Chang Keun Lee

Interleukin-33 stimulates formation of functional osteoclasts from human CD14(+) monocytes.

Interleukin (IL)-33 is a recently described pro-inflammatory cytokine. Here we demonstrate IL-33 as a regulator of functional osteoclasts (OCs) from human CD14+ monocytes. IL-33 stimulates formation of tartrate-resistant acid phosphatase (TRAP)+ multinuclear OCs from monocytes. This action was suppressed by anti-ST2 antibody, suggesting that IL-33 acts through its receptor ST2, but not by the receptor activator of NF-κB ligand (RANKL) decoy, osteoprotegerin, or anti-RANKL antibody. IL-33 stimulated activating phosphorylations of signaling molecules in monocytes that are critical for OC development. These included Syk, phospholipase Cγ2, Gab2, MAP kinases, TAK-1, and NF-κB. IL-33 also enhanced expression of OC differentiation factors including TNF-α receptor-associated factor 6 (TRAF6), nuclear factor of activated T cells cytoplasmic 1, c-Fos, c-Src, cathepsin K, and calcitonin receptor. IL-33 eventually induced bone resorption. This study suggests that the osteoclastogenic property of IL-33 is mediated through TRAF6 as well as the immunoreceptor tyrosine-based activation motif-dependent Syk/PLCγ pathway in human CD14+ monocytes.

Clinical features and outcomes of microscopic polyangiitis in Korea.

Microscopic polyangiitis (MPA) is a systemic vasculitis affecting small vessels. To determine the clinical features and outcomes of MPA in Korean patients, we retrospectively reviewed the medical records of patients diagnosed with MPA at a single medical center in Korea between 1989 and 2006. The 18 patients who met the Chapel Hill criteria for MPA had a mean (±SD) age at the time of diagnosis of 62.4±12.7 yr. Renal manifestations and general symptoms were the most common features of MPA, with lung involvement also very common. Antineutrophil cytoplasmic antibodies (ANCA) were present in 17 of the 18 patients (94%). Of 17 patients treated with steroids and cyclophosphamide, 11 (65%) had stable or improved course. One patient treated with steroids without cyclophosphamide showed disease progression. Ten of the 18 patients (56%) died at a median follow-up of 8 months. MPA in Korean patients was distinguished by a higher rate of lung involvement, especially alveolar hemorrhage, which was the leading cause of death in our patients. Korean patients were also older at MPA onset and were more likely positive for ANCA. Other overall clinical manifestations did not differ significantly.

Identification of human UGT isoforms responsible for glucuronidation of efavirenz and its three hydroxy metabolites.

Uridine 5′-diphosphate-glucuronosyltransferases (UGTs) involved in the glucuronide formation of efavirenz (EFV) and its three hydroxy metabolites, 8-hydroxyefavirenz (8-OH EFV), 7-hydroxyefavirenz (7-OH EFV), and 8,14-dihydroxyefavirenz (8,14-diOH EFV), were assessed. Among 12 recombinant UGT isoforms tested, only UGT2B7 showed catalytic activity in the formation of EFV-N-glucuronide (EFV-G) as previously reported. On the other hand, almost all UGT isoforms were involved in the glucuronidation of the three hydroxy metabolites, although their relative contribution is unclear. The catalytic activities in the formation of EFV-G by 17 different human liver microsomes exhibit a more than 40-fold inter-individual variability, whereas those of glucuronidation of the three hydroxy metabolites showed almost identical activity. The formation of EFV-G showed a significant correlation (ru2009=u20090.920; pu2009<u20090.0001) with UGT2B7-catalysed azidothymidine glucuronidation in 17 different human liver microsomes. Furthermore, fluconazole, a known UGT2B7 inhibitor, potently inhibited the formation of EFV-G up to 80%. This suggests that EFV might be a specific UGT2B7 substrate in vitro. This is the first study identifying specific UGT isozymes that glucuronidate EFV and its three hydroxy metabolites. Continued identification and characterisation of these pathways may help reduce adverse effects such as CNS toxicity in EFV therapy.

Clinical significance of serum autoantibodies in idiopathic interstitial pneumonia.

Although autoantibodies are routinely screened in patients with idiopathic interstitial pneumonia, there are no reliable data on their clinical usefulness. The aim of this study was to investigate the prognostic value of autoantibodies for predicting the development of new connective tissue disease in these patients and also mortality. We conducted retrospective analysis of the baseline, and follow-up data for 688 patients with idiopathic interstitial pneumonia (526 with idiopathic pulmonary fibrosis, 85 with nonspecific interstitial pneumonia, and 77 with cryptogenic organizing pneumonia) at one single tertiary referral center. The median follow-up period was 33.6 months. Antinuclear antibody was positive in 34.5% of all subjects, rheumatoid factor in 13.2%, and other specific autoantibodies were positive between 0.7%-6.8% of the cases. No significant difference in patient survival was found between the autoantibody-positive and -negative groups. However, the presence of autoantibodies, especially antinuclear antibody with a titer higher than 1:320, was a significant predictor for the future development of new connective tissue diseases (relative risk, 6.4), although the incidence was low (3.8% of all subjects during follow-up). In conclusion, autoantibodies are significant predictors for new connective tissue disease development, although they have no prognostic value.

Multicenter retrospective analysis of the effectiveness and safety of rituximab in korean patients with refractory systemic lupus erythematosus.

Objective. Although two recent randomized placebo-controlled trials of rituximab (RTX) failed to demonstrate efficacy in systemic lupus erythematosus (SLE), clinicians continue to use off-label RTX for cases refractory to current treatments. We evaluated the effectiveness and safety of rituximab for patients with refractory SLE in Korea. Methods. We retrospectively analyzed multicenter patients treated with RTX in Korea. Results. 39 SLE patients treated with RTX were included in the following manner: lupus nephritis 43.6%, hematologic 33.3%, arthritis 7.8%, myositis 7.8%, and others 7.7%. All patients had responded poorly to at least one conventional immunosuppressive agent (mean 2.5 ± 1.1, cyclophosphamide 43.6%, mycophenolate mofetil 48.7%, and other drugs) before RTX. Clinical improvements (complete or partial remission) occurred in patients with renal disease, hematologic disease, arthritis, myositis, and other manifestations at 6 months after RTX. The SLEDAI score was significantly decreased from 10.8 ± 7.1 at baseline to 6.7 ± 4.0 at 6 months, 6.2 ± 4.1 at 12 months, and 5.5 ± 3.6 at 24 months after RTX (P < 0.05). Among 28 clinical responders, 4 patients experienced a relapse of disease at 25 ± 4 months. Infections were noted in 3 patients (7.7%). Conclusion. RTX could be an effective and relatively safe therapeutic option in patients with severe refractory SLE until novel B-cell depletion therapy is available.

Role of Protein Phosphatase Magnesium‐Dependent 1A and Anti–Protein Phosphatase Magnesium‐Dependent 1A Autoantibodies in Ankylosing Spondylitis

Although ankylosing spondylitis (AS) is driven by immune‐mediated processes, little is known about the presence and role of autoantibodies in this disease. This study was undertaken to investigate whether autoantibodies occur in and are involved in AS.

Design of a Time-Frequency Distribution for Vibration Monitoring under Corrosions in the Pipe

To monitor the wear and degradation on a pipe by corrosion during a plant operation, the vibration signals were measured by an accelerometer and analyzed by several analysis techniques. From the conventional methods, it was difficult to identify the wear and degradation on the pipe. And hence, the time-frequency distribution (TFD) and the adaptive cone-kernel distribution (ACKD) devised for reducing the interfering cross-terms are applied to the acquired data. They can provide the distinguishing peak patterns between the normal and corrosion signals.

Extravascular manifestations of Takayasu arteritis: focusing on the features shared with spondyloarthritis

BackgroundTakayasu arteritis (TAK) is a systemic disease characterized by large vessel involvement. Although the vascular characteristics of TAK are well characterized, there is no well-organized study demonstrating the extravascular manifestations of TAK. We aimed to evaluate the characteristics of extravascular manifestations of TAK, and to identify the association between vascular and extravascular manifestations of TAK.MethodsTAK patients from two independent cohorts between January 2012 and October 2017 were included in the study. Patient characteristics were retrospectively collected from the electronic dataset. The computed tomography scans of all subjects were reviewed to evaluate the pattern of vascular involvement and presence of sacroiliitis. Clinical findings including uveitis, skin lesions, oral ulcers, arthritis, and inflammatory bowel disease (IBD) were reviewed. Logistic regression analysis was performed to evaluate the association between vascular and extravascular manifestations.ResultsFor the 268 TAK patients, the mean age at diagnosis was 41.2u2009±u200914.2xa0years and 88.1% were female. The extravascular manifestation of TAK was observed in 19.0% of patients, the most common being arthritis including sacroiliitis (11.9%) followed by recurrent oral ulcers (8.6%) and IBD (2.6%). A multivariate logistic regression analysis revealed type IIB vascular involvement (adjusted odds ratio (OR) 2.956, 95% confidence interval (CI) 1.337–6.537, pu2009=u20090.007) and the erythrocyte sedimentation rate (ESR) (adjusted OR 1.014, 95% CI 1.003–1.025, pu2009=u20090.012) as significantly associated with the presence of axial and peripheral arthritis.ConclusionsExtravascular manifestations of TAK were observed in up to one-fifth of patients. The most common extravascular manifestation was arthritis, which was associated with a type IIB vascular involvement pattern and a high ESR.

Integrated Approach for On-Line Condition Monitoring of Piping

There are several efforts for an advanced on-line health monitoring of a piping system by using a chemical condition monitoring, a X-ray radiography and a ultrasonic techniques. In order to increase the confidence of the understanding on the health condition of the underlying piping system, an integrated and multi-disciplinary approach has been adopted in this paper. Flow-Accelerated Corrosion (FAC) under an undesirable combination of the water chemistry, flow velocity and material composition has usually caused a pipe wall thinning. The condition monitoring tests on a piping elbow of a piping system have been conducted by using several advanced sensors such as an accelerometer, ultrasonic device, and chemical sensors.

Fiber-Optic Displacement Sensor to Detect the Vibration of the Thinned U-Section by FAC

This paper deals with the reflective displacement optical fiber sensor for detecting the vibration of U-sections, which are thinned according to flow-accelerated corrosion (FAC). Surrounding the U-section, the reflecting surface, is a support frame, inside which is two bundles of optical fibers that form two displacement sensors. The natural vibration frequency was in the vicinity of 8 Hz and 22 Hz in the stable condition and in the case of pump off and a charging pump on. The peak from the fiber optic sensor was clearer and sharper than an accelerometer and a capacitance displacement sensor. Through the simulated FAC test, the vibration frequency of the U-section wall, thinned according to flow-accelerated corrosion (FAC) was increased to 10Hz. Introduction There is an international collaborative effort, part of the International Nuclear Energy Research Initiative (INERI) program, to develop and demonstrate advanced sensor and computational technology for the continuous monitoring of the condition of the components, structures, and systems in advanced and next-generation nuclear power plants (NPPs) [1]. Over the past 25 or 30 years, optical fiber sensors have emerged as an important enabler for sensing techniques. Unique fiber optic sensors have been developed for various scientific applications, especially to measure the vibration and displacement of components, which have benefited from their sensing capabilities, small size of fiber optic components, access to remote areas, and accuracy and reliability[2, 3]. In the nuclear industries, fiber optic sensors have been considered for these benefits for the past decade[4]. This paper deals with the reflective displacement fiber optic sensors for detecting the vibration of U-sections, which are thinned according to flow-accelerated corrosions (FACs)[5]. To evaluate the characteristics and performance of the developed fiber optic sensors, they were compared with the micro piezoelectric accelerometer and the capacitance displacement sensor through the magnetic pull-down test and the simulated FAC test. Flow-accelerated corrosion (FAC) is a process whereby the normally protective oxide layer on carbon or low-alloy steel dissolves into a stream of flowing water or a water-steam mixture. The u-section and piping systems made of carbon or low-alloy steel are operating in a very aggressive erosion/corrosion environment with a turbulent flow, high temperature and pressure. These adverse operating environments make a piping system very vulnerable to accelerated wear and degradation. In Key Engineering Materials Online: 2004-08-15 ISSN: 1662-9795, Vols. 270-273, pp 762-767 doi:10.4028/www.scientific.net/KEM.270-273.762