bluuebunny/crossref_metadata_2025_split huggingface dataset:
Value of anti–modified citrullinated vimentin and third‐generation anti–cyclic citrullinated peptide compared with second‐generation anti–cyclic citrullinated peptide and rheumatoid factor in predicting disease outcome in undifferentiated arthritis and rheumatoid arthritis
Authors: van der Linden Michael P. M. , van der Woude Diane , Ioan‐Facsinay Andreea , Levarht E. W. Nivine , Stoeken‐Rijsbergen Gerrie , Huizinga Tom W. J. , Toes René E. M. , van der Helm‐van Mil Annette H. M. 
Published: July 2009

AbstractObjectiveAutoantibodies such as rheumatoid factor (RF) and anti–citrullinated protein autoantibodies (ACPAs) determined by testing with second‐generation anti–cyclic citrullinated peptide (anti–CCP‐2) are frequently measured in clinical practice because of their association with disease outcome in undifferentiated arthritis (UA) and rheumatoid arthritis (RA). Recently, 2 new ACPA tests were developed: third‐generation anti‐CCP (anti–CCP‐3) and anti–modified citrullinated vimentin (anti‐MCV) autoantibody tests. To facilitate the decision on which autoantibody to test in daily practice, this study evaluated the capability of these autoantibodies and combinations of them to predict 3 outcome measures: progression from UA to RA, the rate of joint destruction in RA, and the chance of achieving sustained disease‐modifying antirheumatic drug (DMARD)–free remission in RA.MethodsPatients with UA (n = 625) were studied for whether UA progressed to RA after 1 year. Patients with RA (n = 687) were studied for whether sustained DMARD‐free remission was achieved and for the rate of joint destruction during a median followup of 5 years. Positive predictive values (PPVs) for RA development and for associations with the disease course in RA were compared between single tests (anti–CCP‐2, anti–CCP‐3, anti‐MCV, and RF) and between combinations of these tests.ResultsAmong the single tests performed in patients with UA, anti–CCP‐2 tended to have the highest PPV for RA development (67.1%), but the 95% confidence intervals of the other tests overlapped. Among the single tests in patients with RA, all 4 tests showed comparable associations with the rate of joint destruction and with the achievement of remission. In both ACPA‐positive and ACPA‐negative RA, the presence of RF was not associated with more joint destruction. For all outcome measures, performing combinations of 2 or 3 autoantibody tests did not increase the predictive accuracy compared with performing a single test.ConclusionFor clinical practice, a single autoantibody test is sufficient for risk estimation in UA and RA.
Mouse dendritic cells matured by ingestion of apoptotic blebs induce T cells to produce interleukin‐17
Authors: Fransen Justin H. , Hilbrands Luuk B. , Ruben Jurjen , Stoffels Monique , Adema Gosse J. , van der Vlag Johan , Berden Jo H. 
Published: July 2009

AbstractObjectiveSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by the formation of antinuclear autoantibodies. Increased apoptosis and reduced clearance of apoptotic material have been assigned a role in the pathogenesis of SLE, but the underlying mechanisms remain elusive. During apoptosis apoptotic blebs are formed in which autoantigens are clustered. The cellular remnants after blebbing are referred to as apoptotic cell bodies. We undertook this study to compare the effects of apoptotic blebs and apoptotic cell bodies on maturation of dendritic cells (DCs) and their T cell stimulatory capacity in a murine setting.MethodsThe uptake by DCs of apoptotic blebs and apoptotic cell bodies was analyzed by flow cytometry and confocal microscopy. DC maturation and DC‐induced T cell activation were determined by measuring expression of costimulatory molecules using flow cytometry and by measuring production of cytokines using enzyme‐linked immunosorbent assay.ResultsDCs internalized apoptotic blebs more efficiently than apoptotic cell bodies. Incubation of DCs with apoptotic blebs resulted in increased CD40 and CD86 expression and increased interleukin‐6 (IL‐6) and tumor necrosis factor α production, while apoptotic cell bodies had no stimulatory effects. Using chloroquine, apoptotic bleb–induced DC maturation was shown to be independent of Toll‐like receptors 3, 7, and 9. Interestingly, in cocultures with allogeneic T cells, bleb‐matured DCs induced production of IL‐2, interferon‐γ, and, in particular, IL‐17, suggesting a Th1/Th17 response.ConclusionApoptotic blebs, in contrast to apoptotic cell bodies, induce DC maturation, thereby providing DCs with increased Th17 cell stimulatory capacity. These data imply that apoptotic bleb–induced DC maturation represents an important driving force in the autoimmune response in SLE.
Vascular cell adhesion molecule 1 as a predictor of severe osteoarthritis of the hip and knee joints
Authors: Schett Georg , Kiechl Stefan , Bonora Enzo , Zwerina Jochen , Mayr Agnes , Axmann Roland , Weger Siegfried , Oberhollenzer Friedrich , Lorenzini Rolando , Willeit Johann 
Published: July 2009

AbstractObjectiveOsteoarthritis (OA) is a leading cause of pain and physical disability in middle‐aged and older individuals. We undertook this study to determine predictors of the development of severe OA, apart from age and overweight.MethodsJoint replacement surgery due to severe hip or knee OA was recorded over a 15‐year period in the prospective Bruneck cohort study. Demographic characteristics and lifestyle and biochemical variables, including the level of soluble vascular cell adhesion molecule 1 (VCAM‐1), were assessed at the 1990 baseline visit and tested as predictors of joint replacement surgery.ResultsBetween 1990 and 2005, hip or knee joint replacement due to OA was performed in 60 subjects. VCAM‐1 level emerged as a highly significant predictor of the risk of joint replacement surgery. Intervention rates were 1.9, 4.2, and 10.1 per 1,000 person‐years in the first, second, and third tertiles, of the VCAM‐1 level, respectively. In multivariable logistic regression analysis, the adjusted relative risk of joint replacement surgery in the highest versus the lowest tertile group of VCAM‐1 level was 3.9 (95% confidence interval 1.7–8.7) (P < 0.001). Findings were robust in various sensitivity analyses and were consistent in subgroups. Addition of the VCAM‐1 level to a risk model already including age, sex, and body mass index resulted in significant gains in model discrimination (C statistic) and calibration and in more accurate risk classification of individual participants.ConclusionThe level of soluble VCAM‐1 emerged as a strong and independent predictor of the risk of hip and knee joint replacement due to severe OA. If our findings can be reproduced in other epidemiologic cohorts, they will assist in routine risk classification and will contribute to a better understanding of the etiology of OA.
Changes in surface markers of human mesenchymal stem cells during the chondrogenic differentiation and dedifferentiation processes in vitro
Authors: Lee Hyun Jung , Choi Byung Hyune , Min Byoung‐Hyun , Park So Ra 
Published: July 2009

AbstractObjectiveTo investigate surface markers showing specific changes during the chondrogenic differentiation and dedifferentiation of human mesenchymal stem cells (MSCs).MethodsHuman MSCs from adult bone marrow were subjected to chondrogenic differentiation in 3‐dimensional (3‐D) alginate culture with or without transforming growth factor β3 (TGFβ3) for 2 weeks, followed by dedifferentiation in monolayer for 1 week. Surface antigens were selected from those previously reported to show changes in expression during dedifferentiation of human articular chondrocytes (HACs).ResultsFlow cytometry was used to identify 3 groups of surface antigens with differential expression patterns that were quite different from those previously reported on HACs. Two groups of antigens were expressed at high levels on human MSCs. The expression of the first group of antigens (CD44, CD58, CD81, CD90, CD105, and CD166) was decreased reversibly by the 3‐D alginate culture and irreversibly in the presence of TGFβ3, except for CD81, which showed reversible changes regardless of TGFβ3. The expression of the second group of antigens (CD49c, CD49e, and CD151) was decreased during chondrogenic differentiation only in the presence of TGFβ3. During all experimental stages, the expression of the third group of antigens (CD14, CD26, CD49f, CD54, CD106, CD119, and CD140a) was maintained at low levels (expressed on <30% of cells), although with some fluctuations.ConclusionWe speculate that the second group of surface antigens could be negative markers for chondrogenic differentiation of human MSCs.
Fcγ receptor–dependent expansion of a hyperactive monocyte subset in lupus‐prone mice
Authors: Santiago‐Raber Marie‐Laure , Amano Hirofumi , Amano Eri , Baudino Lucie , Otani Masako , Lin Qingshun , Nimmerjahn Falk , Verbeek J. Sjef , Ravetch Jeffrey V. , Takasaki Yoshinari , Hirose Sachiko , Izui Shozo 
Published: July 2009

AbstractObjectiveLupus‐prone BXSB mice develop monocytosis characterized by selective accumulation of the Gr‐1– monocyte subset. The aim of this study was to explore the possible role of activating IgG Fc receptors (FcγR) in the development of monocytosis and to characterize the functional phenotype of the Gr‐1– subset that accumulates in lupus‐prone mice bearing the NZB‐type defective Fcgr2b allele for the inhibitory FcγRIIB.MethodsThe development of monocytosis was analyzed in BXSB and anti‐IgG2a rheumatoid factor–transgenic C57BL/6 mice deficient in activating FcγR. Moreover, we assessed the expression levels of activating FcγR and inhibitory FcγRIIB on Gr‐1+ and Gr‐1– monocyte subsets in C57BL/6 mice bearing the C57BL/6‐type or the NZB‐type Fcgr2b allele.ResultsWe observed monocytosis with expansion of the Gr‐1– subset in anti‐IgG2a–transgenic C57BL/6 mice expressing IgG2a, but not in those lacking IgG2a. Moreover, monocytosis barely developed in BXSB and anti‐IgG2a–transgenic C57BL/6 mice deficient in activating FcγR. The Gr‐1– subset that accumulated in lupus‐prone mice displayed a unique hyperactive phenotype. It expressed very low levels of inhibitory FcγRIIB, due to the presence of the NZB‐type Fcgr2b allele, but high levels of activating FcγRIV. This was in contrast to high levels of FcγRIIB expression and no FcγRIV expression on the Gr‐1+ subset.ConclusionOur results demonstrated a critical role of activating FcγR in the development of monocytosis and in the expansion of a Gr‐1–FcγRIIBlowFcγRIV+ hyperactive monocyte subset in lupus‐prone mice. Our findings further highlight the importance of the NZB‐type Fcgr2b susceptibility allele in murine lupus, the presence of which induces increased production of hyperactive monocytes as well as dysregulated activation of autoreactive B cells.
Determinants of self‐reported health status in a population‐based sample of persons with radiographic knee osteoarthritis
Authors: Reichmann William M. , Katz Jeffrey N. , Kessler Courtenay L. , Jordan Joanne M. , Losina Elena 
Published: July 2009

AbstractObjectiveKnee osteoarthritis (OA) is highly prevalent and disabling. Patients with radiographic knee OA may experience pain and functional impairment, which can diminish their health status. Our objective was to determine factors associated with self‐reported health status in a national population‐based sample with radiographic knee OA.MethodsOur sample included all of the Third National Health and Nutrition Examination Survey (NHANES‐III) participants who underwent a knee radiograph and were found to have radiographic OA (defined as Kellgren/Lawrence grade 2 or higher). Self‐reported health status was determined by asking the participant to rate their overall health as excellent, very good, good, fair, or poor. Self‐reported health status was analyzed as an ordinal variable using cumulative logit regression, as a dichotomous variable (excellent/very good/good versus fair/poor) using logistic regression, and as a continuous variable after transformation using linear regression.ResultsA total of 1,021 (42%) of NHANES‐III participants with a knee radiograph were included in this analysis. The multivariable analyses were performed on 1,009 (99%) of the eligible participants with complete data. We found that nonwhite race, lower income, more comorbidities, and greater functional limitation were associated with worse self‐reported health status in all 3 multivariable analyses.ConclusionThis study has quantified the role of clinical, radiographic, and socioeconomic factors associated with self‐reported health status in a population‐based sample of patients with knee OA. Self‐reported health status in patients with knee OA was associated with functional status and comorbidity.
Pena‐Shokeir phenotype (Fetal akinesia deformation sequence) revisited
Authors: Hall Judith G. 
Published: July 2009

AbstractBACKGROUND: Pena and Shokeir described the phenotype of two sisters in 1974, and subsequently their features have become recognized as a sequence of deformational changes related to decreased or absent fetal movement (fetal akinesia deformation sequence [FADS]), because of the work of Moessinger (1983). METHODS: Identification of reported cases by searching Online Mendelian Inheritance in Man, Medlines, the London Dysmorphology Database, and the references found in these articles. These case reports were reviewed, tabulated, and summarized. RESULTS: It is now possible to recognize at least 20 familial types of Pena‐Shokeir phenotype (PSP), based on the differences found in the reports of the natural history and pathology found at fetal and newborn autopsy. In addition, characteristic changes in the central nervous system seen with embryonic/fetal vascular compromise have been recognized in many reported cases. Most of the reported cases of PSP/FADS related to vascular compromise are sporadic, but familial cases have also been reported. CONCLUSION: Lack of fetal movement (fetal akinesia) in humans produces a recognizable sequence of deformations. Many developmental processes must be accomplished for fetal movement to be normal, and for extra‐uterine life to be sustainable. Prenatal diagnosis is possible through real‐time ultrasound studies as early as 12 weeks. Most reported cases die in utero, at birth, or in the newborn period. Advances in embryo/fetus pathology have led to the recognition of the many familial subtypes, allowing improved genetic counseling and early recognition in subsequent pregnancies. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.
Extremely low frequency pulsed electromagnetic field designed for antinociception does not affect microvascular responsiveness to the vasodilator acetylcholine
Authors: McKay Julia C. , Corbacio Michael , Tyml Karel , Prato Frank S. , Thomas Alex W. 
Published: July 2009

AbstractA 225 µT, extremely low frequency, pulsed electromagnetic field (PEMF) that was designed for the induction of antinociception, was tested for its effectiveness to influence blood flow within the skeletal microvasculature of a male Sprague–Dawley rat model (n = 103). Acetylcholine (0.1, 1.0, or 10 mM) was used to perturb normal blood flow and to delineate differential effects of the PEMF, based on degree of vessel dilation. After both 30 and 60 min of PEMF exposure, we report no effects on peak perfusion response to acetylcholine (with only 0.2% of the group difference attributed to exposure). Spectral analysis of blood flow data was generated to obtain information related to myogenic activity (0.15–0.40 Hz), respiratory rate (0.4–2.0 Hz), and heart rate (2.0–7.0 Hz), including the peak frequency within each of the three frequency regions identified above, peak power, full width at half maximum (FWHM), and mean within band. No significant effects due to exposure were observed on myogenic activity of examined blood vessels, or on heart rate parameters. Anesthesia‐induced respiratory depression was, however, significantly reduced following PEMF exposure compared to shams (although exposure only accounted for 9.4% of the group difference). This set of data suggest that there are no significant acute physiological effects of 225 µT PEMF after 30 and 60 min of exposure on peak blood flow, heart rate, and myogenic activity, but perhaps a small attenuation effect on anesthetic‐induced respiratory depression. Bioelectromagnetics 31:64–76, 2010. © 2009 Wiley‐Liss, Inc.
Evolutionary formation of new protein folds is linked to metallic cofactor recruitment
Authors: Ji Hong‐Fang , Chen Lei , Jiang Ying‐Ying , Zhang Hong‐Yu 
Published: July 2009

AbstractTo explore whether the generation of new protein folds could be linked to metallic cofactor recruitment, we identified the oldest examples of folds for manganese, iron, zinc, and copper proteins by analyzing their fold‐domain mapping patterns. We discovered that the generation of these folds was tightly coupled to corresponding metals. We found that the emerging order for these folds, i.e., manganese and iron protein folds appeared earlier than zinc and copper counterparts, coincides with the putative bioavailability of the corresponding metals in the ancient anoxic ocean. Therefore, we conclude that metallic cofactors, like organic cofactors, play an evolutionary role in the formation of new protein folds. This link could be explained by the emergence of protein structures with novel folds that could fulfill the new protein functions introduced by the metallic cofactors. These findings not only have important implications for understanding the evolutionary mechanisms of protein architectures, but also provide a further interpretation for the evolutionary story of superoxide dismutases.
Pannexins, distant relatives of the connexin family with specific cellular functions?
Authors: D'hondt Catheleyne , Ponsaerts Raf , De Smedt Humbert , Bultynck Geert , Himpens Bernard 
Published: July 2009

AbstractIntercellular communication (IC) is mediated by gap junctions (GJs) and hemichannels, which consist of proteins. This has been particularly well documented for the connexin (Cx) family. Initially, Cxs were thought to be the only proteins capable of GJ formation in vertebrates. About 10 years ago, however, a new GJ‐forming protein family related to invertebrate innexins (Inxs) was discovered in vertebrates, and named the pannexin (Panx) family. Panxs, which are structurally similar to Cxs, but evolutionarily distinct, have been shown to be co‐expressed with Cxs in vertebrates. Both protein families show distinct properties and have their own particular function. Identification of the mechanisms that control Panx channel gating is a major challenge for future work. In this review, we focus on the specific properties and role of Panxs in normal and pathological conditions.
Expanding roles for AMP‐activated protein kinase in neuronal survival and autophagy
Authors: Poels Jeroen , Spasić Miloš R. , Callaerts Patrick , Norga Koenraad K. 
Published: July 2009

AbstractAMP‐activated protein kinase (AMPK) is an evolutionarily conserved cellular switch that activates catabolic pathways and turns off anabolic processes. In this way, AMPK activation can restore the perturbation of cellular energy levels. In physiological situations, AMPK senses energy deficiency (in the form of an increased AMP/ATP ratio), but it is also activated by metabolic insults, such as glucose or oxygen deprivation. Metformin, one of the most widely prescribed anti‐diabetic drugs, exerts its actions by AMPK activation. However, while the functions of AMPK as a metabolic regulator are fairly well understood, its actions in neuronal cells only recently gained attention. This review will discuss newly emerged functions of AMPK in neuroprotection and neurodegeneration. Additionally, recent views on the role of AMPK in autophagy, an important catabolic process that is also involved in neurodegeneration and cancer, will be highlighted.
Trans‐splicing of organelle introns – a detour to continuous RNAs
Authors: Glanz Stephanie , Kück Ulrich 
Published: July 2009

AbstractIn eukaryotes, RNA trans‐splicing is an important RNA‐processing form for the end‐to‐end ligation of primary transcripts that are derived from separately transcribed exons. So far, three different categories of RNA trans‐splicing have been found in organisms as diverse as algae to man. Here, we review one of these categories: the trans‐splicing of discontinuous group II introns, which occurs in chloroplasts and mitochondria of lower eukaryotes and plants. Trans‐spliced exons can be predicted from DNA sequences derived from a large number of sequenced organelle genomes. Further molecular genetic analysis of mutants has unravelled proteins, some of which being part of high‐molecular‐weight complexes that promote the splicing process. Based on data derived from the alga Chlamydomonas reinhardtii, a model is provided which defines the composition of an organelle spliceosome. This will have a general relevance for understanding the function of RNA‐processing machineries in eukaryotic organelles.
Randomized clinical trial comparing laparoscopic and open surgery in patients with rectal cancer
Authors: Lujan J , Valero G , Hernandez Q , Sanchez A , Frutos M D , Parrilla P 
Published: July 2009

Abstract

Background
The laparoscopic treatment of rectal cancer is controversial. This study compared surgical outcomes after laparoscopic and open approaches for mid and low rectal cancers.

Methods
Some 204 patients with mid and low rectal adenocarcinomas were allocated randomly to open (103) or laparoscopic (101) surgery. The surgical team was the same for both procedures. Most patients had stage II or III disease, and received neoadjuvant therapy with oral capecitabine and 50–54 Gy external beam radiotherapy.

Results
Sphincter-preserving surgery was performed in 78·6 and 76·2 per cent of patients in the open and laparoscopic groups respectively. Blood loss was significantly greater for open surgery (P &lt; 0·001) and operating time was significantly greater for laparoscopic surgery (P = 0·020), and return to diet and hospital stay were longer for open surgery. Complication rates, and involvement of circumferential and radial margins were similar for both procedures, but the number of isolated lymph nodes was greater in the laparoscopic group (mean 13·63 versus 11·57; P = 0·026). There were no differences in local recurrence, disease-free or overall survival.

Conclusion
Laparoscopic surgery for rectal cancer has a similar complication rate to open surgery, with less blood loss, rapid intestinal recovery, shorter hospital stay, and no compromise of oncological outcomes. Registration number: NCT00782457 (http://www.clinicaltrials.gov).
Phase II study of neoadjuvant chemotherapy and extended surgery for locally advanced gastric cancer
Authors: Yoshikawa T , Sasako M , Yamamoto S , Sano T , Imamura H , Fujitani K , Oshita H , Ito S , Kawashima Y , Fukushima N 
Published: July 2009

Abstract

Background
Locally advanced gastric cancer with extensive lymph node metastasis is usually considered unresectable and so treated by chemotherapy. This trial explored the safety and efficacy of preoperative chemotherapy followed by extended surgery in the management of locally advanced gastric adenocarcinoma.

Methods
Patients with gastric cancer with extensive lymph node metastasis received two or three 28-day cycles of induction chemotherapy with irinotecan (70 mg/m2 on days 1 and 15) and cisplatin (80 mg/m2 on day 1), and then underwent gastrectomy with curative intent with D2 plus para-aortic lymphadenectomy. Primary endpoints were 3-year overall survival and incidence of treatment-related death.

Results
The study was terminated because of three treatment-related deaths when 55 patients had been enrolled (mortality rate above 5 per cent). Two deaths were due to myelosuppression and one to postoperative complications. Clinical response and R0 resection rates were 55 and 65 per cent respectively. The pathological response rate was 15 per cent. Median overall survival was 14·6 months and the 3-year survival rate 27 per cent.

Conclusion
This multimodal treatment of locally advanced gastric cancer provides reasonable 3-year survival compared with historical data, but at a considerable cost in terms of morbidity and mortality.