IgG from the serum ofa rheumatoid arthritis patient has been shown to be arthritogenic in the murine passive transfer system (11). These latter observations are consistent with the hypothesis that localized synovial anti-type II collagen autoantibody production in human patients with rheumatoid arthritis may contribute to joint destruction.Despite the excellent correlation between disease activity and level of agalactosyl IgG in rheumatoid arthritis, it is still unclear whether this form of IgG is simply a marker for inflammation or is more directly involved in pathogenesis. In this paper, we attempt to resolve this issue by using the murine CIA model. MATERIALS AND METHODS

Objective. This study examined the effect of exogenous dehydroepiandrosterone (DHEA) on the onset, incidence, and severity of collagen-induced arthritis (CIA).Methods. DHEA was administered subcutaneously prior to arthritis induction in DBN1 mice, and the severity of the subsequent arthritis was monitored. Serum levels of total IgG and IgG isotype-specific anti-murine type I1 collagen were measured.Results. Repeated administration of DHEA during arthritis induction delayed the onset and decreased the severity of arthritis in male and female DBN1 mice. DHEA failed to have an observable effect on established arthritis. IgG isotype autoantibody levels were found to be decreased in the sera of DHEA-treated mice.Conclusion. Administration of exogenous DHEA offered protection against the development of CIA. These data support the results of human studies in which low DHEA levels have been identified as a potential risk factor for the development of rheumatoid arthritis. These findings also highlight DHEA as a potential therapy worthy of further investigation. dition in New Zealand black X New Zealand white mice (for review, see ref.

This study examines the relationship between the serum levels of IgG antibodies to heterologous and homologous type II collagen and the subsequent arthritic severity in a collagen induced arthritis model. Arthritis was induced in DBA-1 mice using intradermal injections of heterologous type II collagen in Freunds complete adjuvant, the time of arthritis onset was noted and the severity was monitored regularly. Serum samples were taken and IgG levels of anti-heterologous and homologous type II collagen were analyzed both pre and post arthritis onset. We observed that post induction/pre arthritic serum IgG anti-heterologous and homologous type II collagen levels showed a significant correlation (both p < 0.01) with the severity of the arthritis that subsequently developed. Mice with early arthritis showed a highly significant correlation (p < 0.002) between sera IgG anti-homologous type II collagen levels and arthritic severity, a lesser correlation was also apparent between anti-heterologous type II collagen titres and arthritic severity (p < 0.05). The high levels of correlation observed in this study between anti-type II collagen titres and arthritic severity before actual onset of arthritis, clearly suggest that the magnitude of the initial humoral response to type II collagen plays a crucial role in determining the resultant arthritic severity. This observation is only apparent due to the use of an arthritis susceptible inbred mouse strain, which removes variables such as H-2 restriction, antigen processing/presentation and possible complement deficiencies, and the early time scale of the analysed sera samples.

The Defence Technology Strategy identifies modular and incremental certification as a key enabler to 'Through-Life Capability Management' as a means of reducing the impact and hence cost of re-certification of changes to systems. The Ministry of Defence has funded the Industrial Avionics Working Group, an industrial research consortium, to undertake a 'hot research' project investigating the production of a modular safety case (SC) for an aerospace software system currently under development. This paper provides feedback and lessons learned from this project.

Modular safety cases provide a means of organising large and/or complex safety cases into separate but interrelated component modules of argument and evidence. Safety case 'contracts' can be used to record the interdependencies that exist between safety case modules -e.g. to show how the claims of one module support the arguments of another.