Medicine and Health Sciences Commons^™

Motility And Adhesion Through Type Iv Pili In Gram-Positive Bacteria, Kurt H. Piepenbrink, Eric J. Sundberg

Food for Health: Publications

Type IV pili are hair-like bacterial surface appendages that play a role in diverse processes such as cellular adhesion, colonization, twitching motility, biofilm formation, and horizontal gene transfer. These extracellular fibers are composed exclusively or primarily of many copies of one or more pilin proteins, tightly packed in a helix so that the highly hydrophobic amino-terminus of the pilin is buried in the pilus core. Type IV pili have been characterized extensively in Gram-negative bacteria, and recent advances in high-throughput genomic sequencing have revealed that they are also widespread in Gram-positive bacteria. Here, we review the current state of knowledge …

Ca2+/Calmodulin/Mlck Pathway Initiates, And Rhoa/Rock Maintains, The Internal Anal Sphincter Smooth Muscle Tone., Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

No abstract provided.

A Generalized Framework For Computational Design And Mutational Scanning Of T-Cell Receptor Binding Interfaces, Timothy P. Riley, Cory M. Ayres, Lance M. Hellman, Nishant K. Singh, Michael Cosiano, Jennifer M. Cimons, Michael J. Anderson, Kurt H. Piepenbrink, Brian G. Pierce, Zhiping Weng, Brian M. Baker

Food for Health: Publications

T-cell receptors (TCRs) have emerged as a new class of therapeutics, most prominently for cancer where they are the key components of new cellular therapies as well as soluble biologics. Many studies have generated high affinity TCRs in order to enhance sensitivity. Recent outcomes, however, have suggested that fine manipulation of TCR binding, with an emphasis on specificity may be more valuable than large affinity increments. Structure-guided design is ideally suited for this role, and here we studied the generality of structure-guided design as applied to TCRs. We found that a previous approach, which successfully optimized the binding of a …

A Rare Case Report Of Spontaneous Resolution Of Hepatic Portal Venous Gas Associated With Cocaine‑Induced Intestinal Ischemia, H. Patel, H. Shaaban, Nihar Shah Md, W. Baddoura

Gastroenterology

Hepatic portal venous gas (HPVG) is a rare disease entity. It is an ominous finding, usually, associated with intraabdominal ischemic necrosis. It frequently requires emergent surgical intervention. Herein, we present a case of a patient who complained of intense abdominal pain, with radiographic findings of HPVG as a result of cocaine-induced vascular insufficiency. After 5 h of nonoperative and conservative management, the HPVG spontaneously resolved. The patient clinically improved and was discharged home in a stable condition.

Aging-Associated Changes In Microrna Expression Profile Of Internal Anal Sphincter Smooth Muscle: Role Of Microrna-133a., Jagmohan Singh, Boopathi Ettickan, Sankar Addya, Benjamin Philllips, Isidore Rigoutsos, Raymond B. Penn, Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

A comprehensive genomic and proteomic, computational, and physiological approach was employed to examine the (previously unexplored) role of microRNAs (miRNAs) as regulators of internal anal sphincter (IAS) smooth muscle contractile phenotype and basal tone. miRNA profiling, genome-wide expression, validation, and network analyses were employed to assess changes in mRNA and miRNA expression in IAS smooth muscles from young vs. aging rats. Multiple miRNAs, including rno-miR-1, rno-miR-340-5p, rno-miR-185, rno-miR-199a-3p, rno-miR-200c, rno-miR-200b, rno-miR-31, rno-miR-133a, and rno-miR-206, were found to be upregulated in aging IAS. qPCR confirmed the upregulated expression of these miRNAs and downregulation of multiple, predicted targets (Eln, Col3a1, Col1a1, Zeb2, …

Changes In Serum Lipid Profile Among Patients Suffering From Chronic Liver Disease Secondary To Hepatitis C, Fakhar Qazi, Shameem Behram Khan, Anam Umar, Noor Ul Saba Shaikh, Fizza Choudhry

Section of Gastroenterology

Objective: To find out the changes in lipid metabolism among patients suffering from chronic liver disease secondary to hepatitis C.

Study Design: Hospital based observational study.

Setting: Medical Unit-I, Ward–5, Jinnah Postgraduate Medical Centre, Karachi.

Duration: July 2013 to December 2013.

Patients and Methods: About 110 patients admitted in Medical Unit-I with a diagnosis of chronic liver disease were included in the study. Patients suffering from DM, HTN, CKD were excluded from the study. Fasting lipid profile was done in all cases.

Results and Observations: There were 44 (40%) male and 66 (60%) female patients. Mean age of the patients …

Ibd Live Case Series-Case 6., Dhyan Rajan, Julia B. Greer, Miguel D. Regueiro, Leonard Baidoo, David G. Binion, Hans H. Herfarth, Corey A. Siegel, Douglas J. Hartman, Francis A. Farraye, Ioannis E. Koutroubakis, Myron H. Brand, Emmanuelle D. Williams, Alka Goyal, Raymond K. Cross

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Celiac Disease Presenting As Intussusception From Giardia Lamblia, Adam R. Paul Do

Department of Pediatrics

No abstract provided.

Immunomodulatory Effects Of Psyllium Extract On Helicobacter Pylori Interaction With Gastric Epithelial Cells., Javed Yakoob, Wasim Jafri, Malik Hassan Mehmood, Z Abbas, Kanwal Tariq

Section of Gastroenterology

Natural plant product Psyllium has anti-inflammatory activity that can modulate the function of cytokines. We determined the effect of Psylliumhusk extract on interleukin (IL)-8 and NF-κB secretion by gastric epithelial cells in response to Helicobacter pylori Human gastricadenocarcinoma cell line (AGS) cells were pretreated with Psyllium extract in different concentrations before H pylori infection. Cell culture supernatant was analyzed for IL-8 and NF-κB by ELISA. RNA from cells was used for real-time polymerase chain reaction for messenger RNA expression of IL-8. Psyllium extract 5 and 10 μg/mL markedly (P < .001) lowered basal IL-8 by 64.71% and 74.51%, respectively, and H pylori-stimulated IL-8 was also (P < .001) lowered by 41.67% and 66.67%, respectively. Psyllium 5 and 10 μg/mL also reduced (P < .0001) cagA-positive H pylori-induced IL-8 mRNA expression by 42.3% and 67.6%, respectively. Psyllium also reduced (P = .0001) NF-κB in response to H pylori strains confirming its role as an anti-inflammatory agent.

Successful Overtube Assisted Ercp: A Single-Center Case Series, Patrick Hickey Do, Shashin Shah Md, Hiral N. Shah Md, Tanveer Imam Md

Department of Medicine

No abstract provided.

Ampullary Carcinoid: A Case Report, Patrick Hickey Do, Shashin Shah Md, Hiral N. Shah Md

Department of Medicine

No abstract provided.

Closing The Gap: Deployment Of An Over-The-Scope Clip After Colonic Endoscopic Mucosal Resection, Matthew Sullivan Do, Shashin Shah Md, Hiral N. Shah Md

Department of Medicine

No abstract provided.

Appearances Can Be Deceiving - Colon Cancer Mimicking Ileocolitis, Abdul Aleem Md, Muhammad Qasim Md, Patrick Hickey Do, Hiral N. Shah Md

Department of Medicine

No abstract provided.

Erdheim-Chester Disease And Neuroendocrine Gastrointestinal Neoplasms, Samer Bolis Do, Patrick Hickey Do, Hiral N. Shah Md, Shashin Shah Md

Department of Medicine

No abstract provided.

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.

Structural Diversity In The Type Iv Pili Of Multidrug-Resistant Acinetobacter, Kurt H. Piepenbrink, Erik Lillehoj, Christian M. Harding, Jason W. Labonte, Xiaotong Zuo, Chelsea A. Rapp, Robert S. Munson Jr, Simeon E. Goldblum, Mario F. Feldman, Jeffrey J. Gray, Eric J. Sundberg

Food for Health: Publications

Acinetobacter baumannii is a Gram-negative coccobacillus found primarily in hospital settings that has recently emerged as a source of hospital-acquired infections. A. baumannii expresses a variety of virulence factors, including type IV pili, bacterial extracellular appendages often essential for attachment to host cells. Here, we report the high resolution structures of the major pilin subunit, PilA, from three Acinetobacter strains, demonstrating thatA. baumannii subsets produce morphologically distinct type IV pilin glycoproteins. We examine the consequences of this heterogeneity for protein folding and assembly as well as host-cell adhesion by Acinetobacter. Comparisons of genomic and structural data with pilin proteins from …

Aging-Associated Changes In Microrna Expression Profile Of Internal Anal Sphincter Smooth Muscle: Role Of Microrna-133a., Jagmohan Singh, Boopathi Ettickan, Sankar Addya, Benjamin Philllips, Isidore Rigoutsos, Raymond B. Penn, Phd, Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

A comprehensive -omic, computational, and physiological approach was employed to examine the (previously unexplored) role of microRNAs (miRNAs) as regulators of IAS smooth muscle contractile phenotype and basal tone. MicroRNA profiling, genome wide expression, validation and network analyses were employed to assess changes in mRNA and miRNA expression in IAS smooth muscles from young vs. aging rats. Multiple miRNAs, including rno-miR-1, rno-miR-340-5p, rno-miR-185, rno-miR-199a-3p, rno-miR-200c, rno-miR-200b, rno-miR-31, rno-miR-133a and rno-miR-206 were found to be up-regulated in aging IAS. qRT-PCR confirmed the up-regulated expression of these miRNAs and down regulation of multiple, predicted targets (Eln, Col3a1, Col1a1, Zeb2, Myocd, SRF, Smad1, …

The Neu1-Selective Sialidase Inhibitor, C9- Butyl-Amide-Dana, Blocks Sialidase Activity And Neu1-Mediated Bioactivities In Human Lung In Vitro And Murine Lung In Vivo, Sang W. Hyun, Anguo Liu, Zhenguo Liu, Alan S. Cross, Avelino C. Verceles, Sadagopan Magesh, Yadagiri Kommagalla, Chandrababunaidu Kona, Hiromune Ando, Irina G. Luzina, Sergei P. Atamas, Kurt H. Piepenbrink, Eric J. Sundberg, Wei Guang, Hideharu Ishida, Erik P. Lillehoj, Simeon E. Goldblum

Food for Health: Publications

Neuraminidase-1 (NEU1) is the predominant sialidase expressed in human airway epithelia and lung microvascular endothelia where it mediates multiple biological processes. We tested whether the NEU1-selective sialidase inhibitor, C9-butyl-amide-2-deoxy-2,3-dehydro-Nacetylneuraminic acid (C9-BA-DANA), inhibits one or more established NEU1-mediated bioactivities in human lung cells. We established the IC50 values of C9-BA-DANA for total sialidase activity in human airway epithelia, lung microvascular endothelia and lung fibroblasts to be 3.74 µM, 13.0 µM and 4.82 µM, respectively. In human airway epithelia, C9-BA-DANA dose-dependently inhibited flagellin-induced, NEU1-mediated mucin-1 ectodomain desialylation, adhesiveness for Pseudomonas aeruginosa and shedding. In lung microvascular endothelia, C9-BA-DANA reversed NEU1-driven restraint of …

Identification Of Pathway-Specific Serum Biomarkers Of Response To Glucocorticoid And Infliximab Treatment In Children With Inflammatory Bowel Disease, Christopher R. Heier, Alyson A. Fiorillo, Ellen Chaisson, Heather A. Gordish-Dressman, Yetrib Hathout, Jesse M. Damsker, Eric P. Hoffman, Laurie S. Conklin

Genomics and Precision Medicine Faculty Publications

Objective:

Serum biomarkers may serve to predict early response to therapy, identify relapse, and facilitate drug development in inflammatory bowel disease (IBD). Biomarkers are particularly important in children, in whom achieving early remission and minimizing procedures are especially beneficial.

Methods:

We profiled protein and micro RNA (miRNA) in serum from patients pre- and post-therapy, to identify molecular markers of pharmacodynamic effect. Serum was obtained from children with IBD before and after treatment with either corticosteroids (prednisone; n=12) or anti-tumor necrosis factor-α biologic (infliximab; n=7). Over 1,100 serum proteins were assayed using aptamer-based SOMAscan proteomics, and 22 miRNAs analyzed …

Obscure Gastrointestinal Bleeding: A Case Series, Eric Nellis Md, Patrick Hickey Do, Shashin Shah Md, Hiral N. Shah Md

Department of Medicine

No abstract provided.

Thrombotic Thrombocytopenic Purpura Induced By Acute Pancreatitis, Socrates G. Roedan Md, Nihar Shah Md, Robert Spira Md

Gastroenterology

Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder characterized by clotting in small blood vessels of the body (microthrombi), resulting in a low platelet count. The disease consists of the pentad of microangiopathic hemolytic anemia, thrombocytopenic purpura, neurologic abnormalities, fever and renal disease. Many symptoms could develop with acute pancreatitis but being able to differentiate when it is associated with any hematological conditions such as TTP is crucial to initiate a proper medical treatment. We present a rare case of a thirty-eight years old African American female, who presented to the Emergency department with an abdominal pain associated with …

Transoral Incisionless Fundoplication: Current Status., Karim Sami Trad

Surgery Faculty Publications

Purpose of review

Transoral incisionless fundoplication (TIF) performed with the EsophyX device (Redmond, Washington, USA) is a totally endoscopic procedure with the objectives to mechanically repair a defective gastroesophageal valve and to reduce small hiatal hernias. The recent publication of randomized controlled trials and long-term follow-up data offers the opportunity to reevaluate this treatment modality and its role in the management of patients with chronic gastroesophageal reflux disease (GERD).

Recent findings

Randomized controlled trials have confirmed the ability of TIF to eliminate troublesome GERD symptoms, heal esophagitis, and improve distal esophageal acid exposure in appropriately selected patient populations. These studies …

Decreased Pregnane X Receptor Expression In Children With Active Crohn's Disease, Valentina Shakhnovich, Carrie A. Vyhlidal, Craig A. Friesen, Amber Hildreth, Vivekanand Singh, James Daniel, Gregory L. Kearns, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

Copyright © 2016 The Author(s). Expression of the pregnane X receptor (PXR) has been reported to be decreased in animal models of inflammatory bowel disease (IBD). To investigate the differential expression of PXR in children with Crohn's disease, a type of IBD, RNA was extracted from archived intestinal biopsies from 18 children with Crohn's disease (CD) and 12 age- and sex-matched controls (aged 7-17yrs). The aim of this investigation was to compare the relative mRNA expression of PXR, cytochrome p450 3A4 (CYP3A4), and villin 1 (VIL1) (a marker of epithelial cell integrity) in the inflamed terminal ileum (TI) versus noninflamed …

Type Iv Pili Promote Early Biofilm Formation By Clostridium Difficile, Grace A. Maldarelli, Kurt H. Piepenbrink, Alison J. Scott, Jeffrey A. Freiberg, Yang Song, Yvonee Achermann, Robert K. Ernst, Mark E. Shirtliff, Eric J. Sundberg, Michael S. Donnenberg, Erik C. Von Rosenvinge

Food for Health: Publications

Increasing morbidity and mortality from Clostridium difficile infection (CDI) present an enormous challenge to healthcare systems. Clostridium difficile express type IV pili (T4P), but their function remains unclear. Many chronic and recurrent bacterial infections result from biofilms, surface-associated bacterial communities embedded in an extracellular matrix. CDI may be biofilm mediated; T4P are important for biofilm formation in a number of organisms. We evaluate the role of T4P in C. difficile biofilm formation using RNA sequencing, mutagenesis and complementation of the gene encoding the major pilin pilA1, and microscopy. RNA sequencing demonstrates that, in comparison to other growth phenotypes, C. difficile …

Hepatocellular Carcinoma After Locoregional Therapy: Magnetic Resonance Imaging Findings In Falsely Negative Exams., David Becker-Weidman, Jesse M. Civan, Sandeep P. Deshmukh, Christopher G. Roth, Steven K. Herrine, Laurence Parker, Donald G. Mitchell

Division of Gastroenterology and Hepatology Faculty Papers

AIM: To elucidate causes for false negative magnetic resonance imaging (MRI) exams by identifying imaging characteristics that predict viable hepatocellular carcinoma (HCC) in lesions previously treated with locoregional therapy when obvious findings of recurrence are absent.

METHODS: This retrospective institutional review board-approved and Health Insurance Portability and Accountability Act-compliant study included patients who underwent liver transplantation at our center between 1/1/2000 and 12/31/2012 after being treated for HCC with locoregional therapy. All selected patients had a contrast-enhanced MRI after locoregional therapy within 90 d of transplant that was prospectively interpreted as without evidence of residual or recurrent tumor. Retrospectively, 2 …

Multiorgan Chronic Inflammatory Hepatobiliary Pancreatic Murine Model Deficient In Tumor Necrosis Factor Receptors 1 And 2, Helieh S. Oz

Physiology Faculty Publications

AIM: To provoke persistent/chronic multiorgan inflammatory response and to contribute to stones formation followed by fibrosis in hepatobiliary and pancreatic tissues.

METHODS: Tumor necrosis factor receptors 1 and 2 (TNFR1/R2) deficient mice reared in-house were given dibutyltin dichloride (DBTC) twice within 10 d by oral gavage delivery. Sham control animals received vehicle treatment and naïve animals remained untreated throughout the study. Animals were monitored daily for symptoms of pain and discomfort. The abdominal and hindpaw hypersensitivity were assessed with von Frey microfilaments. Exploratory behaviors were recorded at the baseline, after initiation of treatment, and before study termination. Histopathological …

Interferon Lambda-3 Rs12979860 Variants And Response To Pegylated Interferon In Chronic Hepatitis-C Genotype-3, Zaigham Abbas, Javed Yakoob, Muhammad A. Umer, Ali A. Azeem, Saeed S. Hamid, Wasim Jafri

Department of Medicine

Objective: To assess the role of single nucleotide polymorphisms (SNPs) near the interferon lambda-3 (IFNλ3) (formal IL-28B) gene rs12979860 in predicting sustained virologic response (SVR) in hepatitis-C virus genotype-3 (HCV-3).

Study Design: Descriptive, analytical study.

Place and Duration of Study: Department of Medicine, The Aga Khan University Hospital, Karachi, from July 2012 to June 2014.

Methodology: Patients with HCV-3 were classified as sustained virologic response (SVR), relapsers and non-responders. SNP rs12979860 was determined by PCR-RFLP protocol. Differences between categorical variables were assessed by chi-square or Fisher's exact test, while those between continuous variables were evaluated using the Mann-Whitney U-test. Binary …

Professional Practices Promoting Health Of Healthcare Workers: Comparison Of Public And Private Hospitals In Pakistan, Nourin Jivany, Javed Yakoob, Shazia Bana, Asima Faisa, Humeira Jawed

Section of Gastroenterology

Background and Objectives: Health and safety of healthcare workers (HCWs) is a determinant of the quality of healthcare delivered to the population at large. This study aimed at comparing various dimension of HCWs’ health and safety between public and private hospitals (PHs) in the Pakistan context.

Methods: A sample of 1146 HCWs from 2 public and 2 PHls in a metropolitan city were invited to response to a structured questionnaire, assessing various aspects of health and safety promotion practices in their hospital. Categorical data were compared using chi-square test or Fisher exact test or likelihood ratio tests.

Findings: According to …

Next Big Threat For Pakistan Hepatocellular Carcinoma (Hcc), Om Parkash, Saeed Hamid

Section of Gastroenterology

In our country, world hepatitis day (28th May 2013) was observed as a liver cancer day to draw global attention on the global health menace caused by Hepatocellular carcinoma (HCC). This is the right time to write a review article to apprise the nation of this growing burden of HCC caused most commonly by viruses in our country. Pakistan is also recognized as one of the countries of the world where hepatitis C virus (HCV) is endemic. Recent large national surveys suggest an overall HCV prevalence of 4.8% and that of HBV as 2.5%. There are however communities where the …

Validation Of The Kinyarwanda-Version Short-Form Leeds Dyspepsia Questionnaire And Short-Form Nepean Dyspepsia Index To Assess Dyspepsia Prevalence And Quality-Of-Life Impact In Rwanda, Arcade Nkurunziza, Vincent Dusabejambo, Kelly Everhart, Steve Bensen, Tim Walker

Dartmouth Scholarship

We aimed to develop and validate Kinyarwanda versions of Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ) and Short-Form Nepean Dyspepsia Index (SF-NDI) to measure the frequency and severity of dyspepsia and associated quality-of-life impact in Rwanda.