bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal performance evaluation and validation of fixed‐flexion radiography of the knee for detection of joint space loss
Authors: Nevitt Michael C. , Peterfy Charles , Guermazi Ali , Felson David T. , Duryea Jeff , Woodworth Thasia , Chen Hepei , Kwoh Kent , Harris Tamara B. 
Published: April 2007

AbstractObjectiveThe ability of nonfluoroscopically guided radiography of the knee to assess joint space loss is an important issue in studies of progression and treatment of knee osteoarthritis (OA), given the practical limitations of protocols involving fluoroscopically guided radiography of the knee. We evaluated the ability of the nonfluoroscopically guided fixed‐flexion radiography protocol to detect knee joint space loss over 3 years.MethodsWe assessed the same‐day test–retest precision for measuring minimum joint space width (JSW), the sensitivity for detection of joint space loss using serial films obtained a median of 37 months (range 23–47 months) apart, and the relationship of joint space loss to radiographic and magnetic resonance imaging (MRI) measures of knee OA. Participants were men and women (ages 70–79 years) with knee pain who were participating in the Health, Aging, and Body Composition Study. We assessed baseline radiographic OA and measured JSW using a computerized algorithm. Serial knee MRIs obtained over the same interval were evaluated for cartilage lesions.ResultsA total of 153 knees were studied, 35% of which had radiographic OA at baseline. The mean ± SD joint space loss for all knees over 3 years was 0.24 ± 0.59 mm (P < 0.001 for change). In knees with OA at baseline, the mean ± SD joint space loss over 3 years was 0.43 ± 0.66 mm (P < 0.001), and in knees with joint space narrowing at baseline, joint space loss was 0.50 ± 0.67 mm (P < 0.001). Joint space loss and its standardized response mean increased with the severity of baseline joint space narrowing and with the presence of cartilage lesions at baseline and worsening during followup.ConclusionRadiography of the knee in the fixed‐flexion view provides a sensitive and valid measure of joint space loss in multiyear longitudinal studies of knee OA, without the use of fluoroscopy to aid knee positioning.
Medical care expenditures and earnings losses among persons with arthritis and other rheumatic conditions in 2003, and comparisons with 1997
Authors: Yelin Edward , Murphy Louise , Cisternas Miriam G. , Foreman Aimee J. , Pasta David J. , Helmick Charles G. 
Published: April 2007

AbstractObjectiveTo obtain estimates of medical care expenditures and earnings losses associated with arthritis and other rheumatic conditions and the increment in such costs attributable to arthritis and other rheumatic conditions in the US in 2003, and to compare these estimates with those from 1997.MethodsEstimates for 2003 were derived from the Medical Expenditures Panel Survey (MEPS), a national probability sample of households. We tabulated medical care expenditures of adult MEPS respondents, stratified by arthritis and comorbidity status, and used regression techniques to estimate the increment of medical care expenditures attributable to arthritis and other rheumatic conditions. We also estimated the earnings losses sustained by working‐age adults with arthritis and other rheumatic conditions. Estimates for 2003 were compared with those from 1997, inflated to 2003 terms.ResultsIn 2003, there were 46.1 million adults with arthritis and other rheumatic conditions (versus 36.8 million in 1997). Adults with arthritis and other rheumatic conditions incurred mean medical care expenditures of $6,978 in 2003 (versus $6,346 in 1997), of which $1,635 was for prescriptions ($899 in 1997). Expenditures for adults with arthritis and other rheumatic conditions totaled $321.8 billion in 2003 ($233.5 billion in 1997). In 2003, the mean increment in medical care expenditures attributable to arthritis and other rheumatic conditions was $1,752 ($1,762 in 1997), for a total of $80.8 billion ($64.8 billion in 1997). Persons with arthritis and other rheumatic conditions ages 18–64 years earned $3,613 less than other persons (versus $4,551 in 1997), for a total of $108.0 billion (versus $99.0 billion). Of this amount, $1,590 was attributable to arthritis and other rheumatic conditions (versus $1,946 in 1997), for a total of $47.0 billion ($43.3 billion in 1997).ConclusionOur findings indicate that the increase in medical care expenditures and earnings losses between 1997 and 2003 is due more to an increase in the number of persons with arthritis and other rheumatic conditions than to costs per case.
Alteration of antigen‐independent immunologic synapse formation between dendritic cells from HLA–B27–transgenic rats and CD4+ T cells: Selective impairment of costimulatory molecule engagement by mature HLA–B27
Authors: Hacquard‐Bouder Cécile , Chimenti Maria‐Sole , Giquel Benoît , Donnadieu Emmanuel , Fert Ingrid , Schmitt Alain , André Claudine , Breban Maxime 
Published: April 2007

AbstractObjectiveTo investigate the molecular mechanism responsible for the reduced capacity of dendritic cells (DCs) from HLA–B27–transgenic rats to form conjugates with naive T cells.MethodsWe monitored interactions between DCs derived from HLA–B27–transgenic, HLA–B7–transgenic control, and nontransgenic rats and naive CD4+ T cells. Chemoattraction was studied in Transwell assays, and the formation of an immunologic synapse was examined by videomicroscopy and electron microscopy. Involvement of specific molecules in the defective interaction was examined in antibody‐blocking assays.ResultsT cells migrated normally toward B27 DCs, but upon contact, the frequency of T cells undergoing a Ca2+response was decreased, indicating impaired immunologic synapse formation. The immunologic synapse formed between B27 DCs and T cells appeared to be normal, as assessed by electron microscopy and by the Ca2+response. Blocking lymphocyte function−associated antigen 1 on T cells or blocking activated leukocyte cell adhesion molecules on DCs inhibited an equivalent proportion of conjugates from forming between B27 or control DCs and T cells, whereas blocking CD86 on DCs and blocking CD28, CD2, or CD4 on T cells inhibited a greater number of conjugates from forming with control DCs, indicating specific involvement of costimulatory molecules in the reduced formation of conjugates with B27 DCs. Mature B27 molecules on the DC surface were responsible for this decreased formation of conjugates.ConclusionIn the HLA–B27–transgenic rat model of spondylarthropathy, mature B27 molecules expressed by DCs impair the formation of an antigen‐independent immunologic synapse with naive CD4+ T cells by interfering with the engagement of costimulatory molecules. This phenomenon could potentially affect the production and/or maintenance of regulatory T cells and contribute to the expansion of pathogenic CD4+ T cells.
Presentation of arthritogenic peptide to antigen‐specific T cells by fibroblast‐like synoviocytes
Authors: Tran Chinh N. , Davis Michael J. , Tesmer Laura A. , Endres Judith L. , Motyl Christopher D. , Smuda Craig , Somers Emily C. , Chung Kevin C. , Urquhart Andrew G. , Lundy Steven K. , Kovats Susan , Fox David A. 
Published: April 2007

AbstractObjectiveTo assess the ability of rheumatoid arthritis (RA) fibroblast‐like synoviocytes (FLS) to function as antigen‐presenting cells (APCs) for arthritogenic autoantigens found within inflamed joint tissues.MethodsHuman class II major histocompatibility complex (MHC)–typed FLS were used as APCs for murine class II MHC–restricted CD4 T cell hybridomas. Interferon‐γ (IFNγ)–treated, antigen‐loaded FLS were cocultured with T cell hybridomas specific for immunodominant portions of human cartilage gp‐39 (HC gp‐39) or human type II collagen (CII). T cell hybridoma activation was measured by enzyme‐linked immunosorbent assay of culture supernatants for interleukin‐2. Both synthetic peptide and synovial fluid (SF) were used as sources of antigen. APC function in cocultures was inhibited by using blocking antibodies to human class II MHC, CD54, or CD58, or to murine CD4, CD11a, or CD2.ResultsHuman FLS could present peptides from the autoantigens HC gp‐39 and human CII to antigen‐specific MHC‐restricted T cell hybridomas. This response required pretreatment of FLS with IFNγ, showed MHC restriction, and was dependent on human class II MHC and murine CD4 for effective antigen presentation. Furthermore, FLS were able to extract and present antigens found within human SF to both the HC gp‐39 and human CII T cell hybridomas in an IFNγ‐dependent and MHC‐restricted manner.ConclusionRA FLS can function as APCs and are able to present peptides derived from autoantigens found within joint tissues to activated T cells in vitro. In the context of inflamed synovial tissues, FLS may be an important and hitherto overlooked subset of APCs that could contribute to autoreactive immune responses.
Identification of distinct gene expression profiles in the synovium of patients with systemic lupus erythematosus
Authors: Toukap A. Nzeusseu , Galant C. , Theate I. , Maudoux A. L. , Lories R. J. U. , Houssiau F. A. , Lauwerys B. R. 
Published: April 2007

AbstractObjectiveSynovitis is a common feature of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), but the pattern of joint involvement differs in each disease. This study was undertaken to investigate the global gene expression profiles in synovial biopsy tissue from the swollen knees of untreated SLE patients (n = 6), RA patients (n = 7), and osteoarthritis (OA) patients (n = 6).MethodsSynovial biopsy samples were obtained from the affected knees of patients in the 3 groups by needle arthroscopy. Half of the material was used for extraction of total RNA, amplification of complementary RNA, and high‐density oligonucleotide spotted hybridization arrays. On the remaining tissue samples, real‐time reverse transcription–polymerase chain reaction (RT‐PCR) and immunohistochemical experiments were performed to confirm the microarray data.ResultsSLE synovial biopsy tissue displayed a significant down‐regulation of genes involved in extracellular matrix (ECM) homeostasis and a significant up‐regulation of interferon‐inducible (IFI) genes. Real‐time RT‐PCR experiments confirmed the up‐regulation of selected IFI genes (IFI27, IFI44, and IFI44L) in the SLE synovial tissue. Immunohistochemical analyses showed that 3 molecules involved in ECM regulation, chondroitin sulfate proteoglycan 2, latent transforming growth factor β binding protein 2, and fibroblast activation protein α, were significantly down‐regulated in SLE synovium. In contrast, immunostaining for IFI27, Toll‐like receptor 4, and STAT‐1 resulted in higher quantitative scores in SLE synovial tissue, which could be attributed to the fact that the RA samples had a large population of inflammatory cell infiltrates that were negative for these markers.ConclusionArthritis in SLE has a very distinct molecular signature as compared with that in OA and RA, characterized by up‐regulation of IFI genes and down‐regulation of genes involved in ECM homeostasis.
Activation signal transduction by β1 integrin in T cells from patients with systemic lupus erythematosus
Authors: Nakayamada Shingo , Saito Kazuyoshi , Nakano Kazuhisa , Tanaka Yoshiya 
Published: April 2007

AbstractObjectiveBeta 1 integrin is a representative adhesion molecule for cell–cell and cell–extracellular matrix interactions, and it provides costimulatory signals to T cells. However, the relevance of β1 integrin to T cell activation in systemic lupus erythematosus (SLE) remains unclear. We undertook this study to perform a quantitative and functional analysis of β1 integrin–mediated signaling to T cells in patients with SLE.MethodsExpression of cell surface molecules was assessed by flow cytometric analysis. Engagement of β1 integrins was performed by crosslinking using a specific monoclonal antibody. To assess tyrosine kinases in β1 integrin–mediated signaling, the cells were transfected with a wild‐type (WT) focal adhesion kinase (FAK), a dominant‐negative truncation of the FAK, or a WT PTEN expression plasmid via nucleofection.ResultsBeta 1 integrin expression was significantly up‐regulated on peripheral blood T cells from patients with active SLE, particularly those with the complication of World Health Organization class IV nephritis, whereas CD28 was significantly decreased in patients with active SLE compared with normal individuals. Beta 1 integrin expression closely correlated with serum hypocomplementemia. Engagement of β1 integrin on T cells from patients with active SLE, but not on those from normal individuals, induced cell proliferation as well as CD40L expression on T cells. Up‐regulation of CD40L expression and T cell proliferation, induced by β1 integrin stimulation, were completely inhibited by transfection of the dominant‐negative truncations of FAK or WT PTEN.ConclusionThese results suggest that engagement of β1 integrins on SLE T cells could induce FAK‐mediated signaling and subsequent CD40L expression and proliferation. Thus, the β1 integrin signaling cascade might serve to enhance autoreactive T cell activation.
Epistatic effect of plasminogen activator inhibitor 1 and β‐Fibrinogen genes on risk of glomerular microthrombosis in lupus nephritis: Interaction with environmental/clinical factors
Authors: Gong Rujun , Liu Zhihong , Li Leishi 
Published: April 2007

AbstractObjectiveGlomerular microthrombosis (GMT) is not uncommon in lupus nephritis and has been associated with active renal injury and progressive kidney destruction. We undertook this study to determine whether genetic variations of hemostasis factors, such as plasminogen activator inhibitor 1 (PAI‐1) and fibrinogen, affect the risk of GMT.MethodsA cross‐sectional cohort of 101 lupus nephritis patients with or without GMT was genotyped for PAI‐1 –675 4G/5G and β‐fibrinogen (FGB) –455 G/A gene polymorphisms and analyzed.ResultsPAI‐1 4G/4G homozygotes and FGB A allele carriers were both at increased risk for GMT. When the data were stratified for both gene polymorphisms, an epistatic effect was detected. The PAI‐1 4G/4G genotype was found to predispose to GMT not equally in all lupus nephritis patients, but only in FGB A allele carriers. Likewise, the association between the FGB A allele and GMT was restricted to lupus nephritis patients homozygous for the PAI‐1 4G allele. This epistatic effect was revalidated by the multifactor dimensionality reduction (MDR) analysis and further assessed by incorporating a variety of environmental and clinical factors into the MDR analysis. The most parsimonious model that had a cross‐validation consistency of 100% included joint effects of PAI‐1 and FGB gene polymorphisms and anticardiolipin antibody (aCL) status and yielded the best prediction of GMT, with 66.6% accuracy.ConclusionOur findings suggest that risk of GMT in lupus nephritis is attributable, at least in part, to an epistatic effect of PAI‐1 and FGB genes, likely via an interaction with environmental/clinical factors, such as aCL.
Induction of increased cAMP levels in articular chondrocytes blocks matrix metalloproteinase–mediated cartilage degradation, but not aggrecanase‐mediated cartilage degradation
Authors: Karsdal Morten Asser , Sumer Eren Ufuk , Wulf Helle , Madsen Suzi H. , Christiansen Claus , Fosang Amanda J. , Sondergaard Bodil‐Cecilie 
Published: April 2007

AbstractObjectiveCalcitonin has been suggested to have chondroprotective effects. One signaling pathway of calcitonin is via the second messenger cAMP. We undertook this study to investigate whether increased cAMP levels in chondrocytes would be chondroprotective.MethodsCartilage degradation was induced in bovine articular cartilage explants by 10 ng/ml oncostatin M (OSM) and 20 ng/ml tumor necrosis factor (TNF). In these cultures, cAMP levels were augmented by treatment with either forskolin (4, 16, or 64 μM) or 3‐isobutyl‐1‐methyl xanthine (IBMX; 4, 16, or 64 μM). Cartilage degradation was assessed by 1) quantification of C‐terminal crosslinking telopeptide of type II collagen fragments (CTX‐II), 2) matrix metalloproteinase (MMP)–mediated aggrecan degradation by 342FFGV‐ G2 assay, 3) aggrecanase‐mediated degradation by 374ARGS‐G2 assay, 4) release of sulfated glycosaminoglycans (sGAG) into culture medium, 5) immunohistochemistry with a monoclonal antibody recognizing the CTX‐II epitope, and 6) toluidine blue staining of proteoglycans. MMP expression and activity were assessed by gelatin zymography.ResultsOSM and TNF induced an 8,000% increase in CTX‐II compared with control (P < 0.001). Both forskolin and IBMX dose‐dependently inhibited release of CTX‐II (P < 0.001). OSM and TNF induced a 6‐fold increase in 342FFGV‐G2, which was abrogated by forskolin and IBMX (by >80%). OSM and TNF stimulated MMP expression as visualized by zymography, and MMP expression was dose‐dependently inhibited by forskolin and IBMX. The highest concentration of IBMX lowered cytokine‐induced release of sGAG by 72%.ConclusionLevels of cAMP in chondrocytes play a key role in controlling catabolic activity. Increased cAMP levels in chondrocytes inhibited MMP expression and activity and consequently strongly inhibited cartilage degradation. Specific cAMP modulators in chondrocytes may be potential treatments for cartilage degenerative diseases.
Linking animal models to human congenital diaphragmatic hernia
Authors: Beurskens Niels , Klaassens Merel , Rottier Robbert , de Klein Annelies , Tibboel Dick 
Published: April 2007

AbstractBACKGROUND:Congenital diaphragmatic hernia (CDH) is a major life‐threatening malformation, occurring in approximately 1 in 3,000 live births. Over the years, different animal models have been used to gain insight into the etiology of this complex congenital anomaly and to develop treatment strategies. However, to date the pathogenic mechanism is still not understood, and treatment remains difficult because of the associated pulmonary hypoplasia and pulmonary hypertension. METHODS: In this review, data available from several animal models will be discussed. The retinoic acid signaling pathway (RA pathway, retinoid pathway) will be addressed as a developmental pathway that is potentially disrupted in the pathogenesis of CDH. Furthermore, genetic factors involved in diaphragm and lung development will be discussed. CONCLUSIONS: With this review article, we aim to provide a concise overview of the current most important experimental genetic data available in the field of CDH. Birth Defects Research (Part A), 2007. © 2007 Wiley‐Liss, Inc.
Zur Tragfähigkeit unbewehrter Betonwände
Authors: Hegger Josef , Dreßen Tobias , Will Norbert 
Published: April 2007

AbstractDem Nachweis von Druckgliedern aus unbewehrtem Beton nach DIN 1045‐1 liegen vereinfachte Ansätze zugrunde, die bei einer Bemessung bei großer Ausmitte und Schlankheit zu unwirtschaftlichen Querschnittsdicken führen. Im vorliegenden Beitrag wird auf Grundlage der Prinzipien nach DIN 1045‐1 ein Bemessungskonzept für Druckglieder hergeleitet, das eine wirtschaftliche, einfache und normenkonforme Bemessung unbewehrter Querschnitte ermöglicht. Die Berücksichtigung der Betonzugfestigkeit erschließt dabei weitere Traglastreserven.
Kathodischer Korrosionsschutz von Stahl in Beton: Instandsetzung des Parkhauses “Am Gericht” in Frankfurt am Main
Authors: Klein Hans‐H. , Schade Andreas , Eichler Thorsten , Isecke Bernd , Pruckner Franz , Michel Stefan 
Published: April 2007

AbstractDie Instandsetzung von Stahlbetonbauteilen bzw.‐werken, welche durch chloridinduzierte Korrosion der Bewehrung gefährdet oder bereits geschädigt sind, hat in den letzten Jahrzehnten weltweit an Bedeutung gewonnen. Der kathodische Korrosionsschutz, als elektrochemisches Instandsetzungsverfahren, bildet in diesem Fall eine zuverlässige und oftmals kostengünstige Methode zur Instandsetzung. Am Beispiel des Parkhauses “Am Gericht” in Frankfurt am Main werden die Durchführung solch einer Maßnahme sowie die Besonderheiten des Verfahrens beschrieben. Es werden die theoretischen Hintergründe erläutert und die praktische Umsetzung sowie zu klärende Detailfragen beschrieben. Die Daten der ersten Depolarisationsmessungen zeigen den aktuellen Zustand der Anlage sowie des Schutzobjektes.
Activity of human P450 2D6 in biphasic solvent systems
Authors: Zhao Jin , Tan Elaine , Ferras Julian , Auclair Karine 
Published: April 2007

AbstractSeveral limitations have restricted the use of P450 enzymes in synthesis, including the narrow substrate specificity of some P450 isoforms, the need for a redox partner and an expensive cofactor, incompatibility with organic solvents, and poor stability. We previously demonstrated that the natural redox partner and cofactor of the promiscuous P450s 3A4 and 2D6 can be efficiently substituted with some cheap hydrogen peroxide donors or organic peroxides. We report here that P450 2D6 maintains as much as 76% of its activity when used in buffer/organic emulsions. Product formation in biphasic solvent systems is comparable whether the natural redox partner and cofactor are used, or a surrogate. As reported for other enzymes, a correlation is observed between the logPand the suitability of a solvent for enzymatic activity. Moreover, the utility of our system was established by demonstrating the transformation of a novel hydrophobic substrate, not modified by P450 2D6 in the absence of organic solvent. Biotechnol. Bioeng. 2007;98; 508–513. © 2007 Wiley Periodicals, Inc.
InXy and SeXy, compact heterologous reporter proteins for mammalian cells
Authors: Fluri David A. , Kelm Jens M. , Lesage Guillaume , Baba Marie Daoud‐El , Fussenegger Martin 
Published: April 2007

AbstractMammalian reporter proteins are essential for gene‐function analysis, drugscreening initiatives and as model product proteins for biopharmaceutical manufacturing. Bacillus subtilis can maintain its metabolism by secreting Xylanase A (XynA), which converts xylan into shorter xylose oligosaccharides. XynA is a family 11 xylanase monospecific for D‐xylose containing substrates. Mammalian cells transgenic for constitutive expression of wild‐type xynA showed substantial secretion of this prokaryotic enzyme. Deletion analysis confirmed that a prokaryotic signal sequence encoded within the first 81 nucleotides was compatible with the secretory pathway of mammalian cells. Codon optimization combined with elimination of the prokaryotic signal sequence resulted in an exclusively intracellular mammalian Xylanase A variant (InXy) while replacement by an immunoglobulin‐derived secretion signal created an optimal secreted Xylanase A derivative (SeXy). A variety of chromogenic and fluorescence‐based assays adapted for use with mammalian cells detected InXy and SeXy with high sensitivity and showed that both reporter proteins resisted repeated freeze/thaw cycles, remained active over wide temperature and pH ranges, were extremely stable in human serum stored at room temperature and could independently be quantified in samples also containing other prominent reporter proteins such as the human placental alkaline phosphatase (SEAP) and the Bacillus stearothermophilus‐derived secreted α‐amylase (SAMY). Glycoprofiling revealed that SeXy produced in mammalian cells was N‐ glycosylated at four different sites, mutation of which resulted in impaired secretion. SeXy was successfully expressed in a variety of mammalian cell lines and primary cells following transient transfection and transduction with adeno‐associated virus particles (AAV) engineered for constitutive SeXy expression. Intramuscular injection of transgenic AAVs into mice showed significant SeXy levels in the bloodstream. InXy and SeXy are highly sensitive, compact and robust reporter proteins, fully compatible with pre‐existing marker genes and can be assayed in high‐throughput formats using very small sample volumes. Biotechnol. Bioeng. 2007;98:655–667. © 2007 Wiley Periodicals, Inc.