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14. Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Author

Bartelt, Luther A., primary, Bolick, David T., additional, Kolling, Glynis L., additional, Roche, James K., additional, Zaenker, Edna I., additional, Lara, Ana M., additional, Noronha, Francisco Jose, additional, Cowardin, Carrie A., additional, Moore, John H., additional, Turner, Jerrold R., additional, Warren, Cirle A., additional, Buck, Gregory A., additional, and Guerrant, Richard L., additional

Published
2016
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22. Intranasal vaccination in mice with an attenuated Salmonella enterica Serovar 908htr A expressing Cp15 of Cryptosporidium: Impact of malnutrition with preservation of cytokine secretion

Author

Roche, James K., primary, Rojo, Ana Lara, additional, Costa, Lourrany B., additional, Smeltz, Ronald, additional, Manque, Patricio, additional, Woehlbier, Ute, additional, Bartelt, Luther, additional, Galen, James, additional, Buck, Gregory, additional, and Guerrant, Richard L., additional

Published
2013
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23. Modeling the Role of Peroxisome Proliferator-Activated Receptor γ and MicroRNA-146 in Mucosal Immune Responses to Clostridium difficile

Author

Viladomiu, Monica, primary, Hontecillas, Raquel, additional, Pedragosa, Mireia, additional, Carbo, Adria, additional, Hoops, Stefan, additional, Michalak, Pawel, additional, Michalak, Katarzyna, additional, Guerrant, Richard L., additional, Roche, James K., additional, Warren, Cirle A., additional, and Bassaganya-Riera, Josep, additional

Published
2012
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34. Immunohistochemical Detection and Quantitation of Cell Surface Receptors for Prostanoids.

Author

Walker, John M., M., Steven, Cosme, Rosana, and Roche, James K.

Abstract

The mucosa of the colon occupies 25% of the intestinal wall, from the muscularis mucosa to the lumen-lining epithelium, and contains a variety of cell types, predominantly B and T lymphocytes, but also monocytes, mast cells, and macrophages (1,2). These cells secrete a variety of cytokines, including interleukins, leakotrienes, and prostaglandins. Most of these are locally active, diffuse throughout the mucosa, and do not substantially contribute to the concentration of cytokines in the blood. [ABSTRACT FROM AUTHOR]

Published
2001
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35. Isolation of a Purified Epithelial Cell Population from Human Colon.

Author

Walker, John M., M., Steven, and Roche, James K.

Abstract

While in situ techniques have been valuable in identifying the presence and localization of cytoplasmic and membrane components in tissue (1), there is often a need to study directly one or more cell types, free from its own microenvironment. For the human colon, isolation techniques to allow direct study have been described for mononuclear cells in the lamina propria, smooth muscle cells at or below the muscularis mucosae, and cells of the enteric nervous system, located between the subserosa and the lamina propria (2-4). More recently, interest has risen to isolate populations of intestinal epithelial cells, for investigations of human colonic adenocarcinoma-which originates from colonic epithelia; as well as for study of the epithelial response to infection and inflammation. The technique for isolating epithelial cells from the human colon involves mechanical dissection to separate mucosa from the muscle layers which are discarded; and enzymatic digestion of collagen, followed by discontinuous gradient centrifugation in Percoll. The goal is to isolate>90% pure epithelial cells. Although the cells appear intact under the microscope, viability is variable from 50-80%. The yield depends on the size of the available tissue. [ABSTRACT FROM AUTHOR]

Published
2001
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43. The Role of Peroxisome Proliferator-Activated Receptor γ in Immune Responses to Enteroaggregative Escherichia coli Infection.

Author

Philipson, Casandra W., Bassaganya-Riera, Josep, Viladomiu, Monica, Pedragosa, Mireia, Guerrant, Richard L., Roche, James K., and Hontecillas, Raquel

Subjects
PEROXISOME proliferator-activated receptors, ESCHERICHIA coli diseases, IMMUNE response, DIARRHEA, IMMUNOSUPPRESSION, GENE expression, ANIMAL models in research
Abstract

Background: Enteroaggregative Escherichia coli (EAEC) is recognized as an emerging cause of persistent diarrhea and enteric disease worldwide. Mucosal immunity towards EAEC infections is incompletely understood due in part to the lack of appropriate animal models. This study presents a new mouse model and investigates the role of peroxisome proliferator-activated receptor gamma (PPARγ) in the modulation of host responses to EAEC in nourished and malnourished mice. Methods/Principal Findings: Wild-type and T cell-specific PPARγ null C57BL/6 mice were fed protein-deficient diets at weaning and challenged with 5×109cfu EAEC strain JM221 to measure colonic gene expression and immune responses to EAEC. Antigen-specific responses to E. coli antigens were measured in nourished and malnourished mice following infection and demonstrated the immunosuppressive effects of malnutrition at the cellular level. At the molecular level, both pharmacological blockade and deletion of PPARγ in T cells resulted in upregulation of TGF-β, IL-6, IL-17 and anti-microbial peptides, enhanced Th17 responses, fewer colonic lesions, faster clearance of EAEC, and improved recovery. The beneficial effects of PPARγ blockade on weight loss and EAEC clearance were abrogated by neutralizing IL-17 in vivo. Conclusions: Our studies provide in vivo evidence supporting the beneficial role of mucosal innate and effector T cell responses on EAEC burden and suggest pharmacological blockade of PPARγ as a novel therapeutic intervention for EAEC infection. [ABSTRACT FROM AUTHOR]

Published
2013
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44. Modeling the Role of Peroxisome Proliferator-Activated Receptor c and MicroRNA-146 in Mucosal Immune Responses to Clostridium difficile.

Author

Viladomiu, Monica, Hontecillas, Raquel, Pedragosa, Mireia, Carbo, Adria, Hoops, Stefan, Michalak, Pawel, Michalak, Katarzyna, Guerrant, Richard L., Roche, James K., Warren, Cirle A., and Bassaganya-Riera, Josep

Subjects
CLOSTRIDIOIDES difficile, PEROXISOME proliferator-activated receptors, INFLAMMATION prevention, T cells, MICRORNA, GENE expression
Abstract

Clostridium difficile is an anaerobic bacterium that has re-emerged as a facultative pathogen and can cause nosocomial diarrhea, colitis or even death. Peroxisome proliferator-activated receptor (PPAR) ϒ has been implicated in the prevention of inflammation in autoimmune and infectious diseases; however, its role in the immunoregulatory mechanisms modulating host responses to C. difficile and its toxins remains largely unknown. To characterize the role of PPARϒ in C. difficile-associated disease (CDAD), immunity and gut pathology, we used a mouse model of C. difficile infection in wild-type and T cell-specific PPARϒ null mice. The loss of PPARϒ in T cells increased disease activity and colonic inflammatory lesions following C. difficile infection. Colonic expression of IL-17 was upregulated and IL-10 downregulated in colons of T cell-specific PPARϒ null mice. Also, both the loss of PPARϒ in T cells and C. difficile infection favored Th17 responses in spleen and colonic lamina propria of mice with CDAD. MicroRNA (miRNA)-sequencing analysis and RT-PCR validation indicated that miR-146b was significantly overexpressed and nuclear receptor co-activator 4 (NCOA4) suppressed in colons of C. difficile-infected mice. We next developed a computational model that predicts the upregulation of miR-146b, downregulation of the PPARϒ co-activator NCOA4, and PPARϒ, leading to upregulation of IL-17. Oral treatment of C. difficile-infected mice with the PPARc agonist pioglitazone ameliorated colitis and suppressed pro-inflammatory gene expression. In conclusion, our data indicates that miRNA-146b and PPARϒ activation may be implicated in the regulation of Th17 responses and colitis in C. difficile-infected mice. [ABSTRACT FROM AUTHOR]

Published
2012
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46. Ethics Environment in Long-Term Care.

Author

McDaniel, Charlotte, Roche, James K., and Veledar, Emir

Abstract

This study assesses three hypotheses regarding a long-term care facility’s ethics environment and the relationships between ethics environment, employees’ work features, and residents’ outcomes. Validated questionnaires measure ethics environment, work satisfaction, managing disagreement, goal attainment, care and work opinion including retention, and mental health status among full-time employees (N = 110; 53%) and residents (N = 139; 57%) who volunteered for this cross-sectional cohort analysis. Ethics environment is rated above average (> 3.0, 1-5 scale) by employees and residents, with statistically significant (p = .001) Spearman correlations between ethics environment and employees’ attainment of goals, opinion of care, and work satisfaction; between residents’ ethics environment and care opinion and mental status (MCS, SF-36). Among others, ethics environment is revealed as a robust correlate to two critical factors for quality care: employees’ care opinion including retention and residents’ mental health. It is possible to develop and sustain ethics environments, thus these findings are applicable to clinical practice. [ABSTRACT FROM PUBLISHER]

Published
2011
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