Initial treatment of systemic lupus erythematosus with a new artificial reticuloendothelial system

Artificial reticuloendothelial system, which was made on an immobilized phenylalanine column, has been developed to remove denatured protein from serum. This system was used to treat systemic lupus erythematosus effectively. Lupus angiitis has been markedly improved with 12 treatments.     

Idiotypic network dysregulation

The pathogenesis of autoimmune disease is still an enigma. Whereas the diverse clinical manifestations of many autoimmune diseases cannot be explained by the existence of autoantibodies, idiotypic dysregulation may provide an alternative explanation. Experimental models, serum level changes of pathogenic idiotypes during exacerbation and remission, and the increased expression of pathogenic idiotypes following common infections all support this notion. In this article we review experimental models of autoimmune disease induction (systemic lupus erythematosus, antiphospholipidsyn drome, Goodpasture's syndrome, autoimmune thyroiditis, and vasculitis) by manipulation of the idiotypic network and discuss the utilization of idiotypes for the immunotherapy of autoimmune diseases and other conditions that involve the immune system (e.g., atherosclerosis).     

Structural models of antibody variable fragments: A method for investigating binding mechanisms

The value of comparative molecular modeling for elucidating structure-function relationships was demonstrated by analyzing six anti-nucleosome autoantibody variable fragments. Structural models were built using the automated procedure developed in the COMPOSER software, subsequently minimized with the AMBER force field, and validated according to several standard geometric and chemical criteria. Canonical class assignment from Chothia and Lesk's [Chottin and Lesk, J. Mol. Biol., 196 (1987) 901; Chothia et al., Nature, 342 (1989) 877] work was used as a supplementary validation tool for five of the six hypervariable loops. The analysis, based on the hypothesis that antigen binding could occur through electrostatic interactions, reveals a diversity of possible binding mechanisms of anti-nucleosome or anti-histone antibodies to their cognate antigen. These results lead us to postulate that anti-nucleosome autoantibodies could have different origins. Since both anti-DNA and anti-nculeosome autoantibodies are produced during the course of systemic lupus erythematosus, a non-organ specific autoimmune disease, a comparative structural and electrostatic analysis of the two populations of autoantibodies may constitute a way to elucidate their origin and the role of the antigen in tolerance breakdown. The present study illustrates some interests, advantages and limits of a methodology based on the use of comparative modeling and analysis of molecular surface properties.     

GRAY WOLF POPULATION PROJECTION WITH INTRASPECIFIC COMPETITION

Competition effects are incorporated into a model of wolf‐population dynamics. A classic single‐state model is augmented into a dual‐state mapping of the evolution of the size of wolf packs and the number of wolf packs. This dual‐state model, unlike the single‐state density dependent model, is amenable to analyzing intraspecific competition. The single‐state, dual‐state and dual‐state with competition models are estimated using Yellowstone National Park (YNP) data on wolf populations and pack structures from 1996 to 2011. The dynamic properties of each model are examined under an array of harvesting policies. Results suggest that intraspecific competition matters when projecting wolf populations. Wolf pack removal has competition‐reducing effects from added territory availability, making populations more sensitive to pack size reduction than reduction in the number of packs. This research suggests that wildlife managers may consider monitoring the composition of wolf kills throughout a harvesting season, adaptively adjusting harvesting quotas and delineating harvesting zones over a few pack territories rather than spreading these effects evenly across all packs.