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The Humoral Theory Of Transplantation: Epitope Analysis And The Pathogenicity Of Hla Antibodies., Edward J Filippone, John Farber 2016 Department of Medicine, Division of Nephrology, Sydney Kimmel School of Medicine, Thomas Jefferson University

The Humoral Theory Of Transplantation: Epitope Analysis And The Pathogenicity Of Hla Antibodies., Edward J Filippone, John Farber

Department of Medicine Faculty Papers

Central to the humoral theory of transplantation is production of antibodies by the recipient against mismatched HLA antigens in the donor organ. Not all mismatches result in antibody production, however, and not all antibodies are pathogenic. Serologic HLA matching has been the standard for solid organ allocation algorithms in current use. Antibodies do not recognize whole HLA molecules but rather polymorphic residues on the surface, called epitopes, which may be shared by multiple serologic HLA antigens. Data are accumulating that epitope analysis may be a better way to determine organ compatibility as well as the potential immunogenicity of given HLA ...


Intrahepatic Cholangiocarcinoma Presenting As Li-Rads 5 "Hcc", Raja K. Dhanekula, MD, Donald Mitchell, MD, John Farber, MD, Ashwin R. Sama, MD, Jesse M. Civan, MD 2016 Division of Gastroenterology and Hepatology, Thomas Jefferson University Hospital

Intrahepatic Cholangiocarcinoma Presenting As Li-Rads 5 "Hcc", Raja K. Dhanekula, Md, Donald Mitchell, Md, John Farber, Md, Ashwin R. Sama, Md, Jesse M. Civan, Md

Department of Gastroenterology and Hepatology Posters

Background

• Hepatocellular Carcinoma (HCC), if within Milan Criteria, is an indication for liver transplantation.

• In contrast, intrahepatic cholangiocarcinoma (IHCC) is a contra-indication to liver transplantation due to high rates of recurrence.

• LI-RADS 5 classification (synonymous with OPTN-5) carries a near 100% positive predictive value for HCC, allowing prioritization of patients for liver transplantation without histological confirmation.

• The “LI-RADS M” classification indicates the presence of malignancy not meeting diagnostic criteria for HCC. In theory, IHCC lesions should be identified as LI-RADS M and not LI-RADS 5.


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 2016 Cleveland Clinic Lerner Research Institute

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 2016 University of Nebraska Medical Center

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 ...


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 2016 Lehigh Valley Health Network

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.


Molecular Characterization Of Staphylococcus Aureus Isolates From Various Healthcare Institutions In Nairobi, Kenya: A Cross Sectional Study, Geoffrey Omuse, Kristien Nel Van Zyl, Kim Hoek, Shima Abdulgader, Samuel Kariuki, Andrew Whitelaw, Gunturu Revathi 2016 Aga Khan University

Molecular Characterization Of Staphylococcus Aureus Isolates From Various Healthcare Institutions In Nairobi, Kenya: A Cross Sectional Study, Geoffrey Omuse, Kristien Nel Van Zyl, Kim Hoek, Shima Abdulgader, Samuel Kariuki, Andrew Whitelaw, Gunturu Revathi

Pathology, East Africa

Background: Staphylococcus aureus (S. aureus) has established itself over the years as a major cause of morbidity and mortality both within the community and in healthcare settings. Methicillin resistant S. aureus (MRSA) in particular has been a major cause of nosocomial infections resulting in significant increase in healthcare costs. In Africa, the MRSA prevalence has been shown to vary across different countries. In order to better understand the epidemiology of MRSA in a setting, it is important to define its population structure using molecular tools as different clones have been found to predominate in certain geographical locations.

Methods: We carried ...


Pd-L1 Expression In Ebv-Negative Diffuse Large B-Cell Lymphoma: Clinicopathologic Features And Prognostic Implications, Wei Xing, Karen A. Dresser, Rui Zhang, Andrew M. Evens, Hongbo Yu, Bruce A. Woda, Benjamin J. Chen 2016 University of Massachusetts Medical School

Pd-L1 Expression In Ebv-Negative Diffuse Large B-Cell Lymphoma: Clinicopathologic Features And Prognostic Implications, Wei Xing, Karen A. Dresser, Rui Zhang, Andrew M. Evens, Hongbo Yu, Bruce A. Woda, Benjamin J. Chen

Open Access Articles

Programmed cell death ligand 1 (PD-L1) is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. PD-L1 is expressed on tumor cells and the immune microenvironment of several human malignancies, including a subset of aggressive lymphomas. We sought to investigate further the clinical and pathologic features of EBV-negative diffuse large B-cell lymphoma (DLBCL) cases that express PD-L1. Immunohistochemical staining using an anti-PD-L1 monoclonal antibody was performed on DLBCL cases from 86 patients. These patients received standard chemotherapy treatment and were followed for up to 175 months. Overall, 14 cases (16%) were ...


Unique Metabolic Features Of Pancreatic Cancer Stroma: Relevance To The Tumor Compartment, Prognosis, And Invasive Potential., Erik S. Knudsen, Uthra Balaji, Elizaveta Freinkman, Peter McCue, Agnieszka K. Witkiewicz 2016 University of Texas; University of Arizona

Unique Metabolic Features Of Pancreatic Cancer Stroma: Relevance To The Tumor Compartment, Prognosis, And Invasive Potential., Erik S. Knudsen, Uthra Balaji, Elizaveta Freinkman, Peter Mccue, Agnieszka K. Witkiewicz

Department of Pathology, Anatomy and Cell Biology Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The aggressiveness and therapeutic recalcitrance of this malignancy has been attributed to multiple factors including the influence of an active desmoplastic stroma. How the stromal microenvironment of PDAC contributes to the fatal nature of this disease is not well defined. In the analysis of clinical specimens, we observed diverse expression of the hypoxic marker carbonic anhydrase IX and the lactate transporter MCT4 in the stromal compartment. These stromal features were associated with the epithelial to mesenchymal phenotype in PDAC tumor cells, and with shorter patient survival. Cultured cancer-associated fibroblasts (CAFs) derived from ...


Extramedullary Hematopoiesis Presented As Cytopenia And Massive Paraspinal Masses Leading To Cord Compression In A Patient With Hereditary Persistence Of Fetal Hemoglobin, Tasleem Katchi, Krishna Kolandaivel, Pallavi Khattar, Taliya Farooq, Humayun Islam, Delong Liu 2016 New York Medical College

Extramedullary Hematopoiesis Presented As Cytopenia And Massive Paraspinal Masses Leading To Cord Compression In A Patient With Hereditary Persistence Of Fetal Hemoglobin, Tasleem Katchi, Krishna Kolandaivel, Pallavi Khattar, Taliya Farooq, Humayun Islam, Delong Liu

NYMC Faculty Publications

BACKGROUND: Extramedullary hematopoeisis (EMH) can occur in various physiological and pathologic states. The spleen is the most common site of EMH.

CASE PRESENTATION: We report a case with hereditary persistence of fetal hemoglobin with extramedullary hematopoiesis presented as cord compression and cytopenia secondary to multi-paraspinal masses.

CONCLUSION: Treatment can be a challenge. Relapse is a possibility.


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 2016 Lehigh Valley Health Network

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 2016 University of Nebraska Medical Center

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 ...


Classic Virilizing Congenital Adrenal Hyperplasia Presenting Late: Case Series From Pakistan, Aysha Habib Khan, Muniba Aban, Rameez-ul-Hassan, Naeem-ul-Haq, Jamal Raza, Abdul Jabbar, Tariq Moatter 2016 Aga Khan University

Classic Virilizing Congenital Adrenal Hyperplasia Presenting Late: Case Series From Pakistan, Aysha Habib Khan, Muniba Aban, Rameez-Ul-Hassan, Naeem-Ul-Haq, Jamal Raza, Abdul Jabbar, Tariq Moatter

Aysha Habib Khan

Deficiency of 21 hydroxylase enzyme deficiency (21OH) activity accounts for 90% cases of congenital adrenal hyperplasia (CAH). This results in deficient cortisol, increased ACTH, adrenal hyperplasia and increased adrenal androgen secretion. There is marked virilization in genetic females which is the hallmark of this disorder. Genetic heterogeneity in 21 OHD is well recognized, and both severe and mild forms occur. We present three cases of adult females with the disease from a larger study to establish genotype, phenotype correlation of Pakistani patients with congenital adrenal hyperplasia (CAH) and to highlight issues such as diagnostic delay, inappropriate gender assignment at birth ...


P27kip1 And P130 Cooperate To Regulate Hematopoietic Cell Proliferation In Vivo, Inês Soeiro, Azim Mohamedali, Hanna M. Romanska, Nicholas C. Lea, Emma S. Child, Janet Glassford, Stephen J. Orr, Claudia Roberts, Kikkeri N. Naresh, El-Nasir Lalani, David J. Mann, Roger J. Watson, N. Shaun B. Thomas, Eric W. -F. Lam 2016 Hammersmith Hospital

P27kip1 And P130 Cooperate To Regulate Hematopoietic Cell Proliferation In Vivo, Inês Soeiro, Azim Mohamedali, Hanna M. Romanska, Nicholas C. Lea, Emma S. Child, Janet Glassford, Stephen J. Orr, Claudia Roberts, Kikkeri N. Naresh, El-Nasir Lalani, David J. Mann, Roger J. Watson, N. Shaun B. Thomas, Eric W. -F. Lam

El Nasir Lalani

To investigate the potential functional cooperation between p27Kip1 and p130 in vivo, we generated mice deficient for both p27Kip1 and p130. In p27Kip1−/−;p130−/− mice, the cellularity of the spleens but not the thymi is significantly increased compared with that of their p27Kip1−/− counterparts, affecting the lymphoid, erythroid, and myeloid compartments. In vivo cell proliferation is significantly augmented in the B and T cells, monocytes, macrophages, and erythroid progenitors in the spleens of p27Kip1−/−; p130−/− animals. Immunoprecipitation and immunodepletion studies indicate that p130 can compensate for the absence of p27Kip1 in binding to and ...


Topographical Expression Of Class Ia And Class Ii Phosphoinositide 3-Kinase Enzymes In Normal Human Tissues Is Consistent With A Role In Differentiation, Soha Salama El Sheikh, Jan Domin, Prakitpunthu Tomtitchong, Paul Abel, Gordon Stamp, El-Nasir Lalani 2016 Imperial College School of Medicine

Topographical Expression Of Class Ia And Class Ii Phosphoinositide 3-Kinase Enzymes In Normal Human Tissues Is Consistent With A Role In Differentiation, Soha Salama El Sheikh, Jan Domin, Prakitpunthu Tomtitchong, Paul Abel, Gordon Stamp, El-Nasir Lalani

El Nasir Lalani

Background: Growth factor, cytokine and chemokine-induced activation of PI3K enzymes constitutes the start of a complex signalling cascade, which ultimately mediates cellular activities such as proliferation, differentiation, chemotaxis, survival, trafficking, and glucose homeostasis. The PI3K enzyme family is divided into 3 classes; class I (subdivided into IA and IB), class II (PI3K-C2α, PI3K-C2β and PI3K-C2γ) and class III PI3K. Expression of these enzymes in human tissue has not been clearly defined.

Methods: In this study, we analysed the immunohistochemical topographical expression profile of class IA (anti-p85 adaptor) and class II PI3K (PI3K-C2α and PI3K-C2β) enzymes in 104 formalin-fixed, paraffin embedded ...


Molecular And Cellular Biology Of Prostate Cancer, El-Nasir Lalani, Marc Elie Laniado, Paul David Abel 2016 Aga Khan University

Molecular And Cellular Biology Of Prostate Cancer, El-Nasir Lalani, Marc Elie Laniado, Paul David Abel

El Nasir Lalani

Prostate cancer is an enigmatic disease. Although prostatic-intraepithelial neoplasia appears as early as the third decade and as many as 80% of 80 year old men have epithelial cells in their prostate that fit the morphological criteria for cancer, only about 10% of men will ever have the clinical disease and less than 3% will die from it. There have been no significant proven interventions which have altered the natural history of the disease since hormone down regulation was introduced in the 1940s and new research has been poorly supported. There is however an urgent need to develop new criteria ...


Body And Organ Measurements In Infants And Neonates: An Autopsy Study, Audrey-Ann M. Evetts 2016 The University of Western Ontario

Body And Organ Measurements In Infants And Neonates: An Autopsy Study, Audrey-Ann M. Evetts

Electronic Thesis and Dissertation Repository

Abstract

Introduction: A pathologist doing a pediatric autopsy will commonly assess child’s development by comparing the postmortem data to standardized population parameters using body and organ measurement charts. Although a number of resources are available, many are outdated and have significant limitations.

Objectives: To create Ontario population-specific organ and body measurement mean charts for infants and to explore relationships between body measurements/organ weights and cause of death, age, and gender of the deceased.

Methods: A database of 900 cases of infant and neonatal deaths that were investigated by Ontario coroners from 2000 to 2010 was retrospectively analyzed.

Results ...


The Genetic Landscape Of Dural Marginal Zone Lymphomas, Karthik A. Ganapathi, Vaidehi Jobanputra, Fabio Iwamoto, Preti Jain, Jinli Chen, Luciano Cascione, Odelia Nahum, Brynn Levy, Yi Xie, Pallavi Khattar, Daniela Hoehn, Francesco Bertoni, Vundavalli V. Murty, Stefania Pittaluga, Elaine S. Jaffe, Bachir Alobeid, Mahesh M. Mansukhani, Govind Bhagat 2016 New York Medical College

The Genetic Landscape Of Dural Marginal Zone Lymphomas, Karthik A. Ganapathi, Vaidehi Jobanputra, Fabio Iwamoto, Preti Jain, Jinli Chen, Luciano Cascione, Odelia Nahum, Brynn Levy, Yi Xie, Pallavi Khattar, Daniela Hoehn, Francesco Bertoni, Vundavalli V. Murty, Stefania Pittaluga, Elaine S. Jaffe, Bachir Alobeid, Mahesh M. Mansukhani, Govind Bhagat

NYMC Faculty Publications

The dura is a rare site of involvement by marginal zone lymphoma (MZL) and the biology of dural MZL is not well understood. We performed genome-wide DNA copy number and targeted mutational analysis of 14 dural MZL to determine the genetic landscape of this entity. Monoallelic and biallelic inactivation of TNFAIP3 by mutation (n=5) or loss (n=1) was observed in 6/9 (67%) dural MZL exhibiting plasmacytic differentiation, including 3 IgG4+ cases. In contrast, activating NOTCH2 mutations were detected in 4/5 (80%) dural MZL displaying variable monocytoid morphology. Inactivating TBL1XR1 mutations were identified in all NOTCH2 mutated ...


Multiple Sclerosis Patients Have A Distinct Gut Microbiota Compared To Healthy Controls, Jun Chen, Nicholas Chia, Krishna R Kalari, Janet Z Yao, Martina Novotna, M Mateo Paz Soldan, David H Luckey, Eric V Marietta, Patricio R Jeraldo, Xianfeng Chen, Brian G Weinshenker, Moses Rodriguez, Orhun H Kantarci, Heidi Nelson, Joseph A Murray, Ashutosh K Mangalam 2016 Mayo Clinic

Multiple Sclerosis Patients Have A Distinct Gut Microbiota Compared To Healthy Controls, Jun Chen, Nicholas Chia, Krishna R Kalari, Janet Z Yao, Martina Novotna, M Mateo Paz Soldan, David H Luckey, Eric V Marietta, Patricio R Jeraldo, Xianfeng Chen, Brian G Weinshenker, Moses Rodriguez, Orhun H Kantarci, Heidi Nelson, Joseph A Murray, Ashutosh K Mangalam

Department of Pathology Publications

Multiple sclerosis (MS) is an immune-mediated disease, the etiology of which involves both genetic and environmental factors. The exact nature of the environmental factors responsible for predisposition to MS remains elusive; however, it's hypothesized that gastrointestinal microbiota might play an important role in pathogenesis of MS. Therefore, this study was designed to investigate whether gut microbiota are altered in MS by comparing the fecal microbiota in relapsing remitting MS (RRMS) (n = 31) patients to that of age- and gender-matched healthy controls (n = 36). Phylotype profiles of the gut microbial populations were generated using hypervariable tag sequencing of the V3-V5 ...


A Rare Case Of The Upper Extremity Diffuse Large B-Cell Lymphoma Mimicking Soft Tissue Sarcoma In An Elderly Patient, Aleksandra Mamorska-Dyga, Faisal Ronny, Carmelo Puccio, Humayun Islam, Delong Liu 2016 New York Medical College

A Rare Case Of The Upper Extremity Diffuse Large B-Cell Lymphoma Mimicking Soft Tissue Sarcoma In An Elderly Patient, Aleksandra Mamorska-Dyga, Faisal Ronny, Carmelo Puccio, Humayun Islam, Delong Liu

NYMC Faculty Publications

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, with about 30% of new cases presenting with extranodal disease. Lesions originating from soft tissues of the upper extremities are extremely rare and may mimic other malignancies like sarcoma. We present a case of an elderly patient with right upper extremity (RUE) mass which was proven to be DLBCL instead of sarcoma. We emphasize the increasing need for investigating new therapeutic options for patients of extreme age and/or with underlying heart disease.


Histological And Molecular Analysis Of A Progressive Diffuse Intrinsic Pontine Glioma And Synchronous Metastatic Lesions: A Case Report., Javad Nazarian, Gary E Mason, Cheng Ying Ho, Eshini Panditharatna, Madhuri Kambhampati, Louis Gilbert Vezina, Roger J. Packer, Eugene I Hwang 2016 George Washington University

Histological And Molecular Analysis Of A Progressive Diffuse Intrinsic Pontine Glioma And Synchronous Metastatic Lesions: A Case Report., Javad Nazarian, Gary E Mason, Cheng Ying Ho, Eshini Panditharatna, Madhuri Kambhampati, Louis Gilbert Vezina, Roger J. Packer, Eugene I Hwang

Integrative Systems Biology Faculty Publications

There is no curative treatment for patients with diffuse intrinsic pontine glioma (DIPG). However, with the recent availability of biopsy and autopsy tissue, new data regarding the biologic behavior of this tumor have emerged, allowing greater molecular characterization and leading to investigations which may result in improved therapeutic options. Treatment strategies must address both primary disease sites as well as any metastatic deposits, which may be variably sensitive to a particular approach.In this case report, we present a patient with DIPG treated with irradiation and serial investigational agents. The clinical, pathological and molecular phenotypes of both the progressive primary ...


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