Gastroenterology Commons^™

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 …

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.

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 …

There Is Relief For Constipated Patients Taking Opioids., Ahmad Mohammadieh, James Choi, Md, Chelsea Gonzalez, Do, Diyanah Elyaman, Md

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Tack J, Lappalainen J, Diva U, Tummala R, Sostek M. Efficacy and safety of naloxegol in patients with opioid-induced constipation and laxative-inadequate response. United European Gastroenterol J. 2015 Oct;3(5):471-80. doi: 10.1177/2050640615604543

Fecal Transplant Vs Vancomycin For Recurrent Clostridium Diffile, Lauren M. Taylor, Todd E. Edwards

Physician Assistant Capstones, 2016 to 2019

Objective: To compare fecal transplant and vancomycin in the treatment of recurrent clostridium difficile to determine which has the higher cure rate. Design: Systematic literature review. Methods: Pubmed, Google Scholar, and TRIP database using the search terms “recurrent clostridium difficile.” Filters were implemented in the Pubmed database including: randomized control trials, English, and published in the past 5 years. Records were screened for RCT with fecal transplant and full-text. Results: van Nood et al. revealed an initial cure rate of 81% for the infusion group, and a re-treated cure rate of 94%, compared to the vancomycin alone group of 31% …

Redesigning Gfp Reporter System For Utilization In Clostridium Difficile, Laura E. Fitzgerald

Biological Sciences Undergraduate Honors Theses

Clostridium difficile (C. difficile) is a gram-positive bacterium that comprises part of the healthy human gut microbiome. When it gains sufficient access to peptides, C. difficile flourishes and releases tissue-damaging toxins, which cause inflammation of the colon that can develop into a Clostridium difficile Infection (CDI).¹⁰ The Ivey Laboratory believes that the best tactic in preventing CDIs is stopping peptide ingestion, which theoretically could be accomplished by manipulating the oligopeptide permease (App) system.⁷ In order to verify that altering the App system would successfully impede peptide uptake, first the expression of the app Promoter Region ( …

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 …

Treatment And Prevention Of Human Rotavirus (Hrv) In Developing Countries: The Potential Of Avian Immunoglobulin Y, Christa Brown

Senior Honors Theses

Rotavirus gastroenteritis is a leading cause of childhood mortality, killing ~1400 children younger than five daily, primarily through severe diarrheal dehydration. Eighty-five percent of this mortality occurs in developing countries where rotavirus vaccines are not widely implemented and are only partially effective. In those countries, it has proven difficult to implement the recommended supportive therapies like oral rehydration therapy (ORT) on a wide scale due to lack of both medical infrastructure and private economic investment combined with cultural bias against ORT. IgY targeting human rotavirus (anti-HRV IgY) shows potential as a passive immunotherapy that reduces rotavirus-associated morbidity and mortality, augments …

Structural And Evolutionary Analyses Show Unique Stabilization Strategies In The Type Iv Pili Of Clostridium Difficile, Kurt H. Piepenbrink, Grace A. Maldarelli, Claudia F. Martinez De La Pena, Tanis C. Dingle, George L. Mulvey, Amanda Lee, Erik Von Rosenvinge, Glen D. Armstrong, Michael S. Donnenberg, Eric J. Sundberg

Food for Health: Publications

Type IV pili are produced by many pathogenic Gram-negative bacteria and are important for processes as diverse as twitching motility, biofilm formation, cellular adhesion and horizontal gene transfer. However, many Gram-positive species, including C. difficile, also produce Type IV pili. Here, we identify the major subunit of the Type IV pili of C. difficile, PilA1, and describe multiple three-dimensional structures of PilA1, demonstrating the diversity found in three strains of C. difficile. We also model the incorporation of both PilA1 and a minor pilin, PilJ, into the pilus fiber. Although PilA1 contains no cysteine residues, and therefore cannot form the …

Recommendations For The Development Of New Hospital Guidelines Due To The Effects Of Antibiotics On Clostridium Difficile Colitis, Megan Kohsel

Honors Theses

Clostridium difficile colitis is an infection that causes inflammation of the colon and diarrhea. This can even lead to death in some cases. The incidence of this infection and its overall effects have been on the rise throughout the last twenty years as antibiotics have been prescribed more frequently. Therefore, it is necessary that the rate of C. difficile infection is lowered by improved guidelines for hospitals, so that fewer people are infected and also that fewer antibiotics are prescribed to avoid the infection with C. difficle.

Neurofibromatosis Type 1 With Ampullary Somatostatinoma, Small Bowel Gists, And Extra-Adrenal Composite Pheochromocytoma-Ganglioneuroma, Patrick Hickey Do, Rohit Sharma Md, Shanth A. Goonewardene Md, Shashin Shah Md, Hiral N. Shah Md

Department of Medicine

No abstract provided.

In The Groove: A Case Series Of Groove Pancreatitis, Matthew Sullivan Do, Jeffrey Brodsky Md, Shashin Shah Md, Hiral N. Shah Md

Department of Medicine

No abstract provided.

Primary Esophageal Adenocarcinoma With Colon Metastases After Esophagectomy, Bonnie Patek Do, Hiral N. Shah Md, Shashin Shah Md

Department of Medicine

No abstract provided.

Attempted Salvage Therapy Through Initiation Of Vedolizumab As An Inpatient In Two Patients With Refractory Active Ulcerative Colitis, Matthew Sullivan Do, Paola Blanco Md, Shashin Shah Md, Hiral N. Shah Md

Department of Medicine

No abstract provided.

Undifferentiated Carcinoma With Osteoclast-Like Giant Cells Of The Pancreatic Tail, Patrick Hickey Do, Ranjit R. Nair Md, Victoria A. Loven Md, Jeffrey Brodsky Md, Hiral N. Shah Md

Department of Medicine

No abstract provided.

Endoscopic Mucosal Resection And Radiofrequency Ablation For Intramucosal Adenocarcinoma In The Background Of Barrett’S Esophagus: A Case Series, Bonnie Patek Do, Patrick Hickey Do, Hiral N. Shah Md, Shashin Shah Md

Department of Medicine

No abstract provided.

Characterization And Investigation Of Fungi Inhabiting The Gastrointestinal Tract Of Healthy And Diseased Humans, Mallory J. Suhr

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Gastrointestinal microbiome studies have failed to include fungi in total community analyses. As a result, their diversity and function in the gut is poorly understood. Recent work has begun to uncover the role intestinal fungi play in diet, immune system development, interactions with other microorganisms in the gut, and pathogenesis of diseases. Advances in sequencing technologies allow for the ability to profile the fungal gut microbiome (“mycobiome”) in healthy and diseased states. This thesis explores the mycobiome in 1) healthy humans with a vegetarian diet and 2) pediatric small bowel transplant recipients that develop fungal bloodstream infections.

The gut mycobiome …

Refractory Case Of Esophageal Web In A Male Patient With Alcoholic Liver Disease, Bonnie Patek Do, Shashin Shah Md, Hiral N. Shah Md

Department of Medicine

No abstract provided.

An Unlikely Cause Of Possible Hormone-Dependent Abdominal Pain In Young Fertile Females: A Case Series, Bonnie Patek Do, Hiral Shah Md, Shashin Shah Md

Department of Medicine

No abstract provided.

Site-Specific Immunomodulator: A Novel Treatment For Crohn's Disease, Brian Bressler, Kevin P. Bethel, Ralf Kleef, Sophie L. Reynolds, Simon Sutcliffe, David W. Mullins, Hal Gunn

Dartmouth Scholarship

We investigated the mechanism of action, safety, and efficacy of the Site-Specific Immunomodulator (SSI) QBECO, a novel immunotherapy for Crohn’s disease (CD). Using human monocytic THP-1 cells, we demonstrate that SSI QBECO (derived from the common colon bacteria E. coli) activates macrophages to an M1 phenotype (associated with enhanced capacity to eliminate bacteria and activate innate immune responses). We assessed SSI QBECO in a compassionate use protocol of ten adult patients with active CD. Patients with moderate to severe clinical symptoms receiving conventional CD treatments and/or complementary therapies were included, except patients receiving anti-TNF medications. SSI QBECO was self-administered subcutaneously …

Female Gender In Esophageal Intramucosal Adenocarcinoma Treated With Endoscopic Mucosal Resection: A Case Series, Patrick Hickey Do, Shashin Shah Md, Hiral N. Shah Md

Department of Medicine

No abstract provided.

Plasticity In The Contribution Of T Cell Receptor Variable Region Residues To Binding Of Peptide-Hla-A2 Complexes, Sheena N. Smith, Daniel Sommermeyer, Kurt H. Piepenbrink, Sydney J. Blevins, Helga Bernhard, Wolfgang Uckert, Brian M. Baker, David M. Kranz

Food for Health: Publications

One hypothesis to account for MHC-restriction by T cell receptors (TCRs) holds that there are several evolutionary-conserved residues in TCR variable regions that contact MHC. While this ‘germline-codon’ hypothesis is supported by various lines of evidence, it has been difficult to test. The difficulty stems in part from the fact that TCRs exhibit low affinities for pep/MHC, thus limiting the range of binding energies that can be assigned to these key interactions using mutational analyses. To measure the magnitude of binding energies involved, here we used high affinity TCRs engineered by mutagenesis of CDR3. The TCRs included a high-affinity, MART-1/ …

Unchain My Heart: Constrictive Pericarditis In The Setting Of Chronic Kidney Disease And Monoclonal Gammopathy Of Undetermined Significance, Neiman Ramjattan Do, Justin L. Guthier Do, Stacey Smith Md, Facp

Department of Medicine

No abstract provided.

Isolated Gastroduodenal Crohn’S Disease, Matthew Sullivan Do, Patrick Hickey Do, Saba Ahmad Md, Jeffrey Brodsky Md, Hiral N. Shah Md, Ronald Bross Md

Department of Medicine

No abstract provided.

Rare Presentation Of A Massive Intermittent Upper Gastrointestinal Bleed, Bonnie Patek Do, Matthew Sullivan Do, Shashin Shah Md

Department of Medicine

No abstract provided.

Markedly Elevated Ca 19-9 In A Case Of Mirizzi’S Syndrome: An Atypical Presentation, Saba Ahmad Md, Hiral N. Shah Md, Patrick Hickey Do, Matthew Sullivan Do

Department of Medicine

No abstract provided.

Microscopic Polyangiitis Presenting With A Pure Sensory Peripheral Symmetric Polyneuropathy, Matthew Sullivan Do, Craig A. Mackaness Do, James Ross Md, Facp

Department of Medicine

No abstract provided.

Recurrent Biliary Obstruction Overcome With Metal Biliary Stent Placement In The Surgically Altered Down Syndrome Patient For Congenital Duodenal Atresia, Patrick Hickey Do, Matthew Sullivan Do, Saba Ahmad Md, Hiral Shah Md

Department of Medicine

No abstract provided.

Adenomyomatous Hyperplasia Of The Ampulla Of Vater Masquerading As Malignancy: A Case Series, Patrick Hickey Do, Saba Ahmad Md, Matthew Sullivan Do, Miriam L. Enriquez Md, Jeffrey Brodsky Md, Hiral Shah Md

Department of Medicine

No abstract provided.

Crohn’S Disease Linked Polymorphisms Associated With Autophagy Contribute To Th17 Cell Induction Through Increasing The Expression Of Il-1Β And Tnf-Α, Daniel Clayton Morse

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Genome wide association studies (GWAS) have linked polymorphisms in autophagy genes to Crohn’s Disease (CD). Interestingly, recent studies have shown that defective autophagy leads to increased levels of the cytokines IL-1b and TNF-a, which play a critical role in Th17 cell differentiation. This is significant because CD is marked by a Th17 cell mediated inflammatory response. This article examines the manners in which defective expression of autophagy linked proteins, can indirectly amplify and sustain Th17 cell induction through increasing the production of Th17 positively differentiating cytokines (IL-1b and TNF-a) and decreasing the production of a Th17 down regulating cytokine, IL-10.