Medical Sciences Commons^™

Survivin As Potential Mediator To Support Autoreactive Cell Survival In Myasthenia Gravis: A Human And Animal Model Study, Linda Louise Kusner, Michael J. Ciesielski, Alexander Marx, Henry J. Kaminski, Robert A. Fenstermaker

Pharmacology and Physiology Faculty Publications

The mechanisms that underlie the development and maintenance of autoimmunity in myasthenia gravis are poorly understood. In this investigation, we evaluate the role of survivin, a member of the inhibitor of apoptosis protein family, in humans and in two animal models. We identified survivin expression in cells with B lymphocyte and plasma cells markers, and in the thymuses of patients with myasthenia gravis. A portion of survivin-expressing cells specifically bound a peptide derived from the alpha subunit of acetylcholine receptor indicating that they recognize the peptide. Thymuses of patients with myasthenia gravis had large numbers of survivin-positive cells with fewer ...

Infectious Diseases, Bert Chapman

Libraries Faculty and Staff Scholarship and Research

Provides information about the role of infectious diseases in the early years of U.S. History, with particular emphasis on how they impacted injuries sustained in military conflict.

Pathscan Enabler At Md Anderson Cancer Center, George Mcnamara

George McNamara

McNamara 20140703 - Additional Pathscan and Tiki_Goddess related resources

http://works.bepress.com/gmcnamara/52

http://home.earthlink.net/~tiki_goddess/

http://works.bepress.com/gmcnamara/1/

http://works.bepress.com/gmcnamara/11/

https://www.linkedin.com/in/georgemcnamara

Our Pathscan Enabler IV, delivered July 2014, uses the QuickScan software to scan a histology slide in "two clicks" (after loading the

slide):

1. Push the QuickScan button on the front of the Pathscan Enabler.

2. Click the Scan button in the QuickScan pop-up application (optional: change scan area in the Prescan image window).

The image gets saved as a TIFF file to ...

Succinate Dehydrogenase Deficiency In Sporadic Pituitary Adenomas: A Potential Mechanism For Tumorigenesis, Edward Andrews, Md, Stacey K. Mardekian, Md, Markku Miettinen, Mark T. Curtis, Md

Pathology, Anatomy and Cell Biology Resident's Posters

In order to determine whether succinate dehydrogenase (SDH) deficiency plays a role in spor-adic, non-familial pituitary adenomas, we analyzed 80 pituitary adenomas for SDH deficiency from patients without familial tumor syndromes or without known SDH deficiency-associated neoplasms. SDH deficiency was determined by immunohistochemical (IHC) stains for SDHB since the loss of any of the four SDH subunits results in the loss of SDHB expression. Three pituitary adenomas showed complete loss of SDHB staining, and of these two also showed loss of SDHA staining. We further characterized these adenomas by looking at Ki67, IGF1R, and 5-hmC levels via IHC. SDHx ...

Frontal White Matter Integrity In Adults With Down Syndrome With And Without Dementia, David K. Powell, Allison Caban-Holt, Greg A. Jicha, William C. Robertson, Roberta Davis, Brian T. Gold, Frederick A. Schmitt, Elizabeth Head

Magnetic Resonance Imaging and Spectroscopy Center Faculty Publications

Adults with Down syndrome (DS) are at high risk for developing Alzheimer's disease after the age of 40 years. To detect white matter (WM) changes in the brain linked to dementia, fractional anisotropy (FA) from diffusion tensor imaging was used. We hypothesized that adults with DS without dementia (DS n = 10), DS with dementia (DSAD n = 10) and age matched non-DS subjects (CTL n = 10) would show differential levels of FA and an association with scores from the Brief Praxis Test and the Severe Impairment Battery. WM integrity differences in DS compared with CTL were found predominantly in the ...

The Regulator Of G Protein Signaling (Rgs) Domain Of G Protein-Coupled Receptor Kinase 5 (Grk5) Regulates Plasma Membrane Localization And Function., Hua Xu, Xiaoshan Jiang, Ke Shen, Christopher C. Fischer, Philip B Wedegaertner

Department of Biochemistry and Molecular Biology Faculty Papers

The G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate activated GPCRs at the plasma membrane (PM). Here GRK5/GRK4 chimeras and point mutations in GRK5 identify a short sequence within the regulator of G protein signaling (RGS) domain in GRK5 that is critical for GRK5 PM localization. This region of the RGS domain of GRK5 coincides with a region of GRK6 and GRK1 shown to form a hydrophobic dimeric interface (HDI) in crystal structures. Coimmunoprecipitation (coIP) and acceptor photobleaching fluorescence resonance energy transfer assays show that expressed GRK5 self-associates in cells, whereas GRK5-M165E/F166E (GRK5-EE), containing hydrophilic mutations in the HDI ...

A New Reinforced Fibrin Collagen Glycosaminoglycan Material To Resist Tissue Contraction In Heart Valves, Claire Brougham, Gerard Cooney, Stefan Jockenhoevel, Thomas Flanagan, Fergal O'Brien

Conference Papers

A crosslinked, multicomponent scaffold of collagen, GAG and fibrin has been characterised for heart valve applications. Fibrin gels reinforced with a 0.75% collagen, 0.044% GAG scaffolds can resist VSMC induced contraction significantly more than fibrin-only gels, while allowing cell proliferation and maintaining excellent cell viability. This improvement in structural integrity may facilitate the use of fibrin based materials for heart valve tissue engineering.

Burkitt Lymphoma In A Pediatric Patient With Hereditary Multiple Exostose, Sara D. Prince, Portia A. Krieger, Md, Andrew W. Walter, Ms, Md

Department of Pathology, Anatomy and Cell Biology Faculty Papers

Introduction

Hereditary multiple exostoses (HME) is an autosomal dominant disorder characterized by the growth of multiple bony tumors. These tumors include benign osteochondromas and less commonly, malignant tumors that arise from transformation of exostoses into secondary osteosarcomas and chondrosarcomas [1,3]. There have been no reported cases of lymphoma in the pediatric HME population. We report a case of a 10 year old boy with HME who developed Burkitt lymphoma of the abdomen.

Small-Molecule Probes Targeting The Viral Ppxy-Host Nedd4 Interface Block Egress Of A Broad Range Of Rna Viruses., Ziying Han, Jianhong Lu, Yuliang Liu, Benjamin Davis, Michael S Lee, Mark A Olson, Gordon Ruthel, Bruce D Freedman, Matthias J. Schnell, Jay E Wrobel, Allen B Reitz, Ronald N Harty

Department of Microbiology and Immunology Faculty Papers

Budding of filoviruses, arenaviruses, and rhabdoviruses is facilitated by subversion of host proteins, such as Nedd4 E3 ubiquitin ligase, by viral PPxY late (L) budding domains expressed within the matrix proteins of these RNA viruses. As L domains are important for budding and are highly conserved in a wide array of RNA viruses, they represent potential broad-spectrum targets for the development of antiviral drugs. To identify potential competitive blockers, we used the known Nedd4 WW domain-PPxY interaction interface as the basis of an in silico screen. Using PPxY-dependent budding of Marburg (MARV) VP40 virus-like particles (VLPs) as our model system ...

Cd27high/Klrg1low Cd8+ T Cells That Persist Throughout Mcmv Infection Are Highly Expansive And Have The Ability To Reestablish Mcmv Immunity, Michael Quinn, Holly Turula, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Abstract

Cytomegalovirus (CMV) is a herpesvirus that establishes life-long latency in 60-80% of Americans. Constant immune surveillance is necessary to prevent viral reactivation from latency and results in the accumulation of functional CMV-specific CD8+ T cells (CD8s) over time, a process termed memory inflation. As such, CMV reactivations remain a clinical concern for immunosuppressed patients and reconstituting CMV immunity is critical for the long-term prevention of CMV disease. Understanding the maintenance of memory inflation may reveal novel approaches to restore CMV immunity.

Previous work has shown that the majority of inflationary CD8s express a terminally-differentiated “effector” (T_EFF) phenotype, have ...

Characterization Of Primary Care Clinicians’ Use Of Genomic And Pharmacogenomic Testing, Brian Stello Md, Heather Bittner-Fagan Md, Mph, Christopher V. Chambers Md, Melanie B. Johnson Mpa, Geoffrey Mills Md, Phd, Michael P. Rosenthal Md, Kyle Shaak Bs

Department of Family Medicine

No abstract provided.

Polycomb Repressive Complex 2 Regulates Mir-200b In Retinal Endothelial Cells: Possible Implications In Diabetic Retinopathy, Michael A. Ruiz

University of Western Ontario - Electronic Thesis and Dissertation Repository

Glucose-induced augmented vascular endothelial growth factor (VEGF) production is a key event in diabetic retinopathy. We have previously demonstrated that downregulation of miR-200b increases VEGF, mediating structural and functional changes in the retina in diabetes. However, mechanisms regulating miR-200b in diabetes are not known. Histone methyltransferase complex, Polycomb Repressive Complex 2 (PRC2), has been shown to repress miRNAs in neoplastic process. We hypothesized that, in diabetes, PRC2 represses miR-200b through its histone H3 lysine-27 trimethylation mark. We show that human retinal microvascular endothelial cells exposed to high levels of glucose regulate miR-200b repression through histone methylation, and that inhibition of ...

Crohn’S Disease Linked Polymorphisms Associated With Autophagy Contribute To Th17 Cell Induction Through Down Regulating Il-10 And Up Regulating Il-1Β And Tnf-Α, Daniel Clayton Morse

Pursuit - The Journal of Undergraduate Research at the University of Tennessee

Abstract

Genome wide association studies (GWAS) have linked polymorphisms in autophagy genes to Crohn’s Disease (CD). Interestingly, recent studies have shown that defective autophagy leads to increased levels of the cytokines IL-1b and TNF-a, which play a critical role in Th17 cell differentiation. This is significant because CD is marked by a Th17 cell mediated inflammatory response. This article examines the manners in which defective expression of autophagy linked proteins, can indirectly amplify and sustain Th17 cell induction through increasing the production of Th17 positively differentiating cytokines (IL-1b and TNF-a) and decreasing the production of ...

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at the University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the ...

Application Of Nuclear Magnetic Resonance Based Metabolomics To Study The Central Metabolism Of Staphylococci, Bo Zhang

Student Research Projects, Dissertations, and Theses - Chemistry Department

Metabolomics studies the collection of small molecules (metabolites) involved in enzymatically catalyzed reactions, cell signaling and cellular structure. Perturbations in metabolite concentrations have been used to reflect the activity of corresponding enzymes or proteins. Nuclear magnetic resonance (NMR) spectroscopy is a well-known approach for the structure determination of biological macromolecules. Alternatively, NMR has recently been established as a valuable tool of metabolomics, in which NMR spectral signals correlate small molecules with cellular activities. This has been accomplished through the chemometric analysis of high-throughput one dimensional ¹H spectra (metabolic fingerprinting) and quantitative metabolite identification based on two dimensional ¹H ...

A Non-Contrast Magnetic Resonance Imaging Technique To Assess Blood-Brain Barrier Permeability, Harini Pandithasekera

University of Western Ontario - Electronic Thesis and Dissertation Repository

The Blood-brain barrier (BBB) regulates the entry of compounds between the blood and the brain, thus plays an important role in brain homeostasis. Studies indicate in disease states such as Alzheimer’s the BBB integrity is compromised. The motive of this project is to investigate the sensitivity of the diffusion-weighted arterial spin labeling (DW-ASL) technique to detect water exchange. Testing the sensitivity requires a reliable method of opening the barrier at specific locations of the brain. Here, a unique technology named focused ultrasound (FUS) has been used to mimic a compromised BBB environment.

A series of experiments were conducted in ...

Mri Relaxation Rates: A Quantitative Approach To Track Tumour Cells Expressing Maga, Anindita Sengupta

University of Western Ontario - Electronic Thesis and Dissertation Repository

Using magnetic resonance imaging, relaxation rate measurements were

performed in cancer cells overexpressing a magnetotactic bacterial gene, MagA.

Measurements of magnetic resonance relaxation rates in this expression

system is important for optimizing cell detection and specificity, for developing

quantification methods, and for refinement of gene-based iron contrast using

magnetosome associated genes. We measured the total transverse

relaxation rate (R2^*), its irreversible and reversible components (R2 and R2^′,

respectively) and the longitudinal relaxation rate (R1) in MDA-MB-435 tumor cells.

Clonal lines overexpressing MagA were cultured in the presence and absence of

iron supplementation, and mounted in a spherical phantom for relaxation ...

Investigating The Viability Of Two Stenotrophomonas Maltophilia Isolates After Air-Drying, Samantha Lane, Joanna Brooke

DePaul Discoveries

Abstract

Stenotrophomonas maltophilia is a water-borne infectious bacterium that is found in both clinical (hospitals) and non-clinical environments. This human pathogen is commonly recovered from respiratory tract infections. A recent study at a hospital in Taiwan suggested that dry patient charts can serve as a vehicle of transmission of this bacterium⁷. As S. maltophilia is not commonly isolated from dry surfaces, this current study tested the hypothesis that this pathogen can remain viable for some time on a dry surface. This study was designed to determine how long S. maltophilia could remain viable after air-drying by observing culture growth ...

New Clues To Understanding Hiv Nonprogressors: Low Cholesterol Blocks Hiv Trans Infection, Vinayaka R. Prasad, Michael I. Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

A small percentage of HIV-infected subjects (2 to 15%) are able to control disease progression for many years without antiretroviral therapy. Years of intense studies of virologic and immunologic mechanisms of disease control in such individuals yielded a number of possible host genes that could be responsible for the preservation of immune functions, from immune surveillance genes, chemokines, or their receptors to anti-HIV restriction factors. A recent mBiopaper by Rappocciolo et al. (G. Rappocciolo, M. Jais, P. Piazza, T. A. Reinhart, S. J. Berendam, L. Garcia-Exposito, P. Gupta, and C. R. Rinaldo, mBio 5:e01031-13, 2014) describes another potential ...

Characterizing The Response Of Multidrug-Resistant Klebsiella Pneumoniae Species To The Application Of A Phage Cocktail, Steven Liu

Symposium

Project Summary: The application of bacteriophages to treat bacterial infections is known as phage therapy, which takes advantage of bacteriophage’s natural ability to infect and lyse bacterial hosts. Phages have been shaped by billions of years of evolution to be highly specialized deliverers of bactericidal agents to the cytoplasm of their target bacteria. Ever since discovery of bacteriophages in 1915, phage therapy was recognized as a potentially powerful tool for eliminating bacterial infections. The effectiveness of phage therapy can be increased by creating a mixture of multiple phages to target a wider variety of bacterial strains. Furthermore, phage therapy ...