bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coffee consumption and risk of rheumatoid arthritis
Authors: Karlson Elizabeth W. , Mandl Lisa A. , Aweh Gideon N. , Grodstein Francine 
Published: November 2003

AbstractObjectiveRecent reports have suggested an association between consumption of coffee or decaffeinated coffee and the risk of rheumatoid arthritis (RA), although data are sparse and somewhat inconsistent. Furthermore, existing studies measured dietary exposures and potential confounders only at baseline and did not consider possible changes in diet or lifestyle over the followup period. We studied whether coffee, decaffeinated coffee, total coffee, tea, or overall caffeine consumption was associated with the risk of RA, using the Nurses' Health Study, a longitudinal cohort study of 121,701 women.MethodsInformation on beverage consumption was assessed with a food frequency questionnaire (FFQ) that was completed every 4 years, from baseline in 1980 through 1998. Among the 83,124 women who completed the FFQ at baseline, the diagnosis of incident RA (between 1980 and 2000) was confirmed in 480 women by a connective tissue disease screening questionnaire and medical record review for American College of Rheumatology criteria. Relationships between intake of various beverages and the risk of RA were assessed in age‐adjusted models and in multivariate Cox proportional hazards models including the cumulative average intake of each beverage during the followup period, adjusted for numerous potential confounders. In addition, for direct comparisons with prior reports, multivariate analyses were repeated using only baseline beverage information.ResultsWe did not find a significant association between decaffeinated coffee consumption of ≥4 cups/day (compared with no decaffeinated coffee consumption) and subsequent risk of incident RA, in either an adjusted multivariate model (relative risk [RR] 1.1, 95% confidence interval [95% CI] 0.5–2.2) or a multivariate model using only baseline reports of decaffeinated coffee consumption (RR 1.0, 95% CI 0.6–1.7). Similarly, there was no relationship between cumulative caffeinated coffee consumption and RA risk (RR 1.1, 95% CI 0.8–1.6 for ≥4 cups per day versus none) or between tea consumption and RA risk (RR 1.1, 95% CI 0.7–1.8 for >3 cups/day versus none). Total coffee and total caffeine consumption were also not associated with the risk of RA.ConclusionIn this large, prospective study, we find little evidence of an association between coffee, decaffeinated coffee, or tea consumption and the risk of RA among women.
Cellular basis of ectopic germinal center formation and autoantibody production in the target organ of patients with Sjögren's syndrome
Authors: Salomonsson Stina , Jonsson Malin V. , Skarstein Kathrine , Brokstad Karl A. , Hjelmström Peter , Wahren‐Herlenius Marie , Jonsson Roland 
Published: November 2003

AbstractObjectiveTo investigate functional properties of the germinal center (GC)–like structures observed in salivary glands of patients with Sjögren's syndrome (SS) and to determine the frequency with which such structures develop.MethodsHematoxylin and eosin–stained sections from 165 minor salivary gland biopsy samples were screened for GC‐like structures. Expression of markers for GCs (CD3, CD20, Ki‐67, CD35, CD31), adhesion molecules (intercellular adhesion molecule 1, lymphocyte function–associated antigen 1, vascular cell adhesion molecule 1, very late activation antigen 4), chemokines (CXCL13, CCL21, CXCL12), and production of autoantibodies (anti‐Ro/SSA and anti‐La/SSB) was investigated by immunohistochemistry. Apoptosis was investigated by TUNEL staining.ResultsGC‐like structures were observed in 28 of 165 patients (17%). When GCs were defined as T and B cell aggregates with proliferating cells with a network of follicular dendritic cells and activated endothelial cells, such microenvironments were found in all patients in whom structures with GC‐like morphology were observed. The defined microenvironments were not found in patients without apparent GC‐like structures. The GCs formed within the target tissue showed functional features with production of autoantibodies (anti‐Ro/SSA and anti‐La/SSB) and apoptotic events (by TUNEL staining), and the local production of anti‐Ro/SSA and anti‐La/SSB autoantibodies was significantly increased (P = 0.04) in patients with GC development.ConclusionLymphoid neogenesis and functional ectopic GC formation take place in salivary glands of a subset of patients with SS. Our data suggest that the ectopic secondary lymphoid follicles contain all elements needed for driving the autoimmune response. Our findings underscore a key role for the target organ in recruitment of inflammatory cells and propagation of the disease process.
A novel polymorphism in the Fcγ receptor IIB (CD32B) transmembrane region alters receptor signaling
Authors: Li Xiaoli , Wu Jianming , Carter Robert H. , Edberg Jeffrey C. , Su Kaihong , Cooper Glinda S. , Kimberly Robert P. 
Published: November 2003

AbstractObjectiveThe low‐affinity receptor Fcγ receptor IIb (FcγRIIb), with an immunoreceptor tyrosine‐based inhibitory motif (ITIM) in the cytoplasmic domain, down‐regulates humoral immune responses and modulates the risk of autoimmunity in animal models. The transmembrane domain of FcγRIIb may also contribute to receptor signaling. Therefore, we investigated the biologic significance of single‐nucleotide polymorphisms (SNPs) throughout the coding region.MethodsDiscovery of SNPs in FCGR2B was performed by direct cycle sequencing of complementary DNA samples derived by reverse transcriptase–polymerase chain reaction. To assess the biologic significance of the nonsynonymous transmembrane SNP, we studied 3 functions influenced by the FcγRIIb transmembrane domain: tyrosine dephosphorylation of CD19, inhibition of B cell receptor (BCR)–induced calcium response, and modulation of BCR‐ or anti‐Fas–induced apoptosis.ResultsThe nonsynonymous C‐to‐T transition in the first cytoplasmic exon, originally reported in the Raji cell line, was not found in either the African‐American or the Caucasian population, but a nonsynonymous T‐to‐C transition at nucleotide 775 in exon 4 of FCGR2B, which changes isoleucine to threonine at residue 187 in the transmembrane domain, was significantly more common in African Americans. Using the FcγRIIb‐negative mouse B cell line IIA1.6, we expressed both allelic forms as both full‐length and truncated cytoplasmic domain constructs. The FCGR2B‐187T allele mediated a higher level of CD19 dephosphorylation (P = 0.029) and a greater degree of inhibition of the calcium response (P = 0.003) when co‐engaged with BCR than did FCGR2B‐187I, independent of the presence of the ITIM. In contrast, FcγRIIb modulation of BCR‐induced and anti‐Fas antibody–induced cell death rates were similar in IIA1.6 cells expressing either the 187I or the 187T allelic form.ConclusionThe differential activity of FCGR2B alleles suggests a novel mechanism of FcγRIIb regulation that may influence the risk of autoimmune disease.
Inflammation and bone resorption as independent factors of accelerated arterial wall thickening in patients with rheumatoid arthritis
Authors: Nagata‐Sakurai Mayumi , Inaba Masaaki , Goto Hitoshi , Kumeda Yasuro , Furumitsu Yutaka , Inui Kentaro , Koyama Hidenori , Emoto Masanori , Ishimura Eiji , Shoji Tetsuo , Nishizawa Yoshiki 
Published: November 2003

AbstractObjectiveWe recently reported that rheumatoid arthritis (RA) patients had increased intima‐media thickness (IMT) of the common carotid artery (CCA). The present longitudinal study was performed to determine whether the change in arterial thickness was accelerated in RA patients and to determine which factor was important in the progression of arterial wall changes.MethodsWe studied 62 female RA patients with stable disease activity and 63 healthy female controls. IMT of the CCA was measured twice by high‐resolution B‐mode ultrasonography. The second examination was performed 18–36 months after the first, and changes were expressed as millimeters of increase per year. Baseline examinations included blood markers of inflammation and urinary calcium excretion (expressed as the calcium‐to‐creatinine ratio).ResultsRA patients showed a significantly greater increase in IMT of the CCA compared with controls. In univariate analyses of the RA patient data, the C‐reactive protein (CRP) level correlated with the increase in CCA IMT. Other markers of inflammation (the erythrocyte sedimentation rate and white blood cell and platelet counts) also showed significant positive associations with the annual increase in CCA IMT in multiple regression models when adjusted for age, smoking status, blood pressure, and serum cholesterol level. The urinary calcium‐to‐creatinine ratio was also significantly associated with an increase in CCA IMT. Moreover, both the CRP level and the urinary calcium‐to‐creatinine ratio were significantly and independently associated with the increase in IMT of the CCA.ConclusionPatients with RA have a higher rate of increase in thickening of the arterial wall. Inflammation and calcium mobilization are factors closely associated with the accelerated arterial wall changes.
Turnover of type II collagen and aggrecan in cartilage matrix at the onset of inflammatory arthritis in humans: Relationship to mediators of systemic and local inflammation
Authors: Fraser Alexander , Fearon Ursula , Billinghurst R. Clark , Ionescu Mirela , Reece Richard , Barwick Thomas , Emery Paul , Poole A. Robin , Veale Douglas J. 
Published: November 2003

AbstractObjectiveTo determine in vivo the extent of damage to, and changes in turnover of, articular cartilage type II collagen (CII) and the proteoglycan aggrecan following the onset of inflammatory arthritis in humans, and to examine the hypothesis that there are direct relationships between cartilage biomarkers of damage/turnover and clinical, histologic, and molecular markers of inflammation.MethodsSynovial fluid (SF) and synovial membrane (SM) were obtained by arthroscopy, and a synovitis score was determined, in 32 patients with rheumatoid arthritis (RA) (13 with early untreated disease, 19 with established disease), 18 with psoriatic arthritis (PsA), and 10 with osteoarthritis (OA). Systemic disease activity markers were recorded, and SM CD3+ T cells, CD4+ T cells, CD68+ macrophages, and lining layer hyperplasia were quantified. SF levels of tumor necrosis factor α (TNFα), interleukin‐10 (IL‐10), matrix metalloproteinase 1 (MMP‐1), MMP‐3, Col2‐3/4CLong mono neoepitope (C2C) (reflecting collagenase cleavage of cartilage CII), C‐propeptide of type II procollagen (PIICP) (a biosynthesis marker), keratan sulfate (KS), and the 846 epitope of aggrecan (turnover) were measured by enzyme‐linked immunosorbent assay or radioimmunoassay.ResultsLevels of cartilage degradation products in early RA or early PsA were not elevated above levels in OA, although in early inflammatory arthritis, TNFα and MMP‐1 levels were similar to those observed in late inflammatory disease and higher than those in OA. PIICP was reduced in early RA. Correlations were observed between the SF C2C neoepitope level and the Health Assessment Questionnaire score, C‐reactive protein level, plasma viscosity, synovitis score, and SF TNFα and MMP‐1 levels. KS epitope content was reduced in direct relation to SM macrophage infiltration in the sublining and lining layers and in the presence of elevated SF MMP‐3. Both SF MMP‐1 and SF MMP‐3 levels correlated with CD4+ T cell infiltration and lining layer hyperplasia in the SM, and MMP‐1 levels correlated with lining layer CD68 levels, but TNFα and IL‐10 levels did not.ConclusionExcept for CII synthesis, there were no significant changes in extracellular matrix turnover of aggrecan or CII in the early stages of human inflammatory arthritis. However, the direct correlation between the increases in TNFα and MMP‐1 production and collagen degradation suggests that collagenase cleavage of cartilage collagen is related to the activities of TNFα and MMP‐1. The reduction in CII synthesis in early RA may contribute to the developing pathology, since a lack of synthesis of this molecule would inhibit maintenance of cartilage matrix.
Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model
Authors: Ferrara Dardo E. , Liu Xiaowei , Espinola Ricardo G. , Meroni Pier Luigi , Abukhalaf Imad , Harris E. Nigel , Pierangeli Silvia S. 
Published: November 2003

AbstractObjectiveAntiphospholipid antibodies (aPL) have thrombogenic properties in vivo, through their interactions with soluble coagulation factors and their ability to modulate the functions of cells involved in coagulation homeostasis. These antibodies have also been shown to enhance the adhesion of leukocytes to endothelial cells (ECs) in vivo. New lipophilic statins such as fluvastatin have antiinflammatory and antithrombogenic effects. This study uses an in vivo mouse model to investigate whether fluvastatin has an effect on decreasing both the adhesion of leukocytes to ECs and the thrombus formation induced by aPL.MethodsTwo groups of CD‐1 male mice, each comprising ∼18 mice, were fed either normal saline solution or 15 mg/kg fluvastatin for 15 days. Each of the 2 groups was further subdivided to receive either purified IgG from patients with the antiphospholipid syndrome (IgG‐APS) or normal IgG from healthy subjects. Analysis of thrombus dynamics was performed in treated and control mice, using a standardized thrombogenic injury procedure, and the area (size) of the thrombus was measured. Adhesion of leukocytes to ECs was analyzed with a microcirculation model of exposed cremaster muscle. Baseline and posttreatment soluble intercellular adhesion molecule 1 (sICAM‐1) levels were determined by enzyme‐linked immunosorbent assay.ResultsIgG‐APS mice treated with fluvastatin showed significantly smaller thrombi, a reduced number of adherent leukocytes, and decreased levels of sICAM‐1 compared with IgG‐APS animals treated with placebo.ConclusionThese findings indicate that fluvastatin significantly diminishes aPL‐mediated thrombosis and EC activation in vivo. These results may have important implications for the design of new treatment strategies aimed at preventing recurrent thrombosis in patients with APS.
Inspirations and aspirations of exemplarian action research
Authors: Coenen Harry , Khonraad Sjaak 
Published: November 2003

AbstractAs a methodology aimed to focus social scientific theorizing on actual social problems and examine new directions and guidelines for emancipation and empowerment, action research is based on a joint learning process of researchers and researched. The model of exemplarian action research tries to capture how this learning process can develop in practice. Before describing this model and its emancipatory aspirations, the authors sketch the theoretical inspirations of the model of exemplarian action research. They then go on to focus on the relationship between researcher and the researched party, particularly on the principles of reciprocal adequacy and explicitness which are necessary both from an epistemologically and critical point of view. The article concludes by outlining some aspects in which exemplarian action research can be distinguished from pragmatic action research and by emphasizing that it does not stand for a post‐modern position, but for a reflexive attitude that hopes to contribute to bringing us beyond a half‐modern society. Copyright © 2003 John Wiley & Sons, Ltd.
The development of an individual, demand driven approach in a long‐lasting exemplarian action research
Authors: Valkenburg Ben 
Published: November 2003

AbstractIn this contribution, the author aims to elucidate the core aspects of the individual, demand driven approach and the way this approach has been developed in action research projects spanning more than 15 years. First the authors describe the developments towards more client centred approaches of labour‐market policies and care, which formed the background against which the individual, demand driven approach took shape. Then the authors sketch the main characteristics of the action research programme they have been involved in. As an example one of the projects of this programme will be elaborated further. In the fourth section of this contribution the authors give an overview of the four most distinctive aspects of the individual, demand driven approach. Then closes of with a few evaluative remarks. Copyright © 2003 John Wiley & Sons, Ltd.
Emancipatory design choices for action research practitioners
Authors: Roberts Gerry , Dick Bob 
Published: November 2003

AbstractThe process choices made in action research can determine how emancipatory an experience it is for participants. Some choices promote an experience of emancipation. Other choices can reduce it. There can be tensions between choices that encourage emancipation and those that pursue other advantages at the expense of emancipation. Here we consider six such tensions.For each choice we suggest how to frame the tension to deliver an experience of emancipation. The suggestions involve practitioners and participants choosing the driving force for the work, acquiring and applying skills for empowerment, mixing action and research to suit the context, choosing an appropriate simplicity of methodology, planning participation, and engaging with the different beliefs of practitioners and participants. We use practitioner and researcher interchangeably. Copyright © 2003 John Wiley & Sons, Ltd.
Helping others: project or research?
Authors: De Zeeuw Gerard 
Published: November 2003

AbstractHelping shows itself as most difficult—as in the exemplary query whether to help by providing the fish or the fishing‐rod. Action research and similar approaches were developed to answer the question what helps the helper. Each provides structure—project‐like, partly starting from science, partly from emancipatory ideology—structure to stimulate personal resources, structure to test, structure to give voice to helpees.This article identifies ways to improve on this structure by the construction of collectives that help increase competences (enable), at the same time providing a method to test whether this succeeds. Such self‐correcting collectives constitute knowledge systems for users to participate in. Emancipation appears directly linked to the number of such systems ([knowledges]) in which people are able to participate simultaneously, each helping to maintain a stable view point. Copyright © 2003 John Wiley & Sons, Ltd.
Stabilisation of RNA Bulges by Oligonucleotide Complements Containing an Adenosine Analogue
Authors: Madder Annemieke , Ehrl Robert , Strömberg Roger 
Published: November 2003

AbstractIncorporation of 2′‐deoxy‐2′‐β‐(1‐naphthylmethyl)tubercidin into an oligodeoxyribonucleotide mostly has little or a slightly negative effect on the Tm values of complexes with DNA complements. With the same naphthylmethyl‐substituted nucleoside at the 3′‐end of a 2′‐O‐methyloligoribonucleotide, however, a stabilisation of 1–2 °C in the corresponding complexes with both DNA and RNA is observed. When the target sequence is an RNA fragment forming a two‐ or three‐nucleotide bulge, complexes with (naphthylmethyl)tubercidin‐modified oligodeoxyribonucleotides, as well as with the corresponding 2′‐O‐methyloligoribonucleotides, give stabilisations of 1–2 °C for the three‐nucleotide bulge and of almost 4 °C for the two‐nucleotide bulge. This stabilisation is specific to RNA, since the corresponding complexes with the DNA fragments do not display this effect. Thus, the (naphthylmethyl)tubercidin‐containing oligonucleotides are the first reported oligonucleotide modifications that specifically stabilise bulged RNA.
Evidence for the Combined Participation of a C10 and a C15 Precursor in the Biosynthesis of Moenocinol, the Lipid Part of the Moenomycin Antibiotics
Authors: Neundorf Ines , Köhler Christian , Hennig Lothar , Findeisen Matthias , Arigoni Duilio , Welzel Peter 
Published: November 2003

AbstractUpon feeding of [2‐13C,4‐2H]‐1‐deoxy‐D‐xylulose to Streptomyces ghanaensis, the deuterium label was retained exclusively at positions C‐7 and C‐17 in the moenocinol part of the moenomycin antibiotics. This result vindicates the hypothesis that the C25 structure of moenocinol is assembled from a C10 and a C15 precursor, each of which requires for its formation the involvement of a dimethylallyl diphosphate starter unit.
A Cyclic CCK8 Analogue Selective for the Cholecystokinin Type A Receptor: Design, Synthesis, NMR Structure and Binding Measurements
Authors: De Luca Stefania , Ragone Raffaele , Bracco Chiara , Digilio Giuseppe , Aloj Luigi , Tesauro Diego , Saviano Michele , Pedone Carlo , Morelli Giancarlo 
Published: November 2003

AbstractA cyclic CCK8 analogue, cyclo29,34[Dpr29,Lys34]‐CCK8 (Dpr=L‐2,3‐diaminopropionic acid), has been designed on the basis of the NMR structure of the bimolecular complex between the N‐terminal fragment of the CCKA receptor and its natural ligand CCK8. The conformational features of cyclo29,34[Dpr29,Lys34]‐CCK8 have been determined by NMR spectroscopy in aqueous solution and in water containing DPC‐d38 micelles (DPC=dodecylphosphocholine). The structure of the cyclic peptide in aqueous solution is found to be in a relaxed conformation, with the backbone and Dpr29 side chain atoms making a planar ring and the N‐terminal tripeptide extending approximately along the plane of this ring. In DPC/water, the cyclic peptide adopts a “boat‐shaped” conformation, which is more compact than that found in aqueous solution. The cyclic constraint between the Dpr29 side chain and the CCK8 carboxyl terminus (Lys34) introduces a restriction in the backbone conformational freedom. However, the interaction of cyclo29,34[Dpr29,Lys34]‐CCK8 with the micelles still plays an important role in the stabilisation of the bioactive conformation. A careful comparison of the NMR structure of the cyclic peptide in a DPC micelle aqueous solution with the structure of the rationally designed model underlines that the turn‐like conformation in the Trp30–Met31 region is preserved, such that the Trp30 and Met31 side chains can adopt the proper spatial orientation to interact with the CCKA receptor. The binding properties of cyclo29,34[Dpr29,Lys34]‐CCK8 to the N‐terminal receptor fragment have been investigated by fluorescence spectroscopy in a micellar environment. Estimates of the apparent dissociation constant, Kd, were in the range of 70–150 nM, with a mean value of 120±27 nM. Preliminary nuclear medicine studies on cell lines transfected with the CCKA receptor indicate that the sulfated‐Tyr derivative of cyclo29,34[Dpr29,Lys34]‐CCK8 displaces the natural ligand with an IC50 value of 15 μM.