Pathology Commons^™

Catabolic Ornithine Carbamoyltransferase Activity Facilitates Growth Of Staphylococcus Aureus In Defined Medium Lacking Glucose And Arginine, Itidal Reslane, Cortney R. Halsey, Amanda Stastny, Barbara J. Cabrera, Jong-Sam Ahn, Dhananjay Shinde, Madeline R. Galac, Margaret F. Sladek, Fareha Razvi, Mckenzie K. Lehman, Kenneth W. Bayles, Vinai Chittezham Thomas, Luke D. Handke, Paul D. Fey

Journal Articles: Pathology and Microbiology

Previous studies have found that arginine biosynthesis in Staphylococcus aureus is repressed via carbon catabolite repression (CcpA), and proline is used as a precursor. Unexpectedly, however, robust growth of S. aureus is not observed in complete defined medium lacking both glucose and arginine (CDM-R). Mutants able to grow on agar-containing defined medium lacking arginine (CDM-R) were selected and found to contain mutations within ahrC, encoding the canonical arginine biosynthesis pathway repressor (AhrC), or single nucleotide polymorphisms (SNPs) upstream of the native arginine deiminase (ADI) operon arcA1B1D1C1. Reverse transcription-PCR (RT-PCR) studies found that mutations within ccpA or ahrC or …

Case Report: Disseminated Mucormycosis In An Ostensibly Immunocompetent Patient, Chad Froes, Matt Gellatly, Brian Watson

South Atlantic Division Research Day 2022

No abstract provided.

Mitochondrial Dynamics Regulation Of The Lung Epithelial Response To Complex Allergen, Sierra White

Graduate College Dissertations and Theses

Asthma is a chronic inflammatory disease of the lungs that affects roughly 25 million Americans, costing the United States upwards of $80 billion annually in management and economic loss. The airway epithelium, which serves as the first line of defense against insults in the lung, are now appreciated as key contributors to initiation of this disease. A key regulator of the epithelial response to allergens and other inhaled irritants that can induce an allergic asthmatic response is the mitochondria. During an allergic response, the airway epithelial energy requirement changes, and mitochondrial function is altered, enhancing production of reactive oxygen species, …

Practices Of Vitamin D Supplementation Leading To Vitamin D Toxicity: Experience From A Low-Middle Income Country, Siraj Muneer, Imran Siddiqui, Hafsa Majid, Nawazish Zehra, Lena Jafri, Aysha Habib

Department of Pathology and Laboratory Medicine

Introduction: The trend of prescribing VD preparations for nonspecific body aches and self-medication has increased significantly. The importance of vitamin D toxicity (VDT) has been underestimated and under recognized. This study was done to determine the frequency toxicity (>150 ng/ml) in subjects for 25-hydroxyvitamin D (25OHD) and evaluate the vitamin D (VD) supplements used by these subjects.
Methodology: This descriptive cross-sectional study was conducted at the Section of Chemical Pathology, Aga Khan University Hospital Karachi from April 2020 to March 2021. Subjects with 25OHD toxicity were contacted and information related to history of calcium and VD supplementation were collected. …

D-Dimer Testing In Covid-19: From Basics To Clinical Application, Bushra Moiz

Department of Pathology and Laboratory Medicine

No abstract provided.

The Curious Case Of Hla-Dr-Positive Apl, Kanta Devi, Natasha Bahadur Ali

Section of Haematology/Oncology

The triad of weak/absent CD34, negative HLA-DR expression, and positivity to CD117 is pathognomonic for the diagnosis of acute promyelocytic leukemia. However, in rare cases, strong positivity to HLD-DR and CD34 may be noted.

Inhibition Of Nadph Oxidase Blocks Netosis And Reduces Thrombosis In Heparin-Induced Thrombocytopenia, Halina H L Leung, Jose Perdomo, Zohra Ahmadi, Feng Yan, Steven E. Mckenzie, Beng H Chong

Department of Medicine Faculty Papers

Heparin-induced thrombocytopenia (HIT) is associated with severe and potentially lethal thrombotic complications. NETosis was recently shown to be an important driver of thrombosis in HIT. We investigated the role of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and their contributions to thrombus development in HIT. We showed that neutrophil activation by HIT immune complexes induced ROS-dependent NETosis. Analysis of thrombi formed in a microfluidics system showed ROS production in both platelets and neutrophils, and abundant neutrophil extracellular traps (NETs) and ROS distributed throughout the clot. Neutrophil-targeted ROS inhibition was sufficient to block HIT-induced NETosis …

Lipid A-Ara4n As An Alternate Pathway For (Colistin) Resistance In Klebsiella Pneumonia Isolates In Pakistan, Kiran I. Masood, Seema Umar, Zahra Hasan, Joveria Farooqi, Safina Abdul Razzak, Nazish Jabeen, Jason Rao Jason Rao, Sadia Shakoor, Rumina Hasan

Department of Pathology and Laboratory Medicine

Objectives: This study aimed to explore mechanism of colistin resistance amongst Klebsiella pneumoniae isolates through plasmid mediated mcr-1 gene in Pakistan. Carbapenem and Colistin resistant K. pneumoniae isolates (n = 34) stored at - 80 °C as part of the Aga Khan University Clinical Laboratory strain bank were randomly selected and subjected to mcr-1 gene PCR. To investigate mechanisms of resistance, other than plasmid mediated mcr-1 gene, whole genome sequencing was performed on 8 clinical isolates, including 6 with colistin resistance (MIC > 4 μg/ml) and 2 with intermediate resistance to colistin (MIC > 2 μg/ml).
Results: RT-PCR conducted revealed absence of …

Primary Localized Amyloidosis Of The Ureter With Osseous Metaplasia Presenting As A Suspicious Ureteral Mass, Nada Shaker, Zofia Tynski, Madeline Hudlak, Roy R Brown, Shadi Qasem, Anil Parwani

Pathology and Laboratory Medicine Faculty Publications

Primary amyloidosis of the ureter is a rare disease that is difficult to distinguish from urothelial carcinoma. Only 50 cases of primary ureter amyloidosis have been reported since it was first described in 1937. Of these, only five cases of ureter amyloidosis with osseous metaplasia were reported. In this study, we report the clinical presentation of ureter primary amyloidosis that presented as a mass with osseous metaplasia. The aim of this study is to provide clinicians with knowledge about the clinical/radiologic manifestation that raise the suspicion of amyloidosis, bearing in mind the importance of differentiating it from other "malignant" processes.

Durable Response To Brentuximab Vedotin Plus Cyclophosphamide, Doxorubicin, And Prednisone (Bv-Chp) In A Patient With Cd30-Positive Ptcl Arising As A Post-Transplant Lymphoproliferative Disorder (Ptld), Jennifer Hong, William T Johnson, Saritha Kartan, Anitha S Gonsalves, Jonathan M. Fenkel, Jerald Z. Gong, Pierluigi Porcu

Department of Medical Oncology Faculty Papers

T-cell PTLDs are lymphoid proliferations that develop in recipients of SOT or allogeneic HSCT. They carry an extremely poor prognosis with a reported median survival of only 6 months. The infrequency with which they are encountered makes treatment a challenge due to the lack of prospective trials to guide management. The significantly higher risk of morbidity and mortality in T-cell PTLD, compared to B-cell PTLD, underscores the challenge of treating these patients and the need for new therapeutic options. Brentuximab vedotin, an ADC targeting CD30, is FDA-approved in combination with CHP as front-line treatment for patients with CD30 expressing PTCL. …

Multiplex Pcr Pathogen Detection In Acute Gastroenteritis Among Hospitalized Us Children Compared With Healthy Controls During 2011-2016 In The Post-Rotavirus Vaccine Era., Christopher J. Harrison, Ferdaus Hassan, Brian R. Lee, Julie Boom, Leila C. Sahni, Coreen Johnson, James Dunn, Daniel C. Payne, Mary E. Wikswo, Umesh Parashar, Rangaraj Selvarangan

Manuscripts, Articles, Book Chapters and Other Papers

Background: Despite vaccine-induced decreases in US rotavirus (RV) disease, acute gastroenteritis (AGE) remains relatively common. We evaluated AGE pathogen distribution in hospitalized US children in the post-RV vaccine era.

Methods: From December 2011 to June 2016, the New Vaccine Surveillance Network (NVSN) conducted prospective, active, population-based surveillance in hospitalized children with AGE. We tested stools from 2 NVSN sites (Kansas City, Houston) with Luminex x-TAG Gastrointestinal Pathogen Panels (Luminex GPP) and analyzed selected signs and symptoms.

Results: For 660 pediatric AGE inpatients and 624 age-matched healthy controls (HCs), overall organism detection was 51.2% and 20.6%, respectively (P < .001). Among AGE subjects, GPP polymerase chain reaction detected >1 virus …

Effect Of 3 Days Of Oral Azithromycin On Young Children With Acute Diarrhea In Low-Resource Settings: A Randomized Clinical Trial, Antibiotics For Children With Diarrhea (Abcd) Study Group, Tahmeed Ahmed, Farah Naz Qamar, Mohammad Tahir Yousafzai, Shahida Qureshi, Sadia Shakoor, Rozina Thobani, Aneeta Hotwani, Furqan Kabir, Jan Mohammed

Department of Paediatrics and Child Health

Importance: World Health Organization (WHO) guidelines do not recommend routine antibiotic use for children with acute watery diarrhea. However, recent studies suggest that a significant proportion of such episodes have a bacterial cause and are associated with mortality and growth impairment, especially among children at high risk of diarrhea-associated mortality. Expanding antibiotic use among dehydrated or undernourished children may reduce diarrhea-associated mortality and improve growth.
Objective: To determine whether the addition of azithromycin to standard case management of acute nonbloody watery diarrhea for children aged 2 to 23 months who are dehydrated or undernourished could reduce mortality and improve linear …

The Role Of Decorin And Biglycan Signaling In Tumorigenesis, Valentina Diehl, Lisa Sophie Huber, Jonel Trebicka, Malgorzata Wygrecka, Renato V. Iozzo, Liliana Schaefer

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The complex and adaptive nature of malignant neoplasm constitute a major challenge for the development of effective anti-oncogenic therapies. Emerging evidence has uncovered the pivotal functions exerted by the small leucine-rich proteoglycans, decorin and biglycan, in affecting tumor growth and progression. In their soluble forms, decorin and biglycan act as powerful signaling molecules. By receptor-mediated signal transduction, both proteoglycans modulate key processes vital for tumor initiation and progression, such as autophagy, inflammation, cell-cycle, apoptosis, and angiogenesis. Despite of their structural homology, these two proteoglycans interact with distinct cell surface receptors and thus modulate distinct signaling pathways that ultimately affect cancer …

Outcomes Of Patients With Double/Triple Expressor Diffuse Large B-Cell Lymphoma (Dlbcl) Treated With R-Da-Epoch/R-Chop: A Single-Center Experience, Kanta Devi, Mohammad Usman Shaikh, Natasha Bahadur Ali, Salman Adil, Maria Khan, Salman Muhammad Soomar

Section of Haematology/Oncology

In Pakistan 76.4% of all NHLs to be diagnosed as DLBCLs. The survival of R-CHOP is better compared to the DA-REPOCH treatment regimen. A prospective follow-up study was conducted with 113 patients to study the outcomes of treatment. Multivariable cox-proportional hazard model was used to estimate the hazard ratios in patients receiving these treatment regimens considering p-value ≤0.05 significant. The survival rate among double/triple expressor lymphoma patients received R-DA-EPOCH was 82.8%, and 83.3% received R-CHOP. For double/triple expressor lymphoma patients received R-DA-EPOCH. The findings of our study demonstrated that the survival rate in both R-CHOP and R-DA-EPOCH is mostly …

Rare Case Of Mediastinal Myeloid Sarcoma, Kanta Devi, Salman Adil, Natasha Bahadur Ali, Nasir Ali, Hammad Khan

Section of Haematology/Oncology

Myeloid sarcoma is a rare tumor mass with extra medullary growth pattern, composed of myeloblast or immature myeloid cells. Myeloid sarcoma (MS) is a distinct clinical presentation of acute myeloid leukemia (AML) where less than 1% of patients present with prominent extra medullary disease which most commonly involves the bone, skin, lymph node, soft tissues, gastrointestinal tract or testes. The recommended treatment regimen in isolated myeloid sarcoma or with bone marrow involvement is upfront systemic chemotherapy. We report a case of a young female with anterior mediastinal mass diagnosed as myeloid sarcoma which was refractory to chemotherapy.

Intracranial Mesenchymal Tumors With Fet-Creb Fusion Are Composed Of At Least Two Epigenetic Subgroups Distinct From Meningioma And Extracranial Sarcomas, Emily A. Sloan, Rohit Gupta, Christian Koelsche, Jason Chiang, Javier E. Villanueva-Meyer, Sanda Alexandrescu, Jennifer E. Eschbacher, Wesley Wang, Manuela Mafra, Nasir Ud Din

Department of Pathology and Laboratory Medicine

Intracranial mesenchymal tumor, FET-CREB fusion-positive' occurs primarily in children and young adults and has previously been termed intracranial angiomatoid fibrous histiocytoma (AFH) or intracranial myxoid mesenchymal tumor (IMMT). Here we performed genome-wide DNA methylation array profiling of 20 primary intracranial mesenchymal tumors with FET-CREB fusion to further study their ontology. These tumors resolved into two distinct epigenetic subgroups that were both divergent from all other analyzed intracranial neoplasms and soft tissue sarcomas, including meningioma, clear cell sarcoma of soft tissue (CCS), and AFH of extracranial soft tissue. The first subgroup (Group A, 16 tumors) clustered nearest to but independent of …

Upregulated Type I Interferon Responses In Asymptomatic Covid-19 Infection Are Associated With Improved Clinical Outcome, Kiran I. Masood, Maliha Yameen, Javeria Ashraf, Saba Shahid, Syed Faisal Mahmood, Asghar Nasir, Nosheen Nasir, Bushra Jamil, Najia Karim Ghanchi, Iffat Khanum, Safina Abdul Razzak, Akber Kanji, Rabia Hussain, Martin E. Rottenberg, Zahra Hasan

Department of Pathology and Laboratory Medicine

Understanding key host protective mechanisms against SARS-CoV-2 infection can help improve treatment modalities for COVID-19. We used a blood transcriptome approach to study biomarkers associated with differing severity of COVID-19, comparing severe and mild Symptomatic disease with Asymptomatic COVID-19 and uninfected Controls. There was suppression of antigen presentation but upregulation of inflammatory and viral mRNA translation associated pathways in Symptomatic as compared with Asymptomatic cases. In severe COVID-19, CD177 a neutrophil marker, was upregulated while interferon stimulated genes (ISGs) were downregulated. Asymptomatic COVID-19 cases displayed upregulation of ISGs and humoral response genes with downregulation of ICAM3 and TLR8. Compared across …

A Biocultural Analysis Of The Impacts Of Interactions Between West Africans And Europeans During The Trans-Atlantic Trade At Elmina, Ghana, Heidi Ellen Miller

USF Tampa Graduate Theses and Dissertations

This project utilizes a biocultural approach to assess the demographics and health of the West African population from Elmina, Ghana. Elmina, selected by the Portuguese in 1482 as the site of the first European trade fort in sub-Saharan Africa, grew from a small coastal fishing village to a large settlement over the course of more than 400 years of trade and cultural entanglement. Taken over by the Dutch and then ceded to the British, the people of Elmina navigated significant cultural changes, changes and experiences that can be detected in their skeletal remains. Bioarchaeological research concerned with the effects of …

Low-Grade Primary Splenic Cd10-Positive Small B-Cell Lymphoma/Follicular Lymphoma, Rami Abdulbaki, Parastou Tizro, Victor E. Nava, Maria Gomes Da Silva, Joao L. Ascensao

Pathology Faculty Publications

No abstract provided.

Metabolic Adaptation To The Chronic Loss Of Ca 2+ Signaling Induced By Ko Of Ip 3 Receptors Or The Mitochondrial Ca 2+ Uniporter, Michael P. Young, Zachary T Schug, David M. Booth, David I Yule, Katsuhiko Mikoshiba, György Hajnóczky, Suresh K Joseph

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Calcium signaling is essential for regulating many biological processes. Endoplasmic reticulum inositol trisphosphate receptors (IP3Rs) and the mitochondrial Ca2+ uniporter (MCU) are key proteins that regulate intracellular Ca2+ concentration. Mitochondrial Ca2+ accumulation activates Ca2+-sensitive dehydrogenases of the tricarboxylic acid (TCA) cycle that maintain the biosynthetic and bioenergetic needs of both normal and cancer cells. However, the interplay between calcium signaling and metabolism is not well understood. In this study, we used human cancer cell lines (HEK293 and HeLa) with stable KOs of all three IP3R isoforms (triple KO [TKO]) or MCU to examine metabolic and bioenergetic responses to the chronic …