bluuebunny/crossref_metadata_2025_split huggingface dataset:
Importance of genetic influences on chronic widespread pain
Authors: Kato Kenji , Sullivan Patrick F. , Evengård Birgitta , Pedersen Nancy L. 
Published: April 2006

AbstractObjectiveTo estimate the relative importance of genetic and environmental factors in chronic widespread pain, and to assess whether there are sex differences in the type or magnitude of these influences.MethodsData were collected from a national sample of twins ≥42 years of age, all of whom were participants in the Swedish Twin Registry. The presence of chronic widespread pain was assessed via computer‐assisted telephone interviews, which were conducted between 1998 and 2002, using the American College of Rheumatology criteria for fibromyalgia. No clinical examinations were performed. In preliminary analyses, probandwise concordance rates and tetrachoric correlations were calculated. Structural equation modeling was then performed to estimate additive genetic, shared environmental, and nonshared environmental sources of variability in susceptibility for the development of chronic widespread pain.ResultsOf 61,355 eligible twins, 44,897 individuals (73.2%) responded to the interview. Both members of 15,950 pairs responded to the items regarding pain symptoms; of these pairs, 4,170 were monozygotic, 5,881 were same‐sex dizygotic, and 5,755 were opposite‐sex dizygotic. The prevalence of chronic widespread pain was 4.1%, and the ratio of women to men was 3.3 to 1. Probandwise concordance rates and tetrachoric correlations suggested modest genetic influences for both women and men. Genetic and shared environmental influences explained approximately half of the total variance, with no indication of sex differences in either the type or magnitude of these influences.ConclusionIndividual differences in the likelihood of developing chronic widespread pain reflect modest genetic influences. There are no significant sex differences in the type or expression of the genes responsible for chronic widespread pain or in the magnitude of the relative importance of these influences on chronic widespread pain.
Performance of an automated computer‐based scoring method to assess joint space narrowing in rheumatoid arthritis: A longitudinal study
Authors: Finckh Axel , de Pablo Paola , Katz Jeffrey N. , Neumann Gesa , Lu Ying , Wolfe Frederick , Duryea Jeffrey 
Published: April 2006

AbstractObjectiveTo compare the diagnostic performance of a computer‐based method for measuring joint space width with the Sharp joint space narrowing (JSN) scoring method in patients with rheumatoid arthritis (RA).MethodsA random sample of patients with early RA, for whom sequential hand radiographs and Sharp scores were available, was selected from the National Data Bank for Rheumatic Diseases. Hand joint space width was measured using an automated, computer‐based method in random order and with blinding for clinical information. We constructed a receiver operating characteristic curve and compared the diagnostic performance of the computer‐based and Sharp methods based on the areas under the curve.ResultsOne hundred twenty‐nine patients with early RA who underwent serial radiography were included. Changes in the computer‐based and Sharp methods were highly correlated (r = 0.75, P < 0.001). The computer‐based method was significantly more discriminant than the Sharp JSN subscale. The area under the curve of the computer‐based method was 0.96 (95% confidence interval [95% CI] 0.94, 0.99) compared with 0.93 (95% CI 0.89, 0.96) for the Sharp subscale (P = 0.024). At the most discriminant cutoff, specificity of the computer‐based method was 88.4% compared with 81.4% for the Sharp subscale (P = 0.11); sensitivity was 87.6% for the computer‐based method compared with 82.2% for Sharp subscale (P = 0.19). The signal‐to‐noise ratio for the computer‐based method was 83% compared with 70% for the Sharp subscale (P = 0.013).ConclusionThe computer‐based method for measuring joint space width is more discriminant than the semiquantitative Sharp JSN subscale.
Hyaluronan molecular reflection by synovial lining is concentration dependent and reduced in dilute effusions in a rabbit model
Authors: Sabaratnam S. , Mason R. M. , Levick J. R. 
Published: April 2006

AbstractObjectiveHyaluronan (HA) has a major role in regulating synovial fluid volume. This role depends on the synovium functioning as an ultrafilter that reflects HA during trans–synovial fluid drainage. Reflection boosts the HA concentration on the membrane surface, leading to osmotic retention of synovial fluid (“buffering”). In arthritic effusions, however, HA concentration and osmotic buffering are greatly reduced. We tested the hypothesis that reflection is reduced (escape increased) when the HA concentration falls below the molecular entanglement concentration (C*).MethodsHA at 0.2 mg/ml (<C*) or 1.5 mg/ml (>C*) was infused continuously into rabbit knee joints to set up a steady trans‐synovial filtration. Joint‐derived lymph was sampled over 3 hours, and subsynovial fluid was sampled at the end of the 3‐hour period. HA was quantified by high‐performance liquid chromatography to evaluate the reflected fraction. C* was determined by viscometry.ResultsViscometry showed that 0.2 mg/ml HA was below C* and 1.5 mg/ml was above it. At 0.2 mg/ml, the mean ± SEM HA reflected fraction was 0.66 ± 0.04 (n = 7). At 1.5 mg/ml the reflection increased to 0.88 ± 0.04 (n = 5) (P < 0.005). HA permeation increased almost 3‐fold, from 12% to 34%, at the lower concentration.ConclusionChain–chain interaction at >C* increases effective molecular domain size and hence HA reflection, promoting effective conservation of synovial fluid in normal joints. HA can fall below C* (∼1 mg/ml) in arthritic effusions, promoting loss of HA. The attendant failure of outflow buffering facilitates fluid escape and periarticular edema.
Recovery from deafness in a patient with Muckle‐Wells syndrome treated with anakinra
Authors: Mirault Tristan , Launay David , Cuisset Laurence , Hachulla Eric , Lambert Marc , Queyrel Viviane , Quemeneur Thomas , Morell‐Dubois Sandrine , Hatron Pierre‐Yves 
Published: April 2006

AbstractMuckle‐Wells syndrome (MWS) is a dominantly inherited autoinflammatory disease characterized by rashes, fever, arthralgia, sensorineural deafness, and the possible development of systemic AA amyloidosis. We used anakinra to treat a 22‐year‐old patient with MWS who had deafness and a high serum level of C‐reactive protein (CRP). Following treatment with anakinra, the patient's CRP level normalized, and she recovered from deafness. The fact that this occurrence has never been previously reported strengthens the role of anakinra in MWS but also raises new questions about the physiopathology of such deafness.
Followup radiographic data on patients with rheumatoid arthritis who participated in a two‐year trial of prednisone therapy or placebo
Authors: Jacobs Johannes W. G. , Everdingen Amalia A. Van , Verstappen Suzan M. M. , Bijlsma Johannes W. J. 
Published: April 2006

AbstractObjectiveIn a previous clinical trial of patients with early rheumatoid arthritis (RA), it was determined that patients who received 10 mg of prednisone per day for 2 years had less radiographic joint damage compared with those who received placebo. Our goal was to investigate whether this beneficial effect persisted after the end of the trial.MethodsA blinded assessment of radiographic joint damage was performed ∼3 years after the end of the original 2‐year study. Twenty‐four patients from the original prednisone group (60%) and 28 patients from the original placebo group (68%) participated in this followup study. At the end of the original trial, prednisone dosages were tapered down in the prednisone group and stopped, if possible. Patients from the original prednisone group took prednisone during 35% of the followup period (∼1 year) at a mean daily dose of ∼5 mg. Two patients from the original placebo group started taking prednisone during followup. Radiographs of the hands and feet were scored according to the van der Heijde modification of the Sharp method.ResultsDuring 3 additional years of followup, radiographic scores showed significantly less progression in the original prednisone group than in the original placebo group. Radiographic damage in the original prednisone group did not show an accelerated rate of progression during the followup period.ConclusionThe inhibition of radiographic joint damage in patients with early active RA treated with 10 mg of prednisone per day for 2 years seems to persist after the end of prednisone therapy.
Vascular endothelial growth factor gene haplotypes in Kawasaki disease
Authors: Breunis W. B. , Biezeveld M. H. , Geissler J. , Ottenkamp J. , Kuipers I. M. , Lam J. , Hutchinson A. , Welch R. , Chanock S. J , Kuijpers T. W. 
Published: April 2006

AbstractObjectiveTo investigate whether common genetic variants in the vascular endothelial growth factor (VEGF) gene are associated with Kawasaki disease (KD) and the subsequent development of coronary artery lesions.MethodsCommon genetic variants in the VEGF gene were analyzed in an association study in a Dutch cohort of 170 KD patients and 300 healthy Dutch Caucasian controls. Genotyping was done with 5′‐nuclease TaqMan assays and 3′‐hybridization–triggered fluorescence minor groove binder Eclipse assays.ResultsAn association with susceptibility to KD was observed with 2 of the 6 single‐nucleotide polymorphisms analyzed in VEGF: –2594 A>C (rs699947) and the 236 bp 3′ of STP C>T (rs3025039). Also for an 18‐bp deletion in the promoter of VEGF a significant difference in the genotype and allele frequencies was observed between the KD patients and the controls. The haplotype CGCC (based on rs699947, rs2010963, rs25648, and rs3025039) was significantly associated with the development of KD (hap score 3.8; P = 0.0002). VEGF plasma levels were significantly higher in patients with the early phase of KD than in the healthy controls, and there was a trend toward higher VEGF plasma levels in KD patients with the –2594 CC and 236 bp 3′ of STP CC genotypes.ConclusionOur results suggest that polymorphisms of the VEGF gene may play a role in the pathogenesis of KD.
Antibodies to ribosomal P proteins: A potential serologic marker for lupus membranous glomerulonephritis
Authors: do Nascimento Ana Patrícia , dos Santos Trindade Viana Vilma , de Abreu Testagrossa Leonardo , Leon Elaine Pires , Borba Eduardo Ferreria , Barros Rui Toledo , Bonfá Eloísa 
Published: April 2006

AbstractObjectiveTo evaluate the relevance of antibodies to ribosomal P proteins (anti‐P antibodies) in discriminating histopathologic patterns of lupus nephritis.MethodsThe study group comprised 81 consecutive patients with systemic lupus erythematosus who underwent renal biopsy and for whom frozen serum was available at the time of biopsy. All biopsy specimens were reviewed in a blinded manner, according to the 2004 criteria of the International Society of Nephrology and the Renal Pathology Society. Anti‐P antibodies were detected by enzyme‐linked immunosorbent assay (ELISA)/immunoblot analysis, and anti–double‐stranded DNA (anti‐dsDNA) was detected by indirect immunofluorescence/ELISA.ResultsAnti‐P antibodies were detected in 18 patients (22%). The demographic and clinical features of patients with and those without anti‐P antibodies were similar. Remarkably, analyses of biopsy specimens revealed that the frequency of anti‐P antibodies in patients with class V lupus nephritis was higher than the frequency among patients with other classes of renal disease (72% versus 28%; P = 0.005). Accordingly, anti‐P antibody–positive patients had a higher mean (±SD) proteinuria level compared with anti‐P antibody–negative patients (6.4 ± 4.8 versus 4.7 ± 3.9 gm/dl; P = 0.046). Renal function was preserved in 6 of 7 patients who had both isolated anti‐P antibodies and class V lupus nephritis. In contrast, anti‐dsDNA was associated with proliferative‐class lupus nephritis (P = 0.050) and higher creatinine levels (P = 0.014). Furthermore, 7 of 9 patients with isolated anti‐P antibodies had class V lupus nephritis, and, more importantly, 5 of these 7 patients (71%) displayed a pure membranous pattern. Conversely, a tendency toward the predominance of class V lupus nephritis (67%) with concomitant proliferative lesions was observed when anti‐P antibody was associated with anti‐dsDNA.ConclusionOur data introduce anti‐P antibody as a novel serologic marker for membranous lupus nephritis and support the notion that the presence of isolated anti‐P antibodies may discriminate patients with pure class V lupus nephritis, whereas the simultaneous presence of anti‐dsDNA antibodies suggests class V disease with concomitant proliferative lesions.
Cardiovascular outcomes in new users of coxibs and nonsteroidal antiinflammatory drugs: High‐risk subgroups and time course of risk
Authors: Solomon Daniel H. , Avorn Jerry , Stürmer Til , Glynn Robert J. , Mogun Helen , Schneeweiss Sebastian 
Published: April 2006

AbstractObjectiveControversy persists regarding the cardiovascular risks of treatment with selective cyclooxygenase 2 inhibitors (coxibs) and nonselective nonsteroidal antiinflammatory drugs (NSAIDs). This study was undertaken to examine, in a large group of new users of coxibs and NSAIDs, the rate of cardiovascular events, their time course, and whether baseline cardiovascular risk modified the rate ratios (RRs) for future events.MethodsThis cohort study included Medicare beneficiaries who enrolled in a state‐run prescription drug plan that fully covered NSAIDs and coxibs without restriction. All study patients started use of a coxib or NSAID after January 1, 1999. The primary composite end point was a hospital admission for either myocardial infarction or ischemic stroke. Predefined exposure groups included the 3 coxibs available in the US during the study period (celecoxib, rofecoxib, and valdecoxib), as well as oral formulations of diclofenac, ibuprofen, naproxen, and a composite of all other NSAIDs. We compared the rate of cardiovascular events associated with each of these agents with that in a reference group of patients who did not use NSAIDs or coxibs, but started other medications unrelated to cardiovascular risk. Daily exposure to all study drugs was assessed based on filled prescription data. A Cox proportional hazards model stratified on calendar year that included other baseline cardiovascular risk factors constituted the primary analysis.ResultsWe identified 74,838 users of NSAIDs or coxibs, and 23,532 comparable users of other drugs comprised the reference group. Adjusted models demonstrated a significant elevation in the event rate for rofecoxib (RR 1.15, 95% confidence interval [95% CI] 1.06–1.25) and a significant reduction in the rate for naproxen (RR 0.75, 95% CI 0.62–0.92). No other coxib or NSAID was associated with a significant increase or decrease in cardiovascular event rate. The increased rate associated with rofecoxib was seen in the first 60 days of use (adjusted RR 1.14, 95% CI 1.01–1.29) and thereafter (adjusted RR 1.14, 95% CI 1.02–1.28). Kaplan‐Meier event curves showed a similar pattern of risk (early and persistent separation of the event curves) among long‐term rofecoxib users at low or high baseline cardiovascular risk.ConclusionWe found an increased cardiovascular event rate among users of rofecoxib, and a decreased rate with naproxen use. Other coxibs and NSAIDs did not appear to be associated with a difference in event rate compared with users of other drugs. The increase in rate associated with rofecoxib was seen within the first 60 days and persisted. There was no important modification of the event rate based on the patient's baseline cardiovascular risk.
On‐line preparation of peroxymonocarbonate and its application for the study of energy transfer chemiluminescence to lanthanide inorganic coordinate complexes
Authors: Liu Meilin , Cheng Xianglei , Zhao Lixia , Lin Jin‐Ming 
Published: April 2006

AbstractIt has been shown that peroxymonocarbonate ion (HCO4−) is a potent oxidant. In this study, a flow‐injection system was developed in order to prepare on‐line HCO4− ion and the optimum conditions for the on‐line preparation of HCO4− were studied in detail. We used 99% 13C‐enriched NaHCO3 to examine peroxymonocarbonate by 13C‐NMR at 25°C. An ultra‐weak chemiluminescence (CL) was observed after mixing H2O2 and sodium bicarbonate in an organic co‐solvent that can accelerate the formation of HCO4− ion. When lanthanide inorganic coordinate complex, Eu(II)–EDTA, was added into this HCO4− system, the CL intensity was significantly enhanced. The CL mechanism was investigated by various methods. The experimental results indicate that peroxymonocarbonate oxidizes Eu(II) to Eu(III) and produces singlet oxygen; meanwhile, the energy originating from dimers of singlet oxygen is accepted by the Eu(III)–EDTA− complex. The excited Eu(III) ions undergo radiative deactivation and emit CL. Copyright © 2006 John Wiley & Sons, Ltd.
Firefly Luciferase Produces Hydrogen Peroxide as a Coproduct in Dehydroluciferyl Adenylate Formation
Authors: Fraga Hugo , Fernandes Diogo , Novotny Jiri , Fontes Rui , Esteves da Silva Joaquim C. G. 
Published: April 2006

AbstractFirefly luciferase catalyzes the synthesis of H2O2 from the same substrates as the bioluminescence reaction: ATP and luciferin (d‐LH2). About 80 % of the enzyme‐bound intermediate d‐luciferyl adenylate (d‐LH2‐AMP) is oxidized into oxyluciferin, and a photon is emitted during this reaction. The enzyme pathway responsible for the generation of H2O2 is a side reaction in which d‐LH2‐AMP is oxidized into dehydroluciferyl adenylate (L‐AMP). Like the bioluminescence reaction, the luciferase‐catalyzed synthesis of H2O2 and L‐AMP is a stereospecific process, involving only the natural D enantiomer. However, the intramolecular electron transfer postulated as essential to the light emission process is not involved in this side reaction.
Reaction of Cytidine Nucleotides with Cyanoacetylene: Support for the Intermediacy of Nucleoside‐2′,3′‐cyclic Phosphates in the Prebiotic Synthesis of RNA
Authors: Crowe Michael A. , Sutherland John D. 
Published: April 2006

AbstractA robust and prebiotically plausible synthesis of RNA is a key requirement of the “RNA World” hypothesis, but, to date, no such synthesis has been demonstrated. Monomer synthesis strategies involving attachment of preformed nucleobases to sugars have failed, and, even if activated 5′‐nucleotides could be made, the hydrolysis of these intermediates in water makes their efficient oligomerisation appear unlikely. We recently reported a synthesis of cytidine‐2′,3′‐cyclic phosphate 1 (C>p) in which the nucleobase was assembled in stages on a sugar‐phosphate template. However, 2′,3′‐cyclic nucleotides (N>p's) also undergo hydrolysis, in this case giving a mixture of the 2′‐ and 3′‐monophosphates. This hydrolysis has previously been seen as making the, otherwise promising, oligomerisation of N>p's seem as unlikely as that of the 5′‐activated nucleotides. We now find that cyanoacetylene, the reagent used for the second stage of nucleobase assembly in the synthesis of C>p, also reverses the effect of the hydrolysis by driving efficient cyclisation of C2′p and C3′p back to C>p. Excess cyanoacetylene also derivatises the nucleobase, but this modification is reversible at neutral pH. These findings significantly strengthen the case for N>p's in a prebiotic synthesis of RNA.
Characterization of BlsM, a Nucleotide Hydrolase Involved in Cytosine Production for the Biosynthesis of Blasticidin S
Authors: Grochowski Laura L. , Zabriskie T. Mark 
Published: April 2006

AbstractBiosynthesis of the antifungal agent blasticidin S in Streptomyces griseochromogenes requires the formation of free cytosine. The blsM gene in the blasticidin S gene cluster is predicted to encode a protein that has sequence homology with several nucleoside transferases. In vitro analysis of recombinant BlsM revealed that the enzyme functions as a nucleotide hydrolase and catalyzes the formation of free cytosine by using cytidine 5′‐monophosphate (CMP) as the preferred substrate. Cytosine production was significantly lower with CDP, CTP, and dCMP as alternate substrates. BlsM was also observed to have low‐level cytidine deaminase activity, converting cytidine and deoxycytidine to uridine and deoxyuridine, respectively. Point mutations were introduced in blsM at putative catalytic residues to generate three mutant enzymes, BlsM Ser98Asp, Glu104Ala, and Glu104Asp. All three mutants lost CMP hydrolysis activity, but the Ser98Asp mutant showed a modest increase in cytidine deaminase activity.
Modulation of Infectivity in Phage Display as a Tool to Determine the Substrate Specificity of Proteases
Authors: Chaparro‐Riggers Javier F. , Breves Roland , Maurer Karl‐Heinz , Bornscheuer Uwe 
Published: April 2006

AbstractProteases play an important role in human and animal diseases. Rapid determination of substrate specificity is possible through the use of substrate phage display; however, current methods possess several drawbacks. They require phage‐immobilization and cannot be used for infectivity‐destroying or affinity tag‐destroying proteases; this can make entire libraries useless. To overcome these limitations, here we introduce infectivity‐modulated phage display (IMOP). IMOP uses a protease‐resistant and infectivity‐reducing tag fused to substrate‐displaying polyvalent phages, and the specific cleavage of the substrate increases the infectivity of the phages by releasing the infectivity‐reducing tag. The resulting phages were first tested with the infectivity‐destroying detergent protease subtilisin; this resulted in a highly specific substrate at a 200‐fold enrichment. In a second example, the protease ompT was used and led to an enrichment of the known double‐arginine motif. The IMOP system thus substantially improves and simplifies previous systems.
Heteropolynuclear Palladium Complexes with Pyrazolate and Its 3‐tert‐Butyl Derivatives: The Effect of Heterometal Ions on the Rate of Isomerization
Authors: Umakoshi Keisuke , Kojima Takashi , Arikawa Yasuhiro , Onishi Masayoshi 
Published: April 2006

AbstractThe heteropolynuclear complexes [Pd2M′2(μ‐pz)6] (M′=Ag (1), Au (2); pzH=pyrazole), HT‐[Pd2M′2(μ‐3‐tBupz)6] (M′=Ag (3 a), Au (4 a); 3‐tBupzH=3‐tert‐butylpyrazole), and HH‐[Pd2Au2(μ‐3‐tBupz)6] (4 b) have been prepared and some of them were structurally characterized. When 3‐tert‐butylpyrazolate was employed as a bridging ligand, two linkage isomers (head‐to‐tail (HT) and head‐to‐head (HH)) arise from the difference in orientation of the substituent groups on the pyrazolate bridges between the two Pd atoms. 1H NMR spectroscopy has been used to identify and to follow the reversible stereochemical rearrangement of the HH isomer of [Pd2Ag2(μ‐3‐tBupz)6] (3 b) to form the HT isomer 3 a in CDCl3 and the HT isomer of [Pd2Au2(μ‐3‐tBupz)6] (4 a) to form the HH isomer 4 b in C6D6. Kinetic studies of the reaction have established the rate law to be −d(HH)/dt=d(HT)/dt=k2[HH]−k1[HT] for 3 b and −d(HT)/dt=d(HH)/dt=k1[HT]−k2[HH] for 4 a, where k1 and k2 denote the rate of isomerization from the HT to the HH isomer and that from the HH to the HT isomer, respectively. For typical runs at 50 °C in C6D6, k1=13.8×10−5 s−1, k2=18.6×10−5 s−1, and Keq=k2/k1=1.24 for 3 b, and k1=1.26×10−5 s−1, k2=3.52×10−5 s−1, and Keq=k1/k2=0.36 for 4 a. Temperature‐dependent rate measurements reveal ΔH≠ and ΔS≠ to be 100(1) kJ mol−1 and 0(3) J mol−1 K−1 for 3 b and 112(5) kJ mol−1 and 20(17) J mol−1 K−1 for 4 a, respectively. The rate of isomerization is essentially unaffected by the concentration of the complex or by the presence of neutral bridging ligands. These data and observations imply that the isomerization involves an intramolecular exchange process.