bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low levels of somatomedin C in patients with the fibromyalgia syndrome. A possible link between sleep and muscle pain
Authors: Bennett Robert M. , Clark Sharon R. , Campbell Stephen M. , Burckhardt Carol S. 
Published: February 2007

AbstractObjective. Fibromyalgia is a common syndrome of musculoskeletal pain and fatigue. Lacking distinctive tissue or laboratory correlations, it has often been considered a form of “psychogenic rheumatism.” In the present study, the notion that the stage‐4 sleep anomaly typically seen in the fibromyalgia syndrome may disrupt growth hormone secretion was tested. Because growth hormone has a very short half‐life, serum levels of somatomedin C were measured; somatomedin C is the major mediator of growth hormone's anabolic actions and is a prerequisite for normal muscle homeostasis.Methods. Serum levels of somatomedin C were measured in 70 female fibromyalgia patients and 55 healthy controls, using a peptide‐specific radioimmunoassay.Results. Significantly lower levels of somatomedin C were observed in the fibromyalgia patients compared with controls (mean ± SD 124.7 ± 47 ng/ml versus 175.2 ± 60 ng/ml; P = 0.000001). These results could not be explained by concomitant therapy or by weight, and in a subset of 21 patients in whom this was investigated, there was no correlation with various indices of disease activity.Conclusion. These findings indicate that there is a distinctive disruption of the growth hormone‐somatomedin C neuroendocrine axis in a majority of fibromyalgia patients. It is hypothesized that this abnormality may explain the link between disturbed sleep and predisposition to muscle pain.
High‐dose immunoglobulin therapy as an immunomodulatory treatment of rheumatoid arthritis
Authors: Tumiati Bruno , Casoli Patrizia , Veneziani Maura , Rinaldi Gabriele 
Published: February 2007

AbstractObjective. To investigate the efficacy of high‐dose intravenous immunoglobulin (IVIg) in the treatment of refractory rheumatoid arthritis (RA).Methods. Ten patients with active, severe RA that was unresponsive to first‐ and second‐line agents were administered IVIg monthly, for 6 months.Results. Following IVIg treatment, there was significant improvement in both subjective and objective parameters of disease activity in all 9 patients who completed the protocol. This improvement was noted to occur as early as after the second infusion of IVIg. After discontinuation of the treatment, all patients had a relapse of the disease within a few weeks.Conclusion. Since the reduction in clinical activity paralleled a decrease in the CD4+CDw29+: CD4+CD45RA+ cell ratio, some of the therapeutic benefits associated with IVIg may be due to a direct influence on the CD4+CD45RA+ subset. Although the possibility of carrying out further controlled studies on a larger scale is limited by the high cost of the treatment, IVIg appears to be an effective therapy for refractory RA.
Methotrexate treatment of recalcitrant childhood dermatomyositis
Authors: Miller L. C. , Sisson B. A. , Tucker L. B. , Denardo B. A. , Schaller J. G. 
Published: February 2007

AbstractObjective. To review the clinical course of 16 children with recalcitrant dermatomyositis (DM), who were treated with oral methotrexate (MTX) in addition to prednisone.Methods. Sixteen patients with recalcitrant DM who were treated with MTX in addition to prednisone were followed between 1984 and 1990. The patients' clinical responses to treatment, including alterations in muscle strength and muscle enzyme levels, changes in prednisone dosage, and development of toxicity or complications were reviewed retrospectively.Results. All 12 patients who received MTX for at least 8 months regained normal muscle strength. In 11 of the 12, the prednisone dosage could eventually be tapered to ⩽5 mg/day. Complications during MTX treatment required discontinuation of MTX in 5 patients, and were unrelated to the cumulative dose of the drug. Active disease recurred in 5 patients in whom MTX had been discontinued after apparent clinical remission had been achieved.Conclusion. MTX, in combination with prednisone, is a useful adjunct in the treatment of recalcitrant childhood DM. However, recurrence of disease after withdrawal of MTX suggests that the drug may have a suppressive, rather than a remittive, effect.
Localization of tumor necrosis factor receptors in the synovial tissue and cartilage‐pannus junction in patients with rheumatoid arthritis. Implications for local actions of tumor necrosis factor α
Authors: Deleuran Bent W. , Chu Cong‐Qiu , Field Max , Brennan Fionula M. , Mitchell Tracey , Feldmann Marc , Maini Ravinder N. 
Published: February 2007

AbstractObjective. We have previously described the location of tumor necrosis factor α (TNFα)–producing cells in synovial tissue and cartilage–pannus junction in rheumatoid arthritis (RA). To further understand the local actions of TNFα, we investigated the expression of TNF receptors (TNF‐R) on cells in the same compartments in patients with RA.Methods. The expression of both p55 TNF‐R and p75 TNF‐R was determined using alkaline phosphatase–conjugated mouse anti–alkaline phosphatase (APAAP) and double immunofluorescence staining techniques with monoclonal antibodies.Results. In RA synovial membrane, both p55 TNF‐R and p75 TNF‐R were detectable in up to 90% of the cells in the lining layer, and were demonstrated on cells in deeper layers of the membrane, including vascular endothelial cells. Cells in lymphoid aggregates expressed both TNF‐R, but with a predominant expression of p75 receptor. At the cartilage–pannus junction, the majority of pannus cells, especially those invading cartilage, expressed both the p55 and the p75 TNF‐R. Sequential section and double immunofluorescence staining showed that the TNF‐R–expressing cells were in the vicinity of TNFα‐containing cells, and some TNFα‐containing cells also expressed TNF‐R. TNF‐R–expressing cells were also detected in osteoarthritic and normal synovial tissue, but in smaller numbers and at a lower intensity.Conclusion. These results provide histologic evidence that both p55 TNF‐R and p75 TNF‐R are expressed by a variety of cell types in RA synovial tissue, reflecting the fact that a wide range of cells are potential targets for TNFα in this tissue. This study further supports the hypothesis that TNFα plays a major role in the pathogenesis of RA.
Expression of human tenascin in synovitis and its regulation by interleukin‐1
Authors: McCachren S. Spence , Lightner Virginia A. 
Published: February 2007

AbstractObjective. Tenascin is an extracellular matrix glycoprotein with effects on cell adhesion, cell migration, and lymphocyte activation. We proposed to identify the expression of human tenascin messenger RNA (mRNA) and protein in inflammatory synovitis and in normal synovium, and to identify potential regulatory cytokines.Methods. Immunohistochemistry and in situ hybridization were used to identify the expression of tenascin in synovium. Northern blot analysis of RNA and both immunoblot analysis and enzyme‐linked immunosorbent assay of proteins were used to identify tenascin in synovial cell cultures.Results. Tenascin was found along the synovial lining layer and in perivascular areas of normal synovium. In inflammatory synovitis, tenascin protein and mRNA expression were shown to be increased in the synovial lining layer, in perivascular areas, in lymphoid aggregates, and in areas of fibrosis. Interleukin‐1, a major mediator of tissue injury in inflammatory synovitis, induced tenascin expression and deposition in primary synovial fibroblast cultures.Conclusion. Tenascin mRNA and protein are increased in inflammatory synovitis, and interleukin‐1 is an inducer of tenascin in synovial fibroblasts. This identifies a new pathway by which interleukin‐1 alters the extracellular matrix composition in synovitis. Since tenascin has effects on lymphocyte activation and cell adhesion, the induction of tenascin in inflammatory synovitis may play a role in the pathophysiology of arthritis.
Antibodies in rabbits immunized with cationized IgG react with histones H3 and H4
Authors: Suzuki Takahiro , Burlingame Rufus W. , Cavalot Franco , Andres Giuseppe , Kashiwazaki Sadao , Tan M. 
Published: February 2007

AbstractObjective. Rabbits immunized with cationized rabbit IgG develop antinuclear antibodies. This study was aimed at identifying the reactive antigens.Methods. Rabbits were immunized with homotypic or allotypic IgG that were physicochemically altered to produce positively charged dimethylpropanamide (polycationic) side chains.Results. Seven of 11 rabbits injected with cationized IgG produced antinuclear antibodies detected by indirect immunofluorescence. By enzyme‐linked immunosorbent assay, these were IgG antibodies reacting with histone (H3–H4)2 tetramer and with individual histone polypeptides H3 and H4. The antihistone antibodies were absorbed by cationized IgG but not by normal IgG.Conclusion. Cationized IgG appears to possess antigenic determinants of sufficient similarity to produce antibody responses cross‐reactive with histones H3 and H4.
The intrinsic migratory capacity of memory T cells contributes to their accumulation in rheumatoid synovium
Authors: Cush John J. , Pietschmann Peter , Oppenheimer‐Marks Nancy , Lipsky Peter E. 
Published: February 2007

AbstractObjective. Mechanisms controlling the infiltration of T cells into rheumatoid synovium have not been fully characterized. These studies were undertaken to investigate the relationship between T cell phenotype and migratory capacity, so as to elucidate mechanisms that might contribute to the accumulation of T cells at inflammatory sites.Methods. The characteristics of in vivo migrating cells were studied by dual‐immunofluorescence FACS (fluorescence‐activated cell sorter) analysis of rheumatoid synovial and peripheral blood T cells. Migratory cells were also characterized using a recently developed in vitro assay, wherein peripheral blood T lymphocytes (PBTL) with the capacity to migrate through endothelial cell monolayers were retrieved and assessed.Results. Migratory CD4+ T cells from rheumatoid arthritis (RA) and normal individuals were characterized as being CD45RA‐, CD29bright, CD11abright, L‐selectin‐, CD54+, and CD58+. Migrating RA PBTL (compared with normal PBTL), however, were significantly enriched in activated HLA—DR+ T cells. RA synovial tissue lymphocytes exhibited a similar phenotype, but with decreased surface density of CD4 and an increase in HLA‐DR and VLA‐1. RA synovial lymphocytes exhibited a 2–3‐fold increase in migratory capacity over normal and RA PBTL.Conclusion. These studies demonstrate the inherent migratory proficiency of CD4+ T cells that express a memory phenotype (CD29bright, CD11abright, and CD58+). In addition, enhanced transendothelial migration was observed for CD4+ T cells that were CD54+ and L‐selectin—. These studies demonstrate that the migratory patterns of circulating lymphocytes may be correlated with their surface phenotype and that the intrinsic migratory capacity of memory T cells is one component contributing to their accumulation in the rheumatoid synovium.
Association of dry eyes and dry mouth with anti—Ro/SS‐A and anti—La/SS‐B Autoantibodies in normal adults
Authors: Jacobsson Lennart , Hansen Bjarne U. , Manthorpe Rolf , Hardgrave Kathy , Neas Barbara , Harley John B. 
Published: February 2007

AbstractObjective. To evaluate the extent to which seemingly healthy, mature adults with mild symptoms of dry eyes or dry mouth share the immunologic features found in patients with Sjögren's syndrome.Methods. Of 705 subjects in Malmö, Sweden (age range 52–72 years) who responded to a questionnaire, 35% reported some symptoms of dry eyes or mouth. A random subgroup of the symptomatic subjects (n = 77) and an age‐ and sex‐matched control group from among the asymptomatic subjects (n = 32) were evaluated objectively by serologic testing and by various measures of exocrine gland function.Results. The symptomatic subjects had relatively impaired exocrine gland function and elevated levels of anti‐Ro and anti‐La (1.54–2.88‐fold increase compared with the asymptomatic subjects, 95% confidence interval [CI] 1.41, 4.03). The 2 autoantibodies correlated with each other (r = 0.64, 95% CI 0.49, 0.78) as well as with selected clinical measures of glandular function.Conclusion. The association between self‐reported symptoms of dry eyes or dry mouth and anti‐Ro and anti‐La, found in more than one‐third of mature adults in this study, suggests that the immune abnormalities and exocrine gland dysfunction found in Sjögren's syndrome affect a substantial proportion of the general population.
Interactions of synovial fluid immunoglobulins with chondrocytes
Authors: Takagi Toshitaka , Jasin Hugo E. 
Published: February 2007

AbstractObjective. To study the interaction of synovial fluid (SF) immunoglobulins with living chondrocytes, and to evaluate the relative contribution of type II collagen (CII) antibodies.Methods. SF of patients with rheumatoid arthritis (RA), osteoarthritis (OA), and gout were incubated with isolated bovine articular chondrocytes. Ig binding was measured by flow cytometry and by quantitation with 125I‐labeled anti‐IgG and anti‐IgM. Complement‐dependent cytotoxicity was determined by 51Cr release. Immunoglobulin binding and cytotoxicity were compared between chondrocytes obtained from the superficial and from the deep cartilage zones.Results. Significantly greater IgG and IgM binding was found with RA SF compared with OA or gout SF. Chondrocytes bound more Ig than did fibroblasts. The relative contribution of anti‐CII antibodies to Ig binding was studied following absorption of the SF with bovine CII, and by incubation with bacterial collagenase‐treated chondrocytes. There was a small but significant reduction in IgG and IgM binding with SF samples that were positive for anti‐CII. RA SF exhibited modest, but significantly greater complement‐dependent cytotoxicity than OA SF. Gel chromatography fractionation indicated that IgM antibodies were responsible for the cytotoxic activity. Additional studies showed that SF IgM antibodies bound preferentially to, and killed chondrocytes obtained from, the superficial layers of cartilage.Conclusion. Anti‐CII antibodies contained in RA SF represent one of many antibody specificities reacting with chondrocyte membrane antigens. Chondrocyte‐reactive SF antibodies may play an important pathogenic role in the processes leading to irreversible cartilage damage in RA. These deleterious effects appear to be exerted particularly on chondrocytes located near the articular surface of cartilage.
Causes of death in systemic lupus erythematosus, long‐term followup of an inception cohort
Authors: Ward Michael M. , Pyun Elise , Studenski Stephanie 
Published: February 2007

AbstractObjective. To describe the causes of death in a cohort of patients with systemic lupus erythematosus (SLE), and to determine if the major causes of death differ according to patient age, sex, race, socioeconomic status, and the duration of SLE.Methods. We examined survival in a cohort of 408 patients with SLE. During a median of 11 years of followup, 144 patients died. The cause of death was determined for 134 patients (93%).Results. SLE was the most common cause of death, occurring in 49 patients (34%), followed by in‐ fection (n = 32; 22%), cardiovascular disease (n = 23; 16%), cerebrovascular disease (n = 8; 6%), and cancer (n = 8; 6%). Deaths due to SLE and due to infections were more common among younger patients, and deaths due to cancer were more common among older patients. Although the risk of death due to SLE was greatest during the first 3 years after diagnosis, deaths due to SLE occurred throughout the course of disease.Conclusion. In this study of patients with SLE who were followed up for an extended period of time beginning soon after diagnosis, SLE was the most common cause of death, and deaths due to SLE occurred throughout the course of illness.
Association of radiographically evident osteoarthritis with higher bone mineral density and increased bone loss with age. The rotterdam study
Authors: Burger Huibert , van Daele Paulus L. A. , Odding Else , Valkenburg Hans A. , Hofman Albert , Grobbee Diederick E. , Schütte Henry E. , Birkenhäger Jan C. , Pols Huibert A. P. 
Published: February 2007

AbstractObjective. To investigate the relationship of osteoarthritis (OA) to bone mineral density (BMD) and rate of bone loss.Methods. The study group consisted of 2,745 persons (1,624 women) from the general elderly population. Disability was assessed by the Health Assessment Questionnaire. Femoral neck BMD was measured at baseline and, in 1,723 subjects, after 2 years of followup. Knee and hip radiographic OA was assessed on anteroposterior radiographs.Results. With the exception of knee radiographic OA in men, radiographic OA was associated with significantly increased BMD (3–8%). BMD increased significantly according to the number of affected sites and the Kellgren score. Radiographic OA was also associated with significantly elevated bone loss with age (in men, only for radiographic OA of the hip). A significant increase in relation to the number of affected sites and the Kellgren score (except with regard to knee OA in men) was found, independent of disability.Conclusion. Radiographic OA is associated with higher BMD and increased rate of bone loss. This suggests a more pronounced difference in BMD earlier in life.
The presence of costimulatory molecules CD86 and CD28 in rheumatoid arthritis synovium
Authors: Liu Ming Fei , Kohsaka Hitoshi , Sakurai Hiroshi , Azuma Miyuki , Okumura Ko , Saito Ichiro , Miyasaka Nobuyuki 
Published: February 2007

AbstractObjective. To investigate the expressions of costimulatory molecules CD86 (B7‐2, B70) and CD28 by cells obtained from the synovial tissues (ST) and synovial fluids (SF) of patients with rheumatoid arthritis (RA).Methods. Monoclonal antibodies (MAb) against CD86 and CD28 were used for immunochemical study of synovia from 18 RA patients, 4 osteoarthritis (OA) patients, and 4 normal subjects. These MAb were also used for flow cytometry of isolated ST cells from 8 RA and 5 OA patients and of SF mononuclear cells from 5 RA and 5 OA patients.Results. Immunohistochemical examination revealed that CD86+ cells occurred in 11 of the 18 RA synovia, but in none of the 4 OA or 4 normal synovia. Most of the positive cells had macrophage‐like morphology, and surrounded lymphoid aggregates. Most cells within lymphoid aggregates were stained positively for CD28. Flow cytometry showed that CD86+ cells comprised 2.9–33.4% (average 14.3%) of the total ST cells and 2.1–14.9% (average 6.1%) of the total SF mononuclear cells from RA patients. Approximately 40% of the CD86+ cells expressed CD14. A majority (mean 72%, range 57–89%) of the T cells in ST and SF expressed CD28. RA synovia expressed more CD86 molecules than did OA synovia (mean frequency of positive cells 14.3% versus 2.8%; mean fluorescence intensity 104.6 versus 40.9).Conclusion. This study has shown that the expression of the CD86 molecule was up‐regulated in RA synovia. The CD86+ cells appeared macrophage‐like and surrounded CD28+ cells in lymphoid aggregates. The simultaneous presence and close localization of CD86+ and CD28+ cells in the RA synovial compartment suggests that their interaction potentially contributes to the sustained immune activation of RA.
Synovial tissue macrophage populations and articular damage in rheumatoid arthritis
Authors: Mulherin Diarmuid , Fitzgerald Oliver , Bresnihan Barry 
Published: February 2007

AbstractObjective. To examine the relative contribution of individual synovial cell populations to polyarticular destruction in rheumatoid arthritis (RA).Methods. Serial measurements of disease activity and articular destruction, obtained prospectively in 28 RA patients followed up for a mean of 5.8 years, were correlated with synovial cell populations quantified using immunohistochemical techniques.Results. The mean radiologic score worsened (from 37 to 86; P = 0.0001) despite significant improvement in disease activity. Synovial lining layer cell depth and sublining layer macrophage, but not lymphocyte, cell counts correlated significantly with radiologic course. Detailed analysis of 11 patients demonstrated reduced synovial lining expression of CD14 compared with CD68 (P = 0.003), whereas sublining expression of CD14 and CD68 was equivalent.Conclusion. Synovial macrophage numbers correlated with articular destruction in RA. In addition, the study results provided further evidence that lining layer macrophages may represent a distinct subpopulation that is of importance in this process. These findings have implications for the development of new therapies for RA.
The antiinflammatory and antiviral effects of hydroxychloroquine in two patients with acquired immunodeficiency syndrome and active inflammatory arthritis
Authors: Ornstein Matthew H. , Sperber Kirk 
Published: February 2007

AbstractObjective. To report the antiinflammatory and antiviral effects of hydroxychloroquine (HCQ) treatment in 2 patients with AIDS and inflammatory arthritis.Methods. Two patients with AIDS and inflammatory arthritis were treated with HCQ, which was given in a loading dose of 600 mg/day. The maintenance dosage was calculated to remain below 6.5 mg/kg/day. Both patients had initial T cell subset studies; 1 patient, had serum and plasma collected before and after 1 year of HCQ treatment. Assays were performed for T cell subsets, recoverable human immunodeficiency virus type 1 (HIV‐1) RNA, mitogen‐ and antigen‐specific proliferation, and interleukin‐6 (IL‐6) levels. New studies on the use of HCQ as an anti–HIV‐1 agent are reviewed.Results. Both patients had a dramatic decrease in their arthritis activity. Neither patient required immunosuppressive therapy or developed an opportunistic infection. In the patient who was studied after 1 year of therapy, there was a 1‐log decrease in recoverable HIV‐1 RNA, improved mitogen‐ and antigen‐specific immune responses, and a large decrease in the IL‐6 level while taking HCQ. Recent in vitro and in vivo assays in patients with HIV infection have shown similar antiviral and antiinflammatory effects from HCQ.Conclusion. HCQ may exert simultaneous antiinflammatory and antiviral effects in patients with HIV infection and inflammatory arthritis. If larger studies confirm this observation, it may be the drug of choice in this population of patients.