bluuebunny/crossref_metadata_2025_split huggingface dataset:
Swelling studies in electrochemically prepared acrylamide/N,N′ methylene bisacrylamide gels
Authors: Yildiz Gülcemal , Paril Ahmet , Giz Ahmet , Çatalgil‐Giz Huceste 
Published: April 2006

AbstractAcrylamide/N,N′ methylene bisacrylamide gels were prepared at different voltages electrochemically. The dependence of the swelling properties on the preparation voltage was investigated. A set of gel samples was swollen as prepared and another set was swollen after being dried to constant weight. Swelling versus time curves were all in stretched exponential form, rather than pure exponential form, indicating that the gels are of heterogeneous nature. Maximum swelling increased with the preparation voltage in both gel types. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 101: 1398–1401, 2006
Systemic lupus erythematosus in a multiethnic US cohort: Clinical features, course, and outcome in patients with late‐onset disease
Authors: Bertoli Ana M. , Alarcón Graciela S. , Calvo‐Alén Jaime , Fernández Mónica , Vilá Luis M. , Reveille John D. 
Published: April 2006

AbstractObjectiveTo examine the clinical differences and the type and extent of organ damage in late‐ versus early‐onset systemic lupus erythematosus (SLE).MethodsA nested case–control study was performed in the context of LUMINA (LUpus in MInorities, NAture versus nurture), a large, longitudinal, multiethnic cohort. Patients who developed SLE at or after the age of 50 years were considered cases. Two controls (patients who developed SLE at age ≤49 years) per case, matched for sex and disease duration, were randomly chosen. Selected baseline socioeconomic/demographic, behavioral, and psychological features, self‐reported quality of life, and cumulative clinical data (clinical manifestations, laboratory data, disease activity, damage, and mortality) were compared between cases and controls. Multivariable analyses with late‐onset lupus, damage accrual, and mortality as dependent variables were then performed.ResultsTwo hundred seventeen patients were studied. Of them, 73 were cases. Cases were more likely to have neurologic involvement, arterial thrombotic events, osteoporosis, and hypertriglyceridemia, while renal involvement and anti‐Sm antibodies were less frequent. Disease activity at baseline was lower among cases. Cases also exhibited more cardiovascular and ocular damage. Late‐onset lupus was an independent predictor of damage accrual (t‐test = 2.23, P = 0.028), any damage at last visit (odds ratio [OR] 23.32, 95% confidence interval [95% CI] 3.98–141.56) (P < 0.001), and mortality (OR 10.74, 95% CI 3.07–37.56) (P < 0.001).ConclusionPatients with late‐onset lupus exhibit distinct clinical features. Although disease activity tends to be lower in these patients, they tend to accrue more damage and experience higher mortality than patients with early‐onset lupus. These findings probably reflect the contribution exerted by other comorbid conditions in the overall impact of lupus in these patients.
Predictors of disease course and remission in systemic juvenile idiopathic arthritis: Significance of early clinical and laboratory features
Authors: Singh‐Grewal D. , Schneider R. , Bayer N. , Feldman B. M. 
Published: April 2006

AbstractObjectiveTo determine whether the disease course in systemic juvenile idiopathic arthritis (JIA) can be characterized as monophasic, polycyclic, or persistent, and to determine whether early clinical and laboratory characteristics can be used to predict the disease course and time to remission.MethodsForty‐five children with systemic JIA diagnosed between 1996 and 2000 were followed up with a standardized data collection protocol, including data on clinical and laboratory features (mean followup 4.9 years). Disease was considered inactive if the clinical and laboratory features were normal. Three definitions of remission were applied to classify disease course. Predictors of disease course were evaluated using multiple logistic regression. Predictors of time to remission were evaluated using Cox proportional hazards regression.ResultsWhen applying a definition of remission requiring inactive disease while not receiving any medications for a period of 3 months, 42.2%, 6.7%, and 51.1% of the patients were classified as having monophasic, polycyclic, and persistent disease, respectively. Fever and active arthritis at 3 months (R2 = 0.42, area under the receiver operating characteristics curve [AUC] = 0.76) and an erythrocyte sedimentation rate (ESR) >26 mm/hour and corticosteroid use at 6 months (R2 = 0.49, AUC = 0.92) were predictive of a nonmonophasic course. Absence of active arthritis, an ESR of <26 mm/hour, and no requirement for corticosteroid therapy at 3 and 6 months were predictors of an earlier time to remission.ConclusionThe disease course in systemic JIA can be characterized as monophasic, polycyclic, or persistent using a definition of remission requiring 3 months of inactive disease while not receiving any therapy. Features at 3 and 6 months are predictive of the disease course and time to remission.
Impaired recognition of apoptotic neutrophils by the C1q/calreticulin and CD91 pathway in systemic lupus erythematosus
Authors: Donnelly Suzanne , Roake Wendy , Brown Simon , Young Philip , Naik Haley , Wordsworth Paul , Isenberg David A. , Reid Kenneth B. M. , Eggleton Paul 
Published: April 2006

AbstractObjectiveA deficiency in a subcomponent of C1q can result in increased susceptibility to autoimmune diseases such as systemic lupus erythematosus (SLE). The monocyte endocytic receptor CD91 is implicated in the endocytosis of apoptotic neutrophils via interactions with C1q and calreticulin. In this clinical study, we studied the binding of C1q to leukocytes and determined whether C1q bound specifically to calreticulin and CD91 on cells undergoing apoptosis in SLE.MethodsProximal antibody phage display, calreticulin‐transfected cells, and immunocytochemical and confocal techniques were used in a comprehensive analysis of direct binding of C1q to apoptotic neutrophils that were obtained from healthy individuals and from patients with SLE. In addition, apoptotic cellular systems were assessed in vitro.ResultsC1q appeared to colocalize to apoptotic blebs on the surface of leukocytes in association with both calreticulin and CD91, as determined by phage display and transfected cell studies. However, C1q did not bind to apoptotic cells isolated from SLE patients, despite the positivity of the cells for both calreticulin and CD91. Surface expression of calreticulin decreased on neutrophils as they aged, but increased on monocytes. In an apoptotic phagocytic assay, the addition of C1q and calreticulin significantly enhanced the phagocytosis of apoptotic cell debris by monocyte‐derived cells.ConclusionThese observations indicate that neutrophils from SLE patients have a reduced ability to be recognized and removed by the C1q/calreticulin/CD91‐mediated apoptotic pathway, despite the presence of main apoptotic recognition partners. This suggests that an additional component, as yet unidentified, acts as a C1q binding partner on apoptotic cells, and this component may be lacking in cells isolated from SLE patients.
Combination treatment with methotrexate, cyclosporine, and intraarticular betamethasone compared with methotrexate and intraarticular betamethasone in early active rheumatoid arthritis: An investigator‐initiated, multicenter, randomized, double‐blind, parallel‐group, placebo‐controlled study
Authors: Hetland Merete Lund , Stengaard‐Pedersen Kristian , Junker Peter , Lottenburger Tine , Ellingsen Torkell , Andersen Lis Smedegaard , Hansen Ib , Skjødt Henrik , Pedersen Jens Kristian , Lauridsen Ulrik Birk , Svendsen Anders , Tarp Ulrik , Pødenphant Jan , Hansen Gert , Lindegaard Hanne , Carvalho Anselmo De , ØStergaard Mikkel , Hørslev‐Petersen Kim 
Published: April 2006

AbstractObjectiveTo investigate whether disease control can be achieved in early active rheumatoid arthritis (RA) by treatment with methotrexate and intraarticular betamethasone, and whether the addition of cyclosporine to the regimen has any additional effect.MethodsPatients (n = 160) were randomized to receive methotrexate 7.5 mg/week plus cyclosporine 2.5 mg/kg of body weight/day (combination therapy) or methotrexate plus placebo‐cyclosporine (monotherapy). At weeks 0, 2, 4, 6, and 8 and every 4 weeks thereafter, betamethasone was injected into swollen joints (maximum 4 joints or 4 ml per visit). Beginning at week 8, if synovitis was present, the methotrexate dosage was increased stepwise up to 20 mg/week, with a subsequent stepwise increase in the cyclosporine or placebo‐cyclosporine dosage up to 4 mg/kg.ResultsAt 52 weeks, 20% improvement according to the American College of Rheumatology criteria (ACR20) was achieved in 85% of the combination therapy group versus 68% of the monotherapy group (P = 0.02). The median individual overall ACR response (ACR‐N) in the 2 groups was 80.0% (interquartile range 40.1–91.8%) and 54.5% (interquartile range 2.4–87.8%), respectively (P = 0.025). At 48 and 52 weeks, ACR remission criteria were met in 35% of the combination therapy group and 28% of the monotherapy group. Progression in the Larsen score at 52 weeks was –0.2 ± 6.5 and 0.4 ± 6.9 (mean ± SD) in the combination therapy and monotherapy groups, respectively. Serum creatinine levels increased by 7%, and hypertrichosis was more prevalent, in the combination therapy group.ConclusionCombined treatment with methotrexate and intraarticular glucocorticoid showed excellent disease control and stopped the progression of erosions in patients with early active RA, who had a poor prognosis. Addition of cyclosporine improved the ACR20 and ACR‐N responses, whereas the ACR50 and ACR70 responses, remission rates, and radiographic changes did not differ between the 2 study groups.
Leflunomide use and the risk of interstitial lung disease in rheumatoid arthritis
Authors: Suissa Samy , Hudson Marie , Ernst Pierre 
Published: April 2006

AbstractObjectiveSpontaneous reports of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) treated with leflunomide, a disease‐modifying antirheumatic drug (DMARD), have been appearing recently. To assess this risk, we conducted a population‐based epidemiologic study.MethodsA cohort of 62,734 patients with RA to whom a DMARD had been dispensed between September 1, 1998 and December 31, 2003 was formed using the PharMetrics claims database. A nested case–control design was used, in which each case of serious ILD requiring hospitalization was matched to 100 controls according to age (calendar time) and equal or greater duration of followup, to estimate adjusted rate ratios (RRs) of serious ILD associated with DMARD use.ResultsThere were 74 cases of serious ILD, which corresponds to a rate of 8.1 per 10,000 patients per year. The risk of ILD was increased with the use of leflunomide (adjusted RR 1.9 [95% confidence interval (95% CI) 1.1–3.6]). Among subjects with no previous methotrexate use and no history of ILD, the risk associated with leflunomide treatment was not elevated (RR 1.2 [95% CI 0.4–3.1]), but it was elevated among the remaining subjects (RR 2.6 [95% CI 1.2–5.6]). Patients with a history of ILD were twice as likely to have been prescribed leflunomide as any other DMARD.ConclusionThe reports of ILD associated with leflunomide use are likely the result of channeling of high‐risk patients to leflunomide treatment, particularly those with a history of methotrexate use or preexisting ILD. Patients with no history of ILD and no previous methotrexate use show no excess risk of developing ILD with leflunomide treatment.
Functional characterization of a soluble gp130 isoform and its therapeutic capacity in an experimental model of inflammatory arthritis
Authors: Richards Peter J. , Nowell Mari A. , Horiuchi Sankichi , McLoughlin Rachel M. , Fielding Ceri A. , Grau Sandra , Yamamoto Naoki , Ehrmann Michael , Rose‐John Stefan , Williams Anwen S. , Topley Nicholas , Jones Simon A. 
Published: April 2006

AbstractObjectiveSoluble gp130 is the naturally occurring antagonist of the interleukin‐6 (IL‐6)/soluble IL‐6 receptor (sIL‐6R) complex and selectively inhibits IL‐6 trans‐signaling. Several isoforms of soluble gp130 have been identified, including an autoantigenic form termed gp130‐RAPS (for gp130 of the rheumatoid arthritis antigenic peptide–bearing soluble form) that is present in the serum and synovial fluid of patients with rheumatoid arthritis. The aim of this study was to evaluate the functional properties of gp130‐RAPS.MethodsTo define a role for gp130‐RAPS in arthritis, a recombinant version was generated using a baculovirus expression system, and its activities were tested in vitro and in vivo.ResultsGp130‐RAPS was shown to bind with high affinity to the stable IL‐6/sIL‐6R complex, hyper–IL‐6, and to effectively modulate leukocyte migration in murine acute peritonitis. A single intraarticular injection of gp130‐RAPS suppressed chronic antigen‐induced arthritis in association with a reduction in local activation of signal transducer and activator of transcription 3. Although gp130‐RAPS contains the previously identified autoantigenic sequence Asn‐Ile‐Ala‐Ser‐Phe (NIASF), no increase in the prevalence of anti– gp130‐RAPS antibodies was observed in serum or synovial fluid obtained from patients with rheumatoid arthritis.ConclusionThe use of inhibitory antibodies to block IL‐6 responses has shown considerable clinical promise. However, the results presented herein suggest that selective targeting of IL‐6 trans‐signaling may represent a viable alternative to this strategy. In this respect, our present results suggest that the soluble gp130 isoform gp130‐RAPS may be useful in the treatment of chronic inflammatory arthritis.
“Endogenous adjuvant” activity of the RNA components of lupus autoantigens Sm/RNP and Ro 60
Authors: Kelly Kindra M. , Zhuang Haoyang , Nacionales Dina C. , Scumpia Philip O. , Lyons Robert , Akaogi Jun , Lee Pui , Williams Bryan , Yamamoto Masahiro , Akira Shizuo , Satoh Minoru , Reeves Westley H. 
Published: April 2006

AbstractObjectiveMost lupus patients produce autoantibodies against small ribonucleoproteins such as Sm/RNP and Ro 60 (containing U1 and Y1–Y5 RNAs, respectively). We undertook this study to investigate whether the RNA components of these antigens, which contain extensive tracts of single‐ and double‐stranded RNA, signatures of viral infection, activate innate immunity.MethodsU1 and Y RNAs were affinity purified from K562 cells. Murine bone marrow–derived dendritic cells (DCs), human HEK 293 cells, and murine RAW264.7 cells were stimulated with U1 RNA and other known Toll‐like receptor (TLR) ligands. Expression of the interferon (IFN)–inducible gene Mx1 and other genes was quantified using real‐time polymerase chain reaction, and cytokine production was measured by enzyme‐linked immunosorbent assay. DC maturation was assessed using flow cytometry.ResultsPurified U1 and Y1–Y5 RNAs and synthetic stem‐loop II of U1 RNA stimulated type I IFN (IFN‐I) production by cell lines and murine bone marrow–derived DCs and promoted DC maturation (CD86 expression). U1 RNA–stimulated, but not TLR‐3 ligand–stimulated, IFN‐I was blocked by bafilomycin A1, indicating that immunostimulation by U1 RNA requires endosomal acidification. Myeloid differentiation factor 88–deficient cells responded poorly to U1 RNA, suggesting that an endosomal TLR, probably TLR‐7, mediates the stimulatory effects of U1 RNA. U1 RNA–induced IFN‐I and interleukin‐6 production also were protein kinase R (PKR) dependent (abrogated by 2‐aminopurine and greatly reduced in PKR−/− cells).ConclusionWe conclude that the RNA components of the Ro 60 (Y1–Y5 RNA) and Sm/RNP (U1 RNA) small ribonucleoproteins act as endogenous adjuvants that could play a role in the pathogenesis of autoimmunity by stimulating DC maturation and IFN‐I production.
Preliminary evidence for a structural benefit of the new bisphosphonate zoledronic acid in early rheumatoid arthritis
Authors: Jarrett Stephen J. , Conaghan Philip G. , Sloan Victor S. , Papanastasiou Philemon , Ortmann Christine‐Elke , O'Connor Philip J. , Grainger Andrew J. , Emery Paul 
Published: April 2006

AbstractObjectiveBisphosphonates inhibit osteoclast activity, which is central to the development of bone damage in rheumatoid arthritis (RA). The aim of this study was to assess whether treatment with zoledronic acid, compared with placebo, could achieve a ≥50% reduction in the development of new erosions on magnetic resonance imaging (MRI) in patients with early RA.MethodsIn this proof‐of‐concept study, 39 patients with early RA and clinical synovitis of the hand/wrist were randomized to receive infusions with either zoledronic acid (5 mg) or placebo, administered at baseline and week 13. Patients in both groups received methotrexate (MTX) at a dosage of 7.5–20 mg/week. MRI and plain radiography were performed at baseline and week 26.ResultsAt week 26, the mean ± SD change in MRI hand and wrist erosions was 61% lower in the zoledronic acid group compared with the placebo group (0.9 ± 1.63 versus 2.3 ± 3.09; P = 0.176). The mean ± SD increase in the number of hand and wrist bones with erosions was 0.3 ± 0.75 for zoledronic acid compared with 1.4 ± 1.77 for placebo (P = 0.029). The proportion of patients in whom new MRI‐visualized bone edema developed was smaller in the zoledronic acid group compared with the placebo group (33% versus 58%; P = 0.121). The zoledronic acid group had a mean change in the number of radiographic erosions of 0.1 compared with 0.5 for the placebo group (P = 0.677). The safety profile of zoledronic acid was similar to that of placebo.ConclusionThe results of this study suggest a structural benefit associated with zoledronic acid therapy in patients with RA, as demonstrated by consistent results in structural end points in favor of zoledronic acid plus MTX compared with MTX alone.
Radiographic joint space width in the fingers of patients with rheumatoid arthritis of less than one year's duration
Authors: Goligher Ewan C. , Duryea Jeffrey , Liang Matthew H. , Wolfe Frederick , Finckh Axel 
Published: April 2006

AbstractObjectiveTo determine the radiographic joint space width (JSW) in undamaged metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of patients with early rheumatoid arthritis (RA) and to identify important clinical determinants of JSW.MethodsRadiographs of patients with RA of <1 year's duration, from an early arthritis cohort at a tertiary care rheumatology clinic, were obtained. JSW was analyzed by joint, finger, age, sex, height, and a number of other clinically relevant variables. Multivariate analysis was also performed, to account for possible confounding between variables.ResultsThirty‐eight patients were included in the study. We found that JSW was greater in the MCP joint than the PIP joint (P < 0.0001). JSW was significantly greater in men (P < 0.0001) and increased with increasing height (P < 0.003), but was not associated with age (P < 0.21). In multivariate analyses, sex was shown to be the most important predictor of JSW.ConclusionIn patients with early RA, MCP and PIP JSW is significantly associated with sex and height. In studies of RA in which JSW measurements are included as an outcome, these differences may need to be accounted for in the analysis.
Association of the IL4R single‐nucleotide polymorphism I50V with rapidly erosive rheumatoid arthritis
Authors: Prots Iryna , Skapenko Alla , Wendler Jörg , Mattyasovszky Stefan , Yoné Clarisse L. , Spriewald Bernd , Burkhardt Harald , Rau Rolf , Kalden Joachim R. , Lipsky Peter E. , Schulze‐Koops Hendrik 
Published: April 2006

AbstractObjectiveTo examine whether single‐nucleotide polymorphisms (SNPs) of the interleukin‐4 receptor gene IL4R influence susceptibility to, or radiographic progression in, rheumatoid arthritis (RA).MethodsThe contribution of 2 SNPs (I50V and Q551R) in the coding region of IL4R to RA susceptibility was analyzed by allele‐specific polymerase chain reaction in a case–control study of 471 RA patients and 371 healthy controls. Patients with available radiographs of the hands and feet obtained 2 years after disease onset (n = 302) were stratified retrospectively according to radiologic outcome into an erosive and a nonerosive group to evaluate the association between IL4R SNPs and disease progression.ResultsNo differences in the genotype and allele frequencies of the I50V or Q551R SNPs were identified between the RA patients and healthy controls. In contrast, significant differences in the distribution of I50V IL4R SNP genotypes between patients with erosive and nonerosive disease were observed (χ2 = 15.68, P = 0.0004). Bone erosions at 2 years after disease onset were present in 68.1% of patients homozygous for the V50 allele compared with 37.0% of patients homozygous for the I50 allele (odds ratio 3.86, P < 0.0001). This association was independent of individual factors previously associated with severe disease, such as rheumatoid factor or the HLA–DR shared epitope. On a cellular level, the V50 allele conferred significantly reduced responsiveness to interleukin‐4, providing a possible mechanism for the association of the I50V IL4R polymorphism with early erosions in RA.ConclusionOur data identify the I50V IL4R SNP as a novel genetic marker in RA, showing high predictive value for early joint destruction.
Solid malignancies among patients in the Wegener's granulomatosis etanercept trial
Authors: Stone John H. , Holbrook Janet T. , Marriott Matthew A. , Tibbs Andrea K. , Sejismundo Lourdes P. , Min Y.‐I. , Specks Ulrich , Merkel Peter A. , Spiera Robert , Davis John C. , St.Clair E. William , McCune W. Joseph , Ytterberg Steven R. , Allen Nancy B. , Hoffman Gary S. 
Published: April 2006

AbstractObjectiveEtanercept is a soluble fusion protein designed to inhibit tumor necrosis factor (TNF). During the Wegener's Granulomatosis Etanercept Trial (WGET), a placebo‐controlled trial of etanercept given in addition to standard therapy for remission induction and maintenance, more solid malignancies were observed in the etanercept group than in the group treated with standard therapy alone. This study was undertaken to further explore the potential association between anti‐TNF therapy and the development of malignancy in these patients.MethodsOne hundred eighty patients with active WG were enrolled and followed up for a median of 27 months. At enrollment, disease characteristics, treatment history, specific medical history items, and information about previous WG treatments and risk factors for malignancy were recorded. During the trial, the occurrence of malignancies and other adverse events was recorded prospectively.ResultsAll 6 solid malignancies observed during the WGET occurred in the etanercept group (P = 0.01 versus placebo group); based on a comparison of age‐ and sex‐specific incidence rates, 1.92 solid malignancies would have been expected in this group. The solid malignancies included 2 cases of mucinous adenocarcinoma of the colon, 1 each of metastatic cholangiocarcinoma, renal cell carcinoma, and breast carcinoma, and 1 recurrent liposarcoma. There were no differences between the 2 treatment groups in sex distribution, disease severity, personal or family history of cancer, or tobacco and alcohol use. The etanercept group was older at baseline and less likely to be newly diagnosed with WG at the time of randomization. Patients who developed solid tumors were older than patients who did not. All etanercept‐treated patients who developed solid tumors were also treated with cyclophosphamide during the trial. However, there were no differences between the groups in the amount of cyclophosphamide received during the trial or the percentage who had received cyclophosphamide before enrollment. There were also no differences in the mean duration of daily cyclophosphamide therapy or the maximum daily cyclophosphamide dosage before enrollment.ConclusionData from the WGET, the first substantial reported experience of the combined use of etanercept and cyclophosphamide in the treatment of WG, indicate that the combination of TNF inhibition and cyclophosphamide may heighten the risk of cancer beyond that observed with cyclophosphamide alone.