bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rheumatology fellows' perception on training and careers in academia: The American College of Rheumatology Fellow Research and Academic Training Survey
Authors:   The Young Investigator Subcommittee of the American College of Rheumatology Committee on Research
Published: January 2009

AbstractObjectiveTo examine the perceptions of rheumatology fellows regarding their research training, mentoring, and interest in a career in academia.MethodsWe solicited by e‐mail 386 fellows in the American College of Rheumatology 2005–2006 fellow database to take an anonymous Internet‐based survey addressing the topics of research training, mentoring, and interest in an academic career.ResultsWe received 176 responses (50% response rate after excluding invalid contacts) to the survey. During their training, 58% of fellows reported an interest in academia and 21% in research. There was great satisfaction with mentoring. However, there were concerns about academic salaries, with 50% of respondents stating a preference for a higher paying community position. Furthermore, there were substantial concerns about the difficulty of generating funds to cover salaries. In addition, several respondents viewed an academic career as incompatible with starting a family. Compared with male fellows, female fellows were more likely to want a career in academics, were less concerned about academic salaries, and were more concerned about funding and family life.ConclusionDespite an interest in academia and satisfaction with current mentoring, several barriers to academia were identified among rheumatology fellows. The concern that academia and family life are incompatible needs further attention. University deans should consider reevaluating promotion programs to make allowances for family and parenting demands. Rheumatology division chairs should better promote the nonfinancial rewards of a career in academia. Programs such as the National Institutes of Health Loan Repayment Program should be strongly advertised to interested applicants with financial concerns.
Proinflammatory role of the Th17 cytokine interleukin‐22 in collagen‐induced arthritis in C57BL/6 mice
Authors: Geboes Lies , Dumoutier Laure , Kelchtermans Hilde , Schurgers Evelien , Mitera Tania , Renauld Jean‐Christophe , Matthys Patrick 
Published: January 2009

AbstractObjectiveTo investigate the role of interleukin‐22 (IL‐22) in collagen‐induced arthritis (CIA), an animal model of rheumatoid arthritis.MethodsC57BL/6 mice were immunized with type II collagen (CII) in Freund's incomplete adjuvant with added Mycobacterium tuberculosis, and levels of IL‐22 and its specific receptor, IL‐22 receptor type I (IL‐22RI), were measured in sera and tissue by enzyme‐linked immunosorbent assay and real‐time quantitative polymerase chain reaction analysis. Clinical and histologic signs of arthritis were recorded and compared with those in C57BL/6 mice deficient in the IL‐22 gene (IL‐22–/–). Humoral and cellular immune responses against CII were analyzed. In vitro osteoclastogenesis assays were performed on splenocytes.ResultsUpon immunization with CII in Freund's incomplete adjuvant plus heat‐killed Mycobacterium tuberculosis, sera from C57BL/6 mice were found to contain high levels of IL‐22, and the specific IL‐22RI was expressed in lymphoid tissue, including splenocytes. IL‐22–/– mice were less susceptible to CIA than were wild‐type mice, as evidenced by their decreased incidence of arthritis and decreased pannus formation. Remarkably, the less severe form of arthritis in IL‐22–/– mice was associated with increased production of CII‐specific and total IgG antibodies, whereas cellular CII responses were unchanged. In vitro, IL‐22 was found to promote osteoclastogenesis, a process that might contribute to its proinflammatory activity in CIA.ConclusionEndogenous IL‐22 plays a proinflammatory role in CIA in C57BL/6 mice. Our data also indicate that IL‐22 promotes osteoclastogenesis and regulates antibody production.
Molecular framework for response to imatinib mesylate in systemic sclerosis
Authors: Chung Lorinda , Fiorentino David F. , BenBarak Maya J. , Adler Adam S. , Mariano Melissa M. , Paniagua Ricardo T. , Milano Ausra , Connolly M. Kari , Ratiner Boris D. , Wiskocil Robert L. , Whitfield Michael L. , Chang Howard Y. , Robinson William H. 
Published: January 2009

AbstractSystemic sclerosis (SSc) is an autoimmune disease in which the tyrosine kinases platelet‐derived growth factor receptor (PDGFR) and Abl are hypothesized to contribute to the fibrosis and vasculopathy of the skin and internal organs. Herein we describe 2 patients with early diffuse cutaneous SSc (dcSSc) who experienced reductions in cutaneous sclerosis in response to therapy with the tyrosine kinase inhibitor imatinib mesylate. Immunohistochemical analyses of skin biopsy specimens demonstrated reductions of phosphorylated PDGFRβ and Abl with imatinib therapy. By gene expression profiling, an imatinib‐responsive signature specific to dcSSc was identified (P < 10−8). The response of these patients and the findings of the analyses suggest that PDGFRβ and Abl play critical, synergistic roles in the pathogenesis of SSc, and that imatinib targets a gene expression program that is frequently dysregulated in dcSSc.
Increased expression of the Akt/PKB inhibitor TRB3 in osteoarthritic chondrocytes inhibits insulin‐like growth factor 1–mediated cell survival and proteoglycan synthesis
Authors: Cravero John D. , Carlson Cathy S. , Im Hee‐Jeong , Yammani Raghunatha R. , Long David , Loeser Richard F. 
Published: January 2009

AbstractObjectiveThe chondrocyte response to insulin‐like growth factor 1 (IGF‐1) is reduced with aging and in osteoarthritis (OA). IGF‐1 signals through the phosphatidylinositol 3‐kinase/Akt pathway. TRB3, a tribbles homolog, has been shown to inhibit IGF‐1–mediated activation of Akt in HEK 293 cells. This study was undertaken to determine if TRB3 is expressed in chondrocytes, and whether the chondrocyte response to IGF‐1 is reduced by TRB3.MethodsHuman articular cartilage was obtained from normal tissue donors and from patients with OA at the time of knee replacement surgery. TRB3 was assessed in the tissue samples by reverse transcription–polymerase chain reaction, immunoblotting, and immunohistochemistry. Overexpression of TRB3 was induced by transient transfection to determine the effects of TRB3 on cell survival and proteoglycan synthesis.ResultsTRB3 messenger RNA was detected in normal human chondrocytes. TRB3 protein levels were low in cells from normal cartilage but significantly increased in cells from OA cartilage. Incubation with 2 agents that induce endoplasmic reticulum stress, tunicamycin and thapsigargin, increased TRB3 levels in normal cells. Overexpression of TRB3 inhibited Akt phosphorylation and reduced chondrocyte survival and proteoglycan synthesis.ConclusionThese results are the first to demonstrate that TRB3 is present in human chondrocytes, and that the level of TRB3 is increased in OA cartilage and in isolated OA chondrocytes. Because it is an inhibitor of Akt activation, elevated TRB3 production could play a role in the increased cell death and reduced response to IGF‐1 observed in OA cartilage.
α‐melanocyte–stimulating hormone suppresses bleomycin‐induced collagen synthesis and reduces tissue fibrosis in a mouse model of scleroderma: Melanocortin peptides as a novel treatment strategy for scleroderma?
Authors: Kokot Agatha , Sindrilaru Anca , Schiller Meinhard , Sunderkötter Cord , Kerkhoff Claus , Eckes Beate , Scharffetter‐Kochanek Karin , Luger Thomas A. , Böhm Markus 
Published: January 2009

AbstractObjectiveRecently, we found that human dermal fibroblasts (HDFs) express melanocortin 1 receptors (MC‐1R) that bind α‐melanocyte–stimulating hormone (α‐MSH). In search of novel therapies for scleroderma (systemic sclerosis [SSc]), we used the bleomycin (BLM) model to investigate the effects of α‐MSH on collagen synthesis and fibrosis.MethodsCollagen expression in HDFs was determined by real‐time reverse transcription–polymerase chain reaction (RT‐PCR) and Western blot analyses. Signal transduction studies included pharmacologic blockade, immunofluorescence analysis, Western blotting, and reporter–promoter assays. Oxidative stress was measured by fluorescence‐activated cell sorter analysis, and anti–oxidative enzyme levels were determined by real‐time RT‐PCR and Western blot analyses. The effect of α‐MSH in the BLM mouse model of scleroderma was assessed by histologic, immunohistochemical, real‐time RT‐PCR, and protein analyses. Expression of MC‐1R and pro‐opiomelanocortin (POMC) in skin and HDF samples from patients with SSc was determined by RT‐PCR and compared with that in samples from normal controls.ResultsTreatment with α‐MSH (and related peptides) suppressed BLM‐induced expression of type I and type III collagen in HDFs, and this effect was cAMP‐dependent. Neither BLM nor α‐MSH altered Smad signaling, but antioxidants inhibited BLM‐induced collagen expression in vitro. In addition, α‐MSH suppressed BLM‐induced oxidative stress and enhanced the expression of superoxide dismutase 2 (SOD2) and heme oxygenase 1 (HO‐1). In the BLM mouse model, α‐MSH reduced skin fibrosis and collagen content and increased tissue levels of SOD2 and HO‐1. In skin and HDFs from patients with SSc, both MC‐1R and POMC messenger RNAs were detected, but there were no differences compared with healthy controls.ConclusionAlpha‐melanocyte–stimulating hormone and related peptides that exert their effects via MC‐1R may provide a novel antifibrogenic therapeutic tool for the treatment of fibrotic diseases such as scleroderma.
Depression, medication adherence, and service utilization in systemic lupus erythematosus
Authors: Julian Laura J. , Yelin Edward , Yazdany Jinoos , Panopalis Pantelis , Trupin Laura , Criswell Lindsey A. , Katz Patricia 
Published: January 2009

AbstractObjectiveForgetting to take medications is an important cause of nonadherence. This study evaluated factors associated with forgetting to take medications in a large cohort of persons with systemic lupus erythematosus (SLE) participating in the University of California, San Francisco Lupus Outcomes Study (LOS). Relationships among adherence problems and service utilization (outpatient visits, emergency department visits, and hospitalizations) were also evaluated.MethodsThe cohort consisted of 834 LOS participants who provided self‐reported frequency of forgetting to take medications as directed. Predictors of adherence and service utilization patterns included self‐reported sociodemographics, disease‐related characteristics (e.g., disease activity, recent SLE flare), and mental health characteristics (Center for Epidemiologic Studies Depression Scale and cognitive function screen). Health care utilization patterns included the presence and quantity of visits to rheumatologists, primary care physicians, other care providers, emergency departments, and hospitalizations.ResultsForty‐six percent of the LOS cohort reported forgetting to take medications at least some of the time. Depressive symptom severity was a strong predictor of adherence difficulties (odds ratio [OR] 1.04, 95% confidence interval [95% CI] 1.02–1.05; P < 0.0001) after accounting for all other predictors. Persons reporting adherence difficulties had significantly greater numbers of outpatient rheumatology and primary care visits, and were more likely to visit the emergency department (OR 1.45, 95% CI 1.04–2.04; P = 0.03).ConclusionDepression may be an important cause of medication adherence problems, and difficulties with adherence are significantly associated with high‐cost service utilization, specifically emergency department visits. In an era of rapidly evolving treatments for lupus, identifying patients at risk for adherence problems may decrease medical expenditures and improve patient outcomes in SLE.
Study of functional variants of the BANK1 gene in rheumatoid arthritis
Authors: Orozco Gisela , Abelson Anna‐Karin , González‐Gay Miguel A. , Balsa Alejandro , Pascual‐Salcedo Dora , García Antonio , Fernández‐Gutierrez Benjamín , Petersson Ingemar , Pons‐Estel Bernardo , Eimon Alicia , Paira Sergio , Scherbarth Hugo R. , Alarcón‐Riquelme Marta , Martín Javier 
Published: January 2009

AbstractObjectiveTo investigate 1 functional (rs17266594) and 2 potentially functional (rs10516487 and rs3733197) BANK1 variants, which were previously identified as systemic lupus erythematosus (SLE) susceptibility markers, to test whether they are associated with rheumatoid arthritis (RA).MethodsFour different cohorts were included in the study: 1,080 RA patients and 1,368 healthy controls from Spain, 278 RA patients and 568 healthy controls from Sweden, 288 RA patients and 287 healthy controls from Argentina, and 288 RA patients and 288 healthy controls from Mexico. Samples were genotyped for BANK1 single‐nucleotide polymorphisms (SNPs) using a TaqMan 5′‐allele discrimination assay. Statistical analysis comparing allele and genotype distributions was performed with the chi‐square test.ResultsWe did not find a significant association between RA and the rs10516487 and rs17266594 BANK1 polymorphisms. However, there was an increase in the major alleles among RA patients. Similarly, for rs3733197, there was an increase in the major allele among patients in every cohort. Nevertheless, this skewing reached statistical significance in the Spanish (P = 0.01, odds ratio [OR] 1.17 [95% confidence interval (95% CI) 1.03–1.32]) and Argentinean (P = 0.04, OR 1.31 [95% CI 1.00–1.72]) populations. We found a significant association of rs10516487 (P = 0.005, OR 1.15 [95% CI 1.04–1.28]) and rs3733197 (P = 0.0009, OR 1.17 [95% CI 1.07–1.29]) with RA in the pooled analysis. In a 3‐SNP haplotype analysis, we found that the major TGG haplotype was significantly associated with RA (P = 0.005, OR 1.14 [95% CI 1.04–1.25]). In addition, we found a common CAA haplotype that was protective against RA (P = 0.0004, OR 0.82 [95% CI 0.74–0.92]).ConclusionThese results suggest that BANK1 SNPs and haplotypes may contribute to RA susceptibility with a low risk.
Replication of the association between the C8orf13–BLK region and systemic lupus erythematosus in a Japanese population
Authors: Ito Ikue , Kawasaki Aya , Ito Satoshi , Hayashi Taichi , Goto Daisuke , Matsumoto Isao , Tsutsumi Akito , Hom Geoffrey , Graham Robert R. , Takasaki Yoshinari , Hashimoto Hiroshi , Ohashi Jun , Behrens Timothy W. , Sumida Takayuki , Tsuchiya Naoyuki 
Published: January 2009

AbstractObjectiveRecent genome‐wide association studies identified an association between single‐nucleotide polymorphisms (SNPs) in the C8orf13 region of BLK, the B lymphoid tyrosine kinase gene, with systemic lupus erythematosus (SLE) in Caucasians. The purpose of this study was to evaluate the significance of this region in the genetic background of Japanese patients with SLE.MethodsFourteen tag SNPs in the C8orf13–BLK region were genotyped in 327 Japanese patients with SLE and 322 healthy Japanese controls. The population‐attributable risk percentage (PAR%) of rs13277113 in Japanese was compared with that in Caucasians as well as with that of other SLE susceptibility genes in Japanese.ResultsAs in Caucasians, rs13277113A demonstrated the strongest association in Japanese (P = 1.73 × 10–6 for the genotype frequency, P = 4.75 × 10–7 for the allele frequency, odds ratio [OR] 2.44 [95% confidence interval (95% CI) 1.43–4.16]). The association in Japanese was consistent with a recessive model (P = 2.74 × 10–7, OR 2.27 [95% CI 1.66–3.11]). In contrast to the Caucasian population, this risk allele was the major allele in the Japanese population. Because both the risk allele frequency and the OR were higher in Japanese than in Caucasians, the PAR% of rs13277113 was estimated to be much higher in Japanese (35.4%) than in Caucasians (16.2%), and the second highest among the 6 confirmed SLE susceptibility genes in Japanese.ConclusionThe association of the C8orf13–BLK region with SLE was replicated in a Japanese population. Contribution of this region to the genetic predisposition to SLE appeared to be greater in Japanese than in Caucasians.
Involvement of the notch pathway in the regulation of matrix metalloproteinase 13 and the dedifferentiation of articular chondrocytes in murine cartilage
Authors: Blaise Régis , Mahjoub Mouna , Salvat Colette , Barbe Ullah , Brou Christel , Corvol Marie‐Thérèse , Savouret Jean‐François , Rannou François , Berenbaum Francis , Bausero Pedro 
Published: January 2009

AbstractObjectiveTo demonstrate the activation of the Notch signaling pathway during changes in the phenotype of chondrocytes in vitro, and to assess the influence of Notch on the production of chondrocyte markers.MethodsSerial monolayer primary cultures of murine articular chondrocytes (MACs), as a model of chondrocyte dedifferentiation, were prepared. MACs were cultured with or without a Notch inhibitor and transfected with different Notch‐expressing vectors. The Notch pathway and chondrocyte marker profiles were assessed by quantitative reverse transcription–polymerase chain reaction, immunoblotting, and immunocytochemistry.ResultsSuccessive passages of MACs resulted in a loss of type II collagen and aggrecan (chondrocyte differentiation markers), an increase in type I collagen (dedifferentiation marker), an increase in Notch ligands, and augmented target gene activity. The Notch inhibitor decreased the type II collagen protein content but had no effect on Col2a1 messenger RNA, while transfection with the constitutive active forms of the Notch1 receptor led to a decrease in type II collagen in transfected cells. In assays to investigate the mechanism of type II collagen breakdown, matrix metalloproteinase 13 (MMP‐13) synthesis was regulated in a Notch‐dependent manner, whereas MMP‐2 synthesis was unchanged.ConclusionThe Notch signaling pathway is associated with decreased type II collagen production during the dedifferentiation of MACs in vitro. This may be correlated with the increase in MMP‐13 production linked to activation of Notch.
Alteration of articular cartilage frictional properties by transforming growth factor β, interleukin‐1β, and oncostatin M
Authors: Gleghorn Jason P. , Jones Aled R. C. , Flannery Carl R. , Bonassar Lawrence J. 
Published: January 2009

AbstractObjectiveTo evaluate the functional effects of transforming growth factor β1 (TGFβ1), interleukin‐1β (IL‐1β), and oncostatin M (OSM) on the frictional properties of articular cartilage and to determine the role of cytokine‐mediated changes in cartilage frictional properties by extracting and redepositing lubricin on the surface of cartilage explants.MethodsNeonatal bovine cartilage explants were cultured in the presence or absence of 10 ng/ml of TGFβ1, IL‐1β, or OSM over 48 hours. Boundary lubrication tests were conducted to determine the effects of endogenously produced surface localized lubricin and of exogenous lubricin at the tissue surface and in the lubricant solution. The initial friction coefficient (μ0), equilibrium friction coefficient (μeq), and Young's modulus (EY) were determined from the temporal load data.ResultsIL‐1β and OSM decreased tissue glycosaminoglycan (GAG) content by ∼20% over 48 hours and decreased EY to a similar extent (11–17%), but TGFβ did not alter GAG content or EY. Alterations in proteoglycan content corresponded to changes in μ0, but endogenous lubricin decreased boundary mode μeq. The addition of exogenous lubricin, either localized at the tissue surface or in the lubricating solution, did not modulate μ0, but it did lower μeq in cytokine‐treated cartilage.ConclusionThis study provides new insight into the functional consequences of cytokine‐mediated changes in friction coefficient. In combination with established pathways of cytokine‐mediated lubricin metabolism, these data provide evidence of distinct biochemical origins of boundary and biphasic pressure‐mediated lubrication mechanisms in cartilage, with boundary lubrication regulated by surface accumulation of lubricants and biphasic lubrication controlled by factors such as GAG content that affect water movement through the tissue.
HLA–E gene polymorphism associated with susceptibility to kawasaki disease and formation of coronary artery aneurysms
Authors: Lin Y.‐J. , Wan L. , Wu J.‐Y. , Sheu J. J.‐C. , Lin C.‐W. , Lan Y.‐C. , Lai C.‐H. , Hung C.‐H. , Tsai Y. , Tsai C.‐H. , Lin T.‐H. , Lin J.‐G. , Hsueh K.‐C. , Huang Y.‐M. , Chang J.‐S. , Tsai F.‐J. 
Published: January 2009

AbstractObjectiveKawasaki disease (KD) is a pediatric systemic vasculitis of unknown cause for which a genetic influence is supposed. The purpose of this study was to identify possible genetic variants in the major histocompatibility complex (MHC) region that are associated with KD and the development of coronary artery aneurysms (CAAs) in a Taiwanese population.MethodsThe 168 genetic variants covering the MHC locus were analyzed in an association study of a Taiwanese cohort of 93 KD patients and 680 unrelated healthy children matched for sex and age with the study patients.ResultsEleven single‐nucleotide polymorphisms (SNPs) were associated with the occurrence of KD. The SNP located at the 3′‐untranslated region of HLA–E (rs2844724) was highly associated (P < 1 × 10−7). In addition, the frequency of the C allele was higher in KD patients without CAAs than in controls (P < 0.001) due to a significantly increased frequency of the CC and CT genotypes. Plasma levels of soluble HLA–E were significantly higher in KD patients than in controls regardless of the presence of CAAs. Furthermore, there was a trend toward higher plasma levels of soluble HLA–E in KD patients with the CT and TT genotypes of the HLA–E gene polymorphism.ConclusionOur results suggest that the HLA–E gene polymorphism may play a role in the pathogenesis of KD.
Efficacy of multicomponent treatment in fibromyalgia syndrome: A meta‐analysis of randomized controlled clinical trials
Authors: Häuser Winfried , Bernardy Kathrin , Arnold Bernhard , Offenbächer Martin , Schiltenwolf Marcus 
Published: January 2009

AbstractObjectiveTo systematically review the efficacy of multicomponent treatment of fibromyalgia syndrome (FMS).MethodsWe screened Medline, PsychINFO, Scopus, and the Cochrane Library (through December 2007), as well as reference sections of original studies, reviews, and evidence‐based guidelines. Randomized controlled trials (RCTs) on the multicomponent treatment (at least 1 educational or other psychological therapy with at least 1 exercise therapy) of FMS were analyzed.ResultsWe included 9 (of 14) RCTs with 1,119 subjects (median treatment time 24 hours) in the meta‐analysis. Effects were summarized using standardized mean differences (SMDs) or weighted mean differences (WMDs). There was strong evidence that multicomponent treatment reduces pain (SMD −0.37; 95% confidence interval [95% CI] −0.62, −0.13), fatigue (WMD −0.85; 95% CI −1.50, −0.20), depressive symptoms (SMD −0.67; 95% CI −1.08, −0.26), and limitations to health‐related quality of life (HRQOL) (SMD −0.59; 95% CI −0.90, −0.27) and improves self‐efficacy pain (SMD 0.54; 95% CI 0.26, 0.82) and physical fitness (SMD 0.30; 95% CI 0.02, 0.57) at posttreatment. There was no evidence of its efficacy on pain, fatigue, sleep disturbances, depressive symptoms, HRQOL, or self‐efficacy pain in the long term. There was strong evidence that positive effects on physical fitness (SMD 0.30; 95% CI 0.09, 0.51) can be maintained in the long term (median followup 7 months).ConclusionsThere is strong evidence that multicomponent treatment has beneficial short‐term effects on the key symptoms of FMS. Strategies to maintain the benefits of multicomponent treatment in the long term need to be developed.