bluuebunny/crossref_metadata_2025_split huggingface dataset:
Auranofin in the treatment of juvenile rheumatoid arthritis
Authors: Giannini Edward H. , Brewer Earl J. , Kuzmina Nina , Shaikov Alexandr , Wallin Bruce 
Published: February 2007

AbstractA 6‐month double‐blind, parallel, randomized, placebo‐controlled multicenter trial of auranofin (0.15–0.20 mg/kg/day) was conducted in 231 children with juvenile rheumatoid arthritis (JRA) in the United States and in the Union of Soviet Socialist Republics. Approximately 80% of the children had polyarticular disease. The auranofin‐treated patients showed greater mean decreases from baseline in 11 of the 12 articular disease indices measured than did the placebo‐treated subjects after 3 months of therapy, and in 9 of the 12 indices after 6 months. However, the actual intergroup mean differences were relatively small and were not statistically significant. According to the physician's global assessment, 69% of the auranofin‐treated patients and 61% of the placebo‐treated patients demonstrated clinically significant improvement from baseline after 6 months (P = 0.24). Children whose disease onset occurred less than 2 years prior to entry improved more than did those who had arthritis for a longer period. In addition, those with polyarticular involvement at baseline improved more than did patients with mild disease. However, these relationships were observed in both the auranofin‐ and placebo‐treated groups, and again, there were no significant intergroup differences. Diarrhea was the most common adverse effect of auranofin. We conclude that the clinical efficacy of auranofin is modestly higher than that of placebo in the treatment of JRA, as evidenced by the consistent trends observed in the data. However, the magnitude of the individual intergroup differences is not statistically significant. Auranofin appears to be very safe in children with JRA.
Synoviocytes synthesize, bind, and respond to basic fibroblast growth factor
Authors: Melnyk Vera O. , Shipley Gary D. , Sternfeld Mark D. , Sherman Larry , Rosenbaum James T. 
Published: February 2007

AbstractRheumatoid arthritis (RA) is a systemic disease characterized by the destructive proliferation of synovial tissue. It has been suggested that this proliferative lesion resembles a malignancy. Although polypeptide growth factors have been implicated in malignant cell growth, their role in the pathogenesis of proliferative but non‐neoplastic diseases such as RA has not been extensively studied. We tested the hypothesis that the synoviocyte itself may be a source of growth factor activity. We demonstrated that culture supernatants from synoviocytes obtained from patients with RA, osteoarthritis, and traumatic joint disease contain mitogenic activity. This activity has biologic properties identical to those of basic fibroblast growth factor (bFGF). Specifically, the mitogenic activity is synergistic with insulin and binds to heparin‐agarose, but elutes with 2.0M NaCl. In addition, synoviocyte extracts contain a peptide with a molecular weight of ∼ 16,000, which reacts with antibody specific for bFGF. Cultured synoviocytes express the bFGF gene, express receptors for bFGF, and proliferate in response to bFGF. We conclude that bFGF derived from the synoviocytes themselves may play a role in stimulating their proliferation in an autocrine manner in disease states such as RA.
Rapid periarticular bone loss in rheumatoid arthritis
Authors: Sambrook P. N. , Shawe Deirdre , Hesp R. , Zanelli Joan M. , Mitchell Rhiannon , Katz D. , Gumpel J. M. , Ansell Barbara M. , Reeve J. 
Published: February 2007

AbstractFor approximately 2 years, bone loss was measured in women with early stages of rheumatoid arthritis (RA) and in control subjects, using serial computed tomography and dual photon absorptiometry. Rapid trabecular bone loss from the distal radius was observed in the RA patients but not the controls. The bone loss correlated with initial plasma levels of parathyroid hormone and 1,25‐dihydroxyvitamin D3 (calcitriol) concentrations. It has been suggested that these humoral factors may interact with cytokines or other mediators produced in the adjacent wrist joint. Losses of the cortical bone of the radial midshaft and the lumbar spine were modest and were comparable in the 2 groups. Indices relating to both bone formation and bone resorption predicted bone loss at these 2 sites, but changes in the parathyroid hormone and calcitriol concentrations did not.
Measurement of increases in anti‐double‐stranded dna antibody levels as a predictor of disease exacerbation in systemic lupus erythematosus
Authors: Ter Borg E. J. , Horst G. , Hummel E. J. , Limburg P. C. , Kallenberg C. G. M. 
Published: February 2007

AbstractTo evaluate the predictive power of changes in levels of antibodies to double‐stranded DNA (anti‐dsDNA) as a predictor of disease exacerbations in systemic lupus erythematosus (SLE), we performed a prospective study on 72 unselected patients with SLE (mean duration of study 18.5 months, range 6–35 months). Patients were seen at least once every 3 months, and disease activity was scored according to a specific protocol. Plasma samples were obtained at least once every month and were assessed for anti‐dsDNA antibody (by the Crithidia luciliae assay, an enzymelinked immunosorbent assay [ELISA], and the Farr assay) and for complement components C3 and C4. Twenty‐seven of 33 disease exacerbations observed during the study period were accompanied by a positive test result for anti‐dsDNA antibody (27 by the Farr assay, 19 by the C luciliae assay, and 23 by the ELISA). Twenty‐four of these exacerbations were preceded by a significant increase in anti‐dsDNA antibody levels (23 by the Farr assay, 12 by the C luciliae assay, and 17 by the ELISA). The first observance of a significant increase in anti‐dsDNA antibody levels preceded the exacerbation by 8–10 weeks. Significant increases in anti‐dsDNA antibody levels not followed by an exacerbation were observed in 5 cases by the Farr assay, in 7 cases by the C luciliae assay, and in 3 cases by the ELISA; however, in 3 cases, 2 cases, and 1 case, respectively, these increases were followed by an increase in disease activity that did not fulfill the criteria for an exacerbation. Serial measurement of anti‐dsDNA antibody levels was more sensitive for predicting exacerbations than was measurement of C3 and/or C4 levels (P < 0.03). Serial assessment of anti‐dsDNA antibody levels, especially by the Farr assay, is a sensitive and reasonably specific method for predicting disease exacerbations in SLE.
Beneficial effect of fibronectin administration on chronic nephritis in rats
Authors: Quirós Javier , Gonzalez‐Cabrero Jesus , Egido Jesus , Herrero‐Beaumont Gabriel , Martinez‐Montero Juan C. 
Published: February 2007

AbstractWe studied the effect of fibronectin (FN) on the course of chronic nephritis (induced by daily injections of ovalbumin) and on the clearance and catabolism of immune complexes in Wistar rats. Rats with chronic nephritis were treated with FN (2.5 mg/kg/48 hours) for 15 days after proteinuria was first detected. In rats with untreated nephritis, urinary protein levels increased from 40 ± 22 mg/day (mean ± SD) to 339 ± 68 mg/day during the 15 days of the study (P < 0.0005). This statistically significant increase was not observed in rats treated with FN (mean ± SD 58 ± 46 mg/day to 124 ± 112 mg/day). Rats treated with FN showed a higher total serum protein level than did the untreated animals (mean ± SD 6.4 ± 0.3 gm/dl versus 5.1 ± 0.5 gm/dl; P < 0.0125), as well as a significant reduction in mesangial and glomerular basement membrane deposits. Untreated nephritic rats demonstrated delayed plasma clearance of 125I‐labeled aggregated IgG (plasma half‐life [T1/2] 3.03 ± 0.6 minutes) and less catabolism of these aggregates at 30 minutes (mean ± SD 15 ± 1.7%) than did the normal rats (T1/2 1.5 ± 0.2 minutes, 22 ± 2.8%, respectively; P < 0.0005). Both parameters were within normal limits in the FN‐treated rats (T1/2 1.6 ± 0.4 minutes, 22 ± 6%, respectively). In vitro, FN induced a significant increase in aggregated IgG catabolism by Kupffer cells and peritoneal macrophages from normal rats. These results show that FN reduces the proteinuria and histologic lesions of chronic nephritis in rats. These beneficial effects of FN could be due to the improved clearance of immune complexes, decreased glomerular deposition, and perhaps, to better renal processing of immune complexes.
Autoantibodies, ly‐1, and immunoglobulin v gene expression in hybridomas obtained from young and from old new zealand black mice
Authors: Fidanza Vincenzo , Mayer Raoul , Zaghouani Habib , Diliberti Mary Ann , Bona Constantin A. 
Published: February 2007

AbstractWe obtained a large number of hybridomas from 1‐month‐old and 16‐month‐old New Zealand black mice to study the fine specificities of the autoantibodies produced, the expression of Ly‐1, and the expression of the immunoglobulin V gene families in this autoimmune strain. Analysis of the autoantibody specificities yielded 2 major classifications: those specific for a single autoantigen and those that exhibited multispecific binding. Among the multispecific antibodies, 2 categories were found: an antigen‐inhibitable group and an antigennoninhibitable group. A large proportion of VHJ558 and VH7183 gene families was observed in hybridomas obtained from 1‐month‐old mice, and in hybridomas obtained from 16‐month‐old mice, there was a large proportion of VHJ558 and VH36–60 gene families. Among the autoantibody k chains secreted by the hybridomas, there was a higher frequency of the Vk1, Vk8, and Vk9 gene families. Autoantibodies were produced by both the Ly‐1+ and the Ly‐1‐B cell subsets.
Biochemical demonstration of calpains and calpastatin in osteoarthritic synovial fluid
Authors: Suzuki Kiichi , Shimizu Katsuji , Hamamoto Takashi , Nakagawa Yasuaki , Hamakubo Takao , Yamamuro Takao 
Published: February 2007

AbstractCalpains (calcium‐dependent cysteine proteinases; optimum pH 7.0–7.5) have been regarded as intracellular proteinases. We examined the cell‐free components of synovial fluid from 14 patients with osteoarthritis and demonstrated the existence of calpains, as the caseinolytic activities of chromatographic fractions, together with calpastatin, the specific endogenous inhibitor of calpains. The presence of these calpains and calpastatin was verified by immunoblotting with their respective specific antibodies. Calpain fractions showed proteoglycan‐degrading activity. The results suggest that the calpain‐calpastatin system may contribute to the turnover of cartilage matrix components.
Depletion of high‐energy phosphates in the central nervous system of patients with systemic lupus erythematosus, as determined by phosphorus‐31 nuclear magnetic resonance spectroscopy
Authors: Griffey Richard H. , Brown Mark S. , Bankhurst Arthur D. , Sibbitt Randy R. , Sibbitt Wilmer L. 
Published: February 2007

AbstractSystemic lupus erythematosus (SLE) can produce profound disturbances in the central nervous system, characterized by encephalopathy, focal neurologic deficits, cerebral infarction, psychosis, and seizures. We used 31P nuclear magnetic resonance (NMR) spectroscopy to determine the in vivo levels of high‐energy phosphates in the central nervous system of 10 patients with SLE and 10 age‐matched normal controls. 31P NMR spectroscopy was performed on a 1.5‐Tesla unit equipped with a dual‐tuned 1H‐31P surface coil and a software‐directed DRESS (depth resolved surface coil spectroscopy) pulse sequence. This procedure detected ADP, ATP, sugar phosphates, phosphocreatine (PCr), inorganic phosphate, phosphomonoesters, and phosphodiesters in the brain tissue of all study subjects. Levels of ATP in the deep white matter of 10 SLE patients were significantly decreased compared with the levels in 10 normal controls, as quantitated by the ratio of ATP:ATP + ADP (mean ± SD 0.81 ± 0.11 versus 0.91 ± 0.05; P < 0.02). In a subgroup of 4 patients, PCr levels were decreased to a greater extent than the ATP levels. NMR spectroscopic alterations were not related to obvious anatomic lesions, as determined by standard cranial proton magnetic resonance imaging. In 4 SLE patients with markedly abnormal 31P NMR spectra, treatment with prednisone (80 mg/day) normalized the levels of ATP and PCr. Restoration of a normal 31P profile was accompanied by an obvious improvement in the patients' mental status and clinical symptoms. 31P NMR spectroscopy is a powerful new technique for monitoring high‐energy phosphate metabolism, and may be particularly useful for characterizing central nervous system disease in patients with neuropsychiatric SLE.
Autoantibodies to lamins in rheumatoid arthritis
Authors: Lassoued Slim , Oksman Françoise , Fournie Bernard , Danon Françoise , Fournie Antoine , Lassoued Kaiss 
Published: February 2007

AbstractThe presence of autoantibodies reacting with lamins A and C was demonstrated in sera from 2 patients with rheumatoid arthritis (RA). One patient developed antilamin antibodies several years after being diagnosed as having RA; she was also found to have chronic active hepatitis. The second patient had severe nodular RA. We describe the other serologic findings in these 2 patients and discuss the relationships between antilamin antibodies and RA.
Biochemical characterization of amyloid derived from the variable region of the k light chain subgroup III
Authors: Picken Maria M. , Gallo Gloria R. , Pruzanski Waldemar , Frangione Blas 
Published: February 2007

AbstractWe report the clinical data and results of biochemical studies of amyloid in a postpartum patient. The amyloidosis was not associated with myeloma, and immunopathologic examination of the amyloid deposits gave inconclusive results. Biochemical analysis of the deposits proved that the amyloid protein JUN was derived from the variable region of the k light chain subgroup III and is homologous to a rarely expressed protein POM, which was previously shown to have rheumatoid factor activity. The significance of this association and the diagnostic problems associated with certain cases of amyloid derived from immunoglobulin light chain (type AL) are discussed.
Decreased activity of reiter's syndrome after urethrectomy
Authors: Rubin Richard A. , Goldfarb Richard A. , Lidsky Martin D. , Abrams Jackie 
Published: February 2007

AbstractReiter's syndrome is a chronic rheumatic disease that develops after infective urethritis or gastroenteritis and has a strong association with the HLA‐B27 antigen. How these factors interact remains unclear. We present a patient with Reiter's syndrome who exhibited 2 novel features: unusually severe urethritis that produced strictures requiring surgery, and dramatic regression of his rheumatic manifestations following a urethrectomy.
Intravenous gamma globulin therapy in systemic juvenile rheumatoid arthritis
Authors: Silverman Earl D. , Laxer Ronald M. , Greenwald Mark , Gelfand Erwin , Shore Abraham , Stein Leonard D. , Roifman Chaim M. 
Published: February 2007

AbstractIntravenous (IV) gamma globulin has been successfully used as replacement therapy for antibody‐deficient patients and, more recently, in the treatment of autoimmune diseases such as idiopathic thrombocytopenic purpura, myasthenia gravis, and Kawasaki disease. In view of the successful treatment of these diseases, we initiated a pilot study of the effect of IV gamma globulin in systemic juvenile rheumatoid arthritis (JRA). Eight patients with active systemic JRA that was unresponsive to first‐line agents, second‐line agents, and/or corticosteroids received this therapy monthly for 6 months. Outcome measures included changes in articular and extraarticular features, steroid dosage, and laboratory parameters. Following IV gamma globulin therapy, there was significant improvement in arthritis and/or morning stiffness in 5 of 8 patients, while extraarticular features significantly improved in 7 of 8 patients. At study entry, 6 of 8 patients were receiving prednisone; at study end, prednisone was discontinued in 3 patients and decreased by more than 50% in the other 3. Overall, there was an 80% reduction in the prednisone dosage. Initially, all patients had anemia, low levels of serum albumin, and an elevated erythrocyte sedimentation rate, while a thrombocytosis was seen in 7 of 8 patients. Serum IgG was initially elevated in 6 patients. IV gamma globulin therapy resulted in a significant increase in hemoglobin and albumin levels and a significant decrease in the mean serum IgG level, platelet count, and erythrocyte sedimentation rate. In only 1 patient did IV gamma globulin fail to significantly improve the clinical or laboratory features of the disease. We suggest that this therapy may be beneficial in the treatment of systemic JRA.
Structural characterization of the second major cross‐reactive idiotype group of human rheumatoid factors. Association with the VH4 Gene Family
Authors: Silverman Gregg J. , Schrohenloher Ralph E. , Accavitti Mary A. , Koopman William J. , Carson Dennis A. 
Published: February 2007

AbstractRheumatoid factors (RF) are the most common type of functional antibodies among naturally occurring human monoclonal IgM proteins. A large subset of these autoantibodies use structurally homologous light chains of the kIII subgroup, which bear the 6B6.6 cross‐reactive idiotype (CRI). Although antibody binding activity requires both heavy and light chains, information about the heavy chains used by these autoantibodies is limited. To investigate these proteins, the murine monoclonal antibodies, 5–14 and 6–10, were generated by immunization with the heavy chains of the 6B6.6 CRI‐positive RF, COR and LEW. These antiidiotypic antibodies reacted with 8 of 11 autoantibodies that coexpressed the 6B6.6 CRI. All 8 RF had heavy chains from the VH4 gene family, as assessed by reactivity with a VH4‐specific primary sequence‐dependent antibody. The same RF were also identified by the previously described murine monoclonal antiidiotype, LCI. Further experiments revealed that the LCI antibody delineates a subfamily of VH4 heavy chains that is preferentially used in KIII‐6B6.6 CRI‐positive IgM‐RF. The cumulative data suggest that 13–22% of RF express both the KIII‐6B6.6 and VH4‐LC1 CRI. These findings document that RF autoantibody activity requires specific VL‐VH pairing, and that a subset of idiotypically related VH4 heavy chains is commonly expressed in disease‐associated monoclonal IgM‐RF.
Cellular immune response toward human articular chondrocytes. T cell reactivities against chondrocyte and fibroblast membranes in destructive joint diseases
Authors: Alsalameh Saifeddin , Mollenhauer JÜRgen , Hain Norbert , Stock Klaus‐Peter , Kalden Joachim R. , Burmester Gerd R. 
Published: February 2007

AbstractArticular cartilage is one of the major targets in destructive joint diseases in humans. We studied cellular immune reactions against cartilage cell‐surface membranes, because it has recently been suggested that these represent possible antigenic structures, based upon the observation of autoantibodies with this specificity in certain joint diseases. A striking T cell reactivity toward chondrocyte membranes was found both in blood and synovial tissue from patients with rheumatoid arthritis. This reactivity was strongly dependent on the presence of monocytes and had all the characteristics of an antigen‐driven process. Clonal analysis demonstrated high precursor frequencies in peripheral blood T cells that were reactive against chondrocyte membranes. This response to chondrocyte membranes greatly exceeded the T cell stimulation induced by membranes from other sources such as fibroblasts or epithelial cells. In contrast to patients with rheumatoid arthritis, individuals with osteoarthritis showed a strong peripheral blood and synovial fluid T cell response not only to chondrocyte membranes, but also to fibroblast membrane material. However, there was no reactivity to epithelial cell membranes. Normal donors generally did not show significant responses to any membrane preparation. These data indicate that there is a strong T cell reactivity toward chondrocyte membranes in destructive joint disorders, and this may significantly contribute to the pathogenetic processes that occur in these diseases.
Relationship of glucocorticoid dosage to serum bone gla‐protein concentration in patients with rheumatologic disorders
Authors: Kotowicz Mark A. , Hall Stephen , Hunder Gene G. , Cedel Sandra L. , Mann Kenneth G. , Riggs B. Lawrence 
Published: February 2007

AbstractSerum bone Gla‐protein (BGP) measurements in 50 rheumatic disease patients receiving long‐term prednisone therapy revealed an inverse relationship (r = −0.71, P < 0.001) between serum BGP levels and prednisone dosage. Multiple regression analysis demonstrated significant relationships (R2 = 0.72, P < 0.001) between serum BGP1/2 and prednisone dosage, dosage2, serum creatinine, age, and an age‐creatinine interaction. This model predicts the suppression of serum BGP with low dosages of steroids and 50% suppression with dosages of 20–25 mg/day.
IgG and IgA antibodies to the collagen‐like region of C1q in rheumatoid vasculitis
Authors: Siegert C. E. H. , Daha M. R. , Van Voort E. A. M. Der , Breedveld F. C. 
Published: February 2007

AbstractWe investigated the presence of IgG and IgA antibodies to C1q in serum samples from 80 patients with rheumatoid arthritis (RA), 31 patients with rheumatoid vasculitis, and 80 healthy controls. IgG and IgA antibodies to C1q, as measured by enzyme‐linked immunosorbent assay, were found in <5% of the sera from RA patients and from healthy controls. In contrast, IgG and IgA antibodies to C1q were found in 29% and 61%, respectively, of the sera from patients with rheumatoid vasculitis. The occurrence of IgA antibodies to C1q has not been previously demonstrated. These results also demonstrate that IgG antibodies to C1q do not occur exclusively in systemic lupus erythematosus patients: Sera of patients with rheumatoid vasculitis frequently contain IgG or IgA antibodies to C1q, which contribute to immune complex formation.
Association of labial salivary gland histopathology with clinical and serologic features of connective tissue diseases
Authors: Shah Farah , Rapini Ronald P. , Arnett Frank C. , Warner Noranna B. , Smith Carolyn A. 
Published: February 2007

AbstractFocal sialadenitis is now widely accepted as an objective criterion for the oral component of Sjögren's syndrome (xerostomia). We investigated the association between labial salivary gland histopathologic changes and the clinical and serologic features of 192 patients with suspected connective tissue disorders. A retrospective review of the medical records of all patients was performed, and historical, physical, laboratory, histologic, and roentgenographic data were abstracted. Each patient had undergone labial salivary gland biopsy as part of a rheumatologic evaluation. There were significant associations between positive findings on lip biopsy and the presence of keratoconjunctivitis sicca (P = 0.013), positive antinuclear antibodies (titer ≥1:80) (P = 2 x 10−8), and positive Ro antibodies (P = 1 x 10−8). However, sicca symptoms and glandular enlargement were not statistically associated with positive findings on lip biopsy. Features predictive of a positive lip biopsy included Ro antibodies (P = 0.914), keratoconjunctivitis sicca (P = 0.700), and positive antinuclear antibodies (P = 0.590).