bluuebunny/crossref_metadata_2025 huggingface dataset:
Properties of molded soy protein isolate plastics
Authors: Wang Hao , Jiang Lin , Fu Lei
Published: August 2007

Thermal property of soy protein isolates (SPI) was studied with differential scanning calorimetry and thermogravimetric analysis. The weight loss of pure SPI is about 300°C. The glass transition temperature (Tg) is above 200°C. The best molding temperature of glycerin plasticized SPI plastics were then given. It is between 125 and 140°C. Subsequently the special property of molded SPI plastics was investigated. Results show that the atmosphere humidity affects the mechanical property and thermal property of SPI plastics. With the increasing humidity, the tensile strength decreases. While the elongation at breakage and peak area of the differential scanning calorimetry curve increases. At high temperature even at 140°C the molding temperature SPI plastics still have tensile strength though it decreases with the increasing test temperature while elongation at breakage increases. Dynamic mechanic thermal analysis test show that the storage modulus decreases with the rising temperature. The mechanical loss peak appears at lower temperature with the increasing amount of glycerin content. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
In situ observation of plerosphere/polypropylene composites in the tensile test
Authors: Zheng Yanhong , Shen Zhigang , Wang Mingzhu , Ma Shulin , Xing Yushan
Published: August 2007

Toughness, strength, and rigidity of the composites can be improved simultaneously by filling plerosphere particles into polypropylene (PP). The mechanism of improving the mechanical properties of the composites is studied on the basis of the energy dissipation theory. By using scanning electron microscopy (SEM), the crack initiation, propagation, and termination on the plerosphere/PP composites are investigated by in situ tensile test. Observation results show that the particles can effectively lead to a number of microcracks instead of the breaking crack. These microcracks formation consumes tremendous energy. As a result, the toughness and strength of the polymer can be improved. Results of the in situ SEM observation and analysis to the dynamic process supply effective test evidence for the toughening mechanism of the plerosphere/PP composite on the basis of the energy dissipation theory. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Calcitonin Gene‐Related Peptide: A Marker for Putative Primary Afferent Neurons in the Pig Small Intestinal Myenteric Plexus?
Authors: Wolf Matthias , Schrödl Falk , Neuhuber Winfried , Brehmer Axel
Published: August 2007

For years, calcitonin gene‐related peptide (CGRP) has been used as a marker peptide for Dogiel type II neurons, putative intrinsic primary afferent neurons, in the pig enteric nervous system. Recently, some studies showed CGRP‐positive neurons displaying distinctly different shapes. The aims of this study were to evaluate (1) the proportion of myenteric type II neurons that contain CGRP and (2) the proportion of myenteric CGRP‐positive neurons that display type II vs. non–type II morphologies and to conclude if this peptide could be suited as a marker for type II neurons. For this purpose, nine myenteric whole‐mounts (each one from duodenum, jejunum, and ileum, respectively, derived from three pigs) were triple‐immunostained for CGRP, neurofilaments (NF), and choline acetyl transferase (ChAT). Each whole‐mount was evaluated twice. First, 50 NF‐stained type II neurons were selected randomly and their coreactivities for CGRP and ChAT were observed. Second, 50 CGRP‐positive neurons were located randomly and their NF morphology and ChAT coreactivity were observed. Altogether, 92% of all type II neurons investigated displayed CGRP immunoreactivity, whereas 94.9% of all CGRP‐reactive neurons recorded displayed type II morphology. We observed three further shapes of CGRP‐positive neurons: 7 type V neurons (all were ChAT‐positive; mainly in the ileal whole‐mounts), 6 type I–like neurons (all were ChAT‐positive), and 14 type III–like neurons (mostly ChAT‐negative; mainly in duodenal and jejunal specimens). We conclude that CGRP‐antibodies can be used as markers for type II neurons in the pig small intestinal myenteric plexus in quantitative studies but it should be kept in mind that up to one‐tenth of CGRP‐reactive neurons may be non–type II neurons. In case of single cell evaluation, CGRP‐immunoreactivity alone is not suited as a marker. In such cases additional, morphological analysis is necessary. Anat Rec, 290:1273‐1279, 2007. © 2007 Wiley‐Liss, Inc.
1‐Cinnamyl‐4‐(2‐methoxyphenyl)piperazines: Synthesis, Binding Properties, and Docking to Dopamine (D2) and Serotonin (5‐HT1A) Receptors
Authors: Penjišević Jelena , Šukalović Vladimir , Andrić Deana , Kostić‐Rajačić Sladjana , Šoškić Vukić , Roglić Goran
Published: August 2007

Clinical properties of atypical antipsychotics are based on their interaction with D2 dopamine receptor and serotonin 5‐HT1A and 5‐HT2A receptors. As a part of our research program on new antipsychotics, we synthesized various derivatives of 1‐cinnamyl‐4‐(2‐methoxyphenyl)piperazines, and evaluated their affinities for D2, 5‐HT1A, 5‐HT2A, and adrenergic (α1) receptors using radioligand‐binding assays. In addition, we performed docking analysis using models for the D2 and 5‐HT1A receptors. All compounds exhibited low to moderate affinity to 5‐HT1A and 5‐HT2A receptors, high affinity to the D2 receptor and large variability in affinities for the α1 receptor. Docking analysis indicated that the binding to D2 and 5‐HT1A receptors is based on (i) interaction between protonated N1 of the piperazine ring and various aspartate residues, (ii) hydrogen bonds between various moieties of the ligand and the residues of threonine, serine, histidine or tryptophane, and (iii) edge‐to‐face interactions of the aromatic ring of the arylpiperazine moiety with phenylalanine or tyrosine residues. Docking data for the D2 receptor can account for the binding properties obtained in binding assays, suggesting that the model is reliable and robust. However, docking data for the 5‐HT1A receptor cannot account for actual binding properties, suggesting that further refinement of the model is required.
Pharmacokinetic Profile of Atenolol Aspirinate
Authors: Montes‐Gil Ana C. , Zanfolin Marcos , Okuyama Cristina E. , Lilla Sergio , Alves Delma P. , Santagada Vincenzo , Perissutti Elisa , Lavecchia Antonio , Fiorino Ferdinando , Severino Beatrice , Caliendo Giuseppe , Priviero Fernanda B. M. , Mendes Gustavo D. , Donato Jose L. , Nucci Gilberto de
Published: August 2007

We report microwave‐assisted synthetic routes, the pharmacokinetic profile along with results from ulcerogenicity and mutagenicity studies of atenolol aspirinate, and an already described derivative, in which acetyl salicylic acid (aspirin®) was connected to atenolol by an ester linkage. Atenolol aspirinate was stable towards aqueous hydrolysis but rapidly hydrolyzed in plasma (t1/2= 7.6 min). The results showed that the rapid and complete hydrolysis generates atenolol salicylate, which assumes a conformation stabilized by two intramolecular H‐bonds, avoiding its further hydrolysis to salicylic acid and atenolol.
Synthesis of 2‐Substituted‐7‐heptyloxy‐4,5‐dihydro‐[1,2,4]‐triazolo[4,3‐a]quinolin‐1(2H)‐ones with Anticonvulsant Activity
Authors: Wei Cheng‐Xi , Li Fu‐Nan , Zhao Long‐Xuan , Zhao Li‐Ming , Quan Zhe‐Shan
Published: August 2007

A series of 2‐substituted‐7‐heptyloxy‐4,5‐dihydro‐[1,2,4]triazolo[4,3‐a]quinolin‐1(2H)‐ones was synthesized. The anticonvulsant effect and neurotoxicity of the compounds were calculated with maximal electroshock (MES) test, subcutaneous pentylenetetrazole (sc‐PTZ), and rotarod tests with intraperitoneally injected mice. Among the synthesized compounds, 2‐propionyl‐7‐heptyloxy‐4,5‐dihydro‐[1,2,4]triazolo[4,3‐a]quinoline‐1(2H)‐one 4b was the most active one and also had the lowest toxicity. In the anti‐MES potency test, it showed median effective dose (ED50) of 8.2 mg/kg, median toxicity dose (TD50) of 318.3 mg/kg, and the protective index (PI) of 39.0 which is much greater than the PI of the reference drugs phenytoin and carbamazepine.
CD19 hyperexpression augments Sle1‐induced humoral autoimmunity but not clinical nephritis
Authors: Shi Xiaoyan , Xie Chun , Chang Sooghee , Zhou Xin J. , Tedder Thomas , Mohan Chandra
Published: August 2007

Objective

B cell hyperactivity is a common denominator in murine and human systemic lupus erythematosus. Some susceptibility genes in lupus are associated with B cell hyperactivity, but others are clearly not. While the Sle1 lupus susceptibility locus of NZM2410/NZW origin leads to chromatin‐focused autoimmunity, genetically engineered overexpression of CD19 leads to “generalized” B cell hyperactivity. We undertook this study to determine the degree to which generalized B cell hyperactivity can amplify lupus pathogenesis.

Methods

To elucidate the impact of generalized B cell hyperactivity on Sle1‐triggered autoimmunity, B6 mice bearing the human CD19 transgene were rendered congenic for the Sle1z genetic locus and phenotyped for serologic, cellular, and pathologic evidence of lupus.

Results

As expected, B6.Sle1.hCD19Tg/Tg mice, homozygous at Sle1 and bearing the hCD19 transgene, exhibited high levels of IgM and IgG anti‐DNA/antiglomerular autoantibodies, skewed B cell subsets, and profoundly activated B and T cells. Despite exhibiting glomerular IgM, IgG, and complement deposits, these mice did not exhibit accelerated mortality or any clinical evidence of renal dysfunction.

Conclusion

Generalized B cell hyperactivity may augment humoral autoimmunity, but this may not suffice to engender end‐organ disease in lupus. These findings allude to the presence of an additional distal checkpoint that dissociates pathogenic autoantibody formation and renal immunoglobulin deposition from the progression to clinical nephritis in lupus.
Febrile temperatures control antineutrophil cytoplasmic autoantibody–induced neutrophil activation via inhibition of phosphatidylinositol 3‐kinase/Akt
Authors: von Vietinghoff Sibylle , Choi Mira , Rolle Susanne , Luft Friedrich C. , Kettritz Ralph
Published: August 2007

Objective

Neutrophil activation by antineutrophil cytoplasmic autoantibodies (ANCAs) is central to the pathogenesis of the ANCA‐associated vasculitides. Febrile infections occur frequently during these diseases, often in the context of immunosuppressive treatment. Heat exposure may affect the underlying pathophysiologic processes of the vasculitis. In this study we tested the hypothesis that short‐term exposure to heat inhibits ANCA‐induced neutrophil activation.

Methods

After exposure to temperatures from 37°C to 42°C, human neutrophils were primed with either tumor necrosis factor α (TNFα) or granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and stimulated with monoclonal antibodies to myeloperoxidase or to proteinase 3. Respiratory burst activity was assayed using rhodamine and a nitroblue tetrazolium reduction assay. Specific inhibition experiments against p38 MAPK, ERK, and phosphatidylinositol 3‐kinase (PI 3‐kinase)/Akt, and Western blotting with phospho‐specific antibodies were used to identify key components in the antibody‐induced respiratory burst.

Results

A temperature‐dependent reduction in ANCA‐induced respiratory burst was observed over a range of heat exposures from 37°C to 42°C. Inhibition of human ANCA–induced neutrophil stimulation was significant at 40°C (after priming with 2 ng/ml TNFα, mean [± SEM] fluorescence intensity [MFI] 114 ± 12 at 37°C versus 53 ± 6 at 40°C; after priming with 20 ng/ml GM‐CSF, MFI 92 ± 16 at 37°C versus 35 ± 6 at 40°C; both P < 0.01). In the priming phase, the transient activation of the p38 MAPK, ERK, and PI 3‐kinase/Akt pathways by TNFα was blocked by prior exposure of the neutrophils to heat, but GM‐CSF–induced activation was unaltered by heat. However, in the second, antibody‐induced wave of kinase activation, exposure to heat inhibited only the PI 3‐kinase/Akt pathway, and these effects were independent of the priming agent used.

Conclusion

Short‐term spikes of modest heat abrogate ANCA‐induced activation of neutrophils via inhibition of PI 3‐kinase/Akt signaling. Febrile responses in ANCA‐mediated diseases may therefore have a physiologic purpose.
HLA–DRB4 as a genetic risk factor for Churg‐Strauss syndrome
Authors: Vaglio Augusto , Martorana Davide , Maggiore Umberto , Grasselli Chiara , Zanetti Adele , Pesci Alberto , Garini Giovanni , Manganelli Paolo , Bottero Paolo , Tumiati Bruno , Sinico Renato A. , Savi Mario , Buzio Carlo , Neri Tauro M.
Published: August 2007

Objective

To explore the association between HLA alleles and Churg‐Strauss syndrome (CSS), and to investigate the potential influence of HLA alleles on the clinical spectrum of the disease.

Methods

Low‐resolution genotyping of HLA–A, HLA–B, and HLA–DR loci and genotyping of TNFA −238A/G and TNFA −308A/G single‐nucleotide polymorphisms were performed in 48 consecutive CSS patients and 350 healthy controls.

Results

The frequency of the HLA–DRB1*07 allele was higher in the CSS patients than in controls (27.1% versus 13.3%; χ2 = 12.64, P = 0.0003, corrected P [Pcorr] = 0.0042, odds ratio [OR] 2.42, 95% confidence interval [95% CI] 1.47–3.99). The HLA–DRB4 gene, present in subjects carrying either HLA–DRB1*04, HLA–DRB1*07, or HLA–DRB1*09 alleles, was also far more frequent in patients than in controls (38.5% versus 20.1%; χ2 = 16.46, P = 0.000058, Pcorr = 0.000232, OR 2.49, 95% CI 1.58–3.09). Conversely, the frequency of the HLA–DRB3 gene was lower in patients than in controls (35.4% versus 50.4%; χ2 = 7.62, P = 0.0057, Pcorr = 0.0228, OR 0.54, 95% CI 0.35–0.84). CSS has 2 major clinical subsets, antineutrophil cytoplasmic antibody (ANCA)–positive, with features of small‐vessel vasculitis, and ANCA‐negative, in which organ damage is mainly mediated by tissue eosinophilic infiltration; analysis of HLA–DRB4 in patients categorized by different numbers of vasculitic manifestations (purpura, alveolar hemorrhage, mononeuritis multiplex, rapidly progressive glomerulonephritis, and constitutional symptoms) showed that its frequency strongly correlated with the number of vasculitis symptoms (P for trend = 0.001).

Conclusion

These findings indicate that HLA–DRB4 is a genetic risk factor for the development of CSS and increases the likelihood of development of vasculitic manifestations of the disease.
A randomized, placebo‐controlled trial of infliximab plus methotrexate for the treatment of polyarticular‐course juvenile rheumatoid arthritis
Authors: Ruperto Nicolino , Lovell Daniel J. , Cuttica Ruben , Wilkinson Nick , Woo Patricia , Espada Graciela , Wouters Carine , Silverman Earl D. , Balogh Zsolt , Henrickson Michael , Apaz Maria‐Teresa , Baildam Eileen , Fasth Anders , Gerloni Valeria , Lahdenne Pekka , Prieur Anne‐Marie , Ravelli Angelo , Saurenmann Rotraud K. , Gamir Maria Luz , Wulffraat Nico , Marodi Laszlo , Petty Ross E. , Joos Rik , Zulian Francesco , McCurdy Deborah , Myones Barry L. , Nagy Kalman , Reuman Peter , Szer Ilona , Travers Suzanne , Beutler Anna , Keenan Greg , Clark Jason , Visvanathan Sudha , Fasanmade Adedigbo , Raychaudhuri Aparna , Mendelsohn Alan , Martini Alberto , Giannini Edward H.
Published: August 2007

Objective

To evaluate the safety and efficacy of infliximab in the treatment of juvenile rheumatoid arthritis (JRA).

Methods

This was an international, multicenter, randomized, placebo‐controlled, double‐blind study. One hundred twenty‐two children with persistent polyarticular JRA despite prior methotrexate (MTX) therapy were randomized to receive infliximab or placebo for 14 weeks, after which all children received infliximab through week 44. Patients received MTX plus infliximab 3 mg/kg through week 44, or MTX plus placebo for 14 weeks followed by MTX plus infliximab 6 mg/kg through week 44.

Results

Although a higher proportion of patients in the 3 mg/kg infliximab group than in the placebo group had achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement at week 14 (63.8% and 49.2%, respectively), the between‐group difference in this primary efficacy end point was not statistically significant (P = 0.12). By week 16, after the crossover from placebo to infliximab 6 mg/kg when all patients were receiving infliximab, an ACR Pedi 30 response was achieved in 73.2% of all patients. By week 52, ACR Pedi 50 and ACR Pedi 70 responses had been reached in 69.6% and 51.8%, respectively, of patients. Infliximab was generally well tolerated, but the safety profile of infliximab 3 mg/kg appeared less favorable than that of infliximab 6 mg/kg, with more frequent occurrences of serious adverse events, infusion reactions, antibodies to infliximab, and newly induced antinuclear antibodies and antibodies to double‐stranded DNA observed with the 3 mg/kg dose.

Conclusion

While infliximab at 3 mg/kg and 6 mg/kg showed durable efficacy at 1 year, achievement of the primary efficacy end point at 3 months did not differ significantly between infliximab‐treated and placebo‐treated patients. Safety data indicated that the 6‐mg/kg dose may provide a more favorable risk/benefit profile. These results warrant further investigation in children with JRA.
Interleukin‐1β impairment of transforming growth factor β1 signaling by DOWN‐REGULATION of transforming growth factor β receptor type II and up‐regulation of Smad7 in human articular chondrocytes
Authors: Baugé C. , Legendre F. , Leclercq S. , Elissalde J. M. , Pujol J. P. , Galéra P. , Boumédiene K.
Published: August 2007

Objective

Extracellular matrix deposition is tightly controlled by a network of regulatory cytokines. Among them, interleukin‐1β (IL‐1β) and transforming growth factor β1 (TGFβ1) have been shown to play antagonistic roles in tissue homeostasis. The purpose of this study was to determine the influence of IL‐1β on TGFβ receptor type II (TGFβRII) regulation and TGFβ1 responsiveness in human articular chondrocytes.

Methods

TGFβ1‐induced gene expression was analyzed through plasminogen activator inhibitor 1 and p3TP‐Lux induction. Receptor‐activated Smad (R‐Smad) phosphorylation, TGFβ receptors, and Smad expression were determined by Western blotting and real‐time reverse transcription–polymerase chain reaction techniques. Signaling pathways were investigated using specific inhibitors, messenger RNA (mRNA) silencing, and expression vectors.

Results

IL‐1β down‐regulated TGFβRII expression at both the protein and mRNA levels and led to inhibition of the TGFβ1‐induced gene expression and Smad2/3 phosphorylation. Moreover, IL‐1β strongly stimulated the expression of inhibitory Smad7. TGFβRII overexpression abolished the loss of TGFβ1 responsiveness induced by IL‐1β. The decrease in TGFβRII required de novo protein synthesis and involved both the NF‐κB and JNK pathways.

Conclusion

We demonstrate that IL‐1β impairs TGFβ1 signaling through down‐regulation of TGFβRII, which is mediated by the p65/NF‐κB and activator protein 1/JNK pathways, and secondarily through the up‐regulation of Smad7. These findings show that there is cross‐talk in the signaling of 2 regulatory cytokines involved in inflammation.
Early changes in serum type ii collagen biomarkers predict radiographic progression at one year in inflammatory arthritis patients after biologic therapy
Authors: Mullan Ronan H. , Matthews Clare , Bresnihan Barry , FitzGerald Oliver , King Lindsay , Poole A. Robin , Fearon Ursula , Veale Douglas J.
Published: August 2007

Objective

To investigate whether short‐term changes in serum biomarkers of type II collagen degradation (C2C) and types I and II collagen degradation (C1,2C), as well as the biomarker for the synthesis of type II procollagen (CPII) can predict radiographic progression at 1 year following initiation of biologic therapy in patients with inflammatory arthritis.

Methods

Serum levels of biomarkers were measured at baseline and at 1, 3, 6, 9, and 12 months after initiation of biologic therapy. A composite score reflecting changes from baseline in all 3 biomarkers (ΔCOL) was calculated. Associations with clinical responses according to the 28‐joint count Disease Activity Score and with radiographic progression according to the modified Sharp/van der Heijde score (SHS) were assessed.

Results

The 1‐year increase in the SHS correlated with the 1‐month change in C2C results (r = 0.311, P = 0.028) and the ΔCOL score (r = 0.342, P = 0.015). Radiographic progression was predicted by increases in serum C2C at 1 month (P = 0.031). The ΔCOL score was significantly associated with 1‐year radiographic progression after 1 (P = 0.022), 3 (P = 0.015), 6 (P = 0.048), and 9 (P = 0.019) months of therapy. Clinical remission was predicted by 1‐month decreases in serum levels of C2C (P = 0.008) and C1,2C (P = 0.036). By regression analysis, 1‐month changes in C2C, C1,2C, and CPII levels were independently associated with, and correctly predicted radiographic outcome in, 88% of the patients.

Conclusion

Short‐term changes in serum levels of collagen biomarkers following initiation of biologic therapy may better predict long‐term clinical and radiographic outcomes. These collagen biomarkers may therefore be valuable new early indicators of short‐term biologic treatment efficacy in clinical trials and in individual patients with inflammatory erosive arthritis.
Differential regulation of matrix metalloproteinase 2 and matrix metalloproteinase 9 by activated protein C: Relevance to inflammation in rheumatoid arthritis
Authors: Xue Meilang , March Lyn , Sambrook Philip N. , Jackson Christopher J.
Published: August 2007

Objective

To investigate the in vitro effect of activated protein C (APC), a natural anticoagulant and novel antiinflammatory agent, on the regulation of the gelatinases matrix metalloproteinase 2 (MMP‐2) and MMP‐9.

Methods

Synovial fibroblasts and peripheral blood monocytes isolated from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) and Mono Mac6 cells were used in this study. After treatment, cells and culture supernatants were collected for zymography, enzyme‐linked immunosorbent assay, reverse transcription–polymerase chain reaction, and Western blot analysis.

Results

Fibroblasts and monocytes from RA patients produced substantially more MMP‐9 than did those from OA patients; however, there was no difference in MMP‐2 production. The addition of recombinant APC markedly reduced MMP‐9 at the gene and protein levels. In contrast, APC up‐regulated and activated MMP‐2. Using a blocking antibody to the endothelial protein C receptor (EPCR), we showed that the inhibition of MMP‐9 by APC was EPCR‐dependent. Furthermore, APC directly suppressed the production of tumor necrosis factor (TNF) and the activation of NF‐κB and MAP kinase p38, and inhibitors of NF‐κB or p38 reduced the production of MMP‐9, suggesting that APC inhibits MMP‐9 by blocking TNF, NF‐κB, and p38. Thus, APC acts on MMP‐9 by binding to EPCRs on the cell surface and, subsequently, inhibiting the intracellular activation of the proinflammatory signaling molecules NF‐κB and p38.

Conclusion

APC appears to be the first physiologic agent to inhibit the production of proinflammatory MMP‐9, yet increase antiinflammatory MMP‐2 activity. Our results provide the initial evidence that APC may be beneficial in the prevention of inflammation and joint destruction in RA.
Association of smoking with the constitution of the anti–cyclic citrullinated peptide response in the absence of HLA–DRB1 shared epitope alleles
Authors: Verpoort K. N. , Papendrecht‐van der Voort E. A. M. , van der Helm‐van Mil A. H. M. , Jol‐van der Zijde C. M. , van Tol M. J. D. , Drijfhout J. W. , Breedveld F. C. , de Vries R. R. P. , Huizinga T. W. J. , Toes R. E. M.
Published: August 2007

Objective

Smoking is a risk factor for anti–cyclic citrullinated peptide (anti‐CCP) antibody–positive rheumatoid arthritis (RA) in patients with HLA–DRB1 shared epitope (SE) alleles. It is unknown whether smoking influences not only the presence of these antibodies, but also other characteristics of the anti‐CCP response, such as isotype usage. The aim of this study was to determine the influence of smoking on anti‐CCP isotypes in RA patients, and to determine whether this influence is observed in the presence and/or absence of SE alleles.

Methods

IgA, IgM, and IgG subclasses of anti‐CCP antibodies were measured by enzyme‐linked immunosorbent assay in serum obtained at the first visit to the Leiden Early Arthritis Clinic from 216 patients with anti‐CCP–positive RA whose smoking habits were also assessed. HLA genotyping data were available for 202 of these patients.

Results

IgA and IgM anti‐CCP were more frequent in RA patients who were smokers than in those who were nonsmokers (odds ratio 2.8 and 1.8, respectively). In addition, levels of all isotypes of anti‐CCP, except IgG3, were significantly higher (P < 0.05) in smokers. The number of anti‐CCP isotypes was higher in smokers compared with nonsmokers, both in SE‐negative RA (P = 0.04) and in SE‐positive RA (P = 0.07).

Conclusion

Patients with anti‐CCP–positive RA who have a current or former tobacco exposure display a more extensive anti‐CCP isotype usage in general, and IgA and IgM in particular, compared with patients with anti‐CCP–positive RA who have never smoked. In contrast to its influence on the incidence of anti‐CCP positivity, the influence of tobacco exposure on the constitution of the anti‐CCP response is significant in SE‐negative RA. These findings suggest a differential effect of tobacco exposure on the induction as compared with the propagation of the anti‐CCP antibody response.
Development of an ex vivo cellular model of rheumatoid arthritis: Critical role of cd14‐positive monocyte/macrophages in the development of pannus tissue
Authors: Nozaki Toshiko , Takahashi Kyoko , Ishii Osamu , Endo Sachio , Hioki Kyoji , Mori Toshihito , Kikukawa Tadahiro , Boumpas Dimitrios T. , Ozaki Shoichi , Yamada Hidehiro
Published: August 2007

Objective

To establish an ex vivo cellular model of pannus, the aberrant overgrowth of human synovial tissue (ST).

Methods

Inflammatory cells that infiltrated pannus tissue from patients with rheumatoid arthritis (RA) were collected without enzyme digestion, and designated as ST‐derived inflammatory cells. Single‐cell suspensions of ST‐derived inflammatory cells were cultured in medium alone. Levels of cytokines produced in culture supernatants were measured using enzyme‐linked immunosorbent assay kits. ST‐derived inflammatory cells were transferred into the joints of immunodeficient mice to explore whether these cells could develop pannus. CD14 and CD2 cells were depleted by negative selection.

Results

Culture of ST‐derived inflammatory cells from 92 of 111 patients with RA resulted in spontaneous reconstruction of inflammatory tissue in vitro within 4 weeks. Ex vivo tissue contained fibroblasts, macrophages, T cells, and tartrate‐resistant acid phosphatase–positive multinucleated cells. On calcium phosphate–coated slides, ST‐derived inflammatory cell cultures showed numerous resorption pits. ST‐derived inflammatory cell cultures continuously produced matrix metalloproteinase 9 and proinflammatory cytokines associated with osteoclastogenesis, such as tumor necrosis factor α, interleukin‐8, and macrophage colony‐stimulating factor. More importantly, transferring ST‐derived inflammatory cells into the joints of immunodeficient mice resulted in the development of pannus tissue and erosive joint lesions. Both in vitro development and in vivo development of pannus tissue by ST‐derived inflammatory cells were inhibited by depleting CD14‐positive, but not CD2‐positive, cells from ST‐derived inflammatory cells.

Conclusion

These findings suggest that overgrowth of inflammatory cells from human rheumatoid synovium simulates the development of pannus. This may prove informative in the screening of potential antirheumatic drugs.
Correlation of the development of knee pain with enlarging bone marrow lesions on magnetic resonance imaging
Authors: Felson David T. , Niu Jingbo , Guermazi Ali , Roemer Frank , Aliabadi Piran , Clancy Margaret , Torner James , Lewis C. Elizabeth , Nevitt Michael C.
Published: August 2007

Objective

Results of cross‐sectional studies have suggested that bone marrow lesions (BMLs) visualized on magnetic resonance imaging (MRI) are related to knee pain, but no longitudinal studies have been done. This study was undertaken to determine whether enlarging BMLs are associated with new knee pain.

Methods

Subjects ages 50–79 years with knee osteoarthritis (OA) or at high risk of knee OA were asked twice at baseline about the presence of knee pain, aching, or stiffness (classified as frequent knee pain) on most days; absence of knee pain was the baseline eligibility criterion. At 15 months' followup, subjects were again queried twice about frequent knee pain. A case knee was defined as absence of knee pain at baseline but presence of knee pain both times at followup. Controls were selected randomly from among knees with absence of pain at baseline. All MR images were scored for volume of BMLs in the medial, lateral, and patellofemoral compartments. We focused on the maximal change in BML score among the knee compartments from baseline to 15 months. Multiple logistic regression, with adjustments for demographic and clinical variables, was used to assess whether an increased BML score is predictive of the development of knee pain.

Results

Among case knees, 54 of 110 (49.1%) showed an increase in BML score within a compartment, whereas only 59 of 220 control knees (26.8%) showed an increase (P < 0.001 by chi‐square test). A BML score increase of at least 2 units was much more common in case knees than in control knees (27.5% versus 8.6%; adjusted odds ratio 3.2, 95% confidence interval 1.5–6.8). Among case knees with increased BMLs, most already had BMLs at baseline, with enlarging BMLs at followup, but among the subset of knees with no BMLs at baseline, new BMLs were more common in case knees (11 [32.4%] of 34) than in control knees (9 [10.8%] of 83).

Conclusion

Development of knee pain is associated with an increase in BMLs as revealed on MRI.
Rituximab for the treatment of juvenile dermatomyositis: A report of four pediatric patients
Authors: Cooper Megan A. , Willingham Donna L. , Brown Diane E. , French Anthony R. , Shih Fei F. , White Andrew J.
Published: August 2007

Objective

Juvenile dermatomyositis (DM) is a chronic inflammatory myopathy of childhood primarily affecting the muscles and skin. Treatment for juvenile DM is often difficult, and conventional therapies include corticosteroids and other immune suppressants. We reviewed the records of 4 patients with juvenile DM who received the B cell–depleting anti‐CD20 monoclonal antibody rituximab to determine whether this therapy resulted in improved control of their juvenile DM.

Methods

This is a retrospective review of 4 pediatric patients ages 10–17 years with juvenile DM who were treated with rituximab. All patients were tested for myositis autoantibodies and received weekly rituximab infusions for a total of 4 doses. Two patients received repeat courses of rituximab 1 year after their first dose. Patients were followed up between 12 and 24 months after their first course of rituximab, and their strength, muscle enzymes, and rash were reviewed.

Results

One patient was positive for a myositis‐specific antibody, anti–Mi‐2, and demonstrated striking reductions in her muscle enzyme levels for 1 year after rituximab therapy. Following a second course of rituximab, this patient remained disease free for 14 months before requiring a third course of rituximab. Two myositis antibody–negative patients showed clinical improvement and tolerated lower doses of corticosteroids following treatment with rituximab. Finally, 1 patient had worsening of her disease following rituximab.

Conclusion

These cases highlight the potential for anti–B cell therapies in the treatment of juvenile DM in both myositis‐specific autoantibody–positive and –negative patients.
A possible mechanism for endogenous activation of the type I interferon system in myositis patients with anti–Jo‐1 or anti–Ro 52/anti–Ro 60 autoantibodies
Authors: Eloranta Maija‐Leena , Barbasso Helmers Sevim , Ulfgren Ann‐Kristin , Rönnblom Lars , Alm Gunnar V. , Lundberg Ingrid E.
Published: August 2007

Objective

To investigate type I interferon (IFN) system activation and its correlation with autoantibodies and organ manifestations in polymyositis (PM), dermatomyositis (DM), and inclusion body myositis.

Methods

Sera from 30 patients and 16 healthy controls, or purified IgG, were combined with material released from necrotized cells to stimulate IFNα production by peripheral blood mononuclear cells (PBMCs) from healthy blood donors. Muscle biopsy specimens from 25 patients and 7 healthy controls were investigated for blood dendritic cell antigen 2 (BDCA‐2)–positive plasmacytoid dendritic cells (PDCs) and IFNα/β‐inducible myxovirus resistance 1 (MX‐1) protein.

Results

Sera from 13 patients who were positive for anti–Jo‐1 or anti–Ro 52/anti–Ro 60 autoantibodies induced IFNα production in PBMCs when combined with necrotic cell material. In addition, IgG prepared from anti–Jo‐1–positive PM sera induced IFNα with necrotic material, but not when the latter was treated with RNase. BDCA‐2 expression in PDCs in muscle tissue was increased in PM patients with anti–Jo‐1 autoantibodies, while MX‐1 staining in capillaries was increased in DM patients, compared with healthy individuals. IFNα‐inducing capacity correlated with interstitial lung disease, while MX‐1 expression in the capillaries correlated with DM.

Conclusion

Immune complexes containing anti–Jo‐1 or anti–Ro 52/anti–Ro 60 autoantibodies and RNA may act as endogenous IFNα inducers that activate IFNα production in PDCs. These PDCs could be of importance for inducing myositis, whereas in DM patients without autoantibodies the presence of MX‐1 protein in capillaries suggests another cellular IFNα source and induction mechanism. Consequently, the type I IFN system may be of importance in both PM and DM, but via different pathways.
Anti–Jo‐1 antibody levels correlate with disease activity in idiopathic inflammatory myopathy
Authors: Stone Kerry B. , Oddis Chester V. , Fertig Noreen , Katsumata Yasuhiro , Lucas Mary , Vogt Molly , Domsic Robyn , Ascherman Dana P.
Published: August 2007

Objective

Previous case series have examined the relationship between anti–Jo‐1 antibody levels and myositis disease activity, demonstrating equivocal results. Using enzyme‐linked immunosorbent assays (ELISAs) and novel measures of myositis disease activity, the current study was undertaken to systematically reexamine the association between anti–Jo‐1 antibody levels and various disease manifestations of myositis.

Methods

Serum anti–Jo‐1 antibody levels were quantified using 2 independent ELISA methods, while disease activity was retrospectively graded using the Myositis Disease Activity Assessment Tool, which measures disease activity in 7 different organ systems via the Myositis Disease Activity Assessment Visual Analog Scale (VAS) and the Myositis Intention‐to‐Treat Index (MITAX) components. Spearman's rank correlation coefficients and mixed linear regression analysis were used to identify associations between anti–Jo‐1 antibody levels and organ‐specific disease activity in cross‐sectional and longitudinal analyses, respectively.

Results

Cross‐sectional assessment of 81 patients with anti–Jo‐1 antibody revealed a modest correlation between the anti–Jo‐1 antibody level and the serum creatine kinase (CK) level, as well as muscle and joint disease activity. Correlation coefficients were similar for CK levels (rs = 0.38, P = 0.002), myositis VAS (rs = 0.36, P = 0.002), and arthritis VAS (rs = 0.40, P = 0.001). In multiple regression analyses of 11 patients with serial samples, anti–Jo‐1 antibody levels correlated significantly with CK levels (R2 = 0.65, P = 0.0002), myositis VAS (R2 = 0.53, P = 0.0008), arthritis VAS (R2 = 0.53, P = 0.006), pulmonary VAS (R2 = 0.69, P = 0.005), global VAS (R2 = 0.63, P = 0.002), and global MITAX (R2 = 0.64, P = 0.0003).

Conclusion

In this large series of patients with idiopathic inflammatory myopathy, anti–Jo‐1 antibody levels correlated modestly with muscle and joint disease, an association confirmed by a custom ELISA using recombinant human Jo‐1. More striking associations emerged in a smaller longitudinal subset of patients that link anti–Jo‐1 antibody levels to muscle, joint, lung, and global disease activity.
Distinct regulation of interleukin‐17 in human T helper lymphocytes
Authors: Chen Zhi , Tato Cristina M. , Muul Linda , Laurence Arian , O'Shea John J.
Published: August 2007

Objective

Interleukin‐17 (IL‐17)–producing T helper cells have been proposed to represent a separate lineage of CD4+ cells, designated Th17 cells, which are regulated by the transcription factor retinoic acid–related orphan receptor γt (RORγt). However, despite advances in understanding murine Th17 differentiation, a systematic assessment of factors that promote the differentiation of naive human T cells to Th17 cells has not been reported. The present study was undertaken to assess the effects on naive human CD4+ T cells of cytokines known to promote murine Th17 cells.

Methods

Human naive and memory CD4+ T cells isolated from peripheral blood were activated and cultured with various cytokines. Cytokine production was measured by enzyme‐linked immunosorbent assay and flow cytometry. Messenger RNA was measured by quantitative polymerase chain reaction.

Results

In response to anti‐CD3/anti‐CD28 stimulation alone, human memory T cells rapidly produced IL‐17, whereas naive T cells expressed low levels. Transforming growth factor β1 and IL‐6 up‐regulated RORγt expression but did not induce Th17 differentiation of naive CD4+ T cells. However, IL‐23 up‐regulated its own receptor and was an important inducer of IL‐17 and IL‐22.

Conclusion

The present data demonstrate the differential regulation of IL‐17 and RORγt expression in human CD4+ T cells compared with murine cells. Optimal conditions for the development of IL‐17–producing T cells from murine naive precursors are ineffective in human T cells. Conversely, IL‐23 promoted the generation of human Th17 cells but was also a very potent inducer of other proinflammatory cytokines. These findings may have important implications in the pathogenesis of human autoimmunity as compared with mouse models.
The performance of anti–cyclic citrullinated peptide antibodies in predicting the severity of radiologic damage in inflammatory polyarthritis: Results from the Norfolk Arthritis Register
Authors: Bukhari M. , Thomson W. , Naseem H. , Bunn D. , Silman A. , Symmons D. , Barton A.
Published: August 2007

Objective

Anti–cyclic citrullinated peptide (anti‐CCP) antibodies are a stronger predictor of the severity of rheumatoid arthritis than is rheumatoid factor (RF). Their role in predicting outcome in unselected patients with new‐onset inflammatory polyarthritis (IP) has not been examined. The aims of this study were to examine the role of baseline RF and anti‐CCP antibodies in determining the likelihood of patients having erosions at presentation or in predicting future radiologic damage, and to determine whether anti‐CCP antibodies or RF is sufficiently robust to be clinically useful in guiding treatment decisions in early IP.

Methods

Patients were recruited from the Norfolk Arthritis Register. Logistic regression models were fitted to test the ability of anti‐CCP antibodies and RF to predict erosions. Further models were investigated to examine the role of anti‐CCP antibodies in patients stratified by RF status.

Results

The presence of anti‐CCP antibodies at baseline was strongly associated with both prevalent erosions (odds ratio [OR] 2.53 [95% confidence interval (95% CI) 1.48–4.30]) and developing erosions at 5 years (OR 10.2 [95% CI 6.2–16.9]). These ORs were higher than those for RF (OR 1.63 [95% CI 0.94–2.82] and OR 3.4 [95% CI 2.2–5.2], respectively). The likelihood ratio (LR) for the prediction of prevalent erosions and erosions at 5 years was highest in the RF−subgroup (LR 2.2 and 5.8, respectively). However, 27% of anti‐CCP−patients had developed erosions by 5 years.

Conclusion

Despite their strong association with the presence, development, and extent of erosions, anti‐CCP antibodies alone are not a sufficiently accurate measure upon which to base clinical treatment decisions. Knowledge of anti‐CCP antibody status is most informative in RF−negative patients.
Association of a CD24 gene polymorphism with susceptibility to systemic lupus erythematosus
Authors: Sánchez Elena , Abelson Anna‐Karin , Sabio Jose M. , González‐Gay Miguel A. , Ortego‐Centeno Norberto , Jiménez‐Alonso Juan , de Ramón Enrique , Sánchez‐Román Julio , López‐Nevot Miguel A. , Gunnarsson Iva , Svenungsson Elisabet , Sturfelt Gunnar , Truedsson Lennart , Jönsen Andreas , González‐Escribano Maria Francisca , Witte Torsten , Alarcón‐Riquelme Marta E. , Martín Javier
Published: August 2007

Objective

To determine the potential role of the CD24 A57V gene polymorphism in systemic lupus erythematosus (SLE).

Methods

We studied 3 cohorts of Caucasian patients and controls. The Spanish cohort included 696 SLE patients and 539 controls, the German cohort included 257 SLE patients and 317 controls, and the Swedish cohort included 310 SLE patients and 247 controls. The CD24 A57V polymorphism was genotyped by polymerase chain reaction, using a predeveloped TaqMan allele discrimination assay. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.

Results

In the Spanish cohort there was a statistically significant difference in the distribution of the CD24 V allele between SLE patients and controls (OR 3.6 [95% CI 2.13–6.16], P < 0.0001). In addition, frequency of the CD24 V/V genotype was increased in SLE patients compared with controls (OR 3.7 [95% CI 2.16–6.34], P < 0.00001). We sought to replicate this association with SLE in a German population and a Swedish population. A similar trend was found in the German group. The CD24 V/V genotype and the CD24 V allele were more frequent in SLE patients than in controls, although this difference was not statistically significant. No differences were observed in the Swedish group. A meta‐analysis of the Spanish and German cohorts demonstrated that the CD24 V allele has a risk effect in SLE patients (pooled OR 1.25 [95% CI 1.08–1.46], P = 0.003). In addition, homozygosity for the CD24 V risk allele significantly increased the effect (pooled OR 2.19 [95% CI 1.50–3.22], P = 0.00007).

Conclusion

These findings suggest that the CD24 A57V polymorphism plays a role in susceptibility to SLE in a Spanish population.
The effect of “open access” on citation impact: An analysis of ArXiv's condensed matter section
Authors: Moed Henk F.
Published: August 2007

This article statistically analyzes how the citation impact of articles deposited in the Condensed Matter section of the preprint server ArXiv (hosted by Cornell University), and subsequently published in a scientific journal, compares to that of articles in the same journal that were not deposited in the archive. Its principal aim is to further illustrate and roughly estimate the effect of two factors, “early view” and “quality bias,” on differences in citation impact between these two sets of papers, using citation data from Thomson Scientific's Web of Science. It presents estimates for a number of journals in the field of condensed matter physics. To discriminate between an “open access” effect and an early view effect, longitudinal citation data were analyzed covering a time period as long as 7 years. Quality bias was measured by calculating ArXiv citation impact differentials at the level of individual authors publishing in a journal, taking into account coauthorship. The analysis provided evidence of a strong quality bias and early view effect. Correcting for these effects, there is in a sample of six condensed matter physics journals studied in detail no sign of a general “open access advantage” of papers deposited in ArXiv. The study does provide evidence that ArXiv accelerates citation due to the fact that ArXiv makes papers available earlier rather than makes them freely available.
The role of Web‐based information in the scholarly communication of chemists: Citation and content analyses of American Chemical Society Journals
Authors: Brown Cecelia
Published: August 2007

Citation and content analyses of eight American Chemical Society (ACS) journals in a range of fields of chemistry were used to describe the use of Web‐based information resources by the authors and readers of the scholarly literature of chemistry. The analyses indicate that even though the number of Web‐based information resources has grown steadily over the past decade, chemists are not taking full advantage of freely available Web‐based resources. They are, however, making use of the ACS Electronic Supporting Information archive. The content of the Web‐based resources that are used is primarily text based, and the URLs are provided in the articles' reference lists and experimental sections. The presence of a reference to a Web‐based resource in a chemistry article does not influence its rate of citation, even though the viability of the URLs was found to erode with time. Comparison of citation and online access data reveals that at the highest levels of citation, articles also garner high levels of online access. This was especially true for articles describing a technique or methodology. Even though chemists do not incorporate large numbers of freely available Web‐based resources into their publications, an increasingly important component of a chemist's information behavior for the direct support of his or her research is unfettered bench‐top access via the Web.
A classification of mental models of undergraduates seeking information for a course essay in history and psychology: Preliminary investigations into aligning their mental models with online thesauri
Authors: Cole Charles , Lin Yang , Leide John , Large Andrew , Beheshti Jamshid
Published: August 2007

The article reports a field study which examined the mental models of 80 undergraduates seeking information for either a history or psychology course essay when they were in an early, exploration stage of researching their essay. This group is presently at a disadvantage when using thesaurus‐type schemes in indexes and online search engines because there is a disconnect between how domain novice users of IR systems represent a topic space and how this space is represented in the standard IR system thesaurus. The study attempted to (a) ascertain the coding language used by the 80 undergraduates in the study to mentally represent their topic and then (b) align the mental models with the hierarchical structure found in many thesauri. The intervention focused the undergraduates' thinking about their topic from a topic statement to a thesis statement. The undergraduates were asked to produce three mental model diagrams for their real‐life course essay at the beginning, middle, and end of the interview, for a total of 240 mental model diagrams, from which we created a 12‐category mental model classification scheme. Findings indicate that at the end of the intervention, (a) the percentage of vertical mental models increased from 24 to 35% of all mental models; but that (b) 3rd‐year students had fewer vertical mental models than did 1st‐year undergraduates in the study, which is counterintuitive. The results indicate that there is justification for pursuing our research based on the hypothesis that rotating a domain novice's mental model into a vertical position would make it easier for him or her to cognitively connect with the thesaurus's hierarchical representation of the topic area.