Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes

Objectives: One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie–adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression. Design: Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals. The expression of CAR was also examined by reverse transcription PCR on microdissected islets (n=5), exocrine tissue (n=5) and on explanted islets infected with EV or exposed to chemokines produced by EV-infected islet cells. Results: An increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p<0.039). CAR staining was detected more frequently in pancreatic islets from patients with T1D and autoantibody-positive subjects (15/27) compared with (6/24) non-diabetic controls (p<0.033). Also in explanted islets cultured in UV-treated culture medium from coxsackievirus B (CBV)-1-infected islets, the expression of the CAR gene was increased compared with controls. Laser microdissection of pancreatic tissue revealed that CAR expression was 10-fold higher in endocrine compared with exocrine cells of the pancreas. CAR was also expressed in explanted islets and the expression level decreased with time in culture. CBV-1 infection of explanted islets clearly decreased the expression of CAR (p<0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR. Conclusions: CAR is expressed in pancreatic islets of patients with T1D and the expression level of CAR is increased in explanted islets exposed to proinflammatory cytokines/chemokines produced by infected islets. T1D is associated with increased levels of certain chemokines/cytokines in the islets and this might be the mechanism behind the increased expression of CAR in TID islets

Bezpecna komunikace v multi-agentnich systemech.

Area of multi-agent systems (MAS) currently evolves rapidly on both, research and application basis. It is necessary to ensure a communication security during data transfer in real applications (in industry or e-business). Currently there are several libraries or programming language extensions offering security services available. However they are tailored to specific operating systems and thus useless, when an agents' mobility is required. WE propose a novel approach to the communication security useable for the mobile agents and with transparency to a programming language (operating system). Role of the central security authority, necessary for a correct function of security in MAS, is discussed here as well. Present-day systems are not able to work when this authority fails, but it is possible to partially eliminate this problem. Proposed approach has been implemented and verified within the multi-agent platform JADE.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Bezpecna komunikace v multi-agentnich systemech.

Area of multi-agent systems (MAS) currently evolves rapidly on both, research and application basis. It is necessary to ensure a communication security during data transfer in real applications (in industry or e-business). Currently there are several libraries or programming language extensions offering security services available. However they are tailored to specific operating systems and thus useless, when an agents' mobility is required. WE propose a novel approach to the communication security useable for the mobile agents and with transparency to a programming language (operating system). Role of the central security authority, necessary for a correct function of security in MAS, is discussed here as well. Present-day systems are not able to work when this authority fails, but it is possible to partially eliminate this problem. Proposed approach has been implemented and verified within the multi-agent platform JADE.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes

Objectives: One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie-adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression. Design: Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals. The expression of CAR was also examined by reverse transcription PCR on microdissected islets (n=5), exocrine tissue (n=5) and on explanted islets infected with EV or exposed to chemokines produced by EV-infected islet cells. Results: An increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p&lt;0.039). CAR staining was detected more frequently in pancreatic islets from patients with T1D and autoantibody-positive subjects (15/27) compared with (6/24) non-diabetic controls (p&lt;0.033). Also in explanted islets cultured in UV-treated culture medium from coxsackievirus B (CBV)-1-infected islets, the expression of the CAR gene was increased compared with controls. Laser microdissection of pancreatic tissue revealed that CAR expression was 10-fold higher in endocrine compared with exocrine cells of the pancreas. CAR was also expressed in explanted islets and the expression level decreased with time in culture. CBV-1 infection of explanted islets clearly decreased the expression of CAR (p&lt;0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR. Conclusions: CAR is expressed in pancreatic islets of patients with T1D and the expression level of CAR is increased in explanted islets exposed to proinflammatory cytokines/chemokines produced by infected islets. T1D is associated with increased levels of certain chemokines/cytokines in the islets and this might be the mechanism behind the increased expression of CAR in TID islets

Agent Exchange - an Agent Trading Environment.

Agent Exchange is a test-bed for experimenting with advanced trading strategies in Agentcities distributed environment. It is developed at Gerstner Laboratory, Czech Technical University in Prague, and funded in part by Agentcities.NET (IST-2000-28384). By developing publicly available test-bed we aim to stimulate the European research in the area of distributed decision making for B2B and B2C, and increase exploitation of the AC environment for other than tourism-like services.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Enterovirus infection of human islets of Langerhans affects beta-cell function resulting in disintegrated islets, decreased glucose stimulated insulin secretion and loss of Golgi structure

Aims/hypothesis: In type 1 diabetes (T1D), most insulin-producing beta cells are destroyed, but the trigger is unknown. One of the possible triggers is a virus infection and the aim of this study was to test if enterovirus infection affects glucose stimulated insulin secretion and the effect of virus replication on cellular macromolecules and organelles involved in insulin secretion. Methods: Isolated human islets were infected with different strains of coxsackievirus B (CVB) virus and the glucose-stimulated insulin release (GSIS) was measured in a dynamic perifusion system. Classical morphological electron microscopy, large-scale electron microscopy, so-called nanotomy, and immunohistochemistry were used to study to what extent virus-infected beta cells contained insulin, and real-time PCR was used to analyze virus induced changes of islet specific genes. Results: In islets infected with CVB, GSIS was reduced in correlation with the degree of virus-induced islet disintegration. The expression of the gene encoding insulin was decreased in infected islets, whereas the expression of glucagon was not affected. Also, in islets that were somewhat disintegrated, there were uninfected beta cells. Ultrastructural analysis revealed that virus particles and virus replication complexes were only present in beta cells. There was a significant number of insulin granules remaining in the virus-infected beta cells, despite decreased expression of insulin mRNA. In addition, no typical Golgi apparatus was detected in these cells. Exposure of islets to synthetic dsRNA potentiated glucose-stimulated insulin secretion. Conclusions/interpretation: Glucose-stimulated insulin secretion; organelles involved in insulin secretion and gene expression were all affected by CVB replication in beta cells

Echovirus 6 infects human exocrine and endocrine pancreatic cells and induces pro-inflammatory innate immune response

Human enteroviruses (HEV), especially coxsackievirus serotype B (CVB) and echovirus (E), have been associated with diseases of both the exocrine and endocrine pancreas, but so far evidence on HEV infection in human pancreas has been reported only in islets and ductal cells. This study aimed to investigate the capability of echovirus strains to infect human exocrine and endocrine pancreatic cells. Infection of explanted human islets and exocrine cells with seven field strains of E6 caused cytopathic effect, virus titer increase and production of HEV protein VP1 in both cell types. Virus particles were found in islets and acinar cells infected with E6. No cytopathic effect or infectious progeny production was observed in exocrine cells exposed to the beta cell-tropic strains of E16 and E30. Endocrine cells responded to E6, E16 and E30 by upregulating the transcription of interferon-induced with helicase C domain 1 (IF1H1), 2ʹ-5ʹ-oligoadenylate synthetase 1 (OAS1), interferon-β (IFN-β), chemokine (C-X-C motif) ligand 10 (CXCL10) and chemokine (C-C motif) ligand 5 (CCL5). Echovirus 6, but not E16 or E30, led to increased transcription of these genes in exocrine cells. These data demonstrate for the first time that human exocrine cells represent a target for E6 infection and suggest that certain HEV serotypes can replicate in human pancreatic exocrine cells, while the pancreatic endocrine cells are permissive to a wider range of HEV

Simultaneous liver-pancreas transplantation for cystic fibrosis-related liver disease: A multicenter experience

Background: Diabetes is associated with increased morbidity and mortality in patients with cystic fibrosis (CF). While liver transplantation is well established for CF-related liver disease (CFLD), the role of simultaneous liver pancreas transplantation is less understood. Methods: We polled 81 pediatric transplantation centers to identify and characterize subjects who had undergone simultaneous liver pancreas transplantation and obtain opinions about this procedure in CFLD. Results: Fifty (61.7%) polled transplant centers responded and 94% reported that they would consider simultaneous liver pancreas transplantation for CFLD and diabetes. A total of 8 patients with simultaneous liver pancreas transplantation were identified with median follow up of 38 months. All patients had pre-existing diabetes. Exocrine and endocrine pancreatic function was initially restored in all patients with later functional loss in one patient. Body mass index Z-score increased between one year pre-transplantation and one year post-transplantation (P = 0.029). Conclusions: Patients with CFLD undergoing initial assessment for liver transplantation may benefit from consideration of simultaneous liver pancreas transplantation. (C) 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved