bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cartilage oligomeric matrix protein induction of chronic arthritis in mice
Authors: Carlsen Stefan , Nandakumar Kutty Selva , Bäcklund Johan , Holmberg Jens , Hultqvist Malin , Vestberg Mikael , Holmdahl Rikard 
Published: June 2008

AbstractObjectiveTo develop a new mouse model for arthritis using cartilage oligomeric matrix protein (COMP) and to study the role of major histocompatibility complex (MHC) and Ncf1 genes in COMP‐induced arthritis (COMPIA).MethodsNative (pentameric) and denatured (monomeric) COMP purified from a rat chondrosarcoma was injected into mice with Freund's adjuvant to induce arthritis. C3H.NB, C3H.Q, B10.P, B10.Q, (B10.Q × DBA/1)F1, (BALB/c × B10.Q)F1, Ncf1 mutated, H‐2Aq, H‐2Ap, and human DR4+‐transgenic mice were used. Anti‐COMP antibodies and COMP levels in the immune sera were analyzed, and passive transfer of arthritis with purified immune sera was tested.ResultsImmunization with rat COMP induced a severe, chronic, relapsing arthritis, with a female preponderance, in the mice. The disease developed in C3H.NB mice, but not in B10.P mice, although they share the same MHC haplotype. Both H‐2q and H‐2p MHC haplotypes allowed the initiation of COMPIA. Using H‐2Aq–transgenic and H‐2Ap–transgenic mice, we demonstrated a role of both the Aq and Ep class II molecules in this model. Interestingly, the introduction of a mutation in the Ncf1 gene, which is responsible for the reduced oxidative burst phenotype, into the COMPIA‐resistant B10.Q mouse strain rendered them highly susceptible to arthritis. In addition, the transfer of anti‐COMP serum was found to induce arthritis in naive mice. Mice transgenic for the rheumatoid arthritis (RA)–associated DR4 molecule were found to be highly susceptible to COMPIA.ConclusionUsing rat COMP, we have developed a new and unique mouse model of chronic arthritis that resembles RA. This model will be useful as an appropriate and alternative model for studying the pathogenesis of RA.
Skewed distribution of Th17 lymphocytes in patients with Wegener's granulomatosis in remission
Authors: Abdulahad Wayel H. , Stegeman Coen A. , Limburg Pieter C. , Kallenberg Cees G. M. 
Published: June 2008

AbstractObjectiveThe recently characterized interleukin‐17 (IL‐17)–producing T helper cell lineage (Th17), rather than the Th1 lineage, is involved in several autoimmune diseases. The possible role of Th17 cells in Wegener's granulomatosis (WG) has not yet been elucidated. We undertook this study to assess the distribution of Th1/Th2/Th17 cells and to investigate the presence of Th17 cells specific for the WG autoantigen proteinase 3 (PR3) in WG.MethodsPeripheral blood from patients with WG in remission (n = 26) and healthy controls (n = 10) was stimulated in vitro with PR3 or with the control stimuli staphylococcal enterotoxin B (SEB), tetanus toxoid (TT), or phorbol myristate acetate/calcium ionophore, together with anti‐CD28 and anti‐CD49d. The frequencies of the various CD4+ T cell phenotypes responsive to stimuli were determined by 7‐color flow cytometric detection of CD3, CD8, an early activation marker (CD69), and intracellular cytokines (IL‐2, interferon‐γ [IFNγ], IL‐17, and IL‐4).ResultsThe percentage of CD69+,CD4+ T cells in patients with WG in remission was significantly decreased in response to PR3 and tended to be lower in response to other stimuli compared with the percentage in healthy controls. The percentages of Th17 cells (IL‐4−,IL‐17+,IFNγ−) and Th2 cells (IL‐4+,IL‐17−,IFNγ–) within the activated CD69+,CD4+ T cell population were significantly increased in patients with WG in remission, while no difference was found in Th1 cells (IL‐4−,IL‐17−,IFNγ+) compared with the percentage in healthy controls. Increased percentages of Th17 cells in response to TT and SEB were found both in antineutrophil cytoplasmic antibody (ANCA)–positive and in ANCA‐negative patients, while an increased frequency of PR3‐specific Th17 cells was restricted to ANCA‐positive patients.ConclusionA skewed Th17 response found in ANCA‐positive WG patients following stimulation with the autoantigen PR3 suggests that IL‐17 is involved in disease pathogenesis and could constitute a new therapeutic target.
(−)‐Epigallocatechin‐3‐gallate suppresses osteoclast differentiation and ameliorates experimental arthritis in mice
Authors: Morinobu Akio , Biao Wang , Tanaka Shino , Horiuchi Marika , Jun Liu , Tsuji Goh , Sakai Yoshitada , Kurosaka Masahiro , Kumagai Shunichi 
Published: June 2008

AbstractObjectiveTo verify the effects of (−)‐epigallocatechin‐3‐gallate (EGCG) on osteoclast differentiation and on experimental arthritis in mice.MethodsHuman osteoclasts were differentiated from peripheral blood monocytes. The effects of EGCG were examined by tartrate‐resistant acid phosphatase (TRAP) staining, bone resorption assay, Western blotting, and quantitative real‐time polymerase chain reaction. Arthritis was induced in mice by injecting a cocktail of monoclonal antibodies against collagen. EGCG (20 μg/gm body weight) was administered intraperitoneally every day from day 0 through the end of the experiments (day 15). The effects of EGCG were determined by assessments of joint swelling, histologic changes, and TRAP staining on day 15.ResultsEGCG reduced the generation of TRAP‐positive multinucleated cells, bone resorption activity, and osteoclast‐specific gene expression without affecting cell viability. EGCG down‐regulated expression of nuclear factor of activated T cells c1 (NF‐ATc1), but not of NF‐κB, c‐Fos, and c‐Jun, suggesting that down‐regulation of NF‐ATc1 is one of the molecular bases of EGCG action. Additionally, EGCG treatment ameliorated clinical symptoms and reduced histologic scores in arthritic mice (P < 0.05). The in vivo effect of EGCG on osteoclast differentiation was not clear in this model, probably because EGCG suppressed the inflammation itself.ConclusionEGCG suppressed osteoclast differentiation and ameliorated experimental arthritis in mice over the short term. It remains to be established whether EGCG is useful for the prevention and treatment of osteoporosis and rheumatoid arthritis.
Association of autoimmunity to peptidyl arginine deiminase type 4 with genotype and disease severity in rheumatoid arthritis
Authors: Harris Michelle L. , Darrah Erika , Lam Gordon K. , Bartlett Susan J. , Giles Jon T. , Grant Audrey V. , Gao Peisong , Scott William W. , El‐Gabalawy Hani , Casciola‐Rosen Livia , Barnes Kathleen C. , Bathon Joan M. , Rosen Antony 
Published: June 2008

AbstractObjectiveProtein citrullination is an important posttranslational modification recognized by rheumatoid arthritis (RA)–specific autoantibodies. One of the citrullinating enzymes, peptidyl arginine deiminase type 4 (PAD‐4), is genetically associated with development of RA in some populations, although the mechanism(s) mediating this effect are not yet clear. There have been descriptions of anti–PAD‐4 autoantibodies in different rheumatic diseases. This study was undertaken to investigate whether anti–PAD‐4 antibodies are specific to RA, are associated with disease phenotype or severity, and whether PAD‐4 polymorphisms influence the anti–PAD‐4 autoantibody response.MethodsSera from patients with established RA, patients with other rheumatic diseases, and healthy adults were assayed for anti–PAD‐4 autoantibodies by immunoprecipitation of in vitro–translated PAD‐4. The epitope(s) recognized by PAD‐4 autoantibodies were mapped using various PAD‐4 truncations. PAD‐4 genotyping was performed on RA patients with the TaqMan assay. Joint erosions were scored from hand and foot radiographs using the Sharp/van der Heijde method.ResultsPAD‐4 autoantibodies were found in 36–42% of RA patients, and were very infrequent in controls. Recognition by anti–PAD‐4 autoantibodies required the 119 N‐terminal amino acids, which encompass the 3 nonsynonymous polymorphisms associated with disease susceptibility. Strikingly, the anti–PAD‐4 immune response was associated with the RA susceptibility haplotype of PADI4. Anti–PAD‐4 antibodies were associated with more severe joint destruction in RA.ConclusionOur findings indicate that anti–PAD‐4 antibodies are specific markers of RA, independently associated with more severe disease, suggesting that an anti–PAD‐4 immune response may be involved in pathways of joint damage in this disease. Polymorphisms in the PADI4 gene influence the immune response to the PAD‐4 protein, potentially contributing to disease propagation.
Application of inflammation‐responsive promoter for an in vitro arthritis model
Authors: Rachakonda P. Sivaramakrishna , Rai Muhammad Farooq , Schmidt Michael F. G. 
Published: June 2008

AbstractObjectiveThe application of inflammation‐regulated therapeutic gene expression in arthritis conditions increases the efficiency of gene therapy by self‐limiting the transgene. Incidentally, constitutive overexpression of transgenes typically leads to detrimental effects in disease conditions; therefore, regulation of expression is warranted. We undertook this study to validate a new gene therapy approach using a cell culture–based inflammation model and a novel self‐limiting, inflammation‐responsive promoter construct.MethodsWe designed a self‐limiting promoter construct that expresses an antiinflammatory gene (interleukin‐4 [IL‐4]) only in the presence of inflammation. Our construct featured a truncated promoter sequence of cyclooxygenase 2 (COX‐2) upstream of the IL‐4 gene. We triggered inflammation in vitro in articular chondrocytes by applying the inflammatory cytokines IL‐1β and tumor necrosis factor α (TNFα) together exogenously, and we studied the extent of IL‐4 expression and its effect on the inflammatory cascade.ResultsUsing articular chondrocytes, we showed that our COX‐2 promoter construct expressed IL‐4 only in the presence of IL‐1β and TNFα. IL‐4 expressed in the presence of IL‐1β and TNFα down‐regulated a series of inflammation mediators, prostaglandins, and matrix metalloproteinases.ConclusionThe use of this construct for the expression of antiinflammatory genes allows production of a therapeutic gene product that is controlled by the severity of the disease. The effectiveness of this promoter construct for combating inflammation makes it a suitable candidate for the development of a new local gene therapy strategy for the treatment of osteoarthritis, in which IL‐1β and TNFα trigger a signal cascade that elevates COX‐2 levels.
Autoinflammatory genes and susceptibility to psoriatic juvenile idiopathic arthritis
Authors: Day T. G. , Ramanan A. V. , Hinks A. , Lamb R. , Packham J. , Wise C. , Punaro M. , Donn R. P. 
Published: June 2008

AbstractObjectiveTo investigate the association of NLRP3, NOD2, MEFV, and PSTPIP1, genes that cause 4 of the autoinflammatory hereditary periodic fever syndromes (HPFS), with juvenile idiopathic arthritis (JIA).MethodsFifty‐one single‐nucleotide polymorphisms (SNPs) across the 4 loci were investigated using MassArray genotyping in 950 Caucasian patients with JIA living in the UK and 728 ethnically matched healthy controls.ResultsPrior to Bonferroni correction for multiple testing, significant genotype associations between 6 SNPs in MEFV and JIA were observed and, in subgroup analysis, associations between 12 SNPs across all 4 loci and the subgroup of patients with psoriatic JIA were found. After Bonferroni correction for multiple testing, 2 genotype associations remained significant in the subgroup of patients with psoriatic JIA (MEFV SNP rs224204 [corrected P = 0.025] and NLRP3 SNP rs3806265 [corrected P = 0.04]).ConclusionThese findings support the use of monogenic loci as candidates for investigating the genetic component of complex disease and provide preliminary evidence of association between SNPs in autoinflammatory genes and psoriatic JIA. Our findings raise the interesting possibility of a shared disease mechanism between the HPFS and psoriatic JIA, potentially involving abnormal production of interleukin‐1β.
Functional outcome after stroke in patients with rheumatoid arthritis and systemic lupus erythematosus
Authors: Nguyen‐Oghalai Tracy U. , Wu Helen , McNearney Terry A. , Granger Carl V. , Ottenbacher Kenneth J. 
Published: June 2008

AbstractObjectiveTo compare outcomes following stroke rehabilitation among patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) versus patients with neither RA nor SLE (non‐RA/SLE).MethodsWe conducted a retrospective analysis using a national database of patients with stroke admitted to inpatient rehabilitation between 1994 and 2001. Primary outcomes were discharge disposition and functional status, rated by the Functional Independence Measure (FIM) Instrument, at discharge and at followup. The independent variable was RA or SLE. Covariates were age, sex, race/ethnicity, admission FIM ratings, additional comorbidities (none, 1–3, and >3), type of stroke, and length of stay.ResultsWe studied 47,853 patients with stroke, 368 with RA, and 119 with SLE. Discharge dispositions were similar for patients with RA and non‐RA/SLE (81% discharged home). At discharge, the average FIM rating for patients with RA was 85.8, compared with 87.8 for non‐RA/SLE patients. At followup, the average FIM rating for patients with RA was 95.9, compared with 99.6 for non‐RA/SLE patients. RA was associated with lower FIM ratings at discharge and followup in multivariate analyses. SLE was associated with younger age (17.5 years). However, patients with SLE had similar discharge dispositions and FIM ratings to non‐RA/SLE patients.ConclusionRA was associated with lower functional status ratings at discharge and followup. Outpatient therapy for patients with RA may reduce long‐term assistance. Patients with SLE were younger, but had similar functional outcomes to patients without RA/SLE, suggesting early morbidity from stroke among patients with SLE.
The internet‐based arthritis self‐management program: A one‐year randomized trial for patients with arthritis or fibromyalgia
Authors: Lorig Kate R. , Ritter Philip L. , Laurent Diana D. , Plant Kathryn 
Published: June 2008

AbstractObjectiveTo determine the efficacy of an Internet‐based Arthritis Self‐Management Program (ASMP) as a resource for arthritis patients unable or unwilling to attend small‐group ASMPs, which have proven effective in changing health‐related behaviors and improving health status measures.MethodsRandomized intervention participants were compared with usual care controls at 6 months and 1 year using repeated‐measures analyses of variance. Patients with rheumatoid arthritis, osteoarthritis, or fibromyalgia and Internet and e‐mail access (n = 855) were randomized to an intervention (n = 433) or usual care control (n = 422) group. Measures included 6 health status variables (pain, fatigue, activity limitation, health distress, disability, and self‐reported global health), 4 health behaviors (aerobic exercise, stretching and strengthening exercise, practice of stress management, and communication with physicians), 5 utilization variables (physician visits, emergency room visits, chiropractic visits, physical therapist visits, and nights in hospital), and self‐efficacy.ResultsAt 1 year, the intervention group significantly improved in 4 of 6 health status measures and self‐efficacy. No significant differences in health behaviors or health care utilization were found.ConclusionThe Internet‐based ASMP proved effective in improving health status measures at 1 year and is a viable alternative to the small‐group ASMP.
Varus malalignment and its association with impairments and functional limitations in medial knee osteoarthritis
Authors: Lim Boon‐Whatt , Hinman Rana S. , Wrigley Tim V. , Bennell Kim L. 
Published: June 2008

AbstractObjectiveTo examine the association of varus malalignment with impairments and functional limitations in people with medial knee osteoarthritis (OA).MethodsAnatomic radiographic knee alignment was assessed in 107 community volunteers with medial tibiofemoral knee OA. Impairments assessed included pain (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), quadriceps and hamstring isometric strength, and knee varus‐valgus laxity. WOMAC, walking speed, step test, and stair climb test were used to assess functional limitations. Participants were categorized into tertiles according to knee alignment (least, moderate, and most varus). Impairments and functional limitations between groups were compared using analyses of variance with and without adjustment for age, sex, and disease severity. Regression analyses were also performed in the entire cohort to further determine the relationship of varus malalignment to impairments and functional limitations.ResultsThe most varus group (mean varus 7.7 degrees) did not demonstrate greater impairments or worse functional limitations compared with the moderate varus (4.2 degrees) and least varus (5.0 degrees) groups. In fact, the most varus participants performed significantly better on the step test compared with moderate (P = 0.006) and least varus (P = 0.004) participants. Knee alignment accounted for a significant but small proportion of the variance in step test performance (7%) and quadriceps strength (4%), but did not contribute significantly to the variance in any other parameter measured.ConclusionGreater varus malalignment was associated with increased quadriceps strength and improved step test performance, but did not influence the severity of other measured impairments and functional limitations.
Synthetic Molecular Machine Based on Reversible End‐to‐Interior and End‐to‐End Loop Formation Triggered by Electrochemical Stimuli
Authors: Lee Jae Wook , Hwang Ilha , Jeon Woo Sung , Ko Young Ho , Sakamoto Shigeru , Yamaguchi Kentaro , Kim Kimoon 
Published: June 2008

AbstractWe have designed and synthesized a novel [2]pseudorotaxane‐based molecular machine in which the interconversion between end‐to‐interior and end‐to‐end loop structures is reversibly controlled by electrochemical stimuli. Cucurbit[8]uril (CB[8]) and the thread molecule 34+ with an electron‐rich hydroxynaphthalene unit and two electron‐deficient viologen units form the 1:1 complex 44+ with an end‐to‐interior loop structure, which is reversibly converted into an end‐to‐end structure upon reduction. Large changes in shape and size of the molecule accompany the reversible redox process. The key feature of the machine‐like behavior is the reversible interconversion between an intramolecular charge‐transfer complex and viologen cation radical dimer inside CB[8] triggered by electrochemical stimuli.
Aerobic Oxidation of Alcohols with Bifunctional Transition‐Metal Catalysts Bearing C–N Chelate Ligands
Authors: Arita Sachiko , Koike Takashi , Kayaki Yoshihito , Ikariya Takao 
Published: June 2008

AbstractThe aerobic oxidation of alcohols with a family of bifunctional Ir, Rh, and Ru complexes bearing C–N chelating ligands derived from primary benzylic amines was investigated. The isolable amido–Ir complexes [Cp*Ir{κ2(N,C)‐(NHCR2‐2‐C6H4)}] (R=C6H5, CH3; Cp*=1,2,3,4,5‐pentamethylcyclopentadienyl) effected the oxidation of secondary alcohols smoothly under atmospheric pressure of air at 30 °C in THF to give the corresponding ketones in good yields. The hydrido(amine)–Ir complexes [Cp*IrH{κ2(N,C)‐(NH2CR2‐2‐C6H4)}] and the combined catalyst system involving the chloro(amine)–Ir complex [Cp*IrCl{κ2(N,C)‐(NH2CR2‐2‐C6H4)}] and KOC(CH3)3 were also found to be effective catalysts, whereas the tertiary amine complex [Cp*IrCl{κ2(N,C)‐(N(CH3)2CH2‐2‐C6H4)}], which does not have a metal/NH moiety, did not show catalytic activity. The employment of primary alcohols in the aerobic reaction with the Cp*IrCl complex and KOC(CH3)3 resulted in the formation of esters through oxidative dimerization.
Impact of preoperative thyroid ultrasonography on the surgical management of primary hyperparathyroidism
Authors: Monroe D P , Edeiken-Monroe B S , Lee J E , Evans D B , Perrier N D 
Published: June 2008

Abstract

Background
Primary hyperparathyroidism (PHPT) with coexisting thyroid disease has been considered a contraindication to minimally invasive parathyroidectomy (MIP). This study assessed the impact of thyroid ultrasonography and guided fine-needle aspiration (FNA) biopsy with cytological review of the aspiration in distinguishing patients eligible for MIP from those requiring open parathyroidectomy with thyroid surgery.

Methods
The records of 194 consecutive patients who had minimally invasive or open parathyroidectomy for sporadic PHPT were reviewed retrospectively. Thyroid ultrasonographic findings and FNA results were compared with surgical and pathology records.

Results
A total of 163 patients (84·0 per cent) were eligible for MIP based on ultrasonographic findings with or without FNA results. Ultrasonography detected concurrent thyroid disease in 163 patients (84·0 per cent). Thirty-nine (23·9 per cent) underwent FNA, of whom 16 had benign findings and were eligible for MIP; the remaining 23 had suspicious FNA results and had open parathyroidectomy combined with thyroid surgery. Postoperative thyroid histopathology confirmed malignancy in nine patients, eight of whom had disease detected ultrasonographically. Micronodular thyroid disease (less than 1 cm) accounted for four of nine malignancies.

Conclusion
Most patients with PHPT are eligible for MIP. Experienced ultrasonographers can diagnose coexisting micronodular and macronodular thyroid disease, and identify patients eligible for MIP.
Clinical and cost effectiveness of sacral nerve stimulation for faecal incontinence
Authors: Muñoz-Duyos A , Navarro-Luna A , Brosa M , Pando J A , Sitges-Serra A , Marco-Molina C 
Published: June 2008

Abstract

Background
Sacral nerve stimulation (SNS) has better results and safety than other surgical procedures for faecal incontinence. This prospective study assessed the clinical effectiveness and costs of SNS at a single centre.

Methods
Patients who had experienced one or more episodes of faecal incontinence were studied for up to 5 years by continence diary, anorectal manometry and quality of life questionnaires. Direct medical costs were calculated and the cost-effectiveness of the treatment was analysed.

Results
Fifty-seven percutaneous nerve evaluations were performed in 47 patients between June 1999 and February 2006; 29 patients underwent permanent implantation. After a median follow-up of 34·7 (range 2·3–81·2) months, 25 of the 29 patients had a significant reduction in incontinence episodes; 14 patients were in complete remission. At 3-year follow-up, the mean reduction in incontinence episodes was 89 per cent. No change was observed in anal manometric values. Patients reported a significant improvement in quality of life. The introduction of SNS has an incremental cost-effectiveness ratio, below the accepted Spanish threshold.

Conclusion
The introduction of SNS to the management of faecal incontinence within the Spanish setting is both effective and efficient.