bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of low‐dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A Controlled Clinical Trial
Authors: Williams H. James , Willkens Robert F. , Samuelson Cecil O. , Alarcón Graciela S. , Guttadauria Maria , Yarboro Cheryl , Polisson Richard P. , Weiner Steven R. , Luggen Michael E. , Billingsley Lynn M. , Dahl Stephen L. , Egger Marlene J. , Reading James C. , Ward John R. 
Published: February 2007

AbstractOne hundred eighty‐nine patients with rheumatoid arthritis were entered into a prospective, controlled, double‐blind multicenter trial comparing placebo and methotrexate (MTX). One hundred ten patients completed 18 weeks of therapy. No remissions were seen, but patients able to tolerate low‐dose pulse MTX therapy were significantly improved, compared with patients receiving placebo therapy, for all clinical variables measured, including joint pain/tenderness and swelling counts, rheumatoid nodules, and patient and physician assessment of disease activity. MTX treatment demonstrated statistically significant improvement over placebo in patients with anemia, elevated erythrocyte sedimentation rate, and rheumatoid factor. However, nearly one‐third of the patients receiving MTX were withdrawn for adverse drug reactions, of which elevated levels of liver enzymes was the most common. Pancytopenia occurred in 2 patients taking MTX. All adverse drug effects resolved without sequelae. MTX appears to be effective in the treatment of active rheumatoid arthritis but requires close monitoring for toxicity.
Pulmonary involvement in systemic sclerosis (scleroderma)
Authors: Steen Virginia D. , Owens Gregory R. , Fino Gregory J. , Rodnan Gerald P. , Medsger Thomas A. 
Published: February 2007

AbstractOne hundred sixty‐five nonsmoking systemic sclerosis patients were evaluated by pulmonary function testing. Restrictive lung disease and an isolated reduction of the diffusing capacity of carbon monoxide were the most frequent abnormalities. Patients with the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias) had a similar frequency and severity of pulmonary involvement compared with the patients who had diffuse scleroderma. CREST syndrome patients with restrictive lung disease rarely had the anticentromere antibody and had more skin and joint involvement of their hands, compared with other CREST syndrome patients. Dyspnea and rales were most commonly found in patients with restrictive lung disease. Fibrosis, shown on chest radiograph, and pulmonary function abnormalities correlated poorly with each other. Dyspnea was associated with restrictive disease, and rales were more commonly found in patients with fibrosis. Patients with a restrictive abnormality had the worst prognosis, with a 5‐year survival rate of 58%, although death from pulmonary causes was uncommon. Comparison of these nonsmoking patients with 137 scleroderma patients who smoked, seen during the same time period, revealed more frequent and severe obstructive changes in smokers. Smoking patients with restrictive lung disease had more severe disease than nonsmoking patients. The single breath diffusing capacity for carbon monoxide was significantly decreased in the patients who smoked compared with the nonsmokers. These data confirm that pulmonary function abnormalities are common in patients with systemic sclerosis including CREST syndrome. Smoking appears to have an additive deleterious effect on pulmonary function and should be strongly discouraged.
Angiographic findings in mixed connective tissue disease. Correlation with fingernail capillary photomicroscopy and digital photoplethysmography findings
Authors: Peller Jeffrey S. , Gabor Gary T. , Porter John M. , Bennett Robert M. 
Published: February 2007

AbstractThirteen patients with mixed connective tissue disease underwent hand angiography to assess the degree of vascular abnormalities and their correlation to nailfold capillary microscopy and digital photoplethysmography findings. Organic obstruction was found in 60% of ulnar arteries, 87% of superficial arches, 13% of deep arches, and 65% of digital arteries. Fingernail capillary abnormalities were seen in 90% of patients. Normal photoplethysmography results had a predictive value of 91% for identifying digits without bilateral occlusions. These findings indicate a hitherto unrecognized propensity for disease of both small and medium‐sized vessels in patients with mixed connective tissue disease.
The association between Mi‐2 antibodies and dermatomyositis
Authors: Targoff Ira N. , Reichlin Morris 
Published: February 2007

AbstractAntibodies to Mi, an antigen in calf thymus extract, have been demonstrated by complement fixation inhibition in polymyositis (PM) and dermatomyositis (DM) sera but not in the sera of individuals without myositis. The original Mi reference serum defined 2 precipitating antibodies, using immunodiffusion (ID). Anti‐Mi‐1 was not active in complement fixation. We have now studied in further detail anti‐Mi‐2, which appears to be the antibody in Mi serum that fixes complement. Mi‐2 antigen was purified by immunoaffinity chromotography. An enzyme‐linked immunosorbent assay (ELISA) to measure Mi‐2 antibody, using this antigen, was used to test the sera of 139 myositis patients: 52 had DM and 87 had PM. Control sera from 35 normal subjects and 93 patients with other connective tissue diseases were also tested. Only 13 sera were considered definitely positive for anti‐Mi‐2. All were from patients who had myositis, 11 of whom had DM. Only DM sera had anti‐Mi‐2 by ID, and all sera with anti‐Mi‐2 by ID were positive by ELISA. A number of other sera, including many from patients with other connective tissue diseases and 2 from normal subjects (all without precipitating antibodies) had lower elevations which were of uncertain significance. Detection of anti‐Mi‐2 by ID as well as by ELISA was significantly more frequent in DM than in PM. Anti‐Mi‐2 appears to be closely linked to DM, and is the first specific serologic marker for this form of myositis.
Release of interleukin‐1 from human synovial tissue in vitro
Authors: Wood David D. , Ihrie Earl J. , Hamerman David 
Published: February 2007

AbstractDuring the enzymatic disaggregation of human synovium, used in the process of isolating synoviocytes, a factor was liberated into the culture medium that exhibited the thymocyte mitogenic properties of interleukin‐1. Like interleukin‐1, this synovial‐derived mitogen could be isolated using an affinity column of antihuman leukocytic pyrogen. By gel filtration and isoelectric focusing, the mitogen cofractionated with human monocyte‐derived interleukin‐1. Finally, the isolated mitogen was shown to exhibit other properties of interleukin‐1: stimulation of the secretion of interleukin‐2, enhancement of the titer of acute‐phase proteins in vivo, and stimulation of the release of prostaglandin E2 from human synoviocyte cultures. These observations suggest that interleukin‐1 can be derived from the human synovium.
Different populations of rheumatoid adherent cells mediate activation versus suppression of t lymphocyte proliferation
Authors: Klareskog Lars , Holmdahl Rikard , Rubin Kristofer , Victorin Åse , Lindgren Jan Åke 
Published: February 2007

AbstractAdherent cells from synovial tissue of rheumatoid arthritis patients were fractionated on Percoll density gradients and analyzed to determine phenotypes, effects on allogeneic T lymphocyte proliferation, and production of prostaglandin E2 (PGE2). Cells expressing HLA‐DR predominated in all fractions, and esterasepositive cells were enriched in light fractions. Heavy cells were potent stimulators in the mixed lymphocyte reaction and produced little PGE2, whereas light cells suppressed the mixed lymphocyte reaction and produced a large quantity of PGE2. These results suggest that macrophage‐like synovial cells that suppress T helper lymphocyte activity are generated secondary to synovial lymphocyte activation in rheumatoid arthritis.
Suppression of rheumatoid factor synthesis by antiidiotypic antibody in rheumatoid arthritis patients with cross‐reactive idiotypes
Authors: Takeuchi Tsutomu , Hosono Osamu , Koide Jun , Homma Mitsuo , Abe Tohru 
Published: February 2007

AbstractThe effect of antiidiotypic antibody on the in vitro production of rheumatoid factor was studied in rheumatoid arthritis patients with cross‐reactive idiotypic determinants. Antiidiotypic antibodies (ascites IgG) were developed against monoclonal rheumatoid factor (Ka m‐RF) by a cell fusion procedure. These antibodies were idiotype‐specific, since: 1) they reacted only with F(ab')2 fragment of Ka m‐RF; 2) they failed to react with normal IgM without rheumatoid factor activity; and 3) their F(ab')2 fragment inhibited the rheumatoid factor activity of Ka m‐RF. The antiidiotypic antibody strongly suppressed the in vitro production of rheumatoid factor by lymphocytes from unrelated rheumatoid arthritis patients with cross‐reactive idiotypes. The suppression was specific, since ascites IgG failed to suppress in vitro anti‐keyhole limpet hemocyanin antibody production by the lymphocytes. These results indicate that antiidiotypic antibody may influence the regulation of rheumatoid factor production in patients with rheumatoid arthritis.
In vitro production and scavenging of hydrogen peroxide by D‐penicillamine. Relationship to copper availability
Authors: Staite Nigel D. , Messner Ronald P. , Zoschke David C. 
Published: February 2007

AbstractThe capacity of D‐penicillamine (DP) to produce or scavenge hydrogen peroxide was investigated. DP added to copper produced H2O2. Greater production was observed with copper sulfate than with copper bound to ceruloplasmin. In contrast, DP in the absence of copper scavenged H2O2, as measured in a direct assay. Furthermore, DP or D‐cysteine alone reversed H2O2‐mediated inhibition of concanavalin A‐stimulated mononuclear cell proliferation. These opposing immunomodulating properties of DP may be relevant to its toxic or therapeutic actions in rheumatoid arthritis.
Detection of cross‐reactive anti‐DNA antibody idiotypes in the serum of systemic lupus erythematosus patients and of their relatives
Authors: Isenberg D. A. , Shoenfeld Y. , Walport M. , Mackworth‐Young C. , Dudeney C. , Todd‐Pokropek A. , Brill S. , Weinberger A. , Pinkas J. 
Published: February 2007

AbstractTwo common cross‐reacting anti‐DNA antibody idiotypes designated 16/6 and 32/15, previously identified in the serum of patients who have systemic lupus erythematosus, were found in 24% and 7%, respectively, of 147 first‐degree relatives. These findings imply that high‐frequency germ‐line genes exist among lupus relatives, as well as patients. These dominant or public anti‐DNA antibody idiotypes are not likely to be pathogenic factors, but are probably a genetically associated phenomenon.
Impaired b cell proliferation by Staphylococcus aureus Cowan 1 in patients with systemic lupus erythematosus
Authors: Sawada Shigemasa , Amaki Satoshi , Takei Masami , Karasaki Miki , Amaki Ichita 
Published: February 2007

AbstractWe examined the proliferative response to Staphylococcus aureus Cowan 1 (SAC) by enriched peripheral blood B cells from patients with systemic lupus erythematosus (SLE). Responses of B cells from patients with active and inactive SLE were significantly lower than those of B cells from normal individuals. Hyporesponsiveness to SAC was not observed in healthy family members of SLE patients. This hyporesponsiveness did not correlate with prednisolone therapy and could not be attributed to serum factors; it did correlate with the presence of suppressor monocytes. However, we could not exclude the possibility of enhanced sensitivity of SLE B lymphocytes to suppressive signals delivered by the monocytes.
Synthesis, secretion, and deposition of fibronectin in cultured human synovium
Authors: Lavietes Beverly B. , Carsons Steven , Diamond Herbert S. , Laskin Richard S. 
Published: February 2007

AbstractWe examined fibronectin synthesis, secretion, and deposition in vitro by primary explants of rheumatoid synovium. Primary cultures initiated from tissue with monocytic infiltrates had higher levels of fibronectin synthesis; addition of dexamethasone at concentrations known to stimulate other tissue fibroblasts increased fibronectin synthesis and secretion. Newly synthesized fibronectin recovered from primary rheumatoid culture medium had a higher apparent molecular weight (240‐245 kd), on sodium dodecyl sulfate‐polyacrylamide gel electrophoresis, compared with fibronectin recovered from passaged normal and rheumatoid cultures (230 kd). Primary rheumatoid explant cultures had a characteristic morphology which correlated with fibronectin deposition. Dense deposits of fibronectin extracellular matrix covered overlapping synoviocytes adjacent to esterase‐positive mononuclear cells. Dexamethasone‐treated cultures showed little fibronectin deposited as extracellular matrix and did not develop overlapping cellular networks. Characteristic patterns of fibronectin synthesis and deposition in primary rheumatoid cultures appear to result from interaction between fibroblastic and monocytic cells. This culture system may provide a model by which to study interactions between cells and extracellular matrix components that regulate synovial cell function.
Low synovial clearance of iodide provides evidence of hypoperfusion in chronic rheumatoid synovitis
Authors: Wallis Wayne J. , Simkin Peter A. , Nelp Wil B. 
Published: February 2007

AbstractIodide clearance was measured in the chronic knee effusions of 11 patients with rheumatoid arthritis and 9 patients with osteoarthritis. The mean (±SE) iodide clearance of 1.92 ± 0.30 ml/minute in rheumatoid arthritis effusions did not differ significantly from the 2.19 ± 0.52 ml/minute found in osteoarthritis effusions. Clearance values in rheumatoid arthritis patients ranged widely (0.79–3.22 ml/minute). Iodide clearance in these patients correlated directly with synovial fluid (SF) pH (r = 0.731, P = 0.005), SF glucose: serum glucose ratio (r = 0.746, P = 0.004), and SF temperature (r = 0.878, P = 0.001), and indirectly with SF lactate (r = −0.782, P = 0.002) and percentage of SF neutrophils (r = −0.581, P = 0.03). These relationships support the hypothesis that rheumatoid synovitis is often marked by tissue hypoperfusion, and that the “sickest” rheumatoid joints (as defined by physiologic indices) are the most ischemic.
Extracellular matrix‐cytoskeletal interactions in rheumatoid arthritis. I. Immunoelectron microscopic analysis of the fibronexus at the adhesive surface of normal porcine type B synoviocytes in vitro
Authors: Singer Irwin I. , Kazazis Diana M. , Kawka Douglas W. , Rupp Elizabeth A. , Bayne Ellen K. 
Published: February 2007

AbstractWe studied cell surface interactions between the fibronectin (FN)‐containing extracellular matrix and the actin cytoskeleton of normal porcine synoviocytes in vitro, using electron microscopic methods. These type B synovial cells were distinguishable from dermal fibroblasts co‐isolated from the same organism, because of their very long cellular processes and their ability to synthesize prostaglandin E2 after stimulation with interleukin‐1. With plastic sections, we found end‐to‐end (tandem) and track‐like (lateral) transmembrane associations of extracellular fibers and cortical 5‐nm microfilaments localized along the attenuated synoviocyte processes in postconfluent cultures. Very similar FN–actin complexes, termed fibronexus (FNX), have been observed on cultured fibroblasts and on granulation tissue myofibroblasts in vivo. Using double‐label immunoelectron microscopy with monospecific antibodies applied to ultrathin frozen sections of synoviocytes cut in situ, we proved that these FNX were indeed composed of associated FN and actin filaments. The striking finding of numerous FNX in cultured type B synoviocytes strongly suggests that the FNX is a major cell surface adhesion site in normal synovium, which may play an important role in pannus formation, connective tissue remodeling, and synoviocyte proliferation in patients with rheumatoid arthritis.
Determination of 16 alpha‐hydroxyestrone by radioimmunoassay in systemic lupus erythematosus
Authors: Lahita Robert G. , Bucala Richard , Bradlow H. Leon , Fishman Jack 
Published: February 2007

AbstractA radioimmunoassay for the feminizing metabolite 16 alpha–hydroxyestrone was applied to a variety of sera from healthy volunteers, patients with active or inactive systemic lupus erythematosus (SLE), and patients with other rheumatic diseases. A significant increase in this metabolite was detected in patients with SLE, especially those with active disease, compared with normal controls (P < 0.001). SLE patients were categorized as having either active or inactive disease by clinical and laboratory criteria. Many patients who had clinically and serologically active disease were found to have normal levels of this estrogenic metabolite, and several explanations for these differences are explored in this report. Despite a poor correlation of hormone levels with age, antibody levels, or complement levels in patients with SLE, those patients with the highest levels of hormone were among those whose disease was clinically most active.
Two histopathologic types of inflammatory vascular disease in MRL/Mp autoimmune mice. Model for human vasculitis in connective tissue disease
Authors: Alexander Elaine L. , Mover Carolyn , Travlos Gregory S. , Roths John B. , Murphy Edwin D. 
Published: February 2007

AbstractWe have recently described 2 histopathologic types of inflammatory vascular disease (IVD) in patients with Sjögren's syndrome (SS): neutrophilic IVD (NIVD) and mononuclear IVD (MIVD). Autoimmune MRL/Mp mice, which have many features of SS, spontaneously develop IVD which is histopathologically indistinguishable from that observed in human SS patients. Both MRL/Mp−+/+ and MRL/Mp‐lpr/lpr mice develop MIVD which evolves into NIVD and results in decreased survival; the transition to NIVD is accelerated by the lpr gene. The presence of the lpr gene on other genetic backgrounds does not result in a similar acceleration of IVD and associated decreased survival. Thus, the spontaneous autosomal recessive mutation lpr appears to modulate the development of IVD in a strain of mice with an underlying propensity for vasculitis. Based on our observations on IVD in SS patients and MRL/Mp mice, we propose a new model which may enhance our understanding of the immunopathogenesis of IVD in connective tissue disease.
Referral of musculoskeletal disease patients by family and general practitioners
Authors: Felson David T. , Meenan Robert F. , Dayno Susan J. , Gertman Paul 
Published: February 2007

AbstractWe surveyed general and family practitioners to evaluate their patterns of referring musculoskeletal disease patients to rheumatologists and orthopedists. Patients who had rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis were most often referred to rheumatologists, whereas patients with osteoarthritis, persistent low back pain, and post‐traumatic knee pain were most often referred to orthopedists. As conditions worsened in severity, referrals were more frequent. Patients with conditions that were difficult to diagnose, such as possible shoulder tendinitis that was unresponsive to initial nonsteroidal therapy, undiagnosed polyarthritis, and intermittent knee swelling with pain, were most often treated without referral and, when referred, were most often sent to orthopedists. Belief in the effectiveness of rheumatologists or orthopedists correlated strongly with reported referral behavior, yet most respondents considered themselves capable of managing the majority of patients with musculoskeletal diseases. Neither practice arrangement, board certification, nor educational background affected referral behavior. However, younger physicians were more likely (P = 0.002) to refer patients to rheumatologists. Multivariate analysis showed that the significant predictors of global referral behavior were belief in the effectiveness of subspecialists and a small number of musculoskeletal problems seen by the generalist. The predictors of referral to rheumatologists were belief in rheumatologist efficacy and young physician age.
Hormonal modulation in systemic lupus erythematosus. Preliminary clinical and hormonal results with cyproterone acetate
Authors: Jungers Paul , Kuttenn Frédérique , Liote Frédéric , Pelissier Clara , Athea Nicole , Laurent Marie‐Christine , Viriot Joëlle , Dougados Maxime , Bach Jean‐François 
Published: February 2007

AbstractWe prospectively studied the effects of hormonal modulation using the antigonadotropic drug, cyproterone acetate (CA), in 7 female patients who had moderately active systemic lupus erythematosus. CA was taken orally at a mean daily dose of 50 mg for 21–33 months by 6 patients (9 months by the seventh patient) without any side effects. The number of clinical lupus exacerbations during CA treatment was lower than that during the corresponding pretreatment period (15 of 170 patient‐months versus 27 of 156 patient‐months P < 0.05), despite a reduction in the daily maintenance dose of corticosteroids or antimalarial drugs. Mean plasma testosterone levels were low initially and remained unchanged (0.66 ± 0.31 to 0.59 ± 0.23 nmoles/ liter), whereas plasma estradiol decreased markedly (from 0.6 ± 0 38 to 0.11 ± 0.03 nmoles/liter), resulting in a significant reduction in the estradiol:testosterone ratio (from 1.19 ± 0.68 to 0.23 ± 0.12) and in the plasma concentration of the sex hormone–binding protein. Thus, cyproterone acetate induced improvement in clinical lupus activity in parallel with the expected lower estradiol:testosterone balance.
Two types of inflammatory vascular disease in Sjögren's syndrome. Differential association with seroreactivity to rheumatoid factor and antibodies to Ro (SS‐A) and with hypocomplementemia
Authors: Molina Rodolfo , Provost Thomas T. , Alexander Elaine L. 
Published: February 2007

AbstractTwo types of inflammatory vascular disease (IVD) occur in Sjögren's syndrome: neutrophilic IVD (NIVD) and mononuclear IVD (MIVD). In 45 patients with Sjögren's syndrome, we examined the 2 types of IVD with respect to serologic associations. NIVD, unlike MIVD, was significantly associated with seroreactivity reflected by hyperglobulinemia (P = 0.01), rheumatoid factor (P = 0.002), antinuclear antibodies (P = 0.02), and antibodies to Ro (SS‐A) (P = 0.00006), and with hypocomplementemia (P = 0.03). The differential association of the 2 types of IVD with serologic reactivity and hypocomplementemia suggests that there may be basic differences in the immunopathogenesis of these 2 forms of IVD in Sjögren's syndrome.