Medical Pathology Commons^™

Data Supporting The Roles Of Bap1, Sting, And Ifn-Β In Isgf3 Activation In Ccrcc, Lauren E Langbein, Eleonora Sementino, Zhijiu Zhong, Wei Jiang, Li Li, Joseph R Testa, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The data presented in this article are companion materials to our manuscript titled "BAP1 maintains HIF-dependent interferon beta induction to suppress tumor growth in clear cell renal cell carcinoma" (Langbein et al., 2022), where we investigated the downstream effects of BAP1 (BRCA1-associated protein 1) expression in clear cell renal cell carcinoma (ccRCC) cell lines and mouse xenograft models. In the manuscript, we showed that BAP1 upregulates STING (stimulator of interferon genes) expression and activity in ccRCC cells, leading to IFN-β transcription and activation of interferon stimulated gene factor 3 (ISGF3), the transcription factor that mediates the effects of type I …

Epidemiology And Antimicrobial Resistance Of Staphylococci Other Than Staphylococcus Aureus From Domestic Animals And Livestock In Africa: A Systematic Review, Remous Ocloo, Justin Nyasinga, Mohammed Munshi, Aisha Hamdy, Tessa Marciniak, Manonmani Soundararajan, Mae Newton-Foot, Wilma Ziebuhr, Manonmani Soundararajan, Gunturu Revathi

Pathology, East Africa

Introduction: Staphylococci other than Staphylococcus aureus (SOSA) in animals are becoming more pathogenic and antibiotic resistant and can potentially disseminate to humans. However, there is little synthesized information regarding SOSA from animals in Africa. This systematic review provides a comprehensive overview of the epidemiology and antimicrobial resistance of SOSA in companion animals (pets) and livestock in Africa.

Method: This systematic review (PROSPERO-CRD42021252303) was conducted according to the PRISMA guidelines, and 75 eligible studies from 13 countries were identified until August 2022. Three electronic databases (Pubmed, Scopus and Web of Science) were employed.

Results: The frequently isolated SOSA …

A Common Mechanism Links Epstein‐Barr Virus Infections And Autoimmune Diseases, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Epstein‐Barr virus (EBV) infection is associated with a variety of the autoimmune diseases. There is apparently no unified model for the role of EBV in autoimmune diseases. In this article, the development of autoimmune diseases is proposed as a simple two‐step process: specific autoimmune initiators may cause irreversible changes to genetic materials that increase autoimmune risks, and autoimmune promoters promote autoimmune disease formation once cells are susceptible to autoimmunity. EBV has several types of latencies including type III latency with higher proliferation potential. EBV could serve as autoimmune initiators for some autoimmune diseases. At the same time, EBV may play …

Altered Expression Of Glycobiology-Related Genes In Parkinson’S Disease Brain, Jay S Schneider, Garima Singh

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The precise mechanisms initiating and perpetuating the cellular degeneration in Parkinson's disease (PD) remain unclear. There is decreased expression of the main brain gangliosides, and GM1 ganglioside in particular, in the PD brain along with decreased expression of the genes coding for the glycosyltranferase and the sialyltransferase responsible for the synthesis of these brain gangliosides. However, potentially important pathogenic mechanisms contributing to the neurodegeneration in PD may also include altered levels of expression of genes involved in glycosylation, sialylation and sphingolipid synthesis and metabolism. Although various studies have described pathological lipid and glycolipid changes in PD brain, there have been …

Pathogenicity And Impact Of Hla Class I Alleles In Aplastic Anemia Patients Of Different Ethnicities, Timothy S Olson, Benjamin F Frost, Jamie L Duke, Marian Dribus, Hongbo M Xie, Zachary D Prudowsky, Elissa Furutani, Jonas Gudera, Yash B Shah, Deborah Ferriola, Amalia Dinou, Ioanna Pagkrati, Soyoung Kim, Yixi Xu, Meilun He, Shannon Zheng, Sally Nijim, Ping Lin, Chong Xu, Taizo A Nakano, Joseph H Oved, Beatriz M Carreno, Yung-Tsi Bolon, Shahinaz M Gadalla, Steven Ge Marsh, Sophie Paczesny, Stephanie J Lee, Dimitrios S Monos, Akiko Shimamura, Alison A Bertuch, Loren Gragert, Stephen R Spellman, Daria V Babushok

Department of Medicine Faculty Papers

Acquired aplastic anemia (AA) is caused by autoreactive T cell-mediated destruction of early hematopoietic cells. Somatic loss of human leukocyte antigen (HLA) class I alleles was identified as a mechanism of immune escape in surviving hematopoietic cells of some patients with AA. However, pathogenicity, structural characteristics, and clinical impact of specific HLA alleles in AA remain poorly understood. Here, we evaluated somatic HLA loss in 505 patients with AA from 2 multi-institutional cohorts. Using a combination of HLA mutation frequencies, peptide-binding structures, and association with AA in an independent cohort of 6,323 patients from the National Marrow Donor Program, we …

Genome-Scale Metabolic Modeling Reveals Sequential Dysregulation Of Glutathione Metabolism In Livers From Patients With Alcoholic Hepatitis, Alexandra Manchel, Radhakrishnan Mahadevan, Ramon Bataller, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease for which there is no efficacious treatment aiding most patients. AH manifests differently in individuals, with some patients showing debilitating symptoms more so than others. Previous studies showed significant metabolic dysregulation associated with AH. Therefore, we sought to analyze how the activity of metabolic pathways differed in the liver of patients with varying degrees of AH severity. We utilized a genome-scale metabolic modeling approach that allowed for integration of a generic human cellular metabolic model with specific RNA-seq data corresponding to healthy and multiple liver disease states to …

Il-33 Promotes Increased Replication Of Theiler’S Murine Encephalomyelitis Virus In Raw264.7 Macrophage Cells With An Irf3-Dependent Response, Ahmed Esmael, Thomas M. Petro

Nebraska Center for Virology: Faculty Publications

Interleukin-33 (IL-33), which promotes M2 macrophage development, may influence the control of viruses, such as Theiler’s Murine Encephalomyelitis Virus (TMEV) that infect macrophages. Because Interferon Regulatory Factor-3 (IRF3) is also critical to control of TMEV infection in macrophages, information on the relationship between IL-33 and IRF3 is important. Thus, RAW264.7 Lucia murine macrophage lineage cells with an endogenous IRF3-ISRE promoter driving secreted luciferase and IRF3KO RAW Lucia, a subline deficient in IRF3, were challenged with TMEV. After the challenge, considerable TMEV RNA detected at 18 and 24 h in RAW cells was significantly elevated in IRF3KO RAW cells. TMEV induction …

A Single Amino Acid Substitution In Porcine Reproductive And Respiratory Syndrome Virus Glycoprotein 2 Significantly Impairs Its Infectivity In Macrophages, Jayeshbhai Chaudhari, Raquel Arruda Leme, Kassandra Durazo-Martinez, Sarah Vitosh-Sillman, Aspen M. Workman, Hiep Vu

Nebraska Center for Virology: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) has a restricted tropism for macrophages and CD163 is a key receptor for infection. In this study, the PRRSV strain NCV1 was passaged on MARC-145 cells for 95 passages, and two plaque-clones (C1 and C2) were randomly selected for further analysis. The C1 virus nearly lost the ability to infect porcine alveolar macrophages (PAMs), as well as porcine kidney cells expressing porcine CD163 (PK15-pCD163), while the C2 virus replicates well in these two cell types. Pretreatment of MARC-145 cells with an anti-CD163 antibody nearly blocked C1 virus infection, indicating that the virus still …

Il-33 Promotes Increased Replication Of Theiler’S Murine Encephalomyelitis Virus In Raw264.7 Macrophage Cells With An Irf3-Dependent Response, Ahmed Esmael, Thomas M. Petro

Nebraska Center for Virology: Faculty Publications

Interleukin-33 (IL-33), which promotes M2 macrophage development, may influence the control of viruses, such as Theiler’s Murine Encephalomyelitis Virus (TMEV) that infect macrophages. Because Interferon Regulatory Factor-3 (IRF3) is also critical to control of TMEV infection in macrophages, information on the relationship between IL-33 and IRF3 is important. Thus, RAW264.7 Lucia murine macrophage lineage cells with an endogenous IRF3-ISRE promoter driving secreted luciferase and IRF3KO RAW Lucia, a subline deficient in IRF3, were challenged with TMEV. After the challenge, considerable TMEV RNA detected at 18 and 24 h in RAW cells was significantly elevated in IRF3KO RAW cells. TMEV induction …

Polyphenolics, Glucosinolates And Isothiocyanates Profiling Of Aerial Parts Of Nasturtium Officinale (Watercress), Sotiris Kyriakou, Kyriaki Michailidou, Tom Amery, Kyle Stewart, Paul G. Winyard, Dimitrios T. Trafalis, Rodrigo Franco, Aglaia Pappa, Mihalis I. Panayiotidis

Nebraska Center for Virology: Faculty Publications

Watercress (Nasturtium officinale) is a rich source of secondary metabolites with disease-preventing and/or health-promoting properties. Herein, we have utilized extraction procedures to isolate fractions of polyphenols, glucosinolates and isothiocyanates to determine their identification, and quantification. In doing so, we have utilized reproducible analytical methodologies based on liquid chromatography with tandem mass spectrometry by either positive or negative ion mode. Due to the instability and volatility of isothiocyanates, we followed an ammonia derivatization protocol which converts them into respective ionizable thiourea derivatives. The analytes’ content distribution map was created on watercress flowers, leaves and stems. We have demonstrated that …

Corneal Edema Associated With Degenerating Soemmering Ring Cataract: Clinical-Pathologic Correlation, Jordan P Safran, Nathan Nataneli, Jayesh Vazirani, Ralph C. Eagle Jr, Tatyana Milman

Wills Eye Hospital Papers

Purpose: To report three patients with an uncommon delayed complication of cataract extraction: corneal edema following dispersion of calcific lens particles from a degenerating Soemmering ring cataract.

Observations: We report three patients, 75-92 years old, presenting with corneal edema and dispersed, degenerated calcific lens material in the anterior chamber and vitreous 20-30 years after cataract surgery. In all patients, calcific particles studded the posterior surface of the cornea in a gravity-dependent distribution without apparent inflammation and were associated with localized corneal edema. In one patient, calcific particles were also associated with secondary open angle glaucoma. Deposits originated from the calcified …

A High-Resolution 3d Atlas Of The Spectrum Of Tuberculous Andcovid-19 Lung Lesions, Gordon Wells, Joel N Glasgow, Kievershen Nargan, Kapongo Lumamba, Rajhmun Madansein, Kameel Maharaj, Leon Y Perumal, Malcolm Matthew, Robert L Hunter, Hayden Pacl, Jacelyn E Peabody Lever, Denise D Stanford, Satinder P Singh, Prachi Bajpai, Upender Manne, Paul V Benson, Steven M Rowe, Stephan Le Roux, Alex Sigal, Muofhe Tshibalanganda, Carlyn Wells, Anton Du Plessis, Mpumelelo Msimang, Threnesan Naidoo, Adrie J C Steyn

Faculty, Staff and Student Publications

Our current understanding of the spectrum of TB and COVID-19 lesions in the human lung is limited by a reliance on low-resolution imaging platforms that cannot provide accurate 3D representations of lesion types within the context of the whole lung. To characterize TB and COVID-19 lesions in 3D, we applied micro/nanocomputed tomography to surgically resected, postmortem, and paraffin-embedded human lung tissue. We define a spectrum of TB pathologies, including cavitary lesions, calcium deposits outside and inside necrotic granulomas and mycetomas, and vascular rearrangement. We identified an unusual spatial arrangement of vasculature within an entire COVID-19 lobe, and 3D segmentation of …

The “Big Six”: Hidden Emerging Foodborne Bacterial Pathogens, Mona G. Alharbi, Rashad R. Al-Hindi, Ahmed Esmael, Ibrahim A. Alotibi, Sheren A. Azhari, Mazen S. Alseghayer, Addisu D. Teklemariam

Nebraska Center for Virology: Faculty Publications

Non-O157 Shiga toxin-producing Escherichia coli (STEC) are emerging serogroups that often result in diseases ranging from diarrhea to severe hemorrhagic colitis in humans. The most common non-O157 STEC are O26, O45, O103, O111, O121, and O145. These serogroups are known by the name “big six” because they cause severe illness and death in humans and the United States Department of Agriculture declared these serogroups as food contaminants. The lack of fast and efficient diagnostic methods exacerbates the public impact of the disease caused by these serogroups. Numerous outbreaks have been reported globally and most of these outbreaks were caused by …

Pi3k Isoform-Specific Regulation Of Leader And Follower Cell Function For Collective Migration And Proliferation In Response To Injury, Morgan D Basta, A. Menko, Janice L Walker

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

To ensure proper wound healing it is important to elucidate the signaling cues that coordinate leader and follower cell behavior to promote collective migration and proliferation for wound healing in response to injury. Using an ex vivo post-cataract surgery wound healing model we investigated the role of class I phosphatidylinositol-3-kinase (PI3K) isoforms in this process. Our findings revealed a specific role for p110α signaling independent of Akt for promoting the collective migration and proliferation of the epithelium for wound closure. In addition, we found an important role for p110α signaling in orchestrating proper polarized cytoskeletal organization within both leader and …

Editorial: Epigenetics And Molecular Genetics Of Rare Tumors, Mauro Tognon, George A. Calin, Luis Del Valle

School of Medicine Faculty Publications

No abstract provided.

B-Lymphoblastic Leukemia With Burkitt-Like Morphology And Aberrant Myeloperoxidase Expression: A Diagnostic Conundrum, Karen A Nahmod, Wei Wang, Karan Saluja, Zhenya Tang, L Jeffrey Medeiros, Beenu Thakral

Faculty, Staff and Student Publications

No abstract provided.

Exploration Of The Minimum Necessary Fviii Level At Different Physical Activity Levels In Pediatric Patients With Hemophilia A, Di Ai, Kun Huang, Gang Li, Yingzi Zhen, Xinyi Wu, Ningning Zhang, Aihua Huo, Zhenping Chen, Runhui Wu

Faculty, Staff and Student Publications

BACKGROUND: Physical activity can increase joint stability and reduce the risk of injury in hemophilia patients. There is limited clinical data on target trough FVIII levels during physical activity in hemophilia A patients. Hence, this study aimed to explore the target trough FVIII level required to avoid bleeding during different physical activities in hemophilia A patients.

METHODS: Patients with severe or moderate hemophilia A, who underwent pharmacokinetics (PK) tests at our center were enrolled in this study. Physical activities and clinical information such as bleeding were recorded. The FVIII level during physical activity was calculated by the WAPPS-Hemo.

RESULTS: A …

Aortic Root Dissection Due To An Automated Fastener Device, Ismael A Salas De Armas, L Maximilian Buja, Manish K Patel, Jayeshkumar Patel, Mehmet H Akay, Emre Gok, Igor D Gregoric

Faculty, Staff and Student Publications

Minimally invasive aortic valve replacement through a right thoracotomy is frequently performed in patients with aortic valve disease. The Cor-Knot Device (LSI Solutions) is an automated fastener that secures valve sutures. This case report is for a patient who developed postcardiotomy shock during a minimally invasive aortic valve surgery. The patient was found to have an aortic root dissection involving 90% of the aortic root circumference, including bilateral coronary ostia. The autopsy revealed that the aortic damage could be explained by a direct aortic intimal tear from the distal tip of the device shaft. The device was most likely not …

Bap1 Maintains Hif-Dependent Interferon Beta Induction To Suppress Tumor Growth In Clear Cell Renal Cell Carcinoma., Lauren Langbein, Rayan El Hajjar, Shen He, Eleonora Sementino, Zhijiu Zhong, Wei Jiang, Benjamin E Leiby, Li Li, Robert G Uzzo, Joseph R Testa, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BRCA1-associated protein 1 (BAP1) is a deubiquitinase that is mutated in 10-15% of clear cell renal cell carcinomas (ccRCC). Despite the association between BAP1 loss and poor clinical outcome, the critical tumor suppressor function(s) of BAP1 in ccRCC remains unclear. Previously, we found that hypoxia-inducible factor 2α (HIF2α) and BAP1 activate interferon-stimulated gene factor 3 (ISGF3), a transcription factor activated by type I interferons and a tumor suppressor in ccRCC xenograft models. Here, we aimed to determine the mechanism(s) through which HIF and BAP1 regulate ISGF3. We found that in ccRCC cells, loss of the von Hippel-Lindau tumor suppressor (VHL) …

Pathologic Predictors Of Response To Treatment Of Immune Checkpoint Inhibitor-Induced Kidney Injury, Ala Abudayyeh, Liye Suo, Heather Lin, Omar Mamlouk, Noha Abdel-Wahab, Amanda Tchakarov

Faculty, Staff and Student Publications

Background: Immune-related adverse events are a management challenge in patients receiving immune checkpoint inhibitors (ICIs). The most common renal immune-related adverse event, acute interstitial nephritis (AIN), is associated with patient morbidity and mortality. AIN, characterized by infiltration of renal tissue with immune cells, may be analogous to kidney transplant rejection. We evaluated clinical variables and pathologic findings to identify predictors of renal response and overall survival (OS) in patients with ICI-induced AIN. Design, setting, participants, and measurements: We reviewed the records and biopsy specimens of all 35 patients treated for ICI-induced AIN at our institution, between August 2007 and August …