bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiologic features in juvenile idiopathic arthritis: A first step in the development of a standardized assessment method
Authors: Van Rossum Marion A. J. , Zwinderman Aeilko H. , Boers Maarten , Dijkmans Ben A. C. , Van Soesbergen Renée M. , Fiselier Theo J. W. , Franssen Marcel J. A. M. , Cate Rebecca ten , Suijlekom‐Smit Lisette W. A. van , Wulffraat Nico M. , Kuis Wietse , Luijk Wilma H. J. van , Oostveen Johanna C. M. , Dijkstra Piet F. ,   on behalf of the Dutch Juvenile Idiopathic Arthritis Study Group
Published: February 2003

AbstractObjectiveTo describe radiologic features of patients with juvenile idiopathic arthritis (JIA) in a standardized manner, to test the reliability and feasibility of this description, and to correlate these features with clinical signs as a first step in the development of a standardized assessment method.MethodsThe placebo‐controlled study of sulfasalazine in patients with oligoarticular, extended oligoarticular, and polyarticular JIA performed by the Dutch Juvenile Idiopathic Arthritis Study Group yielded the data for this study. All trial entry radiographs (clinically involved joints and contralateral joints) were scored (in consensus by a skeletal radiologist and pediatric rheumatologist) for the presence of swelling, osteopenia, joint space narrowing, growth abnormalities, subchondral bone cysts, erosions, and malalignment.ResultsData on 67 of 69 patients were analyzed. The mean age was 9.1 years (range 2.5–17.6 years), and the median disease duration was 24 months (range 5–176 months). Thirteen percent of the patients were IgM rheumatoid factor (IgM‐RF) positive, and 16% were HLA–B27 positive. All 68 clinically evaluated joints were included in the maximum of 19 radiographed joints (or joint groups) per patient. The mean number of radiographed joints per patient was 7 (range 2–15); knees, hands, ankles, and feet were most frequently affected. Fifty‐eight patients (87%) had radiologic abnormalities in at least one joint (soft‐tissue swelling in 63% of patients, growth disturbances in 48%, joint space narrowing in 28%, and erosions in 15%). In total, half of the radiographs of the clinically involved joints showed radiologic abnormalities, including two‐thirds of the radiographs of the clinically affected hands and knees. Univariate analysis revealed a good correlation between the overall articular (clinical) severity and the presence of radiologic abnormalities (odds ratio [OR] 1.38, P < 0.0001). Multivariate analysis showed increased ORs for the presence of radiologic abnormalities and IgM‐RF positivity (OR 4.6, P = 0.005) or HLA–B27 positivity (OR 3.0, P = 0.004). In general, reproducibility of the radiologic scoring method was good (mean kappa coefficient of 0.74 [range 0.40–0.86]), although there were scoring discrepancies for swelling, osteopenia, and growth disturbances. The scoring took 10–20 minutes per patient.ConclusionOur model of describing and scoring radiologic abnormalities of radiographed joints in JIA was feasible, mostly reproducible, correlated well with the overall articular severity score, and added substantial new information not available on clinical examination.
Diagnostic value of high‐resolution B‐mode and doppler sonography for imaging of hand and finger joints in rheumatoid arthritis
Authors: Weidekamm C. , Köller M. , Weber M. , Kainberger F. 
Published: February 2003

AbstractObjectiveHigh‐resolution sonography enables a detailed assessment of intraarticular and extraarticular soft tissue abnormalities of joints affected by rheumatoid arthritis (RA). This study was undertaken to evaluate the diagnostic value of B‐mode sonography and power Doppler compared with that of clinical examinations and conventional radiography.MethodsThe study group comprised 47 patients (14 men, 33 women) with different grades of RA; 31 patients were rheumatoid factor (RF) positive, and 16 were RF negative. The wrists, first through fifth metacarpophalangeal joints, and second through fifth proximal interphalangeal joints of these patients were scored with ultrasound in B‐mode and power Doppler application, using a standardized technique. Involvement and severity of inflammation, as well as vascularization, were scored according to a new 3‐point scale. The results were correlated with benchmarks of the clinical and radiologic investigations. Clinical status and conventional radiologic status were determined according to the Disease Activity Score and the Larsen score.ResultsAfter preliminary studies in 15 patients, 39% of 704 joints were found to be abnormal by clinical investigation. Erosions were detected by radiography and sonography in 23% and 43% of joints, respectively. Hypervascularization was observed in 34% of 704 joints by power Doppler application. There was a significant correlation (P < 0.001) between the different methods for the detection of the severity of lesions. Use of a modern, state‐of‐the‐art power Doppler program was necessary for semiquantification, and a standardized investigation technique and scoring system provided sufficient quality measures.ConclusionSonography detects 20% more abnormalities than does radiography, and sonography has the potential to provide simple grading of disease activity. The rate of detection of abnormalities was slightly higher with clinical examination compared with sonography.
The inheritance of hand osteoarthritis in Iceland
Authors: Jonsson Helgi , Manolescu Ileana , Stefansson Stefan Einar , Ingvarsson Thorvaldur , Jonsson Hjortur H. , Manolescu Andrei , Gulcher Jeff , Stefansson Kari 
Published: February 2003

AbstractObjectiveTo assess the contribution of genetics to hand osteoarthritis (HOA) and its subsets in the Icelandic population.MethodsA list of 2,919 HOA patients, constituting 1% of the Icelandic population, was compiled through nationwide sources. This patient list was cross‐referenced with a comprehensive Icelandic genealogy database, enabling the use of algorithms to assess familiality of HOA. Two methods were used: the average pairwise kinship coefficient (KC) of the patients, and the relative risk (RR) of HOA in relatives of patients. In each case, the results were compared with 1,000 control sets of similar composition with regard to number, age, and sex, generated from the genealogy database.ResultsThe KC for patients was significantly higher than for the control sets and was proportional to the degree of both interphalangeal (IP) and thumb base (first carpometacarpal [CMC] joint) involvement. The RR of HOA in sisters of women in the study was 2.0 (P < 0.001), while the RR in spouses was not significantly different from that in controls. The RR increased with the severity of the disease. Thus, sisters of women with severe IP HOA had an RR of 5.0 and sisters of those with severe first CMC involvement had an RR of 6.9. The increased risk also extended beyond the nuclear family, with significantly increased risk in cousins.ConclusionPatients seeking medical services for HOA are more related to each other than matched controls, supporting the role of a genetic component in the disease. The genetic influence in both IP and first CMC HOA appears to be similar and increases with increasing severity of the disease.
Expression of the dendritic cell–associated C‐type lectin DC‐SIGN by inflammatory matrix metalloproteinase–producing macrophages in rheumatoid arthritis synovium and interaction with intercellular adhesion molecule 3–positive T cells
Authors: van Lent Peter L. E. M. , Figdor Carl G. , Barrera Pilar , van Ginkel Karin , Slöetjes Annet , van den Berg Wim B. , Torensma Ruurd 
Published: February 2003

AbstractObjectiveTo determine whether matrix metalloproteinase (MMP)–producing inflammatory macrophages in the synovium of rheumatoid arthritis (RA) patients express the novel dendritic cell (DC)–specific C‐type lectin DC‐SIGN and whether this expression is associated with the presence of naive T cells expressing the DC‐SIGN ligand, intercellular adhesion molecule 3 (ICAM‐3).MethodsReverse transcription–polymerase chain reaction was performed to study the expression of DC‐SIGN in synovium samples from RA, osteoarthritis (OA), and trauma patients. DC‐SIGN expression on RA monocytes or on monocytes stimulated with granulocyte–macrophage colony‐stimulating factor and interleukin‐4 was further investigated by flow cytometry. To localize DC‐SIGN in the synovium, the DC markers ICAM‐3 and MMP‐1 were analyzed by immunohistochemistry (single and double labeling) on serial cryostat sections.ResultsSeventy percent of the inflammatory cells in the synovium of RA patients showed high expression of DC‐SIGN. DC‐SIGN was expressed by 80% of CD68‐positive macrophages, but not by CD83‐positive, DC‐LAMP–positive, or Fascin‐positive cells. Normal numbers of DC‐SIGN–positive cells were found in the peripheral blood of RA patients, suggesting that DC‐SIGN is up‐regulated locally in the joint. In RA synovium, ICAM‐3–positive resting T cells were found in close proximity to DC‐SIGN cells. Unexpectedly, a lower percentage of DC‐SIGN–expressing cells was found in OA synovium compared with RA synovium. Furthermore, ICAM‐3–expressing T cells, which are known to bind DC‐SIGN, were almost absent within the synovium of OA and trauma patients. DC‐SIGN–positive macrophages adjacent to these T cells were located in close proximity to the cartilage‐degrading proteins extracellular MMP inducer (EMMPRIN) and MMP‐1.ConclusionThe C‐type lectin DC‐SIGN is almost absent in the synovium of trauma patients but is highly expressed by most CD68‐positive macrophages in the synovium of RA patients. The lack of correlation between DC‐SIGN expression and the expression of CD83, DC‐LAMP, or Fascin indicates that multiple DC/macrophage subsets are present in RA synovium. Expression of DC‐SIGN and its ligand, ICAM‐3, is found in substantial amounts only in RA synovium, suggesting that their interaction is implicated in the additional activation of synovial macrophages that leads to the production of EMMPRIN and MMP‐1.
Synergistic induction of nitric oxide synthase type II: In vitro effect of leptin and interferon‐γ in human chondrocytes and ATDC5 chondrogenic cells
Authors: Otero Miguel , Reino Juan Jesús Gomez , Gualillo Oreste 
Published: February 2003

AbstractObjectiveTo study, in vitro, the effect of leptin (OB), alone or in combination with interferon‐γ (IFNγ), on inducible nitric oxide synthase (iNOS) and NO production in human primary chondrocytes and in mouse embryonic chondrogenic ATDC5 cells.MethodsLeptin receptor expression and iNOS messenger RNA expression were evaluated by reverse transcriptase–polymerase chain reaction. Then, iNOS activity was indirectly studied by measuring nitrite accumulation, using the Griess colorimetric reaction, in culture medium of human primary chondrocytes and ATDC5 cells.ResultsATDC5 mouse embryonic cells expressed functional OB receptor. Alone, neither OB nor IFNγ produced nitrite accumulation in culture medium. However, costimulation with OB and IFNγ resulted in dose‐dependent up‐regulation of the expression of iNOS and NO production in human primary chondrocytes and ATDC5 cells. Production of NO was blunted by the iNOS‐specific inhibitors L‐NG‐nitroarginine methyl ester and aminoguanidine. In addition, the janus‐activated kinase 2 (JAK2)–specific inhibitor Tyrphostin AG 490 completely blocked OB + IFNγ–driven up‐regulation of iNOS and NO production.ConclusionOur data show for the first time a putative proinflammatory role of OB via iNOS induction and NO production. This occurs via activation of JAK2.
Assessment of peripheral enthesitis in the spondylarthropathies by ultrasonography combined with power Doppler: A cross‐sectional study
Authors: D'Agostino Maria‐Antonietta , Said‐Nahal Roula , Hacquard‐Bouder Cécile , Brasseur Jean‐Louis , Dougados Maxime , Breban Maxime 
Published: February 2003

AbstractObjectiveTo assess the prevalence and severity of peripheral enthesitis among the different subtypes of spondylarthropathy (SpA) by using ultrasonography (US) in B mode with power Doppler.MethodsOne hundred sixty‐four consecutive patients with SpA (according to the criteria of the European Spondylarthropathy Study Group) and 64 control patients (34 with mechanical low back pain [MBP] and 30 with rheumatoid arthritis [RA]) underwent US examination of major entheses of their limbs. Particular attention was given to the detection of vascularization at the following sites: cortical bone insertion of entheses, junction between tendon and entheses, body of tendon, and bursa.ResultsAbnormal US findings consistent with at least one enthesitis were observed in 161 of 164 SpA patients (98%), affecting 1,131 of 2,952 entheses examined (38%). In contrast, only 132 of 1,152 entheses (11%) were found to be abnormal in 33 of 64 control patients (52%). US enthesitis was most commonly distributed in the distal portion of the lower limbs, irrespective of SpA subtype and of skeletal distribution of clinical symptoms. None of the abnormal entheses in control patients showed vascularization, compared with 916 of 1,131 abnormal entheses in SpA patients (81%), where it was always detected at the cortical bone insertion and sometimes also in the bursa. In SpA patients, the US pattern depended on the clinical presentation, with a higher prevalence of the most severe stages in those with peripheral forms.ConclusionUS in B mode combined with power Doppler allowed the detection of peripheral enthesitis in a majority of SpA patients, but not in MBP or RA patients. The presence of entheseal involvement was independent of SpA subtype, but its degree of severity appeared to be greater in peripheral forms. US could be very useful for both the diagnosis and the assessment of SpA activity.
Fc receptor–independent development of autoimmune glomerulonephritis in lupus‐prone MRL/lpr mice
Authors: Matsumoto Keiko , Watanabe Norihiko , Akikusa Bunshiro , Kurasawa Kazuhiro , Matsumura Ryutaro , Saito Yasushi , Iwamoto Itsuo , Saito Takashi 
Published: February 2003

AbstractObjectiveTo determine the role of Fc receptors (FcR), which play crucial roles in antibody and immune complex–mediated inflammation and autoimmunity, including glomerulonephritis (GN), in the development of autoimmune GN and vasculitis in MRL/lpr mice, one of the most widely used lupus‐prone mouse models.MethodsFcRγ−/− MRL/lpr mice were generated by backcrossing for 8 generations. The development of GN and vasculitis of various sized vessels was analyzed histopathologically in the kidney, lung, and skin. Autoantibody and immune complex levels were determined biochemically at 16–24 weeks of age and compared with the findings in FcRγ+ MRL/lpr mice. The lifespan of the mice was also recorded.ResultsDiffuse proliferative GN, with deposition of IgG and C3, developed in both FcRγ−/− and FcRγ+ MRL/lpr mice. There was no difference in the survival rate and degree of proteinuria between FcRγ+ and FcRγ−/− MRL/lpr mice. Regardless of the level of FcR expression, there were no significant differences in the levels of serum IgG, anti‐DNA antibody, or circulating immune complexes between the two types of mice. Necrotizing vasculitis in medium‐sized arteries of the kidneys and lungs as well as small‐vessel vasculitis in the skin was observed in both in FcRγ+ and FcRγ−/− MRL/lpr mice. In contrast, the Arthus reaction was induced in FcRγ+ MRL/lpr mice, but not in FcRγ−/− MRL/lpr mice.ConclusionUnlike (NZB × NZW)F1, the other strain of lupus‐prone mice that develops GN in an FcR‐dependent manner, the development of autoimmune GN and vasculitis in MRL/lpr mice was FcR‐independent, implying heterogeneity of the contribution of FcR to the development of autoimmune disease.
Association of interleukin‐18 expression with enhanced levels of both interleukin‐1β and tumor necrosis factor α in knee synovial tissue of patients with rheumatoid arthritis
Authors: Joosten Leo A. B. , Radstake Timothy R. D. , Lubberts Erik , van den Bersselaar Liduine A. M. , van Riel Piet L. C. M. , van Lent Peter L. E. M. , Barrera Pilar , van den Berg Wim B. 
Published: February 2003

AbstractObjectiveTo examine the expression patterns of interkeukin‐18 (IL‐18) in synovial biopsy tissue of patients with rheumatoid arthritis (RA), and to determine whether expression of this primary cytokine is related to the expression of other cytokines and adhesion molecules and related to the degree of joint inflammation.MethodsBiopsy specimens of knee synovial tissue either without synovitis (n = 6) or with moderate or severe synovitis (n = 11 and n = 12, respectively) were obtained from 29 patients with active RA. Paraffin‐embedded, snap‐frozen sections were used for immunohistochemical detection of IL‐18, tumor necrosis factor α (TNFα), IL‐1β, IL‐12, and IL‐17. Furthermore, adhesion molecules, such as intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E‐selectin, and cell markers CD3, CD14, and CD68 were stained.ResultsIL‐18 staining was detectable in 80% of the RA patients, in both the lining and sublining of the knee synovial tissue. IL‐18 expression in the synovial tissue was strongly correlated with the expression of IL‐1β (in the sublining r = 0.72, in the lining r = 0.71; both P < 0.0001) and TNFα (in the sublining r = 0.59, P < 0.0007, and in the lining r = 0.68, P < 0.0001). In addition, IL‐18 expression in the sublining correlated with macrophage infiltration (r = 0.64, P < 0.0007) and microscopic inflammation scores (r = 0.78, P < 0.0001), and with the acute‐phase reaction as measured by the erythrocyte sedimentation rate (r = 0.61, P < 0.0004). Interestingly, RA synovial tissue that coexpressed IL‐18 and IL‐12 demonstrated enhanced levels of the Th1‐associated cytokine IL‐17.ConclusionOur results show that expression of IL‐18 is associated with that of IL‐1β and TNFα and with local inflammation in the synovial tissue of patients with RA. In addition, synovial IL‐18 expression correlates with the acute‐phase response. These data indicate that IL‐18 is a primary proinflammatory cytokine in RA that drives the local production of IL‐1β and TNFα.
Eligibility of patients in routine care for major clinical trials of anti–tumor necrosis factor α agents in rheumatoid arthritis
Authors: Sokka Tuulikki , Pincus Theodore 
Published: February 2003

AbstractObjectiveTo identify the proportion of patients with rheumatoid arthritis (RA) in 2 cohorts from Nashville, Tennessee, who met basic criteria for inclusion in 2 important recent clinical trials of anti–tumor necrosis factor α (anti‐TNFα) agents, the early RA (ERA) trial of etanercept versus methotrexate, and the anti‐TNFα trial in RA with concomitant therapy (ATTRACT) study of infliximab plus methotrexate versus methotrexate.MethodsTwo cohorts of patients, all of whom had met the American College of Rheumatology criteria for RA at some time, were studied. Cohort E (early) comprised 232 patients who were under the care of 5 private practice rheumatologists, whose duration of RA was fewer than 3 years, and who were reviewed for basic inclusion criteria for the ERA clinical trial. Cohort L (long‐term) comprised 152 consecutive patients who had been under care at a weekly academic rheumatology clinic for a mean of 4.5 years, and were reviewed for basic inclusion criteria for the ATTRACT study.ResultsIn cohort E, basic inclusion criteria for the ERA trial were met by 11 of 36 patients (31%) who had not taken methotrexate, 8 of 19 patients (42%) who were at their first visit and had not taken methotrexate, and 37 of all 232 patients (16%). In cohort L, 5% of patients met the basic inclusion criteria for the ATTRACT study.ConclusionMost patients who were seen in routine care in these 2 cohorts did not meet the criteria for inclusion in these 2 important recent clinical trials. The conclusion that anti‐TNFα therapy has greater efficacy than methotrexate may be valid only in a limited number of patients with the most severe RA. Anti‐TNFα therapy may be desirable in most patients with RA, but this possibility has not been studied formally. Criteria for inclusion in RA clinical trials might be modified for greater generalizability of results.
Effects of anti‐CD154 treatment on B cells in murine systemic lupus erythematosus
Authors: Wang Xiaobo , Huang Weiqing , Schiffer Lena E. , Mihara Masahiko , Akkerman Alla , Hiromatsu Kenji , Davidson Anne 
Published: February 2003

AbstractObjectiveTo determine the immunologic effects of anti‐CD154 (CD40L) therapy in the (NZB × NZW)F1 mouse model of systemic lupus erythematosus.MethodsTwenty‐week‐old and 26‐week‐old (NZB × NZW)F1 mice were treated with continuous anti‐CD154 therapy. Mice were followed up clinically, and their spleens were studied at intervals for B and T cell numbers and subsets and frequency of anti–double‐stranded DNA (anti‐dsDNA)–producing B cells. T cell–dependent immunity was assessed by studying the humoral response to the hapten oxazolone.ResultsIgG anti‐dsDNA antibodies decreased during therapy and disease onset was delayed, but immune tolerance did not occur. During treatment, there was marked depletion of CD19+ cells in the spleen; however, autoreactive IgM‐producing B cells could still be detected by enzyme‐linked immunospot assay. In contrast, few IgG‐ and IgG anti‐dsDNA–secreting B cells were detected. Eight weeks after treatment cessation, the frequency of B cells producing IgG anti‐dsDNA antibodies was still decreased in 50% of the mice, and activation and transition of T cells from the naive to the memory compartment were blocked. Anti‐CD154 treatment blocked both class switching and somatic mutation and induced a variable period of relative unresponsiveness of IgG anti‐dsDNA–producing B cells, as shown by decreased expression of the CD69 marker and failure to generate spontaneous IgG anti‐dsDNA–producing hybridomas. Treated mice mounted an attenuated IgM response to the hapten oxazolone and produced no IgG antioxazolone antibodies.ConclusionAnti‐CD154 is a B cell–depleting therapy that affects multiple B cell subsets. Activation of both B and T cells is prevented during therapy. After treatment cessation, autoreactive B cells progress through a series of activation steps before they become fully competent antibody‐producing cells. The general immunosuppression induced during treatment will need to be taken into account when using B cell–depleting regimens in humans.
Identification of IgG subclasses and C‐reactive protein in lupus nephritis: The relationship between the composition of immune deposits and FCγ receptor type IIA alleles
Authors: Zuniga Ricardo , Markowitz Glen S. , Arkachaisri Thaschawee , Imperatore Edward A. , D'Agati Vivette D. , Salmon Jane E. 
Published: February 2003

AbstractObjectiveTo characterize the subclass composition of IgG deposited in lupus glomeruli, to examine its relationship to allelic polymorphisms of IgG receptors (Fcγ receptors [FcγR]), and to determine whether C‐reactive protein (CRP), a ligand for FcγRIIa, is present in these immune deposits.MethodsRenal biopsy samples from 80 patients with lupus nephritis were examined by light microscopy and indirect immunofluorescence with IgG‐subclass–specific monoclonal antibodies. FcγRIIA genotypes were determined using allele‐specific polymerase chain reaction. Immunostaining for CRP was performed on lupus and nonlupus glomerulonephritis specimens.ResultsIgG2 and IgG3 were the predominant subclasses in immune deposits in all World Health Organization classes of nephritis. The frequency of genotypes containing the low‐binding IgG2 allele, FcγRIIa‐R131, was significantly greater than expected in patients with class III or class IV nephritis and in patients with intense IgG2 deposition. CRP, a ligand with particular affinity for FcγRIIa‐R131, was consistently present in the renal immune deposits of lupus nephritis specimens.ConclusionFcγRIIA genes are associated with proliferative renal disease and may contribute to disease pathogenesis. FcγRIIa‐R131, the variant with low affinity for IgG2, has high affinity for CRP. Thus, FcγRIIa‐R131 may contribute to impaired removal of circulating immune complexes, as well as efficiently triggering phagocyte activation and the release of inflammatory mediators within glomeruli.