bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coagulation aggravates blood‐induced joint damage in dogs
Authors: van Meegeren Monique E. R. , Roosendaal Goris , Barten‐van Rijbroek Angelique D. , Schutgens Roger E. G. , Lafeber Floris P. J. G. , Mastbergen Simon C. 
Published: September 2012

AbstractObjectiveJoint bleeding due to trauma, major joint surgery, or hemophilia leads to joint damage. It is unclear if there are differences between coagulating blood and anticoagulated blood with respect to joint degeneration, especially in vivo. Therefore, we undertook this study to evaluate in a canine in vivo model whether intraarticular exposure to coagulating blood is more destructive than exposure to anticoagulated blood, and whether inflammation plays a role in the cartilage‐ damaging process.MethodsIn 7 dogs the left knees were injected with coagulating blood 4 times a week during weeks 1 and 4, and the right knees were injected with saline. In 7 other dogs, anticoagulated heparinized blood was injected, and heparinized saline was used as control. Ten weeks after the last injection, cartilage matrix turnover and synovial inflammation were analyzed. To study inflammation‐independent cartilage damage, explants of cartilage from at least 6 human donors per group were exposed in vitro to coagulating and anticoagulated blood, plasma, and serum for 4 days. Cartilage matrix turnover was determined after a recovery period of 12 days.ResultsCanine knees injected with coagulating blood showed more disturbed proteoglycan turnover than knees injected with anticoagulated blood. Synovial inflammation was present only after intraarticular injections with coagulating blood. In in vitro experiments, exposure of human cartilage explants to coagulating blood resulted in more damage than did exposure to anticoagulated blood, while exposure to plasma and serum did not alter cartilage matrix turnover.ConclusionThis study shows that coagulating blood causes more long‐lasting in vivo joint damage than anticoagulated blood, thereby suggesting that along with joint bleeding in hemophilia, exposure to intraarticular blood should also be avoided during surgery and trauma to prevent joint damage.
The mesenchymal stem cell marker CD248 (endosialin) is a negative regulator of bone formation in mice
Authors: Naylor Amy J. , Azzam Eman , Smith Stuart , Croft Adam , Poyser Callum , Duffield Jeremy S. , Huso David L. , Gay Steffen , Ospelt Caroline , Cooper Mark S. , Isacke Clare , Goodyear Simon R. , Rogers Michael J. , Buckley Christopher D. 
Published: September 2012

AbstractObjectiveCD248 (tumor endothelial marker 1/endosialin) is found on stromal cells and is highly expressed during malignancy and inflammation. Studies have shown a reduction in inflammatory arthritis in CD248‐knockout (CD248−/−) mice. The aim of the present study was to investigate the functional effect of genetic deletion of CD248 on bone mass.MethodsWestern blotting, polymerase chain reaction, and immunofluorescence were used to investigate the expression of CD248 in humans and mice. Micro–computed tomography and the 3‐point bending test were used to measure bone parameters and mechanical properties of the tibiae of 10‐week‐old wild‐type (WT) or CD248−/− mice. Human and mouse primary osteoblasts were cultured in medium containing 10 mM β‐glycerophosphate and 50 μg/ml ascorbic acid to induce mineralization, and then treated with platelet‐derived growth factor BB (PDGF‐BB). The mineral apposition rate in vivo was calculated by identifying newly formed bone via calcein labeling.ResultsExpression of CD248 was seen in human and mouse osteoblasts, but not osteoclasts. CD248−/− mouse tibiae had higher bone mass and superior mechanical properties (increased load required to cause fracture) compared to WT mice. Primary osteoblasts from CD248−/− mice induced increased mineralization in vitro and produced increased bone over 7 days in vivo. There was no decrease in bone mineralization and no increase in proliferation of osteoblasts in response to stimulation with PDGF‐BB, which could be attributed to a defect in PDGF signal transduction in the CD248−/− mice.ConclusionThere is an unmet clinical need to address rheumatoid arthritis–associated bone loss. Genetic deletion of CD248 in mice results in high bone mass due to increased osteoblast‐mediated bone formation, suggesting that targeting CD248 in rheumatoid arthritis may have the effect of increasing bone mass in addition to the previously reported effect of reducing inflammation.
Rituximab mediates loss of CD19 on B cells in the absence of cell death
Authors: Jones Jonathan D. , Hamilton B. JoNell , Rigby William F. C. 
Published: September 2012

AbstractObjectiveTo evaluate loss of the B cell–specific marker CD19 after the addition of rituximab (RTX) to healthy donor blood and to determine the role of complement‐mediated cytotoxicity in these cells.MethodsWhole blood and peripheral blood mononuclear cells (PBMCs) from healthy donors were evaluated for the loss of CD19 in the presence of RTX using flow cytometry. The effect of complement on CD19 loss was examined using serum‐free media, C3‐ and C5‐deficient sera, and a C5‐blocking antibody. Evidence of B cell death was evaluated by measuring messenger RNA (mRNA) levels as well as by flow cytometry. Transfer of CD19 antigen to monocytes and neutrophils was evaluated by flow cytometry and confocal microscopy.ResultsRTX induced a rapid decrease in CD19 count (mean 51%; n = 37) in PBMCs. This reduction occurred in the absence of complement. Despite the decrease in CD19 expression, B cell death did not occur, as evidenced by a lack of change in CD19 or CD20 mRNA levels and a lack of change in CD19 levels determined by intracellular staining and through the use of viability dyes. The CD19 antigen was shown to be transferred to monocytes and neutrophils in an Fc‐dependent manner.ConclusionOur findings indicate that the addition of RTX to healthy donor PBMCs in vitro results in complement‐independent loss of CD19 without causing B cell death. CD19 is transferred from B cells to monocytes and neutrophils during shaving of the RTX–CD20 complex in an Fc‐dependent manner. These data suggest that monitoring the effect of RTX by measuring the CD19+ cell count may be compromised by this activity.
Th17 cells are restrained by Treg cells via the inhibition of interleukin‐6 in patients with rheumatoid arthritis responding to anti–tumor necrosis factor antibody therapy
Authors: McGovern Jenny L. , Nguyen Dao X. , Notley Clare A. , Mauri Claudia , Isenberg David A. , Ehrenstein Michael R. 
Published: September 2012

AbstractObjectiveThe importance of interleukin‐17 (IL‐17) is underscored both by its resistance to control by Treg cells and the propensity of Treg cells to produce this highly inflammatory cytokine. This study sought to address whether Th17 cells are inhibited by Treg cells in rheumatoid arthritis (RA) patients responding to anti–tumor necrosis factor (anti‐TNF) therapy, and if so defining the underlying mechanisms of suppression.MethodsInhibition of Th17 cell responses was determined by Treg cell suppression assays. The Treg cell phenotype was analyzed using flow cytometry and enzyme‐linked immunosorbent assay. Mechanisms of suppression were tested by cytokine addition or antibody blockade.ResultsTh17 responses were inhibited by Treg cells from RA patients responding to the anti‐TNF antibody adalimumab (Tregada), but not by Treg cells from healthy individuals or patients with active RA. Furthermore, Tregada cells secreted less IL‐17, even when exposed to proinflammatory monocytes from patients with active RA. Tregada cells suppressed Th17 cells through the inhibition of monocyte‐derived IL‐6, but this effect was independent of IL‐10 and transforming growth factor β, which mediated the suppression of Th1 responses. Adalimumab therapy led to a reduction in retinoic acid receptor–related orphan nuclear receptor C–positive Th17 cells and an increase in FoxP3+ Treg cells lacking expression of the transcription factor Helios. However, this acquisition of IL‐17–suppressor function was not observed in RA patients responding to treatment with etanercept, a modified TNF receptor–Fc fusion protein. Indeed, there was no alteration in Treg cell number, function, or phenotype in etanercept‐treated patients, and Th17 responses remained unchecked.ConclusionTh1 and Th17 responses are controlled through distinct mechanisms by Treg cells from patients responding to anti‐TNF antibody therapy. Adalimumab therapy, but not etanercept therapy, induces a potent and stable Treg cell population with the potential to restrain the progression of IL‐17–associated inflammation in RA via regulation of monocyte‐derived IL‐6.
European genetic ancestry is associated with a decreased risk of lupus nephritis
Authors: Richman Ilana B. , Taylor Kimberly E. , Chung Sharon A. , Trupin Laura , Petri Michelle , Yelin Edward , Graham Robert R. , Lee Annette , Behrens Timothy W. , Gregersen Peter K. , Seldin Michael F. , Criswell Lindsey A. 
Published: September 2012

AbstractObjectiveAfrican Americans, East Asians, and Hispanics with systemic lupus erythematosus (SLE) are more likely to develop renal disease than are SLE patients of European descent. This study was undertaken to investigate whether European genetic ancestry protects against the development of lupus nephritis, with the aim of exploring the genetic and socioeconomic factors that might explain this effect.MethodsThis was a cross‐sectional study of SLE patients from a multiethnic case collection. Participants were genotyped for 126 single‐nucleotide polymorphisms (SNPs) informative for ancestry. A subset of participants was also genotyped for 80 SNPs in 14 candidate genes for renal disease in SLE. Logistic regression was used to test the association between European ancestry and renal disease. Analyses were adjusted for continental ancestries, socioeconomic status (SES), and candidate genes.ResultsParticipants (n = 1,906) had, on average, 62.4% European, 15.8% African, 11.5% East Asian, 6.5% Amerindian, and 3.8% South Asian ancestry. Among the participants, 656 (34%) had renal disease. A 10% increase in the proportion of European ancestry estimated in each participant was associated with a 15% reduction in the odds of having renal disease, after adjustment for disease duration and sex (odds ratio 0.85, 95% confidence interval 0.82–0.87; P = 1.9 × 10−30). Adjustment for other genetic ancestries, measures of SES, or SNPs in the genes most associated with renal disease (IRF5 [rs4728142], BLK [rs2736340], STAT4 [rs3024912], and HLA–DRB1*0301 and DRB1*1501) did not substantively alter this relationship.ConclusionEuropean ancestry is protective against the development of renal disease in SLE, an effect that is independent of other genetic ancestries, candidate risk alleles, and socioeconomic factors.
Association of anti–citrullinated vimentin and anti–citrullinated α‐enolase antibodies with subsets of rheumatoid arthritis
Authors: Montes Ariana , Perez‐Pampin Eva , Calaza Manuel , Gomez‐Reino Juan J. , Gonzalez Antonio 
Published: September 2012

AbstractObjectiveTo determine whether the anti–citrullinated vimentin peptide 60–75 (anti–Cit‐vimentin) and the immunodominant anti–citrullinated α‐enolase peptide 1 (anti–CEP‐1) antibodies are associated with subsets of patients with rheumatoid arthritis (RA) independently of the associations between anti–cyclic citrullinated peptide (anti‐CCP) antibodies and clinical features of RA.MethodsThe 3 antibody types were quantified by enzyme‐linked immunosorbent assay (ELISA) in serum samples from 521 patients with RA and 173 healthy controls of Spanish ancestry. Genotypes for HLA–DRB1 alleles and rs2476601 in PTPN22 were available for these patients and controls plus an additional 106 healthy controls. A combined analysis of the 3 antibodies was conducted using stratified contingency tables and logistic regression models.ResultsA differential, particularly strong, and independent association was observed between the presence of anti–Cit‐vimentin antibodies and the presence of shared epitope (SE) alleles, specifically in patients carrying 2 SE alleles, and between the presence of anti– Cit‐vimentin antibodies and the prevalence of joint erosion. Associations were observed between anti–CEP‐1 positivity and the presence of HLA–DRB1 and PTPN22 risk alleles and their additive interaction. These associations were not accounted for by the anti‐CCP status.ConclusionOur results indicate that the 2 antibodies against citrullinated peptides analyzed in this study add specific information beyond that obtained with the anti‐CCP status. They define subgroups of patients with RA in which genetic factors have different weight and there is an observed difference in the prevalence of erosions.
Brief Report: IRF5 systemic lupus erythematosus risk haplotype is associated with asymptomatic serologic autoimmunity and progression to clinical autoimmunity in mothers of children with neonatal lupus
Authors: Cherian Tharian S. , Kariuki Silvia N. , Franek Beverly S. , Buyon Jill P. , Clancy Robert M. , Niewold Timothy B. 
Published: September 2012

AbstractObjectiveVariation in the interferon regulatory factor 5 (IRF5) gene has been associated with risk of developing systemic lupus erythematosus (SLE), and this association is largely dependent upon anti‐Ro autoantibodies. This study was undertaken to determine if the IRF5 genotype is associated with maternal diagnosis or progression of autoimmunity.MethodsGenotyping of haplotype‐tagging polymorphisms in IRF5 was performed in 93 subjects of European ancestry who were recruited to the Research Registry for Neonatal Lupus. All subjects had high‐titer anti‐Ro autoantibodies and had a child with neonatal lupus (NL); allele frequencies were compared to those in nonautoimmune controls. The mothers had SLE, Sjögren's syndrome (SS), or undifferentiated autoimmune syndrome (UAS), or were asymptomatic.ResultsThe SLE risk haplotype of IRF5 was enriched in all anti‐Ro–positive subjects except in those with SS (odds ratio [OR] 2.55, P = 8.8 × 10−4). The SLE risk haplotype was even enriched in asymptomatic individuals with anti‐Ro antibodies (OR 2.69, P = 0.019). The same haplotype was more prevalent in subjects who were initially asymptomatic but developed symptomatic SLE during followup (OR 5.83, P = 0.0024). Interestingly, SS was associated with 2 minor IRF5 haplotypes, and these same haplotypes were decreased in frequency in mothers with SLE and those with UAS.ConclusionThe IRF5 SLE risk haplotype was associated with anti‐Ro antibody positivity in asymptomatic individuals, as well as with progression to SLE in asymptomatic anti‐Ro–positive individuals. SS in mothers of children with NL was associated with different IRF5 haplotypes. These data suggest that IRF5 polymorphisms play a role in serologic autoimmunity in humans and may promote the progression to clinical autoimmunity.
Methylation alterations of WT1 and homeobox genes in inflamed muscle biopsy samples from patients with untreated juvenile dermatomyositis suggest self‐renewal capacity
Authors: Wang Min , Xie Hehuang , Shrestha Sheela , Sredni Simone , Morgan Gabrielle A. , Pachman Lauren M. 
Published: September 2012

AbstractObjectiveTo determine the effect of methylation alteration in inflamed muscles from children with juvenile dermatomyositis (DM) and other idiopathic inflammatory myopathies (IIMs).MethodsMagnetic resonance imaging–directed diagnostic muscle biopsies yielded samples from 20 children with juvenile DM, which were used for genome‐wide DNA methylation profiling, as were muscle biopsy samples from 4 healthy controls. Bisulfite treatment followed by pyrosequencing confirmed methylation status in juvenile DM and other IIMs. Immunohistochemistry defined localization and expression levels of WT1.ResultsComparison of genome‐wide DNA methylation profiling between juvenile DM muscle and normal control muscle revealed 27 genes with a significant methylation difference between the groups. These genes were enriched with transcription factors and/or cell cycle regulators and were unrelated to duration of untreated disease. Six homeobox genes were among them; ALX4, HOXC11, HOXD3, and HOXD4 were hypomethylated, while EMX2 and HOXB1 were hypermethylated. WT1 was significantly hypomethylated in juvenile DM (Δβ = –0.41,P< 0.001). Bisulfite pyrosequencing verification in samples from 56 patients with juvenile DM confirmed the methylation alterations of these genes. Similar methylation alterations were observed in juvenile polymyositis (n = 5) and other IIMs (n = 9). Concordant with the other findings, WT1 protein was increased in juvenile DM muscle, with average positive staining of 11.6%, but was undetectable in normal muscle (P< 0.001).ConclusionThese results suggest that affected muscles of children with juvenile DM and IIMs have the capacity to be repaired, and that homeobox and WT1 genes are epigenetically marked to facilitate this repair process, potentially suggesting new avenues of therapeutic intervention.
Cherry consumption and decreased risk of recurrent gout attacks
Authors: Zhang Yuqing , Neogi Tuhina , Chen Clara , Chaisson Christine , Hunter David J. , Choi Hyon K. 
Published: September 2012

AbstractObjectiveTo study the relationship between cherry intake and the risk of recurrent gout attacks among individuals with gout.MethodsWe conducted a case–crossover study to examine the associations of a set of putative risk factors with recurrent gout attacks. Individuals with gout were prospectively recruited and followed up online for 1 year. Participants were asked to provide the following information regarding gout attacks: the onset date of the gout attack, symptoms and signs, medications (including antigout medications), and exposure to potential risk factors (including daily intake of cherries and cherry extract) during the 2‐day period prior to the gout attack. We assessed the same exposure information over 2‐day control periods. We estimated the risk of recurrent gout attacks related to cherry intake using conditional logistic regression. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.ResultsOur study included 633 individuals with gout. Cherry intake over a 2‐day period was associated with a 35% lower risk of gout attacks compared with no intake (multivariate OR 0.65 [95% CI 0.50–0.85]). Cherry extract intake showed a similar inverse association (multivariate OR 0.55 [95% CI 0.30–0.98]). The effect of cherry intake persisted across subgroups stratified by sex, obesity status, purine intake, alcohol use, diuretic use, and use of antigout medications. When cherry intake was combined with allopurinol use, the risk of gout attacks was 75% lower than during periods without either exposure (OR 0.25 [95% CI 0.15–0.42]).ConclusionThese findings suggest that cherry intake is associated with a lower risk of gout attacks.
Enzyme Immobilization and Direct Electrochemistry Based on a New Matrix of Phospholipid‐Monolayer‐Functionalized Graphene
Authors: Liu Jiyang , Han Lei , Wang Tianshu , Hong Wei , Liu Yaqing , Wang Erkang 
Published: October 2012

AbstractA new nanocomposite material for enzyme immobilization and subsequent direct electrochemistry and electrocatalysis was developed by using 1,2‐dimyristoyl‐sn‐glycero‐3‐phospho‐(1‐rac‐glycerol)‐phospholipid‐monolayer‐membrane‐modified graphene (DMPG‐G). Microperoxidase‐11 (MP11) was chosen as a model enzyme to investigate the composite system. Owing to the improved conductivity and biocompatible microenvironment, MP11 that was immobilized in the matrix of the DMPG‐G nanocomposite (DMPG‐G‐MP11) effectively retained its native structure and bioactivity. DMPG‐G‐MP11‐modified glassy carbon electrode (DMPG‐G‐MP11/GCE) exhibited a pair of well‐defined quasi‐reversible redox peaks of MP11 and showed high electrocatalytic activity towards hydrogen peroxide (H2O2). The linear response of the developed biosensor for the determination of H2O2 ranged from 2.0×10−6 to 4.5×10−4 M with a detection limit of 7.2×10−7 M. This biosensor exhibited high reproducibility and long‐term storage stability. The promising features of this biosensor indicate that these lipid–graphene nanocomposites are ideal candidate materials for the direct electrochemistry of redox proteins and that they could serve as a versatile platform for the construction of a third‐generation biosensor.
Fine Tuning the Performance of DSSCs by Variation of the π‐Spacers in Organic Dyes that Contain a 2,7‐Diaminofluorene Donor
Authors: Baheti Abhishek , Thomas K. R. Justin , Lee Chuan‐Pei , Ho Kuo‐Chuan 
Published: September 2012

AbstractOrganic dyes that contain a 2,7‐diaminofluorene‐based donor, a cyanoacrylic‐acid acceptor, and various aromatic conjugation segments, which are composed of benzene, fluorene, carbazole, and thiophene units, as a π‐bridge have been synthesized and characterized by optical, electrochemical, and theoretical investigations. The trends in the absorption and electrochemical properties of these dyes are in accordance with the electron‐donating ability of the conjugating segment. Consequently, the dyes that contained a 2,7‐carbazole unit in the π‐spacer exhibited red‐shifted absorption and lower oxidation potentials than their corresponding fluorene‐ and phenylene‐bridged dyes. However, the enhanced power‐conversion efficiency that was exhibited by the fluorene‐bridged dyes in the DSSCs was attributed to their broader and intense absorption. Despite the longer‐wavelength absorption and reasonable optical density, carbazole‐bridged dyes exhibited lower power‐conversion efficiencies, which were ascribed to the poor alignment of the LUMO level in these dyes, thereby leading to the inhibition of electron injection into the TiO2 conduction band.
Luminescence in Li3Al2(PO4)3:Eu2+
Authors: Shinde K. N. , Park K. 
Published: September 2012

ABSTRACTA series of efficient Li3Al2(PO4)3:Eu2+ novel phosphors were synthesized by the facile combustion method. The effects of dopant on the luminescence behavior of Li3Al2(PO4)3 phosphor were also investigated. The phosphors were characterized by X‐ray diffraction, field emission scanning electron microscope and photoluminescence techniques. The result shows that all samples can be excited efficiently by near‐ultraviolet excitation under 310 nm. The emission was observed for Li3Al2(PO4)3:Eu2+ phosphor at 425 nm, which corresponded to the d → f transition. The concentration quenching of Eu2+ was observed in Li3Al2(PO4)3:Eu2+ when the Eu concentration was at 0.5 mol%. The prepared powders exhibited intense blue emission at the 425 nm owing to the Eu2+ ion by Hg‐free excitation at 310 nm (i.e., solid‐state lighting excitation). Consequently, the availability of such a phosphor will significantly help in the development of blue‐emitting solid‐state lighting applications. Copyright © 2012 John Wiley & Sons, Ltd.
Quantitative assessment of the relative contributions of steric repulsion and chemical interactions to macromolecular crowding
Authors: Minton Allen P. 
Published: September 2012

AbstractThe term “macromolecular crowding” denotes the combined effects of high volume fractions of nominally unrelated macromolecules upon the equilibrium and transport properties of all macrosolutes, dilute as well as concentrated, in the crowded medium. We present a formal partitioning of the total crowding effect into contributions from steric exclusion (excluded volume) and weak, nonspecific attractive interactions between a concentrated “crowding agent” and reactant and product species present at trace concentration. A numerical example of the combined effect of both steric and chemical interactions between crowder and tracer upon the reversible dimerization of tracer is presented, based upon reasonable estimates of the magnitude of both repulsive and attractive interactions between tracer and crowder species. © 2012Wiley Periodicals, Inc. Biopolymers 99: 239–244, 2013.