bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of the transcription factor nuclear factor‐κB in human inflamed synovial tissue
Authors: Marok R. , Winyard P. G. , Coumbe A. , Kus M. L. , Gaffney K. , Blades S. , Mapp P. I. , Morris C. J. , Blake D. R. , Kaltschmidt C. , Baeuerle P. A. 
Published: February 2007

AbstractObjective. The transcription factor–κB (NF‐κB) has been implicated in the inflammatory response and is known to be activated by a process involving reactive oxygen intermediates. The purpose of the present study was to demonstrate the presence and distribution of activated NF‐κB in synovium samples from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and from autopsy subjects with no known history of arthritis.Methods. Immunohistochemical staining was performed using both polyclonal and monoclonal “activity‐specific” antibodies to the Rel‐A (p65) subunit of NF‐κB (anti‐Rel‐A nuclear location sequences). Histologic features of inflammation were also scored.Results. Both antibodies demonstrated positive staining of synovial tissue, with a cellular distribution that was nuclear. The staining was associated with specific cell types within the tissue, in particular, type A synoviocytes and vascular endothelium. Notably, lymphoid aggregates were unstained. Using the monoclonal antibody, a further study was carried out to investigate the distribution of staining in tissues from patients with different disease activities and clinical diagnoses, as well as in normal control tissue obtained at autopsy. Patients with acute RA more commonly showed vessel staining (P = 0.05) and, conversely, showed less frequent staining of the synovial lining (P < 0.005) compared with OA patients. Synovial tissue from controls exhibited either no staining or only weak staining in the synovial lining.Conclusion. The activation of NF‐κB in vascular endothelium and type A synovial lining cells is a feature of synovial tissue from both RA and OA patients. The distribution of this staining appears to be related to the clinical diagnosis.
Reduction in long‐term disability in patients with rheumatoid arthritis by disease‐modifying antirheumatic drug–based treatment strategies
Authors: Fries James F. , Williams Catherine A. , Morfeld Dianne , Singh Gurkirpal , Sibley John 
Published: February 2007

AbstractObjective. Therapeutic strategies for rheumatoid arthritis (RA) have been evolving from the traditional “pyramid” approach toward one based upon early and sustained use of disease‐modifying antirheumatic drugs (DMARDs), in the hope of improving long‐term health outcomes. However, few data to have been presented to document the effects of this approach. We sought to directly assess associations between consistent DMARD use and long‐term functional outcomes.Methods. We studied 2,888 RA patients who were followed up prospectively for up to 20 years (average 9 years) at 8 databank centers. The independent variable was the proportion of patient encounters that resulted in treatment with ⩾1 DMARD (hydroxychloroquine, sulfasalazine, auranofin, intramuscular gold, D‐penicillamine, methotrexate, and/or azathioprine). The dependent variable was each patient's last recorded Disability Index value from the Health Assessment Questionnaire (HAQ).Results. Increased DMARD use was strongly associated with better long‐term Disability Index values (P < 0.0001). The association was strengthened when restricted to more seriously affected (rheumatoid factor (RF)–positive) patients. The magnitude of the effect, unadjusted, was a difference of 0.53 HAQ Disability units (scale 0–3) between 100% DMARD use and 0%. Correlation coefficients ranged up to 0.26. Effects were similar for all disease duration periods (0–4, 5–9, 10–14, 15–19, and 20+ years). “Control” correlations, with variables computed to represent the proportion of time in which patients were taking either nonsteroidal antiinflammatory drugs or prednisone, failed to show positive associations. A multiple linear regression model, which controlled for age, disease duration, sex, RF positivity, proportion of visits under a prednisone regimen, and initial disability level, included the proportion of time in which patients were taking DMARDs (P < 0.0001), with a model R2 of 0.54. These results were obtained despite an adverse selection bias in which more severely affected individuals were given DMARDs more frequently, and despite absence of data on drug use early in the disease course of many patients. Thus, these results, which suggest up to a 30% reduction in longterm disability with consistent DMARD use, are most likely conservative.Conclusion. An association between consistent DMARD use and improvement in long‐term functional outcomes in RA is supported by these data.
A prospective long‐term study of fibromyalgia syndrome
Authors: Kennedy Maura , Felson David T. 
Published: February 2007

AbstractObjective. To ascertain the long‐term natural history of fibromyalgia syndrome (FMS).Methods. Patients with a history of FMS, seen in an academic rheumatology referral practice, were originally surveyed soon after onset of symptoms, and then were reinterviewed 10 years later in a prospective followup cohort study. A validated telephone survey was administered that inquired into current symptoms, medical care and treatments used, and work disability. The results were compared with the prior surveys.Results. Of the original 39 patients, there were 4 deaths. Of the remaining 35 patients, 29 (83%) were reinterviewed. Mean age at current survey was 55 years, and mean duration of symptoms was 15.8 years. All patients had persistence of some fibromyalgia symptoms, although almost half (48%) had not seen a doctor for them in the last year. Moderate to severe pain or stiffness was reported in 55% of patients; moderate to a lot of sleep difficulty was noted in 48%; and moderate to extreme fatigue was noted in 59%. These symptoms showed little change from earlier surveys. In 79% of patients, medications were still being taken to control FMS symptoms. Despite continuing symptoms, 66% of patients reported that FMS symptoms were a little or a lot better than when first diagnosed. Fifty‐five percent of patients said they felt well or very well in terms of FMS symptoms, and only 7% felt they were doing poorly. With the exception of sleep trouble, which was persistent, baseline survey symptoms correlated poorly with symptoms at the 10‐year followup.Conclusion. FMS symptoms last, on average, at least 15 years after illness onset. However, most patients experience some improvement in symptoms after FMS onset.
Coexistence of two antisynthetases in a patient with the antisynthetase syndrome
Authors: Gelpí Carmen , Kanterewicz Eduardo , Gratacos Jordi , Targoff Ira N. , Rodriguez‐Sanchez José Luis 
Published: February 2007

AbstractWe describe the immunologic findings in a patient with the antisynthetase syndrome characterized by prominent arthritis, lung fibrosis, and subclinical myositis. At disease onset and during the followup, this patient's serum showed 2 different subsets of antisynthetase autoantibodies: anti–Jo‐1, which reacted with histidyl–transfer RNA (tRNA) synthetase by immunoblot and inhibited its enzymatic function; and anti‐OJ, which immunoprecipitated the multi‐enzyme complex of synthetases, and reacted with lysyl‐tRNA synthetase by immunoblot. This is the first report of anti–Jo‐1 and another antisynthetase antibody being found together in the same patient.
Mixed monoclonal cryoglobulinemia and monoclonal rheumatoid factor cross‐reactive idiotypes as predictive factors for the development of lymphoma in primary Sjögren's syndrome
Authors: Tzioufas Athanasios G. , Boumba Dimitra S. , Skopouli Fotini N. , Moutsopoulos Haralampos M. 
Published: February 2007

AbstractObjective. To prospectively investigate whether mixed monoclonal cryoglobulinemia (MMC) and monoclonal rheumatoid factor (mRF)–associated crossreactive idiotypes (CRI) serve as predictive factors for the development of lymphoma in patients with primary Sjögren's syndrome (SS).Methods. One hundred three consecutive patients with primary SS were evaluated from 1986 to 1991. In all patients, the amount of cryoglobulin was measured by ultraviolet absorption at 280 nm and 260 nm. The type of cryoglobulinemia was identified by agarose gel electrophoresis, combined with immunofixation. Sera from all patients were evaluated by enzyme‐linked immunosorbent assay, using the corresponding monoclonal or polyclonal antibodies, for the presence of immunoglobulins bearing the idiotypes 17109 (VκIIIb associated), G‐6 (VH1 associated), and 3rd SS (a rabbit polyclonal antibody raised against the Fab fragment of an IgMκ mRF from a patient with primary SS). Data analysis was performed by logistic regression.Results. Eighteen of the patients with primary SS (17.4%) had MMC during the first evaluation. There was a statistically significant correlation between the presence of MMC and a higher prevalence of autoantibodies to Ro/SS‐A and La/SS‐B, as well as extraglandular manifestations. During a 5‐year period, 7 patients developed lymphoma. Six of the 7 (86%) had MMC before the appearance of lymphoma, compared with 12 of 96 (12.4%) of the remainder (r = 0.421, P < 0.0009). Patients who developed lymphoma had higher amounts of cryoglobulin than those who did not (mean ± SD 53.4 ± 44.7 mg/dl versus 26.8 ± 20.6 mg/dl). CRIs 17109 and G‐6 were also correlated with lymphoma development (r = 0.321, P < 0.006 and r = 0.22, P < 0.03, respectively). For both CRIs, this correlation was dependent on the presence of MMC, since a stepwise multiple comparison analysis revealed that their individual significance was abolished when their correlation with lymphoma in association with MMC was assessed.Conclusion. The determination of MMC can be used as a laboratory predictive factor for lymphoma development in primary SS. CRIs 17109 and G‐6 may also be used to predict lymphoma development, especially when the monoclonal component is absent.
Increased expression of human thioredoxin/adult T cell leukemia–derived factor in Sjögren's syndrome
Authors: Saito Ichiro , Shimuta Misa , Terauchi Kumiko , Tsubota Kazuo , Yodoi Junji , Miyasaka Nobuyuki 
Published: February 2007

AbstractObjective. To determine the involvement of human thioredoxi/adult T cell leukemia–derived factor (TRX/ADF) in Sjögren's syndrome (SS) and the correlation with Epstein‐Barr virus (EBV).Methods. Indirect immunohistochemical techniques and reverse transcriptase polymerase chain reaction were utilized to analyze TRX/ADF expression and the presence of EBV, using 6 normal tissues and 23 surgical specimens. The kinetics of expression of TRX/ADF induced by EBV was examined in vitro with peripheral blood B cells from EBV‐seronegative donors.Results. Marked expression of TRX/ADF was found in the infiltrating B cells and the epithelial cells of salivary gland tissues from patients with SS (11 of 12 cases), but not in those from patients with other salivary gland inflammatory conditions (0 of 11 cases) or those of normal individuals (0 of 6 cases). In immunohistologic analyses, a striking topographic correlation between TRX/ADF and EBV was found. The coexistence of TRX/ADF messenger RNA and EBV DNA was detected by polymerase chain reaction (r = 0.75, P < 0.01). Peripheral blood B cells from EBV‐seronegative donors showed de novo synthesis of TRX/ADF following in vitro infection with EBV. EBV‐infected B cell lines all expressed TRX/ADF. TRX/ADF was not detected in non‐EBV‐infected cells. Tumors in SCID mice reconstituted with mononuclear cells of salivary glands from SS patients, which were composed of human B cells carrying EBV DNA, were positive for TRX/ADF.Conclusion. These findings suggest that TRX/ADF expression closely reflects the intracellular event of EBV reactivation in SS. This is also the first report to show the ectopic in vivo expression of TRX/ADF in human autoimmune disease.
Anticytokine treatment of established type II collagen–induced arthritis in DBA/1 mice: A comparative study using anti‐TNFα, anti–IL‐1α/β, and IL‐1Ra
Authors: Joosten Leo A. B. , Helsen Monique M. A. , van de Loo Fons A. J. , van den Berg Wim B. 
Published: February 2007

AbstractObjective. To examine the role of tumor necrosis factor α (TNFα), interleukin‐1α (IL‐1α), and IL‐1β in collagen‐induced arthritis (CIA), immediately after onset and during the phase of established arthritis.Methods. Male DBA/1 mice with collagen‐induced arthritis were treated with antibodies against murine TNFα and IL‐1α/β at different time points of the disease. IL‐1 receptor antagonist (IL‐1Ra) was administered using Alzet osmotic minipumps. The effect of anticytokine treatment was monitored by visual scoring. Histology and cytokine reverse transcription polymerase chain reaction (RT‐PCR) analyses were performed at the end of the treatment period.Results. Anti‐TNFα treatment showed efficacy shortly after onset of the disease, but had little effect on fully established CIA. Histologic analysis after early treatment revealed that anti‐TNFα significantly reduced joint pathology, as determined by infiltration of inflammatory cells and cartilage damage. Anti–IL‐1α/β treatment ameliorated both early and full‐blown CIA. This clear suppression of established arthritis was confirmed by administration of high doses of IL‐1Ra. Dose‐response experiments showed that a continuous supply of 1 mg/day was needed for optimal suppression. Histologic analysis showed markedly reduced cartilage destruction both in the knee and the ankle joints. Autoradiography demonstrated full recovery of chondrocyte synthetic function of articular cartilage. In addition, we found that the IL‐1β isoform plays a dominant role in established CIA. Profound suppression of CIA was observed with anti–IL‐1β, although elimination of both IL‐1α and IL‐1β still gave better protection. Analysis of messenger RNA with RT‐PCR revealed that IL‐1β was highly upregulated in synovium and cartilage at late stages of CIA, whereas anti–IL‐1β treatment markedly reduced IL‐1β message in the synovium.Conclusion. The present study identified different TNFα/IL‐1 dependencies in various stages of CIA and revealed that blocking of TNFα does not necessarily eliminate IL‐1. Continuous, high doses of IL‐1Ra are needed to block CIA.
An epitope on Ki antigen recognized by autoantibodies from lupus patients shows homology with the sv40 large t antigen nuclear localization signal
Authors: Takasaki Yoshinari , Yano Tetsuro , Hirokawa Kaoru , Takeuchi Ken , Ando Soichiro , Takahashi Toshimitsu , Shimada Kohichiro , Hashimoto Hiroshi 
Published: February 2007

AbstractObjective. Epitopes on Ki antigen were analyzed using synthetic peptides, including KILT, a 16‐mer peptide with an amino acid sequence homologous to the SV40 large T antigen nuclear localization signal (SV40 T NLS).Methods. In addition to KILT, 4 synthetic peptides, all potential epitopes on Ki antigen according to computer analysis, were prepared and tested for reactivity with 49 anti‐Ki–positive lupus sera by enzyme‐linked immunosorbent assay.Results. Eighteen sera reacted with KILT, but not with other peptides. The reaction of anti‐Ki sera with KILT was specifically inhibited by recombinant Ki antigen. Eight of 49 anti‐Ki sera reacted with a 7‐mer synthetic peptide of SV40 T NLS, and the reaction was specifically inhibited by KILT.Conclusion. The 16‐mer Ki peptide containing the sequence homologous to the SV40 T NLS is one of the antigenic epitopes recognized by anti‐Ki antibodies in lupus sera.
Oligoclonal T cell proliferation in patients with rheumatoid arthritis and their unaffected siblings
Authors: Waase Inge , Kayser Corinna , Carlson Paula J. , Goronzy Jörg J. , Weyand Corelia M. 
Published: February 2007

AbstractObjective. To analyze whether patients with rheumatoid arthritis (RA) have an intrinsic defect in T cell proliferation and survival, possibly contributing to the infiltration of the synovial membrane with CD4+ T cells.Methods. Fifteen patients with seropositive RA, 11 patients with psoriatic arthritis, 20 normal controls, and 9 affected and 13 unaffected siblings from 7 multiplex families with RA were analyzed for clonal proliferation. To investigate this clonal T cell proliferation, CD4+ T cells were purified from peripheral blood and synovial fluid by magnetic bead separation. T cell receptor (TCR) β‐chain sequences were amplified by reverse transcriptase–polymerase chain reaction, using TCR BV and BJ gene segment–specific primer sets. Clonally expanded T cell specificities were identified by size fractionation and sequencing of the amplified product.Results. All RA patients carried clonally expanded CD4+ T cells in the peripheral blood compartment. Such expanded CD4+ T cell clonotypes were only infrequently observed both in normal individuals (P < 0.0001) and in patients with psoriatic arthritis (P = 0.004). Lymphoproliferation of selected CD4+ T cells was shared by affected and unaffected siblings from RA multiplex families (P = 0.005 and P = 0.0003, respectively, compared with normal controls). Expanded clonotypes persisted for several years and contributed to the T cell infiltrate in the joint. Clonal T cell proliferation involved a diverse spectrum of TCR molecules.Conclusion. RA patients have an abnormality in the homeostasis of CD4+ T cells, characterized by the emergence of clonally proliferating populations. The presence of clonal outgrowth of selected CD4+ T cell specificities in unaffected siblings of RA patients suggests that oligoclonality of CD4+ T cells is inherited and is a risk factor for, rather than a result of, synovial inflammation.
Expression and functional expansion of fibroblast growth factor receptor T cells in rheumatoid synovium and peripheral blood of patients with rheumatoid arthritis
Authors: Byrd Victor , Zhao Xiao‐Ming , McKeehan Wallace L. , Miller Geraldine G. , Thomas James W. 
Published: February 2007

AbstractObjective. Rheumatoid arthritis (RA) is an inflammatory disorder of the diarthrodial joints, characterized by fibroblast proliferation, angiogenesis, and perivascular CD4+ T cell infiltration. The present study examined the interactions between fibroblast growth factor–1 (FGF‐1) and T cells.Methods. Synovial tissues from patients with RA or noninflammatory arthritis were examined for the expression of FGF‐1 and its receptor, FGFR‐1, by immunohistology and reverse transcriptase–polymerase chain reaction. Functional assays were used to detect enrichment of FGF‐1–responsive peripheral CD4+ T cells in RA.Results. FGF‐1 is abundantly expressed by rheumatoid synovium. Enhanced expression of its receptor, FGFR‐1, was found in perivascular CD4+ T cells. In addition, T cells that are activated by FGF‐1 are increased in the peripheral blood of patients with RA, as compared with other inflammatory conditions.Conclusion. The increased frequency of peripheral T cells that respond to FGF‐1 in RA is consistent with expansion of FGFR‐1‐expressing T cells in the rheumatoid synovium.
Inhibition of synoviocyte collagenase gene expression by adenosine receptor stimulation
Authors: Boyle David L. , Sajjadi Fereydoun G. , Firestein Gary S. 
Published: February 2007

AbstractObjective. To characterize the regulation of matrix metalloproteinases (MMPs) by adenosine.Methods. Cultured fibroblast‐like synoviocytes (FLS) were stimulated with interleukin‐1 (IL‐1) in the presence or absence of adenosine receptor agonists. Immunoreactive MMPs were measured using specific enzyme‐linked immunosorbent assays, and gene expression was assessed by Northern blot analysis.Results. The nonselective adenosine receptor agonist 5′‐N‐ethylcarboxamidoadenosine (NECA) decreased collagenase production by IL‐1‐stimulated synoviocytes from 196 ± 28 ng/ml (mean ± SEM) to 66 ± 9 ng/ml (P < 0.001). There was minimal effect on stromelysin production (decrease from 107 ± 16 ng/ml to 97 ± 15 ng/ml). Selective adenosine receptor agonists implicated the A2b adenosine receptor in this activity, and reverse transcriptase–polymerase chain reaction studies confirmed that FLS express this receptor. Northern blot analysis demonstrated that the mechanism of action was pre‐translational since NECA decreased collagenase, but not stromelysin or tissue inhibitor of metalloproteinases 1 (TIMP‐1), messenger RNA levels. Cyclic AMP levels were increased by NECA, and a direct adenylate cyclase activator (forskolin) also suppressed collagenase gene expression. These data suggest that cAMP mediates the inhibitory effect of NECA on collagenase production.Conclusion. Stimulation of the A2b receptor on FLS decreases collagenase gene expression, with little or no effect on stromelysin and TIMP‐1. The combination of antiinflammatory and MMP‐regulating properties of adenosine of adenosine‐regulating agents suggests that treatment based on this approach might be useful in rheumatoid arthritis.
Clinical correlations with HLA type in Japanese patients with connective tissue disease and anti–U1 small nuclear RNP antibodies
Authors: Kuwana Masataka , Okano Yutaka , Kaburaki Junichi , Inoko Hidetoshi 
Published: February 2007

AbstractObjective. To elucidate the roles of HLA genes in the clinical presentation of patients with connective tissue disease and serum anti–U1 small nuclear RNP antibody.Methods. HLA class I antigens and HLA class II alleles were determined in 43 Japanese patients with anti–U1 RNP antibody alone, by microcytotoxicity testing and DNA typing, respectively. Prospectively recorded clinical and laboratory features were analyzed in relation to HLA class I and class II types.Results. DQB1*0303 was associated with lupusrelated symptoms including fever, malar rash, oral ulcers, hypocomplementemia, and high‐titer anti–double‐stranded DNA antibody. Other HLA–clinical associations included DR2 with pleuritis, DR4 with hand swelling, and DRB1*0405 with arthritis.Conclusion. These HLA–clinical associations explain, in part, the heterogeneous clinical presentation in patients with anti–U1 RNP antibody.
Normal expression of type 1 insulin‐like growth factor receptor by human osteoarthritic chondrocytes with increased expression and synthesis of insulin‐like growth factor binding proteins
Authors: Tardif Ginette , Reboul Pascal , Pelletier Jean‐Pierre , Geng Changshan , Cloutier Jean‐Marie , Martel‐Pelletier Johanne 
Published: February 2007

AbstractObjective. Our previous research demonstrated that, in contrast to normal chondrocytes, human osteoarthritic (OA) chondrocytes were hyporesponsive to stimulation by insulin‐like growth factor 1 (IGF‐1). The aim of the present investigation was to examine whether this finding was due to an alteration in the level of IGF receptors (IGFRs) and/or IGF binding proteins (IGFBP).Methods. A quantitative reverse transcriptase polymerase chain reaction technique (RT‐PCR) was used to measure the type 1 IGFR messenger RNA (mRNA) level, and Northern blotting was used to measure type 2 IGFR and IGFBP mRNA levels. Western immunoblotting was used to identify and measure IGFBP levels.Results. There were similar levels of type 1 IGFR mRNA in normal and OA chondrocytes. The level of type 2 IGFR mRNA, in which an increased amount of which can interfere with the biologic effects of IGF‐1, was lower in OA chondrocytes compared with normal chondrocytes. Articular chondrocytes produced IGFBP‐2, IGFBP‐3, and IGFBP‐4, and OA chondrocytes secreted and expressed higher amounts than did normal chondrocytes. There was also an increased level of IGFBP‐3 in the OA chondrocyte lysates. IGFBPs 1, 5, and 6 were not detectable.Conclusion. OA chondrocytes synthesize and express a larger amount of 3 IGFBPs. This observation, along with a lack of detectable change in type 1 IGFR mRNA level, suggests that the hyporesponsiveness of OA chondrocytes to IGF‐1 might implicate the involvement of IGFBPs in this pathologic process.