bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protection of obstetric dimensions in a small‐bodied human sample
Authors: Kurki Helen K. 
Published: May 2007

AbstractIn human females, the bony pelvis must find a balance between being small (narrow) for efficient bipedal locomotion, and being large to accommodate a relatively large newborn. It has been shown that within a given population, taller/larger‐bodied women have larger pelvic canals. This study investigates whether in a population where small body size is the norm, pelvic geometry (size and shape), on average, shows accommodation to protect the obstetric canal. Osteometric data were collected from the pelves, femora, and clavicles (body size indicators) of adult skeletons representing a range of adult body size. Samples include Holocene Later Stone Age (LSA) foragers from southern Africa (n = 28 females, 31 males), Portuguese from the Coimbra‐identified skeletal collection (CISC) (n = 40 females, 40 males) and European‐Americans from the Hamann–Todd osteological collection (H‐T) (n = 40 females, 40 males). Patterns of sexual dimorphism are similar in the samples. Univariate and multivariate analyses of raw and Mosimann shape‐variables indicate that compared to the CISC and H‐T females, the LSA females have relatively large midplane and outlet canal planes (particularly posterior and A‐P lengths). The LSA males also follow this pattern, although with absolutely smaller pelves in multivariate space. The CISC females, who have equally small stature, but larger body mass, do not show the same type of pelvic canal size and shape accommodation. The results suggest that adaptive allometric modeling in at least some small‐bodied populations protects the obstetric canal. These findings support the use of population‐specific attributes in the clinical evaluation of obstetric risk. Am J Phys Anthropol, 2007. © 2007 Wiley‐Liss, Inc.
Serum matrix metalloproteinase 3 is an independent predictor of structural damage progression in patients with ankylosing spondylitis
Authors: Maksymowych Walter P. , Landewé Robert , Conner‐Spady Barbara , Dougados Maxime , Mielants Herman , van der Tempel Hille , Poole A. Robin , Wang Nandi , van der Heijde Désirée 
Published: May 2007

AbstractObjectiveIn prospective studies, only baseline radiographic damage has been identified as an independent predictor of radiographic progression in ankylosing spondylitis (AS). Several biomarkers have been identified as independent predictors of radiographic progression in rheumatoid arthritis, however, and these may be of use in AS. This study was undertaken to analyze serologic biomarkers as predictors of radiographic progression in AS.MethodsWe measured a panel of biomarkers reflecting cartilage turnover and osteoclasis. These biomarkers were cartilage oligomeric matrix protein, human cartilage gp‐39 (YKL‐40), type II collagen epitopes detected by the C2C and C1,2C degradation assays and the CPII synthesis assay, aggrecan 846 epitope, osteoprotegerin, and matrix metalloproteinase 3 (MMP‐3). The analysis was performed in a cohort of AS patients from the Netherlands, Belgium, and France enrolled in a longitudinal study, the Outcome Assessments in Ankylosing Spondylitis International Study. We examined 2‐year radiographic progression data scored using the modified Stoke AS Spine Score (mSASSS).ResultsComplete data were available on 97 patients. Only the biomarkers YKL‐40 and MMP‐3 showed weak to moderate univariate correlation with 2‐year progression. After adjustment for sex, age, disease duration, C‐reactive protein level, and baseline mSASSS, only MMP‐3 was significantly associated with 2‐year progression (β = 0.29, P = 0.004). Logistic regression analysis revealed MMP‐3 (cutoff 68 ng/ml; odds ratio 9.4 [95% confidence interval 1.6–56]) and baseline mSASSS (cutoff 10 mSASSS units; odds ratio 18.6 [95% confidence interval 2.5–138]) as the only independent predictors of 2‐year progression (cutoff 3 mSASSS units; model R2 = 50%). MMP‐3 was primarily contributory in patients who already had substantial baseline damage (>10 mSASSS units).ConclusionThese results indicate that MMP‐3 is a significant independent predictor of radiographic progression in patients with AS, particularly in those with preexisting radiographic damage.
Urinary lipocalin‐2 is associated with renal disease activity in human lupus nephritis
Authors: Pitashny Milena , Schwartz Noa , Qing Xiaoping , Hojaili Bernard , Aranow Cynthia , Mackay Meggan , Putterman Chaim 
Published: May 2007

AbstractObjectivePathogenic monoclonal anti–double‐stranded DNA (anti‐dsDNA) antibodies up‐regulate the expression of lipocalin‐2 in glomerular mesangial cells. This study was undertaken to investigate whether polyclonal anti‐dsDNA antibodies promote the local secretion of lipocalin‐2 in the kidneys of patients with systemic lupus erythematosus (SLE), and whether urinary lipocalin‐2 represents a marker of kidney involvement in SLE.MethodsHispanic, African American, and white patients with SLE and normal healthy control subjects from affiliated hospitals of the Albert Einstein College of Medicine were recruited for this cross‐sectional study. Patients were classified based on the presence of active renal disease according to the SLE Disease Activity Index (SLEDAI). Correlations of clinical and laboratory data with urinary and serum levels of lipocalin‐2 were assessed.ResultsAmong SLE patients, urinary lipocalin‐2 levels were significantly higher in those with lupus nephritis (LN) (median 17.1 ng/mg creatinine, interquartile range [IQR] 10.3–45.4; n = 32) than in those without LN (median 11.2 ng/mg creatinine, IQR 3.1–20.3; n = 38) (P = 0.023). Compared with the values in normal controls (median 4 ng/ml, IQR 0–11.1; n = 14), urinary levels of lipocalin‐2 in SLE patients were significantly higher (non‐normalized median 19.3 ng/ml, IQR 8–34.2) (P = 0.004). The presence of lipocalin‐2 in the urine of patients with LN correlated significantly with the renal SLEDAI score (r = 0.452, P = 0.009), but not with extrarenal disease activity.ConclusionThe high prevalence of LN in SLE patients and the prognostic significance of kidney disease support the need for identifying early biomarkers to assess the risk of nephritis development and for following up patients with established disease. These findings indicate that urinary lipocalin‐2 is a potential marker of the presence and severity of renal involvement in adult patients with SLE.
Anti–tumor necrosis factor α therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis
Authors: Schneeweiss Sebastian , Setoguchi Soko , Weinblatt Michael E. , Katz Jeffrey N. , Avorn Jerry , Sax Paul E. , Levin Raisa , Solomon Daniel H. 
Published: May 2007

AbstractObjectiveTo assess the association between the initiation of anti–tumor necrosis factor α (anti‐TNFα) therapy and the risk of serious bacterial infections in routine care.MethodsThis was a cohort study of patients with rheumatoid arthritis (RA) in whom specific disease‐modifying antirheumatic drugs (DMARDs) were initiated. Patients were Medicare beneficiaries ages 65 years and older (mean age 76.5 years) who were concurrently enrolled in the Pharmaceutical Assistance Contract for the Elderly provided by the state of Pennsylvania. A total of 15,597 RA patients in whom a DMARD was initiated between January 1, 1995 and December 31, 2003 were identified using linked data on all prescription drug dispensings, physician services, and hospitalizations. Initiation of anti‐TNFα therapy, cytotoxic agents other than methotrexate (MTX), noncytotoxic agents, and glucocorticoids was compared with initiation of MTX. The main outcome measure was serious bacterial infections that required hospitalization.ResultsThe incidence of serious bacterial infections was, on average, 2.2 per 100 patient‐years in this population (95% confidence interval [95% CI] 2.0–2.4). Glucocorticoid use doubled the rate of serious bacterial infections as compared with MTX use, independent of previous DMARD use (rate ratio [RR] 2.1 [95% CI 1.5–3.1]), with a clear dose‐response relationship for dosages >5 mg/day (for ≤5 mg/day, RR 1.34; for 6–9 mg/day, RR 1.53; for 10–19 mg/day, RR 2.97; and for ≥20 mg/day, RR 5.48 [Pfor trend < 0.0001]). Adjusted models showed no increase in the rate of serious infections among initiators of anti‐TNFα therapy (RR 1.0 [95% CI 0.6–1.7]) or other DMARDs as compared with initiators of MTX.ConclusionIn a large cohort of patients with RA, we found no increase in serious bacterial infections among users of anti‐TNFα therapy compared with users of MTX. Glucocorticoid use was associated with a dose‐dependent increase in such infections.
Targeted mast cell silencing protects against joint destruction and angiogenesis in experimental arthritis in mice
Authors: Kneilling Manfred , Hültner Lothar , Pichler Bernd J. , Mailhammer Reinhard , Morawietz Lars , Solomon Samuel , Eichner Martin , Sabatino Joseph , Biedermann Tilo , Krenn Veit , Weber Wolfgang A. , Illges Harald , Haubner Roland , Röcken Martin 
Published: May 2007

AbstractObjectiveInduction of arthritis with autoantibodies against glucose‐6‐phosphate isomerase (GPI) is entirely independent of T cells and B cells but is strictly dependent on the presence of mast cells. Here, we used this disease model to analyze whether exclusive intraarticular mast cell reconstitution is sufficient for disease induction and whether targeted mast cell silencing can prevent neoangiogenesis and joint destruction, 2 hallmarks of rheumatoid arthritis.MethodsAnkle swelling and clinical index scores were determined after injection of either K/BxN mouse–derived serum or control serum in wild‐typeKit+/Kit+mice, congenic mast cell–deficientKitW/KitW‐vmice, or mast cell–deficientKitW/KitW‐vmice reconstituted with mast cells, either by intraperitoneal or selective intraarticular injection. Angiogenesis was quantified in vivo by measuring activated αvβ3 integrin using18F–galacto‐RGD and positron emission tomography. In addition, staining of joint tissue with hematoxylin and eosin, Giemsa, β3, and α‐actin was performed. The effect of mast cell stabilization by treatment with cromolyn or salbutamol was investigated in C57BL/6 or BALB/c mice.ResultsComparing wild‐type mice, mast cell–deficientKitW/KitW‐vmice, and mast cell–reconstitutedKitW/KitW‐vmice, we first showed that intraarticular and intraperitoneal mast cell engraftment fully restores susceptibility to antibody‐induced arthritis, angiogenesis, and αvβ3 integrin activation. Importantly, selective mast cell silencing with either salbutamol or cromolyn prevented αvβ3 integrin activation, angiogenesis, and joint destruction.ConclusionMast cell engraftment fully restores susceptibility to αvβ3 integrin activation, angiogenesis, and joint destruction in GPI antibody–induced arthritis. Importantly, selective mast cell stabilization prevents αvβ3 integrin activation, angiogenesis, and joint destruction.
Fluvastatin reverses endothelial dysfunction and increased vascular oxidative stress in rat adjuvant‐induced arthritis
Authors: Haruna Yoshisuke , Morita Yoshitaka , Yada Toyotaka , Satoh Minoru , Fox David A. , Kashihara Naoki 
Published: May 2007

AbstractObjectiveTo investigate the effect of statins on vascular dysfunction in rat adjuvant‐induced arthritis (AIA).MethodsFluvastatin (5 mg/kg/day) was administered orally to rats with AIA, for 21 days after the onset of arthritis. The vasodilatory response to acetylcholine of aortic rings isolated from rats with AIA that were not treated or were treated with fluvastatin and from normal rats was determined. The amounts of 4‐hydroxy‐2‐nonenal (HNE) and nitrotyrosine in aortas were measured by Western blotting. In vitro and in situ superoxide production in aortas was evaluated based on fluorogenic oxidation of dihydroethidium to ethidium. Expression of NAD(P)H components and endothelial nitric oxide synthase (eNOS) in aortas was examined by real‐time reverse transcriptase–polymerase chain reaction and Western blotting. Serum levels of tetrahydrobiopterin, a critical eNOS cofactor, were determined by high‐performance liquid chromatography.ResultsFluvastatin reversed endothelial dysfunction in AIA without affecting the clinical severity of arthritis or serum cholesterol concentration. Fluvastatin reduced the amounts of HNE and nitrotyrosine in the aorta, and the levels of superoxide expressed in endothelial cells and smooth muscle cells in the tissue, in rats with AIA. NADH‐ or L‐arginine–induced superoxide production was not observed in the aortic samples from fluvastatin‐treated rats with AIA. Fluvastatin decreased the levels of expression of messenger RNA for p22phox, a NAD(P)H oxidase component, in the aortas of rats with AIA, but did not affect the expression of eNOS. Serum levels of tetrahydrobiopterin were significantly reduced in rats with AIA, and were increased by administration of fluvastatin.ConclusionOur findings demonstrate that fluvastatin has potent vascular protective effects in AIA and provide additional scientific rationale for the use of statins to reduce cardiovascular mortality in patients with rheumatoid arthritis.
Reduced expression of decay‐accelerating factor 1 on CD4+ T cells in murine systemic autoimmune disease
Authors: Cauvi David M. , Cauvi Gabrielle , Pollard K. Michael 
Published: May 2007

AbstractObjectiveDeficiency of decay‐accelerating factor 1 (termed Daf1 in mice) has been shown to exacerbate autoimmunity, and recent studies have suggested that this may be explained by Daf1 acting as a regulator of T cell immunity. The aim of this study was to determine whether Daf1 expression on T cells is modulated during development of autoimmunity in mice.MethodsTo test this hypothesis, we examined Daf1 levels in NZB, DBA/2, and B10.S mice before and after induction of murine mercury‐induced autoimmunity (mHgIA). Daf1 was measured by real‐time polymerase chain reaction and flow cytometry, and levels of Daf1 were correlated with markers of lymphocyte activation and cytokine production.ResultsAutoimmune‐prone NZB mice had low endogenous levels of Daf1 irrespective of the induction of mHgIA. Induction of autoimmunity reduced Daf1 expression in mHgIA‐sensitive B10.S mice, particularly on activated/memory (CD44high) CD4+ T cells that accumulate as a result of exposure to mercury. Murine mercury‐induced autoimmunity–resistant DBA/2 mice, which fail to accumulate CD44high T cells, showed no change in Daf1 expression. Modulation of Daf1 expression was found to require CD4+ T cell costimulation, since B10.S mice deficient in CD28 were unable to down‐regulate Daf1 or accumulate activated/memory CD4+ T cells. In B10.S mice exposed to mercury, the production of interleukin‐4 (IL‐4), but not that of IL‐2 or interferon‐γ, in the spleen was associated with CD44high,Daf1low,CD4+ T cells.ConclusionThese findings demonstrate that reduction of Daf1 expression is closely associated with CD4+ T cell activation and the accumulation of CD44high(activated/memory),CD4+ T cells in both spontaneous and induced systemic autoimmune disease.
A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent‐onset rheumatoid arthritis
Authors: Wessels Judith A. M. , van der Kooij Sjoerd M. , le Cessie Saskia , Kievit Wietske , Barerra Pilar , Allaart Cornelia F. , Huizinga Tom W. J. , Guchelaar Henk‐Jan ,   Pharmacogenetics Collaborative Research Group
Published: May 2007

AbstractObjectiveTo develop a clinical pharmacogenetic model to predict the efficacy of methotrexate (MTX) in rheumatoid arthritis (RA).MethodsTwo hundred five patients with newly diagnosed RA and active disease were treated with MTX (initiated at a dosage of 7.5 mg/week and increased to 15 mg/week after 4 weeks) and folic acid (1 mg/day). If the Disease Activity Score (DAS) was >2.4 at 3 months, the dosage of MTX was increased up to 25 mg/week. Twenty‐four baseline variables possibly influencing disease state and drug response were selected. In addition, 17 polymorphisms in 13 genes related to the MTX mechanism of action, purine and pyrimidine synthesis, were determined. Factors were compared between responders (defined as patients with a DAS ≤2.4 at 6 months) and nonresponders. In case of differences, a stepwise selection procedure identified the predictors for response. A clinical score was designed by simplifying regression coefficients of the independent variables. Cutoff levels were chosen based on the clinical score, and positive and negative response rates were calculated. An evaluation of the model was performed in a second group of patients.ResultsThe model for MTX efficacy consisted of sex, rheumatoid factor and smoking status, the DAS, and 4 polymorphisms in the AMPD1, ATIC, ITPA, and MTHFD1 genes. This prediction model was transformed into a scoring system ranging from 0 to 11.5. Scores of ≤3.5 had a true positive response rate of 95%. Scores of ≥6 had a true negative response rate of 86%. Sixty percent of the patients were categorized as either responders or nonresponders, whereas 32% of the patients were categorized using a nongenetic model. Evaluation of the model in 38 additional patients with RA supported the results.ConclusionThis study established a model for predicting the efficacy of MTX in patients with RA. This pharmacogenetic model may lead to better‐tailored initial treatment decisions in patients with RA.
Specific gene expression profiles in systemic juvenile idiopathic arthritis
Authors: Ogilvie Emma Mary , Khan Arshad , Hubank Mike , Kellam Paul , Woo Patricia 
Published: May 2007

AbstractObjectivePatients with systemic juvenile idiopathic arthritis (JIA) have arthritis, quotidian fevers, and other extraarticular features. This disease often remains severe and debilitating. The purpose of this study was to compare gene expression profiles in peripheral blood mononuclear cells (PBMCs) from patients with active and inactive systemic JIA to define and better understand the cause of active disease.MethodsGene expression profiles of PBMCs were determined in cells from 9 patients with active systemic JIA and 8 patients with inactive systemic JIA. Unsupervised clustering and significance analysis were performed. We compared the systemic JIA profile with data from patients with polyarticular JIA, chronic infantile neurologic, cutaneous, articular syndrome, Kawasaki disease, and systemic lupus erythematosus to identify disease‐specific genes. Quantitative reverse transcription–polymerase chain reaction of selected genes was performed on negatively selected B cells, T cells, and monocytes.ResultsUnsupervised clustering of expressed genes resulted in 2 groups that corresponded to the clinical status of the patients (active and inactive disease) and was independent of their medications. A total of 286 genes were identified as significantly up‐regulated in patients with active disease and 86% of them were specific to systemic JIA. Interleukin‐6 (IL‐6) was expressed in monocytes and B cells, IL‐10 in monocytes, and suppressor of cytokine signaling 3 in monocytes and T cells from patients with active disease.ConclusionGene expression profiles in PBMCs identified disease‐specific genes in patients with systemic JIA. Cell type analyses should allow further insight into the mechanisms of the disease.
Tumor necrosis factor α activates release of B lymphocyte stimulator by neutrophils infiltrating the rheumatoid joint
Authors: Assi Lakhvir K. , Wong See Heng , Ludwig Andreas , Raza Karim , Gordon Caroline , Salmon Michael , Lord Janet M. , Scheel‐Toellner Dagmar 
Published: May 2007

AbstractObjectiveThe tumor necrosis factor (TNF) family member B lymphocyte stimulator (BLyS) is an important regulator of B cell–dependent autoimmunity. Similar to other TNF family members, it is generally expressed as a transmembrane protein and cleaved from the surface to release its active soluble form. This study was undertaken to investigate the expression of BLyS and regulation of BLyS release from the surface of neutrophils infiltrating the rheumatoid joint.MethodsBLyS expression was studied in neutrophils from the synovial fluid and peripheral blood of patients with rheumatoid arthritis (RA) and healthy controls, by flow cytometry, Western blotting, and immunofluorescence analyses. Peripheral blood neutrophils cultured with 50% RA synovial fluid were study for membrane expression of BLyS. Neutrophils were exposed to a range of proinflammatory cytokines to study the mechanisms of surface loss of BLyS.ResultsExpression of BLyS was detected on the surface of peripheral blood neutrophils from both RA patients and healthy controls, whereas BLyS expression on synovial fluid neutrophils was very low. Constitutive expression of BLyS was observed in neutrophils, both on the cell membrane and in intracellular stores; however, BLyS release from each of these sites was found to be regulated independently. Of the various cytokine stimuli, only TNFα triggered release of BLyS from the neutrophil membrane. This process led to release of physiologically relevant quantities of soluble BLyS, which was dependent on the presence of the pro‐protein convertase furin. In contrast, stimulation of neutrophils with granulocyte colony‐stimulating factor induced BLyS release from the intracellular stores. Incubation of peripheral blood neutrophils with RA synovial fluid led to TNFα‐dependent shedding of BLyS from the cell surface.ConclusionThese findings indicate that as neutrophils enter the site of inflammation, they release surface‐expressed BLyS in a TNFα‐dependent manner, and thus may contribute to local stimulation of autoimmune B cell responses.
Protection against renal disease in (NZB × NZW)F1 lupus‐prone mice after somatic B cell gene vaccination with anti‐DNA immunoglobulin consensus peptide
Authors: Ferrera Francesca , Hahn Bevra H. , Rizzi Marta , Anderson Marissa , FitzGerald John , Millo Enrico , Indiveri Francesco , Shi Fu‐Dong , Filaci Gilberto , La Cava Antonio 
Published: May 2007

AbstractObjectiveIg molecules contain epitopes that can induce T cell–mediated immune responses. B cells can process and present such epitopes and activate T cells. The purpose of the present study was to test our hypothesis that T cells that recognize an Ig consensus sequence presented by B cells will modulate lupus‐like disease in mice.Methods(NZB × NZW)F1 (NZB/NZW) lupus mice received somatic B cell gene transfer of a DNA plasmid encoding a consensus sequence of T cell determinants of murine anti‐DNA IgG or control plasmids. Treated animals were monitored for the production of antibody, the development of renal disease, and the phenotype, number, and function of T cells.ResultsTreatment of mice with Ig consensus plasmid induced transforming growth factor β–producing CD8+,CD28– T cells that suppressed the antigen‐specific stimulation of CD4+ T cells in a cell‐contact–independent manner, reduced antibody production, retarded the development of nephritis, and improved survival. Significantly, adoptive transfer of CD8+,CD28– T cells from protected mice into hypergammaglobulinemic NZB/NZW mice effectively protected the transferred mice from the development of renal disease.ConclusionGene expression of anti‐DNA Ig consensus sequence induces immunoregulatory T cells that delay the development of lupus nephritis by suppressing hypergammaglobulinemia and renal disease.