bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clonal expansion of mycobacterial heat‐shock protein–reactive T lymphocytes in the synovial fluid and blood of rheumatoid arthritis patients
Authors: Celis Linda , Vandevyver Caroline , Geusens Piet , Dequeker Jan , Raus Jef , Zhang Jingwu 
Published: February 2007

AbstractObjective. To examine the reactivity pattern and T cell receptor (TCR) characteristics of mycobacterial heat‐shock protein 65 (hsp65)‐reactive T cells generated from paired synovial fluid (SF) and peripheral blood (PB) samples obtained from rheumatoid arthritis (RA) patients and from healthy subjects.Methods. The reactivity pattern of hsp65‐reactive T cell clones generated under limiting‐dilution conditions was analyzed in 3H‐thymidine incorporation assays. The TCR variable regions of these hsp65‐reactive T cells were characterized by polymerase chain reaction with TCR AV‐ and BV‐specific primers and by DNA sequence analysis of the third complementarity‐determining region (CDR3).Results. The hsp65‐reactive T cells derived both from RA patients and controls preferentially recognized the 1–170 and 303–540 regions of hsp65 and did not cross‐react with human hsp60. The hsp65‐reactive T cell clones derived from RA patients displayed a restricted TCR AV and BV gene usage, which can be attributed to the limited clonal origin(s) of the independent T cell clones, as evidenced by CDR3 sequence analysis. These clonally expanded T cells were found in both PB and SF and in different inflamed joints of RA patients.Conclusion. Our study suggests that there is in vivo clonal activation and expansion of mycobacterial hsp65‐reactive T cells in patients with RA.
The effects of functional suppression of a membrane‐bound complement regulatory protein, CD59, in the synovial tissue in rats
Authors: Mizuno Masashi , Nishikawa Kazuhiro , Goodfellow Rhian M. , Piddlesden Sara J. , Morgan B. Paul , Matsuo Seiichi , Matsuo Seiichi 
Published: February 2007

AbstractObjective. To investigate the roles of CD59 in the synovial tissue by functional suppression of CD59.Methods. Rats treated with cobra venom factor to deplete complement or untreated rats were injected intraarticularly with 0.3 mg of the F(ab′)2 fraction of a monoclonal antibody, 6D1, that inhibits the function of rat CD59. The circumference of knee joints was measured, and histologic changes in the synovium were studied.Results. Joint swelling, thickening of the synovial tissues, infiltration of inflammatory cells into the synovium, and deposition of membrane attack complex (MAC) on the synovial surface were observed after intraarticular injection of 6D1. The inflammatory reaction reached its peak at 24 hours after injection, and finally subsided to normal within 3 days. It was suggested that functional suppression of CD59 in the synovium induced MAC formation followed by synovitis. Serum complement depletion did not completely suppress this reaction. This indicates that complement existing in the joint space is important for the formation of MAC on the synovial surface and for induction of synovitis.Conclusion. The membrane‐bound complement regulatory protein, CD59, plays a key role in the protection of joints against MAC‐mediated synovial injury and in maintaining the normal integrity of the joint.
Surgical management of calcinosis cutis universalis in systemic lupus erythematosus
Authors: Cousins Marleen A. M. , Jones Daniel B. , Whyte Michael P. , Monafo William W. 
Published: February 2007

AbstractCalcinosis cutis is common in several connective tissue diseases but rare in systemic lupus erythematosus (SLE). A 43‐year‐old woman with a 12‐year history of SLE who presented with calcinosis cutis at the time of SLE diagnosis developed a large, ulcerated, draining mass on her left hip. The lesion was excised and skin was grafted, with an excellent early result. The clinical variants and mechanisms of ectopic calcification are discussed, as well as the proposed medical therapies for calcinosis cutis.
Low‐level increases in serum C‐reactive protein are present in early osteoarthritis of the knee and predict progressive disease
Authors: Spector T. D. , Hart D. J. , Nandra D. , Doyle D. V. , Mackillop N. , Gallimore J. R. , Pepys M. B. 
Published: February 2007

AbstractObjective. To examine the role of low‐grade inflammation in the etiology and progression of early osteoarthritis (OA) of the knee.Methods. We used a new, high‐sensitivity, automated monoclonal antibody immunoassay for the classic acute‐phase protein, C‐reactive protein (CRP), in serum. Anteroposterior radiographs of the knee with weight bearing were obtained on 845 women (ages 44–67) on entry into a population‐based study of OA in Chingford, North London. In those defined radiologically as “cases,” the knee radiographs were repeated after 4 years.Results. Levels of CRP were higher in 105 women with knee OA defined radiologically as Kellgren‐Lawrence grade 2+ (median 2.4 mg/liter, interquartile range [IQR] 1.0–5.1), compared with 740 women without OA (median 0.7 mg/liter, IQR 0.3–1.8) (P < 0.001). Median levels of CRP were higher in the 31 women whose disease progressed at least 1 Kellgren‐Lawrence grade (median 2.6 mg/liter, IQR 1.9–4.6), compared with the 39 whose disease did not (median 1.3 mg/liter, IQR 0.6–2.4) (P = 0.006). The significance of these differences persisted after adjustment for age, weight, height, smoking, knee pain, or injury. Classifying disease by the presence of joint space narrowing or osteophytes alone produced similar results.Conclusion. CRP levels are modestly but significantly increased in women with early knee OA, and higher levels predict those whose disease will progress over 4 years, suggesting that low‐grade inflammation may be a significant aspect of early OA and may be amenable to therapeutic intervention and secondary prevention.
Treatment of early Rheumatoid Arthritis with minocycline or placebo. Results of a Randomized, double‐blind, placebo‐controlled trial
Authors: O'Dell James R. , Haire Claire E. , Palmer William , Drymalski Walter , Wees Steven , Blakely Kent , Churchill Melvin , Eckhoff P. James , Weaver Arthur , Doud Deborah , Erikson Nils , Dietz Fred , Olson Rich , Maloley Pierre , Klassen Lynell W. , Moore Gerald F. 
Published: February 2007

AbstractObjective. To determine if minocycline is an effective therapy for seropositive rheumatoid arthritis (RA) when used within the first year of disease.Methods. The Rheumatoid Arthritis Investigational Network enrolled 46 patients with RA of <1 year duration into a 6‐month study of minocycline (100 mg twice daily) versus placebo. All patients were rheumatoid factor positive. The primary end point of the study was successful completion of 6 months of treatment with no drug toxicity while maintaining 50% improvement in composite symptoms of arthritis.Results. Eighteen of the 46 patients who were enrolled met 50% improvement criteria at 3 months, and maintained at least a 50% improvement for 6 months with no significant drug toxicity. Among them were 15 of the 23 patients (65%) treated with minocycline and 3 of 23 patients (13%) treated with placebo (P < 0.001).Conclusion. In patients with early seropositive RA, therapy with minocycline is superior to placebo.
Role of nitric oxide in Sjögren's syndrome
Authors: Konttinen Yrjö T. , Platts Louise A. M. , Tuominen Susanne , Eklund Kari K. , Santavirta Nina , Törnwall Jyrki , Sorsa Timo , Hukkanen Mika , Polak Julia M. 
Published: February 2007

AbstractObjective. To measure levels of salivary nitrite (NO2‐) and to localize nitric oxide synthases (NOS) in the labial salivary glands (LSGs) of patients with Sjögren's syndrome (SS).Methods. NO2‐ was measured by the Griess reaction. LSGs were analyzed using NADPH‐diaphorase histochemical and immunohistochemical studies to determine the constitutive NOS (neuronal [ncNOS] and endothelial [ecNOS]) and inducible NOS (iNOS) isoforms.Results. The NO2‐ concentration (mean ± SEM 307 ± 51 μM versus 97 ± 16 μM; P < 0.05) and output (166 ± 46 nmoles/minute versus 37 ± 7 nmoles/minute) were increased in SS patients compared with healthy control subjects. NADPH‐diaphorase was found in some nerve fibers and endothelial cells, and, in SS, was found in myoepithelial, acinar, and ductal epithelial cells, but in only a few inflammatory cells. In SS, ncNOS‐immunoreactive nerve fibers were sparse and ecNOS was found in a minority of the CD31‐positive vascular endothelial cells and acinar cells, whereas iNOS was localized in myoepithelial, acinar, and ductal epithelial cells, often together with tumor necrosis factor α.Conclusion. Nitrite was found in normal human saliva. NO produced by ncNOS probably acts as a non‐adrenergic, noncholinergic neurotransmitter, whereas that produced by ecNOS exerts a vasodilatory effect. SS patients had increased NO2‐ concentrations, with most of the superfluous salivary NO being produced not by the immigrant inflammatory cells, but rather, by the resident salivary gland cells. NO may contribute to inflammatory damage and acinar cell atrophy in SS.
Reduction in the incidence and severity of collagen‐induced arthritis in DBA/1 mice, using exogenous dehydroepiandrosterone
Authors: Williams Phil J. , Jones Richard H. V. , Rademacher Thomas W. 
Published: February 2007

AbstractObjective. This study examined the effect of exogenous dehydroepiandrosterone (DHEA) on the onset, incidence, and severity of collagen‐induced arthritis (CIA).Methods. DHEA was administered subcutaneously prior to arthritis induction in DBA/1 mice, and the severity of the subsequent arthritis was monitored. Serum levels of total IgG and IgG isotype‐specific anti‐murine type II collagen were measured.Results. Repeated administration of DHEA during arthritis induction delayed the onset and decreased the severity of arthritis in male and female DBA/1 mice. DHEA failed to have an observable effect on established arthritis. IgG isotype autoantibody levels were found to be decreased in the sera of DHEA‐treated mice.Conclusion. Administration of exogenous DHEA offered protection against the development of CIA. These data support the results of human studies in which low DHEA levels have been identified as a potential risk factor for the development of rheumatoid arthritis. These findings also highlight DHEA as a potential therapy worthy of further investigation.
Direct evidence of high DNA binding activity of transcription factor AP‐1 in rheumatoid arthritis synovium
Authors: Asahara Hiroshi , Fujisawa Koushi , Kobata Tetsuji , Hasunuma Tomoko , Maeda Toshiro , Asanuma Masato , Ogawa Norio , Inoue Hajime , Sumida Takayuki , Nishioka Kusuki 
Published: February 2007

AbstractObjective. To investigate the possible activation of transcription factor AP‐1 in rheumatoid arthritis (RA) and its involvement in the pathogenesis of RA.Methods. Synovial tissues and peripheral blood samples were obtained from 25 patients with RA and 5 patients with osteoarthritis (OA) during arthroplasty and synovectomy. The synovial tissue was digested with collagenase and separated into adherent and nonadherent cells by plastic‐adhesion methods. Nuclear extracts obtained from each sample were examined by electrophoretic mobility shift assay to determine the DNA binding activity of AP‐1. The expression of c‐fos and c‐jun messenger RNA (mRNA) was examined by in situ reverse transcription assay.Results. A markedly high DNA binding activity of AP‐1 was detected in the synovial tissues of RA patients, while virtually no activity or only a little activity was observed in OA patients. Following separation of adherent and nonadherent cells, the AP‐1 activity was mainly detected in adherent cells, which consisted of synovial cells and macrophages. However, the activity was significantly higher in the mononuclear cells infiltrating into RA synovium than in RA peripheral blood mononuclear cells. The high DNA binding activity of AP‐1 in RA correlated with the expression of c‐fos and c‐jun mRNA in situ. Furthermore, AP‐1 binding activity also correlated with disease activity.Conclusion. In RA synovium, AP‐1 DNA binding activity was constitutively up‐regulated. These findings suggest that AP‐1 may play an important role in the pathogenesis of RA, including synovial hyperplasia and abnormal immune responses.
Recognition of chlamydial antigen by HLA‐B27‐restricted cytotoxic T cells in HLA‐B*2705 transgenic CBA (H‐2k) mice
Authors: Kuon Wolfgang , Lauster Roland , Böttcher Ute , Koroknay Armin , Ulbrecht Matthias , Hartmann Matthias , Grolms Martina , Ugrinovic Sanja , Braun Jürgen , Weiss Elisabeth H. , Sieper Joachim 
Published: February 2007

AbstractObjective. The association of reactive arthritis (ReA) with HLA‐B27 and the presence of bacterial antigen in joints with ReA suggest that bacterial peptides might be presented by the HLA‐B27 molecule and thus stimulate CD8 T cells. This study was performed to investigate the B27‐restricted cytotoxic T lymphocyte (CTL) response to Chlamydia trachomatis, using the model of HLA‐B27 transgenic mice.Methods. CBA (H‐2k) mice homozygous for HLA‐B*2705 and human β2‐microglobulin expression were immunized with C trachomatis or with the chlamydial 57‐kd heat‐shock protein (hsp57) coupled to latex beads. Cytotoxicity of lymphocytes from in vivo—primed transgenic mice was tested against C trachomatis—infected targets. Blocking experiments were performed with monoclonal antibodies (MAb) against class I major histocompatibility complex molecules.Results. A Chlamydia‐specific lysis of both B27‐transfected and nontransfected target cells was observed. This response could be inhibited by anti‐B27 and anti‐H2 MAb. CTL from mice immunized with hsp57 were not able to lyse Chlamydia‐infected target cells, and Chlamydia‐specific CTL could not destroy targets loaded with hsp57.Conclusion. These results suggest the existence of at least 2 CTL populations in this mouse model: one recognizing peptide of bacteria‐infected cells restricted by HLA‐B*2705 and the other recognizing peptide of bacteria‐infected cells restricted by the murine H‐2Kk molecule. It does not appear that hsp57 is a major target for the CD8 T cell response directed against Chlamydia. This animal model opens the way for identifying bacterial epitopes presented by HLA‐B27, and might thus help to clarify the pathogenesis of B27‐associated diseases.
Endothelial activation in monosodium urate monohydrate crystal‐induced inflammation. In vitro and in vivo studies on the roles of tumor necrosis factor α and interleukin‐1
Authors: Chapman Peter T. , Yarwood Helen , Harrison Andrew A. , Stocker Claire J. , Jamar François , Gundel Robert H. , Peters A. Michael , Haskard Dorian O. 
Published: February 2007

AbstractObjective. There is relatively little direct evidence for the roles of interleukin‐1 (IL‐1) and tumor necrosis factor α (TNFα) in activating endothelium in vivo. The aim of this study was to use in vitro and in vivo models to investigate the contribution of these cytokines to both E‐selectin expression and the recruitment of polymor‐phonuclear cells (PMN) in monosodium urate monohydrate (MSU) crystal‐induced inflammation.Methods. MSU crystals were incubated with freshly isolated mononuclear cells, after which the harvested supernatants were tested for their ability to induce E‐selectin expression during coculture with human umbilical vein endothelial cells. Subsequent experiments were performed with the addition of neutralizing anticytokine antibodies/antisera. The role of TNFα was then studied in an MSU crystal‐induced monarthritis model, in the presence or absence of anti‐TNFα (5 mg/kg intravenously). 99mtechnetium (99mTc)‐labeled PMN cells and 111indium (111In)‐labeled anti‐E‐selectin monoclonal antibody (MAb) 1.2B6 were intravenously administered 4 hours after intraarticular injection to quantify PMN recruitment and E‐selectin expression in inflamed joints.Results. MSU crystals were a potent stimulus for IL‐1 and TNFα production by monocytes in vitro, and these cytokines fully accounted for MSU crystalstimulated, monocyte‐mediated endothelial activation. In the MSU crystal‐induced monarthritis model, TNFα blockade was very effective in suppressing both E‐selectin expression and PMN emigration into the inflamed joints, as judged by gamma‐camera image analysis and postmortem tissue counting following the intravenous injection of 99mTc‐PMN and 111In‐anti‐E‐selectin MAb.Conclusion. IL‐1 and TNFα appear to be the only factors released by monocytes following incubation with MSU crystals, which induce E‐selectin expression in vitro. Anti‐TNFα is effective in suppressing endothelial activation and PMN recruitment in vivo E‐selectin imaging can be used to assess the endothelial response to therapy and may prove useful for clinical studies.
Transglutaminase activity in aging articular chondrocytes and articular cartilage vesicles
Authors: Rosenthal Ann K. , Derfus Beth A. , Henry Lisa A. 
Published: February 2007

AbstractObjective. Transglutaminases (TGases) (E.G. 2.3.2.13) catalyze a posttranslational modification of proteins and are associated with biomineralization in growth plate cartilage. Type II TGase participates in the activation of latent transforming growth factor β (TGFß), a crucial factor for both normal cartilage mineralization and the pathologic mineralization that results in calcium pyrophosphate dihydrate (CPPD) crystal formation in aging articular cartilage. To explore a possible association between TGase levels and CPPD crystal formation in mature articular cartilage, TGase activity in articular chondrocytes from old and young pigs and in the articular cartilage vesicle (ACV) fraction of porcine articular cartilage was examined. In addition, the effects of TGase inhibitors on the production of inorganic pyrophosphate (PPi), a process necessary for CPPD crystallogenesis, were determined.Methods. TGase activity was measured with a radiometric assay in cultured articular chondrocytes from the knee joints of old (3–5 years old) and young (2–6 weeks old) pigs and in the ACVs. PPi levels were measured in chondrocyte‐conditioned media in the presence of TGase inhibitors or control compounds.Results. Levels of TGase activity in the cytosolic fraction of old chondrocytes were 7‐fold higher than those in identically cultured young chondrocytes. The mean ± SD activity level in the membrane fraction of lysed chondrocytes was 6.0 ± 0.6 units/mg protein in old articular chondrocytes and was undetectable in young chondrocytes. In ACVs, the mean ± SD TGase activity level was 1.23 ± 0.1 units/mg protein. Type II TGase protein was present in chondrocyte cytosol and in ACVs. TGase activity was increased by TGFß to 120% of control values (P < 0.01), and decreased by insulin‐like growth factor 1 to 80% of control values (P < 0.01). TGase inhibitors blocked media accumulation of PPi, an essential precursor of CPPD crystal formation, and a sensitive marker of TGFß effect.Conclusion. These data suggest a potential link between TGase activity and processes of pathologic biomineralization that result in CPPD crystal formation in aging articular cartilage.
In vivo suppression of early experimental osteoarthritis by interleukin‐1 receptor antagonist using gene therapy
Authors: Pelletier Jean‐Pierre , Caron John P. , Evans Christopher , Robbins Paul D. , Georgescu Helga I. , Jovanovic Dragan , Fernandes Julio C. , Martel‐Pelletier Johanne 
Published: February 2007

AbstractObjective. This study explored the therapeutic effect of interleukin‐1 receptor antagonist (IL‐1Ra), administered by gene transfer, on the progression of osteoarthritic (OA) lesions in an experimental dog model.Methods. Seventeen mature mongrel dogs were divided into 3 groups. Group 1 (n = 7) had an anterior cruciate ligament (ACL) section of the right knee through a stab wound incision. Groups 2 and 3 (n = 5 per group), had an ACL section of the right knee and partial synovectomy of the left knee. Each dog's synovium was subjected to enzymatic digestion, and the synovial fibroblasts were propagated in monolayer culture. Synovial cells from each dog were transduced in vitro using the retrovirus MFG with either the Escherichia coli β‐galactosidase (lac Z) gene (group 2) or the human IL‐1Ra gene (group 3). Two days after surgery, the dogs received intraarticular injections as follows: group 1 phosphate buffered saline (PBS) (2 ml); group 2 autologous cells (60 × 106 cells/2 ml of PBS) transduced with the lac Z gene; group 3 autologous cells transduced with the IL‐1Ra gene. Synovial fluid was aspirated at 2 weeks and 4 weeks. All dogs were euthanized at 4 weeks postsurgery. The right knees were dissected, and lesions were scored for macroscopic and microscopic changes. Synovial explants were dissected and representative specimens were used for histology or were cultured for 48 hours. The levels of IL‐1Ra in synovial fluid and synovial explant conditioned medium were measured by specific enzyme‐linked immunosorbent assay.Results. The level of IL‐1Ra in synovial fluid of group 3 was 202.8 ± 131.5 ng/ml (mean ± SEM) at 2 weeks and 2.8 ± 2.2 ng/ml at 4 weeks after surgery. Membrane explants isolated from dogs that received synovial cells transduced with the IL‐1Ra gene (group 3) actively produced IL‐1Ra (4.0 ± 2.0 ng/gm of tissue wet weight). The severity of OA cartilage lesions was similar in groups 1 and 2. In contrast, group 3 dogs had a marked reduction in macroscopic lesion severity on the tibial plateaus (P < 0.01 for grade; P < 0.04 for size) and femoral condyles. Moreover, the histologic lesion severity was decreased on both plateaus (P < 0.06) and condyles.Conclusion. This study showed that a local increase in IL‐1Ra production in OA knee joints by intraarticular injection of transduced synovial cells can reduce the progression of experimentally induced lesions.
Interleukin‐17 up‐regulation of nitric oxide production in human osteoarthritis cartilage
Authors: Attur Mukundan G. , Patel Rajesh N. , Abramson Steven B. , Amin Ashok R. 
Published: February 2007

AbstractObjective. To examine the effect of human interleukin‐17 (IL‐17) on nitric oxide (NO) production in human osteoarthritis (OA) cartilage under ex vivo conditions.Methods. OA cartilage from patients undergoing knee replacement surgery was used in explant assays to assess the effect of IL‐17. NO production was measured by estimating the stable NO metabolite, nitrite, in conditioned medium.Results. IL‐17 augmented the spontaneous production of nitric oxide. This augmentation was sensitive to cycloheximide and pyrrolidine dithiocarbamate, but not to dexamethasone or soluble IL‐1 receptor.Conclusion. IL‐17 augments nitric oxide production in OA cartilage via nuclear factor KB activation, but independently of IL‐1β signaling.