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Articles 1 - 11 of 11
Full-Text Articles in Medicine and Health Sciences
A New Class Of Inhibitors Of The Arac Family Virulence Regulator Vibrio Cholerae Toxt, Anne K. Woodbrey, Evans O. Onyango, Maria Pellegrini, Gabriela Kovacikova, Ronald Taylor, Gordon Gribble, F. Jon Kull
A New Class Of Inhibitors Of The Arac Family Virulence Regulator Vibrio Cholerae Toxt, Anne K. Woodbrey, Evans O. Onyango, Maria Pellegrini, Gabriela Kovacikova, Ronald Taylor, Gordon Gribble, F. Jon Kull
Dartmouth Scholarship
Vibrio cholerae is responsible for the diarrheal disease cholera that infects millions of people worldwide. While vaccines protecting against cholera exist, and oral rehydration therapy is an effective treatment method, the disease will remain a global health threat until long-term solutions such as improved sanitation and access to clean water become widely available. Because of this, there is a pressing need for potent therapeutics that can either mitigate cholera symptoms, or act prophylactically to prevent the virulent effects of a cholera infection. Here we report the design, synthesis, and characterization of a set of compounds that bind and inhibit ToxT, …
Association Of Igg4 Response And Autoimmune Pancreatitis With Intraductal Papillary-Mucinous Neoplasms, Amin A. Hedayat, Mikhail Lisovsky, Arief A. Suriawinata
Association Of Igg4 Response And Autoimmune Pancreatitis With Intraductal Papillary-Mucinous Neoplasms, Amin A. Hedayat, Mikhail Lisovsky, Arief A. Suriawinata
Dartmouth Scholarship
Objectives: Concurrent intraductal papillary-mucinous neoplasm (IPMN) and autoimmune pancreatitis (AIP) was observed in a patient (index case) at our institution. Cases of coincidental IPMN and type 1 AIP and concurrent ductal adenocarcinoma (PDAC) and AIP have been previously reported. In this study we evaluate the hypothesis that IPMN elicits an IgG4 response. Methods: Twenty-one pancreases (including the index case) with IPMN resected at our institution were studied. H&E stained slides were reviewed and blocks of peritumoral pancreas were immunostained with IgG4 to look for IgG4-positive plasma cells. Results: We found evidence of variable IgG4 overexpression in 4/21 (19%) of IPMN. …
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
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 …
Total Pancreatectomy With Islet Autologous Transplantation: The Cure For Chronic Pancreatitis?, Samuel J. Kesseli, Kerrington A. Smith, Timothy B. Gardner
Total Pancreatectomy With Islet Autologous Transplantation: The Cure For Chronic Pancreatitis?, Samuel J. Kesseli, Kerrington A. Smith, Timothy B. Gardner
Dartmouth Scholarship
Chronic pancreatitis (CP) is a debilitating disease that leads to varying degrees of pancreatic endocrine and exocrine dysfunction. One of the most difficult symptoms of CP is severe abdominal pain, which is often challenging to control with available analgesics and therapies. In the last decade, total pancreatectomy with autologous islet cell transplantation has emerged as a promising treatment for the refractory pain of CP and is currently performed at approximately a dozen centers in the United States. While total pancreatectomy is not a new procedure, the endocrine function-preserving autologous islet cell isolation and re-implantation have made the prospect of total …
Requirements For Vibrio Cholerae Hapr Binding And Transcriptional Repression At The Hapr Promoter Are Distinct From Those At The Apha Promoter, Wei Lin, Gabriela Kovacikova, Karen Skorupski
Requirements For Vibrio Cholerae Hapr Binding And Transcriptional Repression At The Hapr Promoter Are Distinct From Those At The Apha Promoter, Wei Lin, Gabriela Kovacikova, Karen Skorupski
Dartmouth Scholarship
Virulence gene expression in certain strains of Vibrio cholerae is regulated in response to cell density by a quorum-sensing cascade that influences the levels of the LuxR homolog HapR through small regulatory RNAs that control the stability of its message. At high cell density, HapR represses the expression of the gene encoding the virulence gene activator AphA by binding to a site between −85 and −58 in the aphA promoter. We show here that a second binding site for HapR lies within the hapR promoter from which it functions to repress its own transcription. This site, as determined by gel …
Identification Of A Tcpc-Tcpq Outer Membrane Complex Involved In The Biogenesis Of The Toxin-Coregulated Pilus Of Vibrio Cholerae, Niranjan Bose, Ronald K. Taylor
Identification Of A Tcpc-Tcpq Outer Membrane Complex Involved In The Biogenesis Of The Toxin-Coregulated Pilus Of Vibrio Cholerae, Niranjan Bose, Ronald K. Taylor
Dartmouth Scholarship
The toxin-coregulated pilus (TCP) of Vibrio cholerae and the soluble TcpF protein that is secreted via the TCP biogenesis apparatus are essential for intestinal colonization. The TCP biogenesis apparatus is composed of at least nine proteins but is largely uncharacterized. TcpC is an outer membrane lipoprotein required for TCP biogenesis that is a member of the secretin protein superfamily. In the present study, analysis of TcpC in a series of strains deficient in each of the TCP biogenesis proteins revealed that TcpC was absent specifically in a tcpQ mutant. TcpQ is a predicted periplasmic protein required for TCP biogenesis. Fractionation …
A Novel Triterpenoid Induces Transforming Growth Factor Β Production By Intraepithelial Lymphocytes To Prevent Ileitis, Laurie A. Minns, Dominique Buzoni-Gatel, Kenneth H. Ely, Nicolas Rachinel, Souphalone Luangsay, Lloyd H. Kasper
A Novel Triterpenoid Induces Transforming Growth Factor Β Production By Intraepithelial Lymphocytes To Prevent Ileitis, Laurie A. Minns, Dominique Buzoni-Gatel, Kenneth H. Ely, Nicolas Rachinel, Souphalone Luangsay, Lloyd H. Kasper
Dartmouth Scholarship
The loss of homeostasis is a hallmark of inflammatory bowel disease. Oral infection of susceptible mice with Toxoplasma gondii results in an acute lethal ileitis characterized by increased interferon γ, tumor necrosis factor α, and inducible nitric oxide synthase; homeostasis results from transforming growth factor β production by intraepithelial lymphocytes. The synthetic oleanane triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) is a potent anti-inflammatory molecule previously shown in vitro to suppress the de novo synthesis of inducible nitric oxide synthase and to induce the transcription and activation of genes from the transforming growth factor β signaling pathway. We evaluated the immune response in …
Ccr5 Mediates Specific Migration Of Toxoplasma Gondii—Primed Cd8+ Lymphocytes To Inflammatory Intestinal Epithelial Cells, Souphalone Luangsay, Lloyd H. Kasper, Nicolas Rachinel, Laurie A. Minns
Ccr5 Mediates Specific Migration Of Toxoplasma Gondii—Primed Cd8+ Lymphocytes To Inflammatory Intestinal Epithelial Cells, Souphalone Luangsay, Lloyd H. Kasper, Nicolas Rachinel, Laurie A. Minns
Dartmouth Scholarship
Toxoplasma gondii, an obligate intracellular parasite, can invade intestinal epithelial cells and elicit a robust Th1 immune response. In this model of intestinal inflammation, CD8+ intraepithelial lymphocytes (IELs) secrete transforming growth factor (TGF)-β, which appears necessary for the maintenance of homeostasis in the intestine. However, the mechanism responsible for the IEL migration to the inflamed intestine is still unclear.An in vitro coculture cell system was used to quantify the IEL attraction by an infected intestinal epithelial cell line (m-ICcl2). We used CCR5-deficient mice to determine which chemokine receptor—chemokine interaction could be responsible for the recruitment of …
Mechanism Of Toxt-Dependent Transcriptional Activation At The Vibrio Cholerae Tcpa Promoter, Robin R. Hulbert, Ronald K. Taylor
Mechanism Of Toxt-Dependent Transcriptional Activation At The Vibrio Cholerae Tcpa Promoter, Robin R. Hulbert, Ronald K. Taylor
Dartmouth Scholarship
The AraC homolog ToxT coordinately regulates virulence gene expression in Vibrio cholerae. ToxT is required for transcriptional activation of the genes encoding cholera toxin and the toxin coregulated pilus, among others. In this work we focused on the interaction of ToxT with the tcpA promoter and investigated the mechanism of ToxT-dependent transcriptional activation at tcpA. Deletion analysis showed that a region from −95 to +2 was sufficient for ToxT binding and activation, both of which were simultaneously lost when the deletion was extended to −63. A collection of point mutations generated by error-prone PCR revealed two small regions required …
Vibrio Cholerae H-Ns Silences Virulence Gene Expression At Multiple Steps In The Toxr Regulatory Cascade, Melinda B. Nye, James D. Pfau, Karen Skorupski, Ronald K. Taylor
Vibrio Cholerae H-Ns Silences Virulence Gene Expression At Multiple Steps In The Toxr Regulatory Cascade, Melinda B. Nye, James D. Pfau, Karen Skorupski, Ronald K. Taylor
Dartmouth Scholarship
H-NS is an abundant nucleoid-associated protein involved in the maintenance of chromosomal architecture in bacteria. H-NS also has a role in silencing the expression of a variety of environmentally regulated genes during growth under nonpermissive conditions. In this study we demonstrate a role for H-NS in the negative modulation of expression of several genes within the ToxR virulence regulon ofVibrio cholerae. Deletion of hns resulted in high, nearly constitutive levels of expression of the genes encoding cholera toxin, toxin-coregulated pilus, and the ToxT virulence gene regulatory protein. For the cholera toxin- and ToxT-encoding genes, elevated expression in an …
Adenoma Characteristics At First Colonoscopy As Predictors Of Adenoma Recurrence And Characteristics At Follow-Up, Rosalind U. Van Stolk, Gerald J. Beck, John A. Baron, Robert Haile, Robert Summers
Adenoma Characteristics At First Colonoscopy As Predictors Of Adenoma Recurrence And Characteristics At Follow-Up, Rosalind U. Van Stolk, Gerald J. Beck, John A. Baron, Robert Haile, Robert Summers
Dartmouth Scholarship
All patients with colorectal adenomas may not require identical follow-up. We aimed to determine if adenoma characteristics at initial colonoscopy could predict adenoma recurrence or characteristics at follow-up. The number of adenomas and the size, type, and degree of atypia in 479 patients in a polyp prevention trial were evaluated as predictors of the same characteristics at follow-up using odds ratios (ORs) with 95% confidence intervals (CIs). Multiple logistic regression analysis was performed to determine if several baseline characteristics were simultaneously associated with outcome.