bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Significance of Antibodies to Native or Denatured 60‐kd or 52‐kd Ro/SS‐A Proteins in Sjögren's Syndrome
Authors: Tsuzaka Kensei , Fujii Takao , Akizuki Masashi , Mimori Tsuneyo , Tojo Takeshi , Fujii Hirohumi , Tsukatani Yasushi , Kubo Atsushi , Homma Mitsuo 
Published: February 2007

AbstractObjective. To evaluate the clinical significance of antibodies to native or denatured (anti‐n or anti‐d) 60‐or 52‐kd Ro/SS‐A proteins (60K or 52K) in Sjögren's syndrome (SS).Methods. The presence of antibodies to denatured and native Ro/SS‐A proteins was determined by immunoblotting and immunoprecipitation, respectively. Salivary gland dysfunction was evaluated by salivary function scintigraphy.Results. The incidence of anti—d‐60K without anti—d‐52K was lower among patients with systemic lupus erythematosus with SS (SLE/SS) and among those with primary SS, compared with patients who had SLE without SS, whereas anti—d‐52K without anti—d‐60K was more common in SLE/SS patients and primary SS patients than in SLE patients without SS. All of the patients with anti—Ro/SS‐A had anti—n‐60K. Serologic abnormalities and salivary gland dysfunction were associated with anti—n‐60K in SS, whereas Hashimoto's thyroiditis in SS was related to anti—d‐60K. anti—d‐52K was not associated with any extraglandular or glandular symptoms in SS.Conclusion. The data indicate that anti—n‐60K, which appears to recognize conformational epitopes, is associated with clinical features of SS characterized by glandular dysfunction.
Antibodies to Hmg Proteins in Patients with Drug‐Induced Autoimmunity
Authors: Ayer Linda M. , Rubin Robert L. , Dixon Gordon H. , Fritzler Marvin J. 
Published: February 2007

AbstractObjective. To determine the prevalence of auto‐antibodies to high‐mobility group (HMG) proteins in sera from patients with drug‐induced lupus (DIL).Methods. Forty‐two patients who developed auto‐antibodies and/or lupus after treatment with procainamide or other drugs were tested for HMG autoantibodies by immunoblotting and enzyme‐linked immunosorbent assay (ELISA).Results. Twenty‐eight of the 42 sera (67%) bound HMG‐14 and/or HMG‐17. In comparison, 9 of 42 (21%) bound HMG‐1 and/or HMG‐2. There was a good correlation between ELISA results and binding on immunoblots.Conclusion. The high prevalence of antibodies to the nucleosomal core HMGs (HMG‐14 and HMG‐17) in DIL patients adds evidence implicating nucleosomes as immunogens in drug‐induced autoimmunity.
Elevations of Neutrophil Proteinase 3 in Serum of Patients with Wegener's Granulomatosis and Polyarteritis Nodosa
Authors: Henshaw Timothy J. , Malone Christine C. , Gabay Joelle E. , Williams Ralph C. 
Published: February 2007

AbstractObjective. To determine serum levels of proteinase 3 (PR3) in normal subjects and patients with Wegener's granulomatosis (WG), polyarteritis nodosa (PAN), chronic renal failure, and systemic lupus erythematosus (SLE).Methods. Serum levels of PR3 were measured by enzyme‐linked immunosorbent assay employing a monospecific rabbit polyclonal antibody against PR3.Results. Quantifiable levels of PR3 were detected in all serum samples examined, including those of normal subjects. Marked elevations of serum PR3, which decreased with treatment, were found in patients with active WG. Patients with PAN, SLE, and chronic renal failure also showed elevated levels of PR3.Conclusion. Quantitating serum PR3 may be useful in the management of patients with WG and other connective tissue diseases.
T Cell Influence on Superantigen‐Induced Arthritis in MRL‐lpr/lpr Mice
Authors: Mountz John D. , Zhou Tong , Long Richard E. , Bluethmann Horst , Koopman William J. , Edwards Carl K. 
Published: February 2007

AbstractObjective. To define the influence of the T cell receptor (TCR) and the lpr autoimmune gene on the induction and progression of superantigen‐induced arthritis in V β8 transgenic MRL‐lpr/lpr mice.Methods. The time to onset and the extent of synovial hyperplasia after the induction of arthritis by intraarticular injection of staphylococcal enterotoxin B (SEB) were compared in mice having T cells that bear the V β8 transgene alone (V β8 TCR transgenic MRL‐+/+), the lpr gene without the V β8 gene (nontransgenic MRL‐lpr/lpr), both the V β8 gene and the lpr gene (V β8 transgenic MRL‐lpr/lpr), or neither gene (nontransgenic MRL‐+/+). Synovial hyperplasia was compared in SEB‐injected V β8 transgenic MRL‐lpr/lpr mice after treatment with cyclosporin A (CSA), anti‐V β8 and anti‐CD4 monoclonal antibodies, and in V β8 transgenic MRL‐lpr/lpr mice after injection of a non—V β8‐reactive superantigen, staphylococcal enterotoxin A (SEA).Results. At day 30, increased synovial cells were observed in all SEB‐treated mice, but the increase was greatest in the V β8 transgenic MRL‐lpr/lpr mice. T cell involvement was indicated by the inability of either heat‐denatured SEB or SEA to induce severe arthritis, the reduction in the severity of the arthritis on systemic treatment with CSA or anti‐V β8, and the correlation of synovial hyperplasia with in vitro SEB reactivity of T cells.Conclusion. These observations suggest that super‐antigens can induce chronic arthritis and that the induction and progression of the arthritis requires an underlying T cell defect in anergy induction in addition to exposure to the superantigen.
The Effects of Orally Administered Calcium Pentosan Polysulfate on Inflammation and Cartilage Degradation Produced in Rabbit Joints by Intraarticular Injection of a Hyaluronate—Polylysine Complex
Authors: Smith Margaret M. , Ghosh Peter , Numata Yukiko , Bansal Mohinder K. 
Published: February 2007

AbstractObjective. To determine the antiinflammatory and cartilage‐protecting activities of orally administered calcium pentosan polysulfate (CaPPS) in a rabbit model of inflammatory arthritis.Methods. A single intraarticular injection of a preformed polycation complex (PC) of poly‐D‐lysine and hyaluronan was used to induce joint inflammation; saline was injected into the contralateral joint as a control. Animals were killed 1, 4, 7, or 10 days post—PC injection. CaPPS, at 5 mg/kg, 10 mg/kg, or 75 mg/kg, was given every 48 hours commencing 7 days prior to PC injection. Serum interleukin‐6 (IL‐6), synovial fluid (SF) prostaglandin E2, cell numbers, and cartilage proteoglycan (PG) content, composition, and biosynthesis were determined for PC‐ and saline‐injected joints.Results. In PC‐injected, non—drug‐treated animals, serum IL‐6 activity, SF leukocyte numbers, and prostaglandin E2 levels were elevated, while cartilage PG content and biosynthesis were reduced. CaPPS at 10 mg/kg, but not at 5 mg/kg, decreased serum IL‐6 levels but maintained cartilage PG concentration and biosynthesis. However, SF leukocyte counts and prostaglandin E2 levels (except on day 1) were not reduced.Conclusion. The ability of CaPPS to attenuate serum IL‐6 levels and preserve cartilage PGs in inflamed rabbit joints suggests that this substance could be of value as an effective orally administered chondroprotective, antiarthritic drug.
Intermittent Spinal ischemia
Authors: Newcombe David S. 
Published: February 2007

AbstractA woman who presented with leg claudication and neurologic dysfunctions is described. Aortic obstruction was defined by aortography, with large collateral vessels observed above the obstruction extending to the femoral arteries and small collaterals extending to the spinal cord. Aorto—femoral bypass surgery resulted in resolution of the patient's symptoms. Prompt recognition and treatment of spinal cord ischemia is essential if permanent and disabling neurologic damage is to be avoided.
Mechanisms of Methotrexate Action in Rheumatoid Arthritis
Authors: Firestein Gary S. , Paine Mary M. , Boyle David L. 
Published: February 2007

AbstractObjective. To measure the effect of methotrexate (MTX) treatment in rheumatoid arthritis (RA) on the expression of synovial collagenase, stromelysin, and tissue inhibitor of metalloproteinase 1 (TIMP‐1) gene expression in a prospective study.Methods. Serial percutaneous synovial biopsies (pretreatment and after 3–4 months) were performed on the knees of 8 patients (7 with RA, 1 with seronegative arthritis) who were beginning oral MTX therapy. Synovial gene expression was determined by quantitative in situ hybridization using computer‐assisted image analysis.Results. After therapy, patients had decreased joint counts, morning stiffness, and erythrocyte sedimentation rates. Synovial inflammation in the biopsy tissues was slightly decreased after therapy. In situ hybridization on pretreatment and posttreatment frozen sections was performed to quantify synovial messenger RNA (mRNA) levels. Collagenase gene expression significantly decreased after MTX therapy (P = 0.006) even though cell density in the region was unchanged. TIMP‐1 and stromelysin mRNA levels were not changed by MTX therapy. To study the mechanism of MTX action in vitro, MTX‐treated and control fibroblast‐like synoviocytes were stimulated with interleukin‐1β (IL‐1β). MTX did not alter collagenase or TIMP‐1 mRNA levels after IL‐1 exposure.Conclusion. MTX therapy decreases collagenase gene expression but not TIMP‐1 or stromelysin gene expression in the synovium. This action is probably an indirect effect due to an alteration in the synovial cytokine milieu, rather than a direct effect on gene expression.
The Effect of Low‐Dose Methotrexate on Bone Metabolism and Histomorphometry in Rats
Authors: May Kimberly P. , West Sterling G. , Mcdermott Michael T. , Huffer William E. 
Published: February 2007

AbstractObjective. To ascertain the effects of low‐dose methotrexate (MTX) on bone metabolism and histomorphometry in rats.Methods. Female Sprague‐Dawley rats (6 months old, n = 42) were divided into the following 4 groups: intraperitoneal (IP) injections of MTX, with and without ovariectomy, and IP saline (controls), with and without ovariectomy. Injections were given for 16 weeks. The MTX dose was equivalent to a standard dose for rheumatoid arthritis in humans that would yield similar serum MTX levels (0.6 ± 0.1 μmoles).Results. Bone formation (assessed by serum alkaline phosphatase and osteocalcin levels and histomorphometry) was significantly lower in the MTX groups, and bone resorption (assessed by urinary hydroxyproline levels and histomorphometry) was increased in the MTX groups. Bone mass was significantly diminished in the MTX groups.Conclusion. Prolonged administration of lowdose MTX in rats causes significant osteopenia via suppression of osteoblast activity and stimulation of osteoclast recruitment, which results in increased bone resorption.
Impaired Glucocorticoid Induction of Mononuclear Leukocyte Lipocortin‐1 in Rheumatoid Arthritis
Authors: Morand Eric F. , Jefferiss Carolyn M. , Dixey Jonathan , Mitra Devashis , Goulding Nicolas J. 
Published: February 2007

AbstractObjective. To investigate leukocyte lipocortin‐1 production in rheumatoid arthritis (RA).Methods. Eight control and 8 RA subjects received 100 mg hydrocortisone intravenously. Leukocyte lipocortin‐1 was measured by enzyme‐linked immunosorbent assay.Results. Hydrocortisone induced significant increases in lipocortin‐1 production by control mononuclear cells (MNC) (P = 0.006 versus baseline) but not by RA MNC (P = 0.44 versus baseline). Peak lipocortin‐1 levels in control MNC were significantly higher than those in RA MNC (P = 0.014).Conclusion. These results indicate that glucocorticoid‐induced MNC lipocortin‐1 production is impaired in RA.
Differential Distribution of Intercellular Adhesion Molecules (ICAM–1, ICAM–2, and ICAM–3) and THE MS–1 Antigen in Normal and Diseased Human Synovia
Authors: Szekanecz Zoltan , Haines G. Kenneth , Lin Theodore R. , Harlow Lisa A. , Goerdt Sergij , Rayan Ghazi , Koch Alisa E. 
Published: February 2007

AbstractObjective. Cellular adhesion and differentiation molecules (CAMs) may play a role in the recruitment and retention of inflammatory cells into rheumatoid arthritis synovial tissue (RA ST). In order to determine if certain CAMs are up‐regulated in RA ST compared with normal ST, we studied the distribution of intercellular adhesion molecules (ICAMs) 1, 2, and 3 in ST. We also studied the MS‐1 antigen since it is preferentially expressed on discontinuous endothelia, such as those found in RA ST; MS‐1 is also expressed differentially upon cytokine activation of cells in vitro or in pathologic conditions in situ. Thus, we postulated a possible similarity between MS‐1 and ICAM‐1 expression in inflamed ST.Methods. Immunohistochemical analysis was used to determine the distribution of ICAMs and MS‐1 in ST from 10 patients with RA, 10 with osteoarthritis (OA), and 4 normal individuals.Results. ICAM‐1 expression was found on significantly more RA ST endothelial cells compared with normal cells, as well as on RA ST macrophages and lining cells. ICAM‐2, also found on endothelial cells, showed no differential staining pattern. ICAM‐3 was present on RA ST macrophages and lining cells as well as on some RA and OA endothelial cells. The MS‐1 antigen was present on most RA and OA ST endothelia, lining cells, and macrophages. ICAM‐1 expression and MS‐1 expression in the lining layer were positively correlated in both RA and OA.Conclusion. ICAM‐1, while found mainly on endothelial cells, is up‐regulated on RA ST macrophages and lining cells, suggesting a role for these cells in the infiltration and tissue damage seen in the RA ST. ICAM‐3, which is present mainly on normal resting leukocytes but not on normal endothelium, is expressed by some diseased ST leukocytes and endothelial cells. MS‐1 is also found on the RA ST specialized, fenestrated endothelium, on macrophages, and in the lining layer. These results suggest that the differential expression of ICAMs and MS‐1 in RA ST compared with normal ST might play a special role in the pathogenesis of RA.
Cytokine Combinations Increase p75 Tumor Necrosis Factor Receptor Binding and Stimulate Receptor Shedding in Rheumatoid Synovial Fibroblasts
Authors: Taylor David J. 
Published: February 2007

AbstractObjective. To identify cytokines responsible for the increased levels of tumor necrosis factor receptor (TNFR) in the joints of patients with rheumatoid arthritis.Methods. Antibodies to TNFR types were used both to inhibit ligand cell binding and to quantify released receptors in rheumatoid synovial fibroblasts.Results. Binding by and shedding of the p75 TNFR was affected by interleukin‐1 (IL‐1), IL‐4, and interferon‐γ.Conclusion. IL‐1 could cause increased TNFα binding and TNFR shedding in inflamed joints.
Cysteine Proteinase Inhibitors Decrease Articular Cartilage and Bone Destruction in Chronic Inflammatory Arthritis
Authors: Esser Ronald E. , Angelo Richard A. , Murphey Mark D. , Watts Lynnetta M. , Thornburg Larry P. , Palmer James T. , Talhouk Jamil W. , Smith Robert E. 
Published: February 2007

AbstractObjective. To determine the effects of peptidyl fluoromethyl ketones on the in vitro activity of purified cathepsins B and L, on tissue cysteine proteinase activity, and on cartilage and bone destruction in experimental arthritis.Methods. The effects of the fluoroketones on cathepsins B and L in vitro and the effects of oral administration of fluoroketones on ex vivo cysteine proteinase activity in tissue homogenates were determined by measuring the inhibition of fluorogenic substrate cleavage. To determine the effects on arthritis, animals were injected with adjuvant or type II collagen, treated orally with the fluoroketones, and the severity of arthritis was assessed by clinical, histologic, and radiologic methods.Results. All of the fluoroketones tested were potent inhibitors of purified cathepsins B and L activity. Oral administration of the fluoroketones reduced tissue cysteine proteinase activity by up to 77%. In addition, fluoroketone treatment significantly reduced the severity of clinical joint disease and decreased the destruction of articular cartilage and bone. Quantitative analysis of radiographic images indicated that treatment significantly reduced soft tissue changes, periosteal proliferation, and bone erosion, but only partially reduced juxtaarticular osteoporosis.Conclusion. These studies suggest that cysteine proteinase inhibitors may limit tissue destruction in diseases such as rheumatoid arthritis.
Anticentromere Autoantibodies
Authors: Vázquez‐Abad Dolores , Wallace Susan , Senécal Jean‐Luc , Joyal France , Roussin Andre , Earnshaw William C. , Rothfield Naomi 
Published: February 2007

AbstractObjective. To evaluate an enzyme‐linked immunosorbent assay (ELISA) for anticentromere autoantibodies (ACA).Methods. Sera from 611 patients with scleroderma, CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), Raynaud's disease, and connective tissue disease control patients were studied by ELISA using the fusion protein CENP‐B, by immunofluorescence on dividing HEp‐2 cells, and by immunoblotting on chromosomes and CENP‐B.Results. Compared with immunofluorescence, the CENP‐B ELISA sensitivity was 94% and the specificity was 93%. In 19.7% of the cases, there was a probability of a false‐positive result and in 1.9%, a probability of a false‐negative result, yielding positive and negative predictive values of 0.80 and 0.98, respectively.Conclusion. The CENP‐B ELISA is a sensitive and specific assay for ACA.
Assessment of Clinical Parameters Associated with Increased Frequency of Mutant T Cells in Patients with Systemic Lupus Erythematosus
Authors: Dawisha Sahar M. , Gmelig‐Meyling Frits , Steinberg Alfred D. 
Published: February 2007

AbstractObjective. To determine the clinical features that contribute to an increased frequency of mutant T cells (FMC) in patients with systemic lupus erythematosus (SLE).Methods. During in vivo T cell division, there are errors in replication which give rise to mutations throughout the genome. An estimate of such mutations may be obtained by focusing on mutations in the hprt gene, which can be screened by assessing relative growth of T cell clones in the presence and absence of 6‐thioguanine. In this study, peripheral blood T cell clones from 47 patients with SLE were assessed, and the frequency of mutant T cells (FMC) determined. An attempt was made to correlate the FMC with disease measures.Results. Patients with SLE had a spectrum of FMC values, ranging from normal to almost 1,000 times normal. Total duration of active disease (rs = 0.94), past highest disease activity index (rs = 0.80), and number of lupus flares (rs = 0.76) correlated most strongly (P < 0.0001) with FMC by Spearman's rank order analysis. In contrast, current disease activity index and current anti‐DNA level did not correlate with FMC. Similar correlations between FMC and cumulative past lupus disease activity were found by linear regression analysis (rp = 0.89 for the correlation between the natural logarithm of FMC and cumulative duration of active disease). By both statistical tests, therapy was found to be only a minor contributor to FMC.Conclusion. In our patient population, a high FMC value appears to reflect cumulative clinical lupus disease activity, involving both intensity and duration of past active disease.
Immunocytochemical Localization and Serologic Detection of Transforming Growth Factor β1
Authors: Higley H. , Persichitte K. , Chu S. , Waegell W. , Vancheeswaran R. , Black C. 
Published: February 2007

AbstractObjective. To determine the presence of transforming growth factor β1 (TGFβ1) and inflammatory cell markers (HLA–DR and Factor XIIIa) and to compare these with the presence of type I procollagen, in clinically uninvolved and involved skin from patients with different subsets of systemic sclerosis (SSc), and to analyze circulating levels of TGFβ1 in SSc patients.Methods. TGFβ1, HLA‐DR, Factor XIIIa, and type I procollagen were detected in skin biopsy sections using a biotin–streptavidin–peroxidase system. Levels of circulating TGFβ1 were measured using a capture enzyme‐linked immunosorbent assay technique.Results. Patients with active diffuse cutaneous SSc (dcSSc) showed minimal TGFβ1 but significant type I procollagen staining in involved skin, while the clinically uninvolved skin of these patients showed moderate extracellular and intra‐epidermal TGFβ1 immunoreactivity. Patients with limited cutaneous SSc (IcSSc) showed elevated TGFβ1 staining in both involved and uninvolved skin, as well as procollagen staining. Significant TGFβ1 reactivity, HLA–DR and Factor XIIIa immunoreactivity, numerous inflammatory cells, and procollagen staining were seen in specimens from patients with morphea. Sequential biopsies suggested the presence of cytokine activity at the earliest stages of disease, which was not maintained with progression of sclerosis. Among the disease groups studied, elevated levels of circulating TGFβ1 were seen only in patients with morphea.Conclusion. The pattern of TGFβ1 staining in dermal sections from patients with dcSSc, IcSSc, and morphea suggests that this cytokine is important in the pathogenesis of scleroderma. Furthermore, the presence of TGFβ1 prior to the onset of fibrosis indicates an early involvement of this growth factor, possibly in the inflammatory stage of the disease.
Rapamycin Prolongs Survival and Arrests Pathophysiologic Changes in Murine Systemic Lupus Erythematosus
Authors: Warner Linda M. , Adams L. M. , Sehgal S. N. 
Published: February 2007

AbstractObjective. To evaluate the effects of oral rapamycin (RAPA), a macrolide immunosuppressant that has been shown to interfere with T cell activation events, on the course of spontaneous disease progression in the MRL/MpJ/lpr/lpr (MRL/I) mouse model of lupus.Methods. RAPA treatment (6, 12, or 25 mg/kg 3 times per week) was evaluated by monitoring survival rates, autoantibody levels, and urinary albumin levels. Additionally, concanavalin A responsiveness, interleukin‐2 (IL‐2) production, lymphoid organ size, and histopathology were evaluated ex vivo.Results. RAPA prevented the typical rise in anti–double‐stranded DNA antibody and urinary albumin levels and prolonged survival. Spleen and lymph node sizes were significantly decreased, inflammatory changes in the lung, liver, kidney, spleen, lymph node, and thymus were significantly reduced, and T cell mitogen–stimulated splenocyte proliferation and IL‐2 production were restored.Conclusion. Data from 3 independent experiments demonstrated that RAPA significantly reduced or prevented many pathologic features of lupus normally seen in the MRL/1 mouse, and suggest that RAPA may be useful as a therapeutic agent in SLE in humans.
CLINICAL RHEUMATOLOGY TRAINING IN AN UNCERTAIN FUTURE. Opinions of Recent and Current Rheumatology Fellows About an Extended Fellowship in Musculoskeletal Medicine
Authors: Mazzuca Steven A. , Brandt Kenneth D. 
Published: February 2007

AbstractObjective. To estimate among recent and current rheumatology fellows the appeal of a 3‐year rheumatology fellowship emphasizing musculoskeletal medicine.Methods. A survey of 348 trainee members of the American College of Rheumatology during 1990–1993, by mailed questionnaire.Results. The response rate was 77.8% (n = 271). Both recent and current fellows indicated that they desired more experience in musculoskeletal medicine. Most notably, 50% of current fellows, and a significantly higher proportion of recent fellows (70%; P < 0.005), indicated that they would have opted for a 3‐year fellowship in musculoskeletal medicine had one been available to them at the completion of their residency.Conclusion. Expertise in musculoskeletal medicine is desired by a sufficient proportion of recent and current rheumatology fellows to warrant the investment in another year of training.