Interaction of inflammatory cytokines and erythropoeitin in iron metabolism and erythropoiesis in anaemia of chronic disease

In chronic inflammatory conditions increased endogenous release of specific cytokines (TNFα, IL-1, IL-6, IFNγ and others) is presumed. It has been shown that those of monocyte lineage play a key role in cytokine expression and synthesis. This may be associated with changes in iron metabolism and impaired erythropoiesis and may lead to development of anaemia in patients with rheumatoid arthritis. Firstly, increased synthesis of acute phase proteins, like ferritin, during chronic inflammation is proposed as the way by which the toxic effect of iron and thereby the synthesis of free oxy-radicals causing the damage on the affected joints, may be reduced. This is associated with a shift of iron towards the mononuclear phagocyte system which may participate in the development of anaemia of chronic disease. Secondly, an inhibitory action of inflammatory cytokines (TNFα, IL-1), on proliferation and differentiation of erythroid progenitors as well as on synthesis of erythropoietin has been shown, thereby also contributing to anaemia. Finally, chronic inflammation causes multiple, complex disturbances in the delicate physiologic equilibrium of interaction between cytokines and cells (erythroid progenitors, cells of mononuclear phagocyte system and erythropoietin producing cells) leading to development of anaemia of chronic disease (Fig. 1)

Spatial representation for navigation in animats

This article considers the problem of spatial representation for animat navigation systems. It is proposed that the global navigation task, or "wayfinding, " is best supported by multiple interacting subsystems, each of which builds its own partial representation of relevant world knowledge. Evidence from the study of animal navigation is reviewed to demonstrate that similar principles underlie the wayfinding behavior of animals, including humans. A simulated wayfinding system is described that embodies and illustrates several of the themes identified with animat navigation. This system constructs a network of partial models of the quantitative spatial relations between groups of salient landmarks. Navigation tasks are solved by propagating egocentric view information through this network, using a simple but effective heuristic to arbitrate between multiple solutions

Monoclonal antibodies against defined regions of the muscular dystrophy protein, dystrophin

AbstractNineteen monoclonal antibodies which bind to native dystrophin in the plasma membrane of frozen muscle sections were obtained using a recombinant fusion protein as immunogen. On Western blots of normal mouse muscle extracts, the antibodies bind specifically to a 400 000 Mr protein which is absent from dystrophic mouse (mdx) muscle. At least four distinct epitopes have been identified by cleavage mapping methods. Although the fusion protein contained 25% of the human dystrophin sequence (Cys816-Asp1747; Mr 108 000), most of the monoclonal antibodies (15 out of 19) recognize a single fragment of Mr 27 500