bluuebunny/crossref_metadata_2025_split huggingface dataset:
RP105‐lacking B cells from lupus patients are responsible for the production of immunoglobulins and autoantibodies
Authors: Kikuchi Yuji , Koarada Syuichi , Tada Yoshifumi , Ushiyama Osamu , Morito Fumitaka , Suzuki Noriaki , Ohta Akihide , Miyake Kensuke , Kimoto Masao , Horiuchi Takahiko , Nagasawa Kohei 
Published: December 2002

AbstractObjectiveWe previously reported that B cells lacking the RP105 molecule, which proved to be highly activated B cells, are increased in the peripheral blood of patients with systemic lupus erythematosus (SLE). In the present study, we attempted to determine whether RP105‐negative B cells obtained from SLE patients would be capable of producing autoantibodies as well as immunoglobulins.MethodsRP105‐positive and RP105‐negative B cells, sorted by cell sorter, were cultured for 5 days without stimulation, or were stimulated with Staphylococcus aureus Cowan 1 strain (SAC) or recombinant interleukin‐6 (IL‐6). For the assay of autoantibodies, RP105‐positive and RP105‐negative B cells were cultured separately for 10 days with anti‐CD3 antibody–stimulated T cells. The production of immunoglobulins and autoantibodies was determined by enzyme‐linked immunosorbent assay.ResultsWe demonstrated that RP105‐negative B cells, but not RP105‐positive B cells, obtained from SLE patients could spontaneously produce IgG and IgM in vitro until day 5. SAC and IL‐6 enhanced production of IgG and IgM by RP105‐negative B cells but failed to induce such production by RP105‐positive B cells. The latter cells, however, when cocultured with activated T cells in the presence of IL‐10, produced IgG, although the amount was very small compared with that produced by RP105‐negative B cells. Most important, under these conditions, anti–double‐stranded DNA antibodies were produced only by the RP105‐negative B cells obtained from SLE patients.ConclusionThese data indicate that RP105‐negative B cells, constituting a subset of B cells in SLE patients, are highly activated and may be responsible for the production of autoantibodies as well as polyclonal immunoglobulins.
Identity of the RNase MRP– and RNase P–associated Th/To autoantigen
Authors: Van Eenennaam Hans , Vogelzangs Judith H. P. , Lugtenberg Dorien , Van Den Hoogen Frank H. J. , Van Venrooij Walther J. , Pruijn Ger J. M. 
Published: December 2002

AbstractObjectiveTo characterize the molecular identity of the Th/To autoantigen, which is targeted by autoantibodies in scleroderma and which is associated with the human RNase MRP and RNase P ribonucleoprotein complexes.MethodsProteins immunoprecipitated by anti‐Th/To+ patient antisera from biotinylated total HeLa cell extracts were analyzed by immunoblotting. The association of autoantigenic proteins with the RNase MRP complex was analyzed by reconstitution experiments and ultraviolet crosslinking. The reactivity of patient sera with all known RNase MRP/RNase P proteins was analyzed by immunoprecipitation of the individual recombinant proteins.ResultsThe previously defined Th40 autoantigen appeared to be identical to the Rpp38 protein. Paradoxically, Rpp38 did not bind to the P3 domain of the RNase MRP RNA, as suggested by previously published data for Th40, and only half of the anti‐Th/To+ sera contained anti‐Rpp38 reactivity. Two other RNase MRP/RNase P subunits, Rpp20 and Rpp25, were found to interact with the P3 domain. The previously reported 40‐kd species associated with this domain appeared to consist of Rpp20 and/or Rpp25 associated with a nuclease‐resistant RNA fragment. Finally, we demonstrated that almost all tested anti‐Th/To+ patient sera contained autoantibodies to Rpp25 and hPop1, indicating that these proteins harbor the most frequently targeted Th/To determinants.ConclusionOur data unequivocally define the identity of the Th/To autoantigen and demonstrate that Th/To autoepitopes are found on several protein subunits of RNase MRP/RNase P.
Infliximab in primary Sjögren's syndrome: One‐year followup
Authors: Steinfeld Serge D. , Demols Paul , Appelboom Thierry 
Published: December 2002

AbstractObjectiveTo evaluate the safety and efficacy of a maintenance regimen of infliximab in patients with active primary Sjögren's syndrome (SS) over a 1‐year period.MethodsThis followup study included 10 of the 16 patients with primary SS who participated in a pilot study. Patients who continued to have symptoms received additional infusions of infliximab for 1 year.ResultsAll patients completed the 1‐year followup for evaluation of efficacy. After 1 year, a statistically significant decrease in global and local disease manifestations was observed in all 10 patients. Treatment was generally well tolerated, with the main side effect being a mild, self‐limited infusion reaction.ConclusionSustained improvement of active primary SS may be possible with infliximab treatment.
Bcl‐3 is an interleukin‐1–responsive gene in chondrocytes and synovial fibroblasts that activates transcription of the matrix metalloproteinase 1 gene
Authors: Elliott Sarah F. , Coon Charles I. , Hays Ezra , Stadheim Terrance A. , Vincenti Matthew P. 
Published: December 2002

AbstractObjectiveTo define the role of Bcl‐3, a member of the inhibitor of nuclear factor κB (NF‐κB) family and a known regulator of NF‐κB, in interleukin‐1 (IL‐1)–induced matrix metalloproteinase 1 (MMP‐1) transcription in chondrocytes and synovial fibroblasts.MethodsSW‐1353 cells, a human chondrosarcoma cell line, were stimulated with IL‐1β, and the harvested RNA was subjected to microarray analysis and quantitative real‐time reverse transcription–polymerase chain reaction (RT‐PCR). The SW‐1353 cells were stimulated with IL‐1 or transfected with a plasmid that constitutively expressed Bcl‐3, and then MMP‐1 messenger RNA (mRNA) expression was assayed by quantitative real‐time RT‐PCR. SW‐1353 cells were transfected with antisense oligonucleotides to Bcl‐3, and IL‐1–induced MMP‐1 mRNA expression was assayed by quantitative RT‐PCR. SW‐1353 cells and rabbit synovial fibroblasts were transfected with a 4.3‐kb human MMP‐1 promoter construct along with Bcl‐3 and NF‐κB1 expression constructs, and MMP‐1 transcription was assayed.ResultsMicroarray analysis and real‐time RT‐PCR showed Bcl‐3 to be an IL‐1β–responsive gene in SW‐1353 cells. Exogenous expression of Bcl‐3 in SW‐1353 cells activated MMP‐1 transcription. Endogenous Bcl‐3 expression was required for IL‐1β induction of MMP‐1 gene expression. Bcl‐3 also activated MMP‐1 transcription in primary synovial fibroblasts. We showed previously that NF‐κB1 contributes to IL‐1β induction of MMP‐1 transcription in stromal cells. We showed here that Bcl‐3 can cooperate with NF‐κB1 to activate MMP‐1 transcription in SW‐1353 cells.ConclusionThese data define a new role for Bcl‐3 in joint cells as an IL‐1β–responsive early gene involved in cell‐mediated cartilage remodeling. Our findings implicate Bcl‐3 as an important contributor to chronic inflammatory disease states, such as osteoarthritis and rheumatoid arthritis.
The geometric architecture of the subtalar and midtarsal joints in rheumatoid arthritis based on magnetic resonance imaging
Authors: Woodburn James , Udupa Jayaram K. , Hirsch Bruce E. , Wakefield Richard J. , Helliwell Philip S. , Reay Naomi , O'Connor Philip , Budgen Adam , Emery Paul 
Published: December 2002

AbstractObjectiveTo compare in vivo the 3‐dimensional (3‐D) geometric architecture of the subtalar and midtarsal joints in normal and rheumatoid arthritic (RA) feet, using magnetic resonance imaging (MRI) analysis.MethodsMRI was performed on 23 patients with RA, all of whom had disease activity in the subtalar and/or midtarsal joints. Image processing techniques were used to create 3‐D reconstructions of the calcaneus (C), cuboid (c), navicular (N), and talus (T) bones. Twenty‐four standard architectural parameters were measured from the reconstructions and were compared with data from 10 normal subjects. These parameters defined both 3‐D distance and angular relationships among the 4 bones studied. Pattern classification techniques were used to establish a geometric architecture foot profile for the RA patients. The degree of individual patient fit to the new RA foot profile and to profiles for normal, pes planus, and pes cavus foot types was derived. Logistic regression was used to examine the relationship of foot architecture to inflammatory disease characteristics and physical examination variables.ResultsSubtalar or midtarsal pain was reported by all 23 patients, and 22 of the 23 patients presented with ≥1 clinical feature of pes planovalgus deformity. In 21 patients, ultrasonography revealed synovitis at ≥1 tarsal joint or surrounding tendon. In the RA group, the normalized distances between the geometric centroids were significantly closer for bone pairs Cc and cT and significantly distracted for bone pair CN compared with the distances in normal subjects. In RA patients (versus normal subjects), the angles subtended at the bone centroids were significantly decreased in 3 bone groups (CNc, TCN, and TNc) and significantly increased in 3 bone groups (CcN, CcT, NTc). The angles formed between the major principal axes of bone pairs CT and cT were significantly increased in RA patients compared with those in normal subjects. Pattern classification defined 11 RA feet as having normal structure and 12 as having abnormal structure. However, the abnormal feet did not fit consistently with structures defined for RA, pes planus, or pes cavus foot types. Logistic regression demonstrated that subtalar joint synovitis was the only predictive factor for abnormal subtalar and midtarsal architecture (odds ratio 19.2, 95% confidence interval 1.77–200.0).ConclusionThis unique 3‐D MRI‐based technique successfully quantified the effects of RA on the geometric architecture of the foot and the patient‐specific nature of these changes. This technique can be used to provide logical therapy for correction.
A new conformational epitope generated by the binding of recombinant 70‐kd protein and U1 RNA to anti–U1 RNP autoantibodies in sera from patients with mixed connective tissue disease
Authors: Murakami Akihiro , Kojima Kazuo , Ohya Kazuhiko , Imamura Koji , Takasaki Yoshinari 
Published: December 2002

AbstractObjectiveTo establish an enzyme‐linked immunosorbent assay (ELISA) using a complex of in vitro–transcribed U1 RNA and recombinant 70‐kd, A, and C proteins (C‐ELISA) to detect anti–U1 RNP antibodies reactive in double immunodiffusion (DID), but not in ELISA using the proteins alone (P‐ELISA).MethodsSera from 196 patients with mixed connective tissue disease were used to test reactivity in P‐ and C‐ELISAs, and the specificity of the sera was also tested by DID and immunoprecipitation (IP).ResultsIn P‐ELISA, 15 of 196 sera positive for anti–U1 RNP in DID did not react, while all sera reacted in C‐ELISA. The reactivity of 15 sera to the U1 RNA was tested by IP and ELISA, and only 3 sera reacted with the U1 RNA. These results indicated that the increased reactivity in C‐ELISA was not due to the U1 RNA itself. We confirmed that the 70‐kd and A proteins were bound directly to the U1 RNA by IP using antibodies to His‐tag, and we tested the reactivity of the sera to the U1 RNA–70‐kd protein complex and the U1 RNA–A protein complex by IP. All sera reacted with the U1 RNA–70‐kd protein complex, and 1 sample reacted with the U1 RNA–A protein complex.ConclusionThese results suggest that some anti–U1 RNP–positive sera specifically recognize the conformational structure altered by the binding of U1 RNA to the proteins, and the ELISA using U1 RNA and recombinant proteins is as useful as the DID method for detecting anti–U1 RNP antibodies.
Relief of inflammatory pain in rats by local use of the selective P2X7 ATP receptor inhibitor, oxidized ATP
Authors: Dell'Antonio Giacomo , Quattrini Angelo , Cin Elena Dal , Fulgenzi Alessandro , Ferrero Maria Elena 
Published: December 2002

AbstractObjectiveOxidized ATP (oATP) is a selective inhibitor of the P2Z/P2X7 ATP receptor for extracellular ATP, which contributes to the antinociceptive effect. This study sought to determine the mechanism by which local administration of oATP is able to relieve inflammatory pain in arthritic rat paws.MethodsArthritis was induced in Wistar rats by injections of Freund's complete adjuvant into one hind paw. Nociceptive thresholds were measured before and after local injection of oATP into the inflamed paws. The influence on pain transmission due to the presence of recruited inflammatory cells at the site of inflammation was determined by inhibiting the initial phase of their migration (by intravenous treatment with fucoidin, which blocks the adhesion molecules of the selectin family). ATP intraplantar content was determined in the different experimental conditions. Histologic features of the hind paws were evaluated by using the anti–P2X7 receptor polyclonal antibody.ResultsIntraplantar administration of oATP into inflamed paws significantly relieved inflammatory pain. The antinociceptive effect of oATP was independent of the immune‐cell recruitment. ATP levels in inflamed tissues were significantly reduced by oATP treatment. A variable presence of P2X7 receptors on cutaneous sensory nerves with respect to the different treatments was observed. Following oATP treatment, there was a reduction in P2X7 expression in the endings of peripheral nerves, as well as in endothelial cells.ConclusionOxidized ATP inhibits inflammatory pain in arthritic rats by inhibition of the P2X7 receptor for ATP, which is localized on nerve terminals.
Tumor necrosis factor antagonist therapy and lymphoma development: Twenty‐six cases reported to the Food and Drug Administration
Authors: Brown S. Lori , Greene Mark H. , Gershon Sharon K. , Edwards Evelyne T. , Braun M. Miles 
Published: December 2002

AbstractObjectiveEtanercept and infliximab are tumor necrosis factor (TNF) antagonists that have been recently approved for the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). This study was undertaken to investigate the occurrence of lymphoproliferative disorders in patients treated with these agents.MethodsRelevant data in the MedWatch postmarket adverse event surveillance system run by the US Food and Drug Administration were reviewed.ResultsWe identified 26 cases of lymphoproliferative disorders following treatment with etanercept (18 cases) or infliximab (8 cases). The majority of cases (81%) were non‐Hodgkin's lymphomas. The interval between initiation of therapy with etanercept or infliximab and the development of lymphoma was very short (median 8 weeks). In 2 instances (1 infliximab, 1 etanercept), lymphoma regression was observed following discontinuation of anti‐TNF treatment, in the absence of specific cytotoxic therapy directed toward the lymphoma.ConclusionAlthough data from a case series such as this cannot establish a clear causal relationship between exposure to these medications and the risk of lymphoproliferative disease, the known predisposition of patients with RA and CD to lymphoma, the known excess of lymphoma in other immunosuppressed populations, and the known immunosuppressive effects of the anti‐TNF drugs provide a biologic basis for concern and justification for the initiation of additional epidemiologic studies to formally evaluate this possible association.
Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti‐CD154: A randomized, double‐blind, placebo‐controlled trial
Authors: Kalunian Kenneth C. , Davis John C. , Merrill Joan T. , Totoritis Mark C. , Wofsy David ,   for the IDEC‐131 Lupus Study Group
Published: December 2002

AbstractObjectiveTo evaluate the safety and efficacy of a humanized monoclonal antibody against CD154 (IDEC‐131) in patients with active systemic lupus erythematosus (SLE).MethodsIn this phase II, double‐blind, placebo‐controlled, multiple‐center, multiple‐dose study, 85 patients with mild‐to‐moderately active SLE were randomized to receive 6 infusions of IDEC‐131, ranging from 2.5 mg/kg to 10.0 mg/kg, or placebo over 16 weeks. Efficacy was assessed at week 20, primarily by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and secondarily, by multiple measures of disease activity. Safety was assessed through week 28 by clinical and laboratory evaluation. Immunogenicity studies were also performed.ResultsSLEDAI scores improved from the baseline levels of disease activity in all groups, including the placebo group. However, these scores were not statistically different among the IDEC‐131 treatment and placebo groups at week 20. Evaluations of secondary variables did not indicate significant differences between the IDEC‐131 treatment and placebo groups. The type and frequency of adverse events were similar between the IDEC‐131 and placebo groups.ConclusionIDEC‐131 administered at doses ranging 2.5–10.0 mg/kg over 16 weeks was safe and well tolerated in patients with SLE. Efficacy of the drug compared with placebo was not demonstrated. There were statistically significant improvements from baseline in all groups, including the placebo group.
The effect of education and income on need and willingness to undergo total joint arthroplasty
Authors: Hawker Gillian A. , Wright James G. , Glazier Richard H. , Coyte Peter C. , Harvey Bart , Williams J. Ivan , Badley Elizabeth M. 
Published: December 2002

AbstractObjectiveIndividuals with lower socioeconomic status (SES) receive less arthritis care, including joint arthroplasty. However, no studies have considered the expectations or needs of the patients. Our objective was to assess the effect of education and income on the potential need for, and the willingness to consider hip and knee arthroplasty.MethodsThrough a mail/telephone survey of 48,218 persons ages 55 years or older residing in 2 areas of Ontario, Canada, 3,307 individuals with moderate‐to‐severe hip/knee problems were identified. These individuals received a questionnaire to assess education, income, arthritis severity, and comorbidity. In a subset of these subjects, we conducted interviews to evaluate the willingness to consider arthroplasty, and we also performed clinical and radiographic examinations of the joints to validate self‐reports of arthritis. The potential need for arthroplasty was defined as the presence of severe arthritis (as scored by the Western Ontario and McMaster Universities Osteoarthritis Index), with no absolute contraindications to surgery. Separate logistic regression models examined the independent effects of education and income on the potential need for, and definite willingness to consider arthroplasty, after controlling for age, sex, and region of residence. Potential unmet need was estimated as the proportion of subjects with the need for arthroplasty who were not already on a surgery waiting list, who were definitely willing to consider arthroplasty, and who had evidence of arthritis by examination and radiography.ResultsResponse rates were at least 72% for all questionnaires and interviews. Less education (adjusted odds ratio [OR] 1.57 for less than high school versus postsecondary education, 95% confidence interval [95% CI] 1.17–2.11) and lower income (adjusted OR 1.83 for ≤$20,000 versus >$40,000, 95% CI 1.24–2.70) were independently associated with a greater likelihood of having the potential need for arthroplasty. Among the subjects with potential need, neither education nor income was independently associated with a definite willingness to consider arthroplasty. Thus, taking willingness into consideration, individuals with less education and/or lower income were more likely to have potential unmet need for arthroplasty.ConclusionPersons with lower SES had a greater need for, and were equally willing to consider arthroplasty, compared with those with higher SES. Thus, observed SES disparities in the rates of performed arthroplasties cannot be explained by a lower need or less willingness to undergo arthroplasty in those with lower SES.
Induction of cell death by sera from patients with acute brain injury as a mechanism of production of autoantibodies
Authors: López‐Escribano Herminio , Miñambres Eduardo , Labrador Moisés , Bartolomé María José , López‐Hoyos Marcos 
Published: December 2002

AbstractObjectiveTo investigate the capacity of blood draining from the central nervous system of patients with acute brain injury to induce cell death, and to determine whether this phenomenon could be a way to induce the production of autoantibodies.MethodsThe induction of cell death of several human leukemia cell lines cultured in vitro in the presence of serum collected from the brain or the systemic circulation of patients with acute brain injury was analyzed by flow cytometry after staining with annexin V and propidium iodide. The percentages of apoptotic lymphocytes derived directly from the patients were also quantified. To investigate the mechanisms responsible for the induction of cell death, the expression of apoptosis‐related molecules, as well as the effect of addition of several molecules known to interfere with apoptosis, was evaluated in the cell cultures. The presence of serum autoantibodies at the time of injury and 6 months later was studied.ResultsSystemic serum and, especially, serum draining from the brain lesions induced the in vitro death of the leukemia cell lines used. Moreover, there were higher percentages of ex vivo dead lymphocytes in regional blood than in systemic blood 48 hours after injury. These effects seemed to be induced by an exogenous and/or endogenous opioid, since they were blocked by the opioid antagonist, naloxone. Furthermore, such effects were mediated by an increased expression of Bax. Importantly, apoptotic Jurkat cells were bound to autoantibodies, and patients with acute brain injury produced serum autoantibodies some months after the injury. However, they did not develop a full autoimmune disease at that time.ConclusionSerum factors from acute brain injuries induce cell death, both in vivo and in vitro. Apoptotic cells and, even more so, necrotic cells in acute brain injury are potential sources for autoantigen presentation that may stimulate autoimmune responses.
Cigarette smoking as a significant risk factor for digital vascular disease in patients with systemic sclerosis
Authors: Harrison Beverley J. , Silman Alan J. , Hider Samantha L. , Herrick Ariane L. 
Published: December 2002

AbstractObjectivePatients with systemic sclerosis (SSc) are at high risk for digital vascular complications, including amputation and gangrene. Cigarette smoking is an important risk factor for vascular disease in the general population. We investigated the influence of cigarette smoking on digital ischemia in patients with SSc.MethodsWe studied 101 patients with SSc (87 women and 14 men, median age 53 years, median disease duration 13 years). Smoking history was defined in terms of current smoking status and total number of pack‐years. Digital ischemic events were classified as debridement, hospital admission for intravenous (IV) administration of vasodilators, and digital amputation. The influence of smoking on digital ischemic events was examined using logistic regression, adjusting for age, sex, and disease duration. Results are expressed as the odds ratio (OR) and 95% confidence interval (95% CI).ResultsOf the 101 patients, 21 (21%) were current smokers, 37 (37%) were ex‐smokers, and 43 (43%) had never smoked. After adjusting for age, sex, and disease duration, current smokers were significantly more likely than never‐smokers to have had debridement (OR 4.5, 95% CI 1.1–18.3) or admission for IV vasodilators (OR 3.8, 95% CI 1.1–12.9). Patients smoking at higher intensity were more likely to require admission for IV vasodilators.ConclusionAmong patients with SSc, current smokers are 3–4 times more likely than never‐smokers to incur digital vascular complications. Resources should be directed to supporting smoking cessation in patients with SSc.