bluuebunny/crossref_metadata_2025 huggingface dataset:
Tenascin distribution in articular cartilage from normal subjects and from patients with osteoarthritis and rheumatoid arthritis
Authors: Chevalier Xavier , Groult Nicole , Larget‐Piet Bruno , Zardi Luciano , Hornebeck William
Published: February 2007

Objective. To determine whether tenascin is present in normal and diseased human cartilage.

Methods. Immunohistochemical and biochemical assays with a monoclonal antibody against all tenascin isoforms (BC‐4) were used.

Results. Cartilage samples from osteoarthritis and rheumatoid arthritis patients contained increased amounts of tenascin compared with the levels in normal cartilage. Human fetal cartilage was also found to contain tenascin. In normal cartilage explants treated with interleukin‐1β, tenascin was present in pericellular areas of all layers. Immunolocalization studies revealed that tenascin was most abundant in the superficial layers of osteoarthritic cartilage. Western blot analysis performed from dissociative extracts of diseased cartilage confirmed the presence of subunits of the native molecule.

Conclusion. Tenascin is increased in arthritic cartilage and is weakly expressed in normal cartilage.
Local anti—type ii collagen antibody production in rheumatoid arthritis synovial fluid
Authors: Rönnelid Johan , Lysholm Jörgen , Engström‐Laurent Anna , Klareskog Lars , Heyman Birgitta
Published: February 2007

Objective. To investigate the production of type II collagen (CII) antibodies in the synovial fluid (SF) of rheumatoid arthritis (RA) patients, and to examine the HLA dependence of this local production.

Methods. The ELISPOT method was used for enumerating anti‐CII—reactive cells. Serologic tissue typing was performed.

Results. Anti‐CII—reactive cells were found in the SF of 16 of 31 patients, but not in any of the peripheral blood samples obtained in parallel. SF anti‐CII antibody production showed no correlation with clinical parameters, but its frequency increased significantly with age. The IgG anti‐CII response occurred exclusively in patients who were positive for HLA—DR4 and was significantly associated with DR4.

Conclusion. Anti‐CII production may be important in local immune complex formation. The indirect demonstration of a DR4‐restricted T cell response to CII is an indication of a pathogenetic role of collagen autoimmunity in RA.
N‐Monomethyl arginine, an inhibitor of nitric oxide synthase, suppresses the development of adjuvant arthritis in rats
Authors: Stefanovic‐Racic M. , Meyers K. , Meschter C. , Coffey J. W. , Hoffman R. A. , Evans C. H.
Published: February 2007

Objective. To test the hypothesis that nitric oxide (NO) is involved in the pathophysiology of arthritis.

Methods. Arthritis was induced in male Lewis rats by the injection of adjuvant into the base of the tail. The NO synthase (NOS) inhibitor, NG‐monomethyl‐L‐arginine (L‐NMA), was administered daily by the oral route for 19 days. Paw swelling, plasma fibrinogen levels, and urinary NO2/NO3 levels were measured to assess the effect of L‐NMA on the arthritic response and whole‐body NO production, respectively. On day 20, the ankle joints were processed for histopathologic evaluation.

Results. The onset of clinical symptoms was preceded by elevated biosynthesis of NO. In a dose‐dependent manner, L‐NMA inhibited both NO biosynthesis and paw swelling; histopathologic changes in the ankle joints were also prevented. D‐NMA had no effect on the development of arthritis, while L‐arginine reversed the effects of L‐NMA. Fibrinogen levels in rats with arthritis were unaffected by L‐NMA.

Conclusion. NO is critical to the development of both the inflammatory and erosive components of adjuvant arthritis in rats. There may be a future clinical role for suitable inhibitors of NO production or activity.
Induction of experimental allergic arthritis with outer surface proteins of borrelia burgdorferi
Authors: Gondolf Klaus B. , Mihatsch Michael , Curschellas Enrico , Dunn John J. , Batsford Steven R.
Published: February 2007

Objective. The arthritogenic potential of the cationic outer surface proteins (Osp) from Borrelia burgdorferi was tested in rats.

Methods. Water‐soluble Osps were prepared by butanol extraction and were administered by intraarticular injection. Tissue injury was assessed by scintigraphy and histology.

Results. A mild arthritis was seen in naive rats. Preimmunized animals had more severe, longer lasting bouts of inflammation.

Conclusion. The Osps of Borrelia burgdorferi are potent arthritogens in rats. These immunodominant antigens may play a role in the development of Lyme arthritis in humans.
Familial spondyloepiphyseal dysplasia tarda, brachydactyly, and precocious osteoarthritis associated with an arginine 75 → cysteine mutation in the procollagen type ii gene in a kindred of chiloe islanders.
Authors: Reginato Antonio J. , Passano Gian M. , Neumann Guillermo , Falasca Gerald F. , Diaz‐Valdez Marcelo , Jimenez Sergio A. , Williams Charlene J.
Published: February 2007

Objective. To characterize a kindred of Chiloe Islanders with spondyloepiphyseal dysplasia tarda (SEDT), brachydactyly, precocious osteoarthritis (OA), and intraarticular calcification.

Methods. Sixteen family members underwent a complete physical examination, anthropometric measurements, radiographic studies of the spine and peripheral joints, and analysis of the type II procollagen gene (COL2A1).

Results. Seven family members presented with SEDT, brachydactyly, precocious OA, and periarticular calcification while 2 others had the same syndrome but without brachydactyly. The inheritance was autosomal dominant, and the disease cosegregated with a base substitution in the COL2A1 gene.

Conclusion. The syndrome of SEDT, precocious OA, and brachydactyly in a kindred of Chiloe Islanders is associated with a point mutation in 1 allele of the COL2A1 gene. The relationship of this type of SEDT to familial calcium pyrophosphate dihydrate deposition disease and idiopathic hip dysplasia, both endemic in Chiloe Islanders, needs to be further investigated.
Coumarin‐induced skin necrosis associated with acquired protein s deficiency and antiphospholipid antibody syndrome
Authors: Wattiaux Marie‐José , Hervé Robert , Robert Annie , Cabane Jean , Housset Bruno , Imbert Jean‐Claude
Published: February 2007

We report a case of skin necrosis occurring during coumarin treatment in a patient with acquired protein S deficiency and the primary antiphospholipid antibody syndrome.
Effects of glucocorticoids in rheumatoid arthritis. Diminished glucocorticoid receptors do not result in glucocorticoid resistance
Authors: Schlaghecke Reiner , Beuscher Ditmar , Kornely Elisabeth , Specker Christof
Published: February 2007

Objective. Lymphocytes of patients with rheumatoid arthritis (RA) have diminished receptor density; thus, patients with RA should show partial resistance to glucocorticoids. We investigated the glucocorticoid sensitivity of lymphocytes in RA patients compared with healthy subjects.

Methods. We determined the effects of glucocorticoids on lymphocyte proliferation and cytokine release.

Results. Proliferation and cytokine release were inhibited in RA patients to the same extent as in healthy controls.

Conclusion. Diminished receptor density in RA patients does not result in glucocorticoid resistance.
Abnormal hypothalamic—pituitary—adrenal axis function in rheumatoid arthritis. Effects of nonsteroidal antiinflammatory drugs and water immersion
Authors: Hall Jane , Morand Eric F. , Medbak Sami , Zaman Molly , Perry Les , Goulding Nicolas J. , Maddison Peter J. , O'Hare J. Paul
Published: February 2007

Objective. To investigate the effects of nonsteroidal antiinflammatory drug (NSAID) therapy and water immersion on hypothalamic—pituitary—adrenal (HPA) axis function in rheumatoid arthritis (RA).

Methods. Plasma levels of adrenocorticotropic hormone (ACTH) and serum and urine levels of cortisol were compared in untreated RA patients, NSAID‐treated RA patients, and healthy control subjects.

Results. ACTH levels were significantly higher in untreated RA patients (mean ± SEM integrated area 11,377 ± 5,246 hours ng/liter) than in NSAID‐treated RA patients (2,285 ± 388 hours ng/liter) or healthy controls (1,845 ± 35.5 hours ng/liter) (P < 0.001). Serum and urine cortisol levels were not significantly different between groups. Two‐hour head‐out water immersion had no effect.

Conclusion. Elevated ACTH levels without hypercortisolemia occur in untreated RA. NSAID therapy alters HPA axis response, but immersion has no effect.
Nonsteroidal antiinflammatory drug‐induced small intestinal inflammation and blood loss. Effects of sulfasalazine and other disease‐modifying antirheumatic drugs
Authors: Hayllar Jeremy , Smith Terry , Macpherson Andrew , Price Ashley B. , Gumpel Michael , Bjarnason Ingvar
Published: February 2007

Objective. To identify the source of intestinal blood loss in rheumatoid arthritis patients being treated with nonsteroidal antiinflammatory drugs (NSAIDs) and assess the response to sulfasalazine and other disease‐modifying antirheumatic drugs (DMARDs).

Methods. Intestinal inflammation, blood loss, and gastroduodenal damage, and the response to treatment with DMARDs, were assessed in 46 patients taking NSAIDs.

Results. Intestinal inflammation and blood loss correlated significantly with one another (r = 0.43, P < 0.003), but not with the macroscopic or microscopic appearance of the gastroduodenal mucosa. Sulfasalazine reduced both intestinal inflammation and blood loss, whereas the other DMARDs did not.

Conclusion. The small intestine is the main site of mild chronic blood loss in patients receiving NSAIDs, and this blood loss can be reduced with sulfasalazine treatment.
Dynamic magnetic resonance imaging for the evaluation of synovitis in patients with rheumatoid arthritis
Authors: Tamai Kazuya , Yamato Minoru , Yamaguchi Takehiko , Ohno Wataru
Published: February 2007

Objective. To investigate whether the findings of magnetic resonance imaging (MRI) reflect rheumatoid synovitis.

Methods. Dynamic imaging enhanced with gadolinium—diethylenetriamine pentaacetic acid was performed on 10 affected knees of 9 patients with rheumatoid arthritis. Changes in signal intensity were correlated with pathologic findings in synovial biopsy specimens obtained during total knee arthroplasty.

Results. Enhancement was greater in regions with a higher degree of fibrin exudation, cellular infiltration, villous hypertrophy, vascular proliferation, and granulation formation.

Conclusion. Dynamic MRI can be used for assessing local disease activity in rheumatoid synovium.
Genetic typing of patients with inflammatory arthritis at presentation can be used to predict outcome
Authors: Gough Andrew , Faint Jeff , Salmon Mike , Hassell Andrew , Wordsworth Paul , Pilling Darrell , Birley Andrew , Emery Paul
Published: February 2007

Objective. To test the hypothesis that genetic characterization of patients at the time they present with inflammatory arthritis can predict subsequent destructive disease.

Methods. We evaluated 177 patients with early arthritis. Patients were serologically tested for rheumatoid factor (RF) and were DNA oligotyped for the presence of conserved base sequences in the third hypervariable region (HVR3) of the DRB1 gene, previously shown to be associated with severe rheumatoid arthritis (RA). Homozygosity in the patient's genotype was confirmed using restriction fragment length polymorphism analysis. The main outcome measure was radiologic erosions at 1 year.

Results. At presentation, 120 patients fulfilled the American College of Rheumatology 1987 criteria for RA, 64% of whom possessed the conserved base sequences, compared with 45% of 347 healthy controls (P < 0.001) and with 56% of 57 patients with other inflammatory arthritis (P not significant). Within the RA population, the frequency of Dw4/Dw14 compound heterozygotes was disproportionately increased. The presence of either HVR3 or RF had a relative risk of 13.49 for erosions, with a sensitivity of 95% (specificity 39%); the presence of both HVR3 and RF had a relative risk of 8.13, with a specificity of 88% (sensitivity 53%). All but 1 patient with the Dw4/Dw14 genotype developed erosions within 1 year.

Conclusion. Knowledge of a patient's HLA—DR type and RF status allows clinically useful prediction of erosive disease; patients possessing Dw4/Dw14 represent a particularly high‐risk subgroup.
Lack of evidence for gender bias in the utilization of total HIP arthroplasty among olmsted county, minnesota residents with osteoarthritis
Authors: Gabriel Sherine E. , Wenger Doris E. , Ilstrup Duane M. , Lewallen David G. , Melton L. Joseph
Published: February 2007

Objective. To evaluate whether women have more advanced osteoarthritis (OA) than men prior to total hip arthroplasty (THA).

Methods. Preoperative clinical and radiographic severity of hip OA was determined among Olmsted County, Minnesota residents who underwent THA. The time from first radiographic changes and first symptoms to THA was compared between genders.

Results. Fifty men and 80 women underwent their first THA between 1985 and 1990. Men had higher disease activity levels preoperatively; however, 16 other clinical severity variables and 2 summary measures of OA severity were similar for both genders. Men had radiographically more advanced hip OA preoperatively. The time from first symptom of hip OA to THA was similar for both genders, while the time from first radiographic change to THA was significantly longer for men.

Conclusion. These results fail to support the hypothesis that hip OA prior to THA is more severe among women compared with men.
Serum levels of insulin‐like growth factor 1 in subjects with osteoarthritis of the knee. Data from the baltimore longitudinal study of aging
Authors: Hochberg Marc C. , Lethbridge‐Cejku Margaret , Scott William W. , Reichle Ralph , Plato Chris C. , Tobin Jordan D.
Published: February 2007

Objective. To examine the relationship between serum levels of insulin‐like growth factor 1 (IGF‐1) and osteoarthritis (OA) of the knee.

Methods. Serum IGF‐1 levels were compared in 162 male and 101 female subjects age ≥20 stratified by presence of radiographic changes of OA of the knee.

Results. Mean serum IGF‐1 levels were significantly lower in subjects with knee OA; however, after adjustment for age‐related changes in IGF‐1 levels, these differences were no longer significant.

Conclusion. These data fail to support the hypothesis that serum IGF‐1 levels are reduced in subjects with OA of the knee independent of the known age‐related changes in these levels.
The prevalence and clinical impact of fibromyalgia in systemic lupus erythematosus
Authors: Middleton Gregg D. , Mcfarlin Jackie E. , Lipsky Peter E.
Published: February 2007

Objective. To ascertain the prevalence of fibromyalgia syndrome (FMS) in systemic lupus erythematosus (SLE) and to evaluate its clinical impact and relationship to SLE disease activity.

Methods. A cross‐sectional analysis of 102 patients from a public hospital SLE clinic. Information was obtained on symptoms of FMS, disability, tender points, pain thresholds, and SLE disease activity.

Results. Twenty‐two SLE patients (22%) met the American College of Rheumatology criteria for FMS, and another 24 (23%) had clinical FMS but did not meet the classification criteria. The patients who met the criteria for FMS had a significantly increased frequency and severity of symptoms commonly associated with FMS, and were much more likely to be unable to perform daily activities. The FMS patients also were less likely to be employed, and more likely to be divorced and to be receiving welfare or medical disability benefits. However, patients with and those without FMS did not differ in measures of SLE activity.

Conclusion. FMS is very common in SLE patients, and accounts for many of the symptoms and much of the disability in these patients.
Prostromelysin and procollagenase genes are differentially UP‐regulated in chondrocytes from the knees of rabbits with experimental osteoarthritis
Authors: Mehraban Fuad , Kuo San‐Yuan , Riera Humberto , Chang Chuan , Moskowitz Roland W.
Published: February 2007

Objective. To determine the relative expressions of matrix metalloprotease (MMP) genes pro‐MMP1 and pro‐MMP3 in the cartilage of rabbits with experimentally induced osteoarthritis (OA), and to assess the role of the chondrocyte in this process.

Methods. OA was induced in rabbits after partial medial meniscectomy. Rabbits were killed at 4 weeks or 8 weeks, and total cellular RNA was prepared from cartilage and probed by Northern blotting with pro‐MMP 32P‐labeled complementary DNA. Monolayer chondrocytes were used to assess MMP‐inducing activity of chondrocyte factor(s).

Results. Pro‐MMP messenger RNAs (mRNAs) were up‐regulated in experimental OA cartilage; pro‐MMP3 mRNA expression exceeded that of pro‐MMP1. Conditioned medium from OA‐derived chondrocytes up‐regulated pro‐MMP mRNAs in normal chondrocytes.

Conclusion. Up‐regulation of MMP genes in this OA model may contribute to cartilage degradation. Chondrocytes up‐regulate MMP genes via an autocrine pathway.
Anti—topoisomerase i antibodies in silica‐associated systemic sclerosis. A model for autoimmunity
Authors: Mchugh Neil John , Whyte Jean , Harvey Georgina , Haustein Uwe F.
Published: February 2007

Objective. To determine the frequency and type of autoantibodies present in patients with systemic sclerosis (SSc) associated with an established environmental toxin.

Methods. Clinical data and sera were available from 14 men with silica‐associated SSc who had developed SSc after at least 2 years of exposure to silica at work. Controls included 27 men with silicosis without SSc. Autoantibodies were measured by immunodiffusion, immunoblotting, and functional inhibition of topoisomerase I (topo I).

Results. Nine of the 14 patients with silica‐associated SSc had anti—topo I antibodies. All anti—topo I antibodies in the patients with silica‐associated SSc and in 14 anti—topo I—positive patients with idiopathic SSc were directed at an active site of topo I, or at least sterically inhibited its function. One patient with silica‐associated SSc had anticentromere antibodies. Unexpectedly, 2 patients with silicosis who had no symptoms of a connective tissue disease had autoantibodies to Ro/SS‐A and La/SS‐B autoantigens.

Conclusion. Anti—topo I antibodies are the predominant autoantibodies present in silica‐associated SSc. The generation of anti—topo I antibodies in genetically susceptible individuals may depend partly on the patient's sex and on the site of organ involvement, and may be triggered by silica particles acting as an immune adjuvant.
CD4+ and CD8+ T cell expansions using selected TCR V and J gene segments at the onset of giant cell arteritis
Authors: Grunewald Johan , Andersson Rune , Rydberg Lennart , Gigliotti Dulceaydee , Schaufelberger Christopher , Hansson Gö Ran K. , Wigzell Hans
Published: February 2007

Objective. To investigate T cell receptor (TCR) Vα/Vβ (and in selected cases, Jβ) usage in CD4+ and CD8+ peripheral blood lymphocytes of patients with giant cell arteritis (GCA), before and after treatment, as well as to analyze the HLA types of these patients.

Methods. Flow cytometry, with 10 anti‐TCR V‐specific monoclonal antibodies (MAb), was used. To analyze Jβ usage by cell populations expressing certain Vβ, we used the polymerase chain reaction (PCR) technique, with Vβ‐ and Cβ‐specific primers, Southern blotting of PCR products, and subsequent hybridization with radiolabeled Jβ‐specific probes. HLA typing was performed using the microlymphocytotoxicity technique.

Results. Seven of the 9 GCA patients had increased anti‐TCR V MAb reactivities (interpreted as T cell expansions), which in many cases, correlated with clinical signs of disease. A strict preference for particular Jβ segments was found in 3 of 3 expanded CD4+ T cell populations.

Conclusion. T lymphocytes expressing specific antigen receptors are implicated in the pathogenesis of GCA.
Suppression of experimental antiphospholipid syndrome and systemic lupus erythematosus in mice by anti‐CD4 monoclonal antibodies
Authors: Tomer Y. , Blank M. , Shoenfeld Yehuda
Published: February 2007

Objective. To investigate whether anti‐CD4 antibodies can suppress experimental antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) induced by an anti‐DNA monoclonal antibody (MAb).

Methods. BALB/c mice were treated with anti‐CD4 MAb either before or 2 months after induction of experimental APS and SLE. Control mice were treated with rat IgG or phosphate buffered saline. Serologic and clinical manifestations of the disease were determined.

Results. Treatment of mice with anti‐CD4 before or 2 months after disease induction prevented the development of experimental APS and SLE. The treated mice did not develop leukopenia or proteinuria, and had fewer episodes of fetal resorption. Similarly, the treated mice did not develop elevated erythrocyte sedimentation rate, prolonged activated partial thromboplastin time, or thrombocytopenia, and had significantly lower levels of antibodies to double‐stranded DNA, histones, MIV‐7, cardiolipin, and phosphatidylserine. Levels of CD4+ cells in the lymph nodes declined temporarily after the treatment and then returned to normal.

Conclusion. Anti‐CD4 antibodies can prevent experimental APS and SLE. These results may suggest a role for anti‐CD4 treatment in human autoimmune diseases.
Familial polyarteritis nodosa
Authors: Mason Justin C. , Cowie Martin R. , Davies Kevin A. , Schofield John B. , Cambridge Jo , Jackson James , So Alex , Allard Simon A. , Walport Mark J.
Published: February 2007

Familial polyarteritis nodosa (PAN) is rare. We describe here two siblings who developed PAN 8 years apart. HLA typing showed that the affected family members shared a common haplotype with their unaffected mother. Further study of the family history suggested the possibility of an inherited disorder of connective tissue predisposing to autoimmunity and aneurysm formation.
Pyoderma gangrenosum in association with psoriatic arthritis
Authors: Smith David L. , White Clifton R.
Published: February 2007

We present a patient with psoriasis and psoriatic arthritis who developed multiple large, painful ulcers that were scattered over his anterior lower legs and were characteristic of pyoderma gangrenosum (PG). This association has not previously been described. We review other forms of arthritis that usually occur with PG and discuss them in light of this observation.
Therapy for severe interstitial lung disease in systemic sclerosis. a retrospective study
Authors: Steen Virginia D. , Lanz James K. , Conte Claudia , Owens Gregory R. , Medsger Thomas A.
Published: February 2007

Objective. This retrospective observational study attempted to determine whether any of the therapies used in the management of systemic sclerosis (SSc) patients held potential benefit for patients with interstitial lung disease.

Methods. All patients with SSc who had a pulmonary function test (PFT) showing a forced vital capacity (FVC) of <70% predicted and an additional PFT at least 4 months later were grouped according to the treatment they received. Changes in pulmonary function were analyzed by the mean percent predicted FVC from the initial and the final test, and by the rate of percent change in FVC (ml/year) in the first 2 years after therapy. Bronchoalveolar lavage was performed in a subset of these patients.

Results. Of 363 SSc patients who had an FVC < 70% predicted, 122 had a second PFT and fulfilled the criteria for one of the following drug groups: high–dose prednisone (n = 21), immunosuppressive other than cyclophosphamide (CYC) (n = 16), CYC (n = 14), D–penicillamine (n = 37), or no drug (n = 34). In both analyses, the CYC–treated group showed significantly more improvement in FVC than did the other groups. Patients with early disease had the greatest likelihood of responding to any drug.

Conclusion. This retrospective study shows that patients treated with CYC had a significant improvement in FVC over time. Prospective controlled studies of CYC treatment in early disease are necessary to determine if it can significantly alter the natural history of interstitial lung disease.
Magnesium deficiency in the eosinophilia—myalgia syndrome. report of clinical and biochemical improvement with repletion
Authors: Clauw Daniel J. , Ward Kathleen , Wilson Beverly , Katz Paul , Rajan Sunder S.
Published: February 2007

We describe a patient with the eosinophilia–myalgia syndrome (EMS) with persistent myalgias, cramping, and weakness that were not responsive to treatment. Despite a normal serum magnesium level, a loading study was performed, and the results suggested low tissue levels of magnesium. He was given parenteral magnesium and had dramatic improvement in symptoms as well as in muscle intracellular levels of this cation. After cessation of magnesium therapy the symptoms recurred, and magnesium repletion again led to an improvement in symptoms and ATP levels. Low tissue levels of magnesium, even in the setting of normal serum levels, may lead to the neuromuscular symptoms in EMS and related disorders.
Antisense oligonucleotides, a novel tool for the control of cytokine effects on human cartilage. focus on interleukins 1 and 6 and proteoglycan synthesis
Authors: Nietfeld J. J. , Duits A. J. , Tilanus M. G. J. , Van Bosch M. E. Den , Den Otter W. , Capel P. J. A. , Bijlsma J. W. J.
Published: February 2007

Objective. To prevent the negative effects of interleukin–1 (IL–1) and IL–1—induced IL–6 on cartilage proteoglycan (PG) synthesis, we used an antisense oligonucleotide (ASO) specific for IL–6 messenger RNA (mRNA) to inhibit IL–6 production.

Methods. Explants of human articular cartilage were cultured in the presence or absence of IL–6—ASO, IL–1, and exogenous IL–6. As metabolic parameters, cartilage production of IL–6 was determined in the B9 bioassay and PG as incorporation of 35SO4.

Results. The IL–6—ASO prevented IL–1—induced production of IL–6 in the cartilage explants, as well as IL–1—induced inhibition of PG synthesis. This inhibition was restored, despite the presence of IL–6—ASO, when exogenous IL–6 was added. A control ASO (not specific for IL–6 mRNA) was not effective.

Conclusion. The IL–6—ASO used can penetrate the extracellular matrix of articular cartilage, enter the chondrocytes, and inhibit the IL–1—induced production of IL–6. Furthermore, IL–6—ASO can prevent the IL–1—induced inhibition of cartilage PG synthesis. The effect of exogenous IL–6 shows that IL–1 requires IL–6 for inhibition of PG synthesis.
Lymphocyte function—associated antigen 1 overexpression and t cell autoreactivity
Authors: Richardson Bruce , Powers Daniel , Hooper Forrest , Yung Raymond L. , O'Rourke Kenneth
Published: February 2007

Objective. To determine if DNA methylation inhibitors make T cells autoreactive by inducing lymphocyte function—associated antigen type 1 (LFA–1) (CD11a/CD18) overexpression.

Methods. T cell clones were treated with 3 distinct DNA methylation inhibitors or were stably transfected with a CD18 cDNA in a mammalian expression vector, and the effects on LFA–1 expression and activation requirements were examined.

Results. LFA–1 overexpression, caused by DNA methylation inhibitors or by transfection, correlates with the development of autoreactivity.

Conclusion. LFA–1 overexpression may contribute to T cell autoreactivity.
Specificity of autoantibodies for recombinant 60–kd and 52–kd ro autoantigens
Authors: Williams Clair E. ST. , Burch James A. , Saitta Michael
Published: February 2007

Objective. To compare patterns of Ro autoantigen recognition in primary Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE).

Methods. Sera were tested by enzyme–linked immunosorbent assay (ELISA) and immunoprecipitation for reactivity with recombinant human 60–kd and 52–kd Ro proteins.

Results. SLE and primary SS sera exhibited similar patterns of reactivity with the recombinant 52–kd protein. However, a greater proportion of sera from primary SS patients than from SLE patients did not react with recombinant 60–kd protein in ELISA yet precipitated its translation product in solution–phase assays.

Conclusion. Disease state can influence recognition of the recombinant 60–kd Ro antigen.
Interleukin–1 receptor antagonist gene polymorphism as a disease severity factor in systemic lupus erythematosus
Authors: Blakemore Alexandra I. F. , Tarlow Joanna K. , J.Cork Michael , Gordon Caroline , Emery Paul , Duff Gordon W.
Published: February 2007

Objective. We have previously described associations between an allele of the interleukin–1 receptor antagonist gene (IL1RN) and several inflammatory diseases. In this study we tested the IL1RN gene as a possible marker in patients with systemic lupus erythematosus (SLE).

Methods. Eighty–one SLE patients and 261 ethnically matched control subjects were genotyped by polymerase chain reaction.

Results. We found an increase in both frequency and carriage rate of IL1RN*2 in the SLE group. This association strengthened with extensive disease and particularly with the presence of photosensitivity and discoid skin lesions.

Conclusion. We describe a novel association between IL1RN*2 and SLE. Carriage of the allele seems to influence severity rather than susceptibility to SLE. We postulate that the association of this polymorphism with disease severity is a widespread feature of common inflammatory and autoimmune diseases.
Migration and homing of lymphocytes to lymphoid and synovial tissues in proteoglycan–induced murine arthritis
Authors: Mikecz Katalin , Glant Tibor T,
Published: February 2007

Objective. To describe the migration and homing of labeled donor lymphocytes to the lymphoid organs and synovial tissues of host animals, during the development of cartilage proteoglycan (PG)—induced arthritis adoptively transferred to syngeneic BALB/c mice.

Methods. Lymphocytes from either nonarthritic or arthritic donor animals were labeled with either fluorescent or radioactive cell linkers (PKH–GL) and injected into syngeneic, immunosuppressed mice. The homing patterns of donor lymphocytes following the injection of labeled cells were studied by fluorescence microscopy and by measurement of radioactivity in tissue samples.

Results. Lymphocytes from arthritic donors retained their ability to transfer the disease after labeling. In the lymphoid organs, arthritic and nonarthritic donor lymphocytes exhibited similar homing patterns, although remarkable differences were found in the number of homing cells derived from nonarthritic and arthritic donors. However, labeled cells only from arthritic animals migrated to the synovial tissue of the recipient mice, and their appearance was associated with the onset of arthritis.

Conclusion. Lymphocytes from mice with PG–induced arthritis, in contrast to lymphocytes from nonarthritic donors, exhibit preferential homing to the synovial tissue of the host. Adoptive transfer of arthritis is linked to the appearance of these cells in the synovium.
High levels of bcl‐2 protein in circulating t lymphocytes, but not b lymphocytes, of patients with systemic lupus erythematosus
Authors: Aringer Martin , Wintersberger Winfried , Steiner Carl W. , Kiener Hans , Presterl Elisabeth , Jaeger Ulrich , Smolen Josef S. , Graninger Winfried B.
Published: February 2007

Objective. Defective regulation of programmed cell death (apoptosis) may play a role in the development of autoimmune diseases, and the proto‐oncogene bcl‐2 is involved in the control of apoptosis in immunocompetent cells. We therefore wished to investigate the expression of bcl‐2 in the peripheral lymphocytes of patients with systemic lupus erythematosus (SLE), a prototypical autoimmune disease.

Methods. Levels of bcl‐2 expression in the lymphocytes of patients with SLE and, for comparison, in the lymphocytes of healthy controls and patients with rheumatoid arthritis (RA), systemic bacterial infections, and chronic B cell lymphocytic leukemia were studied by 2‐color cytofluorography and RNA analysis.

Results. In SLE patients, a significant proportion of T cells expressed increased amounts of bcl‐2 protein. By fluorescence‐activated cell sorter analysis, bcl‐2‐enriched lymphocytes were found in the CD45RO+ as well as in the CD45RO‐, and also in the CD4+ and CD8+, lymphocyte subpopulations. Mononuclear cells of patients with SLE showed increased amounts of bcl‐2 messenger RNA. An increased percentage of strongly bcl‐2 positive peripheral T lymphocytes was found in patients with bacterial infections, but not in those with RA.

Conclusion. Although the occurrence of circulating T lymphocytes with abnormally high bcl‐2 expression is not specific for SLE, it is evidence for a dysregulation of lymphocytic programmed cell death in this autoimmune disease.
Increased frequency of vβ17‐positive t cells in patients with rheumatoid arthritis
Authors: Zagon Gary , Tumang Joseph R. , Li Yixin , Friedman Steven M. , Crow Mary K.
Published: February 2007

Objective. To identify the T lymphocytes that mediate disease in rheumatoid arthritis (RA).

Methods. A panel of monoclonal antibodies reactive with T cell receptor (TCR) Vβ gene products was used to analyze the RA T cell repertoire.

Results. Of 5 TCR Vβ gene products studied, only Vβ17‐positive T cells were increased in peripheral blood and synovial fluid (SF) from RA patients, compared with controls (P < 0.01 and P = 0.0006, respectively). Thirty‐one percent of the 49 RA SF samples and none of the 19 non‐RA SF samples contained >10% Vβ17‐positive T cells. Activated (Tac‐positive) T cells were enriched among Vβ17‐positive synovial T cells.

Conclusion. The selective increase of Vβ17‐positive T cells suggests a role for those T cells in the pathogenesis of RA.
β2‐Glycoprotein i reactivity of monoclonal anticardiolipin antibodies from patients with the antiphospholipid syndrome
Authors: Ichikawa Kenji , Khamashta Munther A. , Koike Takao , Matsuura Eiji , Hughes Graham R. V.
Published: February 2007

Objective. To elucidate the specificity of anticardiolipin antibodies (aCL) from patients with the antiphospholipid syndrome (APS) to various phospholipids (PLs), DNA, and β2‐glycoprotein I (β2‐GPI).

Methods. Five monoclonal aCL were established from peripheral blood lymphocytes of 3 patients with the APS. The reactivity of monoclonal aCL with various PLs, with DNA, and with β2‐GPI was examined by enzyme‐linked immunosorbent assay (ELISA).

Results. All of the monoclonal aCL bound to anionic PLs, only in the presence of β2‐GPI. Neither monoclonal aCL nor β2‐GPI bound to DNA. Monoclonal aCL bound to solid‐phase β2‐GPI on polystyrene ELISA plates that had carboxyl groups on their surface, but did not react with solid‐phase β2‐GPI on ordinary polystyrene plates. A mixture of β2‐GPI and CL inhibited the binding of monoclonal aCL to β2‐GPI, but CL or β2‐GPI alone did not.

Conclusion. Monoclonal aCL may recognize a cryptic epitope, which appears as a result of β2‐GPI binding to anionic PLs or to polystyrene with carboxyl groups.
Molecular cloning of a soluble form of the granulocyte‐‐macrophage colony‐stimulating factor receptor α chain from a myelomonocytic cell line. expression, biologic activity, and preliminary analysis of transcript distribution
Authors: Williams William V. , Vonfeldt Joan M. , Rosenbaum Helga , Ugen Kenneth E. , Weiner David B.
Published: February 2007

Objective. To analyze the molecular and functional characteristics of a soluble form of the granulocytemacrophage colony‐stimulating factor receptor α chain (sGM‐CSFRα), and analyze transcript expression in immune cells and the cellular constituents of rheumatoid arthritis synovial tissue.

Methods. We amplified, cloned, and expressed the sGM‐CSFRα and transmembrane form of the receptor (tmGM‐CSFRα) from complementary DNA derived from a human myelomonocytic cell line. Competitive polymerase chain reaction assays were developed to determine the absolute and relative amounts of tmGM‐CSFRα versus sGM‐CSFRα message synthesized by various cell lines and tissues.S

Results. sGM‐CSFRα transcripts were detected in bone marrow, monocyte/macrophages (cultured in GM‐CSF), rheumatoid synovial tissue, and rheumatoid synovial tissue T cell lines, and represented the predominant transcript in synovial fibroblasts and osteoarthritis synovial tissue. Levels of expression in monocyte/macrophages and some synovial fibroblast and T cell lines approached those seen in transfected cell lines producing functional sGM‐CSFRα.

Conclusion. sGM‐CSFRα represents a functional antagonist of GM‐CSF activity in vitro. Expression of sGM‐CSFRα in bone marrow, rheumatoid synovial tissue T cells, and synovial fibroblasts suggests an important role in vivo, both in regulating myelopoiesis and in modulating the immune response.
The efficacy and toxicity of combination therapy in rheumatoid arthritis. a meta‐analysis
Authors: Felson David T. , Anderson Jennifer J. , Meenan Robert F.
Published: February 2007

Objective. To evaluate the efficacy and toxicity of combination therapy, compared with single second‐line drug therapy, in rheumatoid arthritis.

Methods. This study was a meta‐analysis of published trials that evaluated combinations of full‐dose second‐line drugs and compared them with single second‐line drugs at full dose. Using a random effects model, we summarized the difference between improvement with combination therapy and improvement with single‐drug therapy.

Results. Five trials that met inclusion criteria, which contained 749 entering patients and 516 completing patients, were identified. The mean ± SEM difference in improvement in tender joint count between combination and single‐drug therapy at end of trial (24–52 weeks) was 2.4 ± 0.7 joints (out of 60) (P < 0.001). At end of trial the difference between therapies in swollen joint counts was 1.0 ± 1.2 joints (P = 0.42). The difference in grip strength improvement was 3.7 ± 4.3 mm Hg (P = 0.40), and for erythrocyte sedimentation rate it was 3.4 ± 3.1 mm/hour (P = 0.27). In general, the differences in efficacy between combination and single‐drug therapy were clinically marginal. Nine percent more combination therapy‐treated patients experienced side effect‐related discontinuation of therapy than patients receiving single‐drug therapy (P = 0.008).

Conclusion. Combination therapy, as it has been used in recent clinical trials, does not offer a substantial improvement in efficacy, but does have higher toxicity than single drug therapy. These combination therapy regimens are not recommended for widespread use. Other more aggressive regimens with additional drugs or higher drug doses than have been studied might be more efficacious, but with an even higher rate of toxicity.
Effect of hormone replacement therapy on bone mass in rheumatoid arthritis patients treated with and without steroids
Authors: Hall Gerard M. , Daniels Maxine , Doyle David V. , Spector Tim D.
Published: February 2007

Objective. To assess the effect of hormone replacement therapy (HRT) on bone mass in rheumatoid arthritis (RA) patients treated with and those not treated with steroids.

Methods. Two hundred postmenopausal women with RA (ages 45‐65 years) were randomly allocated to receive transdermal estradiol (hormone replacement therapy; HRT) (50 μg daily) or calcium supplementation (400 mg daily) for 2 years. Forty‐two of the patients (21%) were taking corticosteroids. Bone mineral density of the lumbar spine (BMDLS) and of the proximal femur (BMDF) was measured at study entry and at 12 months and 24 months.

Results. In the HRT group overall, mean BMDLS had changed by +2.22% (95% confidence interval [95% CI] +0.72, +3.72) and mean BMDF by −0.41 % (95% CI −1.89, +1.07) after 24 months. In the calcium group, mean BMDLS changed by −1.19% (95% CI −2.29, −0.09) and mean BMDF by −0.56% (95% CI −2.60, +1.48). Differences between treatment groups were significant for the spine only (P < 0.001). In the 21 HRT‐treated patients taking steroids, BMDLS increased by 3.75% (95% CI +0.72, +6.78) and BMDF by 1.62% (95% CI −1.27, +4.51).

Conclusion. This study shows that HRT increases spinal BMD and maintains femoral BMD in postmenopausal RA. HRT is also an effective agent in preserving bone mass in patients taking low‐dose corticosteroids.
Somatostatin receptor imaging. the presence of somatostatin receptors in rheumatoid arthritis
Authors: Vanhagen P. M. , Markusse H. M. , Lamberts S. W. J. , Kwekkeboom D. J. , Reubi J. C. , Krenning E. P.
Published: February 2007

Objective. To investigate the in vivo and in vitro expression of somatostatin receptors (SS‐R) on synovial membranes of patients with rheumatoid arthritis (RA).

Methods. The joints of 14 consecutive patients with active RA, 4 patients with severe osteoarthritis (OA), and 30 control patients were studied. The somatostatin analog [111In‐DTPA‐D‐Phe1]‐octreotide was used for in vivo SS‐R scintigraphy, and the somatostatin analog [125I‐Tyr3]‐octreotide for in vitro SS‐R autoradiography.

Results. Seventy‐six percent (220 of 290) of the painful joints and 76% (207 of 274) of the swollen joints of the patients with RA were visualized by SS‐R scintigraphy. The degree of pain and swelling correlated well with positive scintigraphy findings in the joints (P < 0.0001). In 2 of the RA patients who underwent scintigraphy, as well as in 4 of 5 other patients, in vitro studies of the synovial membranes showed the presence of specific SS‐R. In patients with OA, uptake of radioactivity in the affected joints was significantly lower than that in patients with RA. None of the joints of the control patients demonstrated uptake of radioactivity.

Conclusion. SS‐R are present in the synovial tissue of patients with active RA, as demonstrated by both in vivo and in vitro techniques. The potential value of SS‐R scintigraphy in the clinical evaluation of patients with active RA is presently unknown.
Long‐term iloprost infusion therapy for severe pulmonary hypertension in patients with connective tissue diseases
Authors: Mata Jose De La , Gomez‐Sanchez Miguel A. , Aranzana Mercedes , Gomez‐Reino Juan J.
Published: February 2007

Objective. To determine the effects of short‐term, maximum‐tolerated‐dose and long‐term, optimum‐dose iloprost treatment of severe pulmonary hypertension associated with systemic sclerosis (SSc) and the primary antiphospholipid syndrome (APS).

Methods. Three patients with SSc and 2 with APS who had failed to respond to oral vasodilator therapy for pulmonary hypertension were enrolled in a 32‐week, open, prospective trial. Short‐term infusion of maximum‐tolerated doses and continuous infusion of optimum doses of iloprost were carried out following baseline cardiac catheterization. Catheterization was repeated at 2 and 32 weeks. All 5 patients completed the study and continued therapy for an average of 82 weeks (range 58–103).

Results. Acute infusion of maximum tolerated doses significantly ameliorated the cardiac index (0.92 liters/minute/m2; P < 0.01), pulmonary artery O2 saturation (10.6%; P < 0.05), and pulmonary resistance (−6.7 units; P < 0.05). After 2 weeks of continuous infusion of optimum doses, there was improvement in pulmonary resistance (⩾16%) and pulmonary artery O2 saturation ( > 30%) in the 2 patients with primary APS. After 2 and 32 weeks, the 3 SSc patients showed variable hemodynamic responses. New York Heart Association functional class and exercise tolerance improved in all patients. There was 1 episode of bacteremia, and 1 patient died after 72 weeks of study.

Conclusion. Continuous iloprost infusion may improve exercise tolerance and quality of life in patients with severe pulmonary hypertension associated with SSc and primary APS.
A broadened spectrum of juvenile myositis. myositis‐specific autoantibodies in children
Authors: Rider Lisa G. , Miller Frederick W. , Targoff Ira N. , Sherry David D. , Samayoa Eduardo , Lindahl Madeleine , Wener Mark H. , Pachman Lauren M. , Plotz Paul H.
Published: February 2007

Objective. Myositis‐specific autoantibodies (MSA) define relatively homogenous clinical and immunogenetic patient groups in adults with idiopathic inflammatory myopathies (IIM). This study explores the usefulness of MSA in defining groups of children with myositis.

Methods. Sera from 77 children with myositis and other connective tissue diseases were tested for MSA by immunoprecipitation and immunodiffusion. Clinical data were collected and analyzed.

Results. The MSA anti‐PL‐12 (alanyl‐transfer RNA synthetase), anti‐Jo‐1 (histidyl‐tRNA synthetase), anti‐signal recognition particle, and anti‐Mi‐2 were each identified in the sera of 12 children with IIM. In these patients, the clinical manifestations, disease courses, and responses to therapy closely resembled those in adults with the same autoantibodies.

Conclusion. These observations suggest that the clinical syndromes defined by particular MSA are similar in children and adults with IIM. By defining similar clinical syndromes in children who have MSA, this study provides a basis for future studies of MSA in the idiopathic inflammatory myopathies of childhood, which may be useful in predicting the clinical courses of a subset of these patients and improving their therapy.
Thoracic aortic aneurysm and rupture in giant cell arteritis. a descriptive study of 41 cases
Authors: Evans Jonathan M. , Bowles Carolyn A. , Bjornsson Johannes , Mullany Charles J. , Hunder Gene G.
Published: February 2007

Objective. To determine the features and outcomes of patients with giant cell arteritis (GCA) who have aneurysms or rupture of the thoracic aorta.

Methods. Patients with GCA seen over a 40‐year period who had aneurysms and/or rupture of the thoracic aorta were identified by assistance of a computerized indexing system. The presence of thoracic aortic aneurysms (TAA), with or without aortic valve insufficiency (AI), was determined by radiographs, computed tomography scans, and ultrasound studies of the thorax, angiograms of the aorta, and postmortem examination.

Results. Ten men and 31 women with GCA were found to have TAA and/or rupture. Three developed TAA before GCA was diagnosed, 5 developed aortic findings near the time of the diagnosis, and 33 after the diagnosis of GCA (median of 7 years after diagnosis). Sixteen patients developed acute aortic dissection, which caused death in 8. Nineteen patients also had AI due to aortic root dilation, 15 of whom developed congestive heart failure. Eighteen patients underwent 21 surgical procedures for TAA resection and/or aortic valve replacement or repair. Aortitis was documented histologically in 10 cases.

Conclusion. Thoracic aortic complications in GCA are associated with serious outcomes that have been underrecognized and may be fatal. Physicians should be alert to the development of these complications at any time in the course of GCA, even many years after usual symptoms have subsided.
Systemic lupus erythematosus presenting as a non‐o:1 vibrio cholerae abscess
Authors: Nedunchezian Deeptha , Cook Michael A. , Rakic Milovan
Published: February 2007

The usual presentations and manifestations of systemic lupus erythematosus (SLE) are well known. We describe a patient with SLE that was discovered in the course of evaluation of an abscess, found to be associated with non‐O:1 Vibrio cholerae.
Elevated cerebrospinal fluid levels of substance p in patients with the fibromyalgia syndrome
Authors: Russell I. Jon , Orr Malcolm D. , Littman Bruce , Vipraio Gilbert A. , Alboukrek David , Michalek Joel E. , Lopez Yolanda , Mackillip Fane
Published: February 2007

Objective. To measure, and seek clinical correlates with, levels of substance P (SP) in the cerebrospinal fluid (CSF) of fibromyalgia syndrome (FMS) patients.

Methods. CSF from 32 FMS patients and 30 normal control subjects was tested for SP by radio‐immunoassay. Clinical measures included tender point examination and standardized questionnaires.

Results. CSF SP levels were 3‐fold higher in FMS patients than in normal controls (P < 0.001), but they correlated only weakly with tenderness found on examination.

Conclusion. SP is significantly elevated in FMS CSF, but other abnormalities must exist in FMS to more fully explain the symptoms.