Anatomy Commons^™

Epithelial-To-Mesenchymal Transition Leads To Disease-Stage Differences In Circulating Tumor Cell Detection And Metastasis In Pre-Clinical Models Of Prostate Cancer, Lori E. Lowes, David Goodale, Ying Xia, Carl Postenka, Matthew M. Piaseczny, Freeman Paczkowski, Alison L. Allan

Anatomy and Cell Biology Publications

Metastasis is the cause of most prostate cancer (PCa) deaths and has been associated with circulating tumor cells (CTCs). The presence of >= 5 CTCs/7.5mL of blood is a poor prognosis indicator in metastatic PCa when assessed by the CellSearch (R) system, the "gold standard" clinical platform. However, similar to 35% of metastatic PCa patients assessed by CellSearch (R) have undetectable CTCs. We hypothesize that this is due to epithelial-to-mesenchymal transition (EMT) and subsequent loss of necessary CTC detection markers, with important implications for PCa metastasis. Two pre-clinical assays were developed to assess human CTCs in xenograft models; one comparable …

Can Bedside Ultrasound Inferior Vena Cava Measurements Accurately Diagnose Congestive Heart Failure In The Emergency Department? A Clin-Iq, Miranda Gaskamp, Mark Blubaugh, Laine H. Mccarthy, Dewey C. Scheid

Journal of Patient-Centered Research and Reviews

Congestive heart failure (CHF) is a major cause of morbidity and mortality. Early diagnosis of CHF in patients presenting to the emergency department with undifferentiated dyspnea would allow clinicians to begin appropriate treatment more promptly. Current guidelines recommend B-type natriuretic peptide (BNP) levels for more accurate diagnosis of CHF in dyspneic patients. Although BNP levels are relatively inexpensive, the test is not usually performed at bedside and results may take up to an hour or more. BNP also may have a “gray zone” in which the values can neither confirm nor rule out CHF. BNP has a reported sensitivity of …

Tgf-Β1 Increases Resistance Of Nih/3t3 Fibroblasts Toward Apoptosis Through Activation Of Smad2/3 And Erk1/2 Pathways, Ulugbek Negmadjanov, Alisher Holmuhamedov, Larisa Emelyanova, Hao Xu, Farhan Rizvi, Gracious R. Ross, A. Jamil Tajik, Yang Shi, Ekhson Holmuhamedov, Arshad Jahangir

Journal of Patient-Centered Research and Reviews

Purpose

Excessive fibrosis has been suggested to result from persistence of fibroblasts in injured tissue due to impaired apoptosis, but signaling pathways are not fully defined.

Methods

Suppression of apoptotic cell death following transforming growth factor-β1 (TGF-β1) exposure was studied using the culture of NIH/3T3 mouse embryonic fibroblasts. Caspase-3 activity, propidium iodide staining and annexin V binding induced by Fas-ligand (FasL) in NIH/3T3 fibroblasts in the absence and presence of TGF-β1 was determined, and relative contribution of signaling through Smad2/3 and noncanonical Erk1/2 and Akt pathways was dissected by assessing phosphorylation status of these kinases and caspase activity in the …

Evaluation Of Preoperative Anemia And Transfusion Requirements In Adult Liver Transplant Recipients, Parissa M.N. Moghimi, Erika A. Aldag, Rachel Pedersen, Ajay Sahajpal, Jacob N. Clendenon, Vikraman Gunabushanam, Mehraboon S. Irani, David J. Kramer

Journal of Patient-Centered Research and Reviews

Background: Liver transplantation is often associated with massive blood loss due to surgical complexity and the hemostatic abnormalities of end-stage liver disease. Blood transfusions have been associated with increased risk of infection, multiorgan dysfunction, graft loss and mortality.

Purpose: To determine for liver transplantation whether correlation exists between preoperative anemia and transfusion requirements, length of stay or incidence of postoperative infection.

Methods: A retrospective review of liver transplantations from Jan. 1, 2012, to June 30, 2015, was conducted. Packed red blood cell (PRBC), fresh frozen plasma (FFP), platelet and cryoprecipitate units were collected preoperatively, intraoperatively and within the first 48 …

Functional Alterations Of Ion Channels From Cardiac Fibroblasts In Heart Diseases, Gracious R. Ross, Arshad Jahangir

Journal of Patient-Centered Research and Reviews

In an aged population, cardiovascular disease is the leading cause of fatality and morbidity. Age-related fibrotic remodeling of the heart contributes to progressive myocardial dysfunction. Cardiac fibroblasts (CF), responsible for the maintenance of extracellular matrix and fibrosis process, play an important role in cardiac health and disease. CFs influence myocardial function by their chemical, electrical and mechanical interactions with cardiomyocytes through extracellular matrix deposition or secretion of cytokines and growth factors. These, in turn, are modulated by ion channels, macromolecular pores in the plasma membrane that allow selective ionic fluxes of major ions like K⁺, Ca²⁺, …

Mesenteric Vascular Dysregulation And Intestinal Inflammation Accompanies Experimental Spinal Cord Injury, Emily Swartz Besecker, Gina M. Deiter, Nicole Pironi, Timothy K. Cooper, Gregory Michael Holmes

Health Sciences Faculty Publications

Cervical and high thoracic spinal cord injury (SCI) drastically impairs autonomic nervous system function. Individuals with SCI at thoracic spinal-level 5 (T5) or higher often present cardiovascular disorders that include resting systemic arterial hypotension. Gastrointestinal (GI) tissues are critically dependent upon adequate blood flow and even brief periods of visceral hypoxia triggers GI dysmotility. The aim of this study was to test the hypothesis that T3-SCI induces visceral hypoperfusion, diminished postprandial vascular reflexes and concomitant visceral inflammation. We measured in vivo systemic arterial blood pressure and superior mesenteric artery (SMA) and duodenal blood flow in anesthetized T3-SCI rats at 3 …

Chronic Binge Alcohol Administration Dysregulates Hippocampal Genes Involved In Immunity And Neurogenesis In Simian Immunodeficiency Virus-Infected Macaques, John K Maxi, Matt Dean, Jovanny Zabaleta, Krzysztof Reiss, Gregory J. Bagby, Steve Nelson, Peter J. Winsauer, Francesca Peruzzi, Patricia E. Molina

School of Graduate Studies Faculty Publications

Alcohol use disorders (AUD) exacerbate neurocognitive dysfunction in Human Immunodeficiency Virus (HIV+) patients. We have shown that chronic binge alcohol (CBA) administration (13-14 g EtOH/kg/wk) prior to and during simian immunodeficiency virus (SIV) infection in rhesus macaques unmasks learning deficits in operant learning and memory tasks. The underlying mechanisms of neurocognitive alterations due to alcohol and SIV are not known. This exploratory study examined the CBA-induced differential expression of hippocampal genes in SIV-infected (CBA/SIV+; = 2) macaques in contrast to those of sucrose administered, SIV-infected (SUC/SIV+; = 2) macaques. Transcriptomes of hippocampal samples dissected from brains obtained at necropsy (16 …

Localization And Distribution Of Primary Cilia In The Adult Mouse Heart, Ali Zarban, Hannah C. Saternos, Andrea L. Kalinoski, Lijun Liu, Surya M. Nauli, Wissam A. Aboualaiwi

Pharmacy Faculty Articles and Research

Although primary cilia have been shown to play crucial roles in the development of embryonic mouse heart, their presence and function in adult mouse heart remains controversial. In this study, the presence of primary cilia in adult mouse heart was investigated. The presence of primary cilia was initially demonstrated in the surface of cardiac cells of mouse hearts from both young and adult mice by immunostaining with acetylated α-tubulin, a ciliary structural marker. The presence of cardiac primary cilia in 1-, 3-, 6- and 12-month old mice was further confirmed by staining heart tissues with an antibody against pericentrin, a …

Parental Refusal Of Surgery In An Infant With Tricuspid Atresia., Alexander A. Kon, Angira Patel, Steven Leuthner, John Lantos

Manuscripts, Articles, Book Chapters and Other Papers

We present a case of a fetal diagnosis of tricuspid atresia (TA). The pregnant woman and her husband requested that the baby be treated with only palliative care. The cardiologist did not think it would be appropriate to withhold life-prolonging surgery once the infant was born. The neonatologist argued that outcomes for TA are similar to those for hypoplastic left heart syndrome, and the standard practice at the institution was to allow parents to choose surgery or end-of-life care for those infants. The team requested an ethics consultation to assist in determining whether forgoing life-prolonging interventions in this case would …

Assessment Of Diastolic Function In Single-Ventricle Patients After The Fontan Procedure., Renee Margossian, Lynn A. Sleeper, Gail D. Pearson, Piers C. Barker, Luc Mertens, Michael D. Quartermain, Jason T. Su, Girish S. Shirali, Shan Chen, Steven D. Colan, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Patients with functional single ventricles after the Fontan procedure have abnormal cardiac mechanics. The aims of this study were to determine factors that influence diastolic function and to describe associations of diastolic function with current clinical status.

METHODS: Echocardiograms were obtained as part of the Pediatric Heart Network Fontan Cross-Sectional Study. Diastolic function grade (DFG) was assessed as normal (grade 0), impaired relaxation (grade 1), pseudonymization (grade 2), or restrictive (grade 3). Studies were also classified dichotomously (restrictive pattern present or absent). Relationships between DFG and pre-Fontan variables (e.g., ventricular morphology, age at Fontan, history of volume-unloading surgery) and …

Grave’S Anatomy: Abolitionists, Body Snatchers, And The Demise Of Winchester Medical College, Kaylyn L. Sawyer

The Gettysburg Compiler: On the Front Lines of History

A census in 1890 listed Chris Baker’s occupation as “Anatomical Man.” While the title sounds like that one of today’s superheroes, the nineteenth century existence of this vocation kept people from lingering around medical colleges after dark. By day, Chris Baker worked as a janitor for the Medical College of Virginia in Richmond. By night, he had the darker task of obtaining corpses for the school. He was a “resurrectionist,” and he was not alone in his eerie nocturnal task of preying on the powerless and recently interred with a shovel, bag, and cart close at hand. Until legislation governing …

Human Anatomy & Physiology Society ( Haps ) Southern Regional Meeting 2016, Cheryl Purvis

Faculty Proceedings, Presentations, Speeches and Lectures

No abstract provided.

Regulation Of Amyloid Oligomer Binding To Neurons And Neurotoxicity By The Prion Protein-Mglur5 Complex, Flavio H. Beraldo, Valeriy G. Ostapchenko, Fabiana A. Caetano, Andre L. S. Guimaraes, Giulia D. S. Ferretti, Nathalie Daude, Lisa Bertram, Katiane O. P. C. Nogueira, Jerson L. Silva, David Westaway, Neil R. Cashman, Vilma R. Martins, Vania F. Prado, Marco A. M. Prado

Anatomy and Cell Biology Publications

The prion protein (PrPC) has been suggested to operate as a scaffold/receptor protein in neurons, participating in both physiological and pathological associated events. PrPC, laminin, and metabotropic glutamate receptor 5 (mGluR5) form a protein complex on the plasma membrane that can trigger signaling pathways involved in neuronal differentiation. PrPC and mGluR5 are co-receptors also for -amyloid oligomers (AOs) and have been shown to modulate toxicity and neuronal death in Alzheimer's disease. In the present work, we addressed the potential crosstalk between these two signaling pathways, laminin-PrPC-mGluR5 or AO-PrPC-mGluR5, as well as their interplay. Herein, we demonstrated that an existing complex …

Noncanonical Sqstm1/P62-Nrf2 Pathway Activation Mediates Proteasome Inhibitor Resistance In Multiple Myeloma Cells Via Redox, Metabolic And Translational Reprogramming., Irene Riz, Teresa S Hawley, Jeffrey W Marsal, Robert G Hawley

Anatomy and Regenerative Biology Faculty Publications

Multiple Myeloma (MM) is a B-cell malignancy characterized by the accumulation of clonal plasma cells in the bone marrow, with drug resistance being a major cause of therapeutic failure. We established a carfilzomib-resistant derivative of the LP-1 MM cell line (LP-1/Cfz) and found that the transcription factor NF-E2 p45-related factor 2 (Nrf2; gene symbol NFE2L2) contributes to carfilzomib resistance. The mechanism of Nrf2 activation involved enhanced translation of Nrf2 as well as its positive regulator, the autophagy receptor sequestosome 1 (SQSTM1)/p62. The eukaryotic translation initiation factor gene EIF4E3 was among the Nrf2 target genes upregulated in LP-1/Cfz cells, suggesting existence …

Vacht Overexpression Increases Acetylcholine At The Synaptic Cleft And Accelerates Aging Of Neuromuscular Junctions, Satoshi Sugita, Leland L. Fleming, Caleb Wood, Sydney K. Vaughan, Matheus P. S. M. Gomes, Wallace Camargo, Ligia A. Naves, Vania F. Prado, Marco A. M. Prado, Cristina Guatimosim, Gregorio Valdez

Anatomy and Cell Biology Publications

Background: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age-and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS). Methods: Chat-ChR2-EYFP (VAChTHyp) mice containing multiple copies of the vesicular acetylcholine transporter (VAChT), mutant superoxide dismutase 1 (SOD1G93A), and Chat-IRES-Cre and tdTomato transgenic mice were used in this …

Deferoxamine Preventable Hepatocellular Damage, Following Hemorrhagic Shock, Charles F. Babbs, David W. Griffin

Weldon School of Biomedical Engineering Faculty Working Papers

To examine the role of iron in mediating hepatocellular damage during reperfusion after hemorrhagic shock, we studied five groups of n=4 or 5 dogs, bled to reduce mean arterial pressure to 35 mmHg (± 5mrnHg) for three hours and subsequently treated 20 minutes prior to reinfusion of shed blood with either 0.9% saline, 5 ml/kg; deferoxamine, 50 μg/kg in 0.9% saline; 6% pentastarch solution, 5 ml/kg; deferoxamine covalently bound to 6% pentastarch, 50 μg/kg; or iron loaded deferoxamine in 0.9% saline. Saturation of iron binding capacity increased during hemorrhagic shock and remained high in all but the def eroxamine pentastarch …

Tgf-Β Signaling: New Insights Into Aortic Aneurysms, Sean E. Thatcher

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

Preterm Neonatal Lateral Ventricle Volume From Three-Dimensional Ultrasound Is Not Strongly Correlated To Two-Dimensional Ultrasound Measurements, Jessica Kishimoto, Sandrine De Ribaupierre, Fateme Salehi, Walter Romano, David S. C. Lee, Aaron Fenster

Anatomy and Cell Biology Publications

The aim of this study is to compare longitudinal two-dimensional (2-D) and three-dimensional (3-D) ultrasound (US) estimates of ventricle size in preterm neonates with posthemorrhagic ventricular dilatation (PHVD) using quantitative measurements of the lateral ventricles. Cranial 2-D US and 3-D US images were acquired from neonatal patients with diagnosed PHVD within 10 min of each other one to two times per week and analyzed offline. Ventricle index, anterior horn width, third ventricle width, and thalamo-occipital distance were measured on the 2-D images and ventricle volume (VV) was measured from 3-D US images. Changes in the measurements between successive image sets …

Early Cumulative Supplemental Oxygen Predicts Bronchopulmonary Dysplasia In High Risk Extremely Low Gestational Age Newborns., Katherine C. Wai, Michael A. Kohn, Roberta A. Ballard, William E. Truog, Dennis M. Black, Jeanette M. Asselin, Philip L. Ballard, Elizabeth E. Rogers, Roberta L. Keller, Trial Of Late Surfactant (Tolsurf) Study Group

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To assess the prognostic accuracy of early cumulative supplemental oxygen (CSO) exposure for prediction of bronchopulmonary dysplasia (BPD) or death, and to evaluate the independent association of CSO with BPD or death.

STUDY DESIGN: We performed a secondary analysis of the Trial of Late Surfactant, which enrolled 511 infants born at ≤28 weeks gestational age who were mechanically ventilated at 7-14 days of life. Our primary outcome was BPD or death at 36 weeks postmenstrual age, as determined by a physiological oxygen/flow challenge. Average daily supplemental oxygen (fraction of inspired oxygen - 0.21) was calculated. CSO was calculated as …

The Effect Of Bony Parameters On The Pediatric Knee: Normal Versus Anterior Cruciate Ligament Injury Versus Tibial Spine Avulsion Fracture., Kenneth A. Shaw, Brian S. Dunoski, Neil J. Mardis, Donna M. Pacicca

Manuscripts, Articles, Book Chapters and Other Papers

Purpose  Anterior cruciate ligament (ACL) injuries can present as a ligamentous disruption or avulsion fracture of the tibial spine in pediatric patients. Differences in knee morphometric parameters have been investigated between pediatric cohorts with ACL disruptions and tibial spine avulsion fractures. However, no study to date has compared morphometric parameters in patients with tibial spine avulsion fracture against a control population. Methods  A retrospective review of pediatric patients undergoing knee magnetic resonance imaging (MRI) studies was performed, identifying 15 patients with tibial spine avulsion fracture between January 1, 2009, and January 1, 2013. Inclusionary criteria consisted of patients who sustained …