bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sera from anti–Jo‐1–positive patients with polymyositis and interstitial lung disease induce expression of intercellular adhesion molecule 1 in human lung endothelial cells
Authors: Helmers Sevim Barbasso , Englund Pernilla , Engström Marianne , Åhlin Erik , Fathi Maryam , Janciauskiene Sabina , Heimbürger Mikael , Rönnelid Johan , Lundberg Ingrid E. 
Published: July 2009

AbstractObjectiveTo investigate whether sera or purified IgG from patients with polymyositis (PM) and patients with dermatomyositis (DM), with or without interstitial lung disease (ILD), can activate endothelial cells (ECs).MethodsPatients' sera were selected based on the presence or absence of anti–Jo‐1, anti‐SSA, or anti–U1 small nuclear RNP autoantibodies. The presence of autoantibodies was determined by line blot assays. Cultured human microvascular ECs derived from lung tissue (HMVEC‐L) were incubated with sera or purified IgG from 22 patients with PM, 7 patients with DM, and 10 healthy individuals as controls. Assessment of intercellular adhesion molecule 1 (ICAM‐1) expression was conducted by immunofluorescence (n = 22) and by cell‐based enzyme‐linked immunosorbent assay (ELISA) (n = 20). Serum levels of soluble ICAM‐1 (sICAM‐1) were determined by ELISA.ResultsSera from PM patients with ILD who were positive for anti–Jo‐1 autoantibodies had a significantly stronger effect on the expression of ICAM‐1 by HMVEC‐L in comparison with sera from healthy controls and patients with other autoantibodies. Purified IgG did not induce ICAM‐1 expression. Higher serum levels of sICAM‐1 were found in patients with myositis compared with healthy controls.ConclusionEC activation with ICAM‐1 expression could contribute to the multiorgan involvement, including the development of myositis and ILD, in patients carrying anti–Jo‐1 autoantibodies. The EC‐activating factors are not the autoantibodies themselves, but might be systemic factors associated with these autoantibodies.
STAT4 is a genetic risk factor for systemic sclerosis having additive effects with IRF5 on disease susceptibility and related pulmonary fibrosis
Authors: Dieudé P. , Guedj M. , Wipff J. , Ruiz B. , Hachulla E. , Diot E. , Granel B. , Sibilia J. , Tiev K. , Mouthon L. , Cracowski J.L. , Carpentier P.H. , Amoura Z. , Fajardy I. , Avouac J. , Meyer O. , Kahan A. , Boileau C. , Allanore Y. 
Published: July 2009

AbstractObjectiveSystemic sclerosis (SSc) belongs to the group of connective tissue disorders (CTDs), among which are several disorders characterized by a type I interferon (IFN) signature. The recent identification of an association between IRF5 and SSc further highlights a key role for IFN. STAT4, which encodes STAT‐4, contributes to IFN signaling, and its genetic variants were found to be associated with CTDs. The aim of this study was to determine whether the STAT4 rs7574865 single‐nucleotide polymorphism is associated with SSc, and whether it interacts with IRF5.MethodsBoth the STAT4 rs7574865 and IRF5 rs2004640 polymorphisms were genotyped in 1,855 individuals of French Caucasian origin comprising a discovery set of 440 patients with SSc and 485 control subjects and a replication set of 445 patients with SSc and an additional 485 control subjects.ResultsSTAT4 rs7574865 was shown to be associated with SSc (P = 0.001, odds ratio [OR] 1.29, 95% confidence interval [95% CI] 1.11–1.51). This association was not restricted to a particular phenotype. An additive effect of the STAT4 rs7574865 T allele and the IRF5 rs2004640 T allele was observed, resulting in a multiplicatively increased 1.28‐fold risk of SSc. The OR for SSc was 2.72 (95% CI 1.86–3.99) for combinations of genotypes with ≥3 risk alleles. An additive effect was also detected for fibrosing alveolitis: carriage of at least 3 risk alleles appeared to be an independent risk factor (P = 2.2 × 10−4, OR 1.97, 95% CI 1.28–3.04).ConclusionOur results establish STAT4 rs7574865 as a new SSc genetic susceptibility factor. STAT4 and IRF5 act with additive effects in terms of susceptibility to both SSc and SSc‐related fibrosing alveolitis.
Detection of coronary artery lesions and myocardial necrosis by magnetic resonance in systemic necrotizing vasculitides
Authors: Mavrogeni S. , Manoussakis M. N. , Karagiorga T. C. , Douskou M. , Panagiotakos D. , Bournia V. , Cokkinos D. V. , Moutsopoulos H. M. 
Published: July 2009

AbstractObjectiveMyocardium and coronary arteries can occasionally be affected in patients with systemic necrotizing vasculitides; however, such involvement has not been systematically assessed using cardiovascular magnetic resonance imaging (MRI).MethodsMagnetic resonance angiography and contrast‐enhanced MRI were applied for the assessment of coronary arteries (the left anterior descending [LAD], left circumflex [LCx], and right coronary artery [RCA]) and myocardium, respectively, in 39 patients with vasculitis who were asymptomatic for cardiac disease (16 with microscopic polyangiitis [MPA], 11 with Wegener's granulomatosis [WG], 9 with Churg‐Strauss syndrome [CSS], and 3 with polyarteritis nodosa [PAN]). Data were compared with age‐matched disease‐control patients with rheumatoid arthritis (n = 20) or systemic lupus erythematosus (n = 13), and with healthy control individuals with normal coronaries (n = 40).ResultsPatients with MPA, WG, and PAN (but not with CSS) were found to display significantly increased maximal diameters of coronary arteries compared with healthy controls (for MPA and WG; P < 0.001 for LAD and RCA, and P < 0.01 for LCx) and with both disease‐control groups (for only MPA; P < 0.01 for LAD and RCA, and P < 0.05 for LCx). Fusiform coronary aneurysms were detected in patients with MPA (4/16) and PAN (2/3), whereas coronary ectasias were evident in patients with MPA (14/16) and WG (2/11). The presence of myocardial necrosis (by assessment of late gadolinium‐enhanced images) was identified only in patients with MPA (2/16) and CSS (3/8 studied).ConclusionCardiovascular MRI assessment of patients with systemic vasculitis revealed coronary ectatic disease in the majority of patients with MPA and PAN, as well as in several patients with WG. Myocardial necrosis can be detected in MPA and CSS.
Efficacy and tolerability of rituximab with or without PEGylated interferon alfa‐2b plus ribavirin in severe hepatitis C virus–related vasculitis: A long‐term followup study of thirty‐two patients
Authors: Terrier Benjamin , Saadoun David , Sène Damien , Sellam Jérémie , Pérard Laurent , Coppéré Brigitte , Karras Alexandre , Blanc François , Buchler Matthias , Plaisier Emmanuelle , Ghillani Pascale , Rosenzwajg Michelle , Cacoub Patrice 
Published: July 2009

AbstractObjectiveTo report on the long‐term followup of a cohort of patients with hepatitis C virus (HCV)–related vasculitis treated with rituximab with or without PEGylated interferon alfa‐2b (PEG–IFN alfa‐2b) plus ribavirin.MethodsThe study group comprised 32 HCV RNA–positive patients with HCV‐related vasculitis: 20 patients were treated with rituximab and PEG–IFN alfa‐2b (9 of whom had not previously received antiviral treatment and 11 of whom had experienced disease resistance to or relapse with antiviral treatment), and 12 antiviral‐intolerant patients were treated with rituximab alone.ResultsTreatment with rituximab and PEG–IFN alfa‐2b plus ribavirin induced a complete clinical response and a partial clinical response in 80% and 15% of patients, respectively, a complete immunologic response and a partial immunologic response in 67% and 33% of patients, respectively, and a sustained virologic response in 55% of patients. Treatment with rituximab alone induced a complete clinical response and a partial clinical response in 58% and 9% of patients, respectively, and a complete immunologic response and a partial immunologic response in 46% and 36% of patients, respectively. B cell depletion was achieved in 96% of patients, and B cell recovery began after a median delay of 12 months. After a mean ± SD followup period of 23 ± 12 months, 22% of patients experienced a clinical relapse, and 34% of patients experienced an immunologic relapse. All relapses were associated with the absence of virologic control, and 78% of relapses were associated with B cell recovery. Six patients were re‐treated with rituximab. All 6 of these patients had a complete clinical response, 50% had a complete immunologic response, and 50% had a partial immunologic response. Rituximab was well tolerated overall.ConclusionRituximab is an effective treatment of severe and/or refractory HCV‐related vasculitis. Relapses were consistently associated with the absence of virologic control. The clinical and immunologic efficacy of rituximab after repeated infusion appeared to be the same as that observed after induction therapy.
Accelerated development of aging‐associated and instability‐induced osteoarthritis in osteopontin‐deficient mice
Authors: Matsui Yuichiro , Iwasaki Norimasa , Kon Shigeyuki , Takahashi Daisuke , Morimoto Junko , Matsui Yutaka , Denhardt David T. , Rittling Susan , Minami Akio , Uede Toshimitsu 
Published: July 2009

AbstractObjectiveTo investigate the role of osteopontin (OPN) in the development of osteoarthritis (OA) under in vivo and in vitro conditions.MethodsBoth instability‐induced and aging‐associated OA models were generated using OPN‐deficient (OPN−/−) and control wild‐type (WT) mice. An in vitro cartilage degradation model was also used, to evaluate the effect of OPN on proteoglycan loss from joint cartilage.ResultsOPN deficiency exacerbated both aging‐associated and instability‐induced OA. Both structural changes and an increased loss of proteoglycan from cartilage tissue were augmented in the absence of OPN. OPN deficiency also led to the induction of matrix metalloproteinase 13 (MMP‐13), which degrades a major component of the cartilage matrix protein type II collagen. Both the loss of proteoglycan and the induction of the collagen‐degrading enzyme MMP‐13 facilitated the development of OA.ConclusionOPN plays a pivotal role in the progression of both instability‐induced and aging‐associated spontaneous OA. OPN is a critical intrinsic regulator of cartilage degradation via its effects on MMP‐13 expression and proteoglycan loss.
Role of p53 in human chondrocyte apoptosis in response to shear strain
Authors: Hashimoto Shingo , Nishiyama Takayuki , Hayashi Shinya , Fujishiro Takaaki , Takebe Ken , Kanzaki Noriyuki , Kuroda Ryosuke , Kurosaka Masahiro 
Published: July 2009

AbstractObjectiveChondrocyte apoptosis plays an important role in cartilage degeneration in osteoarthritis (OA), and mechanical injury to cartilage induces chondrocyte apoptosis. In response to DNA damage, p53 expression is up‐regulated, transcription activity is increased, and apoptosis signals are initiated. The p53‐regulated apoptosis‐inducing protein 1 (p53AIP‐1) is one of the p53‐regulated genes, and is activated in response to DNA damage. This study was undertaken to analyze p53 function after induction of apoptosis by shear strain in chondrocytes.MethodsOA cartilage samples were obtained from subjects undergoing total knee replacement surgery, and normal cartilage samples were obtained from subjects undergoing surgery for femoral neck fracture. Chondrocytes were isolated from human cartilage and cultured. Expression of p53 and p53AIP in chondrocytes was detected by reverse transcriptase–polymerase chain reaction and Western blotting. Shear strain was introduced in normal human knee chondrocytes. To explore p53 function, normal human knee chondrocytes were pretreated with pifithrin‐α or p53 small interfering RNA (siRNA) before induction of shear strain. Chondrocyte apoptosis was detected by expression of cleaved caspase 9 with Western blotting and TUNEL staining. Expression of p53 and p53AIP‐1 was analyzed by Western blotting.ResultsOA and normal chondrocytes expressed p53. OA chondrocytes showed much higher expression of p53 and p53AIP‐1 than did normal chondrocytes. TUNEL‐positive cells and expression of p53, p53AIP‐1, and cleaved caspase 9 were increased by shear strain, but chondrocyte apoptosis was suppressed after pretreatment with pifithrin‐α or p53 siRNA.ConclusionOur findings indicate that p53 and p53AIP‐1 play important roles in human chondrocyte apoptosis. Down‐regulation of p53 expression prevents cartilage from undergoing apoptosis introduced by shear strain.
European population substructure is associated with mucocutaneous manifestations and autoantibody production in systemic lupus erythematosus
Authors: Chung Sharon A. , Tian Chao , Taylor Kimberly E. , Lee Annette T. , Ortmann Ward A. , Hom Geoffrey , Graham Robert R. , Nititham Joanne , Kelly Jennifer A. , Morrisey Jean , Wu Hui , Yin Hong , Alarcón‐Riquelme Marta E. , Tsao Betty P. , Harley John B. , Gaffney Patrick M. , Moser Kathy L. , Manzi Susan , Petri Michelle , Gregersen Peter K. , Langefeld Carl D. , Behrens Timothy W. , Seldin Michael F. , Criswell Lindsey A. 
Published: July 2009

AbstractObjectiveTo determine whether genetic substructure in European‐derived populations is associated with specific manifestations of systemic lupus erythematosus (SLE), including mucocutaneous phenotypes, autoantibody production, and renal disease.MethodsSLE patients of European descent (n = 1,754) from 8 case collections were genotyped for >1,400 ancestry informative markers that define a north–south gradient of European substructure. Using the Structure program, each SLE patient was characterized in terms of percent Northern (versus percent Southern) European ancestry based on these genetic markers. Nonparametric methods, including tests for trend, were used to identify associations between Northern European ancestry and specific SLE manifestations.ResultsIn multivariate analyses, increasing levels of Northern European ancestry were significantly associated with photosensitivity (Ptrend = 0.0021, odds ratio for highest quartile of Northern European ancestry versus lowest quartile [ORhigh–low] 1.64, 95% confidence interval [95% CI] 1.13–2.35) and discoid rash (Ptrend = 0.014, ORhigh–low 1.93, 95% CI 0.98–3.83). In contrast, increasing levels of Northern European ancestry had a protective effect against the production of anticardiolipin autoantibodies (Ptrend = 1.6 × 10−4, ORhigh–low 0.46, 95% CI 0.30–0.69) and anti–double‐stranded DNA autoantibodies (Ptrend = 0.017, ORhigh–low 0.67, 95% CI 0.46–0.96).ConclusionThis study demonstrates that specific SLE manifestations vary according to Northern versus Southern European ancestry. Thus, genetic ancestry may contribute to the clinical heterogeneity and variation in disease outcomes among SLE patients of European descent. Moreover, these results suggest that genetic studies of SLE subphenotypes will need to carefully address issues of population substructure based on genetic ancestry.
Delayed acquisition of somatic hypermutations in repopulated IGD+CD27+ memory B cell receptors after rituximab treatment
Authors: Muhammad Khalid , Roll Petra , Einsele Hermann , Dörner Thomas , Tony Hans‐Peter 
Published: July 2009

AbstractObjectiveTransient B cell depletion by rituximab has been used with clinical efficacy in the treatment of patients with rheumatoid arthritis (RA). Previous studies of B cell repopulation have shown long‐term numerical reduction in memory B cells. Non–class‐switched IgD+CD27+ memory B cells, in particular, repopulate slowly. This study was undertaken to determine whether mutational acquisition in individual B cell receptors in repopulating class‐switched and non–class‐switched memory B cells is affected by rituximab.MethodsCells obtained from 16 RA patients, 4 healthy donors, and 3 patients who underwent allogeneic stem cell transplantation (ASCT) were analyzed using single B cell sorting followed by nested polymerase chain reaction and Ig VH3 sequencing.ResultsThere was a delayed acquisition of mutations in Ig receptors of IgD+ memory B cells over a period of 6 years after a single course of rituximab. One year after rituximab treatment, 84% of single repopulating IgD+CD27+ B cells were unmutated, and no highly mutated Ig receptors were found (compared with 52% before therapy). Over time, increasing numbers of mutations were detected. Even 6 years after rituximab treatment, however, mutations in IgD+ memory B cells were still significantly reduced. In contrast, class‐switched memory B cells repopulated with quantitatively normal mutations. In comparison, in patients undergoing ASCT, IgD+ memory cells repopulated earlier with higher mutations in Ig receptors.ConclusionOur data suggest that IgD+ memory B cells are particularly susceptible to the effects of rituximab, with delayed acquisition of mutations in their Ig receptors still evident 6 years after a single course of rituximab. Our findings indicate that these cells have different requirements for mutational acquisition compared with class‐switched memory B cells.
Longitudinal effect of vigorous physical activity on patella cartilage morphology in people without clinical knee disease
Authors: Teichtahl Andrew J. , Wluka Anita E. , Forbes Andrew , Wang Yuanyuan , English Dallas R. , Giles Graham G. , Cicuttini Flavia M. 
Published: July 2009

AbstractObjectiveThere are few data concerning possible long‐term effects of physical activity on cartilage change in the patellofemoral compartment. We examined the effect of participation in vigorous physical activity on changes to patella cartilage over 2 years.MethodsA total of 297 healthy adults ages 50–79 years with no history of knee injury or symptoms were recruited from an existing study. Physical activity data were obtained by questionnaire at baseline (2003–2004). Patella cartilage volume and defects were determined by magnetic resonance imaging at baseline (2003–2004) and followup (2006–2007).ResultsParticipation in vigorous physical activity at baseline was associated with a reduced rate of patella cartilage volume loss (−21.2 mm3 per annum [95% confidence interval (95% CI) −41.5, −1.0; P = 0.04]) and a trend toward less risk of worsening patella cartilage defects (odds ratio 0.4; 95% CI 0.2, 1.1 [P = 0.07]) over the subsequent 2 years. In the subgroup with no significant patella cartilage defects at baseline (n = 192), participation in vigorous physical activity was associated with a reduced annual rate of patella cartilage volume loss (95% CI −53.8, −7.8; P = 0.03) and a trend for fewer new patella cartilage defects (95% CI 0.1, 1.1; P = 0.08). No significant relationships were found between vigorous physical activity and cartilage volume change or defect progression in the subgroup with prevalent patella cartilage defects at baseline.ConclusionThese observations suggest that vigorous physical activity is beneficial to patellofemoral joints for people without preexisting cartilage damage. Weight‐bearing vigorous physical activity might, therefore, be useful in the prevention of patellofemoral osteoarthritis.
Effectiveness of two finger splints for swan neck deformity in patients with rheumatoid arthritis: A randomized, crossover trial
Authors: van der Giesen F. J. , van Lankveld W. J. , Kremers‐Selten C. , Peeters A. J. , Stern E. B. , Le Cessie S. , Nelissen R. G. H. H. , Vliet Vlieland T. P. M. 
Published: July 2009

AbstractObjectiveTo compare the effectiveness and acceptability of silver ring splints (SRS) and commercial prefabricated thermoplastic splints (PTS) in treating swan neck deformities in patients with rheumatoid arthritis (RA).MethodsConsecutive patients with RA and a mobile swan neck deformity were included in a randomized, crossover trial. In 2 different sequences, patients used both splints for 4 weeks, with a washout period of 2 weeks. Afterward, patients used the preferred splint for another 12 weeks. The primary outcome measure was dexterity measured with the Sequential Occupational Dexterity Assessment (SODA). Secondary outcome measures included other measures of hand function, satisfaction with the splints, and splint preference.ResultsFifty patients were included, and 47 (94%) of those completed the study. Eighteen patients (36%) had 1 swan neck deformity, whereas the other patients had 2 or more. The improvement of the total SODA score with the SRS (11.2; 95% confidence interval [95% CI] 8.1, 14.3) and PTS (10.8; 95% CI 7.5, 14.1) was similar (difference −0.5; 95% CI −2.2, 1.2). In addition, there were no significant differences in change scores regarding the other clinical outcome measures, or satisfaction. Twenty‐four patients preferred the SRS, 21 preferred the PTS, and 2 patients chose neither. A comparison in the 12‐week followup period yielded similar clinical outcomes, with the exception of a significantly higher score in 3 items of satisfaction in the SRS group.ConclusionFor patients with RA and a mobile swan neck deformity, SRS and PTS are equally effective and acceptable.
The effect of thalidomide in chicken embryos
Authors: Stephens Trent D. 
Published: July 2009

AbstractEarly in the history of the thalidomide disaster, chick embryos were “eliminated” as useful in the study of thalidomide. One reason for that conclusion was that many of the early experiments were flawed. We employed a number of experiments to expose chick embryos to thalidomide. Our data show that thalidomide does cause limb reduction defects in chick embryos as long as the embryos are directly exposed to the drug. The most useful techniques are implanting thalidomide‐soaked beads into the embryo immediately adjacent to the limb territory or soaking presumptive chick limb territories in thalidomide and then grafting the explants to a host embryo celom. Thalidomide affects the chick limb grafted to a host embryo in a dose response fashion. Furthermore, S‐thalidomide and S‐EM12 are more teratogenic than R‐thalidomide and R‐EM12. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.
Developmental control of inositol phosphate biosynthesis is altered in the brain of both curly and phenotypically normal straight tail mutant mice
Authors: Alebous Hana Dawood Ali , Cartee Robert , Vaccari David , Wright Oneil A. , Ahmed Altan , Hood Ronald D. , Johnson Margaret Dean 
Published: July 2009

AbstractBACKGROUND: Altered levels of inositol phosphate in the central nervous system (CNS) are hypothesized to produce distorted brain signaling and lead to numerous neurologic maladies. Little is known of mechanisms controlling the complex metabolic flux of inositol phosphate. Less is known of controls that regulate inositol‐phosphate biosynthesis in the mammalian brain. The expression of 1L‐myo‐inositol−1 phosphate synthase (MIP), the only enzyme known to synthesize inositol phosphate, was studied in the brain of normal (CBA) and curly tail (CT) mutant mice. The CT strain exhibits a neural tube defect, spina bifida, responsive to inositol supplementation, but not to folic acid treatment. METHODS: Utilizing enzyme assays to determine the specific activity of MIP, Western blotting to detect expression, gas chromatography/mass spectrometry to measure inositol concentration, and statistical analyses to evaluate quantitative data, MIP expression was analyzed in newborn, young, and adult brains of CBA and CT (curly tail [ct‐CT] and straight tail [st‐CT]) mutant mice. RESULTS: Data analyses suggest there is a significant difference in MIP activity in the brain of CBA mice as compared to that of CT mutant mice and that temporal and spatial control of MIP expression and inositol concentrations are altered in the brain of both the ct‐CT and phenotypically normal st‐CT mutant. Moreover, two differentially expressed forms of MIP were identified in the adult mouse brain. CONCLUSIONS: These findings implicate a role for MIP in the maturation of the CNS and evoke a hypothesis regarding the regulation of inositol phosphate biosynthesis in brain development. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.