™

An Assessment Of The Use Of Chimpanzees In Hepatitis C Research Past, Present And Future: 2. Alternative Replacement Methods, Jarrod Bailey

Experimentation Collection

The use of chimpanzees in hepatitis C virus (HCV) research was examined in the report associated with this paper (1: Validity of the Chimpanzee Model), in which it was concluded that claims of past necessity of chimpanzee use were exaggerated, and that claims of current and future indispensability were unjustifiable. Furthermore, given the serious scientific and ethical issues surrounding chimpanzee experimentation, it was proposed that it must now be considered redundant — particularly in light of the demonstrable contribution of alternative methods to past and current scientific progress, and the future promise that these methods hold. This paper builds on …

An Assessment Of The Use Of Chimpanzees In Hepatitis C Research Past, Present And Future: 1. Validity Of The Chimpanzee Model, Jarrod Bailey

Experimentation Collection

The USA is the only significant user of chimpanzees in biomedical research in the world, since many countries have banned or limited the practice due to substantial ethical, economic and scientific concerns. Advocates of chimpanzee use cite hepatitis C research as a major reason for its necessity and continuation, in spite of supporting evidence that is scant and often anecdotal. This paper examines the scientific and ethical issues surrounding chimpanzee hepatitis C research, and concludes that claims of the necessity of chimpanzees in historical and future hepatitis C research are exaggerated and unjustifiable, respectively. The chimpanzee model has several major …

Imaging Of Lung Function Using Hyperpolarized Helium-3 Magnetic Resonance Imaging: Review Of Current And Emerging Translational Methods And Applications, Sean Fain, Mark L Schiebler, David G Mccormack, Grace Parraga

Medical Biophysics Publications

During the past several years there has been extensive development and application of hyperpolarized helium-3 (HP (3)He) magnetic resonance imaging (MRI) in clinical respiratory indications such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, radiation-induced lung injury, and transplantation. This review focuses on the state-of-the-art of HP (3)He MRI and its application to clinical pulmonary research. This is not an overview of the physics of the method, as this topic has been covered previously. We focus here on the potential of this imaging method and its challenges in demonstrating new types of information that has the potential to influence clinical …

Protocol Variation Analysis Of Whole Brain Ct Perfusion In Acute Ischemic Stroke, Peter T. Heiberger

UNLV Theses, Dissertations, Professional Papers, and Capstones

Computed tomography perfusion (CTP) analysis is a rapidly advancing imaging modality that is improving diagnosis of brain abnormalities in patients suffering from hemorrhagic or ischemic stroke, traumatic brain injury, vascular occlusion and numerous other conditions. Through the advancements of computed tomography (CT) imaging, including the introduction of the 320-detector row CT with a 16 centimeter range in the z-axis enabling whole brain CTP, perfusion analysis now has a significantly increased clinical utility that is useful for both diagnosis and treatment of central nervous system (CNS) conditions. This study focuses on the procedural and analytical approach to the diagnostic evaluation of …

Development Of Novel Biomarkers In Cancer: Detection Of Circulating Mir-141 As A Potential Prognostic Marker For Prostate Cancer, Jason Cadaoas Gonzales

UNLV Theses, Dissertations, Professional Papers, and Capstones

Prostate cancer (CAP) is the most common epithelial malignancy and the second leading cause of cancer deaths in American men. The identification of predictive and prognostic biomarkers in CAP patients is critical for improving clinical outcomes. Although the measurement of prostate-specific antigen (PSA) and radiographic studies are clinically approved to predict response to therapy, these tests can oftentimes prove to be inadequate in certain patients. Thus, it is important to discover new biomarkers to improve chances of survivability. We and others have shown that longitudinal measurements of circulating tumor cells (CTC) and lactate dehydrogenase (LDH) may aid in predicting response …

Neurochemical Effects Of Amyloid-Beta Oligomers In Rats, John J. Panos

Dissertations

Alzheimer’s disease is a progressive neurodegenerative disease characterized by memory loss and cognitive decline. Although the symptomology of Alzheimer’s disease is well defined, its precise etiology remains elusive. Animal models are invaluable for understanding the pathogenesis of this devastating disease. Knowledge of the neurochemical actions of amyloid-β oligomers in specific brain structures is essential for validating animal models of Alzheimer’s disease and for determining the most appropriate behavioral assays of memory. The specific aim of this project was to investigate the neurochemical effects of direct intracerebral infusion of amyloid-β oligomers in the rat. Experiment 1 investigated direct infusions of synthetic …

Long-Term Hypoxia Regulates Cortisol Biosynthesis In The Ovine Fetal Adrenal Cortex, Vladimir Enrique Vargas

Loma Linda University Electronic Theses, Dissertations & Projects

Previous studies demonstrated enhanced fetal adrenal cortisol biosynthesis following exposure to long-term hypoxia (LTH). The studies presented here were designed to determine the mechanism(s) regulating this important adaptive endocrine response. Ewes were maintained at high altitude (3,820 m) from approximately day 40 to 138-141 of gestation. Fetal adrenal glands were then collected from LTH and age matched normoxic controls. Dispersed fetal adrenal cortical cells (FACs) were untreated, treated with ACTH, treated in combination with ACTH precursors (POMC and 22-kDa pro-ACTH), or pre-treated with H-89 and or UO126 followed by ACTH treatment. Following ACTH treatment, cortisol biosynthesis increased in both groups …

Cerebral Amyloid Angiopathy And Transition Metals In Alzheimer's Disease, Matthew Schrag

Loma Linda University Electronic Theses, Dissertations & Projects

Alterations in brain metals homeostasis and particularly brain iron overload have been postulated to play a role in Alzheimer's disease, contributing to oxidative stress and neuronal injury; however, the source of this iron is not clear and may be due to metabolic derangement(s), failed iron clearance mechanisms or exogenous deposition such as through bleeding. This series of studies was designed to evaluate the extent of metals dyshomeostasis in the Alzheimer's disease brain and specifically whether microvascular bleeding is a major contributor to Alzheimer's disease-related iron overload. Cerebral amyloid angiopathy (CAA) is a vascular manifestation of Alzheimer's disease present to some …

New To Ols For Monitoring Gamma Camera Uniformity, Brad K. Lofton

Dissertations and Theses (Open Access)

Detector uniformity is a fundamental performance characteristic of all modern gamma camera systems, and ensuring a stable, uniform detector response is critical for maintaining clinical images that are free of artifact. For these reasons, the assessment of detector uniformity is one of the most common activities associated with a successful clinical quality assurance program in gamma camera imaging. The evaluation of this parameter, however, is often unclear because it is highly dependent upon acquisition conditions, reviewer expertise, and the application of somewhat arbitrary limits that do not characterize the spatial location of the non-uniformities. Furthermore, as the goal of any …

Analysis Of Β8 Integrin In Neurogenesis And Neurovascular Homeostasis, Aaron K. Mobley

Dissertations and Theses (Open Access)

Neurogenesis in the adult mouse brain occurs within the subventricular zone (SVZ) of the lateral ventricle. In the SVZ, neural stem cells (NSC) reside in a specialized microenvironment, or vascular niche, consisting of blood vessels and their basement membranes. Most NSCs in the SVZ differentiate into progenitor cells, which further differentiate to generate neuroblasts, which then migrate from the SVZ to the olfactory bulbs (OB) along the rostral migratory stream (RMS). ECM-mediated adhesion and signaling within the vascular niche likely contribute to proper NSC self-renewal, survival, differentiation and neuroblast motility. The mechanisms that control these events are poorly understood. Previous …

Exhausted Or Unlicensed: Can Field-Of-Use Restrictions In Biotech License Agreements Still Prevent Off-Label Use Promotion After Quanta Computer?, Kristal M. Wicks

The University of New Hampshire Law Review

[Excerpt] “In the biotechnology (biotech) industry, companies must be increasingly aware of their intellectual property and how their licensing strategies can impact their rights. When licensing patented technology, it is common practice for biotech companies to include restricted field-of-use provisions in their license agreements. Such provisions permit a licensee to only use licensed technology in a defined field and restrict use or development in another field. This licensing strategy plays an important role within the biotech industry because it allows companies to more effectively control their intellectual property and to more efficiently research and develop pharmaceutical products.

A problem that …

Hydroxyurea And Acute Painful Crises In Sickle Cell Anemia: Effects On Hospital Length Of Stay And Opioid Utilization During Hospitalization, Outpatient Acute Care Contacts, And At Home, Samir K. Ballas, Md, Facp, Robert L. Bauserman, Phd, William F. Mccarthy, Phd, Oswaldo L. Castro, Md, Wally R. Smith, Md, Myron A. Waclawiw, Phd

Department of Medicine Faculty Papers

Recurrent acute sickle cell painful crises are the hallmark of sickle cell anemia. These events may be mild, moderate or severe in nature and often require treatment at home, in acute care facilities as outpatients, and in the hospital with oral and/or parenteral opioids. The type, dose, route & frequency of administration of opioids, as well as the length of hospital stay (LOS), are not well known for adults with sickle cell anemia (SS). We analyzed these aspects in the 299 patients enrolled in the Multicenter Study of Hydroxyurea (MSH) in SS. For these patients there were 16818 home diaries, …

Donepezil And Galanin Interactions In An Animal Model Of Alzheimer’S Disease, Jonathan J. Sabbagh

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer's disease (AD) is a neurodegenerative disorder marked by a progressive loss of cognitive function. One of the neurobiological hallmarks of AD is a progressive loss of cholinergic neurons and a decrease in the amount of acetylcholine in the brain. Pharmacological therapies have targeted the cholinergic system, specifically first-line, palliative treatment using acetylcholinesterase (AChE) inhibitors, such as donepezil. Donepezil has been shown to increase cholinergic tone and ameliorate some of the cognitive deficits in AD patients. Galanin, a neuropeptide that inhibits the evoked release of several neurotransmitters including acetylcholine as well as modulates seveal intracellular cascades, is overexpressed in AD …

Mechanism Of N-Methylation By The Trna M1g37 Methyltransferase Trm5., Thomas Christian, Georges Lahoud, Cuiping Liu, Katherine Hoffmann, John J Perona, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Trm5 is a eukaryal and archaeal tRNA methyltransferase that catalyzes methyl transfer from S-adenosylmethionine (AdoMet) to the N(1) position of G37 directly 3' to the anticodon. While the biological role of m(1)G37 in enhancing translational fidelity is well established, the catalytic mechanism of Trm5 has remained obscure. To address the mechanism of Trm5 and more broadly the mechanism of N-methylation to nucleobases, we examined the pH-activity profile of an archaeal Trm5 enzyme, and performed structure-guided mutational analysis. The data reveal a marked dependence of enzyme-catalyzed methyl transfer on hydrogen ion equilibria: the single-turnover rate constant for methylation increases by one …

Elucidating The Role Of Cd44 Expression On Mesenchymal Stem Cells Within The Tumor Microenvironment, Erika L. Spaeth

Dissertations and Theses (Open Access)

The tumor microenvironment is comprised of a vast array of heterogeneous cells including both normal and neoplastic cells. The tumor stroma recruitment process has been exploited for an effective gene delivery technique using bone marrow derived MSC. Targeted migration of the MSC toward the tumor microenvironment, while successful, is not yet fully understood. This study was designed to assess the role of CD44 in the migration of MSC toward the tumor microenvironment and to determine the implications of CD44-deficient MSC within the tumor stroma. Inhibition of MSC migration was evaluated through a variety of methods in vitro and in vivo …

Levo-Tetrahydropalmatine Attenuates Cocaine Self-Administration Under A Progressive-Ratio Schedule And Cocaine Discrimination In Rats, John R. Mantsch, Samantha Wisniewski, Oliver Vranjkovic, Corey Peters, Amanda Becker, Abbey Valentine, Shi-Jiang Li, David A. Baker, Zheng Yang

Biomedical Sciences Faculty Research and Publications

Levo-tetrahydropalmatine (l-THP) is an alkaloid found in many traditional Chinese herbal preparations and has a unique pharmacological profile that includes dopamine receptor antagonism. Previously we demonstrated that l-THP attenuates fixed-ratio (FR) cocaine self-administration (SA) and cocaine-induced reinstatement in rats at doses that do not alter food-reinforced responding. This study examined the effects of l-THP on cocaine and food SA under progressive-ratio (PR) schedules of reinforcement and the discriminative stimulus effects of cocaine. In adult male Sprague–Dawley rats self-administering cocaine (0.5 or 1.0 mg/kg/inf), l-THP significantly reduced breaking points at the 1.875, 3.75 and 7.5 mg/kg …

Fat Taste Transduction In Mouse Taste Cells: The Role Of Transient Receptor Potential Channel Type M5, Pin Liu

All Graduate Theses and Dissertations, Spring 1920 to Summer 2023

A number of studies have demonstrated the ability of free fatty acids to activate taste cells and elicit behavioral responses consistent with there being a taste of fat. Here I show for the first time that long chain unsaturated free fatty acid, linoleic acid, depolarizes taste cells and elicits a robust intracellular calcium rise via the activation of transient receptor potential channel type M5. The linoleic acid-induced responses depend on G protein-phospholipase C pathway indicative of the involvement of G protein-coupled receptors in the transduction of fatty acids. Mice lacking transient receptor potential channel type M5 exhibit no preference for …

Development Of Near Real-Time Assessment System For Cancer Cells., Nahrizul Adib Kadri

Student Works (2010-2019)

Dielectrophoresis (DEP) is an electrical phenomenon that occurs when a polarisable particle is placed in non-uniform electrical fields, generating DEP force (FDEP) that is dependent upon the electrophysiological make-up of the particle in use. In cell cytometry studies, DEP offers the advantage of conducting various cell manipulations in vitro without the need of specific surface markers. Its drawbacks, namely the time-consuming processes involved and the inability to conduct large batch cell assays, had limited its usage. This thesis presents the work that offered solution to the said obstacles, by developing a system capable of conducting DEP experiments within a very …

The Face Of Felt Stigma: Experiences Of Puerto Ricans Living With Hiv In Allentown, Pa, M Reyes Ba, Julio Jiménez Md, Joseph L. Yozviak Do, Facp, Timothy J. Friel Md, D Adams Psyd, Cynthia Beitler, Eric J. Gertner Md, Mph, E Rivera Ba, L Santiago Phd

Department of Medicine

No abstract provided.

The Role Of Pkd1 In Mouse Inner Ear Hair Cells, Katherine Ann Steigelman

Theses and Dissertations (ETD)

The polycystic kidney disease-1 (Pkd1) gene encodes a large transmembrane protein (polycystin-1 or PC-1) that is reported to function as a fluid flow-sensor in the kidney. As a member of the transient receptor potential (TRP) family, PC-1 has also been hypothesized to play a role in the elusive mechanoelectrical transduction (MET) channel in inner ear hair cells based on PC-1 role of fluid flow sensing and calcium uptake into renal epithelial cells. However, two independent mouse lines with PC-1 mutations exhibit normal MET channel function despite hearing loss and ultra-structural abnormalities of stereocilia that remain properly polarized at …

Acetate Causes Alcohol Hangover Headache In Rats., Christina R Maxwell, Rebecca Jay Spangenberg, Jan B Hoek, Stephen D Silberstein, Michael L Oshinsky

Department of Neurology Faculty Papers

BACKGROUND: The mechanism of veisalgia cephalgia or hangover headache is unknown. Despite a lack of mechanistic studies, there are a number of theories positing congeners, dehydration, or the ethanol metabolite acetaldehyde as causes of hangover headache.

METHODS: We used a chronic headache model to examine how pure ethanol produces increased sensitivity for nociceptive behaviors in normally hydrated rats.

RESULTS: Ethanol initially decreased sensitivity to mechanical stimuli on the face (analgesia), followed 4 to 6 hours later by inflammatory pain. Inhibiting alcohol dehydrogenase extended the analgesia whereas inhibiting aldehyde dehydrogenase decreased analgesia. Neither treatment had nociceptive effects. Direct administration of acetate …

Influence Of Sex On Long-Term Outcomes After Percutaneous Coronary Intervention With The Paclitaxel-Eluting Coronary Stent: Results Of The "Taxus Woman" Analysis, Ghada W. Mikhail Md, Robert T. Gerber Md, Phd, David A. Cox Md, Stephen G. Ellis Md, John M. Lasala Md, Phd, John A. Ormiston Mbchb, Gregg W. Stone Md, Mark A. Turco Md, Anita A. Joshi Phd, Donald S. Baim Md, Antonio Colombo Md

Department of Medicine

No abstract provided.

Role Of Extracellular Signal-Regulated Kinase (Erk) In Regulation Of Intestinal Epithelial Tight Junctions, Sudhir Aggarwal

Theses and Dissertations (ETD)

Evidence indicates that MAP kinase (ERK1/2) is involved in regulation of epithelial tight junctions. There are different opinions expressed by investigators as to whether ERK disrupts the junctions or protects them. ERK has also been demonstrated to mediate the EGF-caused protection of the intestinal epithelial tight junctions (TJ) from hydrogen peroxide. Studies using pharmacological inhibitors have shown that EGF increases Thr-phosphorylation of occludin by a MAP kinase-dependent mechanism. This study aimed at looking at the role of ERK in regulation of tight junctions using pharmacological and molecular techniques.

Hypothesis: ERK protects tight junctions in differentiated Caco-2 cells, while it is …

Interactions Of Francisella Tularensis With Components Of The Host Fibrinolytic System, Shawn Russell Clinton

Theses and Dissertations (ETD)

Francisella tularensis (FT) is a Gram-negative coccobacillus and causative agent of a life-threatening disease commonly referred to as tularemia. Due to the highly infectious nature of the organism, its previous development as a biowarfare agent and its potential use in acts of bioterrorism, this bacterium is listed as a Category A select agent by the Centers for Disease Control and Prevention (CDC). Efforts to understand the pathogenic mechanisms of FT within the host environment are vital for the development of safe and effective vaccines, as well as treatments, against tularemia. Though considered an intracellular pathogen, FT research of late has …

Effect Of Fixation Using Locked Compression Plate Versus Lag Screws On Biomechanics Of Talonavicular Joint: A Human Cadaveric Foot Model, Rahul Sudheer Ghotge

Theses and Dissertations (ETD)

Introduction: Talonavicular fusion is a surgery used for treating many hind foot pathologies. A problem associated with the procedure is non-union which may be due to inadequate stabilization. The objective of our study was to compare the effect of two surgical fixation techniques on the motion and biomechanics of the talonavicular joint in a human cadaveric foot model.

Materials and Methods: Thirteen human cadaveric foot specimens were prepared, mounted in a multi-axis programmable robot, and loaded using four loading scenarios. Each of the four loading scenarios consisted of a constant Achilles tendon load of 350N followed by either internal or …

D2r Dopamine Receptor Mediates Changes In Dual Specificity Phosphatase Expression In A Small Cell Lung Cancer Cell Line, Scott Lemar Lattimer

Theses and Dissertations (ETD)

Bromocriptine, a D2 dopamine receptor (D2R) agonist, is used clinically as a treatment for pituitary tumors of a lactotroph origin. Many questions remain unanswered about the mechanism of this effect. The antiproliferative effect has not been demonstrated in DMS 53 cell line, a Small Cell Lung Cancer (SCLC). In this thesis, we have shown that treatment with NPA (N‑propylnorapomorphine), a dopamine receptor agonist inhibits ERK phosphorylation and proliferation in DMS 53 cells. NPA treatment causes significant increases in DUSP‑1 (MKP‑1), DUSP‑4 (MKP‑2) and DUSP5 mRNA. NPA treatment also correlates with increases in DUSP5 (hVHR3) protein visualized using Western Blot. These …

The Mglur2/3 Agonist Ly397268 Improves Morphometric And Behavioral Outcomes In R6/2 Huntington's Disease Mice, Dennis Craig Lafferty

Theses and Dissertations (ETD)

A prominent theory for the pathology of Huntington's Disease (HD) is the excitotoxic injury to the striatum. Continual exposure of ionotropic NMDA receptors to glutamate from the cortex can be excitotoxic in HD and leave striatal neurons vulnerable to damage. Activation of presynaptic mGluR2/3 by an agonist dampens glutamate release from corticostriatal terminals. Treatments that target excitoxicity and oxidative stress thus may improve some of the symptoms in HD patients and it is therefore logical to pursue therapies aimed in this direction. LY379268 is an inviting mGluR2/3 agonist that has been shown to be neuroprotective in hypoxic and ischemic injuries …

Cd151 Reinforces Vascular Stability By Balancing Endothelial Cell Adhesion And Cytoskeletal Tension, Feng Zhang

Theses and Dissertations (ETD)

Tetraspanin CD151 is highly expressed in endothelial cells and regulates pathological angiogenesis. However, the mechanism by which CD151 promotes vascular morphogenesis and whether CD151 engages other vascular functions are unclear. We observed that CD151 is required for the maintenance of endothelial capillary-like structures formed in vitro and the integrity of lung endothelial cell-cell contacts in vivo. As a master regulator of endothelial cell-matrix and cell-cell adhesions, CD151 is needed for the optimal functions of various cell adhesion proteins such as integrin, cadherin, and CD44. The loss of CD151 elevates the cellular intrinsic contraction by upregulating RhoA signaling and downregulating of …

Biological Rationale For The Use Of Dna Methyltransferase Inhibitors As New Strategy For Modulation Of Tumor Response To Chemotherapy And Radiation., Giovanni L Gravina, Claudio Festuccia, Francesco Marampon, Vladimir M Popov, Richard G Pestell, Bianca M Zani, Vincenzo Tombolini

Kimmel Cancer Center Faculty Papers

Epigenetic modifications play a key role in the patho-physiology of many tumors and the current use of agents targeting epigenetic changes has become a topic of intense interest in cancer research. DNA methyltransferase (DNMT) inhibitors represent a promising class of epigenetic modulators. Research performed yielded promising anti-tumorigenic activity for these agents in vitro and in vivo against a variety of hematologic and solid tumors. These epigenetic modulators cause cell cycle and growth arrest, differentiation and apoptosis. Rationale for combining these agents with cytotoxic therapy or radiation is straightforward since the use of DNMT inhibitor offers greatly improved access for cytotoxic …

Attitudes Of Health Professionals To Electronic Data Sharing Within An Integrated Care Electronic Health Record (Icehr), Charyl O'Malley, Damon Berry, Mary Sharp

Conference Papers

It is estimated that 98,000 people die in hospitals yearly in the USA as a result of medical errors (Agency for Healthcare Research and Quality, 2009). Electronic Health Records (EHR) can offer improved patient safety. EHRs are being implemented by many countries, however, not all health professionals have welcomed them (MORI Social Research Institute, 2006). As outlined in the National Health Information Strategy (NHIS) document, Ireland has plans to introduce an EHR. Attitudes of health professionals are a significant factor for the successful implementation and adoption of a new clinical information system. This study aimed to gauge the attitude of …