Digital Commons Network^™

Spontaneous Idiopathic Arteritis Of The Testicular Artery In Raccoons (Procyon Lotor), A. N. Hamir, M. V. Palmer, H. Li, J. Stasko, D. G. Rogers

School of Veterinary and Biomedical Sciences: Faculty Publications

The testes and the spermatic cord of raccoons (Procyon lotor, kits to adult breeders; n = 48) were examined. Segmental arteritis confined to the extratesticular portions of the testicular artery was present in raccoons of all ages. The arterial changes were seen in laboratory-confined experimental and control animals as well as in wild-caught raccoons. The lesions consisted of proliferative endarteritis with presence of inflammatory cells within the intima, media, and the adventitial regions of most affected vessels. Some aspects of the proliferative arterial lesions were reminiscent of systemic necrotizing vasculitis (polyarteritis nodosa), an immunologically mediated condition of animals and humans. …

The Acute Onset Of Insulin Resistance In Adipose Tissue Following Trauma And Hemorrhage, Vanessa L. Williams

All ETDs from UAB

Insulin resistance and hyperglycemia are common findings in patients following acute illnesses or injuries, such as surgical trauma, thermal injury, infection, hemorrhage, and sepsis. Insulin has three main target tissues: liver, skeletal muscle, and adipose tissue. Insulin resistance in the liver results in an increase in gluconeogenesis. In skeletal muscle, insulin resistance causes a decrease in insulin-stimulated glucose uptake. However, little is known about the contribution that adipose tissue makes to the insulin resistant state. The goals of the research presented in this dissertation were to: 1) determine whether insulin resistance developed in adipose tissue following acute trauma and hemorrhage; …

Polycistronic Lentiviral Vector For Hit And Run Reprogramming Of Mouse And Human Somatic Cells To Induced Pluripotent Stem Cell, Chia-Wei Chang

All ETDs from UAB

Embryonic stem (ES) cells are pluripotent and, therefore, can differentiate into most if not all somatic cell types. Because of this characteristic, ES cells have great potential for medical therapies. Since the first cloned mammal, Dolly the sheep, was published in 1996 (1), several groups have successfully cloned other animals by the same nuclear transfer method (2). Isogenic ES cell lines can also be established from donor cells by the same technique (3). However, to date there has been no report of successful derivation of human ES cells by nuclear transfer. Based on the cell fusion (4) and nuclear transfer …

The Effect Of Zinc On Cytokine Release And Signal Transduction In Airway Epithelial Cells, Nai-Lin Cheng

All ETDs from UAB

Zinc is an essential cation for life that is involved in numerous physiology and pathophysiology processes. Despite its wide use as a cytoprotective agent in medications, its cellular and molecular mechanisms of action have not been well established. In order to define the potential therapeutic benefit of zinc, I used several Cystic Fibrosis (CF) and non-CF human airway epithelial cell lines as models in my studies. Extracellular zinc caused release calcium from the endoplasmic reticulum though zinc-sensitive Gq-coupled receptor(s) that may subsequently modulate ion channels. In addition, zinc also exhibited anti-inflammatory effects. Zinc inhibited pro-inflammatory molecular TNFα-induced cytokine and chemokine …

Exopolysaccharides Of Mycoplasma Pulmonis, James Michael Daubenspeck

All ETDs from UAB

Capsule has been associated with virulence in numerous bacterial pathogens. The Mollicutes are a host-specific group of pathogens that cause a variety of economically relevant diseases important to man. Mycoplasma pneumoniae is responsible for 2 million cases of atypical pneumonia and 100,000 hospitalizations every year in the United States (Atkinson et al., 2008) (Krause and Taylor-Robinson, 1992). There was a toxic galactan molecule described as early as 1958 in Mycoplasma mycoides subsp. mycoides (Plackett and Buttery, 1958), although no evidence was presented that it was produced by the bacteria. Over the intervening fifty years the evidence to support the production …

Calreticulin And Its Role In Collagen Regulation, Lauren Van Duyn

All ETDs from UAB

Calreticulin (CRT), classically known for its chaperone functions in the endoplasmic reticulum and as a calcium regulator, also is found on the cell surface and in the extracellular matrix. It is involved in many cellular processes including signaling, adhesion, migration, apoptotic cell clearance, gene regulation, and production of a fibronectin matrix. CRT has been suggested to play a role in wound healing and fibrosis. Therefore, these studies investigated the role of CRT in collagen production, an important extracellular matrix molecule in wounding and fibrosis. We demonstrated that CRT regulates collagen through transcription, secretion, and processing. We also investigated the role …

Biological Characterization Of Fc Receptor-Like 6 (Fcrl6), Daniel M. Schreeder

All ETDs from UAB

Members of the Fc receptor-like (FCRL) family are cell-surface proteins with ancient conservation, distinct lymphocyte expression patterns, and tyrosine-based signaling capa-bilities that imply a fundamental role for them in modulating immune responses. Though they share many features with the Fc receptors (FCR) for IgG and IgE, FCRLs have not been found to bind immunoglobulin. In these studies, we sought to characterize the cellu-lar expression pattern, binding partner, and function of a recently identified FCRL family member, human FCRL6. By developing specific monoclonal antibodies (mAbs) we determined that FCRL6 is dis-tinctly expressed by cytotoxic lymphocytes, namely NK cells, CD8+ T cells, …

The Role Of Transforming Growth Factor Beta-1 In Bone Remodeling, Yi Tang

All ETDs from UAB

Bone remodeling depends on the precise coordination of bone resorption by the osteoclasts and bone formation by the osteoblasts. It is proposed that osteoclastic bone resorption releases factors to initiate bone formation, thereby, coupling the bone resorption and formation. Mesenchymal stem cells (MSCs) are progenitors of osteoblasts. Recruitment of MSCs in response to osteoclastic bone resorption may be an initial step for bone formation during bone remodeling process. Therefore, we have established an in vitro osteoclastic bone resorption system. Bone resorption condition medium have been tested to identify the factor inducing the migration of human bone marrow mesechymal stem cells …

Characterizing The Role Of Primary Cilia In The Hair Follicle And Skin, Jonathan Merle Lehman

All ETDs from UAB

Primary cilia have been established as a nearly ubiquitous microtubule based signaling organelle, yet their function in many organs, including the hair and skin, is unknown. We hypothesized that the primary cilium would play vital roles in the hair follicle and skin based on the cilium's well characterized interactions with the Shh and Wnt developmental signaling pathways. This dissertation describes our efforts to determine the localization of the primary cilia in the murine hair follicle and assess the function of this organelle in the hair and skin. We used confocal immunofluorescence microscopy to virtually section the entire hair follicle and …

Mitochondrial Bioenergetics And Cellular Stress, Brian Dranka

All ETDs from UAB

Mitochondria are responsible for most of the energy produced in human tissues, and this is dependent on the reduction of oxygen (O2) to water by the mitochondrial respiratory chain. Defects in mitochondrial energy production are now recognized to be involved in diabetes, cancer, cardiovascular disease, and other pathologies. To date, studies of these defects have employed quantification of O2 consumption in isolated, purified mitochondria. By using this strategy however, the cellular context, role of glycolysis, and normal regulation of mitochondrial function by metabolite availability are lost. Thus, an understanding of how mitochondria function and respond to stimuli in an intact …

Oxidative Stress-Stimulated Vascular Calcification, Chang Hyun Byon

All ETDs from UAB

Oxidative stress plays a critical role in pathogenesis of atherosclerosis. However, the effect of oxidative stress-induced molecular signaling in development of vascular calcification, a feature of advanced atherosclerosis, has not been defined. Osteogenic differentiation of vascular smooth muscle cells (VSMC) is critical in development of vascular calcification. We determined hydrogen peroxide (H2O2)-induced oxidative stress promoted a phenotypic switch of mouse primary VSMC from contractile to osteogenic phenotype. This effect was associated with increased expression and transactivity of Runx2, a key transcription factor for osteogenic differentiation. Inhibition of Runx2 using short hairpin RNA blocked oxidative stress-induced VSMC calcification. By contrast, adenovirus-mediated …

The Effects Of Bisphenol A (Bpa) On Erbb2-Positive Breast Cancer, Sarah Jenkins

All ETDs from UAB

Bisphenol A (BPA) is a synthetically made compound used to produce a myriad of consumer goods. Recent studies have shown BPA to leach from these products in appreciable amounts, resulting in nearly ubiquitous exposure. In this study, we assessed whether chronic administration to a range of low concentrations of BPA could accelerate spontaneously developing mammary cancer using a transgenic model that over-expresses wild type ErbB2/neu transgene (MMTV-erbB2). MMTV-erbB2 mice were provided drinking water containing 0 (control), 2.5 (BPA 2.5), 25 (BPA 25), 250 (BPA 250), or 2500 (BPA 2500) µg BPA/L from eight weeks of age until sacrifice. This range …

The Effect Of Stearic Acid On Breast Cancer Development And Progression, Lynda Michelle Evans

All ETDs from UAB

earate is an 18-carbon saturated fatty acid that is found in many foods in the western diet including beef and chocolate. Cell culture studies indicate stearate may have various anti-cancer properties including inhibition of cancer cell proliferation and invasion, morphological changes, and induction of apoptosis. Animal studies have found that dietary stearate delays tumor development and decreases tumor incidence. To date, many of the mechanisms underlying these processes are unclear. In this study, evidence is presented showing stearate induces morphological changes in breast cancer cells. Inhibition of de novo diacylglycerol (DAG) generation and subsequent protein kinase C (PKC) activation inhibits …

The Protective Role Of Transglutaminase 2 In Ischemic Stroke, Anthony J. Filiano

All ETDs from UAB

Stroke is a leading cause of long term disabilities in the US. Currently, administration of thrombolytics is the only approved therapy. Due to the variability, small management time window, and lack of options for effective treatment, there is a clear need for new compounds to alleviate cell death post-stroke. Transglutaminase 2 (TG2) can decrease apoptotic signaling during stroke and lead to increased neuronal survival making it a potential target for therapeutic intervention. TG2, a multifunction enzyme that has both transamidase (TG) and GTPase activities, amongst others, has recently been shown to be upregulated in numerous neurodegenerative conditions, including stroke. In …

Epigenetic Control Mechanisms In Somatic Cells Mediated By Dna Methyltransferase 1, Bongyong Lee

Electronic Theses and Dissertations

DNA methylation regulates gene expression through a complex network of protein/protein and protein/DNA interactions in chromatin. The maintenance methylase, DNA methyltransferase 1 (DNMT1), is a prominent enzyme in the process that is linked to DNA replication and drives the heritable nature of epigenetic modifications in somatic cells. The mechanistic details that explain how DNMT1 catalytic action is directed in a chromatin setting are not well understood. We hypothesize that post translational modifications and a variety of protein-protein interactions processes are key regulatory elements that set the methylation of CpG elements essential for normal growth behavior in somatic cells. These fundamental …

Determinants Of Growth Hormone Receptor Downregulation, Luqin Deng

All ETDs from UAB

Growth hormone (GH), a 22 kD polypeptide primarily produced in the anterior pituitary gland, is a key regulator of postnatal growth and affects carbohydrate, protein and lipid metabolism. Growth hormone receptor (GHR) is a single membrane-spanning type Ⅰ glycoprotein of the cytokine receptor family and is initially synthesized as a precursor and undergoes carbohydrate processing during transport through the Golgi. It has no intrinsic kinase activity. One molecule of GH binding to predimerized GHR on the cell surface induces the receptor conformational change activating the cytoplasmic domainassociated tyrosine kinase, Janus Kinase 2 (JAK2), which phosphorylates GHR, followed by the activation …

Insulin Signaling And Function In Osteoblasts, Keertik S. Fulzele

All ETDs from UAB

Insulin and insulin-like growth factor-1 (IGF-1) are evolutionarily conserved hormonal signaling pathways with structurally similar ligands and receptors. Recent stu-dies suggest that that insulin and IGF-1 exert distinct as well as overlapping functions to regulate different aspects of skeletal development. A major problem in distinguishing the actions of insulin and IGF-1 is the fact that the receptors are co-expressed in many cell types and each ligand is able to cross-activate the other ligands' receptor. To distinguish direct skeletal actions of insulin from that of IGF-1, we have conditionally disrupted each receptor in vitro and in vivo specifically in osteoblasts. Studies …

Regulation Of The Human Heme Oxygenase-1 Gene By Nitro-Linoleic Acid, Macienne M. Wright

All ETDs from UAB

Nitro-fatty acids (NO-FA) exert anti-inflammatory effects in the vasculature. Heme oxygenase-1 (HO-1) degrades heme into iron, biliverdin, and carbon monoxide and is up-regulated as an adaptive and protective response to inflammatory processes. This dissertation examined whether nitro-linoleic acid (LNO2) induced HO-1 gene expression and evaluated the molecular mechanism of induction in human aortic endothelial (HAEC), human embryonic kidney 293 (HEK 293) and mouse embryonic fibroblast (MEF) cells. LNO2 induced HO-1 mRNA and protein in HAEC at the level of transcription. NO scavenging by carboxy-PTIO partially reversed LNO2–mediated induction of HO-1, suggesting that LNO2 acts via NO-dependent and NO-independent mechanisms of …

Protective Mechanisms Of Apoa-I Mimetic Peptide Action In Sepsis-Induced Tissue Injury, Zhenghao Zhang

All ETDs from UAB

Sepsis is among the top ten causes of death in the US, and it is associated with severe inflammatory tissue damage and organ dysfunction. Reduced plasma high density lipoprotein (HDL) is associated with increased mortality in septic patients. Since raising plasma apolipoprotein (apo) A-I and HDL may reduce sepsis complications, we tested the hypothesis that the apoA-I mimetic peptide 4F confers similar protective effects in two animal models of sepsis, and explored the possible mechanisms. In endotoxemic rats, inflammatory mediators were significantly induced while blood pressure was significantly reduced by 6hr. The impaired arterial response to vasoconstrictors was related to …

Regulation Of Tissue Remodeling Through The Calreticulin Binding Domain Of Thrombospondin-1, Mariya Ts'ana Sweetwyne

All ETDs from UAB

Thrombospondin-1 (TSP1) is a multifunctional matricellular protein released by platelets in response to injury and secreted by cells under stress. TSP1 is cleaved into functional N- and C-terminal domain fragments, which have paradoxical actions with respect to angiogenesis, cell survival, and cell adhesion. Wound healing studies by others demonstrated that TSP1 knockout mice have delayed rates of wound closure, which was attributed to actions of the C-terminal domain. We wished to investigate the specific role of the N-terminal domain in tissue remodeling. Previously, we established that a sequence (aa 17-35) in the N-terminal domain of TSP1 induces focal adhesion disassembly, …

Understanding The Regulatory Mechanisms Of Ubp-M And H2a Deubiquitination In Chromatin And Cellular Functions, Heui Yun Joo

All ETDs from UAB

Posttranslational modifications of histones regulate important chromatin and cellular functions. Among them, ubiquitination of histone H2A is correlated to transcriptional repression, such as HOX gene silencing and X chromosome inactiviation. Little was known about the removal of ubiquitin from histones, the enzyme(s) involved and its function in chromatin dynamics. We have identified the protein Ubp-M (USP16) to be the H2A- and nucleosome-specific deubiquitinase. We also demonstrated that Ubp-M-mediated H2A deubiquitination is involved in cell cycle progression to M-phase, HOX gene expression, and posterior development in Xenopus laevis. Furthermore, we have also purified USP12 and USP46 which contain an Ubp-M independent …

Mechanisms Of Growth Hormone Action In Skeletal Muscle, Mahendra Devaraj Mavalli

All ETDs from UAB

Growth hormone (GH) and insulin like growth factor-1 (IGF-1) exert profound growth promoting actions during pre and postnatal skeletal muscle development. GH and IGF-1 seem to promote their anabolic actions by influencing skeletal muscle cell prolif-eration and fusion. However, because GH stimulates the production of IGF-1 from the liver and other GH-responsive peripheral tissues, including skeletal muscle, the individual contributions of these two growth factors to anabolic responses in skeletal muscle remains poorly defined. In this dissertation research, I sought to distinguish the mechanisms responsible for growth hormone's (GH) anabolic actions in skeletal muscle. To accomplish this, I analyzed the …

Cystic Fibrosis Transmembrane Conductance Regulator (Cftr) Modulators And Their Mechanistic Basis: Relevance To Emerging Therapies For Cystic Fibrosis, Louise Clare Pyle

All ETDs from UAB

Cystic fibrosis (CF) is a lethal genetic disorder leading to pulmonary decline and premature death. The gene responsible for CF, the cystic fibrosis transmembrane conductance regulator (CFTR), serves as a chloride and bicarbonate channel situated at the apical cell surface of epithelia. The discovery of small molecules that augment channel gating of mutant CFTR (so-called `potentiators') represents a major theme of CF research, and offers hope for new therapeutic interventions. High-throughput screening (HTS) provides a means to test millions of agents in an unbiased manner for CFTR potentiating properties. New agents identified by HTS have undergone extensive pre-clinical and clinical …

The Role Of Mitochondria And Plasma Membrane Ca2+ Transport Systems In Ca2+-Dependent Glutamate Release From Rat Cortical Astrocytes, Reno Cervo Reyes

All ETDs from UAB

Astrocytes, a type of glial cell in the central nervous system, are recognized for their support roles to neurons. They supply neurons with metabolites, maintain ion homeostasis and clear the synaptic space of neurotransmitters. However, it has been found that some astrocytes have receptors for neurotransmitter and neuroligands, exhibit Ca2+ excitability when stimulated via these receptors, and secrete gliotransmitters as an output of this Ca2+ excitability. In the Ca2+-dependent release of glutamate, it has been shown that the endoplasmic reticulum is the predominant source and the extracellular space is the auxiliary source of free Ca2+ necessary for triggering exocytosis. Because …

Neuroinflammation And Fragile X Syndrome: Regulation By Glycogen Synthase Kinase-3, Christopher Joseph Yuskaitis

All ETDs from UAB

Neuroinflammation and Fragile X syndrome (FXS) are two particularly devastating neurologic conditions for which no adequate treatment exists and much is still unknown about the underlying cellular and molecular processes. Neuroinflammation contributes to the pathogenesis of many neurologic and psychiatric disorders, thus treatment of the underlying inflammation has broad implications. FXS is the most common cause of inherited intellectual and developmental delay and one of the few known genetic causes of autism. Neuroinflammation and FXS have potential links with glycogen synthase kinase-3 (GSK3) and its inhibitor, lithium. Therefore, the overall goal of this research was to examine the role of …

Diffusion Pathways Through The Outer Membrane Of Mycobacteria, Olga Danilchanka

All ETDs from UAB

The extraordinary capacity of Mycobacterium tuberculosis (Mtb) to adapt to environmental changes during infection contributes to its success as a pathogen. While the unique outer membrane (OM) of mycobacteria functions as a permeability barrier for toxic molecules, uptake of nutrients is required to sustain viability of Mtb. Whereas hydrophobic molecules can diffuse through membranes, uptake of small hydrophilic compounds is mediated by water-filled channels, porins. For example, Msp-like porins of M. smegmatis (Ms) were shown to be required for uptake of hydrophilic beta-lactam antibiotics, which are also known to diffuse through porins in gram-negative bacteria. Because the structure of the …

Faculty Publications 2008, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 629 publications.

Angiotensin Ii Induction Of Regional Effects In Murine Vasculature, Albert Phillip Owens Iii

University of Kentucky Doctoral Dissertations

The renin angiotensin system (RAS) exerts many diverse physiological functions throughout the body, mediated by its effector peptide, angiotensin II (AngII). AngII has been linked with a variety of different functions ranging from the initiation of severe vascular pathologies, such as atherosclerosis and abdominal aortic aneurysm (AAA), to mundane physiological processes of fluid homeostasis, vascular contraction, and regulation of blood pressure. To provide a potential link between these functions, an in-depth analysis of regional effects of AngII on aortic vasculature was performed.

The studies presented in this dissertation tested the overall hypothesis of whether regional changes exist in the vasculature …

The Interplay Between The Expression And Functions Of Wnt13 Isoforms During Apoptosis In Bovine Aortic Endothelial Cells, Tao Tang

University of Kentucky Doctoral Dissertations

Wnt proteins are crucial for development/homeostasis by controlling cell fate including apoptosis (Moon RT et al. 1997). Three humanWnt13 isoforms were identified: the secreted Wnt13A, mitochondrial Wnt13B, and nuclear Wnt13C forms; and nuclear Wnt13 had an increased sensitivity to LPS/TNF-induced apoptosis in primary endothelial cells (EC); both Wnt13B and C mRNA contain two start codons (AUG+1 and +74), but the same protein encoded from AUG+74 by Wnt13C was expressed lower than Wnt13B (Struewing IT et al.2006). We hypothesize that during EC apoptosis, the nuclear Wnt13C expression is regulated translationally; nuclear Wnt13 favors apoptosis through regulating the activity/expression of apoptosis-related factors; …

Role Of Aryl Hydrocarbon Receptor In Chronic Inflammatory Diseases, Violeta Arsenescu

University of Kentucky Doctoral Dissertations

Aryl Hydrocarbon Receptor (AhR) is a ligand-actviated receptor known as the dioxin receptor. Environmental pollutants called dioxin-like toxicants are found in food, cigarette smoke, automobile exhaust and air. Therefore, they could chronically amplify the pathology of numerous chronic inflammatory diseases. AhR is a well known target of these environmental chemicals that disrupt endocrine signaling. By the year 2020, the number of people older than 60 years is expected to top 1 billion. The burden of treating chronic disease is significant both in dollars spent and in lost productivity. The need to identify risk factors for chronic diseases must be evaluated …