bluuebunny/crossref_metadata_2025 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

Objective

Autoantibodies 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.

Methods

Highly 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.

Results

Flow 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.

Conclusion

These 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

Objective

Ankylosing 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.

Methods

Serum 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.

Results

At 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.

Conclusion

In 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

Objective

Recent 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.

Methods

Association 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.

Results

All 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.

Conclusion

Functional 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

Objective

To 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.

Methods

Nuclear 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.

Results

In 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.

Conclusion

These 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

Objective

To 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.

Methods

MRI 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.

Results

The 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).

Conclusion

ACL 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

Objective

To 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.

Methods

An 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.

Results

MRA 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.

Conclusion

MRA 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

Objective

We 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.

Methods

We 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.

Results

A 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.

Conclusion

Our 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

Objective

Several 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.

Methods

An 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.

Results

From 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.

Conclusion

Our 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

Objective

To evaluate the expression of CD44v6 on chondrocytes from hyaline cartilage over the course of osteoarthritis (OA).

Methods

In 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.

Results

There 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.

Conclusion

The 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

Recent 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

This 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

We 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.
Testing the Pairwise Additive Potential Approximation Using DFT: Coadsorption of CO and N on Rh(100)
Authors: Curulla Ferré Daniel , van Bavel Alexandre P. , Niemantsverdriet J. W.
Published: March 2005

The interaction between adsorbates is a key issue in surface science, because these interactions can influence strongly the properties of chemisorbed species with consequences for the thermodynamics and kinetics of surface processes. The simplest representation of adsorbate–adsorbate interactions is based on the assumption that all interactions are pairwise additive. This approach has been satisfactorily used in the modeling of temperature‐programmed desorption (TPD) spectra using both continuum and Monte Carlo methods. However, the energies estimated within the pairwise approximation have never been compared to the energies calculated using density functional theory (DFT) methods. We demonstrate that the pairwise additive potential approximation is indeed a good representation of the adsorbate–adsorbate interactions, and that we do not need to include three‐body interactions or higher‐order terms to estimate the perturbation of the adsorption energy of an adsorbate by the presence of other coadsorbates. Moreover, we show for the first time how DFT can be used to explain the desorption features that one finds in TPD experiments, thus linking the TPD desorption features with actual microscopic configurations.
Fabrication of Ultrathin Films with Large Third‐Order Nonlinear Optical Properties
Authors: Jiang Li , Lu Fushen , Chang Qing , Liu Yang , Liu Huibiao , Li Yuliang , Xu Wei , Cui Guanglei , Zhuang Junpeng , Li Xiaofang , Wang Shu , Song Yinglin , Zhu Daoben
Published: March 2005

An ultrathin composite film containing anionic Ag‐His complexes (His: L‐Histidine) and oppositely charged BH‐PPV was fabricated by means of the electrostatic layer‐by‐layer self‐assembly technique. UV/Vis spectra showed a continuous deposition process of Ag‐His complexes and BH‐PPV. The film structure was characterized by using small‐angle X‐ray diffraction, AFM, and SEM. The nonlinear optical properties of the ultrathin film were studied by using the Z‐scan technique with a laser duration of 8 ns at a wavelength of 532 nm. The film sample exhibited a strong nonlinear saturated absorption, with an α2 value of −3.9×10−5 m W−1 and a self‐defocusing effect with an n2 value of −4.78×10−12 m2 W−1.
Complexes and Clusters of Water Relevant to Atmospheric Chemistry: H2O Complexes with Oxidants
Authors: Sennikov Petr G. , Ignatov Stanislav K. , Schrems Otto
Published: March 2005

Experimental observations and data from quantum chemical calculations on complexes between water molecules and small, oxygen‐containing inorganic species that play an important role as oxidants in the atmosphere (O(1D), O(3P), O2(X3Σg), O2(b1Σg+), O3, HO, HOO, HOOO, and H2O2) are reviewed, with emphasis on their structure, hydrogen bonding, interaction energies, thermodynamic parameters, and infrared spectra. In recent years, weakly bound complexes containing water have increasingly attracted scientific attention. Water in all its phases is a major player in the absorption of solar and terrestrial radiation. Thus, complexes between water and other atmospheric species may have a perceivable influence on the radiative balance and contribute to the greenhouse effect, even though their concentrations are low. In addition, they can play an important role in the chemistry of the Earth's atmosphere, particularly in the oxidation of trace gases. Apart from gas‐phase complexes, the interactions of oxidants with ice surfaces have also received considerable advertency lately due to their importance in the chemistry of snow, ice clouds, and ice surfaces (e.g., ice shields in polar regions). In paleoclimate—respectively paleoenvironmental—studies, it is essential to understand the transfer processes from the atmosphere to the ice surface. Consequently, special attention is being paid here to the intercomparison of the properties of binary complexes and the complexes and clusters of more complicated compositions, including oxidants adsorbed on ice surfaces, where ice is considered a kind of large water cluster. Various facts concerning the chemistry of the Earth's atmosphere (concentration profiles and possible influence on radical reactions in the atmosphere) are discussed.
Theoretical Study of the Electronic Excited States of Tetracyanoethylene and Its Radical Anion
Authors: Milián Begoña , Pou‐Amérigo Rosendo , Merchán Manuela , Ortí Enrique
Published: March 2005

The low‐lying electronic states of tetracyanoethylene (TCNE) and its radical anion were studied using multiconfigurational second‐order perturbation theory (CASPT2) and extended atomic natural orbital (ANO) basis sets. The results obtained yield a full interpretation of the electronic absorption spectra, explain the spectral changes undergone upon reduction, give support to the occurrence of a bound excited state for the anionic species, and provide valuable information for the rationalization of the experimental data obtained with electron transmission spectroscopy.
Large eddy simulation of compressible turbulence using high‐resolution methods
Authors: Hahn M. , Drikakis D.
Published: March 2005

The paper presents a numerical investigation of high‐resolution schemes for solving the compressible Euler and Navier–Stokes equations in the context of implicit large eddy simulation (ILES), also known as monotone integrated LES (MILES). We have employed three high‐resolution schemes: a flux vector splitting (FVS), a characteristics‐based (Godunov‐type) and a hybrid total variation diminishing (TVD) scheme; and carried out computations of: (i) decaying turbulence in a triply periodic cube and (ii) compressible flow around open cavities for low and high Reynolds numbers, at transonic and supersonic speeds. The decaying turbulence simulations show that all high‐resolution schemes employed here provide plausible solutions without adding explicit dissipation with the energy spectra being dependent on the numerics. Furthermore, the ILES results for cavity flows agree well with previously published direct numerical simulations and experimental data. Copyright © 2004 John Wiley & Sons, Ltd.
Triage using HPV‐testing in persistent borderline and mildly dyskaryotic smears: Proposal for new guidelines
Authors: Bais Aagje G. , Rebolj Matejka , Snijders Peter J.F. , de Schipper Frits A. , van der Meulen Dries A.J. , Verheijen René H.M. , Voorhorst Feja , van Ballegooijen Marjolein , Meijer Chris J.L.M. , Helmerhorst Theo J.M.
Published: March 2005

In the Netherlands 2% of cervical smears in the cervical cancer screening program are read as borderline or mildly dyskaryotic cytology (BMD smear). Only in about 10% of these women a high‐grade CIN lesion (CIN II–III) is present; therefore referral is for the majority unnecessary. In our study triage with high‐risk HPV (hrHPV) testing was used to identify women at risk for development of high‐grade CIN lesions after a repeat BMD smear. A “wait‐and‐see” period was incorporated allowing clearance of HPV and regression of the lesion. Women with a low‐grade lesion, irrespective of their HPV status, were monitored at 12 months; women with a high‐grade lesion were monitored at 6 and 12 months. Fifty‐one of the 105 women (49%) were hrHPV negative at baseline; none of them showed progression of the lesion within the first year of follow‐up (NPV 100%). High‐grade CIN was present in 1 patient who was HPV negative at baseline (2%); she demonstrated regression after 12 months. Nineteen of the hrHPV positive women (35%) demonstrated a high‐grade CIN lesion at baseline and 3 cleared hrHPV after 6 months, with a subsequent regression of CIN. Ten women remained hrHPV positive with persistence of high‐grade CIN and were eventually treated. At baseline, 35 hrHPV positive women demonstrated a low‐grade lesion, 19 remained hrHPV positive after 12 months and 5 developed high‐grade CIN. Sixteen out of the 35 cleared the hrHPV infection without progression of the lesion. In conclusion, triage, using hrHPV testing for women with persistent BMD cytology, can select women who are not at risk for development of high‐grade CIN. We recommend return to the screening program without referral for colposcopic examination if hrHPV is absent. For hrHPV positive women, a repeat hrHPV test after another 6 months is suggested. Referral is only required if persistence of hrHPV is established. © 2005 Wiley‐Liss, Inc.
Epigenetic silencing of the imprinted gene ZAC by DNA methylation is an early event in the progression of human ovarian cancer
Authors: Kamikihara Tetsuya , Arima Takahiro , Kato Kiyoko , Matsuda Takao , Kato Hidenori , Douchi Tsutomu , Nagata Yukihiro , Nakao Mitsuyoshi , Wake Norio
Published: March 2005

ZAC is a paternally expressed, imprinted gene located on chromosome 6q24, within a region known to harbor a tumor suppressor gene for several types of neoplasia, including human ovarian cancer (HOC). We have failed to identify genetic mutations in the ZAC gene in tumor material. Many imprinted genes contain differentially allele‐specific‐methylated regions (DMR) and harbor promoter activity that is regulated by the DNA methylation. Aberrant DNA methylation is a common feature of neoplasia and changes in DNA methylation at the ZAC locus have been reported in some cases of HOC. We investigated the DNA methylation and ZAC mRNA expression levels in a larger sample of primary HOC material, obtained by laser capture microdissection. ZAC mRNA expression was reduced in the majority of samples and this correlated with hypermethylation of the ZAC‐DMR. Treatment of hypermethylated cells lines with a demethylating agent restored ZAC expression. Our studies indicate that transcriptional silencing of ZAC is likely to be caused by DNA methylation in HOC. Forced expression of ZAC resulted in a reduction in proliferation and marked induction of apoptotic cell death. The ZAC‐mediated apoptosis signal is p53‐independent and eliminated by inhibitors of caspase 3, 8 and 9. Reduced expression of ZAC would therefore favor tumor progression. As there were no significant differences in either DNA methylation or expression of ZAC mRNA between localized and advanced tumors, our data indicates that loss of ZAC is a relatively early event in HOC. (Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat/index.html.) © 2005 Wiley‐Liss, Inc.
Mucin‐depleted foci have β‐catenin gene mutations, altered expression of its protein, and are dose‐ and time‐dependent in the colon of 1,2‐dimethylhydrazine‐treated rats
Authors: Femia Angelo Pietro , Bendinelli Benedetta , Giannini Augusto , Salvadori Maddalena , Pinzani Pamela , Dolara Piero , Caderni Giovanna
Published: March 2005

Mucin‐depleted foci (MDF) are purported preneoplastic lesions that can be easily visualized in the unsectioned colon of carcinogen‐treated rats stained with high‐iron diamine alcian blue (HID‐AB). In F344 rats treated twice with 150 mg/kg of 1,2‐dimethylhydrazine (DMH) and sacrificed after 5, 9, 13 and 28 weeks, MDF increased over time from 5 to 13 weeks, whereas they decreased at 28 weeks, when tumors appear. MDF multiplicity (crypts/MDF) linearly increased with time. Increasing doses of DMH (100, 150 and 200 mg/kg × 2 times) caused a dose‐related increase in MDF. Mutations in Ctnnb1 gene codifying for β‐catenin were identified with PCR amplification and direct sequencing in 6/15 tumors (40%), 7/28 MDF (25%) and 2/27 (7%) aberrant crypt foci (ACF) identified in HID‐AB‐stained colon. All mutations in tumors and MDF caused amino acid substitution, while one mutation in ACF was silent. β‐catenin detected at membrane level by immunohistochemistry was markedly reduced in MDF and tumors and, to a lesser extent, in ACF identified with HID‐AB. By contrast, nuclear localization of β‐catenin was significantly increased in MDF and tumors, while no variation was observed in ACF. β‐catenin cytoplasmic expression was also significantly increased in MDF and tumors but to a lesser extent in ACF. In conclusion, MDF are induced dose‐dependently by DMH, increase in size with time, have mutations in the β‐catenin gene and marked alterations in β‐catenin cellular localization. Since all these phenomena are considered specific steps for colon tumorigenesis, these results further support the hypothesis that MDF are cancer precursors and can be proposed as endpoints in short‐term carcinogenesis experiments. © 2005 Wiley‐Liss, Inc.
Theoretical study for the reaction of CH3OCl with Cl atom
Authors: He Hong‐Qing , Liu Jing‐Yao , Li Ze‐Sheng , Sun Chia‐Chung
Published: March 2005

A direct dynamics method is employed to study the kinetics of the multiple channel reaction CH3OCl + Cl. The potential energy surface (PES) information is explored from ab initio calculations. Two reaction channels, Cl‐ and H‐abstractions, have been identified. The optimized geometries and frequencies of the stationary points and the minimum‐energy paths (MEPs) are calculated at the MP2 level of theory using the 6‐311G(d, p) and cc‐pVTZ basis sets, respectively. The single‐point energies along the MEPs are further refined at the G3(MP2)//MP2/6‐311G(d, p), G3//MP2/6‐311G(d, p), as well as by the multicoefficient correlation method based on QCISD (MC‐QCISD) using the MP2/cc‐pVTZ geometries. The enthalpies of formation for the species CH3OCl and CH2OCl are calculated via isodesmic reactions. The rate constants of the two reaction channels are evaluated by using the variational transition‐state theory over a wide range of temperature, 220–2200 K. The calculated rate constants exhibit the slightly negative temperature dependence and show good agreement with the available experimental data at room temperature at the G3(MP2)//MP2/6‐311G(d, p) level. The present calculations indicate that the two channels are competitive at low temperatures while H‐abstraction plays a more important role with the increase of temperature. The calculated k1a/k1 ratio of 0.5 at 298 K is in general agreement with the experimental one, 0.8 ± 0.2. The high rate constant for CH3OCl + Cl shows that removal by reaction with Cl atom is a potentially important loss process for CH3OCl in the polar stratosphere. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 642–650, 2005
Collision‐induced fragmentation of negative ions from N‐linked glycans derivatized with 2‐aminobenzoic acid
Authors: Harvey David J.
Published: March 2005

N‐Linked glycans from bovine ribonuclease B, chicken ovalbumin, bovine fetuin, porcine thyroglobulin and human α1‐acid glycoprotein were derivatized with 2‐aminobenzoic acid by reductive amination and their tandem mass spectra were recorded by negative ion electrospray ionization with a quadrupole time‐of‐flight mass spectrometer. Derivatives were also prepared from 2‐amino‐5‐methyl‐ and 2‐amino‐4,5‐dimethoxybenzoic acid in order to confirm the identity of fragment ions containing the reducing terminus. Major fragments from the [M − H]− ions from the neutral glycans retained the derivative (Y‐type cleavages) and provided information on sequence and branching. Other major fragments were products of A‐type cross‐ring cleavages giving information on antenna structure. Singly doubly and triply charged ions were formed from sialylated glycans. They produced major fragments by loss of sialic acid and a series of singly charged ions that were similar to those from the neutral analogues. Doubly charge ions were also produced by the neutral glycans and were fragmented to form product ions with one and two charges. Again, the fragment ions with a single charge were similar to those from the singly charged parents, but branching information was less obvious because of the occurrence of more abundant ions produced by multiple cleavages. Detection limits were around 200 fmol (3 : 1 signal‐to‐noise ratio). Copyright © 2005 John Wiley & Sons, Ltd.
Inhibition of polyphenol oxidase obtained from various sources by 2,3‐diaminopropionic acid
Authors: Arslan Oktay , Doğan Serap
Published: March 2005

This paper reports for the first time the inhibition of the catecholase activities of mushroom, artichoke (Cynara scolymus L) and Ocimum basilicum L polyphenol oxidase by 2,3‐diaminopropionic acid. Polyphenol oxidases from artichoke and O basilicum L were purified by ammonium sulfate precipitation, dialysis and a Sepharose 4B‐L‐tyrosine‐p‐aminobenzoic acid‐affinity column. In inhibition studies, 2,3‐diaminopropionic acid showed uncompetitive inhibition for mushroom PPO using catechol and pyrogallol as substrates, competitive inhibition for O basilicum L PPO using catechol as a substrate, and uncompetitive inhibition for artichoke PPO using catechol as a substrate. Furthermore, sodium azide, which is an inhibitor of PPO, was used as an inhibitor for comparison with the inhibition potency of 2,3‐diaminopropionic acid. The highest 2,3‐diaminopropionic acid inhibition observed with O basilicum L (Ki = 0.89 mM), followed by artichoke (Ki = 1.42 mM) and mushroom (Ki = 2.47 mM), respectively. Copyright © 2005 Society of Chemical Industry
Chemical composition and nutritive value of peach palm (Bactris gasipaes Kunth) in rats
Authors: Leterme Pascal , García Maria‐Fernanda , Londoño Angela‐Maria , Rojas Miriam‐Gisela , Buldgen André , Souffrant Wolfgang‐Bernhard
Published: March 2005

The peach palm (Bactris gasipaes Kunth) is the starchy fruit of a palm tree widely cultivated in Central and South America. The present study aimed at determining its chemical composition and its nutritive value in rats. The average chemical composition of 17 samples was as follows: 410 g kg−1 water and, in g kg−1 of dry matter (DM), 54 g crude protein, 114 g oil, 39 g neutral detergent fibre, 716 g starch, 21 g sugars and 18 g ash. The main variability was observed for the oil (60–180 g kg−1 DM) and starch (590–780 g DM) contents. The proteins contained, on average, in g kg−1 of proteins, 49 g lysine, 13 g methionine, 19 g cysteine, 39 g threonine and 7 g tryptophan. The mineral fraction contained, per kg DM: 1.0 g Ca, 0.8 g P, 0.6 g Mg, 0.3 g Na, 44 mg Fe, 4 mg Cu and 10 mg Zn. The digestibility of four peach palm genotypes was determined in rats fed a diet composed of 350 g kg−1 of peach palm and 650 g of a control diet based on maize and soybean meal. The digestibility of DM, energy, starch and protein of peach palm alone reached, on average 91, 87, 96 and 95%, respectively. No difference was observed between varieties, except for starch (p < 0.05). On average, peach palm contained 51 g of truly digestible protein kg−1 DM and 3.691 kcal digestible energy kg−1 DM. A growth trial was also carried out for 1 month on rats (initial weight: 78 g) fed a diet containing 0, 200, 400, 600 or 800 g peach palm kg−1, at the expense of a diet composed of maize starch and casein. The growth rate of the rats decreased (p < 0.05) as the peach palm concentration increased. The growth decrease was due to a decrease (p < 0.05) in DM intake and to the lower quality of the peach palm protein. It is concluded that peach palm is mainly an energy source for humans and animals. It is poor in protein and minerals but can be consumed in large amounts. Copyright © 2005 Society of Chemical Industry
Familial cortical myoclonic tremor with epilepsy: A single syndromic classification for a group of pedigrees bearing common features
Authors: Van Rootselaar Anne‐Fleur , van Schaik Ivo N. , van den Maagdenberg Arn M.J.M. , Koelman Johannes H.T.M. , Callenbach Petra M.C. , Tijssen Marina A.J.
Published: March 2005

Fifty Japanese and European families with cortical myoclonic tremor and epilepsy have been reported under various names. Unfamiliarity with the syndrome often leads to an initial misdiagnosis of essential tremor or progressive myoclonus epilepsy. A detailed overview of the literature is lacking and is the scope of this study. Disease characteristics are adult onset, distal action tremor and myoclonus, epileptic seizures, autosomal dominant inheritance, benign course, effectiveness of antiepileptic drugs, and possibly cognitive decline. A channelopathy is hypothesized to be the basis of the disease. Despite phenotypic and genetic differences between the Japanese and European pedigrees, the clinical and electrophysiological data point toward one syndrome. To avoid confusion in literature and possible misdiagnosis of patients, we propose to use one description and suggest “familial cortical myoclonic tremor with epilepsy” (FCMTE). In addition, we put forward diagnostic criteria to give a starting point from which to conduct genetic studies. © 2005 Movement Disorder Society
Mesh and solver co‐adaptation in finite element methods for anisotropic problems
Authors: Du Qiang , Huang Zhaohui , Wang Desheng
Published: March 2005

Mesh generation and algebraic solver are two important aspects of the finite element methodology. In this article, we are concerned with the joint adaptation of the anisotropic triangular mesh and the iterative algebraic solver. Using generic numerical examples pertaining to the accurate and efficient finite element solution of some anisotropic problems, we hereby demonstrate that the processes of geometric mesh adaptation and the algebraic solver construction should be adapted simultaneously. We also propose some techniques applicable to the co‐adaptation of both anisotropic meshes and linear solvers. © 2005 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2005
Expression of the interferon‐inducible chemokine IP‐10 (CXCL10), a chemokine with proposed anti‐neoplastic functions, in Hodgkin lymphoma and nasopharyngeal carcinoma
Authors: Teichmann Martina , Meyer Birgit , Beck Andreas , Niedobitek Gerald
Published: March 2005

Hodgkin lymphoma (HL) and nasopharyngeal carcinoma (NPC) are characterized by their association with Epstein–Barr virus (EBV) and an abundant infiltrate of reactive lymphoid cells. The presence of this lymphoid stroma may influence the effect of anti‐viral immunotherapy. The interferon‐inducible chemokine IP‐10 has anti‐neoplastic effects in several model systems mediated by T‐cells expressing the CXCR3 chemokine receptor. Using in situ hybridization, it is shown that IP‐10 is expressed in neoplastic cells of HL and correlates both with the mixed cellularity histotype and with EBV infection. IP‐10 expression was also detected in tumour cells of most NPCs as well as in EBV‐negative squamous cell carcinomas of the tongue. Thus, in carcinomas, IP‐10 expression showed no correlation with EBV infection. Numerous CXCR3‐positive lymphocytes were detected in the lymphoid stroma of HL and NPC, raising the possibility of a Th1‐predominant immune response in these cases. In view of the proposed anti‐neoplastic functions of IP‐10 and CXCR3‐positive lymphocytes, these findings are unexpected and raise the possibility that endogenous IP‐10 expression in the context of human tumours may not exert the anti‐tumour effects ascribed to it by in vitro experiments. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Temperature‐sensitive hydrogel microspheres formed by liquid–liquid phase transitions of aqueous solutions of poly(N,N‐dimethylacrylamide‐co‐allyl methacrylate)
Authors: Yin Xiangchun , Stöver Harald D. H.
Published: March 2005

Poly(N,N‐dimethylacrylamide‐co‐allyl methacrylate) (DMA‐co‐AMA) copolymers were prepared by the copolymerization of N,N‐dimethylacrylamide with allyl methacrylate (AMA). The methacryloyl group of AMA reacted preferentially, and this resulted in pendant allyl groups along the copolymer chains. Aqueous solutions of these DMA‐co‐AMA copolymers were thermoresponsive and showed liquid–liquid phase transitions at temperatures that depended on the AMA content. Hydrogel microspheres were prepared from these thermally phase‐separated liquid microdroplets by the free‐radical crosslinking of the pendant allyl groups. The morphologies of the resulting thermoresponsive microspheres as a function of the reaction temperature and the amount of the initiator were examined. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1641–1648, 2005