bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rheumatic diseases in an MRL strain of mice with a deficit in the functional Fas ligand
Authors: Ito Mituko R. , Terasaki Shizuko , Itoh Junpei , Katoh Hideki , Yonehara Shin , Nose Masato 
Published: February 2007

AbstractObjective. To characterize Fas antigen expression on the cell surface, and to determine the effect of this expression in rheumatic diseases using a newly established gld‐congenic MRL strain of mice (MRL/gld), which is defective in its functional Fas ligand (Fas‐L).Methods. Flow cytometric analyses of lymphoid cells and macrophages were performed using anti‐Fas and other cell surface markers. Histopathologic manifestations were examined using immunochemistry and light and electron microscopy. Serum levels of IgG and anti‐DNA antibodies were measured by single radial immunodiffusion and enzyme‐linked immunosorbent assay, respectively.Results. MRL/gld mice developed systemic lymph‐adenopathy with an accumulation of Thy1.2+, B220+ and CD4‐, CD8‐ T cells, which both express the Fas antigen. Splenic B cells positive for surface IgM and/or surface IgD, and resident peritoneal macrophages exhibited up‐regulated expression of the Fas antigen, at much higher levels than those observed in MRL/MpJ‐+/+ (MRL/+) mice. Forms of rheumatic disease were observed in these mice, although not in C3H/HeJ‐gld/gld mice. These forms included diffuse glomerulonephritis, granulomatous arteritis, and arthritis, and were associated with the infiltration of mononuclear cells expressing the Fas antigen. Serum levels of IgG and anti‐DNA antibodies were significantly increased in MRL/gld mice compared with MRL/+ mice.Conclusion. Rheumatic disease was generated by the gld gene in mice with an MRL background, as it is by the lpr gene, which is a Fas deletion mutant, associated with autoimmune traits. Rheumatic disease in this MRL strain was initiated by an incapacity for Fas/Fas‐L‐induced apoptosis, resulting in the development of autoimmunity and allowing for a persistent immune response in the affected lesions.
Impaired nonrestricted cytolytic activity in systemic lupus erythematosus
Authors: Stohl William , Elliott Julie E. , Li Lily , Podack Eckhard R. , Lynch David H. , Jacob Chaim O. 
Published: February 2007

AbstractObjective. To determine the cytolytic effector pathway involved in impaired generation of nonrestricted cytolytic activity in systemic lupus erythematosus (SLE).Methods. Peripheral blood mononuclear cells (PBMC) from normal subjects and SLE patients were stimulated in vitro with anti‐CD3 monoclonal antibody (MAb) and interleukin‐2 to promote the generation of nonrestricted cytolytic activity. On day 13 of culture, the PBMC were assayed for cytolytic activity against Fas‐Daudi cells and Fas+ Jurkat cells. The effects on cytotoxicity of calcium chelation, antagonist anti‐Fas MAb, tumor necrosis factor (TNF) α and β, and ATP were measured. Intracellular perforin expression was determined by intracellular staining, and perforin messenger RNA levels were determined by quantitative competitive reverse transcription‐polymerase chain reaction.Results. We demonstrated the existence of a cytolytic pathway that is independent of Fas, TNFα, TNFβ, and ATP, but is dependent upon extracellular calcium. Despite its calcium dependence, this pathway is associated with low‐to‐undetectable levels of perforin.Conclusion. Impaired generation of nonrestricted cytolytic activity in SLE is likely due to decreased activity of this Fas‐, TNFα‐, TNFβ‐, ATP‐independent pathway associated with very low levels of perforin.
Molecular analysis of major histocompatibility complex allelic associations with systemic lupus erythematosus in Taiwan
Authors: Lu Ling‐Ying , Ding Wei‐Zi , Fici Dolores , Deulofeut Richard , Cheng He‐Hsiung , Cheu Ching‐Cheng , Sung Ping‐Kuang , Schur Peter H. , Fraser Patricia A. 
Published: February 2007

AbstractObjective. To investigate the association of HLA class II alleles/haplotypes, type I C2 deficiency gene, and tumor necrosis factor α gene promoter allele (TNF2) with systemic lupus erythematosus (SLE) in the Chinese population in Taiwan.Methods. The HLA‐DRB1 and DQB1 alleles were studied in 105 SLE patients and 115 controls by the polymerase chain reaction (PCR)/sequence‐specific oligonucleotide probe method, the subtyping of DRB1*15/16 and DRB5 by PCR with sequence‐specific primers, type I C2 deficiency gene by PCR, and TNF2 by PCR‐Nco I restriction fragment length polymorphism.Results. The frequencies of the HLA class II alleles DRB1*02, DRB1*1502, DRB5*0102, DQB1*0501, and DQB1*0602 and DR2‐associated haplotypes DRB1* 1501,DRB5*0101,DQB1*0602 and DRB1*1502,DRB5* 0102,DQB1*0501 were higher among SLE patients than among controls; however, only DQB1*0501 was statistically significantly associated with SLE. No specific allele/haplotype was significantly associated with lupus nephritis. No subject had type I C2 deficiency. SLE patients had a marginally higher percentage of TNF2, which was in linkage disequilibrium with DR3. Since DR3 was not associated with SLE in this Taiwanese Chinese population, TNF2 might play a role in the immunopathogenesis of SLE.Conclusion. Although no HLA‐DRB1 allele was found to be significantly associated with SLE, the associations with DQB1*0501 and TNF2 suggest that DQB1 and tumor necrosis factor α may be important genetic factors in SLE susceptibility in the Chinese population in Taiwan.
The palpable tendon friction rub
Authors: Steen Virginia D. , Medsger Thomas A. 
Published: February 2007

AbstractObjective. To evaluate the clinical and prognostic significance of palpable tendon friction rubs in patients with systemic sclerosis (SSc).Methods. SSc patients evaluated prospectively at the University of Pittsburgh were examined serially for the presence of tendon friction rubs on physical examination. Demographic, clinical, and laboratory features of disease were obtained by patient examination, annual patient questionnaire, and medical record review. Patients were classified as having limited or diffuse scleroderma according to standard definitions. The prognostic significance of the presence of tendon friction rubs was determined using this comprehensive database.Results. The SSc patients (n = 1,305) were first evaluated during 1972 through 1991 and were followed up for a mean of 6.3 years. Tendon friction rubs were detected most frequently in patients who had or who developed diffuse cutaneous involvement. There were strong correlations between the presence of tendon friction rubs and symptoms and signs typical of diffuse scleroderma, including more severe skin thickening, more frequent heart and kidney involvement, and decreased survival. In multiple regression analyses, the presence of 1 or more tendon friction rubs was one of the best predictors of both evolution to diffuse scleroderma and reduced survival.Conclusion. The palpable tendon friction rub is an easily detected, inexpensively obtained physical examination finding which is highly associated with diffuse cutaneous scleroderma and decreased survival. This observation should lead to the early diagnosis of diffuse scleroderma and should identify patients at high risk for serious visceral involvement who are thus candidates for potential disease‐modifying therapy.
Interleukin‐1β‐stimulated invasion of articular cartilage by rheumatoid synovial fibroblasts is inhibited by antibodies to specific integrin receptors and by collagenase inhibitors
Authors: Wang Allan Z. , Wang Jane C. , Fisher Gregory W. , Diamond Herbert S. 
Published: February 2007

AbstractObjective. To study the role of integrin receptors in the invasion of cartilage by rheumatoid synovial fibroblasts (RSF).Methods. RSF were cocultured with cartilage slices alone or in the presence of various potential activators or inhibitors. The penetration of the cartilage surface by RSF was determined by live‐cell imaging of fluorescent‐labeled cells.Results. Interleukin‐1β (IL‐1β) and IL‐8 stimulated the RSF invasion of cartilage. Invasion was specific for RSF and required a concentration gradient of IL‐1β. The IL‐1β‐activated invasion of cartilage was inhibited by anti‐IL‐1 antibodies, IL‐1 receptor antagonist, and collagenase inhibitors. RSF invasion was also inhibited by antibodies to α4, α5, αV, and β1 integrins.Conclusion. In this study, an IL‐1β concentration gradient was required for RSF invasion into cartilage, raising the possibility that in vivo invasion may be induced by IL‐1β released by chondrocytes. The IL‐1β activation of RSF assayed in vitro may contribute to the RSF invasion of cartilage in vivo. Cartilage invasion requires the availability of β1 and α4, α5, and αV integrins and the presence of collagenase activity.
Mechanisms of drug‐induced lupus. IV. Comparison of procainamide and hydralazine with analogs in vitro and in vivo
Authors: Yung Raymond , Chang Sandra , Hemati Nahid , Johnson Kent , Richardson Bruce 
Published: February 2007

AbstractObjective. T cells treated with DNA methylation inhibitors overexpress lymphocyte function‐associated antigen 1 (LFA‐1), which results in autoreactivity, and the autoreactive cells cause a lupus‐like disease in vivo, suggesting a mechanism by which some agents may cause drug‐induced lupus. This study compared the effects of procainamide (Pca) and hydralazine (Hyd) with those of structural analogs, to determine if the degree of LFA‐1 overexpression and T cell autoreactivity correlated with the ability of the agents to induce autoimmunity.Methods. Cloned murine T helper 2 cells were treated with Pca, N‐acetylprocainamide, Hyd, Phthalazine, or hydroxyurea (HU). The treated cells were then compared for LFA‐1 overexpression, autoreactivity, and the ability to induce autoimmunity in vivo.Results. Pca and Hyd were more potent than their analogs or HU in all 3 assays.Conclusion. The results support a relationship between LFA‐1 overexpression, T cell autoreactivity, and autoimmunity, and suggest a mechanism by which Pca and Hyd, but not the analogs, may cause drug‐induced lupus.
Incidence of hydroxychloroquine retinopathy in 1,207 patients in a large multicenter outpatient practice
Authors: Levy G. D. , Munz S. J. , Paschal J. , Cohen H. B. , Pince K. J. , Peterson T. 
Published: February 2007

AbstractObjective. To define the true risk of hydroxychloroquine (HCQ) retinal toxicity by studying the largest single group yet evaluated.Methods. Retrospective chart review of all patients in the Kaiser Permanente Medical Care Program, Southern California Region, who had HCQ prescriptions filled from 1991 through 1993 (1,556 patients in 11 medical centers). Of 1,207 charts of patients who took HCQ and had documented ophthalmologic examinations, initial screening identified 21 charts (1.7%) that indicated possible HCQ toxicity.Results. We identified 1 patient with definite toxicity (1 of 1,207; 0.08%) and 5 other patients with indeterminate but probable toxicity (5 of 1,207; 0.4%). The incidence of definite HCQ retinal toxicity in patients treated with HCQ at <6.5 mg/kg/day was 0.Conclusion. In HCQ‐treated patients whose renal function is normal, routine ophthalmic screening is not indicated if the daily dosage is <6.5 mg/kg. In patients whose daily dosage is >6.5 mg/kg or who have taken HCQ continuously for > 10 years, annual screening may be appropriate.
Deposition of antibodies to the collagen‐like region of C1Q in renal glomeruli of patients with proliferative lupus glomerulonephritis
Authors: Mannik Mart , Wener Mark H. 
Published: February 2007

AbstractObjective. To determine if antibodies to the collagen‐like region of C1q (C1q‐CLR) are present in the glomerular immune deposits of patients with systemic lupus erythematosus (SLE).Methods. Kidney tissues were obtained at autopsy, glomeruli were isolated, and glomerular basement membrane fragments were prepared. Antibodies were extracted with low pH or with DNase.Results. The concentrations of antibodies to C1q‐CLR recovered from the glomeruli were ⩾50‐fold higher per unit of IgG than that found in the serum or in the serum and interstitial fluid entrained in glomeruli. Antibodies to C1q‐CLR were recovered from glomeruli of 4 of 5 patients with proliferative glomerulonephritis at autopsy.Conclusion. This is the first demonstration that antibodies to C1q‐CLR are deposited and concentrated in the renal glomeruli of patients with SLE. These antibodies, thus, have the potential of contributing to the pathogenesis of lupus glomerulonephritis.
Health status and disease severity in fibromyalgia. Results of a six‐center longitudinal study
Authors: Wolfe Frederick , Anderson Janice , Harkness Deborah , Bennett Robert M. , Caro Xavier J. , Goldenberg Don L. , Russell I. Jon , Yunus Muhammad B. 
Published: February 2007

AbstractObjective. To determine the intermediate and long‐term outcomes of fibromyalgia in patients seen in rheumatology centers in which there is special interest in the syndrome.Methods. We conducted a longitudinal outcome study by mailed comprehensive Health Assessment Questionnaire administered every 6 months to 538 patients, from 6 rheumatology centers, whose median duration of disease at first assessment was 7.8 years. The final assessment took place after 7 years. In addition, there was study followup on 85 patients who had attended the Wichita center for > 10 years.Results. Although functional disability worsened slightly and health satisfaction improved slightly, measures of pain, global severity, fatigue, sleep disturbance, anxiety, depression, and health status were markedly abnormal at study initiation and were essentially unchanged over the study period. Correlations between first and last assessment values were as high as r = 0.82. For some variables, abnormalities were 3 times greater at one center compared with another.Conclusion. Patients with established fibromyalgia, seen in rheumatology centers in which there a special interest in the disease and followed up for as long as 7 years, have markedly abnormal scores for pain, functional disability, fatigue, sleep disturbance, and psychological status, and these values do not change substantially over time. Half the patients are dissatisfied with their health, and 59% rate their health as fair or poor. There are marked differences in disease severity among the various centers, but <14% of the variance in outcomes can be explained by demographic or center factors. Values at the first assessment are predictive of final values.
Range of antinuclear antibodies in “healthy” individuals
Authors: Tan E. M. , Feltkamp T. E. W. , Smolen J. S. , Butcher B. , Dawkins R. , Fritzler M. J. , Gordon T. , Hardin J. A. , Kalden J. R. , Lahita R. G. , Maini R. N. , McDougal J. S. , Rothfield N. F. , Smeenk R. J. , Takasaki Y. , Wiik A. , Wilson M. R. , Koziol J. A. 
Published: February 2007

AbstractObjective. To determine the range of antinuclear antibodies (ANA) in “healthy” individuals compared with that in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc; scleroderma), Sjögren's syndrome (SS), rheumatoid arthritis (RA), or soft tissue rheumatism (STR).Methods. Fifteen international laboratories experienced in performing tests for ANA by indirect immunofluorescence participated in analyzing coded sera from healthy individuals and from patients in the 5 different disease groups described above. Except for the stipulation that HEp‐2 cells should be used as substrate, each laboratory used its own in‐house methodology so that the data might be expected to reflect the output of a cross‐section of worldwide ANA reference laboratories. The sera were analyzed at 4 dilutions: 1:40, 1:80, 1:160, and 1:320.Results. In healthy individuals, the frequency of ANA did not differ significantly across the 4 age subgroups spanning 20–60 years of age. This putatively normal population was ANA positive in 31.7% of individuals at 1:40 serum dilution, 13.3% at 1:80, 5.0% at 1:160, and 3.3% at 1:320. In comparison with the findings among the disease groups, a low cutoff point at 1:40 serum dilution (high sensitivity, low specificity) could have diagnostic value, since it would classify virtually all patients with SLE, SSc, or SS as ANA positive. Conversely, a high positive cutoff at 1:160 serum dilution (high specificity, low sensitivity) would be useful to confirm the presence of disease in only a portion of cases, but would be likely to exclude 95% of normal individuals.Conclusion. It is recommended that laboratories performing immunofluorescent ANA tests should report results at both the 1:40 and 1:160 dilutions, and should supply information on the percentage of normal individuals who are positive at these dilutions. A low‐titer ANA is not necessarily insignificant and might depend on at least 4 specific factors. ANA assays can be a useful discriminant in recognizing certain disease conditions, but can create misunderstanding when the limitations are not fully appreciated.
Mono‐iodoacetate‐induced experimental osteoarthritis. A dose‐response study of loss of mobility, morphology, and biochemistry
Authors: Guingamp Corinne , Gegout‐Pottie Pascale , Philippe Lionel , Terlain Bernard , Netter Patrick , Gillet Pierre 
Published: February 2007

AbstractObjective. To characterize the doseresponsiveness of morphologic and biochemical chondral changes relative to mobility in mono‐iodoacetate (MIA)‐induced osteoarthritis (OA) in rats.Methods. Rat mobility was assessed by biotelemetry. Articular lesions were characterized by macroscopic and histologic examinations. Cartilage proteoglycan metabolism was evaluated by the 1,9‐dimethylmethylene blue dye binding assay and by radiosulfate incorporation in patellar cartilage.Results. Spontaneous locomotor activity was rapidly, transiently, and dose‐dependently decreased after MIA injection into rat knees (primary response). Thereafter, only high doses (0.3 mg and 3.0 mg) led to a secondary progressive long‐term loss of spontaneous mobility on day 15, when subchondral bone was exposed. These 2 doses resulted in significant changes in cartilage proteoglycan concentration at day 15 and a strong inhibition of anabolism in the peripheral patellae by day 2, contrasting with the effects of lower doses (0.01, 0.03, and 0.1 mg).Conclusion. When a sufficient dose of MIA is used, this model can easily and quickly reproduce OA‐like lesions and functional impairment in rats, similar to that observed in human disease. These parameters, as well as proteoglycan metabolism, could serve as indicators for studying chondroprotective drugs, or for evaluating the ability of imaging techniques to detect and evaluate chondral lesions.
Molecular cloning of a novel 97‐kd Golgi complex autoantigen associated with Sjögren's syndrome
Authors: Griffith Kevin J. , Chan Edward K. L. , Lung Chien‐Cheng , Hamel John C. , Guo Xiaoying , Miyachi Kiyomitsu , Fritzler Marvin J. 
Published: February 2007

AbstractObjective. To identify a Golgi complex autoantigen bound by Sjögren's syndrome (SS) autoantibodies.Methods. Serum from a patient with secondary SS and anti‐Golgi antibodies was used as a probe to isolate a complementary DNA (cDNA) insert from a HeLa cDNA library.Results. A 3.7‐kb cDNA encoding a 56‐kd recombinant protein was immunoprecipitated by the human anti‐Golgi serum and immune rabbit serum. Western blot analysis showed that the immune rabbit sera recognized a protein of 97 kd (golgin‐97), suggesting that the isolated clone contained a partial cDNA. The 5′ upstream sequence was obtained by rapid amplification of the cDNA ends. The complete cDNA contained 4,860 basepairs, encoding a protein with a calculated Mr of 88 kd. Antibodies to golgin‐97 were found in 12 (20%) of 60 sera known to have anti‐Golgi autoantibodies, and the majority of these sera (8 of 12, or 75%) were from patients who had secondary SS.Conclusion. Golgin‐97 is a unique Golgi complex antigen that appears to be a target of SS autoantibodies.
Histologic/histochemical grading system for osteoarthritic articular cartilage. Reproducibility and validity
Authors: Ostergaard Keld , Petersen Jorgen , Andersen Claus B. , Bendtzen Klaus , Salter Donald M. 
Published: February 2007

AbstractObjective. To evaluate the reproducibility and validity of the histologic/histochemical grading system (HHGS) for osteoarthritis (OA) developed by Mankin and coworkers.Methods. Sections of human articular cartilage from macroscopically normal and osteoarthritic femoral heads were graded by the HHGS (0‐14 scale) twice by 3 observers, and intra‐ and interobserver reproducibility was determined.Results. The exact intra‐ and interobserver reproducibilities ranged from 22% to 33% and from 13% to 25%, respectively. Intra‐ and interobserver variation ranged from −7 to 5. Although scores were generally higher in cartilage from osteoarthritic joints as compared with cartilage from normal joints, the difference reached statistical significance for only 2 observers. Additionally, the average scores from all observers were within the definitive range for OA (>5) in 30% of sections from normal joints, and in only 47% of sections from OA joints.Conclusion. The results indicate that the reproducibility and the validity of the HHGS are inadequate, and an improved histopathologic grading system for OA is needed.
Significant correlation between thrombospondin 1 and serine proteinase expression in rheumatoid synovium
Authors: Gotis‐Graham Ian , Hogg Philip J. , McNeil H. Patrick 
Published: February 2007

AbstractObjective. Thrombospondin 1 (TSP1) is a potent active site inhibitor of leukocyte elastase and cathepsin G. This effect is markedly dependent on the disulfidebond conformation of TSPI, with one isoform, TSPI0.1, being the most potent. The aims of this study were to examine the expression of different disulfide‐bonded isoforms of TSP1 in inflammatory environments in which elastase and cathepsin G are present in variable amounts, and to determine the relationship between these proteinases and their potential inhibitor.Methods. Immunohistochemical staining and histomorphometric analysis were used to examine adjacent sections of synovial tissue from patients with rheumatoid arthritis (RA), osteoarthritis (OA), and meniscal trauma (MT), for expression of TSPl and the TSPl0.1 isoform, elastase, cathepsin G, and chymase.Results. TSPl localized to vessels and cells within the synovium. TSPl expression was highly up‐regulated in RA (mean density 98 cells and vessels / mm2, compared with 13 / mm2 in OA and 17 / mm2 in MT). The TSPl0.1 isoform was found virtually exclusively in RA, with 44% of vascular TSPl staining being due to the TSPl0.1 isoform in RA, as compared with 7% in OA (P = 0.0047). Elastase‐ and cathepsin G‐positive cells were abundant in RA, with mean densities of 106 cells / mm2 and 103 cells / mm2, respectively, compared with 2 cells / mm2 and 11 cells / mm2 in OA. There was a wide range of both TSPl and proteinase expression within the RA group, but samples containing large numbers of elastase‐ and cathepsin G‐positive cells also showed high expression of TSPl, especially TSPl0.1,. A strong correlation was found between elastase or cathepsin G densities and TSPl0.1 expression in blood vessels (r = 0.86 and r = 0.76 respectively, P < 0.01).Conclusion. TSPl0.1, with the most potent inhibitory activity in vitro, is specifically up‐regulated in RA, and this up‐regulation is in proportion to the numbers of surrounding leukocytes containing elastase and cathepsin G. One role of TSPl may be to act as a matrix‐based regulator of leukocyte‐derived serine proteinases in vivo.