bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased percentage of cd3+, cd57+ lymphocytes in patients with rheumatoid arthritis. correlation with duration of disease
Authors: D'Angeac Arnaud Dupuy , Monier Serge , Jorgensen Christian , Gao Qinglin , Travaglio‐Encinoza Adolfo , Bologna Christophe , Combe Bernard , Sany Jacques , Reme Thierry
Published: February 2007

Objective. To determine whether a small CD3+ lymphocyte population expressing 110‐kd CD57 antigens (HNK1) is expanded in patients with rheumatoid arthritis (RA), as it is in patients who have undergone bone marrow transplantation and patients with the acquired immunodeficiency syndrome, and to investigate whether it is involved in the pathogenesis of RA.

Methods. The phenotype of CD3+, CD57+ lymphocytes was analyzed by flow cytometry, and correlations between the percentage of these cells in the blood and various clinical and biologic parameters were investigated.

Results. The percentage of CD3+, CD57+ lymphocytes was increased in RA patients compared with controls. These lymphocytes expressed T cell receptor α/β. Eighty percent expressed the CD8 accessory molecule, and 20% expressed the CD4 accessory molecule. The leukocyte common antigen CD45RA isoform was expressed by these CD3+, CD57+ lymphocytes in blood. The HLA–DR antigen was expressed in synovial fluid but not in blood. Finally, the percentage of these lymphocytes in the blood correlated with the duration of RA.

Conclusion. The expansion of the CD3+, CD57+ lymphocyte population and their activation in the synovial fluid of RA patients suggest that these cells are involved in the inflammatory process.
The effects of drug therapy on radiographic progression of rheumatoid arthritis. results of a 36‐week randomized trial comparing methotrexate and auranofin
Authors: Weinblatt Michael E. , Polisson Richard , Blotner Steven D. , Leland Sosman J. , Aliabadi Piran , Baker Nancy , Weissman Barbara N.
Published: February 2007

Objective. To determine the effects of drug therapy (methotrexate [MTX] versus auranofin [AUR]) on radiographic progression in patients with active rheumatoid arthritis (RA).

Methods. We conducted a 9‐month randomized, multicenter, double‐blind trial comparing MTX and AUR. Standardized radiographs of the hands and wrists were obtained at baseline and at completion of the study. Four experienced bone radiologists graded the radiographs for erosions, joint space narrowing, erosion healing, and reparative bone formation.

Results. Two hundred eighty‐one patients were enrolled in the study. Radiographs were available on 167 of the 183 who completed the trial. After 9 months of therapy, there was a significantly greater worsening of the erosion score in the AUR group (mean ± SEM change of 1.67 ± 0.4) compared with the change in the MTX group (0.60 ± 0.3) (P = 0.040). There was also a significantly greater worsening of the joint space narrowing score in the AUR group compared with the MTX group (1.36 ± 0.3 versus 0.42 ± 0.2) (P = 0.007). There was no difference demonstrated between groups in healing of erosions or in reparative bone formation.

Conclusion. The rate of radiographic progression in patients with RA, as measured by erosion score and joint space narrowing score, was demonstrated to be lower in those treated with MTX, as compared with AUR, over a 36‐week period.
Effects of administration of an anti‐cd5 plus immunoconjugate in rheumatoid arthritis. results of two phase ii studies
Authors: Strand Vibeke , Lipsky Peter E. , Cannon Grant W. , Calabrese Leonard H. , Wiesenhutter Craig , Cohen Stanley B. , Olsen Nancy J. , Lee Martin L. , Lorenz Todd J. , Nelson Betty , Wolfe Frederick , Fleischmann Roy M. , Karr Reynold M. , Krick George H. , Medsger Thomas A. , Rigby William F. C. , Fox David A. , Swartz Timothy J. , Multz Carter V. , Weisman Michael H.
Published: February 2007

Objective. To evaluate the safety and activity of an immunoconjugate of ricin A chain and anti‐CD5 monoclonal antibody (anti‐CD5 IC), with and without concomitant methotrexate and/or azathioprine, in the treatment of rheumatoid arthritis (RA).

Methods. Seventy‐nine patients with active RA were enrolled in 2 prospective open‐label protocols.

Results. Using composite criteria, response rates were 50–68% at 1 month and 22–25% at 6 months. Transient depletion of CD3/CD5 T cells was observed on days 2 and 5 of treatment, with reconstitution on day 15 or day 29. Treatment‐associated adverse effects were common but resolved rapidly without sequelae.

Conclusion. These findings suggest activity of anti‐CD5 IC in active RA and warrant confirmation in a multicenter randomized study (currently underway).
Analysis of immunoglobulin gamma heavy chain expression in synovial tissue of a patient with rheumatoid arthritis
Authors: Louis S. Bridges, , Lee Soo Kon , Koopman William J. , Schroeder Harry W.
Published: February 2007

Objective. To gain insight into mechanisms underlying local immune responses in rheumatoid arthritis (RA), we analyzed the utilization of variable‐region heavy chain (VH), diversity (DH), and joining (JH) gene segments expressed in synovial tissue of a patient with RA.

Methods. An unrestricted complementary DNA (cDNA) library was generated from unselected cells extracted from synovial tissue obtained at the time of joint replacement. Southern blot analysis for VH, JH, and Cγ subclass utilization was performed on the first 50 Cγ‐ and JH‐positive recombinants for which phage DNA was isolated. Eighteen of the clones were selected at random for sequence analysis. The VH gene segments were compared with an extensive database of germline and cDNA sequences.

Results. All transcripts utilized gene segments from the VH1 (28%), VH3 (56%), and VH4 (15%) families. There was a predominance of JH4, JH5, and JH6 gene segment utilization. Fourteen of 18 randomly sequenced clones contained sufficient VH‐region information for analysis. Eight (57%) were most closely related to VH gene segments that are preferentially expressed in human fetal liver or that encode antibodies with self‐reactivity. The variable domains were heavily mutated, and replacement‐to‐silent substitution ratios (R:S ratios) in the antigen‐binding domains (complementarity‐determining regions [CDRs]) were disproportionately high. CDR3 lengths were quite variable, due to extensive N‐region addition and 5′‐exonuclease activity in the VH–DH–JH joins.

Conclusion. Plasma cells in this synovial tissue sample appear to express VH gene segments that are preferentially utilized during fetal development or in autoantibodies. The JH repertoire is similar to that seen in adult peripheral blood lymphocytes, but much different from that found during fetal development. The large number of somatic mutations and the high R:S ratios in the CDRs suggest an antigen‐driven response.
Pressure pain threshold in pain‐free subjects, in patients with chronic regional pain syndromes, and in patients with fibromyalgia syndrome
Authors: Granges Gerald , Littlejohn Geoffrey
Published: February 2007

Objective. We hypothesized that change in pain threshold to pressure reflects a generalized change in the pain system affecting both tender and control points.

Methods. We assessed 18 tender points and 4 control points using an algometer in 60 patients with generalized fibromyalgia/fibrositis syndrome, 60 patients with localized chronic pain syndromes, and in 60 pain‐free subjects.

Results. A significant correlation was found between myalgia scores at tender points and control points in these subjects.

Conclusion. These results suggest that there is a diffuse change in pain modulation in fibromyalgia, as hypothesized, but the tender point is still clinically useful.
Characteristics of anti‐type ii collagen antibody binding to articular cartilage
Authors: Jasin Hugo E. , Noyori Koji , Takagi Toshitaka , Taurog Joel D.
Published: February 2007

Objective. Previous studies suggested that it was possible to characterize the intact surface of articular cartilage by probing it with antibodies against matrix macromolecules. The present studies were undertaken to investigate type II collagen (CII) epitope availability on the intact surface of articular cartilage.

Methods. Normal bovine, rabbit, and human cartilage specimens were used to measure binding of anti‐CII antibodies to the articular and cut surfaces of cartilage. Antisera were raised against the material obtained after brief extraction of the cartilage surface with 4M guanidine solution.

Results. Anti‐CII did not bind to the intact surface of rabbit articular cartilage when compared with control rat sera, but did bind significantly to the cut surface. With normal human articular cartilage, the cut surfaces bound approximately 4 times as much anti‐CII antibody as the intact articular surfaces. These findings suggested that the CII epitopes are normally protected by the superficial cartilage layer. In experiments carried out to characterize this layer, binding of anti‐CII antibodies was unchanged after exhaustive washing of bovine or rabbit cartilage with phosphate buffered saline or 1M NaCl solution, whereas it was significantly increased after brief exposure to 4M guanidine solution or after incubation with neutrophil elastase. No restoration of the protection of CII epitopes in guanidine‐treated cartilage could be achieved by incubation with undiluted normal bovine synovial fluid; however, 8‐day culture of elastase‐treated cartilage explants resulted in partial restoration of protection of the CII epitopes. Rat and rabbit antisera raised against the cartilage surface material extracted with 4M guanidine contained antibodies that bound to the cartilage surface. By Western blotting, rat antibodies identified 50–65‐kd protein bands present in the guanidine extract, but not present either in the material obtained from brief digestion of cartilage with neutrophil elastase or in synovial fluid. The rabbit antisera identified a broad 70–95‐kd band. Exposure of elastase‐treated cartilage to the guanidine‐extracted material resulted in a partial decrease of anti‐CII antibody binding.

Conclusion. These results suggest that CII on intact cartilage is protected from antibody binding, and that the protective material is at least partly proteinaceous in nature, is unlikely to be derived from synovial fluid, is noncovalently bound to the underlying intercellular matrix, and is synthesized by resident chondrocytes. Further characterization of the protective material may provide important information on the mechanisms of early cartilage damage in inflammatory arthritis.
Susceptibility to relapsing polychondritis is associated with hla–‐dr4
Authors: Lang Bernhard , Rothenfusser Anna , Lanchbury Jerry S. , Rauh Günter , Breedveld Ferdinand C. , Urlacher Arlette , Albert Ekkehard D. , Peter Hans‐Hartmut , Melchers Inga
Published: February 2007

Objective. To determine the frequency of HLA class II antigens in Caucasian central European patients with relapsing polychondritis (RP).

Methods. HLA class I, DR, and DQ specificities were identified in 41 patients with RP, and the frequencies were compared with those in 204 healthy, unrelated control subjects. HLA typing was performed using the standard complement‐dependent microcytotoxicity assay. HLA–DR genotyping of 12 DR4‐positive RP patients and 57 controls was performed by allele‐specific oligonucleotide probing after amplification of genomic DNA by polymerase chain reaction.

Results. A significant increase in DR4 antigen frequency was found in the patients (56.1%) as compared with that in healthy controls (25.5%) (Pcorr < 0.001). Genotyping of DR4‐positive patients and controls revealed no predominance of any DR4 subtype.

Conclusion. There are important clinical similarities and overlaps between RP and rheumatoid arthritis (RA). In RA, the association with DR4 has been well established. Our findings show that although there is a DR4 association with RP, the situation is sufficiently distinct from that of RA to imply considerable differences in pathogenesis of the two conditions.
The polymerase chain reaction for the detection of borrelia burgdorferi in human body fluids
Authors: Liebling Michael R. , Nishio Midori Jane , Rodriguez Annette , Sigal Leonard H. , Jin Tian , Louie James S.
Published: February 2007

Objective. To analyze clinical fluids for the presence of Borrelia burgdorferi DNA using the polymerase chain reaction (PCR).

Methods. We utilized a modified, nested PCR to detect the presence of Borrelia DNA in 99 samples of serum, urine, cerebrospinal fluid (CSF), or synovial fluid obtained from 44 patients with various stages of Lyme disease and 47 control subjects. Primer specificity was corroborated by examining 2 DNA data banks, testing against DNA from other organisms, and confirming results with a second set of nested primers.

Results. Nested PCR was capable of detecting DNA from fewer than 10 organisms in 1 ml of fluid. The specificity of this technique was 96.4%, with a sensitivity of 76.7%. Although the specificity was uniformly high, the sensitivity was dependent upon the body fluid being tested: CSF 100%, urine 100%, synovial fluid 80%, and serum 59%. The rate of false‐positive results was 3.6%.

Conclusion. These data demonstrate the potential utility of PCR in confirming the clinical diagnosis of Lyme disease as well as providing insight into the pathogenesis of various stages of this disorder.
Treatment of refractory, systemic lupus erythematosus–associated thrombocytopenia with intermittent low‐dose intravenous cyclophosphamide
Authors: Roach Barbara A. , Hutchinson Gordon J.
Published: February 2007

We describe a patient with systemic lupus erythematosus and severe, treatment‐resistant thrombocytopenia. Prolonged treatment with high‐dose steroids eventually led to reversal of the thrombocytopenia, but the dosage could not be tapered without relapse. Low‐dose intravenous bolus cyclophosphamide was given, producing a response within 1 week. The steroid dosage was tapered, without relapse. Other than reversible alopecia, no toxicity was seen. The use of this treatment should be considered in patients in whom more conventional therapies are not effective or cannot be tolerated.
Cold‐induced potentiation of α2‐adrenergic vasoconstriction in primary raynaud's disease
Authors: Freedman Robert R. , Moten Marriyam , Migaly Peter , Mayes Maureen
Published: February 2007

Objective. To determine the effects of local cooling on α‐adrenergic responses in the fingers of patients with idiopathic Raynaud's disease.

Methods. Clonidine HCl and phenylephrine HCl were administered through a brachial artery catheter while blood flow was measured by plethysmography in cooled and uncooled fingers.

Results. Cooling potentiated α2‐adrenergic vasoconstriction in the patients but depressed this response in the controls. Vasoconstrictive responses to phenylephrine were not significantly affected by cooling but were significantly greater in the patients than in the controls.

Conclusion. Cold‐induced sensitization of peripheral vascular α2‐adrenoceptors may be involved in the mechanism by which cooling triggers the vasospastic attacks of Raynaud's disease.
Sarcoidosis accompanied by pulmonary tuberculosis and complicated by sacroiliitis
Authors: Griep Eduard N. , Van Spiegel Paul I. , Van Soesbergen Renée M.
Published: February 2007

We report the unique occurrence of a unilateral sacroiliitis in a patient with active sarcoidosis accompanied by pulmonary tuberculosis. Convincing (clinical) evidence of sarcoidosis as the extremely rare cause of this articular involvement is presented. Discussion is focused on comparison of sarcoidosis and tuberculosis, particularly with respect to their articular involvement, and the literature of previously reported cases of sarcoid sacroiliitis is briefly reviewed.
The American college of rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials
Authors: Felson David T. , Anderson Jennifer J. , Boers Maarten , Bombardier Claire , Chernoff Miriam , Fried Bruce , Furst Daniel , Goldsmith Charles , Kieszak Stephanie , Lightfoot Robert , Paulus Harold , Tugwell Peter , Weinblatt Michael , Widmark Rudolph , James Williams H. , Wolfe Frederick
Published: February 2007

Objective. To develop a set of disease activity measures for use in rheumatoid arthritis (RA) clinical trials, as well as to recommend specific methods for assessing each outcome measure. This is not intended to be a restrictive list, but rather, a core set of measures that should be included in all trials.

Methods. We evaluated disease activity measures commonly used in RA trials, to determine which measures best met each of 5 types of validity: construct, face, content, criterion, and discriminant. The evaluation consisted of an initial structured review of the literature on the validity of measures, with an analysis of data obtained from clinical trials to fill in gaps in this literature. A committee of experts in clinical trials, health services research, and biostatistics reviewed the validity data. A nominal group process method was used to reach consensus on a core set of disease activity measures. This set was then reviewed and finalized at an international conference on outcome measures for RA clinical trials. The committee also selected specific ways to assess each outcome.

Results. The core set of disease activity measures consists of a tender joint count, swollen joint count, patient's assessment of pain, patient's and physician's global assessments of disease activity, patient's assessment of physical function, and laboratory evaluation of 1 acute‐phase reactant. Together, these measures sample the broad range of improvement in RA (have content validity), and all are at least moderately sensitive to change (have discriminant validity). Many of them predict other important long‐term outcomes in RA, including physical disability, radiographic damage, and death. Other disease activity measures frequently used in clinical trials were not chosen for any one of several reasons, including insensitivity to change or duplication of information provided by one of the core measures (e.g., tender joint score and tender joint count) The committee also proposes specific ways of measuring each outcome.

Conclusion. We propose a core set of outcome measures for RA clinical trials. We hope this will decrease the number of outcomes assessed and standardize outcomes assessments. Further, we hope that these measures will be found useful in long‐term studies.
An organizational model for developing multidisciplinary clinical research in the academic medical center
Authors: Charlson Mary E. , Allegrante John P. , Hollenberg James P. , Szatrowski Ted P. , Peterson Margaret G. E. , Robbins Laura , Gordon Karen A. , Ronald Mackenzie C. , Williams‐Russo Pamela , Paget Stephen A.
Published: February 2007

Objective. To assess the impact of a new organizational model designed to stimulate multidisciplinary clinical research.

Methods. We conducted a prospective, 3½‐year follow up of a research training program for residents, fellows, faculty, nurses, and allied health professionals in rheumatology and orthopedic surgery. Program components included a multidisciplinary clinical research conference, a clinical research methods curriculum, consultations, a patient registry, and regular meetings of a Research Methodology Core group. Measures included participation in each program component and the number of new investigators who developed funded clinical research projects.

Results. The multidisciplinary clinical research conference was attended by 369 new health professionals; 218 professionals participated in at least one of the courses; and 280 consultations were provided to 108 professionals. Thirteen new investigators developed 17 new grant proposals, of which 14 were externally funded. Investigators who successfully procured funding for new projects demonstrated significantly more participation in program components compared with those who did not (P < 0.001 overall).

Conclusion. Participation in the program was significantly correlated with the development of new prospective patient‐based studies. We conclude that our model has the potential to foster such research in other settings.
Quality of life issues in women with vertebral fractures due to osteoporosis
Authors: Cook Deborah J. , Guyatt Gordon H. , Adachi Jonathan D. , Clifton Joanne , Griffith Lauren E. , Epstein Robert S. , Juneper Elizabeth F.
Published: February 2007

Objective. To learn about the physical, emotional, and social limitations experienced by postmenopausal women who have back pain due to vertebral fractures resulting from osteoporosis.

Methods. We conducted a cross‐sectional survey of female patients with persistent pain due to vertebral fractures.

Results. Respondents had a mean (±SD) bone density of 0.87 ± 0.13 gm/cm2 and a mean (±SD) of 2.48 ± 2.18 fractures. Disability was identified in pain, movement, activities of daily living, and emotion. There was a poor correlation between quality of life and findings on radiography or densitometry.

Conclusion. To evaluate the effects of osteoporosis on a patient's functional status, direct questioning is required.
Expression of monocyte chemotactic and activating factor in rheumatoid arthritis. regulation of its production in synovial cells by interleukin‐1 and tumor necrosis factor
Authors: Akahoshi Tohru , Wada Chieki , Endo Hirahito , Hirota Kazuhisa , Hosaka Shigeru , Takagishi Kenji , Kondo Hirobumi , Kashiwazaki Sadao , Matsushima Kouji
Published: February 2007

Objective. To investigate whether monocyte chemotactic and activating factor (MCAF) contributes to the accumulation of macrophages in the joints of patients with rheumatoid arthritis (RA).

Methods. MCAF was measured by radioimmunoassay. MCAF gene expression was determined by Northern blotting and reverse‐transcriptase polymerase chain reaction. Recombinant human MCAF was injected into rabbit joints to evaluate the effect of MCAF on infiltration of macrophages.

Results. High levels of MCAF were detected in synovial fluid from patients with RA. Cells freshly isolated from synovial fluid expressed MCAF messenger RNA (mRNA). Fibroblast‐like synoviocytes were found to express MCAF mRNA and to secrete MCAF in response to interleukin‐1 (IL‐1) and tumor necrosis factor in vitro. IL‐1 also promoted MCAF gene expression in rabbit synovial tissue in vivo. MCAF caused marked infiltration of macrophages in rabbit synovial tissue.

Conclusion. Our findings suggest that MCAF may contribute to the accumulation of macrophages in inflamed rheumatoid joints.
Stimulation of the secretion of latent cysteine proteinase activity by tumor necrosis factor α and interleukin‐1
Authors: Huet Guillemette , Flipo René‐Marc , Colin Cécile , Janin Anne , Hemon Brigitte , Collyn‐D'Hooghe Maud , Lafyatis Robert , Duquesnoy Bernard , Degand Pierre
Published: February 2007

Objective. Cultured synovial fibroblast‐like cells from 3 patients with rheumatoid arthritis (RA) and 3 patients with osteoarthritis (OA) were evaluated for their potential to secrete cysteine proteinases spontaneously and after stimulation by tumor necrosis factor α (TNFα) or interleukin‐1 (IL‐1).

Methods. Culture media and cell lysates were analyzed before and after high performance liquid chromatography (HPLC) using the enzymatic substrate, Z‐Phe‐Arg‐AMC, and by immunoblotting with anti–cathepsin B antiserum. Immunolocalization of cathepsin B was studied on cell monolayers.

Results. Latent cysteine proteinase activity was found to be secreted spontaneously by cultured synovial fibroblast‐like cells. This activity was increased after treatment with either TNFα or IL‐1. Stimulated protease activity was eluted by HPLC at a peak coincident with that of purified cathepsin B. By immunoblot, cell supernatants contained a 43‐kd form of cathepsin B, while cell lysates contained a 30‐kd form, consistent, respectively, with cathepsin B before and after cleavage of its propeptide. An intracellular increase in cathepsin B after treatment with TNFα was also seen with immunohistochemical studies.

Conclusion. TNFα (in the 6 cases studied) and IL‐1 (in 4 cases) stimulated the secretion of a latent cysteine proteinase activity from synovial fibroblast‐like cells, which appears to represent primarily cathepsin B.
Production of leukemia inhibitory factor by human articular chondrocytes and cartilage in response to interleukin‐1 and tumor necrosis factor α
Authors: Campbell Ian K. , Waring Paul , Novak Ulrike , Hamilton John A.
Published: February 2007

Objective. To investigate the production of leukemia inhibitory factor (LIF) by human articular chondrocytes and cartilage.

Methods. Chondrocytes and cartilage were cultured with and without added cytokines, and the conditioned media assayed for LIF by a specific radioreceptor competition assay.

Results. Interleukin‐1 (IL‐1) and tumor necrosis factor α (TNFα) stimulated LIF production by chondrocyte monolayers and cartilage. LIF was generally not detected in unstimulated cultures. Northern blot analysis showed increased amounts of LIF messenger RNA in IL‐1– and TNFα‐treated chondrocyte cultures.

Conclusion. Chondrocytes, stimulated by IL‐1 and/or TNFα, are potential contributors to the elevated levels of LIF observed in the synovial fluids of patients with rheumatoid arthritis and other inflammatory arthritides.
Low‐dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis. results of a multicenter randomized, double‐blind, placebo‐controlled trial
Authors: Shiroky Jeffrey B. , Neville Carolyn , Esdaile John M. , Choquette Denis , Zummer Michel , Hazeltine Mark , Bykerk Vivian , Kanji Mohamed , St‐Pierre Anne , Robidoux Lise , Bourque Lucienne
Published: February 2007

Objective. To determine whether the side effects of methotrexate can be decreased by the concurrent use of leucovorin, without affecting the efficacy of the methotrexate.

Methods. We conducted a multicenter randomized, double‐blind, placebo‐controlled trial of leucovorin administration, 2.5–5.0 mg orally, to be given 24 hours after the single, weekly, oral dose of methotrexate. Every 3 weeks for 52 weeks, patients were evaluated for rheumatic disease activity and side effects. Dosage adjustments for both methotrexate and leucovorin were made as needed, according to a defined protocol. The primary outcome evaluated was the frequency of study withdrawals because of side effects and/or inefficacy. Secondary outcomes evaluated included the frequency of side effects and the relative efficacy of methotrexate in the leucovorin and placebo treatment groups.

Results. Ninety‐two evaluable patients were analyzed (44 took leucovorin and 48 placebo). Twenty‐two patients withdrew early because of side effects unresponsive to our protocol, and 1 because of inefficacy; 17 had been taking placebo and 6 had been taking leucovorin (35% versus 14%,P < 0.02). The number of visits during which side effects were reported was reduced by almost 50% in the leucovorin treatment group (P < 0.001). There were significant reductions in the frequencies of all common side effects. At 52 weeks, disease activity was similar in both patient groups.

Conclusion. The methotrexate–leucovorin protocol used significantly reduces common side effects of methotrexate therapy without significantly altering efficacy.
Differential effects of diclofenac and aspirin on serum glutamic oxaloacetic transaminase elevations in patients with rheumatoid arthritis and osteoarthritis
Authors: Furst Daniel E. , Anderson William
Published: February 2007

Objective. To examine elevations in levels of serum glutamic oxaloacetic transaminase (SGOT) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) taking placebo, aspirin, or diclofenac, and to seek possible explanations for the occurrence of these elevations.

Methods. We conducted a metaanalysis of individual case reports from 3 RA protocols and 5 OA protocols, encompassing 814 diclofenac‐treated patients, 443 aspirin‐treated patients, and 359 placebotreated patients. All of the RA protocols had nearly identical inclusion and exclusion criteria, as well as safety studies and followup; the same was true for the OA protocols. Analysis included correlation analysis and multiple linear and logistic regression, accounting for numerous potential confounding variables, with the SGOT as the dependent variable. F tests were used for hypothesis testing.

Results. By several analytic approaches, the principal determinants of SGOT concentrations were found to be baseline SGOT value, the use of aspirin in RA patients, and the use of diclofenac in OA patients. Other significant factors contributing to an increase in SGOT concentrations were duration of therapy and, perhaps, daily dosage (mg/Ib). Hypothesis testing supported these results. Given a statistically average patient, we predicted a 1–2% chance of a mildly elevated SGOT level occurring among placebo‐treated patients, a 6–7% chance among diclofenac‐ or aspirin‐treated patients with RA, a 12% chance among diclofenac‐treated patients with OA, and a 2% chance among aspirin‐treated patients with OA.

Conclusion. This study demonstrates a powerful method for performing metaanalysis, using available individual patient data to examine numerous factors that may affect an outcome of interest. In this case, mild elevations of SGOT were examined and found to be related to baseline SGOT levels, diclofenac use (in OA), and aspirin use (in RA). Of numerous other potential factors examined, including age, sex, alcohol use, concomitant medications, and concomitant diagnoses, only duration of therapy and, to a small extent, daily dosage, were also consistent determinants of SGOT elevation. The SGOT elevations were minimal and were not related to the occurrence of clinical hepatitis: No clinical hepatitis occurred.
Association of hla–dr4‐dw15 (drb1*0405) and dr10 with rheumatoid arthritis in a spanish population
Authors: Yelamos José , Raül Garcia‐Lozano J. , Moreno Isabel , Aguilera Isabel , Francisca Gonzalez M. , Garcia Alicia , Nuñez‐Roldan Antonio , Sanchez Berta
Published: February 2007

Objective. To analyze the associations of HLA class II antigens with rheumatoid arthritis (RA) in a Spanish population.

Methods. We used DNA oligotyping to determine DR types, DQA1 and DQB1 alleles, and DR4 variants in 70 unrelated seropositive RA patients and 189 healthy controls living in Spain.

Results. A significantly higher frequency of DR4 was seen in RA patients compared with controls (relative risk [RR] = 2.40). The DR10 specificity correlated most strongly with disease susceptibility (RR = 3.84). A significant decrease in the frequency of DR7 was observed in the RA patients (RR = 0.48). DR4‐Dw15 (DRB1*0405) was found to be the unique DR4 allele associated with RA (RR = 4.27, P < 0.05), whereas Dw4 (DRB1*0401) and Dw14 (DRB1*0404/0408) showed no association, and both D10 (DRB1*0402) and Dw13 (DRB1*0403/0407) were negative risk factors for the disease. Approximately one‐third of the cases of RA could not be explained by the “shared epitope” hypothesis. Investigation of the DQ alleles associated with DR4 showed that the haplotype Dw15‐DQ8 (DRB1*0405‐DQB1*0302) was a susceptibility factor for RA (RR = 6.36, P < 0.05).

Conclusion. Our results suggest that HLA class II alleles involved in RA susceptibility can vary among different Caucasian populations.
Association of hla–dr and hla–dq antigens with congenital dislocation and dysplastic osteoarthritis of the hip joints in japanese people
Authors: Torisu Takehiko , Fujikawa Yousuke , Yano Hirokazu , Masumi Shogo
Published: February 2007

Objective. To investigate the frequency of HLA‐DR and DQ antigens among patients with congenital dislocation of the hip joint or dysplastic osteoarthritis (OA) and to determine whether tissue typing might contribute to better understanding of these disorders.

Methods. HLA–DR and DQ typing was undertaken in 18 patients with congenital dislocation of the hip joints, 65 patients with dysplastic OA of the hip, 42 patients with primary OA of the knee, and 40 normal controls. Typing for HLA–D antigens was performed using the standard microlymphocytotoxicity method.

Results. The frequency of HLA–DR4 in patients with congenital dislocation of the hip joint (61.1%) and patients with dysplastic OA of the hip (58.5%) was significantly increased compared with normal controls (27.5%) (Pcorr < 0.05 and P < 0.01, respectively). The relative risk for HLA–DR4 was 4.1428 and 3.7104, respectively, in these 2 disease groups. The frequency of HLA–DR4 in the patients with primary OA of the knee (35.7%) did not differ significantly from that in normal controls.

Conclusion. The results strongly indicate that development of congenital dislocation of the hip joint and progression of dysplastic OA of the hip are associated with genes of the HLA–D region.
Serum amyloid p component scintigraphy and turnover studies for diagnosis and quantitative monitoring of aa amyloidosis in juvenile rheumatoid arthritis
Authors: Hawkins P. N. , Richardson S. , Vigushin D. M. , David J. , Kelsey C. R. , Gray R. E. S. , Hall M. A. , Woo P. , Lavender J. P. , Pepys M. B.
Published: February 2007

Objective. To evaluate aspects of the natural history of AA amyloidosis complicating juvenile rheumatoid arthritis (JRA), and its response to therapy with chlorambucil.

Methods. Scintigraphy and 7‐day turnover studies were performed in JRA patients with histologically proven (n = 35) or clinically suspected (n = 30) AA amyloidosis, following intravenous injection of 123I and 125I–labeled serum amyloid P component (SAP). Prospective monitoring studies were performed over 2–3 years in 20 patients with amyloidosis. All but 2 amyloidosis patients were treated with chlorambucil.

Results. Positive scanning results were obtained in all patients in whom imaging was performed within 12 years of positive biopsy findings of amyloid and in 5 patients with clinically suspected amyloidosis. Negative scanning results with normal SAP metabolism, indicating regression of amyloid, were obtained in 4 patients whose amyloidosis had been in full clinical remission for more than 12 years. Prospective monitoring studies in patients whose JRA‐associated inflammatory activity was in remission demonstrated regression of amyloid in 8 patients and no substantial changes in 8 others; however, in 4 further patients with active inflammation, there was accumulation of amyloid. There was a very poor correlation between the amount of amyloid present at a particular site and the resultant organ dysfunction.

Conclusion. Radiolabeled SAP scintigraphy and turnover studies are useful complementary tools in the diagnosis, screening, and quantitative monitoring of type AA amyloidosis in JRA. The amyloid deposits may progress and/or regress at different rates in different anatomic sites over short periods.
Hemorrhagic cystitis complicating untreated necrotizing vasculitis
Authors: Block Joel A.
Published: February 2007

Although the genitourinary system is frequently affected in polyarteritis nodosa, involvement of the wall of the urinary bladder is extremely uncommon; moreover, when reported, it has been merely as an incidental finding late in the disease course. In contrast, hemorrhagic cystitis is a well‐recognized complication of cyclophosphamide therapy for the systemic vasculitides, but has not previously been reported to complicate untreated vasculitis. Herein is described a patient who presented with non–treatment‐related hemorrhagic cystitis which was found to be due to nongranulomatous necrotizing vasculitis of the wall of the urinary bladder. This represents both a novel presentation of polyarteritis and a previously unreported etiology of hemorrhagic cystitis. The differential diagnosis of apparently spontaneous hemorrhagic cystitis should therefore include active necrotizing vasculitis, independent of prior therapy.
Reduced synovial membrane macrophage numbers, elam‐1 expression, and lining layer hyperplasia in psoriatic arthritis as compared with rheumatoid arthritis
Authors: Veale Douglas , Yanni Ghada , Rogers Sarah , Barnes Louise , Bresnihan Barry , Fitzgerald Oliver
Published: February 2007

Objective. To define the immunohistologic features of the synovial membrane (SM) of patients with psoriatic arthritis (PA) and to compare them with those of an age‐ and disease‐duration–matched population of patients with rheumatoid arthritis (RA).

Methods. Synovial membrane needle biopsy was performed on 15 PA patients with knee involvement (8 had asymmetric oligoarthritis and 7 had symmetric polyarthritis) and on 15 RA controls. Specimens were stained with monoclonal antibodies against T cells (CD3, CD8, CD4, CD45RO), B cells (CD20), macrophages (Mac387, CD14), and cells bearing class II antigens (DAKO‐DR). Vascular endothelium was examined using a polyclonal antibody to Factor VIII–related antigen, and adhesion molecule expression was examined using antibodies 1.3B6, 6.5B5, and 1.4C3, which identify endothelial leukocyte adhesion molecule 1 (ELAM‐1), intercellular adhesion molecule 1 (ICAM‐1), and vascular cell adhesion molecule 1 (VCAM‐1), respectively.

Results. There was significantly less lining layer hyperplasia, fewer macrophages, and a greater number of blood vessels in PA SM than in RA SM. ELAM‐1 expression was less intense in PA than in RA SM, while there was no difference in expression of ICAM‐1 and VCAM‐1. Numbers of B cells, T cells, and T cell subsets (predominantly CD4, CD45RO T cells) were similar in both groups of patients.

Conclusion. Our findings demonstrate important differences in the immunohistologic features of PA and RA SM. The PA SM is more vascular, ELAM‐1 expression is less intense, and fewer macrophages invade the stroma and migrate to the lining layer than in RA SM. However, the lymphocytic infiltrate in the SM of both groups is similar.
Increased levels of leukemia inhibitory factor in synovial fluid from patients with rheumatoid arthritis and other inflammatory arthritides
Authors: Waring P. M. , Carroll G. J. , Kandiah D. A. , Buirski G. , Metcalf D.
Published: February 2007

Objective. To examine synovial fluid (SF) from patients with arthritis, for the presence of the cytokine leukemia inhibitory factor (LIF).

Methods. SF from 152 subjects was examined for LIF, using a radioreceptor competition assay.

Results. LIF was present at concentrations of 1–43 ng/ml in the SF of 23% of patients with rheumatoid arthritis (RA) or other inflammatory or infectious arthritides but in only 1 of 29 patients with osteoarthritis (P < 0.01). In the RA patients, the SF LIF concentration correlated significantly with the peripheral blood white blood cell count (WBC) (P < 0.05) and the SF WBC count (P < 0.01), but not with other clinical or radiologic parameters of disease activity or progression.

Conclusion. LIF is implicated as a potential mediator of the local or systemic inflammatory response or the joint destruction seen in inflammatory arthritis.
Characterization of gangliosides from normal and osteoarthritic human articular cartilage
Authors: David Marie Jeanne , Portoukalian Jacques , Rebbaa Abdeladi , Vignon Eric , Carret Jean‐Paul , Richard Michel
Published: February 2007

Objective. Glycosphingolipids (GSLs) are biologically active molecules in the physiology and pathology of cells. Since changes in GSLs might be associated with the impaired metabolism of articular cartilage in osteoarthritis (OA), we investigated gangliosides from normal and OA human cartilage.

Methods. OA and control cartilage was obtained from patients with hip OA and femoral neck fracture, respectively. Gangliosides were extracted and quantified by determining their lipid‐bound sialic acid concentration. Major gangliosides were identified by immunodetection on thin‐layer plates, purified by high performance liquid chromatography, and analyzed for their carbohydrate, fatty acid, and long‐chain base composition.

Results. The total ganglioside content of OA cartilage was decreased by 40% (per mg of DNA). Major gangliosides, GM3 and GD3, separated into 3 on thin‐layer chromatography bands. All were decreased except for the lowest migrating band of GM3, which was increased 5‐fold. This ganglioside had the same carbohydrate moiety and fatty acids as the other two, but differed by a long‐chain base composed mainly of C20‐sphingosine.

Conclusion. OA cartilage is characterized by a decrease in all gangliosides except GM3, which demonstrates a large increase in the lowest band. These results indicate that there are changes in the biochemical composition of chondrocyte membranes in OA. The causes and roles of these changes remain to be determined.
Autoantibodies to hmg‐17 nucleosomal protein in autoimmune rheumatic diseases
Authors: Tzioufas Athanasios G. , Boumba Vassiliki A. , Seferiadis Konstantin , Tsolas Orestes , Moutsopoulos Haralampos M.
Published: February 2007

Objective. Previous studies have shown that serum from patients with systemic lupus erythematosus (SLE) contains antibodies directed against HMG‐17, a nucleosomal nonhistone high mobility group (HMG) protein found in chromatin. The aim of the present study was to investigate any associations between the presence of antibodies to HMG‐17 and clinical and serologic features of SLE.

Methods. Using porcine thymus as a source, HMG‐17 was purified by Sephacryl S‐200 chromatography followed by high performance liquid chromatography. An enzyme‐linked immunosorbent assay utilizing the purified HMG‐17 as antigen was developed and was used to evaluate sera from patients with autoimmune rheumatic diseases, for the presence of autoantibodies.

Results. Anti–HMG‐17 antibodies were found in the serum of 34.8% of the patients with SLE, compared with 11.5% of patients with primary Sjögren's syndrome, 4.4% of patients with rheumatoid arthritis, and 4.1% of normal blood donors. Analysis of the clinical features of SLE using 2 different lupus activity indices revealed that anti‐HMG‐17 antibodies were more frequently found in patients with active disease. A positive correlation was also observed between anti–HMG‐17 and anti‐dsDNA levels, and levels of both of these autoantibodies demonstrated a negative correlation with C4. Analysis of sequentially obtained serum samples from 4 SLE patients revealed that, in 2 patients, anti‐HMG‐17 levels fluctuated in parallel with both disease activity and anti‐dsDNA levels, and in the remaining 2, anti–HMG‐17 levels fluctuated in parallel with disease activity.

Conclusion. Antibodies to HMG‐17 are found in patients with many different autoimmune rheumatic diseases, although they are more frequently observed in those with SLE. Their presence appears to be associated with lupus disease activity as well as with anti‐dsDNA and C4 levels.
Antibodies to vesicular stomatitis virus proteins in patients with systemic lupus erythematosus and in normal subjects
Authors: Hardgrave Kathy L. , Neas Barbara R. , Scofield R. Hal , Harley John B.
Published: February 2007

Objective. To determine the presence of antibodies that bind vesicular stomatitis virus (VSV) proteins in systemic lupus erythematosus (SLE) patient sera, as well as to examine any relationship between antibodies binding the viral nucleocapsid (N) protein and anti‐Ro autoantibodies.

Methods. Eighty SLE patient sera, 80 normal control sera, 47 rheumatic disease patient control sera, and 9 sera from Panamanian subjects (6 of whom were infected with VSV) were evaluated by immunoblot of purified VSV proteins.

Results. Findings on immunoblots of the Panamanian subjects' sera were consistent with histories of endemic exposure to VSV, as determined by virus neutralization assays. Significantly different binding to viral proteins was seen in the group of 80 SLE patients compared with the normal control group and with the rheumatic disease control group, by a variety of measures. For example, most of the reactivity in the SLE patient sera included binding to the internal viral matrix (M) and N proteins, while the reactivity in the normal control sera was mostly against the surface viral glycoprotein (G) protein alone or the N protein alone. Within this SLE patient cohort, associations were found between binding to N protein and anti‐Ro precipitins and between binding to M protein and anti–nuclear RNP autoantibody precipitins.

Conclusion. The data are consistent with the original specific hypotheses of a relationship between 60‐kd Ro autoantigenicity and VSV, as well as with the suggestion that a rhabdovirus may be important in SLE. They do not, however, make possible any conclusions concerning the role of rhabdoviruses in the development of SLE or of anti‐Ro autoimmunity.
Acetylation phenotypes and environmental chemical exposure of people with idiopathic systemic lupus erythematosus
Authors: Reidenberg Marcus M. , Drayer Dennis E. , Lorenzo Beverly , Strom Brian L. , West Suzanne L. , Snyder Ellen S. , Freundlich Bruce , Stolley Paul D.
Published: February 2007

Objective. To test the hypotheses that there is an excess percentage of slow acetylators among patients with idiopathic systemic lupus erythematosus (SLE) and that these patients had excessive exposure to environmental amines and hydrazines before the onset of illness.

Methods. Case–control study with structured interview and acetylation phenotyping.

Results. No excess proportion of slow acetylators or environmental amine exposure was found.

Conclusion. Slow acetylation phenotype and exposure to environmental amines are not principal causes of idiopathic SLE.
The synthetic retinoid (4‐hydroxyphenyl)retinamide decreases collagen expression in vitro and in the tight‐skin mouse
Authors: Delany Anne M. , Brinckerhoff Constance E.
Published: February 2007

Objective. We documented the effect of the retinoid (4‐hydroxyphenyl)retinamide on collagen expression in a tissue culture and in an animal model of scleroderma.

Methods. We used RNA analysis, chloramphenicol acetyltransferase assays, organ culture, and histologic evaluation.

Results. We showed that (4‐hydroxyphenyl)retinamide decreases αl(I) collagen messenger RNA and transcription in cultured cells, and decreases collagen levels in the dermis of tight‐skin mice.

Conclusion. These results provide a basis for further experiments to address the efficacy of (4‐hydroxyphenyl)retinamide in the treatment of scleroderma.
Cross‐reactivity of igm‐ and igg‐secreting b cells in autoimmune mice
Authors: Ishigatsubo Yoshiaki , Igarashi Toshihisa , Ohno Shigeru , Ueda Atsuhisa , Okubo Takao , Klinman Dennis M.
Published: February 2007

Objective. To determine the frequency with which in vivo–activated B cells secrete cross‐reactive antibodies in lupus‐prone mice.

Methods. Analysis of freshly isolated splenic lymphocytes by chamber enzyme‐linked immunospot assay.

Results. Young New Zealand black, New Zealand black X New Zealand white, and MRL/lpr mice expressed repertoires in which 16–20% of IgM‐secreting cells and 0–2% of IgG‐secreting cells were crossreactive. By comparison, 21–31% of IgM‐ and 4–14% of IgG‐secreting cells in adult animals with active lupus were cross‐reactive (P < 0.01).

Conclusion. Cross‐reactive B cells constitute an abnormally large proportion of the repertoire expressed in mice with active autoimmune disease.