Isao Kitajima, Naohiro Hanyu, Koichi Kawahara, Yasuko Soejima, Toshikazu Kubo, Ryo Yamada, Yasufumi Kaneda, and Ikuro Maruyama 2118

HTLV-1 is a cause of chronic arthropathy. Ribozymes targeted against HTLV-1 tax/rex mRNA were developed as gene therapy aimed at extinguishing specifically activated viral genes in the infected synovial cells from patients with HTLV-1-associated arthropathy (HAAP). The liposome-based technique of gene transfer was used. The ribozymes successfully cleaved tax/rex mRNA in HAAP patient synovial cells in vitro. The ribozyme-dependent ablation of Tax protein synthesis led to inhibition of proliferation and induction of synovial apoptosis. This technique appeared to be applicable to the introduction of ribozymes into synovial cells of the affected regions in HAAP patients.

Yuko Takeba, Noboru Suzuki, Mitsuhiro Takeno, Tomiaki Asai, Seiji Tsuboi, Takashi Hoshino, and Tsuyoshi Sakane 2128

This report describes the involvement of somatostatin in the autocrine regulation of synovial cell function in patients with RA. The results suggest the beneficial effects of somatostatin on the pathologic processes of RA and the clinical application of somatostatin in patients with RA.

Carrie Langdon, Jonathon Leith, Frank Smith, and Carl D. Richards 2139

The effect of locally elevated levels of the IL-6/LIF family cytokines in the synovial tissue and fluid of RA patients is not clear. This study examined levels of oncostatin M (an IL-6/LIF group member) in the synovial fluid of inflamed joints, and defined the activities of oncostatin M on human synovial fibroblasts, which may help characterize its role in local inflammation. The results suggest that oncostatin M has potentially proinflammatory actions that participate in the chronic joint inflammation and destruction of RA.

Olga Sanchez-Pernaute, Maria Jose Lopez-Armada, Purificacion Hernandez, Itziar Palacios, Francisco Navarro, Javier Mart|finez, Jesus Egido, and Gabriel Herrero-Beaumont 2147

The fibroproliferative changes of synovium lead to tissue damage and dysfunction in chronic arthritis. This work explored tenidap's regulation of synovial overgrowth in an experimental model of chronic arthritis. In healthy cultured synovial cells, the effect of tenidap on cell proliferation and fibronectin gene expression, as well as the potential implication of transforming growth factor β, were characterized.

Klaus Huch, Berry Wilbrink, Johannes Flechtenmacher, Holger E. Koepp, Margaret B. Aydelotte, T. Kuber Sampath, Klaus E. Kuettner, Juergen Mollenhauer, and Eugene J.-M. A. Thonar 2157

IL-1, an inflammatory cytokine present in the joint fluid of patients with osteoarthritis and rheumatoid arthritis, inhibits 35S-proteoglycan synthesis by human articular chondrocytes. This study shows that recombinant human osteogenic protein 1, a bone morphogenetic protein, is effective in counteracting the IL-1β-induced down-regulation of 35S-proteoglycan synthesis by human articular chondrocytes cultured in the presence of 10% fetal bovine serum. This finding could lead to the development of a new approach to the treatment of joint disease.

Reinhard E. Voll, Edith A. Roth, Irute Girkontaite, Holger Fehr, Martin Herrmann, Hanns-Martin Lorenz, and Joachim R. Kalden 2162

Th cells may play an important role in the pathogenesis of SLE by providing T cell help for autoreactive B cells. However, little is known about the antigen specificity and cytokine secretion profile of autoreactive Th cells. Potentially pathogenic histone-specific Th0 and Th1 clones from SLE patients are described, which may help in our understanding of the derangement of the immune system that leads to the manifestations of SLE.

David Stanek, Jir|fi Vencovsky, Jarmila Kafkova, and Ivan Raska 2172

This report describes a novel autoantibody-antigen system found in a patient with coexisting systemic sclerosis and psoriatic arthritis. The autoantibody recognizes C1 and C2 proteins of the heterogenous nuclear ribonucleoproteins. It is further evidence of the humoral autoimmune response against the spliceosome components in patients with connective tissue diseases.

Kristina Nilsson Ekdahl, Lars Ronnblom, Gunnar Sturfelt, and Bo Nilsson 2178

This study demonstrates the phosphorylation of plasma proteins C3, fibrinogen, and vitronectin by activated platelets in patients with SLE. Furthermore, patients who had inactive SLE and were prone to thrombosis were observed to have increased levels of phosphate. These results suggest that impairments of the complement and coagulation systems due to increased phosphorylation might explain many of the anomalies of the disease.

Loic Guillevin, Jean-Francois Cordier, Francois Lhote, Pascal Cohen, Bernard Jarrousse, Isabelle Royer, Philippe Lesavre, Christian Jacquot, Pascal Bindi, Philippe Bielefeld, Jean-Francois Desson, Frederick Detree, Alain Dubois, Eric Hachulla, Bruno Hoen, Dominique Jacomy, Christian Seigneuric, Dominique Lauque, Marc Stern, and Maite Longy-Boursier 2187

In this prospective, randomized study, 27 patients with newly diagnosed systemic WG were treated with steroids plus pulse CYC and 23 with steroids plus oral CYC, and outcomes in the 2 groups were compared. Pulse CYC was shown to be as effective as oral CYC in achieving initial remission, with fewer side effects. However, remission was better maintained in the long term with oral CYC. Future investigations should be conducted to further weigh the choices between the lower rate of adverse effects found with pulse CYC and the lower frequency of relapse with oral CYC.

Alison J. Partridge, Elizabeth W. Karlson, Lawren H. Daltroy, Robert A. Lew, Elizabeth A. Wright, Anne H. Fossel, Karin V. Straaton, Steven H. Stern, Arthur F. Kavanaugh, W. Neal Roberts, and Matthew H. Liang 2199

Strategies for preventing or reversing work disability have had little study in SLE. This study addresses potentially modifiable factors associated with early work disability in SLE. Multivariate analysis showed that education level, higher physical demands of the job, and higher disease activity at diagnosis were significant predictors of work disability.

Kathleen E. Sullivan, Candra Wooten, Barbara J. Schmeckpeper, Daniel Goldman, and Michelle A. Petri 2207

TNFα is both a proinflammatory cytokine and a regulator of T cell and B cell apoptosis. This report describes the association of a promoter polymorphism of TNFα, which is thought to be responsible for increased transcription of TNFα, with SLE in Africian-Americans. Understanding the role of this cytokine in the development of SLE may allow for novel interventions targeted at TNFα.

Athanasios G. Tzioufas, Styliani I. Kokori, Constantinos I. Petrovas, and Haralampos M. Moutsopoulos 2212

Using a simple ELISA, the presence of antibodies to erythropoietin was demonstrated for the first time in the sera of SLE patients, and the antibodies were associated with severe anemia and active disease. These results are important in identifying a biologic role for autoantibodies to erythropoietin.

Zahir Amoura, Jean-Charles Piette, Henri Chabre, Patrice Cacoub, Thomas Papo, Bertrand Wechsler, Jean-Francois Bach, and Sophie Koutouzov 2217

The nucleosome, a 180-200-bp DNA wrapped around a core histone octamer, plays a key role in the triggering of the autoantibody response in both murine and human lupus. This study assessed plasma levels of nucleosome in patients with SLE, and examined correlations with selected serum antibody levels and disease activity.

Philip J. Hashkes, William F. Balistreri, Kevin E. Bove, Edgar T. Ballard, and Murray H. Passo 2226

This study is the first systematic assessment of the long-term hepatotoxic effect of MTX in patients with JRA. While minor histologic changes were commonly found, no patient developed significant fibrosis that would have required discontinuation of the MTX. Hepatotoxic risk factors in this cohort, especially biochemical abnormalities reflective of liver injury and alcohol consumption, are also described.

Lynne S. Peterson, Tom Mason, Audrey M. Nelson, W. Michael O'Fallon, and Sherine E. Gabriel 2235

This retrospective, controlled cohort study describes the psychosocial and physical outcome in adults who have had JRA, compared with age- and sex-matched controls. Adults with a history of this chronic childhood illness will often continue to experience important physical and social disabilities throughout their lives. This should be taken into account in the prognosis of JRA.

Kenshi Higami, Masayuki Hakoda, Yuko Matsuda, Hiroyuki Ueda, and Sadao Kashiwazaki 2241

To evaluate the role of HLA-DRB1 alleles on the development and progression of the disease process in RA, 198 patients with polyarthritis of [gt]1 year's duration at presentation were followed up for 1 year. Homozygous state for HLA-DRB1 alleles with the RA-related shared epitope (SE) was associated with increased susceptibility for the development of polyarthritis. However, none of the DRB1 alleles or SE genotypes correlated with the presence of bone erosion at presentation or 1 year later. Identification of a genetic marker defining severe disease would be valuable in selecting patients for early aggressive therapy.

Ulrich R. KaSer, Christiane Gleissner, Florian Dehne, Alexander Michel, Brita Willershausen-Zonnchen, and Wolfgang W. Bolton 2248

This study demonstrates an increased frequency and severity of periodontal disease in patients with longstanding RA. Because of this high risk, dental cleaning instructions should be included in RA education programs, and dental examinations should be routinely performed in these patients.

Gabrio Bassotti, Edda Battaglia, Valeria Debernardi, Ugo Germani, Fabrizio Quiriconi, Luca Dughera, Giuseppena Buonafede, Paolo Puiatti, Antonio Morelli, Fabrizio Spinozzi, Pier Roberto Mioli, and Giorgio Emanuelli 2252

Esophageal motor function is frequently claimed to be abnormal in scleroderma patients, particularly in late cutaneous disease, in which visceral involvement is more likely to occur. The present study examined a large group of scleroderma patients who were classified into disease subsets. The results indicate a direct relationship between the degree of esophageal involvement and the extent of cutaneous disease among the various subsets. Manometric studies, in particular, revealed widespread gut involvement and showed a significant correlation with disease severity. These findings provide a rationale for a more targeted therapeutic approach.

Yi-Chung Pai, W. Zev Rymer, Rowland W. Chang, and Leena Sharma 2260

This study investigates age- and OA-related declines in knee proprioception, which are thought to be a critical link in the neuromuscular function that protects a joint. The results show that patients with knee OA have a greater reduction in knee position sense than age-matched elderly controls. New rehabilitation strategies may be warranted to emphasize modification in motor behavior and retraining aimed at facilitating neuromuscular joint-protective mechanisms to slow the progression of knee OA.