Medicine and Health Sciences Commons^™

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 …

Assessment For Risk Factors Associated With Local Recurrence In Chordoma, John A. Abraham, Md, Wei Jiang, Md, Phd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Chordoma is a rare but locally aggressive malignant neoplasm showing notochordal differentiation. The clinical differential diagnoses can be extensive, and definitive diagnosis often relies on histopathologic evaluation. Histologically, chordoma shows dual epithelial and mesenchymal differentiation, with various morphologies. Despite surgical resection and use of adjuvant radiation therapy, the local recurrence rate of chordoma remains high. We aim to establish factors associated with the increased risk of recurrence and help guide treatment decisions.

Age-Related Ebv-Associated Lymphoproliferative Disorder With Widespread Gastrointestinal Involvement And Subsequent Development Of T-Cell Lymphoma, Guldeep Uppal, Md, Alaina Chodoff, Msii, Zi-Xuan Wang, Phd, Jeffrey P. Baliff Md, Jerald Z. Gong, Md

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background

Age-related EBV-associated lymphoproliferative disorder (AR-EBVLPD) has emerged as a new subset of B-cell lymphoproliferative disorders. We report a unique case of AR-EBVLPD with a widespread gastrointestinal presentation and subsequent transformation to EBV-associated T-cell lymphoma. To our knowledge, this is the first report of a generalized polymorphic extranodal AR-EBVLPD with subsequent transformation to EBV-induced T-cell lymphoma.

Post-Transcriptional Modifications To Trna--A Response To The Genetic Code Degeneracy., Ya-Ming Hou, Wei Yang

Department of Biochemistry and Molecular Biology Faculty Papers

No abstract provided.

G Protein Βγ Subunits Regulate Cardiomyocyte Hypertrophy Through A Perinuclear Golgi Phosphatidylinositol 4-Phosphate Hydrolysis Pathway., S Malik, R G Derubio, M Trembley, R Irannejad, Philip B Wedegaertner, A V Smrcka

Department of Biochemistry and Molecular Biology Faculty Papers

We recently identified a novel GPCR-dependent pathway for regulation of cardiac hypertrophy that depends on Golgi phosphatidylinositol 4-phosphate (PI4P) hydrolysis by a specific isoform of phospholipase C (PLC), PLCε, at the nuclear envelope. How stimuli are transmitted from cell surface GPCRs to activation of perinuclear PLCε is not clear. Here we tested the role of G protein βγ subunits. Gβγ inhibition blocked ET-1-stimulated Golgi PI4P depletion in neonatal and adult ventricular myocytes. Blocking Gβγ at the Golgi inhibited ET-1-dependent PI4P depletion and nuclear PKD activation. Translocation of Gβγ to the Golgi stimulated perinuclear Golgi PI4P depletion and nuclear PKD activation. …

Lymph Node But Not Intradermal Injection Site Macrophages Are Critical For Germinal Center Formation And Antibody Responses To Rabies Vaccination., Andrew G Lytle, Shixue Shen, James Mcgettigan

Department of Microbiology and Immunology Faculty Papers

UNLABELLED: Replication-deficient rabies virus (RABV)-based vaccines induce rapid and potent antibody responses via T cell-independent and T cell-dependent mechanisms. To further investigate early events in vaccine-induced antibody responses against RABV infections, we studied the role of macrophages as mediators of RABV-based vaccine immunogenicity. In this report, we show that a recombinant matrix gene-deleted RABV-based vaccine (rRABV-ΔM) infects and activates primary murine macrophages in vitro. Immunization of mice with live RABV-based vaccines results in accumulation of macrophages at the site of immunization, which suggests that macrophages in tissues support the development of effective anti-RABV B cell responses. However, we show that …

The Onchocerciasis Vaccine For Africa-Tova-Initiative., Peter J Hotez, Maria Elena Bottazzi, Bin Zhan, Benjamin L Makepeace, Thomas R Klei, David Abraham, David W Taylor, Sara Lustigman

Department of Microbiology and Immunology Faculty Papers

No abstract provided.

Management Of Cerebral Cavernous Malformations: From Diagnosis To Treatment, Nikolaos Mouchtouris, Nohra Chalouhi, Md, Ameet Chitale, Robert Starke, Stavropoula Tjoumakaris, Robert H. Rosenwasswer Md, P. M. Jabbour

Department of Neurosurgery Faculty Papers

No abstract provided.

Expression Of Interferon Gamma By A Recombinant Rabies Virus Strongly Attenuates The Pathogenicity Of The Virus Via Induction Of Type I Interferon., Darryll A Barkhouse, Samantha A Garcia, Emily K Bongiorno, Aurore Lebrun, Milosz Faber, D Craig Hooper, Phd

Department of Cancer Biology Faculty Papers

UNLABELLED: Previous animal model experiments have shown a correlation between interferon gamma (IFN-γ) expression and both survival from infection with attenuated rabies virus (RABV) and reduction of neurological sequelae. Therefore, we hypothesized that rapid production of murine IFN-γ by the rabies virus itself would induce a more robust antiviral response than would occur naturally in mice. To test this hypothesis, we used reverse engineering to clone the mouse IFN-γ gene into a pathogenic rabies virus backbone, SPBN, to produce the recombinant rabies virus designated SPBNγ. Morbidity and mortality were monitored in mice infected intranasally with SPBNγ or SPBN(-) control virus …