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共215条结果
  • 1.

    【2hr】Suppl 2: The p38 MAPK Pathway in Rheumatoid Arthritis: A Sideways Look

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    机译 补充2：类风湿关节炎中的p38 MAPK途径：侧身看
    摘要：The p38 mitogen-activated protein kinase (MAPK) signaling pathway has been strongly implicated in many of the processes that underlie the pathology of rheumatoid arthritis (RA). For many years it has been considered a promising target for development of new anti-inflammatory drugs with which to treat RA and other chronic immune-mediated inflammatory diseases. However, several recent clinical trials have concluded in a disappointing manner. Why is this so, if p38 MAPK clearly contributes to the excessive production of inflammatory mediators, the destruction of bone and cartilage? We argue that, to explain the apparent failure of p38 inhibitors in the rheumatology clinic, we need to understand better the complexities of the p38 pathway and its many levels of communication with other cellular signaling pathways. In this review we look at the p38 MAPK pathway from a slightly different perspective, emphasising its role in post-transcriptional rather than transcriptional control of gene expression, and its contribution to the off-phase rather than the on-phase of the inflammatory response.
  • 2.

    【2hr】Suppl 2: c-Jun N-Terminal Kinase in Inflammation and Rheumatic Diseases

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    机译 补充2：c-Jun N末端激酶在炎症和风湿性疾病中的作用
    摘要：The c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase (MAPK) family and are activated by environmental stress. JNK is also activated by proinflammatory cytokines, such as TNF and IL-1, and Toll-like receptor ligands. This pathway, therefore, can act as a critical convergence point in immune system signaling for both adaptive and innate responses. Like other MAPKs, the JNKs are activated via the sequential activation of protein kinases that includes two dual-specificity MAP kinase kinases (MKK4 and MKK7) and multiple MAP kinase kinase kinases. MAPKs, including JNKs, can be deactivated by a specialized group of phosphatases, called MAP kinase phosphatases. JNK phosphorylates and regulates the activity of transcription factors other than c-Jun, including ATF2, Elk-1, p53 and c-Myc and non-transcription factors, such as members of the Bcl-2 family. The pathway plays a critical role in cell proliferation, apoptosis, angiogenesis and migration. In this review, an overview of the functions that are related to rheumatic diseases is presented. In addition, some diseases in which JNK participates will be highlighted.
  • 3.

    【2hr】Suppl 2: JAK Kinases in Health and Disease: An Update

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    机译 补充2：健康和疾病中的JAK激酶：最新进展
    摘要：Janus kinases (Jaks) are critical signaling elements for a large subset of cytokines. As a consequence they play pivotal roles in the patho-physiology of many diseases including neoplastic and autoimmune diseases. Small molecule Jak inhibitors as therapeutic agents have become a reality and the palette of such inhibitors will likely expand. This review will summarize our current knowledge on these key enzymes and their associated pharmaceutical inhibitors.
  • 4.

    【2hr】Suppl 2: The Therapeutic Potential for PI3K Inhibitors in Autoimmune Rheumatic Diseases

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    机译 补充2：PI3K抑制剂在自身免疫性风湿性疾病中的治疗潜力
    摘要：The class 1 PI3Ks are lipid kinases with key roles in cell surface receptor-triggered signal transduction pathways. Two isoforms of the catalytic subunits, p110γ and p110δ, are enriched in leucocytes in which they promote activation, cellular growth, proliferation, differentiation and survival through the generation of the second messenger PIP3. Genetic inactivation or pharmaceutical inhibition of these PI3K isoforms in mice result in impaired immune responses and reduced susceptibility to autoimmune and inflammatory conditions. We review the PI3K signal transduction pathways and the effects of inhibition of p110γ and/or p110δ on innate and adaptive immunity. Focusing on rheumatoid arthritis and systemic lupus erythematosus we discuss the preclinical evidence and prospects for small molecule inhibitors of p110γ and/or p110δ in autoimmune disease.
  • 5.

    【2hr】Suppl 2: Signal Transduction Pathways in Chronic Inflammatory Autoimmune Disease: Small GTPases

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    机译 补充2：慢性炎症性自身免疫疾病的信号转导途径：小GTP酶
    摘要：Ras superfamily small GTPases represent a wide and diverse class of intracellular signaling proteins that are highly conserved during evolution. These enzymes serve as key checkpoints in coupling antigen receptor, growth factor, cytokine and chemokine stimulation to cellular responses. Once activated, via their ability to regulate multiple downstream signaling pathways, small GTPases amplify and diversify signaling cascades which regulate cellular proliferation, survival, cytokine expression, trafficking and retention. Small GTPases, particularly members of the Ras, Rap, and Rho family, critically coordinate the function and interplay of immune and stromal cells during inflammatory respones, and increasing evidence indicates that alterations in small GTPase signaling contribute to the pathological behavior of these cell populations in human chronic inflammatory diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Here, we review how Ras, Rap, and Rho family GTPases contribute to the biology of cell populations relevant to human chronic inflammatory disease, highlight recent advances in understanding how alterations in these pathways contribute to pathology in RA and SLE, and discuss new therapeutic strategies that may allow specific targeting of small GTPases in the clinic.
  • 6.

    【2hr】Personality and Fibromyalgia Syndrome

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    机译 人格与纤维肌痛综合征
    摘要：Objectives: We aimed to review how personality characteristics contribute to the onset, maintenance or modulation of fibromyalgia.
  • 7.

    【2hr】Rituximab (RTX) as an Alternative to TNF-Alpha Antagonists in Patients with Rheumatoid Arthritis and High Risk of Severe Infections: A Systematic Analysis of the Experience in One Center

    包量

    机译 利妥昔单抗（RTX）替代类风湿关节炎高危重症感染患者的TNF-α拮抗剂：对一个中心经验的系统分析
    摘要：Objectives: The use of TNF-alpha antagonists may be associated with an increased rate of infections in risk populations of patients with RA. Our hypothesis was that in patients with a high risk of infection Rituximab (RTX) could be a safer alternative.
  • 8.

    【2hr】Foot Problems in a Group of Patients with Rheumatoid Arthritis: An Unmet Need for Foot Care

    包量

    机译 类风湿关节炎患者的足部问题：足部护理需求未得到满足
    摘要：Objectives: The aim of this study was to evaluate the foot involvement in a group of RA patients in regard to symptoms, type and frequency of deformities, location, radiological changes, and foot care.
  • 9.

    【2hr】Is the Deficit in Pain Inhibition in Fibromyalgia Influenced by Sleep Impairments?

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    机译 睡眠障碍会影响纤维肌痛的疼痛抑制不足吗？
    摘要：It has been proposed that a deficit in inhibitory conditioned pain modulation (ICPM) underlies the pathophysiology of fibromyalgia (FM), but there is high variability in ICPM efficacy in this syndrome that remains poorly understood. Based on emerging data showing that age, anxiety, depression and sleep can modulate ICPM efficacy, the main objective of this study was to determine the clinical correlates of experimentally-induced pain perception in FM. Fifty FM patients and 39 healthy controls (HC) were tested. Anxiety, depression, sleep and FM symptoms were measured with questionnaires or interview-type scales. Experimental pain testing consisted of two tonic heat pain stimulations separated by a 2-minute cold pressor test (CPT). Thermal pain thresholds and tolerance were higher in HC compared to FM patients. Pain ratings during the CPT were lower in HC relative to FM patients. ICPM efficacy was stronger in HC compared to FM patients. Finally, sleep quality was the only factor significantly related to ICPM efficacy. To our knowledge, this is the first study to report this association in FM. Future studies will need to replicate this finding, to determine whether impaired sleep is primary or secondary to deficient pain inhibition, and to characterize the neurobiological mechanisms underlying this association.
  • 10.

    【2hr】The Effect of Stopping Smoking on Disease Activity in Rheumatoid Arthritis (RA). Data from BARFOT a Multicenter Study of Early RA

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    机译 停止吸烟对类风湿关节炎（RA）疾病活动的影响。 BARFOT数据早期RA的多中心研究
    摘要：Objective:We studied the effect of stopping smoking on disease activity in patients with RA.
  • 11.

    【2hr】Septic Arthritis Due to Staphylococcus Warneri: A Diagnostic Challenge

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    机译 由于金黄色葡萄球菌引起的化脓性关节炎：诊断上的挑战
    摘要：A septic arthritis due to an indolent infection is a challenge for timely diagnosis. In recent years septic arthritides due to Staphylococcus Warneri are increasingly reported, mostly as a complication in patients with prosthetic devices. We report on a case of a 38 year old immunocompetent male with an indolent infection with this commensal of the skin after a stay at an intensive care unit and review the available literature. Tissue cultures obtained by arthroscopy might be helpful in obtaining a correct diagnosis.
  • 12.

    【2hr】Targeted Therapy with Rituximab in Felty’s Syndrome: A Case Report

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    机译 利妥昔单抗在富蒂综合征中的靶向治疗：病例报告
    摘要：Felty’s syndrome is a rare, severe extra-articular manifestation of rheumatoid arthritis (RA). There is no standard therapy, and several disease-modifying antirheumatic drugs have been used with varying success. Only very few reports exist in literature on the use of biologicals in this indication and this with a variable efficacy. We report the case of a 53-year-old woman with severe refractory/partly undertreated RA who presented with Felty’s syndrome and pancytopenia, in whom treatment with rituximab led to an marked increase of red blood cells, neutrophils and thrombocytes. In addition, the RA disease activity status improved dramatically and treatment with steroids could be reduced. The current sparse literature on this topic is reviewed.
  • 13.

    【2hr】Anti-Tumor Necrosis Factor-α Induced Systemic Lupus Erythematosus

    包量

    机译 抗肿瘤坏死因子-α诱导的系统性红斑狼疮
    摘要：Anti-tumor necrosis factor-alpha induced lupus (ATIL) represents a major diagnostic and therapeutic challenge. Most cases of ATIL are caused by infliximab, followed by etanercept and adalimumab. Symptoms can range from common, mild cutaneous lesions to rare, serious pleural or pericardial effusions, deep venous thrombosis, life-threatening pneumonitis, and neuritis. Constitutional symptoms often present in association with positive autoantibody serology. Diagnosis can be considered if there is a temporal relationship between symptoms and anti-tumor necrosis factor-α (TNF- α) therapy and at least one serologic and one non-serologic American College of Rheumatology criteria. Since it is contraindicated to use anti-TNF-α drugs in patients with systemic lupus erythematosus, it is recommended to perform a thorough immunological screening in any patient with polyarthritis to assure accurate diagnosis. In addition, prior to anti- TNF therapy, baseline immunological investigations (including antinuclear antibodies) should be performed, and there should be close follow up to assess the development of lupus manifestations. The main approach in the treatment of ATIL is withdrawal of the offending drug. Traditional therapy with corticosteroids and immunosuppressive agents may be required to achieve full resolution of lupus symptoms. In this review, we discuss the pathogenesis, clinical manifestations, and management of ATIL.
  • 14.

    【2hr】Pain Treatment in Arthritis-Related Pain: Beyond NSAIDs

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    机译 关节炎相关疼痛的疼痛治疗：NSAID以外的治疗
    摘要：Managing pain from chronic conditions, such as, but not limited to, osteoarthritis and rheumatoid arthritis, requires the clinician to balance the need for effective analgesia against safety risks associated with analgesic agents. Osteoarthritis and rheumatoid arthritis pain is incompletely understood but involves both nociceptive and non-nociceptive mechanisms, including neuropathic mechanisms. Prevailing guidelines for arthritis-related pain do not differentiate between nociceptive and non-nociceptive pain, sometimes leading to recommendations that do not fully address the nature of pain. NSAIDs are effective in treating the nociceptive arthritis-related pain. However, safety concerns of NSAIDs may cause clinicians to undertreat arthritis-related pain. In this context, combination therapy may be more appropriate to manage the different pain mechanisms involved. A panel convened in November 2010 found that among the currently recommended analgesic products for arthritis-related pain, fixed-low-dose combination products hold promise for pain control because such products allow lower doses of individual agents resulting in decreased toxicity and acceptable efficacy due to synergy between the individual drugs. Better evidence and recommendations are required to improve treatment of chronic arthritis-related pain.
  • 15.

    【2hr】Long Term Effects of Cyclophosphamide Treatment on Lung Function and Survival in Scleroderma Patients with Interstitial Lung Disease

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    机译 环磷酰胺治疗对间质性肺病硬皮病患者肺功能和生存的长期影响
    摘要：Background:Scleroderma (SSc) patients with active interstitial lung disease (ILD) experience a decline in lung function and increased mortality; cyclophosphamide (CYC) therapy may stabilize lung function at one and two years follow-up. Long-term lung function and survival outcomes of SSc patients with ILD following CYC treatment remain largely unknown.
  • 16.

    【2hr】Hand Osteoarthritis Severity is Associated with Total Knee Joint Replacements Independently of BMI. The Ages-Reykjavik Study

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    机译 手骨关节炎的严重程度独立于BMI与全膝关节置换相关。时代雷克雅未克研究
    摘要：Objective:To identify factors associated with having total knee replacement due to osteoarthritis in the AGES-Reykjavik Study, a large population based study of elderly Icelanders.
  • 17.

    【2hr】Melatonin and Its Day and Night Rhythm of Alterations in Familial Mediterranean Fever: A Brief Research Letter

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    机译 褪黑素及其在家族性地中海热中昼夜节律变化的研究简报
    摘要：Objective: The pineal hormone melatonin plays a crucial role in immunomodulation, mainly by effecting T cells. The aims of the present study were to compare the melatonin levels in patients with Familial Mediterranean Fever (FMF) and healthy controls and to find out if it associates with interferon(IFN)γ and interleukin(IL)-10.
  • 18.

    【2hr】Induction of Experimental Arthritis by Borrelial Lipoprotein and CpG Motifs: Are Toll-Like Receptors 2 4 9 or CD-14 Involved?

    包量

    机译 硼酸脂蛋白和CpG基序诱导实验性关节炎：是否涉及Toll样受体2、4、9或CD-14？
    摘要：Bacterial lipoproteins and CpG-DNA are ligands for Toll-Like-Receptors (TLR) 2 and 9 respectively. Both classes of molecules were reported to induce experimental arthritis in rodents following direct intra-articular injection. Here we studied: 1) whether arthritis induction by Outer surface (Lipo)protein A (OspA) (B.burgdorferi) involved the TLR-2 as well as the TLR-4 or the CD-14 receptors in addition, and 2) re-examined the arthritogenic potential of CpG-DNA motifs in mice.Following intra-articular injection of the test substances [20µg recombinant, lipidated OspA; 1nM(6µg) to 10nM(60µg) synthetic CpG-DNA], inflammation was monitored by 99Tc scintigraphy (ratio left/right knee joint uptake > 1.1 indicates inflammation) and by histology.Lipoprotein OspA induced severe, acute arthritis in TLR-2+/+ w.t. but not in TLR-2-/- mice (p<0.01). There were no significant differences in the severity of arthritis induced in TLR-4+/+ w.t. and TLR-4-/- mutant mice, or between CD14+/+ w.t. and CD14-/- mice.CpG-DNA (1or 10 nM) did not cause notable inflammation in C57BL/6 mice; 99Tc ratios were < 1.0 and histology showed only minimal changes.Induction of arthritis by the OspA lipoprotein of B.burgdorferi involves the TLR-2 receptor, no evidence for additional participation of TLR-4 or CD14 receptors was found. Intra-articular injection of CpG-DNA did not produce manifest joint injury in mice, at variance with previous reports.
  • 19.

    【2hr】The Frequency of A1298C and C677T Polymorphisms of the Methylentetrahydrofolate Gene in Turkish Patients with Rheumatoid Arthritis: Relationship with Methotrexate Toxicity

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    机译 土耳其类风湿关节炎患者A1298C和C677T基因多态性的频率：与甲氨蝶呤毒性的关系
    摘要：The C677T and A1298C polymorphisms of methylenetatrahydrofolate reductase (MTHFR) gene are reported to have a relationship to methotrexate (MTX) metabolism, with conflicting results. The aim of this study was to determine the frequency of MTHFR C677 T and A1298C gene polymorphisms in a group of Turkish RA patients and evaluate its association with MTX toxicity.Sixty-four patients with RA and 31 control subjects with a mean age of 48.7 ±12.5 and 46.2 ± 13.4 years, were enrolled to the study. Demographic characteristics were obtained and MTX-related adverse effects were recorded in the patient group. The A1298C and C677T polymorphisms of the MTHFR gene were analyzed and the distribution of genotypes according side effects, were determined.The frequency of MTHFR C677T and A1298C polymorphisms were similar in the patient and control groups. Folic acid supplementation with a mean dose of 5mg folic acid/week, was present in all patients. Thirty-six of the 64 patients showed adverse effects to MTX treatment, and MTX had been discontinued in 12 (18.8%) patients due to side effects and/or inefficacy. MTHFR C677T and A1298C gene polymorphisms were found to be similar in patients with and without MTX-related adverse events.In conclusion, A1298C and C677T polymorphisms in the MTHFR gene, were not related with MTX-related toxicity in RA patients receiving folate supplementation. Further studies are needed to illuminate the polymorphisms in other enzymes that might be responsible from the MTX toxicity in patients suffering from RA.
  • 20.

    【2hr】Mononuclear Phagocytes in Rheumatoid Arthritis Patients and their Relatives – Family Similarity

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    机译 类风湿关节炎患者及其亲属的单核吞噬细胞-家庭相似性
    摘要：The aim of this work was to study the peripheral blood monocyte functions in patients with advanced RA and their predisposed to RA relatives in comparison with those in women, not hereditary tainted with autoimmune diseases (donors). In groups comprising 24 RA patients, 24 relatives, and 24 donors the following monocyte functions were assessed: engulfment and digestion (radioisotope method); release of lysosomal glucuronidase in response to opsonized zymosan (fluorescent method); reactive oxygen species (ROS) generation (chemiluminescence), and serum levels of proinflammatory cytokines (ELISA). The monocyte specific feature in patients and their relatives is chiefly extracellular digestion due to the delayed engulfment. The digestive activity, probably inhibited in relatives, is increased in advanced RA. ROS generation by the cells and serum levels of TNF-alpha and IL-1-beta are abundant both in the patients and their relatives. High levels of pro-inflammatory cytokines, presumably, of monocyte origin, and increased levels of stimulated ROS generation may be due to the priming and prolonged activation of monocytes in relatives.Conclusion:We show for the first time that the functioning of circulating mononuclear phagocytes in the assumed to be healthy predisposed to RA individuals differs from that in the healthy people not hereditary tainted with autoimmune diseases and in general resembles the functioning of the cells in the patients with advanced RA.
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