48 results on '"Kim, Kyung-Hee"'
Search Results
2. Structural and functional characterization of USP47 reveals a hot spot for inhibitor design.
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Shin, Sang Chul, Park, Jinyoung, Kim, Kyung Hee, Yoon, Jung Min, Cho, Jinhong, Ha, Byung Hak, Oh, Yeonji, Choo, Hyunah, Song, Eun Joo, and Kim, Eunice EunKyeong
- Subjects
DRUG discovery ,CATALYTIC domains ,CANCER cell growth ,MYOCARDIAL infarction ,CATALYTIC activity ,UBIQUITINATION - Abstract
USP47 is widely involved in tumor development, metastasis, and other processes while performing a more regulatory role in inflammatory responses, myocardial infarction, and neuronal development. In this study, we investigate the functional and biochemical properties of USP47, whereby depleting USP47 inhibited cancer cell growth in a p53-dependent manner—a phenomenon that enhances during the simultaneous knockdown of USP7. Full-length USP47 shows higher deubiquitinase activity than the catalytic domain. The crystal structures of the catalytic domain, in its free and ubiquitin-bound states, reveal that the misaligned catalytic triads, ultimately, become aligned upon ubiquitin-binding, similar to USP7, thereby becoming ready for catalysis. Yet, the composition and lengths of BL1, BL2, and BL3 of USP47 differ from those for USP7, and they contribute to the observed selectivity. Our study provides molecular details of USP47 regulation, substrate recognition, and the hotspots for drug discovery by targeting USP47. Crystal structures of USP47's catalytic domain in its free and ubiquitin-bound states and functional assays reveal molecular details of USP47 regulation, substrate recognition, and hotspots for drug discovery. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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3. Artificial Intelligence Applied to Cardiomyopathies: Is It Time for Clinical Application?
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Kim, Kyung-Hee, Kwon, Joon-Myung, Pereira, Tara, Attia, Zachi I., and Pereira, Naveen L.
- Abstract
Purpose of Review: Artificial intelligence (AI) techniques have the potential to remarkably change the practice of cardiology in order to improve and optimize outcomes in heart failure and specifically cardiomyopathies, offering us novel tools to interpret data and make clinical decisions. The aim of this review is to describe the contemporary state of AI and digital health applied to cardiomyopathies as well as to define a potential pivotal role of its application by physicians in clinical practice. Recent Findings: Many studies have been undertaken in recent years on cardiomyopathy screening especially using AI-enhanced electrocardiography (ECG). Even with mild left ventricular (LV) dysfunction, AI-ECG screening for amyloidosis, hypertrophic cardiomyopathy, or dilated cardiomyopathy is now feasible. Introduction of AI-ECG in routine clinical care has resulted in higher detection of LV systolic dysfunction; however, clinical research on a broader scale with diverse populations is necessary and ongoing. In the area of cardiac-imaging, AI automatically assesses the thickness and characteristics of myocardium to differentiate cardiomyopathies, but research on its prognostic capability has yet to be conducted. AI is also being applied to cardiomyopathy genomics, especially to predict pathogenicity of variants and identify whether these variants are clinically actionable. Summary: While the implementation of AI in the diagnosis and treatment of cardiomyopathies is still in its infancy, an ever-growing clinical research strategy will ascertain the clinical utility of these AI tools to help improve diagnosis of and outcomes in cardiomyopathies. We also need to standardize the tools used to monitor the performance of AI-based systems which can then be used to expedite decision-making and rectify any hidden biases. Given its potential important role in clinical practice, healthcare providers need to familiarize themselves with the promise and limitations of this technology. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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4. Artificial intelligence assessment for early detection and prediction of renal impairment using electrocardiography.
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Kwon, Joon-myoung, Kim, Kyung-Hee, Jo, Yong-Yeon, Jung, Min-Seung, Cho, Yong-Hyeon, Shin, Jae-Hyun, Lee, Yoon-Ji, Ban, Jang-Hyeon, Lee, Soo Youn, Park, Jinsik, and Oh, Byung-Hee
- Abstract
Purpose: Although renal failure is a major healthcare burden globally and the cornerstone for preventing its irreversible progression is an early diagnosis, an adequate and noninvasive tool to screen renal impairment (RI) reliably and economically does not exist. We developed an interpretable deep learning model (DLM) using electrocardiography (ECG) and validated its performance. Methods: This retrospective cohort study included two hospitals. We included 115,361 patients who had at least one ECG taken with an estimated glomerular filtration rate measurement within 30 min of the index ECG. A DLM was developed using 96,549 ECGs of 55,222 patients. The internal validation included 22,949 ECGs of 22,949 patients. Furthermore, we conducted an external validation with 37,190 ECGs of 37,190 patients from another hospital. The endpoint was to detect a moderate to severe RI (estimated glomerular filtration rate < 45 ml/min/1.73m
2 ). Results: The area under the receiver operating characteristic curve (AUC) of a DLM using a 12-lead ECG for detecting RI during the internal and external validation was 0.858 (95% confidence interval 0.851–0.866) and 0.906 (0.900–0.912), respectively. In the initial evaluation of 25,536 individuals without RI patients whose DLM was defined as having a higher risk had a significantly higher chance of developing RI than those in the low-risk group (17.2% vs. 2.4%, p < 0.001). The sensitivity map indicated that the DLM focused on the QRS complex and T-wave for detecting RI. Conclusion: The DLM demonstrated high performance for RI detection and prediction using 12-, 6-, single-lead ECGs. [ABSTRACT FROM AUTHOR]- Published
- 2022
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5. Insights into Bacterial Community Structure and Metabolic Diversity of Mercury-Contaminated Sediments from Hyeongsan River, Pohang, South Korea.
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Chaudhary, Dhiraj Kumar, Kim, Kyung Hee, Lee, Mikyung, Kim, Hwansuk, and Hong, Yongseok
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This study investigated the bacterial community structure and metabolic diversity and their relationship with Hg and other environmental variables in sediments collected from different locations (HSR-1–HSR-6) in the Hyeongsan River estuary in South Korea. The results showed that the highest total mercury (THg) and methylmercury (MeHg) concentrations were in HSR-2, with values of 4585.3 µg/kg and 13.4 µg/kg, respectively. The lowest THg (31.9 µg/kg) and MeHg (0.1 µg/kg) concentrations were found in HSR-1. Sulfate and organic matter (OM) were more influential environmental variables, revealing a positive association with THg and MeHg and negatively affecting bacterial and metabolic diversities. Bacterial and metabolic diversities were also negatively impacted by the THg and MeHg concentrations. Proteobacteria and Bacteroidetes were abundantly distributed in all the sediments. The dominance of Proteobacteria was upscaled in all the heavily Hg-contaminated sites (HSR-2–HSR-6), and it was the only phylum that showed a significant positive correlation with THg, MeHg, and OM. The genera Sulfurovum and Sulfurimonas were abundantly observed in sites with high Hg contamination, whereas Congregibacter, Gaetbulibacter, Ilumatobacter, Methylotenera, Nevskia, and Sediminibacter were only detected in low Hg-contaminated sites (HSR-1). The community-level physiological profile data showed the highest (1.0) average well color development (AWCD) value in HSR-1 and the lowest (0.45) AWCD value in HSR-2. Overall, these results demonstrated the inhibitory effects of THg, MeHg, and other environmental variables on microbial communities and metabolic diversity. These findings broaden the current knowledge on the dynamics of bacterial and metabolic diversities in Hg-contaminated sediments and might be useful in the management of Hg pollution. [ABSTRACT FROM AUTHOR]
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- 2022
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6. Plasma complement C7 as a target in non-small cell lung cancer patients to implement 3P medicine strategies.
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Park, Jae Gwang, Choi, Beom Kyu, Lee, Youngjoo, Jang, Eun Jung, Woo, Sang Myung, Lee, Jun Hwa, Kim, Kyung-Hee, Hwang, Heeyoun, Choi, Wonyoung, Lee, Se-Hoon, and Yoo, Byong Chul
- Abstract
Background: Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) significantly affect outcomes in non-small cell lung cancer (NSCLC) patients. However, differences in reactions toward PD-1/PD-L1 ICI among patients impose inefficient treatment. Therefore, developing a reliable biomarker to predict PD-1/PD-L1 ICI reaction is highly necessary for predictive, preventive, and personalized (3P) medicine. Materials and methods: We recruited 63 patients from the National Cancer Center (NCC) and classified them into the training and validation sets. Next, 99 patients were recruited for inclusion into the external validation set at the Samsung Medical Center (SMC). Proteomic analysis enabled us to identify plasma C7 levels, which were significantly different among groups classified by their overall response to the RECIST V 1.1–based assessment. Analytical performance was evaluated to predict the PD-1/PD-L1 ICI response for each type of immunotherapy, and NSCLC histology was evaluated by determining the C7 levels via ELISA. Results: Plasma C7 levels were significantly different between patients with and without clinical benefits (PFS ≥ 6 months). Among the groups sorted by histology and PD-1/PD-L1 immunotherapy type, only the predicted accuracy for pembrolizumab-treated patients from both NCC and SMC was greater than 73%. In patients treated with pembrolizumab, C7 levels were superior to those of the companion diagnostics 22C3 (70.3%) and SP263 (62.1%). Moreover, for pembrolizumab-treated patients for whom the PD-L1 tumor proportion score (TPS) was < 50%, the predictive accuracy of C7 was nearly 20% higher than that of 22C3 and SP263. Conclusion: Evaluation of plasma C7 levels shows an accurate prediction of NSCLC patient reactions on pembrolizumab. It demonstrates plasma C7 is an alternative and supportive biomarker to overcome the predictive limitation of previous 22C3 and SP263. Thus, it is clear that clinical use of plasma C7 allows predictive diagnosis on lung cancer patients who have not been successfully treated with current CDx and targeted prevention on metastatic diseases in secondary care caused by a misdiagnosis of current CDx. Reduction of patients' financial burden and increased efficacy of cancer treatment would also enable prediction, prevention, and personalization of medical service on NSCLC patients. In other words, plasma C7 provides efficient medical service and an optimized medical economy followed which finally promotes the prosperity of 3P medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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7. Initial diastolic dysfunction is a powerful predictor of 5-year mortality in peripheral arterial disease patients undergoing percutaneous transluminal angioplasty.
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Kim, Kyung-Hee, Vallabhajosyula, Saarwaani, Rha, Seung-Woon, Choi, Byoung Geol, Byun, Jae-Kyung, and Choi, Cheol Ung
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TRANSLUMINAL angioplasty , *PERIPHERAL vascular diseases , *HEART failure , *MYOCARDIAL ischemia , *CORONARY disease , *LOGISTIC regression analysis , *VENTRICULAR ejection fraction - Abstract
Peripheral arterial disease (PAD) and heart failure share common risks and are associated with increased morbidity and mortality. However, it is unknown whether cardiac function can be an independent predictor of long-term mortality in patients with PAD. In total, 902 patients who underwent percutaneous transluminal angioplasty for PAD were enrolled. The patients were categorized into three groups according to the left ventricular ejection fraction (LVEF): reduced EF (< 40%, n = 62); mid-range EF (40–49%, n = 76); and preserved EF (≥ 50%, n = 764). Echocardiographic (EF, ratio of mitral inflow velocity to annular velocity E/eʹ ≥ 15, and others) and clinical parameters were tested using stepwise logistic regression analysis to determine independent predictors of 5-year mortality. A higher proportion of patients with reduced EF had ischemic heart disease than those with preserved EF (77.4% vs. 56.8%, p < 0.001). Up to 5 years, patients with reduced EF and mid-range EF showed a higher incidence of total death than those with normal EF. However, there was no difference in the incidence of myocardial infarction, stroke, and revascularization among the three groups. After multivariable adjustment, the ratio of E/eʹ ≥ 15 was the only strong predictor of total mortality (hazard ratio 6.14; 95% confidence interval 3.7–10.1; p < 0.01). Patients with PAD and reduced EF undergoing PTA had a higher incidence of total death during the 5-year follow-up. Initial tissue Doppler E/eʹ ≥ 15, a non-invasive estimate of left atrial filling pressure, was the only independent predictor of long-term mortality. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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8. Assessment of liver fibrosis with gadoxetic acid-enhanced MRI: comparisons with transient elastography, ElastPQ, and serologic fibrosis markers.
- Author
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Jang, Hyeon Ji, Min, Ji Hye, Lee, Jeong Eun, Shin, Kyung Sook, Kim, Kyung-Hee, and Choi, Seo-Youn
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ASPARTATE aminotransferase ,RECEIVER operating characteristic curves ,FIBROSIS ,MAGNETIC resonance imaging ,ELASTOGRAPHY ,LIVER - Abstract
Objectives: To compare the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging (MRI), ultrasonography (US)—based elastography, and serologic fibrosis markers in assessing the stage of liver fibrosis. Materials and methods: This retrospective study included 67 patients (55 male and 12 female; mean age 62.5 years) who underwent gadoxetic acid-enhanced MRI and liver stiffness measurements before liver biopsy or surgery between January 2014 and January 2018. Measurements were performed using transient elastography (TE), ultrasound shear wave elastography point quantification (ElastPQ), and blood tests. The following MRI-based fibrosis markers were assessed: contrast enhancement index (CEI), liver–spleen contrast ratio (LSC), liver–portal vein contrast ratio (LPC), and signal intensity ratio (SIR). The diagnostic performances of fibrosis markers were compared using the area under the receiver operating characteristic curve (AUC), with histopathologic fibrosis stage as the reference standard. Results: The fibrosis stages were F0–F1 (n = 17), F2 (n = 7), F3 (n = 20), and F4 (n = 23). MRI-based fibrosis markers negatively correlated with histologic stage: CEI (r = –0.786); LSC (r = − 0.718); LPC (r = − 0.448); and SIR (r = − 0.617; all P < 0.001). For diagnosis of either significant liver fibrosis (≥ F2) or cirrhosis (F4), the CEI provided better diagnostic accuracy (AUC = 0.898 and 0.881) than the aspartate aminotransferase-to-platelet ratio index (APRI) (AUC = 0.699 and 0.715; all P < 0.05). The CEI displayed similar diagnostic accuracy for ≥ F2 or F4 when using TE (AUC = 0.866 and 0.884, both P > 0.05) or ElastPQ [AUC = 0.751 (P = 0.021) and AUC = 0.786 (P = 0.234)]. Conclusions: The CEI measured by gadoxetic acid-enhanced MRI allows the staging of liver fibrosis, with a diagnostic accuracy comparable to that of TE and superior to that of ElastPQ or APRI. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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9. Determinants of binge eating disorder among normal weight and overweight female college students in Korea.
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Kim, Youl-Ri, Hwang, Bo In, Lee, Gi Young, Kim, Kyung Hee, Kim, Mirihae, Kim, Kwang Kee, and Treasure, Janet
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- 2018
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10. Allosteric inhibition site of transglutaminase 2 is unveiled in the N terminus.
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Kim, Nayeon, Kang, Joon Hee, Lee, Won-Kyu, Kim, Seul-Gi, Lee, Jae-Seon, Lee, Seon-Hyeong, Park, Jong Bae, Kim, Kyung-Hee, Gong, Young-Dae, Hwang, Kwang Yeon, and Kim, Soo-Youl
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TRANSGLUTAMINASES ,ENZYME inhibitors ,RENAL cell carcinoma ,P53 antioncogene ,AUTOPHAGY - Abstract
Previously we have demonstrated transglutaminase 2 (TGase 2) inhibition abrogated renal cell carcinoma (RCC) using GK921 (3-(phenylethynyl)-2-(2-(pyridin-2-yl)ethoxy)pyrido[3,2-b]pyrazine), although the mechanism of TGase 2 inhibition remains unsolved. Recently, we found that the increase of TGase 2 expression is required for p53 depletion in RCC by transporting the TGase 2 (1-139 a.a)-p53 complex to the autophagosome, through TGase 2 (472-687 a.a) binding p62. In this study, mass analysis revealed that GK921 bound to the N terminus of TGase 2 (81-116 a.a), which stabilized p53 by blocking TGase 2 binding. This suggests that RCC survival can be stopped by p53-induced cell death through blocking the p53-TGase 2 complex formation using GK921. Although GK921 does not bind to the active site of TGase 2, GK921 binding to the N terminus of TGase 2 also inactivated TGase 2 activity through acceleration of non-covalent self-polymerization of TGase 2 via conformational change. This suggests that TGase 2 has an allosteric binding site (81-116 a.a) which changes the conformation of TGase 2 enough to accelerate inactivation through self-polymer formation. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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11. The Effect of Fibronectin-Immobilized Microgrooved Titanium Substrata on Cell Proliferation and Expression of Genes and Proteins in Human Gingival Fibroblasts.
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Kim, Eun-Cheol, Lee, Do Yun, Lee, Myung-Hyun, Lee, Hong Jae, Kim, Kyung-Hee, Leesungbok, Richard, Ahn, Su-Jin, Park, Su-Jung, Yoon, Joon-Ho, Jee, Yu-Jin, Lee, Sang Cheon, and Lee, Suk Won
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- 2018
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12. Individualized metabolic profiling stratifies pancreatic and biliary tract cancer: a useful tool for innovative screening programs and predictive strategies in healthcare.
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Lee, Jun Hwa, Yu, Seung Eun, Kim, Kyung-Hee, Yu, Myung Hyun, Jeong, In-Hye, Cho, Jae Youl, Park, Sang-Jae, Lee, Woo Jin, Han, Sung-Sik, Kim, Tae Hyun, Hong, Eun Kyung, Woo, Sang Myung, and Yoo, Byong Chul
- Abstract
Background: Pancreatic cancer (PC) and biliary tract cancer (BTC) are highly aggressive cancers, characterized by their rarity, difficulty in diagnosis, and overall poor prognosis. Diagnosis of PC and BTC is complex and is made using a combination of appropriate clinical suspicion, imaging and endoscopic techniques, and cytopathological examination. However, the late-stage detection and poor prognosis of this tumor have led to an urgent need for biomarkers for early and/or predictive diagnosis and improved personalized treatments.Working hypothesis: There are two hypotheses for focusing on low-mass metabolites in the blood. First, valuable information can be obtained from the masses and relative amounts of such metabolites, which present as low-mass ions (LMIs) in mass spectra. Second, metabolic profiling of individuals may provide important information regarding biological changes in disease states that is useful for the early diagnosis of PC and BTC.Materials and methods: To assess whether profiling metabolites in serum can serve as a non-invasive screening tool for PC and BTC, 320 serum samples were obtained from patients with PC (n = 51), BTC (n = 39), colorectal cancer (CRC) (n = 100), and ovarian cancer (OVC) (n = 30), and from healthy control subjects (control) (n = 100). We obtained information on the relative amounts of metabolites, as LMIs, via triple time-of-flight mass spectrometry. All data were analyzed according to the peak area ratios of discriminative LMIs.Results and conclusions: The levels of the 14 discriminative LMIs were higher in the PC and BTC groups than in the control, CRC and OVC groups, but only two LMIs discriminated between PC and BTC: lysophosphatidylcholine (LysoPC) (16:0) and LysoPC(20:4). The levels of these two LysoPCs were also slightly lower in the PC/BTC/CRC/OVC groups compared with the control group. Taken together, the data showed that metabolic profiling can precisely denote the status of cancer, and, thus, could be useful for screening. This study not only details efficient methods to identify discriminative LMIs for cancer screening but also provides an example of metabolic profiling for distinguishing PC from BTC. Furthermore, the two metabolites [LysoPC(16:0), LysoPC(20:4)] shown to discriminate these diseases are potentially useful when combined with other, previously identified protein or metabolic biomarkers for predictive, preventive and personalized medical approach. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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13. Evaluating protective and therapeutic effects of alpha-lipoic acid on cisplatin-induced ototoxicity.
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Kim, Kyung-Hee, Lee, Byeonghyeon, Kim, Ye-Ri, Kim, Min-A, Ryu, Nari, Jung, Da Jung, Kim, Un-Kyung, Baek, Jeong-In, and Lee, Kyu-Yup
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- 2018
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14. Transcriptome analysis for identifying possible gene regulations during maize root emergence and formation at the initial growth stage.
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Hwang, Sun-Goo, Kim, Kyung-Hee, Lee, Byung-Moo, and Moon, Jun-Cheol
- Abstract
The root plays an important role during plant development and growth, i.e., the plant body maintenance, nutrient storage, absorption of water, oxygen and nutrient from the soil, and storage of water and carbohydrates, etc. The objective of this study was attempted to determine root-specific genes at the initial developmental stages of maize by using network-based transcriptome analysis. The raw data obtained using RNA-seq were filtered for quality control of the reads with the FASTQC tool, and the filtered reads were pre-proceed using the TRIMMOMATIC tool. The enriched BINs of the DEGs were detected using PageMan analysis with the ORA_FISHER statistical test, and genes were assigned to metabolic pathways by using the MapMan tool, which was also used for detecting transcription factors (TFs). For reconstruction of the co-expression network, we used the algorithm for the reconstruction of accurate cellular networks (ARACNE) in the R package, and then the reconstructed co-expression network was visualized using the Cytoscape tool. RNA-seq. was performed using maize shoots and roots at different developmental stages of root emergence (6-10 days after planting, VE) and 1 week after plant emergence (V2). A total of 1286 differentially expressed genes (DEGs) were detected in both tissues. Many DEGs involved in metabolic pathways exhibited altered mRNA levels between VE and V2. In addition, we observed gene expression changes for 113 transcription factors and found five enriched cis-regulatory elements in the 1-kb upstream regions of both DEGs. The network-based transcriptome analysis showed two modules as co-expressed gene clusters differentially expressed between the shoots and roots during plant development. The DEGs of one module exhibited gene expressional coherence in the maize root tips, suggesting that their functional relationships are associated with the initial developmental stage of the maize root. Finally, we confirmed reliable mRNA levels of the hub genes in the potential sub-network related to initial root development at the different developmental stages of VE, V2, and 2 weeks after plant emergence. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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15. A tabersonine 3-reductase Catharanthus roseus mutant accumulates vindoline pathway intermediates.
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Edge, Alison, Qu, Yang, Easson, Michael L. A. E., Thamm, Antje M. K., Kim, Kyung Hee, and De Luca, Vincenzo
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CATHARANTHUS roseus ,VINDOLINE ,MONOTERPENOIDS ,ALKALOIDS ,BIOSYNTHESIS - Abstract
Main conclusion: Monoterpenoid indole alkaloids (MIAs) have remarkable biological properties that have led to their medical uses for a variety of human diseases. Mutagenesis has been used to generate plants with new alkaloid profiles and a useful screen for rapid comparison of MIA profiles is described. The MIA mutants identified are useful for investigating MIA biosynthesis and for targeted production of these specialised metabolites. The Madagascar periwinkle ( Catharanthus roseus) is the sole source of the dimeric anticancer monoterpenoid indole alkaloids (MIAs), 3′,4′-anhydrovinblastine and derivatives, which are formed via the coupling of the MIAs, catharanthine and vindoline. While intense efforts to identify parts of the complex pathways involved in the assembly of these dimers have been successful, our understanding of MIA biochemistry in C. roseus remains limited. A simple thin layer chromatography screen of 4000 ethyl methanesulfonate-metagenized M2 plants is described to identify mutant lines with altered MIA profiles. One mutant (M2-1865) accumulated reduced levels of vindoline inside the leaves in favour of high levels of tabersonine-2,3-epoxide and 16-methoxytabersonine-2,3-epoxide on the leaf surface. This MIA profile suggested that changes in tabersonine 3-reductase (T3R) activity might be responsible for the observed phenotype. Molecular cloning of mutant and wild type T3R revealed two nucleotide substitutions at cytosine residues 565 (CAT to TAT) and 903 (ACC to ACA) in the mutant corresponding to substitution (H189Y) and silent (T305T) amino acid mutations, respectively, in the protein. The single amino acid substitution in the mutant T3R protein diminished the biochemical activity of T3R by 95% that explained the reason for the low vindoline phenotype of the mutant. This phenotype was recessive and exhibited standard Mendelian single-gene inheritance. The stable formation and accumulation of epoxides in the M2-1865 mutant provides a dependable biological source of these two MIAs. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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16. Evaluation of a Heart Transplant Candidate.
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Lee, Sook Jin, Kim, Kyung Hee, Hong, Suk Keun, and Hankins, Shelley
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- 2017
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17. Fostering Creativity Using Robotics among Students in Stem Fields to Reverse the Creativity Crisis.
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Kim, Kyung Hee and Coxon, Steve V.
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- 2016
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18. Isoprenyl carboxyl methyltransferase inhibitors: a brief review including recent patents.
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Yang, Woo, Yeo, Seung-Gu, Yang, Sungjae, Kim, Kyung-Hee, Yoo, Byong, and Cho, Jae
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ISOPRENYLATION ,CARBOXYL group ,METHYLTRANSFERASES ,ENZYME inhibitors ,CANCER chemotherapy - Abstract
Among the enzymes involved in the post-translational modification of Ras, isoprenyl carboxyl methyltransferase (ICMT) has been explored by a number of researchers as a significant enzyme controlling the activation of Ras. Indeed, inhibition of ICMT exhibited promising anti-cancer activity against various cancer cell lines. This paper reviews patents and research articles published between 2009 and 2016 that reported inhibitors of ICMT as potential chemotherapeutic agents targeting Ras-induced growth factor signaling. Since ICMT inhibitors can modulate Ras signaling pathway, it might be possible to develop a new class of anti-cancer drugs targeting Ras-related cancers. Researchers have discovered indole-based small-molecular ICMT inhibitors through high-throughput screening. Researchers at Duke University identified a prototypical inhibitor, cysmethynil. At Singapore University, Ramanujulu and his colleagues patented more potent compounds by optimizing cysmethynil. In addition, Rodriguez and Stevenson at Universidad Complutense De Madrid and Cancer Therapeutics CRC PTY Ltd., respectively, have developed inhibitors based on formulas other than the indole base. However, further optimization of chemicals targeted to functional groups is needed to improve the characteristics of ICMT inhibitors related to their application as drugs, such as solubility, effectiveness, and safety, to facilitate clinical use. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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19. Inter-molecular crosslinking activity is engendered by the dimeric form of transglutaminase 2.
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Kim, Nayeon, Lee, Won-Kyu, Lee, Seon-Hyeong, Jin, Kyeong, Kim, Kyung-Hee, Lee, Younho, Song, Minsoo, and Kim, Soo-Youl
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TRANSGLUTAMINASES ,INTERMOLECULAR interactions ,MONOMERS ,X-ray scattering ,DIMERIZATION - Abstract
Transglutaminase 2 (TGase 2) catalyzes a crosslink between protein bound-glutamine and -lysine. We proposed the mechanism of TGase 2 activation depends on conformation change from unfolded monomer to unfolded dimer. We found that TGase 2 has temperature-sensitive conformation change system at 30 °C. Small-angle X-ray scattering analysis showed that the enzyme was maintained as an unfolded monomer at temperatures below 30 °C, but changed to an unfolded dimer at over 30 °C. Mass analysis revealed that the C-terminus of TGase 2 was the critical region for dimerization. Furthermore, this conformational switch creates new biochemical reactivity that catalyzed inter-molecular crosslink at above 30 °C as an unfolded dimer of TGase 2 while catalyzed intra-molecular crosslink at below 30 °C as an unfolded monomer of TGase 2. The mechanism of TGase 2 activation depends on temperature-sensitive conformation change from unfolded monomer to unfolded dimer at over 30 °C. Furthermore, inter-molecular crosslinking activity is generated by the dimeric form of TGase 2. TGase 2 switches its conformation from a monomer to a dimer following a change in temperature, which engendered unique catalytic function of enzyme as inter-molecular crosslinking activity with calcium. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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20. Investigation of early and advanced stages in ovarian cancer using human plasma by differential scanning calorimetry and mass spectrometry.
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Kim, Nam, Jin, Jing, Kim, Kyung-Hee, Lim, Dae, Cheong, Heesun, Kim, Yun, Ju, Woong, Kim, Seung, and Jeong, Seong
- Abstract
Ovarian cancer is recognized with high mortality due to asymptomatic nature of the disease and difficulties in diagnosing early stage of the cancer. The present study evaluates the use of differential scanning calorimetry (DSC) in differentiating the severity of ovarian cancer from healthy women. 47 diseased women were subdivided into four stages with respect to clinical relevance and severity. Stages I-II were regarded as early stages and stages III-IV were regarded as advanced stages. The two average transition temperatures ( T ) increased with disease severity from 64.84 and 70.32 °C (healthy) to 68.46 and 75.24 °C (stage IV), respectively. T were increased depending on clinical groups. In addition, the change in heat capacity was also dependent on the disease severity. To further support and investigate the nature of the proposed interactions, matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis is employed. The results suggest the differences in peptide expression between early and advanced stage of ovarian cancer, affected abundant proteins in plasma. The combined DSC and MS approach was supportive in identifying a unique signature of ovarian cancer stages, and demonstrates the potential of DSC as a complementary diagnostic tool in the evaluation of early stage ovarian cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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21. Therapeutic effects of udenafil on pressure-overload cardiac hypertrophy.
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Kim, Hack-Lyoung, Kim, Yong-Jin, Kim, Kyung-Hee, Lee, Seung-Pyo, Kim, Hyung-Kwan, Sohn, Dae-Won, Oh, Byung-Hee, and Park, Young-Bae
- Published
- 2015
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22. The prognostic significance of Smad3, Smad4, Smad3 phosphoisoform expression in esophageal squamous cell carcinoma.
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Cho, Soo, Ha, Sang, Huang, Song-Mei, Kim, Jeong, Kang, Myung, Yoo, Hae-yong, Kim, Hyeon-ho, Park, Cheol-Keun, Um, Sung-Hee, Kim, Kyung-Hee, and Kim, Seok-Hyung
- Abstract
Smad3 functions as an integrator of diverse signaling, including transforming growth factor β signaling and the function of Smad3 is complexly regulated by differential phosphorylation at various sites of Smad3. Despite the importance of Smad3 and its various phosphoisoforms, their prognostic significance has rarely been studied. In this study, we demonstrated the prognostic significance of Smad3, its phosphoisoforms, and Smad4 expression by immunohistochemistry in 126 esophageal squamous cell carcinomas. The phosphoisoforms of Smad3 studied in this article included phosphorylation at C-terminal (pSmad3C)(Ser) and phosphorylation at the linker region (pSmad3L)(Ser). High expression of Smad3 was associated with shorter overall survival. Co-existence of high expression of pSmad3L(S213) and low expression of pSmad3C(S423/425) were associated with advanced N stage and an independent prognostic factor for overall [hazard ratio (HR) 2.03, 95 % confidence interval (CI) (1.10-3.75), p = 0.023] and disease-free survival [HR 2.41, 95 % CI (1.32-4.39), p = 0.004]. In conclusion, co-existence of high pSmad3L(Ser) expression and low pSmad3C(Ser) expression can be considered as immunohistochemical biomarkers for predicting prognosis as well as future therapeutic targets. In addition, our results of combinatory effect of differential phosphorylation of Smad3 on prognosis suggest the mode of action of Smad3 might be logically determined by its phosphorylation pattern. [ABSTRACT FROM AUTHOR]
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- 2014
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23. Performance Evaluation and Comparison of Two Random Walk Models in the PCS Network.
- Author
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Baek, Jang Hyun, Seo, Jae Young, and Kim, Kyung Hee
- Abstract
In this paper, we evaluate the performance of the MBR (movement–based registration) scheme using a modified one-dimensional random walk model and a two–dimensional random walk model to compare the accuracy of two random walk models. The difference between these two models is identified and the performance difference in a mathematical approach is presented to support it. Analytical results are provided to demonstrate that the modified one–dimensional random walk always overestimates the performance of the MBR and that the two–dimensional random walk model should be used to obtain the exact performance of the MBR, and other registration schemes. [ABSTRACT FROM AUTHOR]
- Published
- 2006
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24. Aragonite undersaturation in Gwangyang Bay, South Korea: Effects of fresh water input.
- Author
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Kim, Dongseon, Yang, Eun-Jin, Baek, Seung, Kim, Kyung-Hee, Jeong, Jin-Hyun, and Kim, Young-Ok
- Abstract
Dissolved inorganic carbon (DIC) and alkalinity were precisely measured for surface and bottom waters in Gwangyang Bay, Korea, during the four seasons to assess seasonal variations of aragonite saturation state (Ω). Both the surface and bottom waters were undersaturated with respect to aragonite during summer but were supersaturated during the other seasons. The summertime undersaturation of the surface waters with respect to aragonite may have been a result of the dilution effect caused by higher seasonal river runoff. In the bottom waters, the average DIC concentration increased by 40.6 μmol kg from spring to summer, while the average alkalinity decreased by 74.7 μeq kg. As a result, the alkalinity/DIC ratio decreased from 1.07 in spring to 1.01 in summer and pH also decreased from 7.91 to 7.48, which resulted in the summertime undersaturation of the bottom waters. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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25. Water quality assessment at Jinhae Bay and Gwangyang Bay, South Korea.
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Kim, Dongseon, Baek, Seung, Yoon, Dong-Young, Kim, Kyung-Hee, Jeong, Jin-Hyun, Jang, Pung-Guk, and Kim, Young-Ok
- Abstract
A new water quality index for evaluating the water quality of Jinhae Bay and Gwangyang Bay was developed. Four water quality parameters were selected as water quality indicators for the water quality index: dissolved inorganic nitrogen (DIN), dissolved inorganic phosphorus (DIP), chlorophyll- a (Chl- a), and dissolved oxygen (DO). Reference levels of DIN, DIP, and Chl- a were determined as 6.22 μmol L, 0.38 μmol L, and 2.32 μmol L, respectively, on the basis of a long-term dataset that was collected monthly in the Korea Strait over a period of seven years (2006-2012). The water quality index established for Jinhae Bay and Gwangyang Bay is (bottom DO grade × 0.33) + (surface Chl- a grade × 0.33) + (surface DIN grade × 0.17) + (surface DIP grade × 0.17). On the basis of a three-year observation, the water quality of Jinhae Bay was classified as 'good' in winter and spring, 'poor' in summer, and 'fair' in autumn and exhibited large spatial variation, with the lowest-quality water observed in Masan Bay. The water quality of Gwangyang Bay was classified as 'good' in winter, 'fair' in spring, 'poor' in summer, and 'fair' in autumn. Unlike Jinhae Bay, the water quality of Gwangyang Bay exhibited minimal spatial variation. In both bays, water quality among the four seasons was worse during summer. It is essential that a survey for water quality evaluation be conducted during summer. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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26. Frequency of KRAS mutations in adult Korean patients with acute myeloid leukemia.
- Author
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Park, Mi-Jung, Park, Soon-Ho, Park, Pil-Whan, Seo, Yiel-Hea, Kim, Kyung-Hee, Jeong, Ji-Hun, Kim, Moon Jin, Ahn, Jeong-Yeal, Lee, Jae Hoon, Park, Jinny, and Hong, Junshik
- Abstract
Mutation of KRAS genes occurs with a frequency of 0.5-32 % in AML. In the present study, mutations of KRAS codon 12, 13, and 61 were detected by pyrosequencing and direct sequencing in AML. Seven KRAS mutations (7/123, 5.7 %) were detected. The most common mutation was a G-to-A transition in the second base of KRAS codon 13. No mutations were detected in KRAS codon 61. Combinations of KRAS and FLT3 mutation were not found in the same patient. There was no statistically significant difference between patients with KRAS mutations and patients with wild-type KRAS in terms of sex, age, CBC at diagnosis, CD34 positivity, MPO positivity, FLT3 mutation, karyotype, progression-free survival, and overall survival, although this may be attributable to the small sample size. To our knowledge, this is the first report of the detection of KRAS mutation in Asian AML patients using pyrosequencing and direct sequencing. These two methods showed identical efficiencies in their ability to detect KRAS mutations in 84 patients. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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27. Frequency of KRAS mutations in adult Korean patients with acute myeloid leukemia.
- Author
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Park, Mi-Jung, Park, Soon-Ho, Park, Pil-Whan, Seo, Yiel-Hea, Kim, Kyung-Hee, Jeong, Ji-Hun, Kim, Moon Jin, Ahn, Jeong-Yeal, Lee, Jae Hoon, Park, Jinny, and Hong, Junshik
- Abstract
Mutation of KRAS genes occurs with a frequency of 0.5–32 % in AML. In the present study, mutations of KRAS codon 12, 13, and 61 were detected by pyrosequencing and direct sequencing in AML. Seven KRAS mutations (7/123, 5.7 %) were detected. The most common mutation was a G-to-A transition in the second base of KRAS codon 13. No mutations were detected in KRAS codon 61. Combinations of KRAS and FLT3 mutation were not found in the same patient. There was no statistically significant difference between patients with KRAS mutations and patients with wild-type KRAS in terms of sex, age, CBC at diagnosis, CD34 positivity, MPO positivity, FLT3 mutation, karyotype, progression-free survival, and overall survival, although this may be attributable to the small sample size. To our knowledge, this is the first report of the detection of KRAS mutation in Asian AML patients using pyrosequencing and direct sequencing. These two methods showed identical efficiencies in their ability to detect KRAS mutations in 84 patients. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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28. Mapping the leaf proteome of Miscanthus sinensis and its application to the identification of heat-responsive proteins.
- Author
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Sharmin, Shamima, Alam, Iftekhar, Rahman, Md., Kim, Kyung-Hee, Kim, Yong-Goo, and Lee, Byung-Hyun
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VEGETATION mapping ,LEAF proteins ,MISCANTHUS ,PLANT proteins ,BIOMASS energy ,PLANT genomes - Abstract
Miscanthus sinensis is a promising bioenergy crop; however, its genome is poorly represented in sequence databases. As an initial step in the comprehensive analysis of the M. sinensis proteome, we report a reference 2-DE protein map of the leaf. A total of 316 protein spots were excised from the gels, digested with trypsin and subjected to matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) or MALDI-TOF/TOF MS. Two hundred and thirty-two protein spots were identified, which are involved in a variety of cellular functions through distinct metabolic pathways. Functional annotation of the proteins revealed a nearly complete C3 and C4 cycle, starch and sugar synthesis pathway, glycolysis pathway, a significant portion of the pentose phosphate pathway, and many enzymes involved in secondary metabolism such as flavonoid/isoflavonoid, kaurene, chalcone, sesquiterpene and lignin biosynthesis. Other proteins belong to primary metabolism, transcription, protein synthesis, protein destination/storage, disease/defense, cell growth/division, transportation and signal transduction. To test the applicability of the constructed map, we studied the effect of heat stress on M. sinensis leaf proteome. Twenty-five protein spots were upregulated, five were newly induced and twenty-five spots were downregulated by heat treatment. The differentially accumulated proteins were involved in photosynthesis, energy metabolism, gene transcription, protein kinases and phosphatases, signal transduction, protein synthesis and heat shock responses. C4-specific pyruvate orthophosphate dikinase, Rubisco large subunit, Rubisco activase and some associated proteins were upregulated during heat stress and tend to restore upon recovery. Identification of these proteins provides some important clues regarding the way M. sinensis copes with hot climate. This work represents the first extensive proteomic description of M. sinensis and provides a reference map and heat-responsive candidates for future molecular and physiological studies of this bioenergy crop. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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29. Smad3 and Smad3 Phosphoisoforms Are Prognostic Markers of Gastric Carcinoma.
- Author
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Kim, Seok-Hyung, Kim, Kyung-Hee, Ahn, Soomin, Hyeon, Jiyeon, and Park, Cheol-Keun
- Subjects
- *
STOMACH cancer , *BIOMARKERS , *TRANSFORMING growth factors , *CELLULAR signal transduction , *CANCER invasiveness , *CARCINOGENESIS , *GENE expression , *PROGNOSIS - Abstract
Background: The transforming growth factor-β/Smads signaling pathway plays an important role in tumorigenesis and progression in cancer, and may closely be related to the biological behaviors of some malignant tumors, such as gastric carcinoma. In this study, we investigated the roles of Smad3 and Smad3 phosphoisoforms in the prognosis of gastric carcinoma. Methods: We investigated the expressions of Smad3, pSmad3C(S423/425), pSmad3L(T179), pSmad3L(S204), and pSmad3L(S213) in tumor tissue microarrays of 442 gastric carcinoma patients who underwent curative surgery using immunohistochemistry and assessed their correlation with clinical outcome. Results: Positive Smad3 expression was observed in 33.5 % of gastric carcinoma. The rates of positive Smad3 phosphoisoforms expression varied according to the location of phosphorylation within Smad3: pSmad3C(S423/425) 28.5 %, pSmad3L(T179) 5.9 %, pSmad3L(S204) 1.8 %, and pSmad3L(S213) 20.8 %. Positive Smad3 expression was associated with diffuse type ( p = 0.003), poorer histologic differentiation ( p = 0.005), more frequent lymph node metastasis ( p = 0.001), and higher AJCC stage ( p = 0.006). Multivariate analyses revealed that Smad3 expression ( p = 0.041), pSmad3L(T179) expression ( p = 0.011), pSmad3L(S213) expression ( p = 0.003), and American Joint Committee on Cancer (AJCC) stage were independent predictors of shorter disease-free survival. Smad3 expression ( p = 0.033), pSmad3L(T179) expression ( p = 0.012), pSmad3L(S213) expression ( p = 0.005), and AJCC stage were also independent predictors of shorter overall survival. pSmad3C(S423/425) expression tended to show favorable influences on both disease-free survival ( p = 0.134) and overall survival ( p = 0.232). Conclusions: Smad3, pSmad3L(T179), and pSmad3L(S213) expression might be independent predictors of both shorter disease-free survival and shorter overall survival in gastric carcinoma patients after curative surgery, and might help clinicians identify patients at high risk of recurrence. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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30. Depletion of cathepsin D by transglutaminase 2 through protein cross-linking promotes cell survival.
- Author
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Kim, Se-Jin, Kim, Kyung-Hee, Ahn, Eu-Ree, Yoo, Byong Chul, and Kim, Soo-Youl
- Published
- 2013
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31. Role of FDG-PET/CT in detecting lymphomatous bone marrow involvement in patients with newly diagnosed diffuse large B-cell lymphoma.
- Author
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Hong, Junshik, Lee, Yukyung, Park, Yeonjeong, Kim, Seog, Hwang, Kyung, Park, Soon, Jeong, Jihoon, Kim, Kyung-Hee, Ahn, Jeong, Park, Sanghui, Park, Jinny, and Lee, Jae
- Subjects
B cells ,LYMPHOMAS ,BONE marrow ,HEMATOPOIETIC system ,IMMUNE system - Abstract
To evaluate the role of FDG-PET/CT in detecting bone marrow (BM) involvement, pre-treatment bilateral bone marrow biopsies (BMBs) and FDG-PET/CT scans of 89 patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab-CHOP were reviewed and analyzed. Fourteen patients (15.7%) had lymphomatous involvement based on BMB (BMB+), and 17 patients (19.1%) had the possibility of BM involvement on FDG-PET/CT (FDG-PET/CT+). Seventy-two patients (80.8%) had concordant results between BMB and FDG-PET/CT (seven patients were positive for both, and 65 patients were negative for both), but 17 patients (19.2%) had a discordant interpretation (seven patients were BMB+ and FDG-PET/CT−, and ten were BMB− and FDG-PET/CT+). Although BMB+ patients had an inferior 2-year EFS (37.0% vs. 79.8%, p < 0.001) and OS (36.3% vs. 81.0%, p < 0.001) compared to BMB− patients, no differences in EFS (62.6% vs. 72.7%, p = 0.185) and OS (59.4% vs. 78.0%, p = 0.146) were shown between FDG-PET/CT+ and FDG-PET/CT− patients. Whereas six of seven patients with diffuse hypermetabolism were BMB+, only one of ten patients with focal hypermetabolism was BMB+. The results suggest that FDG-PET/CT had a limited value to detect BM involvement in patients with DLBCL. Focal hypermetabolism of hematopoietic BM in FDG-PET/CT had no impact on survival. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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32. Establishment and characterization of six human gastric carcinoma cell lines, including one naturally infected with Epstein-Barr virus.
- Author
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Ku, Ja-Lok, Kim, Kyung-Hee, Choi, Jin-Sung, Kim, Sung-Hee, Shin, Young-Kyoung, Chang, Hee, Bae, Jae-Moon, Kim, Young-Woo, Lee, Jun, Yang, Han-Kwang, Kim, Woo-Ho, Jeong, Seung-Yong, and Park, Jae-Gahb
- Subjects
- *
STOMACH cancer , *CELL lines , *TUMORS , *DNA , *EPSTEIN-Barr virus - Abstract
We report the characterization of six new gastric carcinoma cell lines (designated NCC-19, NCC-20, NCC-24, NCC-59, SNU-1750 and SNU-1967) established from primary tumor samples of Korean patients. Four cell lines grew as adherent monolayers, one as both adherent and floating cell clumps and one as floating cell aggregates. The cell phenotypes, including the histopathology of the primary tumors and in vitro growth characteristics, were determined. We also performed molecular characterization, including DNA fingerprinting analysis and abnormalities of K-ras, p53, β-catenin, and TGF-βRII genes by PCR-SSCP and sequencing analyses. Population doubling times varied from 47-135 h. All cell lines showed relatively high viability, absence of mycoplasma or bacteria contamination and genetic heterogeneity by DNA fingerprinting analysis. Three lines had p53 mutations; one line had mutations in codon 13 (Gly13Asp) in K-ras and no line had a β−catenin mutation. NCC-59 cell line had a -1-bp mutation in 10-bp poly deoxy adenine repeat tract of the TGF-βRII gene. Moreover, NCC-24 gastric cancer cell line was found to be infected with Epstein-Barr virus (EBV). EBV infection was also shown in the original carcinoma tissue of the NCC-24 cell line. These well-characterized six gastric cancer cell lines should serve as useful tools for investigating the biological characteristics of gastric cancer and, in particular, NCC-24 may serve as a valuable model system to clarify the precise role of EBV in gastric carcinogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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33. Identification of MsHsp23 gene using annealing control primer system.
- Author
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Lee, Ki-Won, Kim, Kyung-Hee, Kim, Yong-Goo, Lee, Byung, and Lee, Sang-Hoon
- Abstract
To identify potential candidates for acquiring stress tolerance, a new annealing control primer (ACP) system was used to identify the differentially expressed genes. Alfalfa ( Medicago sativa L.) seedlings were exposed to various abiotic stresses such as cold (4°C for 6 h), heat (42°C for 6 h), salt (300 mM for 6 h), drought (withdrawing irrigation for 48 h), copper (500 μM for 6 h), cadmium (500 μM for 6 h), and arsenic (500 μM for 6 h). Primer sets 41 and 93 were differentially expressed and identified as same sequence, which represents a mitochondrial small heat-shock protein encoding gene, MsHsp23. This band was markedly increased or induced in alfalfa under heat, salt, and arsenic stresses. Differential expression of MsHsp23 was further evaluated by Northern blot analysis. Temporal expression analysis showed that mRNA pool was altered as early as 1 h of treatment. Thus, differential accumulation of MsHsp23 under heat, salt, and arsenic stresses suggests its potential involvement in diverse abiotic stress tolerance, and thereby making a target for further molecular analysis. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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34. Overexpression of a chloroplast-localized small heat shock protein OsHSP26 confers enhanced tolerance against oxidative and heat stresses in tall fescue.
- Author
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Kim, Kyung-Hee, Alam, Iftekhar, Kim, Yong-Goo, Sharmin, Shamima, Lee, Ki-Won, Lee, Sang-Hoon, and Lee, Byung-Hyun
- Subjects
HEAT shock proteins ,AGROBACTERIUM ,TURFGRASSES ,TALL fescue ,TRANSGENIC organisms ,PLANT genetic engineering - Abstract
Small heat shock proteins are involved in stress tolerance. We previously isolated and characterized a rice cDNA clone, Oshsp26, encoding a chloroplast-localized small heat shock protein that is expressed following oxidative or heat stress. In this study, we transferred this gene to tall fescue plants by an Agrobacterium-mediated transformation system. The integration and expression of the transgene was confirmed by PCR, Southern, northern, and immunoblot analyzes. Compared to the control plants, the transgenic plants had significantly lower electrolyte leakage and accumulation of thiobarbituric acid-reactive substances when exposed to heat or methyl viologen. The photochemical efficiency of photosystem II (PSII) (Fv/Fm) in the transgenic tall fescue plants was higher than that in the control plants during heat stress (42°C). These results suggest that the OsHSP26 protein plays an important role in the protection of PSII during heat and oxidative stress in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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35. Overexpression of alfalfa mitochondrial HSP23 in prokaryotic and eukaryotic model systems confers enhanced tolerance to salinity and arsenic stress.
- Author
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Lee, Ki-Won, Cha, Joon-Yung, Kim, Kyung-Hee, Kim, Yong-Goo, Lee, Byung-Hyun, and Lee, Sang-Hoon
- Subjects
ALFALFA ,NATIVE element minerals ,NONMETALS ,ARSENIC ,MITOCHONDRIAL DNA - Abstract
The cloning and characterization of a gene ( MsHSP23) coding for a heat shock protein in alfalfa in a prokaryotic and model plant system is described. MsHSP23 contains a 633 bp ORF encoding a polypeptide of 213 amino acids and exhibits greater sequence similarity to mitochondrial sHSPs from dicotyledons than to those from monocotyledons. When expressed in bacteria, recombinant MsHSP23 conferred tolerance to salinity and arsenic stress. Furthermore, MsHSP23 was cloned in a plant expressing vector and transformed into tobacco, a eukaryotic model organism. The transgenic plants exhibited enhanced tolerance to salinity and arsenic stress under ex vitro conditions. In comparison to wild type plants, the transgenic plants exhibited significantly lower electrolyte leakage. Moreover, the transgenic plants had superior germination rates when placed on medium containing arsenic. Taken together, these overexpression results imply that MsHSP23 plays an important role in salinity and arsenic stress tolerance in transgenic tobacco. This approach could be useful to develop stress tolerant crops including forage crops. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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36. Comparative proteomic approach to identify proteins involved in flooding combined with salinity stress in soybean.
- Author
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Alam, Iftekhar, Sharmin, Shamima, Kim, Kyung-Hee, Kim, Yong-Goo, Lee, Jeung, Bahk, Jeong, and Lee, Byung-Hyun
- Subjects
PROTEOMICS ,SOIL salinity ,WATERLOGGING (Soils) ,CELL membranes ,SOYBEAN - Abstract
Salinity together with waterlogging or flooding, a condition that occurs frequently in the field, can cause severe damage to crops. Combined flooding and salinity decreases the growth and survival of plants more than either stress alone. We report here the first proteomic analysis to investigate the global effects of saline flooding on multiple metabolic pathways. Soybean seedlings at the emergence (VE) stage were treated with 100 mM NaCl and flooded with water or 100 mM sodium chloride solution for 2 days. Proteins were extracted from hypocotyl and root samples and analyzed by two-dimensional gel electrophoresis followed by MALDI-TOF, MALDI-TOF/TOF mass spectrometry or immunoblotting. A total of 43 reproducibly resolved, differentially expressed protein spots visualized by Coomassie brilliant blue staining were identified by MALDI-TOF MS. Identities of several proteins were also validated by MS/MS analysis or immunoblot analysis. Twenty-nine proteins were upregulated, eight proteins were downregulated and six spots were newly induced. The identified proteins include well-known salt and flooding induced proteins as well as novel proteins expressed by the salinity-flooding combined stress. The comparative analysis identified changes at the proteome level that are both specific and part of a common or shared response. The identification of such differentially expressed proteins provides new targets for future studies that will allow assessment of their physiological roles and significance in the response of glycophytes to a combination of flooding and salinity. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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37. Defining virologic relapse in chronic hepatitis B.
- Author
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Kim, Kyung, Sinn, Dong, Yun, Won, Cho, Hyun, Lee, Yun, Gwak, Geum-Youn, Choi, Moon, Lee, Joon, Koh, Kwang, Yoo, Byung, Paik, Seung, Kim, Kyung Hee, Sinn, Dong Hyun, Yun, Won Kyoung, Cho, Hyun Chin, Lee, Yun Young, Choi, Moon Seok, Lee, Joon Hyeok, Koh, Kwang Cheol, and Yoo, Byung Chul
- Subjects
HEPATITIS B ,VIROLOGY ,DNA ,SERUM ,POLYMERASE chain reaction ,BIOCHEMISTRY ,RETROSPECTIVE studies ,ANTIVIRAL agents ,ORGANOPHOSPHORUS compounds ,LAMIVUDINE ,HEPATITIS viruses ,LONGITUDINAL method ,PURINES ,VIRAL antigens ,DISEASE relapse ,VIRAL load ,TREATMENT effectiveness ,CHRONIC hepatitis B ,THERAPEUTICS - Abstract
Background and Aims: Different definitions of virologic relapse (VR) are being used. One way of defining VR is "reappearance of HBV DNA in the serum," while another definition is an "increase in HBV DNA level greater than 1 log in two determinations at least 4 weeks apart." The aim of this study was to see the effectiveness of these two definitionsMethods: Forty-five HBeAg-positive chronic hepatitis B patients with a virologic response [negative PCR (<12 IU/ml)] who had discontinued therapy were analyzed retrospectively for VR, HBeAg reversion and biochemical flare.Results: HBV DNA reappeared in the serum (≥12 IU/ml) of all 45 patients (100%). An increase in HBV DNA level greater than 1 log in two determinations at least 4 weeks apart was identified in 20 of 25 patients (80%). Biochemical flare and HBeAg reversion were observed in 18 (40%) and 14 (31%) patients, respectively. Peak off-therapy HBV DNA level was significantly associated with biochemical flare (r=0.758, P<0.001) and HBeAg reversion (r=0.645, P<0.001). Two patients with high initial off-therapy HBV DNA levels (≥4.0 log(10) IU/ml) were reassessed at 4 weeks, and both experienced a biochemical flare and HBeAg reversion. Two patients had an increase in HBV DNA level greater than 1 log at a very low level (1 log to 2 or 3 log), but did not experience biochemical flare or HBeAg reversion during follow-up.Conclusions: Reappearance of HBV DNA was universal when sensitive HBV DNA assay was used. Waiting 4 weeks to confirm VR may be harmful for patients with a high HBV DNA level, and was ineffective to indicate re-therapy for patients with increase in HBV DNA at a very low level. There is a need for improved and standardized definitions of VR. [ABSTRACT FROM AUTHOR]- Published
- 2011
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38. Proteome alteration in human colon cancer cells by the treatment of HangAmDan-B.
- Author
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Kim, Kyung-Hee, Park, Byung-Rok, Cho, Chong-Kwan, Lee, Yeon-Weol, Cho, Eun-Jin, Yea, Sung-Chul, Yoo, Byong, and Yoo, Hwa-Seung
- Abstract
Korean traditional medicine, HangAmDan (HAD) was developed in 1996 for anti-tumor purpose, and has shown positive results in clinical case studies. Recently, HAD has been recently modified as HAD-B to increase therapeutic effects. Our present study focused on the effect of HAD-B on proteome alteration in human colon cancer cells with highly aggressive invasiveness. Before the proteome assessment, invasiveness of 4 human colon cancer cell lines, SNU-407, SNU-C4, LoVo, and DLD-1 have been determined. Among cell lines tested, DLD-1 showed higher invasiveness, and was selected for investigating proteome affected by HAD-B. HAD-B reduced invasiveness of DLD-1, but it did not lead to either synergistic effect with 5-fluorouracil or apoptosis. Phosphorylation of eukaryotic initiation factor 4E (eIF-4E) binding protein 1 (4EBP1) and mammalian target of rapamycin (mTOR) in DLD-1 was increased by HAD-B treatment whereas level of AKT phosphorylation was reduced. Furthermore, expression of eIF-5A-2 and the balance between tissue inhibitor of metalloproteinases-1 (TIMP-1) and matrix metalloproteinase 9 (MMP9) were deranged in DLD-1 after treatment of HAD-B. In conclusion, overall results from our proteome assessment may provide useful information on how HAD-B suppresses proliferation and invasion of human colon cancer cells. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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39. Establishment and characterization of six human lung cancer cell lines: EGFR, p53 gene mutations and expressions of drug sensitivity genes.
- Author
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Ku, Ja-Lok, Kim, Kyung-Hee, Choi, Jin-Sung, Jeon, You-Kyung, Kim, Sung-Hee, Shin, Young-Kyoung, Kim, Tae-You, Bang, Yung-Jue, Kim, Woo, and Park, Jae-Gahb
- Subjects
- *
LUNG cancer , *CELL lines , *GENETIC mutation , *CADHERINS , *HISTOPATHOLOGY , *DNA fingerprinting , *ANTINEOPLASTIC agents , *HUMAN genetic variation , *MESSENGER RNA - Abstract
Background: Six human lung cancer cell lines (SNU-371, SNU-963, SNU-1327, SNU-1330, SNU-2292 and SNU-2315) were newly established through primary cell cultures. These cell lines were derived from a pulmonary blastoma, a small cell lung cancer, three adenocarcinomas and a squamous cell carcinoma of the lung of six Korean lung cancer patients. Methods: The histopathology of the primary tumors and their in vitro growth characteristics were described. DNA fingerprinting analysis and genetic alterations in the p53, β -catenin, TGFβ RII, K-ras and EGFR genes were conducted. mRNA expressions levels of E-cadherin, COX-2, MDR1, MXR, CGA, synatophysin and TTF1 genes were investigated and sensitivity to anticancer drugs was screened. Results: Five cell lines grew as adherent cells and one cell line grew as floating aggregates. All lines were free of mycoplasma or bacteria and were proven unique by DNA fingerprinting analysis. A significant polymorphism at codon 72 (Arg to Pro) of the p53 gene was found in one line (SNU-1327) and a mutation at codon 176 was found in SNU-2292. No mutations in the K-ras, β -catenin and TGF-β RII genes were observed. E-cadherin was not expressed in SNU-371 and COX-2 was overexpressed in SNU-1330, SNU-2292 and SNU-2315 cell lines. MDR1 was overexpressed in SNU-371 and SNU-2292 cell lines and MXR was overexpressed in SNU-1327 cell line. Interestingly, the SNU-371 cell line derived from a pulmonary blastoma and which overexpressed MDR1 displayed cross resistance for several anticancer drugs. Neuroendocrine markers, chromogranin A and synaptophysin, were overexpressed in the small cell lung cancer cell line, SNU-963 and thyroid transcription factor-1 was also over expressed in this cell line. Two mutations (p.Glu746_Ser752delinsVal and p.Glu746_Ala750del) in exon 19 of EGFR were found in SNU-1330 and SNU-2315 cell lines, respectively. Conclusion: These well-characterized lung cancer cell lines may be useful tools for investigations of the biological characteristics of lung cancers, particularly for investigations related to mutations of EGFR. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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40. Responses of MxPPO overexpressing transgenic tall fescue plants to two diphenyl-ether herbicides, oxyfluorfen and acifluorfen.
- Author
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Lee, Ki-Won, Ahsan, Nagib, Lee, Sang-Hoon, Lee, Dong-Gi, Kim, Kyung-Hee, Alam, Iftekhar, Kwon, Suk-Yoon, Kim, Jin-Seog, Back, Kyoungwhan, Lee, Sung, and Lee, Byung-Hyun
- Abstract
We generated transgenic tall fescue ( Festuca arundinacea Schreb. cv. Kentucky-31) plants harboring a synthetic Myxococcus xanthus protoporphyrinogen oxidase ( MxPPO) gene through Agrobacterium-mediated gene transfer. Successful integration of the transgene into the genome of transgenic plants confirmed by polymerase chain reaction (PCR) and Southern blot analysis, and the functional expression of the MxPPO gene at the mRNA level in transgenic lines was validated by Northern blot analysis. Responses of transgenic and non-transgenic tall fescue plants to diphenyl-ether herbicides such as oxyfluorfen and acifluorfen have been evaluated in respect of various physiological and biochemical parameters. Differential responses were observed in chlorophyll content, in vivo H
2 O2 deposition and lipid peroxidation in both transgenic and non-transgenic plants exposed to oxyfluorfen or acifluorfen. Isozyme profiles of four antioxidant-enzymes, including peroxidase (POD), catalase (CAT), superoxide dismutase (SOD) and ascorbate peroxidase (APX), were also investigated in transgenic and non-transgenic plants using native PAGE analysis. Compared to the transgenic lines, higher staining activities of the examined antioxidant-enzymes observed in non-transgenic plants subjected to 100 μM of oxyfluorfen or acifluorfen suggests that non-transgenic plants are unable to prevent the photodynamic induced oxidative stress caused by herbicides. In addition, both transgenic and non-transgenic plants exposed to oxyfluorfen exhibited proportionally increased band-staining patterns in contrast to acifluorfen, which suggests that oxyfluorfen has relatively greater or more rapid effects on leaves than acifluorfen. [ABSTRACT FROM AUTHOR]- Published
- 2008
- Full Text
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41. Characterization of 458 single nucleotide polymorphisms of disease candidate genes in the Korean population.
- Author
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Lee, Jong-Keuk, Kim, Hung-Tae, Cho, Sung-Mi, Kim, Kyung-Hee, Jin, Hee-Jeong, Ryu, Gil-Mi, Oh, Bermseok, Park, Chan, Kimm, Kuchan, Jo, Sangmee Ahn, Jung, Sung-Chul, Kim, Sook, In, Sun Mi, Lee, Jong-Eun, and Jo, Inho
- Subjects
GENETIC polymorphisms ,HUMAN genetic variation ,ETHNICITY - Abstract
Single nucleotide polymorphisms (SNPs) are considered as very promising genetic markers for complex disease gene hunting. However, it has been demonstrated that there are significant ethnic di3erences in genetic variations. In order to investigate the genetic variations in the Korean population and their ethnic di3erences, a large number of SNPs of 161 disease candidate genes were collected from a publicly available SNP database and then tested for the distribution of allele frequency in the Korean population. Of all 458 SNPs tested, approximately 43.9% were polymorphic in the Korean population, whereas 44.5% were monomorphic. The remaining 11.6% were failed in the test. Significant di3erences have been observed when SNP allele frequency pattern of Koreans was compared with those of Caucasians and Africans, whereas this pattern was highly similar between Korean and Japanese populations. Our data indicate that although many of the SNPs available in publicly available database, especially coding-region SNPs (cSNPs), can be used as informative genetic markers for disease association studies, an extensive verification of public SNPs in a particular population studied should be undertaken prior to their association studies. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
42. Artificial intelligence algorithm for detecting myocardial infarction using six-lead electrocardiography.
- Author
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Cho, Younghoon, Kwon, Joon-myoung, Kim, Kyung-Hee, Medina-Inojosa, Jose R., Jeon, Ki-Hyun, Cho, Soohyun, Lee, Soo Youn, Park, Jinsik, and Oh, Byung-Hee
- Subjects
ARTIFICIAL intelligence ,MYOCARDIAL infarction ,ELECTROCARDIOGRAPHY ,MORTALITY prevention ,CORONARY angiography - Abstract
Rapid diagnosis of myocardial infarction (MI) using electrocardiography (ECG) is the cornerstone of effective treatment and prevention of mortality; however, conventional interpretation methods has low reliability for detecting MI and is difficulty to apply to limb 6-lead ECG based life type or wearable devices. We developed and validated a deep learning-based artificial intelligence algorithm (DLA) for detecting MI using 6-lead ECG. A total of 412,461 ECGs were used to develop a variational autoencoder (VAE) that reconstructed precordial 6-lead ECG using limb 6-lead ECG. Data from 9536, 1301, and 1768 ECGs of adult patients who underwent coronary angiography within 24 h from each ECG were used for development, internal and external validation, respectively. During internal and external validation, the area under the receiver operating characteristic curves of the DLA with VAE using a 6-lead ECG were 0.880 and 0.854, respectively, and the performances were preserved by the territory of the coronary lesion. Our DLA successfully detected MI using a 12-lead ECG or a 6-lead ECG. The results indicate that MI could be detected not only with a conventional 12 lead ECG but also with a life type 6-lead ECG device that employs our DLA. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
43. Echocardiographic Diastolic Stress Testing: What Does It Add?
- Author
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Kim, Kyung-Hee, Kane, Garvan C., Luong, Christina L., and Oh, Jae K.
- Abstract
Purpose of Review: Diastolic stress echocardiography may help facilitate the attribution of exertional dyspnea to cardiac and non-cardiac disease. It represents a non-invasive hemodynamic test to assess the patients with unexplained dyspnea. It can improve the diagnosis of heart failure with preserved ejection fraction (HFpEF) or diastolic heart failure. Recent Findings: A number of studies have validated exercise E/e′ as a measure of left ventricular (LV) filling pressure against invasively measured LV filling pressure using simultaneous exercise echocardiography-catheterization studies. Addition of E/e′ during exercise echocardiography improved sensitivity for diagnosis of HFpEF compared with resting assessment alone, and its specificity can be improved if tricuspid regurgitation velocity also increases above the normal range with exercise. The independent prognostic value of exercise E/e′ has also been well delineated in a number of studies. Summary: Diastolic stress exercise echocardiography should be considered for all patients with unexplained or exertional dyspnea and normal diastolic filling pressure or grade 1 diastolic dysfunction on resting echocardiography. Addition of diastolic assessment with exercise echocardiography improves the sensitivity of the test in patients with dyspnea and there are sufficient data to integrate diastolic exercise test into our clinical practice. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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- View/download PDF
44. Generation of Human Pluripotent Stem Cell-derived Endothelial Cells and Their Therapeutic Utility.
- Author
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Lee, Shin-Jeong, Kim, Kyung Hee, and Yoon, Young-sup
- Abstract
Purpose of Review: Human pluripotent stem cell-derived endothelial cells (hPSC-ECs) emerged as an important source of cells for cardiovascular regeneration. This review summarizes protocols for generating hPSC-ECs and provides an overview of the current state of the research in clinical application of hPSC-derived ECs.Recent Findings: Various systems were developed for differentiating hPSCs into the EC lineage. Stepwise two-dimensional systems are now well established, in which various growth factors, small molecules, and coating materials are used at specific developmental stages. Moreover, studies made significant advances in clinical applicability of hPSC-ECs by removing undefined components from the differentiation system, improving the differentiation efficiency, and proving their direct vascular incorporating effects, which contrast with adult stem cells and their therapeutic effects in vivo. Finally, by using biomaterial-mediated delivery, investigators improved the survival of hPSC-ECs to more than 10 months in ischemic tissues and described long-term behavior and safety of in vivo transplanted hPSC-ECs at the histological level.Summary: hPSC-derived ECs can be as a critical source of cells for treating advanced cardiovascular diseases. Over the past two decades, substantial improvement has been made in the differentiation systems and their clinical compatibility. In the near future, establishment of fully defined differentiation systems and proof of the advantages of biomaterial-mediated cell delivery, with some additional pre-clinical studies, will move this therapy into a vital option for treating those diseases that cannot be managed by currently available therapies. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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45. Corrigendum: IL-13Rα2 uses TMEM219 in chitinase 3-like-1-induced signalling and effector responses.
- Author
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Lee, Chang-Min, He, Chuan Hua, Nour, Adel M., Zhou, Yang, Ma, Bing, Park, Jin Wook, Kim, Kyung Hee, Cruz, Charles Dela, Sharma, Lokesh, Nasr, Mahmoud L., Modis, Yorgo, Lee, Chun Geun, and Elias, Jack A.
- Published
- 2016
- Full Text
- View/download PDF
46. IL-13Rα2 uses TMEM219 in chitinase 3-like-1-induced signalling and effector responses.
- Author
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Lee, Chang-Min, He, Chuan Hua, Nour, Adel M., Zhou, Yang, Ma, Bing, Park, Jin Wook, Kim, Kyung Hee, Cruz, Charles Dela, Sharma, Lokesh, Nasr, Mahmoud L., Modis, Yorgo, Lee, Chun Geun, and Elias, Jack A.
- Published
- 2016
- Full Text
- View/download PDF
47. Erratum to: Enhanced tolerance of transgenic tall fescue plants overexpressing 2-Cys peroxiredoxin against methyl viologen and heat stresses.
- Author
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Kim, Kyung-Hee, Alam, Iftekhar, Lee, Ki-Won, Sharmin, Shamima, Kwak, Sang-Soo, Lee, Sang, and Lee, Byung-Hyun
- Subjects
TALL fescue - Abstract
A correction to the article "Enhanced Tolerance of Transgenic Tall Fescue Plants Overexpressing 2-Cys Peroxiredoxin Against Methyl Viologen and Heat stresses," that was published in the January 7, 2010 issue is presented.
- Published
- 2010
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48. Acute myeloid leukemia with t(4;12)(q12;p13): report of 2 cases.
- Author
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Kim KH, Kim MJ, Ahn JY, Park PW, Seo YH, and Jeong JH
- Published
- 2016
- Full Text
- View/download PDF
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