Paul Brennan, Ali Hajeer, Kai Ren Ong, Jane Worthington, Sally John, Wendy Thomson, Alan Silman, and Bill Ollier 1383

The results of this study suggest that the contribution of prolactin to both rheumatoid arthritis and systemic lupus erythematosus might be under control of genes linked to HLA. This raises the possibility that treatment aimed at reducing the proinflammatory effect of prolactin may be of value in a genetically determined subgroup of affected individuals.

F. Cornelis, L. Hardwick, R. M. Flipo, M. Martinez, S. Lasbleiz, J. F. Prud'homme, T. H. Tran, S. Walsh, A. Delaye, A. Nicod, M. N. Loste, V. Lepage, K. Gibson, K. Pile, S. Djoulah, P. M. Danze, F. Liote, D. Charron, J. Weissenbach, D. Kuntz, T. Bardin, and B. P. Wordsworth 1387

The T cell receptor genes, for which allelic variations leading to amino-acid changes were recently described, are major candidates for contributing susceptibility to RA. In this large case-control study, an association was found, and was replicated between RA and such a variation.

Otso Lindy, Yrjo T. Konttinen, Timo Sorsa, Yanli Ding, Seppo Santavirta, Arnoldas Ceponis, and Carlos Lopez-Ot|fin 1391

Irreversible destruction of articular cartilage type II collagen has been ascribed to interstitial collagenases of the fibroblast-type collagenase-1 (MMP-1) and neutrophil-type collagenase-2 (MMP-8). A new collagenase, collagenase-3 (MMP-13) has been found in malignant breast tumors, and in cartilage and, at the mRNA level, in RA and OA synovial membranes. The presence of MMP-13 enzyme protein, its cellular localization and up-regulation in the rheumatoid synovial tissue, and the effects of some known collagenase inhibitors are reported in this paper. Due to its synovial-tissue-specific localization, substrate profile, and increased expression, efforts should be targeted to find and/or develop collagenase inhibitors against MMP-13.

Peter P. Youssef, David R. Haynes, Sophie Triantafillou, Angela Parker, Jenny R. Gamble, Peter J. Roberts-Thomson, Michael J. Ahern, and Malcolm D. Smith 1400

Pulse corticosteroids are potent antiinflammatory agents used in the treatment of rheumatoid arthritis. This in vivo study shows that their effects can be partly mediated by rapidly reducing the expression of TNFα and IL-8 in the synovial compartment.

Ulrike Rudolphi, Rita Rzepka, Stephen Batsford, Stefan H. E. Kaufmann, Klaus von der Mark, Hans H. Peter, and Inga Melchers 1409

A specific immune response is believed to play a role in the induction of RA; however, evidence supporting a role of defined antigens is still missing. This work details the first analysis of the synovial B cell receptor repertoire at the level of mature B cells, and compares it with the repertoire of peripheral blood B cells. The results provide evidence that antigen-specific B cells are involved in local processes, and suggest the use of synovial B cells to pinpoint relevant antigens. This information will enhance our understanding of the pathogenesis and etiology of RA and be of use for diagnostic and therapeutic purposes.

Olaf Schultz, Gernot Keyszer, Josef Zacher, Michael Sittinger, and Gerd R. Burmester 1420

Advanced in vitro models of RA allow us to study distinct aspects of destructive joint diseases. Three-dimensional interactive cultures of synovial cells and chondrocytes offer the opportunity to supplement the data obtained with animal systems.

Luis Llorente, Yvonne Richaud-Patin, Jacques Couderc, Donato Alarcon-Segovia, Rodrigo Ruiz-Soto, Natasha Alcocer-Castillejos, Jorge Alcocer-Varela, Julio Granados, Susana Bahena, Pierre Galanaud, and Dominique Emilie 1429

Various studies have demonstrated increased production of IL-10 in patients with SLE. A large proportion of relatives of these patients display impaired cell-mediated immunity and B lymphocyte hyperactivity. The present study provides evidence that relatives of SLE patients may have dysregulated IL-10 production, which may contribute to the immunologic irregularities they exhibit.

Raymond Yung, Sandra Chang, Nahid Hemati, Kent Johnson, and Bruce Richardson 1436

Using a recently described murine model of drug-induced lupus, the effects of procainamide and hydralazine were compared with those of structural analogs believed to cause less autoimmunity. Both agents were found to be more potent than their analogs in increasing T cell LFA-1 expression, and in inducing autoreactivity in vitro and autoimmunity in vivo. These results further support the hypothesis that procainamide and hydralazine cause drug-induced lupus by modifying T cells, resulting in autoreactivity and subsequent autoimmunity, and suggest an explanation as to why the analogs are more benign.

R. W. Keen, D. J. Hart, J. S. Lanchbury, and T. D. Spector 1444

Osteoporosis and OA are two common, chronic skeletal conditions that are both under strong genetic control. The finding that a genetic variant of the vitamin D receptor, which has been previously related to high bone mass, is also associated with an increased risk of OA at the knee suggests that common genetic factors may influence the development of both conditions. This will lead to an increased understanding of the pathophysiologic processes underlying these two diseases, and may ultimately result in improved therapeutic options and diagnostic tools.

Haiko Sprott, Andreas Muller, and Hartmut Heine 1450

This study sought to determine whether abnormal collagen metabolism is a characteristic of fibromyalgia. The results indicate that decreased levels of collagen crosslinking in fibromyalgia may contribute to remodeling of the extracellular matrix and collagen deposition around the nerve fibers, and may contribute to a lower pain threshold at the tender points. Biopsy of fibromyalgia skin, or preferably, analysis of collagen metabolites in urine and serum may prove useful in determining the structural basis and diagnosis of fibromyalgia.

Richard F. Loeser, Brian C. Varnum, Cathy S. Carlson, Mary B. Goldring, Edison T. Liu, Sagypash Sadiev, Tim E. Kute, and Reidar Wallin 1455

Chondrocytes produce autocrine factors which are important for regulation of their growth and survival. This study presents evidence of a novel autocrine signaling pathway in human cartilage, consisting of a protein called Gas-6 and its receptor, axl. Gas-6 and axl likely work in concert with other growth factor systems to control the growth and survival of chondrocytes. Disruption of these pathways could contribute to the cartilage loss seen in arthritis.

Steven A. Mazzuca, Kenneth D. Brandt, Barry P. Katz, Mary Chambers, Donna Byrd, and Mark Hanna 1466

Recently published guidelines for the management of OA of the hip and knee emphasize early intervention with an array of nonpharmacologic treatments (e.g., exercise, practice of joint protection principles). Patient education and close followup are also recommended to support the acquisition and maintenance of self-care behavior. The results of the attention-controlled trial reported herein, conducted with inner-city primary care patients with knee OA, demonstrate the therapeutic benefit of self-care education with respect to function and resting joint pain, but also point to the need to assure long-term reinforcement of self-care practices.

Stephan F. Lanes, Lee L. Lanza, Paul W. Radensky, Robert A. Yood, Robert F. Meenan, Alexander M. Walker, and Nancy A. Dreyer 1475

This work quantifies patterns of care and costs of services for patients with rheumatoid arthritis or osteoarthritis. Understanding the costs of medical services facilitates informed decisions about disease management.

G. D. Levy, S. J. Munz, J. Paschal, H. B. Cohen, K. J. Pince, and T. Peterson 1482

The results of this study indicate that the incidence of hydroxychloroquine retinal toxicity is very low. It is therefore concluded that, in hydroxychloroquine-treated patients with normal renal function, routine ophthalmic screening is not indicated if the daily dosage is [gt]6.5 mg/kg. Annual screening is recommended in patients who have had long-term use, high daily doses, or renal insufficiency.

Frank C. Arnett, John D. Reveille, and Benigno C. Valdez 1487

Gastric antral vascular ectasia, or watermelon stomach, may complicate systemic sclerosis. An antinucleolar autoantibody, anti-RNA helicase, has recently been found in a patient with watermelon stomach. The present study demonstrates the presence of anti-RNA helicase antibodies in small percentages of patients with systemic sclerosis, lupus, and undifferentiated connective tissue disease, but shows no association with watermelon stomach.

Margaret-Mary Holyst, Don L. Hill, Sallie O. Hoch, and Robert W. Hoffman 1493

This study provides a comprehensive analysis of both B cell and T cell reactivity with U snRNP 70-kd, B, and D polypeptides among patients with connective tissue diseases. These patients were shown to have snRNP-reactive T helper cells that parallel the specificity of snRNP-reactive antibodies in their sera and that produce cytokines which are important in B cell help and differentiation.

Mart Mannik and Mark H. Wener 1504

This study provides evidence for the presence and concentration of antibodies to the collagen-like region of C1q in the glomeruli of patients with proliferative lupus glomerulonephritis. The finding of these antibodies in glomeruli indicates the potential importance of their role in disease pathogenesis.

P. Hilliquin, D. Borderie, A. Hernvann, C. J. Menkes, and O. G. Ekindjian 1512

This study demonstrates for the first time the presence of nitric oxide complexed in S-nitrosoproteins (S-NP) in patients with active RA. Serum S-NP levels were reduced by corticosteroid treatment, suggesting that S-NP could be a marker of the presence of active nitric oxide in RA.

Leena Sharma, Yi-Chung Pai, Kelly Holtkamp, and W. Zev Rymer 1518

This study seeks to address whether proprioception impairment in knee OA is exclusively a local result of disease, which would help determine whether this impairment is a factor in pathogenesis. The intrinsic repair capacity of the osteoarthritic knee and the response to chondroprotective therapy may depend upon mechanical and neuromuscular factors such as proprioception. Treatment of the proprioception impairment itself might have a disease-modifying effect.

Lauren M. Pachman, Jennifer R. Hayford, Marc C. Hochberg, Mark A. Pallansch, Ahn Chung, Claire D. Daugherty, Balu H. Athreya, Suzanne L. Bowyer, Chester W. Fink, Harry L. Gewanter, Rita Jerath, Bianca A. Lang, Ilona S. Szer, James Sinacore, Mary L. Christensen, and Alan R. Dyer 1526

Several lines of evidence suggest that juvenile DM may have an infectious trigger. This study compares clinical and laboratory features in children with new-onset juvenile DM versus healthy controls and children with JRA. The results document an increased frequency of autoimmune disease in families of children with JRA but not those with juvenile DM or healthy children. There are no differences in antibody titers to agents implicated in the etiology of juvenile DM, with the exception of increased enteroviral titers in juvenile DM patients and healthy controls under 7 years of age.