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Spinal Cord Stimulation: An Update., Steven Falowski, Amanda Celii, Ashwini Sharan

Department of Neurosurgery Faculty Papers

Spinal cord stimulation has been used in the treatment of many chronic pain disorders since 1967. In this update, the indications for spinal cord stimulation are reviewed with attention to recent publications. A focused review of the literature on abdominal and visceral pain syndromes is also provided. Furthermore, the technology has evolved from the use of monopolar electrodes to complex electrode arrays. Similarly, the power source has changed from a radio frequency-driven system to a rechargeable impulse generator. These topics are covered, along with a short discussion of implant technique. Finally, we include a review of complications of such therapy. …

Transcriptional Regulatory Network Analysis During Epithelial-Mesenchymal Transformation Of Retinal Pigment Epithelium., Craig H Pratt, Rajanikanth Vadigepalli, Praveen Chakravarthula, Gregory E Gonye, Nancy J Philp, Gerald B Grunwald

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

PURPOSE: Phenotypic transformation of retinal pigment epithelial (RPE) cells contributes to the onset and progression of ocular proliferative disorders such as proliferative vitreoretinopathy (PVR). The formation of epiretinal membranes in PVR may involve an epithelial-mesenchymal transformation (EMT) of RPE cells as part of an aberrant wound healing response. While the underlying mechanism remains unclear, this likely involves changes in RPE cell gene expression under the control of specific transcription factors (TFs). Thus, the purpose of the present study was to identify TFs that may play a role in this process.

METHODS: Regulatory regions of genes that are differentially regulated during …

Growth Hormone Signaling And Action In Osteoblasts, Douglas J. Digirolamo

All ETDs from UAB

Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) exert profound growth promoting actions during pre- and post-natal skeletal development. GH and IGF- 1 appear to cause these anabolic actions by influencing a variety of effects on osteoblast proliferation, differentiation, and survival. However, because GH stimulates the production of IGF-1 from the liver and other GH-responsive peripheral tissues, including bone, the individual contributions of these two molecules to anabolic responses in bone remains poorly defined. In this dissertation research, I sought to distinguish the direct and indirect (IGF-1 dependent) GH actions on osteoblasts. In the first section of this thesis, I …

Effects Of Aerobic Exercise On The Asthmatic Lung, Matthew M. Hewitt

All ETDs from UAB

Asthma is identified by the clinical symptoms of wheezing, chest tightness, dyspnea and cough, and by the presence of airway hyperresponsiveness (AHR) to inhaled stimuli. We have reported previously that repeated bouts of moderate intensity aerobic exercise attenuate airway inflammatory responses in a mouse model of atopic asthma. Because the effects of exercise on physiological responses are dependent upon several variables, including total exercise duration, the hypothesis of the current work was that differing amounts of moderate intensity aerobic exercise exert dissimilar effects on AHR and airway inflammation. The aims to test this hypothesis included: 1) determine the effect of …

Mapks Regulate Nuclear Import Of Human Papillomavirus Type 11 Replicative Helicase E1, Jei-Hwa Yu

All ETDs from UAB

Papillomaviruses (PV) are prevalent pathogens that infect human or animal squamous epithelia. Its genome is a double strand circular DNA of approximately 7.9 kb. It contains origin of replication (ori) and encodes early viral proteins for viral DNA amplication, and late capsid proteins for packaging viron. The viral DNA replicates as extrachromosomal nuclear plasmid in the host cell. Infections by low risk virus, such as HPV-6 and -11, can result in benign papillomas, condylomata, and low grade squamous intraepithelial dysplasias (SIL), whereas infection by high risk virus, such as HPV-16 and -18, can progress to high grade SIL, carcinoma in …

Faculty Publications 2007, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 623 publications.

Large Scale Variation In Enterococcus Faecalis Illustrated By The Genome Analysis Of Strain Og1rf, Agathe Bourgogne, Danielle A Garsin, Xiang Qin, Kavindra V Singh, Jouko Sillanpaa, Shailaja Yerrapragada, Yan Ding, Shannon Dugan-Rocha, Christian Buhay, Hua Shen, Guan Chen, Gabrielle Williams, Donna Muzny, Arash Maadani, Kristina A Fox, Jason Gioia, Lei Chen, Yue Shang, Cesar A Arias, Sreedhar R Nallapareddy, Meng Zhao, Vittal P Prakash, Shahreen Chowdhury, Huaiyang Jiang, Richard A Gibbs, Barbara E Murray, Sarah K Highlander, George M Weinstock

Faculty, Staff and Student Publications

BACKGROUND: Enterococcus faecalis has emerged as a major hospital pathogen. To explore its diversity, we sequenced E. faecalis strain OG1RF, which is commonly used for molecular manipulation and virulence studies.

RESULTS: The 2,739,625 base pair chromosome of OG1RF was found to contain approximately 232 kilobases unique to this strain compared to V583, the only publicly available sequenced strain. Almost no mobile genetic elements were found in OG1RF. The 64 areas of divergence were classified into three categories. First, OG1RF carries 39 unique regions, including 2 CRISPR loci and a new WxL locus. Second, we found nine replacements where a sequence …

Models Of Phototransduction In Rod Photoreceptors, Harihar Khanal, Vasilios Alexiades

Publications

Phototransduction is the process by which photons of light generate an electrical response in retinal rod and cone photoreceptors, thereby initiating vision. We compare the electrical response in salamander rods from increasingly more (spacialy) detailed models of phototransduction: 0-dimensional (bulk), 1-dimensional (longitudinal), 2-dimensional (axisymmetric), and 3-dimensional (with incisures). We discuss issues of finding physical parameters for simulation and validation of models, and also present some computational experiments for rods with geometry of mouse and human photoreceptors.

Effects Of Hexosamine Biosynthesis On An In Vitro Model Of Cardiacischemia, Voraratt Champattanachai

All ETDs from UAB

Increased levels of protein O-linked-N-acetylglucosamine (O-GlcNAc) have been correlated with increased cell survival following stress. Therefore the goal of this study was to determine whether enhanced flux through the hexosamine biosynthesis pathway (HBP), which leads to elevated levels of O-GlcNAc, improved the tolerance of isolated neonatal rat ventricular myocytes (NRVMs) to ischemia/reperfusion (I/R) injury. NRVMs were exposed to hypoxic medium for 4 hours, followed by oxygenated complete medium for 16 hours. Acute treatment with 5 mM glucosamine showed an increase in viability and decreased both necrosis and apoptosis following I/R. Glucosamine increased O-GlcNAc levels maximally at 2 hours and went …

Microbial Biofilm Attachment To Caenorhabditis Elegans, Kevin Drace

All ETDs from UAB

The closely related bacterial species Xenorhabdus nematophila, Yersinia pestis and Y. pseudotuberculosis make biofilms capable of adhering to the head of the model nematode Caenorhabditis elegans. Y. pestis uses biofilms to block the digestive tract of its vector, the flea, in order to enhance its efficiency of transmission. I investigated the role of biofilms in X. nematophila and found that, like its Yersinia sp. counterparts, production of biofilm requires a four-gene operon: hmsHFRS. X. nematophila is an insect pathogen and an obligate symbiont of the nematode Steinernema carpocapsae. However, an X. nematophila hmsH mutant that failed to make biofilms on …

Role Of The Gm/Gn Glycoprotein Complex In The Final Assembly And Egress Of The Human Cytomegalovirus (Hcmv), Magdalena Anna Krzyzaniak

All ETDs from UAB

HCMV consists of a dsDNA genome enclosed by, an icosahedral capsid surrounded by a layer of tegument proteins; the virion structure is enclosed in a lipid envelope rich in virus expressed glycoproteins. The HCMV envelope contains an incompletely defined number of glycoproteins. The glycoprotein M (gM) and glycoprotein N (gN) form a gM/gN protein complex which is the most abundant protein component of the HCMV envelope. Recent studies have indicated that deletion of the viral gene encoding either gM or gN is lethal for HCMV. The gM C-terminal cytoplasmic tail (gM-CT) revealed an acidic cluster and a tyrosine-based trafficking motifs. …

Transcriptional Regulation Of Cd40 And Class Ii Mhc Molecules In Macrophages And Microglia By Statins, Sun Jung Lee

All ETDs from UAB

Microglia/macrophages are the main intrinsic immune effector cells and the first cell types that respond to a variety of CNS injures. They have important functions including secretion of cytokines/chemokines and antigen presentation, thereby regulating immune responses. Interferon-γ (IFN-γ) is a cytokine involved in many aspects of the immune response, and activates microglia/macrophages to express cell surface antigens such as class II MHC, and co-stimulatory molecules such as CD40. CD40 and class II MHC molecules play a critical role in immune reactivity such as antigen presentation and subsequent T cell activation. However, aberrant CD40 and class II MHC expression have been …

The Au-Rich Element Mrna Decay-Promoting Activity Of Brf1 Is Regulated By Mitogen-Activated Protein Kinase Activated Protein Kinase 2, Sushmit Maitra

All ETDs from UAB

Regulated mRNA decay is a highly important process for the tight control of gene expression. Inherently unstable mRNAs contain AU-rich elements (AREs) in the 3’ untranslated regions that direct rapid mRNA decay by interaction with decay-promoting ARE-binding proteins (ARE-BPs). The decay of ARE-containing mRNAs is regulated by signaling pathways, which are believed to directly target ARE-BPs. Here, we show that BRF1 involved in ARE-mediated mRNA decay (AMD) is phosphorylated by MAPK-activated protein kinase 2, MK2. In vitro kinase assays using different BRF1 fragments suggest that MK2 phosphorylates BRF1 at four distinct sites, S54, S92, S203, and an unidentified site at …

Modulation Of Transforming Growth Factor (Tgf)-Ss1 And Its Implications In Breast Cancer Metastasis, Lakisha Dionne Moore

All ETDs from UAB

Overexpresssion of transforming growth factor (TGF)-β has been implicated in promoting immune suppression, tumor angiogenesis, tumor cell migration, and invasion in many cancers including carcinoma of the breast. Thus, targeted downregulation of TGF-β1 expression in breast cancer in situ and determination of its implications potentially could provide new treatment approaches for disease management. siRNA constructs targeting TGF-β1 were validated and used to develop clonal derivatives of the MDA-MB-435 metastatic breast cancer cell line. Inhibition of TGF-β1 expression in MDA-MB-435 cells showed decrease in migration and invasion in vitro with an increase in proliferation. In vivo analysis indicated a 90% decrease …

Changes In Short-Term Facilitation Are Opposite At Schaffer Collateral And Temporoammonic Ca1 Synapses In The Developing Rat Hippocampus, Haley E. Speed

All ETDs from UAB

Hippocampal CA1 pyramidal neurons integrate and filter spatial, temporal, and sensory information from the entorhinal cortex (EC) for memory storage. Synaptic transmission mediates the processing of incoming information, and recent studies have demonstrated that long-term changes in synaptic strength at CA1 synapses are important for learning and memory. Short-term changes in synaptic strength, occurring on a timescale of milliseconds to minutes, do not require lasting modifications and are rapidly reversible. Termed short-term plasticity, it is known to be important for dynamic gain control of synaptic transmission and neural computation. During late postnatal development, there are extensive developmental changes in rat …

Analysis Of The Hedgehog Pathway In Pancreatic Adenocarcinoma, Adam Steg

All ETDs from UAB

Pancreatic adenocarcinoma (PAC) is the fourth leading cause of cancer mortality in the United States. Despite the use of highly aggressive treatment regimens (surgery, chemotherapy and radiation), almost all patients succumb to metastatic disease within 6-10 months of diagnosis. The hedgehog (HH) signaling pathway was originally discov-ered to play a critical role in mammalian embryological development. Interestingly, re-cent studies have suggested that aberrant expression of this pathway is involved in the initiation and continued growth of PAC. Small molecules that antagonize the transmem-brane protein Smoothened (Smo), a critical signaling component of the HH pathway, have proven effective in decreasing PAC …

A Dual-Action, Armed Replicating Adenovirus For The Treatment Of Bone Metastases Of Breast Cancer, James Joseph Cody

All ETDs from UAB

Most patients with advanced breast cancer develop osteolytic bone metastases, which have numerous complications. Because current therapies are not curative, new treatments are needed. Conditionally replicating adenoviruses (CRAds) are anti-cancer agents designed to infect and lyse tumor cells. For increased efficacy, CRAds have been armed with therapeutic transgenes. Osteoprotegerin (OPG), an inhibitor of osteoclastic bone resorption, represents a promising candidate with which to arm a CRAd intended to treat osteolytic bone metastases. We hypothesize that a CRAd armed with OPG will inhibit breast cancer bone metastasis and reduce tumor burden in the bone by directly lysing tumor cells and by …

Thrombospondin Type-1 Repeats And Their Potential Role In Inhibiting Glioblastoma Angiogenesis, Joshua C. Anderson

All ETDs from UAB

Thrombospondin-1 (TSP-1) is a 420 kilodalton homotrimeric protein; it is one of the first identified anti-angiogenic proteins found to be expressed in some normal tissues. Peptides derived from the type-1 repeat (TSR) domains of full length TSP-1 have been shown to have anti-angiogenic activity, and thus anti-tumor activity in some non-glioma tumor models. I hypothesized that peptides derived from the TSRs of TSP-1, such as ABT-510, could inhibit angiogenesis and thus malignant glioma tumor growth in vivo. I found that ABT-510 inhibited angiogenesis of the human brain microvascular endothelial cell (MvEC) in an in vitro tubulomorphogenesis assay. To determine the …

Human Papillomavirus: Segregation And Replication, Luan D. Dao

All ETDs from UAB

Human papillomavirus are small DNA tumor viruses. The viral genome is a small circular double stranded DNA that replicates autonomously as an extrachromosomal plasmid. Occasionally infections by the high risk HPV viruses can lead to DNA integration and progression to cancer. How the HPV DNA is maintained and becomes established in the dividing host cells is not well understood. Additionally, as a double-stranded DNA virus it is likely that double-stranded DNA breaks in the viral genome, either from replication or random damage, will trigger a DNA repair response from the host cell. Such responses have been alternatively reported to be …

Metabolism Of Neutrophil-Deprived Chlorinated Isoflavones, Tracy Lyn D'Alessandro

All ETDs from UAB

Despite medical advances in both drug therapy and surgical techniques, Americans mostly die from heart disease. Many belong to the low- and middle-class families who do not have sufficient access to medical care due to its high costs. An alternative is the development of healthier lifestyles such as diet which may play a positive role in chronic disease management. Epidemiological and migratory studies suggest that soy plays a pivotal role in the decreased incidence of heart disease in East Asian countries, such as China, Japan, and Korea. The role of soy in cardiovascular disease progression has been the subject of …

Perception Of Motion-In-Depth: Induced Motion Effects On Monocular And Binocular Cues, John Eric Gampher

All ETDs from UAB

Three cues are available to the visual system to determine motion: image displacement across the retina (retinal slip), eye movements, and configuration changes within a scene (Becklen and Wallach, 1985). Any one may lead to the false perception of motion. Induced motion is the illusory movement of one object (or objects) as a result of other movement in the visual field. A wide variety of displays have been used to study induced motion, leading to apparently different classes of induced motion. Current theories of induced motion can be categorized based on local motion, global motion, eye movement suppression, and cognitive …

Functionalizing Hydroxyapatite Biomaterials With Biomimetic Peptides Of Integrin Ligands, Kristin Marie Hennessy

All ETDs from UAB

Hydroxyapatite (HA) coatings of hard tissue implants have been shown to increase osseointegration, but the mechanisms by which HA improves implant integration are not well understood. Numerous studies have shown that modifying HA with adhesive peptides, including RGD, and the collagen I mimetics, DGEA and P15, stimulates the adhesion of mesenchymal stem cells (MSCs), a cell type that differentiates along the osteoblast lineage. However, HA is a highly adsorptive biomaterial, and therefore it is unlikely that cells at the implant site would ever encounter a peptidemodified HA surface in the absence of an adsorbed protein layer. In fact, our laboratory …

Function Of Human Retinol Dehydrogenase 12 (Rdh12) In Retinoid Metabolism, Seung-Ah Lee

All ETDs from UAB

Retinol dehydrogenase 12 (RDH12) is a member of the microsomal short-chain dehydrogenase/reductase superfamily of proteins that is highly expressed in photorecep-tor cells. Mutations in RDH12 are associated with severe early-onset autosomal recessive retinal dystrophy, leading to legal blindness. Disease-associated RDH12 variants exhibit lower protein levels when expressed in eukaryotic cells. However, the physiological role of RDH12 remains unclear. As established previously, RDH12 recognizes both retinoids and lipid peroxidation products (medium-chain aldehydes) as substrates and exhibits the highest catalytic efficiency for all-trans-retinaldehyde. As the main goal of this dissertation, we characterized the catalytic properties of RDH12 and its naturally occurring mutants …

Changes In Hippocampal Excitability During Withdrawal From Chronic Nicotine, Rachel E. Penton

All ETDs from UAB

seeking behavior following chronic drug use lasts for many months or even years. Short-term withdrawal experiments have suggested that the neuroadaptations thought to underlie learning and memory may also contribute to addictive behavior. However, there is little information about the physiological mechanisms that participate in craving and relapse following long-term withdrawal. Here I show in hippocampal slices from rats treated with nicotine for 1 week that there is a change in the excitability of CA1 pyramidal cells that persists for up to 9 months following the cessation of drug treatment. The expression of this enhanced excitability is dependent on different …

Roles Of Extracellular Atp And Zinc In Pancreatic Ss-Cell Physiology, Clintoria Richards-Williams

All ETDs from UAB

Insulin secretory defects within pancreatic beta-cells (β-cells) of islets of Langerhans play a role in the pathogenesis of diabetes mellitus. Furthermore, it is also well established that ATP and zinc are co-secreted with insulin in response to elevated extracellular glucose. Despite this knowledge, the physiological roles of extracellular secreted ATP and zinc within islets are ill-defined. We hypothesized that secreted ATP and zinc are autocrine purinergic signaling molecules that activate P2X purinergic receptor (P2XR) channels expressed by β-cells to enhance glucose-stimulated insulin secretion (GSIS). To test this postulate, ELISA, luciferin/luciferase-based bioluminescence and zinquin-based fluorescence assays were utilized to examine insulin, …

Adenovirus As A Platform For Assembly And Targeted Delivery Of Gold Nanoparticles To Tumor Cells, Vaibhav Saini

All ETDs from UAB

Novel combinatorial strategies need to be explored to achieve tumor eradication. In this regard, viral vector based gene therapy and nanotechnology offer unique possibilities for cancer therapy. As an example, multifunctional adenoviral (Ad) vectors capable of targeting, imaging, and successful cancer gene therapy have been advanced into multiple clinical trials. Similarly, novel multifunctional gold nanoparticles (AuNPs) have been utilized for drug delivery, targeting, imaging, and hyperthermia tumor therapy. Therefore, to accrue the benefits of both gene therapy and nanotechnology for cancer therapy, we proposed to combine Ad vectors and AuNPs in a single multifunctional nanodevice. Towards this goal, herein, we …

The Role Of Tgf-Ss And Wnt5a In Mammary Gland Development And Tumurorigenesis, Kevin Patrick Roarty

All ETDs from UAB

cancer is the second most common cancer worldwide behind lung cancer, affecting women of all ages, races, ethnicities, and socioeconomic strata. Concerted efforts have been made to understand this heterogeneous disease from the clinical stage down to the molecular level. Importantly, it has become clear that an understanding of the normal biology of the breast at all stages of development is needed to gain insight into how alterations in normal regulatory networks contribute to the initiation and development of breast cancer. TGF-ß plays a role in growth and patterning of the mammary gland and alterations in its signaling exhibit biphasic …

Correction Of Sickle Cell Disease By Homologous Recombination, Li-Chen Wu

All ETDs from UAB

The hematological disorder sickle cell disease (SCD) is a prevalent human genetic disease. It causes severe tissue damage that can result in strokes, splenic infarction, kidney failure, liver and lung disorders, painful crises, and other complications. Although palliative therapies and allogenic stem cell transplantation therapies have been developed for this disorder, there is still no optimal treatment and SCD patients continue to suffer significant morbidity. Recently, several powerful technologies have been developed that increase the possibility for developing therapeutic treatments for SCD. Previously, our lab group demonstrated that SCD can be corrected in our humanized mouse model by transduction of …

Physiological Charactterization Of The Light Response Of Rod Photoreceptors In The Light Damaged Rat, Yuquan Wen

All ETDs from UAB

Constant light exposure has long been known to induce photoreceptor degeneration. However, it is not known whether photoreceptors alter their physiology to adapt to the environmental stress caused by constant light exposure. In this study, we have developed a slow light damage model in rats to study changes in single rod physiology and retinal morphology after light damage. Rod physiology was documented by single rod recording using a suction electrode at 3 days (R3), 5 days (R5), 15 days (R15), and 30 days (R30) after 10 days of light damage, or sham light damage for controls. In addition, we used …

The Use Of Molecular Imaging To Evaluate Te Efficacy Of Treatments For Metastatic Breast Cancer, April Adams Szafran

All ETDs from UAB

The development of molecular imaging technologies has allowed biomedical researchers to study the process of cancer metastasis in animal models of disease. Bioluminescence imaging has been a crucial tool for non-invasive monitoring of tumor growth, dissemination, and response to therapies. In this report, we have applied bioluminescence imaging to evaluate the efficacy of Death Receptor 5 agonist therapy for the treatment of breast cancer metastasis, predominately to the skeleton, in an athymic nude mouse model. Initially, we determined that bioluminescence imaging was the most ideal technology for studying secondary bone lesions in vivo when compared to both x-ray Computed Tomography …