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Miyazaki T Tanaka S Sanjay A Baron R 《Modern rheumatology / the Japan Rheumatism Association》2006,16(2):68-74
The targeted disruption of c-Src impairs osteoclast bone resorbing activity, causing osteopetrosis. Although it has been reported
that restoring only the c-Src adaptor function at least partly rescues the skeletal phenotypes, the importance of c-Src kinase
activity remains controversial. We here highlight the contributions of the Src adaptor and kinase activities in cytoskeletal
organization and osteoclast function using adenovirus vectors containing various mutants of Src or Pyk2. In addition, we describe
the importance of c-Src in mitochondria, where it phosphorylates cytochrome c oxidase (Cox). Src-induced Cox activity is also required for bone resorbing activity of osteoclasts that require high levels
of ATP. Thus, c-Src kinase activity not only on the plasma membrane but also within mitochondria is essential for the regulation
of osteoclastic bone resorption. 相似文献
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Reika Maezawa Kazuhiro Kurasawa Satoko Arai Harutsugu Okada Takayoshi Owada Takeshi Fukuda 《Modern rheumatology / the Japan Rheumatism Association》2013,23(1):62-70
Objectives
Trimethoprim–sulphamethoxazole (TMP–STX), an agent used for prophylaxis against pneumocystis pneumonia (PCP) in immunocompromised hosts, causes serious adverse effects (AEs) in some patients. The objective of this study was to identify the risk factors for AEs caused by TMP–STX in connective tissue disease (CTD) patients and to describe the clinical features of the AEs.Methods
The medical records of 539 patients (CTDs 312, pulmonary diseases 227) receiving TMP–STX for prophylaxis against PCP were reviewed retrospectively. Patients with human immunodeficiency virus were excluded. Univariate and multivariate analyses were conducted to identify the risk factors.Results
Adverse events caused by TMP–STX occurred in 22 of 312 (7.05 %) CTD patients, while only six of 227 (2.64 %) pulmonary disease patients developed AEs. The incidence of AEs was significantly higher in systemic lupus erythematosus (SLE) (11.0 %) and mixed connective tissue disease (MCTD) (33.3 %) patients than in other CTD patients. AEs occurred in 25 % of patients with anti-RNP antibody. Univariate analysis revealed that SLE, MCTD, and anti-RNP antibody were risk factors for AEs in CTD patients. Further multivariate analyses demonstrated that only anti-RNP antibody positivity was a risk factor for AEs. Systemic inflammation, including fever, was a characteristic manifestation of the AEs in CTD patients, particularly those with anti-RNP antibody.Conclusions
Positivity for anti-RNP antibody is a risk factor for AEs caused by TMP–STX in CTD patients. Systemic inflammation, including fever, might be a characteristic feature of the AEs in CTD patients, particularly those with anti-RNP antibody. 相似文献4.
Pulmonary function in children with juvenile idiopathic arthritis and effects of methotrexate therapy 总被引:2,自引:0,他引:2
Summary
Objective To evaluate impairment of lung function as an adverse effect associated with methotrexate therapy in patients with juvenile
idiopathic arthritis (JIA). Methods We performed pulmonary function testing including diffusion capacity for carbon monoxide as measured by the single breath
method (DLCO-SB) in 89 children with juvenile idiopathic arthritis. Forty (45%) were treated with methotrexate for a median
of 24 months (range 3 to 120 months). Except for the presence of asthma in two children, there was no clinical or radiological
evidence of pulmonary disease. Results Pulmonary function testing demonstrated moderate airway obstruction in two children with known bronchial asthma. Neither
obstructive nor restrictive alteration of ventilation was found in any other patient. Two juvenile idiopathic arthritis patients
showed a reduced CO diffusion capacity of 64 and 67%. One of them was treated with methotrexate. Conclusions With regard to lung function impairment treatment with low dose methotrexate appears to be safe even when performed for several
years reaching a total amount of up to 3.5 g. In contrast to studies performed in adult rheumatoid arthritis patients, in
children with juvenile idiopathic arthritis impairment of lung function is a rare event.
Received: 23 February 2001 Accepted: 16 May 2001 相似文献
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The ainich of study was to investigate the efficacy and toxicity of sulphasalazine (SASP) in the treatment of children with chronic arthritis. The medical records of 36 children (25 boys, 11 girls) who received SASP for the treatment of chronic arthritis were reviewed. Twenty-one patients had juvenile spondyloarthropathies (JSA) (eight juvenile ankylosing spondylitis (JAS), 13 undifferentiated JSA (uJSA) and 15 had juvenile rheumatoid arthritis (JRA). The patients received SASP therapy for a mean of 2.5 years (range 3 weeks to 8.1 years). Clinical and laboratory data were reviewed retrospectively to determine the effects of treatment. A clinically significant response occurred in 23 (64%) children: remission in 14 (39%) (JRA 5, JSA 9) and improvement (25% reduction in joint count) in nine (25%) (JRA 4, JSA 5). There was no difference in response rate between JR and JSA patients (p=0.11), but the time to remission shorter in JSA patients (mean 5 months) JRA patients (mean 25 months) (p=0.024). Twelve of the 36 patients discontinued non-steroidal anti-inflammatory drugs, and six of eight patients discontinued prednisolone. A significant fall in erythrocyte sedimentation rate and rise in haemoglobin occurred in SASP-treated patients (p<0.005) comparing most recent results with pretreatment levels. Side-effects occurred in four of 36 patients (11%); only one patient who had persisting severe diarrhoea required discontinuation of SASP. It was concluded that SASP appears to be effective and safe in the treatment of JRA and JSA patients. As a second-line agent, SASP is the drug of first choice for patients with JSA; for JRA patients SASP may be a useful, possibly less toxic alternative to methotrexate. 相似文献
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G. Camiciottoli S. Trapani W. Castellani R. Ginanni M. Ermini F. Falcini 《Rheumatology international》1998,18(1):11-16
We evaluated lung function in a group of patients affected by juvenile rheumatoid arthritis (JRA), without clinical and/or
radiological signs of respiratory involvement. We compared the effects on pulmonary function of methotrexate (MTX) therapy
combined with non-steroid anti-inflammatory drugs (NSAIDs) to those of NSAIDs alone and correlated lung function to subtype
onset, disease duration and disease activity. Our patients were 27 JRA children, subdivided into two groups according to the
therapy (group A=14 patients, treated with a low dose of MTX and NSAIDs; group B=13 patients, treated with NSAIDs alone).
Clinical evaluation, haematological data and pulmonary function tests (PFTs) were obtained in each group at baseline (time
0) and at 1 year (time 1). At time 0 and time 1 PFTs were altered in 51.8% of JRA patients. The restrictive pattern (reduced
forced vital capacity, FVC) was the most frequent feature, observed in 22.2% of patients. In group A the mean values of FVC,
FEV1 (forced expiratory flow in 1 s), FRC (functional residual capacity), TLC (total lung capacity) and DLCO (diffusing lung
capacity of carbon monoxide) were significantly lower compared to those of group B, at time 0 and at time 1. No functional
parameter was correlated to subtype, duration or activity of the disease. Our study confirms that abnormalities in PFTs may
be detected in JRA patients, even in the absence of clinical and/or radiological signs of lung disease; MTX in combination
with NSAIDs does not seem to affect lung function at 1 year more than NSAIDs alone.
Received: 3 November 1997 / Accepted: 21 December 1997 相似文献
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Ochi S Shinohara M Sato K Gober HJ Koga T Kodama T Takai T Miyasaka N Takayanagi H 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(27):11394-11399
Abnormal T cell immune responses induce aberrant expression of inflammatory cytokines such as TNF-alpha, leading to osteoclastmediated bone erosion and osteoporosis in autoimmune arthritis. However, the mechanism underlying enhanced osteoclastogenesis in arthritis is not completely understood. Here we show that TNF-alpha contributes to inflammatory bone loss by enhancing the osteoclastogenic potential of osteoclast precursor cells through inducing paired Ig-like receptor-A (PIR-A), a costimulatory receptor for receptor activator of NF-kappaB (RANK). In fact, bone erosion and osteoporosis, but not inflammation, caused by aberrant TNF-alpha expression were ameliorated in mice deficient in Fc receptor common gamma subunit or beta(2)-microglobulin, in which the expression of PIR-As and PIR-A ligands is impaired, respectively. These results establish the pathological role of costimulatory receptors for RANK in bone loss in arthritis and may provide a molecular basis for the future therapy of inflammatory diseases. 相似文献
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Davinder Singh‐Grewal Jane Schneiderman‐Walker Virginia Wright Oded Bar‐Or Joseph Beyene Hiran Selvadurai Bonnie Cameron Ronald M. Laxer Rayfel Schneider Earl D. Silverman Lynn Spiegel Shirley Tse Claire Leblanc Janice Wong Samantha Stephens Brian M. Feldman 《Arthritis care & research》2007,57(7):1202-1210
Objective
To examine the effectiveness of high‐intensity aerobic training compared with low‐intensity training in terms of energy cost of locomotion, peak oxygen uptake, peak power, and self‐reported physical function in children with juvenile idiopathic arthritis (JIA).Methods
Eighty children with JIA, ages 8–16 years, were enrolled in a randomized, single‐blind controlled trial. Both groups participated in a 12‐week, 3‐times–weekly training program consisting of high‐intensity aerobics in the experimental group and qigong in the control group. Subjects underwent exercise testing measuring submaximal oxygen uptake at 3 km/hour (VO 2submax) as the primary outcome, maximal oxygen uptake, and peak power at the beginning and end of the program. Physical function was measured using the Child Health Assessment Questionnaire (C‐HAQ).Results
The exercise program was well tolerated in both groups. There was no difference in VO 2submax or any other exercise testing measures between the groups through the study period and no indication of improvement. Both groups showed significant improvements in C‐HAQ with no difference between the groups. Adherence was higher in the control group than the experimental group.Conclusion
Our findings suggest that activity programs with or without an aerobic training component are safe and may result in an important improvement in physical function. The intensity of aerobic training did not seem to provide any additional benefits, but higher adherence in the qigong program may suggest that less intensive regimens are easier for children with JIA to comply with, and provide a degree of benefit equivalent to more intensive programs. 相似文献9.
Brunner JK Scholl-Bürgi S Hössinger D Wondrak P Prelog M Zimmerhackl LB 《Rheumatology international》2008,28(9):949-950
Juvenile idiopathic arthritis (JIA) is an inflammatory joint disease of unknown etiology. The pathogenesis is driven by T and B cells. The role of macrophages remains unclear. Chitotriosidase belongs to the chitinase protein family and is secreted by activated macrophages. The chitinases are able to catalyze the hydrolysis of chitin or chitin-like substrates such as 4-methylumbelliferyl chitotrioside. Chitotriosidase activity was determined using the substrate 4-methylumbelliferyl beta-DNN'N'-triacetylchitotrioside (4-MU-TCT, SIGMA Chemical Co.). The substrate and serum were incubated with the serum in a citrate/phosphate buffer. The reaction was stopped by adding a buffer (Na(2)CO(3)). The fluorescence of 4-methylumbelliferone was evaluated by fluorimeter at excitation 360 nm and emission 450 nm. We report about chitotriosidase measurements in patients with JIA. The chitotriosidase level in synovial fluid was up to approximately 1,000 nmol/(h ml) at disease onset before therapy. The level in the sera was below 600 nmol/(h ml). Serum chitotriosidase levels could represent the activity of macrophages in the synovial fluid in JIA. 相似文献
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Francisco Hélder C. Félix Luzia Kalyne A. M. Leal Juvenia Bezerra Fontenele 《Rheumatology international》2009,29(8):973-974
Adult onset Still’s disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology. Systemic onset juvenile idiopathic
arthritis (SoJIA) is the preferred nomenclature of Still’s disease. Strong association with so-called macrophage activation
syndrome (MAS) may provide a clue to the understanding of the distinctive pathogenetic features of SoJIA. MAS is a severe,
potentially life-threatening complication characterized by the excessive activation of well-differentiated macrophages. It
is more appropriately named autoimmune disease associated reactive hemophagocytic lymphohistiocytosis (ReHLH), a subset of
a histiocytic disorder: class II histiocytosis hemophagocytic lymphohistiocytosis (HLH). The relation of SoJIA with HLH is
still under debate. We propose that MAS, HLH, SoJIA, and AOSD are indeed the same disease, in different clinical presentations
that may be classified based on severity and laboratory findings, but with essentially the same physiopathogenesis. We propose
that the case described by Hong & Lee (Rheumatol Int 2008) was actually an AOSD-associated MAS/RHS/ReHLH fulminant disease. 相似文献
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Nerome Y Imanaka H Nonaka Y Takei S 《Modern rheumatology / the Japan Rheumatism Association》2007,17(6):526-528
Tumor necrosis factor α (TNFα)-blocking agents have been used increasingly in the treatment of severe refractory juvenile
idiopathic arthritis (JIA). However, some patients have been forced to discontinue these agents because of the lack of efficacy
or adverse events. In these situations, cases of switching from one TNF-blocking agent to another are reported in rheumatoid
arthritis, but there are few cases in JIA. This report documents the case of a patient with JIA who improved following a switch
from etanercept to infliximab. 相似文献
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《Modern rheumatology / the Japan Rheumatism Association》2013,23(6):526-528
AbstractTumor necrosis factor α (TNFα)-blocking agents have been used increasingly in the treatment of severe refractory juvenile idiopathic arthritis (JIA). However, some patients have been forced to discontinue these agents because of the lack of efficacy or adverse events. In these situations, cases of switching from one TNF-blocking agent to another are reported in rheumatoid arthritis, but there are few cases in JIA. This report documents the case of a patient with JIA who improved following a switch from etanercept to infliximab. 相似文献
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There is currently no agreement on how to classify and diagnose reactive arthritis (ReA) and what kind of clinical and laboratory findings are specific for the diagnosis. This study retrospectively analyzed the initial clinical manifestations and laboratory findings in children diagnosed with ReA and juvenile idiopathic arthritis (JIA). A comparison was also made between these two groups to see if there were differences. A retrospective chart review was performed and 44 patients diagnosed with ReA and 80 patients with JIA were enrolled in this study. Their initial clinical manifestations and laboratory findings were also analyzed and compared. The initial clinical manifestations in ReA were analyzed including the demographic data, the preceding infection history, the duration of the infectious episode to the onset of arthritis, the duration of arthritic symptoms, and the involved joint pattern. Comparison of the initial laboratory findings between patients with ReA and JIA showed significant differences between erythrocyte sedimentation rates (ESR) in the first hour, platelet counts (p<0.05), and ESR in the second hour (p=0.052). Further, comparing ReA with the subtypes of JIA, significant differences were noted between ReA and the systemic type in terms of hemoglobin level, platelet counts, C-reactive protein, and first and second hour ESR (p<0.05). However, if compared with the polyarticular or pauciarticular type, only the platelet counts showed any significant statistical difference (p<0.05). This study summarizes clinical experiences in ReA. The differences in laboratory findings of ReA and JIA may provide a clue in making a differential diagnosis. 相似文献
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Jun-ichi Kawada Yoshiro Kitagawa Naomi Iwata Yoshinori Ito 《Modern rheumatology / the Japan Rheumatism Association》2013,23(5):972-976
Background
Inhibition of interleukin-6 (IL-6) signaling by tocilizumab is highly effective for treatment of refractory juvenile idiopathic arthritis (JIA). It appears that IL-6 plays an important role in the immune response to the influenza virus, but it is not clear whether treatment with tocilizumab affects the severity of influenza.Methods
We retrospectively collected clinical and laboratory data from JIA patients (n = 33) treated with tocilizumab. Ten patients who developed influenza (tocilizumab group; 10.1 %, 10/99 patient-years) were analyzed. Eleven JIA patients who experienced influenza during conventional treatments, without tocilizumab (control group), were compared with the tocilizumab group.Results
Of the 10 patients in the tocilizumab group, 6 patients did not have high fever (>38 °C), and the other 4 febrile patients recovered from fever in 1 day. White blood cell counts and lymphocyte counts were significantly lower at the acute phase of infection compared with data from before influenza infection. The degree of fever and level of C-reactive protein in the tocilizumab group were significantly reduced compared with the control group.Conclusions
IL-6 inhibition by tocilizumab reduced inflammation associated with infection and resulted in mild symptoms during influenza. Leukopenia might be a useful indicator of viral infection, including influenza, during tocilizumab treatment. 相似文献17.
Nerome Y Imanaka H Nonaka Y Tsuru Y Maeno N Takezaki T Mori H Akaike H Kubota T Kawano Y Takei S 《Modern rheumatology / the Japan Rheumatism Association》2008,18(2):189-192
We report a 27-year-old case of juvenile idiopathic arthritis (JIA) having been stopped infliximab during pregnancy. She was
safely treated by infliximab therapy with premedications for preventing infusin reactions after her delivery, and then improved
in the same manner as when she had been treated with infliximab therapy before pregnancy. As a result, it remains unclear
whether or not we can use infliximab to control disease activities during pregnancy. In addition, it is also important to
clarify whether or not premedications should be used when resuming infliximab treatment in such patients after pregnancy.
These problems still remain controversial. More definitive data are needed in order to allow rheumatologists to better select
the optimal TNF-alpha inhibitor therapy when treating pregnant JIA patients. 相似文献
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H. I. Brunner E. Ivaskova J. P. Haas A. Andreas E. Keller J. Hoza S. Havelka S. Scholz G. Sierp E. D. Albert 《Rheumatology international》1993,13(2):83-88
Summary A total of 94 patients with juvenile chronic arthritis (JCA) was tested for HLA class I by serology and for class II by RFLP typing. Early onset JCA (EOPA) is associated with HLA-A2, DR5 and DR8 in both males and females. The combination (joint occurrence) of these JCA associated alleles (A2, DR5, DR8) is frequently seen in patients with chronic iridocyclitis. Late onset pauciarticular disease has an increased frequency of HLA-B27, especially in males. Our data confirm that polyarticular JCA with early childhood onset (4 years) is associated with DR5 and DR8 and has a different immunogenetic background from polyarticular JCA with later childhood (>4 years) onset (associated with DR4). 相似文献
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Xiaolin Ma Fengqi Wu Le Xin Gaixiu Su Feng He Yang Yang 《Modern rheumatology / the Japan Rheumatism Association》2016,26(2):224-232
Objectives. To identify potential novel biomarkers for juvenile idiopathic arthritis (JIA), we evaluated the correlation between plasma expression levels of specific miRNAs and disease characteristics of JIA.Methods. Differentially expressed miRNAs in JIA plasma were identified by microarray analysis. Five candidate plasma miRNAs with differential expression were further evaluated by qRT-PCR. The correlation between the expression of candidate plasma miRNAs and clinical parameters of JIA patients was assessed.Results. The expression of miR-16, miR-146a, and miR-223 was higher, and miR-132 was lower, in the plasma of JIA patients as compared with healthy subjects and juvenile ankylosing spondylitis patients (p < 0.05). Plasma miR-16 concentrations were considerably higher for polyarticular JIA patients than oligoarticular JIA patients and correlated with the juvenile arthritis magnetic resonance imaging scores for the hip and plasma interleukin-6 or IL-6 levels. Additionally, miR-146a levels correlated directly with the Juvenile Arthritis Disease Activity Scores in 27 joints, the swollen joint count, the limited joint count, and the juvenile arthritis magnetic resonance imaging scores for the hip, but correlated inversely with plasma tumor necrosis factor-α or TNF-α levels.Conclusions. This study demonstrates that the expression of plasma miRNAs correlates with JIA disease and suggests that plasma miR-16 and miR-146a have potential novel value for JIA diagnosis. 相似文献
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Mervat I. Abd El-Azeem Hanan A. Taha Ashraf M. El-Sherif 《The Egyptian Rheumatologist》2012,34(2):75-82
Aim of the WorkTo evaluate the role of MRI in diagnosing hip arthritis and correlating it with clinical and laboratory assessments in juvenile idiopathic arthritis (JIA).Patients and MethodsThe study included 30 patients with JIA with mean age of 13.5 ± 4.5. Disease activity was evaluated by DAS28 score, physician’s global assessment (PGA–VAS), patient’s global assessment (VASglobal) and the assessment of functional ability by (CHAQ). Hip joint evaluation was assessed by hip pain on movement and the degree of limitation of motion (score 0–3). Plain radiography and MRI of the hip joint were performed for all patients. MRI score was done.ResultsMRI of hips was abnormal in 12 (40%) of all patients: 2/8 (25%) of the oligoarticular group, 4/13 (30.8%) of the polyarticular group, 5/7 (71.4%) of the systemic onset group and 1/2(50%) of the enthesitis related group. Comparing mean values of MR scores of the four clinical subsets showed significant difference (p < 0.001). Patients with active disease showed higher MR scores (3.7 ± 1.5) than those with inactive disease (2.1 ± .9) [p < 0.002]. Presence of effusion and gadolinium enhancement were significantly higher in active hips (p < 0.01 and p < 0.001 respectively). VAS–PGA and ESR were significantly correlated with MRI score (p < 0.02 and <0.05 respectively).ConclusionMRI of the hip plays an important role in the study of patients with JIA as it reveals early joint involvement and evaluates the extent of joint disease. This permits intervention at an appropriate time with suitable treatment. Clinical and laboratory findings are inadequate diagnostic tools for the assessment of hip arthritis when comparing with MRI. 相似文献