Shigeo Nakamura, Kyoko Kamihagi, Hisashi Satakeda, Masahiko Katayama, Haiou Pan, Hiroshi Okamato, Mitsuhide Noshiro, Koichiro Takahashi, Yasuo Yoshihara, Masayuki Shimmei, Yasunori Okada, and Yukio Kato 539

In this study, SPARC (osteonectin) synthesis was found to be enhanced in arthritic joints, and the average SPARC level in synovial fluids from rheumatoid arthritis patients was higher than in fluid from osteoarthritis patients. TGFβ1 and bone morphogenetic protein 2 increased SPARC synthesis by chondrocytes, whereas interleukin-1, tumor necrosis factor α, lipopolysaccharide, basic fibroblast growth factor, and dexamethasone caused a marked decrease in SPARC levels. These findings suggest that SPARC is involved in the pathogenesis of arthritis.

Rainer Maier, Hans-Georg Wisniewski, Jan Vilcek, and Martin Lotz 552

The hyaluronan binding protein TSG-6 forms a stable complex with the serum protein inter-α-inhibitor and potentiates the inhibition of plasmin activity. It was previously shown that TSG-6 can be detected in synovial fluids from arthritic joints. This study identifies cytokine-activated chondrocytes and cartilage as a source of TSG-6. This protein may be involved in cartilage remodeling and serve as an indicator of chondrocyte activation in arthritis.

Osamu Nemoto, Harumoto Yamada, Masahiro Mukaida, and Masayuki Shimmei 560

This study demonstrates that the IL-6 family cytokines, particularly oncostatin M, stimulate TIMP-1 expression in human articular chondrocytes. These results suggest that oncostatin M may be characterized as one of the chondroprotective mediators in the cartilage destruction that is associated with OA.

Takeshi Hayashi, Etsuko Abe, and Hugo E. Jasin 567

Fibronectin plays a major role in cell adhesion to damaged cartilage surfaces. Results of the present study suggest that modulation of fibronectin synthesis near the articular surface of cartilage may be one of the factors that protects cartilage following an inflammatory insult to the joint.

Matthew P. Vincenti, Charles I. Coon, Lori Anne White, Aaron Barchowsky, and Constance E. Brinckerhoff 574

Interstitial collagenase is induced by inflammatory cytokines in RA and contributes to the degradation of cartilage that is observed in this disease. Studies such as the present one, which examine the signal transduction pathway in synovial fibroblasts that regulate collagenase gene expression, will expand our understanding of the pathophysiology of RA.

R. Marok, P. G. Winyard, A. Coumbe, M. L. Kus, K. Gaffney, S. Blades, P. I. Mapp, C. J. Morris, D. R. Blake, C. Kaltschmidt, and P. A. Baeuerle 583

The transcription factor NF-[gk]B is involved in the transcription of many proinflammatory genes, including those of TNFα, IL-1, IL-6, and cell adhesion molecules. It is thus likely to play a central role in human inflammatory diseases such as RA. This study demonstrates the presence of activated NF-[gk]B in endothelial cells and type A synoviocytes within the synovia of both RA and OA patients. Furthermore, there was an association between the distribution of staining in these tissues and the clinical diagnosis.

Jan Czyzyk, Philip Fernsten, Melody Shaw, and John B. Winfield 592

SLE, especially during periods of disease activity, is characterized by a variety of poorly understood cellular immune abnormalities that are expressed clinically as partial anergy, hypergammaglobulinemia, and autoantibody formation. This report characterizes autoantibodies to CD45, a cell surface tyrosine phosphatase that regulates lymphocyte activation, and discusses mechanisms by which anti-CD45 autoantibodies might contribute to cellular immune dysfunction in this disorder.

George C. Tsokos, Birgit Kovacs, Peter P. Sfikakis, Stamatis Theocharis, Scott Vogelgesang, and Charles S. Via 600

Mononuclear cells from patients with SLE display decreased responses to recall antigens such as tetanus toxoid and influenza. The present study addresses whether defective antigen-presenting cell-dependent T cell proliferation in SLE patients reflects a defect in antigen-presenting cell-derived costimulatory activity. The results indicate that surface molecules important in costimulation are defective in patients with SLE.

Mark A. Beilke, Vicki Traina-Dorge, John D. England, and James L. Blanchard 610

HTLV-I is associated with polymyositis, arthritis, uveitis, thyroiditis, and possibly Sjogren's syndrome. This report describes the development of multiple rheumatic diseases in a rhesus macaque experimentally infected with HTLV-I, suggesting that a nonhuman primate model of HTLV-I infection with disease can be developed.

James F. Fries, Catherine A. Williams, Dianne Morfeld, Gurkirpal Singh, and John Sibley 616

On theoretical grounds, there have been many calls to replace the traditional ``therapeutic pyramid'' approach to treatment of RA with a strategy of early and consistent DMARD use. Yet, there has been little documentation that the new approach is better than the old. This report provides evidence for the long-term benefits of DMARD-based strategies, and will assist in providing clinical guidance for the practicing rheumatologist.

Martha L. Barnett, Daniel Combitchi, and David E. Trentham 623

This report describes a pilot trial of oral type II collagen in the treatment of JRA. This form of therapy is postulated to work by inducing peripheral immune tolerance to a fed antigen, in this case, type II collagen. The trial demonstrates a favorable safety profile and some suggestion of clinical efficacy in this disabling disease, and it is proposed that further study of this novel therapeutic agent is warranted.

Byung Ok Lee, Katsuhiko Ishihara, Kakuro Denno, Yoshiko Kobune, Motoyuki Itoh, Osamu Muraoka, Tsuneyasu Kaisho, Takeshi Sasaki, Takahiro Ochi, and Toshio Hirano 629

BST-1 is strongly expressed on bone marrow stromal and synovial cell lines derived from patients with RA. In this study, an ELISA system was established to detect the soluble form of BST-1, and it was shown that levels of soluble BST-1 were increased in the sera of some patients with severe RA. This suggests that BST-1 has a pathophysiologic role in RA.

Matthijs van de Rijn, Michael L. Cleary, Daina Variakojis, Roger A. Warnke, Pearl P. Chang, and Onsi W. Kamel 638

The data presented in this report strongly support a causative role for immunosuppression-induced EBV transformation as an initial step in the development of B cell lymphoma in a subset of patients with RA. The identification of B lymphomas associated with EBV in patients with rheumatic disease is of clinical significance since withdrawal of immunosuppressive antirheumatic therapy, rather than institution of chemotherapy, may be indicated in a first attempt at cure.

Peter S. Grabowski, Amanda J. England, Roelf Dykhuizen, Mhairi Copland, Nigel Benjamin, David M. Reid, and Stuart H. Ralston 643

Nitric oxide has been implicated as a mediator in human inflammatory joint diseases, where it may contribute to destructive processes that result in cartilage degradation and periarticular bone loss. This report describes a procedure for detecting increased nitric oxide production, using the urinary nitrate: creatinine ratio in a morning sample of urine following an overnight fast. Assessment of nitric oxide production will help us to understand its role in inflammatory conditions such as RA.

Timothy E. McAlindon, Paul Jacques, Yuqing Zhang, Marian T. Hannan, Piran Aliabadi, Barbara Weissman, David Rush, Daniel Levy, and David T. Felson 648

Since cumulative tissue damage, mediated by reactive oxygen species, may lead to many of the degenerative changes associated with aging, high intake of antioxidant micronutrients might be associated with reduced risk of knee OA. This study of 640 participants in the Framingham OA cohort showed strong protective effects in relation to knee OA progression from vitamin C, and less robust effects from beta carotene and vitamin E. No significant association with incident knee OA was found for any of the micronutrients investigated.

Jorge Sanchez-Guerrero, Elizabeth W. Karlson, Graham A. Colditz, David J. Hunter, Frank E. Speizer, and Matthew H. Liang 657

Hair dye use has been linked to connective tissue disease. Use of permanent hair dye in SLE was studied in a long-term prospective cohort study. No increased risk of SLE development was found among subjects who had ever used permanent hair dyes.

Jason H. Slingsby, Peter Norsworthy, Glen Pearce, Akshay K. Vaishnaw, Helen Issler, Bernard J. Morley, and Mark J. Walport 663

Homozygous deficiencies of the early proteins of the classical pathway of complement represent the most powerful disease susceptibility genes that have been identified in humans for the development of SLE, although they account for only a few cases. Understanding this association may give novel insight into the etiology of some cases of SLE.

Joseph Press, Karen Palayew, Ronald M. Laxer, Keith Elkon, Allison Eddy, David Rakoff, and Earl D. Silverman 671

This study of antiribosomal P antibodies in children with SLE with and without psychosis showed that elevated serum levels of this antibody can distinguish SLE-associated psychosis from primary psychosis in pediatric patients. Elevated levels of these antibodies were not specific for psychosis in patients with SLE, although monitoring antibody levels was useful for evaluating the activity of the SLE.

Virginia D. Steen, William P. Follansbee, Claudia G. Conte, and Thomas A. Medsger, Jr. 677

Patients with systemic sclerosis who previously underwent thallium perfusion scans were carefully followed up over the next 10 years. Those with large defects were at a significantly increased risk for future serious cardiac disease or death.

Maura Kennedy and David T. Felson 682

In this 10-year prospective followup cohort study of FMS, the majority of patients reported ongoing moderate to severe pain or stiffness and active global FMS symptoms, yet perceived their condition to be improved since diagnosis. Therefore, persistent symptoms with perceptions of improvement typify the natural history of FMS.