47 results on '"Yun SR"'
Search Results
2. Structural dynamics of protein-protein association involved in the light-induced transition of Avena sativa LOV2 protein.
- Author
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Kim C, Yun SR, Lee SJ, Kim SO, Lee H, Choi J, Kim JG, Kim TW, You S, Kosheleva I, Noh T, Baek J, and Ihee H
- Subjects
- Models, Molecular, Protein Binding, Protein Domains, Avena metabolism, Plant Proteins metabolism, Plant Proteins chemistry, Light, Protein Multimerization
- Abstract
The Light-oxygen-voltage-sensing domain (LOV) superfamily, found in enzymes and signal transduction proteins, plays a crucial role in converting light signals into structural signals, mediating various biological mechanisms. While time-resolved spectroscopic studies have revealed the dynamics of the LOV-domain chromophore's electronic structures, understanding the structural changes in the protein moiety, particularly regarding light-induced dimerization, remains challenging. Here, we utilize time-resolved X-ray liquidography to capture the light-induced dimerization of Avena sativa LOV2. Our analysis unveils that dimerization occurs within milliseconds after the unfolding of the A'α and Jα helices in the microsecond time range. Notably, our findings suggest that protein-protein interactions (PPIs) among the β-scaffolds, mediated by helix unfolding, play a key role in dimerization. In this work, we offer structural insights into the dimerization of LOV2 proteins following structural changes in the A'α and Jα helices, as well as mechanistic insights into the protein-protein association process driven by PPIs., (© 2024. The Author(s).)
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- 2024
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3. Serial X-ray liquidography: multi-dimensional assay framework for exploring biomolecular structural dynamics with microgram quantities.
- Author
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Kim SO, Yun SR, Lee H, Jo J, Ahn DS, Kim D, Kosheleva I, Henning R, Kim J, Kim C, You S, Kim H, Lee SJ, and Ihee H
- Subjects
- Kinetics, X-Rays, Protein Conformation, Lasers, Bacterial Proteins chemistry, Bacterial Proteins metabolism, Proteins chemistry
- Abstract
Understanding protein structure and kinetics under physiological conditions is crucial for elucidating complex biological processes. While time-resolved (TR) techniques have advanced to track molecular actions, their practical application in biological reactions is often confined to reversible photoreactions within limited experimental parameters due to inefficient sample utilization and inflexibility of experimental setups. Here, we introduce serial X-ray liquidography (SXL), a technique that combines time-resolved X-ray liquidography with a fixed target of serially arranged microchambers. SXL breaks through the previously mentioned barriers, enabling microgram-scale TR studies of both irreversible and reversible reactions of even a non-photoactive protein. We demonstrate its versatility in studying a wide range of biological reactions, highlighting its potential as a flexible and multi-dimensional assay framework for kinetic and structural characterization. Leveraging X-ray free-electron lasers and micro-focused X-ray pulses promises further enhancements in both temporal resolution and minimizing sample quantity. SXL offers unprecedented insights into the structural and kinetic landscapes of molecular actions, paving the way for a deeper understanding of complex biological processes., (© 2024. The Author(s).)
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- 2024
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4. Plasma presepsin for mortality prediction in patients with sepsis-associated acute kidney injury requiring continuous kidney replacement therapy.
- Author
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Lee GB, Lee JW, Yoon SH, Hwang WM, Yun SR, Koh DH, and Park Y
- Abstract
Background: The reliability of presepsin as a biomarker of sepsis may be reduced in patients with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT). This study analyzed the utility of plasma presepsin values in predicting mortality in patients with AKI requiring CKRT, particularly those with sepsis-associated AKI., Methods: This single-center retrospective study included 57 patients who underwent CKRT, with plasma presepsin measurements, from April 2022 to March 2023; 35 had sepsis-associated AKI. The predictive values of plasma presepsin, as well as Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, for 28-day mortality were analyzed using receiver operating characteristic curves. Multivariate Cox regression analysis was performed to identify risk factors for 28-day mortality in the sepsis-associated AKI subgroup., Results: Overall, plasma presepsin showed a lower area under the curve value (0.636; 95% confidence interval [CI], 0.491-0.781) than the APACHE II (0.663; 95% CI, 0.521-0.804) and SOFA (0.731; 95% CI, 0.599-0.863) scores did. However, in sepsis-associated AKI, the area under the curve increased to 0.799 (95% CI, 0.653-0.946), which was higher than that of the APACHE II (0.638; 95% CI, 0.450-0.826) and SOFA (0.697; 95% CI, 0.519-0.875) scores. In the multivariate Cox regression analysis, a high presepsin level was an independent risk factor for 28-day mortality in sepsis-associated AKI (hazard ratio, 3.437; p = 0.03)., Conclusion: Presepsin is a potential prognostic marker in patients with sepsis-associated AKI requiring CKRT.
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- 2024
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5. Usefulness of the heart rate variability test in predicting intradialytic hypotension in patients undergoing chronic haemodialysis.
- Author
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Park Y, Lee JW, Yoon SH, Hwang WM, Yun SR, Son JY, Chung BH, and Min J
- Abstract
Background: Intradialytic hypotension (IDH) is the primary complication of haemodialysis (HD); however, its diverse pathophysiology and inconsistent definitions complicate its prediction. Despite attempts using the heart rate variability (HRV) test for IDH prediction, studies on its usefulness for predicting IDH diagnosed per the nadir 90 criterion are lacking. We aimed to evaluate HRV test efficacy and reproducibility in predicting IDH based on the nadir 90 criterion., Methods: Seventy patients undergoing HD participated in this multicentre prospective observational study. The HRV test was performed during non-HD periods and IDH was monitored during 12 HD sessions. IDH was diagnosed according to the nadir 90 criterion, defined as a decrease in systolic blood pressure of ≤90 mmHg during HD. After monitoring, the HRV test was repeated. An HRV-IDH index was developed using multivariate logistic regression analysis employing HRV test parameters. The predictive power of the HRV-IDH index was analysed using the area under the receiver operating characteristics curve (AUROC). Reproducibility was evaluated using correlation analysis of two HRV tests on the same patient., Results: There were 37 and 33 patients in the IDH and non-IDH groups, respectively. The HRV-IDH index predicted IDH occurrence with AUROCs of 0.776 and 0.803 for patients who had experienced at least one or repeated IDH episodes, respectively. Spearman's correlation coefficient for HRV-IDH indices was 0.859 for the first and second HRV tests., Conclusions: The HRV test holds promise for predicting IDH, particularly for patients with recurring IDH diagnosed based on the nadir 90 criterion., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)
- Published
- 2024
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6. Author Correction: Importance of dialysis specialists in early mortality in elderly hemodialysis patients: a multicenter retrospective cohort study.
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Park Y, Lee JW, Yoon SH, Yun SR, Kim H, Bae E, Hyun YY, Chung S, Kwon SH, Cho JH, Yoo KD, Park WY, Sun IO, Yu BC, Ko GJ, Yang JW, Song SH, Shin SJ, Hong YA, and Hwang WM
- Published
- 2024
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7. Maternal histone methyltransferases antagonistically regulate monoallelic expression in C. elegans .
- Author
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Sands B, Yun SR, Oshima J, and Mendenhall AR
- Abstract
Undefined epigenetic programs act to probabilistically silence individual autosomal alleles, generating unique individuals, even from genetic clones. This sort of random monoallelic expression can explain variation in traits and diseases that differences in genes and environments cannot. Here, we developed the nematode Caenorhabditis elegans to study monoallelic expression in whole tissues, and defined a developmental genetic regulation pathway. We found maternal H3K9 histone methyltransferase (HMT) SET-25/SUV39/G9a works with HPL-2/HP1 and LIN-61/L3MBTL2 to randomly silence alleles in the intestinal progenitor E-cell of 8-cell embryos to cause monoallelic expression. SET-25 was antagonized by another maternal H3K9 HMT, MET-2/SETDB1, which works with LIN-65/ATF7ZIP and ARLE-14/ARL14EP to prevent monoallelic expression. The HMT-catalytic SET domains of both MET-2 and SET-25 were required for regulating monoallelic expression. Our data support a model wherein SET-25 and MET-2 regulate histones during development to generate patterns of somatic monoallelic expression that are persistent but not heritable.
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- 2024
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8. Importance of dialysis specialists in early mortality in elderly hemodialysis patients: a multicenter retrospective cohort study.
- Author
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Park Y, Lee JW, Yoon SH, Yun SR, Kim H, Bae E, Hyun YY, Chung S, Kwon SH, Cho JH, Yoo KD, Park WY, Sun IO, Yu BC, Ko GJ, Yang JW, Song SH, Shin SJ, Hong YA, and Hwang WM
- Subjects
- Aged, Humans, Retrospective Studies, Health Facilities, Multivariate Analysis, Renal Dialysis, Cognition
- Abstract
The early mortality rate in elderly patients undergoing hemodialysis is more than twice that in young patients, requiring more specialized healthcare. We investigated whether the number of professional dialysis specialists affected early mortality in elderly patients undergoing hemodialysis. This multicenter retrospective cohort study analyzed data from 1860 patients aged ≥ 70 years who started hemodialysis between January 2010 and December 2017. Study regions included Seoul, Gyeonggi-do, Gangwon-do, Daejeon/Chungcheong-do, Daegu/Gyeongsangbuk-do, and Busan/Ulsan/Gyeongsangnam-do. The number of patients undergoing hemodialysis per dialysis specialist was calculated using registered data from each hemodialysis center. Early mortality was defined as death within 6 months of hemodialysis initiation. Gangwon-do (28.3%) and Seoul (14.5%) showed the highest and lowest early mortality rate, respectively. Similarly, Gangwon-do (64.6) and Seoul (43.9) had the highest and lowest number of patients per dialysis specialist, respectively. Relatively consistent results were observed for the regional rankings of early mortality rate and number of patients per dialysis specialist. Multivariate Cox regression analysis-adjusted for previously known significant risk factors-revealed that the number of patients per dialysis specialist was an independent risk factor for early mortality (hazard ratio: 1.031, p < 0.001). This study underscores the growing need for dialysis specialists for elderly hemodialysis patients in Korea., (© 2024. The Author(s).)
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- 2024
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9. Ultrahigh resolution lipid mass spectrometry imaging of high-grade serous ovarian cancer mouse models.
- Author
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Ma X, Botros A, Yun SR, Park EY, Kim O, Park S, Pham TH, Chen R, Palaniappan M, Matzuk MM, Kim J, and Fernández FM
- Abstract
No effective screening tools for ovarian cancer (OC) exist, making it one of the deadliest cancers among women. Considering that little is known about the detailed progression and metastasis mechanism of OC at a molecular level, it is crucial to gain more insights into how metabolic and signaling alterations accompany its development. Herein, we present a comprehensive study using ultra-high-resolution Fourier transform ion cyclotron resonance matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to investigate the spatial distribution and alterations of lipids in ovarian tissues collected from double knockout ( n = 4) and triple mutant mouse models ( n = 4) of high-grade serous ovarian cancer (HGSOC). Lipids belonging to a total of 15 different classes were annotated and their abundance changes were compared to those in healthy mouse reproductive tissue ( n = 4), mapping onto major lipid pathways involved in OC progression. From intermediate-stage OC to advanced HGSC, we provide direct visualization of lipid distributions and their biological links to inflammatory response, cellular stress, cell proliferation, and other processes. We also show the ability to distinguish tumors at different stages from healthy tissues via a number of highly specific lipid biomarkers, providing targets for future panels that could be useful in diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ma, Botros, Yun, Park, Kim, Park, Pham, Chen, Palaniappan, Matzuk, Kim and Fernández.)
- Published
- 2024
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10. Ultrahigh Resolution Lipid Mass Spectrometry Imaging of High-Grade Serous Ovarian Cancer Mouse Models.
- Author
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Ma X, Botros A, Yun SR, Park EY, Kim O, Chen R, Palaniappan M, Matzuk MM, Kim J, and Fernández FM
- Abstract
No effective screening tools for ovarian cancer (OC) exist, making it one of the deadliest cancers among women. Considering little is known about the detailed progression and metastasis mechanism of OC at a molecular level, it is crucial to gain more insights on how metabolic and signaling alterations accompany its development. Herein, we present a comprehensive study using ultra-high-resolution Fourier transform ion cyclotron resonance matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to investigate the spatial distribution and alterations of lipids in ovarian tissues collected from double knockout ( n = 4) and a triple mutant mouse models ( n = 4) of high-grade serous ovarian cancer (HGSC). Lipids belonging to a total of 15 different classes were annotated and their abundance changes compared to those in healthy mouse reproductive tissue ( n = 4), mapping onto major lipid pathways involved in OC progression. From intermediate-stage OC to advanced HGSC, we provide a direct visualization of lipid distributions and their biological links to inflammatory response, cellular stress, cell proliferation, and other processes. We also show the ability to distinguish tumors at different stages from healthy tissues via a number of highly specific lipid biomarkers, providing targets for future panels that could be useful in diagnosis.
- Published
- 2023
- Full Text
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11. Visualizing Heterogeneous Protein Conformations with Multi-Tilt Nanoparticle-Aided Cryo-Electron Microscopy Sampling.
- Author
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Kim C, Kim Y, Lee SJ, Yun SR, Choi J, Kim SO, Yang Y, and Ihee H
- Subjects
- Cryoelectron Microscopy methods, Gold chemistry, Protein Conformation, Calmodulin, Metal Nanoparticles chemistry
- Abstract
Obtaining the heterogeneous conformation of small proteins is important for understanding their biological role, but it is still challenging. Here, we developed a multi-tilt nanoparticle-aided cryo-electron microscopy sampling (MT-NACS) technique that enables the observation of heterogeneous conformations of small proteins and applied it to calmodulin. By imaging the proteins labeled by two gold nanoparticles at multiple tilt angles and analyzing the projected positions of the nanoparticles, the distributions of 3D interparticle distances were obtained. From the measured distance distributions, the conformational changes associated with Ca
2+ binding and salt concentration were determined. MT-NACS was also used to track the structural change accompanied by the interaction between amyloid-beta and calmodulin, which has never been observed experimentally. This work offers an alternative platform for studying the functional flexibility of small proteins.- Published
- 2023
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12. Comparison of the association intensity of creatinine and cystatin C with hyperphosphatemia and hyperparathyroidism in patients with chronic kidney disease.
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Min B, Yun SR, Yoon SH, Kim JD, Hwang WJ, Hwang WM, and Park Y
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- Humans, Aged, Cystatin C, Creatinine, Glomerular Filtration Rate physiology, Hyperphosphatemia complications, Renal Insufficiency, Chronic, Hyperparathyroidism, Secondary complications
- Abstract
Herein, we compared the association intensity of estimated glomerular filtration rate (eGFR) equations using creatinine (Cr) or cystatin C (CysC) with hyperphosphatemia and secondary hyperparathyroidism occurrence, which reflect the physiological changes occurring during chronic kidney disease (CKD) progression. This study included 639 patients treated between January 2019 and February 2022. The patients were divided into low- and high-difference groups based on the median value of the difference between the Cr-based eGFR (eGFR
Cr ) and CysC-based eGFR (eGFRCysC ). Sociodemographic and laboratory factors underlying a high difference between eGFRCr and eGFRCysC were analyzed. The association intensity of eGFRCr , eGFRCysC and both Cr- and CysC-based eGFR (eGFRCr-CysC ) was compared using the area under the receiver operating characteristic curve (AuROC) values for hyperphosphatemia and hyperparathyroidism occurrence in the overall cohort and the low- and high-difference groups. Age > 70 years and CKD grade 3 based on eGFRCr were significant factors affecting the high differences. eGFRCysC and eGFRCr-CysC showed higher AuROC values than that of eGFRCr , especially in the high-difference group and in patients with CKD grade 3. Our results show that CysC should be evaluated in patients with significant factors, including age > 70 years and CKD grade 3, to accurately assess kidney function to better determine the physiological changes in CKD progression and predict prognosis accurately., (© 2023. The Author(s).)- Published
- 2023
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13. Combined impact of the inter and intra-patient variability of tacrolimus blood level on allograft outcomes in kidney transplantation.
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Park Y, Lee H, Eum SH, Ko EJ, Min JW, Yoon SH, Hwang WM, Yun SR, Yang CW, Shin J, and Chung BH
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- Humans, Transplantation, Homologous, Tissue Donors, Allografts, Tacrolimus therapeutic use, Kidney Transplantation adverse effects
- Abstract
Introduction: Tacrolimus (TAC) has been widely used as an immunosuppressant after kidney transplantation (KT); however, the combined effects of intra-patient variability (IPV) and inter-patient variability of TAC-trough level (C0) in blood remain controversial. This study aimed to determine the combined impact of TAC-IPV and TAC inter-patient variability on allograft outcomes of KT., Methods: In total, 1,080 immunologically low-risk patients who were not sensitized to donor human leukocyte antigen (HLA) were enrolled. TAC-IPV was calculated using the time-weighted coefficient variation (TWCV) of TAC-C0, and values > 30% were classified as high IPV. Concentration-to-dose ratio (CDR) was used for calculating TAC inter-patient variability, and CDR < 1.05 ng•mg/mL was classified as rapid metabolizers (RM). TWCV was calculated based on TAC-C0 up to 1 year after KT, and CDR was calculated based on TAC-C0 up to 3 months after KT. Patients were classified into four groups according to TWCV and CDR: low IPV/non-rapid metabolizer (NRM), high IPV/NRM, low IPV/RM, and high IPV/RM. Subgroup analysis was performed for pre-transplant panel reactive antibody (PRA)-positive and -negative patients (presence or absence of non-donor-specific HLA-antibodies). Allograft outcomes, including deathcensored graft loss (DCGL) and biopsy-proven allograft rejection (BPAR), were compared., Results: The incidences of DCGL, BPAR, and overall graft loss were the highest in the high-IPV/RM group. In addition, a high IPV/RM was identified as an independent risk factor for DCGL. The hazard ratio of high IPV/RM for DCGL and the incidence of active antibody-mediated rejection were considerably increased in the PRA-positive subgroup., Discussion: High IPV combined with RM (inter-patient variability) was closely related to adverse allograft outcomes, and hence, more attention must be given to pre-transplant PRA-positive patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Park, Lee, Eum, Ko, Min, Yoon, Hwang, Yun, Yang, Shin and Chung.)
- Published
- 2022
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14. Targeted Microchip Capillary Electrophoresis-Orbitrap Mass Spectrometry Metabolomics to Monitor Ovarian Cancer Progression.
- Author
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Sah S, Yun SR, Gaul DA, Botros A, Park EY, Kim O, Kim J, and Fernández FM
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The lack of effective screening strategies for high-grade serous carcinoma (HGSC), a subtype of ovarian cancer (OC) responsible for 70-80% of OC related deaths, emphasizes the need for new diagnostic markers and a better understanding of disease pathogenesis. Capillary electrophoresis (CE) coupled with high-resolution mass spectrometry (HRMS) offers high selectivity and sensitivity for ionic compounds, thereby enhancing biomarker discovery. Recent advances in CE-MS include small, chip-based CE systems coupled with nanoelectrospray ionization (nanoESI) to provide rapid, high-resolution analysis of biological specimens. Here, we describe the development of a targeted microchip (µ) CE-HRMS method, with an acquisition time of only 3 min and sample injection volume of 4nL, to analyze 40 target metabolites in serum samples from a triple-mutant (TKO) mouse model of HGSC. Extracted ion electropherograms showed sharp, baseline resolved peak shapes, even for structural isomers such as leucine and isoleucine. All calibration curves of the analytes maintained good linearity with an average R
2 of 0.994, while detection limits were in the nM range. Thirty metabolites were detected in mouse serum with recoveries ranging from 78 to 120%, indicating minimal ionization suppression and good accuracy. We applied the µCE-HRMS method to biweekly-collected serum samples from TKO and TKO control mice. A time-resolved analysis revealed characteristic temporal trends for amino acids, nucleosides, and amino acid derivatives. These metabolic alterations are indicative of altered nucleotide biosynthesis and amino acid metabolism in HGSC development and progression. A comparison of the µCE-HRMS dataset with non-targeted ultra-high performance liquid chromatography (UHPLC)-MS results showed identical temporal trends for the five metabolites detected with both platforms, indicating the µCE-HRMS method performed satisfactorily in terms of capturing metabolic reprogramming due to HGSC progression while reducing the total data collection time three-fold.- Published
- 2022
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15. Light-induced protein structural dynamics in bacteriophytochrome revealed by time-resolved x-ray solution scattering.
- Author
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Lee SJ, Kim TW, Kim JG, Yang C, Yun SR, Kim C, Ren Z, Kumarapperuma I, Kuk J, Moffat K, Yang X, and Ihee H
- Abstract
Bacteriophytochromes (BphPs) are photoreceptors that regulate a wide range of biological mechanisms via red light-absorbing (Pr)-to-far-red light-absorbing (Pfr) reversible photoconversion. The structural dynamics underlying Pfr-to-Pr photoconversion in a liquid solution phase are not well understood. We used time-resolved x-ray solution scattering (TRXSS) to capture light-induced structural transitions in the bathy BphP photosensory module of Pseudomonas aeruginosa . Kinetic analysis of the TRXSS data identifies three distinct structural species, which are attributed to lumi-F, meta-F, and Pr, connected by time constants of 95 μs and 21 ms. Structural analysis based on molecular dynamics simulations shows that the light activation of PaBphP accompanies quaternary structural rearrangements from an "II"-framed close form of the Pfr state to an "O"-framed open form of the Pr state in terms of the helical backbones. This study provides mechanistic insights into how modular signaling proteins such as BphPs transmit structural signals over long distances and regulate their downstream biological responses.
- Published
- 2022
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16. Space- and Time-Resolved Metabolomics of a High-Grade Serous Ovarian Cancer Mouse Model.
- Author
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Sah S, Ma X, Botros A, Gaul DA, Yun SR, Park EY, Kim O, Moore SG, Kim J, and Fernández FM
- Abstract
The dismally low survival rate of ovarian cancer patients diagnosed with high-grade serous carcinoma (HGSC) emphasizes the lack of effective screening strategies. One major obstacle is the limited knowledge of the underlying mechanisms of HGSC pathogenesis at very early stages. Here, we present the first 10-month time-resolved serum metabolic profile of a triple mutant (TKO) HGSC mouse model, along with the spatial lipidome profile of its entire reproductive system. A high-coverage liquid chromatography mass spectrometry-based metabolomics approach was applied to longitudinally collected serum samples from both TKO ( n = 15) and TKO control mice ( n = 15), tracking metabolome and lipidome changes from premalignant stages to tumor initiation, early stages, and advanced stages until mouse death. Time-resolved analysis showed specific temporal trends for 17 lipid classes, amino acids, and TCA cycle metabolites, associated with HGSC progression. Spatial lipid distributions within the reproductive system were also mapped via ultrahigh-resolution matrix-assisted laser desorption/ionization (MALDI) mass spectrometry and compared with serum lipid profiles for various lipid classes. Altogether, our results show that the remodeling of lipid and fatty acid metabolism, amino acid biosynthesis, TCA cycle and ovarian steroidogenesis are critical components of HGSC onset and development. These metabolic alterations are accompanied by changes in energy metabolism, mitochondrial and peroxisomal function, redox homeostasis, and inflammatory response, collectively supporting tumorigenesis.
- Published
- 2022
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17. Ceria-Zirconia nanoparticles reduce intracellular globotriaosylceramide accumulation and attenuate kidney injury by enhancing the autophagy flux in cellular and animal models of Fabry disease.
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An JH, Hong SE, Yu SL, Kang J, Park CG, Lee HY, Lee SK, Lee DC, Park HW, Hwang WM, Yun SR, Park Y, Park MH, Yoon KR, and Yoon SH
- Subjects
- Animals, Autophagy, Disease Models, Animal, Kidney pathology, Male, Mice, Trihexosylceramides, Zirconium, Fabry Disease drug therapy, Fabry Disease genetics, Fabry Disease pathology, Nanoparticles
- Abstract
Background: Fabry disease (FD) is a lysosome storage disease (LSD) characterized by significantly reduced intracellular autophagy function. This contributes to the progression of intracellular pathologic signaling and can lead to organ injury. Phospholipid-polyethyleneglycol-capped Ceria-Zirconia antioxidant nanoparticles (PEG-CZNPs) have been reported to enhance autophagy flux. We analyzed whether they suppress globotriaosylceramide (Gb3) accumulation by enhancing autophagy flux and thereby attenuate kidney injury in both cellular and animal models of FD., Results: Gb3 was significantly increased in cultured human renal proximal tubular epithelial cells (HK-2) and human podocytes following the siRNA silencing of α galactosidase A (α-GLA). PEG-CZNPs effectively reduced the intracellular accumulation of Gb3 in both cell models of FD and improved both intracellular inflammation and apoptosis in the HK-2 cell model of FD. Moreover these particles attenuated pro fibrotic cytokines in the human podocyte model of FD. This effect was revealed through an improvement of the intracellular autophagy flux function and a reduction in reactive oxygen species (ROS). An FD animal model was generated in which 4-week-old male B6;129-Gla
tm1Kul /J mice were treated for 8 weeks with 10 mg/kg of PEG-CZNPs (twice weekly via intraperitoneal injection). Gb3 levels were reduced in the kidney tissues of these animals, and their podocyte characteristics and autophagy flux functions were preserved., Conclusions: PEG-CZNPs alleviate FD associated kidney injury by enhancing autophagy function and thus provide a foundation for the development of new drugs to treat of storage disease., (© 2022. The Author(s).)- Published
- 2022
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18. Acute kidney injury due to intravenous detergent poisoning: A case report.
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Park S, Ryu HS, Lee JK, Park SS, Kwon SJ, Hwang WM, Yun SR, Park MH, and Park Y
- Abstract
Background: Detergent poisoning mostly occurs through oral ingestion (> 85%), ocular exposure (< 15%), or dermal exposure (< 8%). Reports of detergent poisoning through an intravenous injection are extremely rare. In addition, there are very few cases of renal toxicity directly caused by detergents. Here, we report a unique case of acute kidney injury caused by detergent poisoning through an accidental intravenous injection., Case Summary: A 61-year-old man was intravenously injected with 20 mL of detergent by another patient in the same room of a local hospital. The surfactant and calcium carbonate accounted for the largest proportion of the detergent. The patient complained of vascular pain, chest discomfort, and nausea, and was transferred to our institution. After hospitalization, the patient's serum creatinine level increased to 5.42 mg/dL, and his daily urine output decreased to approximately 300 mL. Renal biopsy findings noted that the glomeruli were relatively intact; however, diffuse acute tubular injury was observed. Generalized edema was also noted, and the patient underwent a total of four hemodiafiltration sessions. Afterward, the patient's urine output gradually increased whereas the serum creatinine level decreased. The patient was discharged in a stable status without any sequelae., Conclusion: Detergents appear to directly cause renal tubular injury by systemic absorption. In treating a patient with detergent poisoning, physicians should be aware that the renal function may also deteriorate. In addition, timely renal replacement therapy may help improve the patient's prognosis., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)
- Published
- 2022
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19. Ultrafast coherent motion and helix rearrangement of homodimeric hemoglobin visualized with femtosecond X-ray solution scattering.
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Lee Y, Kim JG, Lee SJ, Muniyappan S, Kim TW, Ki H, Kim H, Jo J, Yun SR, Lee H, Lee KW, Kim SO, Cammarata M, and Ihee H
- Subjects
- Kinetics, Molecular Dynamics Simulation, Myoglobin chemistry, Protein Conformation, Protein Multimerization, Solutions, X-Ray Diffraction, Hemoglobins chemistry
- Abstract
Ultrafast motion of molecules, particularly the coherent motion, has been intensively investigated as a key factor guiding the reaction pathways. Recently, X-ray free-electron lasers (XFELs) have been utilized to elucidate the ultrafast motion of molecules. However, the studies on proteins using XFELs have been typically limited to the crystalline phase, and proteins in solution have rarely been investigated. Here we applied femtosecond time-resolved X-ray solution scattering (fs-TRXSS) and a structure refinement method to visualize the ultrafast motion of a protein. We succeeded in revealing detailed ultrafast structural changes of homodimeric hemoglobin involving the coherent motion. In addition to the motion of the protein itself, the time-dependent change of electron density of the hydration shell was tracked. Besides, the analysis on the fs-TRXSS data of myoglobin allows for observing the effect of the oligomeric state on the ultrafast coherent motion.
- Published
- 2021
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20. Ceria-Zirconia Antioxidant Nanoparticles Attenuate Hypoxia-Induced Acute Kidney Injury by Restoring Autophagy Flux and Alleviating Mitochondrial Damage.
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Hong SE, An JH, Yu SL, Kang J, Park CG, Lee HY, Lee DC, Park HW, Hwang WM, Yun SR, Park MH, Yoon KR, and Yoon SH
- Subjects
- Antioxidants, Apoptosis, Autophagy, Humans, Hypoxia, Oxidative Stress, Reactive Oxygen Species, Zirconium, Acute Kidney Injury, Nanoparticles
- Abstract
Oxidative stress is one of the principal causes of hypoxia-induced kidney injury. The ceria nanoparticle (CNP) is known to exhibit free radical scavenger and catalytic activities. When zirconia is attached to CNPs (CZNPs), the ceria atom tends to remain in a Ce
3+ form and its efficacy as a free radical scavenger thus increases. We determined the effectiveness of CNP and CZNP antioxidant activities against hypoxia-induced acute kidney injury (AKI) and observed that these nanoparticles suppress the apoptosis of hypoxic HK-2 cells by restoring autophagy flux and alleviating mitochondrial damage. In vivo experiments revealed that CZNPs effectively attenuate hypoxia-induced AKI by preserving renal structures and glomerulus function. These nanoparticles can successfully diffuse into HK-2 cells and effectively counteract reactive oxygen species (ROS) to block hypoxia-induced AKI. This suggests that these particles represent a novel approach to controlling this condition.- Published
- 2020
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21. Bioelectrical Impedance Analysis Is Not Sufficient for Determining Water Deficit in Hypernatremic Patients.
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Yoon SH, Kim SG, Jeong IB, Hwang WM, and Yun SR
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- Adult, Body Composition, Body Water physiology, Dehydration diagnosis, Electric Impedance, Extracellular Space, Female, Humans, Male, Middle Aged, Water, Hypernatremia diagnosis, Hypernatremia metabolism, Organism Hydration Status physiology
- Abstract
BACKGROUND Hypernatremia is associated with poor outcomes in critically ill patients, and an accurate assessment of water volume is important to determine appropriate fluid hydration. Bioelectrical impedance analysis (BIA) is a new, noninvasive, and relatively easy method for measuring hydration status. This study aimed to investigate whether bioelectrical impedance measurements of body water could reduce the frequency of blood sampling for fluid replacement in patients with hypernatremia. MATERIAL AND METHODS Fifty-one hospitalized patients were studied with hypernatremia, defined as a serum sodium ≥150 mmol/L determined by laboratory testing. Laboratory and BIA measurements were compared, and water deficiency was calculated with a conventional formula (sodium-corrected Watson formula) and measured by BIA. RESULTS The value of the absolute fluid overload (AFO) equivalent to the overhydration (OH) value, determined using BIA, did not accurately represent water deficit in patients with hypernatremia (r=0.137, P=0.347). Although the total body water (TBW) measured by BIA showed a significant correlation with that determined by the conventional formula (r=0.861, P<0.001), there was a proportional bias (r=0.617, P<0.001). The intracellular water (ICW) measured by BIA underestimated the TBW level calculated by the conventional formula by about 14.06±4.0 L in the Bland-Altman analysis. CONCLUSIONS It is not currently possible to replace blood testing with BIA for assessing volume status in hypernatremic patients. However, ICW value measured by BIA might represent plasma sodium level more accurately than extracellular water (ECW) or TBW value in patients with hypernatremia.
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- 2019
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22. NADPH oxidase 4 mediates TGF-β1/Smad signaling pathway induced acute kidney injury in hypoxia.
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Cho S, Yu SL, Kang J, Jeong BY, Lee HY, Park CG, Yu YB, Jin DC, Hwang WM, Yun SR, Song HS, Park MH, and Yoon SH
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- Acute Kidney Injury physiopathology, Animals, Apoptosis drug effects, Cell Hypoxia drug effects, Cell Line, Cell Survival drug effects, Female, Humans, Kidney Function Tests, MAP Kinase Signaling System drug effects, Mitochondria drug effects, Mitochondria metabolism, Models, Biological, NADPH Oxidase 4 antagonists & inhibitors, Oxidation-Reduction, Oxidative Stress drug effects, Pyrazoles pharmacology, Pyrazolones, Pyridines pharmacology, Pyridones, Rats, Sprague-Dawley, Reactive Oxygen Species metabolism, Transforming Growth Factor beta1 pharmacology, Acute Kidney Injury metabolism, Acute Kidney Injury pathology, NADPH Oxidase 4 metabolism, Signal Transduction, Smad Proteins metabolism, Transforming Growth Factor beta1 metabolism
- Abstract
Hypoxia is an important cause of acute kidney injury (AKI) in various conditions because kidneys are one of the most susceptible organs to hypoxia. In this study, we investigated whether nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidase 4 (Nox4) plays a role in hypoxia induced AKI in a cellular and animal model. Expression of Nox4 in cultured human renal proximal tubular epithelial cells (HK-2) was significantly increased by hypoxic stimulation. TGF-β1 was endogenously secreted by hypoxic HK-2 cells. SB4315432 (a TGF-β1 receptor I inhibitor) significantly inhibited Nox4 expression in HK-2 cells through the Smad-dependent cell signaling pathway. Silencing of Nox4 using Nox4 siRNA and pharmacologic inhibition with GKT137831 (a specific Nox1/4 inhibitor) reduced the production of ROS and attenuated the apoptotic pathway. In addition, knockdown of Nox4 increased cell survival in hypoxic HK-2 cells and pretreatment with GKT137831 reproduce these results. This study demonstrates that hypoxia induces HK-2 cell apoptosis through a signaling pathway involving TGF-β1 via Smad pathway induction of Nox4-dependent ROS generation. In an ischemia/reperfusion rat model, pretreatment of GKT137831 attenuated ischemia/reperfusion induced acute kidney injury as indicated by preserved kidney function, attenuated renal structural damage and reduced apoptotic cells. Therapies targeting Nox4 may be effective against hypoxia-induced AKI., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
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23. Exceptional mucocutaneous manifestations with amyloid nephropathy: a case report.
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Yoon SH, Cho JH, Jung HY, Hwang WM, Yun SR, Choi JY, Park SH, Kim CD, Kim MS, and Kim YL
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- Amyloid immunology, Amyloidosis immunology, Biopsy, Female, Humans, Kidney immunology, Kidney Diseases immunology, Male, Middle Aged, Skin Diseases immunology, Amyloidosis pathology, Kidney pathology, Kidney Diseases pathology, Lip pathology, Skin Diseases pathology
- Abstract
Background: Amyloidosis is a very rare disease that is difficult to diagnose because of the unspecific early clinical manifestations of the disease. Accurate and early diagnosis is extremely important because the effect of treatment is dependent on the extent of disease progression. Sicca syndrome and nail dystrophy are very rare symptoms of amyloidosis. We report here a case of sicca syndrome and nail dystrophy with renal dysfunction in a 52-year-old Korean woman who was diagnosed as having systemic amyloidosis., Case Presentation: We present the case of a 52-year-old Korean woman complaining of dry mouth and nail dystrophy for 4 months as an initial symptom. A slit lamp examination revealed superficial keratoconjunctival erosion in both eyes. A laboratory test showed anemia, azotemia, and proteinuria. Urine protein electrophoresis showed increased gamma globulin excretion. Serum free light chain of kappa and lambda were increased. Histopathological studies of biopsy specimens of minor salivary glands and kidney revealed deposits of amyloid fibrils. A bone marrow aspiration biopsy showed hypercellular marrow with 5% plasma cells. She was diagnosed as having primary systemic amyloidosis then started on chemotherapy., Conclusion: Such atypical mucocutaneous manifestations of amyloidosis can serve as important early diagnostic signs with less invasive biopsy confirmation in patients with systemic amyloidosis.
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- 2018
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24. TGF-β-mediated NADPH oxidase 4-dependent oxidative stress promotes colistin-induced acute kidney injury.
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Jeong BY, Park SR, Cho S, Yu SL, Lee HY, Park CG, Kang J, Jung DY, Park MH, Hwang WM, Yun SR, Jung JY, and Yoon SH
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- Animals, Cell Line, Disease Models, Animal, Epithelial Cells drug effects, Epithelial Cells physiology, Humans, Models, Biological, Rats, Sprague-Dawley, Acute Kidney Injury chemically induced, Anti-Bacterial Agents adverse effects, Colistin adverse effects, NADPH Oxidase 4 metabolism, Oxidative Stress, Transforming Growth Factor beta metabolism
- Abstract
Background: Colistin (polymyxin E) is an important constituent of the polymyxin class of cationic polypeptide antibiotics. Intrarenal oxidative stress can contribute to colistin-induced nephrotoxicity. Nicotinamide adenine dinucleotide 3-phosphate oxidases (Noxs) are important sources of reactive oxygen species. Among the various types of Noxs, Nox4 is predominantly expressed in the kidney., Objectives: We investigated the role of Nox4 and benefit of Nox4 inhibition in colistin-induced acute kidney injury using in vivo and in vitro models., Methods: Human proximal tubular epithelial (HK-2) cells were treated with colistin with or without NOX4 knockdown, or GKT137831 (most specific Nox1/4 inhibitor). Effects of Nox4 inhibition on colistin-induced acute kidney injury model in Sprague-Dawley rats were examined., Results: Nox4 expression in HK-2 cells significantly increased following colistin exposure. SB4315432 (transforming growth factor-β1 receptor I inhibitor) significantly inhibited Nox4 expression in HK-2 cells. Knockdown of NOX4 transcription reduced reactive oxygen species production, lowered the levels of pro-inflammatory markers (notably mitogen-activated protein kinases) implicated in colistin-induced nephrotoxicity and attenuated apoptosis by altering Bax and caspase 3/7 activity. Pretreatment with GKT137831 replicated these effects mediated by downregulation of mitogen-activated protein kinase activities. In a rat colistin-induced acute kidney injury model, administration of GKT137831 resulted in attenuated colistin-induced acute kidney injury as indicated by attenuated impairment of glomerulus function, preserved renal structures, reduced expression of 8-hydroxyguanosine and fewer apoptotic cells., Conclusions: Collectively, these findings identify Nox4 as a key source of reactive oxygen species responsible for kidney injury in colistin-induced nephrotoxicity and highlight a novel potential way to treat drug-related nephrotoxicity.
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- 2018
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25. Current characteristics of dialysis therapy in Korea: 2016 registry data focusing on diabetic patients.
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Jin DC, Yun SR, Lee SW, Han SW, Kim W, Park J, and Kim YK
- Abstract
Diabetic nephropathy is the most frequent cause of end-stage renal disease worldwide. Dialysis patients with diabetes mellitus (DM) have more complications and shorter survival duration than non-DM dialysis patients, requiring more clinical attention and difficult management. The registry committee of the Korean Society of Nephrology has collected data about dialysis therapy in Korea through an on-line registry program and analyzed the characteristics of patients. A survey of dialysis patients in 2016 showed that 50.2% of new dialysis patients had DM nephropathy as the cause of end-stage renal disease. The proportion of patients receiving hemodialysis (HD) for more than 5 years was 38% in DM patients and 51% in non-DM patients. The mean pulse pressure in DM HD patients was 71.5 mmHg, compared with 62.6 mmHg in non-DM patients. The proportion of DM patients with native vessel arteriovenous fistula as vascular access for HD was lower than that of non-DM patients (73% vs. 78%). Mean serum creatinine of DM and non-DM dialysis patients was 8.4 mg/dL and 9.5 mg/dL respectively. As vascular access of the DM HD patients was poor, the dialysis adequacy of DM patients was slightly lower than that of non-DM patients. The 5-year survival rate for DM HD patients was 53.9%, which was much lower than that of chronic glomerulonephritis patients (78.2%). The proportion of patients with a full-time job was 17% for DM patients and 28% for non-DM patients., Competing Interests: Conflicts of interest All authors have no conflicts of interest to declare.
- Published
- 2018
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26. Oxidative stress caused by activation of NADPH oxidase 4 promotes contrast-induced acute kidney injury.
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Jeong BY, Lee HY, Park CG, Kang J, Yu SL, Choi DR, Han SY, Park MH, Cho S, Lee SY, Hwang WM, Yun SR, Ryu HM, Oh EJ, Park SH, Kim YL, and Yoon SH
- Subjects
- Acute Kidney Injury chemically induced, Animals, Apoptosis drug effects, Cell Line, Enzyme Activation, Gene Silencing, Humans, Iohexol pharmacology, Kidney Tubules, Proximal cytology, Kidney Tubules, Proximal drug effects, Kidney Tubules, Proximal metabolism, Male, Mice, Mice, Inbred C57BL, NADPH Oxidase 4 genetics, Reactive Oxygen Species metabolism, Real-Time Polymerase Chain Reaction, Superoxides metabolism, Acute Kidney Injury metabolism, Contrast Media adverse effects, NADPH Oxidase 4 metabolism, Oxidative Stress
- Abstract
Contrast-induced acute kidney injury (CIAKI) is a leading cause of acute kidney injury following radiographic procedures. Intrarenal oxidative stress plays a critical role in CIAKI. Nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidases (Noxs) are important sources of reactive oxygen species (ROS). Among the various types of Noxs, Nox4 is expressed predominantly in the kidney in rodents. Here, we evaluated the role of Nox4 and benefit of Nox4 inhibition on CIAKI using in vivo and in vitro models. HK-2 cells were treated with iohexol, with or without Nox4 knockdown, or the most specific Nox1/4 inhibitor (GKT137831). Effects of Nox4 inhibition on CIAKI mice were examined. Expression of Nox4 in HK-2 cells was significantly increased following iohexol exposure. Silencing of Nox4 rescued the production of ROS, downregulated pro-inflammatory markers (particularly phospho-p38) implicated in CIAKI, and reduced Bax and caspase 3/7 activity, which resulted in increased cellular survival in iohexol-treated HK-2 cells. Pretreatment with GKT137831 replicated these effects by decreasing levels of phospho-p38. In a CIAKI mouse model, even though the improvement of plasma blood urea nitrogen was unclear, pretreatment with GKT137831 resulted in preserved structure, reduced expression of 8-hydroxy-2'-deoxyguanosine (8OHdG) and kidney injury molecule-1 (KIM-1), and reduced number of TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)-positive cells. These results suggest Nox4 as a key source of reactive oxygen species responsible for CIAKI and provide a novel potential option for prevention of CIAKI.
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- 2018
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27. A toolkit for DNA assembly, genome engineering and multicolor imaging for C. elegans .
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Sands B, Burnaevskiy N, Yun SR, Crane MM, Kaeberlein M, and Mendenhall A
- Abstract
One way scientists can observe and quantify processes in living cells is to engineer the genomes of animals to express multiple fluorescent proteins and then quantify those signals by various imaging techniques. To allow our laboratories to confidently quantify mixed (overlapping) fluorescent signals for our studies in the basic biology of gene expression and aging in C. elegans , we developed a comprehensive toolkit for C. elegans that we describe here. The Toolkit consists of two components: 1) a series of vectors for DNA assembly by homologous recombination (HR) in the yeast, Saccharomyces cerevisiae, and 2) a set of ten worm strains that each express a single, spectrally distinct fluorescent protein, under control of either the daf21 or eft-3 promoters. We measured the in vivo emission spectrum (3nm resolution) for each fluorescent protein in live C. elegans and showed that we can use those pure spectra to unmix overlapping fluorescent signals in spectral images of intestine cells. Seven of ten fluorescent proteins had signals that appeared to be localized in vesicular/elliptical foci or tubules in the hypodermis. We conducted fluorescence recovery after photobleaching (FRAP) experiments and showed that these structures have recovery kinetics more consistent with freely diffusing protein than aggregates (Q35::YFP). This toolkit will allow researchers to quickly and efficiently generate mutlti-fragment DNA assemblies for genome editing in C. elegans. Additionally, the transgenic C. elegans and the measured emission spectra should serve as a resource for scientists seeking to perform, or test their ability to perform, multidimensional (multi-color) imaging experiments.
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- 2018
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28. Correction to "Photocycle of Photoactive Yellow Protein in Cell-Mimetic Environments: Molecular Volume Changes and Kinetics".
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Yang C, Kim SO, Kim Y, Yun SR, Choi J, and Ihee H
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- 2017
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29. HELLP syndrome in a pregnant patient with Gitelman syndrome.
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Lee M, Kim DI, Lee KH, Byun JH, Hwang J, Hwang WM, Yun SR, and Yoon SH
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Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypocalciuria, and hypomagnesemia. The clinical course of Gitelman syndrome in pregnant women remains unclear, but it is thought to be benign. We report here the first Korean case of atypical eclampsia in a 31-year-old who was diagnosed with Gitelman syndrome incidentally during an antenatal screening test. The patient did well during pregnancy despite significant hypokalemia. At 33 weeks' gestation, the patient exhibited eclampsia, hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and renal insufficiency without significant hypertension or proteinuria. We explain this unusual clinical course through a review of the relevant literature.
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- 2017
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30. Photocycle of Photoactive Yellow Protein in Cell-Mimetic Environments: Molecular Volume Changes and Kinetics.
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Yang C, Kim SO, Kim Y, Yun SR, Choi J, and Ihee H
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- Biomimetics, Halorhodospira halophila chemistry, Kinetics, Photochemical Processes, Bacterial Proteins chemistry, Bacterial Proteins metabolism, Halorhodospira halophila metabolism, Photoreceptors, Microbial chemistry, Photoreceptors, Microbial metabolism
- Abstract
Using various spectroscopic techniques such as UV-visible spectroscopy, circular dichroism spectroscopy, NMR spectroscopy, small-angle X-ray scattering, transient grating, and transient absorption techniques, we investigated how cell-mimetic environments made by crowding influence the photocycle of photoactive yellow protein (PYP) in terms of the molecular volume change and kinetics. Upon addition of molecular crowding agents, the ratio of the diffusion coefficient of the blue-shifted intermediate (pB) to that of the ground species (pG) significantly changes from 0.92 and approaches 1.0. This result indicates that the molecular volume change accompanied by the photocycle of PYP in molecularly crowded environments is much smaller than that which occurs in vitro and that the pB intermediate under crowded environments favors a compact conformation due to the excluded volume effect. The kinetics of the photocycle of PYP in cell-mimetic environments is greatly decelerated by the dehydration, owing to the interaction between the protein and small crowding agents, but is barely affected by the excluded volume effect. The results lead to the inference that the signaling transducer of PYP may not necessarily utilize the conformational change of PYP to sense the signaling state.
- Published
- 2017
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31. Current characteristics of dialysis therapy in Korea: 2015 registry data focusing on elderly patients.
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Jin DC, Yun SR, Lee SW, Han SW, Kim W, and Park J
- Abstract
Because of increases in the elderly population and diabetic patients, the proportion of elderly among dialysis patients has rapidly increased during the last decades. The mortality and morbidity of these elderly dialysis patients are obviously much higher than those of young patients, but large analytic studies about elderly dialysis patients' characteristics have rarely been published. The registry committee of the Korean Society of Nephrology has collected data about dialysis therapy in Korea through an Internet online registry program and analyzed the characteristics. A survey on elderly dialysis patients showed that more than 50% of elderly (65 years and older) patients had diabetic nephropathy as the cause of end-stage renal disease, and approximately 21% of elderly dialysis patients had hypertensive nephrosclerosis. The proportion of elderly hemodialysis (HD) patients with native vessel arteriovenous fistula as vascular access for HD was lower than that of young (under 65 years) HD patients (69% vs. 80%). Although the vascular access was poor and small surface area dialyzers were used for the elderly HD patients, the dialysis adequacy data of elderly patients were better than those of young patients. The laboratory data of elderly dialysis patients were not very different from those of young patients, but poor nutrition factors were observed in the elderly dialysis patients. Although small surface area dialyzers were used for elderly HD patients, the urea reduction ratio and Kt/V were higher in elderly HD patients than in young patients.
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- 2016
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32. Overhydration Negatively Affects Quality of Life in Peritoneal Dialysis Patients: Evidence from a Prospective Observational Study.
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Yoon HE, Kwon YJ, Song HC, Kim JK, Song YR, Shin SJ, Kim HW, Lee CH, Lee TW, Kim YO, Kim BS, Moon KH, Chang YK, Kim SS, Bang K, Cho JT, Yun SR, Na KR, Kim YW, Han BG, Chung JH, Lee KY, Jeong JH, Hwang EA, and Kim YS
- Subjects
- Adult, Aged, Dehydration complications, Dielectric Spectroscopy, Female, Heart Failure etiology, Humans, Kidney Diseases complications, Kidney Diseases physiopathology, Male, Middle Aged, Quality of Life, Vascular Stiffness physiology, Dehydration physiopathology, Heart Failure physiopathology, Kidney Diseases therapy, Peritoneal Dialysis adverse effects
- Abstract
Unlabelled: Backgound: This study evaluated whether the hydration status affected health-related quality of life (HRQOL) during 12 months in peritoneal dialysis (PD) patients., Methods: The hydration status and the HRQOL were examined at baseline and after 12 months using a bioimpedance spectroscopy and Kidney Disease Quality of Life-Short Form, respectively in PD patients. Four hundred eighty-one patients were included and divided according to the baseline overhydration (OH) value; normohydration group (NH group, -2L≤ OH ≤+2L, n=266) and overhydration group (OH group, OH >+2L, n=215). Baseline HRQOL scores were compared between the two groups. The subjects were re-stratified into quartiles according to the OH difference (OH value at baseline - OH value at 12 months; <-1, -1 - -0.1, -0.1 - +1, and ≥+1L). The relations of OH difference with HRQOL scores at 12 months and the association of OH difference with the HRQOL score difference (HRQOL score at baseline - HRQOL score at 12 months) were assessed., Results: The OH group showed significantly lower baseline physical and mental health scores (PCS and MCS), and kidney disease component scores (KDCS) compared with the NH group (all, P<0.01). At 12 months, the adjusted PCS, MCS, and KDCS significantly increased as the OH difference quartiles increased (P<0.001, P=0.002, P<0.001, respectively). In multivariate analysis, the OH difference was independently associated with higher PCS (β = 2.04, P< .001), MCS (β=1.02, P=0.002), and KDCS (β=1.06, P<0.001) at 12 months. The OH difference was independently associated with the PCS difference (β = -1.81, P<0.001), MCS difference (β=-0.92, P=0.01), and KDCS difference (β=-0.90, P=0.001)., Conclusion: The hydration status was associated with HRQOL and increased hydration status negatively affected HRQOL after 12 months in PD patients., Competing Interests: The authors have declared that no competing interest exists.
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- 2016
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33. An Adult Case of Bartter Syndrome Type III Presenting with Proteinuria.
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Cha EJ, Hwang WM, Yun SR, and Park MH
- Abstract
Bartter syndrome (BS) I-IV is a rare autosomal recessive disorder affecting salt reabsorption in the thick ascending limb of the loop of Henle. This report highlights clinicopathological findings and genetic studies of classic BS in a 22-year-old female patient who presented with persistent mild proteinuria for 2 years. A renal biopsy demonstrated a mild to moderate increase in the mesangial cells and matrix of most glomeruli, along with marked juxtaglomerular cell hyperplasia. These findings suggested BS associated with mild IgA nephropathy. Focal tubular atrophy, interstitial fibrosis, and lymphocytic infiltration were also observed. A genetic study of the patient and her parents revealed a mutation of the CLCNKB genes. The patient was diagnosed with BS, type III. This case represents an atypical presentation of classic BS in an adult patient. Pathologic findings of renal biopsy combined with genetic analysis and clinicolaboratory findings are important in making an accurate diagnosis.
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- 2016
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34. Lessons from 30 years' data of Korean end-stage renal disease registry, 1985-2015.
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Jin DC, Yun SR, Lee SW, Han SW, Kim W, Park J, and Kim YK
- Abstract
The Korean Society of Nephrology (KSN) launched a nationwide official survey program about dialysis therapy in 1985. Nowadays, the accumulated data for 30 years by this "Insan Prof. Min Memorial end-stage renal disease (ESRD) Registry" program have been providing the essential information for dialysis clinical practice, academic nephrology research, and health management policy. We reviewed 30 years of data to identify important changes and implications for the future improvement of dialysis therapy in Korea. Hemodialysis patients, especially diabetics and elderly patients have increased in number very rapidly during recent years in Korea. The Korean prevalence rate of ESRD patients was about 70% of the United States and about 50% of Japan according to the international comparisons in the annual data report of United States Renal Data System. The blood pressure control, anemia control, and dialysis adequacy have continuously improved year by year. The importance of calcium and phosphorus control has also been increasing because of the increase in long-term dialysis patients. In addition, chronic dialysis complications should be closely monitored and dialysis modifications, such as hemodiafiltration therapy, might be considered. Because of the increase of private clinics and nursing hospitals in dialysis practice, the role of dialysis specialists and continuing education are thought to be essential. For strict cost-effective dialysis control of increasing elderly, diabetic, and long-term dialysis patients, the KSN ESRD patient registration should be run by the KSN and health ministry in cooperation, in which the dialysis fee reimbursement should be accompanied.
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- 2015
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35. End stage renal disease caused by thromboangiitis obliterans: a case report.
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Yun HJ, Kim DI, Lee KH, Lim SJ, Hwang WM, Yun SR, and Yoon SH
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- Humans, Kidney Failure, Chronic therapy, Male, Middle Aged, Renal Artery diagnostic imaging, Renal Dialysis, Tomography, X-Ray Computed, Kidney Failure, Chronic diagnostic imaging, Kidney Failure, Chronic etiology, Thromboangiitis Obliterans complications
- Abstract
Introduction: Thromboangiitis obliterans or Buerger's disease is a nonatherosclerotic, segmental, inflammatory vasculitis that is strongly associated with tobacco products and commonly affects the small- and medium-sized arteries of the upper and lower extremities. However, the disease can, rarely, involve large central or visceral arteries. We report here the case of end stage renal disease due to renal artery thrombosis caused by thromboangiitis obliterans., Case Presentation: A 51-year-old Korean man who had previously required amputation of both great toes due to thromboangiitis obliterans presented with left flank pain and oliguria. Both his renal arteries were occluded on contrast-enhanced abdominal computed tomography and abdominal angiography. He also had abdominal angina. He had no risk factor of thromboembolism from cardiac origin, atherosclerosis except for tobacco abuse, collagen diseases or hypercoagulable disorders. Renal failure and mesenteric ischemia associated with thromboangiitis obliterans progression was diagnosed., Conclusions: Renal failure due to renal artery thrombosis and mesenteric ischemia represents an unusual manifestation of thromboangiitis obliterans. But once it occurs, it can be life-threatening. When we care for a patient with thromboangiitis obliterans, we should pay attention to this rare disease course, and encourage cessation of the smoking of tobacco products.
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- 2015
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36. Synthesis of licochalcone analogues with increased anti-inflammatory activity.
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Kim SJ, Kim CG, Yun SR, Kim JK, and Jun JG
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- Animals, Anti-Inflammatory Agents, Non-Steroidal chemical synthesis, Anti-Inflammatory Agents, Non-Steroidal chemistry, Cell Proliferation drug effects, Cell Survival drug effects, Chalcones chemical synthesis, Chalcones chemistry, Chalcones pharmacology, Dose-Response Relationship, Drug, Mast Cells, Molecular Structure, Nitric Oxide biosynthesis, Rats, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Nitric Oxide antagonists & inhibitors
- Abstract
Licohalcones have been reported to have various biological activities. However, most of licochalcones also showed cytotoxicity even though their versitile utilities. Licochalcones B and D, which have common substituents at aromatic ring B, are targeted to modify the structure at aromatic ring A for inflammatory studies. Licochalcone derivatives (1-6) thus prepared are compared for their suppression ability of nitric oxide (NO) production and showed 9.94, 4.72, 10.1, 4.85, 2.37 and 4.95μM of IC50 values, respectively., (Copyright © 2013 Elsevier Ltd. All rights reserved.)
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- 2014
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37. Is there a difference in the prevalence of gastroesophageal reflux disease between peritoneal dialysis and hemodialysis patients?
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Song HJ, Kim SM, Lee YM, Hwang JA, Moon KM, Moon CG, Koo HS, Song KH, Kim YS, Lee TH, Huh KC, Choi YW, Kang YW, Hwang WM, and Yun SR
- Subjects
- Aged, Body Mass Index, Diabetes Mellitus, Type 2 complications, Esophagitis, Peptic complications, Esophagitis, Peptic epidemiology, Female, Gastroesophageal Reflux complications, Gastroscopy, Helicobacter Infections complications, Humans, Male, Middle Aged, Peritoneal Dialysis statistics & numerical data, Prevalence, Renal Dialysis statistics & numerical data, Risk Factors, Smoking, Surveys and Questionnaires, Gastroesophageal Reflux epidemiology, Kidney Failure, Chronic complications
- Abstract
Background/aims: Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal disorder in patients with chronic kidney disease (CKD). However, little is known about the prevalence of GERD in dialysis patients. The aim of the present study was to investigate the difference in the prevalence of GERD in peritoneal dialysis and hemodialysis patients., Methods: From July 2010 to August 2011, peritoneal dialysis patients (n=30) and hemodialysis patients (n=38) were enrolled. The prevalences of GERD were assessed at a single center with endoscopic findings and interviews using a questionnaire. Also, risk factors of GERD were evaluated., Results: The prevalences of GERD in peritoneal dialysis and hemodialysis patients were 33.3% and 39.5% (p=0.748), respectively. The prevalences of erosive reflux esophagitis (ERD) in peritoneal dialysis and hemodialysis patients were 16.7% and 23.7% (p=0.477), respectively. The prevalences of nonerosive reflux disease (NERD) in peritoneal dialysis and hemodialysis patients were 16.7% and 13.2% (p=0.685), respectively. The prevalences of GERD, ERD and NERD were higher than those of the general population. The risk factor for GERD was age in hemodialysis patients., Conclusions: The prevalence of GERD in dialysis patients was higher than that in the general population. However, there was no significant difference between peritoneal dialysis and hemodialysis patients.
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- 2013
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38. Diversity and homogeneity in responses of midbrain dopamine neurons.
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Fiorillo CD, Yun SR, and Song MR
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- Animals, Appetitive Behavior, Avoidance Learning physiology, Choice Behavior physiology, Conditioning, Operant, Female, Macaca mulatta, Male, Motivation physiology, Photic Stimulation, Reaction Time physiology, Reinforcement, Psychology, Reward, Statistics as Topic, Action Potentials physiology, Brain Mapping, Dopaminergic Neurons classification, Dopaminergic Neurons physiology, Mesencephalon cytology, Neural Inhibition physiology
- Abstract
Dopamine neurons of the ventral midbrain have been found to signal a reward prediction error that can mediate positive reinforcement. Despite the demonstration of modest diversity at the cellular and molecular levels, there has been little analysis of response diversity in behaving animals. Here we examine response diversity in rhesus macaques to appetitive, aversive, and neutral stimuli having relative motivational values that were measured and controlled through a choice task. First, consistent with previous studies, we observed a continuum of response variability and an apparent absence of distinct clusters in scatter plots, suggesting a lack of statistically discrete subpopulations of neurons. Second, we found that a group of "sensitive" neurons tend to be more strongly suppressed by a variety of stimuli and to be more strongly activated by juice. Third, neurons in the "ventral tier" of substantia nigra were found to have greater suppression, and a subset of these had higher baseline firing rates and late "rebound" activation after suppression. These neurons could belong to a previously identified subgroup of dopamine neurons that express high levels of H-type cation channels but lack calbindin. Fourth, neurons further rostral exhibited greater suppression. Fifth, although we observed weak activation of some neurons by aversive stimuli, this was not associated with their aversiveness. In conclusion, we find a diversity of response properties, distributed along a continuum, within what may be a single functional population of neurons signaling reward prediction error.
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- 2013
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39. Multiphasic temporal dynamics in responses of midbrain dopamine neurons to appetitive and aversive stimuli.
- Author
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Fiorillo CD, Song MR, and Yun SR
- Subjects
- Acoustic Stimulation, Action Potentials physiology, Animals, Choice Behavior physiology, Conditioning, Classical, Female, Judgment, Macaca mulatta, Male, Mesencephalon physiology, Neural Inhibition physiology, Nonlinear Dynamics, Reaction Time physiology, Regression Analysis, Reinforcement, Psychology, Time Factors, Appetitive Behavior physiology, Avoidance Learning physiology, Dopaminergic Neurons physiology, Mesencephalon cytology, Motivation physiology
- Abstract
The transient response of dopamine neurons has been described as reward prediction error (RPE), with activation or suppression by events that are better or worse than expected, respectively. However, at least a minority of neurons are activated by aversive or high-intensity stimuli, casting doubt on the generality of RPE in describing the dopamine signal. To overcome limitations of previous studies, we studied neuronal responses to a wider variety of high-intensity and aversive stimuli, and we quantified and controlled aversiveness through a choice task in which macaques sacrificed juice to avoid aversive stimuli. Whereas most previous work has portrayed the RPE as a single impulse or "phase," here we demonstrate its multiphasic temporal dynamics. Aversive or high-intensity stimuli evoked a triphasic sequence of activation-suppression-activation extending over a period of 40-700 ms. The initial activation at short latencies (40-120 ms) reflected sensory intensity. The influence of motivational value became dominant between 150 and 250 ms, with activation in the case of appetitive stimuli, and suppression in the case of aversive and neutral stimuli. The previously unreported late activation appeared to be a modest "rebound" after strong suppression. Similarly, strong activation by reward was often followed by suppression. We suggest that these "rebounds" may result from overcompensation by homeostatic mechanisms in some cells. Our results are consistent with a realistic RPE, which evolves over time through a dynamic balance of excitation and inhibition.
- Published
- 2013
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40. Application of a bridging ELISA for detection of anti-erythropoietin binding antibodies and a cell-based bioassay for neutralizing antibodies in human sera.
- Author
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Shin SK, Ha SK, Lee KW, Yoo TH, Yun SR, Yoon SH, Kim SJ, Lee SK, and Heo TH
- Subjects
- Biological Assay methods, Humans, Recombinant Proteins, Antibodies, Anti-Idiotypic immunology, Antibodies, Neutralizing immunology, Enzyme-Linked Immunosorbent Assay methods, Erythropoietin immunology, Serum immunology
- Abstract
Although erythropoietin (EPO)-related pure red-cell aplasia (PRCA) is a rare disorder, attention still needs to be paid because underline mechanism of EPO immunogenicity is various and controversial. Among several assay systems for screening of anti-EPO binding antibodies (Abs), we adopted and setup the bridging ELISA using streptavidin-coated plate. To test their neutralizing activities, cell-based neutralizing (NT) bioassay was setup. When we analyzed serum samples by using these two assays, we found two positive results in the two samples. In the sample 1, 411.9 ng/ml of anti-EPO Abs were found and neutralizing activity of 36.2% at 1:5 serum dilution was detected. In the sample 2, 40.5 ng/ml of anti-EPO Abs were found and neutralizing activity of 96.7% was detected. Our results indicate that the higher anti-EPO antibody (Ab) level in a serum does not always lead to the stronger neutralizing activity. This report gives crucial consideration to the needs of establishing clear criteria to link various assay parameters with the onset of PRCA and its progression., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
41. Detecting bacterial growth in continuous ambulatory peritoneal dialysis effluent using two culture methods.
- Author
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Yoon SH, Choi NW, and Yun SR
- Subjects
- Culture Media, Dialysis Solutions, Gram-Negative Bacterial Infections microbiology, Gram-Positive Bacterial Infections microbiology, Humans, Peritonitis microbiology, Sensitivity and Specificity, Gram-Negative Bacterial Infections diagnosis, Gram-Positive Bacterial Infections diagnosis, Kidney Failure, Chronic therapy, Microbiological Techniques methods, Peritoneal Dialysis, Continuous Ambulatory adverse effects, Peritonitis diagnosis
- Abstract
Background/aims: The aim of this study was to evaluate the peritonitis-causing bacteria detected in peritoneal fluid using a blood culture bottle in patients undergoing continuous ambulatory peritoneal dialysis (CAPD)., Methods: One-hundred and eleven dialysates from 43 patients suspected of peritonitis related to CAPD were retrospectively evaluated between May 2000 and February 2008. In all cases, 5 to 10 mL of dialysate was inoculated into a pair of BacT/Alert blood culture bottles, and 50 mL of centrifuged dialysate was simultaneously inoculated into a solid culture media for conventional culture. The results were compared to those of the conventional culture method. Isolated microorganisms were compared between the two methods., Results: The blood culture method was positive in 78.6% (88 / 112) of dialysate specimens and the conventional culture method in 50% (56 / 112, p < 0.001)., Conclusions: The blood culture method using the BacT/Alert system is useful for culturing dialysates and improves the positive culture rate in patients with suspected peritonitis compared to the conventional culture method.
- Published
- 2010
- Full Text
- View/download PDF
42. Pulmonary dysfunction is possibly a marker of malnutrition and inflammation but not mortality in patients with end-stage renal disease.
- Author
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Yoon SH, Choi NW, and Yun SR
- Subjects
- Adult, Aged, Body Composition, Body Mass Index, C-Reactive Protein, Chronic Disease, Cytokines metabolism, Diabetes Complications physiopathology, Female, Humans, Hypertension complications, Inflammation blood, Inflammation complications, Kidney Failure, Chronic blood, Kidney Failure, Chronic mortality, Kidney Failure, Chronic therapy, Male, Malnutrition blood, Malnutrition etiology, Malnutrition pathology, Middle Aged, Muscle Weakness etiology, Muscle Weakness physiopathology, Muscle, Skeletal pathology, Renal Replacement Therapy, Respiratory Muscles physiopathology, Serum Albumin analysis, Inflammation physiopathology, Kidney Failure, Chronic complications, Lung physiopathology, Malnutrition physiopathology, Pulmonary Ventilation
- Abstract
Background: Various studies have indicated that malnutrition and chronic inflammation are strong predictors of morbidity and mortality in patients with chronic kidney disease (CKD). The purpose of this study was to investigate the relationship between pulmonary function, malnutrition and chronic inflammation in patients with CKD., Methods: One hundred and six consenting patients with CKD were enrolled in the study between 2005 and 2007. Pulmonary function was assessed by forced vital capacity (FVC), forced expiratory volume in the first second (FEV(1)) and peak expiratory flow (PEF), expressed as the normal percentage of predicted values (%FEV(1), %FVC and %PEF, respectively). Nutritional status was evaluated by skeletal muscle index (SMI), subjective global nutritional assessment (SGA), lean body mass, body mass index and serum albumin. Inflammation was assessed by the serum measurement of high-sensitive C reactive protein (hsCRP) levels., Results: Malnutrition (defined as SMI > or =1) and inflammation (defined as hsCRP >2 mg/l) in ESRD patients had significant negative associations with percentage predicted values for pulmonary function tests except %PEF (SMI: %FEV(1), p = 0.009, %FVC, p = 0.001; hsCRP: %FEV(1), p = 0.025, %FVC, p = 0.022). Multivariate Cox analysis showed that the ejection fraction in echocardiography and SGA were associated with poor survival, but there was no association for %FEV(1)., Conclusions: Impaired pulmonary function was associated with malnutrition and inflammation in these dialysis patients. We were not able to determine a significant relationship between pulmonary function and mortality., (Copyright 2008 S. Karger AG, Basel.)
- Published
- 2009
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43. Protective effects of sanjoinine A against N-methyl-D-aspartate-induced seizure.
- Author
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Ma Y, Yun SR, Nam SY, Kim YB, Hong JT, Kim Y, Choi H, Lee K, and Oh KW
- Subjects
- Animals, Calcium metabolism, Cell Survival drug effects, Cells, Cultured, Electroencephalography drug effects, Electroshock, Female, Male, Mice, Mice, Inbred ICR, Neurons drug effects, Neurons pathology, Peptides, Cyclic isolation & purification, Rats, Rats, Sprague-Dawley, Tetrazolium Salts, Thiazoles, Ziziphus chemistry, Anticonvulsants, Excitatory Amino Acid Agonists toxicity, N-Methylaspartate antagonists & inhibitors, N-Methylaspartate toxicity, Peptides, Cyclic pharmacology, Seizures chemically induced, Seizures prevention & control
- Abstract
Sanjoinine A is a component of the alkaloid fraction of Zizyphi Spinosi Semen. This experiment was performed to investigate whether sanjoinine A acts as an anticonvulsive in the N-methyl-D-aspartate (NMDA)-induced experimental seizure model. We also examined whether it protects against seizure-form electroencephalogram (EEG) alterations induced by NMDA in vivo and/or cell killing due to NMDA in cultured cerebellar granule cells. Administration of sanjoinine A increased the survival rate and the latency of seizure onset, and decreased the seizure scores and the weight-loss induced by NMDA in mice, in a dose-dependent manner. In addition, sanjoinine A blocked seizure-form EEG alterations induced by NMDA and inhibited NMDA-induced cell killing in cultured rat cerebellar granule cells, measured by both the trypan blue exclusion test and the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Moreover, sanjoinine A inhibited the elevation of intracellular calcium influx induced by NMDA, which was measured using a fluorescent dye, Furo 3-AM. It is suggested that sanjoinine A protects against NMDA-induced seizures by inhibiting intracellular calcium influx.
- Published
- 2008
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44. [A case of Henoch-Schönlein purpura with psoas muscle abscess and full-blown gastrointestinal complications].
- Author
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Lee HJ, Kim SM, Yun SR, Lee TH, Im EH, Huh KC, Choi YW, and Kang YW
- Subjects
- Abdominal Pain, Anti-Inflammatory Agents therapeutic use, Colonoscopy, Gastrointestinal Diseases etiology, Gastrointestinal Diseases pathology, Gastrointestinal Hemorrhage diagnosis, Humans, IgA Vasculitis pathology, Male, Middle Aged, Prednisolone therapeutic use, Psoas Abscess etiology, Tomography, X-Ray Computed, Gastrointestinal Diseases diagnosis, IgA Vasculitis complications, IgA Vasculitis diagnosis, Psoas Abscess diagnostic imaging
- Abstract
Henoch-Schönlein purpura (HSP) is a vasculitis involving small vessels of skin, joints, gastrointestinal (GI) tract, and kidneys. The patients typically show palpable purpura with one or more characteristic manifestations including abdominal pain, hematuria or arthritis. HSP shows gastrointestinal symptoms in 50~85% of patients, and in 14~40% of patients GI symptoms precede purpuric rash which makes the diagnosis of HSP difficult. We present a case of Henoch-Schonlein purpura with GI bleeding, septic shock by ileal microperforation, small bowel obstruction as a result of ileal stricture and psoas muscle abscess.
- Published
- 2007
45. Changing prescribing practice in CAPD patients in Korea: increased utilization of low GDP solutions improves patient outcome.
- Author
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Lee HY, Choi HY, Park HC, Seo BJ, Do JY, Yun SR, Song HY, Kim YH, Kim YL, Kim DJ, Kim YS, Kim MJ, and Shin SK
- Subjects
- Adult, Aged, Dialysis Solutions metabolism, Dialysis Solutions therapeutic use, Female, Humans, Kaplan-Meier Estimate, Korea, Longitudinal Studies, Male, Middle Aged, Multivariate Analysis, Prospective Studies, Treatment Outcome, Dialysis Solutions chemistry, Glucose metabolism, Peritoneal Dialysis, Continuous Ambulatory methods
- Abstract
Background: Novel, biocompatible peritoneal dialysis (PD) solutions have become available in recent years. In 2001, low glucose degradation products (GDP), neutral pH solutions became commercially available in Korea. To date, there are no reports regarding the large scale adoption of these solutions in clinical practice and regarding what, if any, impact these solutions have on patient outcomes., Methods: Using a database of almost 4000 patients treated by PD in Korea, we conducted a prospective, longitudinal observational study documenting the patterns of use of one novel low GDP solution (balance, Fresenius Medical Care, St Wendel, Germany) in 1909 PD incident patients between 1 January 2002 and midyear 2005. Outcomes including patient and technique survival and peritonitis rates were analysed using univariate and multivariate analysis., Results: Prescription of low GDP solutions reached between 70 and 80% by the year 2003 and persisted at this level. Patients prescribed low GDP PD solution tended to be younger and were more likely to be treated in centres with larger enrollment in the database. Survival of diabetic patients treated with the new PD solution was identical to that of the non-diabetic patients treated with standard PD fluids (PDF) and treatment with low GDP PDF independently reduced the relative risk (RR) of death (RR = 0.613; CI 0.50-0.74; P < 0.00001) in a proportional hazards model which included age, diabetes and centre experience. In a univariate analysis, low GDP PD solution was associated with a longer technique survival (P = 0.049) but this effect was not significant in multivariate analysis. No significant differences in peritonitis-free interval or peritonitis rate could be attributed to the prescribed PDF., Conclusion: Prescription of low GDP, pH-neutral PD solutions has rapidly increased in Korea. This change has resulted in a significant improvement in patient and technique survival without any measurable change in peritonitis incidence or rate. Reasons for the improved patient survival cannot be determined from this analysis and require further study.
- Published
- 2006
- Full Text
- View/download PDF
46. Superior patient survival for continuous ambulatory peritoneal dialysis patients treated with a peritoneal dialysis fluid with neutral pH and low glucose degradation product concentration (Balance).
- Author
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Lee HY, Park HC, Seo BJ, Do JY, Yun SR, Song HY, Kim YH, Kim YL, Kim DJ, Kim YS, Ahn C, Kim MJ, and Shin SK
- Subjects
- Adult, Aged, Female, Humans, Hydrogen-Ion Concentration, Korea, Male, Middle Aged, Peritonitis etiology, Peritonitis prevention & control, Retrospective Studies, Survival Rate, Treatment Outcome, Dialysis Solutions chemistry, Glucose Solution, Hypertonic chemistry, Glycation End Products, Advanced analysis, Kidney Failure, Chronic mortality, Kidney Failure, Chronic therapy, Peritoneal Dialysis, Continuous Ambulatory adverse effects
- Abstract
Background: In recent years, laboratory and clinical research has suggested the need for peritoneal dialysis fluids (PDFs) that are more biocompatible than the conventional PDFs commonly used today. Bioincompatibility of PDF has been attributed to low pH, lactate, glucose, glucose degradation products (GDPs), and osmolality. PDFs with neutral pH and low GDPs are now available commercially. In vitro and early clinical studies suggest that these solutions are indeed more biocompatible but, as of now, there is no evidence that their use improves patient outcome., Methods: Using a dedicated database of over 2000 patients treated with PD in Korea, we were able to conduct a retrospective observational study comparing outcomes for incident continuous ambulatory PD patients treated with a standard, conventional, heat-sterilized PDF to the outcomes for patients treated with a novel, low GDP, neutral-pH PDF prepared in a dual-compartment, double-bag PD system (Balance; Fresenius Medical Care, St. Wendel, Germany). In an intention-to-treat analysis, patient and technique survival, peritonitis-free survival, and peritonitis rates were compared in 611 patients treated with Balance for up to 30 months and 551 patients with a standard PDF (stay . safe; Fresenius Medical Care) treated in the same era and with equivalent follow-up., Results: The patients were well matched for most relevant characteristics except older age distribution for the patients treated with the standard PDF. Patients treated with Balance had significantly superior survival compared to those treated with the standard PDF (74% vs 62% at 28 months, p = 0.0032). In a multivariate Cox regression model including age, diabetes, and gender, the survival advantage persisted (relative risk of death for Balance 0.75, 95% confidence interval 0.56 - 0.99, p = 0.0465). Modality technique survival was similarin Kaplan-Meieranalysis for both PDFs. No differences were detected in peritonitis-free survival or in peritonitis rates between the two solutions., Conclusion: This study, for the first time, suggests that treatment with a novel biocompatible PDF with low GDP concentration and neutral pH confers a significant survival advantage. The exact mechanisms for such a survival advantage cannot be determined from this study. The usual criticisms of observational studies apply and the results reported here strongly warrant the undertaking of appropriately designed, randomized, controlled clinical trials.
- Published
- 2005
47. Large-scale growth and taxane production in cell cultures of Taxus cuspidata (Japanese yew) using a novel bioreactor.
- Author
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Son SH, Choi SM, Lee YH, Choi KB, Yun SR, Kim JK, Park HJ, Kwon OW, Noh EW, Seon JH, and Park YG
- Abstract
A novel type of bioreactor was successfully developed for the production of taxol and its precursors by culturing cells of Taxus cuspidata (Japanese yew) on a pilot-scale. Rapidly growing cell lines were selected from callus cultures derived from immature embryos of yew. The cells were inoculated in 20-l capacity bioreactors of different types to test the growth performance. The models of small-scale bioreactors incorporated in this study included a balloon-type bubble bioreactor (BTBB), a bubble-column bioreactor (BCB), a BCB with a split-plate internal loop, a BCB with a concentric draught-tube internal loop, a BCB with a fluidized bed bioreactor, and two different models of stirred tank reactors. Among the reactors, BTBB appeared to be the most efficient in promoting cell growth. The doubling time of cell growth in BTBB was 12 days with a 30% inoculation cell density. The optimum time for medium replacement or feeding was 12-15 days after inoculation as determined by monitoring both the levels of sugars and medium conductivity. When yew tree cells were grown in different sizes (100-500-l) of BTBBs, more than 70% cell viability was recorded at the time of harvest. The growth pattern of the cells in the pilot-scale BTBB appeared to be the same as that of cells in the 20-l bioreactors. Approximately 3 mg/l of taxol and 74 mg/l total taxanes were obtained after 27 days of culture.
- Published
- 2000
- Full Text
- View/download PDF
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