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Increased Density Of Axonal Spheroids In The Nucleus Gracilis Of The Lower Brainstem In Diabetic Versus Non-Diabetic Patients, Tiffany Morrison, MSIV, Lawrence C. Kenyon, MD, PhD 2017 Thomas Jefferson University

Increased Density Of Axonal Spheroids In The Nucleus Gracilis Of The Lower Brainstem In Diabetic Versus Non-Diabetic Patients, Tiffany Morrison, Msiv, Lawrence C. Kenyon, Md, Phd

Pathology, Anatomy and Cell Biology Posters

Abstract

The presence of axonal spheroids is unusual in the absence of a clinical history of CNS injury. Nevertheless, increased numbers of axonal spheroids in the lower brainstem have been consistently observed in autopsied diabetic patients. A prospective comprehensive investigation of the density, size, and distribution of axonal spheroids in the brainstem and spinal cord was undertaken in 22 patients and correlated with comorbidities, age, and gender. In most cases, an increased density of axonal spheroids was identified within the nucleus gracilis of the lower brainstem. Moreover, the highest densities (p = 0.013) and circumferences (p = 0.002) of axonal ...


A Comparative Analysis Of The Paris System And Institutional Reporting System For Urine Cytology In Upper Tract Urothelial Specimens, Kim Hookim, MD, James P. Casey, MD, Rossitza Draganova-Tacheva, MD, Marluce Bibbo, MD, Charalambos C. Solomides, MD 2017 Thomas Jefferson University

A Comparative Analysis Of The Paris System And Institutional Reporting System For Urine Cytology In Upper Tract Urothelial Specimens, Kim Hookim, Md, James P. Casey, Md, Rossitza Draganova-Tacheva, Md, Marluce Bibbo, Md, Charalambos C. Solomides, Md

Pathology, Anatomy and Cell Biology Posters

The authors of this abstract have no conflicts of interest

Introduction

Cytology is integral in the assessment of urothelial cell carcinoma (UCC). However, upper urinary tract (UUT) specimens are cytologically challenging due to limited tissue and reactive atypia. At our institution UUT biopsies are processed as cell blocks (CB). We compared our institution’s reporting system (IRS) with the recently proposed Paris System for Reporting Urine Cytology (PRS) (Table 1) in UUT specimens and correlated the findings with CB and follow-up resections.


Lysine Residues Of Interferon Regulatory Factor 7 Affect The Replication And Transcription Activatormediated Lytic Replication Of Kaposi’S Sarcomaassociated Herpesvirus/Human Herpesvirus 8, Tianzheng Zhang, Ying Wang, Li Zhang, Bin Liu, Jinhui Xie, Charles Wood, Jinzhong Wang 2017 Nankai University

Lysine Residues Of Interferon Regulatory Factor 7 Affect The Replication And Transcription Activatormediated Lytic Replication Of Kaposi’S Sarcomaassociated Herpesvirus/Human Herpesvirus 8, Tianzheng Zhang, Ying Wang, Li Zhang, Bin Liu, Jinhui Xie, Charles Wood, Jinzhong Wang

Virology Papers

Kaposi’s sarcoma-associated herpesvirus (KSHV) infection goes through latent and lytic phases, which are controlled by the viral replication and transcription activator (RTA). Upon KSHV infection, the host responds by suppressing RTA-activated lytic gene expression through interferon regulatory factor 7 (IRF-7), a key regulator of host innate immune response. Lysine residues are potential sites for post-translational modification of IRF-7, and were suggested to be critical for its activity. In this study, we analysed the 15 lysine residues for their effects on IRF-7 function by site-directed mutagenesis. We found that some mutations affect the ability of IRF-7 to activate interferon (IFN ...


Diagnosis Of Lchad/Tfp Deficiency In An At Risk Newborn Using Umbilical Cord Blood Acylcarnitine Analysis, Donna Raval, Kristina Cusmano-Ozog, Omar Ayyub, Callie Jenevein, Laura Kofman, Brendan Lanpher, Natalie Hauser, Debra Regier 2017 George Washington University

Diagnosis Of Lchad/Tfp Deficiency In An At Risk Newborn Using Umbilical Cord Blood Acylcarnitine Analysis, Donna Raval, Kristina Cusmano-Ozog, Omar Ayyub, Callie Jenevein, Laura Kofman, Brendan Lanpher, Natalie Hauser, Debra Regier

Pathology Faculty Publications

Trifunctional protein deficiency/Long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHAD/TFP) deficiency is a disorder of fatty acid oxidation and ketogenesis. Severe neonatal lactic acidosis, cardiomyopathy, and hepatic dysfunction are caused by the accumulation of toxic long-chain acylcarnitines. The feasibility of umbilical cord blood use in screening for acylcarnitine analysis and free carnitine has been hypothesized but not reported in LCHAD/TFP neonates.

We present a 4 week old female who was at risk of inheriting LCHAD/TFP deficiency and was diagnosed at the time of delivery using umbilical cord blood. Umbilical cord blood was collected at delivery and sent for acylcarnitine ...


The Prognostic Utility Of The Transcription Factor Srf In Docetaxel-Resistant Prostate Cancer: In-Vitro Discovery And In-Vivo Validation., Dara J. Lundon, Amy Boland, Maria Prencipe, G Hurley, Amanda O'Neill, Elaine W. Kay, Sinead T. Aherne, Padraig Doolan, Stephen F. Madden, Martin Clynes, Colm Morrissey, J M. Fitzpatrick, R William Watson 2017 University College Dublin

The Prognostic Utility Of The Transcription Factor Srf In Docetaxel-Resistant Prostate Cancer: In-Vitro Discovery And In-Vivo Validation., Dara J. Lundon, Amy Boland, Maria Prencipe, G Hurley, Amanda O'Neill, Elaine W. Kay, Sinead T. Aherne, Padraig Doolan, Stephen F. Madden, Martin Clynes, Colm Morrissey, J M. Fitzpatrick, R William Watson

Pathology Articles

BACKGROUND: Docetaxel based therapy is one of the first line chemotherapeutic agents for the treatment of metastatic castrate-resistant prostate cancer. However, one of the major obstacles in the treatment of these patients is docetaxel-resistance. Defining the mechanisms of resistance so as to inform subsequent treatment options and combinations represents a challenge for clinicians and scientists. Previous work by our group has shown complex changes in pro and anti-apoptotic proteins in the development of resistance to docetaxel. Targeting these changes individually does not significantly impact on the resistant phenotype but understanding the central signalling pathways and transcription factors (TFs) which control ...


Follicular Dendritic Cell Sarcoma: A Rare Entity With Variable Pathologic Features And Prognosis, Sharif A. Ali MD, Miriam L. Enriquez MD, Shereen M. Gheith MD 2017 Lehigh Valley Health Network

Follicular Dendritic Cell Sarcoma: A Rare Entity With Variable Pathologic Features And Prognosis, Sharif A. Ali Md, Miriam L. Enriquez Md, Shereen M. Gheith Md

Shereen M.F. Gheith, M.D., PhD.

No abstract provided.


Delaying Chemotherapy In The Treatment Of Stage Iv Non-Small Cell Lung Cancer Does Not Adversely Affect Survival Outcome, Mohammad Mozayen MD, Mohamed Alsharedi, Inderjit Mehmi, Todd W. Gress MD, Maria Tria Tirona MD 2017 Marshall University

Delaying Chemotherapy In The Treatment Of Stage Iv Non-Small Cell Lung Cancer Does Not Adversely Affect Survival Outcome, Mohammad Mozayen Md, Mohamed Alsharedi, Inderjit Mehmi, Todd W. Gress Md, Maria Tria Tirona Md

Mohamed Alsharedi

Background: Whether a delay in the initiation of chemotherapy for advanced non-small cell lung cancer (NSCLC) can affect overall survival is not well studied. We aim to evaluate the effect of the time interval between diagnosis and initiation of chemotherapy on overall survival in patients with stage IV NSCLC.

Methods: A retrospective review of newly diagnosed stage IV NSCLC patients who received chemotherapy between 1995 and 2012 was conducted. Demographics, histology and site(s) of metastases of patients were reviewed. Time interval between the date of diagnosis and the date of starting chemotherapy was calculated in days. Patients were divided ...


Bcl-W Has A Fundamental Role In B Cell Survival And Lymphomagenesis., Clare M. Adams, Annette S. Kim, Ramkrishna Mitra, John K Choi, Jerald Z. Gong, Christine M. Eischen 2017 Thomas Jefferson University

Bcl-W Has A Fundamental Role In B Cell Survival And Lymphomagenesis., Clare M. Adams, Annette S. Kim, Ramkrishna Mitra, John K Choi, Jerald Z. Gong, Christine M. Eischen

Department of Cancer Biology Faculty Papers

Compromised apoptotic signaling is a prerequisite for tumorigenesis. The design of effective therapies for cancer treatment depends on a comprehensive understanding of the mechanisms that govern cell survival. The antiapoptotic proteins of the BCL-2 family are key regulators of cell survival and are frequently overexpressed in malignancies, leading to increased cancer cell survival. Unlike BCL-2 and BCL-XL, the closest antiapoptotic relative BCL-W is required for spermatogenesis, but was considered dispensable for all other cell types. Here, however, we have exposed a critical role for BCL-W in B cell survival and lymphomagenesis. Loss of Bcl-w conferred sensitivity to growth factor deprivation-induced ...


Reactivation Of Hiv-1 Proviruses In Immune-Compromised Mice Engrafted With Human Voa-Negative Cd4+ T Cells, Zhe Yuan, Guobin Kang, Wuxun Lu, Qingsheng Li 2017 University of Nebraska-Lincoln

Reactivation Of Hiv-1 Proviruses In Immune-Compromised Mice Engrafted With Human Voa-Negative Cd4+ T Cells, Zhe Yuan, Guobin Kang, Wuxun Lu, Qingsheng Li

Virology Papers

Background: HIV-1 infection remains incurable on antiretroviral therapy (ART) due to virus latency. To date, enhanced co-culture assays, including viral outgrowth assays (VOA), are commonly used to measure HIV-1 latent reservoirs and evaluate latency-reversing agents (LRAs). However, VOA can only reactivate a small fraction of intact proviruses.

Methods: To explore the utility of NOD scid gamma (NSG) mice as an in vivo model to reactivate HIV-1 proviruses from VOA-negative CD4+ T cells, resting CD4+ T cells from an HIV-1 latently infected individual were isolated and the human CD4+ T cells corresponding to VOA-positive and VOA-negative CD4+ T cells were engrafted ...


Distinct Transcriptome Profiles Of Gag-Specific Cd8+ T Cells Temporally Correlated With The Protection Elicited By Sivδnef Live Attenuated Vaccine, Wuxun Lu, Yanmin Wu, Fangrui Ma, R. Paul Johnson, Qingsheng Li 2017 University of Nebraska - Lincoln

Distinct Transcriptome Profiles Of Gag-Specific Cd8+ T Cells Temporally Correlated With The Protection Elicited By Sivδnef Live Attenuated Vaccine, Wuxun Lu, Yanmin Wu, Fangrui Ma, R. Paul Johnson, Qingsheng Li

Virology Papers

The live attenuated vaccine (LAV) SIVmac239Δnef (SIVΔnef) confers the best protection among all the vaccine modalities tested in rhesus macaque model of HIV-1 infection. This vaccine has a unique feature of time-dependent protection: macaques are not protected at 3±5 weeks post vaccination (WPV), whereas immune protection emerges between 15 and 20 WPV. Although the exact mechanisms of the time-dependent protection remain incompletely understood, studies suggested that both cellular and humoral immunities contribute to this time-dependent protection. To further elucidate the mechanisms of protection induced by SIVΔnef, we longitudinally compared the global gene expression profiles of SIV Gag-CM9+ CD8+ (Gag-specific ...


Calcium Uptake Hotspots In The Mitochondria Of Cardiac Muscle At The Interface With Dyadic Sr, Sergio De La Fuente, Celia Fernandez-Sanz, Caitlin Vail, Elorm J. Agra, Kira Holmstrom, Junhui Sun, Jyotsna Mishra, Toren Finkel, Elizabeth Murphy, Suresh K. Joseph, Shey-Shing Sheu, György Csordás 2016 Thomas Jefferson University

Calcium Uptake Hotspots In The Mitochondria Of Cardiac Muscle At The Interface With Dyadic Sr, Sergio De La Fuente, Celia Fernandez-Sanz, Caitlin Vail, Elorm J. Agra, Kira Holmstrom, Junhui Sun, Jyotsna Mishra, Toren Finkel, Elizabeth Murphy, Suresh K. Joseph, Shey-Shing Sheu, György Csordás

Pathology, Anatomy and Cell Biology Posters

Introduction

• Control of the mitochondrial ATP production by SR-derived Ca2+ signals includes local, nanodomain Ca2+ transfer from ryanodine receptors (RyR2) to the mitochondrial matrix (excitation-bioenergetics coupling).

• Ca2+ crosses the inner mitochondrial membrane (IMM) via the mtCU, a low-affinity Ca2+-activated Ca2+ channel complex.

• The surface area of cardiac IMM is extensively enhanced by cristae folding; however, mitoplast patch clamp studies showed mtCU current density the lowest amongst a range of tissues (Fieni 2012. Nat Commun).


Fulminant Necrotizing Eosinophilic Myocarditis: A Case Report And Comprehensive Literature Review, Bennet George, Matthew Hager, Virgilius Cornea, William O'Connor, Maya Guglin 2016 University of Kentucky; Department of Cardiology

Fulminant Necrotizing Eosinophilic Myocarditis: A Case Report And Comprehensive Literature Review, Bennet George, Matthew Hager, Virgilius Cornea, William O'Connor, Maya Guglin

The VAD Journal

Acute eosinophilic myocarditis is a relatively rare disorder with serious morbidity and mortality. Due to its infrequency, standardized management guidelines are wanting. We present a case of acute, necrotizing eosinophilic myocarditis requiring several levels of critical care. We reviewed similar cases reported in the literature to highlight common clinical features, describe natural disease course and associated complications, and review varying approaches to medical therapy.


Gradenigo Syndrome: A Rare Complication Of Otitis Media, Paul Brent Ferguson, MD 2016 Marshall University

Gradenigo Syndrome: A Rare Complication Of Otitis Media, Paul Brent Ferguson, Md

Paul Ferguson

Gradenigo syndrome is a very rare complication of otitis media that if left unrecognized and subsequently untreated will result in severe neurologic sequelae. Gradenigo Syndrome clinically represented by the triad of otitis media, ipsilateral, abducens nerve palsy and dysasthesia within the V1 and V2 divisions of the trigeminal nerve branches. We describe a 4 year-old patient who presented with headache, facial pain, diplopia and a recent history of upper respiratory tract symptomatology. Examination revealed an abducens palsy with subsequent magnetic resonance imaging demonstrating inflammation in the left petrous apex and along the tracts of the 6th, 7th, and ...


Clinical Utility Of Immature Platelet Fraction - An Advanced Parameter In Laboratory Hematology, Muhammad Shariq Shaikh, Sidra Asad Ali 2016 Aga Khan University

Clinical Utility Of Immature Platelet Fraction - An Advanced Parameter In Laboratory Hematology, Muhammad Shariq Shaikh, Sidra Asad Ali

Department of Pathology and Laboratory Medicine

No abstract provided.


Topographical Expression Of Class Ia And Class Ii Phosphoinositide 3-Kinase Enzymes In Normal Human Tissues Is Consistent With A Role In Differentiation, Soha Salama El Sheikh, Jan Domin, Prakitpunthu Tomtitchong, Paul Abel, Gordon Stamp, El-Nasir Lalani 2016 Imperial College School of Medicine

Topographical Expression Of Class Ia And Class Ii Phosphoinositide 3-Kinase Enzymes In Normal Human Tissues Is Consistent With A Role In Differentiation, Soha Salama El Sheikh, Jan Domin, Prakitpunthu Tomtitchong, Paul Abel, Gordon Stamp, El-Nasir Lalani

El Nasir Lalani

Background: Growth factor, cytokine and chemokine-induced activation of PI3K enzymes constitutes the start of a complex signalling cascade, which ultimately mediates cellular activities such as proliferation, differentiation, chemotaxis, survival, trafficking, and glucose homeostasis. The PI3K enzyme family is divided into 3 classes; class I (subdivided into IA and IB), class II (PI3K-C2α, PI3K-C2β and PI3K-C2γ) and class III PI3K. Expression of these enzymes in human tissue has not been clearly defined.

Methods: In this study, we analysed the immunohistochemical topographical expression profile of class IA (anti-p85 adaptor) and class II PI3K (PI3K-C2α and PI3K-C2β) enzymes in 104 formalin-fixed, paraffin embedded ...


Activated Clotting Time (Act): Comparison Of The Hemochron Signature Elite And The Abbott I-Stat, Lilah Evans, Susanne Gallo, Joseph J. Leo, Barbara Goldsmith, PhD, FACB 2016 Thomas Jefferson University Hospitals, Philadelphia, PA, USA

Activated Clotting Time (Act): Comparison Of The Hemochron Signature Elite And The Abbott I-Stat, Lilah Evans, Susanne Gallo, Joseph J. Leo, Barbara Goldsmith, Phd, Facb

Pathology, Anatomy and Cell Biology Posters

BACKGROUND

ACT is commonly used for heparin anticoagulation monitoring during procedures including cardiopulmonary bypass surgery, coronary angioplasty, and interventional radiology. To prevent thrombosis, moderate to high levels of heparin anticoagulation are required. The Hemochron Signature Elite (HSE, Accriva Diagnostics, formerly ITC, San Diego, CA) was implemented at TJUH as a replacement for the older model Hemochron Response (Accriva/ITC Model HRS.110, San Diego, CA). Operating room (OR) perfusionists reported irreproducible high results using HSE that could not be explained clinically. In consideration of use of i-STAT analyzers (Abbott Point of Care, Princeton, NJ) as an alternative to HSE, we ...


Performance Of Creatinine And Chloride On The Epoc Analyzer, Lilah Evans, Susanne Gallo, Stacey K. Mardekian, Barbara Goldsmith, PhD, FACB 2016 Thomas Jefferson University Hospitals, Philadelphia, PA, USA

Performance Of Creatinine And Chloride On The Epoc Analyzer, Lilah Evans, Susanne Gallo, Stacey K. Mardekian, Barbara Goldsmith, Phd, Facb

Pathology, Anatomy and Cell Biology Posters

BACKGROUND

The epoc Blood Analysis System (Alere, Orlando, FL) performs blood gases, electrolytes, and metabolites using a Blood Gas Electrolyte and Metabolite (BGEM) Test Card panel on 92 uL of whole blood. The BGEM test card uses potentiometric sensors to measure sodium, potassium, ionized calcium, pH, pCO2; amperometric sensors to measure pO2, glucose, and lactate; and a conductometric sensor to measure hematocrit. Results are available in 3-10 minutes, depending upon the time between calibration and patient testing. TJUH implemented the epoc in its ICUs in 2012 to provide Point of Care (POC) results. Alere recently added creatinine and chloride sensors ...


Hepatic Fibrosis And Immune Phenotype Vary By Hcv Viremia In Hcv/Hiv Co-Infected Subjects: A Women's Interagency Hiv Study., Seema N Desai, Jennifer L Dodge, Alan L Landay, Marshall J Glesby, Patricia S. Latham, Maria C Villacres, Audrey L French, Stephen J Gange, Ruth M Greenblatt, Marion G Peters 2016 George Washington University

Hepatic Fibrosis And Immune Phenotype Vary By Hcv Viremia In Hcv/Hiv Co-Infected Subjects: A Women's Interagency Hiv Study., Seema N Desai, Jennifer L Dodge, Alan L Landay, Marshall J Glesby, Patricia S. Latham, Maria C Villacres, Audrey L French, Stephen J Gange, Ruth M Greenblatt, Marion G Peters

Pathology Faculty Publications

HCV and HIV independently lead to immune dysregulation. The mechanisms leading to advanced liver disease progression in HCV/HIV coinfected subjects remain unclear.

In this cross-sectional study, we assessed the association of HCV viremia, liver fibrosis, and immune response patterns in well-characterized HIV phenotypes: Elite controllers (Elites), HIV controlled (ARTc), and HIV uncontrolled (ARTuc) matched by age and race. Groups were stratified by HCV RNA status. Regulatory T-cell frequencies, T-cell activation (HLADR+CD38+), apoptosis (Caspase-3+), and intracellular cytokines (interferon-γ, IL-2, IL-17) were assessed using multiparametric flow-cytometry. Liver fibrosis was scored by AST to platelet ratio index (APRI).

We found liver ...


Routine Screening For Abdominal Aortic Aneurysm: Is It For Everyone?, Catherine E. Nowak 2016 James Madison University

Routine Screening For Abdominal Aortic Aneurysm: Is It For Everyone?, Catherine E. Nowak

Physician Assistant Capstones

Objective: Determine whether routine abdominal ultrasound screening in all men ages 65 and over, not just those who are symptomatic or at risk, would be beneficial in reducing the mortality rate from abdominal aortic aneurysms (AAA). Design: Systematic literature review. Methods: The clinical question investigated is whether routine ultrasound screening of AAA for men over age 65 reduces AAA-related mortality as compared to not routinely screening. Searches were done through PubMed using the keywords: screening, abdominal aortic aneurysm, reduce, and mortality. Citations used by the USPSTF AAA screening guidelines were also added to the literature search. In PubMed, further limitations ...


Left Ventricular Noncompaction Syndrome: A Rare Congenital Cardiomyopathy, Ashwini V. Mallad, MBBS, Waseem Ahmed, MD, Madhulika Urella, MD, Dr. Mehiar El-Hamdani, MD, FACC, FSCAI 2016 Marshall University School of Medicine

Left Ventricular Noncompaction Syndrome: A Rare Congenital Cardiomyopathy, Ashwini V. Mallad, Mbbs, Waseem Ahmed, Md, Madhulika Urella, Md, Dr. Mehiar El-Hamdani, Md, Facc, Fscai

Marshall Journal of Medicine

Isolated left ventricular noncompaction cardiomyopathy (LVNC) is a rare congenital condition occurring due to arrest of myocardial compaction in the first trimester, resulting in a thin layer of compacted epicardium and thick hypertrabeculated myocardium containing deep recesses. This article presents a 44-year-old female with progressive dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and pleuritic chest pain. Examination revealed elevated jugular venous distention, lower extremity edema, and bibasilar crackles on lung auscultation, while the electrocardiogram (EKG) exhibited left bundle branch block. Two-dimensional echocardiography (2D-Echo) showed a dilated left ventricle (LV) with ejection fraction (EF) of 25% and severe diffuse hypokinesia. Cardiac magnetic resonance ...


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