bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRAF1 polymorphisms associated with rheumatoid arthritis susceptibility in Asians and in Caucasians
Authors: Han Tae‐Un , Bang So‐Young , Kang Changwon , Bae Sang‐Cheol 
Published: August 2009

AbstractObjectiveRecent genome‐wide association scans and replication studies of European populations have disclosed several single‐nucleotide polymorphisms (SNPs) associated with rheumatoid arthritis (RA) susceptibility. The aim of this study was to evaluate the RA‐associated loci by genotyping previously reported SNPs and additional tag SNPs in a Korean population.MethodsA total of 1,316 unrelated RA patients and 1,006 controls were genotyped for 12 SNPs identified in genome‐wide scans and for 12 additional tag SNPs in IL2RB, OLIG3–TNFAIP3, PTPN22, and TRAF1–C5, and the findings were statistically compared.ResultsNone of the SNPs tested was associated with RA susceptibility, except rs7021206 in TRAF1 intron 3 (P = 0.0032) and, among the SNPs previously reported, rs6457617 in HLA (P = 4.6 × 10−35). The association of rs7021206 was positive in patients who were seropositive for rheumatoid factor (P = 0.0051) or for anti–cyclic citrullinated peptide autoantibodies (P = 0.0062). However, Korean patients were negative for the association of rs3761847 in the TRAF1–C5 intergenic region previously reported in Caucasians. Linkage disequilibrium between rs3761847 and rs7021206 was not as high in Koreans (r2 = 0.37) as in Caucasians (r2 = 0.67), which explains the lack of association of rs3761847 in Koreans. Accordingly, RA susceptibility was localized to an extended haplotype marked by rs7021206 rather than rs3761847, and SNPs highly correlated with rs7021206 (r2 ≥ 0.81) extended from rs1953126 in the PHF19–TRAF1 intergenic region to rs2900180 in the TRAF1–C5 intergenic region, spanning 66 kb.ConclusionOur results demonstrate that within and around TRAF1, excluding PHF19 and C5, SNPs highly correlated with rs7021206, but not those correlated with rs3761847, are associated with RA in both Asians and Caucasians and are possibly correlated with causative variations.
Regression of systemic lupus erythematosus after development of an acquired Toll‐like receptor signaling defect and antibody deficiency
Authors: Visentini Marcella , Conti Valentina , Cagliuso Maria , Tinti Francesca , Siciliano Giulia , Trombetta Amelia C. , Mitterhofer Anna Paola , Fiorilli Massimo , Quinti Isabella 
Published: August 2009

AbstractToll‐like receptor 9 (TLR‐9) and TLR‐7 may have a role in the production of anti‐DNA and anti‐RNA autoantibodies, respectively, but murine models do not clearly demonstrate their contribution to the development of systemic lupus erythematosus (SLE). Herein we describe a patient with SLE who had long‐lasting remission of her autoimmune disease after development of an antibody deficiency resembling common variable immunodeficiency (CVID). After CVID had developed, anti–double‐stranded DNA antibodies disappeared, although antinuclear antibodies remained positive for >10 years. In vitro studies revealed that the patient's B cells proliferated poorly and failed to differentiate into plasmablasts after stimulation of either TLR‐9 or TLR‐7, providing evidence for an acquired defect of the signaling pathway downstream of these TLRs. These observations suggest, although indirectly, that signaling through TLR‐9 and TLR‐7 is important in the pathogenesis of human SLE, and indicate that investigation of potential treatment strategies with TLR antagonists is warranted.
Induction of apoptosis in the synovium of mice with autoantibody‐mediated arthritis by the intraarticular injection of double‐stranded MicroRNA‐15a
Authors: Nagata Yoshihiko , Nakasa Tomoyuki , Mochizuki Yu , Ishikawa Masakazu , Miyaki Shigeru , Shibuya Hayatoshi , Yamasaki Keiichiro , Adachi Nobuo , Asahara Hiroshi , Ochi Mitsuo 
Published: August 2009

AbstractObjectiveMicroRNA is a family of noncoding RNAs that exhibit tissue‐specific or developmental stage–specific expression patterns and are associated with human diseases. MicroRNA‐15a (miR‐15a) is reported to induce cell apoptosis by negatively regulating the expression of Bcl‐2, which suppresses the apoptotic processes. The purpose of this study was to investigate whether double‐stranded miR‐15a administered by intraarticular injection could be taken up by cells and could induce Bcl‐2 dysfunction and cell apoptosis in the synovium of arthritic mice in vivo.MethodsAutoantibody‐mediated arthritis was induced in male DBA/1J mice. In the experimental group, double‐stranded miR‐15a labeled with FAM–atelocollagen complex was injected into the knee joint. In the control group, control small interfering RNA–atelocollagen complex was injected into the knee joint. Synovial expression of miR‐15a was analyzed by quantitative polymerase chain reaction, FAM by fluorescence microscopy, Bcl‐2 by Western blotting, and Bcl‐2 and caspase 3 by immunohistochemistry.ResultsThe expression of miR‐15a in the synovium of the experimental group was significantly higher than that in the control group. Green fluorescence emission of FAM was observed in the synovium of the experimental group. Bcl‐2 protein was down‐regulated and the expression of caspase 3 was increased as compared with that in the control group.ConclusionThese results indicate that the induction of cell apoptosis after intraarticular injection of double‐stranded miR‐15a occurs through inhibition of the translation of Bcl‐2 protein in arthritic synovium.
HLA–B27 misfolding and the unfolded protein response augment interleukin‐23 production and are associated with Th17 activation in transgenic rats
Authors: DeLay Monica L. , Turner Matthew J. , Klenk Erin I. , Smith Judith A. , Sowders Dawn P. , Colbert Robert A. 
Published: August 2009

AbstractObjectiveTo determine whether HLA–B27 misfolding and the unfolded protein response (UPR) result in cytokine dysregulation and whether this is associated with Th1 and/or Th17 activation in HLA–B27/human β2‐microglobulin (Huβ2m)–transgenic rats, an animal model of spondylarthritis.MethodsCytokine expression in lipopolysaccharide (LPS)–stimulated macrophages was analyzed in the presence and absence of a UPR induced by chemical agents or by HLA–B27 up‐regulation. Cytokine expression in colon tissue and in cells purified from the lamina propria was determined by real‐time reverse transcription–polymerase chain reaction analysis, and differences in Th1 and Th17 CD4+ T cell populations were quantified after intracellular cytokine staining.ResultsInterleukin‐23 (IL‐23) was found to be synergistically up‐regulated by LPS in macrophages undergoing a UPR induced by pharmacologic agents or by HLA–B27 misfolding. IL‐23 was also increased in the colon tissue from B27/Huβ2m‐transgenic rats concurrently with the development of intestinal inflammation, and IL‐17, a downstream target of IL‐23, exhibited robust up‐regulation in a similar temporal pattern. IL‐23 and IL‐17 transcripts were localized to CD11+ antigen‐presenting cells and CD4+ T cells, respectively, from the colonic lamina propria. Colitis was associated with a 6‐fold expansion of CD4+ IL‐17–expressing T cells.ConclusionThe IL‐23/IL‐17 axis is strongly activated in the colon of B27/Huβ2m‐transgenic rats with spondylarthritis‐like disease. HLA–B27 misfolding and UPR activation in macrophages can result in enhanced induction of the pro‐Th17 cytokine IL‐23. These results suggest a possible link between HLA–B27 misfolding and immune dysregulation in this animal model, with implications for human disease.
Inhibition of lymphangiogenesis and lymphatic drainage via vascular endothelial growth factor receptor 3 blockade increases the severity of inflammation in a mouse model of chronic inflammatory arthritis
Authors: Guo Ruolin , Zhou Quan , Proulx Steven T. , Wood Ronald , Ji Rui‐Cheng , Ritchlin Christopher T. , Pytowski Bronislaw , Zhu Zhenping , Wang Yong‐Jun , Schwarz Edward M. , Xing Lianping 
Published: August 2009

AbstractObjectiveThis study was undertaken to investigate the effect of lymphatic inhibition on joint and draining lymph node (LN) pathology during the course of arthritis progression in mice.MethodsTumor necrosis factor (TNF)–transgenic mice were used as a model of chronic inflammatory arthritis. Mice were subjected to contrast‐enhanced magnetic resonance imaging to obtain ankle and knee joint synovial volumes and draining popliteal LN volumes before and after 8 weeks of treatment with vascular endothelial growth factor receptor 3 (VEGFR‐3) neutralizing antibody, VEGFR‐2 neutralizing antibody, or isotype IgG. Animals were subjected to near‐infrared lymphatic imaging to determine the effect of VEGFR‐3 neutralization on lymph transport from paws to draining popliteal LNs. Histologic, immunohistochemical, and reverse transcriptase–polymerase chain reaction analyses were used to examine lymphatic vessel formation and the morphology of joints and popliteal LNs.ResultsCompared with IgG treatment, VEGFR‐3 neutralizing antibody treatment significantly decreased the size of popliteal LNs, the number of lymphatic vessels in joints and popliteal LNs, lymphatic drainage from paws to popliteal LNs, and the number of VEGF‐C–expressing CD11b+ myeloid cells in popliteal LNs. However, it increased the synovial volume and area of inflammation in ankle and knee joints. VEGFR‐2 neutralizing antibody, in contrast, inhibited both lymphangiogenesis and joint inflammation.ConclusionThese findings indicate that lymphangiogenesis and lymphatic drainage are reciprocally related to the severity of joint lesions during the development of chronic arthritis. Lymphatic drainage plays a beneficial role in controlling the progression of chronic inflammation.
Type II collagen levels correlate with mineralization by articular cartilage vesicles
Authors: Jubeck Brian , Muth Emily , Gohr Claudia M. , Rosenthal Ann K. 
Published: August 2009

AbstractObjectivePathologic mineralization is common in osteoarthritic (OA) cartilage and may be mediated by extracellular organelles known as articular cartilage vesicles (ACVs). Paradoxically, ACVs isolated from OA human cartilage mineralize poorly in vitro compared with those isolated from normal porcine cartilage. We recently showed that collagens regulate ACV mineralization. We sought to determine differences between collagens and collagen receptors on human and porcine ACVs as a potential explanation of their different mineralization behaviors.MethodsACVs were enzymatically released from old and young human and porcine hyaline articular cartilage. Western blotting was used to determine the presence of types I, II, VI, and X collagen and various collagen receptors on ACVs. Type II collagen was quantified by enzyme‐linked immunosorbent assay. Biomineralization was assessed by measuring the uptake of 45Ca by isolated ACVs in agarose gels and by ACVs in situ in freeze‐thawed cartilage.ResultsAs previously shown, isolated human ACVs mineralized poorly in response to ATP compared with porcine ACVs, but human and porcine ACVs mineralized similarly in situ in freeze‐thawed cartilage. Type II collagen levels were 100‐fold higher in isolated human ACVs than in porcine ACVs. Type II collagen in human ACVs was of high molecular weight. Transglutaminase‐crosslinked type II collagen showed increased resistance to collagenase, suggesting a possible explanation for residual collagen on human ACVs. Expression of other collagens and collagen receptors was similar on human and porcine ACVs.ConclusionHigher levels of type II collagen in human ACV preparations, perhaps mediated by increased transglutaminase crosslinking, may contribute to the decreased mineralization observed in isolated human ACVs in vitro.
Outside‐to‐inside signaling through transmembrane tumor necrosis factor reverses pathologic interleukin‐1β production and deficient apoptosis of rheumatoid arthritis monocytes
Authors: Meusch Undine , Rossol Manuela , Baerwald Christoph , Hauschildt Sunna , Wagner Ulf 
Published: August 2009

AbstractObjectiveMonocytes are a major source of proinflammatory cytokines in rheumatoid arthritis (RA), and inhibitors of monocytic cytokines are highly efficient agents for treatment of the disease. The aim of this study was to analyze the effects of a therapeutic anti–tumor necrosis factor α (anti‐TNFα) antibody on monocytes from patients with RA and healthy control subjects.MethodsPeripheral blood monocytes from patients with RA and healthy control subjects were incubated in the presence of anti‐TNFα antibody or IgG. Annexin V staining, caspase activation, poly(ADP‐ribose) polymerase cleavage, and DNA staining with propidium iodide were used to analyze apoptosis. The signaling events elicited in monocytes by infliximab were analyzed by Western blotting and electromobility shift assay.ResultsPeripheral blood monocytes from patients with RA were characterized by increased expression of transmembrane TNFα, spontaneous in vitro production of interleukin‐1β (IL‐1β), and a decreased rate of spontaneous ex vivo apoptosis. Incubation with infliximab induced significantly increased apoptosis in monocytes from patients with RA but not in monocytes from healthy control subjects. This apoptosis was triggered by reverse signaling of transmembrane TNF after ligation by infliximab and was independent of caspase activation. Instead, transmembrane TNF reverse signaling inhibited the constitutive NF‐κB activation in RA monocytes, suppressed IL‐1β secretion, and normalized spontaneous in vitro apoptosis. This normalization was reversible by the addition of exogenous IL‐1β.ConclusionThis study demonstrates that outside‐to‐inside signaling through transmembrane TNF after ligation by infliximab inhibits constitutive NF‐κB activation and suppresses spontaneous IL‐1β production by monocytes from patients with RA. Besides the induction of monocyte apoptosis, this inhibition could also contribute to the therapeutic effects observed during treatment with TNFα inhibitors.
Magnetic resonance imaging‐based cartilage loss in painful contralateral knees with and without radiographic joint space narrowing: Data from the osteoarthritis initiative
Authors: Eckstein Felix , Benichou Olivier , Wirth Wolfgang , Nelson David R. , Maschek Susanne , Hudelmaier Martin , Kwoh C. Kent , Guermazi Ali , Hunter David 
Published: August 2009

AbstractObjectiveTo determine by magnetic resonance imaging (MRI), whether knees with advanced radiographic disease (medial joint space narrowing [mJSN]) encounter greater longitudinal cartilage loss than contralateral knees with earlier disease (no or less mJSN).MethodsParticipants were selected from 2,678 cases in the Osteoarthritis Initiative, based on exhibition of bilateral pain, body mass index >25 (kg/m2), mJSN in 1 knee, no or less mJSN in the contralateral knee, and no lateral JSN in both knees. Eighty participants (mean ± SD age 60.6 ± 9.1 years) fulfilled these criteria. Medial tibial and femoral cartilage morphology was analyzed from the baseline and the 1‐year followup MRI (sagittal double echo at steady state by 3.0T) of both knees by experienced readers blinded to the time point and mJSN status.ResultsKnees with more radiographic mJSN displayed greater medial cartilage loss (−80 μm) assessed by MRI than contralateral knees with less mJSN (−57 μm). The difference reached statistical significance in participants with an mJSN grade of 2 or 3 (P = 0.005–0.08), but not in participants with an mJSN grade of 1 (P = 0.28–0.98). In knees with more mJSN, cartilage loss increased with higher grades of mJSN (P = 0.003 in the medial femur). Knees with an mJSN grade of 2 or 3 displayed greater cartilage loss in the weight‐bearing medial femur than in the posterior femur or in the medial tibia (P = 0.048).ConclusionKnees with advanced mJSN displayed greater cartilage loss than contralateral knees with less mJSN. These data suggest that radiography can be used to stratify fast structural progressors, and that MRI cartilage thickness loss is more pronounced at advanced radiographic disease stage.
Aggregating conclusive and inconclusive information: Data and a model based on the assessment of threat
Authors: Baranski Joseph V. , Petrusic William M. 
Published: August 2009

AbstractThis study examined the process of combining conclusive and inconclusive information using a Naval threat assessment simulation. On each of 36 trials, participants interrogated 10 pieces of information (e.g., speed, direction, bearing, etc.) about “targets” in a simulated radar space. The number of hostile, peaceful, and inconclusive cues was factorially varied across targets. Three models were developed to understand how inconclusive information is used in the judgment of threat. According to one model, inconclusive information is ignored and the judgment of threat is based only on the conclusive information. According to a second model, the amount of dominant conclusive information is normalized by all of the available information. Finally, according to a third model, inconclusive information is partitioned under the assumption that it equally represents both dominant and non‐dominant evidence. In Experiment 1, the data of novices (i.e., civilians) were best described by a model that assumes a partitioning of inconclusive evidence. This result was replicated in a second experiment involving variation of the global threat context. In a third experiment involving experts (i.e., Canadian Navy officers), the data of half of the participants were best described by the partitioning model and the data of the other half were best described by the normalizing model. In Experiments 1 and 2, the presence of inconclusive information produced a “dilution effect”, whereby hostile (peaceful) targets were judged as less hostile (peaceful) than the predictions of the Partitioning model. The dilution effect was not evident in the judgments of the Navy officers. Copyright © 2009 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.
Early development of the primordial mammalian diaphragm and cellular mechanisms of nitrofen‐induced congenital diaphragmatic hernia
Authors: Clugston Robin D. , Zhang Wei , Greer John J. 
Published: August 2009

AbstractCongenital diaphragmatic hernia (CDH) is a frequently occurring cause of neonatal respiratory distress and is associated with high mortality and long‐term morbidity. Evidence from animal models suggests that CDH has its origins in the malformation of the pleuroperitoneal fold (PPF), a key structure in embryonic diaphragm formation. The aims of this study were to characterize the embryogenesis of the PPF in rats and humans, and to determine the potential mechanism that leads to abnormal PPF development in the nitrofen model of CDH. Analysis of rat embryos, and archived human embryo sections, allowed the timeframe of PPF formation to be determined for both species, thus delineating a critical period of diaphragm development in relation to CDH. Experiments on nitrofen‐exposed NIH 3T3 cells in vitro led us to hypothesize that nitrofen might cause diaphragmatic hernia in vivo by two possible mechanisms: through decreased cell proliferation or by inducing apoptosis. Data from nitrofen‐exposed rat embryos indicates that the primary mechanism of nitrofen teratogenesis in the PPF is through decreased cell proliferation. This study provides novel insight into the embryogenesis of the PPF in rats and humans, and it indicates that impaired cell proliferation might contribute to abnormal diaphragm development in the nitrofen model of CDH. Birth Defects Research (Part A) 2010. © 2009 Wiley‐Liss, Inc.
Maternal obesity and morbid obesity: The risk for birth defects in the offspring
Authors: Blomberg Marie I. , Källén Bengt 
Published: August 2009

AbstractBACKGROUND: The objective of this study was to assess, in a large data set from Swedish Medical Health Registries, whether maternal obesity and maternal morbid obesity were associated with an increased risk for various structural birth defects. METHODS: The study population consisted of 1,049,582 infants born in Sweden from January 1, 1995, through December 31, 2007, with known maternal weight and height data. Women were grouped in six categories of body mass index (BMI) according to World Health Organization classification. Infants with congenital birth defects were identified from three sources: the Swedish Medical Birth Registry, the Register of Birth Defects, and the National Patient Register. Maternal age, parity, smoking, and year of birth were thought to be potential confounders and were included as covariates in the adjusted odds ratio analyses. RESULTS: Ten percent of the study population was obese. Morbid obesity (BMI ≥ 40) occurred in 0.7%. The prevalence of congenital malformations was 4.7%, and the prevalence of relatively severe malformations was 3.2%. Maternal prepregnancy morbid obesity was associated with neural tube defects OR 4.08 (95% CI 1.87–7.75), cardiac defects OR 1.49 (95% CI 1.24–1.80), and orofacial clefts OR 1.90 (95% CI 1.27–2.86). Maternal obesity (BMI ≥ 30) significantly increased the risk of hydrocephaly, anal atresia, hypospadias, cystic kidney, pes equinovarus, omphalocele, and diaphragmatic hernia. CONCLUSION: The risk for a morbidly obese pregnant woman to have an infant with a congenital birth defect is small, but for society the association is important in the light of the ongoing obesity epidemic. Birth Defects Research (Part A), 2010. © 2009 Wiley‐Liss, Inc.
Exposure of non‐target tissues in medical diathermy
Authors: Leitgeb N. , Omerspahic A. , Niedermayr F. 
Published: August 2009

AbstractWith different prevalence in different regions, radio frequency (RF) electromagnetic fields (EMF) are widely used for therapeutic tissue heating. Although short‐wave diathermy (27.12 MHz) is the most popular treatment modality, quantitative data on patient's exposure have been lacking. By numerical simulation with the numerical anatomical model NORMAN, intracorporal distributions of specific absorption rates (SAR) were investigated for different treatment scenarios and applicators. Quantitative data are provided for exposures of target treatment areas as well as for vulnerable regions such as the eye lenses, central nervous system, and testes. Different applicators and distances were investigated. Capacitive and inductive applicators exhibit quite a different heating efficiency. It could be shown that for the same output power therapeutic heat deposition can vary by almost one order of magnitude. By mimicking therapist's practice to use patient's heat perception as an indicator for output power setting, numerical data were elaborated demonstrating that muscle tissue exposures may be several times higher for inductive than for capacitive applicators. Presented quantitative data serve as a guide for power adjustment preventing relevant overexposures without compromising therapy; they also provide a basis for estimating target tissue heat load and developing therapeutic guidelines. Bioelectromagnetics 31:12–19, 2010. © 2009 Wiley‐Liss, Inc.
Resonance scattering spectral detection of ultratrace Hg(II) using herring sperm DNA modified nanogold probe as catalyst
Authors: Wen Guiqing , Liang Aihui , Jiang Zhiliang , Liao Xianjiu , Li Jianfu , Jiang Hesheng 
Published: August 2009

AbstractHerring sperm DNA (hsDNA) was used to modify 10 nm nanogold to obtain a resonance scattering (RS) probe (AuhsDNA) for detection of Hg2+. In the presence of salt, Hg2+ interacts with AuhsDNA to form stable Hg2+–hsDNA complexes, and releases nanogold particles to form larger nanogold clusters that can be removed by membrane filtration. The excess AuhsDNA in the filtrate solution exhibits a catalytic effect on the reaction between hydroxylamine (NH2OH) and Cu(II). The excess AuhsDNA decreased with the addition of Hg2+, which led the RS intensity at 602 nm to decrease. The decreased RS intensity (Δl602 nm) had a linear response to Hg2+ concentration in the range of 0.4–400 nM, with a detection limit of 0.2 nM Hg2+. This RS method was applied for the detection of Hg2+ in water samples, with sensitivity, selectivity and simplicity. Copyright © 2009 John Wiley & Sons, Ltd.