bluuebunny/crossref_metadata_2025 huggingface dataset:
Transgenic disruption of glucocorticoid signaling in mature osteoblasts and osteocytes attenuates K/BxN mouse serum–induced arthritis in vivo
Authors: Buttgereit Frank , Zhou Hong , Kalak Robert , Gaber Timo , Spies Cornelia M. , Huscher Dörte , Straub Ranier H. , Modzelewski James , Dunstan Colin R. , Seibel Markus J.
Published: June 2009

Objective

Endogenous glucocorticoids (GCs) modulate numerous biologic systems involved in the initiation and maintenance of arthritis. Bone cells play a critical role in the progression of arthritis, and some of the effects of GCs on inflammation may be mediated via these cells. The aim of this study was to investigate the impact of osteoblast‐targeted disruption of GC signaling on joint inflammation, cartilage damage, and bone metabolism in the K/BxN mouse serum transfer model of autoimmune arthritis.

Methods

Intracellular GC signaling was disrupted in osteoblasts through transgenic overexpression of 11β‐hydroxysteroid dehydrogenase type 2 under the control of a type I collagen promoter. Arthritis was induced in 5‐week‐old male transgenic mice and their wild‐type (WT) littermates, and paw swelling was assessed daily until the mice were killed. The mice were examined by histology, histomorphometry, and microfocal computed tomography, and serum was analyzed for cytokines, adrenocorticotropic hormone, and corticosterone.

Results

Acute arthritis developed in both transgenic and WT mice treated with K/BxN mouse serum. However, the arthritis and local inflammatory activity were significantly attenuated in transgenic mice, as judged by clinical and histologic indices of inflammation and cartilage damage. Bone turnover and bone volume remained unchanged in arthritic transgenic mice, while WT mice exhibited stimulated bone resorption, suppressed osteoblast activity, and significantly reduced bone volume, compatible with the known effects of active inflammation on bone. Circulating levels of proinflammatory cytokines tended to be lower in arthritic transgenic mice than in control transgenic mice.

Conclusion

Disruption of GC signaling in osteoblasts significantly attenuates K/BxN mouse serum–induced autoimmune arthritis in mice. These data suggest that osteoblasts modulate the immune‐mediated inflammatory response via a GC‐dependent pathway.
Pivotal role of connective tissue growth factor in lung fibrosis: MAPK‐dependent transcriptional activation of type I collagen
Authors: Ponticos Markella , Holmes Alan M. , Shi‐Wen Xu , Leoni Patricia , Khan Korsa , Rajkumar Vineeth S. , Hoyles Rachel K. , Bou‐Gharios George , Black Carol M. , Denton Christopher P. , Abraham David J. , Leask Andrew , Lindahl Gisela E.
Published: June 2009

Objective

Connective tissue growth factor (CTGF; CCN2) is overexpressed in systemic sclerosis (SSc) and has been hypothesized to be a key mediator of the pulmonary fibrosis frequently observed in this disease. CTGF is induced by transforming growth factor β (TGFβ) and is a mediator of some profibrotic effects of TGFβ in vitro. This study was undertaken to investigate the role of CTGF in enhanced expression of type I collagen in bleomycin‐induced lung fibrosis, and to delineate the mechanisms of action underlying the effects of CTGF on Col1a2 (collagen gene type I α2) in this mouse model and in human pulmonary fibroblasts.

Methods

Transgenic mice that were carrying luciferase and β‐galactosidase reporter genes driven by the Col1a2 enhancer/promoter and the CTGF promoter, respectively, were injected with bleomycin to induce lung fibrosis (or saline as control), and the extracted pulmonary fibroblasts were incubated with CTGF blocking agents. In vitro, transient transfection, promoter/reporter constructs, and electrophoretic mobility shift assays were used to determine the mechanisms of action of CTGF in pulmonary fibroblasts.

Results

In the mouse lung tissue, CTGF expression and promoter activity peaked 1 week after bleomycin challenge, whereas type I collagen expression and Col1a2 promoter activity peaked 2 weeks postchallenge. Fibroblasts isolated from the mouse lungs 14 days after bleomycin treatment retained a profibrotic expression pattern, characterized by greatly elevated levels of type I collagen and CTGF protein and increased promoter activity. In vitro, inhibition of CTGF by specific small interfering RNA and neutralizing antibodies reduced the collagen protein expression and Col1a2 promoter activity. Moreover, in vivo, anti‐CTGF antibodies applied after bleomycin challenge significantly reduced the Col1a2 promoter activity by ∼25%. The enhanced Col1a2 promoter activity in fibroblasts from bleomycin‐treated lungs was partly dependent on Smad signaling, whereas CTGF acted on the Col1a2 promoter by a mechanism that was independent of the Smad binding site, but was, instead, dependent on the ERK‐1/2 and JNK MAPK pathways. The CTGF effect was mapped to the proximal promoter region surrounding the inverted CCAAT box, possibly involving CREB and c‐Jun. In human lung fibroblasts, the human COL1A2 promoter responded in a similar manner, and the mechanisms of action also involved ERK‐1/2 and JNK signaling.

Conclusion

Our results clearly define a direct profibrotic effect of CTGF and demonstrate its contribution to lung fibrosis through transcriptional activation of Col1a2. Blocking strategies revealed the signaling mechanisms involved. These findings show CTGF to be a rational target for therapy in fibrotic diseases such as SSc.
RNA helicase encoded by melanoma differentiation–associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease
Authors: Sato Shinji , Hoshino Kana , Satoh Takashi , Fujita Tomonobu , Kawakami Yutaka , Fujita Takashi , Kuwana Masataka
Published: June 2009

Objective

To identify the autoantigen recognized by the autoantibody that is associated with clinically amyopathic dermatomyositis (C‐ADM) and rapidly progressive interstitial lung disease (ILD).

Methods

An anti–CADM‐140 antibody–positive prototype serum sample was used to screen a HeLa cell–derived complementary DNA (cDNA) library. Selected cDNA clones were further evaluated by immunoprecipitation of their in vitro–transcribed and in vitro–translated products using anti–CADM‐140 antibody–positive and anti‐CADM‐140 antibody–negative sera. The lysates of COS‐7 cells transfected with the putative antigen were similarly tested. An enzyme‐linked immunosorbent assay (ELISA) to detect the anti–CADM‐140 antibody was established using a recombinant CADM‐140 antigen, and its specificity and sensitivity for C‐ADM and rapidly progressive ILD were assessed in 294 patients with various connective tissue diseases.

Results

By cDNA library screening and immunoprecipitation of in vitro–transcribed and in vitro–translated products, we obtained a cDNA clone encoding melanoma differentiation–associated gene 5 (MDA‐5). The anti–CADM‐140 antibodies in patients' sera specifically reacted with MDA‐5 protein expressed in cells transfected with full‐length MDA‐5 cDNA, confirming the identity of MDA‐5 as the CADM‐140 autoantigen. The ELISA, using recombinant MDA‐5 protein as the antigen, showed an analytical sensitivity of 85% and analytical specificity of 100%, in comparison with the “gold standard” immunoprecipitation assay, and was useful for identifying patients with C‐ADM and/or rapidly progressive ILD.

Conclusion

Given that RNA helicase encoded by MDA‐5 is a critical molecule involved in the innate immune defense against viruses, viral infection may play an important role in the pathogenesis of C‐ADM and rapidly progressive ILD. Moreover, our ELISA using recombinant MDA‐5 protein makes detection of the anti–CADM‐140 antibody routinely available.
Adipocytokines are associated with radiographic joint damage in rheumatoid arthritis
Authors: Rho Young Hee , Solus Joseph , Sokka Tuulikki , Oeser Annette , Chung Cecilia P. , Gebretsadik Tebeb , Shintani Ayumi , Pincus Theodore , Stein C. Michael
Published: June 2009

Objective

Obesity protects against radiographic joint damage in rheumatoid arthritis (RA) through poorly defined mechanisms. Adipocytokines are produced in adipose tissue and modulate inflammatory responses and radiographic joint damage in animal models. The purpose of this study was to examine the hypothesis that adipocytokines modulate inflammation and radiographic joint damage in patients with RA.

Methods

We compared serum concentrations of leptin, resistin, adiponectin, and visfatin in 167 RA patients and 91 control subjects. The independent association between adipocytokines and body mass index (BMI), measures of inflammation (C‐reactive protein [CRP], interleukin‐6 [IL‐6], and tumor necrosis factor α [TNFα]), and radiographic joint damage (Larsen score; n = 93 patients) was examined in RA patients by multivariable regression analysis first controlling for age, race, and sex, and then for obesity (BMI) and inflammation (TNFα, IL‐6, and CRP).

Results

Concentrations of all adipocytokines were significantly higher in RA patients than in controls; for visfatin and adiponectin, this association remained significant after adjusting for BMI, inflammation, or both. Visfatin concentrations were associated with higher Larsen scores, and this association remained significant after adjustment for age, race, sex, disease duration, BMI, and inflammation (odds ratio [OR] 2.38 [95% confidence interval (95% CI) 1.32–4.29], P = 0.004). Leptin concentrations showed a positive association with the BMI (ρ = 0.58, P < 0.01) and showed a negative association with the Larsen score after adjustment for inflammation (OR 0.32 [95% CI 0.17–0.61], P < 0.001), but not after adjustment for BMI (OR 0.86 [95% CI 0.42–1.73], P = 0.67).

Conclusion

Concentrations of adipocytokines are increased in patients with RA and may modulate radiographic joint damage. Visfatin is associated with increased, and leptin with reduced, levels of radiographic joint damage.
Systemic activation of the immune system induces aberrant BAFF and APRIL expression in B cells in patients with systemic lupus erythematosus
Authors: Chu Van Trung , Enghard Philipp , Schürer Stefanie , Steinhauser Gudrun , Rudolph Birgit , Riemekasten Gabriela , Berek Claudia
Published: June 2009

Objective

Elevated levels of BAFF and APRIL are characteristic of patients with systemic lupus erythematosus (SLE). The reasons for enhanced cytokine production are not well understood. This study was undertaken to identify the cells responsible for the overproduction of these cytokines.

Methods

BAFF expression was analyzed on peripheral blood mononuclear cells by multiparameter flow cytometry and in tissue samples by immunofluorescence staining. The levels of BAFF and APRIL mRNA were quantified in sorted B cells. In vitro cultures were used to analyze whether B cell survival and differentiation was supported by autocrine BAFF and/or APRIL.

Results

Aberrant activation of B cells in patients with SLE was associated with a significant up‐regulation of BAFF expression in naive, memory, and plasma cells. Furthermore, strong expression of BAFF and APRIL was found in plasma cells from the lymph node, bone marrow, and kidney. The levels of BAFF and APRIL mRNA in CD19+ B cells correlated both with the titer of anti‐double stranded DNA antibodies and with the SLE Disease Activity Index. In vitro experiments demonstrated that B cells released functional BAFF/APRIL upon activation.

Conclusion

Our data show that B cells contribute to the enhanced levels of circulating BAFF and APRIL. The aberrant up‐regulation of these cytokines may initiate a vicious circle in which enhanced levels of BAFF and APRIL act in an autocrine manner to reinforce the systemic activation of the humoral immune system.
Alterations of the synovial T cell repertoire in anti–citrullinated protein antibody–positive rheumatoid arthritis
Authors: Cantaert Tineke , Brouard Sophie , Thurlings Rogier M. , Pallier Annaick , Salinas Gabriela Franco , Braud Christophe , Klarenbeek Paul L. , de Vries Niek , Zhang Yiping , Soulillou Jean‐Paul , Tak Paul P. , Baeten Dominique
Published: June 2009

Objective

The association of HLA–DRB1 alleles with anti–citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) suggests the potential involvement of T lymphocytes in ACPA‐seropositive disease. The purpose of this study was to investigate this hypothesis by systematic histologic and molecular analyses of synovial T cells in ACPA+ versus ACPA– RA patients.

Methods

Synovial biopsy samples were obtained from 158 RA patients. Inflammation was determined histologically and immunohistochemically. RNA was extracted from peripheral blood mononuclear cells and synovial tissues obtained from 11 ACPA+ RA patients, 7 ACPA– RA patients, and 10 spondylarthritis (SpA) patients (arthritis controls). T lymphocyte clonality was studied by combined quantitative and qualitative T cell receptor CDR3 length distribution (LD) analysis and direct sequencing analysis.

Results

ACPA+ and ACPA– RA patients were similar at both the clinical and histologic levels. At the molecular level, however, patients with ACPA+ synovitis displayed a marked elevation of qualitative CDR3 LD alterations as compared with those with ACPA– synovitis and with the SpA controls. These differences in CDR3 LD were not observed in the peripheral blood, indicating a selective recruitment and/or local expansion of T cells in the synovial compartment. The CDR3 LD alterations reflected true monoclonal or oligoclonal expansions, as confirmed by direct sequencing of the T cell receptor. The CDR3 LD alterations in RA synovium did not correlate with B cell clonal expansions but were inversely associated with synovial lymphoid neogenesis.

Conclusion

The T cell repertoire is specifically restricted in RA patients with ACPA+ synovitis. Whereas the origin and role of these clonal alterations remain to be determined, our data suggest the preferential involvement of T lymphocytes in ACPA‐seropositive RA.
A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody–associated vasculitis
Authors: Jones Rachel B. , Ferraro Alastair J. , Chaudhry Afzal N. , Brogan Paul , Salama Alan D. , Smith Kenneth G. C. , Savage Caroline O. S. , Jayne David R. W.
Published: June 2009

Objective

B cell depletion with rituximab has allowed remissions in relapsing or refractory antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis in small studies. The aim of this study was to determine the efficacy and safety of rituximab for ANCA‐associated vasculitis in a larger multicenter cohort. This permitted comparison of rituximab dosing regimens, the value of continuing immunosuppression, and investigation of ANCA and B cell levels as re‐treatment biomarkers.

Methods

Retrospective, standardized data collection from 65 sequential patients receiving rituximab for refractory ANCA‐associated vasculitis at 4 centers in the UK was used.

Results

All patients achieved B cell depletion. Complete remission occurred in 49 of the 65 patients (75%), partial remission in 15 (23%), and no response in 1 (2%). The prednisolone dosage was reduced from 12.5 mg/day (median) to 9.0 mg/day at 6 months (P = 0.0006). Immunosuppressive therapy was withdrawn in 37 of 60 patients (62%). Twenty‐eight of 49 patients who achieved full remission (57%) experienced relapse (median 11.5 months). B cell return preceded relapse in 14 of 27 patients (52%). Although ANCA levels fell after rituximab therapy, relapse was not associated with ANCA positivity or a rise in ANCA levels. Neither the initial rituximab regimen (4 infusions of 375 mg/m2 each given 1 week apart or 2 infusions of 1 gm each given 2 weeks apart) nor withdrawal of immunosuppressive therapy (37 of 60 patients [62%]) influenced the timing of relapse. Thirty‐eight patients received ≥2 courses of rituximab, and complete remission was induced or maintained in 32 of them (84%). IgM levels fell, although IgG levels remained stable. Forty‐six serious adverse events occurred, including 2 episodes of late‐onset neutropenia, which were attributed to rituximab.

Conclusion

Rituximab was effective remission induction therapy for refractory ANCA‐associated vasculitis in this study. There was no difference in efficacy between the 2 main treatment regimens. Continuing immunosuppression did not reduce relapses. Relapses occurred, but re‐treatment was effective and safe. There was no clear influence of rituximab on the frequency of serious adverse events. ANCA and B cell levels lacked sufficient sensitivity to guide the timing of re‐treatment.
Variables associated with the progression of hip osteoarthritis: A systematic review
Authors: Wright Alexis A. , Cook Chad , Abbott J. Haxby
Published: June 2009

Objective

As populations age and the prevalence of hip osteoarthritis (OA) increases, health care providers must manage increasing demands for services. Evidence regarding the progression of hip OA can assist health care practitioners in determining expected patient prognosis and planning care. This systematic review of prospective cohort studies examines prognostic variables in patients with hip OA.

Methods

Articles were selected following a comprehensive search of Medline, EMBase, CINAHL, and Allied and Complementary Medicine from database inception to October 2008 and hand searches of the reference lists of retrieved articles. Inclusion criteria involved 1) estimates of the association between prognostic variables and progression of OA, 2) prospective cohort design, 3) patients diagnosed with hip OA based on established criteria, 4) at least 1 year of followup, and 5) access to the full published text. Two independent reviewers assessed the methodologic quality of each study and the association between prognostic variables and OA progression.

Results

Eighteen articles met the inclusion criteria; 17 were considered to be of high quality. Strong evidence of progression was associated with age, joint space width at entry, femoral head migration, femoral osteophytes, bony sclerosis, Kellgren/Lawrence hip grade 3, baseline hip pain, and Lequesne index score ≥10. Strong evidence of no association with progression was associated with acetabular osteophytes. Evidence was weak or inconclusive regarding associations between various other radiographic or clinical variables, molecular biomarkers, or use of nonsteroidal inflammatory drugs.

Conclusion

Overall, few variables were found to be strongly associated with the progression of hip OA, and a variety of other variables were weakly predictive of outcome.
Multicenter, randomized, double‐blind, controlled trial of treatment of active rheumatoid arthritis with T‐614 compared with methotrexate
Authors: Lu Liang‐jing , Bao Chun‐de , Dai Min , Teng Jia‐lin , Fan Wei , Du Fang , Yang Nan‐ping , Zhao Yin‐huan , Chen Zhi‐wei , Xu Jian‐hua , He Pei‐gen , Wu Hua‐xiang , Tao Yi , Zhang Miao‐jia , Han Xing‐hai , Li Xing‐fu , Gu Jie‐ruo , Li Jian‐hua , Yu Hao
Published: June 2009

Objective

To assess the efficacy and safety of T‐614 versus methotrexate (MTX) in patients with active rheumatoid arthritis (RA).

Methods

In this multicenter, double‐blind trial, 489 patients randomly received either T‐614 25 mg/day for the first 4 weeks and 50 mg/day for the subsequent 20 weeks (group 1, n = 163), T‐614 50 mg/day for 24 weeks (group 2, n = 163), or MTX 10 mg/week for the first 4 weeks and 15 mg/week for the subsequent 20 weeks (n = 163). Clinical and laboratory parameters were analyzed at baseline and at 4, 10, 17, and 24 weeks.

Results

After 24 weeks of treatment, the American College of Rheumatology 20% improvement criteria response rate for patients in T‐614 group 2 (63.8%) was not statistically significantly different from that for patients receiving MTX treatment (62.0%), and was superior to that for patients in T‐614 group 1 (50.9%). The result of the noninferiority analysis indicated that the efficacy of T‐614 (50 mg/day) was not lower than that of MTX by <10%. Rheumatoid factor and IgA, IgG, and IgM demonstrated a statistically significant decrease in all groups. Frequently reported adverse events included hematologic disorder, skin reactions, gastrointestinal symptoms, and transient liver enzyme elevations in the T‐614 therapy groups. Side effects in the T‐614 groups were generally fewer and milder than in the MTX group, except for skin reactions. There were no prominent cardiovascular adverse events and gastrointestinal ulcers found in the T‐614 groups.

Conclusion

Results indicate that T‐614 therapy 50 mg/day is effective and well tolerated, and represents a new option for the treatment of patients with active RA.
Feasibility of second‐generation ultrasound contrast media in the detection of active sacroiliitis
Authors: Klauser Andrea S. , De Zordo Tobias , Bellmann‐Weiler Rosa , Feuchtner Gudrun M. , Sailer‐Höck Michaela , Sögner Peter , Gruber Johann
Published: June 2009

Objective

To determine whether a recently available contrast‐enhanced ultrasound (CEUS) technique using second‐generation microbubbles allows for the detection of active sacroiliitis, and to measure CEUS enhancement depth at the dorsocaudal part of the sacroiliac (SI) joints in healthy volunteers compared with patients with sacroiliitis.

Methods

Forty‐two consecutive patients (84 SI joints) presenting with a clinical diagnosis of sacroiliitis in 50 SI joints and 21 controls (42 SI joints) were investigated by CEUS using a standardized low mechanical index ultrasound protocol. Detected vascularity was used to retrospectively measure the enhancement depth in the dorsocaudal part of the SI joints.

Results

CEUS detected enhancement in all clinically active SI joints, showing an enhancement depth into the dorsal SI joint cleft of 18.5 mm (range 16–22.1), which was significantly higher compared with both inactive joints of patients (3.6 mm, range 0–12; P < 0.001) and healthy controls (3.1 mm, range 0–7.8; P < 0.001). All inactive joints were correctly classified based on a lack of deep enhancement in patients with sacroiliitis and controls (42 of 42, 100% sensitivity, 100% specificity; Cohen's κ = 1).

Conclusion

CEUS allowed the differentiation of active sacroiliitis from inactive SI joints, and proved to be a feasible method for the detection of vascularity in clinically active sacroiliitis by showing deep contrast enhancement into the SI joints not detectable in inactive joints of patients or controls. If this technique might add information to the earlier detection of sacroiliitis, it should be addressed in further studies.
Effect of baseline quadriceps activation on changes in quadriceps strength after exercise therapy in subjects with knee osteoarthritis
Authors: Scopaz Kristen A. , Piva Sara R. , Gil Alexandra B. , Woollard Jason D. , Oddis Chester V. , Fitzgerald G. Kelley
Published: June 2009

Objective

To examine whether pretreatment magnitude of quadriceps activation (QA) helps predict changes in quadriceps strength after exercise therapy in subjects with knee osteoarthritis (OA). We hypothesized that subjects with lower magnitudes of QA (greater failure of muscle activation) would have smaller gains in strength compared with those with higher magnitudes of QA following exercise therapy.

Methods

One hundred eleven subjects with knee OA (70 women) participated. Baseline measures included demographic information, quadriceps muscle strength, and QA using a burst‐superimposition isometric torque test. Following baseline testing, subjects underwent a 6‐week supervised exercise program designed to improve strength, range of motion, balance and agility, and physical function. On completion of the program, quadriceps strength and QA were reassessed. Multiple regression analysis was used to determine whether baseline QA predicted quadriceps strength scores at the 2‐month followup.

Results

Bivariate correlations demonstrated that baseline QA was significantly associated with quadriceps strength at baseline (ρ = 0.30, P < 0.01) and 2‐month followup (ρ = 0.23, P = 0.01). Greater magnitude of baseline QA correlated with higher strength. While controlling for baseline quadriceps strength and type of exercise therapy, the level of QA did not predict quadriceps strength at the 2‐month followup (β = −0.04, P = 0.18).

Conclusion

Baseline QA did not predict changes in quadriceps strength following exercise therapy. Measurement of QA using the central activation ratio method does not appear to be helpful in identifying subjects with knee OA who will have difficulty improving quadriceps strength with exercise therapy.
Association of adrenergic receptor gene polymorphisms with different fibromyalgia syndrome domains
Authors: Vargas‐Alarcón Gilberto , Fragoso José‐Manuel , Cruz‐Robles David , Vargas Angélica , Martinez Aline , Lao‐Villadóniga José‐Ignacio , García‐Fructuoso Ferrán , Vallejo Maite , Martínez‐Lavín Manuel
Published: June 2009

Objective

Fibromyalgia (FM) patients have signs of relentless sympathetic hyperactivity associated with hyporeactivity to stress. Adrenergic receptors (ARs) are parts of the sympathetic nervous system that are fundamental for maintenance of homeostasis. We undertook this study to correlate α‐AR and β‐AR gene polymorphisms with the presence of FM and with different domains of the FM syndrome as measured by the Fibromyalgia Impact Questionnaire (FIQ).

Methods

We studied 78 Mexican FM patients and 48 age‐matched controls as well as 78 Spanish FM patients and 71 controls. All subjects studied were women. Single‐nucleotide polymorphisms (SNPs) of α1A‐AR (rs574584, rs1383914, rs1048101, and rs573542), β2‐AR (rs1042713 and rs1042714), and β3‐AR (rs4994) were analyzed by 5′ exonuclease TaqMan polymerase chain reaction. Polymorphic haplotypes were constructed after linkage disequilibrium analysis.

Results

The β2‐AR AC haplotype was a risk factor for the presence of FM. This haplotype had an increased frequency in Mexican patients compared with Mexican controls (42.1% versus 30.5%; P = 0.04). Similarly, 50.4% of Spanish patients had this haplotype compared with 40.0% of Spanish controls (P = 0.05). In Spanish patients, the α1A‐AR SNP rs1383914 was associated with the presence of FM (P = 0.01), and the α1A‐AR SNP rs1048101 was linked with FIQ disability (P = 0.02). Mexican patients with the rs574584 GG genotype presented the highest FIQ score compared with Mexican patients with other genotypes (P = 0.01), and in Mexicans SNP rs574584 was associated with FIQ morning stiffness (P = 0.04) and with FIQ tiredness upon awakening (P = 0.02).

Conclusion

AR gene polymorphisms are related to the risk of developing FM and are also linked to different domains of the FM syndrome.
PAN–DR‐Binding Hsp60 self epitopes induce an interleukin‐10–mediated immune response in rheumatoid arthritis
Authors: de Jong Huib , Lafeber Floris F. P. , de Jager Wilco , Haverkamp Margje H. , Kuis Wietse , Bijlsma Johannes W. J. , Prakken Berent J. , Albani Salvatore
Published: June 2009

Objective

Human Hsp60 is expressed in the joints of patients with rheumatoid arthritis (RA) and can elicit a regulatory T cell response in the peripheral blood and synovial fluid. However, Hsp60 can also trigger strong proinflammatory pathways. Thus, to understand the nature of these Hsp60‐directed responses in RA, it is necessary to study such responses at the molecular, epitope‐specific level. This study was undertaken to characterize the disease specificity and function of pan–DR‐binding Hsp60–derived epitopes as possible modulators of autoimmune inflammation in RA.

Methods

Lymphocyte proliferation assays (using 3H‐thymidine incorporation and carboxyfluorescein diacetate succinimidyl ester [CFSE] staining) and measurement of cytokine production (using multiplex immunoassay and intracellular staining) were performed after in vitro activation of peripheral blood mononuclear cells from patients with RA, compared with healthy controls.

Results

A disease (RA)–specific immune recognition, characterized by T cell proliferation as well as increased production of tumor necrosis factor α (TNFα), interleukin‐1β (IL‐1β), and IL‐10, was found for 3 of the 8 selected peptides in patients with RA as compared with healthy controls (P < 0.05). Intracellular cytokine staining and CFSE labeling showed that CD4+ T cells were the subset primarily responsible for both the T cell proliferation and the cytokine production in RA. Interestingly, the human peptides had a remarkably different phenotype, with a 5–10‐fold higher IL‐10:TNFα ratio, compared with that of the microbial peptides.

Conclusion

These results suggest a disease‐specific immune‐modulatory role of epitope‐specific T cells in the inflammatory processes of RA. Therefore, these pan–DR‐binding epitopes could be used as a tool to study the autoreactive T cell response in RA and might be suitable candidates for use in immunotherapy.
Intravenous immunoglobulin and salicylate differentially modulate pathogenic processes leading to vascular damage in a model of Kawasaki disease
Authors: Lau Andrew C. , Duong Trang T. , Ito Shinya , Yeung Rae S. M.
Published: June 2009

Objective

Kawasaki disease (KD) is a multisystem vasculitis affecting children and is characterized by immune activation in the acute stage of disease. Systemic inflammation eventually subsides, although coronary arteritis persists, resulting in aneurysm formation. KD is the leading cause of acquired heart disease among children in North America. Accepted treatment guidelines include high‐dose intravenous immunoglobulin (IVIG) and aspirin in the acute phase. Although this therapy is effective, the cellular and molecular mechanisms involved are not clear. The aim of this study was to examine the effect of IVIG and salicylate at each stage of disease development.

Methods

Using a murine model of KD, we established and validated several in vitro techniques to reflect 3 key steps involved in disease pathogenesis, as follows: thymidine incorporation to evaluate T cell activation, enzyme‐linked immunosorbent assay to measure tumor necrosis factor α (TNFα) production, and real‐time polymerase chain reaction to examine TNFα‐mediated expression of matrix metalloproteinase 9 (MMP‐9).

Results

At therapeutic concentrations, IVIG, but not salicylate, effectively reduced the immune response leading to TNFα expression. Unexpectedly, pharmacologic doses of salicylate were not able to inhibit TNFα production and in fact enhanced its production. Neither drug directly regulated MMP‐9 expression but did so only indirectly via modulating TNFα. TNFα activity was a prerequisite for local expression of MMP‐9 at the coronary artery.

Conclusion

Therapeutic concentrations of IVIG and salicylate differentially modulate the expression of TNFα and its downstream effects. Further dissection of the biologic effects of aspirin in acute KD is necessary for the rational design of therapy.
Analysis of Borrelia burgdorferi genotypes in patients with lyme arthritis: High frequency of ribosomal RNA intergenic spacer type 1 strains in antibiotic‐refractory arthritis
Authors: Jones Kathryn L. , McHugh Gail A. , Glickstein Lisa J. , Steere Allen C.
Published: June 2009

Objective

Most of the Borrelia burgdorferi genotypes have been isolated from erythema migrans (EM) skin lesions in patients with Lyme disease. OspC type K strains, which are 16S–23S ribosomal RNA intergenic spacer type 2 (RST2) strains, are most commonly recovered, but a higher percentage of OspC type A strains (RST1), the next most commonly recovered type, is detectable in blood. The goal of this study was to determine the B burgdorferi genotypes in the joints of patients with Lyme arthritis.

Methods

Joint fluid samples from 124 patients seen over a 30‐year period were analyzed for OspC types by semi‐nested polymerase chain reaction (PCR) and sequencing, and for RSTs by nested PCR and restriction fragment length polymorphism analysis. These results were correlated with clinical outcome.

Results

OspC and RST genotypes were identified in 49 of the 124 joint fluid samples (40%). In these 49 samples, OspC type K strains (RST2) were identified in 21 samples (43%), OspC type A strains (RST1) were identified in 11 samples (22%), and 8 other OspC types and all 3 RSTs were identified among the remaining 17 samples (35%). However, among the 17 patients who had been treated with antibiotics according to current guidelines, all 7 patients who were infected with RST1 strains had antibiotic‐refractory arthritis, compared with 4 of 6 patients infected with RST2 strains and only 1 of 4 infected with RST3 strains (P = 0.03).

Conclusion

Most of the B burgdorferi genotypes, particularly OspC type K (RST2), were identified in the joint fluid of patients with Lyme arthritis, and the genotype frequencies found in joints reflected those in EM skin lesions. However, RST1 strains were most frequent in patients with antibiotic‐refractory arthritis. Our results help to further the understanding of the differential pathogenicity of strains of B burgdorferi.
Addressable DNA–Myoglobin Photocatalysis
Authors: Kuo Chi‐Hsien , Fruk Ljiljana , Niemeyer Christof M.
Published: June 2009

In the spotlight: A hybrid myoglobin, containing a single‐stranded DNA anchor and a redox‐active ruthenium moiety tethered to the heme center can be used as a photocatalyst. The catalyst can be selectively immobilized on a surface‐bound complementary DNA molecule and thus readily recycled from complex reaction mixtures. This principle may be applied to a range of heme‐dependent enzymes allowing the generation of novel light‐triggered photocatalysts.

magnified image

Photoactivatable myoglobin containing a DNA oligonucleotide as a structural anchor was designed by using the reconstitution of artificial heme moieties containing Ru3+ ions. This semisynthetic DNA–enzyme conjugate was successfully used for the oxidation of peroxidase substrates by using visible light instead of H2O2 for the activation. The DNA anchor was utilized for the immobilization of the enzyme on the surface of magnetic microbeads. Enzyme activity measurements not only indicated undisturbed biofunctionality of the tethered DNA but also enabled magnetic separation‐based enrichment and recycling of the photoactivatable biocatalyst.
“Seeing is believing”: The effects of facial expressions of emotion and verbal communication in social dilemmas
Authors: Stouten Jeroen , De Cremer David
Published: June 2009

In social dilemmas, verbal communication of one's intentions is an important factor in increasing cooperation. In addition to verbal communication of one's intentions, also the communication of emotions of anger and happiness can influence cooperative behavior. In the present paper, we argue that facial expressions of emotion moderate verbal communication in social dilemmas. More specifically, three experiments showed that if the other person displayed happiness he or she was perceived as honest, trustworthy, and reliable, and cooperation was increased when verbal communication was cooperative rather than self‐interested. However, if the other person displayed anger, verbal communication did not influence people's decision behavior. Results also showed interactive effects on people's perceptions of trustworthiness, which partially mediated decision behavior. These findings suggest that emotion displays have an important function in organizational settings because they are able to influence social interactions and cooperative behavior. Copyright © 2009 John Wiley & Sons, Ltd.
Cell fate transitions during stomatal development
Authors: Serna Laura
Published: June 2009

Stomata, the most influential components in gas exchange with the atmosphere, represent a revealing system for studying cell fate determination. Studies in Arabidopsis thaliana have demonstrated that many of the components, functioning in a signaling cascade, guide numerous cell fate transitions that occur during stomatal development. The signaling cascade is initiated at the cell surface through the activation of the membrane receptors TOO MANY MOUTHS (TMM) and/or ERECTA (ER) family members by the secretory peptide EPIDERMAL PATTERNING FACTOR1 (EPF1) and/or a substrate processed proteolytically by the subtilase STOMATAL DENSITY AND DISTRIBUTION1 (SDD1) and transduced through cytoplasmic MAP kinases (YODA (YDA), MKK4/MKK5, and MPK3/MPK6) towards the nucleus. In the nucleus, these MAP kinases regulate the activity of the basic helix‐loop‐helix (bHLH) proteins SPEECHLESS (SPCH), MUTE, and FAMA, which act in concert with the bHLH‐Leu zipper protein SCREAM (SCRM) (and/or its closely related paralog, SCREAM2). This article reviews current insights into the role of this signaling cascade during stomatal development.
Acetyl derivate of quercetin increases the sensitivity of human leukemia cells toward apoptosis
Authors: Sakao Kozue , Fujii Makoto , Hou De‐Xing
Published: June 2009

The hydroxyl groups of flavonoids are important for their bioactive functions and also prone to oxidation to quinones. To block the potential oxidation of quercetin, and generate a stronger bioactive compound, we synthesized acetyl and methyl derivatives of quercetin, 3,7,3′,4′‐O‐tetraacetylquercetin (4Ac‐Q) and 3,7,3′,4′‐O‐tetramethylquercetin (4Me‐Q), which substituted the hydroxyl groups of quercetin with acetyl or methyl groups at the 3,7,3′,4′ positions of quercetin, and then evaluated the ability to cause cell proliferation inhibition and apoptosis in HL‐60 cells. The results revealed that 4Ac‐Q and quercetin, but not 4Me‐Q, significantly inhibit cell proliferation by caspase‐mediated apoptosis when characterized by DNA fragmentation, activation of caspase‐3 and PARP cleavage while 4Me‐Q lost this ability. Interestingly, 4Ac‐Q revealed stronger apoptotic activity than parent quercetin via a ROS‐independent pathway. These findings provide a valuable strategy to increase the sensitivity of human leukemia HL‐60 cells toward apoptosis by modifying quercetin structure. © 2009 International Union of Biochemistry and Molecular Biology, Inc.
Selectivity of Competitive Multivalent Interactions at Interfaces
Authors: André Thomas , Reichel Annett , Wiesmüller Karl‐Heinz , Tampé Robert , Piehler Jacob , Brock Roland
Published: June 2009

The development of synthetic, low‐molecular‐weight ligand receptor systems for the selective control of biomolecular interactions remains a major challenge. Binding of oligohistidine peptides to chelators containing Ni2+‐loaded nitrilotriacetic acid (NTA) moieties is one of the most widely used and best‐characterised recognition systems. Recognition units containing multiple NTA moieties (multivalent chelator headgroups, MCHs) recognise oligohistidines with substantially increased binding affinities. Different multivalencies both at the level of the MCH and at that of the oligohistidine ligand provide a powerful means to vary the affinity of the interaction systematically. Here we have explored the selectivity for the binding of different oligohistidines to immobilised MCH. Using microarrays of mono‐, bis‐, tris‐ and tetrakis‐NTA chelators spotted at different surface densities, we explored the ability of these binders to discriminate fluorescently labelled hexa‐ and decahistidine peptides. When hexa‐ and decahistidine were tested alone, the discrimination of ligands showed little dependence either on the nature or on the density of the chelator. In contrast, coincubation of both peptides decreased the affinity of hexahistidine, increased the affinity of decahistidine, and made the binding of decahistidine highly dependent on MCH density. Kinetic binding assays by dual‐colour total internal reflection fluorescence spectroscopy revealed active exchange of His6 by His10 and confirmed the high selectivity towards His10. Our results establish the key role of surface multivalency for the selectivity of multivalent interactions at interfaces.
Modern Biocatalysis: Stereoselective and Environmentally Friendly Reactions. Edited by Wolf‐Dieter Fessner and Thorleif Anthonsen.
Authors: Turner Nicholas
Published: June 2009

Wiley‐VCH, Weinheim 2009, XXIII+375 pp., € 129.00.—ISBN 978‐3‐527‐32071‐4

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(Self) hypnosis in the prevention of burnout and compassion fatigue for caregivers: theory and induction
Authors: Ruysschaert Nicole
Published: June 2009

Caregivers are particularly at risk of compassion fatigue and burnout. Empathy, activity of mirror neurons and mirroring increase the risks. Some research has been done on the relationship between hypnotizability and empathy. In the prevention of burnout and compassion fatigue a positive approach with increase of ‘compassion satisfaction’ and ‘resilience’ makes sense. Hypnosis with its emphasis on mobilizing positive resources and positive psychology is helpful at different levels of intervention. (Self) hypnosis is integrated in strategies for self care, setting boundaries and increasing inner strength and resilience. In hypnosis attitude changes can be made with promotion of compassion satisfaction and job engagement. Resource development is also part of the hypnotic work. After initial training in hypnosis, caregivers can help themselves further in remaining more resilient and keeping positively engaged, enjoying compassion satisfaction. Copyright © 2009 British Society of Experimental & Clinical Hypnosis. Published by John Wiley & Sons, Ltd.
Fluorinated Quinine Alkaloids: Synthesis, X‐ray Structure Analysis and Antimalarial Parasite Chemotherapy
Authors: Bucher Christoph , Sparr Christof , Schweizer W. Bernd , Gilmour Ryan
Published: June 2009

Herein we report the synthesis of a series of C9‐fluorinated quinine alkaloids by direct nucleophilic deoxyfluorination. This transformation gives rise to products bearing both S‐ and R‐configured monofluoromethylene functionalities, consistent with an SN1‐like mechanism. Furthermore, a series of ring‐expanded 1‐azabicyclo[3.2.2]nonane systems were generated by a skeletal rearrangement of the quinuclidine core. The modified alkaloids were converted to the corresponding hydrochloride salts and characterised by single‐crystal X‐ray diffraction analysis. The preference of the benzylic fluorine atom to adopt a gauche conformation relative to the protonated quinuclidine nitrogen atom was consistently observed throughout the cage‐conserved compounds. Conversely, the molecular architecture of the 1‐azabicyclo[3.2.2]nonane systems enforced an anti relationship between the fluorine atom and the protonated tertiary amine. This constitutes the first X‐ray evidence of a vicinal fluorine atom at a stereogenic centre positioned anti to a substituted ammonium cation. The pharmacological efficacy of these compounds was assessed in vitro against the NF54 strain of Plasmodium falciparum (sensitive to all known antimalarial drugs). IC50 values of as low as 267 nM were observed; this highlights the potential of these materials in developing novel agents for parasite chemotherapy.
ChemInform Abstract: Defects in Half‐Heusler Type Antimonides ScTSb (T: Ni, Pd, Pt).
Authors: Harmening Thomas , Eckert Hellmut , Poettgen Rainer
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: The Crystal Structure of Li2B4O7 Compound in the Temperature Range 10‐290 K.
Authors: Adamiv V. T. , Burak Ya. V. , Teslyuk I. M.
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Structure, Heat Capacity, and High‐Temperature Thermal Properties of Yb14Mn1‐xAlxSb11.
Authors: Cox Catherine A. , Toberer Eric S. , Levchenko Andrey A. , Brown Shawna R. , Snyder G. Jeffrey , Navrotsky Alexandra , Kauzlarich Susan M.
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Improvement in the Thermoelectric Figure of Merit by La/Ag Cosubstitution in PbTe.
Authors: Ahn Kyunghan , Li Changpeng , Uher Ctirad , Kanatzidis Mercouri G.
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Ba2AlSi5N9 — A New Host Lattice for Eu2+‐Doped Luminescent Materials Comprising a Nitridoalumosilicate Framework with Corner‐ and Edge‐Sharing Tetrahedra.
Authors: Kechele Juliane A. , Hecht Cora , Oeckler Oliver , Schmedt auf der Guenne Joern , Schmidt Peter J. , Schnick Wolfgang
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Anomalous Electrical Conductivity of Nanosheaves of CeO2.
Authors: Kim Sangtae , Lee Jong Soo , Mitterbauer Christoph , Ramasse Quentin M. , Sarahan Michael C. , Browning Nigel D. , Park Hee Jung
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Leakage and Proton Conductivity in the Predicted Ferroelectric CsBiNb2O7.
Authors: Goff Richard J. , Keeble Dean , Thomas Pamela A. , Ritter Clemens , Morrison Finlay D. , Lightfoot Philip
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Novel Urchin‐Like CuO Synthesized by a Facile Reflux Method with Efficient Olefin Epoxidation Catalytic Performance.
Authors: Xu Linping , Sithambaram Shanthakumar , Zhang Yashan , Chen Chun‐Hu , Jin Lei , Joesten Raymond , Suib Steven L.
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Sm1.5Sr0.5MO4 (M: Ni, Co, Fe) Cathode Catalysts for Ammonia Synthesis at Atmospheric Pressure and Low Temperature.
Authors: Xu Gaochao , Liu Ruiquan
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform Abstract: Superacidity of Boron Acids H2(B12X12) (X: Cl, Br).
Authors: Avelar Amy , Tham Fook S. , Reed Christopher A.
Published: June 2009

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.