Medicine and Health Sciences Commons^™

Oxidative Stress And Micrornas In Endothelial Cells Under Metabolic Disorders, Morgan Minjares, Wendy Wu, Jie-Mei Wang

Pharmaceutical Sciences Faculty Publications

Reactive oxygen species (ROS) are radical oxygen intermediates that serve as important second messengers in signal transduction. However, when the accumulation of these molecules exceeds the buffering capacity of antioxidant enzymes, oxidative stress and endothelial cell (EC) dysfunction occur. EC dysfunction shifts the vascular system into a pro-coagulative, proinflammatory state, thereby increasing the risk of developing cardiovascular (CV) diseases and metabolic disorders. Studies have turned to the investigation of microRNA treatment for CV risk factors, as these post-transcription regulators are known to co-regulate ROS. In this review, we will discuss ROS pathways and generation, normal endothelial cell physiology and ROS-induced …

Topical Anesthetic Gel Interferes With Antibacterial Efficacy Of Povidone-Iodine Both In Vitro And In Vivo, Cecilly Kelleher Bs, Jacob Im Md, Linda Kang Bs, Aleksey Mishulin Md, Sukhvinder Singh Phd, Ashok Kumar Phd

Medical Student Research Symposium

Purpose: To evaluate the effects of viscous lidocaine gel on the antimicrobial efficacy of povidone-iodine (PI) and their order of application in both in vitro and in vivo models.

Methods: In vitro antibacterial effects were tested against Staphylococcus aureus (S. aureus) with disc diffusion methods for application of lidocaine alone, PI alone, PI before lidocaine, and lidocaine before PI. Zones of inhibition were measured after incubation at 37°C overnight. Mouse eyes were colonized with S. aureus for in vivo study to which PI and/or lidocaine were applied in various combinations. Eyes were then rinsed with saline, and …

Streptococcus Cristatus – An Oral Bacterium Causing A Case Of Mild Bacteremia And “Possible Endocarditis”, Camilo Guzman, Adi Zaclli, John Molinari

Medical Student Research Symposium

Streptococcus cristatus is a member of the Mitis streptococcus group. Like other members of this group, it resides in mucosal surfaces of the oral cavity but rarely causes disease. We present a case of S. cristatus bacteremia and “possible endocarditis” (per the modified Duke criteria) in a 59-year-old male suffering from end- stage cryptogenic cirrhosis. To date, it is the fifth reported case of disease caused by the microbe, and the first adult case in which S. cristatus was the sole microbe identified. Our patient had a history of dental caries and poor dentition, which were likely the source of …

Autoantibodies To Agrin In Myasthenia Gravis Patients, Bin Zhang, Chengyong Shen, Beverly Bealmear, Samia Ragheb, Wen-Cheng Xiong, Richard A. Lewis, Robert P. Lisak, Lin Mei

Immunology and Microbiology Faculty Research Publications

To determine if patients with myasthenia gravis (MG) have antibodies to agrin, a proteoglycan released by motor neurons and is critical for neuromuscular junction (NMJ) formation, we collected serum samples from 93 patients with MG with known status of antibodies to acetylcholine receptor (AChR), muscle specific kinase (MuSK) and lipoprotein-related 4 (LRP4) and samples from control subjects (healthy individuals and individuals with other diseases). Sera were assayed for antibodies to agrin. We found antibodies to agrin in 7 serum samples of MG patients. None of the 25 healthy controls and none of the 55 control neurological patients had agrin antibodies. …

Lack Of An Association Of Mir-938 Snp In Iddm10 With Human Type 1 Diabetes, Xiaofan Mi, Hongzhi He, Yangxin Deng, Abert M. Levin, Jin-Xiong She, Qing-Sheng Mi, Li Zhou

Wayne State University Associated BioMed Central Scholarship

Abstract

MicroRNAs (miRNAs) are a newly discovered type of small non-protein coding RNA that function in the inhibition of effective mRNA translation, and may serve as susceptibility genes for various disease developments. The SNP rs12416605, located in human type 1 diabetes IDDM10 locus, changes the seeding sequence (UGU[G/A]CCC) of miRNA miR-938 and potentially alters miR-938 targets, including IL-16 and IL-17A. In an attempt to test whether miR-938 may be a susceptibility gene for IDDM10, we assessed the possible association of the miR-938 SNP with T1D in an American Caucasian cohort of 622 patients and 723 healthy controls by TaqMan assay. …

Incorporation Of Membrane-Bound, Mammalian-Derived Immunomodulatory Proteins Into Influenza Whole Virus Vaccines Boosts Immunogenicity And Protection Against Lethal Challenge, Andrew S. Herbert, Lynn Heffron, Roy Sundick, Paul C. Roberts

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Influenza epidemics continue to cause morbidity and mortality within the human population despite widespread vaccination efforts. This, along with the ominous threat of an avian influenza pandemic (H5N1), demonstrates the need for a much improved, more sophisticated influenza vaccine. We have developed an in vitro model system for producing a membrane-bound Cytokine-bearing Influenza Vaccine (CYT-IVAC). Numerous cytokines are involved in directing both innate and adaptive immunity and it is our goal to utilize the properties of individual cytokines and other immunomodulatory proteins to create a more immunogenic vaccine.

Results

We have evaluated the immunogenicity of inactivated cytokine-bearing influenza …

Autoimmune-Induced Preferential Depletion Of Myelin-Associated Glycoprotein (Mag) Is Genetically Regulated In Relapsing Eae (B6 × Sjl) F1 Mice, Dusanka S. Skundric, Rujuan Dai, Vaagn L. Zakarian, Weili Zhou

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Experimental autoimmune encephalomyelitis (EAE) is commonly used to investigate mechanisms of autoimmune-mediated damage to oligodendrocytes, myelin, and axons in multiple sclerosis (MS). Four distinct autoimmune mechanisms with subsequently distinct patterns of demyelination have been recognized in acute MS lesions. EAE correlates for those distinct patterns of MS lesions are unknown. An excessive loss of myelin-associated glycoprotein (MAG), as a result of distal oligodendrogliopathy, is found exclusively in the subtype III lesion. We sought to answer if types of demyelination in acute lesions during onset and relapse of EAE can replicate the specific patterns observed in MS acute lesions. …

A Stable Explant Culture Of Her2/Neu Invasive Carcinoma Supported By Alpha-Smooth Muscle Actin Expressing Stromal Cells To Evaluate Therapeutic Agents, Marie P. Piechocki

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

To gain a better understanding of the effects of therapeutic agents on the tumor microenvironment in invasive cancers, we developed a co-culture model from an invasive lobular carcinoma. Tumor cells expressing HER2/neu organize in nests surrounded by alpha-Smooth Muscle Actin (α-SMA) expressing tumor stroma to resemble the morphology of an invading tumor. This co-culture, Mammary Adenocarcinoma Model (MAM-1) maintains a 1:1 ratio of HER2/neu positive tumor cells to α-SMA-reactive stromal cells and renews this configuration for over 20 passages in vitro.

Methods

We characterized the cellular elements of the MAM-1 model by microarray analysis, and immunocytochemistry. We developed …

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 …

Production Of Il-16 Correlates With Cd4+ Th1 Inflammation And Phosphorylation Of Axonal Cytoskeleton In Multiple Sclerosis Lesions, Dusanka S. Skundric, Juan Cai, William W. Cruikshank, Djordje Gveric

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Multiple sclerosis (MS) is a central nervous system-specific autoimmune, demyelinating and neurodegenerative disease. Infiltration of lesions by autoaggressive, myelin-specific CD4+Th1 cells correlates with clinical manifestations of disease. The cytokine IL-16 is a CD4+ T cell-specific chemoattractant that is biased towards CD4+ Th1 cells. IL-16 precursor is constitutively expressed in lymphocytes and during CD4+ T cell activation; active caspase-3 cleaves and releases C-terminal bioactive IL-16. Previously, we used an animal model of MS to demonstrate an important role for IL-16 in regulation of autoimmune inflammation and subsequent axonal damage. This role of IL-16 in MS is largely unexplored. Here …

Increased Production Of Pro-Inflammatory Cytokines And Enhanced T Cell Responses After Activation Of Human Dendritic Cells With Il-1 And Cd40 Ligand, Amy Wesa, Anne Galy

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Various microbial, inflammatory and immune signals regulate the activation of dendritic cells (DC), determining their ability to interact with naïve T cells and to produce cytokines that direct T cell development. In particular, CD40L and IL-1 cooperatively activate DC to secrete high levels of IL-12. The immuno-stimulatory capacity of such DC is otherwise not well-defined prompting further characterization of the effects of IL-1 and family members on DC activation in comparison with other pro-inflammatory stimuli.

Results

Human DC co-activated in vitro by CD40L and IL-1β expressed numerous cytokine genes including IL-12β, IL-23 p19, IL-1β, IL-1α, IL-1Ra, IL-10, IL-6, …