bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term iloprost infusion therapy for severe pulmonary hypertension in patients with connective tissue diseases
Authors: Mata Jose De La , Gomez‐Sanchez Miguel A. , Aranzana Mercedes , Gomez‐Reino Juan J. 
Published: February 2007

AbstractObjective. To determine the effects of short‐term, maximum‐tolerated‐dose and long‐term, optimum‐dose iloprost treatment of severe pulmonary hypertension associated with systemic sclerosis (SSc) and the primary antiphospholipid syndrome (APS).Methods. Three patients with SSc and 2 with APS who had failed to respond to oral vasodilator therapy for pulmonary hypertension were enrolled in a 32‐week, open, prospective trial. Short‐term infusion of maximum‐tolerated doses and continuous infusion of optimum doses of iloprost were carried out following baseline cardiac catheterization. Catheterization was repeated at 2 and 32 weeks. All 5 patients completed the study and continued therapy for an average of 82 weeks (range 58–103).Results. Acute infusion of maximum tolerated doses significantly ameliorated the cardiac index (0.92 liters/minute/m2; P < 0.01), pulmonary artery O2 saturation (10.6%; P < 0.05), and pulmonary resistance (−6.7 units; P < 0.05). After 2 weeks of continuous infusion of optimum doses, there was improvement in pulmonary resistance (⩾16%) and pulmonary artery O2 saturation ( > 30%) in the 2 patients with primary APS. After 2 and 32 weeks, the 3 SSc patients showed variable hemodynamic responses. New York Heart Association functional class and exercise tolerance improved in all patients. There was 1 episode of bacteremia, and 1 patient died after 72 weeks of study.Conclusion. Continuous iloprost infusion may improve exercise tolerance and quality of life in patients with severe pulmonary hypertension associated with SSc and primary APS.
A broadened spectrum of juvenile myositis. myositis‐specific autoantibodies in children
Authors: Rider Lisa G. , Miller Frederick W. , Targoff Ira N. , Sherry David D. , Samayoa Eduardo , Lindahl Madeleine , Wener Mark H. , Pachman Lauren M. , Plotz Paul H. 
Published: February 2007

AbstractObjective. Myositis‐specific autoantibodies (MSA) define relatively homogenous clinical and immunogenetic patient groups in adults with idiopathic inflammatory myopathies (IIM). This study explores the usefulness of MSA in defining groups of children with myositis.Methods. Sera from 77 children with myositis and other connective tissue diseases were tested for MSA by immunoprecipitation and immunodiffusion. Clinical data were collected and analyzed.Results. The MSA anti‐PL‐12 (alanyl‐transfer RNA synthetase), anti‐Jo‐1 (histidyl‐tRNA synthetase), anti‐signal recognition particle, and anti‐Mi‐2 were each identified in the sera of 12 children with IIM. In these patients, the clinical manifestations, disease courses, and responses to therapy closely resembled those in adults with the same autoantibodies.Conclusion. These observations suggest that the clinical syndromes defined by particular MSA are similar in children and adults with IIM. By defining similar clinical syndromes in children who have MSA, this study provides a basis for future studies of MSA in the idiopathic inflammatory myopathies of childhood, which may be useful in predicting the clinical courses of a subset of these patients and improving their therapy.
Thoracic aortic aneurysm and rupture in giant cell arteritis. a descriptive study of 41 cases
Authors: Evans Jonathan M. , Bowles Carolyn A. , Bjornsson Johannes , Mullany Charles J. , Hunder Gene G. 
Published: February 2007

AbstractObjective. To determine the features and outcomes of patients with giant cell arteritis (GCA) who have aneurysms or rupture of the thoracic aorta.Methods. Patients with GCA seen over a 40‐year period who had aneurysms and/or rupture of the thoracic aorta were identified by assistance of a computerized indexing system. The presence of thoracic aortic aneurysms (TAA), with or without aortic valve insufficiency (AI), was determined by radiographs, computed tomography scans, and ultrasound studies of the thorax, angiograms of the aorta, and postmortem examination.Results. Ten men and 31 women with GCA were found to have TAA and/or rupture. Three developed TAA before GCA was diagnosed, 5 developed aortic findings near the time of the diagnosis, and 33 after the diagnosis of GCA (median of 7 years after diagnosis). Sixteen patients developed acute aortic dissection, which caused death in 8. Nineteen patients also had AI due to aortic root dilation, 15 of whom developed congestive heart failure. Eighteen patients underwent 21 surgical procedures for TAA resection and/or aortic valve replacement or repair. Aortitis was documented histologically in 10 cases.Conclusion. Thoracic aortic complications in GCA are associated with serious outcomes that have been underrecognized and may be fatal. Physicians should be alert to the development of these complications at any time in the course of GCA, even many years after usual symptoms have subsided.
Systemic lupus erythematosus presenting as a non‐o:1 vibrio cholerae abscess
Authors: Nedunchezian Deeptha , Cook Michael A. , Rakic Milovan 
Published: February 2007

AbstractThe usual presentations and manifestations of systemic lupus erythematosus (SLE) are well known. We describe a patient with SLE that was discovered in the course of evaluation of an abscess, found to be associated with non‐O:1 Vibrio cholerae.
Elevated cerebrospinal fluid levels of substance p in patients with the fibromyalgia syndrome
Authors: Russell I. Jon , Orr Malcolm D. , Littman Bruce , Vipraio Gilbert A. , Alboukrek David , Michalek Joel E. , Lopez Yolanda , Mackillip Fane 
Published: February 2007

AbstractObjective. To measure, and seek clinical correlates with, levels of substance P (SP) in the cerebrospinal fluid (CSF) of fibromyalgia syndrome (FMS) patients.Methods. CSF from 32 FMS patients and 30 normal control subjects was tested for SP by radio‐immunoassay. Clinical measures included tender point examination and standardized questionnaires.Results. CSF SP levels were 3‐fold higher in FMS patients than in normal controls (P < 0.001), but they correlated only weakly with tenderness found on examination.Conclusion. SP is significantly elevated in FMS CSF, but other abnormalities must exist in FMS to more fully explain the symptoms.
Magnetic resonance imaging in systemic lupus erythematosus patients without a history of neuropsychiatric lupus erythematosus
Authors: Jarek Mark J. , West Sterling G. , Baker Michael R. , Rak Kevin M. 
Published: February 2007

AbstractObjective. To determine the prevalence of magnetic resonance imaging (MRI) lesions in systemic lupus erythematosus (SLE) patients without a history of neuropsychiatric symptoms and to correlate any MRI abnormalities with the patient's other disease manifestations or treatment.Methods. Prospective study of 32 consecutive patients with SLE without a history of neuropsychiatric symptoms, from inpatient and outpatient rheumatology services, who underwent MRI scan during a 3‐year period.Results. Five patients had MRI abnormalities consisting of white matter lesions or periventricular hyperintensities; this is similar to the prevalence of these abnormalities in the general population.Conclusion. The prevalence of silent brain MRI abnormalities is not increased in SLE patients who do not have a history of neuropsychiatric manifestations.
Increased usage of vβ2 and vβ6 in rheumatoid synovial fluid t cells
Authors: Cooper Sheldon M. , Roessner Karen D. , Naito‐Hoopes Mikako , Howard Diantha B. , Gaur Lakshmi K. , Budd Ralph C. 
Published: February 2007

AbstractObjective. To determine if the T cell antigen receptor Vβ usage of unstimulated rheumatoid arthritis (RA) synovial fluid (SF) T cells is biased compared with those in peripheral blood (PB).Methods. Freshly isolated, matched synovial fluid and peripheral blood T cells were analyzed for Vβ gene expression using quantitative polymerase chain reaction (PCR) methods. Ten synovial fluid samples from the knees of 7 patients with RA were studied. The PCR assay used 26 Vβ primers with a constant region Cβ primer, and 2 Cα primers that co‐amplified a product that served as an internal standard. Cycle number and complementary DNA content were controlled to ensure the linear accumulation of PCR products. Labeled products were separated on 10% polyacrylamide gels and counted with a Betascope blot analyzer.Results. There were consistent differences between the Vβ gene usage of SF and PB T cells directly isolated from patients with RA, regardless of HLA–DR haplotype. In all synovial specimens, Vβ2 was increased relative to the peripheral blood, while Vβ13.1 and Vβ13.2 were decreased. Vβ6 and Vβ21 were increased in 9 of the 10 synovial samples. Analyses of bilateral SF specimens from 2 subjects and serial specimens from the same knee of 1 subject revealed virtually identical patterns in each patient. The SF Vβ bias was not solely due to differences in the proportion of CD4+ and CD8+ cells, because the CD4:CD8 ratios in SF and PB were similar. However, Vβ gene usage of separated CD4+ and CD8+ synovial T cells showed that Vβ2 and Vβ6 were more highly expressed on CD4 cells.Conclusion. Freshly isolated synovial T cells from inflamed (not end‐stage) knees of patients with RA have a remarkably consistent biased Vβ gene usage compared with PB T cells. Vβ2 and Vβ6 are uniformly increased, and this increase is primarily in CD4+ T cells. The same Vβ bias in the SF T cells of several RA patients suggests that shared antigens may be stimulating the T cell response.
Elevated expression of cd80 (b7/bb1) and other accessory molecules on synovial fluid mononuclear cell subsets in rheumatoid arthritis
Authors: Ranheim Erik A. , Kipps Thomas J. 
Published: February 2007

AbstractObjective. To assess the expression of important accessory molecules such as CD80 (B7/BB1) and CD54 (intercellular adhesion molecule 1) on potential antigen‐presenting cells (APC) in the synovial fluid (SF) of patients with rheumatoid arthritis (RA).Methods. The level of expression of various accessory molecules on T cells, monocytes, and CD5+ or CD5– B cells from RA SF was compared, by multiparameter flow cytometric analysis, with the expression on peripheral blood (PB) mononuclear cells from the same patients and from normal controls. The functional significance of increased expression of these accessory molecules was assessed by the ability of the different cell populations to stimulate T cells in the mixed lymphocyte reaction.Results. Monocytes, T cells, and B cells isolated from the SF of inflamed joints of patients with RA expressed significantly higher levels of CD80 and CD54 than those from the PB of RA patients or normal controls. CD11b and CD11c expression also were increased on SF B cells, while SF monocytes exhibited enhanced levels of CD40. Further, we found that the elevated CD80 and CD54 levels in RA SF cells may enhance the capacity of these cells to act as stimulatory APC.Conclusion. This is the first demonstration that specific cell subsets constitutively express increased levels of CD80 at a site of autoimmune pathology, which could potentially contribute to the initiation or maintenance of autoimmune disease.
Inhibition of human fibroblast adhesion by cartilage surface proteoglycans
Authors: Noyori Koji , Jasin Hugo E. 
Published: February 2007

AbstractObjective. Recent studies from our laboratory have identified the nonaggregating, collagen‐binding proteoglycans, fibromodulin (FM) and decorin, and fibronectin (Fn) and albumin, noncovalently bound at the articular surface of cartilage. The present studies were designed to investigate the interactions between these cartilage macromolecules and the underlying collagen matrix and their role as a barrier to cell adhesion in intact articular cartilage.Methods. Cell adhesion studies were carried out with human skin fibroblasts incubated on the articular surface of bovine cartilage explants and on collagencoated and/or Fn‐coated plastic surfaces. Interactions of collagen and Fn with either FM or decorin were studied by radioimmunoassay of the same surfaces, using specific antibodies.Results. The present studies show that 1) Fn is immunologically detectable at the intact articular surface of cartilage; 2) fibroblast adhesion to Fn is inhibited by cartilage surface extract proteins and by purified FM, but not by purified decorin; 3) FM has binding affinity for Fn; 4) FM interferes with the binding of a monoclonal antibody specific for the cell‐binding domain of Fn; and 5) FM and decorin inhibit collagendependent fibroblast adhesion.Conclusion. These results indicate that the small proteoglycans at the normal articular surface may act as a barrier to cell adhesion. Since protective cartilage surface proteins break down readily after the induction of acute arthritis in experimental animals, and in rheumatoid cartilage specimens, it is postulated that proteolytic degradation of the surface proteoglycans may be responsible for increasing cell adhesion to, and subsequent pannus invasion of, articular cartilage in inflammatory arthritis.
A new model for rheumatoid arthritis generated by engraftment of rheumatoid synovial tissue and normal human cartilage into scid mice
Authors: Geiler Thomas , Kriegsmann JÖUrg , Keyszer Gernot M. , Gay Renate E. , Gay Steffen 
Published: February 2007

AbstractObjective. A new animal model was used to study the interaction between rheumatoid synovial cells and cartilage and to explore the cellular basis of rheumatoid joint destruction.Methods. Fresh synovial tissue derived from patients with rheumatoid arthritis was implanted with normal human cartilage into SCID mice, either subcutaneously or under the renal capsule, for up to 304 days. The implants were analyzed by light and electron microscopy, as well as by immunohistochemistry and in situ hybridization.Results. Human synovial tissue and cartilage implanted in SCID mice are maintained by the animals for up to 304 days. After 35 days, focal erosions occur at the site of attachment of synovial lining cells to the cartilage. After 105 days, a pannus‐like formation, consisting of proliferating synovial fibroblast‐like cells invading the cartilage, is observed. The fibroblast nature of these cells was supported by observation of only focal expression of the macrophage markers CD14 and CD68. Cells at the immediate site of cartilage destruction express messenger RNA for cathepsin L, whereas cathepsin D messenger RNA was detected in subsynovial regions away from the site of destruction. The human origin of the tissue involved in cartilage destruction was demonstrated using monoclonal antibodies to HLA‐ABC and human type IV collagen.Conclusion. The present approach introduces a novel in vivo model of rheumatoid arthritis for the study of the molecular and cellular mechanisms of rheumatoid joint destruction at sites of synovial attachment to cartilage. In this model, the SCID mouse acts as a useful host for studying the properties of rheumatoid synovium in the absence of circulating human blood components.
Nucleosome‐restricted antibodies are detected before anti‐dsdna and/or antihistone antibodies in serum of mrl‐mp lpr/lpr and +/+ mice, and are present in kidney eluates of lupus mice with proteinuria
Authors: Amoura Zahir , Chabre Henri , Koutouzov Sophie , Lotton Chantal , Cabrespines Alban , Bach Jean‐Françlois , Jacob Laurent 
Published: February 2007

AbstractObjective. To compare the humoral response to nucleosomes with the response to their individual components (double‐stranded DNA [dsDNA] and histones) and to assess the involvement of antinucleosome antibodies in immune deposits in the kidney of MRL mice.Methods. We used enzyme‐linked immunosorbent assays of sera and kidney eluates for antibody activity against purified nucleosomes, dsDNA, and histones.Results. Antinucleosome antibodies emerged before anti‐dsDNA and antihistone antibodies. A fraction of antinucleosome antibodies reacted exclusively with nucleosomes and not with their components, dsDNA and histones. These nucleosome‐restricted antibodies were detected in the proteinuric MRL mouse kidney eluate.Conclusion. Our findings support the notion that nucleosomes play a major role in the emergence of antinuclear autoantibodies and that antinucleosome antibodies might be involved in the nephritogenic process in murine lupus.
Concentration of autoantibodies to native 60‐kd ro/ss‐a and denatured 52‐kd ro/ss‐a in eluates from the heart of a child who died with congenital complete heart block
Authors: Reichlin Morris , Brucato Antonio , Frank Mark B. , Maddison Peter J. , Mccubbin Victoria R. , Wolfson‐Reichlin Marianne , Lee Lela A. 
Published: February 2007

AbstractObjective. To determine the serologic specificity of acid eluates from tissues of a child who died with congenital complete heart block (CCHB).Methods. Tissues were extracted, acid eluted, and the IgG and antibody titers determined on the eluates by enzyme‐linked immunosorbent assay.Results. Antibodies to native 60‐kd and denatured 52‐kd Ro/SS‐A were found to be enriched only in the heart eluate, and not in the eluates from brain, kidney, and skin.Conclusion. These findings indicate a major role for anti–native 60‐kd Ro/SS‐A in the immunopathogenesis of CCHB.
Interleukin‐4 inhibits bone resorption through an effect on osteoclasts and proinflammatory cytokines in an ex vivo model of bone resorption in rheumatoid arthritis
Authors: Miossec Pierre , Chomarat Pascale , Dechanet Julie , Moreau Jean‐François , Roux Jean‐Paul , Delmas Pierre , Banchereau Jacques 
Published: February 2007

AbstractObjective. To assess local bone resorption in the context of rheumatoid synovitis and its modulation by interleukin‐4 (IL‐4).Methods. We developed an ex vivo model of bone resorption using juxtaarticular samples of bone obtained during joint surgery. We studied the histomorphometric parameters of bone resorption and the regulation of the production of IL‐6, leukemia inhibitory factor (LIF), and the collagen cross‐link pyridinoline, which is released during bone resorption in vivo.Results. This was a sensitive and dynamic model of bone resorption. The bone samples produced high levels of pyridinoline and as much cytokine as synovium pieces obtained from the same joint. IL‐4 induced a 70% reduction of IL‐6 and LIF production by bone pieces and reduced pyridinoline levels. Histomorphometric studies performed on bone samples indicated a 35% increase in the mean total bone area after 7 days of treatment with IL‐4. More importantly, with IL‐4, osteoclasts were not detectable in the bone sections.Conclusion. The inhibitory effect of IL‐4 on bone resorption extends our knowledge of its antiinflammatory properties and suggests that the inflammatory cytokine imbalance in rheumatoid synovium also contributes to defects in bone resorption in RA.
Relationship between α1‐antitrypsin inactivation and tumor necrosis factor α concentration in the synovial fluid of patients with rheumatoid arthritis
Authors: Chidwick Keith , Whichelow Catherine E. , Zhang Zhi , Fairburn Kevin , Sachs John A. , Blake David R. , Winyard Paul G. 
Published: February 2007

AbstractObjective. To examine the relationship between α1‐antitrypsin (α1AT) specific activity and tumor necrosis factor α (TNFα) concentration in synovial fluid from 48 patients with rheumatoid arthritis.Methods. The specific activity of α1AT was calculated from the measurement of α1AT concentration (by rocket immunoelectrophoresis) and elastase inhibitory capacity. TNFα was detected by enzyme‐linked immuno‐sorbent assay.Results. TNFα concentrations correlated with the extent of α1AT inactivation.Conclusion. Our findings are consistent with a role of elastase in TNFα release within the inflamed joint.
Doxycycline disrupts chondrocyte differentiation and inhibits cartilage matrix degradation
Authors: Cole Ada A. , Chubinskaya Susan , Luchene Lawrence J. , Chlebek Kim , Orth Michael W. , Greenwald Robert A. , Kuettner Klaus E. , Schmid Thomas M. 
Published: February 2007

AbstractObjective. The effects of doxycycline were tested in an in vitro system in which the cartilages of embryonic avian tibias are completely degraded.Methods. Tibias were cultured with 5, 20, or 40 μg/ml doxycycline. Control tibias were cultured without doxycycline. Conditioned media and tissue sections were examined for enzyme activity and matrix loss.Results. Cartilages were not resorbed in the presence of doxycycline, whereas control cartilages were completely degraded. Collagen degradation was reduced in association with treatment with doxycycline at all doses studied. Higher concentrations of doxycycline reduced collagenase and gelatinase activity and prevented proteoglycan loss, cell death, and deposition of type X collagen in the cartilage matrix; in addition, treatment with doxycycline at higher concentrations caused increases in the length of the hypertrophic region.Conclusion. The effects of doxycycline extend beyond inhibition of the proteolytic enzymes by stimulating cartilage growth and disrupting the terminal differentiation of chondrocytes.
Granzyme‐positive cytotoxic cells are specifically increased in early rheumatoid synovial tissue
Authors: Tak Paul P. , Kummer J. Alain , Hack C. Erik , Daha Mohamed R. , Smeets Tom J. M. , Erkelens G. Wilhelmina , Meinders A. Edo , Kluin Philip M. , Breedveld Ferdinand C. 
Published: February 2007

AbstractObjective. To define the expression and the phenotype of granzyme (Gran) A and B positive cytotoxic cells in synovial tissue (ST) from patients with rheumatoid arthritis (RA) with respect to disease duration and activity.Methods. Using antibodies against GranA and GranB, which serve as markers of activated natural killer (NK) cells and cytotoxic T lymphocytes, ST sections from 10 patients with early RA, 10 patients with longstanding RA, and 10 patients with osteoarthritis were examined. The phenotype of Gran+ cells was determined with double‐labeling techniques.Results. Gran+ cells, the majority of which were NK cells, were found in ST from patients in all groups. Several of these cells did not express the surface markers CD16, CD56, and CD57. The highest ST expression of GranB was found in patients with early RA. In RA patients, there was a positive correlation of GranB expression with serum levels of acute‐phase reactants, but not with histologic scores for inflammation.Conclusion. Gran+ cells are mainly NK cells, a substantial proportion of which do not express conventional NK cell surface markers. GranB expression is specifically increased in the synovial tissues of patients with RA of short duration.