bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross‐reactivity of igm‐ and igg‐secreting b cells in autoimmune mice
Authors: Ishigatsubo Yoshiaki , Igarashi Toshihisa , Ohno Shigeru , Ueda Atsuhisa , Okubo Takao , Klinman Dennis M. 
Published: February 2007

AbstractObjective. To determine the frequency with which in vivo–activated B cells secrete cross‐reactive antibodies in lupus‐prone mice.Methods. Analysis of freshly isolated splenic lymphocytes by chamber enzyme‐linked immunospot assay.Results. Young New Zealand black, New Zealand black X New Zealand white, and MRL/lpr mice expressed repertoires in which 16–20% of IgM‐secreting cells and 0–2% of IgG‐secreting cells were crossreactive. By comparison, 21–31% of IgM‐ and 4–14% of IgG‐secreting cells in adult animals with active lupus were cross‐reactive (P < 0.01).Conclusion. Cross‐reactive B cells constitute an abnormally large proportion of the repertoire expressed in mice with active autoimmune disease.
Inflammation‐induced cartilage degradation in female rodents. protective role of sex hormones
Authors: Da Silva Joséa. P. , Colville‐Nash Paul , Spector Tim D. , Scott David L. , Willoughby Derek A. 
Published: February 2007

AbstractObjective. To investigate the effects of physiologic levels of sex steroids on inflammation and cytokine production and their consequential cartilage degradation.Methods. We used an in vivo model of inflammation‐induced cartilage degradation in female mice to study the effects of ovariectomy and hormone treatment, and in vitro culture systems to examine the influence of sex steroids on cartilage metabolism, interleukin‐1 (IL‐1) production by granulomatous tissue, and its effects on female mouse articular cartilage.Results. Ovariectomy resulted in accelerated cartilage breakdown associated with increased production of IL‐1 by granulomatous tissue. The effects of ovariectomy on cartilage were reversed by treatment with estradiol and androgen, but not by progesterone treatment. Estradiol and progesterone reduced both spontaneous and IL‐1–induced cartilage degradation in vitro. Testosterone antagonized the effects of IL‐1 on both proteoglycan loss and proteoglycan synthesis.Conclusion. These data suggest that sex steroids have an important influence on inflammation‐induced cartilage breakdown in female animals, with protective effects of both estradiol and androgens. Multiple mechanisms may be involved, and they are likely to include direct immunomodulatory effects as well as interactions with the effects of cytokine and of the glucocorticoid response to inflammation.
Rheumatoid arthritis and mortality. A longitudinal study in pima indians
Authors: Jacobsson LENNART T. H. , Knowler William C. , Pillemer Stanley , Hanson Robert L. , Pettitt David J. , Nelson Robert G. , Puente Antonio Del , Mccance David R. , Charles Marie‐Aline , Bennett Peter H. 
Published: February 2007

AbstractObjective. To determine the effect of rheumatoid arthritis (RA) on mortality rates.Methods. Longitudinal analyses of data from a cohort of Pima Indians from the Gila River Indian Community in Arizona, who were followed up during the period February 1965 through December 1989.Results. Among 2,979 study subjects aged ≤25 years, there were 858 deaths, 79 of which occurred in subjects with RA (36 men, 43 women). Age and sex‐adjusted mortality rates were slightly higher in subjects with RA than in those without (mortality rate ratio 1.28, 95% confidence interval [95% CI] 1.01–1.62). Among those with RA, mortality rates were higher in older subjects (mortality rate ratio 1.51 per 10‐year increase in age, 95% CI 1.22–1.88), in male subjects (mortality rate ratio 2.23, 95% CI 1.44–3.45, adjusted for age), and in subjects with proteinuria (mortality rate ratio 1.88, 95% CI 1.02–3.46, adjusted for age and sex). Mortality rate ratios for these risk factors were similar in subjects without RA. In addition, among subjects with RA, rheumatoid factor (RF) positivity was predictive of death (mortality rate ratio 1.94, 95% CI 1.10–3.43), and the excess mortality was found primarily among subjects who were seropositive. The death rate from cardiovascular disease (mortality rate ratio 1.77, 95% CI 1.10–2.84) and from liver cirrhosis or other alcohol‐related disease (mortality rate ratio 2.52, 95% CI 1.06–6.01) was increased in persons with RA.Conclusion. The results of this population‐based study suggest that although the risk of mortality in subjects with RA is significantly higher than in those without RA, the risk ratio is in the lower range of that described previously in studies of clinic‐based cohorts. RF positivity as a predictor of early death among subjects with RA indicates that the immunologic processes in seropositive RA may contribute to the events that eventually lead to early death.
Antineutrophil cytoplasmic antibodies in rheumatoid arthritis. characterization and clinical correlations
Authors: Mulder A. H. L. , Horst G. , Van Leeuwen M. A. , Limburg P. C. , Kallenberg C. G. M. 
Published: February 2007

AbstractObjective. To study the prevalence, interrelationships, and target antigens of antineutrophil cytoplasmic antibodies (ANCA) in rheumatoid arthritis (RA) and to relate their presence to disease duration and to the occurrence of extraarticular manifestations, including vasculitis.Methods. Sera from 94 patients with RA (31 with recent‐onset disease, 35 with longstanding disease but without extraarticular manifestations, and 28 with extraarticular disease) were studied for the presence of ANCA by indirect immunofluorescence. All sera were tested by enzyme‐linked immunosorbent assay (ELISA) for the presence of antibodies to proteinase 3, myeloperoxidase (MPO), elastase, lactoferrin (LF), and cathepsin G (CG), and by Western blotting for antibodies to neutrophil proteins.Results. Seventy percent of the 94 sera showed staining of the nuclei of ethanol‐fixed neutrophils; 32% of the 94 were proven to have ANCA, as manifested by their cytoplasmic staining pattern on paraformaldehyde‐fixed neutrophils. In the ELISA, 19 sera reacted with LF, 1 with MPO, and 1 with CG. By Western blotting, 21 sera reacted with LF, and 15 reacted with previously unknown polypeptides (7 sera with a 67/66‐kd doublet and 8 with a 63/54‐kd doublet). Neither of these antibodies was associated with a particular subset of the disease, but the prevalence of the antibodies tended to increase among patients with longstanding disease.Conclusion. ANCA in RA patients are directed toward diverse cytoplasmic antigens of the neutrophil, in particular, LF and other, not yet fully characterized polypeptides. The antibodies are not a marker for a disease subset, but are probably a corollary of chronic inflammation.
Circulating soluble tumor necrosis factor receptors, interleukin‐2 receptors, tumor necrosis factor α, and interleukin‐6 levels in rheumatoid arthritis.
Authors: Barrera Pilar , Th. Boerbooms Agnes M. , Janssen Elly M. , Sauerwein Robert W. , Gallati H. , Mulder Jan , Boo Theo De , Demacker Pierre N. M. , Van De Putte Levinus B. A. , Van Der Meer JOS W. M. 
Published: February 2007

AbstractObjective. To assess whether circulating concentrations of soluble tumor necrosis factor receptors (sTNFR; p55 and p75), soluble interleukin‐2 receptors (sIL‐2R), tumor necrosis factor α (TNFα), and interleukin‐6 (IL‐6) reflect clinical response and whether changes are dependent on the drug used in rheumatoid arthritis (RA) patients taking methotrexate (MTX) or azathioprine (AZA).Methods. These cytokines and soluble receptors were assessed in 20 control subjects and serially for up to 48 weeks in 61 RA patients, by bioassay (IL‐6) and immunoassays (sTNFR, sIL‐2R, TNFα, and IL‐6).Results. Concentrations of p55 and p75, sIL‐2R, and TNFα (but not IL‐6) were significantly higher in RA patients than in controls. Significant decreases in sIL‐2R and p55 concentrations were associated with clinical improvement and were observed in patients treated with MTX, but not AZA. Both treatments induced decreases in IL‐6 concentrations, but circulating AZA (or its metabolites) appears to interfere with the measurement of IL‐6 bioactivity. TNFα and p75 levels did not show significant changes.Conclusion. Measurement of circulating sIL‐2R, p55, and IL‐6 may be useful in the evaluation of RA disease activity and response to therapy. Interference by circulating levels of drugs must be ruled out when bioassays are used to evaluate cytokine levels.
Detection of herpesviruses by polymerase chain reaction in lymphocytes from patients with rheumatoid arthritis
Authors: Zhang Lijuan , Nikkari Simo , Skurnik Mikael , Ziegler Thedi , Luukkainen Reijo , Möttönen Timo , Toivanen Paavo 
Published: February 2007

AbstractObjective. To investigate the occurrence of herpesviruses, including Epstein‐Barr virus (EBV), herpes simplex viruses types 1 and 2 (HSV‐1; HSV‐2), and human herpes virus 6 (HHV‐6), in lymphocytes from patients with rheumatoid arthritis (RA) of less than 1 year's duration.Methods. The polymerase chain reaction was applied to cells isolated from synovial fluid and peripheral blood. Indirect immunofluorescence and enzyme immunoassay techniques were used to detect antibodies against EBV and HSV, respectively.Results. EBV DNA was present in synovial fluid lymphocytes from 19% (7 of 37) of the RA patients and 33% (5 of 15) of the patients with reactive arthritis (ReA). Peripheral blood lymphocytes harbored EBV DNA in 39% of the RA patients, 39% of the ReA patients, 27% of the patients with other arthropathies, and in 31% of the healthy control subjects. HSV‐1, HSV‐2, and HHV‐6 viral DNA was not detected in cells from the synovial fluid or peripheral blood.Conclusion. Our findings do not support the participation of EBV, HSV‐1, HSV‐2, or HHV‐6 in the pathogenesis of RA. A role for the highly prevalent EBV cannot be excluded, however, since potential contributions may become manifest only when other necessary factors are involved. RA pathogenesis caused by an overproduction of the EBV virus is nevertheless highly unlikely.
Presence of estrogen‐binding sites on macrophage‐like synoviocytes and cd8+, cd29+, cd45ro+ t lymphocytes in normal and rheumatoid synovium
Authors: Cutolo Maurizio , Accardo Silvano , Villaggio Barbara , Clerico Paolo , Bagnasco Marcello , Coviello Domenico A. , Carruba Giuseppe , Casto Michele Lo , Castagnetta Luigi 
Published: February 2007

AbstractObjective. To study the presence of estrogen‐binding sites (EBS) in the synovial tissues of male and female patients with rheumatoid arthritis (RA) and in age and sex‐matched healthy controls.Methods. Both type 1 (high affinity, low binding capacity) and type 2 (reduced affinity, higher binding capacity) EBS were investigated in both soluble and nuclear fractions of homogenized synovial tissue samples by a dextran‐coated charcoal method. To determine what type of synovial cell was positive for EBS, cryosections of synovial tissues were immunostained with a specific monoclonal anti–estrogen receptor antibody (anti‐ER MAb) using both immunofluorescence and immunoperoxidase techniques. Double immunostaining with the anti‐ER MAb and with specific MAb to detect different macrophage antigens (Ber‐MAC3, MAC387, CD68) and CD8+ T cell subsets (CD29+, CD45RO+ and CD29–, CD45RO–) was performed.Results. Higher affinity EBS were found mostly in nuclear cell fractions of either RA or control synovial tissues (28 of the 33). These EBS were present to a lesser extent in soluble cell fractions (11 of the 33). Immunostaining showed the estrogen receptor–positive cells to be the macrophage‐like synoviocytes and the CD8+, CD29+ T cells both in RA and in control synovial tissues. Higher nuclear content of EBS was consistent with more intense nuclear staining of synoviocytes and T cells.Conclusion. It is conceivable that the immunomodulatory activity exerted by estrogens is at least partly mediated through their interaction with EBS that are present on macrophage‐like synoviocytes, functioning as antigen‐processing and antigen‐presenting cells, and on antigen‐experienced (memory) CD8+ T lymphocytes (CD29+, CD45RO+).
Increased levels of circulating intercellular adhesion molecule 1 in the sera of patients with rheumatoid arthritis
Authors: Cush John J. , Rothlein Robert , Lindsley Herbert B. , Mainolfi Elizabeth A. , Lipsky Peter E. 
Published: February 2007

AbstractObjectdive. We sought to assess whether circulating levels of intercellular adhesion molecule 1 (ICAM‐1) in patients with rheumatoid arthritis (RA) are elevated and correlate with clinical measures of disease activity and whether this ICAM‐1 originates from the synovium.Methods. Circulating ICAM‐1 (cICAM‐1) levels were determined by sandwich enzyme‐linked immunosorbent assay of serum from 61 RA, 18 osteoarthritis (OA), and 11 inflammatory arthritis (IA) patients. In addition, paired serum and synovial fluid samples were collected from 17 RA, 9 OA, and 4 IA patients. The stability of cICAM‐1 was assessed by overnight incubation at 37°C. Finally, the potential degradative effects of synovial fluid proteases were assessed by incubation of recombinant soluble ICAM‐1 with patient synovial fluid.Results. RA sera contained significantly greater (P < 0.001) levels of cICAM‐1 compared with RA synovial fluid and compared with sera or synovial fluid from the OA and IA patients. Circulating ICAM‐1 levels were unaffected by overnight incubation at 37°C and were unaffected by exposure to RA, OA, or IA synovial fluid. Serum levels of cICAM‐1 demonstrated a weak, but significant (P < 0.05) correlation with the joint score and erythrocyte sedimentation rate in 25 RA patients treated with nonsteroidal antiinflammatory drugs.Conclusion. The greatest elevations of cICAM‐1 were seen in RA patient sera. In both RA and OA, synovial fluid cICAM‐1 levels were consistently lower than serum levels, suggesting that cICAM‐1 did not originate in the synovium. Because the production of cICAM‐1 can be increased by cytokines (e.g., interleukin‐1, tumor necrosis factor α), elevated levels of circulating ICAM‐1 in RA may be reflective of systemic exposure to elevated cytokine levels.
Integrin‐mediated attachment of articular chondrocytes to extracellular matrix proteins
Authors: Loeser Richard F. 
Published: February 2007

AbstractObjective. To investigate the interactions between chondrocytes and their extracellular matrix (ECM). An attachment assay was used to determine the extent of integrin‐mediated attachment of chondrocytes to a variety of ECM proteins and the effect of monolayer culturing on attachment activity.Methods. Bovine and human articular cartilage chondrocytes were grown in high‐density monolayer cultures for 3–21 days and used in the assays. Cell shape and production of 3H‐proline–labeled collagen were monitored to assess phenotypic changes with time in culture. Cultured chondrocytes were incubated in wells coated with purified proteins, with and without specific inhibitors of integrin‐mediated attachment, and cell attachment was determined.Results. Compared with bovine serum albumin, chondrocytes showed significant attachment to fibronectin, matrix Gla protein (MGP), osteopontin, bone sialoprotein II (BSP II), vitronectin, and types II and VI collagen. A synthetic peptide containing the integrin‐recognition sequence Arg‐Gly‐Asp inhibited attachment to all the proteins tested, except types II and VI collagen. A monoclonal antibody (MAb) to the β1integrin subunit inhibited attachment to fibronectin, MGP, and type II collagen, and a MAb to the β3integrin subunit inhibited attachment to BSP II and osteopontin. An increase in cell attachment was seen with time in culture, and this increase was followed by a change in the chondrocytes to flattened, type I collagen–producing cells.Conclusion. Chondrocytes can attach to a variety of cartilage and bone proteins; this attachment is mediated via integrins, including members of both the β1 and β3 subunit families. The modulation of the chondrocyte phenotype during monolayer culture may be related to activation or increased expression of integrins.
Correlation between serum levels of soluble tumor necrosis factor receptor and disease activity in systemic lupus erythematosus
Authors: Aderka Dan , Wysenbeek Arjeh , Engelmann Hartmut , Cope Andrew P. , Brennan Fionula , Molad Yair , Hornik Vered , Levo Yoram , Maini Ravinder N. , Feldmann Marc , Wallach David 
Published: February 2007

AbstractObjective. To determine the value of measurement of serum soluble tumor necrosis factor receptor (sTNFR), compared with established parameters such as anti–double‐stranded DNA, in monitoring systemic lupus erythematosus (SLE) disease activity, and to determine whether serum sTNFR are bioactive and can effectively inhibit TNF bioactivity.Methods. Fifty‐three consecutive ambulatory or hospitalized SLE patients and 140 consecutive healthy subjects were enrolled in a prospective cohort study. Serum levels of sTNFR were measured by a unique 2‐sided capture enzyme‐linked immunosorbent assay using mouse monoclonal antibodies and rabbit antisera against the sTNFR.Results. The mean ± SD concentrations of both the p55 (type I) and p75 (type II) soluble receptors were significantly higher in a group of 46 SLE patients than in controls: 1.89 ± 0.89 ng/ml versus 0.77 ± 0.19 ng/ml and 7.25 ± 3.89 ng/ml versus 3.02 ± 0.57 ng/ml, respectively (P < 0.0001 for both). The incidence and the extent of the increase among the healthy subjects and these patients (as well as in 7 additional patients on whom sequential studies were performed) correlated with disease activity more than did the occurrence of serum anti‐DNA antibodies (correlation coefficients with disease activity 0.81 and 0.85 for p55 and p75 sTNFR, respectively, and 0.51 for anti‐DNA antibodies). The increase in sTNFR levels seems to reflect, largely, enhanced formation, and only to a minor extent, reduced clearance due to impairment of renal function. Sera of the SLE patients had a marked inhibitory effect on the in vitro cytocidal activity of TNF, and this was shown to result entirely from their higher sTNFR receptor concentration.Conclusion. An increase in serum levels of sTNFR may become a useful marker for SLE activity since it shows a stronger correlation than do any other laboratory or clinical parameters employed presently in the daily clinical setting. At the concentrations attained in the serum of SLE patients, sTNFR effectively inhibit the bioactivity of TNF and may thus be a significant determinant of the intensity of the manifestations of SLE.
Lymphoproliferation in primary sjögren's syndrome. evidence of selective expansion of a b cell subset characterized by the expression of cross‐reactive idiotypes
Authors: Shokri Fazel , Mageed Rizgar A. , Robert Maziak B. , Talal Norman , Amos Nicholas , Williams Bryan D. , Jefferis Roy 
Published: February 2007

AbstractObjective. To evaluate the possibility that lymphoproliferation in primary Sjögren's syndrome (SS) arises within a subset of B cells.Methods. A panel of monoclonal antibodies (MAb) specific for rheumatoid factor (RF)–associated cross‐reactive idiotypes (CRI) and anti‐VK and anti‐VH subgroup antibodies were used to define the clonality of B lymphocytes undergoing neoplastic transformation in 5 patients with primary SS. Anti‐CRI antibodies were also used to study longitudinal variations in serum paraprotein levels and in vitro regulation of IgM and IgM‐RF production by peripheral blood lymphocytes. The levels of CRI, IgM, and IgM‐RF were quantitated in serum and culture supernatants by enzyme‐linked immunosorbent assay. Heavy and light chain isotypes and VH subgroups of the paraproteins were determined by immunoelectrophoresis, immunofixation, and Western blotting.Results. Paraproteins from all patients expressed an epitope associated with VKIIIb sub‐subgroup of light chains. Three of the paraproteins were cryoglobulins with RF activity, all of which expressed the VKIIIb‐associated CRI (detected by MAb 17–109) and the VHI‐associated CRI (detected by MAb G6 and G8). None of the paraproteins expressed the VHIII‐associated CRI (detected by MAb B6 and D12). The CRI were consistently expressed over a period of 5–6 years. The anti‐CRI and anti‐subgroup antibodies substantially inhibited spontaneous production of IgM‐RF and IgM by peripheral blood B lymphocytes from 3 of the SS patients.Conclusion. These results suggest that lymphoproliferation in primary SS is highly selective, and that the anti‐CRI antibodies can be used as an aid to early diagnosis as well as for monitoring and modulating the lymphoproliferative process in primary SS.
Antihistone antibodies in patients with localized scleroderma
Authors: Sato Shinichi , Ihn Hironobu , Soma Yoshinao , Igarashi Atsuyuki , Tamaki Takeshi , Kikuchi Kanako , Ishibashi Yasumasa , Takehara Kazuhiko 
Published: February 2007

AbstractObjective. To study the prevalence and antigen specificity of antihistone antibodies (AHA) in localized scleroderma.Methods. Forty‐nine serum samples from patients with localized scleroderma were examined by an enzyme‐linked immunosorbent assay (ELISA) and by immunoblottin.Results. By ELISA, AHA were demonstrated in 47% (23 of 49) of patients with localized scleroderma and in 87% (13 of 15) of patients with generalized morphea. Immunoblotting revealed that the predominant antigens were histones H1 and H3. The presence of AHA correlated with that of anti–single‐stranded DNA antibody.Conclusion. Some of the major antigens for antinuclear antibodies in patients with localized scleroderma are histones.
The spectrum of vasculitis in human immunodeficiency virus–infected patients. a clinicopathologic evaluation
Authors: Gherardi Romain , Belec Laurent , Mhiri Chokri , Gray Francoise , Lescs Marie‐Claude , Sobel Alain , Guillevin Loïc , Wechsler Janine 
Published: February 2007

AbstractObjective. To delineate the different types of inflammatory vascular diseases (IVD) occurring in patients with human immunodeficiency virus (HIV) infection.Methods. Muscle, nerve, or skin biopsy specimens from 148 symptomatic HIV‐infected individuals were reviewed, and subgroups of vasculitis were identified using the American College of Rheumatology (ACR) 1990 clinicopathologic criteria for the classification of vasculitis.Results. IVD was documented in 34 patients (23%) and included necrotizing arteritis (3 patients), non‐necrotizing arteritis (1 patient), neutrophilic IVD (7 patients), mononuclear IVD (17 patients), and other small vessel inflammatory changes (6 patients). According to the ACR criteria, 11 patients could be classified as having a distinct category of vasculitis, including polyarteritis nodosa (4 patients), Henoch‐Schönlein purpura (1 patient), and drug‐induced hypersensitivity vasculitis (6 patients), and 23 were classified in the group ‘other vasculitis, type unspecified.’ One patient had hepatitis B virus surface antigenemia, 2 had cryoglobulinemia, and 2 were coinfected by human T lymphotropic virus type I. Cytomegalovirus inclusions and antigens were found in endothelial cells in 1 patient. HIV antigens and genome were detected in perivascular cells of 2 of the 3 patients with necrotizing arteritis; in 1, HIV‐like particles were seen by electron microscopy. Immune deposits were found in small vessel walls in 5 skin biopsy samples showing small vessel vasculitis and in the muscle of the 3 patients with necrotizing arteritis.Conclusion. A wide range of inflammatory vascular diseases may occur in HIV‐infected individuals. Vascular inflammation appears multifactorial and may result from HIV‐induced immunologic abnormalities and exposure to a variety of xenoantigens, such as HIV itself, other infectious agents, and drugs.