Medical Cell Biology Commons^™

A Rare Fatal Case Of Adenovirus Serotype 4 Associated Acute Disseminated Encephalomyelitis In An Adult: A Case Report, Zahra Qamar, Catherine Tucker, Lawrence C. Kenyon, Tricia. Royer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Acute disseminated encephalomyelitis (ADEM) is an autoimmune demyelinating disease directed against the myelin sheath of the central nervous system that typically presents 1–4 weeks after an infection or vaccination, most commonly in children. We describe a case of a young female who presented with rapidly progressive mental deterioration and died secondary to ADEM following an adenovirus upper respiratory tract infection.

Immune Cells In Lens Injury Repair And Fibrosis, Janice L Walker, A. Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Immune cells, both tissue resident immune cells and those immune cells recruited in response to wounding or degenerative conditions, are essential to both the maintenance and restoration of homeostasis in most tissues. These cells are typically provided to tissues by their closely associated vasculatures. However, the lens, like many of the tissues in the eye, are considered immune privileged sites because they have no associated vasculature. Such absence of immune cells was thought to protect the lens from inflammatory responses that would bring with them the danger of causing vision impairing opacities. However, it has now been shown, as occurs …

Mapping The Little Brain At The Heart By An Interdisciplinary Systems Biology Team., Rajanikanth Vadigepalli, James S. Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

No abstract provided.

Dabigatran Reduces Thrombin-Induced Neuroinflammation And Ad Markers In Vitro: Therapeutic Relevance For Alzheimer's Disease, Syed Waseem Bihaqi, Haripriya Vittal Rao, Abhik Sen, Paula Grammas

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Vascular risk factors such as atherosclerosis, diabetes, and elevated homocysteine levels are strongly correlated with onset of Alzheimer's disease (AD). Emerging evidence indicates that blood coagulation protein thrombin is associated with vascular and non-vascular risk factors of AD. Here, we examined the effect of thrombin and its direct inhibitor dabigatran on key mediators of neuro-inflammation and AD pathology in the retinoic acid (RA)-differentiated human neuroblastoma cell line SH-SY5Y. Methods: SH-SY5Y cells exposed to thrombin concentrations (10–100 nM) +/- 250 nM dabigatran for 24 h were analyzed for protein and gene expression. Electrophoretic mobility shift assay (EMSA) was used to …

Impaired 26s Proteasome Assembly Precedes Neuronal Loss In Mutant Ubqln2 Rats., Wenjuan Zhang, Bo Huang, Limo Gao, Cao Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Proteasomal dysfunction is known to be associated with amyotrophic lateral sclerosis and frontotemporal degeneration (ALS/FTD). Our previous reports have shown that a mutant form of ubiquilin-2 (UBQLN2) linked to ALS/FTD leads to neurodegeneration accompanied by accumulations of the proteasome subunit Rpt1 in transgenic rats, but the precise pathogenic mechanisms of how this mutation impairs the proteasome remains to be elucidated. Here, we reveal that this UBQLN2 mutation in rats disrupted the proteasome integrity prior to neurodegeneration, that it dissociated the 26S proteasome in vitro, and that its depletion did not affect 26S proteasome assembly. During both disease progression and in …

Characterization And Clinical Significance Of Eif1ax Mutations And Co-Mutations In Cytologically Indeterminate Thyroid Nodules: A 5-Year Retrospective Analysis., Stacey Gargano, Nitika Badjatia, Yanina Nikolaus, Stephen C Peiper, Zi-Xuan Wang, Phd

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVE: Mutations in the EIF1AX gene have been recently detected in a small percentage of benign and malignant thyroid lesions. We sought to investigate the prevalence and clinical significance of EIF1AX mutations and co-mutations in cytologically indeterminate thyroid nodules at our institution.

MATERIALS AND METHODS: A 5-year retrospective analysis was performed on thyroid nodules with a cytologic diagnosis of Bethesda category III or IV, which had undergone testing by our in-house next generation sequencing panel. Surgically resected nodules with EIF1AX mutations were identified, and mutation type and presence of co-mutations were correlated with histopathologic diagnosis.

RESULTS: 41/904 (4.5%) cases overall …

Resident Immune Cells Of The Avascular Lens: Mediators Of The Injury And Fibrotic Response Of The Lens., A. Menko, Jodirae Dedreu, Caitlin M. Logan, Heather Paulson, Alex V Levin, Janice L Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Tissues typically harbor subpopulations of resident immune cells that function as rapid responders to injury and whose activation leads to induction of an adaptive immune response, playing important roles in repair and protection. Since the lens is an avascular tissue, it was presumed that it was absent of resident immune cells. Our studies now show that resident immune cells are a shared feature of the human, mouse, and chicken lens epithelium. These resident immune cells function as immediate responders to injury and rapidly populate the wound edge following mock cataract surgery to function as leader cells. Many of these resident …

Goblet Cell Carcinoma Of The Appendix: A Case Report On Goblet Cell Carcinoid, Sheliza Kabani, Aubtin Saedi, Austin Lehr, Lina O'Brien

HCA Healthcare Journal of Medicine

Goblet cell carcinoid of the appendix is a rare neoplasm with histological features of both neuroendocrine and adenocarcinomas. The combination of its aggressive behavior, infrequent occurrence, and variable clinical presentation convolutes the management of this tumor. We report the case of a 75-year-old female presenting with acute appendicitis. A laparoscopic appendectomy was performed. The pathology report showed goblet cell carcinoid at the base of the appendix with involvement of the proximal surgical margins. At her postoperative visit, the patient’s pathology report and options for management were reviewed, and the patient agreed to proceed with a right hemicolectomy 8-10 weeks after …

Specimens, Sara Kapadia

The Transdisciplinary STEAM+ Journal

A short rumination on specimens

Educational Case: A Case Of Transfusion-Transmitted Babesiosis: Diagnostic Perspectives Across The Clinical Laboratory., Kaitlyn Dykes, Alexis R. Peedin

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology.

Diurnal Patterns Of Gene Expression In The Dorsal Vagal Complex And The Central Nucleus Of The Amygdala - Non-Rhythm-Generating Brain Regions, Mary M Staehle, Sean O'Sullivan, Rajanikanth Vadigepalli, Kate F Kernan, Gregory E Gonye, Babatunde A Ogunnaike, James S. Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Genes that establish the circadian clock have differential expression with respect to solar time in central and peripheral tissues. Here, we find circadian-time-induced differential expression in a large number of genes not associated with circadian rhythms in two brain regions lacking overt circadian function: the dorsal vagal complex (DVC) and the central nucleus of the amygdala (CeA). These regions primarily engage in autonomic, homeostatic, and emotional regulation. However, we find striking diurnal shifts in gene expression in these regions of male Sprague Dawley rats with no obvious patterns that could be attributed to function or region. These findings have implications …

How Can We Stop Cancer?, Joseph R. Current

The Review: A Journal of Undergraduate Student Research

Cancer is a disease that humans have been struggling to combat for centuries. It originates from the accumulation of several mutations over the life of a cell that causes it to evade cell death and multiply rapidly. It can affect any tissue in the body and can spread to other parts of the body through metastasis. Cancer comes in numerous shapes and sizes with different levels of aggression, growth speeds, and health risks. Many treatments for cancer exist today, three of the most popular being surgery, chemotherapy, and radiation therapy, which can be used in combinations with other treatments to …

Ribonucleotide Reductase Inhibitor 3-Ap Induces Oncogenic Virus Infected Cell Death And Represses Tumor Growth, Lu Dai, Jungang Chen, Yueyu Cao, Luis Del Valle, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several human malignancies, particularly Kaposi's Sarcoma (KS), which preferentially arise in immunocompromised patients such as HIV+ subpopulation while still lacking of effective therapeutic options. We recently found that the ribonucleotide reductase (RR) subunit M2 is potentially regulated by the key oncogenic HGF/c-MET pathway in KSHV-related lymphoma cells. One of RR inhibitor, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) effectively induced apoptosis of KSHV+ lymphomas and suppressed tumor progression . In the current study, we found that 3-AP treatment selectively inhibited the proliferation of KSHV-infected endothelial cells, the major cellular components of KS, through inducing DNA …

The Comparison Of Spectral Domain Optical Coherence Tomography (Sd-Oct) To Histopathology In A Patient With Diffuse Macular Drusen, Harold Salmons, Ralph Eagle, Md

Department of Pathology Honors Program Student Research Symposium

Background: Spectral Domain Optical Coherence Tomography (SD-OCT) has become a gold standard technique in ophthalmologic practice, and has revolutionized the diagnosis and treatment of retinal disease. As SD-OCT uses low interference interferometry and mathematical algorithms to produce detailed theoretical cross-sectional images of the retina, it is crucial to examine correlations between SD-OCT images and their corresponding histopathologic slides.

Methods: In the present study, careful correlative light microscopy was performed on the eye that was enucleated from an elderly patient who had a uveal melanoma and early agerelated macular degeneration evident clinically as soft drusen. SD-OCT was performed prior to enucleation …

The Use Of Liquid Biopsy In The Fight Against Cancer, Chamaka Kalutota, Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

In recent years, liquid biopsy has emerged as a potential alternative/adjunct to standard tissue biopsy in the diagnosis of malignancies. Current use of this technique, which tracks distinctive molecules released from neoplastic cells including circulating tumor cells (CTCs), exosomes, circulating tumor DNA (ctDNA), cell-free DNA (cfDNA) and miRNA, has generally been limited to determining therapies in lung cancer based on detectable mutations (EFGR, EML4-ALK). However, recent studies have demonstrated the possibility for using these molecules as more efficient prognostic and diagnostic biomarkers in breast, colon, rectum, lung, liver, and pancreatic cancer. Due to the need for standardization in sampled material …

Genome Editing Technology, Crispr Cas-9, Provides A Potential Future For Xenotransplantation: Can Pigs Become Our New Organ Donors?, Shelby Smith, Bs, Emanual Rubin, Md

Department of Pathology Honors Program Student Research Symposium

Organ shortage has been a significant issue in United States for many decades. There were over 116,000 people on the transplant waiting list as of August 2017, with a new person added every 10 minutes. Animals have been considered as potential organ donors for humans, with the pig being the most ideal candidate because of its excellent breeding profile, low maintenance costs, large litters, rapid growth and organ similarity. A notable challenge that comes with porcine organs are endogenous retroviruses that establish themselves in the DNA of offspring in utero, thereby allowing for no time to prevent infection and integration. …

Acquired Resistance Mutations To Egfr Treatment In Non-Small Cell Lung Cancer, Benjamen Schoenberg, Gregory Omerza, Phd

Department of Pathology Honors Program Student Research Symposium

Non-small cell lung cancer (NSCLC) is currently the number one cause of cancer death in the United States for both men and women.1 Mutations in the epidermal growth factor receptor (EGFR) gene are detected in approximately 30% of individuals with advanced NSCLC in Asia and 10-15% in Western countries.2 For patients harboring activating EGFR mutations, treatment includes the use of first or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as afatinib, gefitinib, or erlotinib.

The purpose of this case study is to review the pathophysiology of the progression of NSCLC in a 63-year-old non-smoking Caucasian woman. The patient presented with worsening …

A New Frontier In Breast Cancer Management: Oncotype Dx, Gabriella Rollo, Jeremy Molligan, Md, Juan P. Palazzo, Md

Department of Pathology Honors Program Student Research Symposium

Diagnosing and prognosticating breast cancer has traditionally relied upon histomorphologic analysis and immunohistochemistry. With the recent advent of multigene molecular assays, traditional methods are being augmented with molecular biomarkers. Implementation of the Oncotype DX assay has led to a change in treatment of patients with early stage, estrogen positive cancer. Oncotype DX uses the expression of 21 genes at the mRNA level to determine a 10 year recurrence risk in node negative and 5 year recurrence risk in node positive cancer. 16 malignancy markers related to estrogen, HER2, cell proliferation, and invasion potential are compared with 5 reference genes and …

Primary Cns Small Mature B-Cell Lymphoma With Plasmacytic Differentiation Presenting As An Amyloidoma: A Case Report And Review Of Literature, Andrew Lynch, Geetha Jagannathan, Md

Department of Pathology Honors Program Student Research Symposium

Primary central nervous system lymphomas (PCNSL) without systemic involvement are rare and account for only 2-3% of all brain tumors and <1% of all non-Hodgkin’s lymphoma (NHL). Close to 40% of PCNSL are associated with immunosuppression, however, the incidence of primary central nervous system (CNS) lymphomas has shown an increasing trend in immunocompetent patients in recent decades due to better control of HIV and drug-induced immunosuppression [2]. Here, we describe a case of a primary CNS non-Hodgkin’s small mature B-cell lymphoma with plasmacytic differentiation in an immunocompetent individual. A previously healthy 87-year-old Caucasian woman presented to the neurology clinic with complaints of slowly progressing left sided weakness, predominantly in the left arm and leg over the last 6 months. Magnetic resonance imaging of the brain revealed a large, confluent white matter T2-hyperintensity in the right frontal lobe with multifocal nodular enhancement involving the left cerebral hemisphere, cerebellum, and leptomeninges, consistent morphologically with lymphoplasmacytic lymphoma. A bone marrow biopsy showed normal trilineage hematopoiesis with no evidence of lymphoma, myeloma or amyloidosis. Our patient was treated with Rituximab but developed an ischemic infarct of the left frontal white matter. She and her family decided to forego further treatment and switch to hospice care.

Ewing’S Sarcoma, Chris Lucasti, Bs, Bruce A. Fenderson, Phd

Department of Pathology Honors Program Student Research Symposium

Ewing’s sarcoma is the second most common malignant tumor of the bone occurring in children and adolescents. Typically, patients present between the ages of 10 and 20, with the disease having a slight predilection for males.1 Tumors often arise in the mid-shaft with the femur being the most frequently affected bone. The most common chromosome translocation, t(11;22)(q24;q12), occurs between the EWS gene and the FLI-1 gene. This translocation has been implicated in these aggressive and malignant tumors.1–4 Oftentimes, patients present with pain and swelling in the area of the affected bone or joint.5 While there has been some improvement in …

Clinico-Pathological Features And Pd-1/Pd-L1 Expression In Primary Mediastinal Large B Cell Lymphoma, Lydia Glick, Geetha Jagannathan, Md, Guldeep Uppal, Md

Department of Pathology Honors Program Student Research Symposium

Primary Mediastinal Large B Cell Lymphoma (PMBCL) is a distinct subtype of Diffuse Large B Cell Lymphoma (DLBCL) that has been historically reported to have a worse prognosis than DLBCL. Occasional studies have reported PD-L1 expression in PMBCL, which can emerge as an important target for immune-check point therapy. This study aimed to evaluate clinico-pathological features and characterize the expression of PD-1 and PD-L1 in a single cohort of 15 patients with PMBCL.

A total of 15 cases of PMBCL were retrieved from records of the department of Pathology; eleven of these had tissue available for additional immunohistochemistry, specifically, PD-L1 …

Comparative Analysis Of Tumor Capsule Thickness And Other Histologic Features In Encapsulated Follicular Variant Of Papillary Thyroid Carcinoma (Efvptc) And Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (Niftp), Brenda French, Stacey K. Mardekian, Md

Department of Pathology Honors Program Student Research Symposium

Recent reclassification of a subset of non-invasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) tumors as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has led to important changes in the clinical management of patients with these indolent lesions. Although there are established diagnostic criteria to differentiate NIFTP from EFVPTC, our objective was to determine further differences in histological characteristics between NIFTP and noninvasive EFVPTC. Additionally, we sought to identify histological differences between non-invasive and invasive EFVPTC lesions beyond the key finding of invasion. 68 encapsulated follicular lesions with papillary-like nuclear features from patients treated at Thomas Jefferson …

Implications Of Hobnail Features In Anaplastic Thyroid Carcinoma And Precursor Lesions, Caroline Dunne, Ba, Stacey K. Mardekian, Md

Department of Pathology Honors Program Student Research Symposium

Anaplastic thyroid carcinoma (ATC) has the poorest prognosis of all thyroid cancers. Morphologically, it is characterized by pleomorphic undifferentiated cells. In some cases, a differentiated precursor lesion, either papillary thyroid carcinoma (PTC) or follicular thyroid carcinoma, can be identified adjacent to the anaplastic component. There are certain morphological variants of PTC that are known to be associated with more aggressive behavior, but a recently described, understudied variant is the hobnail variant. It is characterized histologically by micropapillary structures lined by cells with abundant eosinophilic cytoplasm and apically-placed bulging nuclei. The aim of this study was to evaluate the frequency of …

Atypical Presentation Of Upshaw Schulman Syndrome: A Case Report, Goutham Ravipati, Bs, David Strayer, Md, Phd, Douglas Drelich, Md

Department of Pathology Honors Program Student Research Symposium

Thrombotic thrombocytopenic purpura (TTP) is a rare coagulation disorder with a typical clinical presentation of low platelets and excessive clotting. Mortality for this disorder may be high if untreated and therefore necessitates a high clinical suspicion. Here we describe a 46-year-old African American woman with a past medical history of multiple cerebrovascular accidents presenting to hematology after a suspected diagnosis of TTP. Presumptive diagnosis of acquired TTP called for treatment with IVIg, but a diagnosis of congenital TTP (Upshaw Schulman syndrome) was made after testing showed a lack of ADAMTS13 antibodies. Treatment with fresh frozen plasma (FFP) showed increase in …

Determining The Role Of Point-Of-Care Hemoglobin Testing In The Resuscitation Of Acutely Hemorrhaging Patients, Eugene P. Warnick, Alexis R. Peedin, Md

Department of Pathology Honors Program Student Research Symposium

Point-of-care hemoglobin (Hb) testing has not been evaluated in the resuscitation of acutely hemorrhaging patients to guide transfusion therapy. This study assessed the correlation of Hb values determined by point-of-care (EPOC) and traditional laboratory (CBC) methods in patients undergoing massive transfusion. All patients transfused per the massive transfusion protocol (MTP) between February 2013 and October 2017 were identified. The EPOC result was most often within 1 g/dL of the CBC result when EPOC resulted in a Hb between 7-10 g/dL and when drawn within 15 minutes of the CBC specimen. In patients on MTP with an EPOC Hb between 7-10 …

Metastatic Lobular Breast Carcinoma In A Meningioma: A Case Study, Sara Chapin, Msii, Lawrence C. Kenyon, Md, Phd

Department of Pathology Honors Program Student Research Symposium

Hormonal relationships between breast carcinoma and meningioma have long been reported in the literature. This association may be related to the widespread expression of progesterone receptors in meningiomas. Indeed, meningiomas are more common in women and may demonstrate increased growth during pregnancy. Women have an increased risk of meningioma following breast carcinoma diagnosis and vice versa. However, much more uncommon is a tumor to tumor metastases of breast carcinoma into a meningioma. We report a case of a 56 year old female with a past medical history of breast cancer, found to have a right sphenoorbital meningioma with metastatic lobular …

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research is …

Puma Amplifies Necroptosis Signaling By Activating Cytosolic Dna Sensors., Dongshi Chen, Jingshan Tong, Liheng Yang, Liang Wei, Donna B. Stolz, Jian Yu, Jianke Zhang, Lin Zhang

Department of Microbiology and Immunology Faculty Papers

Necroptosis, a form of regulated necrotic cell death, is governed by RIP1/RIP3-mediated activation of MLKL. However, the signaling process leading to necroptotic death remains to be elucidated. In this study, we found that PUMA, a proapoptotic BH3-only Bcl-2 family member, is transcriptionally activated in an RIP3/MLKL-dependent manner following induction of necroptosis. The induction of PUMA, which is mediated by autocrine TNF-α and enhanced NF-κB activity, contributes to necroptotic death in RIP3-expressing cells with caspases inhibited. On induction, PUMA promotes the cytosolic release of mitochondrial DNA and activation of the DNA sensors DAI/Zbp1 and STING, leading to enhanced RIP3 and MLKL …

A Functional Signature Ontology (Fusion) Screen Detects An Ampk Inhibitor With Selective Toxicity Toward Human Colon Tumor Cells, Binita Das, Beth K. Neilsen, Kurt W. Fisher, Drew Gehring, Youcai Hu, Deanna J. Volle, Hyun Seok Kim, Jamie L. Mccall, David L. Kelly, John B. Macmillian, Michael A. White, Robert E. Lewis

Faculty & Staff Scholarship

AMPK is a serine threonine kinase composed of a heterotrimer of a catalytic, kinase-containing α and regulatory β and γ subunits. Here we show that individual AMPK subunit expression and requirement for survival varies across colon cancer cell lines. While AMPKα1 expression is relatively consistent across colon cancer cell lines, AMPKα1 depletion does not induce cell death. Conversely, AMPKα2 is expressed at variable levels in colon cancer cells. In high expressing SW480 and moderate expressing HCT116 colon cancer cells, siRNA-mediated depletion induces cell death. These data suggest that AMPK kinase inhibition may be a useful component of future therapeutic strategies. …

Effect Of Hemiepiphysiodesis On The Growth Plate: The Histopathological Changes And Mechanism Exploration Of Recurrence In Mini Pig Model., Jing Ding, Jin He, Zhi-Qiang Zhang, Zhen-Kai Wu, Fang-Chun Jin

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Hemiepiphysiodesis has been widely used to correct angular deformity of long bone in immature patients. However, there is a limited knowledge about the biomechanical effect of this technique on the histopathological changes of the growth plate and the mechanism of recurrence of malformation after implant removal. We aimed to evaluate the biomechanical effect of hemiepiphysiodesis on the histopathological changes of the growth plate and the mechanism of recurrence of malformation after implant removal in Bama miniature pigs, and to explore the role of asymmetric stress during this procedure.

Methods: Eight 3-month-old male Bama miniature pigs sustained surgeries on the …