The immunobiology of primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease histologically characterized by the presence of intrahepatic and/or extrahepatic biliary duct concentric, obliterative fibrosis, eventually leading to cirrhosis. Approximately 75% of patients with PSC have inflammatory bowel disease. The male predominance of PSC, the lack of a defined, pathogenic autoantigen, and the potential role of the innate immune system suggest that it may be due to dysregulation of immunity rather than a classic autoimmune disease. However, PSC is associated with several classic autoimmune diseases, and the strongest genetic link to PSC identified to date is with the human leukocyte antigen DRB01*03 haplotype. The precise immunopathogenesis of PSC is largely unknown but likely involves activation of the innate immune system by bacterial components delivered to the liver via the portal vein. Induction of adhesion molecules and chemokines leads to the recruitment of intestinal lymphocytes. Bile duct injury results from the sustained inflammation and production of inflammatory cytokines. Biliary strictures may cause further damage as a result of bile stasis and recurrent secondary bacterial cholangitis. Currently, there is no effective therapy for PSC and developing a rational therapeutic strategy demands a better understanding of the disease

De blinde vlek van de filosofie: een leven leiden

Age-old philosophical texts, from Plato to Montaigne or from Lao-tse to Rousseau, are still being read by many. What makes these texts so attractive and ‘contemporary’ today, other than scientific texts from long ago? Most of the time these texts do not address empirical or conceptual questions, but address the problem to understand ourselves as creatures that try to live a life. Academic philosophy has left this question more and more aside, in an ongoing process of ‘scientification’, and concentrated more on conceptual and epistemological questions or on the reconstruction of the philosophical tradition. Yet, in the margins of academic philosophy, in neighboring fields of research and in the public sphere, we can discern examples of a philosophical practice that rephrases the classical philosophical question in a new manner. In this essay an attempt is made to draw the contours of this new practice of philosophy and the writings it produces. Starting with (among others) Nietzsche and Benjamin, and inspired by recent lectures by Norman Lear, a portrait is created of an author who operates somewhere on the borders between science and literature, as a placeholder ‐ or more precise: as an ethnographer who, more than the average scholar, is closely involved with the object of his research, and who, more than the average novelist, addresses ‘the weird problem of having a life’ in a direct way, starting with the problematic and problematizing experiences of others. This philosophical attitude comes close to what Michel Foucault called ‘an ontology of the present’ that writes about the question of who or what we are here and now from a ironical involvement with everyday problematizations of our cultural, political or personal identity. The essay ends with some concrete examples of this philosophical practice and with some suggestions for a philosophical institute in which such a practice could be a central concern