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Association Between T Cells-Related Gene Expression And Fibrosis Progression In Hcv Recurrence Disease., Alexander Philip Aug 2011

Association Between T Cells-Related Gene Expression And Fibrosis Progression In Hcv Recurrence Disease., Alexander Philip

Theses and Dissertations

Hepatitis C virus (HCV) is the major cause of chronic hepatitis worldwide and a leading cause for liver transplant. Unfortunately, graft HCV infection is a universal phenomenon despite of pre-transplant prophylactic strategies. Acute HCV infection and innate immune responses elicit an inflammatory scenario that triggers the recruitment of adaptive immune response cells. Of those chronically infected, 30% experience accelerated fibrosis with concomitant cirrhosis development within 5 years post-LT and require re-transplant. With many patients responding unfavorably to antivirals and ineffective vaccines, much attention is now placed on T cell immunity in controlling HCV infection. This study represents a retrospective analysis …


Molecular Pathways Involved In Calcineurin Inhibitor Nephrotoxicity In Kidney Allograft Transplants, Huong Nguyen Aug 2011

Molecular Pathways Involved In Calcineurin Inhibitor Nephrotoxicity In Kidney Allograft Transplants, Huong Nguyen

Theses and Dissertations

ABSTRACT MOLECULAR MECHANISMS AND GENE SIGNATURES INVOVLED IN CALCINEURIN INHIBITOR NEPHROTOXICITY IN KIDNEY ALLOGRAFT By Huong Le Diem Nguyen, M.S. A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Physiology at Virginia Commonwealth University. Virginia Commonwealth University, 2011. Major Director: Valeria Mas, Ph.D. Associate Professor, Department of Surgery and Pathology Director of Molecular Transplant Research Laboratory, Division of Transplant Calcineurin inhibitors (CNI), cyclosporin A and tacrolimus, are potent immunosuppressive agents but induce toxicities causing damages and graft dysfunction, and have been suggested to contribute to late-term loss of graft in kidney transplant …


Opioid Addiction Treatments During Pregnancy And Their Effects On Axonal Growth And Myelination In The Developing Central Nervous System, Manisha Magar Jul 2011

Opioid Addiction Treatments During Pregnancy And Their Effects On Axonal Growth And Myelination In The Developing Central Nervous System, Manisha Magar

Theses and Dissertations

Treatment with buprenorphine represents a promising alternative for pregnant opioid addicts but there is a need to understand potential effects on nervous system development. We previously showed effects of perinatal exposure to buprenorphine on axonal caliber and myelination in 26-day-old rat corpus callosum. These changes, detected at the end of rapid brain myelination and accompanied by earlier oligodendrocyte maturation, suggested interference with mechanisms coordinating axonal growth and myelination. To better understand buprenorphine actions and to establish whether these effects extend to the spinal cord, we analyzed the corpus callosum and corticospinal tract at 16 days of age, just before the …


Quantitative Analysis Of Contactin-Associated Protein And Voltage-Gated Sodium Channel Isoform 1.6 Following Experimental Diffuse Traumatic Brain Injury, Daniel Gardiner Jul 2011

Quantitative Analysis Of Contactin-Associated Protein And Voltage-Gated Sodium Channel Isoform 1.6 Following Experimental Diffuse Traumatic Brain Injury, Daniel Gardiner

Theses and Dissertations

Traumatic axonal injury (TAI) contributes to the mortality and morbidity following diffuse traumatic brain injury (TBI). Previous work has shown that following TBI, alterations in the molecular domains of axons result in TAI. It is currently posited that injury induced ionic flux is responsible for activating deleterious proteolytic cascades, resulting in altered distributions of axonal components. However, the underlying mechanism of this progressive pathology remains elusive. This study further explores the hypothesis that altered molecular domains contributes to the progressive intra-axonal changes that characterize TAI. Using a rodent model of impact acceleration TBI we examined the expression of nodal and …


Receptor Influences In Girk Current Activation And Desensitization, Gyu Park Jul 2011

Receptor Influences In Girk Current Activation And Desensitization, Gyu Park

Theses and Dissertations

G protein-coupled receptors (GPCRs) are seven-transmembrane domain receptors that sense extracellular signal and activate intracellular signaling pathways. Metabotropic glutamate receptor 2 (mGluR2) is one of the GPCRs coupled to Gi/o proteins whose Gβγ subunits stimulate G protein-gated inwardly rectifying K+ channels (GIRKs). Previous experiments demonstrated that in planar lipid bilayer both active forms of G proteins [Gα (GTPγS-stimulated) and Gβγ subunits] were required to activate GIRK channels in the absence of the receptor, but surprisingly, the Gβγ subunit alone could activate GIRK channel in the presence of GPCR. Currently, it is not clear whether GPCRs play a role beyond catalyzing …


Kinase Pathways Underlying Muscarinic Activation Of Colonic Longitudinal Muscle, Charles Dudley Anderson Jr. Apr 2011

Kinase Pathways Underlying Muscarinic Activation Of Colonic Longitudinal Muscle, Charles Dudley Anderson Jr.

Theses and Dissertations

The longitudinal muscle layer in gut is the functional opponent to the circular muscle layer during the peristalsis reflex. Differences in innervation of the layers allow for the contraction of one layer that corresponds with the simultaneous relaxation of the other, enabling the passage of gut contents in a controlled fashion. Differences in development have given the cells of the two layers differences in receptor populations, membrane lipid handling, and calcium handling profiles/behaviors. The kinase signaling differences between the two layers is not as well characterized. Upon activation of cells from the circular muscle layer, it is known that Rho …


Differential Regulation Of Mlc20 Phosphorylation In Tonic And Phasic Smooth Muscles Of The Stomach, Othman Al-Shboul Apr 2011

Differential Regulation Of Mlc20 Phosphorylation In Tonic And Phasic Smooth Muscles Of The Stomach, Othman Al-Shboul

Theses and Dissertations

Gastrointestinal (GI) smooth muscle possesses distinct regional and functional properties that distinguish it from other types of visceral and vascular smooth muscle. On the basis of electrical properties and contractile phenotype, GI smooth muscles have been classified into phasic (non-sphinteric) and tonic (sphinteric) smooth muscles. The biochemical basis of phasic and tonic phenotypes of smooth muscle is not clear and is the major question of inquiry of the present study. Phosphorylation of Ser19 on the 20 kDa myosin light chain (MLC) is essential for acto-myosin interaction and contraction in both phasic and tonic muscles. The levels of MLC20 phosphorylation are …


Renal Epithelial Sodium Channel (Enac) Regulation Of Pregnancy Mediated Hemodynamic Adaptations: Mechanistic Insights, Crystal West Jan 2011

Renal Epithelial Sodium Channel (Enac) Regulation Of Pregnancy Mediated Hemodynamic Adaptations: Mechanistic Insights, Crystal West

Theses and Dissertations

Pregnancy-mediated sodium (Na) retention is required to provide an increase in plasma volume for the growing fetus. The mechanisms responsible for this Na retention are not clear. In the first study, we generated a renal tubule protein profile indicating α ENaC as the only sodium transport protein upregulated in mid and late pregnancy. To determine the in vivo activity of ENaC we conducted in vivo studies in late pregnant rats (day 18-20) and virgin rats to measure the natriuretic response to ENaC blockade (with benzamil). The in vivo activity of ENaC (UNaV post benzamil - UNaV post vehicle) was markedly …


Changes In The Expression Of Thin Filament-Associated Proteins In Colonic Smooth Muscle From Mice During Inflammation, Reem Alkahtani Jan 2011

Changes In The Expression Of Thin Filament-Associated Proteins In Colonic Smooth Muscle From Mice During Inflammation, Reem Alkahtani

Theses and Dissertations

The contractility of smooth muscle in inflammatory bowel disease and experimental colitis is reduced due to inhibition of neurotransmitter release and a decrease in the response of smooth muscle to contractile agonists. We and others have shown that inflammation induced by TNBS treatment alters the expression and/or activity of signaling molecules involved in the regulation of Ca2+ mobilization, MLC20 phosphorylation and contraction in colonic smooth muscle. Although, thin filament- associated proteins such as calponin, caldesmon, tropomyosin and smoothelin do not directly participate in contraction, they regulate acto-myosin interaction and thus, muscle contraction. Calponin, caldesmon and tropomyosin inhibit actomyosin interaction and …


The Characterization Of Pg0228 In Porphyromonas Gingivalis W83, Courtney Schlenker Jan 2011

The Characterization Of Pg0228 In Porphyromonas Gingivalis W83, Courtney Schlenker

Theses and Dissertations

Periodontitis affects 10 to 15 percent of most adult populations and can contribute to numerous systemic diseases. Porphyromonas gingivalis, a gram-negative anaerobic bacterium, is a recognized prime causative agent in periodontitis. Studies have shown a number of small non-coding RNAs (sRNAs) have been related to bacterial virulence. Many of these sRNAs require the facilitation of the bacterial Sm-like protein, Hfq, for optimum function. Hfq is a RNA chaperone involved in RNA stability, sRNA function, and polyadenylation. Mutants lacking in Hfq often show pleiotropic phenotypes, although the extent and severity of hfq null phenotypes is often species-specific. Hfq has been encoded …


Characterization Of The Expression Of Bdnf And Cgrp And Their Regulatory Pathways In Dorsal Root Ganglion During Cystitis., Sharon Yu Jan 2011

Characterization Of The Expression Of Bdnf And Cgrp And Their Regulatory Pathways In Dorsal Root Ganglion During Cystitis., Sharon Yu

Theses and Dissertations

Interstitial cystitis is a chronic debilitating disease that causes pain and increased frequency of micturition, amongst other symptoms, without any identifiable cause. This disease affects a large number of the population, yet the etiology is still unknown. The present study aimed to characterize BDNF and CGRP—two neuropeptides that have both been proven to play an important role in the transmission of pain as well as in hypersensitivity. The signaling pathways regulating the expression of the two neuropeptides were also examined. Results revealed that BDNF protein expression levels increased in both L1 and L6 DRG following 48 hours post CYP-induced cystitis. …