bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic lupus international collaborating clinics renal activity/response exercise: Development of a renal activity score and renal response index
Authors: Petri Michelle , Kasitanon Nuntana , Lee Shin‐Seok , Link Kimberly , Magder Laurence , Bae Sang‐Cheol , Hanly John G. , Isenberg David A. , Nived Ola , Sturfelt Gunnar , van Vollenhoven Ronald , Wallace Daniel J. , Alarcón Graciela S. , Adu Dwomoa , Avila‐Casado Carmen , Bernatsky Sasha R. , Bruce Ian N. , Clarke Ann E. , Contreras Gabriel , Fine Derek M. , Gladman Dafna D. , Gordon Caroline , Kalunian Kenneth C. , Madaio Michael P. , Rovin Brad H. , Sanchez‐Guerrero Jorge , Steinsson Kristjan , Aranow Cynthia , Balow James E. , Buyon Jill P. , Ginzler Ellen M. , Khamashta Munther A. , Urowitz Murray B. , Dooley Mary Anne , Merrill Joan T. , Ramsey‐Goldman Rosalind , Font Josef , Tumlin James , Stoll Thomas , Zoma Asad 
Published: May 2008

AbstractObjectiveTo develop a measure of renal activity in systemic lupus erythematosus and use it to develop a renal response index.MethodsAbstracted data from the medical records of 215 patients with lupus nephritis were sent to 8 nephrologists and 29 rheumatologists for rating. Seven nephrologists and 22 rheumatologists completed the ratings. Each physician rated each patient visit with respect to renal disease activity (none, mild, moderate, or severe). Using the most commonly selected rating for each patient as the gold standard, stepwise regression modeling was performed to identify the variables most related to renal disease activity, and these variables were then used to create an activity score. This activity score could then be applied to 2 consecutive visits to define a renal response index.ResultsThe renal activity score was computed as follows: proteinuria 0.5–1 gm/day (3 points), proteinuria >1–3 gm/day (5 points), proteinuria >3 gm/day (11 points), urine red blood cell count >10/high‐power field (3 points), and urine white blood cell count >10/high‐power field (1 point). The chance‐adjusted agreement between the renal response index derived from the activity score applied to the paired visits and the plurality physician response rating was 0.69 (95% confidence interval 0.59–0.79).ConclusionRatings derived from this index for rating of renal response showed reasonable agreement with physician ratings in a pilot study. The index will require further refinement, testing, and validation. A data‐driven approach to create renal activity and renal response indices will be useful in both clinical care and research settings.
Association of a nonsynonymous single‐nucleotide polymorphism of matrix metalloproteinase 9 with giant cell arteritis
Authors: Rodríguez‐Pla A. , Beaty T. H. , Savino P. J. , Eagle R. C. , Seo P. , Soloski M. J. 
Published: May 2008

AbstractObjectiveGiant cell arteritis (GCA) is the most common type of primary vasculitis. Matrix metalloproteinase 9 (MMP‐9) is present in arterial lesions of GCA and may be involved in its pathogenesis. We investigated whether certain genotypes of 4 single‐nucleotide polymorphisms (SNPs) of MMP‐9 are overrepresented in patients with histologically confirmed GCA.MethodsFour SNPs of MMP‐9, rs3918242 in the promoter region and 3 nonsynonymous coding SNPs (rs3918252, rs17576, and rs2250889) were genotyped by polymerase chain reaction–restriction fragment length polymorphism analysis in 58 white patients for whom there was a clinical suspicion of GCA. Thirty of these patients had histologically confirmed GCA (group 1), and 28 patients had negative results of a temporal artery biopsy for GCA (group 2). Estimates of the genotype distributions of each of these SNPs in a white population were determined using publicly available genotype data for a panel of 23 individuals (group 3).ResultsAlthough 1 SNP was monomorphic in all 3 groups, we observed statistically significant differences in the genotype distributions for rs2250889 between group 1 and group 2 (P = 0.005) and between group 1 and group 3 (P = 0.009), but not between groups 2 and 3 (P = 0.965).ConclusionThese data derived from a sample of patients with GCA suggest that the G allele of MMP‐9 polymorphism rs2250889 is overrepresented in patients with histologically confirmed GCA. Clearly, larger sample sizes will be necessary to confirm this suggestive association and better characterize a possible linkage disequilibrium structure among polymorphisms.
Evidence of a novel aggrecan‐degrading activity in cartilage: Studies of mice deficient in both ADAMTS‐4 and ADAMTS‐5
Authors: Rogerson Fraser M. , Stanton Heather , East Charlotte J. , Golub Suzanne B. , Tutolo Leonie , Farmer Pamela J. , Fosang Amanda J. 
Published: May 2008

AbstractObjectiveTo characterize aggrecan catabolism and the overall phenotype in mice deficient in both ADAMTS‐4 and ADAMTS‐5 (TS‐4/TS‐5 Δ‐cat) activity.MethodsFemoral head cartilage from the joints of TS‐4/TS‐5 Δ‐cat mice and wild‐type mice were cultured in vitro, and aggrecan catabolism was stimulated with either interleukin‐1α (IL‐1α) or retinoic acid. Total aggrecan release was measured, and aggrecanase activity was examined by Western blotting using neoepitope antibodies for detecting cleavage at EGE373–374ALG, SELE1279–1280GRG, FREEE1467–1468GLG, and AQE1572–1573AGEG. Aggrecan catabolism in vivo was examined by Western blotting of cartilage that had been extracted immediately ex vivo.ResultsTS‐4/TS‐5 Δ‐cat mice were viable, fertile, and phenotypically normal. TS‐4/TS‐5 Δ‐cat cartilage explants did not release aggrecan in response to IL‐1α, and there was no detectable increase in aggrecanase neoepitopes. TS‐4/TS‐5 Δ‐cat cartilage explants released aggrecan in response to retinoic acid. There was no retinoic acid–stimulated cleavage at either EGE373–374ALG or AQE1572–1573AGEG. There was a low level of cleavage at SELE1279–1280GRG and major cleavage at FREEE1467–1468GLG. Ex vivo, cleavage at FREEE1467–1468GLG was substantially reduced, but still present, in TS‐4/TS‐5 Δ‐cat mouse cartilage compared with wild‐type mouse cartilage.ConclusionAn aggrecanase other than ADAMTS‐4 and ADAMTS‐5 is expressed in mouse cartilage and is up‐regulated by retinoic acid but not IL‐1α. The novel aggrecanase appears to have different substrate specificity from either ADAMTS‐4 or ADAMTS‐5, cleaving E–G bonds but not E–A bonds. Neither ADAMTS‐4 nor ADAMTS‐5 is required for normal skeletal development or aggrecan turnover in cartilage.
Association between findings on delayed gadolinium‐enhanced magnetic resonance imaging of cartilage and future knee osteoarthritis
Authors: Owman Henrik , Tiderius Carl Johan , Neuman Paul , Nyquist Fredrik , Dahlberg Leif E. 
Published: May 2008

AbstractObjectiveTo examine the predictive value of the delayed gadolinium‐enhanced magnetic resonance imaging of cartilage (dGEMRIC) index with regard to future radiographic osteoarthritis (OA).MethodsIn 1998, 17 knees in 11 men and 4 women with knee pain, normal results of weight‐bearing radiography, and arthroscopic cartilage changes ranging from superficial fibrillation to fissuring and softening were examined using dGEMRIC. Six years later, 16 of the 17 knees were reassessed for radiographic OA changes.ResultsAt followup, 9 of the 16 knees showed radiographic OA changes. Two of them had undergone a knee joint replacement due to OA. In the knees with radiographic OA, the dGEMRIC index at baseline was lower than that in the knees without radiographic OA (P = 0.03).ConclusionThe results of the present study support the dGEMRIC index as a clinically relevant measure of cartilage integrity and suggest that a low index may be predictive of the development of knee OA.
Suppressor activity among CD4+,CD25++ T cells is discriminated by membrane‐bound tumor necrosis factor α
Authors: Wang Jun , van Dongen Henrike , Scherer Hans Ulrich , Huizinga Tom W. J. , Toes Rene E. M. 
Published: May 2008

AbstractObjectivePrevious studies have shown that the suppressive capacity of CD4+,CD25++ T cells is compromised in patients with rheumatoid arthritis (RA) and restored by anti–tumor necrosis factor α (anti‐TNFα) therapy. Given the lack of specific cell surface markers for human Treg cells, this study aimed to define surface markers for identifying and enriching Treg cells with enhanced regulatory ability within the CD4+,CD25++ T cell compartment and to provide additional understanding of the effects of anti‐TNFα antibodies in humans.MethodsThe expression of membrane‐bound TNFα in human peripheral blood CD4+ T cells was analyzed by flow cytometry in healthy individuals and RA patients before and after anti‐TNFα treatment. Membrane‐bound TNFα‐positive and TNFα‐negative CD4+,CD25++ T cells were purified by fluorescence‐activated cell sorting, and their suppressive capacity was assessed in vitro by a standard suppression assay.ResultsA substantial number of CD4+,CD25++ T cells expressed membrane‐bound TNFα. Membrane‐bound TNFα‐positive CD4+,CD25++ T cells displayed reduced antiinflammatory cytokine production and less potent suppressor capacity, since 4 times more cells were required to achieve 50% inhibition compared with their membrane‐bound TNFα‐negative counterparts. Treatment of RA patients with TNFα‐specific antibodies led to a reduction in the number of membrane‐bound TNFα‐positive CD4+,CD25++ T cells from peripheral blood.ConclusionOur data indicate that the absence of membrane‐bound TNFα on CD4+,CD25++ T cells can be used to characterize and enrich for Treg cells with maximal suppressor potency. Enrichment of membrane‐bound TNFα‐negative CD4+,CD25+ cells in the CD4+,CD25++ T cell compartment may contribute to restoring the compromised suppressive ability of CD4+,CD25++ T cell populations in RA patients after anti‐TNFα treatment.
Effects of long‐term strontium ranelate treatment on the risk of nonvertebral and vertebral fractures in postmenopausal osteoporosis: Results of a five‐year, randomized, placebo‐controlled trial
Authors: Reginster Jean‐Yves , Felsenberg Dieter , Boonen Steven , Diez‐Perez Adolfo , Rizzoli Rene , Brandi Maria‐Luisa , Spector Tim D. , Brixen Kim , Goemaere Stefan , Cormier Catherine , Balogh Adam , Delmas Pierre D. , Meunier Pierre J. 
Published: May 2008

AbstractObjectiveThis study was undertaken to assess the effect of strontium ranelate on nonvertebral and vertebral fractures in postmenopausal women with osteoporosis in a 5‐year, double‐blind, placebo‐controlled trial.MethodsA total of 5,091 postmenopausal women with osteoporosis were randomized to receive either strontium ranelate at 2 gm/day or placebo for 5 years. The main efficacy criterion was the incidence of nonvertebral fractures. In addition, incidence of hip fractures was assessed, by post hoc analysis, in the subset of 1,128 patients who were at high risk of fractures (age 74 years or older with lumbar spine and femoral neck bone mineral density T scores −2.4 or less). The incidence of new vertebral fractures was assessed, using the semiquantitative method described by Genant, in the 3,646 patients in whom spinal radiography (a nonmandatory procedure) was performed during the course of the study. Fracture data were analyzed using the Kaplan‐Meier survival method.ResultsOf the 5,091 patients, 2,714 (53%) completed the study up to 5 years. The risk of nonvertebral fracture was reduced by 15% in the strontium ranelate group compared with the placebo group (relative risk 0.85 [95% confidence interval 0.73–0.99]). The risk of hip fracture was decreased by 43% (relative risk 0.57 [95% confidence interval 0.33–0.97]), and the risk of vertebral fracture was decreased by 24% (relative risk 0.76 [95% CI 0.65–0.88]) in the strontium ranelate group. After 5 years, the safety profile of strontium ranelate remained unchanged compared with the 3‐year findings.ConclusionOur findings indicate that treatment of postmenopausal osteoporosis with strontium ranelate results in a sustained reduction in the incidence of osteoporotic nonvertebral fractures, including hip fractures, and vertebral fractures over 5 years.
Relationship of meniscal damage, meniscal extrusion, malalignment, and joint laxity to subsequent cartilage loss in osteoarthritic knees
Authors: Sharma Leena , Eckstein Felix , Song Jing , Guermazi Ali , Prasad Pottumarthi , Kapoor Dipali , Cahue September , Marshall Meredith , Hudelmaier Martin , Dunlop Dorothy 
Published: May 2008

AbstractObjectiveProgressive knee osteoarthritis (OA) is believed to result from local factors acting in a systemic environment. Previous studies have not examined these factors concomitantly or compared quantitative and qualitative cartilage loss outcomes. The aim of this study was to test whether meniscal damage, meniscal extrusion, malalignment, and laxity each predicted tibiofemoral cartilage loss after controlling for the other factors.MethodsLaxity and alignment were measured at baseline in individuals with knee OA. Magnetic resonance imaging included spin‐echo coronal and sagittal imaging for meniscal scoring and axial and coronal spoiled gradient echo sequences with water excitation for cartilage quantification. Tibial and weight‐bearing femoral condylar subchondral bone area and cartilage surface were segmented. Cartilage volume, denuded bone area, and cartilage thickness were quantified in each plate, with progression defined as cartilage loss >2 times the coefficient of variation for each plate. Qualitative outcome was assessed as worsening of the cartilage score. Logistic regression analysis with generalized estimating equations yielded odds ratios for each factor, adjusting for age, sex, body mass index, and the other factors.ResultsWe studied 251 knees in 153 persons. After full adjustment, medial meniscal damage predicted medial tibial cartilage volume loss and tibial and femoral denuded bone increase, while varus malalignment predicted medial tibial cartilage volume and thickness loss and tibial and femoral denuded bone increase. Lateral meniscal damage predicted every lateral outcome. Laxity and meniscal extrusion had inconsistent effects. After full adjustment, no factor except medial laxity predicted qualitative outcome.ConclusionUsing quantitative cartilage loss assessment, local factors that independently predicted tibial and femoral loss included medial meniscal damage and varus malalignment (medially) and lateral meniscal damage (laterally). A measurement of quantitative outcome was more sensitive at revealing these relationships than a qualitative approach.
Cardiac involvement in systemic sclerosis assessed by tissue‐doppler echocardiography during routine care: A controlled study of 100 consecutive patients
Authors: Meune Christophe , Avouac Jérôme , Wahbi Karim , Cabanes Laure , Wipff Julien , Mouthon Luc , Guillevin Loïc , Kahan André , Allanore Yannick 
Published: May 2008

AbstractObjectiveTo assess the prevalence of primary cardiac complications in a large population of patients with systemic sclerosis (SSc), using recently developed echocardiographic techniques.MethodsWe prospectively studied 100 consecutive patients (mean ± SD age 54 ± 14 years; 86 women) presenting with SSc without pulmonary arterial hypertension or clinical manifestations of heart failure. All patients underwent standard echocardiography, along with measurements of longitudinal velocities by tissue Doppler imaging (TDI) to assess left ventricular (LV) and right ventricular (RV) contractility and LV diastolic function. Results were compared with those in 26 age‐ and sex‐matched healthy controls.ResultsPatients with SSc had a wider mean left atrial diameter and impaired relaxation compared with the controls. A trend was observed toward a smaller LV ejection fraction (EF) in the patients (mean ± SD 64.9 ± 0.6%) than in the controls (67.2 ± 0.7%), as well as higher pulmonary artery pressure (mean ± SD 33.3 ± 0.6 mm Hg versus 30.8 ± 1.0 mm Hg). LVEF was <55% in 7 patients versus none of the controls. Peak systolic mitral annular velocity as measured by TDI was <7.5 cm/second in 14 patients versus none of the controls (P = 0.040). Mitral annulus early diastolic velocity was <10 cm/second in 30 patients versus 2 of the controls (P = 0.022). Fifteen patients and none of the controls had reduced peak systolic tricuspid annular velocity (P = 0.039). The TDI results correlated with each other, but not with lung abnormalities or other disease characteristics.ConclusionDepression of LV and RV systolic and LV diastolic function is common in patients with SSc and is due to primary myocardial involvement. Considering the major contributions of TDI, the addition of this simple technique to standard measurements may improve the detection of heart involvement in patients with SSc.
Function of CD4+,CD25+ Treg cells in MRL/lpr mice is compromised by intrinsic defects in antigen‐presenting cells and effector T cells
Authors: Parietti Véronique , Monneaux Fanny , Décossas Marion , Muller Sylviane 
Published: May 2008

AbstractObjectiveNaturally occurring CD4+,CD25+ Treg cells are central in the maintenance of peripheral tolerance. Impaired activity and/or a lower frequency of these cells is involved in the emergence of autoimmunity. We undertook this study to analyze relative proportions and functional alterations of Treg cells in MRL/lpr mice.MethodsThe frequency of CD4+,CD25+ T cells in the peripheral blood of healthy and autoimmune mice was compared by flow cytometry. The capacity of CD4+,CD25+ T cells to inhibit the proliferation and cytokine secretion of CD4+,CD25− T cells was assessed after polyclonal activation.ResultsMRL/lpr mice exhibited a normal percentage of CD4+,CD25high T cells, and forkhead box P3 messenger RNA and protein expression in Treg cells was not altered. However, MRL/lpr Treg cells displayed a reduced capacity to suppress proliferation and to inhibit interferon‐γ secretion by syngeneic effector CD4+,CD25− T cells, as compared with syngeneic cocultures of CBA/J T cells. Moreover, effector MRL/lpr CD4+,CD25− T cells were substantially less susceptible to suppression even when cultured with CBA/J or MRL/lpr Treg cells. Crossover experiments led us to conclude that in MRL/lpr mice, each partner engaged in T cell regulation displays altered functions. Molecules involved in suppressive mechanisms (CTLA‐4 and CD80/CD86) are underexpressed, and antigen‐presenting cells (APCs) produce raised levels of interleukin‐6, which is known to abrogate suppression.ConclusionOur results suggest that although the frequency and phenotype of Treg cells in MRL/lpr mice are similar to those in normal mice, Treg cells in MRL/lpr mice are not properly stimulated by APCs and are unable to suppress proinflammatory cytokine secretion from effector T cells.
Anti‐CD20 therapy in patients with rheumatoid arthritis: Predictors of response and B cell subset regeneration after repeated treatment
Authors: Roll Petra , Dörner Thomas , Tony Hans‐Peter 
Published: May 2008

AbstractObjectiveB cell depletion with the anti‐CD20 antibody rituximab has proven efficacy in patients with rheumatoid arthritis (RA). The effects on B cell homeostasis after repeated treatments and the relationship of certain B cell subsets to clinical response or relapse are currently not known.MethodsIn this open‐label study, 17 patients with RA refractory to standard therapy were treated with 1 cycle of rituximab. Of these 17 patients, 11 received a second cycle of rituximab therapy. Immunophenotyping was performed before therapy and during B cell recovery.ResultsTwelve of 17 patients showed a good European League Against Rheumatism response after receiving 1 cycle of rituximab therapy. At the time of B cell recovery, the IgD+,CD27+ memory B cell subset was significantly larger (P = 0.019) in the nonresponder group. Within the group of 12 responders, 6 patients, whose disease was characterized by a significantly higher proportion of overall CD27+ memory B cells before therapy, experienced an early relapse (weeks 24–40 posttreatment). Eleven patients were re‐treated, again resulting in a good clinical response. B cell reconstitution followed a similar pattern after each cycle. The early reconstitution phase was characterized by immature CD38++,IgD+,CD10+ B cells, whereas the number of naive B cells increased continuously thereafter. The number of memory B cells was still reduced at the time of the second depletion but recovered to levels similar to those following the first cycle of therapy.ConclusionData derived from repeated B lymphocyte depletion with rituximab in patients with RA suggest that analysis of certain memory B cell subsets provides information on efficacy, response, and late as well as early relapse, consistent with the conclusion that targeting memory B cells is a key to its mechanism of action.
A diagnostic score for molecular analysis of hereditary autoinflammatory syndromes with periodic fever in children
Authors: Gattorno M. , Sormani M. P. , D'Osualdo A. , Pelagatti M. A. , Caroli F. , Federici S. , Cecconi M. , Solari N. , Meini A. , Zulian F. , Obici L. , Breda L. , Martino S. , Tommasini A. , Bossi G. , Govers A. , Touitou I. , Woo P. , Frenkel J. , Koné‐Paut I. , Baldi M. , Ceccherini I. , Martini A. 
Published: May 2008

AbstractObjectiveTo identify a set of clinical parameters that can predict the probability of carrying mutations in one of the genes associated with hereditary autoinflammatory syndromes.MethodsA total of 228 consecutive patients with a clinical history of periodic fever were screened for mutations in the MVK, TNFRSF1A, and MEFV genes, and detailed clinical information was collected. A diagnostic score was formulated based on univariate and multivariate analyses in genetically positive and negative patients (training set). The diagnostic score was validated in an independent set of 77 patients (validation set).ResultsYoung age at onset (odds ratio [OR] 0.94, P = 0.003), positive family history of periodic fever (OR 4.1, P = 0.039), thoracic pain (OR 4.6, P = 0.05), abdominal pain (OR 33.1, P < 0.001), diarrhea (OR 3.3, P = 0.028), and oral aphthosis (OR 0.2, P = 0.007) were found to be independently correlated with a positive genetic test result. These variables were combined in a linear score whose ability to predict a positive result on genetic testing was validated in an independent data set. In this latter set, the diagnostic score revealed high sensitivity (82%) and specificity (72%) for discriminating patients who were genetically positive from those who were negative. In patients with a high probability of having a positive result on genetic testing, a regression tree analysis provided the most reasonable order in which the genes should be screened.ConclusionThe proposed approach in patients with periodic fever will increase the probability of obtaining positive results on genetic testing, with good specificity and sensitivity. Our results further help to optimize the molecular analysis by suggesting the order in which the genes should be screened.