Medical Pathology Commons^™

A Double Humanized Blt-Mice Model Featuring A Stable Human-Like Gut Microbiome And Human Immune System, Lance Daharsh, Jianshui Zhang, Amanda E. Ramer-Tait, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Humanized mice (hu-mice) that feature a functional human immune system have fundamentally changed the study of human pathogens and disease. They can be used to model diseases that are otherwise difficult or impossible to study in humans or other animal models. The gut microbiome can have a profound impact on human health and disease. However, the murine gut microbiome is very different than the one found in humans. There is a need for improved pre-clinical hu-mice models that have an engrafted human gut microbiome. Therefore, we created double hu-mice that feature both a human immune system and stable human-like gut …

The Vaccinia Virus (Vacv) B1 And Cellular Vrk2 Kinases Promote Vacv Replication Factory Formation Through Phosphorylation-Dependent Inhibition Of Vacv B12, Annabel T. Olson, Zhigang Wang, Annabel Olson, Alexandria C. Linville, Brianna L. Bullard, Eric A. Weaver, Clinton Jones, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Comparative examination of viral and host protein homologs reveals novel mechanisms governing downstream signaling effectors of both cellular and vi- ral origin. The vaccinia virus B1 protein kinase is involved in promoting multiple facets of the virus life cycle and is a homolog of three conserved cellular enzymes called vaccinia virus-related kinases (VRKs). Recent evidence indicates that B1 and VRK2 mediate a com- mon pathway that is largely uncharacterized but appears independent of previous VRK substrates. Interestingly, separate studies described a novel role for B1 in inhibiting vac- cinia virus protein B12, which otherwise impedes an early event in the …

The Role Of Botulinum Toxin Type-A In Spasticity: Research Trends From A Bibliometric Analysis, Christine A Liang, Jing Liu, Jaiyeola Thomas Ogunniyi, Hui Zhu, Songlin Zhang

Faculty, Staff and Student Publications

AIMS: Since the six-tier Milan salivary gland classification has been introduced, there are very limited studies in literature reporting the risk stratification of the Milan classification.

METHODS: We retrospectively classified a total of 285 salivary gland cytology cases into Milan reporting categories; there were 23 (8.1%) nondiagnostic, 48 (16.8%) nonneoplastic, 19 (6.7%) atypia of undetermined significance (AUS), 138 (48.4%) benign neoplasm, 13 (4.6%) neoplasm of uncertain malignant potential (NUMP), 8 (2.8%) suspicious for malignancy, and 36 (12.6%) malignant. Almost 110 cases (38.6%) had surgical follow-up resections.

RESULTS: The overall risk for malignancy (ROM) was 12.5% for AUS, 3.2% for benign …

Conjugated Bile Acid And Sphingosine 1-Phosophate Prompt Cholangiocarcinoma Cell Growth Via Releasing Exosomes, Waad A. Alruwaili

Theses and Dissertations

Cholangiocarcinoma (CCA) is a fatal primary malignancy that is formed in the bile ducts. Cancer-associated myofibroblasts play a crucial role in CCA proliferation and invasion. Furthermore, there is a growing interest in the role of the exosome in the interaction between the cancer-associated myofibroblasts and cholangiocarcinoma which lead to CCA growth. However how cholangiocarcinoma-derived exosome affect the cancer-associated myofibroblasts in the tumor microenvironment remain unknown. In this study, we examined whether exosome produced by cholangiocarcinoma could involve in the prompt of CCA cells growth by regulation of myofibroblast. We found that cholangiocarcinoma-derived exosome could prompt elevated α-smooth muscle actin and …

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 …

High Affinity Binding Of H3k14ac Through Collaboration Of Bromodomains 2, 4 And 5 Is Critical For The Molecular And Tumor Suppressor Functions Of Pbrm1., Lili Liao, Nilda L. Alicea-Velázquez, Lauren Langbein, Xiaohua Niu, Weijia Cai, Eun-Ah Cho, Meiling Zhang, Celeste B. Greer, Qin Yan, Michael S. Cosgrove, Haifeng Yang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Polybromo-1 (PBRM1) is an important tumor suppressor in kidney cancer. It contains six tandem bromodomains (BDs), which are specialized structures that recognize acetyl-lysine residues. While BD2 has been found to bind acetylated histone H3 lysine 14 (H3K14ac), it is not known whether other BDs collaborate with BD2 to generate strong binding to H3K14ac, and the importance of H3K14ac recognition for the molecular and tumor suppressor function of PBRM1 is also unknown. We discovered that full-length PBRM1, but not its individual BDs, strongly binds H3K14ac. BDs 2, 4, and 5 were found to collaborate to facilitate strong binding to H3K14ac. Quantitative …

Efficacy Of A T Cell-Biased Adenovirus Vector As A Zika Virus Vaccine, Brianna L. Bullard, Brigette N. Corder, Matthew J. Gorman, Michael S. Diamond, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV) is a major public health concern due to the risk of congenital Zika syndrome in developing fetuses and Guillain-Barre syndrome in adults. Currently, there are no approved vaccines available to protect against infection. Adenoviruses are safe and highly immunogenic vaccine vectors capable of inducing lasting humoral and cellular immune responses. Here, we developed two Adenovirus (Ad) vectored Zika virus vaccines by inserting a ZIKV prM-E gene expression cassette into human Ad types 4 (Ad4-prM-E) and 5 (Ad5-prM-E). Immune correlates indicate that Ad5-prM-E vaccination induces both an anti-ZIKV antibody and T-cell responses whereas Ad4-prM-E vaccination only induces a …

Community-Acquired Pneumonia In Adults: Diagnostic Reliability Of Physical Examination Techniques And Their Teaching In Academia, Amber Tordoff, Lauren A. Williams

Physician Assistant Capstones, 2016 to 2019

Background: Chest physical examination techniques are taught in academia, but their usefulness in the evaluation and diagnosis of patients in the clinical setting is controversial. Objective: To investigate the accuracy of physical examination techniques and their reliability in diagnosing community acquired pneumonia (CAP) and suggest a modified teaching approach to be used in academia. Design: Systematic Literature Review. Methods: Database search of PubMed and Google Scholar using the search terms “prediction of pneumonia in adults” and “prediction rule for pulmonary infiltrates.” Filters were implemented to include articles that only dealt with human subjects and were full text. Articles …

Dietary Polyunsaturated Fatty Acids Regulate Mammary Tumor Growth And Metastasis By Modulating Tissue Microenvironments, Saraswoti Khadge

Theses & Dissertations

Omega (ω)-6 and ω-3 polyunsaturated fatty acids (PUFAs) are essential fatty acids (FAs) and the precursors of pro- and anti-inflammatory mediators respectively. Epidemiological studies have shown a lower incidence of breast cancer (BC) in the countries where long-chain (LC)-ω-3FAs consumption is higher; however, the role of ω-3FAs in BC growth and metastasis is poorly understood. We used isocaloric, isolipidic ω-6 and ω-3 (contains LC-ω-3FAs) diets and a pair-fed model to evaluate the effects of dietary PUFAs in mammary tumor metastasis. Our studies have resulted in several novel observations including that dietary LC-ω-3FAs modulate mammary gland (MG) microenvironments in non-tumor bearing …

Notch Signaling Regulates Mitochondrial Metabolism And Nf-Κb Activity In Triple-Negative Breast Cancer Cells Via Ikkα-Dependent Non-Canonical Pathways, Fokhrul Hossain, Claudia Sorrentino, Deniz A. Ucar, Yin Peng, Margarite Matossian, Dorota Wyczechowska, Judy Crabtree, Jovanny Zabaleta, Silvana Morello, Luis Del Valle, Matthew Burow, Bridgette Collins-Burow, Antonio Pannuti, Lisa M. Minter, Todd E. Golde, Barbara A. Osborne, Lucio Miele

School of Medicine Faculty Publications

Triple negative breast cancer (TNBC) patients have high risk of recurrence and metastasis, and current treatment options remain limited. Cancer stem-like cells (CSCs) have been linked to cancer initiation, progression and chemotherapy resistance. Notch signaling is a key pathway regulating TNBC CSC survival. Treatment of TNBC with PI3K or mTORC1/2 inhibitors results in drug-resistant, Notch-dependent CSC. However, downstream mechanisms and potentially druggable Notch effectors in TNBC CSCs are largely unknown. We studied the role of the AKT pathway and mitochondrial metabolism downstream of Notch signaling in TNBC CSC from cell lines representative of different TNBC molecular subtypes as well as …

Distinct White Matter Changes Associated With Cerebrospinal Fluid Amyloid-Β1-42 And Hypertension, Omar M. Al-Janabi, Christopher A. Brown, Ahmed A. Bahrani, Erin L. Abner, Justin M. Barber, Brian T. Gold, Larry B. Goldstein, Richard R. Murphy, Peter T. Nelson, Nathan F. Johnson, Leslie M. Shaw, Charles D. Smith, John Q. Trojanowski, Donna M. Wilcock, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Alzheimer's disease (AD) pathology and hypertension (HTN) are risk factors for development of white matter (WM) alterations and might be independently associated with these alterations in older adults.

OBJECTIVE: To evaluate the independent and synergistic effects of HTN and AD pathology on WM alterations.

METHODS: Clinical measures of cerebrovascular disease risk were collected from 62 participants in University of Kentucky Alzheimer's Disease Center studies who also had cerebrospinal fluid (CSF) sampling and MRI brain scans. CSF Aβ_1-42 levels were measured as a marker of AD, and fluid-attenuated inversion recovery imaging and diffusion tensor imaging were obtained to assess …

Radiofrequency Renal Denervation Attenuates Kidney Fibrosis In Spontaneously Hypertensive Rats (2267), Juan Gao, Ian Bart Denys, Luis Del Valle, Mihran V. Naljayan, Daniel R. Kapusta

School of Medicine Faculty Publications

No abstract provided.

Kaposi’S Sarcoma-Associated Herpesvirus Seropositivity Is Associated With Type 2 Diabetes Mellitus: A Case–Control Study In Xinjiang, China, Meng Cui, Qiwen Fang, Jun Zheng, Zhanjun Shu, Yin Chen, Yage Fan, Juan Zhao, Charles Wood, Tiejun Zhang, Yan Zeng

Nebraska Center for Virology: Faculty Publications

Objective: To assess the potential relationship between Kaposi’s sarcoma-associated herpesvirus (KSHV) infection and type 2 diabetes mellitus (DM-2) in Xinjiang, China.

Methods: A case–control study of consecutively included DM-2 patients and normal controls was conducted among the Uygur and Han populations in Xinjiang Uygur Autonomous Region, China. Blood samples were collected and KSHV seroprevalence, antibody titers, and viral load were investigated. Logistic regression analysis and multiple linear regression analysis were applied to explore determinants of the main outcome measures.

Results: A total of 324 patients with DM-2 and 376 normal controls were included. The seroprevalence of KSHV was 49.1% (95% …

Gene Gangs Of The Chloroviruses: Conserved Clusters Of Collinear Monocistronic Genes, Phillip Seitzer, Adrien Jeanniard, Fangrui Ma, James L. Van Etten, Marc T. Facciotti, David D. Dunigan

Nebraska Center for Virology: Faculty Publications

Chloroviruses (family Phycodnaviridae) are dsDNA viruses found throughout the world’s inland waters. The open reading frames in the genomes of 41 sequenced chloroviruses (330 + 40 kbp each) representing three virus types were analyzed for evidence of evolutionarily conserved local genomic “contexts”, the organization of biological information into units of a scale larger than a gene. Despite a general loss of synteny between virus types, we informatically detected a highly conserved genomic context defined by groups of three or more genes that we have termed “gene gangs”. Unlike previously described local genomic contexts, the definition of gene gangs requires only …

The Path Report Volume 2 Issue 2, Pathology Department, New York Medical College

The Path Report

No abstract provided.

A Brief Report Of Immunohistochemical Markers To Identify Aggressive Hepatoblastoma., Vivekanand Singh, Michelle Manalang, Meenal Singh, Udayan Apte

Manuscripts, Articles, Book Chapters and Other Papers

Hepatoblastoma (HB) is the most common malignant liver tumor in children. Although survival of patients has improved significantly over the last 2 decades, a significant number of patients do not respond to standard chemotherapy. We conducted a pilot study to understand if there was immunophenotypic difference between tumors that respond well to chemotherapy versus that do not. We selected 10 cases of HB from children presenting at our hospital. All patients had initial tissue diagnosis, underwent chemotherapy followed by surgical resection. The cases were divided into 2 groups: aggressive group with 5 cases (all of which had a poor response …

Henle's Ligament: A Comprehensive Review Of Its Anatomy And Terminology Over Almost One And A Half Centuries., Raja Gnanadev, Joe Iwanaga, Rod J Oskouian, Marios Loukas, R Shane Tubbs

Articles, Abstracts, and Reports

Henle's ligament was first described by German physician and anatomist, Friedrich Henle, in 1871. This review article will cover Henle's original description of the ligament, historical changes in terminology, embryological studies of the ligament, and the clinical significance of Henle's ligament. This article has a particular focus on the variation in the terminology of this structure and the implications of this.

Prothrombin Complex Concentrates Or Recombinant Factor Viia Are More Effective Than Fresh-Frozen Plasma At Lowering Inr In Patients With Liver Disease, Abel J. Ignatius

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Kwon JO, MacLaren R. Comparison of fresh-frozen plasma, four-factor prothrombin complex concentrates, and recombinant factor VIIa to facilitate procedures in critically ill patients with coagulopathy from liver disease: a retrospective cohort study. Pharmacotherapy. 2016;36(10):1047-1054. doi: 10.1002/phar.1827

Susceptibility Genes To Plant Viruses, Hernan Garcia-Ruiz

Nebraska Center for Virology: Faculty Publications

Plant viruses use cellular factors and resources to replicate and move. Plants respond to viral infection by several mechanisms, including innate immunity, autophagy, and gene silencing, that viruses must evade or suppress. Thus, the establishment of infection is genetically determined by the availability of host factors necessary for virus replication and movement and by the balance between plant defense and viral suppression of defense responses. Host factors may have antiviral or proviral activities. Proviral factors condition susceptibility to viruses by participating in processes essential to the virus. Here, we review current advances in the identification and characterization of host factors …

Coping With Chronic Fungal Rhinosinusitis: Diagnosis To Therapy, Veronica Corcino, Leslie Beavin, Shengli Lu, Ashley Ross, Carmen V. Sciortino Jr.

The University of Louisville Journal of Respiratory Infections

No abstract provided.