In knee osteoarthritis (OA) damage to meniscal cartilage is associated with the changes in articular cartilage. Using double-contrast macroradiographs we determined whether the degree of meniscal cartilage damage was similar to or different from that at the corresponding regions of the articular cartilage on the tibia and femur.

To investigate whether surgery is appropriate for elderly rheumatoid arthritis patients who are already approaching their statistical life expectancy.

A primary therapeutic goal in rheumatoid arthritis (RA) is to reduce functional disability. The recent introduction of several new drugs for RA creates a need for readily assessing the effectiveness of therapy. Because the consistent use of disease-modifying anti-rheumatic drugs (DMARDs) reduces long-term disability, we analysed the large database of 1817 RA patients from leflunomide trials to assess if changes in the Health Assessment Questionnaire (HAQ) can measure the effectiveness of RA therapy.

To evaluate two monotherapies followed by step-up combination therapy with two or three complementary drugs in active rheumatoid arthritis (RA) in comparison with sulphasalazine (SSZ) alone.

To compare the time- and concentration-dependent effects of tumour necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) on the induction of nitric oxide synthase (NOS), the production of nitric oxide (NO) and the expression of aggrecan and hyaluronan (HA) in chondrocytes.

Mycophenolate mofetil (MMF) is an immunosuppressive drug widely used in solid organ transplantation, and it may play an increasing role in autoimmune disease. MMF has been introduced as a novel immunosuppressive agent in systemic lupus erythematosus (SLE), often in patients intolerant of or resistant to conventional immunosuppressive regimens.

To determine the expression of molecular markers of prostanoid/fatty acid signalling in leucocytes of patients with systemic sclerosis (SSc).

The strong association of the HLA class 1 allele HLA B27 with ankylosing spondylitis (AS) has been recognized for over 25 yr, however the pathogenic mechanism linking HLA B27 with AS and other spondyloarthropathies remains a mystery. We now know that the principal natural function of HLA B27 is an immunologic one, namely to bind antigenic peptides and then present them to T lymphocytes. I have shown that HLA B27 functions as an excellent antigen-presenting molecule in both spondyloarthropathy patients and healthy individuals. A working molecular model of how T cells recognize HLA B27 has been generated and tested. Evidence that T cells have a role in spondyloarthritis has also been found. First, expanded populations of T lymphocytes were found in both the blood and synovial fluid of patients with reactive arthritis (ReA). Secondly, a strong cytotoxic T-cell response to an HLA B27-restricted peptide epitope from Chlamydia trachomatis was found in a patient with ReA. This peptide, derived from a bacterium known to trigger ReA, is thus a candidate 'arthritogenic' peptide. We have also found evidence that HLA B27 has an unusual cell biology compared with other HLA molecules. HLA B27 demonstrates an unusual ability to form heavy chain homodimers in vitro. Dimerization is dependent upon disulphide bonding through an unpaired cysteine at position 67. Remarkably these dimers lack beta2 microglobulin, previously thought to be an essential component of all mature MHC class 1 molecules. HLA B27 homodimer formation has also been demonstrated in certain cell lines in vivo, and preliminary data suggest that significant numbers of T cells from patients with spondyloarthropathy express a ligand for HLA B27 homodimers. These findings have extended our understanding of the beneficial immunologic function of HLA B27, and have also led us to propose the testable new hypothesis that HLA B27 heavy chain dimerization may be involved in the pathogenesis of spondyloarthritis.

The development of transgenic technology has made possible the generation of targeted gene-mutated mouse lines suitable for use in experimental osteoarthritis (OA) research. Transgenic mice harbouring mutations in cartilage collagen types II and IX develop early-onset OA and are therefore promising models of age-related OA, even though the mice often show signs of chondrodysplasia. Also, mouse lines harbouring other engineered mutations of the extracellular molecules have given rise to early OA. The molecular background of a few spontaneous mutations in mice has also been clarified and the characterization of the OA phenotype is now in progress. These mutations cause severe chondrodysplasia and death in homozygous mice, but the heterozygous offspring develop the early-onset OA phenotype.