Digital Commons Network^™

Whole Genome Expression Profiling Reveals A Significant Role For Immune Function In Human Abdominal Aortic Aneurysms, Guy M. Lenk, Gerard Tromp, Shantel Weinsheimer, Zoran Gatalica, Ramon Berguer, Helena Kuivaniemi

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Abdominal aortic aneurysms are a common disorder with an incompletely understood etiology. We used Illumina and Affymetrix microarray platforms to generate global gene expression profiles for both aneurysmal (AAA) and non-aneurysmal abdominal aorta, and identified genes that were significantly differentially expressed between cases and controls.

Results

Affymetrix and Illumina arrays included 18,057 genes in common; 11,542 (64%) of these genes were considered to be expressed in either aneurysmal or normal abdominal aorta. There were 3,274 differentially expressed genes with a false discovery rate (FDR) ≤ 0.05. Many of these genes were not previously known to be involved in …

Repressor Element-1 Silencing Transcription Factor/Neuronal Restrictive Silencer Factor (Rest/Nrsf) Can Regulate Hsv-1 Immediate-Early Transcription Via Histone Modification, Rajeswara C. Pinnoji, Gautam R. Bedadala, Beena George, Thomas C. Holland, James M. Hill, Shao-Chung V. Hsia

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

During primary infection of its human host, Herpes Simplex Virus Type-1 (HSV-1) establishes latency in neurons where the viral genome is maintained in a circular form associated with nucleosomes in a chromatin configration. During latency, most viral genes are silenced, although the molecular mechanisms responsible for this are unclear. We hypothesized that neuronal factors repress HSV-1 gene expression during latency. A search of the HSV-1 DNA sequence for potential regulatory elements identified a Repressor Element-1/Neuronal Restrictive Silencer Element (RE-1/NRSE) located between HSV-1 genes ICP22 and ICP4. We predicted that the Repressor Element Silencing Transcription Factor/Neuronal Restrictive Silencer Factor …

Comparison Of The Systemic And Pulmonary Inflammatory Response To Endotoxin Of Neutropenic And Non-Neutropenic Rats, Sabrina M. Heidemann, Maria Glibetic

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Neutrophil infiltration commonly occurs in acute lung injury and may be partly responsible for the inflammatory response. However, acute lung injury still occurs in the neutropenic host. The objectives of this study are to determine if inflammation and acute lung injury are worse in neutropenic versus the normal host after endotoxemia.

Methods

Rats were divided into four groups: 1) control, 2) neutropenic, 3) endotoxemic and 4) endotoxemic and neutropenic. Tumor necrosis factor (TNF)-α and macrophage inflammatory protein (MIP-2) were measured in the blood, lung lavage and for mRNA in the lung. Arterial blood gases were measured to determine …

The Effects Of 17Β-Estradiol And Tamoxifen On Cell Cycle Distribution And F-Actin Expression In Mcf-7 Cells, Kirk Kangaloo, Latoya Jenkins, Nicole Clarke, Samir S. Raychoudhury

Journal of the South Carolina Academy of Science

No abstract provided.

Ghrelin May Be A Universal Peptide In All Living Organisms, Süleyman Aydin

Turkish Journal of Medical Sciences

No abstract provided.

Effect Of Different Drugs Influencing Monoamine Neurotransmission On Haloperidol-Induced Catalepsy In Mice, Omar Mohamed Abdel-Salam, Ayman Ragab Baiuomy

Turkish Journal of Medical Sciences

Aim: Catalepsy occurs following high dopamine D2 receptor blockade by the typical antipsychotic drug haloperidol. The present study investigated the effect of different drugs affecting monoamine neurotransmission in this animal model of Parkinson's disease in mice. Materials and Methods: Drugs were intraperitoneally administered with haloperidol 30 min prior to testing. Catalepsy was measured using the bar test. Results: Catalepsy duration was reduced by the non-selective noradrenaline and serotonin reuptake inhibitors imipramine and amitriptyline (21.1% and 22.3% reduction by 20 mg/kg imipramine and amitriptyline, respectively). Catalepsy duration was increased by the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, fluvoxamine, and citalopram and …

The Endogenous Cannabinoid Anandamide Inhibits Cromakalim-Activated K+ Currents In Follicle-Enclosed Xenopus Oocytes, Murat Oz, Keun-Hang Susan Yang, Meral Dinc, Toni S. Shippenberg

Mathematics, Physics, and Computer Science Faculty Articles and Research

The effect of the endogenous cannabinoid anandamide on K+ currents activated by the ATP-sensitive potassium (KATP) channel opener cromakalim was investigated in follicle-enclosed Xenopus oocytes using the two-electrode voltage-clamp technique. Anandamide (1–90 μM) reversibly inhibited cromakalim-induced K+ currents, with an IC50 value of 8.1 ± 2 μM. Inhibition was noncompetitive and independent of membrane potential. Coapplication of anandamide with the cannabinoid type 1 (CB1) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR 141716A) (1 μM), the CB2 receptor antagonist N-[(1S)endo-1,3,3-trimethyl bicyclo heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) (1 μM), or pertussis toxin (5 μg/ml) did not alter the inhibitory effect of anandamide, suggesting that known cannabinoid receptors …

Visualizing The Function And Migration Of T Cells, Kari J. Dugger

All ETDs from UAB

Lymphocytes are highly mobile cells that can travel throughout the body in response to a multitude of stimuli. Identifying lymphocyte trafficking patterns in vivo is essential for a complete understanding of immune function. Cell-cell and cell-tissue interactions in immune development and in lymphocyte response to stimuli can be comprehended with these investigations. Although the location of cell populations in various tissues at any given point in time may be investigated by techniques such as flow cytometry and immunofluorescence, these methods are not easily used in the assessment of dynamic cell migration patterns in vivo. In the past years, technologies for …

The Role Of Chloride In The Volume Regulation Of Human Glioma Cells, Nola Jean Ernest

All ETDs from UAB

According to the Central Brain Tumor Registry of the United States, the most common primary brain tumors are gliomas, tumors composed of cells of glial origin, most commonly astrocytes and oligodendrocytes. The most aggressive of these tumors are characterized by hyperproliferation, marked cellular and nuclear atypia, extensive infiltration into surrounding normal brain tissue, and large areas of cell and tissue death. Previous data published by our lab and others suggest that these biological processes may involve regulated cell volume changes. Using cell volume regulation in the presence of an anisosmotic challenge as a model for cell swelling and shrinkage, cell …

Characterization Of Human Immunodeficiency Virus Type 1 Monomeric And Trimeric Gp120 Glycoproteins Stabilized In The Cd4-Bound State: Antigenicity, Biophysics, And Immunogenicity, Barna Dey, Marie Pancera, Krisha Svehla, Yuuei Shu, Shi-Hua Xiang, Jeffrey Vainshtein, Yuxing Li, Joseph Sodroski, Peter D. Kwong, John R. Mascola, Richard Wyatt

Nebraska Center for Virology: Faculty Publications

The human immunodeficiency virus type 1 exterior gp120 envelope glycoprotein is highly flexible, and this flexibility may contribute to the inability of monomeric gp120 immunogens to elicit broadly neutralizing antibodies. We previously showed that an S375W modification of a critical interfacial cavity central to the primary receptor binding site, the Phe43 cavity, stabilizes gp120 into the CD4-bound state. However, the immunological effects of this cavity-altering replacement were never tested. Subsequently, we screened other mutations that, along with the S375W alteration, might further stabilize the CD4-bound state. Here, we define a selected second cavity-altering replacement, T257S, and analyze the double mutations …

Georgeoral Immunization Of Rhesus Macaques With Adenoviral Hiv Vaccines Using Enteric-Coated Capsules, George T. Mercier, Pramod N. Nehete, Marco F. Passeri, Bharti N. Nehete, Eric A. Weaver, Nancy Smyth Templeton, Kimberly Schluns, Stephanie S. Buchl, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag …

Differential Engagement Of Tim-1 During Activation Can Positively Or Negatively Costimulate T Cell Expansion And Effector Function, Vijay K. Kuchroo, Sheng Xiao, Nader Najafian, Jay Reddy, Monica Albin, Chen Zhu, Eric Jensen, Jaimie Imitola, Thomas Korn, Ana C. Anderson, Zheng Zhang, Cristina Gutierrez, Thomas Moll, Raymond A. Sobel, Dale T. Umetsu, Hideo Yagita, Hisaya Akiba, Terry Strom, Mohamed H. Sayegh, Rosemarie H. Dekruyff, Samia J. Khoury

School of Veterinary and Biomedical Sciences: Faculty Publications

It has been suggested that T cell immunoglobulin mucin (Tim)-1 expressed on T cells serves to positively costimulate T cell responses. However, crosslinking of Tim-1 by its ligand Tim-4 resulted in either activation or inhibition of T cell responses, thus raising the issue of whether Tim-1 can have a dual function as a costimulator. To resolve this issue, we tested a series of monoclonal antibodies specifi c for Tim-1 and identifi ed two antibodies that showed opposite functional effects. One anti–Tim-1 antibody increased the frequency of antigen-specifi c T cells, the production of the proinfl ammatory cytokines IFN-γ and IL-17, …

Modulation Of Cd4 Co-Receptor Limits Spontaneous Autoimmunity When High-Affinity Transgenic Tcr Specific For Self-Antigen Is Expressed On A Genetically Resistant Background, Zsolt Illés, Hanspeter Waldner, Jay Reddy, Ana C. Anderson, Raymond A. Sobel, Vijay K. Kuchroo

Jay Reddy Publications

Myelin proteolipid protein (PLP) 139–151 is an immunodominant peptide that induces experimental autoimmune encephalomyelitis (EAE) in H-2^s SJL/J mice. While PLP 139–151-specific TCR transgenic (tg) 4E3 mice develop fulminant spontaneous disease on the susceptible SJL/J background, spontaneous EAE is dramatically reduced on the H-2^s congenic B10.S background. On this resistant background, we observed a high frequency of positively selected tg CD42CD82 (DN) thymocytes and peripheral DN tg T cells. Splenic DN tg T cells responded to anti-CD3 stimulation similarly to CD41 cells, but proliferative and cytokine responses to PLP 139–151 were blunted, implying that CD4 coreceptor down-regulation modulated …

Su.32. Myelin-Specific Regulatory T Cells Accumulate In The Central Nervous System, But Fail To Suppress Pathogenic Effector T Cells At The Peak Of Autoimmune Inflammation [Abstract Only], Thomas Korn, Mohamed Oukka, Jay Reddy, Estelle Betelli, Amit Awasthi, Raymond Sobel, Kai Wucherpfennig, Vijay K. Kuchroo

Jay Reddy Publications

Treatment with ex vivo generated regulatory T cells (Treg) has been regarded as highly attractive therapeutic approach for autoimmune diseases. However, the dynamics and function of T-reg in autoimmunity are not well understood. Thus, we developed Foxp3gfp “knock-in” mice and myelin oligodendrocyte glycoprotein (MOG)35–55/IAb tetramers to track autoantigen-specific effector T cells (T-eff) and T-reg in vivo during experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis. Following immunization with the encephalitogenic peptide MOG35–55 emulsified in complete Freund's adjuvant, MOG35–55-tetramer-reactive, Foxp3+ T-reg expanded in the peripheral lymphoid compartment and readily accumulated in the central nervous system (CNS), but did not prevent …

Characterization And Functional Analysis Of Usp14, Stephen Lewis Crimmins

All ETDs from UAB

The ubiquitin proteasome system (UPS) is essential for regulated protein degrada-tion, a requirement for numerous neuronal process, including vesicle cycling, neuro-transmitter release, spine morphology, and synaptic plasticity. Better understanding of UPS function in neurons will increase our knowledge of neurological diseases caused by alterations in ubiquitin signaling. I utilized the ataxia (axJ) mice as a tool to study the UPS in the nervous system. The axJ mice have lowered expression of ubiquitin-specific protease 14 (Usp14) in all tissues; this decreased expression results from an intracisternal-A particle insertion into Usp14. The axJ mice are phenotypically indistinguishable from wild type littermates at …

Protease Dysregulation: Role In Neutrophilic Inflammation In Cystic Fibrosis, Amit Gaggar

All ETDs from UAB

Cystic fibrosis (CF) is a lethal disorder characterized by abnormal epithelial ion transport; this disorder is characterized by an ongoing airway remodeling and neutrophilic inflammation. Much of the airway remodeling is due to activation of a group of enzymes known as proteases; human neutrophil elastase (HNE) is a prominent protease found in the CF airway. While specific cytokines/chemokines are well-known for their role in the inflammation seen in CF, it is unknown how the protease-rich environment in CF lung disease influences airway inflammation. Recently, our group has characterized a novel collagen-derived fragment, proline-glycine-proline (PGP), which causes neutrophil influx through mechanisms …

Interference With Hiv-1 Primer Selection By Sirna Directed To The Hiv-1 Primer Binding Site, Wenlong Han

All ETDs from UAB

The replication of Human immunodeficiency virus type 1 (HIV-1) is characterized by the process of reverse transcription, which converts the viral RNA genome into a DNA intermediate prior to integration into the host cell chromosome. The initiation of reverse transcription needs a cellular tRNA primer, which binds to a region in the viral RNA genome, designated as the primer binding site (PBS). The 18-nucleotide PBS region of HIV-1, which is complementary to the 3′ terminal 18 nucleotides of tRNALys,3, is absolutely conserved among all HIV-1. The highly conserved PBS is a very good target for HIV-1 therapy. My dissertation research …

On The Immunological Roles Of Tlt2 And Hsh2, R Glenn King

All ETDs from UAB

The evolution of multicellular organisms necessitated the ability to detect and remove harmful parasitic microorganisms from the host. This simple requirement for self non-self discrimination has evolved in vertebrates into an elaborate system consisting of a variety of effector mechanisms to perform this process. The immune system is often described as consisting of two distinct yet complimentary components, the innate and adaptive immune systems. It is now recognized that the immune system relies on the highly coordinated interplay between a variety of cell types which cooperate to maintain the health of the organism. The work outlined in this dissertation addresses …

The Effect Of The Aml1-Eto Translocation On Cell Cycle Tumor Suppressor Gene Function, Rose Marie Ko

All ETDs from UAB

The t(8;21)(q22;q22) AML1-ETO translocation is one of the most frequent translocations in acute myeloid leukemia (AML), occurring in approximately 12% of cases. Our laboratory has generated a mouse model in which AML1-ETO is expressed in hematopoietic progenitor cells using a retroviral vector and assayed using bone marrow transplantation. Animals transplanted with AML1-ETO-expressing cells failed to develop leukemia. However, AML1-ETO promoted significant expansion of immature myeloid cells suggesting a “pre-leukemic” state that requires secondary mutations for disease progression. In addition, analysis of cell cycle kinetics in AML1-ETOexpressing myeloid progenitor cells showed that AML1- ETO slowed G1 to S phase progression compared …

Effects Of Specific Alterations In Capsule Structure On Streptococcus Pneumoniae Capsule Assembly And Virulence, Bobbi Xayarath

All ETDs from UAB

The polysaccharide capsules of Streptococcus pneumoniae represent the most important virulence determinant produced by this organism. Ninety-one different serotypes have been identified, but only a small number of these serotypes are responsible for most of the infections caused by S. pneumoniae. The reasons why certain serotypes predominate in infections over others are not well understood. One common serotype found in invasive diseases is type 2, however, it is unclear what characteristics of a type 2 capsule makes strains producing it virulent. The type 2 capsule consists of repeat units made of a backbone of Glc-Rha-Rha-Rha, with a side chain Glc-GlcUA …

Localization And Function Of G2e3, William Samuel Brooks

All ETDs from UAB

A microarray study was performed which identified G2E3 as a novel, putative ubiquitin ligase that was both G2/M-specific in expression and down regulated at the transcriptional level following DNA damage by γ-irradiation. The initial characterization of this protein is described herein. G2E3 is composed of three PHD/RING (plant homoedomain/really interesting new gene) domains within its amino-terminal half and a carboxy-terminal HECT (homologous to E6AP carboxy-terminus) domain. G2E3 is regulated in part by its subcellular localization. The protein normally resides within the nucleoplasm of cultured cells and distinctly within the nucleolus of HeLa cells. G2E3 is a nucleo-cytoplasmic shuttling protein with …

Loss Of Pias3 Expression In Glioblastoma Multiforme Tumors:Implications For Stat-3 Activation And Gene Expression, Emily Claire Brantley

All ETDs from UAB

Glioblastoma multiforme (GBM) is the most common form of cancer in the central nervous system in adults. Because of the infiltrative and aggressive nature of GBM, current treatments including surgical resection, radiation and chemotherapy provide little benefit to patients diagnosed with this tumor. Median survival, after treatment, is less than one year. Despite advances in the basic understanding of cancer biology, this poor prognosis has remained virtually unchanged for several decades. Given the continuing difficulty of clinical treatment of GBMs, a molecular appreciation of relevant signaling pathways has grown. Signal Transducers and Activators of Transcription (STATs) function to activate gene …

Characterization Of A Novel Acetyltransferase Found Only In Pathogenic Strains Of Mycobacterium Tuberculosis, David K. Crossman

All ETDs from UAB

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is still a major threat to the human population. Roughly one third of the world population is asymptomatically infected and two million people die each year of TB. Effective treatments are available as a multi-drug regimen, but there is an ever increasing problem with the rise of multi-drug resistant strains that newer drug targets and a better understanding of how M. tuberculosis affects the host need to be elucidated. The primary target of M. tuberculosis in the human host is the macrophage where M. tuberculosis secretes virulence factors that inhibit various signal …

Pneumococcal Choline-Binding Protein A: Its Role In Virulence And Its Utility As A Streptococcus Pneumoniae Vaccine Antigen, David Tawayne Glover

All ETDs from UAB

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. S. pneumoniae is a leading cause of pneumonia, meningitis, septicemia, and otitis media. Although all age groups can be affected, children and the elderly are espccially susceptible to infection. Currently there is a conjugate vaccine available for use, but this vaccine only contains capsular polysaccahride antigens from the seven most prevelant S. pneumoniae serotypes. The use of the conjugate vaccine has led to serotype shift, with more disease being caused by non-vaccine serotype bacteria. The studies presented in this dissertation identify and characterize a novel S. penumoniae vaccine candidate …

Prostate Cancer Chemoprevention With Genistein And Resveratrol In Models Of Spontaneously Developing Prostate Cancer, Curt E. Harper

All ETDs from UAB

Prostate cancer is the second leading cause of cancer-related death among men in the United States. The goal of this research was to investigate the potential of three nutriceutical polyphenols, genistein, resveratrol, and epigallocatechin-3-gallate (EGCG), to suppress prostate cancer. Cancer chemoprevention and mechanism of action studies were carried out in transgenic models of prostate cancer. In TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model, resveratrol suppressed poorly differentiated tumors by 86%, whereas EGCG suppressed precancerous lesions, but failed to prevent late-stage prostate cancer. Agents that were chemopreventive in the TRAMP model were subsequently evaluated alone, and in combination, in the …

Mcmv Induced Cerebellar Maldevelopment, Thadeus B. Koontz

All ETDs from UAB

Congenital Human Cytomegalovirus (HCMV) infection represents a significant cause of morbidity and mortality in infants and children. While most of the systemic damage incurred by the infant in the course of the infection resolves without permanent consequence, the pathological manifestations of infection in the central nervous system (CNS) are often permanent. Children born with congenital HCMV infection may exhibit hearing loss and cognitive impairment in various degrees. These neurological disabilities are correlated with pathological findings in various permutations including infection of the inner ear, ventricular calcifications, ventriculomegaly, microgyria, lissencephaly, and cerebellar hypoplasia. To develop a therapeutic or preventive strategy, HCMV …

Kainate Receptor Modulation Of Synaptic Transmission In Neocortex, Seena S. Mathew

All ETDs from UAB

The actions of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) are tightly regulated to ensure effective information processing as well as prevention of excess excitatory activity, which can lead to seizures and neurological disorders such as epilepsy. Drugs which enhance the effects of GABA are used as anesthetics, sedatives and anticonvulsants. Using whole-cell patch clamp recordings from neocortical neurons, we examined the mechanisms of GABAergic modulation that occur when kainate receptors (KARs) are activated. First, we address a novel signaling mechanism for the KAR-mediated facilitation of GABAergic synaptic transmission. Our first observation involved the presence of presynaptic KARs located on the …

Regulation Of Vertebrate Gastrulation By Erbb Signaling, Shuyi Nie

All ETDs from UAB

ErbB receptor tyrosine kinases have long been implicated in cancer formation and progression by regulating cell division, migration, and survival. ErbBs are also essential in multiple processes during invertebrate development; however, their activities during vertebrate embryogenesis are not well understood. For functional characterization of ErbB signaling during vertebrate development, frog model Xenopus laevis was used in our studies. The expression pattern and the general activities of ErbB receptors during early frog development were first analyzed and results shown that ErbBs regulate gastrulation, somite organization and head patterning. As gastrulation is the first major morphogenetic event in vertebrate development, I focused …

Trafficking Of Hantaviral Nucleocapsid Proteins, Harish N. Ramanathan

All ETDs from UAB

Hantaviruses are enveloped, negative-sense RNA viruses belonging to genus Hantavirus, within the family Bunyaviridae. Hantaviruses include many serious human pathogens and are classified as Old and New World based on the geographic distribution of rodent reservoirs and their ability to in induce distinct illnesses in humans. Currently there are no reservoirs known for hantaviruses other than the rodents. Human transmission of hantaviruses occurs via inhalation of aerosolized rodent excreta leading to hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). Hantavirus genome consists of small (S), medium (M) and large (L) segments that encode nucleocapsid (N) protein, two …

The Role Of Complement In Experimental Autoimmune Uveitis, Russell W. Read

All ETDs from UAB

The complement system has been increasingly implicated in the pathophysiology of autoimmune disease. Complement expression in the normal human eye had not been previously completely defined. We performed immunohistochemical studies for membrane complement proteins in normal human retina to provide a baseline for future studies. We found expression of the anaphylatoxin receptors, CD55, and CD59 in the inner retina and CD46 in a polarized fashion on the retinal pigment epithelium. Previous studies in uveitis have shown activated fragments of complement in human eyes with uveitis and animal models have shown an effect on disease by complement depletion with cobra venom …