bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Embryonic Staging Table for In Ovo Development of Eublepharis macularius, the Leopard Gecko
Authors: Wise Patrick A.D. , Vickaryous Matthew K. , Russell Anthony P. 
Published: July 2009

AbstractSquamates constitute a major vertebrate radiation, representing almost one‐third of all known amniotes. Although speciose and morphologically diverse, they remain poorly represented in developmental studies. Here, we present an embryonic staging table of in ovo development for the basal gekkotan Eublepharis macularius (the leopard gecko) and advocate this species as a laboratory‐appropriate developmental model. E. macularius, is a hardy and tractable species of relatively large body size (with concomitantly relatively large eggs and embryos), that is widely available and easy to maintain and propagate. Additionally, E. macularius displays a body plan appropriate to the study of the plesiomorphic quadrupedal condition of early pentadactylous terrestrial amniotes. Although not unexpected, it is worth noting that the morphological events characterizing limb development in E. macularius are comparable with those described for the avian Gallus gallus. Therefore, E. macularius holds great promise as a model for developmental studies focusing on pentadactyly and the formation of digits. Furthermore, it is also attractive as a developmental model because it demonstrates temperature‐dependent sex determination. The staging table presented herein is based on an all‐female series and represents the entire 52 day in ovo period. Overall, embryogenesis of E. macularius is similar to that of other squamates in terms of developmental stage attained at the time of oviposition, patterns of limb and pharyngeal arch development, and features of the appearance of scalation and pigmentation, indicative of a conserved developmental program. Anat Rec, 292:1198–1212, 2009. © 2009 Wiley‐Liss, Inc.
A Reevaluation of the Unusual Abdominal Musculature of Squamate Reptiles (Reptilia: Squamata)
Authors: Bhullar Bhart‐Anjan S. 
Published: July 2009

AbstractThe abdominal muscles of lizards and snakes (Squamata) have been the subject of periodic attention from anatomists, embryologists, and systematists. Until now, the presence of a superficial portion of the m. rectus abdominis, named the m. rectus abdominis lateralis, has been considered a key synapomorphy of the clade Autarchoglossa, which includes all extant squamates save Gekkota and Iguania. However, the precise anatomical relations of the m. rectus abdominis lateralis have never been fully investigated. Here, I show that the m. rectus abdominis lateralis is present in Iguania. Its absence in Gekkota represents rare gross anatomical support for recent molecular‐structure‐based hypotheses of squamate relationships placing geckoes as sister to the remaining squamates. Where present, it is the most superficial trunk muscle, exterior to the m. obliquus externus. The separation of the m. rectus abdominis lateralis from the m. rectus abdominis occurs as the m. obliquus externus aponeurosis and part of the m. obliquus internus aponeurosis emerge superficially to form the outer portion of the rectus sheath. In Autarchoglossa, the contralateral mm. recti abdomines laterales meet at the midline and are attached to the imbricae of the transverse scale rows characteristic of the clade, suggesting developmental, functional, and evolutionary association. Because the m. rectus abdominis lateralis is sometimes continuous with the pectoralis, its exclusive association with the m. rectus abdominis is questionable. It may be a neomorphic layer that is part of the abaxial developmental system, comprising those muscles whose connective tissue is largely derived from lateral plate as opposed to somatic mesoderm. Anat Rec, 292:1154–1161, 2009. © 2009 Wiley‐Liss, Inc.
Architecture of the Blood‐Spleen Barrier in the Soft‐Shelled Turtle, Pelodiseus Sinensis
Authors: Bao Hui‐Jun , Li Mei‐Ying , Wang Jiang , Qin Jun‐Hui , Xu Chun‐Sheng , Hei Nai‐Nan , Yang Ping , Gandahi J.A. , Chen Qiu‐Sheng 
Published: July 2009

AbstractThe soft‐shelled turtle, Pelodiseus sinensis, and its spleen section showing carbon particles of injected Indian ink mainly in the ellipsoid which composed the blood‐spleen barrier. See Bao et al, on page 1079, in this issue. Anatomical Record 292:1079–1087.
The role of neutrophil apoptosis in juvenile‐onset systemic lupus erythematosus
Authors: Midgley Angela , McLaren Zoe , Moots Robert J. , Edwards Steven W. , Beresford Michael W. 
Published: July 2009

AbstractObjectiveAccumulation of apoptotic cells may lead to the development of systemic lupus erythematosus (SLE) through a breakdown in immune tolerance. Altered neutrophil apoptosis may contribute to nuclear autoantigen exposure, ultimately leading to autoantibody generation. This study aimed to determine whether neutrophil apoptosis is altered in patients with juvenile‐onset SLE as compared with controls.MethodsApoptosis was measured in neutrophils from patients with juvenile‐onset SLE (n = 12), adult‐onset SLE (n = 6), and pediatric patients with inflammatory (n = 12) and noninflammatory (n = 12) conditions. Annexin V staining and flow cytometry were used to determine neutrophil apoptosis. Proapoptotic and antiapoptotic proteins were measured in sera and in neutrophil cell lysates.ResultsNeutrophil apoptosis was significantly increased in patients with juvenile‐onset SLE as compared with the noninflammatory controls at time 0. Incubation of neutrophils with sera from patients with juvenile‐onset SLE further increased neutrophil apoptosis as compared with incubation with sera from pediatric controls. Concentrations of TRAIL and FasL were significantly increased in sera from patients with juvenile‐onset SLE, whereas interleukin‐6, tumor necrosis factor α, and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) were significantly decreased. Addition of GM‐CSF to sera from patients with juvenile‐onset SLE significantly decreased neutrophil apoptosis as compared with juvenile‐onset SLE sera alone. The expression of proapoptotic proteins (caspase 3, Fas, and FADD) was elevated in juvenile‐onset SLE neutrophils, whereas the expression of antiapoptotic proteins (cellular inhibitor of apoptosis 1 and 2 and X‐linked inhibitor of apoptosis) was decreased. Neutrophil apoptosis correlated with biomarkers of disease activity (erythrocyte sedimentation rate and double‐stranded DNA concentration) and the British Isles Lupus Assessment Group disease activity score.ConclusionOur data demonstrate an imbalance in proapoptotic and antiapoptotic factors in both neutrophils and sera from patients with juvenile‐onset SLE. This imbalance results in increased neutrophil apoptosis in these patients. Correlations with markers of disease activity indicate that altered neutrophil apoptosis in juvenile‐onset SLE patients may play a pathogenic role in this condition.
Golimumab, a human anti–tumor necrosis factor α monoclonal antibody, injected subcutaneously every four weeks in methotrexate‐naive patients with active rheumatoid arthritis: Twenty‐four–week results of a phase III, multicenter, randomized, double‐blind, placebo‐controlled study of golimumab before methotrexate as first‐line therapy for early‐onset rheumatoid arthritis
Authors: Emery Paul , Fleischmann Roy M. , Moreland Larry W. , Hsia Elizabeth C. , Strusberg Ingrid , Durez Patrick , Nash Peter , Amante Eric Jason B. , Churchill Melvin , Park Won , Pons‐Estel Bernardo Antonio , Doyle Mittie K. , Visvanathan Sudha , Xu Weichun , Rahman Mahboob U. 
Published: July 2009

AbstractObjectiveTo assess the safety and efficacy of golimumab in methotrexate (MTX)–naive patients with active rheumatoid arthritis (RA).MethodsMTX‐naive patients with RA (n = 637) were randomized to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Subcutaneous injections of golimumab or placebo were administered every 4 weeks. The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week. The primary end point, the proportion of patients meeting the American College of Rheumatology 50% improvement criteria (achieving an ACR50 response) at week 24, required significant differences between groups 3 and 4 combined (combined group) versus group 1 and significant differences in a pairwise comparison (group 3 or group 4 versus group 1).ResultsAn intent‐to‐treat (ITT) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 (38.4% and 29.4%, respectively; P = 0.053), while a post hoc modified ITT analysis (excluding 3 untreated patients) of the ACR50 response showed statistically significant differences between the combined group and group 1 (38.5% versus 29.4%; P = 0.049) and between group 3 (40.5%; P = 0.038) but not group 4 (36.5%; P = 0.177) and group 1. Group 2 was noninferior to group 1 for the ACR50 response at week 24 (33.1%; 95% confidence interval lower bound −5.2%; predefined delta value for noninferiority −10%). The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters, including response/remission according to the Disease Activity Score in 28 joints. Serious adverse events occurred in 7%, 3%, 6%, and 6% of patients in groups 1, 2, 3, and 4, respectively.ConclusionAlthough the primary end point was not met, the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than, and the efficacy of golimumab alone is similar to, the efficacy of MTX alone in reducing RA signs and symptoms in MTX‐naive patients, with no unexpected safety concerns.
Determinants of red blood cell methotrexate polyglutamate concentrations in rheumatoid arthritis patients receiving long‐term methotrexate treatment
Authors: Stamp Lisa K. , O'Donnell John L. , Chapman Peter T. , Zhang Mei , Frampton Christopher , James Jill , Barclay Murray L. 
Published: July 2009

AbstractObjectiveMethotrexate (MTX) is the most commonly used disease‐modifying antirheumatic drug (DMARD) in the management of rheumatoid arthritis (RA). MTX is transported into cells, where additional glutamate moieties are added and it is retained as MTX polyglutamates (MTXGlu [referred to as a group as MTXGlun]). There is large interpatient variability in MTXGlunconcentrations. This study was undertaken to determine nongenetic factors that influence red blood cell (RBC) MTXGlunconcentrations in patients receiving long‐term stable low‐dose oral MTX.MethodsOne hundred ninety‐two patients receiving long‐term oral MTX for the treatment of RA were recruited. Trough MTXGlunconcentrations were measured by high‐performance liquid chromatography. Univariate analysis was performed to determine variables influencing MTXGlunconcentrations. Backward stepwise multivariate regression analysis was done to determine variables that affect individual MTXGlunconcentrations; variables withPvalues of <0.1 in the univariate analysis for any MTXGlunwere included.ResultsUnivariate analysis revealed that increased age, lower estimated glomerular filtration rate (GFR), higher MTX dosage, longer duration of MTX treatment, and use of prednisone were associated with significantly higher MTXGlunconcentrations. Smokers had significantly lower concentrations of MTXGlu3, MTXGlu3–5, and MTXGlu1–5. Sex, rheumatoid factor and anti–cyclic citrullinated peptide status, RBC folate level, and body mass index had no significant effect on MTXGlunlevels. Concomitant use of other DMARDs was associated with lower MTXGlu2levels, and treatment with nonsteroidal antiinflammatory drugs was associated with lower MTXGlu3and MTXGlu1–5concentrations. Multivariate regression analysis revealed that age, MTX dosage, and estimated GFR were the major determinants of MTXGlunconcentrations.ConclusionLarge interpatient variability in MTXGlunconcentrations can be explained, at least in part, by a combination of factors, particularly age, MTX dosage, and renal function. There are complex interactions between smoking, RBC folate levels, and concentrations of MTXGlun.
A polymorphism within IL21R confers risk for systemic lupus erythematosus
Authors: Webb Ryan , Merrill Joan T. , Kelly Jennifer A. , Sestak Andrea , Kaufman Kenneth M. , Langefeld Carl D. , Ziegler Julie , Kimberly Robert P. , Edberg Jeffrey C. , Ramsey‐Goldman Rosalind , Petri Michelle , Reveille John D. , Alarcón Graciela S. , Vilá Luis M. , Alarcón‐Riquelme Marta E. , James Judith A. , Gilkeson Gary S. , Jacob Chaim O. , Moser Kathy L. , Gaffney Patrick M. , Vyse Timothy J. , Nath Swapan K. , Lipsky Peter , Harley John B. , Sawalha Amr H. 
Published: July 2009

AbstractObjectiveInterleukin‐21 (IL‐21) is a member of the type I cytokine superfamily that has a variety of effects on the immune system, including B cell activation, plasma cell differentiation, and immunoglobulin production. The expression of IL‐21 receptor (IL‐21R) is reduced in the B cells of patients with systemic lupus erythematosus (SLE), while serum IL‐21 levels are increased both in lupus patients and in some murine lupus models. We recently reported that polymorphisms within the IL21 gene are associated with increased susceptibility to SLE. The aim of this study was to examine the genetic association between single‐nucleotide polymorphisms (SNPs) within IL21R and SLE.MethodsWe genotyped 17 SNPs in the IL21R gene in 2 large cohorts of lupus patients (a European‐derived cohort and a Hispanic cohort) and in ethnically matched healthy controls.ResultsWe identified and confirmed the association between rs3093301 within the IL21R gene and SLE in the 2 cohorts (meta‐analysis odds ratio 1.16 [95% confidence interval 1.08–1.25], P = 1.0 × 10−4).ConclusionOur findings indicate that IL21R is a novel susceptibility gene for SLE.
Naturopathic treatment of rotator cuff tendinitis among Canadian postal workers: A randomized controlled trial
Authors: Szczurko Orest , Cooley Kieran , Mills Edward J. , Zhou Qi , Perri Dan , Seely Dugald 
Published: July 2009

AbstractObjectiveTo explore the effectiveness of naturopathic care (NC) on rotator cuff tendinitis using a prospective randomized clinical trial design.MethodsCanadian postal workers with rotator cuff tendinitis for a duration of >6 weeks were randomized to receive NC (n = 43) or standardized physical exercises (PEs; n = 42) over 12 weeks. Participants in the NC group received dietary counseling, acupuncture, and Phlogenzym (2 tablets 3 times/day). The PE intervention group received passive, active‐assisted, and active range of motion exercises and matched placebo. The primary outcome measure was the Shoulder Pain and Disability Index (SPADI), and secondary outcomes were the pain visual analog scale (VAS), Short Form 36 (SF‐36), Measure Yourself Medical Outcomes Profile (MYMOP), and shoulder maximal range of motion. Participants and assessors were blinded to group and placebo allocation.ResultsSeventy‐seven participants (87%) completed ≥8 weeks of the trial. Final total SPADI scores decreased by 54.5% (P < 0.0001) in the NC group and by 18% (P = 0.0241) in the PE group. Between‐group differences in changes to SPADI scores showed statistically significant decreases in shoulder pain and disability in the NC group compared with the PE group (P < 0.0001). Significant differences between groups were also observed in the pain VAS, MYMOP, SF‐36, and shoulder extension, flexion, and abduction, with the NC group showing superiority in each outcome. No serious adverse reactions were observed.ConclusionNC and PE provided significant improvements, with greater improvement in shoulder function in the NC group compared with the PE group. Statistically significant improvements in quality of life measures were observed in the NC group as compared with the PE group.
Health‐related quality of life in systemic sclerosis: A systematic review
Authors: Hudson Marie , Thombs Brett D. , Steele Russell , Panopalis Pantelis , Newton Evan , Baron Murray ,   Canadian Scleroderma Research Group
Published: July 2009

AbstractObjectiveA number of studies (all n <200) have assessed health‐related quality of life (HRQOL) in patients with systemic sclerosis (SSc), but no systematic review of the effect of SSc on HRQOL has been done. The objective of this study was to systematically review the literature on HRQOL in SSc measured using the Medical Outcomes Trust Short Form 36 (SF‐36).MethodsA comprehensive search was conducted in August 2007 using Medline, CINAHL, and EMBase to identify original research studies reporting SF‐36 scores of SSc patients. Selected studies were reviewed and characteristics of the study samples and SF‐36 data were extracted. Bayesian meta‐analysis and meta‐regression were performed to obtain pooled estimates of SF‐36 physical component summary (PCS) and mental component summary (MCS) scores for all patients as well as by limited and diffuse disease status.ResultsTwelve data sets with a total of 1,127 SSc patients were included in the systematic review. HRQOL was impaired in patients with SSc, with pooled SF‐36 PCS scores being more than 1 SD below the general population (38.3; 95% credible interval [95% CI] 35.2, 41.5) and pooled SF‐36 MCS scores being ∼0.5 SDs below the general population (46.6; 95% CI 44.2, 49.1). SF‐36 PCS scores were 3.5 points (95% CI −1.0, 8.0) lower in patients with diffuse compared with limited disease.ConclusionThis study provides robust evidence of the presence and magnitude of impairment in HRQOL in patients with SSc. Although the impairment appears greater in physical health, mental health impairment is also reported.
Profiling microRNA expression in bovine articular cartilage and implications for mechanotransduction
Authors: Dunn Walter , DuRaine Grayson , Reddi A. Hari 
Published: July 2009

AbstractObjectiveArticular cartilage is an avascular tissue with precise polarity and organization comprising 3 distinct functional zones: the surface, middle, and deep zones. Each zone has a different gene expression pattern that plays a specific role in articular cartilage development and maintenance. MicroRNA (miRNA) are small noncoding gene products that play an important regulatory role in determining cell differentiation and function. The purpose of this study was to test our hypothesis that miRNA expression profiles in the different articular cartilage zones as well as between regions subjected to different levels of weight‐bearing stresses are unique.MethodsUsing an miRNA microarray approach in conjunction with quantitative reverse transcription–polymerase chain reaction, we identified miRNA in bovine articular cartilage that were differentially expressed in the different functional zones and in the anterior weight‐bearing and posterior non–weight‐bearing regions of the medial femoral condyle (M1 and M4, respectively).ResultsWe identified miRNA‐221 and miR‐222 as part of a subset of differentially expressed miRNA that were up‐regulated in articular cartilage in the anterior, M1, greater weight‐bearing location. Additionally, miR‐126, miR‐145, and miR‐335 were down‐regulated in monolayers of tissue‐cultured chondrocytes as compared with levels determined directly from intact native cartilage.ConclusionIn conclusion, miR‐222 expression patterns in articular cartilage are higher in the weight‐bearing anterior medial condyle as compared with the posterior non–weight‐bearing medial condyle. Thus, miR‐222 might be a potential regulator of an articular cartilage mechanotransduction pathway. These data implicate miRNA in the maintenance of articular cartilage homeostasis and are therefore targets for articular cartilage tissue engineering and regenerative medicine.
Regulation of plasminogen activator inhibitor 1 expression in human osteoarthritic chondrocytes by fluid shear stress: Role of protein kinase Cα
Authors: Yeh Chih‐Chang , Chang Hsin‐I , Chiang Jui‐Kun , Tsai Wang‐Ting , Chen Li‐Ming , Wu Chean‐Ping , Chien Shu , Chen Cheng‐Nan 
Published: July 2009

AbstractObjectiveTo test a fluid flow system for the investigation of the influence of shear stress on expression of plasminogen activator inhibitor 1 (PAI‐1) in human osteoarthritic (OA) articular chondrocytes (from lesional and nonlesional sites) and human SW‐1353 chondrocytes.MethodsHuman SW‐1353 chondrocytes and OA and normal human articular chondrocytes were cultured on type II collagen–coated glass plates under static conditions or placed in a flow chamber to form a closed fluid‐circulation system for exposure to different levels of shear stress (2–20 dyn/cm2). Real‐time polymerase chain reaction was used to analyze PAI‐1 gene expression, and protein kinase C (PKC) inhibitors and small interfering RNA were used to investigate the mechanism of shear stress–induced signal transduction in SW‐1353 and OA (lesional and nonlesional) articular chondrocytes.ResultsThere was a significant reduction in PAI‐1 expression in OA chondrocytes obtained from lesional sites compared with those obtained from nonlesional sites. In SW‐1353 chondrocytes subjected to 2 hours of shear flow, moderate shear stresses (5 and 10 dyn/cm2) generated significant PAI‐1 expression, which was regulated through PKCα phosphorylation and Sp‐1 activation. These levels of shear stress also increased PAI‐1 expression in articular chondrocytes from nonlesional sites and from normal healthy cartilage through the activation of PKCα and Sp‐1 signal transduction, but no effect of these levels of fluid shear stress was observed on OA chondrocytes from lesional sites.ConclusionOA chondrocytes from lesional sites and those from nonlesional sites of human cartilage have differential responses to shear stress with regard to PAI‐1 gene expression, and therefore diverse functional consequences can be observed.
Amelioration of alphavirus‐induced arthritis and myositis in a mouse model by treatment with bindarit, an inhibitor of monocyte chemotactic proteins
Authors: Rulli Nestor E. , Guglielmotti Angelo , Mangano Giorgina , Rolph Michael S. , Apicella Claudia , Zaid Ali , Suhrbier Andreas , Mahalingam Suresh 
Published: July 2009

AbstractObjectiveAlphaviruses such as chikungunya virus, Sindbis virus, o'nyong‐nyong virus, Mayaro virus, and Ross River virus (RRV), are commonly associated with arthralgias and overt arthritides worldwide. Understanding the processes by which arthritogenic viruses cause disease is a prerequisite in the quest for better treatments. In this regard, we have recently established that monocyte/macrophages are mediators of alphavirus‐induced arthritis in mice. We hypothesized that chemokines associated with monocyte/macrophage recruitment may play an important role in disease. The aim of the present investigations was to determine whether bindarit, an inhibitor of monocyte chemotactic protein (MCP) synthesis, could ameliorate alphavirus‐induced rheumatic disease in mice.MethodsUsing our recently developed mouse model of RRV‐induced arthritis, which has many characteristics of RRV disease (RRVD) in humans, the effects of bindarit treatment on RRVD in mice were determined via histologic analyses, immunohistochemistry, flow cytometry, real‐time polymerase chain reaction analysis, enzyme‐linked immunosorbent assay, and electrophoretic mobility shift assay.ResultsBindarit‐treated RRV‐infected mice developed mild disease and had substantially reduced tissue destruction and inflammatory cell recruitment as compared with untreated RRV‐infected mice. The virus load in the tissues was not affected by bindarit treatment. Bindarit exhibited its activity by down‐regulating MCPs, which in turn led to inhibition of cell infiltration and lower production of NF‐κB and tumor necrosis factor α, which are involved in mediating tissue damage.ConclusionOur data support the use of inhibitors of MCP production in the treatment of arthritogenic alphavirus syndromes and suggest that bindarit may be useful in treating RRVD and other alphavirus‐induced arthritides in humans.