bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic gadolinium‐enhanced magnetic resonance imaging of the wrist in patients with rheumatoid arthritis can discriminate active from inactive disease
Authors: Cimmino Marco A. , Innocenti Stefania , Livrone Fabrizio , Magnaguagno Francesca , Silvestri Enzo , Garlaschi Giacomo 
Published: May 2003

AbstractObjectiveTo determine the efficacy of dynamic gadolinium‐enhanced magnetic resonance imaging (MRI) of the wrist in the evaluation of disease activity in patients with rheumatoid arthritis (RA).MethodsThirty‐six patients with RA (with different degrees of disease activity) and 5 healthy controls were studied. MRI was performed with a low‐field (0.2T), extremity‐dedicated machine. After an intravenous bolus injection of gadolinium–diethylenetriamine pentaacetic acid, 20 consecutive fast spin‐echo images of 3 slices of the wrist were obtained every 18 seconds.ResultsThe curves of synovial membrane enhancement identified the following 2 groups: controls and RA patients in remission, and RA patients with active or intermediately active disease. Both the rate of early enhancement (REE) and relative enhancement (RE) were significantly higher in patients with active RA than in those with inactive RA and controls. The REE and RE were significantly correlated with the number of swollen joints (P < 0.00001 and P = 0.003, respectively), the number of tender joints (P < 0.00001 and P = 0.004, respectively), the Ritchie index (P = 0.0002 for both REE and RE), the Disease Activity Score (P = 0.0004 and P = 0.0008, respectively), the Health Assessment Questionnaire (HAQ) (P = 0.0002 and P = 0.0007, respectively), early morning stiffness (P = 0.001 and P = 0.009, respectively), the C‐reactive protein level (P = 0.015 and P = 0.03, respectively), the erythrocyte sedimentation rate (P = 0.03, RE only), and α2 globulins (P = 0.036 and P = 0.028, respectively).ConclusionOur data support use of dynamic MRI for discriminating active from inactive RA. Enhancement curves are associated not only with laboratory and clinical indicators of inflammation, but also with the HAQ, a relevant predictor of RA functional outcome. This technique can be repeated frequently and is an excellent candidate for the ideal method for the followup of patients with RA.
Role of metacarpophalangeal joint anatomic factors in the distribution of synovitis and bone erosion in early rheumatoid arthritis
Authors: Tan Ai Lyn , Tanner Steven F. , Conaghan Philip G. , Radjenovic Aleksandra , O'Connor Philip , Brown Andrew K. , Emery Paul , McGonagle Dennis 
Published: May 2003

AbstractObjectiveTo investigate the role of metacarpophalangeal (MCP) joint anatomic and biomechanical factors in the distribution of synovitis and bone erosion in early rheumatoid arthritis (RA).MethodsThirty‐three patients with early RA with clinically diagnosed MCP joint disease and 28 healthy controls were examined by magnetic resonance imaging of the second to fifth MCP joints of the dominant hand. T1 and T2 fat‐suppressed coronal sequences were obtained to assess erosion, and dynamic contrast‐enhanced images were acquired to assess synovitis in all of the RA patients and in 8 of the controls. Erosions were defined as bone defects with sharp margins observed using T1‐weighted imaging in 2 planes, with a cortical break seen in at least 1 plane. The location of erosions was recorded. The volume of synovitis surrounding each MCP joint (divided into 8 regions) was calculated by summation of voxels derived from the maximal enhancement parameters. The synovial volumes adjacent to MCP joint collateral ligaments were determined by correcting synovial volumes for the positions of asymmetrically placed flexor tendons.ResultsIn patients with early RA in whom bone erosions were present, there was a propensity for involvement of the radial side of the second (P < 0.0001), third (P = 0.002), and fourth (P = 0.056) MCP joints, but not the fifth. Fifty‐two of the 110 erosions (47.3%) occurred adjacent to the radial collateral ligaments of the second, third, and fourth MCP joints. The volume of synovitis was also greater on the radial side of the second (P < 0.0001) and third (P < 0.001) MCP joints. A predilection for synovitis in all of the MCP joints adjacent to the radial collateral ligaments was evident when the positional effects of the flexor tendon were considered. The position of radial collateral ligaments had an effect on erosion formation that was independent of synovitis. A predilection for radial bone damage was also evident in the controls, although lesions were 5‐fold less frequent, were generally smaller, and had well‐defined margins.ConclusionThis study shows that there is a predilection for both synovitis and bone erosion formation on the radial side of the MCP joints in early RA, and that joint inflammation appears to drive the inherent tendency for bone damage on the radial side of joints. These findings have implications regarding the pathogenesis of joint damage in RA.
Amyloid‐enhancing factor mediates amyloid formation on fibroblasts via a nidus/template mechanism
Authors: Magy Nadine , Liepnieks Juris J. , Benson Merrill D. , Kluve‐Beckerman Barbara 
Published: May 2003

AbstractObjectiveTo determine the mechanism by which amyloid‐enhancing factor (AEF) promotes amyloid deposition, and to test whether AEF seeds deposition of serum amyloid A (SAA) and facilitates conversion to beta‐sheet structure.MethodsFibroblasts were cultured with mouse recombinant SAA1.1 and AEF, SAA1.1, or AEF. AEF was prepared as a glycerol extract of spleen from amyloidotic mice. Amyloid was identified by staining with Congo red and examining for green birefringence under polarized light. SAA was localized immunohistochemically. Texas Red–labeled SAA was visualized in living cultures by fluorescence confocal microscopy. AEF was characterized by Western blot analysis using anti‐SAA antiserum and N‐terminal sequence analysis. Subunits comprising amyloid in fibroblast cultures were characterized by sodium dodecyl sulfate–polyacrylamide gel electrophoresis.ResultsAmyloid was produced in fibroblast cultures by an AEF‐dependent mechanism. AEF, added to culture medium as insoluble protein precipitates, adhered to fibroblast monolayers. SAA bound preferentially to the adherent precipitates. Coincident with SAA binding, precipitates developed an affinity for Congo red. Over time, as more SAA was added, networks of Congo red–positive material producing bright green birefringence also developed outward from AEF precipitates. Amyloid built upon AEF in this manner was composed of full‐length SAA. No amyloid was produced in cultures treated with either SAA or AEF alone. SAA and SAA peptides processed in the C‐terminal region were the most prominent proteins in the glycerol‐extracted AEF preparation.ConclusionAEF binds to fibroblast monolayers and acts as a sink for SAA. SAA that collects on AEF assembles into an amyloid structure. Thus, it is concluded that AEF serves as both a nidus and a template for amyloid formation.
Nonsteroidal antiinflammatory drugs and a selective cyclooxygenase 2 inhibitor uncouple mitochondria in intact cells
Authors: Krause Manja M. , Brand Martin D. , Krauss Stefan , Meisel Christian , Vergin Hartmut , Burmester Gerd‐Rüdiger , Buttgereit Frank 
Published: May 2003

AbstractObjectiveUncoupling of isolated mitochondria by nonsteroidal antiinflammatory drugs (NSAIDs) has been considered relevant to the development of gastrointestinal (GI) side effects. We investigated the occurrence of NSAID‐induced uncoupling of mitochondria in intact cells (rat thymocytes) compared with the effects of a selective cyclooxygenase 2 (COX‐2) inhibitor.MethodsOxygen consumption and mitochondrial membrane potential were simultaneously measured amperometrically and by distribution of radioactive tracer molecules, respectively, in the presence and absence of pharmacologically relevant concentrations of the NSAIDs indomethacin and diclofenac and the selective COX‐2 inhibitor SC‐236. Analysis of data by a technique related to top‐down elasticity analysis permitted assessment of the influence of these compounds on individual components of cellular energy metabolism.ResultsIndomethacin, diclofenac, and SC‐236 increased proton leak in isolated mitochondria. Both diclofenac and SC‐236 significantly stimulated proton leak in intact cells and simultaneously inhibited substrate oxidation and ATP turnover. Oxygen consumption rates of isolated cells remained unchanged over a wide concentration range of the drugs, despite significant effects on subsystems of cellular energy metabolism.ConclusionNSAIDs and selective COX‐2 inhibitors have significant and equally directed effects on cellular energy metabolism. They both uncouple mitochondrial respiration and inhibit substrate oxidation and ATP turnover. However, the topical effect and selective COX‐2 inhibition may not be sufficient to cause NSAID‐like damage to the GI tract.
Deposition of nucleosomal antigens (histones and DNA) in the epidermal basement membrane in human lupus nephritis
Authors: Grootscholten Cecile , van Bruggen Mieke C. J. , van der Pijl Johan W. , de Jong Elke M. G. J. , Ligtenberg Gerry , Derksen Ronald H. W. M. , Berden Jo H. M. ,   for the Dutch Working Party on Systemic Lupus Erythematosus
Published: May 2003

AbstractObjectiveAntinuclear autoantibodies complexed to nucleosomes can bind to heparan sulfate (HS) in the glomerular basement membrane. This binding is due to the binding of the positively charged histones to the strongly anionic HS. Nucleosomes and histones have been identified in glomerular deposits in human lupus nephritis. We investigated whether nucleosomes are present in the basement membrane of nonlesional skin of lupus patients.MethodsSkin biopsy samples from patients with systemic lupus erythematosus (SLE) (30 with active lupus nephritis and 15 with inactive disease) and controls (with parapemphigus or diabetes) were stained for IgG, histones, DNA, and nucleosomes.ResultsIgG deposits were found in 87% of the patients with lupus nephritis, in 33% of the patients with inactive disease, and in 71% of the parapemphigus patients. Using polyclonal antihistone antibodies, histones were detected in 87% of lupus nephritis patients, but in none of the other SLE patients or the diabetes controls (P < 0.0001). Among the parapemphigus controls, 14% of samples stained positive in one of the polyclonal antihistone stainings (P < 0.0001). Using monoclonal antibodies, histones and DNA were identified in 21% of the lupus nephritis patients. Although none of the other groups showed positive staining for nucleosomes, 7% of the lupus nephritis biopsy samples were positive using antinucleosome monoclonal antibodies. Colocalization of nucleosomal antigens and IgG was confirmed using confocal laser microscopy.ConclusionThese findings suggest that nucleosome‐mediated binding of autoantibodies to basement membranes may also occur at sites in the body other than in the glomerulus.
Correlation of serum anti‐DNA topoisomerase I antibody levels with disease severity and activity in systemic sclerosis
Authors: Hu Paul Q. , Fertig Noreen , Medsger Thomas A. , Wright Timothy M. 
Published: May 2003

AbstractObjectiveTo investigate correlations between serum levels of topoisomerase I–specific antibody (anti–topo I) and clinical features of systemic sclerosis (SSc), including disease severity (the total skin score [TSS]) and disease activity.MethodsUsing highly sensitive enzyme‐linked immunosorbent assays, we measured the levels of anti–topo I antibody, including total IgG, individual IgG subclasses, and IgA, and analyzed their correlations with the TSS in 59 patients with SSc, all of whom had diffuse cutaneous involvement. Serial serum samples were obtained from 11 of these patients.ResultsThe titers of anti–topo I antibody, including IgG and IgA, were positively correlated with the TSS, a measure of SSc disease severity. In 8 of the 11 patients from whom serial serum samples were obtained, changes in the levels of both IgG and IgA, when detectable, paralleled changes in the TSS. In 3 patients, an increasing anti–topo I IgG level preceded an increase in the TSS. The level of each IgG subclass also correlated with and tended to parallel the TSS. The patients with very active disease had higher mean IgG (P < 0.001) and IgA (P < 0.05) titers than did those with inactive disease.ConclusionSerum levels of anti–topo I antibody correlate positively with disease severity and disease activity in SSc.
Increased ubiquitination and reduced expression of LCK in T lymphocytes from patients with systemic lupus erythematosus
Authors: Jury Elizabeth C. , Kabouridis Panagiotis S. , Abba Amina , Mageed Rizgar A. , Isenberg David A. 
Published: May 2003

AbstractObjectiveTo explore regulation of proximal signaling and composition of lipid rafts in T lymphocytes from patients with systemic lupus erythematosus (SLE).MethodsThe expression, phosphorylation, and degradation of lipid raft–associated signaling molecules in T lymphocytes from 50 patients with SLE compared with 28 healthy controls and 22 rheumatoid arthritis patients were investigated. Lipid raft and nonraft fractions from T cells were isolated by ultracentrifugation. Proteins in the lipid raft and nonraft fractions were analyzed by Western blotting and probed for phosphotyrosine activity and for LCK, LAT, and CD3ε. Immunoprecipitation experiments were performed to assess protein ubiquitination in T cell lysates. T cell phenotype and levels of intracellular LCK were determined by flow cytometry.ResultsLCK, an essential signaling molecule for T cell activation, was significantly reduced in both lipid raft and nonraft fractions of T lymphocytes from patients with active SLE compared with controls, and the reduction was independent of treatment. To identify the likely causes of reduced LCK, we explored the possibility that chronic activation of T lymphocytes underlies LCK degradation. The results revealed an increase in protein ubiquitination, and specifically LCK ubiquitination, in T cells from SLE patients. However, our findings suggest that the increase in ubiquitination is independent of T cell activation.ConclusionLCK is reduced in T cell lipid rafts from patients with SLE. This reduction appears to be independent of activation and may be associated with abnormal ubiquitin‐mediated regulation mechanisms.
Intravertebral clefts in osteoporotic vertebral compression fractures
Authors: McKiernan Fergus , Faciszewski Tom 
Published: May 2003

AbstractObjectiveTo describe the characteristics, radiographic appearance, and significance of intravertebral clefts in vertebral compression fractures (VCFs) of patients with osteoporosis presenting for vertebroplasty.MethodsThis was a prospective radiographic study of 50 consecutive patients with 82 VCFs who underwent vertebroplasty at a tertiary referral center. Patients underwent imaging preoperatively with standing lateral and supine cross‐table lateral radiographs and magnetic resonance imaging (MRI). Standing lateral radiographs were also obtained postoperatively. Clefts were defined at the time of vertebroplasty as confluent reservoirs for polymethylmethacrylate (PMMA). Postoperatively, all images were reexamined for the presence and characterization of intravertebral clefts.ResultsTwenty‐four of 50 patients (48%) had clefted VCFs, and 30 of 82 VCFs (37%) contained clefts. Clefted VCFs were severe, dynamically mobile, and occurred primarily in the thoracolumbar junction. Clefts were detectable by standing lateral radiography in 14%, by supine cross‐table radiography in 64%, and by MRI in 96% of fractured vertebrae. Clefts occurred primarily in the anterosuperior portion of the vertebral body, and cleft margins appeared increasingly sclerotic in persistently mobile VCFs. PMMA fill patterns of clefted and unclefted VCFs were distinct.ConclusionIntravertebral clefts occur frequently in osteoporotic VCFs of patients who present for vertebroplasty. The radiographic characteristics of clefts evolve over time and can be indistinguishable from Kümmell's disease in severe, persistently mobile, clefted osteoporotic VCFs.
Insulin‐like growth factor 1–induced interleukin‐1 receptor II overrides the activity of interleukin‐1 and controls the homeostasis of the extracellular matrix of cartilage
Authors: Wang Jun , Elewaut Dirk , Veys Eric M. , Verbruggen Gust 
Published: May 2003

AbstractObjectiveWe examined the effect of the insulin‐like growth factor 1 (IGF‐1)/IGF receptor I (IGFRI) autocrine/paracrine anabolic pathway on the extracellular matrix (ECM) of human chondrocytes and the mechanism by which IGF‐1 reverses the catabolic effects of interleukin‐1 (IL‐1).MethodsPhenotypically stable human articular cartilage cells were obtained from normal cartilage and maintained in culture in alginate beads for 1 week to reach equilibrium of accumulated cell‐associated matrix (CAM) compounds. Levels of CAM components aggrecan and type II collagen (CII) and levels of intracellular IGF‐1, IL‐1α, and IL‐1β and their respective plasma membrane–bound receptors IGFRI, IL‐1 receptor I (IL‐1RI), and the decoy receptor IL‐1RII were assayed using flow cytometry to investigate the relationship between the autocrine/paracrine pathways and the homeostasis of ECM molecules in the CAM. The effects of IGF‐1 on the expression of IGF‐1, IL‐1α, and IL‐1β and their respective receptor systems, the aggrecan core protein, and CII were determined by flow cytometry.ResultsCause–effect relationship experiments showed that IGF‐1 up‐regulates the levels of IGF‐1, IGFRI, aggrecan, and CII in the CAM. No effects on the expression of IL‐1α and IL‐1β and their signaling receptor IL‐1RI were observed. However, IGF‐1 was able to reverse IL‐1β–mediated degradation of aggrecan and the repression of the aggrecan synthesis rate. Interestingly, levels of aggrecan and CII in the CAM strongly correlated not only with IGF‐1, but also with IL‐1RII, which acts as a decoy receptor for IL‐1α and IL‐1β. This suggests that IGF‐1 and IL‐1RII may cooperate in regulating ECM homeostasis. Additional experiments demonstrated that IGF‐1 up‐regulated IL‐1RII, thereby overriding the catabolic effects of IL‐1.ConclusionThese findings reveal a new paradigm by which IGF‐1 influences chondrocyte metabolism, by reversing the IL‐1–mediated catabolic pathway through up‐regulation of its decoy receptor.
Inflammatory cytokine gene expression in the urinary sediment of patients with lupus nephritis
Authors: Chan Rebecca Wing‐Yan , Tam Lai‐Shan , Li Edmund Kwok‐Ming , Lai Fernand Mac‐Moune , Chow Kai‐Ming , Lai Ka‐Bik , Li Philip Kam‐Tao , Szeto Cheuk‐Chun 
Published: May 2003

AbstractObjectiveLupus nephritis is characterized by intrarenal inflammation and lymphocyte activation. In the present study, the expression of cytokine genes in the urinary sediment of patients with systemic lupus erythematosus (SLE) was examined.MethodsWe studied 3 SLE patient groups (25 with active lupus nephritis [active group], 25 with inactive SLE and previous renal involvement [remission group], 20 with inactive SLE and no history of renal involvement [nonrenal SLE group]) and 2 control groups (10 patients with noninflammatory renal diseases [non‐SLE group] and 10 healthy volunteers [healthy group]). Cytokine gene expression in the urinary sediment was studied by real‐time quantitative polymerase chain reaction.ResultsExpression of interferon‐γ (IFNγ) in urinary sediment was significantly higher in the active group than in all other groups (P < 0.001 by Kruskal‐Wallis test). Among the SLE patient groups, there was a close correlation between IFNγ expression and the overall SLE Disease Activity Index (SLEDAI) score (Spearman's r = 0.590, P < 0.001) and the SLEDAI renal score (r = 0.642, P < 0.001). Urinary expression of interleukin‐2 (IL‐2) in the active group was significantly higher than that in the healthy group (P = 0.046) but not in the remission or nonrenal SLE groups. There was no difference in the levels of IL‐4 expression among the SLE groups.ConclusionWe found a predominance of Th1 cytokine in the urinary sediment of patients with active lupus nephritis. Measurement of cytokine gene expression in urinary sediment may be a useful noninvasive tool for assessing the severity of renal involvement in SLE.
CD25+ cell depletion hastens the onset of severe disease in collagen‐induced arthritis
Authors: Morgan Mary E. , Sutmuller Roger P. M. , Witteveen Hendrik J. , van Duivenvoorde Leonie M. , Zanelli Eric , Melief Cornelis J. M. , Snijders Alies , Offringa Rienk , de Vries René R. P. , Toes René E. M. 
Published: May 2003

AbstractObjectiveCD4+,CD25+ T regulatory cells may offer opportunities to intervene in the course of autoimmune disease. We wished to evaluate their potential for influencing systemic and chronic joint inflammation by investigating their involvement in collagen‐induced arthritis (CIA).MethodsWe depleted DBA/1 mice of CD25+ regulatory cells by injection of a depleting monoclonal antibody specific for CD25 14 days before a single immunization with type II collagen (CII) in Freund's complete adjuvant. CD4+,CD25+ T cells were adoptively transferred to some groups of mice during immunization. Mice were then scored for signs of arthritis, and blood was taken periodically to measure the amounts of CII‐specific antibodies. Splenocytes of treated mice were examined in vitro to determine the effects of depletion on proliferation to CII and control antigens.ResultsCD25+ cell–depleted DBA/1 mice had significantly more severe disease than control mice following collagen immunization. The magnified severity was also accompanied by higher antibody titers against collagen, and in vitro tests showed increased proliferation of collagen‐specific T cells. Adoptively transferring CD4+,CD25+ T cells into depleted mice was shown to reverse the heightened severity. Control mice, which were depleted and immunized with the neoantigen keyhole limpet hemocyanin (KLH), had neither an increased antibody response toward KLH nor an augmented proliferative response, indicating that CD25+ cell depletion preferentially affects immunity against self antigen.ConclusionThese results establish a link between CD4+,CD25+ regulatory cells and CIA and provide a rationale for investigating CD4+,CD25+ T regulatory cells in the treatment and prevention of arthritis.
Quantitative morphologic classification of layer 5 neurons from mouse primary visual cortex
Authors: Tsiola Areti , Hamzei‐Sichani Farid , Peterlin Zita , Yuste Rafael 
Published: May 2003

AbstractThe understanding of any neural circuit requires the identification and characterization of all its components. Morphologic classifications of neurons are, therefore, of central importance to neuroscience. We use a quantitative method to classify neurons from layer 5 of mouse primary visual cortex, based on multidimensional clustering. To reconstruct neurons, we used Golgi impregnations and biocytin injections, as well as DiOlistics, a novel technique of labeling neurons with lipophilic dyes. We performed computerized 3‐D reconstructions of 158 layer 5 cells to measure a series of morphologic variables. Principal component analysis and cluster analysis were used for the classification of cell types. Five major classes of cells were found: group 1 includes large pyramidal neurons with apical dendrites that reach layer 1 with an apical tuft; group 2 consists of short pyramidal neurons and large multipolar cells with “polarized” dendritic trees; group 3 is composed of less extensive pyramidal neurons; group 4 includes small cells; and group 5 includes another set of short pyramidal neurons in addition to “atypically oriented” cells. Our sample included a relatively homogeneous group of 27 neurons that project to the superior colliculus, which clustered mainly in group 1, thus supporting the validity of the classification. Cluster analysis of neuronal morphologies provides an objective method to quantitatively define different neuronal phenotypes and may serve as a basis for describing neocortical circuits. J. Comp. Neurol. 461:415–428, 2003. © 2003 Wiley‐Liss, Inc.