bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis
Authors: Bang Holger , Egerer Karl , Gauliard Anke , Lüthke Kirsten , Rudolph Paul E. , Fredenhagen Gert , Berg Wigbert , Feist Eugen , Burmester Gerd‐R. 
Published: July 2007

AbstractObjectiveModification of antigens represents a trigger for the generation of autoantibodies. In the pathogenesis of rheumatoid arthritis (RA), citrullination of proteins has been shown to be a critical process, and the determination of antibodies against citrullinated antigens has been a diagnostic milestone. We undertook this study to determine whether antibodies to mutated and citrullinated vimentin (MCV) could serve as a diagnostic and prognostic marker for RA.MethodsWe identified novel isoforms of human MCV in the synovial fluid of RA patients. The significance of these disease‐related modifications was investigated by the analysis of autoantibody reactivities. In a group of 1,151 RA patients, the diagnostic significance and the prognostic value of an anti‐MCV enzyme‐linked immunosorbent assay (ELISA) were compared with that of an anti–cyclic citrullinated peptide (anti‐CCP) ELISA.ResultsIn RA, sensitivities of 82% and 72% were calculated for the anti‐MCV and anti‐CCP assays, respectively. The specificity of both assays was comparable (98% and 96%, respectively). In followup analyses of 16 RA patients with moderate disease activity (mean Disease Activity Score in 28 joints [DAS28] of 2.72) and 26 RA patients with active disease (mean DAS28 of 5.07), disease stratification of RA was possible using the anti‐MCV assay (P = 0.0084). A significant correlation of anti‐MCV antibodies with the DAS28 was documented (r = 0.5334, P = 0.0003), in 42 RA patients (n = 427 antibody determinations at different time points).ConclusionAntigenic properties of vimentin were determined by mutation and citrullination. Anti‐MCV antibodies are a novel diagnostic marker for RA. Furthermore, they may allow monitoring and—if confirmed in even larger series of patients—stratification of disease.
Identification of previously unrecognized predisposing factors for ankylosing spondylitis from analysis of HLA–B27 extended haplotypes in sardinia
Authors: Cascino Isabella , Paladini Fabiana , Belfiore Francesca , Cauli Alberto , Angelini Claudia , Fiorillo Maria Teresa , Mathieu Alessandro , Sorrentino Rosa 
Published: July 2007

AbstractObjectiveTo define the contribution of HLA genes other than HLA–B27 in conferring susceptibility to ankylosing spondylitis (AS), through analysis of HLA–B27 haplotypes in Sardinian subjects.MethodsNinety‐eight patients with AS, 133 HLA–B27–positive controls (of whom 33 were positive for HLA–B*2709), and 190 randomly selected controls were genotyped for microsatellites and single‐nucleotide polymorphisms (SNPs) spanning the HLA region.ResultsHaplotypes carrying either the B*2705 or the B*2709 allele were found to share a conserved region downstream of the HLA–B gene and a functional polymorphism in the HLA–E gene (R128G), while differing in all other markers. Notably, the presence of an A at SNP rs1264457, encoding for Arg‐128, was significantly increased in the cohort of patients (P= 6 × 10−6, correctedP= 3 × 10−5) but not in B*2705‐ or B*2709‐positive controls. Comparing the alleles co‐occurring at each HLA marker, we identified a region differentiating patients with AS and B*2705‐matched controls. In particular, there was a markedly increased prevalence of heterozygosity at rs1264457 among B27‐positive controls (74%, versus 47% in patients and 54% in random controls), suggesting a protective role of G128 in AS. Moreover, other markers around the HLA–B gene were also differentially represented.ConclusionThese results demonstrate a significant difference in the frequency of some HLA markers between AS patients and B*2705‐positive controls, which could be attributed to the opposite chromosome. In particular, the differential distribution of a functional polymorphism in the HLA–E gene suggests a possible role of natural killer function in AS pathogenesis.
In vivo inhibition of angiogenesis by interleukin‐13 gene therapy in a rat model of rheumatoid arthritis
Authors: Haas Christian S. , Amin M. Asif , Ruth Jeffrey H. , Allen Brittany L. , Ahmed Salahuddin , Pakozdi Angela , Woods James M. , Shahrara Shiva , Koch Alisa E. 
Published: July 2007

AbstractObjectiveInterleukin‐13 (IL‐13) is a pleiotropic cytokine that can affect vessel formation, an important component of the rheumatoid arthritis (RA) synovial tissue pannus. The purpose of this study was to use a gene therapy approach to investigate the role of IL‐13 in angiogenesis in vivo, using a rat adjuvant‐induced arthritis model of RA.MethodsAnkle joints of female rats were injected preventatively with an adenovirus vector containing human IL‐13 (AxCAIL‐13), a control vector with no insert (AxCANI), or phosphate buffered saline (PBS). Joints were harvested at the peak of arthritis, and histologic and biochemical features were evaluated.ResultsAxCAIL‐13–treated joint homogenates had lower hemoglobin levels, suggesting reduced joint vascularity, and both endothelial cell migration and tube formation were significantly inhibited (P < 0.05). Similarly, AxCAIL‐13 inhibited capillary sprouting in the rat aortic ring assay and vessel growth in the Matrigel plug in vivo assay. IL‐13 gene delivery resulted in up‐regulation and association of phosphorylated ERK‐1/2 and protein kinase Cα/βII, suggesting a novel pathway in IL‐13–mediated angiostasis. The angiostatic effect of AxCAIL‐13 was associated with down‐regulation of proangiogenic cytokines (IL‐18, cytokine‐induced neutrophil chemoattractant 1/CXCL1, lipopolysaccharide‐induced CXC chemokine/CXCL5) and up‐regulation of the angiogenesis inhibitor endostatin. The expression and activity of matrix metalloproteinases 2 and 9, which participate in angiogenesis, was impaired in response to IL‐13 as compared with AxCANI and PBS treatment.ConclusionOur findings support a role for IL‐13 as an in vivo antiangiogenic factor and provide a rationale for its use in RA to control pathologic neovascularization.
Modified aquaporin 5 expression and distribution in submandibular glands from NOD mice displaying autoimmune exocrinopathy
Authors: Soyfoo Muhammad S. , De Vriese Carine , Debaix Huguette , Martin‐Martinez Maria D. , Mathieu Chantal , Devuyst Olivier , Steinfeld Serge D. , Delporte Christine 
Published: July 2007

AbstractObjectiveTo investigate the expression and localization of aquaporin 5 (AQP5) in salivary glands and salivary gland function in the NOD mouse.MethodsAll experiments were performed using NOD and BALB/c mice (ages 8 weeks and 24 weeks). Real‐time reverse transcription–polymerase chain reaction, Western blotting, and immunohistochemical analysis were used to study the expression and distribution of AQP5 in salivary glands. In addition, salivary gland function was determined.ResultsCompared with the levels in BALB/c mice, relative AQP5 messenger RNA levels were not significantly modified in the parotid glands from NOD mice of both ages but were significantly increased in the submandibular glands from NOD mice of both ages. Western blot analyses of both salivary gland membranes revealed that the level of AQP5 protein was increased in 24‐week‐old NOD mice. Important inflammatory infiltrates were observed in the submandibular glands, but not in the parotid glands, from 24‐week‐old NOD mice. The 8‐week‐old and 24‐week‐old BALB/c mice and the 8‐week‐old NOD mice showed AQP5 primarily at the apical membrane of the salivary gland acinus. In contrast, in acini from the submandibular glands (but not the parotid glands) from 24‐week‐old NOD mice, AQP5 staining was reduced at the apical membrane but was increased at the basal membrane. A moderately statistically significant decrease in pilocarpine‐stimulated salivary flow was observed in 24‐week‐old NOD mice compared with that in age‐matched BALB/c mice.ConclusionSubmandibular glands from 24‐week‐old NOD mice displayed inflammatory infiltrates, increased AQP5 protein expression, and impaired AQP5 distribution. However, the moderately statistically significant decrease in the salivary flow rate in these mice did not match the extent of AQP5 misdistribution.
Low salivary dehydroepiandrosterone and androgen‐regulated cysteine‐rich secretory protein 3 levels in Sjögren's syndrome
Authors: Laine Mikael , Porola Pauliina , Udby Lene , Kjeldsen Lars , Cowland Jack B. , Borregaard Niels , Hietanen Jarkko , Ståhle Mona , Pihakari Antti , Konttinen Yrjö T. 
Published: July 2007

AbstractObjectiveSjögren's syndrome (SS), an autoimmune disease of exocrine glands, typically starts at the time of adrenopause. We undertook this study to test the hypothesis that SS is characterized by an insufficient androgen effect at the target tissue level.MethodsWe searched for androgen response elements (AREs) in the cysteine‐rich secretory protein 3 (crisp‐3) gene. Dehydroepiandrosterone (DHEA) responsiveness was experimentally studied using quantitative reverse transcriptase–polymerase chain reaction and immunofluorescence staining of human submandibular gland–derived acinar cells and labial salivary gland explants with or without DHEA. Finally, glandular and salivary CRISP‐3 in healthy controls and SS patients was analyzed using immunohistochemistry, in situ hybridization, and enzyme‐linked immunosorbent assay. Serum DHEA sulfate (DHEAS) and salivary DHEA levels were measured using a radioimmunometric method.ResultsLiterature analysis and a search for AREs in gene banks suggested androgen dependency of human CRISP‐3, and this was verified by studies of human submandibular gland acinar cells cultured with or without DHEA, in which DHEA increased CRISP‐3 messenger RNA (mRNA) levels (P = 0.018). This finding was confirmed by the results of DHEA stimulation of labial salivary gland explants. Glandular CRISP‐3 mRNA and protein labeling was weak and diffuse, coupled with low secretion in saliva (mean ± SEM 21.1 ± 2.7 μg CRISP‐3/15 minutes in SS patients versus 97.6 ± 12.0 μg CRISP‐3/15 minutes in healthy controls; P < 0.0001). Compared with healthy controls, SS patients had low serum levels of DHEAS (P = 0.008) and also low salivary levels of DHEA (mean ± SEM 224 ± 33 pmoles versus 419 ± 98 pmoles; P = 0.005).ConclusionCRISP‐3 pathology was seen in acini remote from lymphocyte foci and is apparently not secondary to local inflammation, but may represent some systemic effect in SS. Indeed, androgen deprivation in the salivary glands of SS patients is evidenced both by low salivary levels of DHEA and by low levels of DHEA‐regulated CRISP‐3. This may explain some of the characteristic features of SS.
Development and validation of a disease‐specific health‐related quality of life measure, the LupusQol, for adults with systemic lupus erythematosus
Authors: McElhone Kathleen , Abbott Janice , Shelmerdine Joanna , Bruce Ian N. , Ahmad Yasmeen , Gordon Caroline , Peers Kate , Isenberg David , Ferenkeh‐Koroma Ada , Griffiths Bridget , Akil Mohamed , Maddison Peter , Teh Lee‐suan 
Published: July 2007

AbstractObjectiveTo develop and validate a disease‐specific health‐related quality of life (HRQOL) instrument for adults with systemic lupus erythematosus (SLE).MethodsThe work consisted of 6 stages. Stage 1 included item generation for questionnaire content from semistructured interviews with SLE patients. In stage 2 item selection for the draft questionnaire was performed by thematic analysis of the patient interview transcripts and expert panel agreement. In stage 3 the content validity of the draft questionnaire was assessed by patients completing the questionnaire and providing critical feedback. In stages 4 and 5 construct validity and internal reliability of the 3 versions of the LupusQoL were evaluated using principal component analysis with varimax rotation and Cronbach's alpha coefficients, respectively. In stage 6 discriminatory validity, concurrent validity, and test–retest reliability were evaluated.ResultsStages 1, 2, and 3 resulted in a preliminary instrument containing 63 items. In stage 4, 8 domains were identified. This factor structure, accounting for 82% of the variance, was confirmed in stage 5. The domains and Cronbach's alpha coefficients were physical health (0.94), emotional health (0.94), body image (0.89), pain (0.92), planning (0.93), fatigue (0.88), intimate relationships (0.96), and burden to others (0.94). Discriminant validity was demonstrated for different levels of disease activity (British Isles Lupus Assessment Group Index) and damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index). High correlations (r = 0.71–0.79) between comparable domains of the Short Form 36 and the LupusQoL assured acceptable concurrent validity. Good test–retest reliability (r = 0.72–0.93) was demonstrated.ConclusionThe LupusQoL is a validated SLE‐specific HRQOL instrument with 34 items across 8 domains defined by patients as being important.
Delay in access to appropriate care for children presenting with musculoskeletal symptoms and ultimately diagnosed with juvenile idiopathic arthritis
Authors: Foster H. E. , Eltringham M. S. , Kay L. J. , Friswell M. , Abinun M. , Myers A. 
Published: July 2007

AbstractObjectiveTo document pathways of care, management, and interval from onset of symptoms to first pediatric rheumatology multidisciplinary team (PRhMDT) assessment for children with incident juvenile idiopathic arthritis (JIA).MethodsWe conducted a retrospective observational study of children with incident JIA over a 3‐year period.ResultsThe study included 152 patients with JIA (87 females). The median interval from symptom onset to first PRhMDT assessment was 20 weeks (range 0–416), with significant variation between JIA subtypes (P = 0.0097); children with extended oligoarticular JIA had the longest interval (median 60 weeks, range 12–320). Prior to pediatric rheumatology assessment, many children had referrals to multiple secondary care specialties and had been subjected to multiple and often invasive procedures including arthroscopy/synovial biopsy (18 [11.8%] of 152), but none were referred for ophthalmologic screening, physical therapy, or nursing input and a diagnosis of JIA was rarely made (98%). At first PRhMDT assessment, most patients had untreated active disease with active joint count ≥1 (135 [89%] of 152), restricted joint count ≥1 (135 [89%] of 152), and functional disability by Child Health Assessment Questionnaire score >0 (53 [68%] of 118); 1 child had undetected uveitis. Following PRhMDT assessment, interventions were invariably indicated, including joint injections (69 [45%] of 152), methotrexate (49 [32%] of 152), and physical therapy programs (all patients).ConclusionDelay in access to pediatric rheumatology assessment is common with complex pathways of referral. Many children were subjected to inappropriate invasive investigations and many had prolonged untreated active disease at the initial PRhMDT assessment. This delay is likely to affect long‐term outcome and warrants further exploration.
Comparison of the EuroQol and short form 6D in Singapore multiethnic asian knee osteoarthritis patients scheduled for total knee replacement
Authors: Xie Feng , Li Shu‐chuen , Luo Nan , Lo Ngai‐nung , Yeo Seng‐jin , Yang Kuang‐ying , Fong Kok‐yong , Thumboo Julian 
Published: July 2007

AbstractObjectiveTo compare the EuroQol (EQ‐5D) and Short Form 6D (SF‐6D) among multiethnic Asian patients with knee osteoarthritis (OA) scheduled for total knee replacement in Singapore.MethodsPatients were asked to complete questionnaires including the EQ‐5D, Short Form 36, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne knee index. EQ‐5D and SF‐6D utility scores were calculated using the scoring algorithms developed from the UK general population. Agreement between the 2 instruments was assessed by comparing their score distributions, means, medians, intraclass correlation coefficients (ICCs), and a Bland‐Altman plot. Correlations of the EQ‐5D and SF‐6D with WOMAC and Lequesne knee index scores were also examined.ResultsA consecutive sample of 258 knee OA patients (127 English‐speaking and 131 Chinese‐speaking) participated. The mean ± SD EQ‐5D utility score was 0.49 ± 0.31 (range −0.25–1.00) and the mean SF‐6D utility score was 0.63 ± 0.12 (range 0.32–0.89). In a hypothetical example, this 0.14‐point difference in mean utility scores yielded a difference of $10,000/quality‐adjusted life year (QALY) in cost‐effectiveness ratios. The score distribution was bimodal for the EQ‐5D and normal for the SF‐6D. This poor agreement was also demonstrated by the Bland‐Altman plot and the low ICC (range 0.18–0.54). Correlations of the WOMAC and Lequesne index with the EQ‐5D were higher than with the SF‐6D.ConclusionUsing different preference‐based health‐related quality of life instruments may yield different utility scores, which could have a great impact on QALY estimates. This highlights the importance of selecting appropriate instruments for economic evaluation. Additional research is needed to determine which instrument (the EQ‐5D or the SF‐6D) should be used in OA patients.
High prevalence of subclinical atherosclerosis in psoriatic arthritis patients without clinically evident cardiovascular disease or classic atherosclerosis risk factors
Authors: Gonzalez‐juanatey Carlos , Llorca Javier , Amigo‐Diaz Encarnacion , Dierssen Trinidad , Martin Javier , Gonzalez‐Gay Miguel A. 
Published: July 2007

AbstractObjectiveTo assess the presence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA) without clinically evident atherosclerosis or its complications, and to assess whether demographic or clinical factors affect the development of atherosclerotic disease in a series of patients with PsA attended to in a community hospital.MethodsFifty‐nine patients with PsA who fulfilled the Moll and Wright criteria were recruited from Hospital Xeral‐Calde (Lugo, Spain). Patients seen during the period of recruitment who had classic cardiovascular risk factors or had experienced cardiovascular or cerebrovascular events were excluded. Fifty‐nine healthy matched controls were also studied. Carotid artery intima‐media thickness (IMT) and carotid plaques were measured in the right common carotid artery. The study was performed using high‐resolution B‐mode ultrasound.ResultsPatients with PsA exhibited greater carotid artery IMT than did matched controls (mean ± SD 0.699 ± 0.165 mm versus 0.643 ± 0.111 mm; P = 0.031; difference of means 0.056; 95% confidence interval 0.005–0.108). Adjusted for age, the carotid IMT was correlated with age at the time of PsA diagnosis (partial correlation coefficient [r] = −0.264, P = 0.04), disease duration (r = 0.264, P = 0.04), total cholesterol (r = 0.233, P = 0.01), and low‐density lipoprotein cholesterol (r = 0.243, P = 0.01).ConclusionThe present study demonstrates that patients with PsA without cardiovascular risk factors or clinically evident cardiovascular disease have a high prevalence of macrovascular disease in the form of increased carotid artery IMT compared with ethnically matched controls.
Using the health assessment questionnaire to estimate preference‐based single indices in patients with rheumatoid arthritis
Authors: Bansback Nick , Marra Carlo , Tsuchiya Aki , Anis Aslam , Guh Daphne , Hammond Tony , Brazier John 
Published: July 2007

AbstractObjectiveTo estimate the relationship between preference‐based measures, EuroQol (EQ‐5D) and SF‐6D, and the Health Assessment Questionnaire (HAQ) disability index (DI) in patients with rheumatoid arthritis (RA), and to characterize components that are predictors of health utility.MethodsPatients with RA participating in 2 studies in the UK (n = 151) and Canada (n = 319) completed the HAQ, EQ‐5D, and Short Form 36 (SF‐36). The SF‐36, a generic measure of quality of life, was converted into the preference‐based SF‐6D. From these results we developed models of the relationship between the HAQ and SF‐6D and EQ‐5D using various regression analyses.ResultsThe optimal model developed for the EQ‐5D entered levels for each item as independent variables (model 5). A root mean square error (RMSE) of 0.18 suggested relatively good predictive ability. For the SF‐6D, RMSEs were lower (0.09), suggesting better predictions than for the EQ‐5D, but models with more explanatory variables did not improve results (model 2 or 4 optimal). The models were able to predict actual SF‐6D and EQ‐5D across the range of the HAQ DI.ConclusionOur approach enabled calculations of quality‐adjusted life years from existing trials where only the HAQ was measured. All aspects of the HAQ may not be reflected in the preference‐based measures, and this method is suboptimal to direct measurement of health state utility in clinical trials. Given this limitation, our approach provides an alternative for researchers who need health‐state utility values, but had not included a preference‐based measure in their clinical study because of resource constraints or a desire to limit patient burden.
Validity and reliability of the Siconolfi Step Test for assessment of physical fitness in patients with systemic lupus erythematosus
Authors: Marcora Samuele M. , Casanova Francesco , Fortes Matthew B. , Maddison Peter J. 
Published: July 2007

AbstractObjectivePatients with systemic lupus erythematosus (SLE) have poor physical fitness as measured by maximal oxygen uptake (VO2max), which is associated with disability and fatigue. The purpose of this study was to validate, in this population, the Siconolfi Step Test (SST) developed to predict VO2max in healthy individuals.MethodsThirty patients with well‐controlled SLE were tested on a cycle ergometer until volitional exhaustion, and 25 women and 4 men (mean ± SD age 48 ± 14 years, weight 71.5 ± 13.7 kg) fulfilled the criteria for maximal effort. VO2max measured during this incremental test was compared with VO2max predicted by the SST using Bland and Altman 95% limits of agreement (LOA) and intraclass correlation coefficient (ICC). The SST was repeated twice to assess its reliability.ResultsThe ICC between predicted and measured VO2max (mean ± SD 1.67 ± 0.41 liters/minute versus 1.57 ± 0.39 liters/minute) was moderately high (0.73, P < 0.001). Bland and Altman analysis revealed a trend for a positive bias (P = 0.083) and 95% LOA of ±0.58 liters/minute. There was a very high ICC (0.97, P < 0.001) between VO2max predicted by the first and second SST (mean ± SD 1.66 ± 0.40 liters/minute versus 1.67 ± 0.41 liters/minute), and no significant bias (P = 0.500). The 95% LOA were ±0.20 liters/minute.ConclusionThe results demonstrate that the SST is well tolerated, reasonably valid, and highly reliable in patients with well‐controlled SLE. Therefore, this simple, submaximal exercise test might be useful for assessing physical fitness in clinical practice and epidemiologic studies.