bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of the european league against rheumatism response criteria for rheumatoid arthritis: Comparison with the preliminary american college of rheumatology and the world health organization/international league against rheumatism criteria
Authors: van Gestel A. M. , Prevoo M. L. L. , van't Hof M. A. , van Rijswijk M. H. , van de Putte L. B. A. , van Riel P. L. C. M. 
Published: February 2007

AbstractObjective. To validate the European League Against Rheumatism (EULAR), the American College of Rheumatology (ACR), and the World Health Organization (WHO)/International League Against Rheumatism (ILAR) response criteria for rheumatoid arthritis (RA).Methods. EULAR response criteria were developed combining change from baseline and level of disease activity attained during followup. In a trial comparing hydroxychloroquine and sulfasalazine, we studied construct (radiographic progression), criterion (functional capacity), and discriminant validity.Results. EULAR response criteria had good construct, criterion, and discriminant validity. ACR and WHO/ILAR criteria showed only good criterion validity.Conclusion. EULAR response criteria showed better construct and discriminant validity than did the ACR and the WHO/ILAR response criteria for RA.
The epidemiology of Wegener's granulomatosis. Estimates of the five‐year period prevalence, annual mortality, and geographic disease distribution from population‐based data sources
Authors: Cotch Mary Frances , Hoffman Gary S. , Yerg Diane E. , Kaufman Gerald I. , Targonski Paul , Kaslow Richard A. 
Published: February 2007

AbstractObjective. To estimate the prevalence, annual mortality, and geographic distribution of Wegener's granulomatosis.Methods. Analysis of national vital statistics data and hospitalization data from a national survey and from all New York State inpatient facilities.Results. Between 1979 and 1988, 1,784 death certificates in the United States listed Wegener's granulomatosis as a cause of death. Nationally, an estimated 10,771 hospitalizations included Wegener's granulomatosis among the discharge diagnoses. In New York State, there were 978 hospitalizations among 571 individuals with Wegener's granulomatosis.Conclusion. The prevalence of Wegener's granulomatosis in the United States is approximately 3.0 per 100,000 persons. Clear differences in the geographic distribution of Wegener's granulomatosis are apparent when analyses consider rates of disease in individual counties. Contrary to previous reports, associations between disease exacerbations and season were not apparent.
Complete remission of multicentric reticulohistiocytosis with combination therapy of steroid, cyclophosphamide, and low‐dose pulse methotrexate. Case report, review of the literature, and proposal for treatment
Authors: Liang George C. , Granston Arthur S. 
Published: February 2007

AbstractWe describe a patient with multicentric reticulohistiocytosis in whom complete remission was achieved by sequential combination therapy with steroid, methotrexate, and cyclophosphamide. We reviewed all cases of complete or near‐complete remissions of multicentric reticulohistiocytosis reported in the English‐language literature and propose a new drug regimen for this rare but potentially disabling disease.
Activation of recombinant human neutrophil procollagenase in the presence of doxycycline results in fragmentation of the enzyme and loss of enzyme activity
Authors: Smith Gerald N. , Brandt Kenneth D. , Hasty Karen A. 
Published: February 2007

AbstractObjective. To determine if reduction of collagenase activity in vitro by doxycycline (doxy) is related to activation of the proenzyme, and to determine how exogenous Ca++ and Zn++ affect the reduction.Methods. Recombinant human neutrophil pro‐collagenase was activated with trypsin or APMA. Activity was assayed on a small peptolide substrate or on 14C‐acetylated collagen fibers. The molecular weight of the proenzyme, active enzyme, and enzyme fragments was determined by Western blotting, using a polyclonal antiserum raised against the recombinant proenzyme. Similar experiments were performed in the presence of EDTA, EGTA, 1,10‐phenanthroline, or doxy. The effects of exogenous Ca++ and Zn++ were also tested.Results. Doxy inhibited activity of the enzyme against both substrates. If the drug was present during activation, the yield of activity was lower than when it was added after activation of the proenzyme. Western blotting showed that activation in the presence of doxy resulted in the appearance of lower molecular weight fragments and accumulation of less active enzyme. APMA generated prominent 28‐ and 26‐kd fragments, while trypsin cleavage yielded 40‐ and 30‐kd fragments. Fragmentation of the enzyme also occurred in the presence of EDTA or EGTA, but not 1,10‐phenanthroline. It was prevented by Ca++ concentrations greater than 50 mM, but was not altered by addition of Zn++ in concentrations as high as 500 μM. Inhibition of collagenase activity by doxy could be overcome by 100 mM Ca++, but addition of Zn++ had no effect.Conclusion. These data suggest that doxy alters the conformation of procollagenase or collagenase by binding enzyme‐associated Ca++, rendering the proteins more susceptible to proteolysis and resulting in irreversible loss of enzyme protein.
Specificity of a porcine 127‐kd nucleotide pyrophosphohydrolase for articular tissues
Authors: Cardenal Antonio , Masuda Ikuko , Haas Arthur L. , McCarty Daniel J. 
Published: February 2007

AbstractObjective. To determine the tissue specificity of a porcine 127‐kd nucleotide pyrophosphohydrolase (NTPPHase) found in vesicles derived from hyaline articular cartilage (ACV).Methods. Homogenates of porcine brain, lung, liver, kidney, urinary bladder, pancreas, spleen, skin, vena cava, marrow, bone (cells), tendon (Achilles), ligament (anterior cruciate), elastic cartilage, meniscus, and hyaline cartilage were analyzed for NTPPHase activity (thymidine monophosphate paranitrophenyl ester substrate) and by Western blot using polyclonal antibodies against 127‐kd NTPPHase and against recombinant PC‐1, another ecto‐NTPPHase.Results. All tissues contained NTPPHase activity; the highest specific activity was found in hyaline articular cartilage, the lowest in brain. ACV‐associated 127‐kd NTPPHase was expressed in cartilage, ligament, and tendon. PC‐1 was also expressed in those tissues and in skin, kidney, bone cells, and (probably) in liver and muscle.Conclusion. The 127‐kd NTPPHase appears to be highly specific for articular tissues.
Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis
Authors: Gutierrez‐Ureña Sergio , Molina Jose F. , García Cesar O. , Cuéllar Marta L. , Espinoza Luis R. 
Published: February 2007

AbstractObjective. To assess the frequency of methotrexate (MTX)‐induced pancytopenia in rheumatoid arthritis (RA).Methods. A MEDLINE literature search was conducted to identify articles published during the last 15 years (1980–1995) that presented data on MTX‐associated pancytopenia. Two case reports of our own experience are also presented. In addition, articles that examined risk factors associated with MTX‐related pancytopenia were identified.Results. A total of 70 patients with pancytopenia related to MTX therapy were identified (68 reported in the literature, 2 from our own experience). Sixty‐one of the patients were described in published case reports, 7 patients were from 5 long‐term prospective studies. In many of these cases, predisposing factors for the development of pancytopenia were described. The 5 long‐term prospective studies reported toxicity data on patients who had been treated with MTX for at least 13 weeks. A total of 511 patients were included in the prospective trials, yielding an overall incidence of pancytopenia of 1.4% (7 of 511). Of the 70 cases reported, 12 patients died (17%). Most of them had impaired renal function, hypoalbuminemia, concurrent infection, and/or concomitant medication with more than 5 drugs. The minimal cumulative MTX dose leading to fatal pancytopenia was 10 mg, observed in one of our patients.Conclusion. Pancytopenia is not an uncommon side effect of low‐dose pulse MTX therapy in RA. It can lead to serious complications, including death.
Laboratory tests as predictors of disease exacerbations in systemic lupus erythematosus. Why some tests fail
Authors: Esdaile John M. , Abrahamowicz Michal , Joseph Lawrence , MacKenzie Todd , Li Yin , Danoff Deborah 
Published: February 2007

AbstractObjective. To evaluate whether changes in laboratory test values are either simultaneous with or precede disease exacerbations in patients with systemic lupus erythematosus (SLE).Methods. At 9, 6, and 3 months preceding a flare in disease activity (defined as a rise of ⩾ points in the modified SLE Disease Activity Index), laboratory tests were performed to measure patients' hematocrit levels, white blood cell, lymphocyte, and platelet counts, erythrocyte sedimentation rate, C1q binding, DNA binding, and levels of C3 and C4. Flares were classified as either present or absent, and were divided into renal, vasculitic, central nervous system, skin, serosal, and musculoskeletal subgroups. The predictive patterns were (1) the simultaneous change in the test value from the mean of 9, 6, and 3 months preceding a flare to the time of the flare; (2) the gradual change, following a linear time trend, in test results for the same time points; and (3) the change from the mean of 9 and 6 months to 3 months preceding a flare, as a measure of predictive ability. These analyses used repeated‐measures analysis of variance models. Multiple linear regression was used to study the cross‐sectional association of average‐overtime differences in test results with patients' flare subgroup.Results. Among 202 patients with SLE (median followup 86.5 months), 83 flares occurred in 53 patients. Of 189 statistical contrasts performed, only 14 were significant (versus 10 expected), and the differences were of minor importance. Nonetheless, evaluation of all test results over each patient's observed disease course revealed significant differences between selected test values in association with specific types of flare.Conclusion. Fluctuations in laboratory test values are poor predictors of disease exacerbations in SLE. Cross‐sectional evaluation of some test results revealed differences at the time of flare for those patients who were destined to have different types of flares, because these values differed over the entire study period. This pattern explains the frequent cross‐sectional association of disease activity with laboratory test results, and the inconsistent association of flares with recent changes in test values.
Interleukin‐10 functions as an antiinflammatory cytokine in rheumatoid synovium
Authors: Isomäki Pia , Luukkainen Reijo , Saario Riitta , Toivanen Paavo , Punnonen Juha 
Published: February 2007

AbstractObjective. Interleukin‐10 (IL‐10) is an antiinflammatory cytokine that has been shown to play a role in rheumatoid arthritis (RA). We therefore investigated the effects of IL‐10 on the function and phenotype of synovial fluid mononuclear cells (SFMC) derived from patients with RA. In addition, we studied the production of IL‐10 in rheumatoid joints, and the role of endogenous IL‐10 in the regulation of SFMC function.Methods. The presence of IL‐10 in rheumatoid joints was studied using IL‐10–specific enzyme‐linked immunosorbent assay (ELISA) and reverse transcriptase–polymerase chain reaction (RT‐PCR) techniques. The effects of recombinant human IL‐10 or neutralizing anti–IL‐10 monoclonal antibodies (MAbs) on both cytokine production and phenotype of SFMC were evaluated using cytokine‐specific ELISAs and flow cytometry. The effect of IL‐10 on proliferation of SFMC was determined by incorporation of tritiated thymidine.Results. IL‐10 was detected by ELISA in 22 of 23 SF samples, and was spontaneously produced by cultured SFMC. IL‐10 messenger RNA was detectable in all 8 SFMC samples, as determined by RT‐PCR. Neutralization of endogenously produced IL‐10 by anti–IL‐10 MAbs resulted in increased production of IL‐1β, tumor necrosis factor α (TNF α), and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) by SFMC, and in enhanced proliferation of SFMC. In particular, the production of TNF α was dramatically increased by anti–IL‐10 MAbs. Moreover, the expression of HLA–DR molecules by SF macrophages was increased, and the expression of CD16 was decreased by anti–IL‐10 MAbs. In contrast, addition of recombinant IL‐10 significantly decreased the production of IL‐1β, TNF α, and GM‐CSF by SFMC, and decreased spontaneous and IL‐2–induced proliferation of SFMC. Finally, IL‐10 decreased HLA–DR expression and increased the expression of the Fcγ receptors, CD16 and CD64, by SF macrophages.Conclusion. These data indicate that endogenously produced IL‐10 functions as an immunoregulatory molecule in rheumatoid synovium. Importantly, exogenous IL‐10 has potent antiinflammatory effects on SFMC, suggesting that IL‐10 may be useful in the treatment of patients with RA.
High frequencies of identical T cell clonotypes in synovial tissues of rheumatoid arthritis patients suggest the occurrence of common antigen‐driven immune responses
Authors: Ikeda Yoko , Masuko Kayo , Nakai Yuta , Kato Tomohiro , Hasunuma Tomoko , Mizushima Yutaka , Nishioka Kusuki , Yamamoto Kazuhiko , Yoshino Shin‐Ichi 
Published: February 2007

AbstractObjective. To investigate T cell antigen receptor (TCR) clonotypes in rheumatoid arthritis (RA) lesions.Methods. Reverse transcriptase–polymerase chain reaction with TCR Vβ family–specific primers and subsequent single‐strand conformation polymorphism (SSCP) analysis were performed. Direct nucleotide sequencing was also conducted.Results. A distinct clonal expansion of T cells was observed in the synovium. Furthermore, identical bands in samples of different areas of the same lesion were obtained by SSCP analysis. Nucleotide sequencing revealed that T cell clonotypes of identical mobility on SSCP analysis had the same nucleotide sequence and thus were identical clones. In 6 RA patients, 60–100% of the expanded T cell clonotypes had identical migration patterns in 2 different samples, indicating that this percentage represents commonly existing T cell clonotypes in the affected joint. Furthermore, the Jβ2.1 gene segment was used predominantly by the TCR Vβ clonotypes that commonly expanded in the different portions of the same joint.Conclusion. These results suggest that the immune response in RA is not random, but rather is driven by common stimuli.
High seroprevalence of anti–HTLV‐I antibody in rheumatoid arthritis
Authors: Eguchi Katsumi , Origuchi Tomoki , Takashima Hiroyuki , Iwata Kokichi , Katamine Shigeru , Nagataki Shigenobu 
Published: February 2007

AbstractObjective. To investigate the association between human T lymphotropic virus type I (HTLV‐I) infection and rheumatoid arthritis (RA) in Nagasaki, an area highly endemic for HTLV‐I infection.Methods. Sera from 113 female patients with RA and 19,796 female blood donors were screened for anti–HTLV‐I antibodies with a gelatin particle agglutination kit and confirmed using an immunoblotting kits.Results. The age‐adjusted summary odds ratio of HTLV‐I infection among RA patients, as compared with blood donors, was 2.8 (95% confidence interval [95% CI] 1.8–4.6). The etiologic fraction, i.e., the proportion of RA in the study population that is attributable to HTLV‐I infection, was estimated to be 13.2% (95% CI 5.1–21.2). There was no significant difference in the clinical and laboratory findings between HTLV‐I–infected and HTLV‐I–uninfected RA patients.Conclusion. These epidemiologic findings support the idea that HTLV‐I infection is a risk factor for RA, and suggest that ∼13% of the cases of RA in females living in Nagasaki are associated with HTLV‐I infection.
The effect of methotrexate on mouse bone cells in culture
Authors: May Kimberly P. , Mercill Don , McDermott Michael T. , West Sterling G. 
Published: February 2007

AbstractObjective. We have recently shown that administration of long‐term, low‐dose methotrexate (MTX) causes severe osteopenia in female rats. This osteopenia is characterized both by decreased osteoblast function without a decrease in osteoblast numbers, and by increased bone resorption that is believed to represent a physiologic remodeling response by osteoclasts. The present study investigates the effects of varying doses of MTX on mouse bone cells in culture.Methods. Cells were obtained by sequential digestion of neonatal mouse calvariae, and cultured with fetal calf serum (10% for osteoblast‐like cells and 2% for osteoclast‐like cells). After 1 week, MTX was added to each culture in concentrations of 0.6 μM, 0.4 μM, 0.2 μM, 0.1 μM, 1 nM, and 0.5 nM. All experiments were done on 24 wells for each MTX concentration and for the controls. The effect on osteoblastic cells was assessed, at 7 days, by cell counts and by measurement of lysate alkaline phosphatase and supernatant osteocalcin levels, and, at 21 days, by analysis of the calcified matrix production, which was cultured with ascorbic acid and β‐glycerophosphate. For osteoclastic cells, cell count and lysate acid phosphatase levels were determined.Results. Levels of osteoblastic cells and lysate alkaline phosphatase were not changed by any of the concentrations of MTX. Matrix calcification and supernatant osteocalcin levels were diminished by MTX in a dose‐responsive manner. Osteoclast‐like cell numbers and acid phosphatase levels were not significantly affected by MTX.Conclusion. These results suggest that diminished mouse osteoblastic cell function occurs with very low mean concentrations of MTX, in a dose‐responsive manner. The mechanism seems to be inability of the cell to synthesize and calcify matrix, possibly through defective osteocalcin production. Thus, low‐dose MTX may have an important impact on bone density by slowing osteoblastic matrix production.
The effect of leukotriene synthesis inhibitors in models of acute and chronic inflammation
Authors: Nickerson‐Nutter Cheryl L. , Medvedeff Eugene D. 
Published: February 2007

AbstractObjective. To assess the efficacy of leukotriene synthesis inhibitors, alone and in combination with a nonsteroidal antiinflammatory drug, as potential treatments for rheumatoid arthritis (RA), using the mouse air pouch model and the collagen‐induced arthritis (CIA) model.Methods. Two selective leukotriene synthesis inhibitors, Bay x 1005 and Bay y 1015, were compared with zileuton in terms of their ability to decrease exudate volume, cell infiltration, and leukotriene B4 (LTB4) production in response to zymosan injection in the mouse air pouch model. The mouse CIA model was used to assess the effect of leukotriene synthesis inhibitors in a model of chronic inflammation. Bay y 1015 and Bay x 1005, and the cyclooxygenase inhibitor naproxen, were evaluated individually and in combination, for their antiarthritic potency in the mouse CIA model.Results. The results indicate that neither zileuton, Bay x 1005, nor Bay y 1015 inhibited exudate production. All 3 compounds decreased LTB4 levels in the air pouch, with Bay y 1015 being the most effective. Cell infiltration was significantly decreased with Bay x 1005, but the degree of this decrease did not appear to correlate with LTB4 levels. No inhibition of arthritis was observed with any compound administered alone. In contrast, a significant inhibition of CIA was observed in animals that received both naproxen and either Bay y 1015 or Bay x 1005.Conclusion. Inhibitors of both cyclooxygenase and leukotriene synthesis in combination may be a more effective treatment of RA than either class of inhibitors alone.
TSG‐6 expression in human articular chondrocytes: Possible implications in joint inflammation and cartilage degradation
Authors: Maier Rainer , Wisniewski Hans‐Georg , Vilcek Jan , Lotz Martin 
Published: February 2007

AbstractObjective. The hyaluronan‐binding protein TSG‐6 (tumor necrosis factor‐stimulated gene 6) forms a stable complex with the serine protease inhibitor, inter‐α‐inhibitor, potentiates the inhibition of plasmin activity, and has antiinflammatory effects in vivo. This study examines the expression of TSG‐6 in human articular chondrocytes and cartilage.Methods. Human articular chondrocytes and cartilage explants were stimulated with cytokines, growth factors, and other agents. TSG‐6 expression was analyzed by imaging‐assisted Northern and Western blotting.Results. TSG‐6 messenger RNA (mRNA) expression was upregulated by cytokines and growth factors, predominantly interleukin‐1β (IL‐1β), tumor necrosis factor α (TNFα), platelet‐derived growth factor AA (PDGF‐AA), and transforming growth factor β1 (TGFβ1). TSG‐6 mRNA induction by TGFβ1 was delayed as compared with IL‐1β. Treatment of the cells with the glucocorticoid dexamethasone neither induced TSG‐6 mRNA nor did it affect IL‐1β‐induced transcript levels. TSG‐6 mRNA induction may involve several signal transduction pathways. The strong transcriptional stimulation by phorbol myristate acetate suggests protein kinase C (PKC)‐mediated signaling. In contrast, PKA‐ and Cadependent signals are only marginally involved as messengers leading to increased TSG‐6 levels after IL‐1β and TNFα treatment. In chondrocyte and cartilage organ cultures, both free TSG‐6 (35 kd) and the complex with inter‐α‐inhibitor (120 kd) were present and upregulated by IL‐1β, TNFα, or TGFβ1.Conclusion. Chondrocytes are a source of TSG‐6 which may play a role in cartilage remodeling and joint inflammation.
Stimulation of TIMP‐1 production by oncostatin m in human articular cartilage
Authors: Nemoto Osamu , Yamada Harumoto , Mukaida Masahiro , Shimmei Masayuki 
Published: February 2007

AbstractObjective. To investigate the effects of the interleukin‐6 (IL‐6) family cytokines, such as IL‐6, IL‐11, leukemia inhibitory factor (LIF), and oncostatin M (OSM), on the production of tissue inhibitor of matrix metalloproteinases 1 (TIMP‐1) in human articular cartilage.Methods. Effects of IL‐6 family cytokines and growth factors on TIMP‐1 production were studied in human articular chondrocytes, grown as monolayer and cartilage explant culture. TIMP‐1 protein levels in the cultured medium were measured by sandwich enzyme immunoassay. TIMP‐1 messenger RNA levels in the cultured chondrocytes were analyzed by Northern blotting. Western blot analysis was performed to evaluate the release of matrix metalloproteinases (MMPs) in the cultured medium. Cell proliferation of chondrocytes was determined by 3H‐thymidine uptake.Results. IL‐6 family cytokines induced TIMP‐1 expression in monolayer and explant culture, and the production of TIMP‐1 was most stimulated by OSM. In contrast, OSM did not modulate the release of MMPs and cell proliferation.Conclusion. These results suggest that OSM may be characterized as one of the chondroprotective mediators in cartilage destruction.