bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of prelymphomatous stages of B cell lymphoproliferation in Sjögren's syndrome
Authors: de Vita Salvatore , Boiocchi Mauro , Sorrentino Dario , Carbone Antonino , Avellini Claudio , Dolcetti Riccardo , Marzotto Alessandra , Gloghini Annunziata , Bartoli Ettore , Beltrami Carlo Alberto , Ferraccioli Gianfranco 
Published: February 2007

AbstractObjective. To determine whether the prelymphomatous stages of B cell lymphoproliferation in Sjögren's syndrome (SS) may be better characterized by the integration of clinical, pathologic, and molecular data, the latter focusing on the expansion, persistence, and dissemination of clonal B cells in the course of the disease.Methods. Multiple tissue lesions (synchronous from different tissues and metachronous from the same tissue) were evaluated in biopsy specimens obtained from 6 consecutive patients with SS who had an associated lymphoproliferative disorder. Fully benign gastric lesions were evaluated in tissue from an additional 11 patients with SS who had no associated lymphoproliferative disorder. Multiple and complementary molecular analyses of B cell clonality were used: Southern blot, polymerase chain reaction, single‐strand conformation polymorphism, DNA sequencing, and hybridization with clonospecific oligoprobes. All the patients were then strictly followed up for the appearance of lymphoma.Results. Different scenarios of SS‐associated B cell lymphoproliferation were identified: 1) the ongoing expansion of the same dominant clone, localized or disseminated, in tissue from 2 patients, 1 of whom later developed an overt B cell lymphoma; 2) different dominant clones in different synchronous or metachronous tissues from the remaining 4 patients with an associated lymphoproliferative disorder; and 3) small oligoclonal expansions in 7 of the 11 benign gastric lymphoid infiltrates.Conclusion. Prelymphomatous B cell lymphoproliferation in SS was better characterized following integration of the findings. The different types of B cell clonal expansion (oligoclonal or monoclonal, smaller or larger in size, fluctuating or established, localized or disseminated) may imply a different risk of lymphoma progression. An accurate clinical, histopathologic, and molecular characterization may therefore be crucial in future studies aimed at clarifying the pathobiology of SS‐associated lymphoproliferation.
Meaningful improvement criteria sets in a rheumatoid arthritis clinical trial
Authors: Pillemer Stanley R. , Fowler Sarah E. , Tilley Barbara C. , Alarcón Graciela S. , Heyse Stephen P. , Trentham David E. , Neuner Rosemarie , Clegg Daniel O. , Leisen James C. C. , Cooper Sheldon M. , Duncan Howard , Tuttleman Marilyn 
Published: February 2007

AbstractObjective. To compare 3 sets of criteria for meaningful improvement in a rheumatoid arthritis (RA) clinical trial, and to evaluate the implications of these criteria sets for RA trial design.Methods. Data were obtained from the Minocycline in Rheumatoid Arthritis (MIRA) trial (primary outcome measures: 50% improvement in joint tenderness and 50% improvement in joint swelling, based on joint scores). These MIRA data were evaluated against 1) the Paulus criteria (20% improvement in 4 of 6 measures: joint tenderness scores, joint swelling scores, physician's and patient's global assessments, erythrocyte sedimentation rate [ESR], and morning stiffness); and 2) the American College of Rheumatology (ACR) criteria (20% improvement in joint tenderness and joint swelling counts, and in 3 of 5 other measures: physician's and patient's global assessments, ESR, modified Health Assessment Questionnaire, and patient's pain assessment). The ACR criteria were modified using 3 of 4 remaining measures, since baseline pain assessment data were not available.Results. Percentages of minocycline‐treated patients versus placebo‐treated patients showing meaningful improvement were as follows: by MIRA criteria, for joint tenderness, 56% versus 41% (P = 0.021), and for joint swelling, 54% versus 39% (P = 0.023); by Paulus criteria, 41% versus 28% (P = 0.040); and by ACR criteria, 44% versus 26% (P = 0.004). Both the modified ACR criteria and the Paulus criteria demonstrated a reduced placebo response rate. Compared with the MIRA criteria, the ACR criteria increased, and the Paulus criteria decreased, absolute between‐group differences in improvement; however, both criteria sets increased relative percentages of patients showing improvement in the minocycline group versus the placebo group. Study design considerations indicated that application of the ACR criteria would reduce the required sample size.Conclusion. Different placebo response rates and treatment group differences were found using the 3 RA improvement criteria sets. These findings support the use of the ACR criteria for defining improvement in RA clinical trials.
Tenosynovial nodulosis in a patient infected with human T cell lymphotropic virus I
Authors: Hasunuma Tomoko , Morimoto Tadanobu , Hoa Tran Thi Minh , Müller‐Ladner Ulf , Aono Hiroyuki , Ogawa Ryokei , Gay Steffen , Nishioka Kusuki 
Published: February 2007

AbstractWe describe a 45‐year‐old man who presented with multiple nodules along the tendons of the scapular region, the elbows, wrists, forearms, thighs, and ankles. The patient was a carrier of human T cell lymphotropic virus I (HTLV‐I), which was probably transmitted from his mother; his mother also had polyarthritis. Histopathologically, the nodules consisted of numerous, small, fibrinoid masses. The synovium adjacent to the tendon sheath was hyperplastic, with fibrinoid necrosis mimicking rheumatoid synovium. However, synovitis was not present inside the adjacent joint. HTLV‐I proviral DNA was detected in the cells of the nodule, in tenosynovial cells, and in peripheral blood lymphocytes, but not in skin fibroblasts. In situ reverse transcription assay showed a high quantity of tax/rex messenger RNA in the proliferating lining cells. Based on these features, we classified this case as an atypical manifestation of HTLV‐I‐associated arthropathy associated with fibrinoid nodules resulting from chronic tenosynovitis.
T cell receptor α‐chain and β‐chain junctional region homology in clonal CD3+, CD8+ T lymphocyte expansions in Felty'S syndrome
Authors: Bowman Simon J. , Hall Margaret A. , Panayi Gabriel S. , Lanchbury Jerry S. 
Published: February 2007

AbstractObjective. Up to 42% of patients with Felty's syndrome (FS) have peripheral blood expansions of CD3+, CD8+ large granular lymphocytes (LGLs). The aim of this study was to determine whether the T cell receptor (TCR) α‐ and β‐chain sequences of these expansions from different patients have features in common that would support the hypothesis of an antigen‐driven process.Methods. Extraction of RNA from peripheral blood lymphocytes followed by synthesis of complementary DNA, inverse polymerase chain reaction (PCR) with TCR‐specific primers, bacteriophage transformation, and sequencing of PCR products.Results. Structural analysis of TCR β‐chain usage in such patients demonstrated a junctional region motif comprising the amino acids ‐LG‐ or ‐RG‐ in 7 of 14 clonal sequences and the motif ‐GXG‐ in 8 of 14. A biased α‐chain junctional region usage of a hydrophobic and/or basic amino acid at position 2 was seen in 5 of 8 expanded sequences. These features differed significantly from control sequences.Conclusion. Given current models of TCR–peptide–major histocompatibility complex interaction, these observations are consistent with an antigen‐driven, rather than a superantigen‐driven, process in at least a subgroup of patients with FS.
Perinuclear antineutrophil cytoplasmic antibody in rheumatoid arthritis. A marker of severe disease with associated nephropathy
Authors: Mustila Anu , Korpel Markku , Mustonen Jukka , Helin Heikki , Huhtala Heini , Soppi Esa , Pasternack Amos , Miettinen Ari 
Published: February 2007

AbstractObjective. To evaluate the clinical significance of antineutrophil cytoplasmic antibodies (ANCA) in patients with rheumatoid arthritis (RA), and especially in those with clinically suspected or histologically proven nephropathy.Methods. A total of 246 RA patients with (n = 149) and without (n = 97) histologically proven (n = 99) or clinically suspected (n = 50) nephropathy were studied for the presence of ANCA by immunofluorescence and enzyme immunoassay.Results. Perinuclear ANCA (pANCA) were found in 52 (21%) of the 246 patients. Patients with clinically suspected or histologically proven nephropathy were significantly more frequently positive for pANCA (30% versus 7%; P < 0.00005) and had significantly higher mean (±SD) pANCA log titers (103 ± 5.6 versus 27 ± 3.0; P = 0.0011) than patients without clinically evident renal disease. Positivity for pANCA was associated with clinical and laboratory findings indicating severe basic disease and increased inflammatory activity. Irrespective of this association, pANCA acted as a significant and independent predictor of RA‐associated nephropathy.Conclusion. Perinuclear ANCA in RA indicate severe disease with increased inflammatory activity. There is an especially strong and independent association between pANCA and RA‐associated nephropathy.
Abnormal homocysteine metabolism in rheumatoid arthritis
Authors: Roubenoff Ronenn , Dellaripa Paul , Nadeau Marie R. , Abad Leslie W. , Muldoon Bernadette A. , Selhub Jacob , Rosenberg Irwin H. 
Published: February 2007

AbstractObjective. To assess total homocysteine (tHcy) metabolism in patients with rheumatoid arthritis (RA).Methods. Assessments were performed to determine the fasting levels of tHcy and the increase in tHcy in response to methionine (Met) challenge in blood samples from 28 patients with RA and 20 healthy age‐matched control subjects.Results. Fasting levels of tHcy were 33% higher in the RA patients than in the control subjects (mean ± SD 11.7 ± 1.5 nmoles/ml versus 8.8 ± 1.1 nmoles/ml; P < 0.01). Four hours after Met challenge, the increase in plasma tHcy levels (ΔtHcy) was higher in the RA patients (20.9 ± 10.4 nmoles/ml) than in the control subjects (15.5 ± 1.6 nmoles/ml) (P < 0.02). In a subgroup analysis, the ΔtHcy in patients taking methotrexate (12.9 ± 2.2 nmoles/ml) did not differ from that in the control group, while the ΔtHcy in patients not taking methotrexate (25.3 ± 1.7 nmoles/ml) was significantly higher (P < 0.0001).Conclusion. Elevated tHcy levels occur commonly in patients with RA, and may explain some of the increased cardiovascular mortality seen in such patients. Studies of the prevalence and mechanism of hyperhomocysteinemia in RA are warranted.
Thrombosis in primary antiphospholipid syndrome. A pivotal role for monocyte tissue factor expression
Authors: Cuadrado Maria José , López‐Pedrera Charo , Khamashta Munther A. , Camps Maria Teresa , Tinahones Francisco , Torres Antonio , Hughes Graham R. V. , Velasco Francisco 
Published: February 2007

AbstractObjective. The antiphospholipid syndrome (APS) is a disorder of recurrent thrombosis, pregnancy loss, and thrombocytopenia associated with the production of anticardiolipin antibodies (aCL) and lupus anticoagulant (LAC). The mechanisms of thrombus formation remain unknown. Tissue factor (TF), an inducible cell glycoprotein, is a major initiator of coagulation in vivo. The present study was therefore undertaken to investigate TF expression and procoagulant activity on monocytes from patients with primary APS and its correlation with thrombotic events.Methods. Three groups of patients were studied: group 1 comprised 23 primary APS patients with thrombosis, group 2 consisted of 10 primary APS patients without thrombosis, and group 3 contained 20 patients with thrombosis but without antiphospholipid antibodies. Twenty age‐ and sex‐matched healthy blood donors were used as controls (group 4). Anticardiolipin antibodies were measured by enzyme‐linked immunosorbent assay (ELISA) and LAC by standard methodology. Cell surface expression of TF on monocytes was assessed by flow cytometry. The amount of TF in cell lysates (TFAg) and soluble TFAg plasma levels were analyzed by ELISA, and the TF‐related procoagulant activity (PCA‐TF) on intact cells and cell lysates by a chromogenic assay. Levels of the cytokines that influence TF production, i.e., tumor necrosis factor α (TNFα) and interleukin‐1β (IL‐1β), were determined by ELISA.Results. Cell surface expression of TF was increased in group 1 (mean ± SEM 50.2 ± 4% positive cells) compared with group 2 (14.6 ± 1.6%), group 3 (16.8 ± 3.7%), and group 4 (14.1 ± 1.6%). TFAg levels were also elevated in group 1 (215.8 ± 11.2 pg/106) compared with group 2 (150.8 ± 15.2), group 3 (101.4 ± 14.8), and group 4 (80.32 ± 5.5). PCA‐TF on intact cells and cell lysates was significantly increased in group 1 (148.8 ± 16.3 units/105 lysate cells, compared with 54.5 ± 11.5, 38.6 ± 9.7, and 22.5 ± 3.1 in groups 2, 3, and 4, respectively). Among group 1 patients, there was a significant increase in the degree of TF expression in those positive for IgG aCL, but not in those positive for IgM aCL or LAC. TNFα and IL‐1β plasma levels did not differ significantly between any of the groups.Conclusion. These results suggest that monocyte TF expression is directly involved in the pathogenesis of thrombotic complications in patients with the primary APS.
The synovial expression and serum levels of interleukin‐6, interleukin‐11, leukemia inhibitory factor, and oncostatin m in rheumatoid arthritis
Authors: Okamoto Hideyuki , Yamamura Masahiro , Morita Yoshitaka , Harada Seishi , Makino Hirofumi , Ota Zensuke 
Published: February 2007

AbstractObjective. To determine the expression of interleukin‐6 (IL‐6), IL‐11, leukemia inhibitory factor (LIF), and oncostatin M (OSM) and their major cellular sources in the joints of rheumatoid arthritis (RA) patients, as well as the correlation of circulating levels of these IL‐6‐type cytokines and C‐reactive protein (CRP).Methods. Messenger RNA (mRNA) and protein levels for IL‐6, IL‐11, LIF, and OSM were determined by using reverse transcription‐polymerase chain reaction and enzyme‐linked immunosorbent assay, respectively.Results. Cells isolated from the synovium of RA patients expressed mRNA for IL‐6, IL‐11, LIF, and OSM at higher levels than did synovial cells from osteoarthritis (OA) patients, and spontaneously released greater quantities of these proteins in culture. Fibroblast cell lines derived from RA synovium were able to produce IL‐6, IL‐11, and LIF, but not OSM, when stimulated with IL‐1 and tumor necrosis factor α. OSM was found to be produced spontaneously by synovial tissue macrophages. IL‐6, IL‐11, LIF, and OSM were present in synovial fluid from the RA patients; levels of IL‐6, LIF, and OSM were present in significantly greater quantities in RA patients than in OA patients. However, only IL‐6 was significantly elevated in the serum of RA patients and correlated with the serum CRP level, while other IL‐6‐type cytokines were not detected.Conclusion. IL‐6, IL‐11, LIF, and OSM are all produced in large amounts at the site of disease activity, but IL‐6 derived from synovial fibroblasts may be the major hormone‐like mediator that induces the hepatic synthesis of acute‐phase proteins in RA.
In vivo mechanisms for the inhibition of T lymphocyte activation by long‐term therapy with tacrolimus (FK‐506)
Authors: Suzuki Noboru , Kaneko Sakae , Ichino Motohide , Mihara Shoji , Wakisaka Sueshige , Sakane Tsuyoshi 
Published: February 2007

AbstractObjective. To examine the in vivo mechanisms of suppression of T lymphocyte function in patients with Behçet's disease (BD) undergoing long‐term treatment with tacrolimus (FK‐506).Methods. Intracellular proteins were analyzed by immunoprecipitation and Western blotting. Messenger RNA expression was studied by a polymerase chain reaction—based technique.Results. Interleukin‐2 production was suppressed in patients treated with tacrolimus. This suppression was found to be due to inhibition of interactions between activated calcineurin (Cn) and nuclear factor of activated T cells (NF‐AT), inhibition of cleavage of the autoinhibitory domain of the CnA subunit, and inhibition of heterodimer formation by CnA and CnB sub‐units, resulting in the absence of NF‐AT in nuclei of the T cells. We found that T lymphocytes in some BD patients treated with tacrolimus had reduced amounts of FK‐506 binding protein (FKBP) in their cytoplasm.Conclusion. Tacrolimus reduces the Cn activity of T cells in vivo by the cumulative effects of several distinct mechanisms. It is plausible that reduced amounts of FKBP may be associated with diminished clinical efficacy in some BD patients receiving prolonged treatment with tacrolimus.
Adenosine A1 receptor promotion of multinucleated giant cell formation by human monocytes. A mechanism for methotrexate‐induced nodulosis in rheumatoid arthritis
Authors: Merrill Joan T. , Shen Christine , Schreibman David , Coffey Dan , Zakharenko Olga , Fisher Robert , Lahita Robert G. , Salmon Jane , Cronstein Bruce N. 
Published: February 2007

AbstractObjective. To determine why methotrexate (MTX) exacerbates rheumatoid nodules in some patients, despite the effective suppression of synovial inflammation.Methods. Phorbol myristate acetate (PMA)‐induced differentiation of monocytes into multinucleated giant cells was used as an in vitro model to study the effects of adenosine on nodulosis.Results. MTX at 200‐2,000 nM or the adenosine A1 agonist N5‐cyclopentyl adenosine (CPA) (10−12 to 10‐9 M) or the A2 antagonist 3,7‐dimethyl‐1‐propargylxanthine markedly enhanced giant cell formation, whereas the adenosine A1 antagonist 8‐cyclopentyl‐dipropylxanthine completely reversed these effects. PMA, CPA, and MTX induced adenosine release by cultured monocytes at concentrations consistent with those associated with predominantly A1 effects. Furthermore, surface expression of A1 receptors was found to remain unchanged on the differentiating cells throughout the culture period.Conclusion. Agents that inhibit adenosine A1 receptors might be useful in the treatment of MTX‐induced rheumatoid nodulosis, while still potentiating the A2‐mediated antiinflammatory effects of MTX on synovitis.
Mechanisms of drug‐induced lupus. III. Sex‐specific differences in T cell homing may explain increased disease severity in female mice
Authors: Yung Raymond , Williams Robert , Johnson Kent , Phillips Carrie , Stoolman Lloyd , Chang Sandra , Richardson Bruce 
Published: February 2007

AbstractObjective. To determine if sex‐specific differences in lymphocyte trafficking could contribute to increased disease severity in female mice.Methods. A lupus‐like disease was induced by injecting male and female mice with procainamide‐treated T cell clones. Trafficking was examined by labeling the injected cells with 51Cr or 5‐chloromethylfluorescein diacetate.Results. Females developed more autoimmune liver disease and greater titers of anti‐DNA antibodies than did males, and 2‐7 times more cells accumulated in the female spleens. Splenectomy prevented the development of autoantibodies and renal and liver disease. Oophorectomy decreased the splenic homing, autoantibody titer, and liver disease severity, to levels found in males.Conclusion. T cells traffic differently to the spleen in male and female mice, and the spleen appears to be essential in the disease process. This suggests that differences in T cell homing could contribute to sex‐specific disease severity in this murine model, and also possibly in human disease.
Human chondrocyte expression of growth‐arrest‐specific gene 6 and the tyrosine kinase receptor axl. Potential role in autocrine signaling in cartilage
Authors: Loeser Richard F. , Varnum Brian C. , Carlson Cathy S. , Goldring Mary B. , Liu Edison T. , Sadiev Sagypash , Kute Tim E. , Wallin Reidar 
Published: February 2007

AbstractObjective. To determine if human articular chondrocytes express the axl tyrosine kinase receptor and its ligand Gas‐6, a protein product of growth‐arrest‐specific gene 6, and to determine if Gas‐6 and axl function in the regulation of chondrocyte growth and survival.Methods. The presence of Gas‐6 and axl was examined in situ in human articular cartilage by immunohistochemistry and in vitro in cell culture studies using primary human chondrocytes and immortalized human chondrocytes. The ability of recombinant Gas‐6 to mediate adhesion of chondrocytes and to stimulate chondrocyte axl phosphorylation was determined. Studies of the role of Gas‐6 and axl in cell proliferation and survival were also performed.Results. Both Gas‐6 and axl were detected in cartilage by immunohistochemical staining. Gas‐6 and axl messenger RNA (mRNA) and protein were also detected in cultures of primary and immortalized human chondrocytes. Compared with cells cultured in medium containing 10% serum, Gas‐6 mRNA levels were increased in immortalized chondrocytes cultured in serum‐free medium, while axl expression decreased. Chondrocytes attached to Gas‐6‐coated plastic, and the attachment was blocked by a soluble Ig fusion protein containing the axl extracellular domain. Recombinant human Gas‐6 and serum‐free conditioned medium from primary and immortalized human chondrocyte cultures stimulated chondrocyte axl tyrosine phosphorylation. A mitogenic effect was noted both when immortalized chondrocytes were stimulated with recombinant Gas‐6 or when they were made to overexpress axl by transfection. Addition of recombinant Gas‐6 to serum‐free medium resulted in increased survival of primary chondrocytes cultured at low density in agarose.Conclusion. These findings present evidence for an autocrine signaling pathway in cartilage involving Gas‐6 and the axl tyrosine kinase adhesion receptor. Stimulation of axl by Gas‐6 may play an important role in the control of chondrocyte growth and survival.
Resource utilization and cost of care for rheumatoid arthritis and osteoarthritis in a managed care setting. The importance of drug and surgery costs
Authors: Lanes Stephan F. , Lanza Lee L. , Radensky Paul W. , Yood Robert A. , Meenan Robert F. , Walker Alexander M. , Dreyer Nancy A. 
Published: February 2007

AbstractObjective. To describe the frequency and costs of medical services for patients with osteoarthritis (OA) or rheumatoid arthritis (RA) in a managed care setting.Methods. Individual utilization records of medical and pharmacy services for OA and RA patients were obtained from a group‐model health maintenance organization (HMO). Estimates were made for costs of drugs and medical services for arthritis from July 1, 1993 to June 30, 1994 using Medicare reimbursement schedules and average wholesale drug prices. Calculated rates for each population were expressed as counts of events or as dollars per person‐year.Results. The average individual cost rate of arthritis‐related care for 365 RA patients was $2,162 per year, and the total cost of RA care to the HMO was $703,053. Prescription medications accounted for 62% ($436,440) of the total cost of RA care, while ambulatory care accounted for 21% ($150,938), and hospital visits accounted for 16% ($115,674). With regard to 10,101 OA patients, the average individual cost rate was $543 per year, and total cost to the HMO was $4,728,425. Hospital care accounted for 46% ($2,170,890) of the total cost of OA care, medications accounted for 32% ($1,509,637), and ambulatory care accounted for 22% ($1,047,898).Conclusion. RA care, in the setting of this study, was characterized by intensive treatment, especially frequent use of medications that were delivered to most patients. Although the cost of RA care per patient was high, cost to the managed care provider was relatively low, owing to the rarity of RA. OA care tended to be infrequent, and the largest component of cost was hospital care for a small proportion of patients (5%). Owing to the greater prevalence of OA, care of OA was nearly 7 times more costly to the managed care provider than was care of RA.