A proinflammatory role for Fas in joints of mice with collagen-induced arthritis

Collagen-induced arthritis (CIA) is a chronic inflammatory disease bearing all the hallmarks of rheumatoid arthritis, e.g. polyarthritis, synovitis, and subsequent cartilage/bone erosions. One feature of the disease contributing to joint damage is synovial hyperplasia. The factors responsible for the hyperplasia are unknown; however, an imbalance between rates of cell proliferation and cell death (apoptosis) has been suggested. To evaluate the role of a major pathway of cell death – Fas (CD95)/FasL – in the pathogenesis of CIA, DBA/1J mice with a mutation of the Fas gene (lpr) were generated. The susceptibility of the mutant DBA-lpr/lpr mice to arthritis induced by collagen type II was evaluated. Contrary to expectations, the DBA-lpr/lpr mice developed significantly milder disease than the control littermates. The incidence of disease was also significantly lower in the lpr/lpr mice than in the controls (40% versus 81%; P < 0.05). However DBA-lpr/lpr mice mounted a robust immune response to collagen, and the expression of local proinflammatory cytokines such as, e.g., tumor necrosis factor α (TNF-α) and IL-6 were increased at the onset of disease. Since the contribution of synovial fibroblasts to inflammation and joint destruction is crucial, the potential activating effect of Fas on mouse fibroblast cell line NIH3T3 was investigated. On treatment with anti-Fas in vitro, the cell death of NIH3T3 fibroblasts was reduced and the expression of proinflammatory cytokines TNF-α and IL-6 was increased. These findings suggest that impairment of immune tolerance by increased T-cell reactivity does not lead to enhanced susceptibility to CIA and point to a role of Fas in joint destruction

Perforin deficiency attenuates collagen-induced arthritis

Collagen-induced arthritis (CIA), an approved animal model for rheumatoid arthritis, is thought to be a T cell-dependent disease. There is evidence that CD8(+ )T cells are a major subset controlling the pathogenesis of CIA. They probably contribute to certain features of disease, namely tissue destruction and synovial hyperplasia. In this study we examined the role of perforin (pfp), a key molecule of the cytotoxic death pathway that is expressed mainly in CD8(+ )T cells, for the pathogenesis of CIA. We generated DBA/1J mice suffering from mutations of the pfp molecule, DBA/1J-pfp(-/-), and studied their susceptibility to arthritis. As a result, pfp-deficient mice showed a reduced incidence (DBA/1J-pfp(+/+), 64%; DBA/1J-pfp(-/-), 54%), a slightly delayed onset (onset of disease: DBA/1J-pfp(+/+), 53 ± 3.6; DBA/1J-pfp(-/-), 59 ± 4.9 (mean ± SEM), and milder form of the disease (maximum disease score: DBA/1J-pfp(+/+), 7.3 ± 1.1; DBA/1J-pfp(-/-), 3.4 ± 1.4 (mean ± SEM); P < 0.05). Concomitantly, peripheral T cell proliferation in response to the specific antigen bovine collagen II was increased in pfp(-/- )mice compared with pfp(+/+ )mice, arguing for an impaired killing of autoreactive T cells caused by pfp deficiency. Thus, pfp-mediated cytotoxicity is involved in the initiation of tissue damage in arthritis, but pfp-independent cytotoxic death pathways might also contribute to CIA

Comment. in Thucyd. III, 37 - 40

vom Oberlehrer Dr. Berthold Nizz

The carnival: king of sand, king of nothing at all/ Karnevalen: kung av sand, kung av ingenting alls

Syftet med detta examensarbete är att synliggöra de karnevaliska aspekterna som yttrar sig i barns lekar på förskolan samt den syn som personalen har på dessa aspekter. I dagens förskola upplevs de karnevaliska aspekterna som störande. De kan upplevas som trots mot personalens auktoritet, vilket resulterar i att de leds bort i förmån för andra lekar. Metoden vi har använt oss av är kvalitativ och det empiriska materialet är insamlat via fältobservationer. Vi har även lämnat enkäter till personalen. Enkäternas frågor är alla, utom en, slutna då en fråga är en öppen fråga relaterad till en tidigare fråga. Materialet har analyserats utifrån stödmaterial såsom tidigare forskning. Vi har även använt oss av artiklar relaterade till karnevaliska aspekter och teoretiska begrepp från bland annat lekforskarna Birgitta Knutsdotter Olofsson och Maria Øksnes. Resultatet visade att personalen generellt ser positivt till de, ibland kaotiska, karnevaliska aspekterna. Brist på utrymme och personal gör dock att dessa lekar leds bort i favör för lugnare lekar med tydligare struktur

Rede, am 15. October 1840 zur Feier der Huldigung und des Allerhöchsten Geburtsfestes S. Maj. des Königs im Gymnasium gehalten

von dem DirectorIn Fraktu

Über die Verbindung von Realklassen mit dem Gymnasium

vom Directo