Impact of diet and genes on murine autoimmune pancreatitis.

The impact of environmental factors, such as diet, and the genetic basis of autoimmune pancreatitis (AIP) are largely unknown. Here, we used an experimental murine AIP model to identify the contribution of diet to AIP development, as well as to fine-map AIP-associated genes in outbred mice prone to develop the disease. For this purpose, we fed mice of an autoimmune-prone intercross line (AIL) three different diets (control, calorie-reduced and western diet) for 6 months, at which point the mice were genotyped and phenotyped for AIP.

Different characteristics of chronic dibutyltin dichloride-induced pancreatitis and cholangitis in mouse and rat.

Background: Current animal models of chronic pancreatitis (CP) often provide only limited pathophysiological insights since they incompletely reflect the human disease. CP induced by injection of dibutyltin dichloride (DBTC-pancreatitis) shares with human CP the important feature of extended fibrosis and would be an even more attractive model if it could be transferred from rats to mice, as recently suggested in the context of combined ethanol and DBTC application. This study aimed to evaluate the effects of DBTC in pancreas and liver of C57BL/6 mice, a strain commonly used to engineer genetic mouse models.

Secondary sclerosing cholangitis in critically ill patients after a traffic accident-a new entity that should be considered in death classification.

A 49-year-old female sustained a polytrauma after being hit by a vehicle in a traffic accident. Following the incident, the woman had various surgical interventions and underwent intensive care over a 6-week period. Eight months later, she died after developing secondary sclerosing cholangitis (SSC).

In vitro studies implicate an imbalanced activation of dendritic cells in the pathogenesis of murine autoimmune pancreatitis.

Objectives: MRL/MpJ mice spontaneously develop an autoimmune pancreatitis (AIP) and are widely used as a model to study the genetic, molecular and immunological basis of the disease. Here, we have addressed the question whether distinctive features of their dendritic cells (DCs) may predispose MRL/MpJ mice to the chronic inflammation.

Methods: Pancreatic lesions were analyzed employing histological methods.

Quantitative Trait Locus Analysis Implicates CD4⁺/CD44high Memory T Cells in the Pathogenesis of Murine Autoimmune Pancreatitis.

The mouse strain MRL/MpJ is prone to spontaneously develop autoimmune pancreatitis (AIP). To elucidate the genetic control towards the development of the phenotype and to characterize contributions of immunocompetent cell types, MRL/MpJ mice were interbred with three additional strains (BXD2/TYJ, NZM2410/J, CAST/EIJ) for four generations in an advanced intercross line. Cellular phenotypes were determined by flow cytometric quantification of splenic leukocytes and complemented by the histopathological evaluation of pancreatic lesions.

VEGF-releasing suture material for enhancement of vascularization: development, in vitro and in vivo study.

As it has been demonstrated that bioactive substances can be delivered locally using coated surgical suture materials, the authors developed a vascular endothelial growth factor (VEGF)-releasing suture material that should promote vascularization and potentially wound healing. In this context, the study focused on the characterization of the developed suture material and the verification of its biological activity, as well as establishing a coating process that allows reproducible and stable coating of a commercially available polydioxanone suture material with poly(l-lactide) (PLLA) and 0.1μg and 1.

The mtDNA nt7778 G/T polymorphism augments formation of lymphocytic foci but does not aggravate cerulein-induced acute pancreatitis in mice.

A polymorphism in the ATP synthase 8 (ATP8) gene of the murine mitochondrial genome, G-to-T transversion at position 7778, has been suggested to increase susceptibility to multiple autoimmune diseases, including autoimmune pancreatitis (AIP). The polymorphism also induces mitochondrial reactive oxygen species generation, secretory dysfunction and β-cell mass adaptation. Here, we have used two conplastic mouse strains, C57BL/6N-mtAKR/J (B6-mtAKR; nt7778 G; control) and C57BL/6N-mtFVB/N (B6-mtFVB; nt7778 T), to address the question if the polymorphism also affects the course of cerulein-induced acute pancreatitis in mice.

Age-dependent effects of UCP2 deficiency on experimental acute pancreatitis in mice.

Reactive oxygen species (ROS) have been implicated in the pathogenesis of acute pancreatitis (AP) for many years but experimental evidence is still limited. Uncoupling protein 2 (UCP2)-deficient mice are an accepted model of age-related oxidative stress. Here, we have analysed how UCP2 deficiency affects the severity of experimental AP in young and older mice (3 and 12 months old, respectively) triggered by up to 7 injections of the secretagogue cerulein (50 μg/kg body weight) at hourly intervals.

Mechanisms and rescue strategies of calcineurin inhibitor mediated tolerance abrogation induced by anti-CD4 mAb treatment.

To ensure safety tolerance induction protocols are accompanied by conventional immunosuppressive drugs (IS). But IS such as calcineurin inhibitors (CNI), for example, cyclosporin A (CsA), can interfere with tolerance induction. We investigated the effect of an additional transient CsA treatment on anti-CD4mAb-induced tolerance induction upon rat kidney transplantation.

Autoimmune pancreatitis in MRL/Mp mice is a T cell-mediated disease responsive to cyclosporine A and rapamycin treatment.

Background: Autoimmune pancreatitis (AIP) in humans invariably responds to steroid treatment, but little is known about the underlying pathogenesis and the benefits of alternative treatments.

Objective: To study the pathogenesis, and the efficacy of alternative immunosuppressant agents in the MRL/Mp mouse model of AIP.

Design: MRL/Mp mice were pretreated for 4 weeks with polyinosinic:polycytidylic acid to induce AIP.

Permanent CNI treatment for prevention of renal allograft rejection in sensitized hosts can be replaced by regulatory T cells.

Recent data suggest that donor-specific memory T cells (T(mem)) are an independent risk factor for rejection and poor graft function in patients and a major challenge for immunosuppression minimizing strategies. Many tolerance induction protocols successfully proven in small animal models e.g.

Senescence determines the fate of activated rat pancreatic stellate cells.

In chronic pancreatitis (CP), persistent activation of pancreatic stellate cells (PSC) converts wound healing into a pathological process resulting in organ fibrosis. Here, we have analysed senescence as a novel mechanism involved in the termination of PSC activation and tissue repair. PSC senescence was first studied in vitro by establishing long-term cultures and by applying chemical triggers, using senescence-associated β-Galactosidase (SA β-Gal) as a surrogate marker.

Putative biomarker genes for grading clear cell renal cell carcinoma.

Objective: The initial objective of this renal cancer study was to identify gene sets in clear cell renal cell carcinoma (ccRCC) to support grading of ccRCC histopathology.

Materials And Methods: Preselected ccRCC tumor tissues of grade 1 (G1, n = 14) and grade 3 (G3, n = 15) as well es 14 normal kidney tissues thereof were subjected to microarray expression analysis using Human Genome U133 Plus 2.0 Array.

Identification of quantitative trait loci for murine autoimmune pancreatitis.

Background And Aims: Autoimmune pancreatitis (AIP) represents a rare but clinically relevant cause of pancreatic inflammation. Using MRL/Mp mice as a model of spontaneous AIP, the genetic basis of the disease was studied.

Methods: To identify quantitative trait loci (QTL) of AIP, an advanced intercross line was studied, originating from MRL/MpJ parental mice and the following three mouse strains: Cast (healthy controls), BXD2 (susceptible to collagen induced arthritis), and NZM (a model of lupus erythematosus).

[Small intestine, pancreas and islet cell transplantation].

The past decade has seen substantial improvements in patient and graft survival after intestinal transplantation. This improvement has been achieved by advances in donor and recipient selection, patient management, immunosuppression and surgical techniques. Intestinal transplantation is therefore considered a therapeutic option in the treatment of short bowel syndrome.

Immunohistochemical expression of retinoblastoma protein and p16 in renal cell carcinoma.

Introduction: The regulation proteins retinoblastoma protein (pRb) and p16 play an important role in the cell cycle as tumor suppressors. pRb is the main substrate for the function of cyclin-dependent kinases during the cell cycle in the transition from G(1) to S phase. In this study, the immunohistochemical expression of pRb and p16 in renal cell carcinoma (RCC) were examined.

Endolymphatic non-langerhans cell histiocytosis of the larynx: report of an uncommon disease manifestation.

We report on an uncommon laryngeal non-Langerhans cell histiocytosis. An 11-year-old boy presented with a 6 months history of progressive breath inhibition. Magnetic resonance imaging showed diffuse laryngeal and local lymph node swelling.

Schistosoma mansoni infection but not egg antigen promotes recovery from colitis in outbred NMRI mice.

Background: The ability of intestinal helminths to manipulate the immune system of their host towards a Th2 response has been proposed to modulate auto-immune and allergic diseases.

Aims: This initial study investigated the anti-inflammatory potential of S. mansoni and soluble egg antigen (SEA) in a murine model of colitis.

Up-regulation of ICAM-1 during cold ischemia triggers early neutrophil infiltration in human pancreas allograft reperfusion.

Background: Graft pancreatitis is induced by ischemia/reperfusion injury in which neutrophil infiltration is believed to be a crucial early event. This observation suggests the presence of adhesion molecules already at the time of reperfusion. Therefore, this study was performed to evaluate the pattern of ICAM-1 and P-Selectin expression on human pancreas allografts following cold ischemia and reperfusion.