bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibodies from patients with rheumatoid arthritis and systemic lupus erythematosus recognize different epitopes of a single heterogeneous nuclear rnp core protein
Authors: Montecucco Carlomaurizico , Caporali Roberto , Negri Claudia , Gennaro Fabio De , Cerino Antonella , Bestagno Marco , Cobianchi Fabio , Astaldi‐Ricotti Giulia C. B. 
Published: February 2007

AbstractAntibodies to recombinant heterogeneous nuclear RNP core protein A1 were detected in sera from 27 of 58 patients with rheumatoid arthritis (RA) and from 7 of 31 patients with systemic lupus erythematosus, by immunoblotting and enzyme‐linked immunosorbent assay. Protein A1 consists of 2 distinct domains: The N‐terminal sequence is identical to a single‐stranded DNA binding protein termed UP1, and the Ckerminal domain shows a partial homology with keratin. All 7 Al‐positive systemic lupus erythematosus sera reacted with UP1, whereas 9 of the 27 Al‐positive RA sera did not. In RA, anti‐A1 activity was significantly associated with antikeratin antibodies (AKA); these antibodies were present in 23 of 27 Al‐positive sera and 10 of 31 Al‐negative sera (P > 0.01). Immunoabsorption with recombinant protein A1 resulted in a significant reduction of AKA titers in 6 of 10 RA sera tested, suggesting that AKA from RA patients may cross‐react with the C‐terminal portion of the heterogeneous nuclear RNP protein Al.
Monoclonal antibody 6b6.6 defines a cross‐reactive kappa light chain idiotope on human monoclonal and polyclonal rheumatoid factors
Authors: Schrohenloher Ralph E. , Accavitti Mary Ann , Bhown Ajit S. , Koopman William J. 
Published: February 2007

AbstractMouse monoclonal antibody (MAb) 6B6.6 was raised against a cross‐reactive idiotope (CRI) present on the light chains of 2 human IgM paraproteins with rheumatoid factor (RF) activity. The MAb inhibited the IgG‐binding activity of these proteins, and thus appears to react with an epitope located at or near the RF‐binding site. Enzyme‐linked immunosorbent assay (ELISA) and Western immunoblotting studies indicate that the 6B6.6 CRI is associated with kIIIa sub‐subgroup light chains, is not related to the Wa, Po, and Bla RF cross‐idiotypic specificities, and is clearly distinct from the kIIIb‐associated CRI detected by MAb 17.109. Using an ELISA, we detected 6B6.6 CRI in 59% of 107 sera and 48% of 50 synovial fluids from patients with seropositive rheumatoid arthritis (RA). However, the quantities of CRI‐positive RF were small, and the amount of CRI‐positive RF did not correlate with the amount of IgM‐RF. The 6B6.6 CRI was shown to occur primarily in the IgM fraction of RA sera by both chromatographic studies and isotype‐specific ELISA, although small quantities appeared to be associated with IgA and IgG in some sera. The presence of 6B6.6 CRI on both monoclonal and polyclonal RF is consistent with the view that both are derived, at least in part, from a common gene pool. However, its occurrence in relatively low levels suggests that the number of germline genes encoding for RF is large or that extensive mutation occurs in the course of RF expression in RA.
Interleukin‐1 release by rat synovial cells is dependent on sequential treatment with γ‐interferon and lipopolysaccharide
Authors: Johnson William J. , Breton John , Newman‐Tarr Tonie , Connor Janice R. , Meunier Paul C. , Dalton Barbara J. 
Published: February 2007

AbstractTo determine the potential regulatory mechanisms involved in synovial cell interleukin‐1 (IL‐1) release, the ability of γ‐interferon (γ‐IFN) to influence IL‐1 release was assessed. Rat synovial cells cultured in the presence of a variety of stimuli, including lipopolysaccharide (LPS), failed to release IL‐1. However, pretreatment of synovial cells with γ‐IFN, followed by LPS stimulation, resulted in increased levels of intracellular IL‐1 as well as release of IL‐1 from the cell. The level of IL‐1 release was dependent on the concentration of both γ‐IFN and LPS, and on length of exposure to the γ‐IFN. The kinetic and dose requirements for γ‐IFN‐dependent IL‐1 release were similar to those for Ia antigen expression, but LPS was necessary for IL‐1 messenger RNA induction, intracellular IL‐1 accumulation, and IL‐1 release. In addition, sequential treatment, i.e., γ‐IFN followed by LPS, was essential for IL‐1 induction. Substitution of phorbol ester or calcium ionophore for γ‐IFN did not result in similar IL‐1 release. In addition, induction of IL‐1 messenger RNA by another stimulus was not sufficient to result in IL‐1 release following LPS treatment. These results suggest that release of IL‐1 by rat synovial cells requires the production of a regulatory signal, which is inducible by γ‐IFN.
Dna autosensitivity in two japanese sisters
Authors: Sugai Susumu , Yasuda Yukio , Shimizu Shiro , Sawada Makoto , Tachibana Junko , Konda Susumu , Kitada Hirohisa , Nakaizumi Hiroko , Tsukada Sadao 
Published: February 2007

AbstractTwo cases of DNA autosensitivity in Japanese sisters are reported. Both patients developed painful ecchymoses and other bleeding disorders. Skin tests with autologous leukocyte lysates and calf thymus DNA produced intermediate‐type reactions that were identical to spontaneous skin reactions. Pretreatment of DNA with either DNase or chloroquine sulfate inhibited these reactions. Our studies suggest that anti‐DNA antibodies might contribute to the clinical symptoms of this disorder.
The relationship between cd5‐expressing b lymphocytes and serologic abnormalities in rheumatoid arthritis patients and their relatives
Authors: Youinou P. , Mackenzie L. , Katsikis P. , Merdrignac G. , Isenberg D. A. , Tuaillon N. , Lamour A. , Le Goff P. , Jouquan J. , Drogou A. , Muller S. , Genetet B. , Moutsopoulos H. M. , Lydyard P. M. 
Published: February 2007

AbstractThe influence of genetic factors on the expression of CD5+ B lymphocytes and their relationship to a broad spectrum of autoantibodies was investigated in a study of 12 patients with rheumatoid arthritis (RA) and 52 of their healthy first‐degree relatives. The proportion of CD5+ B cells was significantly higher in RA patients (mean ± SEM 23.9 ± 2.7%) compared with that in their relatives (18.3 ± 1.1%; P < 0.05) and compared with that in a group of healthy control subjects (16.1 ± 1.8%; P < 0.05). Much more striking, however, were the high levels of CD5+ B cells found in the patients and their relatives in 5 of the families studied. Increases in total immunoglobulin levels and autoantibody levels were frequently observed in RA patients (∼20–40%) and their relatives (∼10–20%). Furthermore, a statistically significant correlation (P < 0.01) between IgM rheumatold factor and the percentage of B lymphocytes expressing CD5 was observed.
Enhanced binding of lupus sera to the polyamine‐induced left‐handed z‐dna form of polynucleotides
Authors: Thomas T. J. , Meryhew Nancy L. , Messner Ronald P. 
Published: February 2007

AbstractThe natural polyamines putrescine, spermidine, and spermine are small polyvalent cations present in all living cells. Spermidine and spermine are excellent promoters of left‐handed Z‐DNA, an immunogenic form of DNA that binds readily with anti‐DNA antibodies in the sera of patients with systemic lupus erythematosus (SLE). We studied the binding of a panel of 16 SLE sera to poly(dA‐dC) poly(dG‐dT) and poly(dG‐m5dC).poly (dG‐m5dC) in the presence and absence of spermidine and spermine using an enzyme‐linked immunosorbent assay. The majority of SLE sera showed a 50–150% mean increase in optical density values when incubated with the polynucleotides and either 0.25 mM spermidine or 0.025 mM spermine than when incubated with the polynucleotides alone. Under these conditions, the polynucleotides assumed the Z‐DNA form. Since polyamines are ubiquitous cellular components and since potential Z‐DNA‐forming alternating purine‐pyrimidine sequences are widely dispersed in native DNA, the increased binding of SLE sera to polyamine‐induced Z‐DNA suggests a pathogenic role for these compounds in SLE.
Soluble interleukin‐2 receptors in patients with systemic sclerosis
Authors: Degiannis Dimitrios , Seibold James R. , Czarnecki Margaret , Raskova Jana , Raska Karel 
Published: February 2007

AbstractPlasma levels of soluble interleukin‐2 receptors (sIL‐2R) were measured by an enzyme‐linked immunosorbent assay in 79 patients with systemic sclerosis (SSc). These levels were significantly elevated in SSc patients, compared with normal controls (mean ± SEM 866.0 ± 63.6 units/ml versus 293.0 ± 20.5; P < 0.001). Soluble IL‐2R levels were highest in patients with generalized disease, were strongly associated with mortality (P < 0.001) and inversely correlated with disease duration (P = 0.003), but were not related to sex, age, specific visceral involvement, serologic status, peripheral lymphocyte count, or therapy. Levels of sIL‐2R in the supernatants of peripheral blood mononuclear cells were low in patients and controls, and showed comparable increases following phytohemagglutinin stimulation. Exposure of peripheral blood mononuclear cells to laminin did not induce sIL‐2R release. Circulating IL‐2 levels were comparably low in patients and controls. Our findings suggest the presence of lymphocyte activation in SSc, and further suggest that measurement of sIL‐2R may prove to be a useful laboratory technique for assessing disease activity.
Analysis of improvement in individual rheumatoid arthritis patients treated with disease‐modifying antirheumatic drugs, based on the findings in patients treated with placebo
Authors: Paulus Harold E. , Egger Marlene J. , Ward John R. , James Williams H. 
Published: February 2007

AbstractA composite index for estimating improvement in individual rheumatoid arthritis (RA) patients during trials of slow‐acting, disease‐modifying antirheumatic drugs (DMARDs) was developed by analyzing the responses of 130 placebo‐treated participants in Cooperative Systematic Studies of Rheumatic Diseases studies. If responses in 4 of 6 selected measures were required for improvement (by ⩾20% for morning stiffness, Westergren erythrocyte sedimentation rate, joint pain/tenderness score, and joint swelling score, and by ⩾2 grades on a 5‐grade scale, or from grade 2 to grade 1 for patient's and physician's overall assessments of current disease severity), few placebo‐treated patients qualified as improved, whereas significantly more DMARD‐treated patients demonstrated improvement. The proposed index appears to be useful in estimating the probability that an RA patient will improve if taking a placebo during a DMARD trial, and may be a useful tool for analysis of DMARD studies.
C3 activation products correlate with antibodies to lipid a in pauciarticular juvenile arthritis
Authors: Olds Lynne C. , Miller John J. 
Published: February 2007

AbstractIgM antibodies to monophosphoryl‐lipid A were found to be elevated in sera from children with all forms of juvenile arthritis (JA) and systemic lupus erythematosus. Of more interest, in patients with pauciarticular JA, IgG antibody titers to monophosphoryl‐lipid A were found to be correlated with the C3a concentration and the C3d:C3 ratio. Although the full specificity of these antibodies is unknown, they are the first that have been found to be correlated with complement activation products in any form of JA.
Septic arthritis
Authors: Williams Riley J. , Lane Smith R. , Schurman David J. 
Published: February 2007

AbstractWe report herein that cartilage proteolytic activity increased in bovine and rabbit articular cartilage after treatment with a purified staphylococcal culture medium or intraarticular infection with Staphylococcus aureus. Staphylococcal culture medium increased the release of gelatinolytic, collagenolytic, and caseinolytic activity into the medium of isolated chondrocytes or cartilage organ culture. The proteolytic activities were determined in assays using radiolabeled substrate and sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. Staphylococcal culture medium was proteolytically inactive by both assay techniques. RNA synthesis of isolated chondrocytes was unaffected by staphylococcal culture medium, whereas overall protein synthesis was inhibited by 84%. An analysis of extracts of Staphylococcus aureus‐infected rabbit knee cartilage by substrate gels showed increased gelatinolytic and caseinolytic activity compared with extracts of uninfected knee cartilage. Our data suggest that the rapid loss of proteoglycan and persistent degradation of cartilage in staphylococcal septic arthritis is due to the production and activation of chondrocyte proteases.
Ly‐1 b cells and disease activity in (new zealand black × new zealand white)f1 mice
Authors: Carmen Fariñas M. , Stall Alan M. , Solovera Jose J. , Tarlinton David M. , Herzenberg Lenore A. , Strober Samuel 
Published: February 2007

AbstractThe treatment of female (New Zealand black × New Zealand white)F1 mice with total lymphoid irradiation resulted in a prolonged remission of autoimmune disease activity. Total lymphoid irradiation‐treated mice also showed a marked reduction of Ly‐1 B cells, which lasted up to 3 months. The subsequent return of Ly‐1 B cells to preirradiation levels was not associated with a simultaneous return of disease when measured by parameters such as IgG anti‐DNA antibodies and spontaneous secretion of IgG by splenic cells. In cell sorting experiments, most of the cells spontaneously secreting IgG were found within the Ly‐1‐ (CD5‐) splenic B cell population.
Association of scleroderma with a t cell antigen receptor γ gene restriction fragment length polymorphism
Authors: Kratz Lisa E. , Boughman Joann A. , Pincus Theodore , Cohen David I. , Needleman Barbara White 
Published: February 2007

AbstractRestriction fragment length polymorphisms (RFLPs) in the T cell receptor (TCR) α, β, and γ genes were analyzed in 61 scleroderma patients and 150 controls. An association was found between scleroderma and an 11.3‐kb Pvu II fragment in the TCR γ gene; this gene was found in 41.0% of the patients, compared with 21.7% of the controls (P < 0.01, odds ratio = 2.50). There were no associations between scleroderma and the tested RFLPs in the TCR α or β genes, and no RFLPs were found in the constant region of the TCR δ gene.
Relationship between clinical efficacy and laboratory correlates of inflammatory and immunologic activity in rheumatoid arthritis patients treated with nonsteroidal antiinflammatory drugs
Authors: Cush John J. , Jasin Hugo E. , Johnson Regina , Lipsky Peter E. 
Published: February 2007

AbstractEighteen rheumatoid arthritis (RA) patients, who had been treated with nonsteroidal antiinflammatory drugs (NSAIDs) only, were enrolled in a 12‐week, open‐label, randomized protocol to determine whether clinical responses might be associated with improvement in laboratory measures of inflammation and immunologic activity in RA patients treated with NSAIDs. Following a 2‐week drug washout period, patients were given either long‐acting ibuprofen (2,400 mg/day) or flurbiprofen (200 mg/day); clinical, laboratory, and immunologic assessments were done biweekly for 10 weeks. A clinical efficacy index, utilizing a combination of measures of disease activity, identified 7 “responders” and 10 “nonresponders” (1 patient discontinued therapy because of a rash). Flow cytometric analysis revealed no abnormalities in the numbers of circulating CD3+, CD4+, or CD8+ lymphocytes in the 17 patients. The density of these T cell markers at enrollment was similar in patients and control subjects. However, following the 2‐week drug washout, significant worsening of morning stiffness, erythrocyte sedimentation rate (ESR), and C‐reactive protein (CRP) was accompanied by a significant decrease (P ⩾ 0.05) in the density of these T cell surface determinants, as is characteristic of activated T cells. After 10 weeks of NSAID therapy, increased density of CD3, CD4, and CD8 was observed in 47%, 73%, and 50% of the patients, respectively. However, in only the responders was the density of these T cell surface markers increased significantly (P ⩾ 0.04). The responders, but not the nonresponders, also demonstrated significant reductions in the ESR, CRP level, serum IgM rheumatoid factor (RF) titer, and spontaneous synthesis of RF by lymphocytes in vitro (P ⩾ 0.05). There were significant correlations between improvements in the clinical parameters (50‐foot walk time, joint score, and global assessment) and reductions in the ESR, CRP level, and serum RF titer (P ⩾ 0.05). These findings demonstrate that clinical improvement in RA patients treated with NSAIDs may be associated with the disappearance of phenotypically activated circulating T cells and functionally activated B cells, as well as with reductions in acute‐phase reactants and serum RF titers.
B cell infiltration of the thymic medulla in new zealand black, new zealand white, and (new zealand black × new zealand white)f1 mice
Authors: Carmen Fariñas M. , Adkins Becky , Stall Alan M. , Weissman Irving , Strober Samuel 
Published: February 2007

AbstractThymuses from female (New Zealand black × New Zealand white)F1 ([NZB × NZW]F1), New Zealand black, and New Zealand white mice of different ages were examined by immunohistochemical and flow cytometric analysis. Two‐and‐a‐half‐month‐old (NZB × NZW)F1 mice showed infiltration of the thymus with B cells, and by 6–8 months of age, showed a disruption of the entire medullary area. More than 80% of the thymic B cells had the phenotypic characteristics of conventional B cells (IgM+, IgD+, Ly‐1—). Total lymphoid irradiation induced a marked depletion of medullary B cells and a restoration of the thymic architecture.
A randomized controlled trial of ciamexon versus placebo in the immunomodulatory treatment of rheumatoid arthritis
Authors: Baerwald Christoph , Goebel Klaus‐M. , Krause Andreas , Heymanns Jochen 
Published: February 2007

AbstractTo determine the efficacy of the new immunosuppressive agent ciamexon in patients with rheumatoid arthritis (RA), we conducted a 6‐month, prospective, double‐blind, placebo‐controlled study. The study included 21 outpatients with confirmed RA, who were randomized into 3 treatment groups of 7 patients each. Group 1 received 400 mg/day of ciamexon, group 2 received 100 mg/day of ciamexon, and group 3 received placebo. We investigated the influence of ciamexon on the clinical course, the systemic inflammatory activity, and the lymphocyte subsets in the peripheral blood. Significant, dose‐dependent improvement was seen in both the clinical and the biochemical activity indexes at the end of the treatment period (P = 0.02 to P = 0.05). The proportion of activated T lymphocytes was significantly decreased (P = 0.05), and the proportion of CD8‐positive lymphocytes was significantly increased (P = 0.03) in patients taking ciamexon. The major adverse effects were hepatotoxicity (2 patients) and rash (2 patients). This study documents the clinical efficacy of ciamexon therapy in RA patients and identifies the agent's potential toxicity.
Signal measurement strategies: are they feasible and do they offer any advantage in outcome measurement in osteoarthritis?
Authors: Bellamy Nicholas , Watson Buchanan W. , Goldsmith Charles H. , Campbell Jane , Duku Eric 
Published: February 2007

AbstractThe applicability of a signal measurement strategy was compared with a traditional method of measuring outcome in osteoarthritis. The signal method detected statistically significant alterations in health status with small sample sizes and with a relative efficiency close to or at unity. The prevalence of deterioration in nonsignal items was low. Signal methods of measurement may provide an alternative approach to outcome measurement in osteoarthritis clinical trials.
Importance of the IgG isotype, not the state of glycosylation, in determining human rheumatoid factor binding
Authors: Newkirk Marianna M. , Lemmo Antonina , Rauch Joyce 
Published: February 2007

AbstractWe investigated the influence of carbohydrate on the binding of human rheumatoid factors (RF) to the Fc fragment of IgG. The monoclonal RF studied were derived from the serum of patients with mixed cryoglobulinemia or from hybridomas generated from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus. Polyclonal RF were derived from patients with RA. The carbohydrate located on the Fc fragment, regardless of whether it contained different amounts of mannose or reduced amounts of galactose, or was removed, did not affect the binding of the RF. In contrast, the isotype of the Fc was found to be critical. Two groups of hybridoma RF could be delineated. One group bound preferentially to IgG1 and/or IgG2, and a second group (primarily from patients with RA) bound preferentially to IgG3 and/or IgG4. Our results indicate that the isotype of the Fc fragment, and not the extent of galactosylation, influences the binding of the RF.
Epitope patterns of Anti‐RNP antibodies in rheumatic diseases evidence for an antigen‐driven autoimmune response
Authors: Habets Winand J. , Hoet Margot H. , Venrooij Walther J.Van 
Published: February 2007

AbstractAutoantibodies against small nuclear ribonucleo‐proteins (snRNP) are common in systemic lupus erythematosus and related disorders. The 3 categories, anti‐(U1)RNP, anti‐(U1,U2)RNP, and anti‐Sm, all contain a common antibody specificity directed against the U1 snRNP‐associated A protein. To determine the specificity of anti‐U1 snRNP A protein antibodies for various antigenic sites, we tested 26 different anti‐snRNP‐positive sera for reactivity with fragments of the U1 snRNP A protein, which was produced using recombinant DNA technology. Several different fragments were shown to contain autoimmune‐reactive epitopes, which indicates that the antibody response against the U1 snRNP A protein is polyclonal. Antibodies against a discontinuous or conformational epitope were found in most of the sera tested, regardless of whether they were classified as anti‐(U1)RNP, anti‐Sm, or anti‐(U1,U2) RNP. These results strongly support the hypothesis that the anti‐snRNP autoimmune response is antigen driven.
Proteoglycan‐induced polyarthritis and spondylitis adoptively transferred to naive (nonimmunized) BALB/c mice
Authors: Mikecz Katalin , Glant Tibor T. , Buzás Edit , Poole A.Robin 
Published: February 2007

AbstractMononuclear cells from BALB/c mice with progressive polyarthritis and spondylitis induced by injection of fetal human articular cartilage proteoglycan (PG) were used to transfer arthritis by intravenous injection into irradiated, nonimmunized syngeneic mice. Successful transfer of arthritis to BALB/c mice required the injection of lymphocytes from mice with arthritis, along with 50 m̈g of human fetal PG, or lymphocytes stimulated in vitro with either fetal human PG or with mouse cartilage PG. In addition, interleukin‐2 or immune sera from animals with arthritis significantly reduced the time to onset of transferred disease. The onset of adoptively transferred arthritis, using cells and antigen, from the time of the first injection (38.2 ± 18.2 days, mean ± SD) was shortened if lymphocytes from mice with transferred arthritis were reinjected (retransferred) into other, irradiated syngeneic mice (6.1 ± 2.6 days). The appearance of autoreactive antibodies to mouse cartilage PG in the sera of mice with adoptively transferred arthritis (secondary or tertiary) preceded the appearance of the first clinical symptoms by a few days. The transfer of arthritis was blocked by pretreatment of donor (arthritic) lymphocytes with either anti‐T cell or anti‐B cell antibodies and complement. Exposure of mononuclear cells from mice with arthritis to PG, and its removal prior to transfer, also resulted in transfer of the arthritis. PG‐induced arthritis was not transferred to nonirradiated mice, nor to irradiated mice injected with lymphocytes from animals with primary arthritis without chondroitinase ABC‐digested fetal human PG. Arthritis never developed after injection of immune sera from mice with arthritis (without cells), nor when cells of nonarthritic animals were used with chondroitinase ABC‐digested fetal human PG, with or without interleukin‐2.