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Rhoa/Rock Pathway Is The Major Molecular Determinant Of Basal Tone In Intact Human Internal Anal Sphincter, Satish Rattan, Jagmohan Singh 2012 Thomas Jefferson University

Rhoa/Rock Pathway Is The Major Molecular Determinant Of Basal Tone In Intact Human Internal Anal Sphincter, Satish Rattan, Jagmohan Singh

Division of Gastroenterology and Hepatology Faculty Papers

Poster presented at: Digestive Disease Week (DDW) International meeting in San Diego, California.

Background and Aims

Knowledge of molecular control mechanisms underlying the basal tone in the intact human IAS is critical for the pathophysiology and rational therapy for debilitating rectoanal motility disorders.


Development Of Myogenic Ias Reconstructs From Human Internal Anal Sphincter (Ias) Smooth Muscle Cells (Smcs) With Functional And Molecular Properties Similar To Intact Human Ias, Jagmohan Singh, Satish Rattan 2012 Thomas Jefferson University

Development Of Myogenic Ias Reconstructs From Human Internal Anal Sphincter (Ias) Smooth Muscle Cells (Smcs) With Functional And Molecular Properties Similar To Intact Human Ias, Jagmohan Singh, Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

Poster presented at: Digestive Disease Week (DDW) International meeting in San Diego, California.

Background and Aims:

Rectoanal incontinence is associated with defective Internal Anal Sphincter (IAS). Current therapies are not satisfactory, raising a potential for the replacement of the dysfunctional IAS with the reconstructs. Present studies were performed to develop human IAS smooth muscle reconstructs with functional and molecular attributes similar to the intact human IAS Smooth muscle (SM).


Effect Of Pooled Human Intravenous Globulin (Ivig) On The Reversal Of Cholinergic Inhibition Of Smooth Muscle By Immunoglobulins (Iggs) From Patients With Scleroderma (Ssc), Jagmohan Singh, Vaibhav Mehendiratta, Sergio A. Jimenez, Sidney Cohen, Anthony J. DiMarino, Satish Rattan 2012 Thomas Jefferson University

Effect Of Pooled Human Intravenous Globulin (Ivig) On The Reversal Of Cholinergic Inhibition Of Smooth Muscle By Immunoglobulins (Iggs) From Patients With Scleroderma (Ssc), Jagmohan Singh, Vaibhav Mehendiratta, Sergio A. Jimenez, Sidney Cohen, Anthony J. Dimarino, Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

Poster presented at: Digestive Disease Week (DDW) International meeting in San Diego, California.

Backgrounds and Aims:

The gastrointestinal (GI) tract is the most common internal organ system affected in SSc. We and others have shown before that the SSc immunoglobulins (IgGs) cause selective blockade of muscarinic type-3 cholinergic (M3-R) in the GI tract. Presently, there is no effective treatment for SSc although numerous cytotoxic and immunomodulatory agents have been employed with limited success and are marred with serious side effects. Present studies investigated the reversibility of SScIgGs-caused M3-R blockade by the pooled Intravenous immunoglobulins (IVIG).


Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof 2012 The University of Texas Graduate School of Biomedical Sciences at Houston

Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof

UT GSBS Dissertations and Theses (Open Access)

Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage ...


Relative Telomere Length: A Novel Non-Invasive Biomarker For The Risk Of Non-Cirrhotic Hepatocellular Carcinoma In Patients With Chronic Hepatitis B Infection., Xiaoying Fu, Shaogui Wan, Hie-Won Hann, MD, Ronald E Myers, PhD, Richard S Hann, Jennifer Au, Bicui Chen, Jinliang Xing, Hushan Yang 2012 Thomas Jefferson University

Relative Telomere Length: A Novel Non-Invasive Biomarker For The Risk Of Non-Cirrhotic Hepatocellular Carcinoma In Patients With Chronic Hepatitis B Infection., Xiaoying Fu, Shaogui Wan, Hie-Won Hann, Md, Ronald E Myers, Phd, Richard S Hann, Jennifer Au, Bicui Chen, Jinliang Xing, Hushan Yang

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND AND AIMS: Telomere length has emerged as a promising risk predictor of various cancers including hepatocellular carcinoma (HCC). However, the majority of studies in this area measured telomere length in hepatocytes and one in lymphocytes with conflicting results. Moreover, no studies have been reported on using circulating DNA telomere length as a non-invasive HCC biomarker.

METHODS: We conducted a nested case-control study to determine the relative telomere length (RTL) in serum DNA from 140 hepatitis B virus (HBV)-related HCC cases and 280 frequency-matched cancer-free HBV controls.

RESULTS: Cases had a significantly longer RTL (median, 0.31; range, 0 ...


The Use Of Infliximab In Older Inflammatory Bowel Disease Patients, Stephanie M. Moleski, Christina C. Lindenmeyer, Patricia L. Kozuch 2012 Thomas Jefferson University Hospital

The Use Of Infliximab In Older Inflammatory Bowel Disease Patients, Stephanie M. Moleski, Christina C. Lindenmeyer, Patricia L. Kozuch

Department of Medicine Faculty Papers

Limited data suggest anti-tumor necrosis factor (TNF) antibodies have equal efficacy but higher morbidity and mortality in older compared to younger inflammatory bowel disease (IBD) patients(1).


Myonectin (Ctrp15), A Novel Myokine That Links Skeletal Muscle To Systemic Lipid Homeostasis, Marcus M. Seldin, Jonathan M. Peterson, Mardi S. Byerly, Zhikui Wei, G. William Wong 2012 Johns Hopkins University School of Medicine

Myonectin (Ctrp15), A Novel Myokine That Links Skeletal Muscle To Systemic Lipid Homeostasis, Marcus M. Seldin, Jonathan M. Peterson, Mardi S. Byerly, Zhikui Wei, G. William Wong

Jonathan Peterson

Skeletal muscle plays important roles in whole-body glucose and fatty acid metabolism. However, muscle also secretes cytokines and growth factors (collectively termed myokines) that can potentially act in an autocrine, a paracrine, and/or an endocrine manner to modulate metabolic, inflammatory, and other processes. Here, we report the identification and characterization of myonectin, a novel myokine belonging to the C1q/TNF-related protein (CTRP) family. Myonectin transcript was highly induced in differentiated myotubes and predominantly expressed by skeletal muscle. Circulating levels of myonectin were tightly regulated by the metabolic state; fasting suppressed, but refeeding dramatically increased, its mRNA and serum levels ...


Microrna Signature In Alcoholic Liver Disease, Shashi Bala, Gyongyi Szabo 2012 University of Massachusetts Medical School

Microrna Signature In Alcoholic Liver Disease, Shashi Bala, Gyongyi Szabo

Gastroenterology Publications and Presentations

Alcoholic liver disease (ALD) is a major global health problem. Chronic alcohol use results in inflammation and fatty liver, and in some cases, it leads to fibrosis and cirrhosis or hepatocellular carcinoma. Increased proinflammatory cytokines, particularly TNF alpha, play a central role in the pathogenesis of ALD. TNF alpha is tightly regulated at transcriptional and posttranscriptional levels. Recently, microRNAs (miRNAs) have been shown to modulate gene functions. The role of miRNAs in ALD is getting attention, and recent studies suggest that alcohol modulates miRNAs. Recently, we showed that alcohol induces miR-155 expression both in vitro (RAW 264.7 macrophage) and ...


Balloon-Occluded Retrograde Transvenous Obliteration For The Treatment Of Gastric Varices., Alia S Dadabhai, Jonathan M Fenkel, Daniel B Brown, Loren Laine 2012 Thomas Jefferson University

Balloon-Occluded Retrograde Transvenous Obliteration For The Treatment Of Gastric Varices., Alia S Dadabhai, Jonathan M Fenkel, Daniel B Brown, Loren Laine

Division of Gastroenterology and Hepatology Faculty Papers

Clinical Perspectives in Hepatology aims to engage two experts with opinions supporting differing perspectives on the management of a case. Typically, the case represents an area of debate or evolving practice in clinical hepatology.

The patient presented below gives us the opportunity to discuss balloon-occluded retrograde transvenous obliteration (BRTO) for treatment of gastric varices. Although described since the mid-1990s and accepted as effective therapy, particularly in Japan, BRTO is used sporadically in the United States and Europe. In fact, it is not mentioned in the U.S. (AASLD) or European (EASL/Baveno V) guidelines. Hopefully, increased awareness of and expertise ...


Oxidative Stress And Inflammation: Essential Partners In Alcoholic Liver Disease, Aditya Ambade, Pranoti Mandrekar 2012 University of Massachusetts Medical School

Oxidative Stress And Inflammation: Essential Partners In Alcoholic Liver Disease, Aditya Ambade, Pranoti Mandrekar

Women’s Health Research Faculty Publications

Alcoholic liver disease (ALD) is a multifaceted disease that is characterized by hepatic steatosis or fat deposition and hepatitis or inflammation. Over the past decade, multiple lines of evidence have emerged on the mechanisms associated with ALD. The key mechanisms identified so far are sensitization to gut-derived endotoxin/lipopolysaccharide resulting in proinflammatory cytokine production and cellular stress due to oxidative processes, contributing to the development and progression of disease. While oxidative stress and inflammatory responses are studied independently in ALD, mechanisms linking these two processes play a major role in pathogenesis of disease. Here we review major players of oxidative ...


Radiotherapy For Liver Metastases: A Review Of Evidence, Michael Lock 2012 University of Western Ontario

Radiotherapy For Liver Metastases: A Review Of Evidence, Michael Lock

Michael Lock

Over the past decade, there has been an increasing use of radiotherapy (RT) for the treatment of liver metastases. Most often, ablative doses are delivered to focal liver metastases with the goal of local control and ultimately improving survival. In contrast, low-dose whole-liver RT may be used for the palliation of symptomatic diffuse metastases. This review examines the available clinical data for both approaches. The review found that RT is effective both for local ablation of focal liver metastases and for palliation of patients with symptomatic liver metastases. However, there is a lack of a high level of evidence from ...


Cellular Signaling Pathways In Alcoholic Liver Disease, Pranoti Mandrekar, Aditya Ambade 2012 University of Massachusetts Medical School

Cellular Signaling Pathways In Alcoholic Liver Disease, Pranoti Mandrekar, Aditya Ambade

Gastroenterology Publications and Presentations

Introduction: The pathogenesis of acute and chronic alcohol consumption is complex with diverse consequences in different tissues. Alcohol abuse is associated with a continuum of liver abnormalities ranging from steatosis or fat deposition, steatohepatitis or fat plus inflammation to cirrhosis and hepatocellular carcinoma. The progression of alcohol-induced liver damage involves both parenchymal and non-parenchymal cells of the liver. The signaling pathways affected by direct or indirect alcohol exposure range from oxidative stress mechanims, metabolism related effects, inflammation, and apoptosis. Understanding the interactions of inter- and intra-cellular signaling pathways in the liver during alcohol exposure will aid in identification of new ...


Boerhaave's Syndrome As A First Presentation Of Eosinophilic Esophagitis, Whitney E. Jackson, Vaibhav Mehendiratta, Juan P. Palazzo, Anthony J. DiMarino, Sidney Cohen 2012 Department of Internal Medicine, Thomas Jefferson University Hospital

Boerhaave's Syndrome As A First Presentation Of Eosinophilic Esophagitis, Whitney E. Jackson, Vaibhav Mehendiratta, Juan P. Palazzo, Anthony J. Dimarino, Sidney Cohen

Division of Internal Medicine Faculty Papers & Presentations

Purpose: Prior studies have reported esophageal rupture following endoscopy or bolus impaction in eosinophilic esophagitis. The purpose of this study is to examine the frequency and characteristics of spontaneous rupture (Boerhaave's Syndrome) associated with vomiting S-435 AGA Abstracts in eosinophilic esophagitis.

Methods: A retrospective search of inpatient and outpatient records was conducted for the diagnoses "Boerhaave's", "eosinophilic esophagitis", and "esophageal rupture" from January 2001 to January 2011 within the gastroenterology division at an urban tertiary care hospital. For each subject identified, medical records, endoscopy reports, biopsy reports and radiographic studies were reviewed. A faculty member of the Department ...


Self Expanding Metal Stents (Sems) For Management Of Peri-Pancreatic Fluid Collections (Pfc): A Single Center Experience, Whitney E. Jackson, Jason Korenblit, Vaibhav Mehendiratta, Jason Lewis, Ali A. Siddiqui, Thomas E. Kowalski, David E. Loren 2012 Department of Internal Medicine, Thomas Jefferson University Hospital

Self Expanding Metal Stents (Sems) For Management Of Peri-Pancreatic Fluid Collections (Pfc): A Single Center Experience, Whitney E. Jackson, Jason Korenblit, Vaibhav Mehendiratta, Jason Lewis, Ali A. Siddiqui, Thomas E. Kowalski, David E. Loren

Division of Internal Medicine Faculty Papers & Presentations

Background

Endoscopic management of peri-pancreatic fluid collections (PFC) with or without organizing necrosis has been shown to decrease morbidity and mortality compared to early surgical management. Plastic stents are often used for transmural drainage, although the use of self-expanding metal stents (SEMS) has been reported. Theoretical benefits of SEMS include a large diameter for drainage and facilitation of endoscopic necrosectomy. We report a single-center experience to evaluate the efficacy and safety of SEMS for management of PFC.

Methods

A single-center retrospective review was performed of patients undergoing endoscopic management of PFC using SEMS from January through November 2011. Electronic database ...


Patterns Of Acetaminophen Use At A Tertiary Care Center: Exposures Exceeding 4 Grams Daily, Jesse Civan, Victor Navarro, Jeffrey Riggio, Paul Adams, Steven Herrine, Simona Rossi 2012 Division of Gastroenterology & Hepatology, Thomas Jefferson University Hospital

Patterns Of Acetaminophen Use At A Tertiary Care Center: Exposures Exceeding 4 Grams Daily, Jesse Civan, Victor Navarro, Jeffrey Riggio, Paul Adams, Steven Herrine, Simona Rossi

Jefferson Hospital Staff Papers and Presentations

Unintentional hepatotoxicity due to acetaminophen use at the recommended daily dose of up to four grams daily has increasingly been recognized as a significant problem. The phrase "therapeutic misadventure" has been coined in the literature, in reference to biochemical evidence of hepatocellular injury associated with acetaminophen use at recommended doses. Previous studies have documented a 25% to 40% incidence of two- to three-fold alanie aminotransferase (ALT) elevation, in healty volunteers administered one gram of acetaminophen every six hours.

The recognition of this problem is reflected in part by recent changes in FDA recommendations, including more stringent controls on the amount ...


The Effect On Colon Visualization During Colonoscopy Of The Addition Of Simethicone To Polyethylene Glycol-Electrolyte Solution: A Randomized Single-Blind Study., Rebecca Matro, Keegan Tupchong, Constantine Daskalakis, Victoria Gordon, Leo Katz, David Kastenberg 2012 Thomas Jefferson University Hospitals

The Effect On Colon Visualization During Colonoscopy Of The Addition Of Simethicone To Polyethylene Glycol-Electrolyte Solution: A Randomized Single-Blind Study., Rebecca Matro, Keegan Tupchong, Constantine Daskalakis, Victoria Gordon, Leo Katz, David Kastenberg

Division of Gastroenterology and Hepatology Faculty Papers

OBJECTIVES: Colonic bubbles associated with polyethylene glycol-electrolyte solution (PEG-ELS) are common and obscure mucosal visualization. This study aimed to determine whether adding simethicone decreases the incidence of bubbles.

METHODS: Prospective, single-blind, randomized comparison of split dose PEG-ELS vs. PEG-ELS+simethicone (PEG-S) for outpatient colonoscopy. Bubble severity for colonic segments was assessed on withdrawal as A=no/minimal bubbles, B=moderate bubbles/interfere with detecting 5 mm polyp, C=severe bubbles/interfere with detecting 10 mm polyp. Primary end point was Grade B or C bubbles in any colon segment. Secondary end points were cleansing quality, incidence and severity of side ...


Comprehensive Analysis Of Common Serum Liver Enzymes As Prospective Predictors Of Hepatocellular Carcinoma In Hbv Patients., Hie-Won Hann, Shaogui Wan, Ronald E Myers, Richard S Hann, Jinliang Xing, Bicui Chen, Hushan Yang 2012 Thomas Jefferson University

Comprehensive Analysis Of Common Serum Liver Enzymes As Prospective Predictors Of Hepatocellular Carcinoma In Hbv Patients., Hie-Won Hann, Shaogui Wan, Ronald E Myers, Richard S Hann, Jinliang Xing, Bicui Chen, Hushan Yang

Department of Medicine Faculty Papers

BACKGROUND: Serum liver enzymes are frequently tested in clinics to aid disease diagnosis. Large observational studies indicated that these enzymes might predict cancer risk and mortality. However, no prospective study has reported on their relationships with the risk of HBV-related hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the predictive values of four routinely tested liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and gamma-glutamyltransferase [GGT]) in HCC risk in a prospectively enrolled clinical cohort of 588 Korean American HBV patients. For all four enzymes, the baseline level as well as the average and maximum levels during ...


Small Intestinal Bacterial Overgrowth And Lactose Intolerance Contribute To Irritable Bowel Syndrome Symptomatology In Pakistan, Javed Yakoob, Zaigham Abbas, Rustam Khan, Saeed Hamid, Safia Awan, Wasim Jafri 2011 Aga Khan University

Small Intestinal Bacterial Overgrowth And Lactose Intolerance Contribute To Irritable Bowel Syndrome Symptomatology In Pakistan, Javed Yakoob, Zaigham Abbas, Rustam Khan, Saeed Hamid, Safia Awan, Wasim Jafri

Department of Medicine

Background /Aim: The symptoms of irritable bowel syndrome resemble those of small intestinal bacterial overgrowth (SIBO). The aim of this study was to determine the frequency of SIBO and lactose intolerance (LI) occurrence in Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) according to Rome III criteria.

PatientS and Methods: In this retrospective case-control study, Patients over 18 years of age with altered bowel habit, bloating, and Patients who had lactose Hydrogen breath test (H 2 BT) done were included. The "cases" were defined as Patients who fulfill Rome III criteria for IBS-D, while "controls" were those having chronic nonspecific diarrhea ...


A Silent Storm: Hepatitis C In Pakistan, Noureen Jiwani, Raisa B. Gul 2011 Aga Khan University

A Silent Storm: Hepatitis C In Pakistan, Noureen Jiwani, Raisa B. Gul

School of Nursing & Midwifery

No abstract provided.


Bioluminescent Imaging Reveals Divergent Viral Pathogenesis In Two Strains Of Stat1-Deficient Mice, And In Αßγ Interferon Receptor-Deficient Mice, Tracy Jo Pasieka, Lynne Collins, Megan A. O'Connor, Yufei Chen, Zachary M. Parker, Brent L. Berwin, David R. Piwnica-Worms, David A. Leib 2011 Washington University School of Medicine

Bioluminescent Imaging Reveals Divergent Viral Pathogenesis In Two Strains Of Stat1-Deficient Mice, And In Αßγ Interferon Receptor-Deficient Mice, Tracy Jo Pasieka, Lynne Collins, Megan A. O'Connor, Yufei Chen, Zachary M. Parker, Brent L. Berwin, David R. Piwnica-Worms, David A. Leib

Open Dartmouth: Faculty Open Access Scholarship

Pivotal components of the IFN response to virus infection include the IFN receptors (IFNR), and the downstream factorsignal transducer and activator of transcription 1 (Stat1). Mice deficient for Stat1 and IFNR (Stat12/2 and IFNaßcR2/2 mice) lack responsiveness to IFN and exhibit high sensitivity to various pathogens. Here we examined herpes simplex virus type 1 (HSV-1) pathogenesis in Stat12/2 mice and in IFNaßcR2/2 mice following corneal infection and bioluminescent imaging. Two divergent and paradoxical patterns of infection were observed. Mice with an N-terminal deletion in Stat1 (129Stat12/2(N-term)) had transient infection of the liver and spleen ...


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