bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractObjectiveB 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.MethodsRetrospective, standardized data collection from 65 sequential patients receiving rituximab for refractory ANCA‐associated vasculitis at 4 centers in the UK was used.ResultsAll 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 Immunosuppressive therapy was withdrawn in 37 of 60 patients (62%).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.ConclusionRituximab 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

AbstractObjectiveAs 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.MethodsArticles 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.ResultsEighteen 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.ConclusionOverall, 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

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

AbstractObjectiveTo 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.MethodsForty‐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.ResultsCEUS 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).ConclusionCEUS 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

AbstractObjectiveTo 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.MethodsOne 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.ResultsBivariate 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).ConclusionBaseline 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

AbstractObjectiveFibromyalgia (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).MethodsWe 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.ResultsThe 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).ConclusionAR 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

AbstractObjectiveHuman 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.MethodsLymphocyte 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.ResultsA 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.ConclusionThese 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

AbstractObjectiveKawasaki 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.MethodsUsing 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).ResultsAt 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.ConclusionTherapeutic 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

AbstractObjectiveMost 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.MethodsJoint 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.ResultsOspC 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).ConclusionMost 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

AbstractIn 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 imagePhotoactivatable 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

AbstractIn 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

AbstractStomata, 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

AbstractThe 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.