bluuebunny/crossref_metadata_2025_split huggingface dataset:
American college of rheumatology preliminary definition of improvement in rheumatoid arthritis
Authors: Felson David T. , Anderson Jennifer J. , Boers Maarten , Bombardier Claire , Furst Daniel , Goldsmith Charles , Katz Linda M. , Lightfoot Robert , Paulus Harold , Strand Vibeke , Tugwell Peter , Weinblatt Michael , James Williams H. , Wolfe Frederick , Kieszak Stephanie 
Published: February 2007

AbstractObjective. Trials of rheumatoid arthritis (RA) treatments report the average response in multiple outcome measures for treated patients. It is more clinically relevant to test whether individual patients improve with treatment, and this identifies a single primary efficacy measure. Multiple definitions of improvement are currently in use in different trials. The goal of this study was to promulgate a single definition for use in RA trials.Methods. Using the American College of Rheumatology (ACR) core set of outcome measures for RA trials, we tested 40 different definitions of improvement, using a 3‐step process. First, we performed a survey of rheumatologists, using actual patient cases from trials, to evaluate which definitions corresponded best to rheumatologists' impressions of improvement, eliminating most candidate definitions of improvement. Second, we tested 20 remaining definitions to determine which maximally discriminated effective treatment from placebo treatment and also minimized placebo response rates. With 8 candidate definitions of improvement remaining, we tested to see which were easiest to use and were best in accord with rheumatologists' impressions of improvement.Results. The following definition of improvement was selected: 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and an acutephase reactant. Additional validation of this definition was carried out in a comparative trial, and the results suggest that the definition is statistically powerful and does not identify a large percentage of placebo‐treated patients as being improved.Conclusion. We present a definition of improvement which we hope will be used widely in RA trials.
Fibromyalgia in women
Authors: Mountz James M. , Bradley Laurence A. , Modell Jack G. , Alexander Ronald W. , Triana‐Alexander Mireya , Aaron Leslie A. , Stewart Katharine E. , AlarcóN Graciela S. , Mountz John D. 
Published: February 2007

AbstractObjective. To determine if regional cerebral blood flow (rCBF) in the left and right hemithalami or the left and right heads of the caudate nucleus is abnormal in women with fibromyalgia (FM).Methods. Resting‐state rCBF in the hemithalami and left and right heads of the caudate nucleus of 10 untreated women with FM and 7 normal control women was measured by single‐photon–emission computed tomography. Pain threshold levels at tender and control points also were assessed in both the women with FM and the controls.Results. The rCBF in the left and right hemithalami and the left and right heads of the caudate nucleus was significantly lower in women with FM than in normal controls (P = 0.01, P = 0.003, P = 0.01, and P = 0.02, respectively). Compared with controls, the women with FM also were characterized by significantly lower cortical rCBF (P = 0.001) and lower pain threshold levels at both tender points (P = 0.0001) and control points (P = 0.0001).Conclusion. The findings of low rCBF and generalized low pain thresholds support the hypothesis that abnormal pain perception in women with FM may result from a functional abnormality within the central nervous system.
High level of interleukin‐10 production by the activated t cell population within the rheumatoid synovial membrane
Authors: Cohen Shara B. A. , Katsikis Peter D. , Chu Cong‐Qiu , Thomssen Henrike , Webb LOUISE M. C. , Maini Ravinder N. , Londei Marco , Feldmann Marc 
Published: February 2007

AbstractObjective. To characterize the cytokine profile of the activated T cell population derived from the synovial membrane of rheumatoid arthritis (RA) patients.Methods. Interleukin‐2 (IL‐2) was used to select for in vivo–activated T cells from the synovial membrane of 2 patients with RA, and the cells were cloned nonspecifically. The cytokine production profile of these clones was compared with that of clones derived from peripheral blood monocytes (PBM) by stimulating all clones for 24 hours with immobilized anti‐CD3 (coated at 10 μg/ml) or phorbol‐12‐myristate‐13‐acetate (10 ng/ml) plus soluble anti‐CD3 (1 μg/ml). Interferon‐γ (IFNγ), IL‐4, and IL‐10, the cytokines that discriminate between Th1 and Th2 cells and are involved in immunoregulation, were assayed by enzyme‐linked immunosorbent assay.Results. There was a difference in the cytokines produced by the clones derived from the rheumatoid membranes compared with clones derived from the periphery. Clones derived from both membranes and PBM were mostly IFNγ‐producers, i.e., either a Th0 or a Th1 profile. There was a high proportion of IFNγ/high IL‐10‐producing cells derived from the joint, but not from the periphery. Of clones derived from the synovial membrane of each of 2 RA patients, 100% and 50% produced both 1–10 ng/ml IFNγ and >7 ng/ml IL‐10, compared with <7% of clones derived from normal or RA peripheral blood. In addition, when autologous membrane and PBM were compared, the mean concentration of IL‐10 produced by the clones derived from the synovial membrane sample was significantly different from those produced by clones derived from peripheral blood (P < 0.02).Conclusion. The cytokine profile of the T cell clones that were obtained from the RA joint after expansion with IL‐2 is distinct from that of the T cells that are predominant in PBM. This supports the concept that the T cell subsets that accumulate in the joint are not a random sample. The high level of IL‐10 production by clones derived from the synovium suggests that this cytokine may be a major contributor to the endogenous immunosuppression that occurs in RA.
Autoepitopes of the 52‐kd ss‐a/ro molecule
Authors: Kato Tomohiro , Sasakawa Hiroko , Suzuki Satoshi , Shirako Manami , Tashiro Fumio , Nishioka Kusuki , Yamamoto Kazuhiko 
Published: February 2007

AbstractObjective. This study was undertaken to clarify the mechanisms responsible for the generation of anti–52‐kd SS‐A/Ro autoantibodies and to elucidate why, as has recently been reported, anti–52‐kd autoantibodies preferentially recognize the denatured form rather than the native 52‐kd molecule.Methods. Using a series of truncated 52‐kd auto‐antigens, produced as β‐galactosidase fusion proteins in Escherichia coli, the B cell epitope distribution was probed with 18 anti‐Ro–positive sera by immunoblotting and by enzyme‐linked immunosorbent assay.Results. Nearly all the antigenicity of the molecule was found to be linked to its leucine zipper region. In a further study using 9 of the 18 sera, the antigenicity of the molecule was found to be mainly formed by multiple conformational epitopes, and one of these epitopes appeared to be universally recognized by all the sera tested.Conclusion. The recognition of multiple epitopes indicates that the Ro 52‐kd antigen itself drives the autoimmunity to this molecule. Further, the concentration of the antigenicity at the leucine zipper region may explain why anti–52‐kd antibodies preferentially recognize the denatured protein rather than its native form.
End‐stage liver disease developing with the use of methotrexate in heterozygous α1‐antitrypsin deficiency
Authors: Hilsden Robert J. , Urbanski Stefan J. , Swain Mark G. 
Published: February 2007

AbstractWe report a case of cirrhosis developing in a man who was heterozygous for α1‐antitrypsin deficiency and who was receiving methotrexate for severe rheumatoid arthritis. The α1‐antitrypsin phenotype PiMZ has been associated with cryptogenic cirrhosis. Our patient had no biochemical or histologic evidence of chronic liver disease during the first year of receiving methotrexate. We postulate that the PiMZ state may result in enhanced susceptibility to methotrexate‐induced hepatic toxicity and should be screened for if liver function abnormalities occur during methotrexate therapy.
Levels of circulating collagenase, stromelysin‐1, and tissue inhibitor of matrix metalloproteinases 1 in patients with rheumatoid arthritis: relationship to serum levels of antigenic keratan sulfate and systemic parameters of inflammation
Authors: Manicourt Daniel‐Henri , Fujimoto Noboru , Obata Ken'ichi , Thonar Eugene j.‐ M. A. 
Published: February 2007

AbstractObjective. To measure serum levels of matrix metalloproteinase–1 (MMP‐1), matrix metalloproteinase–3 (MMP‐3), and tissue inhibitor of MMP–1 (TIMP‐1) in patients with rheumatoid arthritis (RA) and in agematched control subjects, and to determine how these correlate with serum levels of antigenic keratan sulfate (KS) and other biochemical and clinical indicators of disease activity.Methods. Immunoassays were used to measure levels of MMP‐1, MMP‐3, TIMP‐1, and antigenic KS. Radiologic and functional joint scores were based upon Steinbrocker's criteria. Erythrocyte sedimentation rates (ESR) and levels of C‐reactive proteins (CRP) were measured.Results. In RA patients, levels of MMP‐3 and TIMP‐1 were significantly increased, and strongly correlated with the ESR and CRP levels but not with radiologic or functional joint scores. Levels of antigenic KS were significantly lower in RA patients and correlated negatively with systemic parameters of inflammation and serum levels of TIMP‐1.Conclusions. The increase in serum levels of MMP‐3 and TIMP‐1 appears to reflect systemic inflammation in RA. The inverse correlation between serum levels of TIMP‐1 and antigenic KS suggests that an upregulation of TIMP‐1 synthesis might be responsible for the apparent suppression of cartilage aggrecan catabolism in patients with severe inflammatory changes.
Differential effects of interleukins 10 and 4 on the production of interleukin‐6 by blood and synovium monocytes in rheumatoid arthritis
Authors: Chomarat Pascale , Banchereau Jacques , Miossec Pierre 
Published: February 2007

AbstractObjective. To determine how the antiinflammatory cytokines interleukin‐10 (IL‐10) and IL‐4 affect the production of IL‐6 in rheumatoid arthritis (RA) and to assess the contribution of IL‐10 production.Methods. IL‐6 production was measured by enzyme‐linked immunosorbent assay (ELISA) in the supernatants of cultured RA synovium pieces (from 23 patients), purified RA synovial tissue monocyte/macrophages, and RA blood monocytes, in the presence of IL‐10 and IL‐4. IL‐10 was also detected by ELISA in culture supernatants and in RA sera.Results. The production of IL‐6 by RA synovium was strongly inhibited by IL‐4 (46.6%; P = 0.0001) and was inhibited to a lower extent by IL‐10 (25.3%; P = 0.03). Likewise, the spontaneous production of IL‐6 by RA synovial tissue monocyte/macrophages was decreased by the addition of IL‐4 (48.8%) and IL‐10 (23.7%). This inhibition of IL‐6 production was significantly lower (P < 0.03) than that observed with RA blood monocytes (83.0% for IL‐10 and 85.2% for IL‐4). Interestingly, and in contrast to RA blood monocytes, RA synovial tissue monocyte/macrophages produced spontaneously high levels of IL‐10, which were inhibited by IL‐4 and interferon‐γ.Conclusion. The ability of IL‐10 and IL‐4 to suppress IL‐6 production was dependent on 1) differences in the state of differentiation of blood and synovial tissue monocytes, and 2) local production of cytokine inside the synovium.
Interleukin‐1 receptor antagonist in patients with active systemic lupus erythematosus: enhanced production by monocytes and correlation with disease activity
Authors: Suzuki Hiroshi , Takemura Hiroyuki , Kashiwagi Heihachiro 
Published: February 2007

AbstractObjective. To evaluate the relationship between the serum concentration of interleukin‐1 receptor antagonist (IL‐1Ra) and systemic lupus erythematosus (SLE) disease activity, and to investigate the expression of IL‐1Ra messenger RNA (mRNA) and its production by monocytes from patients with SLE.Methods. Serum IL‐1Ra was measured by enzyme‐linked immunosorbent assay, and expression of IL‐1Ra mRNA was determined by Northern blotting.Results. Serum IL‐1Ra concentrations were significantly higher in patients with active SLE compared with normal subjects and patients with other rheumatic diseases, and showed a strong correlation with SLE disease activity. IL‐1Ra mRNA expression in freshly isolated monocytes from patients with active SLE was considerably higher than that in normal monocytes. Moreover, monocytes from patients with active SLE produced increased amounts of IL‐1Ra in response to adherent IgG, compared with monocytes from normal subjects.Conclusion. A high serum concentration of IL‐1Ra is a pathophysiologic feature of active SLE and a good indicator of disease activity. Functional changes of monocytes, such as increased secretion of IL‐1Ra in response to adherent IgG and enhanced expression of IL‐1Ra mRNA in freshly isolated cells, may be involved in the enhanced IL‐1Ra production in active SLE. High concentrations of IL‐1Ra in the circulation and possibly in peripheral lymphoid tissues may influence immunologic and inflammatory features of SLE.
Effects of cyclophosphamide on the development of malignancy and on long‐term survival of patients with rheumatoid arthritis a 20‐year followup study
Authors: Radis Charles D. , Kahl Leslie E. , Baker Gary L. , Wasko Mary Chester Morgan , Cash Joseph M. , Gallatin Aileen , Stolzer Bertrand L. , Agarwal Amrit K. , Medsger Thomas A. , Kwoh C. Kent 
Published: February 2007

AbstractObjective. To examine the effects of cyclophosphamide (CYC) on the development of malignancies and on the long‐term survival of patients with rheumatoid arthritis (RA).Methods. We used a longitudinal cohort design in which 119 patients (76 women and 43 men) with refractory RA who were treated with oral CYC between 1968 and 1973 were compared with 119 control patients with RA (matched for age, sex, disease duration, and functional class) who were evaluated during the same time period but did not receive CYC.Results. There was increased risk of malignancy in the CYC‐treated group, with 50 cancers found in 37 patients in the CYC group compared with 26 cancers in 25 of the control patients (P < 0.05). The relative risk of cancer for those treated with CYC was 1.5 (95% confidence interval 0.93–5.5). Nine of the malignancies in the CYC group were bladder cancers and 19 were skin cancers, compared with no bladder cancers and 6 skin cancers in the control group. The total dose of CYC was higher in those who developed cancer, particularly in those with bladder cancer. Three of the bladder cancers occurred 14, 16, and 17 years after CYC had been discontinued.Conclusion. The risk of malignancy, particularly bladder cancer, in RA patients treated with oral CYC continues even 17 years after discontinuation of the drug.
Treatment of active refractory rheumatoid arthritis with humanized monoclonal antibody campath‐1h administered by daily subcutaneous injection
Authors: Matteson Eric L. , Yocum David E. , St. Clair E. William , Achkar Antonio A. , Thakor Michael S. , Jacobs Mary R. , Hays Anita E. , Heitman Catherine K. , Johnston Jeffrey M. 
Published: February 2007

AbstractObjective. To investigate the dose tolerance and potential clinical activity of a humanized antilymphocyte monoclonal antibody, CAMPATH‐1H (C1H), in patients with active, refractory rheumatoid arthritis (RA).Methods. Thirty adult patients with active, refractory RA were treated in an open‐label, 3‐center, dose‐escalation study of subcutaneously injected C1H. Six patients were assigned to each of 5 dosage groups (0.3, 1.0, 3.0, 10.0 or 30.0 mg/day), and received 10 daily injections of C1H over a 12‐day period.Results. Side effects occurred primarily during the first 1–2 days of dosing, and included mild fever, chills, nausea, vomiting, headache, and, in a minority of patients, hypotension. All patients developed some discomfort at the injection site. Self‐limited infections occurred in 5 patients during the 6‐month study period. Peripheral blood lymphocyte counts fell promptly after initial dosing and recovered slowly, usually over 2–3 months. Serum antibodies to C1H developed in 54% of patients following treatment. Clinical improvement was observed in 56% of patients, based on the composite Paulus criteria, with a median time‐to‐response of 22 days and a median response duration of 32 days.Conclusion. C1H is a lymphocyte‐depleting antibody that exhibits biologic potency when administered subcutaneously to patients with refractory RA. Its use is associated with mild to moderate toxicity and short‐term amelioration of disease activity.
Light and electron microscopic analysis of sequential liver biopsy samples from rheumatoid arthritis patients receiving long‐term methotrexate therapy followup over long treatment intervals and correlation with clinical and laboratory variables
Authors: Kremer Joel M. , Kaye Gordon I. , Kaye Nancy W. , Ishak Kamal G. , Axiotis Constantine A. 
Published: February 2007

AbstractObjective. To describe liver histopathologic features and ultrastructural changes in a prospectively studied cohort of rheumatoid arthritis (RA) patients receiving long‐term methotrexate (MTX) therapy, and to seek correlations between these changes and simultaneously measured laboratory indices of liver function.Methods. This was a long‐term, prospective, open observational study. Twenty‐seven outpatients with RA who began therapy with MTX and continued treatment for extended periods underwent baseline and followup liver biopsies. One hundred seventy liver biopsy specimens were analyzed by light microscopy (LM) and assessed according to a modified Roenigk score and a newly devised numerical grading system. Ninety‐three biopsy specimens were also analyzed by electron microscopy (EM). Blood samples were obtained at 4–6‐week intervals for determination of bilirubin, alkaline phosphatase, aspartate aminotransferase (AST), and albumin levels, and the weekly dosage of MTX was adjusted if there were abnormalities in the AST or albumin level. A mean of 6.3 liver biopsies per patient were obtained over a mean followup period of 8.2 years (range 2–13 years).Results. The modified Roenigk score was significantly different from baseline at year 3, when it increased from a mean of 1.8 to 2.3 (P = 0.05) and at year 6, when it increased to 2.4 (P = 0.04), but this was not considered clinically meaningful. No other significant changes from baseline were observed by either LM grading system. No significant progression was observed by EM over the course of the investigation. Increases in serial measurements of AST correlated with both the modified Roenigk score (r = 0.21, P = 0.016) and the numerical rating score (r = 0.19, P = 0.027).Conclusion. Patients with RA who are receiving weekly single‐dose oral MTX therapy exhibit little deterioration in hepatic architecture by LM or EM when the dosage of the drug is adjusted for abnormalities in AST and serum albumin, monitored at frequent intervals.
Incidence of systemic lupus erythematosus race and gender differences
Authors: Mccarty Daniel J. , Manzi Susan , Medsger Thomas A. , Ramsey‐Goldman Rosalind , Laporte Ronald E. , Kwoh C. Kent 
Published: February 2007

AbstractObjective. To examine racial differences in the incidence of systemic lupus erythematosus (SLE).Methods. A population‐based registry of SLE patients in Allegheny County, Pennsylvania, was used to identify incident cases of SLE diagnosed between January 1, 1985 and December 31, 1990, from 3 sources, by medical record review (University of Pittsburgh Lupus Databank, rheumatologists, and hospitals). Capture‐recapture methods using log‐linear models were used to estimate the level of case‐finding and to calculate 95% confidence intervals (CI). Incidence rates were calculated per 100,000 population.Results. A total of 191 definite and 78 probable incident cases of SLE were identified, and the overall annual incidence rates were 2.4 (95% CI 2.1–2.8) and 1.0 (95% CI 0.8–1.3), respectively. The crude incidence rates of definite SLE were 0.4 for white males, 3.5 for white females, 0.7 for African‐American males, and 9.2 for African‐American females. The annual incidence rates of definite SLE remained fairly constant over the study interval. African‐American females with definite SLE had a younger mean age at diagnosis compared with white females (P < 0.05). Since the overall ascertainment rate was high (85%; 95% CI 78–92%), the ascertainment‐corrected incidence rate for definite SLE, 2.8 (95% CI 2.6–3.2), was similar to the crude rate.Conclusion. Our rates clearly confirm previous reports of an excess incidence of SLE among females compared with males and among African‐Americans compared with whites. We have used capture–recapture methods to improve the accuracy of SLE incidence rates, and we advocate their use to facilitate comparisons across studies.
Characterization of the binding region for the yersinia enterocolitica adhesin yada on types i and ii collagen
Authors: Schulze‐Koops Hendrik , Burkhardt Harald , Heesemann JÜRgen , Mark Klaus Von Der , Emmrich Frank 
Published: February 2007

AbstractObjective. The plasmid‐encoded adhesin YadA confers pathogenic functions on Yersinia enterocolitica, a microorganism associated with reactive arthritis. While emerging evidence has indicated that the persistence of the bacteria in individuals with reactive arthritis is a prerequisite for the development of the disease, the tissue specificity of this immunologic disease sequela remains elusive. The present study was undertaken to investigate YadA‐mediated binding of Y enterocolitica to the most abundant collagens in joints, types I and II collagen.Methods. Binding studies were performed with recombinant Y enterocolitica strains and highly purified type II collagen and the α1(I) chain of type I collagen, or fragments of these collagens generated by various enzymatic and nonenzymatic cleavage procedures. Interactions of bacteria with the proteins were determined in binding assays with radiolabeled proteins.Results. Binding regions for YadA were identified at the 181–amino acid fragment α1(I)78CBN of type I collagen and the CB10 fragment of type II collagen. From binding and blocking experiments with α1(I) fragments, cyanogen bromide–derived or mammalian collagenase–derived type II collagen fragments, and synthetic peptides with collagen‐like structures, it was concluded that the binding site for YadA on collagen is determined by a restricted amino acid sequence and is defined within a highly homologous 134–amino acid region. Furthermore, the binding site is not affected by mammalian collagenase digest. Binding of YadA‐positive yersiniae to collagen could be inhibited by an antiserum specific for YadA.Conclusion. This study provides the first evidence of a binding site for bacterial proteins on collagens which is not determined by the repetitive sequence Gly‐X‐Y of collagens. We speculate that the binding region is conserved between types I and II collagen, the most abundant collagens in the joints. Specific binding of Yersinia products to joint collagens might contribute to the arthritogenic potential of enteropathogenic yersiniae.