bluuebunny/crossref_metadata_2025_split huggingface dataset:
Access to the Spleen Microenvironment through Lymph Shows Local Cytokine Production, Increased Cell Flux, and Altered Signaling of Immune Cells during Lipopolysaccharide-Induced Acute Inflammation
Authors: Semaeva Elvira , Tenstad Olav , Skavland Jørn , Enger Marianne , Iversen Per Ole , Gjertsen Bjørn Tore , Wiig Helge 
Published: March 2010

Abstract
The spleen is involved in fluid volume regulation, immune responses, and hematopoiesis. Yet, the composition of the fluid phase within the spleen microenviroment, the migratory routes of lymphocytes as well as the splenic response to bacterial endotoxin is incomplete. To address these issues, we isolated postnodal lymph in rats by cannulating an efferent lymphatic draining the spleen, and assessed the secretion of signaling substances during a septic response induced by LPS. Spleen lymph flow increased 8-fold after LPS exposure. The spleen exhibited a permeable microvasculature with low sieving of macromolecules that was absent after exposure to LPS. Furthermore, after LPS exposure the spleen contributed significantly to the production of pro- and anti-inflammatory cytokines, and experiments in splenectomized rats suggested it may induce a protracted inflammation because of a dominant role in IL-6 production. A significant amount of lymphocytes exited via lymphatics draining the spleen in control rats. LPS-induced inflammation resulted in increased T cell and reduced B cell subset fractions, and gave a significant increase in CD4+ and CD8+ subset T cell efflux and a reduced B cell efflux in spleen lymph. Exposure of leukocytes to the spleen microenvironment affected their signaling status, and by phosphorylation specific flow cytometry we could identify STAT3 and CREB as important mediators in the cellular signaling occurring during endotoxemia. We conclude that analysis of spleen lymph may unravel immune cell migration patterns and local signaling, and immune cells exit via lymph having acquired specific activation signatures after exposure to the spleen microenvironment.
Lysophosphatidylcholine Increases Neutrophil Bactericidal Activity by Enhancement of Azurophil Granule-Phagosome Fusion via Glycine·GlyRα2/TRPM2/p38 MAPK Signaling
Authors: Hong Chang-Won , Kim Taek-Keun , Ham Hwa-Yong , Nam Ju-Suk , Kim Yong Ho , Zheng Haifeng , Pang Bo , Min Tae-Kwon , Jung Jun-Sub , Lee Si-Nae , Cho Hyun-Jeong , Kim Ee-Jin , Hong In-Hwan , Kang Tae-Cheon , Lee Jongho , Oh Seog Bae , Jung Sung Jun , Kim Sung Joon , Song Dong-Keun 
Published: March 2010

Abstract
Neutrophils are the first-line defense against microbes. Enhancing the microbicidal activity of neutrophils could complement direct antimicrobial therapy for controlling intractable microbial infections. Previously, we reported that lysophosphatidylcholine (LPC), an endogenous lipid, enhances neutrophil bactericidal activity (Yan et al. 2004. Nat. Med. 10: 161–167). In this study we show that LPC enhancement of neutrophil bactericidal activity is dependent on glycine, and is mediated by translocation of intracellularly located glycine receptor (GlyR) α2 to the plasma membrane, and subsequent increase in azurophil granule-phagosome fusion/elastase release. LPC induced GlyRα2-mediated [Cl−]i increase, leading to transient receptor potential melastatin (TRPM)2-mediated Ca2+ influx. Studies using human embryonic kidney 293 cells heterologously expressing TRPM2 and neutrophils showed that TRPM2 channel activity is sensitive to [Cl−]i. Finally, LPC induced p38 MAPK phosphorylation in an extracellular calcium/glycine dependent manner. SB203580, a p38 MAPK inhibitor, blocked LPC-induced enhancement in Lucifer yellow uptake, azurophil granule-phagosome fusion, and bactericidal activity. These results propose that enhancement of azurophil granule-phagosome fusion via GlyRα2/TRPM2/p38 MAPK signaling is a novel target for enhancement of neutrophil bactericidal activity.
Polycomb Group Gene Product Ring1B Regulates Th2-Driven Airway Inflammation through the Inhibition of Bim-Mediated Apoptosis of Effector Th2 Cells in the Lung
Authors: Suzuki Akane , Iwamura Chiaki , Shinoda Kenta , Tumes Damon J. , Y. Kimura Motoko , Hosokawa Hiroyuki , Endo Yusuke , Horiuchi Shu , Tokoyoda Koji , Koseki Haruhiko , Yamashita Masakatsu , Nakayama Toshinori 
Published: March 2010

Abstract
Polycomb group (PcG) gene products regulate the maintenance of homeobox gene expression in Drosophila and vertebrates. In the immune system, PcG molecules control cell cycle progression of thymocytes, Th2 cell differentiation, and the generation of memory CD4 T cells. In this paper, we extended the study of PcG molecules to the regulation of in vivo Th2 responses, especially allergic airway inflammation, by using conditional Ring1B-deficient mice with a CD4 T cell-specific deletion of the Ring1B gene (Ring1B−/− mice). In Ring1B−/− mice, CD4 T cell development appeared to be normal, whereas the differentiation of Th2 cells but not Th1 cells was moderately impaired. In an Ag-induced Th2-driven allergic airway inflammation model, eosinophilic inflammation was attenuated in Ring1B−/− mice. Interestingly, Ring1B−/− effector Th2 cells were highly susceptible to apoptosis in comparison with wild-type effector Th2 cells in vivo and in vitro. The in vitro experiments revealed that the expression of Bim was increased at both the transcriptional and protein levels in Ring1B−/− effector Th2 cells, and the enhanced apoptosis in Ring1B−/− Th2 cells was rescued by the knockdown of Bim but not the other proapoptotic genes, such as Perp, Noxa, or Bax. The enhanced apoptosis detected in the transferred Ring1B−/− Th2 cells in the lung of the recipient mice was also rescued by knockdown of Bim. Therefore, these results indicate that Ring1B plays an important role in Th2-driven allergic airway inflammation through the control of Bim-dependent apoptosis of effector Th2 cells in vivo.
Isolation of Legionella‐Containing Vacuoles by Immuno‐Magnetic Separation
Authors: Urwyler Simon , Finsel Ivo , Ragaz Curdin , Hilbi Hubert 
Published: March 2010

AbstractThe environmental bacterium Legionella pneumophila naturally parasitizes free‐living amoebae. L. pneumophila is an opportunistic human pathogen that grows in macrophages, thus causing a life‐threatening pneumonia termed Legionnaires' disease. The bacteria replicate intracellularly in environmental and immune phagocytes within a unique compartment, the Legionella‐containing vacuole (LCV). Formation of LCVs is a complex and robust process involving >150 secreted bacterial effector proteins, which are believed to subvert host cell signaling and vesicle trafficking pathways. This unit describes a simple approach to purify intact LCVs from Dictyostelium discoideum amoebae. The method comprises a two‐step purification protocol that includes immuno‐magnetic separation by means of an antibody against an effector protein specifically binding to LCVs, followed by density gradient centrifugation. The use of D. discoideum producing a fluorescent LCV marker and fluorescently labeled L. pneumophila allow tracking the enrichment of LCVs by light microscopy. Curr. Protoc. Cell Biol. 46:3.34.1‐3.34.14. © 2010 by John Wiley & Sons, Inc.
Quantitative Analysis of Endocytosis and Turnover of Epidermal Growth Factor (EGF) and EGF Receptor
Authors: Sorkin Alexander , Duex Jason E. 
Published: March 2010

AbstractBinding of epidermal growth factor (EGF) to the EGF receptor (EGFR) initiates signal transduction, ultimately leading to altered gene expression. Ligand‐activated EGFR is also rapidly internalized and then targeted to lysosomes for degradation or recycled back to the plasma membrane. Endocytosis is a major regulator of EGFR signaling. Therefore, elucidation of the mechanisms of EGFR endocytosis is essential for a better understanding of EGFR biology. In order to achieve a comprehensive analysis of these mechanisms, reliable methods for measuring the rates of EGFR protein turnover and the rate parameters for individual steps of EGFR endocytic trafficking must be employed. The protocols in this unit describe methodologies to measure the rates of EGFR synthesis and degradation, to monitor EGF‐induced down‐regulation of surface EGFR, to measure the kinetic rate parameters of internalization, recycling, and degradation of radiolabeled EGF, and to perform radioiodination of EGF by the chloramine T method. Curr. Protoc. Cell Biol. 46:15.14.1‐15.14.20. © 2010 by John Wiley & Sons, Inc.
Therapeutic effects of hyaluronate injections in patients with chronic painful shoulder: A meta‐analysis of randomized controlled trials
Authors: Saito Seiji , Furuya Takefumi , Kotake Shigeru 
Published: March 2010

AbstractObjectiveTo elucidate the therapeutic efficacy and safety of injection of hyaluronate (HA) for chronic painful shoulder.MethodsThe meta‐analysis comprised randomized controlled trials (RCTs) that compared the efficacy of HA injections with that of a placebo. Articles were retrieved through systematic searches of databases, including Medline, EMBase, and Japana Centra Revuo Medicina. The outcome end points were classified into 5 categories: pain, shoulder range of motion (ROM), total functional score, comparison between HA and steroid injections, and HA safety. The primary outcome measures of the efficacy of HA injections were the standardized mean differences (SMDs) and the relative risk (RR) or odds ratio (OR) between HA and placebo groups.ResultsNineteen RCTs (2,120 participants) were pooled for the meta‐analysis. Injection of HA can decrease symptoms of chronic painful shoulder. An improvement was found in pain outcomes (SMD 0.39; 95% confidence interval [95% CI] 0.26, 0.53 and OR 1.84; 95% CI 1.49, 2.26) and total functional scores (SMD 0.36; 95% CI 0.01, 0.71), with few adverse events (RR 1.01; 95% CI 0.57, 1.77). Improvement in shoulder ROM was not effectively achieved. HA injection was modestly more effective than steroid injection, as estimated by the total functional score (SMD 0.36; 95% CI 0.02, 0.70), which indicated a likely benefit of injection of HA over steroid injection.ConclusionThis meta‐analysis confirms that HA injection is effective in relief of pain and is a safe alternative therapy for chronic painful shoulder.
Validity of ultrasonography and measures of adult shoulder function and reliability of ultrasonography in detecting shoulder synovitis in patients with rheumatoid arthritis using magnetic resonance imaging as a gold standard
Authors: Bruyn G. A. W. , Pineda C. , Hernandez‐Diaz C. , Ventura‐Rios L. , Moya C. , Garrido J. , Groen H. , Pena A. , Espinosa R. , Möller I. , Filippucci E. , Iagnocco A. , Balint P. V. , Kane D. , D'Agostino M.‐A. , Angulo M. , Ponte R. , Fernandez‐Gallardo J. M. , Naredo E. 
Published: March 2010

AbstractObjectiveTo assess the intra‐ and interobserver reproducibility of musculoskeletal ultrasonography (US) in detecting inflammatory shoulder changes in patients with rheumatoid arthritis, and to determine the agreement between US and the Shoulder Pain and Disability Index (SPADI) and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, using magnetic resonance imaging (MRI) as a gold standard.MethodsEleven rheumatologists investigated 10 patients in 2 rounds independently and blindly of each other by US. US results were compared with shoulder function tests and MRI.ResultsThe positive and negative predictive values (NPVs) for axillary recess synovitis (ARS) were 0.88 and 0.43, respectively, for posterior recess synovitis (PRS) were 0.36 and 0.97, respectively, for subacromial/subdeltoid bursitis (SASB) were 0.85 and 0.28, respectively, and the NPV for biceps tenosynovitis (BT) was 1.00. The intraobserver kappa was 0.62 for ARS, 0.59 for PRS, 0.51 for BT, and 0.70 for SASB. The intraobserver kappa for power Doppler US (PDUS) signal was 0.91 for PRS, 0.77 for ARS, 0.94 for SASB, and 0.53 for BT. The interobserver maximum kappa was 0.46 for BT, 0.95 for ARS, 0.52 for PRS, and 0.61 for SASB. The interobserver reliability of PDUS was 1.0 for PRS, 0.1 for ARS, 0.5 for BT, and 1.0 for SASB. P values for the SPADI and DASH versus cuff tear on US were 0.02 and 0.01, respectively; all other relationships were not significant.ConclusionOverall agreements between gray‐scale US and MRI regarding synovitis of the shoulder varied considerably, but excellent results were seen for PDUS. Measures of shoulder function have a poor relationship with US and MRI. Improved standardization of US scanning technique could further reliability of shoulder US.
Predictors for remission in rheumatoid arthritis patients: A systematic review
Authors: Katchamart Wanruchada , Johnson Sindhu , Lin Hsing‐Ju Lucy , Phumethum Veerapong , Salliot Carine , Bombardier Claire 
Published: March 2010

AbstractObjectiveTo summarize the potential predictors of remission in patients with rheumatoid arthritis (RA).MethodsWe performed a systematic review of prognostic studies that identified the predictors of remission in RA patients. Studies were identified in Medline, EMBase, and the Cochrane Registry, and by hand search. We included only studies performing multivariate analysis.ResultsA total of 18 studies from 2,062 citations were included. The following variables were found to be the independent predictors of RA remission: male sex; young age; late‐onset RA; short disease duration; nonsmoker; low baseline disease activity; mild functional impairment; low baseline radiographic damage; absence of rheumatoid factor and anti–citrullinated peptide; low serum level of acute‐phase reactant, interleukin‐2, and RANKL at baseline; MTHFR 677T alleles and 1298C alleles in the methotrexate (MTX)–treated patients; magnetization transfer ratio 2756A allele ± either the SLC 19A180A allele or the TYMS 3R‐del6 haplotype in the MTX plus sulfasalazine combination–treated patients; early treatment with nonbiologic disease‐modifying antirheumatic drug (DMARD) combinations; the use of anti–tumor necrosis factor (anti‐TNF); the concurrent use of DMARDs in anti‐TNF–treated patients; and moderate or good response to treatments at the first 6 months. The magnitude of the association in the individual predictor was diverse among the studies depending on the patient characteristics, the study characteristics, and the variables used to adjust for in the models.ConclusionA number of independent predictors of remission, i.e., baseline clinical and laboratory characteristics and genetic markers, were summarized. The predictive value of prognostic factors recently identified needs to be confirmed.
A national survey of Veterans Affairs Rheumatologists for relevance of quality of care indicators for Gout management
Authors: Singh Jasvinder A. , Alpert Michael D. , Kerr Gail 
Published: March 2010

AbstractObjectiveTo determine the relevance of current gout quality indicators (QIs).MethodsMembers of the Veterans Affairs (VA) Rheumatology Consortium were invited to participate in an online survey and provide opinions (rank 0–10) regarding existing gout QIs. Opinions sought on each QI were 1) relevance to US veterans, 2) likelihood to improve gout care, and 3) ease of electronic capture. Participants were also asked to rank their top 3 gout QIs.ResultsParticipating VA rheumatologists were mainly men, with a mean age of 51.3 years, and experienced in the management of gout. All 10 gout QIs were considered relevant, with a score of 8.2 or higher. The initiation of urate‐lowering therapy, monitoring of urate levels after initiation of urate‐lowering therapy, and treatment of acute gout with antiinflammatory agents scored the highest with regard to likelihood of improving gout care, with the first 2 QIs also thought to be the most relevant. Adjustment of initial allopurinol dosing in patients with renal impairment and in those receiving concurrent azathioprine/6‐mercaptopurine were perceived as the QIs most amenable to electronic capture. The top‐ranked QIs were initiation of urate‐lowering therapy with frequent gout attacks, serum urate monitoring after initiation of urate‐lowering therapy, and adjustment of initial allopurinol dose to renal function.ConclusionIn a national survey of VA rheumatologists, most gout QIs were thought to be highly relevant. QIs related to initiation of urate‐lowering therapy, serum urate monitoring, and initial dosing of allopurinol were ranked the most important for veterans with gout.
Full‐Field Characterization of Wishboning Strain in the Colobine Mandibular Symphysis
Authors: Bucinell Ronald B. , Daegling David J. , Scott Mcgraw W. , Rapoff Andrew J. 
Published: March 2010

AbstractThe masticatory loading regime of lateral transverse bending (wishboning) is hypothesized to be instrumental in the evolution of symphyseal form among primates. The biomechanics of wishboning have largely been inferred by assuming that the mandible behaves as a curved beam under this load; however, the characterization of stress and strain in the anthropoid symphysis has been interpretively challenging. This is due, in part, to both limitations of sampling strain in an in vivo context and the incongruence of beam theory assumptions on the one hand, and the anatomical complexity of mandibular morphology on the other. Utilizing three‐dimensional (3D) Digital Image Correlation (DIC), we employ an in vitro approach to characterize the strain field in a sample of colobine mandibles under simulated wishboning loads in order to assess the utility of idealized curved beam models for characterizing strain gradients in symphyseal bone. Conventional theory of curved beams suggest that colobine mandibles should exhibit reduced disparity of labial and lingual stresses relative to papionin primates given differences in overall mandibular architecture. This prediction is borne out by our analysis: whereas macaques experience lingual:labial strain disparities of 3.5:1, the colobine mandibles exhibit ratios on the order of 2–3:1. However, despite the fact that wishboning loads represent a case of asymmetric bending, details of the wishboning strain field do not conform to expected stress distribution under this model. Anat Rec, 293:549–556, 2010. © 2010 Wiley‐Liss, Inc.
Edentulation Alters Material Properties of Cortical Bone in the Human Craniofacial Skeleton: Functional Implications for Craniofacial Structure in Primate Evolution
Authors: Dechow Paul C. , Wang Qian , Peterson Jill 
Published: March 2010

AbstractSkeletal adaptations to reduced function are an important source of skeletal variation and may be indicative of environmental pressures that lead to evolutionary changes. Humans serve as a model animal to investigate the effects of loss of craniofacial function through edentulation. In the human maxilla, it is known that edentulation leads to significant changes in skeletal structure such as residual ridge resorption and loss of cortical thickness. However, little is known about changes in bone tissue structure and material properties, which are also important for understanding skeletal mechanics but are often ignored. The aims of this study were to determine cortical material properties in edentulous crania and to evaluate differences with dentate crania and thus examine the effects of loss of function on craniofacial structure. Cortical bone samples from 15 edentulous human skulls were measured for thickness and density. Elastic properties and directions of maximum stiffness were determined by using ultrasonic techniques. These data were compared to those from dentate crania reported in a previous investigation. Cortical bone from all regions of the facial skeleton of edentulous individuals is thinner than in dentate skulls. Elastic and shear moduli, and density are similar or greater in the zygoma and cranial vault of edentulous individuals, whereas these properties are less in the maxilla. Most cortical bone, especially in edentulous maxillae, has reduced directional orientation. The loss of significant occlusal loads following edentulation may contribute to the change in material properties and the loss of orientation over time during the normal process of bone remodeling. These results suggest that area‐specific cortical microstructural changes accompany bone resorption following edentulation. They also suggest that functional forces are important for maintaining bone mass throughout the craniofacial skeleton, even in areas such as the browridges, which have been thought to be little affected by function, because of low in vivo strains found there in several primate studies. Anat Rec, 293:618–629, 2010. © 2010 Wiley‐Liss, Inc.
Shouldering the Burdens of Locomotion and Posture: Glenohumeral Joint Structure in Prosimians
Authors: Wright‐Fitzgerald Adrian S. , Balceniuk Mark D. , Burrows Anne M. 
Published: March 2010

AbstractDespite its importance in movement of the upper limb, the soft‐tissue morphology of the shoulder joint complex (the acromioclavicular, coracoclavicular, and glenohumeral joints) across primates is poorly understood. This study compares soft‐tissue morphology of these three shoulder joint components among broad phylogenetic, locomotor, and postural behavior ranges in prosimian primates. Two adult specimens of Galago moholi (a vertical clinger and leaper) were dissected for study, along with one adult each of Cheirogaleus medius (an arboreal quadruped), Eulemur macaco (an arboreal quadruped that also frequently engages in suspensory behavior), and Tarsius syrichta (a vertical clinger and leaper). Because of their role in glenohumeral joint movement and stabilization, the rotator cuff muscles were also dissected and weighed among the species. Results showed that muscle mass of individual components of the rotator cuff musculature may be adaptive to locomotor and postural behaviors of the taxa in this study. Two soft‐tissue components of the glenohumeral joint, but not the acromioclavicular and coracoclavicular joints, were also considered adaptive. The quadrupedal species, C. medius and E. macaco, both had glenohumeral ligaments and E. macaco had a relatively deeper glenoid articular surface for the humerus because of the shape of the glenoid labrum. Additionally, this study noted a lack of a teres minor muscle in G. moholi, C. medius, and E. macaco despite previous studies describing them. A relatively robust teres minor muscle was found in T. syrichta. Even with the limited sample dissected here, these results suggest that soft‐tissue joint morphology itself may be as adaptive to locomotory and postural styles as osseous morphology. Anat Rec, 293:680–691, 2010. © 2010 Wiley‐Liss, Inc.