Selective Translational Repression of Truncated Proteins from Frameshift Mutation-Derived mRNAs in Tumors

You, Kwon Tae,Li, Long Shan,Kim, Nam-Gyun,Kang, Hyun Ju,Koh, Kwi Hye,Chwae, Yong-Joon,Kim, Kyoung Mi,Kim, Yoon Ki,Park, Sung Mi,Jang, Sung Key,Kim, Hoguen,Wickens, Marv Public Library of Science 2007 PLoS biology Vol.5 No.5

<▼1><P>Frameshift and nonsense mutations are common in tumors with microsatellite instability, and mRNAs from these mutated genes have premature termination codons (PTCs). Abnormal mRNAs containing PTCs are normally degraded by the nonsense-mediated mRNA decay (NMD) system. However, PTCs located within 50–55 nucleotides of the last exon–exon junction are not recognized by NMD (NMD-irrelevant), and some PTC-containing mRNAs can escape from the NMD system (NMD-escape). We investigated protein expression from NMD-irrelevant and NMD-escape PTC-containing mRNAs by Western blotting and transfection assays. We demonstrated that transfection of NMD-irrelevant PTC-containing genomic DNA of <I>MARCKS</I> generates truncated protein. In contrast, NMD-escape PTC-containing versions of <I>hMSH3</I> and <I>TGFBR2</I> generate normal levels of mRNA, but do not generate detectable levels of protein. Transfection of NMD-escape mutant <I>TGFBR2</I> genomic DNA failed to generate expression of truncated proteins, whereas transfection of wild-type <I>TGFBR2</I> genomic DNA or mutant PTC-containing <I>TGFBR2</I> cDNA generated expression of wild-type protein and truncated protein, respectively. Our findings suggest a novel mechanism of gene expression regulation for PTC-containing mRNAs in which the deleterious transcripts are regulated either by NMD or translational repression.</P></▼1><▼2><P><B>Author Summary</B></P><P><B/></P><P>A class of mutations found in many cancers introduces aberrant termination signals during the synthesis of mRNA. In mammalian cells, abnormal mRNAs containing premature termination codons (PTCs) are normally degraded by a process called nonsense-mediated mRNA decay (NMD), thus avoiding potentially deleterious effects from abnormal protein production. However, some PTC-containing mRNAs are known to escape from NMD. By screening protein expression from genes with serious mutations in colon cancers, we confirmed that PTC-containing mRNAs of some genes escape from NMD. However, their abnormal proteins were not found in the tumor cells. To study the means by which these proteins were regulated, we transfected separate cell lines with NMD-escape mutant genomic DNA, wild-type genomic DNA, and mutant cDNA. We found that truncated proteins are not generated from the NMD-escape mutant genomic DNA, whereas wild-type protein and truncated protein were generated normally. These results indicate that the translation of PTC-containing mutant mRNAs is repressed in the cytoplasm.</P></▼2><▼3><P>A novel mechanism for regulating the products of nonsense mRNAs that contain premature termination codons involves repression at the level of translation.</P></▼3>

POSTER PRESENTATION 2: Critical Care/Experimental Medicine : PS2-36 ; Plasma Glutathione Reductase Activity Is Associated with The Prognosis of Septic Shock

( Kyoung Min You ),( Woon Yong Kwon ),( Gil Joon Suh ),( Kyung Su Kim ),( Jae Seong Kim ),( Ji Hwan Bu ),( Se Jong Lee ) 대한응급의학회 2014 대한응급의학회 학술대회초록집 Vol.2014 No.2

We performed this study to investigate whether plasma glutathione reductase (GR) activity is correlated with the erythrocyte reduced glutathione (GSH)/glutathione disulfide (GSSG) ratio in endotoxemic rats and if the decrease in GR activity is asociated with the increase in the mortality of patients with septic shock. This study consisted of a laboratory study conducted on male SD rats and a prospective observational study conducted in a 12-bed ICU of a tertiary referal hospital.To induce endotoxemia in rats, vehicle, LPS at dosages of 5 (LD-LPS), or 10 mg/kg (HD-LPS) were injected into a tail vein. Survival was observed for 72 hours,and a separated set of animals were euthanized at 6 hours post-LPS. Consecutive patients admitted to the ICU with septic shock were enrolled. Acording to the 28-day mortality, the enrolled patients were divided into the two groups: the survivors and the non-survivors. We obtained plasma samples at admission (0 h), 24 (24 h), and 72 hours after admision (72 h). The survival rate in the HD-LPS group was lower than that in the LD-LPS group. Erythrocyte GSH level, GSH/GSSG ratio, and GR and glutathione peroxidase (GPx) activities in the HD-LPS group were lower than those in the LD-LPS group, but GSSG and MDA levels in the HD-LPS group were higher than the LD-LPS group. The Spearman``s correlation coefficient between the erythrocyte GSH/GSSG ratio and the plasma GR activity was 0.782. Among 50 patients, 34 were the survivors and 16 were the non-survivors. The decreases in plasma total glutathione level and GR activity at 24 h were asociated with the increase in the mortality of patients with septic shock. Plasma GR activity was well correlated with erythrocyte GSH/GSSG ratio and the decreases in plasma total glutathione level and GR activity were asociated with the increase in the mortality of patients with septic shock.

Linalyl acetate prevents olmesartan-induced intestinal hypermotility mediated by interference of the sympathetic inhibitory pathway in hypertensive rat

Kwon, Soonho,Hsieh, Yu Shan,Shin, You Kyoung,Kang, Purum,Seol, Geun Hee Elsevier 2018 Biomedicine & pharmacotherapy Vol.102 No.-

<P><B>Abstract</B></P> <P>Olmesartan-associated enteropathy (OAE) is a life-threatening pathological condition, but its underlying mechanisms have not been elucidated. Although intestinal hypermotility is frequently accompanied by chronic diarrhea, there have been no studies of olmesartan-induced hypermotility. Intestinal motility should be well regulated by the enteric nervous system, but degeneration of enteric neurons has been reported in patients with chronic diarrheal diseases, such as irritable bowel syndrome, suggesting a connection between OAE and intestinal hypermotility. In this study, interference with this inhibitory pathway was analyzed in a model of olmesartan-induced intestinal hypermotility (OIH) in rats with nicotine-induced hypertension exposed to chronic immobilizing stress. The effects of the potent inhibitory neurotransmitters norepinephrine (NE) and sodium nitroprusside (SNP), which act via different pathways, were assessed ex vivo, with only NE-modulated frequency and amplitude of spontaneous contractions found to be elevated in OIH rat jejunum. Clinical symptoms frequent in OAE, including atrophy of the intestinal epithelium and weight loss, were observed in these rats. Interestingly, olmesartan significantly elevated heart rate while lowering blood pressure in OIH rats. These abnormal conditions were prevented by adding linalyl acetate (LA), while the blood pressure-lowering effects of olmesartan were maintained. These findings suggest that olmesartan induces intestinal hypermotility by interfering with the sympathetic inhibitory pathway, and reduces epithelial cell size or body weight in hypertensive rats. As LA prevented these effects, combination treatment with olmesartan plus LA may provide better antihypertensive efficacy without inducing OAE.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Olmesartan induced intestinal hypermotility in hypertensive rats. </LI> <LI> Olmesartan induced weight loss and atrophy of intestinal epithelium in hypertensive rats. </LI> <LI> Linalyl acetate alleviated olmesartan-induced tachycardia in hypertensive rats. </LI> <LI> Linalyl acetate prevented NE-modulated intestinal hypermotility by olmesartan in hypertensive rats. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Eye, Ear, Nose & Oral : Clinical Features of Acute Epiglottitis in Adults in the Emergency Department

( Kyoung Min You ),( Woon Yong Kwon ),( Gil Joon Suh ),( Kyung Su Kim ),( Jae Seong Kim ),( Min Ji Park ) 대한응급의학회 2016 대한응급의학회지 Vol.27 No.1

Purpose: Acute epiglottitis is a potentially fatal condition that can result in airway obstruction. The aim of this study is to examine the clinical features of adult patients who visited the emergency department (ED) with acute epiglottitis. Methods: This retrospective observational study was conducted at a single tertiary hospital ED from November 2005 to October 2015. We searched our electronic medical records (EMR) system for a diagnosis of “acute epiglottitis”and selected those patients who visited the ED. Results: A total of 28 patients were included. There was no pediatric case with acute epiglottitis during the study period. The mean age of the patients was 58.0±14.8 years. The peak incidences were in the sixth (n=7, 25.0%) and eighth (n=8, 28.6%) decades. The male-to-female ratio was 2.1:1. The most common symptom was sore throat (n=23, 82.1%), followed by dyspnea (n=15, 53.6%), hoarseness (n=7, 25.0%), fever (n=6, 21%), and dysphagia (n=5, 17.9%). The diagnosis of acute epiglottitis was confirmed when edema and hyperemia of the epiglottis were visualized by laryngoscopy. Twenty-six patients were treated conservatively with antibiotics and steroids without definite airway management. Two patients were intubated, but no patients required tracheostomy. Conclusion: In adult patients with acute epiglottitis, sore throat and dyspnea were the most common symptoms but fever was infrequent. Most patients improved with conservative management only. Definite airway management was required in only two patients in whom endotracheal intubations were performed successfully in the ED by emergency physicians, and surgical airway management was not required.

척수손상 환자의 체위변화에 따른 뇌혈관 및 심혈관계 변화 -예비연구-

최경효,성인영,하상배,권순억,이재홍,최기준,김유호 大韓再活醫學會 1999 Annals of Rehabilitation Medicine Vol.23 No.4

흑색극세포증에 동반된 당뇨병성 케톤산혈증 1예

유성수,권현희,박경찬,윤현대,이지현,손호상 대한당뇨병학회 2002 임상당뇨병 Vol.3 No.3

저자들은 전신 쇠약감을 주소로 내원 한 환자에서 흑색극세포증과 당뇨병성 케톤산혈증이 동반된 1예를 경험하였기에 이를 문헌 고찰과 함께 보고한다. Acanthosis nigricans is a skin lesion characterized by localized areas of brown hyperpigmented and velvety hyperplastic skin. Typically, it is found at body folds such as the neck and axilla. This condition is frequently accompanied by insulin resistance, hyperinsulinemia and obesity or it may be a signal of underlying malignant disorder, such as gastric cancer. Although diabetic ketoacidosis may develop in patients with type 2 diabetes when they experience severe metabolic stress, it usually occurs only in individuals whose circulating insulin is virtually absent. Because acanthosis nigricans is seen in insulin-resistant states or hyperinsulinemic states, patients with acanthosis nigricans are not likely to develop diabetic ketoacidosis. Because of the unexpected occurrence of diabetic ketoacidosis in association with acanthosis nigricans, we report this case.

Heterogeneous Electrocatalyst of Palladium-Cobalt-Phosphorus on Carbon Support for Oxygen Reduction Reaction in High Temperature Proton Exchange Membrane Fuel Cells

You, Dae Jong,Pak, Chanho,Jin, Seon-Ah,Lee, Kang Hee,Kwon, Kyungjung,Choi, Kyoung Hwan,Heo, Pil Won,Jang, Hongchul,Kim, Jun Young,Kim, Ji Man American Scientific Publishers 2016 Journal of Nanoscience and Nanotechnology Vol.16 No.5

<P>Palladium-cobalt-phosphorus (PdCoP) catalysts supported on carbon (Ketjen Black) were investigated as a cathode catalyst for oxygen reduction reaction (ORR) in high temperature proton exchange membrane fuel cells (HT-PEMFCs). The PdCoP catalyst was synthesized via a modified polyol process in teflon-sealed reactor by microwave-heating. From X-ray diffraction and transmission electron microscopic analysis, the PdCoP catalyst exhibits a face-centered cubic structure, similar to palladium (Pd), which is attributed to form a good solid solution of Co atoms and P atoms in the Pd lattice. The PdCoP nanoparticles with average diameter of 2.3 nm were uniformly distributed on the carbon support. The electrochemical surface area (ECSA) and ORR activity of PdP, PdCo and PdCoP catalysts were measured using a rotating disk electrode technique with cyclic voltammetry and the linear sweep method. The PdCoP catalysts showed the highest performances for ECSA and ORR, which might be attributed both to formation of small nanoparticle by phosphorus atom and to change in lattice constant of Pd by cobalt atom. Furthermore, The HT-PEMFCs single cell performance employing PdCoP catalyst exhibited an enhanced cell performance compared to a single cell using the PdP and PdCo catalysts. This result indicates the importance of electric and geometric control of Pd alloy nanoparticles that can improve the catalytic activity. This synergistic combination of Co and P with Pd could provide the direction of development of non-Pt catalyst for fuel cell system.</P>

SET 기반 전자지불프로토콜에서의 전자영수증 발행절차에 관한 연구

권영직,박유경,김우헌 大邱大學校 科學技術硏究所 2000 科學技術硏究 Vol.7 No.2

This research presents a repudiation of transaction and a protocol which is more effective in the Digital Receipt publication procedure in SET based electronic payment protocol. The biggest feature in this paper is that the merchant publish Digital Receipt through the digital signaturing in M which is consist with hashed order infomnation and hashed payment instruction. The cardholder can confirm transaction details through the comparison of stored M which is sent to the merchant with received M which is received from the merchant. Presented merchant's Digital Receipt publication procedure reduce extra procedure for malting digital receipt and prevent the repudiation of transaction between Merchant and Cardholder through the M.

Subclinical hypothyroidism diagnosed by thyrotropin-releasing hormone stimulation test in infertile women with ovulatory disorders

( You Jeong Lee ),( Kyung Hee Lee ),( Su Kyoung Kwon ),( Sung Hoon Kim ),( Hee Dong Chae ),( Byung Moon Kang ),( Chung Hoon Kim ) 대한산부인과학회 2012 대한산부인과학회 학술대회 Vol.99 No.-

This study was performed to assess the prevalence of subclinical hypothyroidism (SH) after a thyrotropin-releasing hormone (TRH) stimulating test in infertile women with ovulatory disorders. Thirty-nine infertile women with ovulatory disorders (group 1) and 27 infertile women with male infertility only (group 2, controls) had a TRH stimulating test on day 2-5 of their cycle. Serum thyroid-stimulating hormone (TSH) levels were measured before TRH injection (TSH0) and also measured at 20 min (TSH1) and 40 min (TSH2) after intravenous injection of 400 mcg TRH. TSH level above 30 mIU/l at any time during the test was considered abnormal. Group 1 was composed of infertile patients with poor responder (subgroup A, n=12), polycystic ovary syndrome (PCOS)(subgroup B, n=14) and WHO group II anovulation except poor responder or PCOS (subgroup C, n=13). The mean value was expressed as the mean ± standard deviation (SD). A Student`s t-test and Kruscal-Wallis test were used to compare the mean values. Chi-square test and Fisher`s exact test were used for the comparisons of fraction. Statistical significance was defined as p<0.05. All analyses were performed using the SPSS statistical package for Windows, version 11.0 (SPSS Inc, Chicago, IL). The prevalence of SH was significantly higher in group 1 of 46.2% (18/39) compared with 7.4% (2/27) in group 2 (p=0.001). TSH0, TSH1 and TSH2 levels were significantly higher in group 1 than the corresponding values in group 2 (p=0.020, p<0.001, p<0.001, respectively). In group 1, no significant difference was found in SH rate among subgroup A, B and C. However, TSH1 and TSH2 levels were significantly lower in subgroup C, as compared with those in subgroup A and B (p=0.015, p=0.012, respectively). Our results suggest that TRH stimulation test should be performed in infertile women suffering from ovulatory disorders to enable appropriate treatment in patients with abnormal results.

Pathological lesions and antigen localization in chicken, ducks and Japanese quail naturally infected by novel highly pathogenic avian influenza (H5N6), Korea, 2016

You chan Bae,Seong joon Joh,Seok chan Park,Hyuk man Kwon,Youn jeong Lee,Eun kyoung Lee,Byung min Song,Yu na Lee,Gyeong beom Heo,Hee soo Lee,Yong kuk Kwon,Kyung hyun Lee,Ji hyeon Kim 한국예방수의학회 2018 예방수의학회지 Vol.42 No.3

Epizootic HPAIV, H5N6, and H5N8 infections produced severe loss in poultry and wild birds in the Republic of Korea from 2016 to 2017. But pathological lesions and antigen distribution of the novel HPAIV H5N6 clade 2.3.4.4 in natural cases have been rarely reported. Herein, we describe the pathological lesions and antigen localization in chickens (layer and Korean native), ducks, and Japanese quail naturally infected by HPAIV H5N6. Grossly, severe reddening, swelling, and some necrotic foci, which were similar to septicemia or viremia, were observed in skin and many visceral organs including trachea, lung, liver, spleen, and pancreas. Histopathologically, pulmonary congestion and edema, as well as necrotizing hepatitis, splenitis, pancreatitis, myocarditis, and encephalitis were observed. Immunohistochemically, numerous HPAIV antigens were detected in necrotic parenchymal cells and in blood vessels of the respiratory, lymphoid, digestive, urinary, nervous, and cardiovascular systems. The results indicate that HPAIV H5N6 spread to the entire body via blood and caused severe damage throughout the entire body. The HPAI H5N6 clade 2.3.4.4 virus was isolated from samples of all four cases.