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Kwon, So-Youn,Bae, Ok-Nam,Noh, Ji-Yoon,Kim, Keunyoung,Kang, Seojin,Shin, Young-Jun,Lim, Kyung-Min,Chung, Jin-Ho U.S. Dept. of Health, Education, and Welfare, Publ 2015 Environmental health perspectives Vol.123 No.2
<P>Background: Nephrotoxicity associated with lead poisoning has been frequently reported in epidemiological studies, but the underlying mechanisms have not been fully described.</P><P>Objectives: We examined the role of erythrocytes, one of the major lead reservoirs, in lead-associated nephrotoxicity.</P><P>Methods and results: Co-incubation of lead-exposed human erythrocytes with HK-2 human renal proximal tubular cells resulted in renal tubular cytotoxicity, suggesting a role of erythrocytes in lead-induced nephrotoxicity. Morphological and flow cytometric analyses revealed that HK-2 cells actively phagocytized lead-exposed erythrocytes, which was associated with phosphatidylserine (PS) externalization on the erythrocyte membrane and generation of PS-bearing microvesicles. Increased oxidative stress and up-regulation of nephrotoxic biomarkers, such as NGAL, were observed in HK-2 cells undergoing erythrophagocytosis. Moreover, TGF-β, a marker of fibrosis, was also significantly up-regulated. We examined the significance of erythrophagocytosis in lead-induced nephrotoxicity in rats exposed to lead via drinking water for 12 weeks. We observed iron deposition and generation of oxidative stress in renal tissues of lead-exposed rats, as well as the histopathological alterations such as tubulointerstitial lesions, fibrosis, and up-regulation of KIM-1, NGAL, and TGF-β.</P><P>Conclusions: Our data strongly suggest that erythrophagocytosis and subsequent iron deposition in renal tubular cells could significantly enhance nephrotoxicity following lead exposure, providing insight on lead-associated kidney damages.</P><P>Citation: Kwon SY, Bae ON, Noh JY, Kim K, Kang S, Shin YJ, Lim KM, Chung JH. 2015. Erythrophagocytosis of lead-exposed erythrocytes by renal tubular cells: possible role in lead-induced nephrotoxicity. Environ Health Perspect 123:120–127; http://dx.doi.org/10.1289/ehp.1408094</P>
Kim, Bo Hyun,Kim, Seong-Jang,Kim, Keunyoung,Kim, Heeyoung,Kim, So Jung,Kim, Won Jin,Jeon, Yun Kyung,Kim, Sang Soo,Kim, Yong Ki,Kim, In Joo Springer Japan 2015 Annals of nuclear medicine Vol.29 No.8
<P><B>Objective</B></P><P>The objective of this study was to investigate whether total lesion glycolysis (TLG) and metabolic tumor volume (MTV) measured by <SUP>18</SUP>F-fluorodeoxyglucose (<SUP>18</SUP>F-FDG) positron emission tomography/computed tomography (PET/CT) could predict the aggressiveness and lymph node metastasis (LNM) in patients with incidentally detected differentiated thyroid carcinoma.</P><P><B>Methods</B></P><P>A total 358 patients with focal FDG-avid thyroid incidentaloma during cancer evaluation were enrolled. Among 235 patients in whom fine-needle aspiration biopsy was performed, 51 patients underwent total thyroidectomy with LN dissection. We analyzed the relationship between volume-based parameters and clinicopathologic characteristics.</P><P><B>Results</B></P><P>The mean age and tumor size were 57.1 ± 11.3 years and 1.15 ± 0.81 cm, respectively. The prevalence of malignancy was 21.7 % (51/235). When SUV<SUB>max</SUB> > 5.91, MTV2.5 > 2.05 cm<SUP>3</SUP>, and TLG2.5 > 9.09 were used as cutoff points, sensitivity, specificity, and area under curve (AUC) for prediction of lateral LNM were 77.9, 69.1 %, 0.716 (<I>P</I> = 0.047), 77.8, 88.1 %, 0.839 (<I>P</I> < 0.001), 77.8, 85.1 %, and 0.815 (<I>P</I> = 0.002), respectively. However, MTV and TLG had no value in prediction of central LNM, extrathyroidal extension, and multifocality. On comparison ROC curve analysis, the MTV and TLG showed the statistical differences for the prediction of lateral LNM compared with SUV<SUB>max</SUB> (all <I>P</I>’s < 0.05).</P><P><B>Conclusions</B></P><P>This study has shown for the first time that volume-based PET functional parameters had a significant value for the prediction of lateral LNM in incidentally detected PTC. These results suggest that higher MTV and TLG can be potential new risk factors for preoperative risk stratification. The usefulness of TLG and MTV in preoperative risk stratification in patients with PTC needs to be confirmed in further large studies.</P>
Kim, Keunyoung,Kim, Seong-Jang,Kim, In-Joo,Seong Kim, Yun,Pak, Kyoungjune,Kim, Heeyoung Lippincott Williams Wilkins, Inc. 2012 Nuclear medicine communications Vol.33 No.6
OBJECTIVES: The aim of this study was to evaluate the usefulness of the tumor burden as characterized by the metabolic tumor volume (MTV) and total lesion glycolysis (TLG) measured by F-18 fluoro-2-deoxyglucose (F-18 FDG) PET-computed tomography (CT) in predicting recurrence-free survival (RFS) and overall survival (OS) in surgically resected non-small-cell lung cancer (NSCLC) patients. METHODS: We retrospectively reviewed 91 patients with pathologically documented stages I–IIIA NSCLC. MTV and TLG were obtained according to various thresholds of the standard uptake value (SUV) of primary tumor using preoperative F-18 FDG PET-CT. We used comparison receiver-operating characteristic curve analysis to test the statistical significance of the differences among the multiple volumetric parameters calculated by various SUV cutoff values. RFS and OS were evaluated with the Kaplan–Meier method and Cox regression analysis. RESULTS: On comparison receiver-operating characteristic curve analysis, no significant difference was found among the volumetric parameters calculated using various thresholds of SUV. Regardless of the thresholds, patients with smaller MTV and lower TLG showed longer RFS and OS. MTV and TLG measured by F-18 FDG PET-CT were found to have better predictive performance than SUVmax for recurrence and death. According to multivariate analyses, MTV2.5 was revealed as a significant prognostic factor for RFS. Tumor size over 3 cm was selected as a significant prognostic indicator of OS. CONCLUSION: Volume-based parameters of F-18 FDG PET-CT may have a role in providing prognostic information in NSCLC patients who have received surgical treatment.
Cyclocurcumin, an Antivasoconstrictive Constituent of <i>Curcuma longa</i> (Turmeric)
Kim, Keunyoung,Kim, Jung-Jun,Jung, Yeryeon,Noh, Ji-Yoon,Syed, Ahmed Shah,Kim, Chul Young,Lee, Moo-Yeol,Lim, Kyung-Min,Bae, Ok-Nam,Chung, Jin-Ho American Chemical Society and American Society of 2017 Journal of natural products Vol.80 No.1
<P>Despite the increasing attention on the therapeutic potential of Curcuma longa (turmeric), the biological activities of curcuminoids other than curcumin are not well understood. Here, we investigated antivasoconstrictive activities of C. longa extract and its ingredients using freshly isolated rat aortic rings. C. longa extract significantly suppressed agonist-stimulated vasoconstriction, and cyclocurcumin was found to be the most potent (IC50 against phenylephrine-induced vasoconstriction: 14.9 +/- 1.0 mu M) among the 10 tested ingredients including four curcuminoids. Cyclocurcumin significantly inhibited contraction of vascular smooth muscle, which was mediated by the suppression of myosin-light-chain phosphorylation and calcium influx via the L-type calcium channel. The inhibitory effect of cyclocurcumin was observed to be reversible and without cytotoxicity. Taken together, we demonstrated that cyclocurcumin, a bioactive ingredient in C. longa, may have a therapeutic potential as a novel antivasoconstrictive natural product.</P>
Pak, Kyoungjune,Kim, Seong-Jang,Kim, In Joo,Kim, Keunyoung,Kim, Heeyoung,Kim, So Jung The Korea Society of Nuclear Medicine 2012 핵의학 분자영상 Vol.46 No.3
Purpose We aimed to evaluate the relation between visceral fat volume and fluorodeoxyglucose (FDG) uptake of the liver measured by maximum or mean standardized uptake value. Methods We retrospectively analyzed 96 consecutive records of positron emission tomography/computed tomography (PET/CT) performed for cancer screening between May 2011 and December 2011. Subjects were divided into 2 groups according to Hounsfield unit (HU) of the liver comparing with that of the spleen. The control group (20 women, 56 men) demonstrating HU of the liver equal or greater than that of the spleen included 76 patients, while the fatty liver group (2 women, 18 men) showing HU of the liver less than that of the spleen included 20 patients. We compared FDG uptake of the liver and visceral fat volume between two groups. We evaluated correlation of hepatic FDG uptake measured by maximum or mean standardized uptake value (SUV) with visceral fat volume and attenuation. Results The fatty liver disease group showed higher aspartate aminotransferase (AST)of ($24.42{\pm}7.22$, p=0.012), alanine aminotransferase (ALT) of ($25.16{\pm}11.68$, p=0.001), body mass index (BMI) of ($24.58{\pm}3.29$, p=0.021), and visceral fat volume ($3063.53{\pm}1561.43$, p=0.011) than the control group. There were no statistically significant differences of mean standardized uptake value of the liver (liver $SUV_{mean}$) ($2.73{\pm}0.19$, p=0.723), maximum standardized uptake value of the liver (liver $SUV_{max}$) ($3.39{\pm}0.53$, p=0.8248) and liver $SUV_{mean}$/spleen $SUV_{mean}$ ($1.13{\pm}0.10$, p=0.081) between the two groups. Strong correlations were shown between liver $SUV_{mean}$ and BMI (r=0.609, p<0.001) and between liver $SUV_{mean}$ and visceral fat volume (r=0.457, p<0.001). Liver $SUV_{max}$ was also strongly correlated with BMI (r=0.622, p=0.001) and visceral fat volume (r=0.547, p<0.001). There was no significant association of mean attenuation value of the liver (liver $HU_{mean}$) with liver $SUV_{mean}$ (r=-0.003, p=0.979) or liver $SUV_{max}$ (r=-0.120, p=0.244). Conclusion Hepatic FDG uptake quantified as $SUV_{mean}$ or $SUV_{max}$ is not correlated with hepatic steatosis but with visceral fat volume in cancer screening.
( Gi-wook Lee ),( Keunyoung Kim ),( Seong-jang Kim ),( Kyung-nam Bae ),( Jin-hwa Son ),( Kihyuk Shin ),( Hoon-soo Kim ),( Hyun-chang Ko ),( Moon-bum Kim ),( Byung-soo Kim ) 대한피부과학회 2021 대한피부과학회 학술발표대회집 Vol.73 No.-
Background: Atopic dermatitis (AD) is an inflammatory skin disease which associated with increased systemic and vascular inflammation. Although dupilumab has been proved to be effective for severe AD, researches analyzing inflammation-reducing effect of dupilumab through imaging test have been rarely reported. Objectives: To assess the effect of dupilumab in reducing systemic and vascular inflammation in severe AD patients using <sup>18</sup>F-fluorodeoxyglucose positron emission tomography-computed tomography (<sup>18</sup>F-FDG PET/CT). Methods: Patients with severe AD underwent <sup>18</sup>F-FDG PET/CT imaging prior to the start of dupilumab treatment. Scans were conducted again at the time of Eczema Area and Severity Index (EASI) of 75 was achieved after the treatment of dupilumab initiated. Results: When compared with baseline imaging, there was no statistically significant difference in the standardized uptake values of major organs and aorta at the time of achieving EASI 75 after dupilumab treatment in severe AD patients. Conclusion: While dupilumab treatment showed significant clinical improvement in severe AD patients, it did not induce any changes on systemic and vascular inflammation in <sup>18</sup>F-FDG PET/CT imaging.
( Gi-wook Lee ),( Keunyoung Kim ),( Seong-jang Kim ),( Kyung-nam Bae ),( Jin-hwa Son ),( Kihyuk Shin ),( Hoon-soo Kim ),( Hyun-chang Ko ),( Moon-bum Kim ),( Byung-soo Kim ) 대한피부과학회 2021 대한피부과학회 학술발표대회집 Vol.73 No.1
Background: Atopic dermatitis (AD) is an inflammatory skin disease which associated with increased systemic and vascular inflammation. Although dupilumab has been proved to be effective for severe AD, researches analyzing inflammation-reducing effect of dupilumab through imaging test have been rarely reported. Objectives: To assess the effect of dupilumab in reducing systemic and vascular inflammation in severe AD patients using <sup>18</sup>F-fluorodeoxyglucose positron emission tomography-computed tomography (<sup>18</sup>F-FDG PET/CT). Methods: Patients with severe AD underwent <sup>18</sup>F-FDG PET/CT imaging prior to the start of dupilumab treatment. Scans were conducted again at the time of Eczema Area and Severity Index (EASI) of 75 was achieved after the treatment of dupilumab initiated. Results: When compared with baseline imaging, there was no statistically significant difference in the standardized uptake values of major organs and aorta at the time of achieving EASI 75 after dupilumab treatment in severe AD patients. Conclusion: While dupilumab treatment showed significant clinical improvement in severe AD patients, it did not induce any changes on systemic and vascular inflammation in <sup>18</sup>F-FDG PET/CT imaging.
Min, Ahrum,Im, Seock-Ah,Jang, Hyemin,Kim, Seongyeong,Lee, Miso,Kim, Debora Keunyoung,Yang, Yaewon,Kim, Hee-Jun,Lee, Kyung-Hun,Kim, Jin Won,Kim, Tae-Yong,Oh, Do-Youn,Brown, Jeff,Lau, Alan,O'Connor, Mar American Association for Cancer Research 2017 Molecular Cancer Therapeutics Vol.16 No.4
<P>These findings suggest synthetic lethality between ATR inhibition and ATM deficiency in gastric cancer cells. Further clinical studies on the interaction between AZD 6738 and ATM deficiency are warranted to develop novel treatment strategies for gastric cancer. (C)2017 AACR.</P>