bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon‐regulated chemokines as biomarkers of systemic lupus erythematosus disease activity: A validation study
Authors: Bauer Jason W. , Petri Michelle , Batliwalla Franak M. , Koeuth Thearith , Wilson Joseph , Slattery Catherine , Panoskaltsis‐Mortari Angela , Gregersen Peter K. , Behrens Timothy W. , Baechler Emily C. 
Published: September 2009

AbstractObjectiveSystemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by unpredictable flares of disease activity and irreversible damage to multiple organ systems. An earlier study showed that SLE patients carrying an interferon (IFN) gene expression signature in blood have elevated serum levels of IFN‐regulated chemokines. These chemokines were associated with more‐severe and active disease and showed promise as SLE disease activity biomarkers. This study was designed to validate IFN‐regulated chemokines as biomarkers of SLE disease activity in 267 SLE patients followed up longitudinally.MethodsTo validate the potential utility of serum chemokine levels as biomarkers of disease activity, we measured serum levels of CXCL10 (IFNγ‐inducible 10‐kd protein), CCL2 (monocyte chemotactic protein 1), and CCL19 (macrophage inflammatory protein 3β) in an independent cohort of 267 SLE patients followed up longitudinally over 1 year (1,166 total clinic visits).ResultsSerum chemokine levels correlated with lupus activity at the current visit (P = 2 × 10−10), rising at the time of SLE flare (P = 2 × 10−3) and decreasing as disease remitted (P = 1 × 10−3); they also performed better than the currently available laboratory tests. Chemokine levels measured at a single baseline visit in patients with a Systemic Lupus Erythematosus Disease Activity Index of ≤4 were predictive of lupus flare over the ensuing year (P = 1 × 10−4).ConclusionMonitoring serum chemokine levels in SLE may improve the assessment of current disease activity, the prediction of future disease flares, and the overall clinical decision‐making.
Association of immunoglobulin‐like transcript 6 deficiency with Sjögren's syndrome
Authors: Kabalak G. , Dobberstein S. B. , Matthias T. , Reuter S. , The Y.‐H. , Dörner T. , Schmidt R. E. , Witte T. 
Published: September 2009

AbstractObjectiveThe immunoglobulin‐like transcript (ILT) family is located in chromosomal region 19q13 and consists of a group of activating and inhibitory receptors. The ILT receptors are expressed on antigen‐presenting cells (macrophages, dendritic cells, B lymphocytes), as well as on T cells and natural killer cells. ILT2 and ILT4 play a role in tolerance induction, and ILT3 has been shown to induce Treg cells. A homozygous deletion of ILT6 has been shown to be associated with multiple sclerosis. Since ILT6 may be a modulator of the immune system, we undertook this study to examine the association of ILT6 deficiency with Sjögren's syndrome (SS).MethodsWe genotyped 149 patients with SS and 749 healthy controls, using polymerase chain reaction to test for the presence or absence of ILT6.ResultsHomozygous ILT6 deficiency was detected in 8% of SS patients and in only 3% of controls.ConclusionOur findings indicate that ILT6 deficiency may be a genetic risk factor for SS.
Association of functional outcome with both personal‐ and area‐level socioeconomic inequalities in patients with inflammatory polyarthritis
Authors: Harrison Mark J. , Farragher Tracey M. , Clarke Alexandra M. , Manning Stephanie C. , Bunn Diane K. , Symmons Deborah P. M. 
Published: September 2009

AbstractObjectiveTo describe the relationship between baseline area‐ and person‐level social inequalities and functional disability at 3 years in patients with early inflammatory polyarthritis (IP).MethodsA total of 1,393 patients with new‐onset IP were recruited and allocated an Index of Multiple Deprivation (IMD) 2004 score based on their area of residence, and a social class based on baseline self‐reported occupation. Differences in the Health Assessment Questionnaire (HAQ) score at baseline and 3 years by IMD or social class were tested. The mean 3‐year change in HAQ score was compared by IMD and social class, and interactions between these measures examined.ResultsPatients from more deprived areas had poorer 3‐year HAQ outcome than those from less deprived areas (P = 0.019, adjusted for baseline HAQ score, age, sex, and symptom duration). The mean difference in HAQ change was most notable between the most deprived (IMD4) and least deprived areas (IMD1) (0.22; 95% confidence interval [95% CI] 0.11, 0.34). There was also a significant difference in HAQ score change between patients of the highest (SCI and II) and lowest social class (SCIV and V) (0.11; 95% CI 0.02, 0.20). For the mean (95% CI) 3‐year change in HAQ score, a significant interaction exists between IMD score and social class and their association with HAQ scores (P = 0.001) to modify outcome: IMD1/SC I and II −0.23 (95% CI −0.40, −0.06) versus IMD 4/SC IV and V 0.15 (95% CI −0.05, 0.34).ConclusionPerson‐ and area‐level inequalities combine to modify outcome for rheumatoid arthritis. A person's social circumstance and residential environment have independent effects on outcome and are not just alternative measures of the same exposure.
The melanocortin system in articular chondrocytes: Melanocortin receptors, pro‐opiomelanocortin, precursor proteases, and a regulatory effect of α‐melanocyte–stimulating hormone on proinflammatory cytokines and extracellular matrix components
Authors: Grässel Susanne , Opolka Alfred , Anders Sven , Straub Rainer H. , Grifka Joachim , Luger Thomas A. , Böhm Markus 
Published: September 2009

AbstractObjectiveThe pro‐opiomelanocortin (POMC)–derived neuropeptide α‐melanocyte–stimulating hormone (α‐MSH) mediates its effects via melanocortin (MC) receptors. This study was carried out to investigate the expression patterns of the MC system and the effects of α‐MSH in human articular chondrocytes.MethodsArticular chondrocytes established from human osteoarthritic joint cartilage were analyzed by reverse transcription–polymerase chain reaction (RT‐PCR) and Western blotting for the expression of MC receptors, POMC, and prohormone convertases (PCs). MC‐1 receptor (MC‐1R) expression in articular cartilage was further studied by immunohistochemistry. Ca2+ and cAMP assays were used to monitor α‐MSH signaling, while studies of α‐MSH function were performed in cultures with chondrocyte micromass pellets stimulated with α‐MSH. Expression of cytokines and extracellular matrix (ECM) components was determined by real‐time RT‐PCR, Western immunoblotting, and enzyme‐linked immunosorbent assays.ResultsMC‐1R expression was detected in articular chondrocytes in vitro and in articular cartilage in situ. In addition, expression of transcripts for MC‐2R, MC‐5R, POMC, and PCs was detected in articular chondrocytes. Stimulation with α‐MSH increased the levels of intracellular cAMP, but not Ca2+, in chondrocytes. Both messenger RNA and protein expression of various proinflammatory cytokines, collagens, matrix metalloproteinases (MMPs), and SOX9 was modulated by α‐MSH.ConclusionHuman articular chondrocytes are target cells for α‐MSH. The effects of α‐MSH on expression of cytokines and MMPs suggest that this neuropeptide plays a role in inflammatory and degenerative processes in cartilage. It is conceivable that inflammatory reactions can be mitigated by the induction of endogenous MCs or administration of α‐MSH to the affected joints. The induction pattern of regulatory and structural ECM components such as collagens as well as SOX9 and anabolic and catabolic cytokines points to a function of α‐MSH as a trophic factor in skeletal development during endochondral ossification rather than as a factor in homeostasis of permanent cartilage.
Continuous occurrence of both insufficient neovascularization and elevated vascular permeability in rabbit proximal femur during inadequate repair of steroid‐associated osteonecrotic lesions
Authors: Zhang Ge , Sheng Hui , He Yi‐Xin , Xie Xin‐Hui , Wang Yi‐Xiang , Lee Kwong‐Man , Yeung Ka‐Wai , Li Zi‐Rong , He Wei , Griffith James F. , Leung Kwok‐Sui , Qin Ling 
Published: September 2009

AbstractObjectiveTo examine the features of the intraosseous vasculature, the size of the marrow stem cell pool (MSCP), and expression of vascular endothelial growth factor A (VEGF) during inadequate repair of steroid‐associated osteonecrotic lesions in rabbits.MethodsSteroid‐associated osteonecrosis was induced in male rabbits. At 0, 1, 2, 4, and 6 weeks postinduction, vascularization and permeability indices were quantified by dynamic magnetic resonance imaging (MRI). In addition, the size of the MSCP in the hematopoietic and mesenchymal compartments was determined, and marrow mononuclear cells expressing specific surface markers for endothelial progenitor cells or periendothelial mural precursor cells were counted. At various time points after the rabbits were killed, the proximal femora were dissected to examine the intraosseous vasculature by angiography, histomorphometry, and ultramorphology. In addition, osteonecrotic lesion repair and marrow VEGF expression were evaluated.ResultsLesion formation without repair was observed at 2 weeks after induction of steroid‐associated osteonecrosis. Rabbits displaying destructive repair (DR+) and those displaying reparative osteogenesis (DR−) from 4 weeks to 6 weeks postinduction were identified. From week 2 to week 6, the vascularization index was significantly lower in DR+ rabbits compared with DR− rabbits, whereas the permeability index was significantly higher in DR+ rabbits compared with DR− rabbits. The features of the intraosseous vasculature determined by angiography, histomorphometry, and ultramorphology were consistent with those determined by dynamic MRI. The MSCP size and number of marrow mononuclear cells expressing specific surface markers were all significantly lower in DR+ rabbits than in DR− rabbits from week 1 to week 6. The increased VEGF expression at 2 weeks was maintained through week 6 in DR+ rabbits, whereas VEGF expression decreased in DR− rabbits from week 2 to week 6.ConclusionContinuous occurrence of both insufficient neovascularization and elevated vascular permeability is accompanied by a continuously low‐ level MSCP and uncontrolled VEGF expression during inadequate repair of steroid‐associated osteonecrotic lesions.
Elevated insular glutamate in fibromyalgia is associated with experimental pain
Authors: Harris Richard E. , Sundgren Pia C. , Craig A. D. , Kirshenbaum Eric , Sen Ananda , Napadow Vitaly , Clauw Daniel J. 
Published: September 2009

AbstractObjectiveCentral pain augmentation resulting from enhanced excitatory and/or decreased inhibitory neurotransmission is a proposed mechanism underlying the pathophysiology of functional pain syndromes such as fibromyalgia (FM). Multiple functional magnetic resonance imaging studies implicate the insula as a region of heightened neuronal activity in this condition. Since glutamate (Glu) is a major cortical excitatory neurotransmitter that functions in pain neurotransmission, we undertook this study to test our hypothesis that increased levels of insular Glu would be present in FM patients and that the concentration of this molecule would be correlated with pain report.MethodsNineteen FM patients and 14 age‐ and sex‐matched pain‐free controls underwent pressure pain testing and a proton magnetic resonance spectroscopy session in which the right anterior insula and right posterior insula were examined at rest.ResultsCompared with healthy controls, FM patients had significantly higher levels of Glu (mean ± SD 8.09 ± 0.72 arbitrary institutional units versus 6.86 ± 1.29 arbitrary institutional units; P = 0.009) and combined glutamine and Glu (i.e., Glx) (mean ± SD 12.38 ± 0.94 arbitrary institutional units versus 10.59 ± 1.48 arbitrary institutional units; P = 0.001) within the right posterior insula. No significant differences between groups were detected in any of the other major metabolites within this region (P > 0.05 for all comparisons), and no group differences were detected for any metabolite within the right anterior insula (P > 0.11 for all comparisons). Within the right posterior insula, higher levels of Glu and Glx were associated with lower pressure pain thresholds across both groups for medium pain (for Glu, r = −0.43, P = 0.012; for Glx, r = −0.50, P = 0.003).ConclusionEnhanced glutamatergic neurotransmission resulting from higher concentrations of Glu within the posterior insula may play a role in the pathophysiology of FM and other central pain augmentation syndromes.
Prevalence of and screening for serious spinal pathology in patients presenting to primary care settings with acute low back pain
Authors: Henschke Nicholas , Maher Christopher G. , Refshauge Kathryn M. , Herbert Robert D. , Cumming Robert G. , Bleasel Jane , York John , Das Anurina , McAuley James H. 
Published: September 2009

AbstractObjectiveTo determine the prevalence of serious pathology in patients presenting to primary care settings with acute low back pain, and to evaluate the diagnostic accuracy of recommended “red flag” screening questions.MethodsAn inception cohort of 1,172 consecutive patients receiving primary care for acute low back pain was recruited from primary care clinics in Sydney, Australia. At the initial consultation, clinicians recorded responses to 25 red flag questions and then provided an initial diagnosis. The reference standard was a 12‐month followup supplemented with a specialist review of a random subsample of participants.ResultsThere were 11 cases (0.9%) of serious pathology, including 8 cases of fracture. Despite the low prevalence of serious pathology, most patients (80.4%) had at least 1 red flag (median 2, interquartile range 1–3). Only 3 of the red flags for fracture recommended for use in clinical guidelines were informative: prolonged use of corticosteroids, age >70 years, and significant trauma. Clinicians identified 5 of the 11 cases of serious pathology at the initial consultation and made 6 false‐positive diagnoses. The status of a diagnostic prediction rule containing 4 features (female sex, age >70 years, significant trauma, and prolonged use of corticosteroids) was moderately associated with the presence of fracture (the area under the curve for the rule score was 0.834 [95% confidence interval 0.654–1.014]; P = 0.001).ConclusionIn patients presenting to a primary care provider with back pain, previously undiagnosed serious pathology is rare. The most common serious pathology observed was vertebral fracture. Approximately half of the cases of serious pathology were identified at the initial consultation. Some red flags have very high false‐positive rates, indicating that, when used in isolation, they have little diagnostic value in the primary care setting.
Estrone/17β‐estradiol conversion to, and tumor necrosis factor inhibition by, estrogen metabolites in synovial cells of patients with rheumatoid arthritis and patients with osteoarthritis
Authors: Schmidt Martin , Hartung Regina , Capellino Silvia , Cutolo Maurizio , Pfeifer‐Leeg Antje , Straub Rainer H. 
Published: September 2009

AbstractObjectiveThe role of estrogens in rheumatoid arthritis (RA) is debated since both proinflammatory and antiinflammatory effects have been reported. Important evidence of the dual role of estrogens is conversion to various proinflammatory or antiinflammatory metabolites. This study was undertaken to examine the downstream conversion of estrogens in synovial cells from patients with RA or osteoarthritis (OA).MethodsWe studied serum levels of estrone, estrone sulfate, and estrone sulfate membrane transporters, intracellular interconversion of estrone and 17β‐estradiol, and conversion of estrone/17β‐estradiol to various estrogen metabolites in RA and OA synovial cells. The effect of estrogen metabolites on tumor necrosis factor (TNF) secretion was also studied in RA and OA synovial cells.ResultsSerum levels of estrone sulfate were similar in healthy controls and RA patients. Estrone sulfate transporters were present in synovial tissue. Interconversion of estrone and 17β‐estradiol and the expression of converting enzymes of the cytochrome P450 family were similar in RA and OA cells. Using estrone and 17β‐estradiol as substrates, RA and OA synovial cells produced 16α‐, 4‐, and 2‐hydroxylated estrogens and their 4‐ and 2‐methylation products. The levels of 16α‐hydroxylated estrone/17β‐estradiol (16αOH‐estrone/16αOH‐17β‐estradiol) were higher than the levels of all other estrogen metabolites. RA synovial cells produced more 16αOH‐estrone than did OA synovial cells. Importantly, the 16αOH estrogens did not inhibit TNF secretion, whereas all other estrogen metabolites had marked inhibitory effects.ConclusionOur findings indicate that precursor estrogens are converted to proinflammatory metabolites, particularly in RA synovial cells. RA synovial cells mainly produce the proproliferative 16αOH‐estrone, which, in addition to 16αOH‐17β‐estradiol, is one of the only 2 estrogens studied that does not inhibit TNF secretion. A preponderance of 16α‐hydroxylated estrogens is an unfavorable sign in synovial inflammation.
Soluble neuropilin‐2, a nerve repellent receptor, is increased in rheumatoid arthritis synovium and aggravates sympathetic fiber repulsion and arthritis
Authors: Fassold Alexander , Falk Werner , Anders Sven , Hirsch Thomas , Mirsky Vladimir M. , Straub Rainer H. 
Published: September 2009

AbstractObjectiveIn inflammatory lesions, sympathetic nerve fibers disappear soon after the start of inflammation. We identified sympathetic nerve repellents as possible causal agents in rheumatoid arthritis (RA). On nerve terminals, repellent factors bind to neuropilin‐2 and its coreceptor. The aim of this study was to investigate the role of neuropilin‐2 in the synovial tissue of patients with RA and patients with osteoarthritis (OA) and in experimental arthritis.MethodsThe density of neuropilin‐2–positive fibers and cells positive for semaphorin 3F (a sympathetic repellent) was investigated using immunofluorescence staining. Enzyme‐linked immunosorbent assay was used to detect soluble neuropilin‐2 in body fluids from patients with RA and patients with OA. An axon outgrowth assay and a neuropilin‐2 Fc fusion construct (neuropilin‐2Fc) were used to investigate semaphorin 3F–induced sympathetic nerve repulsion. In an animal model of type II collagen–induced arthritis, soluble neuropilin‐2Fc was studied in vivo.ResultsThe synovial density of neuropilin‐2–positive sympathetic nerve fibers was lower in RA than in OA, but the density of cells positive for semaphorin 3F was similar. In synovial fluid, the level of soluble neuropilin‐2 was markedly higher in RA compared with OA. Mouse sympathetic ganglia served as an excellent model with which to study semaphorin 3F–induced nerve fiber repulsion. Neuropilin‐2 and its coreceptor were present on sympathetic neurons, and semaphorin 3F bound to neuropilin‐2Fc (binding constant 96 nmoles/liter). Semaphorin 3F dose‐dependently increased sympathetic nerve fiber repulsion (at a 50% maximum response concentration of 160–210 nmoles/liter). In contrast to our expectations, soluble neuropilin‐2Fc did not inhibit repulsion but increased the repellent effect of semaphorin 3F. In experimental arthritis, therapy with neuropilin‐2Fc aggravated arthritis.ConclusionSoluble neuropilin‐2 has no antirepellent activity but aggravates sympathetic nerve fiber repulsion and arthritis. Increased shedding of neuropilin‐2 is probably an unfavorable sign in RA.
Reversible Mechanical Induction of Optical Activity in Solutions of Soft‐Matter Nanophases
Authors: Arteaga Oriol , Escudero Carlos , Oncins Gerard , El‐Hachemi Zoubir , Llorens Joan , Crusats Joaquim , Canillas Adolf , Ribó Josep M. 
Published: September 2009

AbstractNanophases of J‐aggregates of several achiral amphiphilic porphyrins, which have thin long acicular shapes (nanoribbons), show the immediate and reversible formation of a stationary mechano‐chiral state in the solution by vortex stirring, as detected by their circular dichroic signals measured by 2‐modulator generallized ellipsometry. The results suggest that when a macroscopic chiral force creates supramolecular chirality, it also creates an enantiomeric excess of screw distortions, which may be detected by their excitonic absorption. An explanation on the effect of the shear flow gradients is proposed on the basis of the orientation of the rotating particles in the vortex and the size, shape, and mechanical properties of the nanoparticles.
Wandsysteme aus Fertigteilen für große Höhen
Authors: Empelmann Martin , Henke Volker , Teutsch Manfred 
Published: September 2009

AbstractBei Hallenbauten werden die Außen‐ oder Innenwände oft aus zwischen den Stützen übereinander angeordneten Wandelementen aus Stahlbeton‐Fertigteilen erstellt. Je nach den individuellen bautechnischen Anforderungen kann auf dem obersten Wandelement noch ein weiterer Wandaufbau aus leichten Porenbetonplatten erfolgen. Die Befestigung derartiger Wandelemente an den seitlich angeordneten Stützen oder anderen Bauteilen erfolgt entweder punktförmig, beispielsweise durch Dollen, oder kontinuierlich, z. B. durch Seilschlaufen. Zusätzlich können diese Wände, bei entsprechender Ausbildung auch als aussteifende Wandscheiben zur Aussteifung des Gesamtsystems oder als Brandwände genutzt werden. Bei der Detailausführung und dem Stabilitätsnachweis derartiger Wandscheiben sind einige Besonderheiten zu beachten, auf die in diesem Aufsatz eingegangen werden soll.Wall Systems for Exceptional HeightsFor industrial hall constructions, the outside and/or inside walls are very often constructed as precast panel wall systems, with single concrete wall panels mounted on top of each other. According to the design requirements the top panel can be loaded by the weight of a further wall system, very often consisting of lighter aereated concrete panels. The wall panels are normally fixed either at defined points by dowels or continuously, e.g. by a wire rope loop system. Furthermore, these wall systems, if appropriately constructed, can be used as stiffening members for the overall construction or as fire walls. For the detailing, dimensioning and stability analysis of these wall panels some special features have to be observed, which will be pointed out in this paper.