Pathology Commons^™

Response Of Eltrombopag In Immune Thrombocytopenia And Acquired Idiopathic Aplastic Anemia: A Single-Center Experience, Abdul Muqtadir Abbasi, Mohammad Usman Shaikh, Natasha Bahadur Ali, Maria Khan, Salman Muhammad Soomar

Section of Haematology/Oncology

Eltrombopag has been used in ITP and found its use in AA armamentarium recently. We retrospectively analyzed 61 patients at a tertiary care center in Pakistan from January 2015 to January 2021. They included patients with severe AA who were refractory to at least one course of immunosuppressive therapy and persistent/chronic ITP who have received at least one previous treatment for ITP. Responses to Eltrombopag in our population were comparable to real-world experiences while tolerable hepatotoxicity and GI issues were notable. We found Eltrombopag to be a safe and efficacious agent for treating patients with ITP and AA.

A Review Of Coronaviruses Associated With Kawasaki Disease: Possible Implications For Pathogenesis Of The Multisystem Inflammatory Syndrome Associated With Covid-19, Fatima Farrukh Shahbaz, Russell Seth Martins, Abdullah Umair, Ronika Devi Ukrani, Kauser Jabeen, M Rizwan Sohail, Erum Khan

Medical College Documents

Multisystem Inflammatory Syndrome in Children (MIS-C), representing a new entity in the spectrum of manifestations of COVID-19, bears symptomatic resemblance with Kawasaki Disease (KD). This review explores the possible associations between KD and the human coronaviruses and discusses the pathophysiological similarities between KD and MIS-C and proposes implications for the pathogenesis of MIS-C in COVID-19. Since 2005, when a case-control study demonstrated the association of a strain of human coronavirus with KD, several studies have provided evidence regarding the association of different strains of the human coronaviruses with KD. Thus, the emergence of the KD-like disease MIS-C in COVID-19 may …

Noncoding-Rna-Based Therapeutics With An Emphasis On Prostatic Carcinoma-Progress And Challenges., Victor E. Nava, Pin-Yu Perera, Nirbhay Kumar, Maneesh Jain

Pathology Faculty Publications

Noncoding RNAs (ncRNAs) defy the central dogma by representing a family of RNA molecules that are not translated into protein but can convey information encoded in their DNA. Elucidating the exact function of ncRNA has been a focus of discovery in the last decade and remains challenging. Nevertheless, the importance of understanding ncRNA is apparent since these molecules regulate gene expression at the transcriptional and post-transcriptional level exerting pleiotropic effects critical in development, oncogenesis, and immunity. NcRNAs have been referred to as "the dark matter of the nucleus", and unraveling their role in physiologic and pathologic processes will provide vast …

Lymphoma With Tuberculous Granulomas, Jyoti Mohan Lal, Anila Rashid

Department of Pathology and Laboratory Medicine

Chronic granulomatous inflammation is a common finding in lymphoproliferative disorders (LPDs), but it is important to exclude coexisting mycobacterium tuberculosis (MTB) especially in patients from areas of high endemicity. This case emphasizes the relevance of performing MTB culture on bone marrow exhibiting LPD and concomitant granulomas

A Summary Of The Inaugural Who Classification Of Pediatric Tumors: Transitioning From The Optical Into The Molecular Era., Stefan M Pfister, Miguel Reyes-Múgica, John K C Chan, Henrik Hasle, Alexander J Lazar, Sabrina Rossi, Andrea Ferrari, Jason A Jarzembowski, Kathy Pritchard-Jones, D. Ashley Hill, Thomas S Jacques, Pieter Wesseling, Dolores H López Terrada, Andreas Von Deimling, Christian P Kratz, Ian A Cree, Rita Alaggio

Pathology Faculty Publications

Pediatric tumors are uncommon, yet are the leading cause of cancer-related death in childhood. Tumor types, molecular characteristics, and pathogenesis are unique, often originating from a single genetic driver event. The specific diagnostic challenges of childhood tumors led to the development of the first World Health Organization (WHO) Classification of Pediatric Tumors. The classification is rooted in a multilayered approach, incorporating morphology, IHC, and molecular characteristics. The volume is organized according to organ sites and provides a single, state-of-the-art compendium of pediatric tumor types. A special emphasis was placed on "blastomas," which variably recapitulate the morphologic maturation of organs from …

Clinical Influenza Testing Practices In Hospitalized Children At United States Medical Centers, 2015-2018., Mark W. Tenforde, Angela P. Campbell, Marian G. Michaels, Christopher J. Harrison, Eileen J. Klein, Janet A. Englund, Rangaraj Selvarangan, Natasha B. Halasa, Laura S. Stewart, Geoffrey A. Weinberg, John V. Williams, Peter G. Szilagyi, Mary A. Staat, Julie A. Boom, Leila C. Sahni, Monica N. Singer, Parvin H. Azimi, Richard K. Zimmerman, Monica M. Mcneal, H Keipp Talbot, Arnold S. Monto, Emily T. Martin, Manjusha Gaglani, Fernanda P. Silveira, Donald B. Middleton, Jill M. Ferdinands, Melissa A. Rolfes

Manuscripts, Articles, Book Chapters and Other Papers

At nine US hospitals that enrolled children hospitalized with acute respiratory illness (ARI) during 2015-2016 through 2017-2018 influenza seasons, 50% of children with ARI received clinician-initiated testing for influenza and 35% of cases went undiagnosed due to lack of clinician-initiated testing. Marked heterogeneity in testing practice was observed across sites.

Distribution Of Serotypes And Antibiotic Resistance Of Invasive Pseudomonas Aeruginosa In A Multi-Country Collection, Shamima Nasrin, Nicolas Hegerle, Shaichi Sen, Joseph Nkeze, Sunil Sen, Jasnehta Permala-Booth, Myeongjin Choi, James Sinclair, Milagritos D. Tapia, Sadia Shakoor

Department of Pathology and Laboratory Medicine

Background: Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of acute and chronic infections and is frequently associated with healthcare-associated infections. Because of its ability to rapidly acquire resistance to antibiotics, P. aeruginosa infections are difficult to treat. Alternative strategies, such as a vaccine, are needed to prevent infections. We collected a total of 413 P. aeruginosa isolates from the blood and cerebrospinal fluid of patients from 10 countries located on 4 continents during 2005-2017 and characterized these isolates to inform vaccine development efforts. We determined the diversity and distribution of O antigen and flagellin types and …

Upregulation Of Cd36, A Fatty Acid Translocase, Promotes Colorectal Cancer Metastasis By Increasing Mmp28 And Decreasing E-Cadherin Expression, James Drury, Piotr G. Rychahou, Courtney O. Kelson, Mariah E. Geisen, Yuanyuan Wu, Daheng He, Chi Wang, Eun Y. Lee, B. Mark Evers, Yekaterina Y. Zaytseva

Surgery Faculty Publications

Altered fatty acid metabolism continues to be an attractive target for therapeutic intervention in cancer. We previously found that colorectal cancer (CRC) cells with a higher metastatic potential express a higher level of fatty acid translocase (CD36). However, the role of CD36 in CRC metastasis has not been studied. Here, we demonstrate that high expression of CD36 promotes invasion of CRC cells. Consistently, CD36 promoted lung metastasis in the tail vein model and GI metastasis in the cecum injection model. RNA-Seq analysis of CRC cells with altered expression of CD36 revealed an association between high expression of CD36 and upregulation …

Disruption Of Mitochondrial Trafficking In Lung Epithelial Cells Potentiates Allergic Asthma Phenotypes, Amelia M. Lamberty

Graduate College Dissertations and Theses

Allergic asthma is a serious socioeconomic and health issue that is characterized by chronic inflammation of the lungs and affects as many 300 million people worldwide of all ages. Inhaled environmental factors, such as allergens, can disrupt the airway epithelium, which is the physical barrier and the first line of defense against external irritants. Consequently, exposure to allergens can cause episodes of airway inflammation, increased mucus production and tissue remodeling, that leads to the obstruction and narrowing of the airways, which may present as difficulty breathing, wheezing, and persistent coughing. Unfortunately, there is no cure for allergic asthma, but allergen …

Insect Cell Expression And Purification Of Recombinant Sars-Cov-2 Spike Proteins That Demonstrate Ace2 Binding, Lucas R. Struble, Audrey L. Smith, William E. Lutz, Gabrielle Grubbs, Satish Sagar, Kenneth W. Bayles, Prakash Radhakrishnan, Surender Khurana, Dalia El-Gamal, Gloria E. O. Borgstahl

Journal Articles: Pathology and Microbiology

The COVID-19 pandemic caused by SARS-CoV-2 infection has led to socio-economic shutdowns and the loss of over 5 million lives worldwide. There is a need for the identification of therapeutic targets to treat COVID-19. SARS-CoV-2 spike is a target of interest for the development of therapeutic targets. We developed a robust SARS-CoV-2 S spike expression and purification protocol from insect cells and studied four recombinant SARS-CoV-2 spike protein constructs based on the original SARS-CoV-2 sequence using a baculovirus expression system: a spike protein receptor-binding domain that includes the SD1 domain (RBD) coupled to a fluorescent tag (S-RBD-eGFP), spike ectodomain coupled …

Improved Database Filtering Technology Enables More Efficient Ab Initio Design Of Potent Peptides Against Ebola Viruses, Thomas Ripperda, Yangsheng Yu, Atul Verma, Elizabeth Klug, Michellie Thurman, St. Patrick Reid, Guangshun Wang

Journal Articles: Pathology and Microbiology

The rapid mutations of viruses such as SARS-CoV-2 require vaccine updates and the development of novel antiviral drugs. This article presents an improved database filtering technology for a more effective design of novel antiviral agents. Different from the previous approach, where the most probable parameters were obtained stepwise from the antimicrobial peptide database, we found it possible to accelerate the design process by deriving multiple parameters in a single step during the peptide amino acid analysis. The resulting peptide DFTavP1 displays the ability to inhibit Ebola virus. A deviation from the most probable peptide parameters reduces antiviral activity. The designed …

Type I Ifn Signaling Protects Mice From Lethal Sars-Cov-2 Neuroinvasion., Md Bashir Uddin, Yuejin Liang, Shengjun Shao, Sunil Palani, Michael Mckelvey, Scott C. Weaver, Keer Sun

Journal Articles: Pathology and Microbiology

Multiple organ damage is common in patients with severe COVID-19, even though the underlying pathogenic mechanisms remain unclear. Acute viral infection typically activates type I IFN (IFN-I) signaling. The antiviral role of IFN-I is well characterized in vitro. However, our understanding of how IFN-I regulates host immune response to SARS-CoV-2 infection in vivo is incomplete. Using a human ACE2-transgenic mouse model, we show in the present study that IFN-I receptor signaling is essential for protection against the acute lethality of SARS-CoV-2 in mice. Interestingly, although IFN-I signaling limits viral replication in the lung, the primary infection site, it is dispensable …

Exploring Epigenetic Reprogramming During Central Nervous System Infection, Zachary Van Roy, Tammy Kielian

Journal Articles: Pathology and Microbiology

Epigenetics involves the study of various modes of adaptable transcriptional regulation, contributing to cell identity, characteristics, and function. During central nervous system (CNS) infection, epigenetic mechanisms can exert pronounced control over the maturation and antimicrobial properties of nearly every immune cell type. Epigenetics is a relatively new field, with the first mention of these marks proposed only a half-century ago and a substantial body of immunological epigenetic research emerging only in the last few decades. Here, we review the best-characterized epigenetic marks and their functions as well as illustrate how various immune cell populations responding to CNS infection utilize these …

Expanding The Landscape Of Amino Acid-Rich Antimicrobial Peptides: Definition, Deployment In Nature, Implications For Peptide Design And Therapeutic Potential, Aaron P. Decker, Abraham F. Mechesso, Guangshun Wang

Journal Articles: Pathology and Microbiology

Unlike the α-helical and β-sheet antimicrobial peptides (AMPs), our knowledge on amino acid-rich AMPs is limited. This article conducts a systematic study of rich AMPs (>25%) from different life kingdoms based on the Antimicrobial Peptide Database (APD) using the program R. Of 3425 peptides, 724 rich AMPs were identified. Rich AMPs are more common in animals and bacteria than in plants. In different animal classes, a unique set of rich AMPs is deployed. While histidine, proline, and arginine-rich AMPs are abundant in mammals, alanine, glycine, and leucine-rich AMPs are common in amphibians. Ten amino acids (Ala, Cys, Gly, His, …

Datasets For The Reporting Of Primary Tumour In Bone: Recommendations From The International Collaboration On Cancer Reporting (Iccr), Judith V. M. G. Bovée, Fleur Webster, Fernanda Amary, Daniel Baumhoer, J. L. Hans Bloem, Julia A. Bridge, Justin M. M. Cates, Enrique De Alava, Angelo Paolo Dei Tos, Kevin B. Jones, Annabelle Mahar, G. Petur Nielsen, Alberto Righi, Andrew J. Wagner, Akihiko Yoshida, Christopher D. M. Fletcher

Journal Articles: Pathology and Microbiology

BACKGROUND AND OBJECTIVES: Bone tumours are relatively rare and, as a consequence, treatment in a centre with expertise is required. Current treatment guidelines also recommend review by a specialised pathologist. Here we report on international consensus-based datasets for the pathology reporting of biopsy and resection specimens of bone sarcomas. The datasets were produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major (inter-)national pathology and cancer organisations.

METHODS AND RESULTS: According to the ICCR's process for dataset development, an international expert panel consisting of pathologists, an oncologic orthopaedic surgeon, a medical oncologist, and …

Biofilms: Formation, Research Models, Potential Targets, And Methods For Prevention And Treatment, Yajuan Su, Jaime T. Yrastorza, Mitchell Matis, Jenna Cusick, Siwei Zhao, Guangshun Wang, Jingwei Xie

Journal Articles: Pathology and Microbiology

Due to the continuous rise in biofilm-related infections, biofilms seriously threaten human health. The formation of biofilms makes conventional antibiotics ineffective and dampens immune clearance. Therefore, it is important to understand the mechanisms of biofilm formation and develop novel strategies to treat biofilms more effectively. This review article begins with an introduction to biofilm formation in various clinical scenarios and their corresponding therapy. Established biofilm models used in research are then summarized. The potential targets which may assist in the development of new strategies for combating biofilms are further discussed. The novel technologies developed recently for the prevention and treatment …

Realistic And Critical Review Of The State Of Systemic Anti-Microbial Peptides, Guangshun Wang, Abraham F. Mechesso

Journal Articles: Pathology and Microbiology

Antimicrobial peptide research remains active not only because of the growing antibiotic resistance problem but also our desire to understand the role of innate immune peptides in host defense. While numerous peptides are currently under active development for topical use, this article highlights peptides with systemic efficacy. The scaffolds of these peptides range from linear to cyclic forms. The neutropenic mouse model is well established to illustrate antimicrobial efficacy from direct killing. The majority of tests, however, are conducted using normal mice so that both direct antimicrobial and immune regulatory effects can be characterized. These systemic examples underscore the possibility …

Ifn-Γ Attenuates Eosinophilic Inflammation But Is Not Essential For Protection Against Rsv-Enhanced Asthmatic Comorbidity In Adult Mice, Abenaya Muralidharan, Md Bashir Uddin, Christopher Bauer, Wenzhe Wu, Xiaoyong Bao, Keer Sun

Journal Articles: Pathology and Microbiology

The susceptibility to respiratory syncytial virus (RSV) infection in early life has been associated with a deficient T-helper cell type 1 (Th1) response. Conversely, healthy adults generally do not exhibit severe illness from RSV infection. In the current study, we investigated whether Th1 cytokine IFN-γ is essential for protection against RSV and RSV-associated comorbidities in adult mice. We found that, distinct from influenza virus, prior RSV infection does not induce significant IFN-γ production and susceptibility to secondary Streptococcus pneumoniae infection in adult wild-type (WT) mice. In ovalbumin (OVA)-induced asthmatic mice, RSV super-infection increases airway neutrophil recruitment and inflammatory lung damage …

The Staphylococcus Aureus Cida And Lrga Proteins Are Functional Holins Involved In The Transport Of By-Products Of Carbohydrate Metabolism, Jennifer L. Endres, Sujata S. Chaudhari, Xinyan Zhang, Janani Prahlad, Shu-Qi Wang, Lily A. Foley, Sorin Luca, Jeffrey L. Bose, Vinai C. Thomas, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

The Staphylococcus aureus cidABC and lrgAB operons encode members of a well-conserved family of proteins thought to be involved in programmed cell death (PCD). Based on the structural similarities that CidA and LrgA share with bacteriophage holins, we have hypothesized that these proteins function by forming pores within the cytoplasmic membrane. To test this, we utilized a "lysis cassette" system that demonstrated the abilities of the cidA and lrgA genes to support bacteriophage endolysin-induced cell lysis. Typical of holins, CidA- and LrgA-induced lysis was dependent on the coexpression of endolysin, consistent with the proposed holin-like functions of these proteins. In …

Ifn-Γ Transforms The Transcriptomic Landscape And Triggers Myeloid Cell Hyperresponsiveness To Cause Lethal Lung Injury, Atul K. Verma, Michael Mckelvey, Md Bashir Uddin, Sunil Palani, Meng Niu, Christopher Bauer, Shengjun Shao, Keer Sun

Journal Articles: Pathology and Microbiology

Acute Respiratory Distress Syndrome (ARDS) is an inflammatory disease that is associated with high mortality but no specific treatment. Our understanding of initial events that trigger ARDS pathogenesis is limited. We have developed a mouse model of inflammatory lung injury by influenza and methicillin-resistant Staphylococcus aureus (MRSA) coinfection plus daily antibiotic therapy. Using this pneumonic ARDS model, here we show that IFN-γ receptor signaling drives inflammatory cytokine storm and lung tissue damage. By single-cell RNA sequencing (scRNA-seq) analysis, we demonstrate that IFN-γ signaling induces a transcriptional shift in airway immune cells, particularly by upregulating macrophage and monocyte expression of genes …