bluuebunny/crossref_metadata_2025_split huggingface dataset:
Splenic suppressor of cytokine signaling 3 transgene expression affects T cell responses and prevents development of collagen‐induced arthritis
Authors: Veenbergen Sharon , Bennink Miranda B. , de Hooge Alfons S. K. , Arntz Onno J. , Smeets Ruben L. , van den Berg Wim B. , van de Loo Fons A. J. 
Published: November 2008

AbstractObjectiveMembers of the suppressor of cytokine signaling (SOCS) family are key negative intracellular regulators of cytokine and growth factor responses, including those that regulate immune responses in autoimmune disorders, such as rheumatoid arthritis (RA). The aim of this study was to investigate modulation of T cell immunity for the treatment of experimental arthritis, via enhanced expression of SOCS‐3 in splenic antigen‐presenting cells (APCs) obtained after intravenous injection of adenovirus encoding SOCS‐3.MethodsDBA/1 mice were immunized with type II collagen, and adenovirus vectors were administered by intravenous injection before the clinical onset of collagen‐induced arthritis (CIA). Splenic cellular responses were analyzed by measuring cytokine production, using Luminex multi‐analyte technology. Th cell populations were analyzed by flow cytometry.ResultsSystemic delivery of adenovirus encoding SOCS‐3 resulted in enhanced transgene expression in splenic APCs, which led to decreased production of interleukin‐23 (IL‐23), IL‐6, and tumor necrosis factor α, but significantly higher production of antiinflammatory IL‐10, by these cells. Fluorescence‐activated cell sorting analysis showed increased numbers of splenic CD4+ T cells after SOCS‐3 treatment. In the presence of SOCS‐3–transduced APCs, however, purified splenic CD3+ T cells showed reduced antigen‐specific proliferation and a significant reduction in the production of interferon‐γ (−43%), IL‐4 (−41%), and IL‐17 (−70%). Interestingly, the altered splenic cellular responses were accompanied by a protective effect on CIA development, and histologic analysis of knee joints showed reduced joint inflammation and connective tissue destruction.ConclusionThis study demonstrates effective prevention of CIA after intravenously induced overexpression of SOCS‐3; this is probably caused by the generation of tolerogenic APCs, which have an inhibitory effect on Th1, Th2, and especially, Th17 cell activity.
Promotion of the local differentiation of murine Th17 cells by synovial macrophages during acute inflammatory arthritis
Authors: Egan Paul J. , van Nieuwenhuijze Annemarie , Campbell Ian K. , Wicks Ian P. 
Published: November 2008

AbstractObjectiveTo examine the generation of proinflammatory Th17 cells at the site of tissue inflammation and in draining lymph nodes using an interleukin‐17 (IL‐17)–dependent model of acute inflammatory arthritis.MethodsArthritis was elicited in mice by intraarticular injection of methylated bovine serum albumin (mBSA) into the knee and subcutaneous injection of IL‐1β. Anti–IL‐17 or control antibodies were administered during arthritis induction. Cytokine expression was evaluated by intracellular cytokine staining of synovial lymphocytes, by polymerase chain reaction analysis of RNA extracted from lymph node cells, and by enzyme‐linked immunosorbent assay of cell culture supernatants. Th17 differentiation of naive CD4+ T cells was assessed in cocultures with macrophages from arthritic mice.ResultsAnti–IL‐17 antibody administered during acute arthritis markedly reduced disease, indicating that the model is IL‐17 dependent. IL‐17 messenger RNA (mRNA), but not protein, was detected in draining lymph node CD4+ T cells and preceded joint inflammation. In addition, mRNA for Th17 cell–stimulatory cytokines (transforming growth factor β, IL‐6) and Th17 cell–inhibitory cytokines (interferon‐γ, IL‐4) was detected in lymph nodes following injection of mBSA and IL‐1β. Th17 cells were clearly identified in the inflamed synovium at the peak of disease. Synovial macrophages supported Th17 cell generation from naive CD4+ T cell precursors stimulated via CD3 in vitro and produced high levels of IL‐6. In contrast, peritoneal macrophages failed to induce Th17 cell differentiation and produced less IL‐6.ConclusionThese results suggest that Th17 cell differentiation is initiated in draining lymph nodes but that IL‐17–producing cells are restricted to the inflamed synovium, being generated in response to local cytokines produced by inflammatory macrophages.
The influence of sex on the chondrogenic potential of muscle‐derived stem cells: Implications for cartilage regeneration and repair
Authors: Matsumoto Tomoyuki , Kubo Seiji , Meszaros Laura B. , Corsi Karin A. , Cooper Gregory M. , Li Guangheng , Usas Arvydas , Osawa Aki , Fu Freddie H. , Huard Johnny 
Published: November 2008

AbstractObjectiveTo explore possible differences in muscle‐derived stem cell (MDSC) chondrogenic differentiation in vitro and articular cartilage regeneration in vivo between murine male MDSCs (M‐MDSCs) and female MDSCs (F‐MDSCs).MethodsThree different populations of M‐ and F‐MDSCs (n = 3 of each sex) obtained via preplate technique, which separates cells based on their variable adhesion characteristics, were compared for their in vitro chondrogenic potential using pellet culture. Cells were assayed with and without retroviral transduction to express bone morphogenetic protein 4 (BMP‐4). The influence of both expression of stem cell marker Sca1 and in vitro expansion on the chondrogenic potential of M‐ and F‐MDSCs was also determined. Additionally, BMP‐4–transduced M‐ and F‐MDSCs were applied to a full‐thickness articular cartilage defect (n = 5 each) on the femur of a nude rat, and the quality of the repaired tissue was evaluated by macroscopic and histologic examination.ResultsWith and without BMP‐4 gene transduction, M‐MDSCs produced significantly larger pellets with a richer extracellular matrix, compared with F‐MDSCs. Sca1 purification influenced the chondrogenic potential of MDSCs, especially M‐MDSCs. Long‐term culture did not affect the chondrogenic potential of M‐MDSCs but did influence F‐MDSCs. M‐MDSCs repaired articular cartilage defects more effectively than did F‐MDSCs at all time points tested, as assessed both macroscopically and histologically.ConclusionOur findings demonstrate that sex influences the chondrogenic differentiation and articular cartilage regeneration potential of MDSCs. Compared with female MDSCs, male MDSCs display more chondrogenic differentiation and better cartilage regeneration potential.
Shift from toll‐like receptor 2 (TLR‐2) toward TLR‐4 dependency in the erosive stage of chronic streptococcal cell wall arthritis coincident with TLR‐4–mediated interleukin‐17 production
Authors: Abdollahi‐Roodsaz Shahla , Joosten Leo A. B. , Helsen Monique M. , Walgreen Birgitte , van Lent Peter L. , van den Bersselaar Liduine A. , Koenders Marije I. , van den Berg Wim B. 
Published: November 2008

AbstractObjectiveToll‐like receptors (TLRs) may activate innate and adaptive immune responses in rheumatoid arthritis (RA) through recognition of microbial as well as endogenous ligands that have repeatedly been found in arthritic joints. The objective of this study was to investigate the involvement of TLR‐2 and TLR‐4 in the development of chronic destructive streptococcal cell wall (SCW)–induced arthritis, in which interleukin‐1 (IL‐1)/IL‐17–dependent T cell–driven pathologic changes replace the macrophage‐driven acute phase.MethodsChronic SCW arthritis was induced by 4 repeated intraarticular injections of SCW fragments in wild‐type, TLR‐2−/−, and TLR‐4−/− mice. Clinical, histopathologic, and immunologic parameters of arthritis were evaluated.ResultsThe TLR‐2 dependency of joint swelling during the acute phase was shifted to TLR‐4 dependency during the chronic phase. Persistent joint inflammation in the latter phase of the model was significantly suppressed in TLR‐4−/− mice. In the chronic phase, TLR‐4 actively contributed to matrix metalloproteinase (MMP)–mediated cartilage destruction and to osteoclast formation, since the expression of the MMP‐specific aggrecan neoepitope VDIPEN and the osteoclast marker cathepsin K was significantly reduced in TLR‐4−/− mice. Furthermore, TLR‐4−/− mice expressed less IL‐1β, tumor necrosis factor α, IL‐6, and IL‐23, cytokines that are implicated in IL‐17 production. Accordingly, SCW‐specific IL‐17 production was found to be dependent on TLR‐4 activation, since T cells from arthritic TLR‐4−/− mice produced markedly less IL‐17 upon SCW stimulation, whereas interferon‐γ production remained unaffected.ConclusionThese data indicate the involvement of TLR‐4 in the chronicity and erosive character of arthritis coincident with the antigen‐specific IL‐17 response. The high position of TLR‐4 in the hierarchy of erosive arthritis provides an interesting therapeutic target for RA.
Investigation of association of the IL12B and IL23R genes with psoriatic arthritis
Authors: Filer Charlotte , Ho Pauline , Smith Rhodri L. , Griffiths Christopher , Young Helen S. , Worthington Jane , Bruce Ian N. , Barton Anne 
Published: November 2008

AbstractObjectiveRecent reports have confirmed association of single‐nucleotide polymorphisms (SNPs) mapping to the interleukin‐23 receptor (IL‐23R) and IL‐12β genes with psoriasis susceptibility. The aim of this study was to determine whether these variants are also associated with susceptibility to psoriatic arthritis (PsA).MethodsTwo IL23R SNPs (rs7530511 and rs11209026) and 2 IL12B SNPs (rs3212227 and rs6887695) were genotyped in DNA samples from 520 white patients with PsA and 2,260 control subjects, all of whom resided in the UK. For SNP rs3212227, data on a larger group of controls (n = 4,681) were publicly available; this information was used in the analysis. Genotype counts were compared between patients with PsA and population controls, using the trend test.ResultsA haplotype comprising carriage of the common variants of both IL23R SNPs was associated with PsA susceptibility (adjusted P = 0.013 [1,000 permutations]). Both IL12B SNPs were independently associated with PsA susceptibility, and this association was strongest under a dominant model, with homozygosity for the common allele being more frequent in patients with PsA than in control subjects: for rs3212227, the odds ratio (OR) for carriage of AA versus other genotypes was 1.43 (95% confidence interval [95% CI] 1.17–1.76); for rs6887695, the OR for carriage of GG versus other genotypes was 1.43 (95% CI 1.18–1.74).ConclusionVariation within IL23R and IL12B is associated with susceptibility to both psoriasis and PsA. The effect sizes observed in patients with PsA appear to be smaller than those previously reported in patients with psoriasis, suggesting that both loci are primarily associated with psoriasis susceptibility. However, this does support the idea that the genetic etiology of the psoriasis present in patients with PsA has susceptibility loci in common with those observed in patients with uncomplicated psoriasis.
Association of three systemic lupus erythematosus susceptibility factors, PD‐1.3A, C4AQ0, and low levels of mannan‐binding lectin, with autoimmune manifestations in icelandic multicase systemic lupus erythematosus families
Authors: Kristjansdottir Helga , Saevarsdottir Saedis , Gröndal Gerdur , Alarcón‐Riquelme Marta E. , Erlendsson Kristjan , Valdimarsson Helgi , Steinsson Kristjan 
Published: November 2008

AbstractObjectiveTo study autoimmune diseases and autoantibodies in Icelandic multicase systemic lupus erythematosus (SLE) families and to determine the association of 3 SLE susceptibility factors, PD‐1.3A, C4AQ0, and low levels of mannan‐binding lectin (MBL), with autoimmune disease in this population.MethodsEight SLE multicase families were studied, comprising a total of 124 family members (23 patients with SLE and 101 relatives). The diagnosis of an autoimmune disease was established and autoantibodies were measured in each family. In addition, PD‐1.3A alleles were genotyped, and C4AQ0 allotypes were established by electrophoresis and haplotype analysis. Low levels of MBL were determined using enzyme‐linked immunosorbent assay and variant‐allele genotyping.ResultsIn the SLE multicase families there was a high frequency of other autoimmune diseases (32.2%) and a high frequency of autoantibodies (53.2%). Of all family members, 59.7% were determined to have SLE, other autoimmune diseases, antinuclear antibodies, and/or other autoantibodies. The families showed genetic heterogeneity for PD‐1.3A, C4AQ0, and low MBL levels; the frequency of each factor ranged from 0% to 85%. The frequencies of PD‐1.3A and C4AQ0 were significantly increased in patients with SLE, relatives with other autoimmune diseases, and non–autoimmune disease relatives compared with controls. In the 7 families whose members had low levels of MBL, this factor was significantly associated with SLE, but the frequency of low MBL was decreased in relatives with other autoimmune diseases as compared with non–autoimmune disease relatives and controls. There were indications of an additive effect, and 91% of patients with SLE, 78% of relatives with other autoimmune diseases, and 75% of non–autoimmune disease relatives carried at least 1 of the 3 factors.ConclusionThese results demonstrate a high frequency of autoimmune diseases and autoantibodies in SLE multicase families. PD‐1.3A and C4AQ0 are part of a predisposing genetic background. Other genetic and/or environmental factors are necessary for disease expression, demonstrated by a high frequency of PD‐1.3A and C4AQ0 in non–autoimmune disease relatives. Low MBL levels may be one such contributing factor. The results of this study provide an example of epistatic genetic effects and overlapping genetics in autoimmune diseases.
S100A12 is a novel molecular marker differentiating systemic‐onset juvenile idiopathic arthritis from other causes of fever of unknown origin
Authors: Wittkowski Helmut , Frosch Michael , Wulffraat Nico , Goldbach‐Mansky Raphaela , Kallinich Tilmann , Kuemmerle‐Deschner Jasmin , Frühwald Michael C. , Dassmann Sandra , Pham Tuyet‐Hang , Roth Johannes , Foell Dirk 
Published: November 2008

AbstractObjectiveFever of unknown origin (FUO) in children presents a diagnostic challenge. The differential diagnosis includes systemic‐onset juvenile idiopathic arthritis (JIA), an autoinflammatory syndrome associated with activation of phagocytic cells that, at presentation, is difficult to differentiate from severe systemic infections. The aim of this study was to investigate whether serum concentrations of the phagocytic proinflammatory protein S100A12 may help in deciding whether to treat patients with FUO with antibiotics or immunosuppressive agents.MethodsSerum samples were obtained from 45 healthy control subjects and from 240 patients (60 with systemic‐onset JIA, 17 with familial Mediterranean fever [FMF], 18 with neonatal‐onset multisystem inflammatory disease [NOMID], 17 with Muckle‐Wells syndrome [MWS], 40 with acute lymphoblastic leukemia [ALL], 5 with acute myeloblastic leukemia [AML], and 83 with systemic infections). All samples were collected at the time of presentation, before the initiation of any treatment, and concentrations of S100A12 were determined by enzyme‐linked immunosorbent assay.ResultsThe mean ± 95% confidence interval serum levels of S100A12 were as follows: in patients with JIA, 7,190 ± 2,690 ng/ml; in patients with FMF, 6,720 ± 4,960 ng/ml; in patients with NOMID, 720 ± 450 ng/ml; in patients with MWS, 150 ± 60 ng/ml; in patients with infections, 470 ± 160 ng/ml; in patients with ALL, 130 ± 80 ng/ml; in patients with AML, 45 ± 60 ng/ml; in healthy control subjects, 50 ± 10 ng/ml. The sensitivity and specificity of S100A12 to distinguish between systemic‐onset JIA and infections were 66% and 94%, respectively.ConclusionS100A12, a marker of granulocyte activation, is highly overexpressed in patients with systemic‐onset JIA or FMF, which may point to as‐yet unknown common inflammatory mechanisms in these diseases. The measurement of S100A12 serum levels may provide a valuable diagnostic tool in the evaluation of FUO.
Population‐based prevalence study of Behçet's disease: Differences by ethnic origin and low variation by age at immigration
Authors: Mahr Alfred , Belarbi Linda , Wechsler Bertrand , Jeanneret Dominique , Dhote Robin , Fain Olivier , Lhote François , Ramanoelina Jacky , Coste Joël , Guillevin Loïc 
Published: November 2008

AbstractObjectiveTo estimate the prevalence of Behçet's disease (BD) in a multiethnic population living in France, with particular focus on disease risk among immigrants.MethodsThe study was conducted in a county in the Paris metropolitan area that is home to 1,094,412 adults (ages ≥15 years), of whom 26% are of non‐European ancestry. Patients with BD living in this area during 2003 were identified using 3 sources (hospitals, community physicians, and the National Health Insurance database), and diagnoses were verified using the International Study Group criteria. Standardized, year‐2003 prevalence rates were computed for the overall population and for each ethnic group. Stratified prevalence rates according to age at immigration to France were calculated to investigate the relationship between age at immigration and BD risk.ResultsSeventy‐nine subjects fulfilled our search criteria. The overall prevalence per 100,000 adults was 7.1 (95% confidence interval [95% CI] 3.5–14.4), and the prevalence for populations of European, North African, and Asian ancestry was 2.4 (95% CI 0.6–7.2), 34.6 (95% CI 24.4–47.5), and 17.5 (95% CI 10.7–27.2), respectively. Within the migrant population of either North African or Asian ancestry, BD prevalences were similar for residents born in France, residents <15 years old at immigration, and residents ≥15 years old at immigration.ConclusionOur findings indicate that the prevalence of BD among immigrants of North African or Asian ancestry is significantly higher than that in the European‐origin population, and comparable with rates reported from North Africa and Asia. Moreover, our results suggest that BD risk is not related to age at immigration. These findings support the hypothesis that BD has a primarily hereditary basis.
gratterpalm uses HR as a strategic tool for growth
Authors: Saunders Helen 
Published: November 2008

PurposeThe aim of this case study is to show how HR can help an organization meet its business goals. Investing strategically in HR can result in cost savings, enhanced productivity and improved customer service.Design/methodology/approachThe case study feature follows the development of HR at a retail marketing agency in the UK and its five‐year journey from being non‐existent to becoming a fully functioning department with a strategic positioning on the board of directors.FindingsWith a team of 70 people, changing employee legislation and large corporate accounts, five years ago the organization was at risk as it had no HR function in place. Also, operating in the creative industry where high employee turnover rates, burnout and job dissatisfaction are common issues, it was missing out on using its human resources and strong culture to gain a competitive advantage and facilitate growth.Originality/valuePutting in place an HR strategy requires buy‐in from the senior management team, and introducing HR for the first time is made easier by involving employees and management early in the process. In this case, an employee survey, supported by a strong communications program, proved to be a key tool in highlighting the issues that needed to be addressed by the new HR function and in providing an ongoing tool for continuous improvement and engagement with employees. Involving clients and taking into account the needs of external stakeholders further boosts the effectiveness of people policies.
Harmony and participation in Arab and Western teams
Authors: Wright Norman S. , Bennett Hadyn 
Published: November 2008

PurposeThe purpose of this paper is to make a cross‐cultural comparison of team harmony and participation of a collectivistic Middle Eastern sample of women and an individualistic Anglo sample of women.Design/methodology/approachTwo independent female samples are compared – Anglos and Arabs. Respondents completed a self‐report survey regarding their perceptions of recent team experiences as well as their own participation within those teams.FindingsThe findings revealed greater sensitivity to inter‐member conflict on the part of the Arabic sample, coupled with increased incidence of behaviors to promote team harmony through the suppression of individual opinions and ideas.Research limitations/implicationsFurther research should be conducted to differentiate the interaction between role and gender. From a practical standpoint, quasi‐experimental research on interventions to reduce the participation problem would be important.Practical implicationsTeam performance and retention of Emirati employees within the United Arab Emirates context can be enhanced to the extent that managers understand the perceptions and participation of local employees. The findings of the current study aid managers in understanding the key role of team harmony sensitivity among Emiratis and its subsequent impact on their participation in team processes.Originality/valueThe paper addresses a significant issue, team member participation, in an understudied but increasingly relevant setting, Middle Eastern teams.
Using an ethnographic case study approach to identify socio‐cultural discourse
Authors: Gallant Monica 
Published: November 2008

PurposeThe purpose of this paper is to describe a research methodology that was used to identify dominant socio‐cultural discourse using a feminist post‐structural lens.Design/methodology/approachBased on a literature‐based study focusing on research methodology and theoretical frameworks, the conduct of an ethnographic case study is described in detail. A discussion of the reporting and analysis of the data is also included.FindingsThe study indicates that using an ethnographic case study approach is a very effective tool for identifying dominant socio‐cultural discourses. This in turn can lead to greater emancipation for women through discourse analysis and re‐positioning.Research limitations/implicationsThis paper presents a focused literature study and contains a description of an effective research methodology for specific purposes. It may be of use to others interested in conducting similar types of research.Practical implicationsThe study indicates that using unstructured interviews and a narrative reporting technique is a valuable way to collect data about socio‐cultural discourses in an Arabic context. The importance of the position, power, and reflexivity of the interviewer is also explored. In addition, the study suggests that successful feminist movements should be gradual and should take into account societal discourses to allow women to gain emancipatory action through re‐positioning themselves within their societal discourses.Originality/valueThe paper is one of the few attempting to describe an ethnographic case study approach with a feminist, post‐structuralist view in an Arab context.