bluuebunny/crossref_metadata_2025_split huggingface dataset:
Release of cartilage macromolecules into the synovial fluid in patients with acute and prolonged phases of reactive arthritis
Authors: Saxne Tore , Glennås Anne , Kvien Tore K. , Melby Kjetil , Heinegård Dick 
Published: February 2007

AbstractObjective. Extensive changes in articular cartilage metabolism occur during the acute phase of reactive arthritis, as indicated by altered release of cartilage macromolecules into synovial fluid (SF) demonstrated immunochemically. Nevertheless, permanent cartilage lesions are rare in this disease. To monitor specific events during the evolution of reactive arthritis, we investigated the content of cartilage macromolecules in sequentially obtained SF samples from 22 patients.Methods. Two groups of proteoglycan epitopes, the glycosaminoglycan‐rich region of aggrecan (referred to as proteoglycan) and its hyaluronan‐binding region (HABr), as well as one matrix protein, cartilage oligomeric matrix protein (COMP), were quantified by immunoassay.Results. SF proteoglycan concentrations, which were initially elevated, decreased significantly with prolonged arthritis, whereas COMP levels changed less markedly and levels of HABr remained stable. There was a positive correlation between SF and serum concentrations of COMP in samples obtained during the early phase of the disease.Conclusion. Cartilage involvement in reactive arthritis is transient, in contrast to findings in rheumatoid arthritis. Reactive arthritis should therefore be a suitable model for studies of repair processes in cartilage, which will facilitate understanding of the pathophysiology of cartilage involvement in arthritis.
Production of monocyte chemotactic protein–1 in human type B synoviocytes. synergistic effect of tumor necrosis factor α and interferon‐γ
Authors: Hachicha Mohamed , Rathanaswami Palaniswami , Schall Thomas J. , Mccoll Shaun R. 
Published: February 2007

AbstractObjective. Since local secretion of chemotactic factors could contribute substantially to the homing of monocytes to the rheumatoid synovium, we investigated the ability of type B, or “fibroblast‐like,” synoviocytes isolated from the synovial tissue of patients with rheumatoid arthritis to synthesize and secrete the novel cytokine monocyte chemotactic protein 1 (MCP‐1).Methods. Synthesis and secretion of MCP‐1 was determined by immunoprecipitation following metabolic labeling of MCP‐1 with 35S‐cysteine. MCP‐1 gene regulation was assessed by Northern blot analysis.Results. Unstimulated type B synoviocytes released little or no MCP‐1, although low levels of MCP‐1 messenger RNA (mRNA) were detected. However, incubation of these cells with tumor necrosis factor α (TNFα) resulted in a time‐ and dose‐dependent release of MCP‐1 into the supernatant, and expression of MCP‐1 mRNA. Use of cycloheximide and actinomycin D confirmed that TNFα was inducing MCP‐1 expression at both the transcriptional and translational levels. Treatment of the synoviocytes with interferon‐γ (IFNγ) also stimulated an increase in both the steady‐state levels of MCP‐1 mRNA, as well as MCP‐1 protein synthesis and secretion. In addition, TNFα and IFNγ in combination exerted a synergistic effect on both MCP‐1 mRNA accumulation and protein secretion.Conclusion. These studies demonstrate that the MCP‐1 gene is regulated by TNFα and IFNγ in type B synoviocytes and indicate that these cells may play an important role in the recruitment of inflammatory cells to the rheumatoid synovial environment, via the production of novel chemotactic cytokines such as MCP‐1.
Transforming growth factor β exerts opposite effects from interleukin‐1β on cultured rabbit articular chondrocytes through reduction of interleukin‐1 receptor expression
Authors: Réadini F. , Mauviel A. , Pronost S. , Loyau G. , Pujol J.‐P. 
Published: February 2007

AbstractObjective. The aim of the study was to determine whether transforming growth factor β (TGFβ) modulates the effects and the receptor expression of interleukin‐1 (IL‐1) in rabbit articular chondrocytes (RAC).Methods. Collagen, glycosaminoglycan, and collagenase production, together with 125I‐labeled IL‐1 binding, were analyzed in RAC cultures.Results. TGFβ reduced both IL‐1 effects on matrix metabolism and IL‐1 receptor expression.Conclusion. TGF/3 acts as an antagonist of the effects of IL‐1 through down‐regulation of its receptor expression.
Degradation of human articular cartilage by neutrophils in synovial fluid
Authors: Winn Chatham W. , Swaim Richard , Frohsin Henry , Heck Louis W. , Miller Edward J. , Blackburn Warren D. 
Published: February 2007

AbstractObjective. To determine whether surface‐adherent immunoglobulins are capable of mediating synovial fluid (SF) neutrophil degradation of proteoglycan and collagen in intact, normal human articular cartilage, and to define the respective roles of neutrophil serine proteases and metalloproteases in degrading these cartilage constituents.Methods. Pellet explants of normal human articular cartilage pretreated with bovine serum albumin (BSA) or IgG were incubated with polymorphonuclear cells suspended in SF (PMN‐SF), or with supernatants derived from neutrophils stimulated with surface‐associated IgG. Proteoglycan degradation was measured by assaying release of 35S‐proteoglycan fragments from cartilage explants prelabeled with 35S‐sulfate. Collagen degradation was measured by assaying hydroxyproline content in the PMN‐SF preparations or neutrophil supernatants following their incubation with unlabeled explants.Results. Significant release of both 35S fragments and hydroxyproline was noted following incubation of PMN‐SF with IgG‐treated pellets, compared with pellets treated with BSA. IgG preparations derived from pooled normal serum or rheumatoid arthritis SF were equally efficacious in mediating PMN degradation of cartilage collagens. Explant release of 35S fragments during incubation with PMN supernatant was completely inhibited when serine proteases were inactivated by diisopropyl fluorophosphate (DFP); however, release of 35S fragments was enhanced when metalloprotease activity was present in the supernatant. Release of hydroxyproline during incubation of explants with PMN supernatant was comparable in the presence of DFP or EDTA, but was markedly enhanced when both serine and metalloprotease activity were present in the supernatant.Conclusion. Neutrophils in SF are capable of degrading both proteoglycans and collagens in intact human articular cartilage. Degradation of these cartilage constituents is facilitated by immunoglobulins adherent to the cartilage surface and by the synergistic action of PMN serine and metalloproteases released during activation of neutrophils with surface‐associated immunoglobulin.
Cyclosporine in systemic sclerosis. results of a forty‐eight–week open safety study in ten patients
Authors: Clements Philip J. , Lachenbruch Peter A. , Sterz Mildred , Danovitch Gabriel , Hawkins Randall , Ippoliti Andrew , Paulus Harold E. 
Published: February 2007

AbstractObjective. To evaluate safety and efficacy of cyclosporin A (CSA) treatment in systemic sclerosis (SSc).Methods. Ten patients with ⩽60 months of SSc were entered into a 48‐week open study of CSA. Patients with hypertension or azotemia were excluded. Concurrent use of nonsteroidal antiinflammatory agents or diuretics was not permitted. The extent of cutaneous and visceral involvement at 48 weeks and at study entry were compared.Results. Adverse reactions (especially nephrotoxicity) were frequent, usually transient, often dose‐limiting, and usually associated with CSA doses ⩾3–4 mg/kg/day. Skin thickening decreased significantly (P <0.001), while pulmonary and cardiac involvement remained unchanged.Conclusion. CSA should undergo blinded controlled study in patients with SSc.
Contrasting molecular patterns of mhc class ii alleles associated with the anti‐sm and anti‐rnp precipitin autoantibodies in systemic lupus erythematosus
Authors: Olsen Mary L. , Arnett Frank C. , Reveille John D. 
Published: February 2007

AbstractObjective. To find evidence of a potential genetic predisposition to the anti‐Sm or anti‐RNP precipitin autoantibody responses.Methods. HLA–DR and DQ alleles determined by restriction fragment length polymorphism and/or oligo‐typing in 49 subjects with either anti‐Sm alone or anti‐RNP alone were compared with those in 139 race‐matched normal control subjects and 59 race‐matched lupus patients without anti‐Sm and anti‐RNP auto‐antibodies.Results. Black patients with anti‐Sm precipitin had increased frequencies of HLA‐DR2 and the DQw6‐associated DQA1*0102 (P = 0.007, odds ratio [OR] = 6.7) and DQB1*0602 (P = 0.001, OR = 9.1) chain alleles compared with normal black control subjects. Black patients with anti‐RNP precipitin showed significant increases in the DQw5‐associated DQA1*0101 (P = 0.03, OR = 5.5) and DQB1*0501 (P = 0.002, OR = 23.3) chain alleles compared with lupus patients without anti‐Sm or RNP. White patients with anti‐RNP precipitin showed an increased frequency of the DQw8‐associated allele DQB1*0302 (P = 0.02, OR = 3.7) compared with normal controls, as well as an increased frequency of the DQw5‐associated alleles DQA1*0101 and DQB1*0501 (P = 0.05, OR = 4.2) compared with lupus patients without anti‐Sm or RNP. There were no specific HLA–DR2 or DR4 subtype associations found with either anti‐Sm or RNP precipitin autoantibodies.Conclusion. There are distinct patterns of major histocompatibility complex class II allele associations with the anti‐Sm versus the anti‐RNP precipitin autoantibody responses, and HLA–DQ associations may be more primary than HLA–DR associations.
Crystal‐induced neutrophil activation. II. evidence for the activation of a phosphatidylcholine‐specific phospholipase D
Authors: Naccache Paul H. , Bourgoin Sylvain , Plante Edith , Roberge Charles J. , De Medicis R. , Lussier André , Poubelle Patrice E. 
Published: February 2007

AbstractObjective. To investigate the involvement of phospholipase D in the signaling pathways activated by 2 pathologically relevant inflammatory microcrystals, monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD).Methods. Human peripheral blood neutrophils were used throughout. Phospholipase D activity was monitored by measuring 3 separate indices: 1) the mass of phosphatidic acid, 2) the levels of alkyl‐phosphatidic acid, and 3) the levels of formation, in the presence of ethanol, of phosphatidylethanol. The latter 2 parameters were measured in cells labeled with 1‐0‐3H–alkyl‐2‐acetyl‐sn‐glycero‐3‐phosphocholine. The cells were stimulated with microcrystals of triclinic morphology.Results. Both MSU and CPPD crystals induced a time‐ and concentration‐dependent accumulation of phosphatidic acid mass and elevation in levels of alkyl‐phosphatidic acid and phosphatidylethanol in prelabeled cells. The activation of phospholipase D by the microcrystals was partially sensitive to colchicine and largely resistant to pertussis toxin. Inhibition of phosphatidic acid formation by wortmannin or ethanol reduced the microcrystal‐stimulated production of superoxide anions.Conclusion. These results indicate that microcrystals stimulate phospholipase D in human neutrophils and that at least some of the functional consequences of neutrophil‐microcrystal interactions may be dependent on this biochemical pathway.
Suppression of adjuvant‐induced arthritis in da rats by incomplete freund's adjuvant
Authors: Cannon Grant W. , Griffiths Marie M. , Woods Marion L. 
Published: February 2007

AbstractObjective. To define the effects of incomplete Freund's adjuvant (ICFA) on subsequent arthritis induced by complete Freund's adjuvant (CFA) and type II collagen (CII) in DA and Lewis rats.Methods. ICFA was injected into DA and Lewis rats before CFA or CII injection.Results. DA rats previously injected with ICFA had significantly less severe arthritis induced by CFA compared with those not receiving ICFA pretreatment (P <0.01). ICFA had no significant impact on CFA‐induced arthritis in Lewis rats or on CII‐induced arthritis in DA rats.Conclusion. The injection of ICFA alone specifically suppresses subsequent CFA‐induced arthritis in DA rats, but not in Lewis rats.
A randomized, controlled trial of arthroscopic surgery versus closed‐needle joint lavage for patients with osteoarthritis of the knee
Authors: Chang Rowland W. , Falconer Judith , David Stulberg S. , Arnold William J. , Manheim Larry M. , Dyer Alan R. 
Published: February 2007

AbstractObjective. To compare arthroscopic surgery and closed‐needle joint lavage for patients with non—end‐stage osteoarthritis (OA) of the knee under controlled, experimental conditions.Methods. Thirty‐two subjects who met specific clinical, radiologic, medical, and rehabilitation criteria were randomized to receive arthroscopic surgery (n = 18) or joint lavage (n = 14). Outcome measures evaluated at baseline and at 3 and 12 months of followup included 3 standard clinical parameters, self‐reported pain and functional status (by the Arthritis Impact Measurement Scales), 50‐foot walk time, 2 global scales, and direct and indirect medical costs.Results. At 3 months of followup, there were no significant between‐group differences in pain, self‐reported and observed functional status, and patient and “blinded” physician global assessments. The arthroscopic procedure cost $3,840 more than did closedneedle joint lavage. After 1 year, there were no between‐group differences in medication costs, utilization of medical services, or indirect costs related to employment or use of household help. After 1 year, 44% of subjects who underwent arthroscopy reported improvement and 58% of subjects who underwent joint lavage improved. Patients with tears of the anterior two‐thirds of the medial meniscus or any lateral meniscus tear had a higher probability of improvement (by “blinded” physician assessment) after arthroscopic surgery (0.63) than did patients with other intraarticular pathology (0.20).Conclusion. The search for and removal of soft tissue abnormalities via arthroscopic surgery does not appear justified for all patients with non—end‐stage OA of the knee who fail to respond to conservative therapy, but it may be beneficial for certain subgroups.
The relative toxicity of disease‐modifying antirheumatic drugs
Authors: Fries James F. , Williams Catherine A. , Ramey Dena , Bloch Daniel A. 
Published: February 2007

AbstractObjective. To compare the toxicities of commonly employed disease‐modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA).Methods. Toxicity Index scores, computed from symptoms, laboratory abnormalities, and hospitalizations attributable to DMARD therapy, were assessed in 2,747 patients with RA receiving 3,053 courses of 6 DMARDs and 1,309 courses of prednisone over 7,278 patient‐years. Results were adjusted for severity of illness and other covariates.Results. Least toxic was hydroxychloroquine (mean ± SEM score 1.38 ± 0.15), followed by intramuscular gold (2.27 ± 0.17) and the closely grouped D‐penicillamine (3.38 ± 0.36), methotrexate (3.82 ± 0.35), and azathioprine (3.92 ± 0.39). Auranofin (5.25 ± 0.32) was most toxic, but this toxicity resulted from a high frequency of minor complications. Hospitalizations because of auranofin or hydroxychloroquine therapy were not noted. Prednisone (3.83 ± 0.39) was of comparable toxicity, although it is likely that not all events of prednisone toxicity were captured. For reference, the toxicity of methotrexate and azathioprine was similar to that of the most toxic nonsteroidal antiinflammatory drugs (NSAIDs) (indomethacin 3.99, tolmetin sodium 3.96, and meclofenamate 3.86). Hydroxychloroquine showed less toxicity than the most commonly used prescription NSAIDs.Conclusion. There are substantial differences in toxicity among DMARDs and less important differences in toxicity between specific DMARDs and specific NSAIDs.
Use of a chimeric monoclonal anti‐CD4 antibody in patients with refractory rheumatoid arthritis
Authors: Moreland Larry W. , Bucy Ralph P. , Tilden Arabella , Pratt Parks W. , Lobuglio Albert F. , Khazaeli M. , Everson Michael P. , Daddona Peter , Ghrayeb John , Kilgarriff Charles , Sanders Martin E. , Koopman William J. 
Published: February 2007

AbstractObjectives. To evaluate the safety, immunogenicity, and biologic effects of chimeric monoclonal anti‐CD4 (cM‐T412) in patients with refractory rheumatoid arthritis (RA), and to obtain preliminary data on the clinical response to this treatment.Methods. Twenty‐five patients with active refractory RA were treated with incremental doses (10 to 700 mg) of cM‐T412 in an open‐label, escalating‐dose phase I trial.Results. Infusion with cM‐T412 was followed by an immediate, rapid decline in CD4+ T cells. The level of circulating CD4+ T cells remained depressed in most patients even at 6 months posttreatment. Following antibody infusion, proliferative responses of peripheral blood lymphocytes to mitogens and antigens were determined; mitogen and antigen responses were decreased compared with pretreatment responses. Mitogen responses tended to return to baseline values more rapidly than did responses to antigen. Adverse events included fever (19 patients), which was associated with myalgias, malaise, and asymptomatic hypotension; these symptoms were self‐limited and appeared to correlate with transient elevations in interleukin‐6. No significant human antibody response to the cM‐T412 variable region was detected; only 2 patients developed transiently low levels of antibodies reactive with cM‐T412. Significant clinical improvement, defined as ≥50% decrease in tender joint counts compared with baseline, was noted in 43% of patients at 5 weeks and 33% at 6 months following cM‐T412 infusion.Conclusions. Treatment of refractory RA with cM‐T412 appears to be safe and is associated with sustained decreases in circulating CD4+ T cell counts and depressed in vitro T cell responses. No significant human antichimeric antibody response was detected. Nonblinded assessment of clinical end points suggests that treatment with cM‐T412 may have beneficial effects in these patients with refractory RA. A double‐blind clinical trial is warranted to determine its clinical efficacy in treating RA.
Chlorambucil
Authors: Sinoway Patricia A. , Callen Jeffrey P. 
Published: February 2007

AbstractObjective. To investigate the effectiveness of oral chlorambucil treatment in patients with dermatomyositis (DM) that is recalcitrant to treatment with prednisone and/or immunosuppressive agents.Methods. Five patients with recalcitrant DM were treated with oral chlorambucil, 4 mg/day, after discontinuation of the other immunosuppressive agent (azathioprine or methotrexate). Three patients were treated with a combination of prednisone and chlorambucil, and 2 with chlorambucil alone.Results. Beneficial effects were noted within 4–6 weeks in all 5 patients, and corticosteroids were eventually discontinued in 4. Currently, only 1 patient is still receiving therapy; the other 4 have stopped chlorambucil after 13–30 months of treatment, and their disease remains in remission. Minimal chlorambucil toxicity was noted, consisting of leukopenia in 2 patients.Conclusion. Our findings suggest that chlorambucil is an effective, corticosteroid‐sparing agent for the control of DM.
Determinants of serious liver disease among patients receiving low‐dose methotrexate for rheumatoid arthritis
Authors: Walker Alexander M. , Funch Donnie , Dreyer Nancy A. , Tolman Keith G. , Kremer Joel M. , Alarcón Graciela S. , Lee Randall G. , Weinblatt Michael E. 
Published: February 2007

AbstractObjective. To assess the risk of serious liver disease in patients with rheumatoid arthritis (RA) taking methotrexate (MTX).Methods. We surveyed members of the American College of Rheumatology to determine previous use of MTX in the treatment of rheumatoid arthritis and to identify cases of cirrhosis and liver failure. Cases were confirmed by review of pathology specimens, findings from diagnostic testing, and clinical presentations. A case—control study was then conducted to ascertain prognostic factors. Case and control medical records were reviewed for information on MTX therapy as well as other possible determinants of serious liver disease.Results. Twenty‐four cases of cirrhosis and liver failure were identified, giving a 5‐year cumulative incidence of ˜ 1/1,000 treated patients. Six of the 24 patients had died: 4 died of the initial liver disease, 1 of hepatic complications of another illness, and 1 of unrelated causes. Two patients continue to have active liver disease. Late age at first use of MTX and duration of therapy with MTX were independent predictors of serious liver disease.Conclusion. Serious liver disease is an uncommon, age‐ and dose‐related complication of low‐dose MTX therapy for RA.
Preliminary criteria for the classification of Sjögren's syndrome. Results of a prospective concerted action supported by the European community
Authors: Vitali Claudio , Bombardieri Stefano , Moutsopoulos Haralampos M. , Balestrieri Genesio , Bencivelli Walter , Bernstein Robert M. , Bjerrum Kirsten B. , Braga Susanna , Coll Joaquin , Vita Salvatore De , Drosos Alexandros A. , Ehrenfeld Michael , Hatron Pierre Y. , Hay Elaine M. , Isenberg David A. , Janin Anne , Kalden Joachim R. , Kater Louis , Konttinen Yrjö T. , Maddison Peter J. , Maini Ravinder N. , Manthorpe Rolf , Meyer Olivier , Ostuni Pierantonio , Pennec Yvon , Prause Jan U. , Richards Andrea , Sauvezie Bernard , Schiødt Morten , Sciuto Maria , Scully Crispian , Shoenfeld Yehuda , Skopouli Fotini N. , Smolen Josef S. , Snaith Michael L. , Tishler Moshe , Todesco Silvano , Valesini Guido , Venables Patrick J. W. , Wattiaux Marie J. , Youinou Pierre 
Published: February 2007

AbstractObjective. Different sets of diagnostic criteria have been proposed for Sjögren's syndrome (SS), but none have been validated with a large series of patients or in a multicenter study. We conducted the present study involving 26 centers from 12 countries (11 in Europe, plus Israel), with the goals of reaching a consensus on the diagnostic procedures for SS and defining classification criteria to be used in epidemiologic surveys and adopted by the scientific community.Methods. The study protocol was subdivided into two parts. For part I, questionnaires regarding both ocular and oral involvement were developed; they included 13 questions and 7 questions, respectively. For part II a limited set of diagnostic tests was selected, and the exact procedure to be followed in performing these tests was defined. Part I of the study ipcluded 240 patients with primary SS and 240 age‐ and sex‐matched controls. Two hundred forty‐six patients with primary SS, 201 with secondary SS, 113 with connective tissue diseases but without associated SS, and 133 control patients were studied in part II.Results. The study resulted in (a) the validation of a simple 6‐item questionnaire for determination of dry eyes and dry mouth, which showed good discriminant power between patients and controls, to be used in the initial screening for sicca syndrome; and (b) the definition of a new set of criteria for the classification of SS. The sensitivity and specificity of the criteria in correctly identifying patients with either the primary or the secondary variant of SS were also determined.Conclusion. Using the findings of this prospective multicenter European study, general agreement can be reached on the diagnostic procedures to be used for patients with SS. Final validation of the preliminary classification criteria for SS is underway.