bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chondrogenic differentiation of bovine synovium: Bone morphogenetic proteins 2 and 7 and transforming growth factor β1 induce the formation of different types of cartilaginous tissue
Authors: Shintani Nahoko , Hunziker Ernst B. 
Published: May 2007

AbstractObjectiveTo compare the potential of bone morphogenetic proteins 2 and 7 (BMP‐2 and BMP‐7) and transforming growth factor β1 (TGFβ1) to effect the chondrogenic differentiation of synovial explants by analyzing the histologic, biochemical, and gene expression characteristics of the cartilaginous tissues formed.MethodsSynovial explants derived from the metacarpal joints of calves were cultured in agarose. Initially, BMP‐2 was used to evaluate the chondrogenic potential of the synovial explants under different culturing conditions. Under appropriate conditions, the chondrogenic effects of BMP‐2, BMP‐7, and TGFβ1 were then compared. The differentiated tissue was characterized histologically, histomorphometrically, immunohistochemically, biochemically, and at the gene expression level.ResultsBMP‐2 induced the chondrogenic differentiation of synovial explants in a dose‐ and time‐dependent manner under serum‐ and dexamethasone‐free conditions. The expression levels of cartilage‐related genes increased in a time‐dependent manner. BMP‐7 was more potent than BMP‐2 in inducing chondrogenesis, but the properties of the differentiated tissue were similar in each case. The type of cartilaginous tissue formed under the influence of TGFβ1 differed in terms of both cell phenotype and gene expression profiles.ConclusionThe 3 tested members of the TGFβ superfamily have different chondrogenic potentials and induce the formation of different types of cartilaginous tissue. To effect the full differentiation of synovial explants into a typically hyaline type of articular cartilage, further refinement of the stimulation conditions is required. This might be achieved by the simultaneous application of several growth factors.
Altered coronary vasomotor function in young patients with systemic lupus erythematosus
Authors: Hirata Kumiko , Kadirvelu Amudha , Kinjo Mitsuyo , Sciacca Robert , Sugioka Kenichi , Otsuka Ryo , Choy AnnaMaria , Chow Sook K. , Yoshiyama Minoru , Yoshikawa Junichi , Homma Shunichi , Lang Chim C. 
Published: May 2007

AbstractObjectiveAccelerated atherosclerosis is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Altered coronary microvascular function may act as a marker of changes that predispose to the development of significant coronary vascular disease. The purpose of this study was to compare coronary flow reserve (CFR) in a group of premenopausal women with SLE and a group of age‐, sex‐, and race‐matched healthy control subjects.MethodsCoronary flow velocity in 18 premenopausal women with SLE (mean ± SD age 29.4 ± 5.9 years) and 19 matched healthy controls (mean ± SD age 28.2 ± 4.3 years) was assessed by transthoracic Doppler echocardiography after an overnight fast. The CFR was calculated as the ratio of hyperemic to baseline coronary blood flow velocity in the left anterior descending coronary artery. Hyperemia was induced by intravenous administration of adenosine triphosphate.ResultsThe mean ± SD duration of SLE was 8.2 ± 7.2 years (range 0.25–25 years), and the mean ± SD score on the Systemic Lupus Erythematosus Disease Activity Index was 11.0 ± 5.3 (range 4.0–21.0). Adequate recordings of flow velocity in the left anterior descending artery under both conditions were obtained using an ultrasound procedure in all study subjects. CFR was significantly lower in SLE patients as compared with control subjects (mean ± SD 3.4 ± 0.8 versus 4.5 ± 0.5; P < 0.0001).ConclusionThese findings provide evidence that coronary vasomotor function is impaired in patients with SLE and support the notion that many of these young patients have subclinical coronary artery disease.
Interaction between smoking, the shared epitope, and anti–cyclic citrullinated peptide: A mixed picture in three large North American rheumatoid arthritis cohorts
Authors: Lee Hye‐Soon , Irigoyen Patricia , Kern Marlena , Lee Annette , Batliwalla Franak , Khalili Houman , Wolfe Frederick , Lum Raymond F. , Massarotti Elena , Weisman Michael , Bombardier Claire , Karlson Elizabeth W. , Criswell Lindsey A. , Vlietinck Robert , Gregersen Peter K. 
Published: May 2007

AbstractObjectiveRecently, Swedish members of the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) provided evidence that smoking may trigger RA‐specific immune reactions to citrullinated protein in carriers of HLA–DR shared epitope alleles. In an effort to confirm this interaction between smoking and shared epitope alleles, we performed a case‐only analysis of 3 North American RA cohorts.MethodsA total of 2,476 white patients with RA were studied, 1,105 from the North American Rheumatoid Arthritis Consortium (NARAC) family collection, 753 from the National Inception Cohort of Rheumatoid Arthritis Patients (Inception Cohort), and 618 from the Study of New Onset Rheumatoid Arthritis (SONORA). All patients were HLA–DRB1 typed, and tested for anti–cyclic citrullinated peptide (anti‐CCP) and rheumatoid factor. Information about smoking history was obtained by questionnaire.ResultsA significant association was found between smoking and the presence of anti‐CCP in the NARAC and the Inception Cohort, but not in the SONORA. The shared epitope alleles consistently correlated with anti‐CCP in all 3 populations. Using multiple logistic regression analyses, shared epitope alleles were still the most significant risk factor for anti‐CCP positivity. Weak evidence of gene–environment interaction between smoking and shared epitope alleles for anti‐CCP formation was found only in the NARAC.ConclusionUnlike the EIRA data, we could not confirm a major gene–environment interaction for anti‐CCP formation between shared epitope alleles and smoking in 3 North American RA cohorts. Our data indicate a need for further studies to address the full range of environmental factors other than smoking that may be associated with citrullination and RA.
Interleukin‐18 induces angiogenic factors in rheumatoid arthritis synovial tissue fibroblasts via distinct signaling pathways
Authors: Amin Mohammad A. , Mansfield Pamela J. , Pakozdi Angela , Campbell Phillip L. , Ahmed Salahuddin , Martinez Rita J. , Koch Alisa E. 
Published: May 2007

AbstractObjectiveInterleukin‐18 (IL‐18) is a proinflammatory cytokine implicated in the pathogenesis of rheumatoid arthritis (RA). This study was undertaken to examine the role of IL‐18 in up‐regulating secretion of the angiogenic factors stromal cell–derived factor 1α (SDF‐1α)/CXCL12, monocyte chemoattractant protein 1 (MCP‐1)/CCL2, and vascular endothelial growth factor (VEGF) in RA synovial tissue (ST) fibroblasts, and the underlying signaling mechanisms involved.MethodsWe used enzyme‐linked immunosorbent assays, Western blotting, and chemical inhibitors/antisense oligodeoxynucleotides to signaling intermediates to assess the role of IL‐18.ResultsIL‐18 significantly enhanced the production of SDF‐1α/CXCL12, MCP‐1/CCL2, and VEGF in RA ST fibroblasts, in a time‐ and concentration‐dependent manner. IL‐18–induced SDF‐1α/CXCL12 up‐regulation was dependent on JNK, p38 MAPK, phosphatidylinositol 3‐kinase (PI3K), and NFκB. While IL‐18–induced production of SDF‐1α/CXCL12 was also dependent on protein kinase Cδ (PKCδ), production of MCP‐1/CCL2 was dependent on PKCα, not PKCδ. Additionally, RA ST fibroblast IL‐18–induced MCP‐1/CCL2 production was mediated by JNK, PI3K, and NFκB. In contrast, IL‐18 did not induce secretion of RA ST fibroblast MCP‐1/CCL2 or VEGF via p38 MAPK. IL‐18–induced RA ST fibroblast production of VEGF was mediated mainly by JNK‐2, PKCα, and NFκB. IL‐18 induced phosphorylation of JNK, PKCδ, p38 MAPK, and activating transcription factor 2 (ATF‐2) in RA ST fibroblasts in a time‐dependent manner, with JNK‐2 being upstream of PKCδ, ATF‐2, and NFκB.ConclusionThese data support the notion that IL‐18 has a unique role in inducing the secretion of angiogenic SDF‐1α/CXCL12, MCP‐1/CCL2, and VEGF in RA ST fibroblasts, via distinct signaling intermediates.
The role of vascular cell adhesion molecule 1/ very late activation antigen 4 in endothelial progenitor cell recruitment to rheumatoid arthritis synovium
Authors: Silverman Matthew D. , Haas Christian S. , Rad Ali M. , Arbab Ali S. , Koch Alisa E. 
Published: May 2007

AbstractObjectiveMarrow‐derived endothelial progenitor cells (EPCs) are important in the neovascularization that occurs in diverse conditions such as cardiovascular disorders, inflammatory diseases, and neoplasms. In rheumatoid arthritis (RA), synovial neovascularization propels disease by nourishing the inflamed and hyperproliferative synovium. This study was undertaken to investigate the hypothesis that EPCs selectively home to inflamed joint tissue and may perpetuate synovial neovascularization.MethodsIn a collagen‐induced arthritis (CIA) model, neovascularization and EPC accumulation in mouse ankle synovium was measured. In an antibody‐induced arthritis model, EPC recruitment to inflamed synovium was evaluated. In a chimeric SCID mouse/human synovial tissue (ST) model, mice were engrafted subcutaneously with human ST, and EPC homing to grafts was assessed 2 days later. EPC adhesion to RA fibroblasts and RA ST was evaluated in vitro.ResultsIn mice with CIA, cells bearing EPC markers were significantly increased in peripheral blood and accumulated in inflamed synovial pannus. EPCs were 4‐fold more numerous in inflamed synovium from mice with anti–type II collagen antibody–induced arthritis versus controls. In SCID mice, EPC homing to RA ST was 3‐fold greater than to normal synovium. Antibody neutralization of vascular cell adhesion molecule 1 (VCAM‐1) and its ligand component α4 integrin potently inhibited EPC adhesion to RA fibroblasts and RA ST cryosections.ConclusionThese data demonstrate the selective recruitment of EPCs to inflamed joint tissue. The VCAM‐1/very late activation antigen 4 adhesive system critically mediates EPC adhesion to cultured RA fibroblasts and to RA ST cryosections. These findings provide evidence of a possible role of EPCs in the synovial neovascularization that is critical to RA pathogenesis.
Global analyses of gene expression in early experimental osteoarthritis
Authors: Appleton C. T. G. , Pitelka V. , Henry J. , Beier F. 
Published: May 2007

AbstractObjectiveTo analyze genome‐wide changes in chondrocyte gene expression in a surgically induced model of early osteoarthritis (OA) in rats, to assess the similarity of this model to human OA, and to identify genes and mechanisms leading to OA pathogenesis.MethodsOA was surgically induced in 5 rats by anterior cruciate ligament transection and partial medial meniscectomy. Sham surgery was performed in 5 additional animals, which were used as controls. Both groups underwent 4 weeks of forced mobilization, 3 times per week. RNA was extracted directly from articular chondrocytes in the OA (operated), contralateral, and sham‐operated knees. Affymetrix GeneChip expression arrays were used to assess genome‐wide changes in gene expression. Expression patterns of selected dysregulated genes, including Col2a1, Mmp13, Adamts5, Ctsc, Ptges, and Cxcr4, were validated by real‐time polymerase chain reaction, immunofluorescence, or immunohistochemistry 2, 4, and 8 weeks after surgery.ResultsAfter normalization, comparison of OA and sham‐operated samples showed 1,619 differentially expressed probe sets with changes in their levels of expression ≥1.5‐fold, 722 with changes ≥2‐fold, 135 with changes ≥4‐fold, and 20 with changes of 8‐fold. Dysregulated genes known to be involved in human OA included Mmp13, Adamts5, and Ptgs2, among others. Several dysregulated genes (e.g., Reln, Phex, and Ltbp2) had been identified in our earlier microarray study of hypertrophic chondrocyte differentiation. Other genes involved in cytokine and chemokine signaling, including Cxcr4 and Ccl2, were identified. Changes in gene expression were also observed in the contralateral knee, validating the sham operation as the appropriate control.ConclusionOur results demonstrate that the animal model mimics gene expression changes seen in human OA, supporting the relevance of newly identified genes and pathways to early human OA. We propose new avenues for OA pathogenesis research and potential targets for novel OA treatments, including cathepsins and cytokine, chemokine, and growth factor signaling pathways, in addition to factors controlling the progression of chondrocyte differentiation.
Activation of invariant natural killer T cells by synthetic glycolipid ligands suppresses autoantibody‐induced arthritis
Authors: Kaieda Shinjiro , Tomi Chiharu , Oki Shinji , Yamamura Takashi , Miyake Sachiko 
Published: May 2007

AbstractObjectiveStimulation of invariant natural killer T (iNKT) cells with SGL‐S23, a novel synthetic glycolipid analog of α‐galactosylceramide with an elongated sphingosine chain, has been shown to strongly suppress K/BxN serum transfer arthritis. This study was designed to evaluate the protective effects of SGL‐S23 in an effector phase of arthritis.MethodsTo induce arthritis, C57BL/6 mice were injected with 150 μl of serum from K/BxN mice (KRN TCR–transgenic mice crossed with nonobese diabetic mice). Subsequently, synthetic glycolipid ligands were administered intraperitoneally twice, either 3 times starting on day 0 (the day of K/BxN serum injection) or twice starting on day 3. Neutralizing antibody against interferon‐γ (IFNγ) interleukin‐4 (IL‐4), IL‐10, or transforming growth factor β was administered 4 hours before injection of SGL‐S23. Recombinant IFNγ was administered subcutaneously every day. The severity of arthritis was monitored using a macroscopic scoring system. Cytokine production and plasma histamine levels were measured by enzyme‐linked immunosorbent assay.ResultsSGL‐S23 strongly suppressed K/BxN serum transfer arthritis by inhibiting inflammatory cell infiltration and subsequent destruction of cartilage and bone. The inhibitory effect mediated by SGL‐S23 was abolished by neutralization of IFNγ. Systemic administration of IFNγ prevented the development of inflammatory arthritis. Histamine release was suppressed by administration of SGL‐S23 or IFNγ. Degranulated mast cells in the synovium were significantly reduced in SGL‐S23–treated mice, suggesting that suppression of mast cell activation contributed to the inhibition of arthritis.ConclusionThese findings suggest that activation of iNKT cells with glycolipid ligands holds promise with regard to the treatment of autoimmune diseases such as rheumatoid arthritis. SGL‐S23 has clinical benefit over α‐galactosylceramide since it induces a weaker cytokine production response in iNKT cells, therefore reducing potential side effects caused by excessive cytokine release.
Female mice are more susceptible to developing inflammatory disorders due to impaired transforming growth factor β signaling in salivary glands
Authors: Nandula Seshagiri R. , Amarnath Shoba , Molinolo Alfredo , Bandyopadhyay Bidhan C. , Hall Bradford , Goldsmith Corinne M. , Zheng Changyu , Larsson Jonas , Sreenath Taduru , Chen WanJun , Ambudkar Indu S. , Karlsson Stefan , Baum Bruce J. , Kulkarni Ashok B. 
Published: May 2007

AbstractObjectiveTransforming growth factor β (TGFβ) plays a key role in the onset and resolution of autoimmune diseases and chronic inflammation. The aim of this study was to delineate the precise function of TGFβ signaling in salivary gland inflammation.MethodsWe impaired TGFβ signaling in mouse salivary glands by conditionally inactivating expression of TGFβ receptor type I (TGFβRI), either by using mouse mammary tumor virus–Cre mice or by delivering adenoviral vector containing Cre to mouse salivary glands via retrograde infusion of the cannulated main excretory ducts of submandibular glands.ResultsTGFβRI–conditional knockout (TGFβRI‐coko) mice were born normal; however, female TGFβRI‐coko mice developed severe multifocal inflammation in salivary and mammary glands and in the heart. The inflammatory disorder affected normal growth and resulted in the death of the mice at ages 4–5 weeks. Interestingly, male TGFβRI‐coko mice did not exhibit any signs of inflammation. The female TGFβRI‐coko mice also showed an increase in Th1 proinflammatory cytokines in salivary glands and exhibited an up‐regulation of peripheral T cells. In addition, these mice showed an atypical distribution of aquaporin 5 in their salivary glands, suggesting likely secretory impairment. Administration of an adenoviral vector encoding Cre recombinase into the salivary glands resulted in inflammatory foci only in the glands of female TGFβRI–loxP‐flanked (floxed) mice (TGFβRI‐f/f mice), but not in those of male and female wild‐type mice or male TGFβRI‐f/f mice.ConclusionThese results suggest that female mice are uniquely more susceptible to developing inflammatory disorders due to impaired TGFβ signaling in their salivary glands.
Coffee, tea, and caffeine consumption and serum uric acid level: The third national health and nutrition examination survey
Authors: Choi Hyon K. , Curhan Gary 
Published: May 2007

AbstractObjectiveCoffee is one of the most widely consumed beverages in the world and may affect serum uric acid levels and risk of gout via various mechanisms. Our objective was to evaluate the relationship between coffee, tea, and caffeine intake and serum uric acid level in a nationally representative sample of men and women.MethodsUsing data from 14,758 participants ages ≥20 years in the Third National Health and Nutrition Examination Survey (1988–1994), we examined the relationship between coffee, tea, and caffeine intake and serum uric acid level using linear regression. Additionally, we examined the relationship with hyperuricemia (serum uric acid >7.0 mg/dl among men and >5.7 mg/dl among women) using logistic regression. Intake was assessed by a food frequency questionnaire.ResultsSerum uric acid level decreased with increasing coffee intake. After adjusting for age and sex, serum uric acid level associated with coffee intake of 4 to 5 and ≥6 cups daily was lower than that associated with no intake by 0.26 mg/dl (95% confidence interval [95% CI] 0.11, 0.41) and 0.43 mg/dl (95% CI 0.23, 0.65; P for trend < 0.001), respectively. After adjusting for other covariates, the differences remained significant (P for trend < 0.001). Similarly, there was a modest inverse association between decaffeinated coffee intake and serum uric acid levels (multivariate P for trend 0.035). Total caffeine from coffee and other beverages and tea intake were not associated with serum uric acid levels (multivariate P for trend 0.15). The multivariate odds ratio for hyperuricemia in individuals with coffee intake ≥6 cups daily compared with those with no coffee use was 0.57 (95% CI 0.35, 0.94; P for trend 0.001).ConclusionThese findings from a nationally representative sample of US adults suggest that coffee consumption is associated with lower serum uric acid level and hyperuricemia frequency, but tea consumption is not. The inverse association with coffee appears to be via components of coffee other than caffeine.
Exploring the use of videotaped objective structured clinical examination in the assessment of joint examination skills of medical students
Authors: Vivekananda‐Schmidt Pirashanthie , Lewis Martyn , Coady David , Morley Catherine , Kay Lesley , Walker David , Hassell Andrew B. 
Published: May 2007

AbstractObjectiveObjective structured clinical examination (OSCE) is a key part of medical student assessment. Currently, assessment is performed by medical examiners in situ. Our objective was to determine whether assessment by videotaped OSCE is as reliable as live OSCE assessment.MethodsParticipants were 95 undergraduate medical students attending their musculoskeletal week at Freeman Hospital, Newcastle (UK). Student performance on OSCE stations for shoulder or knee examinations was assessed by experienced rheumatologists. The stations were also videotaped and scored by a rheumatologist independently. The examinations consisted of a 14‐item checklist and a global rating scale (GRS).ResultsMean values for the shoulder OSCE checklist were 17.9 by live assessment and 17.4 by video (n = 50), and 20.9 and 20.0 for live and video knee assessment, respectively (n = 45). Intraclass correlation coefficients for shoulder and knee checklists were 0.55 and 0.58, respectively, indicating moderate reliability between live and video scores for the OSCE checklists. GRS scores were less reliable than checklist scores. There was 84% agreement in the classification of examination grades between live and video checklist scores for the shoulder and 87% agreement for the knee (κ = 0.43 and 0.51, respectively; P < 0.001).ConclusionVideo OSCE has the potential to be reliable and offers some advantages over live OSCE including more efficient use of examiners' time, increased fairness, and better monitoring of standards across various schools/sites. However, further work is needed to support our findings and to implement and evaluate the quality assurance issues identified in this work before justifiable recommendations can be made.
Do proton‐pump inhibitors confer additional gastrointestinal protection in patients given celecoxib?
Authors: Rahme Elham , Barkun Alan N. , Toubouti Youssef , Scalera Alissa , Rochon Sophie , Lelorier Jacques 
Published: May 2007

AbstractObjectiveCelecoxib has a superior upper‐gastrointestinal (GI) safety profile compared with nonselective nonsteroidal antiinflammatory drugs (NS‐NSAIDs). It is unclear whether the utilization of a proton‐pump inhibitor (PPI) with celecoxib confers additional protection in elderly patients. We assessed the association between GI hospitalizations and use of celecoxib with a PPI versus celecoxib alone, and NS‐NSAIDs with a PPI or NS‐NSAIDs alone in elderly patients.MethodsWe conducted a population‐based retrospective cohort study using the government of Quebec health services administrative databases. Elderly patients were included at their first dispensing date for celecoxib or an NS‐NSAID between April 1999 and December 2002. Prescriptions were separated into 4 groups: celecoxib, celecoxib plus PPI, NS‐NSAIDs, and NS‐NSAIDs plus PPI. Cox regression models with time‐dependent exposure were used to compare the hazard rates of GI hospitalization between the 4 groups adjusting for patient characteristics at baseline.ResultsThere were 1,161,508 prescriptions for celecoxib, 360,799 for celecoxib plus PPI, 715,176 for NS‐NSAIDs, and 148,470 for NS‐NSAIDs plus PPI. The adjusted hazard ratios (HRs; 95% confidence intervals [95% CIs]) were 0.69 (0.52–0.93) for celecoxib plus PPI versus celecoxib, 0.98 (0.67–1.45) for NS‐NSAIDs plus PPI versus celecoxib, and 2.18 (1.82–2.61) for NS‐NSAIDs versus celecoxib. Subgroup analyses showed that use of a PPI with celecoxib may be beneficial in patients ages ≥75 years but was not better than celecoxib alone among those ages 66–74 years (HR 0.98, 95% CI 0.63–1.52).ConclusionAddition of a PPI to celecoxib conferred extra protection for patients ages ≥75 years. PPI did not seem necessary with celecoxib for patients ages 66–74 years.