bluuebunny/crossref_metadata_2025_split huggingface dataset:
The presence of interleukin‐13 in rheumatoid synovium and its antiinflammatory effects on synovial fluid macrophages from patients with rheumatoid arthritis
Authors: Isomäki Pia , Luukkainen Reijo , Toivanen Paavo , Punnonen Juha 
Published: February 2007

AbstractObjective. To study the production of interleukin‐13 (IL‐13) in rheumatoid synovium and the effects of recombinant IL‐13 on the phenotype and function of synovial fluid (SF) macrophages and T cells derived from patients with rheumatoid arthritis (RA).Methods. The presence of IL‐13 in SF was studied using an IL‐13—specific enzyme‐linked immunosorbent assay (ELISA); the production of IL‐13 was studied in SF mononuclear cells (SFMC) by reverse transcriptase—polymerase chain reaction. The effects of recombinant IL‐13 on cytokine production by and phenotype of SFMC were evaluated using cytokine‐specific ELISAs and flow cytometry, respectively. The effect of IL‐13 on the proliferation of SFMC was determined by 3H‐thymidine incorporation. The production and the effects of IL‐13 were compared with those of IL‐4.Results. IL‐13 was present in 27 of 28 SF samples, and IL‐13 messenger RNA (mRNA) was detectable in SFMC. Importantly, IL‐13 levels were significantly higher than those of IL‐4, and IL‐13 protein and mRNA were expressed in several samples, although IL‐4 synthesis was undetectable. Recombinant IL‐13 significantly reduced the production of IL‐1β and tumor necrosis factor α and the expression of CD16 and CD64 by SF macrophages, whereas the expression of HLA—DR and CD23 was increased. These effects on SF macrophages were similar to those observed with IL‐4, but in contrast to IL‐4, IL‐13 had no growth‐promoting effect on SF T cells.Conclusion. IL‐13 is consistently present in rheumatoid synovium. The ability of exogenous IL‐13 to decrease the production of proinflammatory cytokines by SFMC suggests that it may have therapeutic potential in the treatment of patients with RA.
Patterns of expression of tumor necrosis factor α, tumor necrosis factor β, and their receptors in synovia of patients with juvenile rheumatoid arthritis and juvenile spondylarthropathy
Authors: Grom Alexei A. , Murray Kevin J. , Luyrink Lorie , Emery Helen , Passo Murray H. , Glass David N. , Bowlin Terry , Edwards Carl 
Published: February 2007

AbstractObjective. To assess the expression of tumor necrosis factor α (TNF α), TNF β, and their receptors in synovia of patients with juvenile rheumatoid arthritis (JRA) and juvenile spondylarthropathy (JSpA), and to determine similarities with and differences from adult RA.Methods. Twenty‐eight synovial tissue samples from patients with JRA, 6 from patients with JSpA, and 6 from patients with RA, selected for the presence of inflammatory infiltrates, were analyzed for the expression of TNF α, TNF β, and their receptors (p55 and p75 TNFR), utilizing the dual approach of reverse transcriptase—polymerase chain reaction and immunohistochemistry analysis.Results. The presence of both TNF α and TNF β expression was demonstrated in most JRA and JSpA tissues, although samples from patients with pauci‐articular JRA had somewhat lesser amounts of these cytokines. TNF β expression correlated significantly with the occurrence of lymphocytic aggregates in tissues. Staining with monoclonal antibodies specific for the p55 and p75 receptors revealed that a diverse range of cell types expressed the receptors, with the most intense p55 staining on vascular endothelial cells. In the vast majority of synovial tissues, far greater numbers of cells expressed the p55 form of the receptor than the p75 form.Conclusion. JRA and JSpA synovia are characterized by the presence of TNF α, TNF β, and cells expressing TNFR. These findings provide further evidence that TNF, through autocrine/paracrine mechanisms, may amplify local inflammation, leading to joint destruction. The prominence of TNF β in the synovium in particular subgroups of JRA patients and in JSpA patients may be a distinguishing feature of these diseases.
Distinct immunologic features of finnish Sjögren's syndrome patients with HLA alleles DRB1*0301, DQA1*0501, and DQB1*0201. Alterations in circulating T cell receptor γ/δ subsets
Authors: Kerttula Tuija O. , Collin Pekka , Polvi Anne , Korpela Markku , Partanen Jukka , Mäki Markku 
Published: February 2007

AbstractObjective. To determine whether there were differences in the circulating T lymphocyte subsets or clinical features of patients with primary Sjögren's syndrome (SS) who were positive for different HLA alleles.Methods. Two‐ and three‐color flow cytometry analyses were performed, using a whole blood lysing method.Results. Patients with SS who had the HLA alleles DRB1*0301, DQA1*0501, and DQB1*0201 had lower levels of circulating Vδ1‐positive T cell receptor γ/δ (TCRγ/δ) cells and higher levels of circulating CD45RO‐positive TCRγ/δ cells compared with patients with SS who did not have these alleles. The patient subgroup with these alleles also had higher levels of anti—SS‐A/Ro and anti—SS‐B/La.Conclusion. These results indicate that patients with primary SS may be immunologically divided into subgroups according to their HLA status. These immunologic changes in SS may also be typical of other autoimmune disorders in patients with the HLA—DR3 haplotype.
Elevated levels of 92‐kd type IV collagenase (matrix metalloproteinase 9) in giant cell arteritis
Authors: Sorbi D. , French D. L. , Nuovo G. J. , Kew R. R. , Arbeit L. A. , Gruber B. L. 
Published: February 2007

AbstractObjective. To determine if circulating gelatinase activity and matrix metalloproteinase 9 (MMP‐9) (gelatinase B, or 92‐kd type IV collagenase) antigenic levels are elevated in sera of patients with giant cell arteritis (GCA), and to ascertain if MMP‐9 messenger RNA (mRNA) is deposited in situ at sites of disease involvement.Methods. Serum samples were collected from 12 patients with GCA and 12 healthy volunteers. Vascular tissue was obtained at the time of temporal artery biopsy. Type IV collagenase activity was determined by gelatin substrate zymography and the quantitative biotinylated gelatin substrate degradation assay. A double‐sandwich immunoassay utilizing 2 different isotypes of monoclonal antibodies generated against MMP‐9 was used for measuring serum MMP‐9 antigenic levels. Finally, to localize sites of MMP‐9 mRNA transcription in inflamed arteries, the method of reverse transcriptase in situ polymerase chain reaction (RTisPCR) was utilized.Results. Serum gelatinase activity and MMP‐9 titers were significantly increased in patients with GCA (mean ± SEM 198.9 ± 36.9 μg gelatin/hour/ml serum, versus 21.2 ± 4.0 in controls; P = 0.0006). The differences in antigenic MMP‐9 levels were even more prominent (3005.4 ± 900.6 ng/ml and 31.6 ± 9.8 ng/ml in GCA and control sera, respectively; P = 0.007). By RTisPCR, MMP‐9 mRNA was mainly detected in cytoplasm of cells resembling smooth muscle cells and fibroblasts in regions of fragmented elastic tissue in the lamina media.Conclusion. Gelatinase activity, and specifically MMP‐9 levels, are substantially elevated in sera of patients with GCA. Detection of MMP‐9 mRNA in the lamina media of inflamed vasculature suggests that degradation of intercellular matrix, particularly elastic fibers, may play a key role in the pathogenesis of GCA. Further studies are needed to determine if the circulating MMP‐9 level could be utilized as a clinical marker of disease activity.
HLA—DRB1 genes and disease severity in rheumatoid arthritis
Authors: Reveille John D. , Alarcón Graciela S. , Fowler Sarah E. , Pillemer Stanley R. , Neuner Rosemarie , Clegg Daniel O. , Mikhail Isis S. , Trentham David E. , Leisen James C. C. , Bluhm Gilbert , Cooper Sheldon M. , Duncan Howard , Tuttleman Marilyn , Heyse Stephen P. , Sharp John T. , Tilley Barbara ,   For the MIRA trial group
Published: February 2007

AbstractObjective. To examine the effect of alleles encoding the “shared”/“rheumatoid” epitope on rheumatoid arthritis (RA) disease severity in patients who participated in the minocycline in RA (MIRA) trial.Methods. Of 205 patients with a week‐48 visit, blood was available for typing of HLA‐DRB1 and HLA‐DQB1 in 174 (85%) and successfully completed in 169 (82%). Baseline erosions were used to assess disease severity and new erosions at the last visit served as a proxy for progression.Results. At baseline, there was no association between the presence of erosive disease or rheumatoid factor status and the dose of rheumatoid epitope (homozygous, heterozygous, none) or the specific alleles identified. At the final visit, a gradient was observed for the 3 allelic subgroups (and their gene doses) in the occurrence of new erosions among the Caucasian placebotreated, but not the minocycline‐treated, patients. A treatment group/HLA‐DR4 epitope interaction was demonstrated in multivariate analyses. Approximately two‐thirds of African‐American patients did not have the rheumatoid epitope.Conclusion. HLA‐DRB1 oligotyping may be useful in predicting the progression of disease in some Caucasian patients. Our study corroborates the infrequency of the epitope among African‐American patients with RA.
Gamma‐linolenic acid treatment of rheumatoid arthritis. A randomized, placebo‐controlled trial
Authors: Zurier Robert B. , Rossetti Ronald G. , Jacobson Eric W. , Demarco Deborah M. , Liu Nancy Y. , Temming Joseph E. , White Bernadette M. , Laposata Michael 
Published: February 2007

AbstractObjective. To assess the clinical efficacy and adverse effects of γ‐linolenic acid (GLA), a plant seed oil‐derived unsaturated fatty acid that suppresses inflammation and joint tissue injury in animal models, in the treatment of active rheumatoid arthritis (RA).Methods. Fifty‐six patients with active RA were randomized to treatment groups in a 6‐month, double‐blind trial of GLA versus placebo. This was followed by a 6‐month, single‐blind trial during which all patients received GLA. Patients were treated with 2.8 gm/day of GLA as the free fatty acid or with sunflower seed oil (placebo) administered in identical capsules.Results. Treatment with GLA for 6 months resulted in statistically significant and clinically relevant reductions in the signs and symptoms of disease activity in patients with RA. Overall meaningful responses (at least 25% improvement in 4 measures) were also better in the GLA treatment group (14 of 22 patients versus 4 of 19 in the placebo group; P = 0.015). During the second 6 months, both groups exhibited improvement in disease activity. Thus, patients taking GLA during the entire study showed progressive improvement during the second 6 months. In this group, 16 of 21 patients showed meaningful improvement at 12 months compared with study entry.Conclusion. GLA at doses used in this study is a well‐tolerated and effective treatment for active RA. GLA is available as a component of several plant seed oils and is usually taken in far lower doses than were used in this trial. It is not approved in the United States for the treatment of any condition, and should not be viewed as therapy for any disease. Further controlled studies of its use in RA are warranted.
Low‐dose corticosteroids in rheumatoid arthritis. A meta‐analysis of their moderate‐term effectiveness
Authors: Saag Kenneth G. , Criswell Lindsey A. , Sems Kelly M. , Nettleman Mary D. , Kolluri Sheela 
Published: February 2007

AbstractObjective. To perform a systematic literature review and meta‐analysis of the effectiveness of low‐dose corticosteroids in the treatment of rheumatoid arthritis (RA).Methods. After identifying all relevant studies meeting preselected inclusion criteria, we performed 2 meta‐analyses. First, we compared the effectiveness of prednisone to placebo and active drug controls (aspirin, chloroquine, or deflazacort) using standard meta‐analysis methods for continuous data. Then, to compare the relative effectiveness of prednisone to second‐line agents, we used methods similar to prior meta‐analyses of second‐line agents for RA treatment. Outcomes assessed were the number of tender and swollen joints, grip strength, and the erythrocyte sedimentation rate (ESR).Results. Very few studies directly assessed the effectiveness of corticosteroids for RA treatment, and many were of poor methodologic quality. Only 9 of 34 studies identified by our search met criteria for inclusion. The results of our standard meta‐analysis indicated that corticosteroids appeared to be more effective than either placebo or active drug controls in improving most conventional outcome measures (effect size 0.90 for the number of tender joints, 1.05 for the number of swollen joints, and 1.20 for the ESR). In our second comparative meta‐analysis, corticosteroids were nearly equivalent to second‐line agents previously examined in meta‐analyses (combined effect size 0.82).Conclusion. Based on the limited data available, during moderate‐term treatment periods averaging slightly over 7 months, corticosteroids appeared to be as effective or more effective than alternative therapies in improving several common RA disease activity measures.
Ribosomal P autoantibodies in systemic lupus erythematosus. Frequencies in different ethnic groups and clinical and immunogenetic associations
Authors: Arnett Frank C. , Reveille John D. , Moutsopoulos Haralampos M. , Georgescu Liviu , Elkon Keith B. 
Published: February 2007

AbstractObjective. To determine the frequencies and clinical associations of antiribosomal P antibodies (anti‐P) in a large multiethnic cohort of patients with systemic lupus erythematosus (SLE), and to assess whether anti‐P was associated with any major histocompatibility complex (MHC) class II alleles or shared amino acid sequences.Methods. Sera from 394 SLE patients were studied for anti‐P using an enzyme‐linked immunosorbent assay, and MHC class II alleles (HLA‐DRB1, DQA1, and DQB1) were determined by DNA oligotyping.Results. Anti‐P antibodies were found in 13‐20% of patients in the majority of ethnic groups, but were perhaps more frequent in Chinese patients (36%) and less common in Bulgarian patients (6%). Neuropsychiatric lupus (psychosis and/or depression) was significantly associated with anti‐P. The HLA‐DR2, DQ6 haplotypes DRB1*1501 or *1503, DQA1*0102, and DQB1*0602 were increased in anti‐P‐positive whites, blacks, and Mexican Americans. The HLA‐DQB1*0602 allele showed the strongest association with anti‐P when these 3 ethnic groups were combined and compared with both race‐matched anti‐P—negative SLE patients and normal controls. The HLA‐DQ8 specificity (DQB1*0302) was increased both in whites and in Mexican‐Americans with anti‐P who were negative for HLA‐DQB1*0602, and perhaps also increased in Greeks, but not in blacks, in whom HLA‐DQB1*0301 was increased. A shared amino acid sequence in HLA‐DQB1 (at position 26 of leucine and position 30 of tyrosine) was strongly associated with anti‐P positivity (70%) versus anti‐P negativity (42%) across ethnic lines.Conclusion. The anti‐P response in SLE patients, occurring in ∼ 15% of patients, was strongly influenced by certain MHC class II alleles and was correlated with diffuse neuropsychiatric dysfunction.
Impaired recovery and cytolytic function of CD56+T and non—T cells in systemic lupus erythematosus following in vitro polyclonal T cell stimulation. Studies in unselected patients and monozygotic disease‐discordant twins
Authors: Stohl William , Elliott Julie E. , Hamilton Ann S. , Deapen Dennis M. , Mack Thomas M. , Horwitz David A. 
Published: February 2007

AbstractObjective. To determine whether there is impaired generation and cytolytic function of CD56+ T cells and non‐T cells in human systemic lupus erythematosus (SLE).Methods. Peripheral blood mononuclear cells (PBMC) were obtained from 73 patients with SLE, 39 normal controls, and 9 pairs of monozygotic (MZ) twins discordant for SLE. PBMC were stimulated with anti‐CD3 monoclonal antibody, maintained in interleukin‐2, and assayed for percentages of total CD56+ cells and CD56+ T cells by flow cytometry, and for cytolytic activity against 51Cr‐labeled Daudi target cells.Results. Despite normal total cell expansion, the percentages of recovered CD56+ T cells and total CD56+ cells were 1.6‐fold and 1.8‐fold lower, respectively, in patients with SLE compared with normal controls (P = 0.011 and P < 0.001, respectively). Cytolytic activities of isolated total CD56+ cells and CD56+ T cells and were also reduced in patients with SLE compared with normal controls (P = 0.033). These defects associated with SLE were independent of disease activity and immunosuppressive medications, and they reflected impaired maturation of cytolytic effector cells rather than a deficiency in precursor cell number. In MZ twins discordant for SLE, recovered percentages of CD56+ cells and cytolytic responses were very low in 4 of 8 and 6 of 9 co‐twins with SLE, respectively. Cell‐mixing experiments with the PBMC of the MZ twins demonstrated that the E+ cell fractions (containing all T cells and CD56+ non‐T cells) from the co‐twins with SLE had decreased ability to generate cytolytic activity compared with the corresponding E+ cell fractions from the healthy co‐twins. However, recovered percentages of CD56+ cells and non‐T cells and cytolytic responses were also depressed in 4 of 8 and 4 of 9 healthy co‐twins, respectively.Conclusion. Impaired CD56+ T cell and non‐T cell responses are a feature of SLE and may antedate the onset of clinical disease.
Recombinant human osteogenic protein 1 is a potent stimulator of the synthesis of cartilage proteoglycans and collagens by human articular chondrocytes
Authors: Flechtenmacher Johannes , Huch Klaus , Thonar Eugene J.‐M. A. , Mollenhauer Juergen A. , Davies Sherri R. , Schmid Thomas M. , Puhl Wolfhart , Sampath T. Kuber , Aydelotte Margaret B. , Kuettner Klaus E. 
Published: February 2007

AbstractObjective. To study the effects of recombinant human osteogenic protein‐1 (rHuOP‐1; bone morphogenetic protein‐7) on proteoglycan and collagen synthesis by human articular chondrocytes.Methods. Articular chondrocytes from fetal, adolescent, and adult human donors were cultured in alginate beads for 4 days in a mixture of Ham's F‐12, Dulbecco's modified Eagle's medium, 10% fetal bovine serum (FBS), then for an additional 3‐10 days in the presence and absence of rHuOP‐1, with and without FBS. Chondrocyte synthetic activity was measured as the amount of incorporation of 35S‐sulfate into proteoglycans and 3H‐proline into hydroxyproline. Sieve chromatography and sodium dodecyl sulfate‐polyacrylamide gel electrophoresis were performed to identify specific proteoglycans and collagens.Results. Recombinant human OP‐1 markedly stimulated the synthesis of proteoglycans (mostly aggrecan) and collagens (predominantly type II) by all chondrocyte preparations. This did not require the presence of FBS and was associated with continued expression of the chondrocyte phenotype.Conclusion. Recombinant human OP‐1 is a more potent stimulator of the synthesis of cartilage‐specific molecules by human articular chondrocytes than are other factors tested for comparison, including TGFβ1 and activin A.
Effects of nitric oxide on chondrocyte migration, adhesion, and cytoskeletal assembly
Authors: Frenkel Sally R. , Clancy Robert M. , Ricci John L. , di Cesare Paul E. , Rediske John J. , Abramson Steven B. 
Published: February 2007

AbstractObjective. The migration of cells of chondrocyte lineage is believed to play a role in cartilage growth and repair. The present study examined 1) whether chondrocytes are capable of migration in vitro; and 2) the effects of nitric oxide (NO) on chondrocyte migration, adhesion, and cytoskeletal assembly.Methods. Chondrocyte migration was evaluated by 2 assays: 1) “centrifugal” migration within a 3‐dimensional collagen matrix (dot culture); and 2) directed migration under agarose in response to bone morphogenetic protein. To assess the effects of NO, chondrocytes were treated with either exogenous NO (S‐nitrosoglutathione [SNO‐GSH]) or a mixture of cytokines known to induce endogenous NO production. The effects of NO on chondrocyte adhesion to fibronectin‐coated surfaces, as well as on actin polymerization (determined by indirect immunofluorescence), were also examined.Results. The capacity of chondrocytes to migrate was demonstrated both by the dot culture and by agarose methods. Both SNO‐GSH and endogenous NO induced by cytokines inhibited this migration. Exposure to NO also inhibited attachment of chondrocytes to fibronectin and disrupted assembly of actin filaments. These effects of SNO‐GSH and cytokine‐induced NO production were reversed in the presence of hemoglobin and the NO synthase inhibitor NG‐monomethyl arginine, respectively.Conclusion. NO interferes with chondrocyte migration and attachment to fibronectin, an extracellular matrix protein, probably via effects on the actin cytoskeleton. These effects of NO may result in impairment of cartilage repair, by interfering with the extracellular matrix regulation of chondrocyte function.
Behçet‐type vasculopathy in a patient without the diagnostic features of Behçet disease
Authors: Golden Brian D. , Goel Archana , Mitnick Hal J. 
Published: February 2007

AbstractBehçet's disease is a multisystem inflammatory disorder which may involve the vascular system. The vasculopathy of Behçet's disease is distinctive among the vasculitides in that it involves both arteries and veins, and vessels of all sizes. Most published diagnostic criteria for Behçet's disease include the classic triad of orogenital ulceration and ocular inflammation. In this report, we describe a patient who had a vasculopathy fitting the Behçet's disease type, but who lacked the other characteristic or diagnostic features of Behçet's disease. This case illustrates an unusual presentation and natural history of a complex vasculitic disease.
Shift toward T lymphocytes with a T helper 1 cytokine‐secretion profile in the joints of patients with rheumatoid arthritis
Authors: Dolhain Radboud J. E. M. , van der Heiden Annette N. , ter Haar Natalja T. , Breedveld Ferdinand C. , Miltenburg André M. M. 
Published: February 2007

AbstractObjective. To investigate whether T cells in the inflamed joints of patients with rheumatoid arthritis (RA) preferentially produce the T helper 1 (Th1) cytokines, interferon‐γ (IFNγ) and interleukin‐2 (IL‐2), or the Th2 cytokine, IL‐4, when compared with corresponding peripheral blood—derived T cells.Methods. Synovial fluid mononuclear cells (SFMC) and corresponding peripheral blood mononuclear cells (PBMC) from 10 patients with RA were analyzed, either directly or after in vitro stimulation, for the intracellular presence of Th1 and Th2 cytokines. The amount of secreted cytokine in the cell culture supernatants was measured by enzyme‐linked immunosorbent assay (ELISA).Results. IFNγ‐containing cells were detected in the unstimulated SFMC, but not in the PBMC, of 3 patients with RA. Cells positive for IL‐2 or IL‐4 were not detected in the unstimulated samples. Following stimulation, the mean percentage of cells containing Th1 cytokines was significantly increased in the SFMC compared with the PBMC; no differences were found in the mean percentage of IL‐4—containing cells. A comparable shift toward Th1 cytokines was observed when the amount of secreted cytokine was determined by ELISA.Conclusion. A shift toward T cells with a Th1 cytokine profile was observed in the joints of patients with RA. Since an imbalance between Th1 and Th2 cells is thought to be of pathogenic significance, this finding might have implications for the development of new therapies for RA.