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Benight N.M.,University of Cincinnati | Waltz S.E.,University of Cincinnati | Waltz S.E.,Cincinnati Veterans Affairs Medical Center
Expert Opinion on Therapeutic Targets | Year: 2012

Introduction: Since its discovery nearly 20 years ago, the Ron receptor tyrosine kinase has been extensively studied. These studies have elucidated many of the major signaling pathways activated by Ron. In the context of the inflammation and cancer, studies have shown that Ron plays differential roles; Ron activation limits the inflammatory response, whereas in cancer, Ron activation is associated with increased metastases and poor prognosis. Areas covered: This review discusses the current literature with regard to Ron signaling and consequences of its activation in cancer as well as its role in cancer therapy. Further, we discuss the mechanisms by which Ron influences the inflammatory response and its role in chronic inflammatory diseases. Finally, we discuss Ron's connection between chronic inflammation and progression to cancer. Expert opinion: The complex nature of Ron's signaling paradigm necessitates additional studies to understand the pathways by which Ron is functioning and how these differ in inflammation and cancer. This will be vital to understanding the impact that Ron signaling has in disease states. Additional studies of targeted therapies, either alone or in conjunction with current therapies are needed to determine if inhibition of Ron signaling will provide long-term benefits to cancer patients. © 2012 Informa UK, Ltd.

Finkelman F.D.,Cincinnati Veterans Affairs Medical Center | Finkelman F.D.,University of Cincinnati | Finkelman F.D.,Cincinnnati Childrens Hospital Medical Center
Current Opinion in Immunology | Year: 2010

Peanuts are a frequent cause of food allergy and the most common cause of fatal food-induced anaphylaxis in the U.S. Advances during the past two years have promoted our understanding of peanut allergens and peanut allergy prevalence, etiology, diagnosis, and therapy. The advances highlighted in this review include evidence that the peanut allergens most important in disease differ in different parts of the world, that early oral exposure to peanuts may decrease the frequency of peanut allergy, while early nonoral exposure may have the opposite effect, that complement activation by peanut constituents appears to promote peanut-induced anaphylaxis and that oral immunotherapy, anti-IgE antibody, and a herbal formulation are promising approaches for the treatment of this disorder. © 2010.

Finkelman F.D.,Cincinnati Veterans Affairs Medical Center | Finkelman F.D.,University of Cincinnati | Finkelman F.D.,Cincinnati Childrens Hospital Medical Center | Wills-Karp M.,Cincinnati Childrens Hospital Medical Center
Journal of Immunology | Year: 2010

Asthma is a common, disabling inflammatory respiratory disease that has increased in frequency and severity in developed nations. We review studies of murine allergic airway disease (MAAD) and human asthma that evaluate the importance of Th2 cytokines, Th2 responsepromoting cytokines, IL-17, and proinflammatory and anti-inflammatory cytokines in MAAD and human asthma. We discuss murine studies that directly stimulate airways with specific cytokines or delete, inactivate, neutralize, or block specific cytokines or their receptors, as well as controversial issues including the roles of IL-5, IL-17, and IL-13Rα2 in MAAD and IL-4Rα expression by specific cell types. Studies of human asthmatic cytokine gene and protein expression, linkage of cytokine polymorphisms to asthma, cytokine responses to allergen stimulation, and clinical responses to cytokine antagonists are discussed as well. Results of these analyses establish the importance of specific cytokines in MAAD and human asthma and have therapeutic implications.

Salehi M.,University of Cincinnati | Prigeon R.L.,University of Maryland, Baltimore | Prigeon R.L.,Geriatric Research Education and Clinical Center | D'Alessio D.A.,University of Cincinnati | D'Alessio D.A.,Cincinnati Veterans Affairs Medical Center
Diabetes | Year: 2011

OBJECTIVE - Gastric bypass (GB) surgery is associated with postprandial hyperinsulinemia, and this effect is accentuated in postsurgical patients who develop recurrent hypoglycemia. Plasma levels of the incretin glucagon-like peptide 1 (GLP-1) are dramatically increased after GB, suggesting that its action contributes to alteration in postprandial glucose regulation. The aim of this study was to establish the role of GLP-1 on insulin secretion in patients with GB. RESEARCH DESIGN AND METHODS - Twelve asymptomatic individuals with previous GB (Asym-GB), 10 matched healthy nonoperated control subjects, and 12 patients with recurrent hypoglycemia after GB (Hypo-GB) had pre- and postprandial hormone levels and insulin secretion rates (ISR) measured during a hyperglycemic clamp with either GLP-1 receptor blockade with exendin-(9-39) or saline. RESULTS - Blocking the action of GLP-1 suppressed postprandial ISR to a larger extent in Asym-GB individuals versus control subjects (33 ± 4 vs.16 ± 5%; P = 0.04). In Hypo-GB patients, GLP-1 accounted for 43 ± 4% of postprandial ISR, which was not significantly higher than that in Asym-GB subjects (P = 0.20). Glucagon was suppressed similarly by hyperglycemia in all groups but rose significantly after the meal in surgical individuals but remained suppressed in nonsurgical subjects. GLP-1 receptor blockade increased postprandial glucagon in both surgical groups. CONCLUSIONS - Increased GLP-1-stimulated insulin secretion contributes significantly to hyperinsulinism in GB subjects. However, the exaggerated effect of GLP-1 on postprandial insulin secretion in surgical subjects is not significantly different in those with and without recurrent hypoglycemia. © 2011 by the American Diabetes Association.

Koucky E.M.,Cincinnati Veterans Affairs Medical Center
CNS spectrums | Year: 2013

Cognitive-behavioral therapy (CBT) is currently the most empirically supported intervention for posttraumatic stress disorder (PTSD) and includes both specific manualized treatments (e.g., cognitive processing therapy, prolonged exposure) and less standardized applications. As CBT for PTSD has become increasingly popular, more advanced questions have emerged regarding its use, including how existing treatments might be enhanced. In the current review, we aimed to discover recent trends in the CBT for PTSD literature by applying rigorous search criteria to peer-reviewed articles published from 2009 to 2012. Results of the 14 studies that were identified are discussed, and future directions for research are suggested.

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