Medicine and Health Sciences Commons^™

Flow-Diversion Panacea Or Poison?, Mario Zanaty, Nohra Chalouhi, Md, Stavropoula I. Tjoumakaris, Robert H. Rosenwasswer Md, L. Fernando Gonzalez, Pascal Jabbour Md

Department of Neurosurgery Faculty Papers

Endovascular therapy is now the treatment of choice for intracranial aneurysms (IAs) for its efficacy and safety profile. The use of flow diversion (FD) has recently expanded to cover many types of IAs in various locations. Some institutions even attempt FD as first line treatment for unruptured IAs. The most widely used devices are the pipeline embolization device (PED), the SILK flow diverter (SFD), the flow redirection endoluminal device (FRED), and Surpass. Many questions were raised regarding the long-term complications, the optimal regimen of dual antiplatelet therapy, and the durability of treatment effect. We reviewed the literature to address these …

Nuclear Interaction Between Adr-Induced P65 And P53 Mediates Cardiac Injury In Inos (−/−) Mice, Marsha P. Cole, Jitbanjong Tangpong, Terry D. Oberley, Luksana Chaiswing, Kinsley K. Kiningham, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Adriamycin (ADR) treatment causes an imbalance in the levels of nitric oxide (^•NO) and superoxide (O₂^•−) production leading to cardiac injury. Previously we demonstrated that mice lacking inducible nitric oxide synthase (iNOS) have increased oxidative stress and mitochondrial injury. The molecular events leading to increased mitochondrial injury in iNOS deficient mice is unknown. ADR in the absence of iNOS preferentially activates a proapoptotic pathway without a concurrent increase in prosurvival pathways. Treatment with ADR leads to an increase in DNA binding activity of nuclear factor kappa B (NFκB) and p53 in wildtype mice. Following ADR …

A Modified Generalized Fisher Method For Combining Probabilities From Dependent Tests., Hongying Dai, J Steven Leeder, Yuehua Cui

Manuscripts, Articles, Book Chapters and Other Papers

Rapid developments in molecular technology have yielded a large amount of high throughput genetic data to understand the mechanism for complex traits. The increase of genetic variants requires hundreds and thousands of statistical tests to be performed simultaneously in analysis, which poses a challenge to control the overall Type I error rate. Combining p-values from multiple hypothesis testing has shown promise for aggregating effects in high-dimensional genetic data analysis. Several p-value combining methods have been developed and applied to genetic data; see Dai et al. (2012b) for a comprehensive review. However, there is a lack of investigations conducted for dependent …

B Cell Tolerance In Health And Disease, Murali Gururajan, Vishal J. Sindhava, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B lymphocyte receptors are generated randomly during the bone marrow developmental phase of B cells. Hence, the B cell repertoire consists of both self and foreign antigen specificities necessitating specific tolerance mechanisms to eliminate self-reactive B cells. This review summarizes the major mechanisms of B cell tolerance, which include clonal deletion, anergy and receptor editing. In the bone marrow presentation of antigen in membrane bound form is more effective than soluble form and the role of dendritic cells in this process is discussed. Toll like receptor derived signals affect activation of B cells by certain ligands such as nucleic acids …

Consistency Between Research And Clinical Diagnoses Of Autism Among Boys And Girls With Fragile X Syndrome, Jessica Klusek, G E. Martin, M Losh

Faculty Publications

No abstract provided.

Ube3a Role In Synaptic Plasticity And Neurodevelopmental Disorders.The Lessons From Angelman Syndrome., Irina Filonova

USF Tampa Graduate Theses and Dissertations

Angelman Syndrome (AS) is a severe neurodevelopmental disorder that affects 1:12000 newborns. It is characterized by mental retardation, delayed major motor and cognitive milestones, seizures, absence of speech and excessive laughter. The majority of AS cases arise from deletions or mutations of UBE3A gene located on the chromosome 15q11-13. UBE3A codes for E3-ubiquitin ligase that target specific proteins for degradation. To date, a wide variety of Ube3a substrates has been identified. The accumulation of Ube3a-dependent proteins and their effect on the multitude of signal transduction pathways are` considered the main cause of the AS pathology. While the majority of research …

Aged Rats Are Hypo-Responsive To Acute Restraint: Implications For Psychosocial Stress In Aging, Heather M. Buechel, Jelena Popovic, Kendra Staggs, Katie L. Anderson, Olivier Thibault, Eric M. Blalock

Pharmacology and Nutritional Sciences Faculty Publications

Cognitive processes associated with prefrontal cortex and hippocampus decline with age and are vulnerable to disruption by stress. The stress/stress hormone/allostatic load hypotheses of brain aging posit that brain aging, at least in part, is the manifestation of life-long stress exposure. In addition, as humans age, there is a profound increase in the incidence of new onset stressors, many of which are psychosocial (e.g., loss of job, death of spouse, social isolation), and aged humans are well-understood to be more vulnerable to the negative consequences of such new-onset chronic psychosocial stress events. However, the mechanistic underpinnings of this age-related shift …

Defining The Role Of The Nurse In Transitions Of Care Within A Comprehensive Stroke Center, Claranne Mathiesen Rn, Msn, Cnrn, Erin M. Conahan Rn, Cnrn

Patient Care Services / Nursing

No abstract provided.

Substance P Differentially Modulates Firing Rate Of Solitary Complex (Sc) Neurons From Control And Chronic Hypoxia-Adapted Adult Rats, Nicole L. Nichols, Frank L. Powell, Jay B. Dean, Robert W. Putnam

Neuroscience, Cell Biology & Physiology Faculty Publications

NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO₂/H⁺-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS). Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus) neurons from control and chronic hypoxia-adapted (CHx) adult rats. We simultaneously measured intracellular pH …

Complexity Of Interferon-Γ Interactions With Hsv-1, Nancy J. Bigley

Neuroscience, Cell Biology & Physiology Faculty Publications

The intricacies involving the role of interferon-gamma (IFN-γ) in herpesvirus infection and persistence are complex. Herpes simplex virus type 1 (HSV-1) uses a variety of receptors to enter cells and is transported to and from the host cell nucleus over the microtubule railroad via retrograde and anterograde transport. IFN-γ exerts dual but conflicting effects on microtubule organization. IFN-γ stimulates production of suppressors of cytokine signaling 1 and 3 (SOCS1 and SOCS3), which are involved in microtubule stability and are negative regulators of IFN-γ signaling when overexpressed. IFN-γ also interferes with the correct assembly of microtubules causing them to undergo severe …

Hilar Mossy Cells Provide The First Glutamatergic Synapses To Adult-Born Dentate Granule Cells, Jessica H. Chancey, David J. Poulsen, Jacques I. Wadiche, Linda Overstreet-Wadiche

Biomedical and Pharmaceutical Sciences Faculty Publications

Adult-generated granule cells (GCs) in the dentate gyrus must establish synapses with preexisting neurons to participate in network activity. To determine the source of early glutamatergic synapses on newborn GCs in adult mice, we examined synaptic currents at the developmental stage when NMDA receptor-mediated silent synapses are first established. We show that hilar mossy cells provide initial glutamatergic synapses as well as disynaptic GABAergic input to adult-generated dentate GCs.

Hiding In Plain Sight: Interplay Between Staphylococcal Biofilms And Host Immunity., Tyler D. Scherr, Cortney E. Heim, John M. Morrison, Tammy Kielian

Journal Articles: Pathology and Microbiology

Staphylococcus aureus and Staphylococcus epidermidis are notable for their propensity to form biofilms on implanted medical devices. Staphylococcal biofilm infections are typified by their recalcitrance to antibiotics and ability to circumvent host immune-mediated clearance, resulting in the establishment of chronic infections that are often recurrent in nature. Indeed, the immunomodulatory lifestyle of biofilms seemingly shapes the host immune response to ensure biofilm engraftment and persistence in an immune competent host. Here, we provide a brief review of the mechanisms whereby S. aureus and S. epidermidis biofilms manipulate host-pathogen interactions and discuss the concept of microenvironment maintenance in infectious outcomes, as …

Anakinra And Related Drugs Targeting Interleukin-1 In The Treatment Of Cryopyrin-Associated Periodic Syndromes, Inessa Bachove, Christopher Chang

Department of Pediatrics Faculty Papers

Anakinra is an interleukin (IL) receptor antagonist that works by blocking the biological activity of IL-1 by competitively inhibiting binding of IL-1 to the type 1 interleukin receptor. IL-1 production is induced in response to inflammatory stimuli and mediates various physiological mechanisms, including inflammation and immunological reactions. Patients with neonatal onset multisystem inflammatory disease (NOMID) produce excess IL-1β, a major proinflammatory cytokine that regulates innate immune responses. Anakinra binds competitively and this results in a rapid reduction in disease severity. NOMID, also known as chronic infantile neurologic, cutaneous, articular syndrome, is the most severe clinical phenotype in the spectrum of …

Intracellular Calcium Stores Drive Slow Non-Ribbon Vesicle Release From Rod Photoreceptors, Minghui Chen, David Križaj, Wallace B. Thoreson

Journal Articles: Pharmacology & Experimental Neuroscience

Rods are capable of greater slow release than cones contributing to overall slower release kinetics. Slow release in rods involves Ca(2+)-induced Ca(2+) release (CICR). By impairing release from ribbons, we found that unlike cones where release occurs entirely at ribbon-style active zones, slow release from rods occurs mostly at ectopic, non-ribbon sites. To investigate the role of CICR in ribbon and non-ribbon release from rods, we used total internal reflection fluorescence microscopy as a tool for visualizing terminals of isolated rods loaded with fluorescent Ca(2+) indicator dyes and synaptic vesicles loaded with dextran-conjugated pH-sensitive rhodamine. We found that rather than …

A Melanin-Independent Interaction Between Mc1r And Met Signalling Pathways Is Required For Hgf-Dependent Melanoma, Agnieszka Wolnicka-Głubisz, Faith M. Strickland, Albert Wielgus, Miriam Anver, Glenn Merlino, Edward C. De Fabo, Frances P. Noonan

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Melanocortin 1 receptor (MC1R) signaling stimulates black eumelanin production through a cAMP-dependent pathway. MC1R polymorphisms can impair this process, resulting in a predominance of red phaeomelanin. The red hair, fair skin and UV sensitive phenotype is a well-described melanoma risk factor. MC1R polymorphisms also confer melanoma risk independent of pigment. We investigated the effect of Mc1r deficiency in a mouse model of UV-induced melanoma. C57BL/6-Mc1r+/+-HGF transgenic mice have a characteristic hyperpigmented black phenotype with extra-follicular dermal melanocytes located at the dermal/epidermal junction. UVB induces melanoma, independent of melanin pigmentation, but UVA-induced and spontaneous melanomas are dependent on black eumelanin. We …

Medial Septal Cholinergic Neurons Modulate Isoflurane Anesthesia., Siew Kian Tai, Jingyi Ma, L Stan Leung

Physiology and Pharmacology Publications

BACKGROUND: Cholinergic drugs are known to modulate the response of general anesthesia. However, the sensitivity of isoflurane or other volatile anesthetics after selective lesion of septal cholinergic neurons that project to the hippocampus is not known.

METHODS: Male Long Evans rats had 192 immunoglobulin G-saporin infused into the medial septum (n = 10), in order to selectively lesion cholinergic neurons, whereas control, sham-lesioned rats were infused with saline (n = 12). Two weeks after septal infusion, the hypnotic properties of isoflurane and ketamine were measured using a behavioral endpoint of loss of righting reflex (LORR). Septal lesion was assessed by …

Activation Of Mglur2/3 Receptors In The Ventro-Rostral Prefrontal Cortex Reverses Sensorimotor Gating Deficits Induced By Systemic Nmda Receptor Antagonists., Bridget Valsamis, Michael Chang, Marei Typlt, Susanne Schmid

Brain and Mind Institute Researchers' Publications

Prepulse inhibition (PPI) of acoustic startle is an operational measure of sensorimotor gating, which is disrupted in schizophrenia. NMDA receptor (NMDAR) antagonist induced PPI disruption has become an important pharmacological model for schizophrenia; however, knowledge of the underlying mechanism remains incomplete. This study examines the role of NMDAR in the caudal pontine reticular nucleus (PnC) and the medial prefrontal cortex (mPFC) in NMDARs antagonist induced PPI deficits, as well as the NMDA receptor subtypes involved. We administered the NMDA antagonist MK-801 locally into the caudal pontine reticular formation (PnC), where the PPI mediating pathway converges with the primary startle pathway, …

Growth Of Nasal And Laryngeal Airways In Children: Implications In Breathing And Inhaled Aerosol Dynamics, Jinxiang Xi, Xiuhua Si, Yue Zhou, Jong Won Kim

University Faculty Publications and Creative Works

The human respiratory airway undergoes dramatic growth during infancy and childhood, which induces substantial variability in air flow pattern and particle deposition. However, deposition studies have typically focused on adult subjects, the results of which cannot be readily extrapolated to children. We developed models to quantify the growth of human nasallaryngeal airways at early ages, and to evaluate the impact of that growth on breathing resistance and aerosol deposition. METHODS: Four image-based nasal-laryngeal models were developed from 4 children, ages 10 days, 7 months, 3 years, and 5 years, and were compared to a nasallaryngeal model of a 53-year-old adult. …

Inflammation Enhances Il-2 Driven Differentiation Of Cytolytic Cd4 T Cells, Aspen M. Workman, Ashley K. Jacobs, Alexander J. Vogel, Shirley Condon, Deborah M. Brown

Nebraska Center for Virology: Faculty Publications

Cytolytic CD4 T cells (CD4 CTL) have been identified in vivo in response to viral infections; however, the factors necessary for driving the cytolytic phenotype have not been fully elucidated. Our previously published work suggests IL-2 may be the master regulator of perforin-mediated cytotoxicity in CD4 effectors. To further dissect the role of IL-2 in CD4 CTL generation, T cell receptor transgenic mice deficient in the ability to produce IL-2 or the high affinity IL-2 receptor (IL-2Rα, CD25) were used. Increasing concentrations of IL-2 were necessary to drive perforin (Prf) expression and maximal cytotoxicity. Granzyme B (GrB) expression and killing …

A Community Of Practice: Librarians In A Biomedical Research Network, Danielle P. De Jager-Loftus, David Midyette, Barbara Harvey

Scholarly Papers and Articles

Providing library and reference services within a biomedical research community presents special challenges for librarians, especially those in historically lower-funded states. These challenges can include understanding needs, defining and communicating the library’s role, building relationships, and developing and maintaining general and subject specific knowledge. This article describes a biomedical research network and the work of health sciences librarians at the lead intensive research institution with librarians from primarily undergraduate institutions and tribal colleges and universities. Applying the concept of a “community of practice” to a collaborative effort suggests how librarians can work together to provide effective reference services to researchers …

Repair Of Oxidative Dna Damage And Cancer: Recent Progress In Dna Base Excision Repair, Timothy L. Scott, Suganya Rangaswamy, Christina A. Wicker, Tadahide Izumi

Toxicology and Cancer Biology Faculty Publications

SIGNIFICANCE: Reactive oxygen species (ROS) are generated by exogenous and environmental genotoxins, but also arise from mitochondria as byproducts of respiration in the body. ROS generate DNA damage of which pathological consequence, including cancer is well established. Research efforts are intense to understand the mechanism of DNA base excision repair, the primary mechanism to protect cells from genotoxicity caused by ROS.

RECENT ADVANCES: In addition to the notion that oxidative DNA damage causes transformation of cells, recent studies have revealed how the mitochondrial deficiencies and ROS generation alter cell growth during the cancer transformation.

CRITICAL ISSUES: The emphasis of this …

Ether Bridge Formation In Loline Alkaloid Biosynthesis, Juan Pan, Minakshi Bhardwaj, Jerome Ralph Faulkner, Padmaja Nagabhyru, Nikki D. Charlton, Richard M. Higashi, Anne-Frances Miller, Carolyn A Young, Robert B. Grossman, Christopher L. Schardl

Toxicology and Cancer Biology Faculty Publications

Lolines are potent insecticidal agents produced by endophytic fungi of cool-season grasses. These alkaloids are composed of a pyrrolizidine ring system and an uncommon ether bridge linking carbons 2 and 7. Previous results indicated that 1-aminopyrrolizidine was a pathway intermediate. We used RNA interference to knock down expression of lolO, resulting in the accumulation of an alkaloid identified as exo-1-acetamidopyrrolizidine based on high-resolution MS and NMR. Genomes of endophytes differing in alkaloid profiles were sequenced, revealing that those with mutated lolO accumulated exo-1-acetamidopyrrolizidine but no lolines. Heterologous expression of wild-type lolO complemented a lolO mutant, resulting in …

A Program For Review Of Residents On Anti-Psychotic (Ap) Medications In A County Owned Nursing Facility, Catherine M. Glew Bm, Bs, Cmd, Beth Berklite Rn, Adon, Terri Bauer Rn

Department of Medicine

No abstract provided.

Variation In Feeding Practices Following The Norwood Procedure., Linda M. Lambert, Nancy A. Pike, Barbara Medoff-Cooper, Victor Zak, Victoria L. Pemberton, Lisa Young-Borkowski, Martha L. Clabby, Kathryn N. Nelson, Richard G. Ohye, Bethany Trainor, Karen Uzark, Nancy Rudd, Louise Bannister, Rosalind Korsin, David S. Cooper, Christian Pizarro, Sinai C. Zyblewski, Bronwyn H. Bartle, Richard V. Williams, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To assess variation in feeding practice at hospital discharge after the Norwood procedure, factors associated with tube feeding, and associations among site, feeding mode, and growth before stage II.

STUDY DESIGN: From May 2005 to July 2008, 555 subjects from 15 centers were enrolled in the Pediatric Heart Network Single Ventricle Reconstruction Trial; 432 survivors with feeding data at hospital discharge after the Norwood procedure were analyzed.

RESULTS: Demographic and clinical variables were compared among 4 feeding modes: oral only (n = 140), oral/tube (n = 195), nasogastric tube (N-tube) only (n = 40), and gastrostomy tube (G-tube) only …

Corticosterone Administration Up-Regulated Expression Of Norepinephrine Transporter And Dopamine Β-Hydroxylase In Rat Locus Coeruleus And Its Terminal Regions, Yan Fan, Ping Ping Chen, Ying Li, Kui Cui, Daniel M. Noel, Elizabeth D. Cummins, Daniel J. Peterson, Russell W. Brown, Meng-Yang Zhu

ETSU Faculty Works

Stress has been reported to activate the locus coeruleus (LC)-noradrenergic system. In this study, corticosterone (CORT) was orally administrated to rats for 21 days to mimic stress status. In situ hybridization measurements showed that CORT ingestion significantly increased mRNA levels of norepinephrine transporter (NET) and dopamine β-hydroxylase (DBH) in the LC region. Immunofluorescence staining and western blotting revealed that CORT treatment also increased protein levels of NET and DBH in the LC, as well as NET protein levels in the hippocampus, the frontal cortex and the amygdala. However, CORT-induced increase in DBH protein levels only appeared in the hippocampus and …

Exploring The Atomic Structure And Conformational Flexibility Of A 320 Å Long Engineered Viral Fiber Using X-Ray Crystallography., Anshul Bhardwaj, Sherwood R Casjens, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

Protein fibers are widespread in nature, but only a limited number of high-resolution structures have been determined experimentally. Unlike globular proteins, fibers are usually recalcitrant to form three-dimensional crystals, preventing single-crystal X-ray diffraction analysis. In the absence of three-dimensional crystals, X-ray fiber diffraction is a powerful tool to determine the internal symmetry of a fiber, but it rarely yields atomic resolution structural information on complex protein fibers. An 85-residue-long minimal coiled-coil repeat unit (MiCRU) was previously identified in the trimeric helical core of tail needle gp26, a fibrous protein emanating from the tail apparatus of the bacteriophage P22 virion. Here, …

Metabolic Reprogramming Induced By Ketone Bodies Diminishes Pancreatic Cancer Cachexia, Surendra K. Shukla, Teklab Gebregiworgis, Vinee Purohit, Nina V. Chaika, Venugopal Gunda, Prakash Radhakrishnan, Kamiya Mehla, Iraklis I. Pipinos, Robert Powers, Fang Yu, Pankaj K. Singh

Robert Powers Publications

Background: Aberrant energy metabolism is a hallmark of cancer. To fulfill the increased energy requirements, tumor cells secrete cytokines/factors inducing muscle and fat degradation in cancer patients, a condition known as cancer cachexia. It accounts for nearly 20% of all cancer-related deaths. However, the mechanistic basis of cancer cachexia and therapies targeting cancer cachexia thus far remain elusive. A ketogenic diet, a high-fat and low-carbohydrate diet that elevates circulating levels of ketone bodies (i.e., acetoacetate, β-hydroxybutyrate, and acetone), serves as an alternative energy source. It has also been proposed that a ketogenic diet leads to systemic metabolic changes. Keeping in …

Role Of Peripheral Immune Response In Microglia Activation And Regulation Of Brain Chemokine And Proinflammatory Cytokine Responses Induced During Vsv Encephalitis, Christina D. Steel, Kimberly Breving, Susan Tavakoli, Woong-Ki Kim, Larry D. Sanford, Richard P. Ciavarra

Biological Sciences Faculty Publications

We report herein that neuroinvasion by vesicular stomatitis virus (VSV) activates microglia and induces a peripheral dendritic cell (DC)-dependent inflammatory response in the central nervous system (CNS). VSV neuroinvasion rapidly induces multiple brain chemokine and proinflammatory cytokine mRNAs that display bimodal kinetics. Peripheral DC ablation or T cell depletion suppresses the second wave of this response demonstrating that infiltrating T cells are primarily responsible for the bimodal characteristics of this response. The robust infiltrate associated with VSV encephalitis likely depends on sustained production of brain CCL19 and CCR7 expression on infiltrating inflammatory cells. © 2013 Elsevier B.V. All rights reserved.

Growth Of Nasal And Laryngeal Airways In Children: Implications In Breathing And Inhaled Aerosol Dynamics, Jinxiang Xi, Xiuhua Si, Yue Zhou, Jong Won Kim

University Faculty Publications and Creative Works

BACKGROUND: The human respiratory airway undergoes dramatic growth during infancy and childhood, which induces substantial variability in air flow pattern and particle deposition. However, deposition studies have typically focused on adult subjects, the results of which cannot be readily extrapolated to children. We developed models to quantify the growth of human nasallaryngeal airways at early ages, and to evaluate the impact of that growth on breathing resistance and aerosol deposition. METHODS: Four image-based nasal-laryngeal models were developed from 4 children, ages 10 days, 7 months, 3 years, and 5 years, and were compared to a nasallaryngeal model of a 53-year-old …

Targeting Fibroblast Activation Protein In Tumor Stroma With Chimeric Antigen Receptor T Cells Can Inhibit Tumor Growth And Augment Host Immunity Without Severe Toxicity., Liang-Chuan S. Wang, Albert Lo, John Scholler, Jing Sun, Rajrupa S. Majumdar, Veena Kapoor, Michael Antzis, Cody E. Cotner, Laura A. Johnson, Amy C. Durham, Charalambos C. Solomides, Md, Carl H. June, Ellen Puré, Steven M. Albelda

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The majority of chimeric antigen receptor (CAR) T-cell research has focused on attacking cancer cells. Here, we show that targeting the tumor-promoting, nontransformed stromal cells using CAR T cells may offer several advantages. We developed a retroviral CAR construct specific for the mouse fibroblast activation protein (FAP), comprising a single-chain Fv FAP [monoclonal antibody (mAb) 73.3] with the CD8α hinge and transmembrane regions, and the human CD3ζ and 4-1BB activation domains. The transduced muFAP-CAR mouse T cells secreted IFN-γ and killed FAP-expressing 3T3 target cells specifically. Adoptively transferred 73.3-FAP-CAR mouse T cells selectively reduced FAP(hi) stromal cells and inhibited the …