bluuebunny/crossref_metadata_2025_split huggingface dataset:
The nuclear autoantigen CENP‐B displays cytokine‐like activities toward vascular smooth muscle cells
Authors: Robitaille Geneviève , Hénault Jill , Christin Marie‐Soleil , Senécal Jean‐Luc , Raymond Yves 
Published: October 2007

AbstractObjectiveA growing number of intracellular autoantigenic polypeptides have been found to play a second biologic role when they are present in the extracellular medium. We undertook this study to determine whether the CENP‐B nuclear autoantigen could be added to this set of bifunctional molecules.MethodsPurified CENP‐B or CENP‐B released from apoptotic cells was tested for surface binding to a number of human cell types by cell‐based enzyme‐linked immunosorbent assay, flow cytometry, and indirect immunofluorescence. The biologic effects of CENP‐B on the migration, interleukin secretion, and signaling pathways of its specific target cells were evaluated.ResultsCENP‐B was found to bind specifically to the surface of human pulmonary artery smooth muscle cells (SMCs) and not to fibroblasts or endothelial cells (ECs). Furthermore, CENP‐B bound preferentially to SMCs of the contractile type rather than to SMCs of the synthetic type. Binding of CENP‐B to SMCs stimulated their migration during in vitro wound healing assays, as well as their secretion of interleukins 6 and 8. The mechanism by which CENP‐B mediated these effects involved the focal adhesion kinase, Src, ERK‐1/2, and p38 MAPK pathways. Finally, CENP‐B released from apoptotic ECs was found to bind to SMCs, thus indicating a plausible in vivo source of extracellular CENP‐B.ConclusionThese novel biologic roles of the nuclear autoantigen CENP‐B open up a new perspective for studying the pathogenic role of anti–CENP‐B autoantibodies.
Association between friction and wear in diarthrodial joints lacking lubricin
Authors: Jay Gregory D. , Torres Jahn R. , Rhee David K. , Helminen Heikki J. , Hytinnen Mika M. , Cha Chung‐Ja , Elsaid Khaled , Kim Kyung‐Suk , Cui Yajun , Warman Matthew L. 
Published: October 2007

AbstractObjectiveThe glycoprotein lubricin (encoded by the gene Prg4) is secreted by surface chondrocytes and synovial cells, and has been shown to reduce friction in vitro. In contrast to man‐made bearings, mammalian diarthrodial joints must endogenously produce friction‐reducing agents. This study was undertaken to investigate whether friction is associated with wear.MethodsThe lubricating ability of synovial fluid (SF) samples from humans with genetic lubricin deficiency was tested in vitro. The coefficient of friction in the knee joints of normal and lubricin‐null mice was measured ex vivo; these joints were also studied by light and electron microscopy. Atomic force microscopy was used to image and measure how lubricin reduces friction in vitro.ResultsSF lacking lubricin failed to reduce friction in the boundary mode. Joints of lubricin‐null mice showed early wear and higher friction than joints from their wild‐type counterparts. Lubricin self‐organized and reduced the work of adhesion between apposing asperities.ConclusionThese data show that friction is coupled with wear at the cartilage surface in vivo. They imply that acquired lubricin degradation occurring in inflammatory joint diseases predisposes the cartilage to damage. Lastly, they suggest that lubricin, or similar biomolecules, will have applications in man‐made devices in which reducing friction is essential.
Microparticles stimulate the synthesis of prostaglandin E2 via induction of cyclooxygenase 2 and microsomal prostaglandin E synthase 1
Authors: Jüngel Astrid , Distler Oliver , Schulze‐Horsel Ursula , Huber Lars C. , Ha Huy Riem , Simmen Beat , Kalden Joachim R. , Pisetsky David S. , Gay Steffen , Distler Jörg H. W. 
Published: October 2007

AbstractObjectiveMicroparticles are small vesicles that are released from activated or dying cells and that occur abundantly in the synovial fluid of patients with rheumatoid arthritis (RA). The goal of these studies was to elucidate the mechanisms by which microparticles activate synovial fibroblasts to express a proinflammatory phenotype.MethodsMicroparticles from monocytes and T cells were isolated by differential centrifugation. Synovial fibroblasts were cocultured with increasing numbers of microparticles. Gene expression was analyzed by real‐time polymerase chain reaction and confirmed by Western blotting and enzyme immunoassay. Arachidonic acid labeled with tritium was used to study the transport of biologically active lipids by microparticles. The roles of NF‐κB and activator protein 1 (AP‐1) signaling were analyzed with electrophoretic mobility shift assay and transfection with small interfering RNA and IκB expression vectors.ResultsMicroparticles strongly induced the synthesis of cyclooxygenase 2 (COX‐2), microsomal prostaglandin E synthase 1 (mPGES‐1), and prostaglandin E2 (PGE2). In contrast, no up‐regulation of COX‐1, mPGES‐2, cytosolic PGES, or phospholipase A2 was observed. The induction of PGE2 was blocked by selective inhibition of COX‐2. Microparticles activated NF‐κB, AP‐1, p38, and JNK signaling in synovial fibroblasts. Inhibition of NF‐κB, AP‐1, and JNK signaling reduced the stimulatory effects. Arachidonic acid was transported from leukocytes to fibroblasts by microparticles. Arachidonic acid derived from microparticles was converted to PGE2 by synovial fibroblasts.ConclusionThese results demonstrate that microparticles up‐regulate the production of PGE2 in synovial fibroblasts by inducing COX‐2 and mPGES‐1. These data provide evidence for a novel mechanism by which microparticles may contribute to inflammation and pain in RA.
Gene expression profiling of peripheral blood from patients with untreated new‐onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome
Authors: Fall Ndate , Barnes Michael , Thornton Sherry , Luyrink Lorie , Olson Judyann , Ilowite Norman T. , Gottlieb Beth S. , Griffin Thomas , Sherry David D. , Thompson Susan , Glass David N. , Colbert Robert A. , Grom Alexei A. 
Published: October 2007

AbstractObjectiveSystemic juvenile idiopathic arthritis (JIA) is frequently associated with the development of macrophage activation syndrome. This study was undertaken to better understand the relationship between systemic JIA and macrophage activation syndrome.MethodsGene expression profiles were examined in 17 patients with untreated new‐onset systemic JIA, 5 of whom showed evidence of subclinical macrophage activation syndrome (of whom 2 eventually developed overt macrophage activation syndrome). Peripheral blood mononuclear cells (PBMCs) were separated on Ficoll gradients, and purified RNA was analyzed using Affymetrix GeneChip expression arrays. A fraction of the PBMCs were used for flow cytometry to define the cellular composition of the samples.ResultsTwo hundred twenty‐five differentially expressed genes (P < 0.05) that distinguished patients with systemic JIA from healthy controls (n = 30) were identified. Clustering analysis indicated that expression patterns correlated with serum ferritin levels. Three main clusters distinguished systemic JIA patients with highly elevated ferritin levels (including those with subclinical macrophage activation syndrome) from those with normal or only moderately elevated ferritin levels. The first cluster comprised genes involved in the synthesis of hemoglobins and structural proteins of erythrocytes. This transcriptional profile was consistent with immature nucleated red blood cells, likely reflective of high red blood cell turnover. Also included were transcripts indicating immature granulocytes. The second cluster was enriched for genes involved in cell cycle regulation. The third cluster was enriched for genes involved in innate immune responses, including those involved in the negative regulation of Toll‐like receptor/interleukin‐1 receptor–triggered inflammatory cascades and markers of the alternative pathway of macrophage differentiation. Additional differentially expressed genes of interest were those involved in the cytolytic pathway, including SH2D1A and Rab27a.ConclusionThese data indicate that gene expression profiling can be a useful tool for identifying early macrophage activation syndrome in patients with systemic JIA.
Deficiency of the type I interferon receptor protects mice from experimental lupus
Authors: Nacionales Dina C. , Kelly‐Scumpia Kindra M. , Lee Pui Y. , Weinstein Jason S. , Lyons Robert , Sobel Eric , Satoh Minoru , Reeves Westley H. 
Published: October 2007

AbstractObjectiveSystemic lupus erythematosus (SLE) is diagnosed according to a spectrum of clinical manifestations and autoantibodies associated with abnormal expression of type I interferon (IFN‐I)–stimulated genes (ISGs). The role of IFN‐I in the pathogenesis of SLE remains uncertain, partly due to the lack of suitable animal models. The objective of this study was to examine the role of IFN‐I signaling in the pathogenesis of murine lupus induced by 2,6,10,14‐tetramethylpentadecane (TMPD).MethodsIFN‐I receptor–deficient (IFNAR−/−) 129Sv mice and wild‐type (WT) 129Sv control mice were treated intraperitoneally with TMPD. The expression of ISGs was measured by real‐time polymerase chain reaction. Autoantibody production was evaluated by immunofluorescence and enzyme‐linked immunosorbent assay. Proteinuria and renal glomerular cellularity were measured and renal immune complexes were examined by immunofluorescence.ResultsIncreased ISG expression was observed in the peripheral blood of TMPD‐treated WT mice, but not in the peripheral blood of TMPD‐treated IFNAR−/− mice. TMPD did not induce lupus‐specific autoantibodies (anti‐RNP, anti‐Sm, anti–double‐stranded DNA) in IFNAR−/− mice, whereas 129Sv controls developed these specificities. Although glomerular immune complexes were present in IFNAR−/− mice, proteinuria and glomerular hypercellularity did not develop, whereas these features of glomerulonephritis were found in the TMPD‐treated WT controls. The clinical and serologic manifestations observed in TMPD‐treated mice were strongly dependent on IFNAR signaling, which is consistent with the association of increased expression of ISGs with lupus‐specific autoantibodies and nephritis in humans.ConclusionSimilar to its proposed role in human SLE, signaling via the IFNAR is central to the pathogenesis of autoantibodies and glomerulonephritis in TMPD‐induced lupus. This lupus model is the first animal model shown to recapitulate the “interferon signature” in peripheral blood.
Efficacy and safety of intraarticular hylan or hyaluronic acids for osteoarthritis of the knee: A randomized controlled trial
Authors: Jüni Peter , Reichenbach Stephan , Trelle Sven , Tschannen Beatrice , Wandel Simon , Jordi Beat , Züllig Maya , Guetg Reto , Jörg Häuselmann Hans , Schwarz Hans , Theiler Robert , Ziswiler Hans Rudolf , Dieppe Paul A. , Villiger Peter M. , Egger Matthias 
Published: October 2007

AbstractObjectiveTo compare the efficacy and safety of intraarticular hylan and 2 hyaluronic acids (HAs) in osteoarthritis (OA) of the knee.MethodsThis was a multicenter, patient‐blind, randomized controlled trial in 660 patients with symptomatic knee OA. Patients were randomly assigned to receive 1 cycle of 3 intraarticular injections per knee of 1 of 3 preparations: a high molecular weight cross‐linked hylan, a non–cross‐linked medium molecular weight HA of avian origin, or a non–cross‐linked low molecular weight HA of bacterial origin. The primary outcome measure was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at 6 months. Secondary outcome measures included local adverse events (effusions or flares) in injected knees. During months 7–12, patients were offered a second cycle of viscosupplementation.ResultsPain relief was similar in all 3 groups. The difference in changes between baseline and 6 months between hylan and the combined HAs was 0.1 on the WOMAC pain score (95% confidence interval [95% CI] −0.2, 0.3). No relevant differences were observed in any of the secondary efficacy outcomes, and stratified analyses provided no evidence for differences in effects across different patient groups. There was a trend toward more local adverse events in the hylan group than in the HA groups during the first cycle (difference 2.2% [95% CI −2.4, 6.7]), and this trend became more pronounced during the second cycle (difference 6.4% [95% CI 0.6, 12.2]).ConclusionWe found no evidence for a difference in efficacy between hylan and HAs. In view of its higher costs and potential for more local adverse events, we see no rationale for the continued use of hylan in patients with knee OA.
Type I interferon as a novel risk factor for endothelial progenitor cell depletion and endothelial dysfunction in systemic lupus erythematosus
Authors: Lee Pui Y. , Li Yi , Richards Hanno B. , Chan Fay S. , Zhuang Haoyang , Narain Sonali , Butfiloski Edward J. , Sobel Eric S. , Reeves Westley H. , Segal Mark S. 
Published: October 2007

AbstractObjectiveThe premature atherosclerosis seen in patients with systemic lupus erythematosus (SLE) is not explained by traditional risk factors. SLE disease activity, such as renal involvement and presence of autoantibodies, is associated with elevated serum levels of type I interferon (IFN‐I), a family of cytokines with potent antiviral and antiproliferative effects. This study was undertaken to test the hypothesis that elevated IFN‐I levels could lead to endothelial dysfunction, a surrogate for cardiovascular disease, by causing a reduction in the number of endothelial progenitor cells (EPCs), bone marrow–derived cells that participate in endothelial repair.MethodsEPCs were enumerated in the peripheral blood of SLE patients (n = 70) and healthy controls (n = 31), using a colony‐forming assay. Serum IFN‐I levels were quantified by real‐time polymerase chain reaction measurement of the expression of the IFN‐I–inducible gene MX1. Endothelial function was determined by peripheral arterial plethysmography.ResultsSLE patients had markedly reduced levels of EPC colony‐forming units compared with controls (median 5.7/ml peripheral blood [interquartile range 1.9–12.8] versus 28.5/ml peripheral blood [14.7–47.3]; P < 0.0001), and the depletion of EPCs was more dramatic in patients with elevated levels of IFN‐I. Stepwise multiple regression analysis showed that MX1 expression and serum levels of C‐reactive protein were independently associated with the reduction of EPCs. Importantly, high IFN‐I levels were associated with impaired endothelial function in patients with SLE.ConclusionThese data support the novel hypothesis that depletion of EPCs caused by excessive IFN‐I may be linked to endothelial dysfunction and increased cardiovascular risk in SLE.
Histopathologic changes at “synovio–entheseal complexes” suggesting a novel mechanism for synovitis in osteoarthritis and spondylarthritis
Authors: Benjamin Michael , McGonagle Dennis 
Published: October 2007

AbstractObjectiveTo determine the extent to which different entheses form part of a “synovio–entheseal complex” (SEC) and whether such SECs are commonly associated with the presence of inflammatory cells and evidence of enthesis microdamage.MethodsSpecimens from 49 cadaveric entheses were processed for histologic study, and all soft tissue components of the entheses or enthesis organs were examined. To exclude articular cartilage degeneration as a triggering factor for synovitis, the selected entheses included 17 that were not immediately adjacent to such cartilage.ResultsAn SEC was present at 82% of entheses. These included 47% of the attachments not adjacent to articular cartilage, where the synovium was that of bursae or tendon sheaths. One or more of a wide variety of degenerative changes were noted on the soft tissue side of every enthesis; the most common changes were cell clustering and/or fissuring (in 76% of entheses). Synovial villus formation or inflammatory cell infiltration was seen in 85% of entheses, and in 73% of attachments there were also inflammatory cells in the enthesis organ itself. The changes included synovial invasion (pannus formation) of the enthesis.ConclusionEntheses are frequently juxtaposed to synovium, thus forming SECs. They are also often associated with both degenerative and inflammatory changes, and the latter may involve the immediately adjacent synovium. These findings suggest a novel mechanism by which synovitis could develop in both degenerative joint disease and spondylarthritis.
Sugarcane ethanol production in Brazil: an expansion model sensitive to socioeconomic and environmental concerns
Authors: Sparovek Gerd , Berndes Göran , Egeskog Andrea , de Freitas Flavio Luiz Mazzaro , Gustafsson Stina , Hansson Julia 
Published: October 2007

AbstractBrazilian agriculture is characteristically dynamic; land and production resources have a skewed ownership distribution; and agricultural production is essential for small holders of rural poor regions. Also, the main agricultural land use is composed of pastures where extensive livestock production prevails. Because of increasing demand Brazil is expected to expand its sugarcane‐based ethanol production. Addressing concerns about social and environmental impacts of such an expansion requires careful consideration of the complexity of Brazilian agriculture in general and specific local conditions in particular. This perspective outlines an expansion model for sugarcane ethanol production that is sensitive to socioeconomic and environmental concerns. Through integration with the prevailing land use, the model avoids the usual displacement of extensive livestock production to remote regions, causing leakage effects with deforestation and promotes milk and beef cattle intensification and investment opportunities for local society. The expansion model is feasible at current market conditions and should have good prospects for complying with sustainability criteria within various certification schemes presently under development. A case study, developed in the Pontal do Paranapanema region (state of São Paulo, Brazil) illustrates the model in agrarian reform settlements. © 2007 Society of Chemical Industry and John Wiley & Sons, Ltd
Continuum molecular electrostatics, salt effects, and counterion binding—A review of the Poisson–Boltzmann theory and its modifications
Authors: Grochowski Paweł , Trylska Joanna 
Published: October 2007

AbstractThis work is a review of the Poisson–Boltzmann (PB) continuum electrostatics theory and its modifications, with a focus on salt effects and counterion binding. The PB model is one of the mesoscopic theories that describes the electrostatic potential and equilibrium distribution of mobile ions around molecules in solution. It serves as a tool to characterize electrostatic properties of molecules, counterion association, electrostatic contributions to solvation, and molecular binding free energies. We focus on general formulations which can be applied to large molecules of arbitrary shape in all‐atomic representation, including highly charged biomolecules such as nucleic acids. These molecules present a challenge for theoretical description, because the conventional PB model may become insufficient in those cases. We discuss the conventional PB equation, the corresponding functionals of the electrostatic free energy, including a connection to DFT, simple empirical extensions to this model accounting for finite size of ions, the modified PB theory including ionic correlations and fluctuations, the cell model, and supplementary methods allowing to incorporate site‐bound ions in the PB calculations. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 93–113, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Neutral and Cationic Phosphoramide Adducts of Silicon Tetrachloride: Synthesis and Characterization of Their Solution and Solid‐State Structures
Authors: Denmark Scott E. , Eklov Brian M. 
Published: October 2007

AbstractThe solution and solid‐state structures of hexamethylphosphoramide (HMPA) adducts of tetrachlorosilane (SiCl4) are discussed. In solution, the meridional and facial isomers of the hexa‐coordinate cationic complex 3 HMPA⋅SiCl3+ Cl− (2) predominate at all HMPA concentrations, and are in equilibrium with the hexa‐coordinate neutral trans‐ and cis‐2 HMPA⋅SiCl4 complexes (1), as well as the penta‐coordinate cationic cis‐2 HMPA⋅SiCl3+ Cl− (3). Single crystal X‐ray analyses are reported for the ionized mer‐3 HMPA⋅SiCl3+ HCl2− and the neutral trans‐2 HMPA⋅SiCl4 complexes.
In vivo phosphorylation of regulatory light chain of myosin II in sea urchin eggs and its role in controlling myosin localization and function during cytokinesis
Authors: Uehara Ryota , Hosoya Hiroshi , Mabuchi Issei 
Published: October 2007

AbstractPhosphorylation of myosin regulatory light chain (RLC) at Ser19 (mono‐phosphorylation) promotes filament assembly and enhances actin‐activated ATPase activity of non‐muscle myosin, while phosphorylation at both Ser19 and Thr18 (di‐phosphorylation) further enhances the ATPase activity. However, it has not well been addressed which type of phosphorylation is important in regulating myosin during cytokinesis. Here, we investigated subcellular localization in sea urchin eggs of mono‐phosphorylated and di‐phosphorylated RLC by both quantitative biochemical and spatiotemporal cytological approaches. Mono‐phosphorylated RLC was dominant in the equatorial cortex throughout the whole process of cytokinesis. Inhibition of myosin light chain kinase (MLCK) decreased mono‐phosphorylated RLC both in the cortex and in the cleavage furrow, and blocked both formation and contraction of the contractile ring. Two different types of ROCK inhibitor gave inconsistent results: H1152 blocked both RLC mono‐phosphorylation in the cleavage furrow and contraction of the contractile ring, while Y27632 affected neither the mono‐phosphorylation nor cell division. These results suggest that there may be other targets of H1152 than ROCK, which is involved in the RLC phosphorylation in the cleavage furrow. Furthermore, it was revealed that localization of myosin heavy chain in the cleavage furrow, but not in the cortex, was perturbed by inhibition of RLC mono‐phosphorylation. These results suggested that RLC mono‐phosphorylation by more than two RLC kinases play a main role in regulation and localization of myosin in the dividing sea urchin eggs. Cell Motil. Cytoskeleton 2007. © 2007 Wiley‐Liss, Inc.