Serological Markers for Inflammatory Bowel Disease in AIDS Patients with Evidence of Microbial Translocation

Background: Breakdown of the gut mucosal barrier during chronic HIV infection allows translocation of bacterial products such as lipopolysaccharides (LPS) from the gut into the circulation. Microbial translocation also occurs in inflammatory bowel disease (IBD). IBD serological markers are useful in the diagnosis of IBD and to differentiate between Crohn's disease (CD) and ulcerative colitis (UC). Here, we evaluate detection of IBD serological markers in HIV-infected patients with advanced disease and their relationship to HIV disease markers.Methods IBD serological markers (ASCA, pANCA, anti-OmpC, and anti-CBir1) were measured by ELISA in plasma from AIDS patients (n = 26) with low CD4 counts (<300 cells/$\mu$l) and high plasma LPS levels, and results correlated with clinical data. For meta-analysis, relevant data were abstracted from 20 articles. Results: IBD serological markers were detected in approximately 65% of AIDS patients with evidence of microbial translocation. An antibody pattern consistent with IBD was detected in 46%; of these, 75% had a CD-like pattern. Meta-analysis of data from 20 published studies on IBD serological markers in CD, UC, and non-IBD control subjects indicated that IBD serological markers are detected more frequently in AIDS patients than in non-IBD disease controls and healthy controls, but less frequently than in CD patients. There was no association between IBD serological markers and HIV disease markers (plasma viral load and CD4 counts) in the study cohort. Conclusions: IBD serological markers may provide a non-invasive approach to monitor HIV-related inflammatory gut disease. Further studies to investigate their clinical significance in HIV-infected individuals are warranted

Focused Examination of the Intestinal lamina Propria Yields Greater Molecular Insight into Mechanisms Underlying SIV Induced Immune Dysfunction

Background: The Gastrointestinal (GI) tract is critical to AIDS pathogenesis as it is the primary site for viral transmission and a major site of viral replication and CD4 + T cell destruction. Consequently GI disease, a major complication of HIV/SIV infection can facilitate translocation of lumenal bacterial products causing localized/systemic immune activation leading to AIDS progression. Methodology/Principal Findings: To better understand the molecular mechanisms underlying GI disease we analyzed global gene expression profiles sequentially in the intestine of the same animals prior to and at 21 and 90d post SIV infection (PI). More importantly we maximized information gathering by examining distinct mucosal components (intraepithelial lymphocytes, lamina propria leukocytes [LPL], epithelium and fibrovascular stroma) separately. The use of sequential intestinal resections combined with focused examination of distinct mucosal compartments represents novel approaches not previously attempted. Here we report data pertaining to the LPL. A significant increase (61.7-fold) in immune defense/inflammation, cell adhesion/migration, cell signaling, transcription and cell division/differentiation genes were observed at 21 and 90d PI. Genes associated with the JAK-STAT pathway (IL21, IL12R, STAT5A, IL10, SOCS1) and T-cell activation (NFATc1, CDK6, Gelsolin, Moesin) were notably upregulated at 21d PI. Markedly downregulated genes at 21d PI included IL17D/IL27 and IL28B/IFNc3 (anti-HIV/viral), activation induced cytidine deaminase (B-cell function) an

The Northern Ireland political process: a viable approach to conflict resolution?

This article explores the possibility of achieving a stable settlement as the result of the current negotiations in Northern Ireland. It looks at the decisions behind the 1994 ceasefires, the perceptions of the parties to the 'talks', and the obstacles in the political process. The main focus is on the applicability and limits of conflict resolution 'theories' in explaining the shift from conflict to negotiation and the possibility of concluding a lasting negotiated settlement. It suggests that while conflict resolution is unlikely, conflict regulation is within the realms of the current negotiations, if combined with a different approach to nationalism and 'Alternative Dispute Resolution'

German Yearbook of International Law: Origins, Development, Prospects

This chapter examines the history, development, function, and future of the German Yearbook of International Law (GYIL). The chapter traces the evolution of the GYIL over many decades, from its inception in the aftermath of the Second World War to the present day, demonstrating how it has moved beyond its origins as a forum in which German scholars could publish their research to become a global platform for the dissemination of scholarship in international law. The chapter also aims to show how the structure and contents of the GYIL have developed in the years since its establishment, reflecting in particular on the impact of the decision to begin to publish contributions authored in English in order to reach the widest possible international audience and the introduction of a double-blind peer review procedure. The chapter concludes that the function and future of the GYIL lie in its capacity to inform a global readership about current research and practice in the sphere of international law taking place in Germany while, at the same time, presenting international viewpoints to a German audience