Medicine and Health Sciences Commons^™

Enpp1 Variants In Patients With Gaci And Pxe Expand The Clinical And Genetic Heterogeneity Of Heritable Disorders Of Ectopic Calcification., Douglas Ralph, Yvonne Nitschke, Michael A Levine, Matthew Caffet, Tamara Wurst, Amir Hossein Saeidian, Leila Youssefian, Hassan Vahidnezhad, Sharon F Terry, Frank Rutsch, Jouni Uitto, Qiaoli Li

Department of Medicine Faculty Papers

Pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI) are clinically distinct genetic entities of ectopic calcification associated with differentially reduced circulating levels of inorganic pyrophosphate (PPi), a potent endogenous inhibitor of calcification. Variants in ENPP1, the gene mutated in GACI, have not been associated with classic PXE. Here we report the clinical, laboratory, and molecular evaluations of ten GACI and two PXE patients from five and two unrelated families registered in GACI Global and PXE International databases, respectively. All patients were found to carry biallelic variants in ENPP1. Among ten ENPP1 variants, one homozygous variant demonstrated uniparental disomy …

Gestational Weight Gain In 4 Low- And Middle-Income Countries And Associations With Birth Outcomes: A Secondary Analysis Of The Women First Trial., Melissa S Bauserman, Carla M Bann, K Michael Hambidge, Ana L Garces, Lester Figueroa, Jamie L Westcott, Jackie K Patterson, Elizabeth M Mcclure, Vanessa R Thorsten, Sumera Ali Aziz, Sarah Saleem, Robert L Goldenberg, Richard Derman, Veena Herekar, Manjunath Somannavar, Marion W Koso-Thomas, Adrien L Lokangaka, Antoinette K Tshefu, Nancy F Krebs, Carl L Bose, Shivaprasad Goudar, Sangappa Dhaded, Bhalchandra Kodkany, Omrana Pasha, Abhik Das, Menachem Miodovnik, N K Raju Tonse

Global Health Articles

BACKGROUND: Adequate gestational weight gain (GWG) is essential for healthy fetal growth. However, in low- and middle-income countries, where malnutrition is prevalent, little information is available about GWG and how it might be modified by nutritional status and interventions.

OBJECTIVE: We describe GWG and its associations with fetal growth and birth outcomes. We also examined the extent to which prepregnancy BMI, and preconception and early weight gain modify GWG, and its effects on fetal growth.

METHODS: This was a secondary analysis of the Women First Trial, including 2331 women within the Democratic Republic of Congo (DRC), Guatemala, India, and Pakistan, …

Targeting Human Langerin Promotes Hiv-1 Specific Humoral Immune Responses., Jérôme Kervevan, Aurélie Bouteau, Juliane S Lanza, Adele Hammoudi, Sandra Zurawski, Mathieu Surenaud, Lydie Dieudonné, Marion Bonnet, Cécile Lefebvre, Hakim Hocini, Romain Marlin, Aurélie Guguin, Barbara Hersant, Oana Hermeziu, Elisabeth Menu, Christine Lacabaratz, Jean-Daniel Lelièvre, Gerard Zurawski, Véronique Godot, Sandrine Henri, Botond Z. Igyártó, Yves Levy, Sylvain Cardinaud

Department of Microbiology and Immunology Faculty Papers

The main avenue for the development of an HIV-1 vaccine remains the induction of protective antibodies. A rationale approach is to target antigen to specific receptors on dendritic cells (DC) via fused monoclonal antibodies (mAb). In mouse and non-human primate models, targeting of skin Langerhans cells (LC) with anti-Langerin mAbs fused with HIV-1 Gag antigen drives antigen-specific humoral responses. The development of these immunization strategies in humans requires a better understanding of early immune events driven by human LC. We therefore produced anti-Langerin mAbs fused with the HIV-1 gp140z Envelope (αLC.Env). First, we show that primary skin human LC and …

An Insulator Blocks Access To Enhancers By An Illegitimate Promoter, Preventing Repression By Transcriptional Interference., Miki Fujioka, Anastasiya Nezdyur, James B. Jaynes

Department of Biochemistry and Molecular Biology Faculty Papers

Several distinct activities and functions have been described for chromatin insulators, which separate genes along chromosomes into functional units. Here, we describe a novel mechanism of functional separation whereby an insulator prevents gene repression. When the homie insulator is deleted from the end of a Drosophila even skipped (eve) locus, a flanking P-element promoter is activated in a partial eve pattern, causing expression driven by enhancers in the 3' region to be repressed. The mechanism involves transcriptional read-through from the flanking promoter. This conclusion is based on the following. Read-through driven by a heterologous enhancer is sufficient to repress, even …

Input-Output Signal Processing Plasticity Of Vagal Motor Neurons In Response To Cardiac Ischemic Injury., Jonathan Gorky, Alison Moss, Marina Balycheva, Rajanikanth Vadigepalli, James S. Schwaber

Computational Medicine Center Faculty Papers

Vagal stimulation is emerging as the next frontier in bioelectronic medicine to modulate peripheral organ health and treat disease. The neuronal molecular phenotypes in the dorsal motor nucleus of the vagus (DMV) remain largely unexplored, limiting the potential for harnessing the DMV plasticity for therapeutic interventions. We developed a mesoscale single-cell transcriptomics data from hundreds of DMV neurons under homeostasis and following physiological perturbations. Our results revealed that homeostatic DMV neuronal states can be organized into distinguishable input-output signal processing units. Remote ischemic preconditioning induced a distinctive shift in the neuronal states toward diminishing the role of inhibitory inputs, with …

Three-Dimensional Structure Of Human Cyclooxygenase (Hcox)-1., Morena Miciaccia, Benny Danilo Belviso, Mariaclara Iaselli, Gino Cingolani, Savina Ferorelli, Marianna Cappellari, Paola Loguercio Polosa, Maria Grazia Perrone, Rocco Caliandro, Antonio Scilimati

Department of Biochemistry and Molecular Biology Faculty Papers

The beneficial effects of Cyclooxygenases (COX) inhibitors on human health have been known for thousands of years. Nevertheless, COXs, particularly COX-1, have been linked to a plethora of human diseases such as cancer, heart failure, neurological and neurodegenerative diseases only recently. COXs catalyze the first step in the biosynthesis of prostaglandins (PGs) and are among the most important mediators of inflammation. All published structural work on COX-1 deals with the ovine isoenzyme, which is easier to produce in milligram-quantities than the human enzyme and crystallizes readily. Here, we report the long-sought structure of the human cyclooxygenase-1 (hCOX-1) that we refined …

The Role Of Mirnas, Mirna Clusters, And Isomirs In Development Of Cancer Stem Cell Populations In Colorectal Cancer., Victoria A Stark, Caroline O B Facey, Vignesh Viswanathan, Bruce M Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

MicroRNAs (miRNAs or miRs) have a critical role in regulating stem cells (SCs) duringdevelopment and altered expression can cause developmental defects and/or disease. Indeed,aberrant miRNA expression leads to wide-spread transcriptional dysregulation which has beenlinked to many cancers. Mounting evidence also indicates a role for miRNAs in the developmentof the cancer SC (CSC) phenotype. Our goal herein is to provide a review of: (i) current researchon miRNAs and their targets in colorectal cancer (CRC), and (ii) miRNAs that are differentiallyexpressed in colon CSCs. MicroRNAs can work in clusters or alone when targeting different SC genesto influence CSC phenotype. Accordingly, we discuss …

Physiochemical Characteristics Of Hot And Cold Brew Coffee Chemistry: The Effects Of Roast Level And Brewing Temperature On Compound Extraction., Niny Z. Rao, Megan Fuller, Meghan D Grim

College of Life Sciences Faculty Papers

The role of roasting in cold brew coffee chemistry is poorly understood. The brewing temperature influences extraction processes and may have varying effects across the roast spectrum. To understand the relationship between brew temperature and roast temperature, hot and cold brew coffees were prepared from Arabica Columbian coffee beans roasted to light, medium, and dark levels. Chemical and physical parameters were measured to investigate the relationships among degree of roast, water temperature, and key characteristics of resulting coffees. Cold brew coffees showed differential extraction marked by decreased acidity, lower concentration of browned compounds, and fewer TDS indicating that cold water …

Mobilizing Toxins For Cancer Treatment: Historical Perspectives And Current Strategies., Jessica Kopenhaver, Robert D Carlson, Adam E Snook

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The level of complexity in a disease like cancer presents a number of challenges for effective treatment development, which require significant innovation to overcome [...].

Structural Basis For The Homotypic Fusion Of Chlamydial Inclusions By The Snare-Like Protein Inca., Gino Cingolani, Michael Mccauley, Anna Lobley, Alexander J Bryer, Jordan Wesolowski, Deanna L Greco, Ravi K Lokareddy, Erik Ronzone, Juan R Perilla, Fabienne Paumet

Department of Biochemistry and Molecular Biology Faculty Papers

Many intracellular bacteria, including Chlamydia, establish a parasitic membrane-bound organelle inside the host cell that is essential for the bacteria's survival. Chlamydia trachomatis forms inclusions that are decorated with poorly characterized membrane proteins known as Incs. The prototypical Inc, called IncA, enhances Chlamydia pathogenicity by promoting the homotypic fusion of inclusions and shares structural and functional similarity to eukaryotic SNAREs. Here, we present the atomic structure of the cytoplasmic domain of IncA, which reveals a non-canonical four-helix bundle. Structure-based mutagenesis, molecular dynamics simulation, and functional cellular assays identify an intramolecular clamp that is essential for IncA-mediated homotypic membrane fusion during …

Single-Cell Gene Expression Analysis Identifies Chronic Alcohol-Mediated Shift In Hepatocyte Molecular States After Partial Hepatectomy., Sirisha Achanta, Aalap Verma, Ankita Srivastava, Harshavardhan Nilakantan, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The analysis of molecular states of individual cells, as defined by their mRNA expression profiles and protein composition, has gained widespread interest in studying biological phenomena ranging from embryonic development to homeostatic tissue function and genesis and evolution of cancers. Although the molecular content of individual cells in a tissue can vary widely, their molecular states tend to be constrained within a transcriptional landscape partly described by the canonical archetypes of a population of cells. In this study, we sought to characterize the effects of an acute (partial hepatectomy) and chronic (alcohol consumption) perturbation on the molecular states of individual …

Download Entire Issue: Gibbon Surgical Review, Volume 2, Issue 1, 2019

Gibbon Surgical Review

Table of Contents

4 - The Gibbon Surgical Externship: A Student’s Perspective

6 - Invited Article: The PCOM Wisely Surgical Association and the Philadelphia Surgery Conference

8 - Interview With Thomas Jefferson Cardiothoracic Surgeon, H. Todd Massey, MD

12 - The Life of a Rwandan Surgical Resident

14 - Role Of Technological Advancement In The Context Of Surgical Planning And Execution: Perspective Of Jefferson Surgical Faculty

16 - Interview with William B. Hughes, MD, Director of the Thomas Jefferson University Hospital Burn Center

19 - Women in Surgery: An Interview with Dr. Karen Chojnacki, Vice Chair of Surgical Education at …

Download Entire Issue: Gibbon Surgical Review, Volume 1, Issue 2, 2018

Gibbon Surgical Review

Table of Contents

• Forward by Charles J. Yeo, MD, FACS
• PERSPECTIVE - An Interview with Dr. Theresa Yeo, Co-Director of the Jefferson Pancreas Tumor Registry (JPTR)
• A PGY-1's Perspective: Conducting Pancreatic Cancer Research as a Medical Student
• INTERVIEW - Jonathan Brody, PhD - Pancreatic Cancer Specialist
• RESEARCH SPOTLIGHT - The Journal of Pancreatic Cancer
• Pancreatic Cancer Research at Jefferson: The Mary Halinski Pancreatic Cancer Research Fund
• The Gibbon Surgical Society
• Contributors
• Samuel D. Gross Professor of Surgery: Charles J. Yeo, MD, FACS

Download Entire Issue: Gibbon Surgical Review, Volume 1, Issue 1, 2018

Gibbon Surgical Review

Table of Contents

• A First Year's Perspective on JeffMD, Somnath Das, MS1
• Spotlight on TJUH's Quality and Safety Group, Samantha L. Savitch, MS1
• Medical Student Involvement in Quality Improvement Research, Tyler M. Bauer, MS3
• Global Surgery: A Shift in the Global Health Paradigm, Myles S. Dworkin, MS3
• Thomas Jefferson University Design Vault, Victor B. Hsue, MS2
• Physician Spotlight: Ernest (Gary) L. Rosato, MD, FACS, Carrie E. Andrews, MS3
• The SCALPELS Program, Emily Papai, MS1

Silencing Of The Pink1 Gene Expression By Conditional Rnai Does Not Induce Dopaminergic Neuron Death In Mice., Hongxia Zhou, Björn H Falkenburger, Jörg B Schulz, Kim Tieu, Zuoshang Xu, Xu Gang Xia

Kim Tieu

Transgenic RNAi, an alternative to the gene knockout approach, can induce hypomorphic phenotypes that resemble those of the gene knockout in mice. Conditional transgenic RNAi is an attractive choice of method for reverse genetics in vivo because it can achieve temporal and spatial silencing of targeted genes. Pol III promoters such as U6 are widely used to drive the expression of RNAi transgenes in animals. Tested in transgenic mice, a Cre-loxP inducible U6 promoter drove the broad expression of an shRNA against the Pink1 gene whose loss-of-functional mutations cause one form of familial Parkinson's disease. The expression of the shRNA …

High-Resolution Physical Map For Chromosome 16q12.1-Q13, The Blau Syndrome Locus., Xiaoju Wang, Helena Kuivaniemi, Gina Bonavita, Charlene J Williams, Gerard Tromp

Charlene Williams

BACKGROUND: The Blau syndrome (MIM 186580), an autosomal dominant granulomatous disease, was previously mapped to chromosome 16p12-q21. However, inconsistent physical maps of the region and consequently an unknown order of microsatellite markers, hampered us from further refining the genetic locus for the Blau syndrome. To address this problem, we constructed our own high-resolution physical map for the Blau susceptibility region. RESULTS: We generated a high-resolution physical map that provides more than 90% coverage of a refined Blau susceptibility region. The map consists of four contigs of sequence tagged site-based bacterial artificial chromosomes with a total of 124 bacterial artificial chromosomes, …

A Delayed H3k27me3 Accumulation After Dna Replication Of Embryonic Stem Cells Opens Chromatin For Lineage Specific Transcription Factors To Bind And Initiate Differentiation, Jingli Cai, Svetlana Petruk, Robyn Sussman, Sina K. Kovermann, Samantha Mariani, Bruno Calabretta, Steven B Mcmahon, Hugh W. Brock, Lorraine Iacovitti, Alexander Mazo

Department of Neuroscience Faculty Papers

Introduction

Pluripotent stem cells (PSCs) have been useful to generate differentiated progenies for cell replacement therapy, and disease models. The Parkinson’s Disease (PD) field was arguably one of the first to have embraced the promise of stem cells. However, regardless of the differentiation protocols used, cultures and grafts continue to contain multiple cell types with midbrain dopamine (mDA) neural progenitors (NPs) and neurons representing only a fraction of total cells in the dish or graft. During cell differentiation, recruitment of transcription factors (TFs) to repressed genes in euchromatin is essential to activate new transcriptional programs, which is impeded by condensed …

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

Department of 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.

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

Department of 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).

The Structure And Regulation Of Cullin 2 Based E3 Ubiquitin Ligases And Their Biological Functions., Weijia Cai, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Cullin-RING E3 ubiquitin ligase complexes play a central role in targeting cellular proteins for ubiquitination-dependent protein turnover through 26S proteasome. Cullin-2 is a member of the Cullin family, and it serves as a scaffold protein for Elongin B and C, Rbx1 and various substrate recognition receptors to form E3 ubiquitin ligases.

MAIN BODY OF THE ABSTRACT: First, the composition, structure and the regulation of Cullin-2 based E3 ubiquitin ligases were introduced. Then the targets, the biological functions of complexes that use VHL, Lrr-1, Fem1b, Prame, Zyg-11, BAF250, Rack1 as substrate targeting subunits were described, and their involvement in diseases …

Use Of Propensity Score Matching To Identify A Strong Association Between Strategic Concentration To Mitochondria-Sr Associations Of The Mitochondrial Ca2+ Uniporter: Ca2+ Uptake Hotspots In The Cardiac Mitochondria, Sergio De La Fuente, Caitlin Vail, Elorm J. Agra, Kira Holmstrom, Junhui Sun, Jyotsna Mishra, Toren Kinkel, Elizabeth Murphy, Suresh K. Joseph, Shey-Shing Shen, György Csordás

Department of 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).

Gaining Competencies During Early Medical Training: Medical Students As Teaching Assistants In Dissection-Based Anatomy Course, Martin T. Brown, Bruce Fenderson, Guiyan Zhang

Department of Pathology, Anatomy, and Cell Biology Posters

Introduction and Objectives

• In 2002, ACGME identified six ACGME Core Competencies: patient care; medical knowledge; practice-based learning and improvement; interpersonal and communication skills; professionalism; and systems-based practice.
• AAMC recommended lists of similar competencies for the curricula of medical schools. Competency based curricula have been widely implemented in medical schools.
• Effective shifting in the graduate medical educational programs has been reported in various clinical specialties.
• There is a lack of reported efforts and development on competency training in early preclinical years of medical education.

Objectives:

• To explore methods for strengthening medical students’ competency training during preclinical undergraduate medical education.
• To measure …

Cells Activated For Wound Repair Have The Potential To Direct Collective Invasion Of An Epithelium., Brigid M Bleaken, A Sue Menko, Janice Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Mechanisms regulating how groups of cells are signaled to move collectively from their original site and invade surrounding matrix are poorly understood. Here we develop a clinically relevant ex vivo injury invasion model to determine whether cells involved in directing wound healing have invasive function and whether they can act as leader cells to direct movement of a wounded epithelium through a three-dimensional (3D) extracellular matrix (ECM) environment. Similar to cancer invasion, we found that the injured cells invade into the ECM as cords, involving heterotypical cell-cell interactions. Mesenchymal cells with properties of activated repair cells that typically locate to …

In-Silico Identification Of Prognostically Inversely Correlated Mirnas And Mrnas (Pic’S) In Multiple Cancers, Chirayu Pankaj Goswami, Zi-Xuan Wang

Department of Pathology, Anatomy, and Cell Biology Posters

Despite numerous methods available to identify potential mRNA targets for miRNAs, prognostic relationship of these molecules in diseases like cancers where deregulation of gene expression is a major pathogenic factor, has not yet been emphasized. We performed in-silico identification of prognostically inversely correlated miRNA - mRNA pairs (PIC’s) in multiple cancers using expression data from The Cancer Genome Atlas. Partners in a PIC show inverse correlation of expression and opposite hazard implication. Using a three step approach, we identified a total of 1,253,443 PIC’s from 23 cancer types, several of which have previously been shown to have a predicted or …

A Phase I Study Of Ad5-Gucy2c-Padre In Stage I And Ii Colon Cancer Patients, Adam E. Snook, Trevor R. Baybutt, Michael J. Mastrangelo, Nancy L. Lewis, Scott D. Goldstein, Walter K. Kraft, Yaa D. Oppong, Terry Hyslop, Ronald E. Myers, Vitali Alexeev, Laurence C. Eisenlohr, Takami Sato, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Posters

Background

Ad5-GUCY2C-PADRE is a replication-deficient human type 5 recombinant adenovirus (Ad5) vaccine encoding guanylyl cyclase C (GUCY2C) fused to the PAn DR Epitope (PADRE). GUCY2C, a paracrine hormone receptor producing the second messenger cyclic GMP (cGMP), is selectively expressed by intestinal epithelial cells and a subset of hypothalamic neurons, but not other tissues. Importantly, GUCY2C is over-expressed in nearly all primary and metastatic human colorectal tumors. Preclinical studies in mice demonstrated selective tolerance of GUCY2C-specific CD4+ T cells, but not CD8+ T or B cells, necessitating inclusion of the exogenous CD4+ T helper cell epitope PADRE to maximize GUCY2C-specific CD8+ …

Association Of Adipokines With Insulin Resistance, Microvascular Dysfunction, And Endothelial Dysfunction In Healthy Young Adults., Cindy Cheng, Md, Phd, Constantine Daskalakis

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Proinflammatory adipokines (inflammation markers) from visceral adipose tissue may initiate the development of insulin resistance (IR) and endothelial dysfunction (ED). This study's objective was to investigate the association of five inflammation markers (CRP and four adipokines: IL-6, TNFα, PAI-1, and adiponectin) with IR (quantitative insulin resistance check index (QUICKI)), microvascular measures (capillary density and albumin-to-creatinine ratio (ACR)), and endothelial measures (forearm blood flow (FBF) increases from resting baseline to maximal vasodilation). Analyses were conducted via multiple linear regression. The 295 study participants were between 18 and 45 years of age, without diabetes or hypertension. They included 24% African Americans and …

An Assessment Of The Reliability Of Platelet-Associated Flags Generated By The Sysmex Xe-5000 Automated Hematology Analyzer In Detecting Platelet Clumps, Jennifer M. Hawkins, Do, Gene Gulati, Ph.D, Guldeep Uppal, Md, Jerald Z. Gong, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

XE-5000 is an automated hematology analyzer utilized by clinical laboratories worldwide to perform CBC and differential leukocyte counts on EDTA-anticoagulated blood specimens. The overall reliability of the results generated by this analyzer has been assessed and found acceptable for clinical use. The CBC results generated on some of the blood specimens are, however, flagged by the analyzer for verification of the result of the flagged parameter by other means. One such parameter of clinical significance is the automated platelet count, which is often unreliable if the blood specimen contains platelet clumps.

Phylogenetic Tree Construction And “Truncal Loss” Analysis Reveal Hidden Associations Between Loss Of Protein Expression In Swi/Snf Complex Components And Tumor Stage And Survival In Clear Cell Renal Cell Carcinoma (Ccrcc), Wei Jiang, Md, Phd, Essel Dulaimi, Karthik Devarajan, Qiong Wang, Raymond O'Neill, Charalambos C. Solomides, Md, Stephen C Peiper, Phd, Robert Uzzo, Joseph R. Testa, Haifeng Yang, Phd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Polybromo-1 (PBRM1), a targeting subunit of the SWI/SNF chromatin remodeling complex, is mutated at a rate of ~40% in clear cell Renal Cell Carcinoma (ccRCC), second only to VHL. Whether its mutation is correlated with tumor stage is controversial. As other components of the SWI/SNF complex were also reported to be mutated in ccRCC, we aim to examine the protein expression patterns of PBRM1, ARID1A, BRG1, and BRM in ccRCC, and to investigate possible association between their loss of expression and tumor stage, as well as survival. We also included a histone modifier, SETD2, which is recently discovered to …

Loss Of Expression Of Swi/Snf Chromatin Remodeling Complex Components And Setd2 Are Heterogeneous, Widespread, And Co-Occur In Clear Cell Renal Cell Carcinoma, Wei Jiang, Md, Phd, Essel Dulaimi, Theodore Parsons, Qiong Wang, Karthik Devarajan, Raymond O'Neill, Charalambos C. Solomides, Md, Stephen C Peiper, Phd, Jospeh R. Testa, Robert Uzzo, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

The subunits of the SWI/SNF chromatin remodeling complex have one of the highest mutation rate in human cancers (see Figure 1). Polybromo-1 (PBRM1), a subunit of the SWI/SNF complex, is the second most mutated gene (40%) in clear cell Renal Cell Carcinoma (ccRCC). ARID1A, another subunit that competes with PBRM1 for binding to the complex, was infrequently mutated. The protein expressions of BRG1 and BRM (two catalytic subunits of the complex), and SETD2, a histone modifier (10-15% mutation rate), are not known in ccRCC. In this study we examined their protein expressions by immunohistochemistry (IHC) in tissue microarrays (TMAs), …

Pathology Encountered During Cadaver Dissection Provides An Opportunity For Integrated Learning And Critical Thinking, Guiyan Zhang, Bruce Fenderson

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Abstract

Cadaver dissection engages medical students in active learning, critical thinking, and problem solving. During dissection, students at SKMC are encouraged to document pathologic findings in their cadavers and discuss the findings with their peers. Here, we describe two cases that provided opportunities for integrating anatomy with pathology and clinical medicine. The first case was a benign ovarian neoplasm. This large pelvic mass displaced the urinary bladder and uterus, and compressed the ureters and rectum. Students discussed clinical complications of this pelvic mass and reviewed pathologic findings that differentiate benign from malignant neoplasms. The second case was breast cancer with …