bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of graft modification with poly(N‐vinylpyrrolidone) on thermal and mechanical properties of poly (3‐hydroxybutyrate‐co‐3‐hydroxyvalerate)
Authors: Wang Wei , Zhang Yu , Zhu Meifang , Chen Yanmo 
Published: April 2008

AbstractPoly(N‐vinylpyrrolidone) (PVP) groups were grafted onto poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV) backbone to modify the properties of PHBV and synthesize a new novel biocompatible graft copolymer. The effect of graft modification with PVP on the thermal and mechanical properties of PHBV was investigated. The thermal stability of grafted PHBV was remarkably improved while the melting temperature (Tm) was almost not affected by graft modification. The isothermal crystallization behavior of samples was observed by polarized optical microscopy and the results showed that the spherulitic radial growth rates (G) of grafted PHBV at the same crystallization temperature (Tc) decreased with increasing graft yield (graft%) of samples. Analysis of isothermal crystallization kinetics showed that both the surface free energy (σe) and the work of chain‐folding per molecular fold (q) of grafted PHBV increased with increasing graft%, implying that the chains of grafted PHBV are less flexible than ungrafted PHBV. This conclusion was in agreement with the mechanical testing results. The Young's modulus of grafted PHBV increased while the elongation decreased with increasing graft%. The hydrophilicity of polymer films was also investigated by the water contact angle measurement and the results revealed that the hydrophilicity of grafted PHBV was enhanced. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Inflammatory stimuli accelerate Sjögren's syndrome–like disease in (NZB × NZW)F1 mice
Authors: Deshmukh Umesh S. , Ohyama Yukiko , Bagavant Harini , Guo Xiaoti , Gaskin Felicia , Fu Shu Man 
Published: April 2008

AbstractObjectiveThis study was undertaken to determine whether induction of systemic inflammation accelerates the development of Sjögren's syndrome (SS) in genetically susceptible mice.MethodsFemale (NZB × NZW)F1 mice were treated with either Freund's incomplete adjuvant (IFA) or phosphate buffered saline (PBS) at monthly intervals. Salivary gland function was monitored by measuring pilocarpine‐induced saliva volume. Mice were killed at different time points and examined for sialadenitis and salivary gland–infiltrating cells. Sera were analyzed for autoantibodies to salivary gland antigens, nuclear antigens, and Ro60.ResultsWhile IFA‐treated mice had significantly decreased salivary secretion 7 weeks after the initial treatment, salivary secretion did not decrease in PBS‐treated controls until 17 weeks. At 7 weeks, the severity of sialadenitis and the number of T and B cells infiltrating the salivary glands did not differ between the 2 groups. However, at this time point IFA‐treated mice showed significantly higher frequencies of CD11clow, B220+, Ly6C+, mouse PDCA‐1+ dendritic cells (DCs) in the salivary glands. While levels of autoantibodies did not differ between the 2 groups at early time points, by late time points IFA‐treated mice had higher levels. The gland dysfunction observed in IFA‐treated mice at earlier time points did not correlate with the severity of sialadenitis or levels of autoantibodies. Instead, it was associated with increased frequency of plasmacytoid DCs in the gland.ConclusionOur data suggest that generalized inflammatory stimuli can accelerate the development of SS‐like disease in (NZB × NZW)F1 mice, and that gland dysfunction in SS can develop prior to the generation of a robust adaptive autoimmune response.
Arthritis develops but fails to resolve during inhibition of cyclooxygenase 2 in a murine model of lyme disease
Authors: Blaho Victoria A. , Jefferson Mitchell W. , Brown Charles R. 
Published: April 2008

AbstractObjectiveRecent studies have implicated products of cyclooxygenase 2 (COX‐2) in not only induction but also resolution of the inflammatory response; however, the contribution of COX‐2 products to the in vivo response to infection is unknown. The aim of this study was to determine the contribution of COX‐2 to temporal regulation of the inflammatory response to infection in a murine model of Lyme arthritis.MethodsExperimental Lyme disease was induced in both arthritis‐resistant DBA/2J and arthritis‐susceptible C3H/HeJ mice by inoculation in the hind footpads withBorrelia burgdorferi. COX‐2 inhibitors were administered daily, and their effect on arthritis pathology was assessed at various time points postinfection. The COX‐2 deficiency was also backcrossed onto both DBA and C3H backgrounds to confirm the findings from COX‐2 inhibitor–treated mice.ResultsIn COX‐2 inhibitor–treated or COX‐2−/−C3H mice, arthritis developed normally but did not resolve. Cessation of COX‐2 inhibitor treatment on day 14 postinfection did not induce resolution of arthritis, indicating an early onset for the molecular mechanisms governing resolution. The lack of resolution of arthritis correlated with altered COX‐2 and cytosolic phospholipase A2messenger RNA levels in the joints of C3H mice. In addition, the proresolution lipid molecule 15‐deoxy‐Δ12,14‐prostaglandin J2was produced in response toB burgdorferiinfection, and its production was attenuated by the inhibition of COX‐2.ConclusionOur results demonstrate that early production of COX‐2 products is necessary for resolution of the inflammatory arthritis induced byBorreliainfection, and that COX‐2 inhibition may result in prolonged inflammatory states, possibly by inhibition of proresolution eicosanoids.
Cardiovascular disease risk awareness in systemic lupus erythematosus patients
Authors: Scalzi Lisabeth V. , Ballou Stanley P. , Park Jean Y. , Redline Susan , Kirchner H. Lester 
Published: April 2008

AbstractObjectiveCardiovascular disease (CVD) is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. The aim of this study was to identify factors associated with patients' recognition of SLE as an independent risk factor for CVD and their perception of their personal CVD risk.MethodsSLE patients were sent questionnaires that assessed demographic characteristics, any CVD risk factors, and information regarding the CVD counseling they had received from their physicians. Variables significantly associated with the outcomes were analyzed using logistic regression models.ResultsInformation obtained from 226 questionnaires was analyzed. Fifty‐eight percent of the respondents reported receiving no CVD counseling from a physician. Patients who recalled receiving counseling from a physician were 2.3 times more likely (P = 0.02) to recognize SLE as a CVD risk factor and 3.2 times more likely (P = 0.02) to perceive themselves as being at risk of CVD compared with those patients who did not receive physician counseling. Receiving physician CVD counseling was the strongest predictor of a patient's self‐perception of CVD risk. Those patients at intermediate to high risk (n = 167) who reported having received counseling were 5.3 times as likely (P = 0.007) to perceive themselves to be at higher risk of CVD compared with similar patients who did not receive counseling. Younger patients were 4.2 times as likely (P = 0.002) as older patients to recognize SLE as a CVD risk factor. Other variables associated with patients' self‐perceptions of CVD risk included family history of CVD and hypertension.ConclusionPhysician counseling regarding CVD in SLE patients has an important impact on patients' awareness of SLE as a CVD risk factor and their self‐perception of CVD risk.
Association of interferon regulatory factor 5 haplotypes, similar to that found in systemic lupus erythematosus, in a large subgroup of patients with rheumatoid arthritis
Authors: Dieguez‐Gonzalez Rebeca , Calaza Manuel , Perez‐Pampin Eva , de la Serna Arturo Rodriguez , Fernandez‐Gutierrez Benjamin , Castañeda Santos , Largo Raquel , Joven Beatriz , Narvaez Javier , Navarro Federico , Marenco Jose Luis , Vicario Jose Luis , Blanco Francisco J. , Fernandez‐Lopez Jesus Carlos , Caliz Rafael , Collado‐Escobar María Dolores , Carreño Luis , Lopez‐Longo Javier , Cañete Juan D. , Gomez‐Reino Juan J. , Gonzalez Antonio 
Published: April 2008

AbstractObjectivePrevious studies have shown either a lack of effect of IRF5 polymorphisms or an association of the IRF5 gene in only a minor subset of rheumatoid arthritis (RA) patients in whom anti–citrullinated protein antibodies (ACPAs) are absent. The present study was undertaken to investigate the role of genetic variation in IRF5 in susceptibility to RA.MethodsNine IRF5 single‐nucleotide polymorphisms (SNPs) were studied in 1,338 patients with RA and 1,342 control subjects in analyses of exploratory and replication sample collections, with stratification according to sex and by the presence or absence of ACPAs, rheumatoid factor, the shared epitope, the 620W PTPN22 allele, and erosions. A meta‐analysis that included results from previous studies was also carried out.ResultsOur findings together with those from previous studies, in a total of 4,620 RA patients and 3,741 controls, showed a significant association of the rs2004640 IRF5 SNP in RA patients as a whole (odds ratio [OR] 0.88, 95% confidence interval [95% CI] 0.83–0.94; P = 6.5 × 10−5 versus controls). This association was stronger in ACPA− patients, but was also present in ACPA+ patients (from 3 sample collections). Further analysis of our exploratory sample collection showed that only patients in the ACPA+ and SE− group lacked an association with IRF5 SNPs. All of the remaining RA patients (ACPA− or SE+) showed a strong association with IRF5 SNPs, which followed a complex pattern of opposing effects mediated by independent haplotypes. The susceptibility haplotype showed an OR of 1.8 (95% CI 1.4–2.3; P = 1.2 × 10−6 versus controls), whereas the protective haplotype showed an OR of 0.76 (95% CI 0.6–0.98; P = 0.046 versus controls).ConclusionIRF5 polymorphisms seem to influence RA susceptibility in a large subgroup of patients, following a pattern of association very similar to that described in patients with systemic lupus erythematosus.
An orally bioavailable spleen tyrosine kinase inhibitor delays disease progression and prolongs survival in murine lupus
Authors: Bahjat Frances Rena , Pine Polly R. , Reitsma Andrea , Cassafer Gail , Baluom Muhammad , Grillo Sunny , Chang Betty , Zhao Fei Fei , Payan Donald G. , Grossbard Elliott B. , Daikh David I. 
Published: April 2008

AbstractObjectiveTo assess whether R788, an orally bioavailable small molecule inhibitor of spleen tyrosine kinase (Syk)–dependent signaling, could modulate disease in lupus‐prone (NZB × NZW)F1 (NZB/NZW) mice via inhibition of Fc receptor (FcR) and B cell receptor signaling.MethodsR788 was administered to NZB/NZW mice before and after disease onset. Proteinuria, blood urea nitrogen levels, and autoantibody titers were examined periodically, and overall survival and renal pathologic features were assessed following long‐term treatment (24–34 weeks). The distribution and immunophenotype of various splenic T cell and B cell subpopulations were evaluated at the time of study termination. Arthus responses in NZB/NZW mice pretreated with R788 or Fc‐blocking antibody (anti‐CD16/32) were also examined.ResultsWhen R788 was administered prior to or after disease onset, it delayed the onset of proteinuria and azotemia, reduced renal pathology and kidney infiltrates, and significantly prolonged survival of lupus‐prone NZB/NZW mice; autoantibody titers were minimally affected throughout the study. Dose‐dependent reductions in the numbers of CD4+ activated T cells expressing high levels of CD44 or CD69 were apparent in spleens from R788‐treated mice. Minimal effects on the numbers of naive T cells expressing CD62 ligand and total CD8+ T cells per spleen were observed following long‐term drug treatment. R788 pretreatment resulted in reduced Arthus responses in NZB/NZW mice, similar to results obtained in mice pretreated with FcR‐blocking antibody.ConclusionWe demonstrate that a novel Syk‐selective inhibitor prevents the development of renal disease and treats established murine lupus nephritis. These data suggest that Syk inhibitors may be of therapeutic benefit in human lupus and related disorders.
Expression of microRNA‐146 in rheumatoid arthritis synovial tissue
Authors: Nakasa Tomoyuki , Miyaki Shigeru , Okubo Atsuko , Hashimoto Megumi , Nishida Keiichiro , Ochi Mitsuo , Asahara Hiroshi 
Published: April 2008

AbstractObjectiveSeveral microRNA, which are ∼22‐nucleotide noncoding RNAs, exhibit tissue‐specific or developmental stage–specific expression patterns and are associated with human diseases. The objective of this study was to identify the expression pattern of microRNA‐146 (miR‐146) in synovial tissue from patients with rheumatoid arthritis (RA).MethodsThe expression of miR‐146 in synovial tissue from 5 patients with RA, 5 patients with osteoarthritis (OA), and 1 normal subject was analyzed by quantitative reverse transcription–polymerase chain reaction (RT‐PCR) and by in situ hybridization and immunohistochemistry of tissue sections. Induction of miR‐146 following stimulation with tumor necrosis factor α (TNFα) and interleukin‐1β (IL‐1β) of cultures of human rheumatoid arthritis synovial fibroblasts (RASFs) was examined by quantitative PCR and RT‐PCR.ResultsMature miR‐146a and primary miR‐146a/b were highly expressed in RA synovial tissue, which also expressed TNFα, but the 2 microRNA were less highly expressed in OA and normal synovial tissue. In situ hybridization showed primary miR‐146a expression in cells of the superficial and sublining layers in synovial tissue from RA patients. Cells positive for miR‐146a were primarily CD68+ macrophages, but included several CD3+ T cell subsets and CD79a+ B cells. Expression of miR‐146a/b was markedly up‐regulated in RASFs after stimulation with TNFα and IL‐1β.ConclusionThis study shows that miR‐146 is expressed in RA synovial tissue and that its expression is induced by stimulation with TNFα and IL‐1β. Further studies are required to elucidate the function of miR‐146 in these tissues.
Association between the level of circulating bioactive tumor necrosis factor α and the tumor necrosis factor α gene polymorphism at −308 in patients with rheumatoid arthritis treated with a tumor necrosis factor α inhibitor
Authors: Marotte Hubert , Arnaud Béatrice , Diasparra Jennifer , Zrioual Saloua , Miossec Pierre 
Published: April 2008

AbstractObjectiveThe tumor necrosis factor α (TNFα) −308A polymorphism has been associated with high production of TNFα and poor response to anti‐TNFα therapy, but these associations remain controversial. The aim of this study was to explore the association between circulating TNFα bioactivity, the TNFα −308 polymorphism, and the clinical response to infliximab in patients with rheumatoid arthritis (RA).MethodsOne hundred ninety‐eight patients with RA were treated with infliximab and methotrexate. Responses at 6 months according to the American College of Rheumatology (ACR) preliminary criteria for improvement in RA were recorded. Genotyping for the TNFα −308 polymorphism was performed by enzyme‐linked oligosorbent assay. Circulating TNFα bioactivity was evaluated in 50 patients with RA by assessing the production of interleukin‐6 (IL‐6) in synoviocytes induced by a small amount of TNFα plus plasma. IL‐6 production in 48‐hour supernatants and the levels of TNFα protein and IL‐6 were measured by enzyme‐linked immunosorbent assay.ResultsThe TNFα −308 polymorphism was not associated with the ACR response to infliximab. The level of circulating TNFα bioactivity was higher in patients with the TNFα −308 A/A or A/G genotype than that in patients with the G/G genotype (median 50.0 ng/ml [interquartile range (IQR) 31.5–62.0] versus 33.0 ng/ml [IQR 16.5–47.5]; P < 0.02). However, no difference was observed for the TNFα protein level according to genotype (median 0.62 pg/ml [IQR 0.00–8.85] for G/G versus 3.35 pg/ml [IQR 1.55–4.63] for A/A or A/G; P not significant). The level of circulating TNFα bioactivity was higher in good responders (≥50% improvement) than in poor responders (≤20% improvement) (median 45.0 ng/ml [IQR 21.0–59.0] versus 28.0 ng/ml [IQR 14.0–39.0]; P = 0.05). However, the level of TNFα protein was similar in both groups.ConclusionThe level of functional circulating TNFα is partially genetically determined and is predictive of the clinical response to infliximab. Nonresponders to anti‐TNFα therapy are likely to have a disease that is not primarily driven by TNFα.
Crucial role of visfatin/pre–B cell colony‐enhancing factor in matrix degradation and prostaglandin E2 synthesis in chondrocytes: Possible influence on osteoarthritis
Authors: Gosset Marjolaine , Berenbaum Francis , Salvat Colette , Sautet Alain , Pigenet Audrey , Tahiri Khadija , Jacques Claire 
Published: April 2008

AbstractObjectiveProstaglandin E2 (PGE2) is one of the main catabolic factors involved in osteoarthritis (OA), and metalloproteinases (MMPs) are crucial for cartilage degradation. PGE2 synthesis under inflammatory conditions is catalyzed by cyclooxygenase 2 and microsomal PGE synthase 1 (mPGES‐1), whereas NAD+‐dependent 15‐hydroxy–PG dehydrogenase (15‐PGDH) is the key enzyme implicated in PGE2 catabolism. The present study was undertaken to investigate the contribution of visfatin, an adipose tissue–derived hormone, to the pathophysiology of OA, by examining its role in PGE2 synthesis and matrix degradation.MethodsThe synthesis of visfatin by human chondrocytes from OA patients, with and without stimulation with interleukin‐1β (IL‐1β) and the role of visfatin in PGE2 synthesis were analyzed by real‐time reverse transcriptase–polymerase chain reaction (RT‐PCR) and immunoblotting. The effects of visfatin (1–10 μg/ml) on mPGES‐1 and 15‐PGDH synthesis, on the subsequent release of PGE2, and on MMP‐3, MMP‐13, ADAMTS‐4, ADAMTS‐5, and PG synthesis by primary immature mouse articular chondrocytes were examined by quantitative RT‐PCR, immunoblotting, and enzyme‐linked immunosorbent assay. Finally, small interfering RNA (siRNA) was used to assess the influence of visfatin on IL‐1β–induced release of PGE2 in immature mouse articular chondrocytes.ResultsHuman OA chondrocytes produced visfatin, and visfatin synthesis was increased by IL‐1β treatment. Visfatin, like IL‐1β, triggered excessive release of PGE2, due to increased mPGES‐1 synthesis and decreased 15‐PGDH synthesis. Visfatin knockout with siRNA reduced IL‐1β–induced PGE2 overrelease. Visfatin triggered ADAMTS‐4 and ADAMTS‐5 expression and MMP‐3 and MMP‐13 synthesis and release, and reduced synthesis of high molecular weight PG by immature mouse articular chondrocytes.ConclusionThe findings of this study indicate that visfatin has a catabolic function in cartilage and may have an important role in the pathophysiology of OA.
A novel tumor necrosis factor α–responsive CCAAT/enhancer binding protein site regulates expression of the cartilage‐derived retinoic acid–sensitive protein gene in cartilage
Authors: Imamura Toshihiro , Imamura Chisako , McAlinden Audrey , Davies Sherri R. , Iwamoto Yukihide , Sandell Linda J. 
Published: April 2008

AbstractObjectiveInflammatory processes in rheumatoid arthritis are primarily regulated by the cytokines tumor necrosis factor α (TNFα) and interleukin‐1β (IL‐1β). Previous studies in our laboratory have shown that IL‐1β represses expression of the cartilage characteristic genes, cartilage‐derived retinoic acid–sensitive protein (cd‐rap) and type II collagen (COL2A1); this mechanism of repression involves activation of a CCAAT/enhancer binding protein (c/EBP) site within promoter regions. The aim of this study was to investigate novel TNFα‐mediated mechanisms that regulate the expression of cd‐rap.MethodsRat chondrosarcoma cells were transiently transfected with complementary DNA constructs encoding cd‐rap, in the presence of TNFα. The expression of c/EBPβ, SOX9, and p300 in rat chondrosarcoma cells and primary human articular chondrocytes after treatment with TNFα was examined by reverse transcription–polymerase chain reaction and Western blotting. The effect of TNFα on endogenous binding of c/EBPβ or SOX9 to the cd‐rap promoter was examined by chromatin immunoprecipitation assays.ResultsWe identified a new c/EBP binding site in the cd‐rap promoter (from position −1059 bp to position −1046 bp). Binding of c/EBP to this site was regulated by TNFα but not IL‐1β, resulting in down‐regulation of cd‐rap expression. This effect was reversed by mutational inactivation of the c/EBP motif. In addition, the activation potential of SOX9 and CREB binding protein/p300 on the cd‐rap promoter was enhanced after mutation of the new c/EBP binding site, indicating that blockage of this site would increase transcription.ConclusionTNFα regulates the expression and/or DNA‐binding potential of key positive‐acting and negative‐acting transcription factors that control the expression of the cartilage matrix gene, cd‐rap.
Glutamate levels and activity of the T cell voltage‐gated potassium Kv1.3 channel in patients with systemic lupus erythematosus
Authors: Poulopoulou C. , Papadopoulou‐Daifoti Z. , Hatzimanolis A. , Fragiadaki K. , Polissidis A. , Anderzanova E. , Davaki P. , Katsiari C. G. , Sfikakis P. P. 
Published: April 2008

AbstractObjectiveAlterations in glutamate homeostasis and Kv1.3 voltage‐gated potassium channel function have been independently associated with T cell dysfunction, whereas selective blockade of Kv1.3 channels inhibits T cell activation and improves T cell–mediated manifestations in animal models of autoimmunity. Because low extracellular glutamate concentrations enhance the activity of this channel in normal T cells ex vivo, we undertook this study to examine serum glutamate concentrations and Kv1.3 channel activity in patients with systemic lupus erythematosus (SLE).MethodsWe used high‐performance liquid chromatography for glutamate measurements, and we used the whole‐cell patch‐clamp technique for electrophysiologic studies performed in freshly isolated, noncultured peripheral T cells.ResultsMean ± SD serum concentrations of glutamate were lower in patients with either clinically quiescent SLE (77 ± 27 μM [n = 18]) or active SLE (61 ± 36 μM [n = 16]) than in healthy controls (166 ± 64 μM [n = 24]) (both P < 0.0001). The intrinsic gating properties of the Kv1.3 channels in lupus T cells were found to be comparable with those in healthy control–derived T cells. Notably, electrophysiologic data from SLE patient–derived T cells exposed to extracellular glutamate concentrations similar to their respective serum levels (50 μM) demonstrated Kv1.3 current responses enhanced by almost 20% (P < 0.01) compared with those subsequently obtained from the same cell in the presence of glutamate concentrations within control serum levels (200 μM).ConclusionBased on the key role of Kv1.3 channel activity in lymphocyte physiology, an enhancing in vivo effect of low serum glutamate concentrations on the functional activity of this channel may contribute to lupus T cell hyperactivity. Studies to further elucidate Kv1.3 responses in SLE, as well as the possible pathogenetic role of this unsuspected metabolic abnormality, may have therapeutic implications for SLE patients.