bluuebunny/crossref_metadata_2025_split huggingface dataset:
Invariant natural killer T cells are natural regulators of murine spondylarthritis
Authors: Jacques Peggy , Venken Koen , Van Beneden Katrien , Hammad Hamida , Seeuws Sylvie , Drennan Michael B. , Deforce Dieter , Verbruggen Gust , Apostolaki Maria , Kollias George , Lambrecht Bart N. , De Vos Martine , Elewaut Dirk 
Published: January 2010

AbstractObjectiveTo investigate the role of invariant natural killer T (iNKT) cells in TNFΔARE/+ mice, an animal model of spondylarthritis (SpA) with both gut and joint inflammation.MethodsThe frequency and activation of iNKT cells were analyzed on mononuclear cells from the lymph nodes and livers of mice, using flow cytometry with α‐galactosylceramide/CD1d tetramers and quantitative polymerase chain reaction for the invariant Vα14–Jα18 rearrangement. Bone marrow–derived dendritic cells (DCs) were obtained by expansion of primary cells with granulocyte–macrophage colony‐stimulating factor followed by coculture with iNKT cell hybridomas, and interleukin‐2 release into the cocultures was then measured by enzyme‐linked immunosorbent assay (ELISA). Cytokine levels were determined by ELISA or cytometric bead array analyses of freshly isolated DCs and iNKT cells in mixed cocultures. TNFΔARE/+ mice were backcrossed onto Jα18−/− and CD1d−/− mice, and disease onset was evaluated by clinical scoring, positron emission tomography, and histology. CD1d levels were analyzed on mononuclear cells in paired blood and synovial fluid samples from patients with SpA compared with healthy control subjects.ResultsIn the absence of iNKT cells, symptoms of gut and joint inflammation in TNFΔARE/+mice were aggravated. Invariant NKT cells were activated during the course of the disease. This was linked to an enrichment of inflammatory DCs, characterized by high levels of CD1d, particularly at draining sites of inflammation. A similar increase in CD1d levels was observed on DCs from patients with SpA. Inflammatory DCs from TNFΔARE/+ mice stimulated iNKT cells to produce immunomodulatory cytokines, in the absence of exogenous stimulation. Prolonged, continuous exposure, but not short‐term exposure, to tumor necrosis factor (TNF) was found to be responsible for the enhanced DC–NKT cell crosstalk.ConclusionThis mode of iNKT cell activation represents a natural counterregulatory mechanism for the dampening of TNF‐driven inflammation.
High versus low dosing of oral colchicine for early acute gout flare: Twenty‐four–hour outcome of the first multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group, dose‐comparison colchicine study
Authors: Terkeltaub Robert A. , Furst Daniel E. , Bennett Katherine , Kook Karin A. , Crockett R. S. , Davis Matthew W. 
Published: January 2010

AbstractObjectiveDespite widespread use of colchicine, the evidence basis for oral colchicine therapy and dosing in acute gout remains limited. The aim of this trial was to compare low‐dose colchicine (abbreviated at 1 hour) and high‐dose colchicine (prolonged over 6 hours) with placebo in gout flare, using regimens producing comparable maximum plasma concentrations in healthy volunteers.MethodsThis multicenter, randomized, double‐blind, placebo‐controlled, parallel‐group study compared self‐administered low‐dose colchicine (1.8 mg total over 1 hour) and high‐dose colchicine (4.8 mg total over 6 hours) with placebo. The primary end point was ≥50% pain reduction at 24 hours without rescue medication.ResultsThere were 184 patients in the intent‐to‐treat analysis. Responders included 28 of 74 patients (37.8%) in the low‐dose group, 17 of 52 patients (32.7%) in the high‐dose group, and 9 of 58 patients (15.5%) in the placebo group (P = 0.005 and P = 0.034, respectively, versus placebo). Rescue medication was taken within the first 24 hours by 23 patients (31.1%) in the low‐dose group (P = 0.027 versus placebo), 18 patients (34.6%) in the high‐dose group (P = 0.103 versus placebo), and 29 patients (50.0%) in the placebo group. The low‐dose group had an adverse event (AE) profile similar to that of the placebo group, with an odds ratio (OR) of 1.5 (95% confidence interval [95% CI] 0.7–3.2). High‐dose colchicine was associated with significantly more diarrhea, vomiting, and other AEs compared with low‐dose colchicine or placebo. With high‐dose colchicine, 40 patients (76.9%) had diarrhea (OR 21.3 [95% CI 7.9–56.9]), 10 (19.2%) had severe diarrhea, and 9 (17.3%) had vomiting. With low‐dose colchicine, 23.0% of the patients had diarrhea (OR 1.9 [95% CI 0.8–4.8]), none had severe diarrhea, and none had vomiting.ConclusionLow‐dose colchicine yielded both maximum plasma concentration and early gout flare efficacy comparable with that of high‐dose colchicine, with a safety profile indistinguishable from that of placebo.
Estradiol inhibits chondrogenic differentiation of mesenchymal stem cells via nonclassic signaling
Authors: Jenei‐Lanzl Zsuzsa , Straub Rainer H. , Dienstknecht Thomas , Huber Marion , Hager Markus , Grässel Susanne , Kujat Richard , Angele Martin K. , Nerlich Michael , Angele Peter 
Published: January 2010

AbstractObjectiveWe undertook this study to examine the effects of estradiol on chondrogenesis of human bone marrow–derived mesenchymal stem cells (MSCs), with consideration of sex‐dependent differences in cartilage repair.MethodsBone marrow was obtained from the iliac crest of young men. Density‐gradient centrifugation–separated human MSCs proliferated as a monolayer in serum‐containing medium. After confluence was achieved, aggregates were created and cultured in a serum‐free differentiation medium. We added different concentrations of 17β‐estradiol (E2) with or without the specific estrogen receptor inhibitor ICI 182.780, membrane‐impermeable E2–bovine serum albumin (E2‐BSA), ICI 182.780 alone, G‐1 (an agonist of G protein–coupled receptor 30 [GPR‐30]), and G15 (a GPR‐30 antagonist). After 21 days, the aggregates were analyzed histologically and immunohistochemically; we quantified synthesized type II collagen, DNA content, sulfated glycosaminoglycan (sGAG) concentrations, and type X collagen and matrix metalloproteinase 13 (MMP‐13) expression.ResultsThe existence of intracellular and membrane‐associated E2 receptors was shown at various stages of chondrogenesis. Smaller aggregates and significantly lower type II collagen and sGAG content were detected after treatment with E2 and E2‐BSA in a dose‐dependent manner. Furthermore, E2 enhanced type X collagen and MMP‐13 expression. Compared with estradiol alone, the coincubation of ICI 182.780 with estradiol enhanced suppression of chondrogenesis. Treatment with specific GPR‐30 agonists alone (G‐1 and ICI 182.780) resulted in a considerable inhibition of chondrogenesis. In addition, we found an enhancement of hypertrophy by G‐1. Furthermore, the specific GPR‐30 antagonist G15 reversed the GPR‐30–mediated inhibition of chondrogenesis and up‐regulation of hypertrophic gene expression.ConclusionThe experiments revealed a suppression of chondrogenesis by estradiol via membrane receptors (GPR‐30). The study opens new perspectives for influencing chondrogenesis on the basis of classic and nonclassic estradiol signaling.
Endogenous estrogen regulation of inflammatory arthritis and cytokine expression in male mice, predominantly via estrogen receptor α
Authors: Yang Y. H. , Ngo D. , Jones M. , Simpson E. , Fritzemeier K. H. , Morand E. F. 
Published: January 2010

AbstractObjectiveA number of experimental observations have associated elevated estrogen levels with amelioration of inflammation. The involvement of estrogen and estrogen receptor (ER) isotypes in the regulation of inflammation in males is not well understood. In this study, we used specific ERα and ERβ agonists in male mice deficient in estrogen because of a deletion of aromatase (aromatase‐knockout [ArKO] mice) to investigate ER isotype utilization in estrogen regulation of inflammation.MethodsLipopolysaccharide (LPS)‐induced cytokine expression and antigen‐induced arthritis (AIA) were investigated in male ArKO and WT littermate mice, as well as in response to selective agonists of ERα (16α‐LE2) and ERβ (8β‐VE2). The therapeutic effect of selective ER agonists was also examined in mice with collagen‐induced arthritis (CIA).ResultsEstrogen deficiency in ArKO mice was associated with significant increases in LPS‐induced serum interleukin‐6 (IL‐6), tumor necrosis factor, monocyte chemotactic protein 1, and interferon‐γ levels, which were significantly abrogated by administration of 16α‐LE2, but not 8β‐VE2. In contrast, both 16α‐LE2 and 8β‐VE2 significantly increased LPS‐induced IL‐10 levels. Estrogen deficiency was also associated with significant exacerbation of AIA and antigen‐specific T cell proliferation, which was reversed by administration of either 16α‐LE2 or 8β‐VE2. ArKO mice showed increased antigen‐specific T cell proliferation in response to immunization with type II collagen (CII). Administration of 16α‐LE2, but not 8β‐VE2, significantly reduced the severity of CIA, which was associated with inhibition of anti‐CII–specific IgG.ConclusionThese data indicate that endogenous estrogen plays an essential inhibitory role in inflammation in male mice and that ERα is the dominant receptor that mediates these effects.
Cutaneous manifestations of neonatal lupus and risk of subsequent congenital heart block
Authors: Izmirly Peter M. , Llanos Carolina , Lee Lela A. , Askanase Anca , Kim Mimi Y. , Buyon Jill P. 
Published: January 2010

AbstractObjectiveCutaneous disease associated with placental transport of maternal anti‐SSA/Ro or anti‐SSB/La antibodies is transient, and children often appear to be otherwise healthy. However, the impact of this manifestation of neonatal lupus (NL) on the risk of cardiac disease occurring in a future pregnancy is critical for family counseling and for powering preventive trials. The purpose of this study was to determine the recurrence rates of NL, with specific focus on cardiac NL following cutaneous NL in a child enrolled in the Research Registry for Neonatal Lupus (RRNL).MethodsFifty‐eight families who were enrolled in the RRNL met the following inclusion criteria for our study: maternal anti‐SSA/Ro or anti‐SSB/La antibodies, a child with cutaneous NL, and a pregnancy subsequent to the child with cutaneous NL.ResultsThe majority of the 58 mothers (78%) were Caucasian. Of 77 pregnancies that occurred following the birth of a child with cutaneous NL, the overall recurrence rate for any manifestation of NL was 49% (95% confidence interval [95% CI] 37–62%); 14 pregnancies (18.2%) were complicated by cardiac NL, 23 (29.9%) by cutaneous NL, and 1 (1.3%) by hematologic/hepatic NL. A subset analysis was restricted to the 39 children who were born after the initial child with cutaneous NL had been enrolled in the RRNL. The overall recurrence rate for NL was 36% (95% CI 20–52%); 5 pregnancies (12.8%) were complicated by cardiac NL and 9 (23.1%) by cutaneous NL. There were no significant differences in the following maternal risk factors for having a subsequent child with cardiac or cutaneous NL: age, race/ethnicity, anti‐SSB/La status, diagnosis, use of nonfluorinated steroids, or breastfeeding. The sex of the subsequent fetus did not influence the development of cardiac or cutaneous NL.ConclusionBased on data from this large cohort, the identification of cutaneous NL in an anti‐SSA/Ro antibody–exposed infant is particularly important, since it predicts a 6–10‐fold risk of a subsequent child developing cardiac NL.
Nucleotide‐binding oligomerization domain 2 and Toll‐like receptor 2 function independently in a murine model of arthritis triggered by intraarticular peptidoglycan
Authors: Rosenzweig Holly L. , Jann Monica J. , Vance Emily E. , Planck Stephen R. , Rosenbaum James T. , Davey Michael P. 
Published: January 2010

AbstractObjectiveBlau syndrome is an autoinflammatory disease resulting from mutations in the NOD2 gene, wherein granulomatous arthritis, uveitis, and dermatitis develop. The mechanisms by which aberrant NOD2 causes joint inflammation are poorly understood. Indeed, very few studies have addressed the function of nucleotide‐binding oligomerization domain 2 (NOD‐2) in the joint. This study was undertaken to investigate NOD‐2 function in an experimental model of arthritis and to explore the potential interplay between Toll‐like receptor 2 (TLR‐2) and NOD‐2 in joint inflammation.MethodsMice deficient in TLR‐2, myeloid differentiation factor 88 (MyD88), or NOD‐2 and their wild‐type controls were given an intraarticular injection of muramyl dipeptide (MDP), peptidoglycan (PG; a metabolite of which is MDP), or palmitoyl‐3‐cysteine‐serine‐lysine‐4 (Pam3CSK4), a synthetic TLR‐2 agonist. Joint inflammation was assessed by near‐infrared fluorescence imaging and histologic analysis.ResultsLocally administered PG resulted in joint inflammation, which was markedly reduced in mice deficient in either TLR‐2 or the TLR signaling mediator MyD88. In addition to TLR‐2 signaling events, NOD‐2 mediated joint inflammation, as evidenced by the fact that mice deficient in NOD‐2 showed significantly reduced PG‐induced arthritis. TLR‐2 or MyD88 deficiency did not influence arthritis induced by the specific NOD‐2 agonist MDP. In addition, NOD‐2 deficiency did not alter the TLR‐2–dependent joint inflammation elicited by the synthetic TLR‐2 agonist Pam3CSK4.ConclusionWhereas NOD‐2 and TLR‐2 are both critical for the development of PG‐induced arthritis, they appear to elicit inflammation independently of each other. Our findings indicate that NOD‐2 plays an inflammatory role in arthritis.
Interleukin‐23 promotes Th17 differentiation by inhibiting T‐bet and FoxP3 and is required for elevation of interleukin‐22, but not interleukin‐21, in autoimmune experimental arthritis
Authors: Mus Adriana M. C. , Cornelissen Ferry , Asmawidjaja Patrick S. , van Hamburg Jan Piet , Boon Louis , Hendriks Rudi W. , Lubberts Erik 
Published: January 2010

AbstractObjectiveTo examine the role of interleukin‐23 (IL‐23) in subgroup polarization of IL‐17A–positive and/or interferon‐γ (IFNγ)–positive T cells in autoimmune disease–prone DBA/1 mice with and without collagen‐induced arthritis.MethodsA magnetic‐activated cell sorting system was used to isolate CD4+ T cells from the spleen of naive and type II collagen (CII)–immunized DBA/1 mice. These CD4+ T cells were stimulated in vitro under Th0, Th1, or different Th17 culture conditions. Intracellular staining for IL‐17A and IFNγ was evaluated by flow cytometry. In addition, Th17 cytokines and T helper–specific transcription factors were analyzed by enzyme‐linked immunosorbent assay and/or quantitative polymerase chain reaction.ResultsIn CD4+ T cells from naive DBA/1 mice, IL‐23 alone hardly induced retinoic acid–related orphan receptor γt (RORγt), Th17 polarization, and Th17 cytokines, but it inhibited T‐bet expression. In contrast, transforming growth factor β1 (TGFβ1)/IL‐6 was a potent inducer of RORγt, RORα, IL‐17A, IL‐17F, IL‐21, and FoxP3 in these cells. In contrast to TGFβ1/IL‐6, IL‐23 was critical for the induction of IL‐22 in CD4+ T cells from both naive and CII‐immunized DBA/1 mice. Consistent with these findings, IL‐23 showed a more pronounced induction of the IL‐17A+IFNγ– subset in CD4+ T cells from CII‐immunized mice. However, in CD4+ T cells from naive mice, IL‐23 significantly increased the TGFβ1/IL‐6–induced Th17 polarization, including elevated levels of IL‐17A and IL‐17F and decreased expression of T‐bet and FoxP3. Of note, the IL‐23–induced increase in IL‐17A and IL‐17F levels was prevented in T‐bet–deficient mice.ConclusionIL‐23 promotes Th17 differentiation by inhibiting T‐bet and FoxP3 and is required for elevation of IL‐22, but not IL‐21, levels in autoimmune arthritis. These data indicate different mechanisms for IL‐23 and TGFβ1/IL‐6 at the transcription factor level during Th17 differentiation in autoimmune experimental arthritis.
Epidemiology of gout in women: Fifty‐two–year followup of a prospective cohort
Authors: Bhole Vidula , de Vera Mary , Rahman M. Mushfiqur , Krishnan Eswar , Choi Hyon 
Published: January 2010

AbstractObjectiveDespite the recent doubling of the incidence of gout among women and its substantial prevalence particularly in the aging female population, the risk factors for gout among women remain unknown. We undertook this study to evaluate purported risk factors for incident gout among women and to compare them with those among men.MethodsUsing prospective data from the Framingham Heart Study, we examined over a 52‐year period (1950–2002) the relationship between purported risk factors and the incidence of gout in 2,476 women and 1,951 men.ResultsWe documented 304 incident cases of gout, 104 of them among women. The incidence rates of gout for women per 1,000 person‐years according to serum uric acid levels of <5.0, 5.0–5.9, 6.0–6.9, 7.0–7.9, and ≥8.0 mg/dl were 0.8, 2.5, 4.2, 13.1, and 27.3, respectively (P for trend < 0.0001). The magnitude of this association was lower than that among men (P for interaction = 0.0002). Multivariate relative risks conferred by increasing age (per 5 years), obesity (body mass index ≥30 kg/m2), alcohol intake (≥7 ounces of pure alcohol/week), hypertension, and diuretic use were 1.24, 2.74, 3.10, 1.82, and 2.39, respectively (all P < 0.05), for women.ConclusionThese prospective data with long‐term followup provide evidence that higher levels of serum uric acid increase the risk of gout in a graded manner among women, but the rate of increase is lower than that among men. Increasing age, obesity, alcohol consumption, hypertension, and diuretic use were associated with the risk of incident gout among women.
Fluorescence Sensing of Phytate in Water Using an Isothiouronium‐attached Polythiophene
Authors: Minami Tsuyoshi , Kubo Yuji 
Published: January 2010

AbstractA water‐soluble isothiouronium‐attached polythiophene (1poly) is prepared for the first time by the oxidative polymerization of 3‐(3‐(N‐(2‐methoxyethoxy)ethyl‐N‐methyl‐S‐isothiouronio)propoxy‐4‐methylthiophene (1) with FeCl3. The gel‐permeation chromatography analysis allows us to estimate the number average molecular weight (Mn) and the polydispersity index (PDI) to be 5.68×105 and 1.4, respectively. The polymers (excited at 438 nm) show an absorption band at 438 nm and fluorescence at 546 nm, with 1.2 % fluorescence quantum yield when fluorescein was used as a reference. The pH‐dependent absorption spectra at varying pH, indicates that aggregation starts at neutral conditions. At pH 5.5, 1poly exhibits a significant quenching in the fluorescence upon the addition of phytate (IP6), as a plausible analyte. This response is higher than that in the case of other anions such as adenosine 5‐triphosphate (ATP), pyrophosphate (PPi), cis,cis‐1,3,5‐cyclohexanetriol triphosphate (CTP3), and H2PO4−. As inferred from the SEM measurement, the phytate‐induced spectral change has been explained on the basis of the π‐stacked aggregation of the polymer.
Spectrofluorimetric determination of bilirubin in serum samples
Authors: Bian Weiwei , Zhang Na , Jiang Chongqiu 
Published: January 2010

AbstractA new spectrofluorimetric method was developed for determination of trace amount of bilirubin. Using oxytetracycline–Eu3+ as a fluorescent probe, in the buffer solution of pH = 7.3, bilirubin can reduce remarkably the fluorescence intensity of the oxytetracycline–Eu3+ complex at λ = 612 nm and the reduced fluorescence intensity was in proportion to the concentration of bilirubin. Optimum conditions for the determination of bilirubin were also investigated. The linear range and limit of detection for the determination of bilirubin were 5.0 × 10−7, 3.0 × 10−5 and 7.7 × 10−8 mol L−1, respectively. This method is simple, practical and relatively free of interference from coexisting substances and can be successfully applied to assess bilirubin in serum samples and compared with the modified Jendrassik–Grof method in clinical analysis. The quenching mechanism of the fluorescence intensity in the system is also discussed. Copyright © 2010 John Wiley & Sons, Ltd.
Spectrofluorimetric determination of folic acid in tablets and urine samples using 1,10‐phenanthroline‐terbium probe
Authors: Manzoori Jamshid L. , Jouyban Abolghasem , Amjadi Mohammad , Soleymani Jafar 
Published: January 2010

AbstractA new spectrofluorimetric method was reported for the determination of folic acid (FA), based on its quenching effect on the fluorescence intensity of Tb3+–1,10‐phenanthroline complex as a fluorescent probe. The quenched fluorescence intensity at an emission wavelength of 545 nm was proportional to the concentration of FA in Tris–HCl buffer solution of pH 6.2. The effects of pH, time, order of addition of reagents, temperature and concentrations of Tb3+, buffer and 1,10‐phenanthroline were investigated and optimized. The linear range for the determination of FA was 0.01–1.1 mg/L. The detection limit was 0.003 mg/L and the relative standard deviation for replicated determination of 1 mg/L of folic acid was 1.2%. This method was simple, practical and relatively free from interference effects. It was successfully applied to assess FA in pharmaceutical tablets and urine samples. Copyright © 2010 John Wiley & Sons, Ltd.
Fluorescence probe enhanced spectrofluorimetric method for the determination of sparfloxacin in tablets and biological fluids
Authors: El‐Didamony Akram M. 
Published: January 2010

AbstractYttrium‐sensitized fluorescence was used to develop a sensitive and simple spectrofluorimetric method for the determination of sparfloxacin. The method is based on the strong fluorescence of sparfloxacin after adding the fluorescence probe yttrium in buffer solution (pH = 8), and various factors influencing fluorescence were investigated. Under optimum conditions, the enhanced fluorescence intensity of the system showed a good linear relationship with the concentration of sparfloxacin over the range 8 × 10−7 to 1.4 × 10−5 mol L−1 with a correlation coefficient of 0.9997. The detection limit (S/N = 3) was determined as 9.01 × 10−8 mol L−1. The mechanism of the sensitizing effect of probe was discussed. This method has been successfully applied for the determination of sparfloxacin in pharmaceuticals, human urine and serum samples; the result obtained was satisfactory. Copyright © 2010 John Wiley & Sons, Ltd.
Pulsatile perfusion preservation of warm ischaemia-damaged experimental kidney grafts
Authors: Schreinemachers M C J M , Doorschodt B M , Florquin S , van den Bergh Weerman M A , Zernecke A , Idu M M , Tolba R H , van Gulik T M 
Published: January 2010

AbstractBackgroundCold storage using histidine–tryptophan–ketoglutarate (HTK) solution is used widely in clinical practice for the preservation of warm ischaemia-damaged kidney grafts. This study assessed the efficacy of pulsatile machine perfusion in combination with Polysol® for the preservation of warm ischaemia-damaged kidney grafts.MethodsAfter induction of warm ischaemia by clamping of the left renal pedicle for 30 min, pigs were subjected to left nephrectomy. Thereafter, grafts were preserved for 20 h by cold storage with HTK (CS-HTK) or Polysol® (CS-PS), or machine preservation with Polysol® (MP-PS). Subsequently, contralateral kidneys were removed and preserved kidneys were transplanted. Control pigs underwent unilateral nephrectomy. Renal function was assessed daily for 1 week. Kidney biopsies were analysed for morphology and proliferative response.ResultsRenal function of warm ischaemia-damaged grafts preserved using MP-PS was comparable to that of non-ischaemic controls. MP-PS and CS-PS groups showed improved renal function compared with the CS-HTK group, with more favourable results for MP-PS than for CS-PS. The proliferative response of tubular cells in the CS-HTK group was higher than in all other groups.ConclusionThis study demonstrated that the function of warm ischaemia-damaged kidney grafts after pulsatile perfusion preservation was comparable to that of non-ischaemic controls.