bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered Expression of Tyrosine Hydroxylase in the Locus Coeruleus Noradrenergic System in Citalopram Neonatally Exposed Rats and Monoamine Oxidase A Knock Out Mice
Authors: Zhang Junlin , Darling Ryan D. , Paul Ian A. , Simpson Kimberly L. , Chen Kevin , Shih Jean C. , Lin Rick C.S. 
Published: September 2011

AbstractIn rodents, noradrenergic (NE) locus coeruleus (LC) neurons are well known to express tyrosine hydroxylase (TH) immunoreactivity. However, due to its very low enzyme activity, NE cortical fibers do not typically express TH immunoreactivity, thus dopamine‐β‐hydroxylase (DBH) immunoreactivity is commonly utilized as a marker for NE cortical fibers. In this study, we performed double and/or triple immunofluorescent staining using antibodies against TH, DBH, and/or norepinephrine transporter (NET) to investigate the altered NE TH expression of cortical fibers in citalopram (CTM)‐exposed rats and monoamine oxidase (MAO) A knock out (KO) mice. We have noted the following novel findings: (1) neonatal exposure to the selective serotonin reuptake inhibitor (SSRI) CTM enhanced NE TH immunoreactive fibers throughout the entire neocortex, and a few of them appeared to be hypertrophic; (2) slightly enhanced NE cortical TH immunoreactive fibers were also noted in MAO A KO mice, and many of them revealed varicosities compared with the rather smooth NE cortical TH immunoreactive fibers in wild‐type (WT) mice; (3) LC dendrites of MAO A KO mice exhibited beaded morphology compared with the smooth LC dendrites in WT mice. Our findings suggest that both genetic and environmental factors during early development may play a critical role in the regulation and proper function of NE TH expression in the neocortex. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.
Jaw Adductor Muscles across Lepidosaurs: A Reappraisal
Authors: Daza Juan Diego , Diogo Rui , Johnston Peter , Abdala Virginia 
Published: September 2011

AbstractThe exact homologies of tetrapod jaw muscles remain unresolved, and this provides a barrier for phylogenetic analysis and tracing character evolution. Here, lepidosaur jaw muscles are surveyed using direct examination of species from 23 families and published descriptions of species from 10 families. A revised nomenclature is applied according to proposed homologies with Latimeria. Among lepidosaurs, variation was found in many aspects of jaw muscle anatomy. The superficial layers mm. levator and retractor anguli oris (LAO and RAO) are present in Sphenodon but not all squamates. The external jaw adductor muscles universally present in lepidosaurs are homologous with the main adductor muscle, A2, of Latimeria and include four layers: superficialis (A2‐SUP), medialis (A2‐M), profundus (A2‐PRO), and posterior (A2‐PVM). The A2‐SUP appears divided in Agamidae, Gekkota, Xantusiidae, and Varanidae. The A2‐M is layered lateromedial in lizards but anteroposterior in snakes. The names pseudotemporalis (PS) and pterygomandibularis (PTM) are recommended for subdivisions of the internal adductors of reptiles and amphibians, because the homology of this muscle with the A3′ and A3 ″ of Latimeria remains inconclusive. The intramandibularis of lepidosaurs and Latimeria (A‐ω) are homologous. The distribution of six jaw muscle characters was found to plot more parsimoniously on phylogenies based on morphological rather than and molecular data. Character mapping indicates that Squamata presents reduction in the divisions of the A2‐M, Scincoidea presents reduction or loss of LAO, and two apomorphic features are found for the Gekkota. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.
Power Doppler ultrasound, but not low‐field magnetic resonance imaging, predicts relapse and radiographic disease progression in rheumatoid arthritis patients with low levels of disease activity
Authors: Foltz Violaine , Gandjbakhch Frédérique , Etchepare Fabien , Rosenberg Carole , Tanguy Marie Laure , Rozenberg Sylvie , Bourgeois Pierre , Fautrel Bruno 
Published: September 2011

AbstractObjectiveSubclinical inflammation and radiographic progression have been described in rheumatoid arthritis (RA) patients whose disease is in remission or is showing a low level of activity. The aim of this study was to compare the ability of ultrasonography and magnetic resonance imaging (MRI) to predict relapse and radiographic progression in these patients.MethodsPatients with RA of short or intermediate duration that was either in remission or exhibiting low levels of activity according to the Disease Activity Score (DAS) were included in the study. Over a period of 1 year, patients underwent clinical and biologic assessments every 3 months and radiographic assessments at baseline and 12 months. Radiographs were graded according to the modified Sharp/van der Heijde score (SHS). At baseline, patients underwent ultrasonography and MRI, which were graded using binary and semiquantitative scoring systems. Relapse was defined as a DAS of ≥2.4, and radiographic progression was defined as an increase in the SHS of ≥1. We tested the association of values by multivariate logistic regression.ResultsA total of 85 RA patients with a mean disease duration of 35.3 months were studied. RA was in remission in 47 of these patients, and 38 had low levels of disease activity. At 1 year, 26 of the 85 patients (30.6%) showed disease relapse, and 9 of the 85 patients (10.6%) showed radiographic progression. The baseline PD synovitis count (i.e., the number of joints at baseline for which the power Doppler [PD] signal indicated synovitis) predicted relapse (adjusted odds ratio [OR] 6.3; 95% confidence interval [95% CI] 2.0–20.3), and the baseline PD synovitis grade predicted disease progression (adjusted OR 1.4 [95% CI 1.1–1.9]). MRI was not predictive of outcomes.ConclusionFor RA patients whose disease is in remission or who have low levels of disease activity, PD signals on ultrasonography could predict relapse or radiographic progression and identify those whose disease is adequately controlled, which is especially helpful when considering treatment tapering or interruption.
Disruption of vascular homeostasis in patients with Kawasaki disease: Involvement of vascular endothelial growth factor and angiopoietins
Authors: Breunis Willemijn B. , Davila Sonia , Shimizu Chisato , Oharaseki Toshiaki , Takahashi Kei , van Houdt Michel , Khor Chiea Chuen , Wright Victoria J. , Levin Michael , Burns Jane C. , Burgner David , Hibberd Martin L. , Kuijpers Taco W. ,   International Kawasaki Disease Genetics Consortium
Published: September 2011

AbstractObjectiveIn Kawasaki disease (KD), a pediatric vasculitis of medium‐sized arteries, the coronary arteries are most commonly affected. Angiopoietins and vascular endothelial growth factor (VEGF) play an important role in maintaining vascular homeostasis. Recently, we identified ANGPT1 and VEGFA as susceptibility loci for KD. This study was undertaken to fine‐map these associations and to gain further insight into their role in this vasculitis of unknown etiology to further the search for improved diagnostic and therapeutic options.MethodsA total of 292 single‐nucleotide polymorphisms (SNPs) located in VEGF and ANGPT and their receptors were genotyped in 574 families, including 462 trios. For replication, 123 cases and 171 controls were genotyped.ResultsA significant association with KD susceptibility was observed with 5 SNPs in the ANGPT1 gene (most significantly associated SNP +265037 C>T; Pcombined = 2.3 × 10−7) and 2 SNPs in VEGFA (most significantly associated SNP rs3025039; Pcombined = 2.5 × 10−4). Both ANGPT1 +265037 C>T and VEGFA rs3025039 are located in 3′ regulatory regions at putative transcription factor binding sites. We observed significantly down‐regulated transcript levels of angiopoietin 1 (Ang‐1) in patients with acute KD compared to patients with convalescent KD. In patients with acute KD, high serum protein levels of VEGF and Ang‐2 were observed compared to patients with convalescent KD and to both controls with and controls without fever. Immunohistochemistry demonstrated VEGF and angiopoietin expression in the coronary artery wall in autopsy tissue.ConclusionOur data support the hypothesis that dysregulation of VEGF and angiopoietins contributes to the disruption of vascular homeostasis in KD.
Safety and efficacy of ocrelizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: Results of a forty‐eight–week randomized, double‐blind, placebo‐controlled, parallel‐group phase III trial
Authors: Rigby W. , Tony H.‐P. , Oelke K. , Combe B. , Laster A. , von Muhlen C. A. , Fisheleva E. , Martin C. , Travers H. , Dummer W. 
Published: September 2011

AbstractObjectiveTo evaluate the efficacy and safety of treatment with ocrelizumab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) and an inadequate response to MTX.MethodsSTAGE was a phase III randomized, double‐blind, parallel‐group international study to evaluate the safety and efficacy of ocrelizumab compared with placebo in patients with active RA continuing MTX treatment. Patients receiving stable doses of MTX were randomized to receive 2 infusions of placebo (n = 320), ocrelizumab 200 mg (n = 343), or ocrelizumab 500 mg (n = 343) on days 1 and 15 as well as weeks 24 and 26. Coprimary end points were the proportion of patients with an American College of Rheumatology 20% improvement criteria (ACR20) response at weeks 24 and 48. Secondary end points included the change from baseline in the modified Sharp/van der Heijde score (SHS) and the ACR50/70 responses.ResultsThe ACR20 response rates were 35.7% in the placebo group, 56.9% in the ocrelizumab 200 mg group, and 54.5% in the ocrelizumab 500 mg group at 24 weeks, and 27.6%, 58.3%, and 62.1%, respectively, at 48 weeks (P < 0.0001 versus placebo for each dose at both time points). At week 48, both of the ocrelizumab doses improved the ACR50 and ACR70 response rates 3‐fold as compared with placebo and showed a statistically significant (P < 0.0001) reduction in joint damage progression relative to placebo (mean change in SHS reduced by 85% and 100% for the 200‐mg and 500‐mg doses, respectively). Rates of serious infection were comparable in the placebo (3.48 per 100 patient‐years) and ocrelizumab 200 mg (3.54 per 100 patient‐years) groups but were elevated in the ocrelizumab 500 mg group (8.66 per 100 patient‐years).ConclusionWith both ocrelizumab doses, the primary end point was met, and the signs and symptoms of RA were significantly improved at weeks 24 and 48. Ocrelizumab also significantly inhibited the progression of joint damage. A higher rate of serious infections was observed with 500 mg of ocrelizumab as compared with ocrelizumab 200 mg or placebo.
Gene–gene interaction of BLK, TNFSF4, TRAF1, TNFAIP3, and REL in systemic lupus erythematosus
Authors: Zhou Xu‐jie , Lu Xiao‐lan , Nath Swapan K. , Lv Ji‐cheng , Zhu Sai‐nan , Yang Hai‐zhen , Qin Lian‐xiang , Zhao Ming‐hui , Su Yin ,   International Consortium on the Genetics of Systemic Lupus Erythematosus, Shen Nan , Li Zhan‐guo , Zhang Hong 
Published: September 2011

AbstractObjectiveAlthough the number of convincingly established genetic associations with systemic lupus erythematosus (SLE) has increased sharply over the last few years, refinement of these associations is required, and their potential roles in gene–gene interactions need to be further investigated. Recent genome‐wide association studies (GWAS) in SLE have produced renewed interest in B cell/T cell responses and the NF‐κB signaling pathway. The aim of this study was to search for possible gene–gene interactions based on identified single‐nucleotide polymorphisms (SNPs), in using an approach based on the role of signaling pathways.MethodsThe SNPs in BLK, TNFSF4, TRAF1, TNFAIP3, and REL were replicated in order to evaluate genetic associations with SLE. TaqMan genotyping was conducted in 804 Chinese patients with SLE and 722 matched control subjects. A multiple logistic regression model was used to estimate the multiplicative interaction effect of the SNPs, and additive interactions were analyzed by 2 × 2 factorial designs. Data from a previously published GWAS conducted by the International Consortium on the Genetics of Systemic Lupus Erythematosus were derived for comparison and validation.ResultsSingle‐marker analysis validated the association of BLK rs2736340 (P = 4.25 × 10−6) as well as TNFSF4 rs2205960 (P = 2.82 × 10−5) and TNFAIP3 rs5029939 (P = 1.92 × 10−3) with SLE susceptibility in Chinese. Multiplicative interaction analysis indicated that BLK had an interactive effect with TNFSF4 in Chinese patients with SLE (P = 6.57 × 10−4). Additive interaction analysis revealed interactions between TRAF1 and TNFAIP3 in both Chinese (P = 2.18 × 10−3) and Caucasians (P = 2.86 × 10−4). In addition, multiple tendencies toward interactions were observed, and an additive effect was observed as the number of risk genotypes increased.ConclusionThe results of this study provide evidence of the possible gene–gene interactions of BLK, TNFSF4, TRAF1, TNFAIP3, and REL in SLE, which may represent a synergic effect of T cells and B cells through the NF‐κB pathway in determining immunologic aberration.
Proinflammatory Th17 cells are expanded and induced by dendritic cells in spondylarthritis‐prone HLA–B27–transgenic rats
Authors: Glatigny Simon , Fert Ingrid , Blaton Marie A. , Lories Rik J. , Araujo Luiza M. , Chiocchia Gilles , Breban Maxime 
Published: September 2011

AbstractObjectiveHLA–B27/human β2‐microglobulin–transgenic (B27‐transgenic) rats, a model of spondylarthritis (SpA), develop spontaneous colitis and arthritis under conventional conditions. CD4+ T cells are pivotal in the development of inflammation in B27‐transgenic rats. This study was undertaken to characterize the phenotype of CD4+ T cells in this model and to determine whether dendritic cells (DCs) induce proinflammatory T cells.MethodsThe phenotype of CD4+ T cells from rat lymph nodes (LNs) draining the sites of inflammation was analyzed by flow cytometry. Immunostaining was used to detect interleukin‐17 (IL‐17)–producing cells in the rat joints. DCs from B27‐transgenic or control rats (transgenic for HLA–B7 or nontransgenic) were cocultured with control CD4+ T cells and stimulated with anti–T cell receptor α/β.ResultsIL‐17A– and tumor necrosis factor α (TNFα)–producing CD4+ T cells were expanded in mesenteric and popliteal LNs from B27‐transgenic rats. The accumulation of Th17 cells correlated with disease development, in contrast to Th1 or Treg cells. IL‐17–positive mononuclear cells were detected in the arthritic joints of B27‐transgenic rats but not in the joints of control rats. Finally, in vitro cocultures demonstrated that Th17 cells were preferentially induced and expanded by DCs from B27‐transgenic rats, by a process that may involve defective engagement of costimulatory molecules.ConclusionOur findings indicate that expanded CD4+ T cells in B27‐transgenic rats exhibit a proinflammatory Th17 phenotype characterized by IL‐17A and TNFα production. Furthermore, this population is preferentially induced by DCs from B27‐transgenic rats. These data point toward an induction of Th17 cells as a possible pathogenic mechanism in this model of SpA. However, their pathogenic role still needs to be shown.
Structural changes of the brain in rheumatoid arthritis
Authors: Wartolowska Karolina , Hough Morgan G. , Jenkinson Mark , Andersson Jesper , Wordsworth B. Paul , Tracey Irene 
Published: September 2011

AbstractObjectiveTo investigate whether structural changes are present in the cortical and subcortical gray matter of the brains of patients with rheumatoid arthritis (RA).MethodsWe used two surface‐based style morphometry analysis programs and a voxel‐based style analysis program to compare high‐resolution structural magnetic resonance imaging data obtained for 31 RA patients and 25 age‐ and sex‐matched healthy control subjects.ResultsWe observed an increase in gray matter content in the basal ganglia of RA patients, mainly in the nucleus accumbens and caudate nucleus. There were no differences in the cortical gray matter. Moreover, patients had a smaller intracranial volume.ConclusionOur results suggest that RA is associated with changes in the subcortical gray matter rather than with cortical gray matter atrophy. Since the basal ganglia play an important role in motor control as well as in pain processing and in modulating behavior in response to aversive stimuli, we suggest that these changes may result from altered motor control or prolonged pain processing. The differences in brain volume may reflect either generalized atrophy or differences in brain development.
Antroquinonol differentially modulates T cell activity and reduces interleukin‐18 production, but enhances Nrf2 activation, in murine accelerated severe lupus nephritis
Authors: Tsai Pei‐Yi , Ka Shuk‐Man , Chang Jia‐Ming , Lai Jenn‐Haung , Dai Ming‐Shen , Jheng Huei‐Lin , Kuo Mao‐Tien , Chen Peini , Chen Ann 
Published: September 2011

AbstractObjectiveAccelerated severe lupus nephritis (ASLN), with an acute onset of severe clinical manifestations and histopathologic renal lesions, may represent transformation of mild LN to a severe form of glomerulonephritis. Abnormal activation of T and B cells and/or oxidative stress may play a major role in the pathogenesis of ASLN. This study tested the hypothesis that antroquinonol, a purified compound and major effective component of Antrodia camphorata with antiinflammatory and antioxidant activities, might prevent the transformation of mild LN into higher‐grade (severe) nephritis in a murine lupus model.MethodsExperimental ASLN was induced in (NZB × NZW)F1 mice by twice weekly intraperitoneal injections of Salmonella‐type lipopolysaccharide (LPS). Starting 2 days after the first dose of LPS, mice were treated daily with antroquinonol, administered by gavage, for different durations up to 5 weeks.ResultsAntroquinonol administration significantly ameliorated the proteinuria, hematuria, impairment of renal function, and development of severe renal lesions, especially cellular crescent formation, neutrophil infiltration, fibrinoid necrosis, and T cell proliferation in the glomerulus, as well as periglomerular interstitial inflammation. Mechanistic analyses revealed that antroquinonol 1) inhibited T cell activation/proliferation, but enhanced Treg cell suppression and reduced renal production of interleukin‐18 (IL‐18); 2) inhibited production of reactive oxygen species and nitric oxide, but increased activation of Nrf2 in the kidney; and 3) suppressed renal inflammation via blocking of NF‐κB activation.ConclusionAntroquinonol may have therapeutic potential for the early treatment of ASLN via its differential regulation of T cell function and lowering of IL‐18 production, but also via the promotion of Nrf2 activation.
Overexpression of T‐bet gene regulates murine autoimmune arthritis
Authors: Kondo Yuya , Iizuka Mana , Wakamatsu Ei , Yao Zhaojin , Tahara Masahiro , Tsuboi Hiroto , Sugihara Makoto , Hayashi Taichi , Yoh Keigyou , Takahashi Satoru , Matsumoto Isao , Sumida Takayuki 
Published: September 2011

AbstractObjectiveTo clarify the role of T‐bet in the pathogenesis of collagen‐induced arthritis (CIA).MethodsT‐bet–transgenic (Tg) mice under the control of the CD2 promoter were generated. CIA was induced in T‐bet–Tg mice and wild‐type C57BL/6 (B6) mice. Levels of type II collagen (CII)–reactive T‐bet and retinoic acid receptor–related orphan nuclear receptor γt (RORγt) messenger RNA expression were analyzed by real‐time polymerase chain reaction. Criss‐cross experiments using CD4+ T cells from B6 and T‐bet–Tg mice, as well as CD11c+ splenic dendritic cells (DCs) from B6 and T‐bet–Tg mice with CII were performed, and interleukin‐17 (IL‐17) and interferon‐γ (IFNγ) in the supernatants were measured by enzyme‐linked immunosorbent assay. CD4+ T cells from B6, T‐bet–Tg, or T‐bet–Tg/IFNγ−/− mice were cultured for Th17 cell differentiation, then the proportions of cells producing IFNγ and IL‐17 were analyzed by fluorescence‐activated cell sorting.ResultsUnlike the B6 mice, the T‐bet–Tg mice did not develop CIA. T‐bet–Tg mice showed overexpression of Tbx21 and down‐regulation of Rorc in CII‐reactive T cells. Criss‐cross experiments with CD4+ T cells and splenic DCs showed a significant reduction in IL‐17 production by CII‐reactive CD4+ T cells in T‐bet–Tg mice, even upon coculture with DCs from B6 mice, indicating dysfunction of IL‐17–producing CD4+ T cells. Inhibition of Th17 cell differentiation under an in vitro condition favoring Th17 cell differentiation was observed in both T‐bet–Tg mice and T‐bet–Tg/IFNγ−/− mice.ConclusionOverexpression of T‐bet in T cells suppressed the development of autoimmune arthritis. The regulatory mechanism of arthritis might involve dysfunction of CII‐reactive Th17 cell differentiation by overexpression of T‐bet via IFNγ‐independent pathways.
Cyclic loading increases friction and changes cartilage surface integrity in lubricin‐mutant mouse knees
Authors: Drewniak Elizabeth I. , Jay Gregory D. , Fleming Braden C. , Zhang Ling , Warman Matthew L. , Crisco Joseph J. 
Published: September 2011

AbstractObjectiveTo investigate the effects of lubricin gene dosage and cyclic loading on whole joint coefficient of friction and articular cartilage surface integrity in mouse knee joints.MethodsJoints from mice with 2 (Prg4+/+), 1 (Prg4+/−), or no (Prg4−/−) functioning lubricin alleles were subjected to 26 hours of cyclic loading using a custom‐built pendulum. Coefficient of friction values were measured at multiple time points. Contralateral control joints were left unloaded. Following testing, joints were examined for histologic evidence of damage and cell viability.ResultsAt baseline, the coefficient of friction values in Prg4−/− mice were significantly higher than those in Prg4+/+ and Prg4+/− mice (P < 0.001). Cyclic loading continuously increased the coefficient of friction in Prg4−/− mouse joints. In contrast, Prg4+/− and Prg4+/+ mouse joints had no coefficient of friction increases during the first 4 hours of loading. After 26 hours of loading, joints from all genotypes had increased coefficient of friction values compared to baseline and unloaded controls. Significantly greater increases occurred in Prg4−/− and Prg4+/− mouse joints compared to Prg4+/+ mouse joints. The coefficient of friction values were not significantly associated with histologic evidence of damage or loss of cell viability.ConclusionOur findings indicate that mice lacking lubricin have increased baseline coefficient of friction values and are not protected against further increases caused by loading. Prg4+/− mice are indistinguishable from Prg4+/+ mice at baseline, but have significantly greater coefficient of friction values following 26 hours of loading. Lubricin dosage affects joint properties during loading, and may have clinical implications in patients for whom injury or illness alters lubricin abundance.