bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti–ribosomal P protein antibody in human systemic lupus erythematosus up‐regulates the expression of proinflammatory cytokines by human peripheral blood monocytes
Authors: Nagai Tatsuo , Arinuma Yoshiyuki , Yanagida Tamiko , Yamamoto Kazuhiko , Hirohata Shunsei 
Published: March 2005

AbstractObjectiveAutoantibodies to ribosomal P proteins (anti‐P antibodies) are detected in 12–16% of patients with systemic lupus erythematosus (SLE) and have been found to be associated with some manifestations of the disease, including lupus psychosis and hepatitis. Recent studies have disclosed that anti‐P antibodies react with activated T cells but not with B cells, suggesting possible direct effects of anti‐P antibodies on immune regulation. The present study was designed to explore the presence of the epitope recognized by anti‐P antibodies on human peripheral blood monocytes.MethodsHighly purified peripheral blood monocytes obtained from healthy donors were cultured with or without interferon‐γ (IFNγ) in the presence of either anti‐P antibodies purified by affinity chromatography from the sera of patients with SLE or control IgG.ResultsFlow cytometry analysis disclosed that fresh (day 0) monocytes did not express the ribosomal P epitope, whereas expression of the ribosomal P epitope was induced on annexin V–negative monocytes after activation through plastic adherence for 48 hours. More important, anti‐P antibodies (compared with normal IgG or IgG from SLE patients devoid of anti‐P antibodies) enhanced the production of tumor necrosis factor α (TNFα) and interleukin‐6 (IL‐6) by activated monocytes. Accordingly, anti‐P antibodies also up‐regulated the expression of TNFα and IL‐6 messenger RNA in activated monocytes. Of note, F(ab′)2 fragments of anti‐P antibodies, which do not result in Fcγ receptor (FcγR) crosslinking, also effectively up‐regulated the expression of TNFα and IL‐6.ConclusionThese results indicate that human peripheral blood monocytes express the ribosomal P epitope upon activation, irrespective of induction of apoptosis. Moreover, the data suggest that anti‐P antibodies might modify a variety of inflammatory responses through up‐regulation of the expression of proinflammatory cytokines in monocytes, in a manner that does not involve FcγR crosslinking.
Cartilage biomarkers in ankylosing spondylitis: Relationship to clinical variables and treatment response
Authors: Kim Tae‐Hwan , Stone Millicent , Payne Ursula , Zhang Xiang , Ionescu Mirela , Lobanok Tatiana , King Lindsay , Poole A. Robin , Inman Robert D. 
Published: March 2005

AbstractObjectiveAnkylosing spondylitis (AS) is a progressive disease in which chronic inflammation can lead to extensive new bone formation throughout the spine. At present, few measures of the activity or extent of the disease are available. In this study, we sought to determine whether markers of cartilage synthesis and degradation could provide such quantitative measures.MethodsSerum samples from 23 patients receiving infliximab treatment for AS were obtained at baseline and at weeks 2, 6, 14, and 22. Patients were stratified with respect to joint involvement and baseline levels of inflammatory markers, and responders were defined according to the Assessments in Ankylosing Spondylitis 20% criteria. Serial measurements of interferon‐γ, tumor necrosis factor α, transforming growth factor β (TGFβ), interleukin‐10 (IL‐10), and IL‐1 were done at each time point. The following biomarkers were measured by enzyme‐linked immunosorbent assay: the proteoglycan aggrecan 846 epitope, a marker of cartilage turnover; C‐propeptide of type II collagen (CPII), a biosynthesis marker; and the Col2‐3/4long mono (C2C) and Col2‐3/4short (C1–2C) neoepitopes, reflecting collagen cleavage of type II collagen and type I/type II collagen, respectively.ResultsAt baseline, patients with AS demonstrated significant elevations in serum levels of CPII, the 846 epitope, and the CPII‐to‐C2C (CPII:C2C) ratio (but not C2C or C1–2C) compared with normal controls. Of the biomarkers examined, only CPII:C2C showed a correlation with the C‐reactive protein (CRP) level. Among the biomarker–cytokine relationships, TGFβ demonstrated a trend toward a positive correlation with the 846 epitope.ConclusionIn AS, elevated serum levels of CPII and the 846 epitope may be related to biosynthetic turnover of hyaline cartilage and the intervertebral discs but may also reflect progressive bone formation as a result of endochondral ossification. The correlation of the CPII:C2C ratio with CRP suggests that the CPII:C2C ratio might prove to be a useful marker of disease activity in AS.
Investigation of the SLC22A4 gene (associated with rheumatoid arthritis in a Japanese population) in a United Kingdom population of rheumatoid arthritis patients
Authors: Barton Anne , Eyre Stephen , Bowes John , Ho Pauline , John Sally , Worthington Jane 
Published: March 2005

AbstractObjectiveRecent studies of 2 complex diseases, rheumatoid arthritis (RA) and Crohn's disease (CD), showed associations with genes mapping to the cytokine gene cluster on 5q31. In particular, a functional single‐nucleotide polymorphism (SNP) mapping to intron 1 of the organic cation transporter 1 (OCTN1; SLC22A4) gene was associated with RA in a Japanese population, and a haplotype of a different SNP in the same gene and one in an adjacent gene, OCTN2 (SLC22A5), was associated with CD. The purpose of this study was to investigate the association between the OCTN locus and RA in a Caucasian population.MethodsAssociation with 11 SNPs spanning the SLC22A4 and SLC22A5 genes, including a putative RA‐causing functional polymorphism (rs3792876 [slc2f2]) and a functional haplotype previously associated with CD, was investigated in 909 RA cases and 594 population controls in the UK. Genotyping was performed using 5′‐allele discrimination assays. Estimated haplotype frequencies were generated using the expectation‐maximization algorithm and were compared between cases and controls.ResultsAll SNPs were in Hardy‐Weinberg equilibrium. We found no evidence for an association between RA and either the SNP (rs3792876 [slc2f2]) or the haplotype previously reported to be associated with RA in a Japanese population. Similarly, no association between RA and the haplotype associated with CD was detected.ConclusionFunctional polymorphisms of the OCTN gene locus that have previously been associated with RA and CD were not found to be associated with RA in a UK population. The findings do not provide support for a major role of these genes in the etiology of RA in this population.
Hyaluronan oligosaccharide–induced activation of transcription factors in bovine articular chondrocytes
Authors: Ohno Shigeru , Im Hee‐Jeong , Knudson Cheryl B. , Knudson Warren 
Published: March 2005

AbstractObjectiveTo document the activity profile of transcription factors following chondrocyte stimulation with hyaluronan (HA) hexasaccharides (HA6) and to determine the expression of genes whose transcriptional activation is tightly associated with the transcription factors.MethodsNuclear extracts from bovine articular chondrocytes treated with HA6 were subjected to transcription factor protein–DNA array analysis. Electrophoretic mobility shift assay (EMSA) analyses were performed to confirm the results of protein–DNA array. The gene expressions of matrix metalloproteinase 3 (MMP‐3), type II collagen, and cartilage oligomeric matrix protein (COMP) were examined by quantitative real‐time reverse transcription–polymerase chain reaction (RT‐PCR), and protease activity was assessed by casein zymography.ResultsIn the protein–DNA array analysis, 12 transcription factors were up‐regulated and 2 transcription factors were down‐regulated in the chondrocytes treated with HA6. The transcription factors retinoic acid receptor (RAR), retinoid X receptor (RXR), and Sp‐1 exhibited >2‐fold increased activity by HA6 treatment, as confirmed by EMSA. RT‐PCR analysis showed that the expression levels of MMP‐3, type II collagen, and COMP messenger RNA, which are tightly associated with the activation of RAR, RXR, or Sp‐1, were up‐regulated by treatment with HA6. Addition of high molecular mass HA after HA6 treatment resulted in abrogation of the MMP‐3 induction.ConclusionThese results suggest that HA6 increase the activity of multiple transcription factors in chondrocytes and signal the enhanced expression of key genes involved in cartilage‐matrix remodeling and turnover. The data also demonstrate that high molecular mass HA has a potential to suppress the signaling activated by HA6.
Cruciate ligament integrity in osteoarthritis of the knee
Authors: Hill Catherine L. , Seo Gwy Suk , Gale Daniel , Totterman Saara , Gale M. Elon , Felson David T. 
Published: March 2005

AbstractObjectiveTo evaluate, using magnetic resonance imaging (MRI), the prevalence of anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) rupture in knees with symptomatic osteoarthritis (OA) compared with those without OA, and the relationship to pain and recalled injury.MethodsMRI and plain radiography of the knee were performed in a group of 360 subjects with painful knee OA (cases; 66.7% male, mean age 67.1 years) and 73 without knee pain (controls; 57.5% male, mean age 66.1 years). MRIs were read for the presence or absence of complete or partial ACL or PCL tear. Subjects with knee pain were asked to quantify severity of pain on a visual analog scale and to report whether they could recall a significant knee injury (requiring use of a cane or crutches). We compared the prevalence of ACL and PCL rupture in those with and those without knee pain and also evaluated whether, in cases, there was any association with recalled knee injury.ResultsThe proportion of cases who had complete ACL rupture was 22.8%, compared with 2.7% of controls (P = 0.0004). PCL rupture was rare both in cases (0.6%) and in controls (0%). Cases with ACL rupture had more severe radiologic OA (P < 0.0001) and were more likely to have medial joint space narrowing (P < 0.0001) than cases with intact ACLs, but did not have higher pain scores. Among cases, only 47.9% of those with complete ACL tears reported a previous knee injury, compared with 25.9% of those without complete ACL tears (P = 0.003).ConclusionACL rupture is more common among those with symptomatic knee OA compared with those without knee OA. Fewer than half of subjects with ACL rupture recall a knee injury, suggesting that this risk factor for knee OA is underrecognized.
Therapeutic efficacy of humanized recombinant anti–interleukin‐6 receptor antibody in children with systemic‐onset juvenile idiopathic arthritis
Authors: Yokota Shumpei , Miyamae Takako , Imagawa Tomoyuki , Iwata Naomi , Katakura Shigeki , Mori Masaaki , Woo Patricia , Nishimoto Norihiro , Yoshizaki Kazuyuki , Kishimoto Tadamitsu 
Published: March 2005

AbstractObjectiveTo investigate the safety and efficacy of a recombinant human anti–interleukin‐6 (anti–IL‐6) receptor monoclonal antibody (MRA) that indirectly inhibits the effects of IL‐6 in children with systemic‐onset juvenile idiopathic arthritis (JIA) refractory to high‐dose, long‐term corticosteroids.MethodsAn individual escalating‐dose trial was conducted in 11 children with active systemic‐onset JIA who met the inclusion criteria. All were first administered an intravenous dose of 2 mg/kg MRA. Each child without active inflammation was given a second identical dose 2 weeks later and a third identical dose 2 weeks after the second dose. Children with disease flares according to laboratory marker values received a 4‐mg/kg dose. Those without disease flares at this dose received a second 4‐mg/kg dose 2 weeks later and a third 4‐mg/kg dose 2 weeks after the second dose, while those with active inflammation received an additional 3 doses of 8 mg/kg MRA. Efficacy was evaluated every 2 weeks according to responses on the JIA core set of improvement criteria and the results of laboratory tests.ResultsMRA abruptly reduced disease activity in 10 of the 11 children, as assessed by the occurrence of febrile episodes, active arthritis, scores on the Childhood Health Assessment Questionnaire, and levels of acute‐phase reactants. However, levels of inflammatory reactants fluctuated until the proper MRA dose for each child was reached. Two weeks after the third fixed dose of MRA, 90.9% of all patients had a 30% improvement response, 90.9% had a 50% improvement response, and 63.6% had a 70% improvement response.ConclusionMRA treatment of children with active systemic disease results in clinical improvement and in normalized levels of acute‐phase reactants. MRA was safe and well tolerated and provided greater clinical benefit than conventional corticosteroids, considering the ill effects of IL‐6 and adverse events.
Patients with antinuclear antibody–positive juvenile idiopathic arthritis constitute a homogeneous subgroup irrespective of the course of joint disease
Authors: Ravelli Angelo , Felici Enrico , Magni‐Manzoni Silvia , Pistorio Angela , Novarini Cristina , Bozzola Elena , Viola Stefania , Martini Alberto 
Published: March 2005

AbstractObjectiveWe recently hypothesized that in the International League of Associations for Rheumatology (ILAR) classification of juvenile idiopathic arthritis (JIA), the presumably homogeneous patient group characterized by early onset of disease, a female predilection, the presence of antinuclear antibodies (ANA), asymmetric arthritis, and the risk for iridocyclitis is classified into different categories. We sought to investigate whether ANA‐positive patients belonging to the ILAR categories of oligoarthritis and rheumatoid factor (RF)–negative polyarthritis share homogeneous features and to compare these features with those of ANA‐negative patients with JIA in the same categories.MethodsWe identified patients who were followed up during a 15‐year period. All patients had JIA according to the ILAR criteria, with oligoarticular or polyarticular onset. ANA positivity was defined as 2 or more positive results at a titer of ≥1:160. Demographic and clinical features, including the number of joints involved over time and measures of JIA severity at the last followup visit, were recorded retrospectively.ResultsA total of 256 patients were included: 190 were ANA positive (109 had persistent oligoarthritis, 48 had extended oligoarthritis, and 33 had RF‐negative polyarthritis), and 66 were ANA negative (35 had RF‐negative polyarthritis, and 31 had oligoarthritis). All patients who were positive for ANA were similar in terms of age at disease presentation, female‐to‐male ratio, and frequency of symmetric arthritis and iridocyclitis. Compared with ANA‐positive patients with polyarticular disease, ANA‐negative patients with polyarticular arthritis were older at disease presentation and had a lower frequency of iridocyclitis, a higher frequency of symmetric arthritis, a greater cumulative number of joints affected over time, and a different pattern of joint disease, with a greater frequency of shoulder and hip involvement. The strong relationship between the presence of ANA and younger age at disease presentation, asymmetric arthritis, and development of iridocyclitis was confirmed by multivariate regression analysis.ConclusionOur results support the hypothesis that patients with similar characteristics are currently classified into different JIA categories. The value of ANA positivity as a possible modifier of the current classification system deserves consideration.
HLA–B27–restricted CD8+ T cell response to cartilage‐derived self peptides in ankylosing spondylitis
Authors: Atagunduz Pamir , Appel Heiner , Kuon Wolfgang , Wu Peihua , Thiel Andreas , Kloetzel Peter‐Michael , Sieper Joachim 
Published: March 2005

AbstractObjectiveSeveral hypotheses have been proposed to explain the strong association between HLA–B27 and ankylosing spondylitis (AS). Among these, the arthritogenic peptide theory proposes that certain B27 subtype alleles bind specific arthritogenic peptide(s) due to their unique amino acid anchor residues. Cartilage antigens have been discussed as candidate targets for the immune response in AS. The recognition of HLA–B27–peptide complexes by self‐reactive CD8+ T cells might contribute to joint‐specific tissue damage. Therefore, we investigated the presence of autoreactive CD8+ T cells specific for cartilage‐derived peptides in patients with AS.MethodsAn HLA–B27–binding prediction program and a proteasome‐cutting prediction program for the human 20S proteasome were used to screen 18 human cartilage proteins for potentially immunogenic nonamer peptides. The peptides identified were used to stimulate peripheral blood mononuclear cells from 20 HLA–B27–positive patients with AS and synovial fluid (SF) mononuclear cells from 7 HLA–B27–positive patients with AS. Activation of T cells was measured by antigen‐specific intracellular cytokine staining and quantified by flow cytometry.ResultsFrom the screening analysis, we identified 121 nonamer peptides. Of these, 1 peptide derived from type II collagen and 1 from type VI collagen were stimulatory for peripheral blood CD8+ T cells in only 1 of 20 patients. However, in 4 of 7 SF samples the same type VI collagen–derived nonamer peptide stimulated SF CD8+ T cells, but none of the other peptides was stimulatory. This CD8+ T cell response could be blocked by an anti–HLA–B27 antibody, confirming an HLA–B27–restricted immune response.ConclusionOur findings suggest that cartilage‐directed cellular autoimmunity might play an important role in joint‐specific tissue damage in patients with AS. Future research is necessary to determine whether the identified peptide is of pathogenetic relevance.
Increase in the expression of the transmembrane surface receptor CD44v6 on chondrocytes in animals with osteoarthritis
Authors: Tibesku Carsten O. , Szuwart Thomas , Ocken Stephanie A. , Skwara Adrian , Fuchs Susanne 
Published: March 2005

AbstractObjectiveTo evaluate the expression of CD44v6 on chondrocytes from hyaline cartilage over the course of osteoarthritis (OA).MethodsIn 12 NZW rabbits, the anterior cruciate ligament (ACL) was resected to create anterior instability of the knee. In 12 control rabbits, only a sham operation, without resection of the ACL, was performed. Four animals from each group were killed at 3, 6, and 12 weeks. After opening the knee joint, OA was macroscopically graded and hyaline cartilage of the load‐bearing area was evaluated histologically according to the Mankin scale and by immunostaining for CD44v6.ResultsThere was a positive linear correlation between the time after surgery and the macroscopic and histologic OA scores. The scores in the control group were constant over the time course. Immunostaining showed constant expression of CD44v6 in the control group. In the experimental group, a positive linear correlation between CD44v6 expression and macroscopic and histologic grades was found.ConclusionThe results show an in vivo increase in the expression of the hyaluronan receptor CD44 over the time course of OA. Further studies are needed to evaluate whether this pattern applies to humans and whether new treatment approaches could evolve from this knowledge.
A web service for biomedical term look‐up
Authors: Harkema Henk , Roberts Ian , Gaizauskas Rob , Hepple Mark 
Published: March 2005

AbstractRecent years have seen a huge increase in the amount of biomedical information that is available in electronic format. Consequently, for biomedical researchers wishing to relate their experimental results to relevant data lurking somewhere within this expanding universe of on‐line information, the ability to access and navigate biomedical information sources in an efficient manner has become increasingly important. Natural language and text processing techniques can facilitate this task by making the information contained in textual resources such as MEDLINE more readily accessible and amenable to computational processing. Names of biological entities such as genes and proteins provide critical links between different biomedical information sources and researchers' experimental data. Therefore, automatic identification and classification of these terms in text is an essential capability of any natural language processing system aimed at managing the wealth of biomedical information that is available electronically. To support term recognition in the biomedical domain, we have developed Termino, a large‐scale terminological resource for text processing applications, which has two main components: first, a database into which very large numbers of terms can be loaded from resources such as UMLS, and stored together with various kinds of relevant information; second, a finite state recognizer, for fast and efficient identification and mark‐up of terms within text. Since many biomedical applications require this functionality, we have made Termino available to the community as a web service, which allows for its integration into larger applications as a remotely located component, accessed through a standardized interface over the web. Copyright © 2005 John Wiley & Sons, Ltd.
The curvelet representation of wave propagators is optimally sparse
Authors: Candès Emmanuel J. , Demanet Laurent 
Published: March 2005

AbstractThis paper argues that curvelets provide a powerful tool for representing very general linear symmetric systems of hyperbolic differential equations. Curvelets are a recently developed multiscale system [7, 9] in which the elements are highly anisotropic at fine scales, with effective support shaped according to the parabolic scaling principle width ≈ length2 at fine scales. We prove that for a wide class of linear hyperbolic differential equations, the curvelet representation of the solution operator is both optimally sparse and well organized.

It is sparse in the sense that the matrix entries decay nearly exponentially fast (i.e., faster than any negative polynomial) and
well organized in the sense that the very few nonnegligible entries occur near a few shifted diagonals.
Indeed, we show that the wave group maps each curvelet onto a sum of curveletlike waveforms whose locations and orientations are obtained by following the different Hamiltonian flows—hence the diagonal shifts in the curvelet representation. A physical interpretation of this result is that curvelets may be viewed as coherent waveforms with enough frequency localization so that they behave like waves but at the same time, with enough spatial localization so that they simultaneously behave like particles. © 2005 Wiley Periodicals, Inc.
A simple PDE and Wiener‐Hopf Riccati equations
Authors: Stroock Daniel W. , Williams David 
Published: March 2005

AbstractWe investigate the PDE (1.1), concentrating on the case when σ < in which the boundary condition (1.1b) is not of Feller's type and we lose the minimum principle. Investigation of nonnegative solutions leads us to Wiener‐Hopf theory and to a Riccati equation. A much‐studied Markov chain analogue is developed further in the hope that it will illuminate all aspects of the PDE case. © 2005 Wiley Periodicals, Inc.