Digital Commons Network^™

Pathogenesis And Therapeutic Potential Of Plasmacytoid Dendritic Cells In Siv/Shiv-Infected Macaques, R Keith Reeves

All ETDs from UAB

Plasmacytoid dendritic cells (pDCs) are among the first responders during acute viral infections and are the primary producers of IFN-α, a cytokine known to inhibit viral replication and to activate natural killer (NK) cells. In HIV patients pDCs are decreased in number, are dysfunctional, and can harbor HIV-1 proviruses. However, since the time of transmission is usually unknown, pDC-virus interactions immediately after exposure to HIV remain unclear. Using the SIV/SHIV-macaque model, we showed that an acute and sustained loss of blood pDCs occurred during SIVmac239 infections, and when compared to those from naïve controls, pDCs were also significantly reduced in …

In Vivo Imaging Studies In Animal Models Of Myocardial Infarction With And Without Cell Injections, Balazs Ruzsics

All ETDs from UAB

After prolonged myocardial ischemia, myocardial infarction occurs. Several tissue changes are associated with myocardial infarction and iron labeled cell injections. In the present thesis our major aim was to develop methods to monitor these tissue changes with MRI and MDCT. In the first chapter we used transendocardial injection to deliver iron labeled allogen skeletal myoblasts one week after myocardial infarction. Our goal was to identify the cells and/or injection sites in the myocardium. We used our new Tissue Characterization Mapping method to delineate tissue edema and hemorrhage in the myocardium. The T2 weighted signal intensity enhancement, T2w SIE region was …

The Characterization Of The Subcellular Localization Of Bile Acid Coa: N-Acyltransferase, Nathan Allen Styles

All ETDs from UAB

The liver plays a central role in metabolism. It controls protein metabolism through deamination and transamination of amino acids, removal of ammonia through urea synthesis, synthesis of non-essential amino acids and synthesis of the majority of plasma proteins such as albumin. The liver regulates blood glucose levels through glyconeogenesis and glyconeolysis of glycogen, as well as gluconeogenesis from amino acids. It regulates fat metabolism through oxidation of triglycerides and fatty acids, as well as synthesis of cholesterol, lipoproteins, and phospholipids. Furthermore, the liver is the only site of formation of bile acids and their conjugates, physiologically important compounds that solubilize …

Bacillus Anthracis Spore-Host Interactions, Melissa K. Swiecki

All ETDs from UAB

The use of Bacillus anthracis as a bioweapon depends on the dispersal of its spores into the environment, entrance into the body, spore uptake by human host cells, germination of the spores in the host and the pathological consequences of the virulence factors produced by the vegetative cells. Prior to 2001, very little was known about the mechanisms of spore entry into the host, including targeting cell types at airway, digestive and skin surfaces, potential spore receptors on these cells and spore encounters with cellular and humoral elements of the innate and adaptive immune systems. To this end, we have …

Relaxation Rate-Based Magnetic Resonance Imaging Quantification Of Myocardial Infarction, Pal Suranyi

All ETDs from UAB

Ischemic heart disease is the leading cause of mortality in western societies. Treatment needs to be tailored for each individual, which requires accurate assessment of the underlying pathology. Magnetic Resonance Imaging (MRI) is a relatively young modality in the field of cardiovascular imaging, and boasts with the lack of harmful radiation, excellent soft tissue contrast, and high spatial-temporal resolution. The very foundation of the concept of MRI was the finding that pathology causes changes in the relaxation rates of tissues. Measurement of relaxation rates is more time consuming than generating simple signal intensity images weighted by the longitudinal or transverse …

The Role Of Cd5 In Experimental Autoimmune Encephalitomyelitis, Robert C. Axtell

All ETDs from UAB

The regulation of activation, differentiation and persistence of effector T-cells are critical for the development of Experimental Autoimmune Encephalomyelitis (EAE), the animal model of Multiple Sclerosis. Until now, the function of CD5 was accepted to be a negative regulator of T-cell activation. This dissertation reports that CD5 has an addi-tional role in T-cell responses, which is to promote cell survival. Observations from EAE experiments revealed that mice deficient in CD5 exhibited decreased disease severity which was associated with the inability of activated T-cells to survive. Moreover, block-ing the engagement of CD5 in mice led to enhanced activation induced cell death …

Cd8+ T-Lymphocytes And The Control Of Cytomegalovirus Infection Of The Newborn Central Nervous System, Glenn Robert Burgner Bantug

All ETDs from UAB

Congenital HCMV infection of the developing brain is the leading viral cause of mental retardation and sensorineural hearing loss. To elucidate the pathogenesis of congenital HCMV CNS infections, we developed a small animal model of CMV infection where newborn Balb/c mice are peripherally inoculated with murine cytomegalovirus. In this model we observed transient deficits in cerebellar/hindbrain development as well as the recruitment of peripheral immune effector cells to the CNS parenchyma. CD8+ T-lymphocytes were the predominant mononuclear cellular infiltrates in the brain and immune-depletion of CD8+ cells resulted in increased viral genome copy numbers in the CNS. CD8+ T-lymphocytes exhibited …

A Comparision Of Delta-9-Tetrahydrocannabinol Dependence In C57bl/6j Mice And Fatty Acid Amide Hydrolase Knock Out Mice, Brittany Leigh Alice Carlson

Theses and Dissertations

The idea that humans and laboratory animals can become physically dependent on marijuana or its primary psychoactive constituent, delta-9-tetrahydrocannabinol (THC), is gaining acceptance. However, there are no currently approved pharmacotherapies to treat cannabinoid withdrawal. The objective of this thesis was to evaluate whether elevating endogenous anandamide levels using mice lacking fatty acid amide hydrolase (FAAH), the enzyme responsible for anandamide metabolism, would ameliorate THC dependence. Mice were treated subchronically with a low or high THC dosing regimen and challenged with the CB1 receptor antagonist, rimonabant, to precipitate withdrawal. Following subchronic THC treatment, rimonabant precipitated a significant increase in paw flutters …

Adenoviral Mediated Gene Transfer Into The Dog Brain In Vivo, Marianela Candolfi, Kurt Kroeger, Elizabeth Pluhar, Chunyan Liu, Carlos Barcia, Josee Bergeron, Mariana Puntel, James Curtin, Elizabeth Mcniel, Andrew Freese, John Ohlfest, Peter Moore, William Kuoy, Pedro Lowenstein, Maria Castro

Articles

OBJECTIVE: Glioblastoma multiforme (GBM) is a devastating brain tumor for which there is no cure. Adenoviral-mediated transfer of conditional cytotoxic (herpes simplex virus [HSV] 1-derived thymidine kinase [TK]) and immunostimulatory (Fms-like tyrosine kinase 3 ligand [Flt3L]) transgenes elicited immune-mediated long-term survival in a syngeneic intracranial GBM model in rodents. However, the lack of a large GBM animal model makes it difficult to predict the outcome of therapies in humans. Dogs develop spontaneous GBM that closely resemble the human disease; therefore, they constitute an excellent large animal model. We assayed the transduction efficiency of adenoviral vectors (Ads) encoding beta-galactosidase (betaGal), TK, …

Faculty Publications 2006, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 638 publications.

Department Of Pathology, Thomas Jefferson University, Identification Of Conserved Gene Expression Features Between Murine Mammary Carcinoma Models And Human Breast Tumors., Jason I Herschkowitz, Karl Simin, Victor J Weigman, Igor Mikaelian, Jerry Usary, Zhiyuan Hu, Karen E Rasmussen, Laundette P Jones, Shahin Assefnia, Subhashini Chandrasekharan, Michael G Backlund, Yuzhi Yin, Andrey I Khramtsov, Roy Bastein, John Quackenbush, Robert I Glazer, Powel H Brown, Jeffrey E Green, Levy Kopelovich, Priscilla A Furth, Juan P Palazzo, Olufunmilayo I Olopade, Philip S Bernard, Gary A Churchill, Terry Van Dyke, Charles M Perou

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors. RESULTS: Unsupervised hierarchical clustering analysis showed that six models (TgWAP-Myc, TgMMTV-Neu, TgMMTV-PyMT, TgWAP-Int3, TgWAP-Tag, and TgC3(1)-Tag) yielded tumors with distinctive and homogeneous expression patterns within each strain. However, in each of four other models (TgWAP-T121, TgMMTV-Wnt1, Brca1Co/Co;TgMMTV-Cre;p53+/- and DMBA-induced), tumors with a variety of …

Silencing Of The Pink1 Gene Expression By Conditional Rnai Does Not Induce Dopaminergic Neuron Death In Mice., Hongxia Zhou, Björn H Falkenburger, Jörg B Schulz, Kim Tieu, Zuoshang Xu, Xu Gang Xia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Transgenic RNAi, an alternative to the gene knockout approach, can induce hypomorphic phenotypes that resemble those of the gene knockout in mice. Conditional transgenic RNAi is an attractive choice of method for reverse genetics in vivo because it can achieve temporal and spatial silencing of targeted genes. Pol III promoters such as U6 are widely used to drive the expression of RNAi transgenes in animals. Tested in transgenic mice, a Cre-loxP inducible U6 promoter drove the broad expression of an shRNA against the Pink1 gene whose loss-of-functional mutations cause one form of familial Parkinson's disease. The expression of the shRNA …

Single Nucleotide Polymorphisms (Snps) Distinguish Indian-Origin And Chinese-Origin Rhesus Macaques (Macaca Mulatta), Betsy Ferguson, Summer L. Street, Hollis Wright, Carlo Pearson, Yibing Jia, Shaun L. Thompson, Patrick Allibone, Christopher J. Dubay, Eliot Spindel, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: Rhesus macaques serve a critical role in the study of human biomedical research. While both Indian and Chinese rhesus macaques are commonly used, genetic differences between these two subspecies affect aspects of their behavior and physiology, including response to simian immunodeficiency virus (SIV) infection. Single nucleotide polymorphisms (SNPs) can play an important role in both establishing ancestry and in identifying genes involved in complex diseases. We sequenced the 3' end of rhesus macaque genes in an effort to identify gene-based SNPs that could distinguish between Indian and Chinese rhesus macaques and aid in association analysis.

RESULTS: We surveyed the …

Intercenter Reliability And Validity Of The Rhesus Macaque Genechip, Fenghai Duan, Eliot R. Spindel, Yu-Hua Li, Robert B. Norgren

Journal Articles: Genetics, Cell Biology & Anatomy

BACKGROUND: The non-human primate (NHP) research community has been intensely interested in obtaining whole-genome expression arrays for their work. Recently, novel approaches were used to generate the DNA sequence information for a rhesus GeneChip. To test the reliability of the rhesus GeneChip across different centers, RNA was isolated from five sources: cerebral cortex, pancreas, thymus, testis, and an immortalized fibroblast cell line. Aliquots of this RNA were sent to each of three centers: Yerkes National Primate Research Center, Oregon National Primate Research Center and the University of Nebraska Medical Center. Each center labeled the samples and hybridized them with two …

Molecular Mechanisms Of Olfactory Neurodegeneration, Radhika Anand Vaishnav

University of Kentucky Doctoral Dissertations

Olfactory sensory decline has been associated with normal aging as well as neurodegenerative disorders, yet the underlying mechanisms are unclear. The overall aim of this dissertation was to investigate the fundamental molecular and cellular mechanisms associated with olfactory neurodegeneration. This investigation uses an integrative approach, combining proteomics and gene expression analyses with cellular and tissuelevel characterization. Using these approaches, two model systems were investigated: 1) normally aging C57BL/6 mice of ages 1.5-, 6- and 20-months; and 2) a mouse model of elevated endogenous oxidative stress-associated neurodegeneration, namely, the Harlequin mutant mouse. The first specific aim was to test the hypothesis …

Caenorhabditis Briggsae Methods, Scott Everet Baird, Helen M. Chamberlin

Biological Sciences Faculty Publications

Caenorhabditis briggsae is being developed in parallel to C. elegans as a model system, primarily for the study of evolution. Like C. elegans, C. briggsae is a protandrous hermaphrodite and like C. elegans, its genome has been sequenced. From this point, these two model systems diverge. The development, behavior, and physiology of C. elegans have been characterized through tens of thousands of genetic and molecular studies. Genetic and molecular characterizations of C. briggsae are relatively few. Experimental resources in C. elegans include a high density recombination map that is well integrated with the genome sequence. The C. briggsae …

An In Vitro Model Of Ovarian Cancer: Studying The Effects Of Talc And Pycnogenol®, Amber Renée Buz'zard

Loma Linda University Electronic Theses, Dissertations & Projects

Ovarian cancer is the sixth most common cancer and accounts for more deaths than any other cancer of the female reproductive system. The American Cancer Society has suggested that poor diet, talc and industrial pollutants may increase the risk of developing ovarian cancer. Talc is ubiquitous and concern is raised about its safety, role as a possible carcinogen and known ability to cause irritation and inflammation. Due to the silent nature of ovarian cancer, chemoprevention is a high priority. The most useful chemopreventive compounds will inhibit, delay or reverse carcinogenesis, and can be taken for long periods of time with …

Biomolecular Tuning Of Electronic Transport Properties Of Carbon Nanotubes Via Antibody Functionalization, Kasif Teker, Dr. Eric Wickstrom, Balaji Panchapakesan

Department of Biochemistry and Molecular Biology Faculty Papers

Carbon nanotubes (CNTs) are remarkable solidstate nanomaterials due to their unique electrical and mechanical properties. The electronic properties of nanotubes combined with biological molecules such as proteins could make miniature devices for biological sensing applications. In this paper, the noncovalent interaction of single-wall CNTs with antibodies is presented for its potential applications for detecting overexpressed cell surface receptors in breast cancer cells. The degree of binding of antibodies on CNTs was found to be more than 80% for an extended sampling area by confocal microscopy. The key to achieve such high degree of functionalization is due to the separation of …

Combined Effects Of Aldehyde Dehydrogenase Variants And Maternal Mitochondrial Genes On Alcohol Consumption, Yedy Israel, Maria E. Quintanilla, Amalia Sapag, Lutske Tampier

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Two lines of rats bred to differ in their voluntary alcohol consumption — the alcohol-abstaining UChA rats and the alcohol-drinking UChB rats — differ in how effectively toxic acetaldehyde is removed during alcohol metabolism. UChB animals carry efficient variants of the aldehyde dehydrogenase 2 (ALDH2) genes and have active mitochondria, resulting in fast removal of acetaldehyde. UChA animals, in contrast, carry less efficient ALDH2 variants and less active mitochondria, which result in transient elevations of acetaldehyde levels after alcohol ingestion. Cross-breeding studies have demonstrated that the presence of active mitochondria inherited from UChB females can fully abolish the reduction of …

Androgen-Regulated Formation And Degradation Of Gap Junctions In Androgen-Responsive Human Prostate Cancer Cells., Shalini Mitra, Lakshmanan Annamalai, Souvik Chakraborty, Kristen E. Johnson, Xiao-Hong Song, Surinder K. Batra, Parmender P. Mehta

Journal Articles: Biochemistry & Molecular Biology

The constituent proteins of gap junctions, called connexins (Cxs), have a short half-life. Despite this, the physiological stimuli that control the assembly of Cxs into gap junctions and their degradation have remained poorly understood. We show here that in androgen-responsive human prostate cancer cells, androgens control the expression level of Cx32-and hence the extent of gap junction formation-post-translationally. In the absence of androgens, a major fraction of Cx32 is degraded presumably by endoplasmic reticulum-associated degradation, whereas in their presence, this fraction is rescued from degradation. We also show that Cx32 and Cx43 degrade by a similar mechanism. Thus, androgens regulate …

Antimicrobial Effects Of Liquid Anesthetic Isoflurane On Candida Albicans, Viachaslau M. Barodka, Edward Acheampong, Garry Powell, Ludmilla Lobach, David A. Logan, Zahida Parveen, Valerie Armstead, Muhammad Mukhtar

Department of Medicine Faculty Papers

Candida albicans is a dimorphic fungus that can grow in yeast morphology or hyphal form depending on the surrounding environment. This ubiquitous fungus is present in skin and mucus membranes as a potential pathogen that under opportunistic conditions causes a series of systemic and superficial infections known as candidiasis, moniliasis or simply candidiasis. There has been a steady increase in the prevalence of candidiasis that is expressed in more virulent forms of infection. Although candidiasis is commonly manifested as mucocutaneous disease, life-threatening systemic invasion by this fungus can occur in every part of the body. The severity of candidal infections …

Cdx4 Dysregulates Hox Gene Expression And Generates Acute Myeloid Leukemia Alone And In Cooperation With Meis1a In A Murine Model, Dimple Bansal, Claudia Scholl, Stefan Frohling, Elizabeth Mcdowell, Benjamin H. Lee, Konstanze Döhner, Patricia Ernst

Dartmouth Scholarship

HOX genes have emerged as critical effectors of leukemogenesis, but the mechanisms that regulate their expression in leukemia are not well understood. Recent data suggest that the caudal homeobox transcription factors CDX1, CDX2, and CDX4, developmental regulators of HOX gene expression, may contribute to HOX gene dysregulation in leukemia. We report here that CDX4 is expressed normally in early hematopoietic progenitors and is expressed aberrantly in approximately 25% of acute myeloid leukemia (AML) patient samples. Cdx4 regulates Hox gene expression in the adult murine hematopoietic system and dysregulates Hox genes that are implicated in leukemogenesis. Furthermore, bone marrow progenitors that …

Sub-Typing Of Prrsv Isolates By Means Of Measurement Of Cross-Neutralization Reactions, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

The degree of similitude or closeness between two different isolates or strains of PRRSV is very important for deciding which strains should be used for immunization, by either vaccinating with commercial vaccines or attempting to stabilize a herd with planned wt PRRSV infection. As previously known for certain important viral diseases, such as in Foot and Mouth Disease, the reciprocal (cross-) neutralization titers between two strains may be of utmost importance to establish the degree of similarity or difference between these. There is currently a void of methods that would allow distinguishing or grouping strains of PRRSV in a manner …

The Role Of Mapks In B Cell Receptor-Induced Down-Regulation Of Egr-1 In Immature B Lymphoma Cells, Jiyuan Ke, Murali Gururajan, Anupam Kumar, Alan Simmons, Lilia Turcios, Ralph Lakshman Chelvarajan, David M. Cohen, David L. Wiest, John G. Monroe, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Cross-linking of the B cell receptor (BCR) on the immature B lymphoma cell line BKS-2 induces growth inhibition and apoptosis accompanied by rapid down-regulation of the immediate-early gene egr-1. In these lymphoma cells, egr-1 is expressed constitutively and has a prosurvival role, as Egr-1-specific antisense oligonucleotides or expression of a dominant-negative inhibitor of Egr-1 also prevented the growth of BKS-2 cells. Moreover, enhancement of Egr-1 protein with phorbol 12-myristate 13-acetate or an egr-1 expression vector rescued BKS-2 cells from BCR signal-induced growth inhibition. Nuclear run-on and mRNA stability assays indicated that BCR-derived signals act at the transcriptional level to …

Neuromechanics Of Multifunctionality During Rejection In Aplysia Californica, Hui Ye, Douglas W. Morton, Hillel J. Chiel

Faculty Scholarship

How are the same muscles and neurons used to generate qualitatively different behaviors? We studied this question by analyzing the biomechanical and neural mechanisms of rejection responses in the marine mollusk Aplysia californica and compared these mechanisms with those used to generate swallowing responses (Ye et al., 2006). During rejection, the central grasper of the feeding structure closes to push inedible food out of the buccal cavity. This contrasts with swallowing, during which the grasper is open as it moves toward the jaws (protracts). We examined how the shape change of the grasper during rejection mechanically reconfigured the surrounding musculature. …

Age-Associated Changes In Hearts Of Male Fischer 344/Brown Norway F1 Rats, Ernest M. Walker Jr., Michael S. Nillas, Elsa I. Mangiarua, Sylvestre Cansino, Ryan G. Morrison, Romaine R. Perdue, William E. Triest, Gary L. Wright, Mark Studeny, Paulette Wehner, Kevin M. Rice, Eric R. Blough

MIIR Faculty Research

Aging is associated with left ventricular hypertrophy, dilatation, and fibrosis of the heart. The Fischer 344/Brown Norway F1 (F344/BNF1) rat is recommended for age-related studies by the National Institutes on Aging because this hybrid rat lives longer and has a lower rate of pathological conditions than inbred rats. However, little is known about age-associated changes in cardiac and aortic function and structure in this model. This study evaluated age-related cardiac changes in male F344/BNF1 rats using ECHO, gross, and microscopic examinations. Rats aged 6-, 30-, and 36-mo were anesthetized and two-dimensional ECHO measurements, two-dimensional guided M-mode, Doppler M-mode, and other …

Genetic Bases Of Executive Control In Preschool Children: Trails-P Performance Is Related To Drd2 Genotype, S. A. Wiebe, M. Y. Chang, J. Huggenvik, T. Jameson, K. A. Espy

Developmental Cognitive Neuroscience Laboratory: Faculty Publications

Several studies link the D2 dopamine receptor (DRD2) with executive control and the ability to adapt behavior to changing contextual contingencies in human adults (Roesch-Ely 2005; Rodriguez-Jimenez 2006) and in animal models (Kruzich 2004). The present study examined relations between DRD2 and executive control in human development. Recently, a version of the Trail-Making Task suitable for preschool children was developed, which does not require knowledge of letters or numbers (TRAILS-P; Espy 2004). The Trail-Making Test is a neuropsychological test sensitive to frontal or executive dysfunction (Reitan 1955) where subjects must connect stimuli on a page in sequence, connecting letters only …

Transcutaneous Immunization With Toxin-Coregulated Pilin A Induces Protective Immunity Against Vibrio Cholerae O1 El Tor Challenge In Mice, Julianne E. Rollenhagen, Anuj Kalsy, Francisca Cerda, Manohar John

Dartmouth Scholarship

Toxin-coregulated pilin A (TcpA) is the main structural subunit of a type IV bundle-forming pilus of Vibrio cholerae, the cause of cholera. Toxin-coregulated pilus is involved in formation of microcolonies of V. cholerae at the intestinal surface, and strains of V. cholerae deficient in TcpA are attenuated and unable to colonize intestinal surfaces. Anti-TcpA immunity is common in humans recovering from cholera in Bangladesh, and immunization against TcpA is protective in murine V. cholerae models. To evaluate whether transcutaneously applied TcpA is immunogenic, we transcutaneously immunized mice with 100 mug of TcpA or TcpA with an immunoadjuvant (cholera toxin [CT], …

2004 Jeffress Research Grant Awards

Virginia Journal of Science

List of winners of the 2004 Jeffress Research Grant Awards.

Unlv Magazine, Cate Weeks, Shane Bevell, Erin O'Donnell, Eric Leake, Lori Bachand, David G. Schwartz, David Ashley

UNLV Magazine

No abstract provided.