bluuebunny/crossref_metadata_2025 huggingface dataset:
Microclimatic buffering by logging residues and forest edges reduces clear‐cutting impacts on forest bryophytes
Authors: Dynesius Mats , Åström Marcus , Nilsson Christer
Published: April 2008

Question:The practice of extracting logging residues after clear‐cutting for bioenergy purposes is spreading. Logging residues constitute a shelter in clear‐cut areas and therefore concerns have been expressed that their removal could make the ground and its vegetation more exposed to extreme microclimatic conditions. We asked whether logging residues and forest edges can protect ground‐dwelling forest bryophytes from fatal microclimate events following clear‐cutting.

Location:Boreal forests of central Sweden.

Methods:Using transplants of eight forest floor bryophyte species we experimentally analysed the sheltering effect (less solar radiation and less wind) of logging residues and forest edges in seven clear‐cut areas. Transplants were placed in two contrasting positions in each area; near a north‐facing forest edge and in the centre of the clear‐cut area. In each position, half of the transplants were covered by a layer of spruce branches and the other half was left uncovered. We estimated proportion of apparently living shoots (apparent vitality) and measured radial growth of transplants during one growing season.

Results:Position in the clear‐cut area, but not cover of spruce branches, clearly influenced radial growth. Vitality scores were higher among transplants covered with branches and the lowest apparent vitality was observed in uncovered transplants in the middle of clear‐cut areas. The change in area of apparently living shoots during the course of the experiment (growth minus mortality) was unaffected by branch cover close to the edge but positively affected in the centre of the clear‐cut area. In general, the effect of branch cover on bryophytes was higher in the centre of clear‐cut areas. Here, climatic measurements showed that branch cover buffers during periods of extreme microclimates.

Conclusions:Extraction of logging residues after clear‐felling may reduce the survival of some ground‐dwelling forest organisms. The additional sheltering provided by branches was unimportant close to forest edges. We suggest smaller clear‐cut areas, green‐tree retention and other ways to make logged areas shadier and less windy to mitigate the reduced shelter caused by harvest of logging residues.
THE CONCEPT MODEL OF SUSTAINABLE BUILDINGS REFURBISHMENT
Authors: Mickaitytė Aistė , Zavadskas Edmundas K. , Kaklauskas Artūras , Tupėnaitė Laura
Published: April 2008

Sustainable development principles reaching many spheres of human activities, public buildings refurbishment is not an exemption in this case. Buildings refurbishment supports excellent opportunities to reduce energy consumption in buildings as well as encourages other sustainable refurbishment principles implementation ‐ citizens’ healthcare, environment protection, rational resources use, information about sustainable refurbishment dissemination and stakeholders groups’ awareness. During the pilot refurbishment FP‐6 project Brita in PuBs, authors of this article have developed conceptual sustainable public buildings refurbishment model. Model was created basing on sustainable development principles, their consideration in decision making process and model efficiency influencing factors. In order to demonstrate models’ application possibilities following the healthcare principle, practical case study of Vilnius Gediminas Technical University main building pollution mapping is given at the end of this article. Santrauka Darnios plėtros principai skverbiasi į daugelį veiklos krypčių, neaplenkdami ir visuomeninių pastatų atnaujinimo proceso. Pastatų atnaujinimas – tai puiki galimybė ne tik sumažinti suvartojamos pastate energijos apimtis, bet ir užtikrinti kitus darnios renovacijos principus – rūpinimąsi gyventojų sveikata, aplinkos tausojimą, racionalų išteklių naudojimą, taip pat ir informacijos apie darnią pastatų renovaciją prieinamumą. Vykdant demonstracinį FP-6 projektą Brita in PuBs, straipsnio autoriai sukūrė koncepcinį darnios visuomeninių pastatų renovacijos modelį, kuriame atsižvelgiama į darnios plėtros principus, jų taikymą priimant sprendimus ir modelio efektyvumą veikiančius veiksnius. Siekiant pademonstruoti modelio realizavimo galimybes, paskutiniame straipsnio skyriuje rūpinimosi sveikata principas iliustruojamas renovuojamo VGTU centrinio pastato užterštumo žemėlapio sudarymu.
Experimental investigation of liquid distribution over structured packing
Authors: Alekseenko S. V. , Markovich D. M. , Evseev A. R. , Bobylev A. V. , Tarasov B. V. , Karsten V. M.
Published: April 2008

The thickness of a liquid film on the structured packing inside a distillation column was measured at the region of counter‐current flow of gas and liquid by fiber‐optic sensors. The local distribution of liquid inside a typical geometrical cell formed by the corrugated Koch 1Y sheets was examined in this study. It is shown that, in the vicinity of the sheet contact points inside the cell, the liquid film thickness is maximal, and peculiar meniscuses are formed where liquid flow redistribution over the corrugation surface occurs. A counter gas flow decreases pulsations of the liquid film thickness by a factor of 1.5–2 on the rib and lateral surfaces of corrugation. Experimental data on the effect of operation parameters on the local distribution of liquid in the cell and the pressure drop in the column are presented. © 2008 American Institute of Chemical Engineers AIChE J, 2008
Synthesis of methyl acrylate graft copolymers by the combination of a polynorbornene containing pendant vinylbenzene groups by using coordination and reverse atom transfer polymerization
Authors: Ma Rui , Song Zhongying , Hou Yubang , Feng Juan , Xing Bin , Bao Feng
Published: April 2008

Copolymerization of norbornene and 1,4‐divinylbenzene was successfully performed using a β‐ketoamine chelate nickel complex–methylaluminoxane, yielding random copolymer of norbornene and 1,4‐divinylbenzene containing a few pendant styrene groups. With the initiation of copper dichloride and 2,2′‐azobisisobutyronitrile, the pendant styrene groups were quantitatively polymerized with methyl acrylates, which allowed the successful synthesis of polynorbornene‐based graft copolymers by reverse atom transfer radical polymerization mechanism. The analyses of the product by 1H NMR and gel permeation chromatography gave the verification of ‘true’ copolymer. The thermal property of the graft copolymer was controlled by varying the monomer feed ratio. Copyright © 2008 John Wiley & Sons, Ltd.
Effect of graft modification with poly(N‐vinylpyrrolidone) on thermal and mechanical properties of poly (3‐hydroxybutyrate‐co‐3‐hydroxyvalerate)
Authors: Wang Wei , Zhang Yu , Zhu Meifang , Chen Yanmo
Published: April 2008

Poly(N‐vinylpyrrolidone) (PVP) groups were grafted onto poly(3‐hydroxybutyrate‐co‐3‐hydroxyvalerate) (PHBV) backbone to modify the properties of PHBV and synthesize a new novel biocompatible graft copolymer. The effect of graft modification with PVP on the thermal and mechanical properties of PHBV was investigated. The thermal stability of grafted PHBV was remarkably improved while the melting temperature (Tm) was almost not affected by graft modification. The isothermal crystallization behavior of samples was observed by polarized optical microscopy and the results showed that the spherulitic radial growth rates (G) of grafted PHBV at the same crystallization temperature (Tc) decreased with increasing graft yield (graft%) of samples. Analysis of isothermal crystallization kinetics showed that both the surface free energy (σe) and the work of chain‐folding per molecular fold (q) of grafted PHBV increased with increasing graft%, implying that the chains of grafted PHBV are less flexible than ungrafted PHBV. This conclusion was in agreement with the mechanical testing results. The Young's modulus of grafted PHBV increased while the elongation decreased with increasing graft%. The hydrophilicity of polymer films was also investigated by the water contact angle measurement and the results revealed that the hydrophilicity of grafted PHBV was enhanced. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
Inflammatory stimuli accelerate Sjögren's syndrome–like disease in (NZB × NZW)F1 mice
Authors: Deshmukh Umesh S. , Ohyama Yukiko , Bagavant Harini , Guo Xiaoti , Gaskin Felicia , Fu Shu Man
Published: April 2008

Objective

This study was undertaken to determine whether induction of systemic inflammation accelerates the development of Sjögren's syndrome (SS) in genetically susceptible mice.

Methods

Female (NZB × NZW)F1 mice were treated with either Freund's incomplete adjuvant (IFA) or phosphate buffered saline (PBS) at monthly intervals. Salivary gland function was monitored by measuring pilocarpine‐induced saliva volume. Mice were killed at different time points and examined for sialadenitis and salivary gland–infiltrating cells. Sera were analyzed for autoantibodies to salivary gland antigens, nuclear antigens, and Ro60.

Results

While IFA‐treated mice had significantly decreased salivary secretion 7 weeks after the initial treatment, salivary secretion did not decrease in PBS‐treated controls until 17 weeks. At 7 weeks, the severity of sialadenitis and the number of T and B cells infiltrating the salivary glands did not differ between the 2 groups. However, at this time point IFA‐treated mice showed significantly higher frequencies of CD11clow, B220+, Ly6C+, mouse PDCA‐1+ dendritic cells (DCs) in the salivary glands. While levels of autoantibodies did not differ between the 2 groups at early time points, by late time points IFA‐treated mice had higher levels. The gland dysfunction observed in IFA‐treated mice at earlier time points did not correlate with the severity of sialadenitis or levels of autoantibodies. Instead, it was associated with increased frequency of plasmacytoid DCs in the gland.

Conclusion

Our data suggest that generalized inflammatory stimuli can accelerate the development of SS‐like disease in (NZB × NZW)F1 mice, and that gland dysfunction in SS can develop prior to the generation of a robust adaptive autoimmune response.
Arthritis develops but fails to resolve during inhibition of cyclooxygenase 2 in a murine model of lyme disease
Authors: Blaho Victoria A. , Jefferson Mitchell W. , Brown Charles R.
Published: April 2008

Objective

Recent studies have implicated products of cyclooxygenase 2 (COX‐2) in not only induction but also resolution of the inflammatory response; however, the contribution of COX‐2 products to the in vivo response to infection is unknown. The aim of this study was to determine the contribution of COX‐2 to temporal regulation of the inflammatory response to infection in a murine model of Lyme arthritis.

Methods

Experimental Lyme disease was induced in both arthritis‐resistant DBA/2J and arthritis‐susceptible C3H/HeJ mice by inoculation in the hind footpads withBorrelia burgdorferi. COX‐2 inhibitors were administered daily, and their effect on arthritis pathology was assessed at various time points postinfection. The COX‐2 deficiency was also backcrossed onto both DBA and C3H backgrounds to confirm the findings from COX‐2 inhibitor–treated mice.

Results

In COX‐2 inhibitor–treated or COX‐2−/−C3H mice, arthritis developed normally but did not resolve. Cessation of COX‐2 inhibitor treatment on day 14 postinfection did not induce resolution of arthritis, indicating an early onset for the molecular mechanisms governing resolution. The lack of resolution of arthritis correlated with altered COX‐2 and cytosolic phospholipase A2messenger RNA levels in the joints of C3H mice. In addition, the proresolution lipid molecule 15‐deoxy‐Δ12,14‐prostaglandin J2was produced in response toB burgdorferiinfection, and its production was attenuated by the inhibition of COX‐2.

Conclusion

Our results demonstrate that early production of COX‐2 products is necessary for resolution of the inflammatory arthritis induced byBorreliainfection, and that COX‐2 inhibition may result in prolonged inflammatory states, possibly by inhibition of proresolution eicosanoids.
Cardiovascular disease risk awareness in systemic lupus erythematosus patients
Authors: Scalzi Lisabeth V. , Ballou Stanley P. , Park Jean Y. , Redline Susan , Kirchner H. Lester
Published: April 2008

Objective

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) patients. The aim of this study was to identify factors associated with patients' recognition of SLE as an independent risk factor for CVD and their perception of their personal CVD risk.

Methods

SLE patients were sent questionnaires that assessed demographic characteristics, any CVD risk factors, and information regarding the CVD counseling they had received from their physicians. Variables significantly associated with the outcomes were analyzed using logistic regression models.

Results

Information obtained from 226 questionnaires was analyzed. Fifty‐eight percent of the respondents reported receiving no CVD counseling from a physician. Patients who recalled receiving counseling from a physician were 2.3 times more likely (P = 0.02) to recognize SLE as a CVD risk factor and 3.2 times more likely (P = 0.02) to perceive themselves as being at risk of CVD compared with those patients who did not receive physician counseling. Receiving physician CVD counseling was the strongest predictor of a patient's self‐perception of CVD risk. Those patients at intermediate to high risk (n = 167) who reported having received counseling were 5.3 times as likely (P = 0.007) to perceive themselves to be at higher risk of CVD compared with similar patients who did not receive counseling. Younger patients were 4.2 times as likely (P = 0.002) as older patients to recognize SLE as a CVD risk factor. Other variables associated with patients' self‐perceptions of CVD risk included family history of CVD and hypertension.

Conclusion

Physician counseling regarding CVD in SLE patients has an important impact on patients' awareness of SLE as a CVD risk factor and their self‐perception of CVD risk.
Association of interferon regulatory factor 5 haplotypes, similar to that found in systemic lupus erythematosus, in a large subgroup of patients with rheumatoid arthritis
Authors: Dieguez‐Gonzalez Rebeca , Calaza Manuel , Perez‐Pampin Eva , de la Serna Arturo Rodriguez , Fernandez‐Gutierrez Benjamin , Castañeda Santos , Largo Raquel , Joven Beatriz , Narvaez Javier , Navarro Federico , Marenco Jose Luis , Vicario Jose Luis , Blanco Francisco J. , Fernandez‐Lopez Jesus Carlos , Caliz Rafael , Collado‐Escobar María Dolores , Carreño Luis , Lopez‐Longo Javier , Cañete Juan D. , Gomez‐Reino Juan J. , Gonzalez Antonio
Published: April 2008

Objective

Previous studies have shown either a lack of effect of IRF5 polymorphisms or an association of the IRF5 gene in only a minor subset of rheumatoid arthritis (RA) patients in whom anti–citrullinated protein antibodies (ACPAs) are absent. The present study was undertaken to investigate the role of genetic variation in IRF5 in susceptibility to RA.

Methods

Nine IRF5 single‐nucleotide polymorphisms (SNPs) were studied in 1,338 patients with RA and 1,342 control subjects in analyses of exploratory and replication sample collections, with stratification according to sex and by the presence or absence of ACPAs, rheumatoid factor, the shared epitope, the 620W PTPN22 allele, and erosions. A meta‐analysis that included results from previous studies was also carried out.

Results

Our findings together with those from previous studies, in a total of 4,620 RA patients and 3,741 controls, showed a significant association of the rs2004640 IRF5 SNP in RA patients as a whole (odds ratio [OR] 0.88, 95% confidence interval [95% CI] 0.83–0.94; P = 6.5 × 10−5 versus controls). This association was stronger in ACPA− patients, but was also present in ACPA+ patients (from 3 sample collections). Further analysis of our exploratory sample collection showed that only patients in the ACPA+ and SE− group lacked an association with IRF5 SNPs. All of the remaining RA patients (ACPA− or SE+) showed a strong association with IRF5 SNPs, which followed a complex pattern of opposing effects mediated by independent haplotypes. The susceptibility haplotype showed an OR of 1.8 (95% CI 1.4–2.3; P = 1.2 × 10−6 versus controls), whereas the protective haplotype showed an OR of 0.76 (95% CI 0.6–0.98; P = 0.046 versus controls).

Conclusion

IRF5 polymorphisms seem to influence RA susceptibility in a large subgroup of patients, following a pattern of association very similar to that described in patients with systemic lupus erythematosus.
An orally bioavailable spleen tyrosine kinase inhibitor delays disease progression and prolongs survival in murine lupus
Authors: Bahjat Frances Rena , Pine Polly R. , Reitsma Andrea , Cassafer Gail , Baluom Muhammad , Grillo Sunny , Chang Betty , Zhao Fei Fei , Payan Donald G. , Grossbard Elliott B. , Daikh David I.
Published: April 2008

Objective

To assess whether R788, an orally bioavailable small molecule inhibitor of spleen tyrosine kinase (Syk)–dependent signaling, could modulate disease in lupus‐prone (NZB × NZW)F1 (NZB/NZW) mice via inhibition of Fc receptor (FcR) and B cell receptor signaling.

Methods

R788 was administered to NZB/NZW mice before and after disease onset. Proteinuria, blood urea nitrogen levels, and autoantibody titers were examined periodically, and overall survival and renal pathologic features were assessed following long‐term treatment (24–34 weeks). The distribution and immunophenotype of various splenic T cell and B cell subpopulations were evaluated at the time of study termination. Arthus responses in NZB/NZW mice pretreated with R788 or Fc‐blocking antibody (anti‐CD16/32) were also examined.

Results

When R788 was administered prior to or after disease onset, it delayed the onset of proteinuria and azotemia, reduced renal pathology and kidney infiltrates, and significantly prolonged survival of lupus‐prone NZB/NZW mice; autoantibody titers were minimally affected throughout the study. Dose‐dependent reductions in the numbers of CD4+ activated T cells expressing high levels of CD44 or CD69 were apparent in spleens from R788‐treated mice. Minimal effects on the numbers of naive T cells expressing CD62 ligand and total CD8+ T cells per spleen were observed following long‐term drug treatment. R788 pretreatment resulted in reduced Arthus responses in NZB/NZW mice, similar to results obtained in mice pretreated with FcR‐blocking antibody.

Conclusion

We demonstrate that a novel Syk‐selective inhibitor prevents the development of renal disease and treats established murine lupus nephritis. These data suggest that Syk inhibitors may be of therapeutic benefit in human lupus and related disorders.
Expression of microRNA‐146 in rheumatoid arthritis synovial tissue
Authors: Nakasa Tomoyuki , Miyaki Shigeru , Okubo Atsuko , Hashimoto Megumi , Nishida Keiichiro , Ochi Mitsuo , Asahara Hiroshi
Published: April 2008

Objective

Several microRNA, which are ∼22‐nucleotide noncoding RNAs, exhibit tissue‐specific or developmental stage–specific expression patterns and are associated with human diseases. The objective of this study was to identify the expression pattern of microRNA‐146 (miR‐146) in synovial tissue from patients with rheumatoid arthritis (RA).

Methods

The expression of miR‐146 in synovial tissue from 5 patients with RA, 5 patients with osteoarthritis (OA), and 1 normal subject was analyzed by quantitative reverse transcription–polymerase chain reaction (RT‐PCR) and by in situ hybridization and immunohistochemistry of tissue sections. Induction of miR‐146 following stimulation with tumor necrosis factor α (TNFα) and interleukin‐1β (IL‐1β) of cultures of human rheumatoid arthritis synovial fibroblasts (RASFs) was examined by quantitative PCR and RT‐PCR.

Results

Mature miR‐146a and primary miR‐146a/b were highly expressed in RA synovial tissue, which also expressed TNFα, but the 2 microRNA were less highly expressed in OA and normal synovial tissue. In situ hybridization showed primary miR‐146a expression in cells of the superficial and sublining layers in synovial tissue from RA patients. Cells positive for miR‐146a were primarily CD68+ macrophages, but included several CD3+ T cell subsets and CD79a+ B cells. Expression of miR‐146a/b was markedly up‐regulated in RASFs after stimulation with TNFα and IL‐1β.

Conclusion

This study shows that miR‐146 is expressed in RA synovial tissue and that its expression is induced by stimulation with TNFα and IL‐1β. Further studies are required to elucidate the function of miR‐146 in these tissues.
Association between the level of circulating bioactive tumor necrosis factor α and the tumor necrosis factor α gene polymorphism at −308 in patients with rheumatoid arthritis treated with a tumor necrosis factor α inhibitor
Authors: Marotte Hubert , Arnaud Béatrice , Diasparra Jennifer , Zrioual Saloua , Miossec Pierre
Published: April 2008

Objective

The tumor necrosis factor α (TNFα) −308A polymorphism has been associated with high production of TNFα and poor response to anti‐TNFα therapy, but these associations remain controversial. The aim of this study was to explore the association between circulating TNFα bioactivity, the TNFα −308 polymorphism, and the clinical response to infliximab in patients with rheumatoid arthritis (RA).

Methods

One hundred ninety‐eight patients with RA were treated with infliximab and methotrexate. Responses at 6 months according to the American College of Rheumatology (ACR) preliminary criteria for improvement in RA were recorded. Genotyping for the TNFα −308 polymorphism was performed by enzyme‐linked oligosorbent assay. Circulating TNFα bioactivity was evaluated in 50 patients with RA by assessing the production of interleukin‐6 (IL‐6) in synoviocytes induced by a small amount of TNFα plus plasma. IL‐6 production in 48‐hour supernatants and the levels of TNFα protein and IL‐6 were measured by enzyme‐linked immunosorbent assay.

Results

The TNFα −308 polymorphism was not associated with the ACR response to infliximab. The level of circulating TNFα bioactivity was higher in patients with the TNFα −308 A/A or A/G genotype than that in patients with the G/G genotype (median 50.0 ng/ml [interquartile range (IQR) 31.5–62.0] versus 33.0 ng/ml [IQR 16.5–47.5]; P < 0.02). However, no difference was observed for the TNFα protein level according to genotype (median 0.62 pg/ml [IQR 0.00–8.85] for G/G versus 3.35 pg/ml [IQR 1.55–4.63] for A/A or A/G; P not significant). The level of circulating TNFα bioactivity was higher in good responders (≥50% improvement) than in poor responders (≤20% improvement) (median 45.0 ng/ml [IQR 21.0–59.0] versus 28.0 ng/ml [IQR 14.0–39.0]; P = 0.05). However, the level of TNFα protein was similar in both groups.

Conclusion

The level of functional circulating TNFα is partially genetically determined and is predictive of the clinical response to infliximab. Nonresponders to anti‐TNFα therapy are likely to have a disease that is not primarily driven by TNFα.
Crucial role of visfatin/pre–B cell colony‐enhancing factor in matrix degradation and prostaglandin E2 synthesis in chondrocytes: Possible influence on osteoarthritis
Authors: Gosset Marjolaine , Berenbaum Francis , Salvat Colette , Sautet Alain , Pigenet Audrey , Tahiri Khadija , Jacques Claire
Published: April 2008

Objective

Prostaglandin E2 (PGE2) is one of the main catabolic factors involved in osteoarthritis (OA), and metalloproteinases (MMPs) are crucial for cartilage degradation. PGE2 synthesis under inflammatory conditions is catalyzed by cyclooxygenase 2 and microsomal PGE synthase 1 (mPGES‐1), whereas NAD+‐dependent 15‐hydroxy–PG dehydrogenase (15‐PGDH) is the key enzyme implicated in PGE2 catabolism. The present study was undertaken to investigate the contribution of visfatin, an adipose tissue–derived hormone, to the pathophysiology of OA, by examining its role in PGE2 synthesis and matrix degradation.

Methods

The synthesis of visfatin by human chondrocytes from OA patients, with and without stimulation with interleukin‐1β (IL‐1β) and the role of visfatin in PGE2 synthesis were analyzed by real‐time reverse transcriptase–polymerase chain reaction (RT‐PCR) and immunoblotting. The effects of visfatin (1–10 μg/ml) on mPGES‐1 and 15‐PGDH synthesis, on the subsequent release of PGE2, and on MMP‐3, MMP‐13, ADAMTS‐4, ADAMTS‐5, and PG synthesis by primary immature mouse articular chondrocytes were examined by quantitative RT‐PCR, immunoblotting, and enzyme‐linked immunosorbent assay. Finally, small interfering RNA (siRNA) was used to assess the influence of visfatin on IL‐1β–induced release of PGE2 in immature mouse articular chondrocytes.

Results

Human OA chondrocytes produced visfatin, and visfatin synthesis was increased by IL‐1β treatment. Visfatin, like IL‐1β, triggered excessive release of PGE2, due to increased mPGES‐1 synthesis and decreased 15‐PGDH synthesis. Visfatin knockout with siRNA reduced IL‐1β–induced PGE2 overrelease. Visfatin triggered ADAMTS‐4 and ADAMTS‐5 expression and MMP‐3 and MMP‐13 synthesis and release, and reduced synthesis of high molecular weight PG by immature mouse articular chondrocytes.

Conclusion

The findings of this study indicate that visfatin has a catabolic function in cartilage and may have an important role in the pathophysiology of OA.
A novel tumor necrosis factor α–responsive CCAAT/enhancer binding protein site regulates expression of the cartilage‐derived retinoic acid–sensitive protein gene in cartilage
Authors: Imamura Toshihiro , Imamura Chisako , McAlinden Audrey , Davies Sherri R. , Iwamoto Yukihide , Sandell Linda J.
Published: April 2008

Objective

Inflammatory processes in rheumatoid arthritis are primarily regulated by the cytokines tumor necrosis factor α (TNFα) and interleukin‐1β (IL‐1β). Previous studies in our laboratory have shown that IL‐1β represses expression of the cartilage characteristic genes, cartilage‐derived retinoic acid–sensitive protein (cd‐rap) and type II collagen (COL2A1); this mechanism of repression involves activation of a CCAAT/enhancer binding protein (c/EBP) site within promoter regions. The aim of this study was to investigate novel TNFα‐mediated mechanisms that regulate the expression of cd‐rap.

Methods

Rat chondrosarcoma cells were transiently transfected with complementary DNA constructs encoding cd‐rap, in the presence of TNFα. The expression of c/EBPβ, SOX9, and p300 in rat chondrosarcoma cells and primary human articular chondrocytes after treatment with TNFα was examined by reverse transcription–polymerase chain reaction and Western blotting. The effect of TNFα on endogenous binding of c/EBPβ or SOX9 to the cd‐rap promoter was examined by chromatin immunoprecipitation assays.

Results

We identified a new c/EBP binding site in the cd‐rap promoter (from position −1059 bp to position −1046 bp). Binding of c/EBP to this site was regulated by TNFα but not IL‐1β, resulting in down‐regulation of cd‐rap expression. This effect was reversed by mutational inactivation of the c/EBP motif. In addition, the activation potential of SOX9 and CREB binding protein/p300 on the cd‐rap promoter was enhanced after mutation of the new c/EBP binding site, indicating that blockage of this site would increase transcription.

Conclusion

TNFα regulates the expression and/or DNA‐binding potential of key positive‐acting and negative‐acting transcription factors that control the expression of the cartilage matrix gene, cd‐rap.
Glutamate levels and activity of the T cell voltage‐gated potassium Kv1.3 channel in patients with systemic lupus erythematosus
Authors: Poulopoulou C. , Papadopoulou‐Daifoti Z. , Hatzimanolis A. , Fragiadaki K. , Polissidis A. , Anderzanova E. , Davaki P. , Katsiari C. G. , Sfikakis P. P.
Published: April 2008

Objective

Alterations in glutamate homeostasis and Kv1.3 voltage‐gated potassium channel function have been independently associated with T cell dysfunction, whereas selective blockade of Kv1.3 channels inhibits T cell activation and improves T cell–mediated manifestations in animal models of autoimmunity. Because low extracellular glutamate concentrations enhance the activity of this channel in normal T cells ex vivo, we undertook this study to examine serum glutamate concentrations and Kv1.3 channel activity in patients with systemic lupus erythematosus (SLE).

Methods

We used high‐performance liquid chromatography for glutamate measurements, and we used the whole‐cell patch‐clamp technique for electrophysiologic studies performed in freshly isolated, noncultured peripheral T cells.

Results

Mean ± SD serum concentrations of glutamate were lower in patients with either clinically quiescent SLE (77 ± 27 μM [n = 18]) or active SLE (61 ± 36 μM [n = 16]) than in healthy controls (166 ± 64 μM [n = 24]) (both P < 0.0001). The intrinsic gating properties of the Kv1.3 channels in lupus T cells were found to be comparable with those in healthy control–derived T cells. Notably, electrophysiologic data from SLE patient–derived T cells exposed to extracellular glutamate concentrations similar to their respective serum levels (50 μM) demonstrated Kv1.3 current responses enhanced by almost 20% (P < 0.01) compared with those subsequently obtained from the same cell in the presence of glutamate concentrations within control serum levels (200 μM).

Conclusion

Based on the key role of Kv1.3 channel activity in lymphocyte physiology, an enhancing in vivo effect of low serum glutamate concentrations on the functional activity of this channel may contribute to lupus T cell hyperactivity. Studies to further elucidate Kv1.3 responses in SLE, as well as the possible pathogenetic role of this unsuspected metabolic abnormality, may have therapeutic implications for SLE patients.
Increased enthesopathy among Behçet's syndrome patients with acne and arthritis: An ultrasonography study
Authors: Hatemi Gulen , Fresko Izzet , Tascilar Koray , Yazici Hasan
Published: April 2008

Objective

Behçet's syndrome is characterized by clusters of disease expression, one of which is the coexistence of acne and arthritis. The aim of this study was to test the hypothesis that enthesopathy is increased in this cluster, having features reminiscent of acne‐associated arthritis.

Methods

The study group comprised 35 patients with Behçet's syndrome who had acne and arthritis (BS‐AA), 38 patients with Behçet's syndrome who did not have arthritis (BS‐WA), 37 patients with ankylosing spondylitis (AS), 25 patients with rheumatoid arthritis (RA), and 25 healthy control subjects. Five entheseal sites (the superior and inferior poles of the patella, the tibial tuberosity, and the superior and inferior poles of the calcaneus) on both lower extremities were examined by 2 independent observers, using ultrasonography. A previously validated composite score was calculated for each patient. The numbers of entheseal sites giving a positive power Doppler signal in each group were also compared.

Results

Patients with AS had the highest enthesopathy score (mean ± SD 4.1 ± 2.4; F [4df] = 8.43, P < 0.001) followed by BS‐AA patients (3.0 ± 1.9; F [3df] = 3.63, P = 0.015). The mean ± SD enthesopathy scores among the remaining 3 groups were similar (for BS‐WA, 1.8 ± 1.4; for RA, 2.2 ± 1.6; for healthy controls, 2.0 ± 1.5 [F (2df) = 0.65, P = 0.53]). Power Doppler scores were highest for the BS‐AA group (mean ± SD 3.0 ± 1.5; F [4df] = 15.54, P < 0.001) followed by the AS group (2.7 ± 1.8; F [3df] = 14.38, P < 0.001), the RA group (2.6 ± 1.8; F [2df] = 13.88, P < 0.001), the BS‐WA group (1.2 ± 1.3; F [1df] = 4.48, P = 0.038), and the control group (0.5 ± 1.1). There was 87% agreement between the 2 observers (κ = 0.55, intraclass correlation coefficient 0.71).

Conclusion

The increased presence of enthesopathy among BS‐AA patients compared with that among BS‐WA patients further supports the hypothesis that patients with Behçet's syndrome who also have arthritis and acne form a distinct cluster.
Combined analysis of monocyte and lymphocyte messenger RNA expression with serum protein profiles in patients with scleroderma
Authors: Duan Hangjun , Fleming Jo , Pritchard David K. , Amon Lynn M. , Xue Jun , Arnett Heather A. , Chen Guang , Breen Patricia , Buckner Jane H. , Molitor Jerry A. , Elkon Keith B. , Schwartz Stephen M.
Published: April 2008

Objective

We attempted to elucidate possible pathogenetic mechanisms in scleroderma by analysis of gene expression patterns of purified monocytes and lymphocytes, as well as protein profiles of cytokines and growth factors.

Methods

Expression analysis was performed on messenger RNA (mRNA) from cells that had been purified with magnetic beads. Plasma samples from the same patients were used for multiplex cytokine analysis. Potential sources of proteins were also examined by in situ hybridization of skin specimens.

Results

A total of 1,800 genes from monocytes and 863 genes from CD4+ T cells were differentially expressed in scleroderma patients. As observed by other investigators using unfractionated peripheral blood cells from patients with autoimmune connective tissue diseases, the cell type–specific analyses of our scleroderma samples showed expression of genes suggesting the presence of interferon‐α (IFNα), despite the apparent absence of this cytokine in plasma. IFNα RNA was, however, expressed at enhanced levels in vascular and perivascular cells in scleroderma skin samples. While levels of interleukin‐1α (IL‐1α) and IL‐16 were among 10 proteins found to be significantly elevated in scleroderma patients, none of the large panel of plasma cytokines we analyzed correlated with the expression levels of putative IFN response genes.

Conclusion

The pattern of up‐regulation of mRNA in both the monocytes and CD4 lymphocytes of scleroderma patients, together with the detection of IFNα RNA in the microvasculature, suggests that leukocytes respond to this cytokine locally in the vessels. Detection of high levels of IL‐1α and IL‐16 in plasma and the independence of these protein levels from the IFN signature, implicates an independent contribution of other cytokines to immune activation and/or inflammation in scleroderma.
Correlation of magnetization transfer ratio histogram parameters with neuropsychiatric systemic lupus erythematosus criteria and proton magnetic resonance spectroscopy: Association of magnetization transfer ratio peak height with neuronal and cognitive dysfunction
Authors: Emmer B. J. , Steup‐Beekman G. M. , Steens S. C. A. , Huizinga T. W. J. , van Buchem M. A. , van der Grond J.
Published: April 2008

Objective

To investigate whether, in neuropsychiatric systemic lupus erythematosus (NPSLE) patients, magnetization transfer ratio (MTR) histogram parameters are related to neurochemical findings obtained using proton magnetic resonance spectroscopy (1H‐MRS) and to determine whether MTR histogram changes are linked to specific SLE and NPSLE characteristics.

Methods

Eighteen SLE patients (15 female, 3 male; mean ± SD age 42.8 ± 12.8 years), 34 NPSLE patients (32 female, 2 male; mean ± SD age 35.9 ± 12.2 years), and 15 healthy controls (14 female, 1 male; mean ± SD age 44.7 ± 9.6 years) underwent magnetization transfer imaging and 1H‐MRS. Whole‐brain MTR histogram parameters were associated with 1H‐MRS metabolite ratios, certain SLE criteria, and neuropsychiatric syndromes.

Results

No differences were found in the MTR histogram parameters between SLE patients and NPSLE patients. NPSLE patients had a lower MTR histogram peak height than did the healthy controls. The MTR histogram peak height and the mean height were significantly associated with the N‐acetylaspartate to creatinine ratio, suggesting neuronal dysfunction. Of all SLE criteria, renal dysfunction and arthritis were associated with MTR histogram parameters. After corrections for age, sex, and these SLE criteria, of the various neuropsychiatric syndromes only cognitive dysfunction was associated with the MTR histogram peak height.

Conclusion

The MTR peak height is lower in NPSLE patients than in healthy controls. MTR peak height reflects neuronal dysfunction, as detected by 1H‐MRS. Furthermore, the MTR peak height is associated with cognitive dysfunction but not with the other neuropsychiatric syndromes evaluated in our study.
Functional characterization of antineutrophil cytoplasmic antibodies in patients with cocaine‐induced midline destructive lesions
Authors: Peikert Tobias , Finkielman Javier D. , Hummel Amber M. , McKenney Maureen E. , Gregorini Gina , Trimarchi Matteo , Specks Ulrich
Published: April 2008

Objective

Antineutrophil cytoplasmic antibodies (ANCA) binding to neutrophil elastase (NE) and proteinase 3 (PR3) are detectable in most patients with cocaine‐induced midline destructive lesions (CIMDL), but the pathogenic role and antigen specificity of these antibodies are unknown. This study was undertaken to assess the effects of NE ANCA on the enzymatic activity of NE, to determine whether these antibodies interfere with the physiologic effect of secretory leukoprotease inhibitor (SLPI), and to investigate the antigen specificity of both NE and PR3 ANCA in patients with CIMDL. We also compared the binding of PR3 ANCA in patients with CIMDL with that in patients with Wegener's granulomatosis (WG).

Methods

PR3 ANCA and NE ANCA were detected by capture enzyme‐linked immunosorbent assays (ELISAs) and by indirect immunofluorescence. IgG was purified from the patients' sera, and the influence of NE ANCA on the enzymatic activity of NE and on the inhibitory activity of SLPI was investigated by determining the hydrolysis of N‐methoxysuccinyl‐Ala‐Ala‐Pro‐Val p‐nitroanilide by NE.

Results

IgG from NE ANCA–positive sera of patients with CIMDL inhibited the enzymatic activity of NE and did not interfere with the activity of SLPI. In contrast to the findings in WG sera, measurement of PR3 ANCA in CIMDL sera showed only fair to moderate concordance between the 2 different capture ELISAs. Cross‐inhibition experiments demonstrated that NE ANCA and PR3 ANCA represent distinct autoantibodies in patients with CIMDL.

Conclusion

The functional effects of NE ANCA on the enzymatic activity of NE or on the activity of SLPI cannot be implicated in the pathogenesis of CIMDL. The autoimmune reaction that targets neutrophil serine proteases in patients with CIMDL is frequently directed against more than one antigen. The ANCA response, including the reactivity of PR3 ANCA, in patients with CIMDL differs from what has been described in patients with WG.
A paradigm of diagnostic criteria for polyarteritis nodosa: Analysis of a series of 949 patients with vasculitides
Authors: Henegar Corneliu , Pagnoux Christian , Puéchal Xavier , Zucker Jean‐Daniel , Bar‐Hen Avner , Guern Véronique Le , Saba Mona , Bagnères Denis , Meyer Olivier , Guillevin Loïc ,   French Vasculitis Study Group
Published: April 2008

Objective

To establish a set of clinical and paraclinical criteria potentially useful as a diagnostic screening tool for polyarteritis nodosa (PAN).

Methods

The abilities of individual descriptive items to predict a diagnosis of PAN were evaluated by screening available data from 949 patients from the French Vasculitis Study Group database, including 262 with PAN and 687 with control vasculitides. Selected items were tested in a logistic regression model to establish a minimal set of nonredundant PAN‐predictive criteria. The discriminative accuracy of these items and of the American College of Rheumatology (ACR) 1990 criteria were assessed by reapplying them to the initial patient sample and a subgroup restricted to PAN and microscopic polyangiitis (MPA) patients. A computer simulation procedure was conducted on artificially generated patient data to evaluate the usefulness of these criteria in predicting a diagnosis of PAN.

Results

The analysis resulted in the retention of 3 positive predictive parameters (hepatitis B virus antigen and/or DNA in serum, arteriographic anomalies, and mononeuropathy or polyneuropathy) and 5 negative predictive parameters (indirect immunofluorescence detection of antineutrophil cytoplasmic antibody; asthma; ear, nose, and throat signs; glomerulopathy; and cryoglobulinemia) for the criteria set. These criteria yielded 70.6% sensitivity for all control vasculitides and 89.7% for MPA controls, with 92.3% specificity for all controls and 83.1% for MPA controls. The discriminant abilities of this set of items outperformed the ACR 1990 criteria in all analytical situations, showing better robustness to variations in the prevalence of individual vasculitides.

Conclusion

The use of positive and negative discriminant criteria could constitute a sound basis for developing a diagnostic tool for PAN to be used by clinicians. Further prospective analyses and validations in different populations are needed to confirm these items as satisfactory diagnostic criteria.
Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept
Authors: van der Heijde D. , Landewé R. , Einstein S. , Ory P. , Vosse D. , Ni L. , Lin S.‐L. , Tsuji W. , Davis J. C.
Published: April 2008

Objective

To investigate the effect of etanercept therapy on radiographic progression in patients with ankylosing spondylitis (AS).

Methods

Patients with AS who had previously participated in a 24‐week randomized, double‐blind, placebo‐controlled trial of etanercept therapy were enrolled in a 72‐week open‐label extension. Radiographs of the cervical and lumbar spine from patients who received etanercept (25 mg twice weekly) for up to 96 weeks were compared with radiographs from patients in a large prevalence cohort (Outcome Assessments in Ankylosing Spondylitis International Study [OASIS]) who had not been treated with anti–tumor necrosis factor α (anti‐TNFα) agents. Radiographs obtained at 2 time points up to 96 weeks apart from patients in both study populations were digitized and read by 2 independent readers who were blinded with regard to patient group and sequence. The primary end point was the 96‐week change in the modified Stoke AS Spine Score (mSASSS).

Results

A total of 257 patients treated with etanercept were compared with 175 unselected patients from the OASIS study. There was no significant difference in the change in the mSASSS from baseline among patients who received etanercept (mean ± SD 0.91 ± 2.45) versus those from the OASIS group (0.95 ± 3.18).

Conclusion

Unlike other inflammatory rheumatic diseases such as rheumatoid arthritis and psoriatic arthritis, structural progression in AS seems to be independent of TNF, despite the fact that TNF is responsible for the signs and symptoms due to inflammation in this disease.
Persistent efficacy of anakinra in patients with tumor necrosis factor receptor–associated periodic syndrome
Authors: Gattorno M. , Pelagatti M. A. , Meini A. , Obici L. , Barcellona R. , Federici S. , Buoncompagni A. , Plebani A. , Merlini G. , Martini A.
Published: April 2008

Objective

To evaluate the efficacy and safety of treatment with the interleukin‐1 receptor antagonist anakinra in patients with tumor necrosis factor receptor–associated periodic syndrome (TRAPS) requiring high cumulative doses of steroids.

Methods

Four children (mean age 9.1 years [range 4–13 years]) and 1 adult (age 33 years) with TRAPS were enrolled in the study. The 3 children with cysteine mutations (C52Y, C55Y, C43R) had prolonged and frequent attacks of fever. One child with the R92Q mutation and the adult patient with the C43R mutation displayed a more chronic disease course, with fluctuating, nearly continuous symptoms and persistent elevation of acute‐phase reactant levels (including serum amyloid A [SAA]). All patients were treated with anakinra (1.5 mg/kg/day).

Results

All of the patients had a prompt response to anakinra, with disappearance of symptoms and normalization of acute‐phase reactant levels, including SAA. In all pediatric patients, anakinra was withdrawn after 15 days of treatment. After a few days (mean 5.6 days [range 3–8]) a disease relapse occurred, which dramatically responded to reintroduction of anakinra. During the following period of observation (mean 11.4 months [range 4–20 months]), the patients did not experience episodes of fever or other disease‐related clinical manifestations. Levels of acute‐phase reactants remained in the normal range. No major adverse reactions or severe infections were observed.

Conclusion

Continuous treatment with anakinra effectively controlled both the clinical and laboratory manifestations in patients with TRAPS and prevented disease relapses.
Nidogen‐1 and nidogen‐2 in healthy human cartilage and in late‐stage osteoarthritis cartilage
Authors: Kruegel Jenny , Sadowski Boguslawa , Miosge Nicolai
Published: April 2008

Objective

To investigate the presence and function of nidogen‐1 and nidogen‐2 in healthy human cartilage and in late‐stage osteoarthritis (OA) cartilage.

Methods

The location and quantity of nidogen‐1 and nidogen‐2 protein and messenger RNA were determined in cartilage tissue obtained from healthy donors and from patients with late‐stage knee OA. Samples were analyzed by immunohistochemistry, in situ hybridization, and real‐time reverse transcription–polymerase chain reaction. Adhesion and inhibition assays, a pre‐embedding method, fluorescence‐activated cell sorting, and ultrastructural investigations with integrins were also carried out.

Results

Developing tissue from human embryos showed strong staining for both nidogens in condensed mesenchyme and in rib anlagen. Homogeneous staining for nidogen‐1 was observed in the extracellular matrix of healthy articular cartilage, whereas nidogen‐2 was localized pericellularly. In late‐stage OA cartilage, expression of nidogen‐1 was decreased pericellularly around diseased chondrocytes, whereas nidogen‐2 was increased. However, both nidogens had strongly increased levels around elongated chondrocytes, especially in areas of deep surface fissures. In vitro, both nidogens functioned as adhesion proteins for cells from the OA defect. In vivo, colocalizations with integrins αv and β1 as well as internalization of nidogens by chondrocytes in vitro were observed.

Conclusion

Nidogens are involved in human limb development. They occur in healthy articular cartilage and show increased expression, primarily around elongated chondrocytes, in OA cartilage. Therefore, the activities of nidogens might be a sign of cartilage regeneration in late‐stage OA. Furthermore, the adhesive character of nidogens, specifically as adhesion proteins for chondrocytes from late‐stage OA, as well as the enhanced chondrocyte–nidogen interaction in OA indicate that both proteins play a key role in the pathogenesis of OA and either could be applied as a diagnostic marker.