bluuebunny/crossref_metadata_2025_split huggingface dataset:
Onset of psoriatic arthritis in patients treated with efalizumab for moderate to severe psoriasis
Authors: Viguier Manuelle , Richette Pascal , Aubin François , Beylot‐Barry Marie , Lahfa Morad , Bedane Christophe , Delesalle Franck , Richard‐Lallemand Marie‐Aleth , Delaporte Emmanuel , Dubertret Louis , Bardin Thomas , Bachelez Hervé 
Published: May 2008

AbstractObjectiveTo investigate the nature of polyarthritis in patients with moderate to severe psoriasis undergoing treatment with efalizumab, a humanized anti‐CD11a monoclonal antibody.MethodsIn a multicenter study, we retrospectively analyzed patients who developed arthritis during treatment with efalizumab. The relationship between joint manifestations and psoriatic disease was addressed by using different classification criteria for psoriatic arthritis (PsA). The course of arthritis and its response to treatment were also investigated.ResultsSixteen patients developed de novo inflammatory rheumatic disease, with a mean delay of 15 weeks following the start of treatment, and with exclusive asymmetric peripheral monarthritis or oligoarthritis (8 patients), inflammatory spinal disease (1 patient), or both (7 patients), associated in some cases with enthesitis and dactylitis. All patients fulfilled at least 2 different sets of classification criteria for PsA. In most of them, an improvement in skin lesions was observed at the onset of PsA, as measured using the Psoriasis Area and Severity Index (mean score 24.88 before efalizumab versus 18.78 at the time of arthritis). Efalizumab treatment was stopped in 11 patients and was followed by the elimination of rheumatologic symptoms in 1 patient, while 8 patients required treatment with nonsteroidal antiinflammatory drugs with or without methotrexate, with 2 later being switched to tumor necrosis factor α inhibitors. Reintroduction of efalizumab (2 patients) was followed by a relapse of PsA.ConclusionThis study questions the role of efalizumab in the induction of PsA. It also emphasizes the discrepancy between the courses of psoriatic skin and joint manifestations under treatment. Prospective case–control studies are needed to accurately investigate the impact of efalizumab on PsA.
Gene expression analysis of macrophages derived from ankylosing spondylitis patients reveals interferon‐γ dysregulation
Authors: Smith Judith A. , Barnes Michael D. , Hong Dihua , DeLay Monica L. , Inman Robert D. , Colbert Robert A. 
Published: May 2008

AbstractObjectiveTo determine whether macrophages, a type of cell implicated in the pathogenesis of ankylosing spondylitis (AS), exhibit a characteristic gene expression pattern.MethodsMacrophages were derived from the peripheral blood of 8 AS patients (median disease duration 13 years [range <1–43 years]) and 9 healthy control subjects over 7 days with the use of granulocyte–macrophage colony‐stimulating factor. Cells were stimulated for 24 hours with interferon‐γ (IFNγ; 100 units/ml), were left untreated for 24 hours, or were treated for 3 hours with lipopolysaccharide (LPS; 10 ng/ml). RNA was isolated and examined by microarray and real‐time quantitative reverse transcription–polymerase chain reaction analysis.ResultsMicroarray analysis revealed 198 probe sets detecting the differential expression of 141 unique genes in untreated macrophages from AS patients compared with healthy controls. Clustering and principal components analysis clearly distinguished AS patients and controls. Of the differentially expressed genes, 78 (55%) were IFN‐regulated, and their relative expression indicated a “reverse” IFN signature in AS patient macrophages, where IFNγ–up‐regulated genes were underexpressed and down‐regulated genes were overexpressed. Treatment of macrophages with exogenous IFNγ normalized the expression of these genes between patients and controls. In addition, the messenger RNA encoded by the IFNγ gene was ∼2‐fold lower in AS patient macrophages at baseline (P = 0.004) and was poorly responsive to LPS (P = 0.018), as compared with healthy controls.ConclusionsOur findings reveal consistent differences in gene expression in macrophages from AS patients, with evidence of a striking “reverse” IFN signature. Together with poor expression and responsiveness of the IFNγ gene, these results suggest that there may be a relative defect in IFNγ gene regulation, with autocrine consequences and implications for disease pathogenesis.
Effective therapy for nephritis in (NZB × NZW)F1 mice with triptolide and tripdiolide, the principal active components of the Chinese herbal remedy Tripterygium wilfordii Hook F
Authors: Tao Xuelian , Fan Fred , Hoffmann Victoria , Gao Chun Y. , Longo Nancy S. , Zerfas Patricia , Lipsky Peter E. 
Published: May 2008

AbstractObjectiveTriptolide and tripdiolide are thought to be active components of the Chinese antirheumatic herbal remedy Tripterygium wilfordii Hook F, which has been shown to be effective in treating murine lupus nephritis. This study was undertaken to examine the therapeutic effect of triptolide and tripdiolide on established lupus nephritis in (NZB × NZW)F1 mice.Methods(NZB × NZW)F1 mice were treated with vehicle, triptolide, or tripdiolide for 15 weeks beginning at the age of 29 weeks (after the development of lupus nephritis). Body weight, proteinuria, and anti–double‐stranded DNA (anti‐dsDNA) antibodies were monitored, and the kidney and spleen were assessed histologically. Culture supernatants of spleen mononuclear cells were assayed for cytokines.ResultsBy 28 weeks, most (NZB × NZW)F1 mice had developed lupus nephritis. Vehicle‐treated mice exhibited progressive proteinuria, hypoalbuminemia, elevated blood urea nitrogen (BUN) levels, and evidence of severe nephritis. In contrast, proteinuria and BUN levels were significantly reduced in mice treated with either triptolide or tripdiolide as compared with those treated with vehicle. There was no hypoalbuminemia or apparent evidence of lupus nephritis in mice treated with either of the 2 diterpenoids. At 44 weeks of age, the survival rate in mice treated with vehicle (35.7%) was markedly lower than that in mice treated with either triptolide (87.5%) or tripdiolide (88.2%). The mean level of anti‐dsDNA antibody in mice treated with tripdiolide was lower than that in the vehicle‐treated mice upon completion of the treatment course. Production of tumor necrosis factor, interleukin‐6, and monocyte chemoattractant protein 1 by spleen cells was also decreased after diterpenoid therapy.ConclusionTherapy with triptolide or tripdiolide significantly ameliorated lupus nephritis in (NZB × NZW)F1 mice, reduced cytokine and chemokine production, and prolonged survival.
Patients with pulmonary tuberculosis are frequently positive for anti–cyclic citrullinated peptide antibodies, but their sera also react with unmodified arginine‐containing peptide
Authors: Kakumanu Prasanthi , Yamagata Hajime , Sobel Eric S. , Reeves Westley H. , Chan Edward K. L. , Satoh Minoru 
Published: May 2008

AbstractObjectiveThe anti–cyclic citrullinated peptide (anti‐CCP) enzyme‐linked immunosorbent assay (ELISA) has high sensitivity and specificity for rheumatoid arthritis (RA). However, detection of anti‐CCP in patients with active pulmonary tuberculosis (TB) has recently been reported. To determine whether this activity was specific for the citrullinated residue, the specificity of anti‐CCP–positive sera for CCP versus that for unmodified arginine‐containing peptide (CAP) was examined in patients with TB and compared with that in patients with RA.MethodsAnti‐CCP and anti‐CAP in sera from patients with pulmonary TB (n = 49), RA patients (n = 36), and controls (n = 18) were tested by ELISA. Sera were available at diagnosis from most TB patients. All TB patients were treated with a combination of 2–4 antibiotics for at least 6 months, and sera were collected over time.ResultsAnti‐CCP was found in 37% of TB patients and in 43% of RA patients. CAP reactivity was more common in TB than in RA. High anti‐CCP:anti‐CAP ratios (>2.0) were seen far more commonly in anti‐CCP–positive RA patients than in anti‐CCP–positive TB patients (94% versus 22%). Anti‐CCP was inhibited by CCP peptide in sera from RA patients, but not in sera from TB patients. A slight increase in anti‐CCP was common after initiating treatment for TB, although the anti‐CCP level decreased after 1–2 months.ConclusionAnti‐CCP is frequently present in patients with active TB. However, many anti‐CCP–positive TB sera also reacted with CAP, and anti‐CCP:anti‐CAP ratios in TB sera were low. Anti‐CCP:anti‐CAP ratios should be useful clinically for distinguishing CCP‐specific reactivity seen in RA from reactivity with both CCP and CAP frequently seen in pulmonary TB.
Direct B cell stimulation by dendritic cells in a mouse model of lupus
Authors: Wan Suigui , Zhou Zhenhai , Duan Biyan , Morel Laurence 
Published: May 2008

AbstractObjectiveDendritic cells (DCs) play a major role in regulating lymphocytes, including B cells, and defective DC functions have been implicated in lupus. The purpose of this study was to assess the contribution of DCs to B cell hyperactivity in the B6.Sle1.Sle2.Sle3 (B6.TC) murine lupus model.MethodsWe compared the effects of B6 and B6.TC bone marrow–derived DCs on naive B cells cocultured in the presence of lipopolysaccharide (LPS), anti‐CD40, or anti‐IgM. We measured the proliferation, antibody production, and expression of activation markers and chemokine receptors for the B cells, as well as DC cytokine production. B cell proliferation was also assessed in Transwell experiments and in response to activated DC supernatants or exosomes. The role of DC‐produced cytokines was evaluated with blocking antibodies and transgenic mice.ResultsLPS‐stimulated or anti‐CD40–stimulated DCs from B6.TC mice increased B cell proliferation, antibody production, and chemokine receptor expression as compared with DCs from B6 mice. Cell‐to‐cell contact was not necessary for the augmented effect of the lupus‐prone DCs. Anti‐CD40 treatment induced a higher production of interleukin‐6 (IL‐6), soluble IL‐6 receptor (sIL‐6R), IL‐10, and tumor necrosis factor α in B6.TC DCs. Blocking these individual cytokines, however, did not abrogate the effects of B6.TC DCs. Additional experiments also ruled out involvement of BAFF, IL‐12, and interferon‐α.ConclusionActivated DCs from B6.TC mice directly increase B cell effector functions. This effect depends on soluble factors released by activated DCs, but none of the single major DC‐produced cytokines known to affect B cells are necessary. Increased sIL‐6R production suggests that increased sensitivity to IL‐6 may be involved.
Hypoxic synovial environment and expression of macrophage inflammatory protein 3γ/CCL20 in juvenile idiopathic arthritis
Authors: Bosco Maria Carla , Delfino Silvana , Ferlito Francesca , Battaglia Florinda , Puppo Maura , Gregorio Andrea , Gambini Claudio , Gattorno Marco , Martini Alberto , Varesio Luigi 
Published: May 2008

AbstractObjectiveSynovial inflammation is a major determinant of juvenile idiopathic arthritis (JIA) pathogenesis and is mediated by local chemokine secretion. Monocytic cells are an important source of chemokines. The purpose of this study was to investigate expression of CCL20, a macrophage inflammatory protein, in synovial fluid (SF) and SF‐derived monocytic cells from JIA patients and its regulation by hypoxia, a common feature of the inflamed synovial environment.MethodsMononuclear cells and monocytic cells were isolated from paired SF and peripheral blood (PB) samples from JIA patients and were maintained in a hypoxic environment or subjected to reoxygenation. CCL20 concentrations in SF, PB, and culture supernatants were measured by enzyme‐linked immunosorbent assay. CCL20 expression was assessed in both freshly purified and cultured cells by reverse transcriptase–polymerase chain reaction and immunocytochemistry. Hypoxia‐inducible factor 1α (HIF‐1α) and HIF‐2α were detected in the synovial tissue and cells of JIA patients by immunohistochemistry and Western blotting.ResultsCCL20 concentrations were significantly higher in SF compared with PB samples (P < 0.0001). SF mononuclear cells, but not matched PB mononuclear cells, constitutively expressed CCL20 messenger RNA. The SF monocytic cell fraction produced higher amounts of CCL20 than did SF lymphocytes, and CCL20 expression was associated with HIF positivity. Reoxygenation abrogated HIF and CCL20 expression, which was maintained in SF monocytic cells exposed to prolonged hypoxia.ConclusionCCL20 is released into the SF of JIA patients, and SF monocytic cells are a major source of this chemokine. The hypoxic synovial microenvironment may directly contribute to the persistent inflammation associated with JIA by increasing CCL20 production by SF monocytic cells, thus representing a potential therapeutic target.
Amelioration of collagen‐induced arthritis in rats by adenovirus‐mediated PTEN gene transfer
Authors: Wang Chrong‐Reen , Shiau Ai‐Li , Chen Shih‐Yao , Lin Ling‐Ling , Tai Ming‐Hong , Shieh Gia‐Shing , Lin Pey‐Ru , Yo Yi‐Te , Lee Che‐Hsin , Kuo Shiao‐Mei , Liu Ming‐Fei , Jou I‐Ming , Yang Chyun‐Yu , Shen Po‐Chuan , Lee Hwei‐Ling , Wu Chao‐Liang 
Published: May 2008

AbstractObjectiveThe phosphatidylinositol 3‐kinase (PI 3‐kinase)/Akt pathway is known to be activated in rheumatoid arthritis (RA) synovial tissue, which impacts cell growth, proliferation, survival, and migration. Phosphatase and tensin homolog deleted from chromosome 10 (PTEN) functions as a negative regulator of PI 3‐kinase signaling, thus blocking Akt activation. The aim of this study was to examine the effect of PTEN gene transfer in rats with collagen‐induced arthritis (CIA).MethodsAdenoviral vectors encoding human PTEN (AdPTEN) or β‐galactosidase (AdLacZ) were injected intraarticularly into rats with CIA, and their treatment responses were monitored by measures of clinical, radiographic, and histologic changes. The expression of phosphorylated Akt, total Akt, vascular endothelial growth factor (VEGF), proinflammatory cytokines, and chemokines, as well as the extent of microvessel density in the ankle joints were determined.ResultsAdPTEN treatment reduced Akt phosphorylation and decreased VEGF production in human RA synovial fibroblasts. Compared with AdLacZ treatment of the rats with CIA, AdPTEN treatment significantly reduced ankle circumference, articular index scores, radiography scores, and histology scores, and also decreased microvessel density and levels of VEGF and interleukin‐1β. Furthermore, PTEN gene transfer led to down‐regulation of Akt activation and increased apoptosis in the ankle joints.ConclusionThis study is the first to demonstrate the in vivo effect of intraarticular gene delivery of PTEN on amelioration of arthritis symptoms in rats with CIA, which involved antiangiogenic, antiproliferative, and antiinflammatory effects of PTEN via inhibition of the PI 3‐kinase/Akt signaling pathway. Our findings also implicate the PI 3‐kinase/Akt pathway as a therapeutic target for the treatment of RA or other inflammatory diseases.
Ciprofloxacin‐mediated cell proliferation inhibition and G2/M cell cycle arrest in rat tendon cells
Authors: Tsai Wen‐Chung , Hsu Chih‐Chin , Tang Fuk‐Tan , Wong Alice M. K. , Chen Yen‐Ching , Pang Jong‐Hwei S. 
Published: May 2008

AbstractObjectiveTo investigate the effect of ciprofloxacin on the proliferation and cell cycle progression of tendon cells, and to explore the potential molecular mechanism of ciprofloxacin‐associated tendinopathy by analyzing the expression of cell cycle–related cyclin and cyclin‐dependent kinase (CDK).MethodsRat Achilles tendon cells were treated with ciprofloxacin and then assessed by MTT assay, flow cytometric analysis, and fluorescence confocal microscopy. Levels of messenger RNA (mRNA) for CDK‐1 and cyclin B were determined by reverse transcriptase–polymerase chain reaction. Protein expression of CDK‐1, cyclin B, checkpoint kinase 1 (CHK‐1), and polo‐like kinase 1 (PLK‐1) was determined by Western blot analysis.ResultsCiprofloxacin inhibited tendon cell proliferation and caused cell cycle arrest at the G2/M phase. Confocal microscopy revealed that chromosomes in ciprofloxacin‐treated cells neither properly aligned along the equatorial planes nor segregated successfully during metaphase. Mitotic arrest, misaligned chromosomes, and poor bipolar spindle formation were observed in ciprofloxacin‐treated cells. CDK‐1 and cyclin B protein and mRNA were both down‐regulated. CHK‐1 protein expression was also suppressed, but PLK‐1 protein expression was up‐regulated by ciprofloxacin.ConclusionOur findings suggest a possible mechanism of ciprofloxacin‐associated tendinopathy. Down‐regulation of CHK‐1 and up‐regulation of PLK‐1 may account for mitotic arrest observed in ciprofloxacin‐treated cells.
Crystal‐induced neutrophil activation: X. Proinflammatory role of the tyrosine kinase Tec
Authors: Popa‐Nita Oana , Marois Louis , Paré Guillaume , Naccache Paul H. 
Published: May 2008

AbstractObjectiveMonosodium urate monohydrate (MSU) crystals are among the most potent proinflammatory stimuli, and an innate immune inflammatory response to the crystal surface is involved in the pathogenesis of gouty arthritis. Release of the crystals into the joint cavity promotes an acute inflammation characterized by massive infiltration of neutrophils, which leads to tissue damage. The aim of the present study was to assess the involvement of the tyrosine kinase Tec in MSU crystal–initiated transduction events in human neutrophils.MethodsImmunoprecipitation and immunoblotting techniques were used for the cellular signaling studies. Chemotaxis and enzyme‐linked immunosorbent assay techniques were used for the functional studies. Silencing of Tec expression using specific small interfering RNA was also performed.ResultsMSU crystals induced the phosphorylation and activation of Tec in a Src‐dependent manner. This activation was necessary for the MSU crystal–induced secretion of interleukin‐1β (IL‐1β) and IL‐8 and for the generation of chemotactic activity in supernatants of MSU crystal–stimulated neutrophils. In addition, colchicine, an effective drug for the treatment of gout, inhibited the MSU crystal–induced tyrosine phosphorylation of Tec, thus modulating its kinase activity.ConclusionOur findings show that Tec is the principal kinase of the Tec family that plays a major role in the responses of human neutrophils to MSU crystals, which are likely to be involved in the initiation and perpetuation of gout. Our results suggest that the specific inhibition of Tec during the acute phase of MSU crystal–induced inflammation may be considered for the treatment of gouty arthritis.
Systemic lupus international collaborating clinics renal activity/response exercise: Comparison of agreement in rating renal response
Authors: Petri Michelle , Kasitanon Nuntana , Singh Sukminder , Link Kimberly , Magder Laurence , Bae Sang‐Cheol , Hanly John G. , Nived Ola , Sturfelt Gunnar , van Vollenhoven Ronald , Wallace Daniel J. , Alarcón Graciela S. , Adu Dwomoa , Avila‐Casado Carmen , Bernatsky Sasha R. , Bruce Ian N. , Clarke Ann E. , Contreras Gabriel , Fine Derek M. , Gladman Dafna D. , Gordon Caroline , Kalunian Kenneth C. , Madaio Michael P. , Rovin Brad H. , Sanchez‐Guerrero Jorge , Steinsson Kristjan , Aranow Cynthia , Balow James E. , Buyon Jill P. , Ginzler Ellen M. , Khamashta Munther A. , Urowitz Murray B. , Dooley Mary Anne , Merrill Joan T. , Ramsey‐Goldman Rosalind , Font Josef , Tumlin James , Stoll Thomas , Zoma Asad 
Published: May 2008

AbstractObjectiveTo assess the degree to which physicians agree with each other and with ratings obtained with 3 existing responder indices, in rating the response to treatment of lupus nephritis.MethodsLupus nephritis patient medical records from 125 pairs of visits (6 months apart) were used to create renal response scenarios. Seven nephrologists and 22 rheumatologists rated each scenario as demonstrating complete response, partial response, same, or worsening. The plurality (most frequent) rating of renal response by the physicians was compared with the calculated score from the renal component of the British Isles Lupus Assessment Group (BILAG) index (original and updated [2004] version) and of the Responder Index for Lupus Erythematosus (RIFLE). The degree of agreement among the physicians was assessed by calculating intraclass correlation coefficients (ICCs). The degree of agreement between the plurality physician rating and ratings obtained with the established response indices was assessed using the kappa statistic.ResultsThe ICC among all physicians was 0.64 (0.62 for nephrologists and 0.67 for rheumatologists). The chance‐adjusted measure of agreement (kappa coefficient) between the plurality physician rating and the calculated score obtained using established indexes was 0.50 (95% confidence interval [95% CI] 0.38–0.61) for the RIFLE, 0.14 (95% CI 0.03–0.25) for the original BILAG, and 0.23 (95% CI 0.21–0.44) for the BILAG 2004.ConclusionThese findings indicate that rheumatologists as a group and nephrologists as a group have equal agreement in their rating of renal response. There was moderate agreement between plurality physician ratings and ratings obtained using the renal component of the RIFLE. Ratings of response using an index based on the original BILAG did not have good agreement with the plurality physician rating.
Trends in Internet information behavior, 2000–2004
Authors: Buente Wayne , Robbin Alice 
Published: June 2008

AbstractBy 2000, the Internet became an information and communication medium that was integrated in our everyday lives. Following an interdisciplinary approach, the research reported in this article analyzes the wide variety of information that people seek on the Internet and investigates trends in Internet information activities between 2000 and 2004, using repeated cross‐sectional data from the Pew Internet and American Life surveys to examine Internet activities that contribute to everyday life and their predictors. The objective is to deepen our understanding of Internet activities and everyday life and contribute to a growing body of research that utilizes large‐scale empirical data on Internet use and everyday life. We ask: who is embedding the Internet into their everyday lives and what are the activities they pursue to facilitate everyday life? Findings demonstrate the differential returns for Internet use, particularly in key demographic categories. The study also contributes to emerging research on the digital divide, namely emphasis on the study of use rather than access to technology. Identifying trends in key Internet use dimensions enables policymakers to target populations who underutilize the potential of networked technologies.
The effects of inverter magnetic fields on early seed germination of mung beans
Authors: Huang Hsin‐Hsiung , Wang Show‐Ran 
Published: June 2008

AbstractThe biological effects of extremely low frequency magnetic fields (ELF MFs) on living organisms have been explored in many studies. Most of them demonstrate the biological effects caused by 50/60 Hz magnetic fields or pulsed magnetic fields. However, as the development of power electronics flourishes, the magnetic fields induced are usually in other different waveforms. This study aims to assess the effects of magnetic fields generated by inverter systems on the early growth of plants using mung beans as an example. In the experiment, an inverter which can produce sinusoidal pulsed width modulation (SPWM) voltages was used to drive 3 specially made circular coils and an AC motor. Six SPWM voltages with different fundamental frequencies (10, 20, 30, 40, 50, and 60 Hz) set on the inverter drive the circuit to produce the specific kinds of MFs. The results indicate that the magnetic field induced by a 20 or 60 Hz SPWM voltage has an enhancing effect on the early growth of mung beans, but the magnetic fields induced by SPWM voltages of other frequencies (30, 40, and 50 Hz) have an inhibitory effect, especially at 50 Hz. Bioelectromagnetics 29:649–657, 2008. © 2008 Wiley‐Liss, Inc.