bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allelic markers close to prolactin are associated with HLA‐DRB1 susceptibility alleles among women with rheumatoid arthritis and systemic lupus erythematosus
Authors: Brennan Paul , Hajeer Ali , Ong Kai Ren , Worthington Jane , John Sally , Thomson Wendy , Silman Alan , Ollier Bill 
Published: February 2007

AbstractObjective. To investigate linkage disequilibrium between HLA‐DRB1 disease susceptibility alleles and microsatellite markers close to the prolactin gene, among women with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and normal controls.Methods. DNA from 89 women with RA, 76 women with SLE, and 94 controls was typed for HLA‐DRB1 status and D6S422 and D6S285, 2 highly polymorphic microsatellite markers close to the prolactin gene. RA patients were stratified by DRB1*0401 status, and SLE patients were stratified by *0301 status.Results. There was an excess frequency of D6S422*1 among SLE patients with DRB1*0301 (odds ratio [OR] 3.1). The frequency of this allele was also slightly in excess among RA patients with DRB1*0401 (OR 1.9). D6S285*5 was also in excess among female RA patients with DRB1*0401 (OR 3.5), and was slightly increased among female SLE patients with DRB1*0301. None of these alleles were found to be increased among *0401‐positive or *0301‐positive controls.Conclusion. These data indicate that there may be linkage disequilibrium between HLA‐DRB1 alleles and microsatellite marker alleles close to the prolactin gene among women with RA and SLE. This suggests the possibility of extended haplotypes encoding for HLA‐DRB1 susceptibility and high prolactin production, which contribute to susceptibility to both RA and SLE.
Matrix metalloproteinase 13 (collagenase 3) in human rheumatoid synovium
Authors: Lindy Otso , Konttinen Yrjö T. , Sorsa Timo , Ding Yanli , Santavirta Seppo , Ceponis Arnoldas , López‐otín Carlos 
Published: February 2007

AbstractObjective. To show the eventual presence and extent of production of matrix metalloproteinase 13 (MMP‐13, or collagenase 3) in rheumatoid synovial tissue samples and extracts, and to assess the inhibition characteristics of recombinant MMP‐13.Methods. Immunohistochemical avidin‐biotin‐peroxidase complex staining/morphometry was used to analyze MMP‐13‐positive cells in situ. Neutral salt extraction of synovial tissue, electrophoresis of the extract in different buffer systems, and Western blotting were also used. The inhibitory properties of doxycycline, clodronate, pamidronate, and D‐penicillamine for recombinant enzyme were determined with a soluble type II collagen assay.Results. MMP‐13 was detected in fibroblast‐ and macrophage‐like mononuclear cells in the synovial lining and stroma and in vascular endothelial cells. The overall expression of MMP‐13 in these cells in the synovial stroma was high in rheumatoid arthritis (86 ± 12%) compared with osteoarthritis (17 ± 5%) patient samples (P = 0.0027). In a high‐pH native electrophoresis gel, immunoreactivity to anti‐MMP‐1 and anti‐MMP‐13 were clearly separated, with anti‐MMP‐13‐immunoreactive material migrating faster than anti‐MMP‐1‐immuno‐reactive material. Finally, in contrast to MMP‐1 and MMP‐8, MMP‐13 was found to be relatively resistant to the inhibitory effects of doxycycline and clodronate in vitro.Conclusion. Due to its localization in synovial tissue, its substrate profile, increased expression, and relative resistance to known MMP inhibitors, MMP‐13 is suggested to play a major role in the pathogenesis of tissue destruction in rheumatoid arthritis.
The B cell repertoire of patients with rheumatoid arthritis. II. Increased frequencies of IgG+ and IgA+ B cells specific for mycobacterial heat‐shock protein 60 or human type II collagen in synovial fluid and tissue
Authors: Rudolphi Ulrike , Rzepka Rita , Batsford Stephen , Kaufmann Stefan H. E. , von der Mark Klaus , Peter Hans H. , Melchers Inga 
Published: February 2007

AbstractObjective. A qualitative and quantitative analysis of the functional, antigen‐specific B cell receptor repertoire of patients with rheumatoid arthritis (RA) in synovial and peripheral compartments.Methods. B cells were activated to grow and differentiate at high efficiency in vitro under limiting‐dilution conditions. Isotype and specificity of the secreted Ig were tested by enzyme‐linked immunosorbent assay.Results. In contrast to peripheral B cells, most synovial B cells had already switched to IgG/IgA in vivo. The frequencies of B cells specifically recognizing foreign antigens were decreased within the synovial population, whereas the frequencies of B cells specific for type II collagen, mycobacterial heat‐shock protein 60 (hsp60), or IgG Fc fragments were significantly increased, revealing a negative correlation in terms of frequencies.Conclusion. B cells specific for human type II collagen, hsp60, and IgG Fc fragments are produced and/or expanded locally within the affected joints of RA patients. Thus, the specific immune system is definitely involved in the local inflammatory and destructive processes.
Development of in vitro model systems for destructive joint diseases. Novel strategies for establishing inflammatory pannus
Authors: Schultz Olaf , Keyszer Gernot , Zacher Josef , Sittinger Michael , Burmester Gerd R. 
Published: February 2007

AbstractObjective. To establish a novel 3‐dimensional (3‐D) in vitro model for the investigation of destructive processes in rheumatoid arthritis (RA).Methods. Two distinct culture systems were developed, consisting of RA synovial membrane and articular cartilage explants or interactive RA synovial cell/chondrocyte cultures embedded in 3‐D fibrin matrices. The expression of proteolytic enzymes, chondrocyte matrix architecture, and matrix degradation parameters was analyzed by immunohistochemistry.Results. Of 28 RA explant cultures, 16 displayed an invasion of synovial tissue into the cartilage explants, compared with 1 of 8 osteoarthritis explants. The expression of collagenase and vascular cell adhesion molecule 1 could be demonstrated at the cartilage‐pannus junction. Of 20 interactive cell cultures, 18 revealed invasive behavior and remained vital for extended periods of time.Conclusion. The models presented allow us to study distinct aspects of destructive joint diseases under in vitro conditions that resemble human pathology. Moreover, our model is able to supplement animal experiments in basic research and drug testing.
Dysregulation of interleukin‐10 production in relatives of patients with systemic lupus erythematosus
Authors: Llorente Luis , Richaud‐Patin Yvonne , Couderc Jacques , Alarcon‐Segovia Donato , Ruiz‐Soto Rodrigo , Alcocer‐Castillejos Natasha , Alcocer‐Varela Jorge , Granados Julio , Bahena Susana , Galanaud Pierre , Emilie Dominique 
Published: February 2007

AbstractObjective. To evaluate interleukin‐10 (IL‐10) production in relatives of patients with systemic lupus erythematosus (SLE).Methods. Production of IL‐10 was evaluated in 13 families in which several members had SLE. The constitutive IL‐10 production in SLE patients (n = 16) was compared with that in healthy members of these multiplex families (n = 70), in 30 SLE patients who had no relatives with SLE, and in 46 healthy unrelated controls.Results. The level of IL‐10 production did not differ between SLE patients who were members and those who were not members of multiplex families (mean ± SEM 4,384 ± 908 pg/ml and 4,709 ± 560 pg/ml, respectively), but was higher in both groups than in healthy unrelated controls (515 ± 88 pg/ml). The healthy members of the multiplex families constitutively produced large amounts of IL‐10 (3,080 ± 311 pg/ml; P < 0.001 compared with healthy unrelated controls). This high IL‐10 production was independent of age and sex, and was similar in first‐ and second‐degree relatives of SLE patients. The IL‐10 was produced both by monocytes and by a subpopulation of B lymphocytes in SLE patients and in their relatives.Conclusion. The dysregulation of IL‐10 production previously identified in SLE patients is also present in healthy members of families with several cases of SLE, and it may contribute to the immunologic abnormalities affecting relatives of SLE patients.
Collagen crosslinks in fibromyalgia
Authors: Sprott Haiko , Müller Andreas , Heine Hartmut 
Published: February 2007

AbstractObjective. To determine if abnormal collagen metabolism is a characteristic of fibromyalgia.Methods. The diagnosis of fibromyalgia was made according to the American College of Rheumatology criteria. Skin biopsy samples were obtained from the trapezius region of 8 patients with fibromyalgia. Urine was collected under standardized conditions from 55 control subjects and 39 patients with fibromyalgia, and serum was obtained from 17 controls and 22 patients with fibromyalgia. Pyridinoline (Pyd), an indicator of connective tissue disease, and deoxypyridinoline (Dpyd), an indicator of bone degradation, both of which represent products of lysyl oxidase‐mediated crosslinking in collagen, were analyzed by ion‐paired and gradient high‐performance liquid chromatography (HPLC) methods with fluorescence detection. Levels of hydroxyproline (Hyp), a collagen turnover marker, were also measured. The findings were related to creatinine levels, and the Pyd:Dpyd ratio was determined.Results. Highly ordered cuffs of collagen were observed around the terminal nerve fibers by electron microscopic examination of biopsy tissue from all 8 patients with fibromyalgia, but were not observed in any of the control skin samples. The Pyd:Dpyd ratios in the urine and serum and the Hyp levels in the urine were significantly lower in patients with fibromyalgia than in healthy controls.Conclusion. Decreased levels of collagen cross‐linking in fibromyalgia may contribute to remodeling of the extracellular matrix and collagen deposition around the nerve fibers, and may contribute to the lower pain threshold at the tender points. Analysis of altered collagen metabolism either by histologic examination on biopsy, or preferably, by HPLC analysis of collagen metabolites in urine or serum may aid in understanding more about the pathogenesis of fibromyalgia.
Effects of self‐care education on the health status of inner‐city patients with osteoarthritis of the knee
Authors: Mazzuca Steven A. , Brandt Kenneth D. , Katz Barry P. , Chambers Mary , Byr Donna , Hanna Mark 
Published: February 2007

AbstractObjective. To evaluate a concise program of self‐care education delivered by an arthritis nurse specialist as an adjunct to primary care for inner‐city patients with knee osteoarthritis (OA).Methods. An attention‐controlled clinical trial; 211 inner‐city patients with knee OA were assigned arbitrarily to education (E) or attention‐control (AC) conditions. Group E received an individualized 30‐60‐minute educational intervention that emphasized non‐pharmacologic management of joint pain, preservation of function by problem‐solving, and practice of principles of joint protection. Brief telephone contacts 1 week and 4 weeks later monitored and reinforced new self‐care activities. Group AC viewed a 20‐minute standardized public education presentation on arthritis and received followup telephone calls (only to encourage continued participation in the study). Outcomes included the Health Assessment Questionnaire (HAQ) Disability and Discomfort Scales, 10‐cm visual analog scales measuring knee pain at rest and while walking, and the Quality of Well‐Being (QWB) scale. Assessments were made at baseline and at 4‐month intervals for 1 year.Results. A total of 165 subjects (78%) completed all assessments. After control for baseline status, group E had significantly lower scores for disability and resting knee pain throughout the year of postintervention followup (P < 0.05 for both). Effects were somewhat discordant. By 12 months, functional benefits had begun to wane, while the effect on resting knee pain had grown. The overall effects of education on walking knee pain, overall joint pain (by HAQ), and general health status (by QWB) were not significant.Conclusion. Self‐care education for inner‐city patients with knee OA, delivered as an adjunct to primary care, was found to result in notable preservation of function and control of resting knee pain. The magnitude of the observed effects compares well with those of more labor‐intensive and time‐consuming intervention models. However, more sustained preservation of function and consistent effects on pain may require prolonged, more proactive followup, either by the patient educator or by a trained clinical assistant dedicated to the task of supporting self‐care by patients with knee OA.
Analysis of human t cell and b cell responses against u small nuclear ribonucleoprotein 70‐kd, b, and d polypeptides among patients with systemic lupus erythematosus and mixed connective tissue disease
Authors: Holyst Margaret‐Mary , Hill Don L. , Hoch Sallie O. , Hoffman Robert W. 
Published: February 2007

AbstractObjective. To analyze T and B cell reactivity with U small nuclear RNP (snRNP) 70‐kd, B, and D polypeptides among patients with connective tissue disease (CTD) and to examine the functional characteristics of snRNP‐reactive T cell clones.Methods. We used an snRNP enzyme‐linked immunosorbent assay and immunoblotting to characterize antibodies in patients' sera. We used human recombinant fusion proteins 70 kd, B, and D to stimulate and clone snRNP‐reactive T cells from CTD patients. We analyzed the cell surface phenotype, antigenic specificity, and cytokine profiles of T cell clones.Results. Patients showed T cell responsiveness to snRNP polypeptides that paralleled their autoantibody reactivities. A total of 256 clones were generated, and clones were identified which were specific for the 70‐kd, B, or D polypeptides. Clones expressed a T helper cell phenotype, and were found to produce substantial quantities of both interleukin‐4 (IL‐4) and interferon‐γ, and lesser quantities of IL‐2 and IL‐6.Conclusion. These results show that CTD patients have clonable circulating snRNP‐reactive T cells that parallel the specificity of snRNP‐reactive antibodies in their sera. The snRNP‐reactive T cells exhibit a helper cell phenotype and produce cytokines which are important in B cell help and differentiation.
Is knee joint proprioception worse in the arthritic knee versus the unaffected knee in unilateral knee osteoarthritis?
Authors: Sharma Leena , Pai Yi‐Chung , Holtkamp Kelly , Rymer W. Zev 
Published: February 2007

AbstractObjective. Neuromuscular joint protection requires proprioceptive input and motor output. Impairment of proprioception in knee osteoarthritis (OA) may contribute to, and/or result from, the disease. If this impairment was exclusively a local result of OA, a between‐knee difference would be expected in patients with unilateral OA (UOA). To explore causal directions, 2 hypotheses were tested: 1) proprioception is worse in UOA patients versus elderly controls; 2) proprioception is worse in the arthritic knee versus the unaffected knee in UOA patients.Methods. Twenty‐eight UOA patients (Kellgren‐Lawrence grade ⩾2 in 1 knee and <2 in the other knee) and 29 elderly controls were enrolled. The unaffected knee of each UOA patient and both knees of the elderly controls were required to meet symptom, examination, and radiographic criteria. Proprioception (detection threshold of joint displacement after slow, passive, automated knee motion), body mass index, pain, functional status, range of motion, and laxity were measured.Results. UOA patients had worse proprioception than did elderly controls, in either knee. A between‐knee difference was not found in UOA patients.Conclusion. Impaired proprioception is not exclusively a local result of disease in knee OA. The relative importance of impaired proprioception in the development and progression of knee OA will require longitudinal study.
New‐onset juvenile dermatomyositis. Comparisons with a healthy cohort and children with juvenile rheumatoid arthritis
Authors: Pachman Lauren M. , Hayford Jennifer R. , Hochberg Marc C. , Pallansch Mark A. , Chung Ahn , Daugherty Claire D. , Athreya Balu H. , Bowyer Suzanne L. , Fink Chester W. , Gewanter Harry L. , Jerath Rita , Lang Bianca A. , Szer Ilona S. , Sinacore James , Christensen Mary L. , Dyer Alan R. 
Published: February 2007

AbstractObjective. To determine, in a case‐control study, if patients with new‐onset juvenile dermatomyositis (juvenile DM) have increased symptoms prior to onset, exposure to certain environmental conditions, frequency of familial autoimmune diseases, or antibody titers, compared with 2 control groups.Methods. A structured interview with the families of 80 children with juvenile DM, 40 children with juvenile rheumatoid arthritis (JRA), or 23 healthy children, from the same geographic area as the children with juvenile DM, was conducted. All children's sera were tested for antibody to Toxoplasma gondii, herpes simplex virus (HSV), or coxsackievirus B (CVB).Results. A high proportion of children with juvenile DM had constitutional symptoms 3 months before the disease‐onset date (P = 0.013 versus control children). Children with JRA had more relatives with rheumatoid arthritis (P = 0.0001) and pernicious anemia (P = 0.003) than did children with juvenile DM or healthy children. Among children ⩽7 years of age, elevated enteroviral titers were more frequent in those with juvenile DM (81%) and in healthy controls (90%) than in those with JRA (64%), suggesting a common environmental exposure. Titers to T gondii, HSV, or CVB 1‐6 were normal.Conclusion. Frequencies of familial autoimmune disease, exposure to environmental factors, or elevated antibody titers to T gondii, HSV, or CVB are not increased in juvenile DM. Children with juvenile DM do have symptoms of illness 3 months before the disease‐onset date, and young patients have elevated enteroviral titers, as do young geographic controls.
A prospective, longitudinal, multicenter study of service utilization and costs in fibromyalgia
Authors: Wolfe Frederick , Anderson Janice , Harkness Deborah , Bennett Robert M. , Caro Xavier J. , Goldenberg Don L. , Russell I. Jon , Yunus Muhammad B. 
Published: February 2007

AbstractObjective. To study, for the first time, service utilization and costs in fibromyalgia, a prevalent syndrome associated with high levels of pain, functional disability, and emotional distress.Methods. Five hundred thirty‐eight fibromyalgia patients from 6 rheumatology centers were enrolled in a 7‐year prospective study of fibromyalgia outcome. Patients were assessed every 6 months with validated, mailed questionnaires which included questions regarding fibromyalgia symptoms and severity, utilization of services, and work disability.Results. Fibromyalgia patients averaged almost 10 outpatient medical visits per year, and when nontraditional treatments were considered, this number increased to ∼1 visit per month. Patients were hospitalized at a rate of 1 hospitalization every 3 years. In each 6‐month study period, patients used a mean of 2.7 fibromyalgia‐related drugs. Costs increased over the course of the study. The mean yearly per‐patient cost in 1996 dollars was $2,274. However, results were skewed by high utilizers, and many patients used few services and had limited costs. Total costs and utilization were independently associated with the number of selfreported comorbid or associated conditions, functional disability, and global disease severity. Compared with patients with other rheumatic disorders, those with fibromyalgia were more likely to have lifetime surgical interventions, including back or neck surgery, appendectomy, carpal tunnel surgery, gynecologic surgery, abdominal surgery, and tonsillectomy, and were more likely than other rheumatic disease patients to report comorbid or associated conditions. Almost 50% of hospitalizations occurring during the study were related to fibromyalgia‐associated symptoms.Conclusion. The average yearly cost for service utilization among fibromyalgia patients is $2,274. Fibromyalgia patients have high lifetime and current rates of utilization of all types of medical services. They report more symptoms and comorbid or associated conditions than patients with other rheumatic conditions, and symptom reporting is linked to service utilization and, to a lesser extent, functional disability and global disease severity.
Rheumatoid arthritis and the risk of malignancy
Authors: Cibere Jolanda , Sibley John , Haga May 
Published: February 2007

AbstractObjective. To determine the relative risks of malignancy and of site‐specific malignancies in patients with rheumatoid arthritis (RA).Methods. In a prospective cohort study, 862 patients with RA (96% white) were enrolled from 1966 to 1974 and were followed up for up to 35 years (mean 17.4 years) at the University of Saskatchewan Rheumatic Disease Unit. All diagnoses of cancer were crossreferenced with the Provincial Cancer Registry. Expected cancer incidence rates were determined based on province of Saskatchewan population statistics matched to each study patient for age, sex, and calendar year. Standardized incidence ratios (SIRs) of the observedto‐expected cancer incidence and 95% confidence intervals (95% CI) were then calculated.Results. A total of 136 cases of cancer were observed compared with 168 expected (SIR 0.80, P = 0.011 [95% CI 0.67–0.95]). The relative risk of colorectal malignancy was significantly reduced in the RA study population (SIR 0.52, P = 0.037 [95% CI 0.25–0.96]). A significant excess of leukemia was found (SIR 2.47, P = 0.026 [95% CI 1.12–4.69]), whereas the incidence rates for Hodgkin's disease and non‐Hodgkin's lymphoma and all other site‐specific malignancies were not found to be significantly different from general population rates.Conclusion. In our cohort of RA patients, colorectal cancer was detected in only half the expected number of patients. This risk reduction may be related to long‐term nonsteroidal antiinflammatory drug (NSAID) use in RA, as has been suggested in several other studies of long‐term NSAID use. An increased risk of leukemia was confirmed. This may be due to the persistent immune stimulation associated with RA itself, since other potential explanatory factors for increased leukemia were not apparent. Despite the excess of hemopoietic malignancy and despite treatment of RA with potentially oncogenic agents, the overall risk of malignancy was reduced in this RA cohort.