Pathology Commons^™

Histopathology Report On Colon Cancer Specimens; Measuring Surgical Quality, An Increasing Stress For Surgeons, Stefan Morarasu, Tudor Frunza, Karina Bilavschi, Ana Maria Patrascu, Sorinel Lunca, Gabriel Dimofte

Journal of Mind and Medical Sciences

Introduction. Improving the quality of surgical resections by evaluating surgical specimens is probably the most important feedback a surgeon can receive. Moreover, prognosis of patients with colon cancer is based on achieving appropriate resection margins and assessment of lymph node status. For these reasons we aim to provide a retrospective analysis on colon cancer specimens operated by a single surgical team.

Materials and Methods. 88 patients operated between 2013 and 2016 were included in the study. Data were gathered prospectively and assessed by multivariate analysis for the main variables (age, gender, tumor staging, specimen length, distance to closest resection margin, …

Spsnet: Subpopulation-Sensitive Network-Based Analysis Of Heterogeneous Gene Expression Data., Abha Belorkar, Rajanikanth Vadigepalli, Limsoon Wong

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Transcriptomic datasets often contain undeclared heterogeneity arising from biological variation such as diversity of disease subtypes, treatment subgroups, time-series gene expression, nested experimental conditions, as well as technical variation due to batch effects, platform differences in integrated meta-analyses, etc. However, current analysis approaches are primarily designed to handle comparisons between experimental conditions represented by homogeneous samples, thus precluding the discovery of underlying subphenotypes. Unsupervised methods for subtype identification are typically based on individual gene level analysis, which often result in irreproducible gene signatures for potential subtypes. Emerging methods to study heterogeneity have been largely developed in the context of …

Head Injury Risk And Car Seat Use For Children In Collisions, Peyton A. Schroeder, M.J. Skhurm, D. Fraser, K. Mcclafferty

Western Research Forum

Background: Motor vehicle collisions (MVCs) are the leading cause of death for people under the age of 17 years. Almost 80% of rear seat motor vehicle passengers are children. Previous studies have shown that a large fraction of injuries to children in MVCs involved the head and chest. In this study, the hypothesis that children under the age of eight using a forward-facing child restraint system (FFCRS) will have more severe head injuries than children using any other type of restraints in an MVC was tested.

Methods: Several datasets obtained from Transport Canada and Level 1 Pediatric Trauma Centre emergency …

Experimental Intravascular Hemolysis Induces Hemodynamic And Pathological Pulmonary Hypertension: Association With Accelerated Purine Metabolism, Victor P. Bilan, Frank Schneider, Enrico M. Novelli, Eric E. Kelley, Sruti Shiva, Mark T. Gladwin, Edwin K. Jackson, Stevan P. Tofovic

Faculty & Staff Scholarship

Pulmonary hypertension (PH) is emerging as a serious complication associated with hemolytic disorders, and plexiform lesions (PXL) have been reported in patients with sickle cell disease (SCD). We hypothesized that repetitive hemolysis per se induces PH and angioproliferative vasculopathy and evaluated a new mechanism for hemolysis-associated PH (HA-PH) that involves the release of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) from erythrocytes. In healthy rats, repetitive admin- istration of hemolyzed autologous blood (HAB) for 10 days produced reversible pulmonary parenchymal injury and vascular remodeling and PH. Moreover, the combination of a single dose of Sugen-5416 (SU, 200mg/kg) and 10-day …

Wdr5 Supports Colon Cancer Cells By Promoting Methylation Of H3k4 And Suppressing Dna Damage, Beth K. Neilsen, Binita Chakraborty, Jamie L. Mccall, Danielle E. Frodyma, Richard L. Sleightholm, Kurt W. Fisher, Robert E. Lewis

Faculty & Staff Scholarship

Background: KMT2/MLL proteins are commonly overexpressed or mutated in cancer and have been shown to support cancer maintenance. These proteins are responsible for methylating histone 3 at lysine 4 and promoting transcription and DNA synthesis; however, they are inactive outside of a multi-protein complex that requires WDR5. WDR5 has been implicated in cancer for its role in the COMPASS complex and its interaction with Myc; however, the role of WDR5 in colon cancer has not yet been elucidated.

Methods: WDR5 expression was evaluated using RT-qPCR and western blot analysis. Cell viability and colony forming assays were utilized to evaluate the …

Metabolic And Transcriptional Modules Independently Diversify Plasma Cell Lifespan And Function, Wing Y. Lam, Arijita Jash, Cong-Hui Yao, Lucas D'Souza, Rachel Wong, Ryan M. Nunley, Gordon P. Meares, Gary J. Patti, Deepta Bhattacharya

Faculty & Staff Scholarship

Plasma cell survival and the consequent duration of immunity vary widely with infection or vaccination. Using fluorescent glucose analog uptake, we defined multiple developmentally independent mouse plasma cell populations with varying life- spans. Long-lived plasma cells imported more fluo- rescent glucose analog, expressed higher surface levels of the amino acid transporter CD98, and had more autophagosome mass than did short-lived cells. Low amino acid concentrations triggered re- ductions in both antibody secretion and mitochon- drial respiration, especially by short-lived plasma cells. To explain these observations, we found that glutamine was used for both mitochondrial respira- tion and anaplerotic reactions, yielding …

Oligomerization Of Bacterially Expressed H1n1 Recombinant Hemagglutinin Contributes To Protection Against Viral Challenge, Tess E. Kuenstling, Anthony R. Sambol, Steven H. Hinrichs, Marilynn A. Larson

Journal Articles: Pathology and Microbiology

Vaccination is the most effective intervention to prevent influenza and control the spread of the virus. Alternatives are needed to the traditional egg-based vaccine strategy for a more rapid response to new outbreaks. Two different hemagglutinin (HA) fragments (rHA1_1-326 and rHA1_53-269) derived from influenza A virus subtype H1N1 were expressed in Escherichia coli and characterized by immunoblot, gel filtration, hemagglutination, and competitive binding assays. rHA1_1-326 included neutralizing epitopes and the trimerization domain, whereas rHA1_53-269 included only the head of HA with the neutralizing epitopes. Mice were immunized with rHA1_1-326 or rHA1_53-269, and …

Searching For Novel Biomarkers Using A Mouse Model Of Cln3-Batten Disease, Derek Timm, Jacob T. Cain, Ryan D. Geraets, Katherine A. White, Seung Yon Koh, Tammy Kielian, David A. Pearce, Michelle L. Hastings, Jill M. Weimer

Journal Articles: Pathology and Microbiology

CLN3-Batten disease is a rare, autosomal recessive disorder involving seizures, visual, motor and cognitive decline, and premature death. The Cln3Δex7/8 mouse model recapitulates several phenotypic characteristics of the most common 1.02kb disease-associated deletion. Identification of reproducible biomarker(s) to facilitate longitudinal monitoring of disease progression and provide readouts for therapeutic response has remained elusive. One factor that has complicated the identification of suitable biomarkers in this mouse model has been that variations in animal husbandry appear to significantly influence readouts. In the current study, we cross-compared a number of biological parameters in blood from Cln3Δex7/8 mice and control, non-disease mice on …

The Pathology Workforce And Clinical Licensure, Robin Lorenz, Donald S. Karcher, Michael Gautreaux, Melvin Limson, Dani Zander

Pathology Faculty Publications

There has been a recent recognition of the need to prepare PhD-trained scientists for increasingly diverse careers in academia, industry, and health care. The PhD Data Task Force was formed to better understand the current state of PhD scientists in the clinical laboratory workforce and collect up-to-date information on the training and certification of these laboratorians. In this report, we summarize the findings of the PhD Data Task Force and discuss the relevance of the data collected to the future supply of and demand for PhD clinical laboratory scientists. It is clear that there are multiple career opportunities for PhD …

Pd-L1 Checkpoint Inhibition And Anti-Ctla-4 Whole Tumor Cell Vaccination Counter Adaptive Immune Resistance: A Mouse Neuroblastoma Model That Mimics Human Disease., Priya Srinivasan, Xiaofang Wu, Mousumi Basu, Christopher Rossi, Anthony D Sandler

Pathology Faculty Publications

BACKGROUND: Adaptive immune resistance induces an immunosuppressive tumor environment that enables immune evasion. This phenomenon results in tumor escape with progression and metastasis. Programmed cell death-ligand 1 (PD-L1) expressed on tumors is thought to inhibit tumor-infiltrating lymphocytes (TILs) through programmed cell death 1 (PD1), enabling adaptive immune resistance. This study investigates the role of PD-L1 in both mouse and human neuroblastoma immunity. The consequence of PD-L1 inhibition is characterized in the context of an established whole tumor cell vaccine.

METHODS AND FINDINGS: A mouse model of neuroblastoma was investigated using an Id2 knockdown whole cell vaccine in combination with checkpoint …

Reducing Discard Blood Draw Volumes From Subcutaneously Implanted Ports (Port) In Patients With End Stage Renal Disease (Esrd), Uttam Garg, Tyson Moore, Renita Trujillo, Penny Monachino, Amy Wiebold, Angela Ferguson, Gabor Oroszi, Vimal Chadha

Posters

Background
•To monitor clinical status, dialysis and transplant patients with ESRD frequently require blood draws.
•To preserve their veins and to avoid frequent intravenous access, these patients, especially young children, require PORT placement.
•The PORT is flushed with saline and filled with heparinized saline to prevent blood clotting between blood draws.
•To avoid contamination from PORT fluids, a fixed amount of blood is withdrawn and discarded before the blood sample is drawn for laboratory analyses. Currently, the recommended discard blood volume is 5 mL (five times the reservoir volume of most PORTs and attached catheters.)
•The volume of discarded blood …

Primary Liver Cancers, Part 2: Progression Pathways And Carcinogenesis, Kun Jiang, Barbara A. Centeno

Pathology and Cell Biology Faculty Publications

Hepatocellular carcinoma (HCC) and primary intrahepatic cholangiocarcinoma (ICC) have been increasing in incidence worldwide and are leading causes of cancer death. Studies of the molecular alterations leading to these carcinomas provide insights into the key mechanisms involved. A literature review was conducted to identify articles with information relevant to current understanding of the etiologies and molecular pathogenesis of HCC and ICC. Chronic inflammatory diseases are the key etiological risk factors for both HCC and ICC, although other diseases play a role, and for many ICCs, an underlying risk factor is not identified. Mutations in catenin beta 1 (CTNBB1) …

Recurrent Aneurysmal Bone Cyst Of The Distal Fibula Treated With Denosumab And Curettage, Philip B. Fontenot, Jose Jesurajan, Marilyn Bui, Damon Reed, Odion Binitie

Pathology and Cell Biology Faculty Publications

We report the case of a 13-year-old girl with multiple recurrences of an aneurysmal bone cyst of the distal fibula successfully treated with denosumab and curettage. Aneurysmal bone cysts are locally aggressive lesions with high rates of recurrence. The novel use of denosumab with curettage in a long bone showed a favorable outcome with no adverse events or signs of recurrence three years after treatment.

Primary Liver Cancers—Part 1: Histopathology, Differential Diagnoses, And Risk Stratification, Kun Jiang, Sameer Al-Diffalha, Barbara A. Centeno

Pathology and Cell Biology Faculty Publications

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) are the 2 most common primary malignant liver tumors, with hepatocellular and bile ductular differentiation, respectively. This article reviews the key histopathological findings of these 2 primary liver cancers and includes a review of the role of ancillary testing for differential diagnosis, risk stratification according to the American Joint Committee on Cancer (AJCC) staging recommendation, and a review of precancerous lesions. A literature review was conducted to identify articles with information relevant to precancerous precursors, current histopathological classification, ancillary testing, and risk stratification of primary malignant liver tumors. The histomorphology of normal liver, preinvasive …

Significant Loss Of Blood Amino Acids And Free Carnitine In Newborns Receiving Continuous Renal Replacement Therapy (Crrt), Uttam Garg, Marita Thompson, Bradley A. Warady, Vimal Chadha

Posters

Background

•Newborns with acute kidney injury (AKI) or end-stage kidney disease (ESKD) often receive prolonged CRRT when the early initiation of peritoneal dialysis is either contraindicated or unable to be performed. •These patients often receive total parenteral nutrition (TPN) to meet their nutritional goals. •Little to no information exists on the loss of blood amino acids (AA) and carnitine during CRRT in these patients. •The objective of this study was to determine the amino acids and carnitine losses in newborns receiving prolonged CRRT and TPN. Material and Methods

•Three newborns who received prolonged (> 2 weeks) CRRT and TPN were …

Down Syndrome, Beta-Amyloid And Neuroimaging, Elizabeth Head, Alex M. Helman, David K. Powell, Frederick A. Schmitt

Sanders-Brown Center on Aging Faculty Publications

This review focuses on the role of Aβ in AD pathogenesis in Down syndrome and current approaches for imaging Aβ in vivo. We will describe how Aβ deposits with age, the posttranslational modifications that can occur, and detection in biofluids. Three unique case studies describing partial trisomy 21 cases without APP triplication, and the occurrences of low level mosaic trisomy 21 in an early onset AD patient are presented. Brain imaging for Aβ includes those by positron emission tomography and ligands (Pittsburgh Compound B, Florbetapir, and FDDNP) that bind Aβ have been published and are summarized here. In combination, we …

Mechanotransduction Signaling In Podocytes From Fluid Flow Shear Stress., Tarak Srivastava, Hongying Dai, Daniel P. Heruth, Uri S. Alon, Robert E. Garola, Jianping Zhou, R Scott Duncan, Ashraf El-Meanawy, Ellen T. Mccarthy, Ram Sharma, Mark L. Johnson, Virginia J. Savin, Mukut Sharma

Manuscripts, Articles, Book Chapters and Other Papers

Recently, we and others have found that hyperfiltration-associated increase in biomechanical forces, namely, tensile stress and fluid flow shear stress (FFSS), can directly and distinctly alter podocyte structure and function. The ultrafiltrate flow over the major processes and cell body generates FFSS to podocytes. Our previous work suggests that the cyclooxygenase-2 (COX-2)-PGE2-PGE2 receptor 2 (EP2) axis plays an important role in mechanoperception of FFSS in podocytes. To address mechanotransduction of the perceived stimulus through EP2, cultured podocytes were exposed to FFSS (2 dyn/cm2) for 2 h. Total RNA from cells at the end of FFSS treatment, 2-h post-FFSS, and 24-h …

Cerebrovascular Pathology In Down Syndrome And Alzheimer Disease, Elizabeth Head, Michael J. Phelan, Eric Doran, Ronald C. Kim, Wayne W. Poon, Frederick A. Schmitt, Ira T. Lott

Sanders-Brown Center on Aging Faculty Publications

People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD) with age. Typically, by age 40 years, most people with DS have sufficient neuropathology for an AD diagnosis. Interestingly, atherosclerosis and hypertension are atypical in DS with age, suggesting the lack of these vascular risk factors may be associated with reduced cerebrovascular pathology. However, because the extra copy of APP leads to increased beta-amyloid peptide (Aβ) accumulation in DS, we hypothesized that there would be more extensive and widespread cerebral amyloid angiopathy (CAA) with age in DS relative to sporadic AD. To test this hypothesis CAA, …

A Customized Quantitative Pcr Microrna Panel Provides A Technically Robust Context For Studying Neurodegenerative Disease Biomarkers And Indicates A High Correlation Between Cerebrospinal Fluid And Choroid Plexus Microrna Expression, Wang-Xia Wang, David W. Fardo, Gregory A. Jicha, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNA (miRNA) expression varies in association with different tissue types and in diseases. Having been found in body fluids including blood and cerebrospinal fluid (CSF), miRNAs constitute potential biomarkers. CSF miRNAs have been proposed as biomarkers for neurodegenerative diseases; however, there is a lack of consensus about the best candidate miRNA biomarkers and there has been variability in results from different research centers, perhaps due to technical factors. Here, we sought to optimize technical parameters for CSF miRNA studies. We examined different RNA isolation methods and performed miRNA expression profiling with TaqMan® miRNA Arrays. More specifically, we developed a customized …

Hne-Modified Proteins In Down Syndrome: Involvement In Development Of Alzheimer Disease Neuropathology, Eugenio Barone, Elizabeth Head, D. Allan Butterfield, Marzia Perluigi

Sanders-Brown Center on Aging Faculty Publications

Down syndrome (DS), trisomy of chromosome 21, is the most common genetic form of intellectual disability. The neuropathology of DS involves multiple molecular mechanisms, similar to AD, including the deposition of beta-amyloid (Aβ) into senile plaques and tau hyperphosphorylating in neurofibrillary tangles. Interestingly, many genes encoded by chromosome 21, in addition to being primarily linked to amyloid-beta peptide (Aβ) pathology, are responsible for increased oxidative stress (OS) conditions that also result as a consequence of reduced antioxidant system efficiency. However, redox homeostasis is disturbed by overproduction of Aβ, which accumulates into plaques across the lifespan in DS as well as …

Characterization Of Different Molecular Markers For Identification Of Salmonella Enterica Serovar Typhi In Pakistani Population, Faizan Muttiullah, Fida Muhammad Khan, Fakhar-I- Abbas, Sabiha Shamim

Journal of Bioresource Management

Typhoid is caused by Salmonella enterica serovar Typhi that is usually diagnosed by using serologic and immuno-chromatographic techniques in developing counties including Pakistan, which is thought to be an unreliable diagnostic method. For accurate diagnosis we used molecular techniques to amplify 204 bp StyR-36 and 498 bp flagellin gene for the identification of Salmonella enterica serovar Typhi. This study was done on 58 individuals diagnosed positive of typhoid via serologic tests and 50 healthy individuals as a control group. Success rate of amplification for flagellin gene was 77.58% while that for StyR-36 gene was 68.97% showing that flagellin gene primer …

Alk-Positive Primary Central Nervous System Anaplastic Large T-Cell Lymphoma: A Unique Case Presentation, Amar Jariwala, M Isabel Almira-Suarez, Elsie Lee

Pathology Faculty Publications

Anaplastic large cell lymphoma (ALCL) is a rare T-cell lymphoma usually ALK⁺ and presenting in immunocompetent young adults and children with a female preponderance. Central nervous system (CNS) involvement of ALCL T-cell lymphoma is extremely rare; approximately 30 cases are reported in the literature, mostly in male patients of Korean and Japanese ancestry and involving the parietal and frontal lobes. We report a unique case of ALK⁺ ALCL in an Asian woman and predominantly involving the occipital lobe. The patient, an immuno-competent 18-year-old woman with a recent history of viral meningitis, presented with left-sided vision changes. Magnetic resonance …

Acute Myelomonocytic Leukemia With Tetrasomy 8: Histologic And Immunophenotypic Features Mimicking Acute Promyelocytic Leukemia, Amar Jariwala, Donald S. Karcher

Pathology Faculty Publications

Rare cases of acute myeloid leukemia (AML) with tetrasomy 8 have been reported. Tetrasomy 8, a poor prognostic factor, has been predominantly associated with AML with monocytic differentiation. We report an unusual case of acute myelomonocytic leukemia (AMML) with tetrasomy 8 showing histologic and immunophenotypic features mimicking acute promyelocytic leukemia (APL). The patient is a 63-year-old African American man with molar pain, gum swelling and bleeding, generalized fatigue, leukocytosis, anemia, and thrombocytopenia. A peripheral blood smear showed increased white cells with many immature granulocytic forms. Approximately 40% of the cells exhibited classical blast morphology, 40% were slightly enlarged and exhibited …

Novel Influences Of Il-10 On Cns Inflammation Revealed By Integrated Analyses Of Cytokine Networks And Microglial Morphology., Warren D. Anderson, Andrew D. Greenhalgh, Aditya Takwale, Samuel David, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Coordinated interactions between cytokine signaling and morphological dynamics of microglial cells regulate neuroinflammation in CNS injury and disease. We found that pro-inflammatory cytokine gene expression in vivo showed a pronounced recovery following systemic LPS. We performed a novel multivariate analysis of microglial morphology and identified changes in specific morphological properties of microglia that matched the expression dynamics of pro-inflammatory cytokine TNFα. The adaptive recovery kinetics of TNFα expression and microglial soma size showed comparable profiles and dependence on anti-inflammatory cytokine IL-10 expression. The recovery of cytokine variations and microglial morphology responses to inflammation were negatively regulated by IL-10. Our novel …

Towards A Personalized Cancer Gene Therapy: A Case Of Clear Cell Renal Cell Carcinoma, Dumitru Iacobas, Sanda Iacobas

NYMC Faculty Publications

No abstract provided.

Zinc Transporters Ybtx And Znuabc Are Required For The Virulence Of Yersinia Pestis In Bubonic And Pneumonic Plague In Mice, Alexander G. Bobrov, Olga Kirillina, Marina Y. Fosso, Jacqueline D. Fetherston, M. Clarke Miller, Tiva T. Vancleave, Joseph A. Burlison, William K. Arnold, Matthew B. Lawrenz, Sylvie Garneau-Tsodikova, Robert D. Perry

Microbiology, Immunology, and Molecular Genetics Faculty Publications

A number of bacterial pathogens require the ZnuABC Zinc (Zn²⁺) transporter and/or a second Zn²⁺ transport system to overcome Zn²⁺ sequestration by mammalian hosts. Previously we have shown that in addition to ZnuABC, Yersinia pestis possesses a second Zn²⁺ transporter that involves components of the yersiniabactin (Ybt), siderophore-dependent iron transport system. Synthesis of the Ybt siderophore and YbtX, a member of the major facilitator superfamily, are both critical components of the second Zn²⁺ transport system. Here we demonstrate that a ybtX znu double mutant is essentially avirulent in mouse models of bubonic and pneumonic …

The Nephrotoxicity Of Vancomycin., Edward J. Filippone, Walter K. Kraft, John L. Farber

Department of Medicine Faculty Papers

No abstract provided.

Chat Expression In Chlamydia Muridarum-Infected Female Murine Genital Tract, Hallie Sartain

Undergraduate Honors Theses

Chlamydia trachomatis is the most prevalent agent of bacterial sexually transmitted infections in the world. However, a profuse number of cases are unreported, as the infection is often asymptomatic. Sequelae such as pelvic inflammatory disease, an increased risk of cervical cancer, premature birth, and perinatal infections in pregnant women can occur. Inflammation occurs in the body in response to infection or injury. Although inflammation can lead to some unwanted secondary effects, such as pain, it serves to return the body to homeostasis by restoring injured tissues and eliminating pathogens. One recently identified connection between the central nervous system and the …

Exploring Therapeutic Approaches For Marfan Syndrome Associated Aortic Aneurysm, Mitra Esfandiarei

Science Seminar Series

Esfandiearei will be discussing her research on understanding the underlying mechanisms contributing to the progression of aortic aneurysm in Marfan syndrome and the protective effects that exercise may have on the disease process in both laboratory animal models and human patients. Her research has been supported by the Canadian Institutes of Health Research (CIHR), Rare Diseases Foundation, and the Marfan Foundation.

Outcomes After Diagnosis Of Mild Cognitive Impairment In A Large Autopsy Series, Erin L. Abner, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Daniela C. Moga, Eseosa T. Ighodaro, Gregory A. Jicha, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Randall L. Woltjer, Julie A. Schneider, Nigel J. Cairns, David A. Bennett, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

OBJECTIVE: To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI).

METHODS: Data were drawn from a large autopsy series (N = 1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States.

RESULTS: Mean follow‐up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group had pathological features resembling those with a final clinical …