bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti–tumor necrosis factor therapy increases synovial osteoprotegerin expression in rheumatoid arthritis
Authors: Catrina Anca Irinel , Klint Erik af , Ernestam Sofia , Catrina Sergiu‐Bogdan , Makrygiannakis Dimitrios , Botusan Ileana Ruxandra , Klareskog Lars , Ulfgren Ann‐Kristin 
Published: December 2005

AbstractObjectiveTreatment of rheumatoid arthritis (RA) with tumor necrosis factor (TNF)–blocking agents, including etanercept and infliximab, has resulted in reductions in the radiographic progression of RA. However, the exact mechanism by which this protection occurs has not been determined. In order to add to such knowledge, we investigated the effect of anti‐TNF therapy on the expression of osteoprotegerin (OPG) and receptor activator of NF‐κB ligand (RANKL) in synovial tissue.MethodsThe expression of OPG and RANKL in synovial biopsy specimens was evaluated by immunohistochemistry. Serial synovial biopsy specimens were obtained from 18 patients with RA, before and after treatment with etanercept (9 patients) or infliximab (9 patients). Biopsy specimens were evaluated by double‐blind semiquantitative analysis and image analysis. The in vitro effect of TNF antagonists on the RANKL/OPG expression in osteoblasts and endothelial cells was evaluated by Western blotting. Statistical analysis was performed using Wilcoxon's signed rank test, followed by the Bonferroni correction for multiple comparisons of paired samples. The results of in vitro experiments were evaluated by one‐way analysis of variance, with Tukey's post hoc test.ResultsTreatment with both infliximab and etanercept increased the expression of OPG in synovial tissue. After 8 weeks of treatment, neither infliximab nor etanercept influenced RANKL expression. In both groups of patients, the RANKL:OPG ratio decreased following therapy. In vitro, both of the TNF antagonists mimicked the in vivo effect, inducing a decrease in the RANKL:OPG ratio in TNF‐primed osteoblasts and endothelial cells.ConclusionTherapy with TNF antagonists in RA modulates the OPG/RANKL system, a potential mechanism that could explain the retardation of radiographic damage observed following anti‐TNF therapy.
Polymorphisms in the mannose‐binding lectin gene as determinants of age‐defined risk of coronary artery lesions in Kawasaki disease
Authors: Biezeveld Maarten H. , Geissler Judy , Weverling Gerrit Jan , Kuipers Irene M. , Lam Jan , Ottenkamp Jaap , Kuijpers Taco W. 
Published: December 2005

AbstractObjectiveTo evaluate the relationship between polymorphisms in the gene coding for mannose‐binding lectin (MBL) and the occurrence of coronary artery lesions (CALs) among different age groups of patients with Kawasaki disease.MethodsThe frequencies of the genotypes, defined as mutations in codons 52, 54, and 57, and the functional promoter variants of the MBL2 gene were determined in 88 patients with acute Kawasaki disease (median age at onset 1.9 years). The possible influence of the MBL2 genotype on the development and progression of CALs in Kawasaki disease was assessed according to age categories and MBL genotypes in univariate and multivariate analyses.ResultsIn patients younger than age 1 year, we found an increased risk of developing CALs in the presence of a variant MBL2 genotype (P = 0.008). In contrast, in patients older than age 1 year, we found an increased risk of CALs in those patients with the wild‐type genotype (P = 0.005).ConclusionOur findings indicate that MBL has an ambiguous role in Kawasaki disease and contributes differently to the pathophysiologic development of CALs, being protective in infants but potentially harmful in patients of older age. The data also imply that the standard treatment of intravenous immunoglobulins to reduce the development of lesions may not be as effective in the very young as it is in the older patients. For the very young, alternative or adjuvant treatment may be indicated, particularly in infants who are MBL‐deficient.
Associations between pain, function, and radiographic features in osteoarthritis of the knee
Authors: Szebenyi Béla , Hollander Anthony P. , Dieppe Paul , Quilty Brian , Duddy John , Clarke Shane , Kirwan John R. 
Published: December 2005

AbstractObjectiveTo assess the associations between pain, loss of function, and radiographic changes in knee osteoarthritis (OA), taking into account both the patellofemoral and tibiofemoral compartments.MethodsBoth knees of 167 community‐based patients with OA in at least 1 of their knees were assessed. Pain was measured by visual analog scale, and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index. Anteroposterior standing radiographs with the knee in extension and lateral 30° flexion were obtained and assessed for the Kellgren/Lawrence score and for individual features (osteophytes, joint space narrowing, and subchondral bone sclerosis) in each compartment.ResultsKnees with structural changes in both compartments were more likely to be painful and to be associated with loss of function than were knees in which only 1 compartment was affected. The individual feature most strongly associated with pain was subchondral bone sclerosis.ConclusionStudies exploring the associations between structural and symptomatic knee OA need to include an assessment of the patellofemoral compartment, and individual radiographic features rather than a global severity score should be considered in these studies.
Interleukin‐6 modulates production of T lymphocyte–derived cytokines in antigen‐induced arthritis and drives inflammation‐induced osteoclastogenesis
Authors: Wong Peter K. K. , Quinn Julian M. W. , Sims Natalie A. , van Nieuwenhuijze Annemarie , Campbell Ian K. , Wicks Ian P. 
Published: December 2005

AbstractObjectiveTo determine the cellular mediators of antigen‐induced arthritis (AIA) and the relative contribution of members of the interleukin‐6 (IL‐6) family and tumor necrosis factor (TNF) in AIA.MethodsAIA was induced in mice deficient in T and B lymphocytes, IL‐6 (IL‐6−/−), TNF (TNF−/−), IL‐11 receptor, and oncostatin M receptor, by immunization with methylated bovine serum albumin (mBSA) followed 7 days later by intraarticular injection of mBSA. Arthritis severity was assessed histologically, and T lymphocyte responses were assessed in vitro. Anti‐TNF neutralizing antibody was administered to wild‐type mice during AIA. Bone marrow osteoclasts were generated in vitro via culture with RANKL and macrophage colony‐stimulating factor.ResultsAIA was dependent on CD4+ T lymphocytes, but not CD8+ T lymphocytes or B cells. IL‐6−/− mice had reduced AIA severity and fewer osteoclasts at sites of bone erosion. This protective effect was not seen with a deficiency of other IL‐6 family members and was similar to that in TNF−/− mice or wild‐type mice receiving TNF blockade treatment. IL‐6−/− CD4+ T lymphocytes from draining lymph nodes had reduced antigen‐induced proliferation and produced less IL‐17 and less RANKL, relative to osteoprotegerin, than cells from wild‐type mice. Bone marrow from IL‐6−/− mice generated fewer osteoclasts in vitro than bone marrow from either wild‐type or TNF−/− mice.ConclusionAIA is driven by CD4+ T lymphocytes. IL‐6 is an important mediator of bone destruction in AIA because it regulates T lymphocyte production of key osteoclastogenic cytokines and inflammation‐induced bone marrow osteoclast differentiation. These findings have implications for reducing bone and joint damage in rheumatoid arthritis.
Pulmonary arterial hypertension is a major mortality factor in diffuse systemic sclerosis, independent of interstitial lung disease
Authors: Trad Salim , Amoura Zahir , Beigelman Catherine , Haroche Julien , Costedoat Nathalie , Boutin Le Thi Huong Du , Cacoub Patrice , Frances Camille , Wechsler Bertrand , Grenier Philippe , Piette Jean‐Charles 
Published: December 2005

AbstractObjectiveTo determine whether pulmonary arterial hypertension (PAH) is a prognostic factor for mortality in diffuse cutaneous systemic sclerosis (dcSSc), independent of interstitial lung disease (ILD).MethodsILD was diagnosed by high‐resolution computed tomography and PAH (pulmonary arterial systolic pressure [PASP] ≥45 mm Hg) by echocardiography. All patients with ILD underwent testing for total lung capacity (TLC), forced vital capacity (FVC), and diffusing capacity for carbon monoxide.ResultsEighty‐six patients with dcSSc (mean age at diagnosis 44.5 years) were followed up for a median of 72.5 months. ILD was found in 52 patients (60%) and PAH in 18 (21%). ILD was associated with PAH in 15 patients. Seventeen patients died (19.8%), 9 of whom had PAH (P = 0.001) and 10 of whom had ILD (P = 0.99). By multivariate analysis, age at SSc diagnosis and PAH were the only independent predictors of death (hazard ratio [HR] 1.057, 95% confidence interval [95% CI] 1.009–1.109, P = 0.020 and HR 4.09, 95% CI 1.47–11.5, P = 0.007, respectively). Mean TLC and mean FVC were similar in ILD patients with and those without PAH (P = 0.71 and P = 0.40, respectively). Among ILD patients, age at SSc diagnosis and PAH were again the sole predictors of death (HR 1.073, 95% CI 1.003–1.149, P = 0.042 and HR 5.07, 95% CI 1.09–23.8, P = 0.038, respectively). Twenty ILD patients received at least 6 monthly pulses of intravenous cyclophosphamide (CYC). In CYC‐treated patients with PAH (n = 8), PASP increased significantly during the CYC regimen (mean ± SD 55 ± 14.5 mm Hg; P = 0.015 versus baseline), while TLC remained stable during the same period.ConclusionThese results indicate that, independent of ILD, PAH is a major prognostic factor for survival in dcSSc.
Accuracy of anti–ribosomal P protein antibody testing for the diagnosis of neuropsychiatric systemic lupus erythematosus: An international meta‐analysis
Authors: Karassa Fotini B. , Afeltra Antonella , Ambrozic Ales , Chang Deh‐Ming , De Keyser Filip , Doria Andrea , Galeazzi Mauro , Hirohata Shunsei , Hoffman Ilse E. A. , Inanc Murat , Massardo Loreto , Mathieu Alessandro , Mok Chi Chiu , Morozzi Gabriella , Sanna Giovanni , Spindler Alberto J. , Tzioufas Athanasios G. , Yoshio Taku , Ioannidis John P. A. 
Published: December 2005

AbstractObjectiveTo quantitatively evaluate the diagnostic accuracy of antibodies to ribosomal P proteins (anti‐P) for neuropsychiatric systemic lupus erythematosus (NPSLE) in general, for psychosis, mood disorder, or both, and for other diffuse manifestations.MethodsThis international meta‐analysis combined standardized data from 1,537 lupus patients contributed by 14 research teams. Weighted estimation of sensitivity and specificity with fixed‐effects and random‐effects models, as well as summary receiver operating characteristic (SROC) curve analysis, was used to summarize test performance. The robustness of the overall estimates was examined in sensitivity analyses that included additional studies published up to November 1, 2004 in the Medline, EMBase, and Cochrane databases.ResultsCombining the data from the 14 teams, the weighted sensitivity and specificity estimates for the diagnosis of NPSLE were 26% (95% confidence interval [95% CI] 15–42%) and 80% (95% CI 74–85%), respectively. For psychosis, mood disorder, or both, the sensitivity and specificity were 27% (95% CI 14–47%) and 80% (95% CI 74–85%), respectively. For other diffuse manifestations, the sensitivity was 24% (95% CI 12–42%), and the specificity was 80% (95% CI 73–85%). The proportion of patients with anti‐P antibodies did not vary markedly across different presentations of NPSLE. Between‐study heterogeneity was substantial, but the SROC curves were consistent with the weighted estimates. In further analyses that included another 24 published studies, only the sensitivity for psychosis and/or mood disorder was slightly improved, but it was still suboptimal (42% [95% CI 30–53%]); the specificity remained essentially the same (81% [95% CI 76–85%]).ConclusionAnti‐P antibody testing has limited diagnostic value for NPSLE, and it is not helpful in differentiating among various disease phenotypes.
Zum Tragverhalten flacher Schalentragwerke unter Kriechbeanspruchung
Authors: Bockhold Jörg 
Published: December 2005

AbstractDie wirklichkeitsnahe Vorhersage des Tragverhaltens von Schalentragwerken aus Stahlbeton stellt nach wie vor einen hohen Anspruch an den planenden Ingenieur. In diesem Beitrag werden beispielhaft anhand einer flachen zylindrischen Dachschale die unterschiedlichen Einflüsse auf die Langzeittragfähigkeit beulgefährdeter Strukturen vorgestellt und auf die besondere Bedeutung des Betonkriechens im Hinblick auf ein Dauerstandversagen des Tragwerkes hingewiesen.
Tragverhalten von Kunststoffdübeln in gerissenem Beton
Authors: Pregartner Thilo , Eligehausen Rolf 
Published: December 2005

AbstractKunststoffdübel bestehen aus einer Dübelhülse aus Kunststoff und einem Spreizelement aus Stahl. Das Spreizelement wird drehend oder schlagend in die Kunststoffhülse eingetrieben. Dabei wird dem Kunststoff eine radiale Dehnung aufgeprägt.Das viskoelastische Verformungsverhalten des Kunststoffes beeinflußt stark das Tragverhalten von Kunststoffdübeln in ungerissenem und gerissenem Beton. In ungerissenem Beton nimmt die Spreizkraft mit zunehmender Zeit infolge Relaxation des Kunststoffes ab. Ein Riß, der durch die Achse des Bohrlochs eines Kunststoffdübels läuft, reduziert die Spreizkraft des Dübels weiter. Bei konstanter Rißbreite nimmt die Spreizkraft des Dübels mit zunehmender Zeit nach der Rißöffnung jedoch wieder zu. Der Reibkoeffizient zwischen Dübelhülse und Beton steigt im ungerissenen und gerissenen Beton mit der Zeit an. Dadurch wachsen auch die Herausziehlasten im gerissenen und ungerissenen Beton mit der Zeit an.
Zur Torsionsbemessung von Stahlbeton‐ und Spannbetonbalken nach DIN 1045‐1
Authors: Zedler Thomas , Stangenberg Friedhelm 
Published: December 2005

AbstractFür die Torsionsbemessung ist nach DIN 1045‐1 neben einer Ermittlung des Druckstrebenwinkels nach Gl. (73) auch der vereinfachte Ansatz eines Neigungswinkels von 45° zulässig. Untersuchungen zeigten, daß bei bestimmten Belastungskombinationen die beiden Verfahren nicht alternativ angewandt werden sollten. Zudem zeigt sich eine generelle Überschätzung der Druckstrebentragfähigkeit unter Torsion nach DIN 1045‐1.Vor dem Hintergrund dieser Ergebnisse werden ein Vorschlag zur Bestimmung des Druckstrebenwinkels für die Torsions‐ und Torsions‐Interaktionsbemessung sowie ein Ansatz zur Beschreibung der Geometrie des effektiven Hohlkastens vorgestellt. Vergleichend werden die Ergebnisse einer Auswertung der Datenbank nach Eurocode 2 in seiner Neufassung vom April 2002 dargestellt.
Die Massivbaukonstruktion der Frankfurter Commerzbank‐Arena
Authors: Retzepis Ioannis , Beier Gunther , Constantinescu Dan 
Published: December 2005

AbstractDie Massivbaukonstruktion der Frankfurter Commerzbank‐Arena (vormals Waldstadion) ist weitgehend eine Fertigteilkonstruktion. Dies war primär aus Bauzeitgründen notwendig und sicherte gleichzeitig die geforderte hohe Qualität der Sichtbetonoberflächen. Außerdem durfte während der Bauarbeiten der Spielbetrieb nicht beeinträchtigt werden. Diese Bedingungen haben das Konzept der gesamten Konstruktion maßgeblich beeinflußt. Der Aufsatz beschreibt die Grundlagen des Tragsystems der Tribünen – die auch die Dachlasten abtragen – und der weiteren Massivkonstruktionen (Medientürme, Tiefgarage usw.), insbesondere die Abtragung der Vertikal‐ und Horizontallasten sowie die statisch‐konstruktive Ausbildung der Fertigteile und deren Anschlüsse.
Umbau der Stadthalle Bremen zum AWD‐Dome
Authors: Eisele Manfred , Bachmann Hubert 
Published: December 2005

AbstractDie im Jahr 1964 erstellte Stadthalle in Bremen wurde zur Vergrößerung des Fassungsvermögens umgestaltet. Nach Abbruch der Giebelwände und des zwischen Nord‐ und Südböcken aufgespannten Hängedachs, werden an der Nord‐ und Südseite zusätzliche Zuschauertribünen über den bestehenden eingebaut und ein neues Dach aus Stahl‐Fachwerk‐Bindern aufgesetzt. Die ausführende Firma beschließt, die neuen Giebelwände in Stahlbetonfertigteil‐Bauweise zu erstellen. Der Aufsatz beschreibt die ungewöhnlichen statischen Systeme und aufwendigen Detaillösungen. Durch eine lange Planungsphase und den hohen Vorfertigungsgrad war eine kurze Bauzeit realisierbar.
Isostructurality, Polymorphism and Mechanical Properties of Some Hexahalogenated Benzenes: The Nature of Halogen⋅⋅⋅Halogen Interactions
Authors: Reddy C. Malla , Kirchner Michael T. , Gundakaram Ravi C. , Padmanabhan K. Anantha , Desiraju Gautam R. 
Published: December 2005

AbstractThe nature of intermolecular interactions between halogen atoms, X⋅⋅⋅X (X=Cl, Br, I), continues to be of topical interest because these interactions may be used as design elements in crystal engineering. Hexahalogenated benzenes (C6Cl6−nBrn, C6Cl6−nIn, C6Br6−nIn) crystallise in two main packing modes, which take the monoclinic space group P21/n and the triclinic space group P$\bar 1$. The former, which is isostructural to C6Cl6, is more common. For molecules that lack inversion symmetry, adoption of this monoclinic structure would necessarily lead to crystallographic disorder. In C6Cl6, the planar molecules form Cl⋅⋅⋅Cl contacts and also π⋅⋅⋅π stacking interactions. When crystals of C6Cl6 are compressed mechanically along their needle length, that is, [010], a bending deformation takes place, because of the stronger interactions in the stacking direction. Further compression propagates consecutively in a snakelike motion through the crystal, similar to what has been suggested for the motion of dislocations. The bending of C6Cl6 crystals is related to the weakness of the Cl⋅⋅⋅Cl interactions compared with the stronger π⋅⋅⋅π stacking interactions. The triclinic packing is less common and is restricted to molecules that have a symmetrical (1,3,5‐ and 2,4,6‐) halogen substitution pattern. This packing type is characterised by specific, polarisation‐induced X⋅⋅⋅X interactions that result in threefold‐symmetrical X3 synthons, especially when X=I; this leads to a layered pseudohexagonal structure in which successive planar layers are inversion related and stacked so that bumps in one layer fit into the hollows of the next in a space‐filling manner. The triclinic crystals shear on application of a mechanical stress only along the plane of deformation. This shearing arises from the sliding of layers against one another. Nonspecificity of the weak interlayer interactions here is demonstrated by the structure of twinned crystals of these compounds. One of the compounds studied (1,3,5‐tribromo‐2,4,6‐triiodobenzene) is dimorphic, adopting both the monoclinic and triclinic structures, and the reasons for polymorphism are suggested. To summarise, both chemical and geometrical models need to be considered for X⋅⋅⋅X interactions in hexahalogenated benzenes. The X⋅⋅⋅X interactions in the monoclinic group are nonspecific, whereas in the triclinic group some X⋅⋅⋅X interactions are anisotropic, chemically specific and crystal‐structure directing.
Substituted Isoxazoles as Potent Inhibitors of p38 MAP Kinase
Authors: Laufer Stefan A. , Margutti Simona , Fritz Martina D. 
Published: December 2005

AbstractIn a continuous effort to develop improved p38 MAP (mitogen‐activated protein) kinase inhibitors, we focused our attention on the suitability of the isoxazole ring as a bioisosteric replacement for the imidazole ring of SB‐203580. 3,4‐ and 4,5‐disubstituted as well as 3,4,5‐trisubstituted isoxazole derivatives were synthesized. These compounds were tested in an in vitro enzyme‐linked immunosorbent assay of isolated p38 MAP kinase and for inhibitory potency against cytochrome P450. Compound 4 a displays a highly promising profile for development as an anti‐inflammatory agent owing to its enhanced suppression of cytokine release, decreased affinity for cytochrome P450 and a twofold decrease in IC50 toward isolated p38 MAP kinase.
MS‐Binding Assays: Kinetic, Saturation, and Competitive Experiments Based on Quantitation of Bound Marker as Exemplified by the GABA Transporter mGAT1
Authors: Zepperitz Christine , Höfner Georg , Wanner Klaus T. 
Published: December 2005

AbstractA new kind of binding assay is described in which the amount of a nonlabeled marker bound to the target is quantified by LC–ESI‐MS–MS. This new approach was successfully implemented with nonlabeled NO 711 as marker and the GABA transporter subtype mGAT1 as target. The native marker bound to the target was liberated from the receptor protein by methanol denaturation after filtration. A reliable and sensitive LC–ESI‐MS–MS method for the quantitation of NO 711 was developed, and data from mass spectrometric detection were analyzed by nonlinear regression. Kinetic MS‐binding experiments yielded values for k+1 and k−1, while in saturation MS‐binding experiments, Kd and Bmax values were determined. In competitive MS‐binding experiments, Ki values were obtained for various test compounds covering a broad range of affinities for mGAT1. All experiments were performed in 96‐well plate format with a filter plate for the separation step which improved the efficiency and throughput of the procedure. The method was validated by classical radioligand‐binding experiments with the labeled marker [3H2]NO 711 in parallel. The results obtained from MS‐binding experiments were found to be in good agreement with the results of the radioligand‐binding assays. The new kind of MS‐binding assay presented herein is further adapted to the conventional radioligand‐binding assay in that the amount of bound marker is securely quantified. This promises easy implementation in accordance with conventional binding assays without the major drawbacks that are inherent in radioligand or fluorescence binding assays. Therefore, MS‐binding assays are a true alternative to classical radioligand‐binding assays.
Individual‐, neighborhood‐, and state‐level socioeconomic predictors of cervical carcinoma screening among U.S. black women
Authors: Datta Geetanjali D. , Colditz Graham A. , Kawachi Ichiro , Subramanian S.V. , Palmer Julie R. , Rosenberg Lynn 
Published: December 2005

AbstractBACKGROUNDCervical carcinoma is the fifth most common cancer among African American women in the U.S. Although the Papanicolaou (Pap) smear is an efficacious screening tool in the early detection of the disease, disparities are known to persist in the utilization of this procedure across socioeconomic groups.METHODSData regarding cervical carcinoma screening and covariates were obtained from the 59,090 Black Women's Health Study participants across the U.S. via a mailed questionnaire in 1995. Logistic regression and multilevel techniques were used to assess the independent effects of the covariates on nonrecent cervical carcinoma screening.RESULTSIn all, 8.3% of the 40,009 women in the present analysis had not undergone a Pap smear examination within the previous 2 years (nonrecent screening). Lower educational attainment, older age, obesity, smoking, and neighborhood poverty were found to be independently related to increased risk of nonrecent screening. The adjusted odds ratio for nonrecent screening was 1.2 (95% confidence interval [95% CI], 1.1–1.4) for women residing in neighborhoods with 20% or more poverty compared with those in neighborhoods with less than 5% poverty. State of residence was also associated with nonrecent cervical carcinoma screening.CONCLUSIONThese results suggest that among black women, residence in high‐poverty (20%) neighborhoods is associated with an increased risk of nonrecent cervical carcinoma screening, independent of individual level risk factors. Cancer 2006. © 2005 American Cancer Society.