bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors for severe Muckle‐Wells syndrome
Authors: Kümmerle‐Deschner Jasmin B. , Tyrrell Pascal N. , Reess Fabian , Kötter Ina , Lohse Peter , Girschick Hermann , Huemer Christian , Horneff Gerd , Haas Johannes‐Peter , Koitschev Assen , Deuter Christoph , Benseler Susanne M. 
Published: August 2010

AbstractObjectiveMuckle‐Wells syndrome (MWS) is an inherited autoinflammatory disease resulting in excessive interleukin‐1 release. It is unknown whether demographic, clinical, or laboratory characteristics at the time of diagnosis may identify patients who are at high risk for severe disease activity. This study was undertaken to analyze clinical and laboratory features of MWS, compare genetically defined subcohorts, and identify risk factors for severe MWS.MethodsA multicenter cohort study of consecutive MWS patients was performed. Parameters assessed included clinical features, MWS Disease Activity Score (MWS‐DAS), inflammation markers, and cytokine levels. E311K mutation–positive patients were compared with E311K mutation–negative patients. Putative risk factors for severe MWS (defined as an MWS‐DAS score of ≥10) were assessed in univariate analyses, and significant predictors were entered into a multivariate model.ResultsThirty‐two patients (15 male and 17 female) were studied. The most frequent organ manifestations were musculoskeletal symptoms and eye and skin disorders. Renal disease and hearing loss were seen in >50% of the patients. Genetically defined subcohorts had distinct phenotypes. Severe disease activity was documented in 19 patients (59%). Predictors of severe MWS identified at the time of diagnosis were female sex, hearing loss, musculoskeletal disease, increased erythrocyte sedimentation rate, and low hemoglobin level. Female sex and hearing loss remained significant after adjustment for age in a multivariate model (relative risk 1.8 and 2.6, respectively).ConclusionMWS patients at high risk for severe disease can be identified at the time of diagnosis. Female patients presenting with hearing loss have the highest likelihood of manifesting severe MWS and should be considered a high‐risk group.
Tonic modulation of spinal hyperexcitability by the endocannabinoid receptor system in a rat model of osteoarthritis pain
Authors: Sagar Devi Rani , Staniaszek Lydia E. , Okine Bright N. , Woodhams Stephen , Norris Leonie M. , Pearson Richard G. , Garle Michael J. , Alexander Stephen P. H. , Bennett Andrew J. , Barrett David A. , Kendall David A. , Scammell Brigitte E. , Chapman Victoria 
Published: August 2010

AbstractObjectiveTo investigate the impact of an experimental model of osteoarthritis (OA) on spinal nociceptive processing and the role of the inhibitory endocannabinoid system in regulating sensory processing at the spinal level.MethodsExperimental OA was induced in rats by intraarticular injection of sodium mono‐iodoacetate (MIA), and the development of pain behavior was assessed. Extracellular single‐unit recordings of wide dynamic range (WDR) neurons in the dorsal horn were obtained in MIA‐treated rats and saline‐treated rats. The levels of endocannabinoids and the protein and messenger RNA levels of the main synthetic enzymes for the endocannabinoids (N‐acyl phosphatidylethanolamine phospholipase D [NAPE‐PLD] and diacylglycerol lipase α [DAGLα]) in the spinal cord were measured.ResultsLow‐weight (10 gm) mechanically evoked responses of WDR neurons were significantly (P < 0.05) facilitated 28 days after MIA injection compared with the responses in saline‐treated rats, and spinal cord levels of anandamide and 2‐arachidonoyl glycerol (2‐AG) were increased in MIA‐treated rats. Protein levels of NAPE‐PLD and DAGLα, which synthesize anandamide and 2‐AG, respectively, were elevated in the spinal cords of MIA‐treated rats. The functional role of endocannabinoids in the spinal cords of MIA‐treated rats was increased via activation of cannabinoid 1 (CB1) and CB2 receptors, and blockade of the catabolism of anandamide had significantly greater inhibitory effects in MIA‐treated rats compared with control rats.ConclusionOur findings provide new evidence for altered spinal nociceptive processing indicative of central sensitization and for adaptive changes in the spinal cord endocannabinoid system in an experimental model of OA. The novel control of spinal cord neuronal responses by spinal cord CB2 receptors suggests that this receptor system may be an important target for the modulation of pain in OA.
Expansion of intestinal CD4+CD25high Treg cells in patients with ankylosing spondylitis: A putative role for interleukin‐10 in preventing intestinal Th17 response
Authors: Ciccia Francesco , Accardo‐Palumbo Antonina , Giardina AnnaRita , Di Maggio Piera , Principato Alfonso , Bombardieri Michele , Rizzo Aroldo , Alessandro Riccardo , Ferrante Angelo , Principe Simona , Peralta Sergio , Conte Francesco , Drago Sandro , Craxì Antonio , De Leo Giacomo , Triolo Giovanni 
Published: August 2010

AbstractObjectiveSubclinical gut inflammation has been demonstrated in patients with ankylosing spondylitis (AS). This study was undertaken to determine the frequency of regulatory CD4+CD25high T cells (Treg cells) and to evaluate Treg cell–related cytokines (interleukin‐2 [IL‐2], transforming growth factor β [TGFβ], and IL‐10) and transcription factors (FoxP3 and STAT‐5) in the ileum of patients with AS.MethodsQuantitative gene expression analysis, by reverse transcriptase–polymerase chain reaction, of Treg‐related cytokines (IL‐2, TGFβ, and IL‐10) and transcription factors (STAT‐5 and FoxP3) was performed on ileal biopsy specimens from 18 patients with AS, 15 patients with active Crohn's disease (CD), and 15 healthy subjects. Tissue and circulating Treg cells were also analyzed by flow cytometry.ResultsA significant up‐regulation of IL‐2, TGFβ, FoxP3, STAT‐5, and IL‐10 transcripts in the terminal ileum of AS patients displaying chronic ileal inflammation was observed. Flow cytometric analysis of Treg cells showed significant peripheral expansion in both patients with AS and chronic inflammation and patients with CD (mean ± SD 1.08 ± 0.4% and 1.05 ± 0.3%, respectively) as compared with healthy subjects (0.25 ± 0.12%) (P < 0.05). Interestingly, a 5‐fold increase in the proportion of Treg cells was observed in the gut of patients with AS (5 ± 3%) as compared with healthy subjects (1.2 ± 0.4%) (P < 0.001), with 70–80% of these cells also producing IL‐10. In vitro studies showed that blocking IL‐10 was sufficient to induce Th17 polarization on lamina propria mononuclear cells isolated from AS patients.ConclusionOur findings provide the first evidence that an active Treg cell response, mainly dominated by IL‐10 production, occurs in the gut of AS patients and is probably responsible for the absence of a clear Th17 polarization in the ileum of AS patients.
Anti–U1 RNP antibodies in cerebrospinal fluid are associated with central neuropsychiatric manifestations in systemic lupus erythematosus and mixed connective tissue disease
Authors: Sato Takeshi , Fujii Takao , Yokoyama Tomoko , Fujita Yoshimasa , Imura Yoshitaka , Yukawa Naoichiro , Kawabata Daisuke , Nojima Takaki , Ohmura Koichiro , Usui Takashi , Mimori Tsuneyo 
Published: August 2010

AbstractObjectiveTo determine the significance of anti–U1 RNP antibodies in the cerebrospinal fluid (CSF) of patients with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MCTD) who have central neuropsychiatric SLE (NPSLE).MethodsThe frequency of antinuclear antibodies including anti–U1 RNP antibodies in the sera and CSF of 24 patients with SLE and 4 patients with MCTD, all of whom had neuropsychiatric syndromes, was determined using an RNA immunoprecipitation assay and an enzyme‐linked immunosorbent assay. The frequency of anti–U1 RNP antibodies in the CSF of patients with central NPSLE was examined, and the anti–U1 RNP index ([CSF anti–U1 RNP antibodies/serum anti–U1 RNP antibodies]/[CSF IgG/serum IgG]) was compared with CSF interleukin‐6 (IL‐6) levels and the albumin quotient (Qalb, an indicator of blood–brain barrier damage). CSF and serum antibodies against U1‐70K, U1‐A, and U1‐C, including autoantigenic regions, were examined, and the U1‐70K, U1‐A, and U1‐C indices as well as the anti–U1 RNP index were calculated.ResultsCSF anti–U1 RNP antibodies with an increased anti–U1 RNP index showed 64.3% sensitivity and 92.9% specificity for central NPSLE. The anti–U1 RNP index did not correlate with CSF IL‐6 levels or the Qalb. The anti–U1‐70K index was higher than the anti–U1‐A and anti–U1‐C indices in the CSF of anti–U1 RNP antibody–positive patients with central NPSLE. The major autoantigenic region for CSF anti–U1‐70K antibodies appeared to be localized in U1‐70K amino acid 141–164 residue within the RNA‐binding domain.ConclusionThe frequency of anti–U1 RNP antibodies in the CSF and the anti–U1 RNP index are useful indicators of central NPSLE in anti–U1 RNP antibody–positive patients. The predominance of anti–U1‐70K antibodies in CSF suggests intrathecal anti–U1 RNP antibody production.
CD248 and its cytoplasmic domain: A therapeutic target for arthritis
Authors: Maia Margarida , de Vriese Astrid , Janssens Tom , Moons Michaël , van Landuyt Kristel , Tavernier Jan , Lories Rik J. , Conway Edward M. 
Published: August 2010

AbstractObjectiveCD248 is a transmembrane glycoprotein expressed on the surface of activated perivascular and fibroblast‐like cells. This study was undertaken to explore the function of CD248 and its cytoplasmic domain in arthritis.MethodsSynovial tissue biopsy samples from healthy controls, from patients with psoriatic arthritis (PsA), and from patients with rheumatoid arthritis (RA) were stained for CD248. Transgenic mice that were CD248‐deficient (CD248‐knockout [CD248KO/KO]) or mice with CD248 lacking the cytoplasmic domain (CD248CyD/CyD) were generated. Collagen antibody–induced arthritis (CAIA) was induced in these mice and in corresponding wild‐type (WT) mice as controls. Clinical signs and histologic features of arthritis were evaluated. Cytokine levels were determined by enzyme‐linked immunosorbent assay, and the number of infiltrating inflammatory cells was quantified by immunohistochemistry. In vitro studies were performed with fibroblasts from CD248‐transgenic mouse embryos to explain the observed effects on inflammation.ResultsImmunostaining of synovium from patients with PsA and patients with RA and that from mice after the induction of CAIA revealed strong CD248 expression in perivascular and fibroblast‐like stromal cells. CD248KO/KO and CD248CyD/CyD mice had less severe arthritis, with lower plasma levels of proinflammatory cytokines, as compared with WT controls. Moreover, the joints of these mice had less synovial hyperplasia, reduced accumulation of inflammatory cells, and less articular cartilage and bone damage. Tumor necrosis factor α–induced monocyte adhesion to CD248CyD/CyD fibroblasts was impaired. CD248CyD/CyD fibroblasts exhibited reduced expression of hypoxia‐inducible factor 1α, placental growth factor, vascular endothelial growth factor, and matrix metalloproteinase 9 activity in response to transforming growth factor β.ConclusionCD248 contributes to synovial hyperplasia and leukocyte accumulation in inflammatory arthritis, the effects of which are mediated partly via its cytoplasmic domain. CD248 is therefore a potential new target in the treatment of arthritis.
Changes in glycosylated hemoglobin after initiation of hydroxychloroquine or methotrexate treatment in diabetes patients with rheumatic diseases
Authors: Rekedal Laura R. , Massarotti Elena , Garg Rajesh , Bhatia Radhika , Gleeson Timothy , Lu Bing , Solomon Daniel H. 
Published: August 2010

AbstractObjectivePrior research demonstrates that hydroxychloroquine (HCQ) lowers glycosylated hemoglobin (HbA1c) in diabetes patients without rheumatic disease. We examined medical records of patients with diabetes mellitus (DM) and concomitant rheumatic illness to measure changes in HbA1c after starting HCQ or methotrexate (MTX).MethodsWe used electronic medical records to identify patients beginning treatment with either HCQ or MTX who had a diagnosis of DM (or a pretreatment HbA1c value of ≥7%) and at least 1 HbA1c measurement both before and within 12 months after initiation of treatment. Using a structured medical record abstraction, we examined rheumatic disease diagnosis, cumulative steroid use, duration (months) between drug initiation and lowest HbA1c value, a change in DM medication, body mass index (BMI), age, and sex. Adjusted linear regression models determined changes in HbA1c from pretreatment values to the lowest posttreatment values within 12 months.ResultsWe identified 45 patients taking HCQ and 37 patients taking MTX who met the inclusion criteria. Rheumatoid arthritis had been diagnosed in approximately half of the patients in each group. Age, sex, and mean pretreatment HbA1c levels were similar across groups. The mean BMI of those taking HCQ (35.4 kg/m2) was slightly higher than that of those taking MTX (32.2 kg/m2) (P = 0.13). Glucocorticoid use appeared more common in those taking MTX (46%) than in those taking HCQ (29%) (P = 0.17). The mean reduction in HbA1c from pretreatment values to the lowest posttreatment values was 0.66% (95% confidence interval [95% CI] 0.26, 1.05) in those taking HCQ compared with 0.11% (95% CI −0.18, 0.40) in those taking MTX. In fully adjusted analyses, the reduction in HbA1c among those taking HCQ was 0.54% greater than the reduction among those taking MTX (P = 0.041).ConclusionHCQ initiation was associated with a significantly greater reduction in HbA1c as compared with MTX initiation among diabetes patients with rheumatic disease.
Characterization of the human nucleus pulposus cell phenotype and evaluation of novel marker gene expression to define adult stem cell differentiation
Authors: Minogue Ben M. , Richardson Stephen M. , Zeef Leo A. H. , Freemont Anthony J. , Hoyland Judith A. 
Published: August 2010

AbstractObjectiveDevelopment of stem cell therapies for regenerating the nucleus pulposus (NP) are hindered by the lack of specific markers by which to distinguish NP cells from articular chondrocytes (ACs). The purpose of this study was to define the phenotype profile of human NP cells using gene expression profiling and to assess whether the identified markers could distinguish mesenchymal stem cell (MSC) differentiation to a correct NP cell phenotype.MethodsAffymetrix MicroArray analyses were conducted on human NP cells and ACs, and differential expression levels for several positive (NP) and negative (AC) marker genes were validated by real‐time quantitative polymerase chain reaction (PCR) analysis. Novel marker gene and protein expression was also assessed in human bone marrow–derived MSCs (BM‐MSCs) and adipose tissue–derived MSCs (AD‐MSCs) following differentiation in type I collagen gels.ResultsAnalysis identified 12 NP‐positive and 36‐negative (AC) marker genes that were differentially expressed ≥20‐fold, and for a subset of them (NP‐positive genes PAX1, FOXF1, HBB, CA12, and OVOS2; AC‐positive genes GDF10, CYTL1, IBSP, and FBLN1), differential expression was confirmed by real‐time quantitative PCR. Differentiated BM‐MSCs and AD‐MSCs demonstrated significant increases in the novel NP markers PAX1 and FOXF1. AD‐MSCs lacked expression of the AC markers IBSP and FBLN1, whereas BM‐MSCs lacked expression of the AC marker IBSP but expressed FBLN1.ConclusionThis study is the first to use gene expression profiling to identify the human NP cell phenotype. Importantly, these markers can be used to determine the in vitro differentiation of MSCs to an NP‐like, rather than an AC‐like, phenotype. Interestingly, these results suggest that AD‐MSCs may be a more appropriate cell type than BM‐MSCs for use in engineering intervertebral disc tissue.
Phenotypic alterations of neurons that innervate osteoarthritic joints in rats
Authors: Ferreira‐Gomes Joana , Adães Sara , Sarkander Jana , Castro‐Lopes José M. 
Published: August 2010

AbstractObjectivePain is a prominent feature of osteoarthritis (OA). To further understand the primary mechanisms of nociception in OA, we studied the expression of the phenotype markers calcitonin gene‐related peptide (CGRP), isolectin B4 (IB4), and neurofilament 200 (NF200) in sensory neurons innervating the OA knee joint in rats.MethodsOA was induced in rats by intraarticular injection of 2 mg of mono‐iodoacetate (MIA) into the knee. Neurons innervating the joint were identified by retrograde labeling with fluorogold in dorsal root ganglia (DRG) and colocalized with neurochemical markers by immunofluorescence. The total number of DRG cells was determined by stereologic methods in Nissl‐stained sections.ResultsA 37% decrease in the number of fluorogold‐backlabeled cells was observed in rats with OA when compared with control rats, even though no decrease in the total number of cells was observed. However, an increase in the number of medium/large cell bodies and a decrease in the number of the smallest cells were observed, suggesting the occurrence of perikarya hypertrophy. The percentage of CGRP‐positive cells increased significantly, predominantly in medium/large cells, suggesting the occurrence of a phenotypic switch. Colocalization of CGRP and NF200 revealed no significant changes in the percentage of double‐labeled cells, but an increase in the number of medium/large double‐labeled cells was observed. No differences in the expression of either IB4 or NF200 were observed in fluorogold‐backlabeled cells.ConclusionThese results indicate that MIA‐induced OA causes an up‐regulation of CGRP in different subpopulations of primary afferent neurons in DRG due to a phenotypic switch and/or cell hypertrophy which may be functionally relevant in terms of the onset of pain in this pathologic condition.
Tract‐based spatial statistics on diffusion tensor imaging in systemic lupus erythematosus reveals localized involvement of white matter tracts
Authors: Emmer Bart J. , Veer Ilya M. , Steup‐Beekman Gerda M. , Huizinga Tom W. J. , van der Grond Jeroen , van Buchem Mark A. 
Published: August 2010

AbstractObjectiveThe aim of this study was to determine whether there are differences in white matter integrity between systemic lupus erythematosus (SLE) patients and healthy controls, as determined using tract‐based spatial statistics (TBSS) analysis of diffusion tensor imaging data.MethodsTwelve patients with SLE (mean age 42 years [range 15–61 years]) diagnosed according to the American College of Rheumatology 1982 revised criteria for SLE and 28 healthy controls (mean age 46 years [range 21–61 years]) were included in the study. Magnetic resonance imaging was performed on a 3.0T scanner. Fractional anisotropy (FA) maps were calculated for each patient. TBSS analysis was used to compare the FA maps. The TBSS technique projects the FA data into a common space through the use of an initial approximate nonlinear registration, followed by projection onto an alignment‐invariant tract representation (mean FA skeleton). The cluster results were corrected for multiple comparisons across space, and a threshold of significance of 0.05 was used.ResultsThe white matter of tracts in the inferior fronto‐occipital fasciculus, the fasciculus uncinatus, as well as the fornix, the posterior limb of the internal capsule (corticospinal tract), and the anterior limb of the internal capsule (anterior thalamic radiation) of patients with SLE showed reduced integrity as compared with normal subjects.ConclusionIn this preliminary study, the integrity of white matter tracts in areas around limbic structures and in the internal capsule was found to be reduced. Larger studies could improve our understanding of the pathologic mechanisms behind the reduced white matter tract integrity in SLE.
Nanotoxicology: The Molecular Science Point of View
Authors: Pumera Martin 
Published: August 2010

AbstractResearch on nanotoxicity is of extremely high scientific, social, and economic value. As nanomaterial‐based products enter the market, there is an urgent need for related research in order to prevent dramatic consequences of any health‐oriented issues caused by nanotechnology‐driven products. The results of research on nanotoxicity have profound significance because the design of nanomaterials used in industry and consumer products should be based on the outcome of such research. The research has multi‐billion dollar significance for industry and an even greater value for consumers and health care. Such research could prevent an enormous burden in terms of the cost of care for chronic health problems of the entire population caused by the widespread use of untested nanomaterials. The tremendous progress of nanotechnology has not been accompanied by sufficient studies of nanomaterial toxicity even though they possess unique, completely new properties. Thus, their toxicity can neither be extrapolated from the toxicity of bulk materials nor from the toxicity of their constituents in ionic form. This Focus Review discusses the current state of nanotoxicity research and nanotoxicology from the point of view of molecular science.
Global cyclotide adventure: A journey dedicated to the discovery of circular peptides from flowering plants
Authors: Gruber Christian W. 
Published: August 2010

AbstractCircular peptides and proteins of great number and diversity have been discovered in bacteria, plants, and animals. Cyclotides—disulfide‐knotted and head‐to‐tail cyclized plant peptides that exhibit various bioactivities—are by far the largest group of circular proteins. Since their first discovery over three decades ago, there has been a lot of progress in the elucidation of structural characteristics and applications of cyclotides as novel peptide drug grafting frameworks, but there is a lack of information about their native occurrence in various plant families. The “global cyclotide adventure” was initiated as a plant collection and analysis project to advance our understanding of the origin and distribution of cyclotides in flowering plants. Here, I will provide a chronological overview of the preparation of this project, including background information on plant taxonomy and morphology, summarize, and comment on the recent progress about the discovery of cyclotide‐producing plants and will give an outlook on the future of cyclotide analysis and further discoveries to be made. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 565–572, 2010.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