bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longterm Outcomes and Treatment After Myocardial Infarction in Patients with Rheumatoid Arthritis
Authors: McCoy Sara S. , Crowson Cynthia S. , Maradit-Kremers Hilal , Therneau Terry M. , Roger Veronique L. , Matteson Eric L. , Gabriel Sherine E. 
Published: February 2013

Objective.To investigate the risk profiles, treatment, and outcomes of patients with rheumatoid arthritis (RA) with myocardial infarction (MI) and matched MI patients without RA.Methods.We used a population-based cohort of Olmsted County, Minnesota, residents with MI from the period 1979–2009. We identified 77 patients who fulfilled the American College of Rheumatology 1987 criteria for RA and 154 MI patients without RA matched for age, sex, and calendar year. Data collection from medical records included RA and MI characteristics, antirheumatic and cardioprotective medications, reperfusion therapy, and outcomes (mortality, heart failure, and recurrent ischemia).Results.The mean age at MI was 72.4 years and 55% of patients were female in both cohorts. Cardiovascular risk factor profiles, MI characteristics, and treatment with reperfusion therapy or cardioprotective medications were similar in MI patients with and those without RA. Patients with RA experienced poorer longterm outcomes compared to patients without RA — for mortality: hazard ratio (HR) 1.47; 95% CI 1.04, 2.08; and for recurrent ischemia: HR 1.51; 95% CI 1.04, 2.18.Conclusion.MI patients with RA received similar treatment with reperfusion therapy and cardioprotective medications and had similar short-term outcomes compared to patients without RA. Patients with RA had poorer longterm outcomes. Despite similar treatment, MI patients with RA had worse longterm outcomes than MI patients without RA.
Radiological Peripheral Involvement in a Cohort of Patients with Polyarticular Juvenile Idiopathic Arthritis at Adulthood
Authors: Elhai Muriel , Bazeli Ramin , Freire Véronique , Feydy Antoine , Drapé Jean-Luc , Quartier Pierre , Kahan André , Deslandre Chantal , Wipff Julien 
Published: February 2013

Objective.Radiographic damage was recently identified as a feature of poor prognosis in polyarticular juvenile idiopathic arthritis (pJIA). However, most radiographic studies did not differentiate pJIA from other subtypes of JIA and little is known about pJIA persisting into adulthood. We describe radiological peripheral involvement in young adults with pJIA compared to patients with rheumatoid arthritis (RA).Methods.All consecutive patients with pJIA followed in a transition program were included. Age, sex, disease duration, and medical or surgical treatment information was collected. Laboratory tests and standard radiographs of the hands and wrists, feet, and hips were analyzed by 2 independent radiologists blinded to the diagnosis. One RA control group (age < 55 yrs), matched for sex and disease duration, was recruited.Results.Forty-three patients with pJIA and 59 with RA were included. Radiographs showed hand lesions in 79% of pJIA and 86% of patients with RA, feet lesions in 74% of pJIA and 80% of patients with RA, and hip damage in 35% of pJIA and 17% of patients with RA (p = nonsignificant). Specific to the juvenile forms were lower frequency of proximal interphalangeal joint involvement (51% vs 76%; p = 0.03) and higher risk of bilateral hip damage (86% vs 25%; p < 0.01) than in adult RA.Conclusion.Structural peripheral damage is as common and as severe in young adults with pJIA as in adults with RA. The main specific feature of pJIA seems to be a high risk of bilateral hip damage. This requires a particular monitoring of pJIA patients with unilateral hip involvement to detect bilateralization.
Cyclosporine in Anti-Jo1-positive Patients with Corticosteroid-refractory Interstitial Lung Disease
Authors: Cavagna Lorenzo , Caporali Roberto , Abdì-Alì Lul , Dore Roberto , Meloni Federica , Montecucco Carlomaurizio 
Published: February 2013

Objective.To describe the longterm effectiveness and safety of cyclosporine (CYC) in patients with anti-Jo1-positive antisynthetase syndrome with corticosteroid-refractory interstitial lung disease (ILD).Methods.All patients with anti-Jo1 antisynthetase syndrome referred to our division between June 1991 and February 2010 were retrospectively evaluated for ILD. ILD was assessed using pulmonary function tests (PFT) and/or high-resolution computed tomography (HRCT). Kazerooni score was used to evaluate the HRCT extent of ILD. Prednisone was the first-line treatment in all cases (1 mg/kg/day orally, then tapering). Patients with corticosteroid-refractory or relapsing ILD were then included in this retrospective study. All patients started CYC (3 mg/kg/day) without increasing prednisone dosage. Both PFT and chest HRCT were regularly reassessed during followup.Results.Over the period of study we evaluated 18 patients with antisynthetase syndrome; 17 had ILD (13 women; median age at ILD onset 57 yrs); all patients failed prednisone within 12 months of ILD onset and subsequently started CYC. The median followup on CYC was 96 months [interquartile range (IQR) 57–120 mo]. Upon starting CYC, median forced vital capacity (FVC) was 60% (IQR 56%–70%), median DLCO 60% (IQR 50%–62.75%), and median Kazerooni score 16 (IQR 7–18). After 1 year of CYC, FVC (p = 0.0006), DLCO (p = 0.0010), and total Kazerooni score (p = 0.0002) improved and prednisone was tapered (median reduced from 25 mg/day to 2.5 mg/day; p < 0.0001). The results were substantially maintained including at last available followup. CYC side effects were hypertension (5 patients) and creatinine increase (6 patients). CYC was reduced in 3 cases and withdrawn in 4. Three out of 4 patients who interrupted CYC experienced ILD relapse; 2 patients recommenced low-dose CYC with subsequent ILD control. One patient refused re-treatment and subsequently died.Conclusion.CYC is effective and substantially safe in patients with anti-Jo1 antisynthetase syndrome with corticosteroid-refractory ILD. CYC withdrawal may be associated with ILD relapse, and low-dose CYC was effective in ILD control.
A Delphi Exercise to Identify Characteristic Features of Gout — Opinions from Patients and Physicians, the First Stage in Developing New Classification Criteria
Authors: Prowse Rebecca L. , Dalbeth Nicola , Kavanaugh Arthur , Adebajo Adewale O. , Gaffo Angelo L. , Terkeltaub Robert , Mandell Brian F. , Suryana Bagus P.P. , Goldenstein-Schainberg Claudia , Diaz-Torne Cèsar , Khanna Dinesh , Lioté Frederic , Mccarthy Geraldine , Kerr Gail S. , Yamanaka Hisashi , Janssens Hein , Baraf Herbert F. , Chen Jiunn-Horng , Vazquez-Mellado Janitzia , Harrold Leslie R. , Stamp Lisa K. , Van De Laar Mart A. , Janssen Matthijs , Doherty Michael , Boers Maarten , Edwards N. Lawrence , Gow Peter , Chapman Peter , Khanna Puja , Helliwell Philip S. , Grainger Rebecca , Schumacher H. Ralph , Neogi Tuhina , Jansen Tim L. , Louthrenoo Worawit , Sivera Francisca , Taylor William J. 
Published: February 2013

Objective.To identify a comprehensive list of features that might discriminate between gout and other rheumatic musculoskeletal conditions, to be used subsequently for a case-control study to develop and test new classification criteria for gout.Methods.Two Delphi exercises were conducted using Web-based questionnaires: one with physicians from several countries who had an interest in gout and one with patients from New Zealand who had gout. Physicians rated a list of potentially discriminating features that were identified by literature review and expert opinion, and patients rated a list of features that they generated themselves. Agreement was defined by the RAND/UCLA disagreement index.Results.Forty-four experienced physicians and 9 patients responded to all iterations. For physicians, 71 items were identified by literature review and 15 more were suggested by physicians. The physician survey showed agreement for 26 discriminatory features and 15 as not discriminatory. The patients identified 46 features of gout, for which there was agreement on 25 items as being discriminatory and 7 items as not discriminatory.Conclusion.Patients and physicians agreed upon several key features of gout. Physicians emphasized objective findings, imaging, and patterns of symptoms, whereas patients emphasized severity, functional results, and idiographic perception of symptoms.
Influence of Environmental Factors on Disease Activity in Spondyloarthritis: A Prospective Cohort Study
Authors: Zeboulon-Ktorza Nadine , Boelle Pierre Yves , Nahal Roula Said , D'agostino Maria Antonietta , Vibert Jean François , Turbelin Clément , Madrakian Homa , Durand Emmanuelle , Launay Odile , Mahr Alfred , Flahault Antoine , Breban Maxime , Hanslik Thomas 
Published: February 2013

Objective.Spondyloarthritis (SpA) is a complex inflammatory disorder. We investigated the influence of environmental factors on SpA disease activity.Methods.A prospective cohort of adults with SpA was followed for 3 years. Patients logged on to a secured Website every 3 months to complete a questionnaire. They reported whether they had been exposed to environmental factors such as stressful or traumatic life events, infections, or vaccinations. Outcome variables included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), and pain and patient global assessment (PGA) on visual numerical scales (each rated 0–10). Analyses were performed using a generalized estimating equation for repeated measures, adjusted for the outcome variable collected by the previous questionnaire.Results.In total, 272 patients were included in the analysis, completing the questionnaire on 2240 occasions. The average time (mean ± SD) between 2 connections to the Website was 4.0 ± 2.0 months. Occurrence of life events was followed by an increase of 0.5 (95% CI 0.4–0.7) in the BASDAI, 0.5 (95% CI 0.3–0.6) in the BASFI, 0.7 (95% CI 0.5–0.9) in the PGA, and 0.8 (95% CI 0.6–1.0) for pain (p < 0.0001 for all variations). A moderately statistically significant link was found between vaccination and an elevation of the BASDAI of 0.3 (95% CI 0.0–0.5; p = 0.032). No influence of other factors was detected.Conclusion.This prospective study in a dedicated SpA cohort shows for the first time a link between stressful events and disease activity. Although this link was statistically highly significant, its clinical meaning remains to be determined because the average magnitude of variation of the different variables studied was rather mild.
Gastric Antral Vascular Ectasia and Its Clinical Correlates in Patients with Early Diffuse Systemic Sclerosis in the SCOT Trial
Authors: Hung Emily W. , Mayes Maureen D. , Sharif Roozbeh , Assassi Shervin , Machicao Victor I. , Hosing Chitra , St. Clair E. William , Furst Daniel E. , Khanna Dinesh , Forman Stephen , Mineishi Shin , Phillips Kristine , Seibold James R. , Bredeson Christopher , Csuka Mary Ellen , Nash Richard A. , Wener Mark H. , Simms Robert , Ballen Karen , Leclercq Sharon , Storek Jan , Goldmuntz Ellen , Welch Beverly , Keyes-Elstein Lynette , Castina Sharon , Crofford Leslie J. , Mcsweeney Peter , Sullivan Keith M. 
Published: February 2013

Objective.To describe the prevalence and clinical correlates of endoscopic gastric antral vascular ectasia (GAVE; “watermelon stomach”) in early diffuse systemic sclerosis (SSc).Methods.Subjects with early, diffuse SSc and evidence of specific internal organ involvement were considered for the Scleroderma: Cyclophosphamide Or Transplant (SCOT) trial. In the screening procedures, all patients underwent upper gastrointestinal endoscopy. Patients were then categorized into those with or without endoscopic evidence of GAVE. Demographic data, clinical disease characteristics, and autoantibody data were compared using Pearson chi-square or Student t tests.Results.Twenty-three of 103 (22.3%) individuals were found to have GAVE on endoscopy. Although not statistically significant, anti-topoisomerase I (anti-Scl70) was detected less frequently among those with GAVE (18.8% vs 44.7%; p = 0.071). Similarly, anti-RNP antibodies (anti-U1 RNP) showed a trend to a negative association with GAVE (0 vs 18.4%; p = 0.066). There was no association between anti-RNA polymerase III and GAVE. Patients with GAVE had significantly more erythema or vascular ectasias in other parts of the stomach (26.1% vs 5.0%; p = 0.003).Conclusion.Endoscopic GAVE was present on screening in almost one-fourth of these highly selected patients with early and severe diffuse SSc. While anti-Scl70 and anti-U1 RNP trended toward a negative association with GAVE, there was no correlation between anti-RNA Pol III and GAVE. Patients with GAVE had a higher frequency of other gastric vascular ectasias outside the antrum, suggesting that GAVE may represent part of the spectrum of the vasculopathy in SSc.
Reduced CD18 Levels Drive Regulatory T Cell Conversion into Th17 Cells in the CD18hypo PL/J Mouse Model of Psoriasis
Authors: Singh Kamayani , Gatzka Martina , Peters Thorsten , Borkner Lisa , Hainzl Adelheid , Wang Honglin , Sindrilaru Anca , Scharffetter-Kochanek Karin 
Published: February 2013

Abstract
Defective development and function of CD4+CD25high+Foxp3+ regulatory T cells (Tregs) contribute to the pathogenesis of psoriasis and other autoimmune diseases. Little is known about the influence of adhesions molecules on the differentiation of Foxp3+ Tregs into proinflammatory Th17 cells occurring in lesional skin and blood of psoriasis patients. In the CD18hypo PL/J mouse model of psoriasis, reduced expression of CD18/β2 integrin to 2–16% of wild-type levels is associated with progressive loss of Tregs, impaired cell–cell contact between Tregs and dendritic cells (DCs), as well as Treg dysfunction as reported earlier. In the present investigation, Tregs derived from CD18hypo PL/J mice were analyzed for their propensity to differentiate into IL-17–producing Th17 cells in vivo and in in vitro Treg–DC cocultures. Adoptively transferred CD18hypo PL/J Tregs were more inclined toward conversion into IL-17–producing Th17 cells in vivo in an inflammatory as well as noninflammatory environment compared with CD18wt PL/J Tregs. Addition of neutralizing Ab against CD18 to Treg–DC cocultures in vitro promoted conversion of CD18wt PL/J Tregs to Th17 cells in a dose-dependent manner similar to conversion rates of CD18hypo PL/J Tregs. Reduced thymic output of naturally occurring Tregs and peripheral conversion of Tregs into Th17 cells therefore both contribute to the loss of Tregs and the psoriasiform dermatitis observed in CD18hypo PL/J mice. Our data overall indicate that CD18 expression levels impact Treg development as well as Treg plasticity and that differentiation of Tregs into IL-17–producing Th17 cells is distinctly facilitated by a subtotal deficiency of CD18.
Comparative Assessment of Clinically Utilized CD20-Directed Antibodies in Chronic Lymphocytic Leukemia Cells Reveals Divergent NK Cell, Monocyte, and Macrophage Properties
Authors: Rafiq Sarwish , Butchar Jonathan P. , Cheney Carolyn , Mo Xiaokui , Trotta Rossana , Caligiuri Michael , Jarjoura David , Tridandapani Susheela , Muthusamy Natarajan , Byrd John C. 
Published: February 2013

Abstract
CD20 is a widely validated, B cell–specific target for therapy in B cell malignancies. Rituximab is an anti-CD20 Ab that prolongs survival of chronic lymphocytic leukemia (CLL) patients when combined with chemotherapy. Ofatumumab and GA101 (obinutuzumab) are CD20-directed Abs currently being developed as alternative agents to rituximab in CLL based upon different properties of enhanced direct cell death, NK cell-mediated Ab-dependent cellular cytotoxicity, or complement-dependent cytotoxicity. Despite widespread study, ofatumumab and GA101 have not been compared with each other, nor studied for their interactions with monocytes and macrophages which are critical for the efficacy of anti-CD20 Abs in murine models. In CLL cells, we show that direct cell death and complement-dependent cytotoxicity are greatest with GA101 and ofatumumab, respectively. GA101 promotes enhanced NK cell activation and Ab-dependent cellular cytotoxicity at high Ab concentrations. Ofatumumab elicits superior Ab-dependent cellular phagocytosis with monocyte-derived macrophages. GA101 demonstrated reduced activation of monocytes with diminished pERK, TNF-α release, and FcγRIIa recruitment to lipid rafts. These data demonstrate that GA101 and ofatumumab are both superior to rituximab against CLL cells via different mechanisms of potential tumor elimination. These findings bear relevance to potential combination strategies with each of these anti-CD20 Abs in the treatment of CLL.
The NF-κB Inhibitory Proteins IκBα and IκBβ Mediate Disparate Responses to Inflammation in Fetal Pulmonary Endothelial Cells
Authors: Tang Jen-Ruey , Michaelis Katherine A. , Nozik-Grayck Eva , Seedorf Gregory J. , Hartman-Filson Marlena , Abman Steven H. , Wright Clyde J. 
Published: February 2013

Abstract
Exposure to intrauterine inflammation impairs lung growth but paradoxically protects the neonatal pulmonary vasculature from hyperoxic injury. The mechanisms mediating these contradictory effects are unknown. The objective is to identify the role of NF-κB in mediating cytoprotective and proinflammatory responses to inflammation in the fetal pulmonary endothelium. In newborn rats exposed to intra-amniotic LPS, we found increased expression of the NF-κB target gene manganese superoxide dismutase (MnSOD) in the pulmonary endothelium. Supporting these in vivo findings, LPS induced NF-κB activation and MnSOD expression in isolated fetal pulmonary arterial endothelial cells. In addition, LPS exposure caused apoptosis and suppressed cellular growth and induced P-selectin expression. LPS-induced NF-κB activation that proceeded through specific isoforms of the inhibitory protein IκB mediated these diverse responses; NF-κB signaling through IκBα degradation resulted in MnSOD upregulation and preserved cell growth, whereas NF-κB signaling through IκBβ degradation mediated apoptosis and P-selectin expression. These findings suggest that selective inhibition of NF-κB activation that results from IκBβ degradation preserves the enhanced antioxidant defense and protects the developing pulmonary vascular endothelium from ongoing inflammatory injury.
Amphisomal Route of MHC Class I Cross-Presentation in Bacteria-Infected Dendritic Cells
Authors: Fiegl Dorothee , Kägebein Danny , Liebler-Tenorio Elisabeth M. , Weisser Tanja , Sens Mareen , Gutjahr Melanie , Knittler Michael R. 
Published: February 2013

Abstract
Dendritic cells (DCs) are among the first professional APCs encountered by the obligate intracellular bacterium Chlamydia during infection. Using an established mouse bone marrow–derived DC line, we show that DCs control chlamydial infection in multiple small inclusions characterized by restricted bacterial growth, impaired cytosolic export of the virulence factor chlamydial protease–like activity factor, and interaction with guanylate-binding protein 1, a host cell factor involved in the initiation of autophagy. During maturation of infected DCs, chlamydial inclusions disintegrate, likely because they lack chlamydial protease–like activity factor–mediated protection. Released cytosolic Chlamydia are taken up by autophagosomes and colocalize with cathepsin-positive amphisomal vacuoles, to which peptide transporter TAP and upregulated MHC class I (MHC I) are recruited. Chlamydial Ags are subsequently generated through routes involving preprocessing in amphisomes via cathepsins and entry into the cytosol for further processing by the proteasome. Finally, bacterial peptides are reimported into the endosomal pathway for loading onto recycling MHC I. Thus, we unravel a novel pathway of MHC I–mediated cross-presentation that is initiated with a host cellular attack physically disrupting the parasitophorous vacuole, involves autophagy to collect cytosolic organisms into autophagosomes, and concludes with complex multistep antigenic processing in separate cellular compartments.
Postthymic Expansion in Human CD4 Naive T Cells Defined by Expression of Functional High-Affinity IL-2 Receptors
Authors: Pekalski Marcin L. , Ferreira Ricardo C. , Coulson Richard M. R. , Cutler Antony J. , Guo Hui , Smyth Deborah J. , Downes Kate , Dendrou Calliope A. , Castro Dopico Xaquin , Esposito Laura , Coleman Gillian , Stevens Helen E. , Nutland Sarah , Walker Neil M. , Guy Catherine , Dunger David B. , Wallace Chris , Tree Timothy I. M. , Todd John A. , Wicker Linda S. 
Published: February 2013

Abstract
As the thymus involutes with age, the maintenance of peripheral naive T cells in humans becomes strongly dependent on peripheral cell division. However, mechanisms that orchestrate homeostatic division remain unclear. In this study we present evidence that the frequency of naive CD4 T cells that express CD25 (IL-2 receptor α-chain) increases with age on subsets of both CD31+ and CD31− naive CD4 T cells. Analyses of TCR excision circles from sorted subsets indicate that CD25+ naive CD4 T cells have undergone more rounds of homeostatic proliferation than their CD25− counterparts in both the CD31+ and CD31− subsets, indicating that CD25 is a marker of naive CD4 T cells that have preferentially responded to survival signals from self-Ags or cytokines. CD25 expression on CD25− naive CD4 T cells can be induced by IL-7 in vitro in the absence of TCR activation. Although CD25+ naive T cells respond to lower concentrations of IL-2 as compared with their CD25− counterparts, IL-2 responsiveness is further increased in CD31− naive T cells by their expression of the signaling IL-2 receptor β-chain CD122, forming with common γ-chain functional high-affinity IL-2 receptors. CD25 plays a role during activation: CD25+ naive T cells stimulated in an APC-dependent manner were shown to produce increased levels of IL-2 as compared with their CD25− counterparts. This study establishes CD25+ naive CD4 T cells, which are further delineated by CD31 expression, as a major functionally distinct immune cell subset in humans that warrants further characterization in health and disease.
Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses
Authors: Vukman Krisztina V. , Adams Paul N. , Metz Martin , Maurer Marcus , O’Neill Sandra M. 
Published: February 2013

Abstract
The parasitic worm Fasciola hepatica induces strong Th2 and T-regulatory immune responses while simultaneously suppressing Th1-driven immune responses to bystander microbial infections. It also prevents the initiation of Th1-mediated autoimmune disorders in mice through the suppression of Th17 and Th1 immune responses, and this can be mimicked by parasite-derived molecules. We have isolated F. hepatica tegumental coat Ag (FhTeg) and demonstrated its suppressive effect in vivo by directly targeting dendritic cells, impairing their ability to drive Th1 responses. Mast cells are critical in promoting Th1 protective immunity during bacterial infection and in driving Th1-mediated pathological conditions in autoimmune diseases. In this article, we show that FhTeg inhibits the ability of mast cells to drive the Th1 immune response by suppressing cytokine secretion (TNF-α, IL-6, IFN-γ, and IL-10) and ICAM1 expression in mast cells stimulated with LPS or heat-inactivated Bordetella pertussis Ag. These heat-inactivated B. pertussis Ag/LPS–stimulated mast cells fail to promote Th1 immune responses in CD4+ T cells when pretreated with FhTeg, and a role for ICAM1 in this process was demonstrated. FhTeg suppresses the activation of transcription factors in the TLR signaling pathway, which explains the decrease in cytokine production and cell surface marker expression. We demonstrated that FhTeg suppresses MAPK and NF-κB activation and enhances SOCS3 expression, which could explain its negative effect on the TLR pathways. We conclude that FhTeg targets innate immune cells, inhibiting their ability to drive Th1 immune responses.