bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrochemical copolymerization of 3,4‐ethylenedioxythiophene and 5‐methylindole and characterizations of the copolymers
Authors: Nie Guangming , Qu Liangyan , Zhang Yan , Xu Jingkun , Zhang Shusheng 
Published: March 2008

AbstractElectrocopolymerization of 3,4‐ethylenedioxythiophene (EDOT) and 5‐methylindole (5MeIn) was successfully carried out in acetonitrile containing lithium perchlorate as supporting electrolyte although the oxidation potentials of 5MeIn and EDOT were quite different. The influence of feed ratios and applied potentials on the copolymerization were investigated. The novel low band gap copolymers own both the advantages of P5MeIn and poly(3,4‐ethylenedioxythiophene), i.e., good redox activity, good thermal stability, and high conductivity. The resulting copolymers were characterized by electrochemistry, FT‐IR and ultra violet‐visible spectroscopy, elemental analysis, thermal analysis, conductivity, and scanning electron microscopy, respectively. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Thermal analysis and topographical characterization of films of styrene‐butadiene blends
Authors: Ihalainen Petri , Backfolk Kaj , Sirviö Petri , Peltonen Jouko 
Published: March 2008

AbstractScanning probe microscopy (SPM) was used to study the thermal characteristics of latex films consisting of blends of two different styrene‐butadiene copolymers with different glass transition temperatures (Tg). The resonance frequency (ω) and the quality factor (Qp) of an SPM probe oscillating above the sample surface were determined at different probe temperatures (Tp). Thermal transitions associated with a change in heat capacity were observed in the Δω‐Tp curves. The results were compared with differential scanning calorimetry measurements. The very slow heating rate used in the SPM method effectively eliminated the contribution of volumetric changes of the films around Tg. Annealing of the samples in an oven did not influence the thermal transitions observed in the Δω‐Tp curves. The SPM method also enabled a novel approach for determining transition‐induced dimensional changes (vertical contraction, expansion) of the films. Annealing was found to increase the dimensional stability of the blend films. The latex blends were also annealed by the SPM probe and the film progressed from particulate phase morphology to a continuous phase. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Strengthening of poly(butylene adipate‐co‐terephthalate) by melt blending with a liquid crystalline polymer
Authors: Iwakura Yuko , Li Yongjin , Nakayama Kazuo , Shimizu Hiroshi 
Published: March 2008

AbstractPoly(butylene adipate‐co‐terephthalate) (PBAT) is a soft biodegradable polymer with a low melting temperature. PBAT has been melt‐blended with a liquid crystalline polymer (LCP) aiming at preparing a new biodegradable polymer blend with improved mechanical properties. The phase structure and crystalline morphologies of the PBAT/LCP blends were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), small‐angle X‐ray scattering (SAXS), and transmission electron microscopy (TEM). It was found that the LCP domains are precisely dispersed in the PBAT matrix and that these domains act as the nuclei for PBAT crystallization. The nonisothermal crystallization temperature from the melt was dramatically shifted from 50°C to about 95°C by the addition of 20% LCP. In addition, the tensile modulus of the prepared blends increases gradually with increasing LCP content, indicating the excellent strengthening effects of LCP on the PBAT matrix. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
A type I collagen defect leads to rapidly progressive osteoarthritis in a mouse model
Authors: Blair‐Levy J. M. , Watts C. E. , Fiorientino N. M. , Dimitriadis E. K. , Marini J. C. , Lipsky P. E. 
Published: March 2008

AbstractObjectiveThis study was undertaken to test the hypothesis that abnormalities of the subchondral bone can result in osteoarthritis (OA).MethodsWe used a knockin model of human osteogenesis imperfecta, the Brittle IV (Brtl) mouse, in which defective type I collagen is expressed in bone. OA in individual mice was documented by micro–magnetic resonance imaging (micro‐MRI) and micro–computed tomography (micro‐CT). Alterations in the knee joints were confirmed by histopathologic and immunohistochemical analysis. In addition, atomic force microscopy (AFM) was used to assess the ultrastructure of the articular cartilage and subchondral bone matrix.ResultsBrtl mice had decreased integrity of bone but initially normal articular cartilage. However, by the second month of life, Brtl mice developed alterations of the cartilage that were characteristic of OA, as documented by micro‐CT, micro‐MRI, and histologic evaluation. In addition, chondrocyte loss and breakdown of the collagen matrix in the residual cartilage were demonstrated using AFM.ConclusionThe Brtl mouse model demonstrates that progressive destruction of articular cartilage characteristic of OA may be secondary to altered architecture of the underlying subchondral bone.
In vivo delivery of lentiviral vectors expressing vasoactive intestinal peptide complementary DNA as gene therapy for collagen‐induced arthritis
Authors: Delgado Mario , Toscano Miguel G. , Benabdellah Karim , Cobo Marien , O'Valle Francisco , Gonzalez‐Rey Elena , Martı´n Francisco 
Published: March 2008

AbstractObjectiveVasoactive intestinal peptide (VIP) has been shown to exert potent immunomodulatory activity, and the use of lentiviral vectors has been found to be an effective means of gene delivery. The present study was therefore undertaken to investigate the feasibility and efficiency of gene therapy using lentiviral vectors expressing VIP (LentiVIP) for the treatment of rheumatoid arthritis (RA).MethodsWe evaluated the therapeutic potential of the gene therapy strategy in the collagen‐induced arthritis (CIA) mouse model, administrating the vectors at different phases of the disease. The inflammatory response was determined by measuring the levels of various inflammatory cytokines and chemokines in the joints and serum. The Th1‐mediated response was evaluated by determining the proliferative response and cytokine profile of T cells stimulated with autoantigen.ResultsA single intraperitoneal injection of LentiVIP was highly effective in treating CIA. Mice with established, severe arthritis showed complete regression of the disease. The therapeutic effect of LentiVIP was associated with widespread biodistribution of the vector and increased VIP levels, especially in joints and lymphoid organs, and was mediated through a striking reduction of the 2 deleterious components of the disease, i.e., the autoimmune response (self‐reactive Th1 cell activity and autoantibody production) and the inflammatory response. LentiVIP treatment also induced the generation and/or activation of CD4+,CD25+,FoxP3+ Treg cells in arthritic mice.ConclusionOur findings show that in vivo administration of lentiviral vector expressing VIP produces one of the most potent therapeutic effects described so far in any animal model of RA. We propose that VIP gene transfer should be further investigated as a potential novel, effective treatment of RA and other chronic autoimmune disorders.
Mathematical modeling of the cause of tuberculosis during tumor necrosis factor blockade
Authors: Wallis Robert S. 
Published: March 2008

AbstractObjectiveTumor necrosis factor (TNF) blockade increases the risk of tuberculosis (TB). The purpose of this study was to use Markov modeling to examine the contributions of reactivation of latent tuberculous infection (LTBI) and the progression of new infection with Mycobacterium tuberculosis to active TB due to TNF blockade. These 2 pathogenic mechanisms cannot otherwise be readily distinguished.MethodsMonte Carlo simulation was used to represent the range of reported values for the incidence of TB associated with infliximab (TNF monoclonal antibody) and etanercept (soluble TNF receptor) therapy. Iterative methods were then used to identify for each pair of incidence rates the Markov model parameters that most accurately represented the distribution of time to onset of TB as reported to the Food and Drug Administration.ResultsModeling revealed an apparent median monthly rate of reactivation of LTBI by infliximab treatment of 20.8%, which was 12.1 times that with etanercept treatment (P < 0.001). In contrast, both drugs appeared to pose a high risk of progression of new M tuberculosis infection to active TB. Progression of new infection appeared to cause nearly half of the etanercept‐associated cases; it became the predominant cause of infliximab‐associated cases only after the first year.ConclusionDespite sharing a common therapeutic target, infliximab and etanercept differ markedly in the rates at which they reactivate LTBI. Confirmation of these findings will require the application of molecular epidemiologic tools to studies of TB in future biologics registries. Hidden Markov modeling and Monte Carlo simulation are powerful tools for revealing otherwise hidden aspects of the pathogenesis of TB.
Defective proliferative capacity and accelerated telomeric loss of hematopoietic progenitor cells in rheumatoid arthritis
Authors: Colmegna Inés , Diaz‐Borjon Alejandro , Fujii Hiroshi , Schaefer Linda , Goronzy Jörg J. , Weyand Cornelia M. 
Published: March 2008

AbstractObjectiveIn rheumatoid arthritis (RA), telomeres of lymphoid and myeloid cells are age‐inappropriately shortened, suggesting excessive turnover of hematopoietic precursor cells (HPCs). The purpose of this study was to examine the functional competence (proliferative capacity, maintenance of telomeric reserve) of CD34+ HPCs in RA.MethodsFrequencies of peripheral blood CD34+,CD45+ HPCs from 63 rheumatoid factor–positive RA patients and 48 controls matched for age, sex, and ethnicity were measured by flow cytometry. Proliferative burst, cell cycle dynamics, and induction of lineage‐restricted receptors were tested in purified CD34+ HPCs after stimulation with early hematopoietins. Telomere sequences were quantified by real‐time polymerase chain reaction. HPC functions were correlated with the duration, activity, and severity of RA as well as its treatment.ResultsIn healthy donors, CD34+ HPCs accounted for 0.05% of nucleated cells; their numbers were strictly age dependent and declined at a rate of 1.3% per year. In RA patients, CD34+ HPC frequencies were age‐independently reduced to 0.03%. Upon growth factor stimulation, control HPCs passed through 5 replication cycles over 4 days. In contrast, RA‐derived HPCs completed only 3 generations. Telomeres of RA CD34+ HPCs were age‐inappropriately shortened by 1,600 bp. All HPC defects were independent of disease duration, disease activity, and smoking status, and were present to the same degree in untreated patients.ConclusionIn RA, circulating bone marrow–derived progenitor cells were diminished, and concentrations stagnated at levels typical of those in old control subjects. HPCs from RA patients displayed growth factor nonresponsiveness and sluggish cell cycle progression; marked telomere shortening indicated proliferative stress‐induced senescence. Defective HPC function independent of disease activity markers suggests bone marrow failure as a potential pathogenic factor in RA.
Biologic drugs for rheumatoid arthritis in the medicare program: A cost‐effectiveness analysis
Authors: Wailoo Allan J. , Bansback Nick , Brennan Alan , Michaud Kaleb , Nixon Richard M. , Wolfe Fred 
Published: March 2008

AbstractObjectiveSince the introduction of the Medicare Prescription Drug Improvement and Modernization Act and its associated demonstration project, coverage of selected biologic drugs has been expanded for Medicare beneficiaries. For rheumatoid arthritis, coverage was extended to etanercept, adalimumab, and anakinra in addition to the previously covered infliximab. We undertook to develop a model to compare the costs and quality‐adjusted life years (QALYs) generated by each of the 4 biologic agents.MethodsData were drawn from meta‐analysis of randomized controlled trials and from a large longitudinal outcomes databank. Uncertainty was addressed using probabilistic and one‐way sensitivity analyses. A lifetime horizon and Medicare viewpoint were adopted.ResultsIn the base case analysis, anakinra was the least effective and least costly strategy. Etanercept, adalimumab, and infliximab were similar in terms of effectiveness, but infliximab was more costly. If decision makers are willing to pay a maximum of $50,000/QALY, the probability that infliximab is cost‐effective is <1%. Findings were robust to a range of sensitivity analyses. Only if the dose of infliximab remains constant over time is this likely to be a cost‐effective strategy.ConclusionInfliximab is unlikely to be cost‐effective in the Medicare population compared with either etanercept or adalimumab. Anakinra is substantially less costly but is also less effective than the 3 tumor necrosis factor α inhibitors.
A B cell apotope of Ro 60 in systemic lupus erythematosus
Authors: Reed Joanne H. , Jackson Michael W. , Gordon Tom P. 
Published: March 2008

AbstractObjectivePrevious studies have attempted to segregate anti–60‐kd Ro/SSA (anti–Ro 60) responses in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (SS) but have shown limited disease preference. The aim of the present study was to determine whether the presence of autoantibodies against an Ro 60 apotope (an epitope expressed on apoptotic cells) distinguishes anti–Ro 60 responses in SLE and primary SS.MethodsMultiparameter flow cytometry was used to select early apoptotic cells and measure the simultaneous binding of annexin V, propidium iodide, and anti–Ro 60–positive IgG from SLE patients (n = 21) and patients with primary SS (n = 19). The specificity of the Ro 60 apotope was determined by inhibition experiments with recombinant and native Ro 60.ResultsAutoantibodies against the Ro 60 apotope were prevalent in SLE patients (13 of 21, 62%) and were rarely observed in patients with primary SS (1 of 19, 5%) (P = 0.0002). Further, within SLE patients, autoantibodies to the Ro 60 apotope strongly distinguished patients with anti–Ro 60 alone (12 of 13, 92%) from those with both anti–Ro 60 and anti‐La (1 of 8, 13%) (P = 0.0005). When we considered all patients with anti–Ro 60 alone, the presence of autoantibodies to the Ro 60 apotope had both high sensitivity (92.3%) and high specificity (85.7%) for SLE compared with primary SS (P = 0.0012). The presence of autoantibodies to the Ro 60 apotope may therefore be of diagnostic value in patients with isolated anti–Ro 60 responses.ConclusionThe preferential targeting of an Ro 60 apotope exposed on early apoptotic cells in a subset of SLE patients implies disease‐specific pathways for the induction of anti–Ro 60 autoimmunity.
CD200‐FC, a novel antiarthritic biologic agent that targets proinflammatory cytokine expression in the joints of mice with collagen‐induced arthritis
Authors: Šimelyte Egle , Criado Gabriel , Essex David , Uger Robert A. , Feldmann Marc , Williams Richard O. 
Published: March 2008

AbstractObjectiveThe CD200 receptor (CD200R) is an inhibitory receptor expressed by myeloid cells that is postulated to play an important role in regulation of the immune system. The purpose of this study was to evaluate the efficacy of a soluble ligand of CD200R in established collagen‐induced arthritis (CIA) in mice and to analyze changes in cytokine expression following therapy in order to understand its primary mechanism of action.MethodsArthritis was induced in DBA/1 mice, and CD200‐Fc fusion protein, an isotype control monoclonal antibody, or TNFR‐Fc fusion protein was administered over a period of 10 days (total of 4 doses). Cytokine expression in the joint was assessed by flow cytometry, enzyme‐linked immunosorbent assay, and quantitative real‐time polymerase chain reaction.ResultsCD200‐Fc significantly reduced the severity of established arthritis at the clinical and histologic levels. The therapeutic effect of CD200‐Fc at 1 mg/kg was comparable with that of TNFR‐Fc at 4 mg/kg. CD200R was found to be expressed in arthritic synovia and in lymph nodes, yet no changes in T cell cytokine levels (interferon‐γ, interleukin‐5 [IL‐5], IL‐10, IL‐17) were detected after CD200‐Fc therapy. There was no evidence of an expansion of forkhead box P3–positive regulatory T cells or a change in serum anticollagen IgG1 and IgG2a levels. However, administration of CD200‐Fc markedly decreased the expression of messenger RNA for tumor necrosis factor α, IL‐1β, IL‐10, and matrix metalloproteinase 13 in the joint to the same extent as administration of TNFR‐Fc.ConclusionCD200‐Fc is an effective therapeutic agent in established CIA that targets proinflammatory cytokine expression in the joint without any obvious systemic immunosuppressive effects. Our findings indicate that CD200‐Fc has considerable potential as a novel therapeutic agent in rheumatoid arthritis in humans.
Fibroblast‐specific perturbation of transforming growth factor β signaling provides insight into potential pathogenic mechanisms of scleroderma‐associated lung fibrosis: Exaggerated response to alveolar epithelial injury in a novel mouse model
Authors: Hoyles Rachel K. , Khan Korsa , Shiwen Xu , Howat Sarah L. , Lindahl Gisela E. , Leoni Patricia , du Bois Roland M. , Wells Athol U. , Black Carol M. , Abraham David J. , Denton Christopher P. 
Published: March 2008

AbstractObjectiveTo explore increased susceptibility to fibrosis following experimental injury to alveolar epithelial cells (AECs) in a novel transgenic mouse model of scleroderma with fibroblast‐specific perturbation of transforming growth factor β (TGFβ) signaling (TβRIIΔk‐fib mice).MethodsWild‐type (WT) and transgenic mice were injured with intratracheally administered saline or bleomycin, and the lungs were harvested for biochemical, histologic, and electron microscopic analysis.ResultsElectron microscopy revealed AEC abnormalities in the lungs of untreated transgenic mice and bleomycin‐treated WT mice; the lungs of transgenic mice treated with bleomycin showed severe epithelial damage. Compared with lungs from bleomycin‐treated WT mice, lungs from bleomycin‐treated transgenic mice demonstrated increased fibroproliferation, myofibroblast persistence, and impaired hyperplasia and increased apoptosis of type II AECs. The lungs from saline‐treated transgenic mice and those from bleomycin‐treated WT mice had phenotypic similarities, suggesting enhanced susceptibility to minor epithelial injury in the transgenic strain. The level of collagen was increased in the lungs from transgenic mice compared with that in the lungs from WT mice after treatment with either bleomycin or saline. Persistent fibrosis in bleomycin‐treated transgenic mice was independent of ongoing neutrophil inflammation but was associated with impaired alveolar epithelial repair.ConclusionThese results suggest that in the context of fibroblast‐specific perturbation of TGFβ signaling, even minor epithelial injury induces significant fibrosis. The model supports a central role for TGFβ in determining fibrosis and demonstrates that lung fibroblasts may regulate the response of AECs to injury. Our findings provide insight into likely pathogenic mechanisms in scleroderma‐associated pulmonary fibrosis.
Articular cartilage repair using dedifferentiated articular chondrocytes and bone morphogenetic protein 4 in a rabbit model of articular cartilage defects
Authors: Lin Lin , Zhou Chunyan , Wei Xuelei , Hou Yu , Zhao Liheng , Fu Xin , Zhang Jiying , Yu Changlong 
Published: March 2008

AbstractObjectiveTo observe redifferentiation of dedifferentiated chondrocytes after transplantation into the joint, and to evaluate the ability of dedifferentiated chondrocytes transduced with adenovirus containing bone morphogenetic protein 4 (BMP‐4) to redifferentiate in vitro and in vivo in a rabbit model of articular cartilage defects.MethodsMonolayer and pellet culture systems were used to evaluate the redifferentiation of dedifferentiated chondrocytes transduced with BMP‐4. A rabbit model of partial‐thickness articular cartilage defects was used to evaluate cartilage repair macroscopically and histologically, 6 and 12 weeks after transplantation with first‐passage, fifth‐passage, or transduced fifth‐passage chondrocytes. Histologic grading of the repaired tissue was performed. Expression of BMP‐4 and the ability of transplanted cells to recover a chondrocytic phenotype were also assessed.ResultsBMP‐4–expressing dedifferentiated chondrocytes recovered a chondrocytic phenotype in vitro. After transplantation into the joint, some of the dedifferentiated chondrocytes in the defect sites could undergo redifferentiation and formed matrix that displayed positive toluidine blue staining for glycosaminoglycans. Histologic scores of the regenerative tissue revealed significantly better cartilage repair in rabbits transplanted with BMP‐4–expressing cells than in the other treatment groups. Staining with toluidine blue revealed expression of BMP‐4 in the cells and in the matrix surrounding the cells.ConclusionSome dedifferentiated chondrocytes can redifferentiate after transplantation into the load‐bearing joint. BMP‐4 can be used to induce redifferentiation of dedifferentiated chondrocytes in vitro and in vivo, which could help enhance articular cartilage repair.
Golimumab in patients with active rheumatoid arthritis despite treatment with methotrexate: A randomized, double‐blind, placebo‐controlled, dose‐ranging study
Authors: Kay Jonathan , Matteson Eric L. , Dasgupta Bhaskar , Nash Peter , Durez Patrick , Hall Stephen , Hsia Elizabeth C. , Han John , Wagner Carrie , Xu Zhenhua , Visvanathan Sudha , Rahman Mahboob U. 
Published: March 2008

AbstractObjectiveTo assess the efficacy, safety, and pharmacology of subcutaneous administration of golimumab in patients with active rheumatoid arthritis (RA) despite treatment with methotrexate (MTX).MethodsPatients were randomly assigned in a double‐blinded manner to receive injections of placebo plus MTX or 50 mg or 100 mg golimumab every 2 or 4 weeks plus MTX through week 48. Patients originally assigned to receive injections every 2 weeks had the interval increased to every 4 weeks starting at week 20. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at week 16. The study was powered to detect a difference in the primary end point when the combined golimumab groups and at least 1 of the individual dose groups were compared with placebo.ResultsThe primary end point was attained. Sixty‐one percent of patients in the combined golimumab plus MTX dose groups achieved an ACR20 response at week 16 compared with 37% of patients in the placebo plus MTX group (P = 0.010). In addition, 79% of patients in the group receiving 100 mg golimumab every 2 weeks achieved an ACR20 response (P < 0.001 versus placebo). Through week 20 (after which patients receiving placebo were switched to active infliximab therapy), serious adverse events were reported in 9% of patients in the combined golimumab groups and in 6% of patients in the placebo group.ConclusionGolimumab plus MTX effectively reduces the signs and symptoms of RA and is generally well tolerated in patients with an inadequate response to MTX.