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Full-Text Articles in Pathology

Microscopic Examination Of Findings Encountered During Cadaver Dissection: Malignant, Benign Or Anatomic Variation?, Maria Cicioni, Vandi Ly, Guiyun Zhang, Bruce Fenderson Mar 2017

Microscopic Examination Of Findings Encountered During Cadaver Dissection: Malignant, Benign Or Anatomic Variation?, Maria Cicioni, Vandi Ly, Guiyun Zhang, Bruce Fenderson

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Pathologic findings encountered during cadaver dissection provide an opportunity for integrating the preclinical basic sciences and encouraging critical thinking. The objective of this study was to determine whether it is possible to make a pathologic diagnosis of an unknown mass from an embalmed cadaver. Diagnoses would have to be based solely on gross and microscopic appearance of tissue, without clinical histories of the cadaveric donors. The tissue samples we removed from each mass were surprisingly well preserved and showed minimal autolysis. Indeed, some of the histological detail was as clear as may be found in any textbook. We were able …


Diagnosis Of Lchad/Tfp Deficiency In An At Risk Newborn Using Umbilical Cord Blood Acylcarnitine Analysis, Donna Raval, Kristina Cusmano-Ozog, Omar Ayyub, Callie Jenevein, Laura Kofman, Brendan Lanpher, Natalie Hauser, Debra Regier Mar 2017

Diagnosis Of Lchad/Tfp Deficiency In An At Risk Newborn Using Umbilical Cord Blood Acylcarnitine Analysis, Donna Raval, Kristina Cusmano-Ozog, Omar Ayyub, Callie Jenevein, Laura Kofman, Brendan Lanpher, Natalie Hauser, Debra Regier

Pathology Faculty Publications

Trifunctional protein deficiency/Long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHAD/TFP) deficiency is a disorder of fatty acid oxidation and ketogenesis. Severe neonatal lactic acidosis, cardiomyopathy, and hepatic dysfunction are caused by the accumulation of toxic long-chain acylcarnitines. The feasibility of umbilical cord blood use in screening for acylcarnitine analysis and free carnitine has been hypothesized but not reported in LCHAD/TFP neonates.

We present a 4 week old female who was at risk of inheriting LCHAD/TFP deficiency and was diagnosed at the time of delivery using umbilical cord blood. Umbilical cord blood was collected at delivery and sent for acylcarnitine analysis. Treatment was started …


Novel Long-Chain Compounds With Both Immunomodulatory And Mena Inhibitory Activities Against Staphylococcus Aureus And Its Biofilm., Seoung-Ryoung Choi, Joel Frandsen, Prabagaran Narayanasamy Jan 2017

Novel Long-Chain Compounds With Both Immunomodulatory And Mena Inhibitory Activities Against Staphylococcus Aureus And Its Biofilm., Seoung-Ryoung Choi, Joel Frandsen, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

Menaquinone (MK) biosynthesis pathway is a potential target for evaluating antimicrobials in gram-positive bacteria. Here, 1,4-dihydroxy-2-naphthoate prenyltransferase (MenA) was targeted to reduce methicillin-resistant Staphylococcus aureus (MRSA) growth. MenA inhibiting, long chain-based compounds were designed, synthesized and evaluated against MRSA and menaquinone utilizing bacteria in aerobic conditions. The results showed that these bacteria were susceptible to most of the compounds. Menaquinone (MK-4) supplementation rescued MRSA growth, suggesting these compounds inhibit MK biosynthesis. 3a and 7c exhibited promising inhibitory activities with MICs ranging 1-8 μg/mL against MRSA strains. The compounds did not facilitate small colony variant formation. These compounds also inhibited the …


The Effect Of Hiv Infection And Hcv Viremia On Inflammatory Mediators And Hepatic Injury-The Women's Interagency Hiv Study., Sheila M Keating, Jennifer L Dodge, Philip J Norris, John Heitman, Stephen J Gange, Audrey L French, Marshall J Glesby, Brian R Edlin, Patricia S Latham, Maria C Villacres, Ruth M Greenblatt, Marion G Peters Jan 2017

The Effect Of Hiv Infection And Hcv Viremia On Inflammatory Mediators And Hepatic Injury-The Women's Interagency Hiv Study., Sheila M Keating, Jennifer L Dodge, Philip J Norris, John Heitman, Stephen J Gange, Audrey L French, Marshall J Glesby, Brian R Edlin, Patricia S Latham, Maria C Villacres, Ruth M Greenblatt, Marion G Peters

Pathology Faculty Publications

Hepatitis C virus infection induces inflammation and while it is believed that HIV co-infection enhances this response, HIV control may reduce inflammation and liver fibrosis in resolved or viremic HCV infection. Measurement of systemic biomarkers in co-infection could help define the mechanism of inflammation on fibrosis and determine if HIV control reduces liver pathology. A nested case-control study was performed to explore the relationship of systemic biomarkers of inflammation with liver fibrosis in HCV viremic and/or seropositive women with and without HIV infection. Serum cytokines, chemokines, growth factors and cell adhesion molecules were measured in HIV uninfected (HIV-, n = …


Gallium Nanoparticles Facilitate Phagosome Maturation And Inhibit Growth Of Virulent Mycobacterium Tuberculosis In Macrophages., Seoung-Ryoung Choi, Bradley E. Britigan, David M. Moran, Prabagaran Narayanasamy Jan 2017

Gallium Nanoparticles Facilitate Phagosome Maturation And Inhibit Growth Of Virulent Mycobacterium Tuberculosis In Macrophages., Seoung-Ryoung Choi, Bradley E. Britigan, David M. Moran, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

New treatments and novel drugs are required to counter the growing problem of drug-resistant strains of Mycobacterium tuberculosis (M.tb). Our approach against drug resistant M.tb, as well as other intracellular pathogens, is by targeted drug delivery using nanoformulations of drugs already in use, as well as drugs in development. Among the latter are gallium (III) (Ga)-based compounds. In the current work, six different types of Ga and rifampin nanoparticles were prepared in such a way as to enhance targeting of M.tb infected-macrophages. They were then tested for their ability to inhibit growth of a fully pathogenic strain (H37Rv) or a …


Neuroprotection Through Flavonoid: Enhancement Of The Glyoxalase Pathway., Joel Frandsen, Prabagaran Narayanasamy Jan 2017

Neuroprotection Through Flavonoid: Enhancement Of The Glyoxalase Pathway., Joel Frandsen, Prabagaran Narayanasamy

Journal Articles: Pathology and Microbiology

The glyoxalase pathway functions to detoxify reactive dicarbonyl compounds, most importantly methylglyoxal. The glyoxalase pathway is an antioxidant defense mechanism that is essential for neuroprotection. Excessive concentrations of methylglyoxal have deleterious effects on cells, leading to increased levels of inflammation and oxidative stress. Neurodegenerative diseases - including Alzheimer's, Parkinson's, Aging and Autism Spectrum Disorder - are often induced or exacerbated by accumulation of methylglyoxal. Antioxidant compounds possess several distinct mechanisms that enhance the glyoxalase pathway and function as neuroprotectants. Flavonoids are well-researched secondary plant metabolites that appear to be effective in reducing levels of oxidative stress and inflammation in neural …


A Rare Case Of Epstein–Barr Virus-Related Plasmacytoma Involving Maxillary Sinus Mucosa, Julie D. Gibbs, Marino E. Leon, Kenia Liu, Johnny Nguyen, Ling Zhang Jan 2017

A Rare Case Of Epstein–Barr Virus-Related Plasmacytoma Involving Maxillary Sinus Mucosa, Julie D. Gibbs, Marino E. Leon, Kenia Liu, Johnny Nguyen, Ling Zhang

Pathology and Cell Biology Faculty Publications

No abstract provided.


Fdg Avid Breast Cancer Bone Metastases Silent On Ct And Scintigraphy: A Case Report With Radiologic-Pathologic Correlation, Daniel Jeong, Marilyn Bui, Daniel Peterson, Jaime Montilla-Soler, Kenneth L. Gage Jan 2017

Fdg Avid Breast Cancer Bone Metastases Silent On Ct And Scintigraphy: A Case Report With Radiologic-Pathologic Correlation, Daniel Jeong, Marilyn Bui, Daniel Peterson, Jaime Montilla-Soler, Kenneth L. Gage

Pathology and Cell Biology Faculty Publications

Bone is the one of the most common distant metastatic sites in breast cancer. Routine initial breast cancer staging evaluation typically includes computed tomography (CT) and skeletal scintigraphy while 18F fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is reserved for clinically high-risk cases. Since FDG PET-CT is not routinely performed during staging or surveillance evaluations, it is important for radiologists and clinicians to appreciate the limitations of bone metastasis detection on CT and scintigraphy. We present a case of bony metastases of invasive ductal carcinoma of the breast which were not detected on diagnostic CT or skeletal scintigraphy but were …


Hematuria Without Microalbuminuria, Angela Ferguson, Vimal Chadha, Amy Wiebold, Uttam Garg Jan 2017

Hematuria Without Microalbuminuria, Angela Ferguson, Vimal Chadha, Amy Wiebold, Uttam Garg

Posters

Background

Microabubiminuria is a condition in which small amounts of albumin are excreted in the urine without overt nephropathy. Based on the

American Diabetic Association classification, microalbuminuria is defined as urinary excretion of albumin of 30–300 mg per 24 hours or 20–200 mcg/min or 30–300 mcg/mg creatinine. Various conditions such as diabetes, hypertension, and impaired renal tubular reabsorption can lead to microalbuminuria. Microalbuminuria is an indicator and predictor of the development of overt nephropathy. If identified and treated early, overt nephropathy can be prevented and averted. Proteinuria and hematuria are the two most common urinary abnormalities encountered during routine urinalysis. …


Yap And The Hippo Pathway In Pediatric Cancer., Atif Ahmed, Abdalla D. Mohamed, Melissa Gener, Weijie Li, Eugenio Taboada Jan 2017

Yap And The Hippo Pathway In Pediatric Cancer., Atif Ahmed, Abdalla D. Mohamed, Melissa Gener, Weijie Li, Eugenio Taboada

Manuscripts, Articles, Book Chapters and Other Papers

The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell-cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis. Dysfunction of this pathway contributes to cancer development in adults and children. Emerging studies have shed light on the upregulation …


Immunodeficiency-Associated Lymphoid Hyperplasia As A Cause Of Intussusception In A Case Of Activated Pi3k-Δ Syndrome., Daniel Mettman, Isabelle Thiffault, Chitra Dinakar, Carol J. Saunders Jan 2017

Immunodeficiency-Associated Lymphoid Hyperplasia As A Cause Of Intussusception In A Case Of Activated Pi3k-Δ Syndrome., Daniel Mettman, Isabelle Thiffault, Chitra Dinakar, Carol J. Saunders

Manuscripts, Articles, Book Chapters and Other Papers

Activated PI3K-δ syndrome refers to a recently described primary immunodeficiency syndrome consisting of recurrent sinopulmonary infections, lymphadenopathy, mucosal lymphoid aggregates, increased susceptibility to Epstein-Barr virus and cytomegalovirus, and increased incidence of B-cell lymphomas. Variants in PIK3CD, which encodes the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta isoform, enhance membrane association and kinase activity, resulting in increased signal transduction through the PI3K-Akt pathway. Whole-exome sequencing revealed a pathogenic PIK3CD variant in a patient with history of immunologic impairment, recurrent sinopulmonary infections, and lymphoid hyperplasia presenting as intussusception. This case illustrates that while lymphoid hyperplasia secondary to immunodeficiency is most often unsurprising and …


Functional Validation Of Novel Compound Heterozygous Variants In B3gat3 Resulting In Severe Osteopenia And Fractures: Expanding The Disease Phenotype., Florian Job, Shuji Mizumoto, Laurie Smith, Natario Couser, Ashley Brazil, Howard Saal, Melanie Patterson, Margaret Gibson, Sarah E. Soden, Neil A. Miller, Isabelle Thiffault, Carol J. Saunders, Shuhei Yamada, Katrin Hoffmann, Kazuyuki Sugahara, Emily G. Farrow Nov 2016

Functional Validation Of Novel Compound Heterozygous Variants In B3gat3 Resulting In Severe Osteopenia And Fractures: Expanding The Disease Phenotype., Florian Job, Shuji Mizumoto, Laurie Smith, Natario Couser, Ashley Brazil, Howard Saal, Melanie Patterson, Margaret Gibson, Sarah E. Soden, Neil A. Miller, Isabelle Thiffault, Carol J. Saunders, Shuhei Yamada, Katrin Hoffmann, Kazuyuki Sugahara, Emily G. Farrow

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: A new disease class of syndromes, described as linkeropathies, which are derived from defects in the glycosaminoglycan-linker region as well as glycosaminoglycan-side chains of proteoglycans is increasingly being recognized as a cause of human disease. Proteoglycans are an essential component of the extracellular matrix. Defects in the enzymatic process of proteoglycan synthesis broadly occur due to the incorrect addition of side chains. Previously, homozygous missense variants within the B3GAT3 gene encoding beta 1,3 glucuronyltransferase 3(GlcAT-I) responsible for the biosynthesis of glycosaminoglycans have been described in 7 individuals.

CASE PRESENTATION: In this study, a 4-year-old patient with a severe phenotype …


Membrane-Active Epithelial Keratin 6a Fragments (Kamps) Are Unique Human Antimicrobial Peptides With A Non-Αβ Structure., Judy T.Y. Lee, Guangshun Wang, Yu Tong Tam, Connie Tam Nov 2016

Membrane-Active Epithelial Keratin 6a Fragments (Kamps) Are Unique Human Antimicrobial Peptides With A Non-Αβ Structure., Judy T.Y. Lee, Guangshun Wang, Yu Tong Tam, Connie Tam

Journal Articles: Pathology and Microbiology

Antibiotic resistance is a pressing global health problem that threatens millions of lives each year. Natural antimicrobial peptides and their synthetic derivatives, including peptoids and peptidomimetics, are promising candidates as novel antibiotics. Recently, the C-terminal glycine-rich fragments of human epithelial keratin 6A were found to have bactericidal and cytoprotective activities. Here, we used an improved 2-dimensional NMR method coupled with a new protocol for structural refinement by low temperature simulated annealing to characterize the solution structure of these kerain-derived antimicrobial peptides (KAMPs). Two specific KAMPs in complex with membrane mimicking sodium dodecyl sulfate (SDS) micelles displayed amphipathic conformations with only …


Il-10 Plays An Important Role In The Control Of Inflammation But Not In The Bacterial Burden In S. Epidermidis Cns Catheter Infection., Yenis M. Gutierrez-Murgas, Gwenn Skar, Danielle Ramirez, Matthew Beaver, Jessica N. Snowden Oct 2016

Il-10 Plays An Important Role In The Control Of Inflammation But Not In The Bacterial Burden In S. Epidermidis Cns Catheter Infection., Yenis M. Gutierrez-Murgas, Gwenn Skar, Danielle Ramirez, Matthew Beaver, Jessica N. Snowden

Journal Articles: Pathology and Microbiology

BACKGROUND: Shunt infection is a frequent and serious complication in the surgical treatment in hydrocephalus. Previous studies have shown an attenuated immune response to these biofilm-mediated infections. We proposed that IL-10 reduces the inflammatory response to Staphylococcus epidermidis (S. epidermidis) CNS catheter infection.

METHODS: In this study, a murine model of catheter-associated S. epidermidis biofilm infection in the CNS was generated based on a well-established similar model for S. aureus. The catheters were pre-coated with a clinically derived biofilm-forming strain of S. epidermidis (strain 1457) which were then stereotactically implanted into the lateral left ventricle of 8-week-old C57BL/6 and IL-10 …


Biallelic Mutations In Tbcd, Encoding The Tubulin Folding Cofactor D, Perturb Microtubule Dynamics And Cause Early-Onset Encephalopathy., Elisabetta Flex, Marcello Niceta, Serena Cecchetti, Isabelle Thiffault, Margaret G. Au, Alessandro Capuano, Emanuela Piermarini, Anna A. Ivanova, Joshua W. Francis, Giovanni Chillemi, Balasubramanian Chandramouli, Giovanna Carpentieri, Charlotte A. Haaxma, Andrea Ciolfi, Simone Pizzi, Ganka V. Douglas, Kara Levine, Antonella Sferra, Maria Lisa Dentici, Rolph R. Pfundt, Jean-Baptist Lepichon, Emily G. Farrow, Frank Baas, Fiorella Piemonte, Bruno Dallapiccola, John M. Graham, Carol J. Saunders, Enrico Bertini, Richard A. Kahn, David A. Koolen, Marco Tartaglia Oct 2016

Biallelic Mutations In Tbcd, Encoding The Tubulin Folding Cofactor D, Perturb Microtubule Dynamics And Cause Early-Onset Encephalopathy., Elisabetta Flex, Marcello Niceta, Serena Cecchetti, Isabelle Thiffault, Margaret G. Au, Alessandro Capuano, Emanuela Piermarini, Anna A. Ivanova, Joshua W. Francis, Giovanni Chillemi, Balasubramanian Chandramouli, Giovanna Carpentieri, Charlotte A. Haaxma, Andrea Ciolfi, Simone Pizzi, Ganka V. Douglas, Kara Levine, Antonella Sferra, Maria Lisa Dentici, Rolph R. Pfundt, Jean-Baptist Lepichon, Emily G. Farrow, Frank Baas, Fiorella Piemonte, Bruno Dallapiccola, John M. Graham, Carol J. Saunders, Enrico Bertini, Richard A. Kahn, David A. Koolen, Marco Tartaglia

Manuscripts, Articles, Book Chapters and Other Papers

Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause neurodevelopmental and neurodegenerative disorders. Growing evidence suggests that altered microtubule dynamics may also underlie or contribute to neurodevelopmental disorders and neurodegeneration. We report that biallelic mutations in TBCD, encoding one of the five co-chaperones required for assembly and disassembly of the αβ-tubulin heterodimer, the structural unit of microtubules, cause a disease with neurodevelopmental and neurodegenerative features characterized by early-onset cortical atrophy, secondary hypomyelination, microcephaly, thin …


Dome-Type Carcinoma Of The Ascending Colon: A Case Report, Patrick Hickey Do, Shanth A. Goonewardene Md, Shashin Shah Md, Hiral N. Shah Md, Anthony G. Auteri Md Oct 2016

Dome-Type Carcinoma Of The Ascending Colon: A Case Report, Patrick Hickey Do, Shanth A. Goonewardene Md, Shashin Shah Md, Hiral N. Shah Md, Anthony G. Auteri Md

Department of Medicine

No abstract provided.


Concurrent Presentation Of Waldenstrom's Macroglobulinemia And Angioimmunoblastic T-Cell Lymphoma, Amar Jariwala, Fadi Alakeel, Elsie Lee, Donald S. Karcher Sep 2016

Concurrent Presentation Of Waldenstrom's Macroglobulinemia And Angioimmunoblastic T-Cell Lymphoma, Amar Jariwala, Fadi Alakeel, Elsie Lee, Donald S. Karcher

Pathology Faculty Publications

A 73-year-old woman presented with generalized lymphadenopathy, atypical peripheral blood lymphocytosis, and Coombs-positive hemolytic anemia. She was diagnosed with Waldenstrom macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL), on the basis of IgM monoclonal gammopathy, significant lymphoplasmacytic infiltrate in bone marrow, circulating plasmacytoid lymphocytes in peripheral blood, monoclonal B lymphocytes with LPL-compatible immunophenotype by flow cytometry in bone marrow and peripheral blood, and clonal immunoglobulin heavy-chain gene rearrangement by polymerase chain reaction in peripheral blood. Molecular study results for MYB deletion and MYD88 mutation were negative. Following brief chemotherapy for WM, the patient's IgM monoclonal gammopathy and hemolytic anemia improved and the number of …


An Unusual Case Of Igg4 Associated Marginal Zone B-Cell Lymphoma Presenting As Subcutaneous Nodules Mimicking Lipomas, Ryan Mayo Md, Ranjit R. Nair Md, Shereen M F Gheith Md, Phd Sep 2016

An Unusual Case Of Igg4 Associated Marginal Zone B-Cell Lymphoma Presenting As Subcutaneous Nodules Mimicking Lipomas, Ryan Mayo Md, Ranjit R. Nair Md, Shereen M F Gheith Md, Phd

Department of Medicine

No abstract provided.


Nox2-Derived Oxidative Stress Results In Inefficacy Of Antibiotics Against Post-Influenza S. Aureus Pneumonia., Keer Sun, Vijaya Kumar Yajjala, Christopher Bauer, G. Talmon, Karl J. Fischer, Tammy Kielian, Dennis W. Metzger Aug 2016

Nox2-Derived Oxidative Stress Results In Inefficacy Of Antibiotics Against Post-Influenza S. Aureus Pneumonia., Keer Sun, Vijaya Kumar Yajjala, Christopher Bauer, G. Talmon, Karl J. Fischer, Tammy Kielian, Dennis W. Metzger

Journal Articles: Pathology and Microbiology

Clinical post-influenza Staphylococcus aureus pneumonia is characterized by extensive lung inflammation associated with severe morbidity and mortality even after appropriate antibiotic treatment. In this study, we show that antibiotics rescue nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (Nox2)-deficient mice but fail to fully protect WT animals from influenza and S. aureus coinfection. Further experiments indicate that the inefficacy of antibiotics against coinfection is attributable to oxidative stress-associated inflammatory lung injury. However, Nox2-induced lung damage during coinfection was not associated with aggravated inflammatory cytokine response or cell infiltration but rather caused by reduced survival of myeloid cells. Specifically, oxidative stress increased …


Binge Ethanol Exposure Causes Endoplasmic Reticulum Stress, Oxidative Stress And Tissue Injury In The Pancreas, Zhenhua Ren, Xin Wang, Mei Xu, Fanmuyi Yang, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo Aug 2016

Binge Ethanol Exposure Causes Endoplasmic Reticulum Stress, Oxidative Stress And Tissue Injury In The Pancreas, Zhenhua Ren, Xin Wang, Mei Xu, Fanmuyi Yang, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Alcohol abuse is associated with both acute and chronic pancreatitis. Repeated episodes of acute pancreatitis or pancreatic injury may result in chronic pancreatitis. We investigated ethanol-induced pancreatic injury using a mouse model of binge ethanol exposure. Male C57BL/6 mice were exposed to ethanol intragastrically (5 g/kg, 25% ethanol w/v) daily for 10 days. Binge ethanol exposure caused pathological changes in pancreas demonstrated by tissue edema, acinar atrophy and moderate fibrosis. Ethanol caused both apoptotic and necrotic cell death which was demonstrated by the increase in active caspase-3, caspase-8, cleaved PARP, cleaved CK-18 and the secretion of high mobility group protein …


Hepatic Fibrosis And Immune Phenotype Vary By Hcv Viremia In Hcv/Hiv Co-Infected Subjects: A Women's Interagency Hiv Study., Seema N Desai, Jennifer L Dodge, Alan L Landay, Marshall J Glesby, Patricia S. Latham, Maria C Villacres, Audrey L French, Stephen J Gange, Ruth M Greenblatt, Marion G Peters Aug 2016

Hepatic Fibrosis And Immune Phenotype Vary By Hcv Viremia In Hcv/Hiv Co-Infected Subjects: A Women's Interagency Hiv Study., Seema N Desai, Jennifer L Dodge, Alan L Landay, Marshall J Glesby, Patricia S. Latham, Maria C Villacres, Audrey L French, Stephen J Gange, Ruth M Greenblatt, Marion G Peters

Pathology Faculty Publications

HCV and HIV independently lead to immune dysregulation. The mechanisms leading to advanced liver disease progression in HCV/HIV coinfected subjects remain unclear.

In this cross-sectional study, we assessed the association of HCV viremia, liver fibrosis, and immune response patterns in well-characterized HIV phenotypes: Elite controllers (Elites), HIV controlled (ARTc), and HIV uncontrolled (ARTuc) matched by age and race. Groups were stratified by HCV RNA status. Regulatory T-cell frequencies, T-cell activation (HLADR+CD38+), apoptosis (Caspase-3+), and intracellular cytokines (interferon-γ, IL-2, IL-17) were assessed using multiparametric flow-cytometry. Liver fibrosis was scored by AST to platelet ratio index (APRI).

We found liver fibrosis (APRI) …


Human Herpesvirus Multiplex Ddpcr Detection In Brain Tissue From Low- And High-Grade Astrocytoma Cases And Controls., Cheng-Te Major Lin, Emily C Leibovitch, M Isabel Almira-Suarez, Steven Jacobson Jul 2016

Human Herpesvirus Multiplex Ddpcr Detection In Brain Tissue From Low- And High-Grade Astrocytoma Cases And Controls., Cheng-Te Major Lin, Emily C Leibovitch, M Isabel Almira-Suarez, Steven Jacobson

Pathology Faculty Publications

BACKGROUND: Glioblastoma (GBM) is a fatal CNS malignancy, representing 50 % of all gliomas with approximately 12-18 months survival time after initial diagnosis. Recently, the human herpesvirus cytomegalovirus (CMV) has been suggested to have an oncogenic role, yet this association remains controversial. In addition, human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have also been associated with low-grade gliomas, but few studies have examined HHV-6 and EBV in glioblastomas. Droplet digital PCR (ddPCR) is a highly precise diagnostic tool that enables the absolute quantification of target DNA. This study examines the association between multiple human herpesviruses and astrocytomas.

METHODS: This …


Mir-27a And Mir-27b Regulate Autophagic Clearance Of Damaged Mitochondria By Targeting Pten-Induced Putative Kinase 1 (Pink1), Jaekwang Kim, Fabienne C. Fiesel, Krystal C. Belmonte, Roman Hudec, Wang-Xia Wang, Chaeyoung Kim, Peter T. Nelson, Wolfdieter Springer, Jungsu Kim Jul 2016

Mir-27a And Mir-27b Regulate Autophagic Clearance Of Damaged Mitochondria By Targeting Pten-Induced Putative Kinase 1 (Pink1), Jaekwang Kim, Fabienne C. Fiesel, Krystal C. Belmonte, Roman Hudec, Wang-Xia Wang, Chaeyoung Kim, Peter T. Nelson, Wolfdieter Springer, Jungsu Kim

Pathology and Laboratory Medicine Faculty Publications

Background: Loss-of-function mutations in PINK1 and PARKIN are the most common causes of autosomal recessive Parkinson’s disease (PD). PINK1 is a mitochondrial serine/threonine kinase that plays a critical role in mitophagy, a selective autophagic clearance of damaged mitochondria. Accumulating evidence suggests mitochondrial dysfunction is one of central mechanisms underlying PD pathogenesis. Therefore, identifying regulatory mechanisms of PINK1 expression may provide novel therapeutic opportunities for PD. Although post-translational stabilization of PINK1 upon mitochondrial damage has been extensively studied, little is known about the regulation mechanism of PINK1 at the transcriptional or translational levels.

Results: Here, we demonstrated that microRNA-27a (miR-27a) and …


Moving Towards Effective Therapeutic Strategies For Neuronal Ceroid Lipofuscinosis., Ryan D. Geraets, Seung Yon Koh, Michelle L. Hastings, Tammy Kielian, David A. Pearce, Jill M. Weimer Apr 2016

Moving Towards Effective Therapeutic Strategies For Neuronal Ceroid Lipofuscinosis., Ryan D. Geraets, Seung Yon Koh, Michelle L. Hastings, Tammy Kielian, David A. Pearce, Jill M. Weimer

Journal Articles: Pathology and Microbiology

The Neuronal Ceroid Lipofuscinoses (NCLs) are a family of autosomal recessive neurodegenerative disorders that annually affect 1:100,000 live births worldwide. This family of diseases results from mutations in one of 14 different genes that share common clinical and pathological etiologies. Clinically, the diseases are subcategorized into infantile, late-infantile, juvenile and adult forms based on their age of onset. Though the disease phenotypes may vary in their age and order of presentation, all typically include progressive visual deterioration and blindness, cognitive impairment, motor deficits and seizures. Pathological hallmarks of NCLs include the accumulation of storage material or ceroid in the lysosome, …


Intimin Likely Used To Cause Disease During Competition With Commensal Escherichia Coli, Dominique J. Richburg Apr 2016

Intimin Likely Used To Cause Disease During Competition With Commensal Escherichia Coli, Dominique J. Richburg

Senior Honors Theses

The intimin gene in the Locus of Enterocyte Effacement (LEE) island of pathogenicity is the primary attachment mechanism in Citrobacter rodentium. Intimin is a bacterial adhesin (protein) that attaches to obtain a niche/nutrient and thrive within the intestine. Intimin was deleted within C. rodentium to study colonization and pathogenesis in the murine intestine. Additionally, C. rodentium is an attaching/effacing pathogen, and a useful murine model in understanding Enterohemorrhagic Escherichia coli (EHEC) infection in humans. E. coli and C. rodentium cause gastroenteritis in humans and mice, respectively. C. rodentium is a murine pathogen commonly used to model gastrointestinal disease because …


Membranoproliferative Glomerulonephritis Recurrence After Kidney Transplantation: Using The New Classification., Sami Alasfar, Naima Carter-Monroe, Avi Z Rosenberg, Robert A Montgomery, Nada Alachkar Jan 2016

Membranoproliferative Glomerulonephritis Recurrence After Kidney Transplantation: Using The New Classification., Sami Alasfar, Naima Carter-Monroe, Avi Z Rosenberg, Robert A Montgomery, Nada Alachkar

Pathology Faculty Publications

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) is an uncommon glomerular disorder that may lead to end stage renal disease (ESRD). With new understanding of the disease pathogenesis, the classical classification as MPGN types I, II, III has changed. Data on post-transplant MPGN, in particular with the newly refined classification, is limited. We present our center's experience of MPGN after kidney transplantation using the new classification.

METHODS: This is a retrospective study of 34 patients with ESRD due to MPGN who received 40 kidney transplants between 1994 and 2014. We reviewed the available biopsies' data using the new classification. We assessed post transplantation …


The Effects Of Allergies And Anaphylaxis On The Body And Mind: A Survey Of Opinions And Knowledge On These Disorders, Kathryn E. O'Brien Jan 2016

The Effects Of Allergies And Anaphylaxis On The Body And Mind: A Survey Of Opinions And Knowledge On These Disorders, Kathryn E. O'Brien

Honors Program: Student Scholarship & Creative Works

Despite common knowledge, allergies and anaphylaxis are considered disabilities. As such, these disorders affect the daily lives of those who have them, including one's mental health. In this paper, all the nuances of allergies and anaphylaxis will be discussed as the etiology and scientific aspects of allergies, anaphylaxis, and hypersensitivity are distinguished from one another. Furthermore, the findings are reported from two surveys; an assessment of how well educated and prepared teachers are for students with allergies and whether other students with food allergies have had similar experiences to the author's and those described in research by other studies concerning …


The Application Of Digital Pathology To Improve Accuracy In Glomerular Enumeration In Renal Biopsies., Avi Z Rosenberg, Matthew Palmer, Lino Merlino, Jonathan P Troost, Adil Gasim, Serena Bagnasco, Carmen Avila-Casado, Duncan Johnstone, Jeffrey B Hodgin, Catherine Conway, Brenda W Gillespie, Cynthia C Nast, Laura Barisoni, Stephen M Hewitt Jan 2016

The Application Of Digital Pathology To Improve Accuracy In Glomerular Enumeration In Renal Biopsies., Avi Z Rosenberg, Matthew Palmer, Lino Merlino, Jonathan P Troost, Adil Gasim, Serena Bagnasco, Carmen Avila-Casado, Duncan Johnstone, Jeffrey B Hodgin, Catherine Conway, Brenda W Gillespie, Cynthia C Nast, Laura Barisoni, Stephen M Hewitt

Pathology Faculty Publications

BACKGROUND: In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent globally sclerotic in renal biopsies by means of registration of serial tissue sections and manual enumeration, compared to the numbers in pathology reports from routine light microscopic assessment.

DESIGN: We reviewed 277 biopsies from the Nephrotic Syndrome Study Network (NEPTUNE) digital pathology repository, enumerating 9,379 glomeruli by means of whole slide imaging. Glomerular number and the percentage of globally sclerotic glomeruli are …


Mitosis In Circulating Tumor Cells Stratifies Highly Aggressive Breast Carcinomas., Daniel L. Adams, Diane K. Adams, Steingrimur Stefansson, Christian Haudenschild, Stuart S. Martin, Monica Charpentier, Saranya Chumsri, Massimo Cristofanilli, Cha-Mei Tang, R Katherine Alpaugh Jan 2016

Mitosis In Circulating Tumor Cells Stratifies Highly Aggressive Breast Carcinomas., Daniel L. Adams, Diane K. Adams, Steingrimur Stefansson, Christian Haudenschild, Stuart S. Martin, Monica Charpentier, Saranya Chumsri, Massimo Cristofanilli, Cha-Mei Tang, R Katherine Alpaugh

Pathology Faculty Publications

BACKGROUND: Enumeration of circulating tumor cells (CTCs) isolated from the peripheral blood of breast cancer patients holds promise as a clinically relevant, minimally invasive diagnostic test. However, CTC utility has been limited as a prognostic indicator of survival by the inability to stratify patients beyond general enumeration. In comparison, histological biopsy examinations remain the standard method for confirming malignancy and grading malignant cells, allowing for cancer identification and then assessing patient cohorts for prognostic and predictive value. Typically, CTC identification relies on immunofluorescent staining assessed as absent/present, which is somewhat subjective and limited in its ability to characterize these cells. …


Metataxonomic And Metagenomic Approaches Vs. Culture-Based Techniques For Clinical Pathology., Sarah K. Hilton, Eduardo Castro-Nallar, Marcos Pérez-Losada, Ian Toma, Timothy A. Mccaffrey, Eric P. Hoffman, Marc O. Siegel, Gary L. Simon, W. Evan Johnson, Keith Crandall Jan 2016

Metataxonomic And Metagenomic Approaches Vs. Culture-Based Techniques For Clinical Pathology., Sarah K. Hilton, Eduardo Castro-Nallar, Marcos Pérez-Losada, Ian Toma, Timothy A. Mccaffrey, Eric P. Hoffman, Marc O. Siegel, Gary L. Simon, W. Evan Johnson, Keith Crandall

Genomics and Precision Medicine Faculty Publications

Diagnoses that are both timely and accurate are critically important for patients with life-threatening or drug resistant infections. Technological improvements in High-Throughput Sequencing (HTS) have led to its use in pathogen detection and its application in clinical diagnoses of infectious diseases. The present study compares two HTS methods, 16S rRNA marker gene sequencing (metataxonomics) and whole metagenomic shotgun sequencing (metagenomics), in their respective abilities to match the same diagnosis as traditional culture methods (culture inference) for patients with ventilator associated pneumonia (VAP). The metagenomic analysis was able to produce the same diagnosis as culture methods at the species-level for five …