bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeat treatment of Rheumatoid Arthritis patients with a murine anti‐intercellular adhesion molecule 1 monoclonal antibody
Authors: Kavanaugh Arthur F. , Schulze‐Koops Hendrik , Davis Laurie S. , Lipsky Peter E. 
Published: February 2007

AbstractObjective. To assess the safety and efficacy of a second course of treatment with a murine monoclonal antibody (MAb) to intercellular adhesion molecule 1 (ICAM‐1; CD54) in active rheumatoid arthritis (RA).Methods. In an open‐label study, 8 patients who had previously received a course of anti‐ICAM‐1 MAb received a second course.Results. The second course of therapy was associated with adverse effects suggestive of immune complex formation. Such adverse effects were not seen during the initial course of therapy. Clinical efficacy associated with the second course of therapy was less than that observed in the first course.Conclusion. Repeated courses of therapy with a murine MAb to ICAM‐1 would probably not be a useful therapeutic strategy in patients with RA, probably because of its immunogenicity.
Polymorphism of the HLA‐DMA and DMB genes in Rheumatoid Arthritis
Authors: Pinet Valérie , Combe Bernard , Avinens Odile , Caillat‐Zucman Sophie , Sany Jacques , Clot Jacques , Eliaou Jean‐François 
Published: February 2007

AbstractObjective. To determine whether the HLA‐DMA and DMB genes, whose encoded molecules are involved in HLA class II‐restricted antigen presentation, contribute to the genetic susceptibility to rheumatoid arthritis (RA).Methods. One hundred ninety‐one RA patients, 147 control subjects, and 218 HLA‐DRBI genotypematched control subjects were oligotyped for DMA and DMB genes.Results. DMA*0103 and DMB*0104 were significantly increased in the RA patients compared with the randomly selected and the matched controls, thus indicating a direct influence of the DM genes. After stratification of the patients and matched controls according to DRB1 genotypes, only DMA*0103 was increased in the RA patients with DRB1*01, as well as in the patients negative for the RA‐susceptibility DR alleles.Conclusion. Our results suggest that DMA*0103 could play an additional role in the genetic susceptibility to RA.
Henoch‐Schönlein purpura in adulthood and childhood. Two different expressions of the same syndrome
Authors: Blanco Ricardo , Martínez‐Taboada Víctor M. , Rodríguez‐Valverde Vicente , García‐Fuentes Miguel , Gonzalez‐Gay Miguel A. 
Published: February 2007

AbstractObjective. To assess the possible differences between children (⩽ 20 years) and adults (> 20 years) with Henoch‐Schönlein purpura (HSP).Methods. A retrospective study of an unselected population of patients with HSP who presented to our teaching hospital between 1975 and 1994. Patients were classified as having HSP according to the criteria proposed by Michel et al.Results. Following the above‐mentioned criteria, 162 white patients (113 male and 49 female) were classified as having HSP; 46 of the patients were adults (mean ± SD age 53.2 ± 16.9 years) and 116 were children (6.9 ± 3.1 years). We were unable to identify any precipitating event in 72% of the adults and 66% of the children. The frequency of previous drug treatment, primarily antibiotics or analgesics, was similar in both groups, whereas previous upper respiratory tract infection was more frequent among the children (P < 0.02). At symptom onset, cutaneous lesions were the main clinical manifestation in both groups. However, adults had a lower frequency of abdominal pain (P < 0.008) and fever (P < 0.01), and a higher frequency of joint symptoms (P < 0.001). During the clinical course, adults had more frequent (P < 0.001) and severe renal involvement. An increased erythrocyte sedimentation rate was also more frequent in the adults (P < 0.001). Adults required more aggressive therapy, consisting of steroids (P < 0.002) and/or cytotoxic agents (P < 0.001).The outcome was relatively good in both age groups, with complete recovery in 107 children (93.9%) and in 33 adults (89.2%) after a mean ± SD followup of 19.4 ± 27.7 (median 12) and 21.8 ± 33.5 (median 15) months, respectively.Conclusion. In adulthood, HSP, as defined by the criteria proposed by Michel et al, represents a more severe clinical syndrome, with a higher frequency of renal involvement. However, the final outcome of HSP is equally good in patients of both age groups.
Cytokine production in muscle tissue of patients with idiopathic inflammatory myopathies
Authors: Lundberg Ingrid , Ulfgren Ann‐Kristin , Nyberg Pernilla , Andersson Ulf , Klareskog Lars 
Published: February 2007

AbstractObjective. To study cytokine expression in muscle tissues of patients with inflammatory myopathies and to compare the profiles of patients with polymyositis (PM), inclusion body myositis (IBM), and dermatomyositis (DM).Methods. We performed indirect immunohistochemistry studies of muscle tissue sections with a panel of 16 different cytokine‐specific monoclonal antibodies, directed against interleukin‐1α, (IL‐1α), IL‐1β, IL‐1 receptor antagonist (IL‐1ra), IL‐2, IL‐3, IL‐4, IL‐6, IL‐8, IL‐10, IL‐13, interferon‐γ (IFNγ), tumor necrosis factor α (TNFα), granulocyte‐macrophage colonystimulating factor (GM‐CSF), transforming growth factor β1 (TGFß1), TGFß2, and TGFß3 in 5 untreated patients each with PM, DM, and IBM and in 4 normal controls. Fresh frozen muscle tissue sections were fixed in formaldehyde before the procedure. The use of saponin as a detergent to permeabilize the cell membranes enabled identification of intracellular cytokine production.Results. The most prominent finding was the expression of IL‐1α observed in all patients but in none of the normal controls. In all patients with PM, DM, and IBM, IL‐1α was expressed in endothelial cells of capillaries, arterioles, and venules in areas surrounded by inflammatory cells, and also in areas with no or scarce inflammatory cells in both endomysium and perimysium. Furthermore, IL‐1α was also expressed in mononuclear inflammatory cells in all 15 cases. IL‐1β was observed in inflammatory cells in 10 of the 15 patients but, in contrast to IL‐1α, it was not expressed in blood vessel walls. TGFß1, TGFß2, and TGFß3 were strongly positive in all 15 patients, but only scattered cells were positive in the normal controls. The remaining cytokines were observed only in relatively few cells and only in occasional patients (although the patients were selected for the presence of large infiltrates), and in none of the controls. The patterns were similar in PM, DM, and IBM.Conclusion. Cytokine expression in muscle tissue of patients with inflammatory myopathy is dominated by IL‐1α, IL‐1β, and TGFß1–3. The predominant IL‐1α expression in the blood vessels indicates an importance of the endothelial cells in the inflammatory process in PM, IBM, and DM. A sustained, local release of T cell‐derived cytokines may not be a requirement for tissue injury in the inflammatory myopathies. There does not appear to be a qualitative difference in cytokine expression patterns in PM, IBM, and DM.
The outcome of bacterial arthritis. A prospective community‐based study
Authors: Kaandorp Carola J. E. , Krijnen Pieta , Moens Hein J. Bernelot , Habbema J. Dik F. , van Schaardenburg Dirkjan 
Published: February 2007

AbstractObjective. To assess the outcome and adverse prognostic factors of bacterial arthritis (BA).Methods. In a prospective community survey of BA, data were collected at the time of diagnosis and at a mean of 2 years later. A poor patient outcome was defined as death due to BA or severe overall functional deterioration. A poor joint outcome was defined as amputation, arthrodesis, prosthetic surgery, or severe functional deterioration. Possible prognostic factors were analyzed by univariate analysis.Results. BA was diagnosed in 154 patients, 121 adults and 33 children. One‐half of the adults had a preexisting joint disease and 29% of the infected joints contained synthetic material. The patient outcome was poor in 21% of all patients, and the joint outcome was poor in 33% of the surviving patients. Adverse prognostic factors were an older age, preexisting joint disease, and an infected joint containing synthetic material. These factors were interrelated. There was no association between a poor outcome and young age, comorbidity, immunosuppressive medication, functional class, multiple infected joints, type of microorganism, or treatment delay.Conclusion. BA had a poor outcome in almost one‐half of the patients. Patients who were older, had a preexisting joint disease, and/or had an infected joint containing synthetic material had the poorest prognosis.
Induction of apoptosis in peripheral blood lymphocytes following treatment in vitro with hydroxychloroquine
Authors: Meng Xue Wei , Feller John M. , Ziegler John B. , Pittman Sally M. , Ireland Christine M. 
Published: February 2007

AbstractObjective. Defective regulation of apoptosis may be central to the development of autoimmune disorders. This study investigated the possibility that the antirheumatic effect of hydroxycholoroquine (HCQ) may be achieved by up‐regulation of apoptosis.Methods. Peripheral blood lymphocytes collected from normal controls and patients with systemic lupus erythematosus (SLE) were cultured in the presence or absence of a range of concentrations of HCQ. Cells undergoing apoptosis were identified by several standard methods, including morphologic changes, DNA fragmentation, and flow cytometry. For some experiments, lymphocytes were simultaneously stained with antibodies to T cell surface markers and with propidium iodide for dual‐stain flow cytometric studies.Results. HCQ was able to induce apoptosis in peripheral blood lymphocytes in a dose‐ and time‐dependent manner. HCQ induced these changes in all T cell subpopulations studied. There was no significant difference between the controls and patients with SLE in terms of the percentage of apoptotic cells detected following treatment with HCQ.Conclusion. The present study demonstrated that HCQ induces apoptosis in peripheral blood lymphocytes, which leads to the speculation that HCQ may exert its antirheumatic effect through this mechanism.
The 52‐kd protein as a target of intermolecular spreading of the immune response to components of the SS‐A/Ro‐SS‐B/La complex
Authors: Tseng Chung‐E , Chan Edward K. L. , Miranda Eugenia , Gross Michael , Donato Francis Di , Buyon Jill P. 
Published: February 2007

AbstractObjective. To determine whether immunization of healthy non‐autoimmune mice with 52‐kd SS‐A/Ro induces a secondary antibody response to other components of the 48‐kd SS‐B/La‐60‐kd SS‐A/Ro RNP complex and vice versa, since anti‐52‐kd antibodies have been invariably linked to these antigens in patients with Sjögren's syndrome and in mothers whose children have neonatal lupus.Methods. Female BALB/c mice were immunized with 100 μg of 6 × His recombinant human 48‐kd SS‐B/La, 52‐kd SS‐A/Ro, or 60‐kd SS‐A/Ro proteins, or the 6 × His polypeptide control, each purified by Ni2+ affinity chromatography. Mice subsequently received booster injections with 50 μg of the same antigen every 10–21 days. Immune responses were measured by enzyme‐linked immunosorbent assay (ELISA), immunoblotting of recombinant antigens, and immunoprecipitation of 35S‐methionine‐labeled in vitro translation products.Results. Immunization with 48‐kd SS‐B/La resulted in anti‐48‐kd SS‐B/La antibodies within 45 days, followed 10 days later by a secondary response to 52‐kd SS‐A/Ro, as measured by ELISA. Antibody spreading to 60‐kd SS‐A/Ro was not detected. Immunization with 52‐kd SS‐A/Ro resulted in rapid high‐titer anti‐52‐kd SS‐A/Ro responses within 27 days. Spreading to 48‐kd SS‐B/La occurred in only 1 mouse and 60‐kd SS‐A/Ro was detected in a minority of the mice after prolonged antigen exposure. Immunization with 60‐kd SS‐A/Ro led to anti‐60‐kd SS‐A/Ro responses within 37 days, followed 3 months later by low‐titer anti‐48‐kd SS‐B/La and anti‐52‐kd SS‐A/Ro antibodies. All primary immune responses were confirmed by immunoblotting and immunoprecipitation. While immunoblotting of the recombinant proteins revealed reciprocal intermolecular spreading in the majority of mice, immunoprecipitation clearly demonstrated that predominant spreading was generated after immunization with 48‐kd SS‐B/La, which consistently resulted in antibodies to 52‐kd SS‐A/Ro.Conclusion. The murine responses observed in the present study, demonstrating reciprocal intermolecular spreading to 48‐kd SS‐B/La, 52‐kd SS‐A/Ro, and 60‐kd SS‐A/Ro, support the linkage of 52‐kd SS‐A/Ro with the other proteins, despite their as‐yet‐undetected association in vivo. The marked recruitment of anti‐52‐kd SS‐A/Ro responses elicited by 48‐kd SS‐B/La may provide a lead to exploring the physical interaction, direct or indirect, of 52‐kd SS‐A/Ro with the SS‐A/Ro‐SS‐B/La RNP particle and its presentation to the immune system. These data should facilitate the establishment of a murine model of neonatal lupus.
Multiple congenital anomalies associated with weekly low‐dose methotrexate treatment of the mother
Authors: Buckley Lenore M. , Bullaboy Charles A. , Leichtman Lawrence , Marquez Mariella 
Published: February 2007

AbstractThis report describes an infant with multiple congenital anomalies born to a 20‐year‐old mother with juvenile rheumatoid arthritis who had been taking weekly low‐dose methotrexate (MTX) during the first trimester of pregnancy. The abnormalities found were consistent with those associated with maternal ingestion of MTX at dosage levels used to induce abortions, i.e., the group of abnormalities referred to as the “aminopterin syndrome.” Although weekly low‐dose MTX has been associated with spontaneous abortions, this is, to our knowledge, the first case report describing multiple congenital abnormalities consistent with MTX embryopathy secondary to weekly low‐dose MTX treatment.
Changes in messenger rna and protein levels of proteoglycans and link protein in human osteoarthritic cartilage samples
Authors: Cs‐Szabó Gabriella , Melching Lee I. , Roughley Peter J. , Glant Tibor T. 
Published: February 2007

AbstractObjective. To determine the steady‐state messenger RNA (mRNA) levels and corresponding protein contents of major matrix components in osteoarthritic (OA) cartilage.Methods. Steady‐state levels of gene‐specific mRNA (relative to GAPDH) were measured by quantitative polymerase chain reaction (PCR), and the relative levels of the corresponding proteins were determined by Western blotting.Results. All mRNA levels and corresponding protein contents of aggrecan and versican (hyaluronan‐binding large proteoglycans), decorin, biglycan, fibromodulin, and lumican (small proteoglycans), and link protein were higher in OA cartilage samples than in age‐matched normal samples. The ratio of increase, however, was different for each component. The mRNA and protein levels of biglycan, decorin, and fibromodulin increased synchronously, whereas message for link protein and lumican were several‐fold higher than expected by their measured protein contents. Versican was also detected in OA cartilage; however, the versican protein content was associated with a relatively low mRNA level.Conclusion. The expression of matrix components was increased in chondrocytes of OA cartilage, especially the expression of small proteoglycans, most likely due to the repair processes. A discoordinate gene expression accompanied with imbalanced accumulation of noncollagenous matrix components may contribute to the disorganization of the cartilage and the development of OA processes.
The influence of silicone implantation on type II collagen‐induced arthritis in mice
Authors: Schaefer Caralee J. , Whalen Janey D. , Knapp Terry , Wooley Paul H. 
Published: February 2007

AbstractObjective. To determine whether silicone implantation exacerbates autoimmune disease in a murine experimental model of arthritis.Methods. DBA/1 mice were implanted with silicone in the form of an elastomer, gel, or oil, and immunized with type II collagen. The influence of silicone implantation on collagen‐induced arthritis and the immune response to type II collagen were determined by comparison against control mice receiving sham implantation. Adjuvant effects of silicone implantation were examined by measuring cytokine levels in implanted animals and assessing autoantibodies against proteins extracted from recovered silicone implants.Results. No adverse influence of silicone implantation on the clinical aspects of collagen‐induced arthritis was observed. Further, polydimethylsiloxane silicone oil failed to serve as an adjuvant in the immune or arthritogenic response to type II collagen in mice. Cytokine analysis indicated that tumor necrosis factor α levels were lower and interleukin‐2 levels were higher in silicone‐implanted mice. The development of arthritis increased protein binding to implanted elastomers and gel, and autoantibodies against silicone‐bound proteins were present in sera from arthritic mice and absent in sera from nonarthritic mice.Conclusion. The data suggest that silicone implantation may result in autoantibodies against silicone‐bound proteins, and the presence of arthritis may either provoke or increase the level of such autoantibodies. However, silicone implantation did not increase the incidence or severity of disease compared with sham‐operated controls. Thus, it appears that autoantibodies against silicone‐bound proteins may not have pathologic significance in this experimental model of arthritis.
Paclitaxel selectively induces mitotic arrest and apoptosis in proliferating bovine synoviocytes
Authors: Hui A. , Kulkarni G. V. , Hunter W. L. , McCulloch C. A. G. , Cruz T. F. 
Published: February 2007

AbstractObjective. Rheumatoid arthritis (RA) is characterized by chronic progressive destruction of joints involving several disease processes, such as villous hypertrophy, proliferation of synovial lining cells, and infiltration of inflammatory cells. Synovial cell activation and proliferation is thought to be a key step in the destruction of cartilaginous and bony tissues in RA joints. In view of the invasive properties of synoviocytes in RA, we conducted in vitro studies to determine the mechanism of action of paclitaxel (Taxol) on synoviocytes, which may account for the inhibition of joint destruction found when this agent is administered.Methods. Cultured synovial cells were treated with various concentrations of paclitaxel and were evaluated by cell viability, fluorescence microscopy, flow cytometry of DAPI‐stained cells, and electron microscopy.Results. The data indicated that paclitaxel inhibited synoviocyte proliferation by a G2/M phase block and was toxic to synoviocytes by inducing apoptosis. Confluent cells such as chondroyctes and synoviocytes were not affected by paclitaxel. Synchronization of synovioyctes at the G1/S boundary effectively abolished paclitaxel‐induced apoptosis.Conclusion. The data indicate that induction of apoptosis in synoviocytes might be dependent on transit through the cell cycle, specifically through G2 and mitosis. Further, paclitaxel was selectively toxic to proliferating synoviocytes but spared nonproliferating synoviocytes and chondrocytes. These results demonstrate that paclitaxel can inhibit synovial cell proliferation and pannus formation in RA joints in vivo. We suggest that paclitaxel be considered as a prototypical compound for a new class of potential chondroprotective agents.
Soluble Fas (APO‐1, CD95) and soluble Fas ligand in rheumatic diseases
Authors: Nozawa Kazuhisa , Kayagaki Nobuhiko , Tokano Yoshiaki , Yagita Hideo , Okumura Ko , Hasimoto Hiroshi 
Published: February 2007

AbstractObjective. To assess levels of soluble Fas (sFas) and soluble Fas ligand (sFas‐L) in sera from patients with various rheumatic diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), mixed connective tissue disease (MCTD), and Sjögren's syndrome (SS).Methods. Levels of sFas and sFas‐L were determined by a sandwich enzyme‐linked immunosorbent assay.Results. In SLE, PM/DM, MCTD, and SS, sFas levels were significantly higher compared with normal controls. Levels of sFas in the SLE patients were significantly higher than in patients with other rheumatic diseases. Levels of sFas‐L were significantly increased in SS patients. SLE and RA patients with high levels sFas‐L tended to have high levels of sFas, while sFas and sFasL levels did not correlate in patients with other diseases. In some of the SLE patients, sFas and sFas‐L levels decreased following steroid therapy.Conclusion. Serum sFas and sFas‐L levels were significantly higher in some rheumatic disease patients. Since these changes are complex in these rheumatic diseases, it may be difficult to directly relate sFas and sFasL to their pathogenesis.
Epstein‐Barr virus strain type and latent membrane protein 1 gene deletions in lymphomas in patients with rheumatic diseases
Authors: Natkunam Yasodha , Elenitoba‐Johnson Kojo S. , Kingma Douglas W. , Kamel Onsi W. 
Published: February 2007

AbstractObjective. Recent studies have shown that immunomodulatory therapy for the treatment of rheumatic diseases can be associated with the development of Epstein‐Barr virus (EBV)‐associated lymphoproliferative disorders. The present study was undertaken to determine the strain type of EBV in lymphoproliferative disorders that occur in patients with rheumatic disease and to investigate EBV latent membrane protein 1 (LMP‐1) gene deletions that occur in these lymphoproliferative disorders.Methods. Ten EBV‐associated lymphoid neoplasms in patients with rheumatoid arthritis or dermatomyositis were analyzed by polymerase chain reaction to determine EBV strain type and to investigate for the presence of a previously characterized 30‐basepair deletion in the LMP‐1 gene.Results. The results indicated that lymphoproliferative disorders in these patients can harbor EBV strain type A or B, with a predominance of type A infection (80%). It was also shown that both wild‐type and mutated LMP‐1 genes can be found in these neoplasms, with the deleted form of the LMP‐1 gene occurring in one‐third of cases in this series.Conclusion. LMP‐1 deletions associated with certain aggressive lymphoid neoplasms are not required for the genesis of lymphoproliferative disorders in patients with rheumatic disease. The relative frequencies of type A and type B EBV strains in these lymphoproliferative disorders show similarities to the frequencies in patients with post‐solid organ transplantation immunosuppression‐associated lymphoproliferative disorders.
Small fiber neuropathy and vasculitis
Authors: Lacomis David , Giuliani Michael J. , Steen Virginia , Powell Henry C. 
Published: February 2007

AbstractVasculitis‐associated neuropathy usually presents as multiple mononeuropathies or sensorimotor polyneuropathies that affect large nerve fibers; painful small fiber sensory neuropathy has not previously been described in association with vasculitis. This report describes 2 patients with small fiber neuropathy in whom vasculitis was found to be present. Patients with small fiber neuropathy for which no other cause has been identified should be evaluated for the presence of vasculitis.