bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial cells as target for antiphospholipid antibodies. Human Polyclonal and Monoclonal Anti‐β2‐Glycoprotein I Antibodies React In Vitro with Endothelial Cells Through Adherent β2‐Glycoprotein I and Induce Endothelial Activation
Authors: Papa N. Del , Guidali L. , Sala A. , Buccellati C. , Khamashta M. A. , Ichikawa K. , Koike T. , Balestrieri G. , Tincani A. , Hughes G. R. V. , Meroni P. L. 
Published: February 2007

AbstractObjective. To investigate the ability of human anti‐β2‐glycoprotein I (anti‐β2GPI) antibodies to recognize the cofactor adherent on endothelial cells (EC) and to modulate endothelial functions.Methods. Six human affinity‐purified polyclonal anti‐β2GPI IgG and 2 IgM monoclonal antibodies (MAb) were obtained from patients with the antiphos‐pholipid syndrome. The antibodies were tested for their ability to 1) bind to endothelial monolayers through the adherent β2GPI and 2) modulate endothelial adhesion molecule expression and interleukin‐6 (IL‐6) and 6‐keto‐prostaglandin F1α (6‐keto‐PGF1α) secretion.Results. The affinity‐purified IgG and the MAb with anti‐β2GPI activity, but not the respective controls, displayed EC binding, which declined on cells incubated in serum‐free medium and was restored in a dose‐dependent manner by exogenous human β2GPI. After EC binding, both polyclonal and monoclonal antibodies up‐regulated adhesion molecule expression. Anti‐β2GPI MAb also significantly increased IL‐6 and 6‐keto‐PGF1α secretion.Conclusion. These findings support the hypothesis that anti‐β2GPI antibodies bind and activate EC through the adherent cofactor β2GPI, likely leading to a procoagulant state.
Suppression of cartilage matrix gene expression in upper zone chondrocytes of osteoarthritic cartilage
Authors: Aigner T. , Vornehm S. I. , Zeiler G. , Dudhia J. , von der Mark K. , Bayliss M. T. 
Published: February 2007

AbstractObjective. To evaluate the anabolic activity of osteoarthritic chondrocytes in situ by investigating the messenger RNA (mRNA) expression of 3 major cartilage components, type II collagen, aggrecan, and link protein.Methods. In situ hybridization experiments and histochemical analysis for proteoglycan content were performed on parallel sections of normal and osteoarthritic (OA) cartilage specimens.Results. Most chondrocytes in the deeper zones of OA cartilage showed an increase in mRNA expression, in particular, of type II collagen and to a lesser extent, aggrecan, compared with normal specimens. However, chondrocytes of the upper zone were largely negative for aggrecan or type II collagen mRNA. The expression of link protein mRNA was low in normal and OA specimens.Conclusion. These observations suggest that suppression of the anabolic activity of chondrocytes in the upper zones contributes to the metabolic imbalance observed in OA cartilage. Stimulation of matrix anabolism in superficial chondrocytes might be a suitable target for therapeutic intervention.
Direct evidence for the expression of multiple endogenous retroviruses in the synovial compartment in rheumatoid arthritis
Authors: Nakagawa Kaku , Brusic Vladimir , McColl Geoffrey , Harrison Leonard C. 
Published: February 2007

AbstractObjective. Circumstantial evidence links retroviruses (RVs) with human autoimmune diseases. The aim of the present study was to obtain direct evidence of RV gene expression in rheumatoid arthritis (RA).Methods. Synovial samples were obtained from patients with RA, patients with osteoarthritis (OA), and normal control subjects. Reverse transcriptionpolymerase chain reaction (RT‐PCR) was performed using synovial RNA and primers to conserved sequences in the polymerase (pol) genes of known RVs.Results. PCR products (n = 857) were cloned and sequenced. Multiple pol transcripts, many with open reading frames, were expressed in every sample. Sequences were aligned and classified into 6 families (F1‐F6) that contained 33 groups of known and unknown endogenous RVs (ERVs), each distinguished by a specific, deduced peptide motif. The frequency of sequences in each family was similar between RA, OA, and normal synovial tissue, but differed significantly in RA synovial fluid cells. F1 sequences (undefined, but related to murine and primate type C RVs) were lower in frequency, F2 (ERV‐9‐related), F4 (HERV‐K‐related), and F6 (HERV‐L‐related) sequences were higher in frequency, and F3 (RTVL‐H‐related) sequences were not detected, in the RA synovial fluid cells compared with the RA synovial tissues.Conclusion. Multiple ERVs are expressed in normal and diseased synovial compartments, but specific transcripts can be differentially expressed in RA.
Soluble oligonucleosomal complexes in synovial fluid from inflamed joints
Authors: Yu Dan , Rumore Peter M. , Liu Qingli , Steinman Charles R. 
Published: February 2007

AbstractObjective. To determine whether soluble oligonucleosomal DNA, typical of that released during apoptotic cell death, is present in synovial fluids from inflamed joints and, if so, whether it is present in sufficient concentrations to have pathophysiologic significance.Methods. Fifty synovial fluid specimens from 46 patients were studied, 41 from joints with a variety of inflammatory disorders and 9 from osteoarthritic joints. DNA from freshly collected synovial fluid was isolated and quantitated by microfluorometry, and the oligonucleosomal fraction was measured by radiolabeling, gel electrophoresis, and autoradiography. Specific immunoprecipitation with monoclonal antihistone antibody, after DNA radiolabeling in whole synovial fluid, was used to detect histone binding.Results. DNA with a typical oligonucleosomal ladder was observed in most specimens. The mean ± SD oligonucleosomal DNA concentration was 14.1 ± 18.5 μg/ml in synovial fluids from inflamed joints, considerably higher than that in osteoarthritic synovial fluids. Additionally, the DNA was shown to be complexed with histone, as would be expected. Control experiments were performed to show that the oligonucleosomal DNA was present in soluble form and did not arise due to in vitro artifact. The DNA concentrations were found to correlate significantly with the concentrations of synovial fluid leukocytes, most of which were neutrophils.Conclusion. Synovial fluids from inflamed joints contain oligonucleosomal DNA typical of that released during apoptotic cell death. The probable source is fluid‐phase neutrophils undergoing apoptotic cell death, although this was not directly demonstrated. The concentrations are sufficient to have biologic activity similar to that shown in vitro, including lymphoproliferation and stimulation of interleukin‐6 secretion. A mechanism by which oligonucleosomal DNA may contribute to perpetuation of rheumatoid synovitis is proposed. If it is generalizable to other sites of inflammation, as seems probable, similar oligonucleosomal DNA release accompanying inflammation may play a pathogenetic role in other disorders, including systemic lupus erythematosus.
Cardiac expression of 52β, an alternative transcript of the congenital heart block‐associated 52‐kd SS‐A/Ro autoantigen, is maximal during fetal development
Authors: Buyon Jill P. , Tseng Chung‐E , Donato Francis Di , Rashbaum William , Morris Allan , Chan Edward K. L. 
Published: February 2007

AbstractObjective. Congenital heart block (CHB), associated with antibodies to SS‐A/Ro and SS‐B/La, is most often detected between 18 and 24 weeks of gestation, yet the maternal heart is unaffected. We recently described an alternatively spliced 52‐kd SS‐A/Ro messenger RNA (mRNA) derived from the skipping of exon 4 which encodes a smaller protein, 52β (MW 45 kd), recognized by CHB maternal antisera. This study was designed to identify whether cardiac expression of 52β and fulllength 52α relates to the development of CHB.Methods. Reverse transcriptase‐polymerase chain reaction was performed using primers flanking exon 4 and mRNA from 22 human fetal hearts (age 11–25 weeks) and 3 adult hearts. The brain, kidney, liver, lung, and spleen were similarly evaluated in a 15‐week, an 18‐week, and a 24‐week fetus.Results. Expression of 52β was greatest and 52α lowest between 14 and 16 weeks of gestation. In fetal hearts ages 22–25 weeks and adult heart, the 52β transcript was markedly diminished and 52α clearly dominated. The 52β mRNA was observed in a 15‐week brain, kidney, lung, and spleen; however, its expression relative to 52α was greatest in the heart.Conclusion. Since expression of the alternative product 52β is maximal at the time of cardiac ontogeny when maternal antibodies gain access to the fetal circulation, just prior to the clinical detection of bradyarrhythmia, a role for 52β in the development of CHB is implicated. Although other fetal tissues express 52β, there may be differences in accessibility of antigen or regenerative capacities.
A major, novel systemic lupus erythematosus autoantibody class recognizes the E, F, and G Sm snRNP proteins as an E‐F‐G complex but not in their denatured states
Authors: Brahms Hero , Raker Veronica A. , van Venrooij Walther J. , Lührmann Reinhard 
Published: February 2007

AbstractObjective. To determine whether the E, F, and G Sm proteins present antigenic determinants recognized by systemic lupus erythematosus (SLE) patient sera, and if so, whether the antigenicity depends on the native conformations of the polypeptides and/or is E‐F‐G complex restricted.Methods. Radioimmunoprecipitation, epitope tagging, expression polymerase chain reaction, in vitro translation, in vitro reconstitution, and immunoblotting.Results. Most of the anti‐Sm SLE patient sera tested reacted with one or more of the E, F, and G proteins in immunoprecipitation studies but not on immunoblots. All sera, however, highly efficiently immunoprecipitated the E‐F‐G complex. This complex recognition was detected exclusively in anti‐Sm patient sera but not in patient sera with other serotypes.Conclusion. We demonstrate the presence of a novel and abundant anti‐Sm autoantibody class in SLE patient sera which exclusively or predominantly recognizes conformational Sm epitopes present on the E‐F‐G complex but not on the denatured proteins. This complex recognition is highly specific for sera of the anti‐Sm serotype and may be relevant for clinical diagnosis as well as for understanding the etiology of anti‐Sm auto‐antibody production.
Affinity columns containing anti‐DNA Id+ human myeloma proteins adsorb human epibodies from intravenous gamma globulin
Authors: Williams Ralph C. , Malone Christine C. , Fry Gentry , Silvestris Franco 
Published: February 2007

AbstractObjective. To study eluates of intravenous gamma globulin (IVGG) prepared from affinity columns of human cationic IgG myeloma proteins bearing anti‐DNA idiotype (Id) markers 16/6, F4, 3I, and 8.12 for possible anti‐Id (combining site) blocking activity.Methods. Anti‐DNA idiotypic antibody activity was studied in 3 preparations of IVGG containing high, medium, and low levels of IgG anti‐F(ab′)2, and in 4 other commercial IVGG preparations. Affinity‐purified IgG anti‐DNA (APAD) from systemic lupus erythematosus (SLE) patients was biotinylated, and binding to DNA coated on enzyme‐linked immunosorbent assay plates was used to measure anti‐DNA antibody activity. IVGG was adsorbed to Sepharose 4B affinity columns linked to a panel of cationic human IgG myeloma proteins positive for anti‐DNA Id markers 16/6, F4, 3I, and 8.12. Material adsorbing to such columns was eluted at low pH (2.5) and after neutralization, tested for its ability to inhibit biotinylated APAD reacting with DNA.Results. Only 0.05–0.9% of IVGGs bound firmly to Id affinity columns. These IVGGs were then eluted, using pH 2.5 glycine‐saline and eluates neutralized to pH 7.4. Column flowthrough and eluate fractions were compared for their ability to block SLE APAD reacting with DNA. Significant inhibition of SLE APAD combining sites was observed with eluates from anti‐DNA Id affinity columns; however, no correlation between IVGG anti‐F(ab′)2 activity and true anti‐Id blocking of APAD was apparent. No residual anti‐Id activity remained in column flowthrough fractions. No anti‐Id blocking activity was recorded for IVGG eluates from human cationic myeloma columns devoid of the 4 anti‐DNA Id markers. DNase treatment of IVGG or Id column eluates did not affect anti‐Id blocking activity. Thus, all detectable anti‐DNA idiotypic antibody capable of blocking SLE anti‐DNA combining sites bound to Id+ affinity columns. Column eluates also showed some relative concentration of IgG anti‐DNA activity, which was of lower affinity for DNA than antibodies also present in eluates which blocked anti‐DNA combining sites.Conclusion. The presence of both anti‐DNA and antiidiotypic (anti‐combining site) activity in human anti‐DNA Id column eluates indicates that epibodies from IVGG are relatively concentrated when this strategy is used. This approach may lead to a new strategy for treatment of SLE nephritis.
Expression OF membrane type 1 matrix metalloproteinase in human articular cartilage
Authors: Büttner Frank H. , Chubinskaya Susan , Margerie Daniel , Huch Klaus , Flechtenmacher Johannes , Cole Ada A. , Kuettner Klaus E. , Bartnik Eckart 
Published: February 2007

AbstractObjective. To detect the message for membrane type 1 (MT1) matrix metalloproteinase (MMP) in articular cartilage and chondrosarcoma cells, to study its expression in osteoarthritis (OA), and to determine whether interleukin‐1β (IL‐1β) influences its expression.Methods. Reverse transcription–polymerase chain reaction methods were used to detect message. Cloning and sequencing were applied to confirm the sequence. Northern blotting was used to quantify the message for MT1‐MMP and to compare its expression in OA cartilage with or without IL‐1β treatment. In situ hybridization was utilized to show MT1‐MMP transcripts in cartilage and to study the influence of IL‐1β.Results. The results show that MT1‐MMP messenger RNA (mRNA) is expressed in chondrosarcoma cells and OA chondrocytes. Results of the in situ hybridization confirmed the expression in OA cartilage as well as in normal cartilage. The level of mRNA was not modulated following IL‐1β stimulation.Conclusion. This study shows that MT1‐MMP is expressed by chondrocytes. The similarities in mRNA levels in OA and normal chondrocytes suggest that regulation of MT1‐MMP mRNA may not be a primary factor in OA.
Racial differences in scleroderma among women in Michigan
Authors: Laing Timothy J. , Gillespie Brenda W. , Toth Mary B. , Mayes Maureen D. , Gallavan Robert H. , Burns Carol J. , Johanns Jewel R. , Cooper Brenda C. , Keroack Brian J. , Wasko Mary Chester M. , Lacey James V. , Schottenfeld David 
Published: February 2007

AbstractObjective.To examine racial differences in disease onset, extent, manifestations, and survival among women with scleroderma.Methods.A retrospective cohort study of women with scleroderma, diagnosed in Michigan between 1980 and 1991, was conducted. Clinical, laboratory, and demographic data were abstracted from the patients' medical records.Results.A total of 514 women with scleroderma were identified: 117 (23%) were black and 397 (77%) were white. Among black women, the mean age at diagnosis was lower (44.5 years versus 51.5 years;P< 0.001) and diffuse disease was more common (49.6% versus 24.9%;P< 0.001) than among white women. The overall incidence of scleroderma was 14.1 per million per year: 22.5 per million per year in black women versus 12.8 per million per year in white women (P< 0.001). Pericarditis (P= 0.009), pulmonary hypertension (P< 0.001), pleural effusions (P= 0.01), myositis (P= 0.02), and an erythrocyte sedimentation rate >40 mm/hour (P< 0.001) were more frequent among black women, while white women were more likely to have digital infarctions (P< 0.001). Survival at 7 years from diagnosis was 72.5% among black women and 77.6% among white women. Age‐adjusted survival was significantly reduced among black women (P= 0.033), most likely because of increased diffuse involvement. Survival among those with renal or pulmonary involvement was also significantly reduced.Conclusion.Black women with scleroderma were significantly more likely than white women to develop diffuse disease, be diagnosed at a younger age, have a higher incidence of inflammatory features, and have a worse age‐adjusted survival rate.
Primary juvenile fibromyalgia. Psychological adjustment, family functioning, coping, and functional disability
Authors: Reid Graham J. , Lang Bianca A. , McGrath Patrick J. 
Published: February 2007

AbstractObjectives. 1) To determine the importance of psychological adjustment and family functioning in primary juvenile fibromyalgia by assessing these factors in children with fibromyalgia and in their parents, compared with children with juvenile rheumatoid arthritis (JRA) and with pain‐free control children and their parents. 2) To examine which of these factors predict functional disability.Methods. Fifteen children in each of the 3 study groups, and their parents, completed self‐report questionnaires and pain diaries. A medical evaluation of each child was performed, including assessment of tender points by palpation and by dolorimetry.Results. All children in the fibromyalgia group met the Yunus and Masi criteria for fibromyalgia, and 11 met the American College of Rheumatology criteria. There were almost no significant group differences in the children's or parents' psychological adjustment, ratings of family functioning, or coping strategies. Significant group differences in functional disability, pain, fatigue, tender point threshold, and control point tolerance were found. A number of the psychological adjustment, pain, fatigue, and coping variables were significantly associated with functional disability.Conclusion. The notion that fibromyalgia is a psychogenic condition is not supported by these results. Fibromyalgia is associated with disability of a magnitude comparable to that of other chronic pain conditions. Disability among children with fibromyalgia or JRA is a function of the children's psychological adjustment and physical state, and of the parents' physical state and method of coping with pain.
Non‐Hodgkin's lymphoma and other cancers among a cohort of patients with systemic lupus erythematosus
Authors: Mellemkjér Lene , Andersen Vagn , Linet Martha S. , Gridley Gloria , Hoover Robert , Olsen Jørgen H. 
Published: February 2007

AbstractObjective. To investigate whether systemic lupus erythematosus (SLE) is associated with non‐Hodgkin's lymphoma or other malignant neoplasms.Methods. Data on a cohort of 1,585 patients with SLE from the nationwide Danish Hospital Discharge Register were linked to information in the Danish Cancer Registry to determine the occurrence of cancer during up to 15 years of followup. The expected number of cancers was calculated from accumulated person‐years and national cancer incidence rates.Results. There was a significant excess of non‐Hodgkin's lymphoma among the SLE patients, based on 8 cases observed against 1.5 expected (relative risk [RR] 5.2, 95% confidence interval 2.2–10.3). In addition, a significantly increased RR was found for cancer of the lung (RR 1.9; n = 15), the liver (RR 8.0; n = 5), and the vagina/vulva (RR 5.7; n = 3).Conclusion. There seemed to be a positive association between SLE and non‐Hodgkin's lymphoma. Other cancers with a possible virus‐related etiology, such as liver and vaginal/vulva cancer, were also observed in excess. In addition, there was an indication of an increased risk of lung cancer among patients who were hospitalized for SLE.
Azathioprine in Behçet's syndrome. Effects on long‐term prognosis
Authors: Hamuryudan Vedat , Özyazgan Yilmaz , Hizli Nail , Mat Cem , Yurdakul Sebahattin , Tüzün Yalçin , Şlenocak Mustafa , Yazici Hasan 
Published: February 2007

AbstractObjective. To assess the effect of azathioprine (AZA) treatment on long‐term prognosis in Behçet's syndrome.Methods. Patients (all male) who took part in a double‐blind, placebo‐controlled trial of AZA a mean ± SD of 94 ± 10 months previously were reevaluated.Results. The emergence of blindness (log rank χ2 = 5.6, P = 0.02) and a 2‐line drop in the visual acuity of the right eye (log rank χ2 = 5.9, P = 0.015) occurred significantly more frequently among the patients originally allocated to the placebo group compared with patients who originally received AZA, despite posttrial treatment for patients in both groups when needed. There was also a trend toward more frequent occurrence of extraocular complications in the placebo group. The beneficial effect of AZA was especially pronounced among patients who had eye involvement of short duration prior to their entry into the trial.Conclusion. Early treatment with AZA tends to favorably affect the long‐term prognosis of Behçet's syndrome.
Treatment of acquired factor VIII inhibitor using intravenous immunoglobulin in two patients with systemic lupus erythematosus
Authors: Lafferty Thomas E. , Smith J. Bruce , Schuster Stephen J. , Dehoratius Raphael J. 
Published: February 2007

AbstractAcquired inhibitors of factor VIII have rarely been reported in the presence of systemic lupus erythematosus (SLE). Treatment is usually corticosteroids, with or without immunosuppressive agents such as cyclophosphamide or azathioprine. We report here case histories of 2 patients, one with documented SLE, the other with a forme fruste of SLE. Both patients had inadequate responses to corticosteroids and immunosuppressive agents. Both responded to intravenous immunoglobulin, with a decrease in their titers of factor VIII inhibitor and significantly decreased frequency of bleeding episodes despite persistent low‐level inhibitor titers. Better control of their SLE symptoms and findings was also observed. Previously reported treatments of acquired factor VIII inhibitors in SLE are discussed.
In situ expression of B7 and CD28 receptor families in skin lesions of patients with lupus erythematosus
Authors: Denfeld Ralf W. , Kind Peter , Sontheimer Richard D. , Schöpf Erwin , Simon Jan C. 
Published: February 2007

AbstractObjective. To examine the expression of costimulatory molecules of the B7 and CD28 receptor families in active skin lesions of patients with systemic lupus erythematosus (SLE), subacute cutaneous lupus erythematosus (SCLE), and chronic discoid lupus erythematosus (CDLE).Methods. The in situ expression of B7‐1, B7‐2, BB‐1, and CD28 was studied by immunohistochemistry, and B7‐1 and B7‐2 RNA expression was examined by reverse transcription‐polymerase chain reaction.Results. Only in lesional skin from SLE, SCLE, and CDLE patients did dermal and epidermal antigenpresenting cells (APC) express B7‐1 and B7‐2, particularly when in apposition to CD28+ T cells. These B7‐1 + and B7‐2+ APC bound CTLA‐4 fusion protein. In lesional (but not in nonlesional) skin, keratinocytes expressed BB‐1. The majority of infiltrating T cells were CD28+. B7‐1 and B7‐2 RNA were expressed in lesional skin from SLE, SCLE, and CDLE patients; when dermis was separated from epidermis, only faint B7‐1 and B7‐2 RNA signals were detectable in the epidermis, indicating that dermal but not epidermal cells were the major source of B7‐1 and B7‐2 RNA. During treatment, both B7‐1 and B7‐2 protein and RNA expression were reduced.Conclusion. These in situ findings suggest that costimulation via the B7‐CD28 pathway may be important for the generation and/or propagation of T cell activity in skin lesions of humans with lupus erythematosus. Thus, the manipulation of this pathway (e.g., by CTLA‐4 fusion protein) could be an important target for the development of future therapies for LE.