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      • Molecular analysis of <i>myocilin</i> and <i>optineurin</i> genes in Korean primary glaucoma patients

        Park, Joonhong,Kim, Myungshin,Park, Chan Kee,Chae, Hyojin,Lee, Seungok,Kim, Yonggoo,Jang, Woori,Chi, Hyun Young,Park, Hae-Young Lopilly,Park, Shin Hae D.A. Spandidos 2016 MOLECULAR MEDICINE REPORTS Vol.14 No.3

        <P>To investigate the underlying genetic influences of primary glaucoma in Korea, molecular analysis was performed in 112 sporadic cases, and results compared with healthy controls. The <I>myocilin</I> (<I>MYOC</I>) and <I>optineurin</I> (<I>OPTN</I>) genes were directly sequenced in 112 unrelated patients, including 17 with primary open-angle glaucoma, 19 with juvenile open-angle glaucoma, and 76 with normal tension glaucoma. Healthy unrelated Korean individuals (n=100) were used as the non-selected population control. A total of three <I>MYOC</I> and four <I>OPTN</I> variants potentially associated with primary glaucoma were identified in 4 and 18 patients, respectively. A novel variant of <I>MYOC</I>, <I>p.Leu255Pro</I>, was predicted to be potentially pathogenic by <I>in silico</I> analysis. Another, <I>p.Thr353Ile</I>, has been previously reported. These two missense variants were detected in patients with a family history of glaucoma. Combined heterozygous variants <I>p.[Thr123=;Ile288=]</I> were identified in 2 of 112 (2%) patients but not in healthy controls. Among <I>OPTN</I> variants, a novel variant <I>p.Arg271Cys</I> was identified. Homozygous <I>p.[Thr34=;Thr34=]</I> (4/112, 4%), homozygous <I>p.[Met98Lys;Met98Lys]</I> (4/112, 4%), or combined heterozygous <I>p.[Thr34=;Arg545Gln]</I> (9/112, 8%) was significantly associated with the development of primary glaucoma [odds ratio (OR)=8.768, 95% confidence interval (CI)=1.972–38.988; relative risk=1.818, 95% CI=1.473–2.244; P=0.001]. The present study provides insight into the genetic or haplotype variants of <I>MYOC</I> and <I>OPTN</I> genes contributing to primary glaucoma. Haplotype variants identified in the present study may be regarded as potential contributing factors of primary glaucoma in Korea. Further studies, including those on additional genes, are required to elucidate the underlying pathogenic mechanism using a larger cohort to provide additional statistical power.</P>

      • SCISCIESCOPUS

        Distribution of somatic mutations of cancer-related genes according to microsatellite instability status in Korean gastric cancer

        Park, Joonhong,Yoo, Han Mo,Jang, Woori,Shin, Soyoung,Kim, Myungshin,Kim, Yonggoo,Lee, Seung-Woo,Kim, Jeong Goo Williams & Wilkins Co 2017 Medicine Vol.96 No.25

        <P><B>Abstract</B></P><P>In studies of the molecular basis of gastric cancer (GC), microsatellite instability (MSI) is one of the key factors. Somatic mutations found in GC are expected to contribute to MSI-high (H) tumorigenesis. We estimated somatic mutation distribution according to MSI status in 52 matched pair GC samples using the Ion Torrent Ion S5 XL with the AmpliSeq Cancer Hotspot panel.</P><P>Seventy-five (9.8%) somatic variants consisting of 34 hotspot mutations and 41 other likely pathogenic variants were identified in 34 GC samples. The <I>TP53</I> mutations was most common (35%, 26/75), followed by <I>EGFR</I> (8%, 6/75), <I>HNF1A</I> (8%, 6/75), <I>PIK3CA</I> (8%, 6/75), and <I>ERBB2</I> (5%, 4/75). To determine MSI status, 52 matched pair samples were estimated using 15 MSI markers. Thirty-nine MS stable (S), 5 MSI-low (L), and 8 MSI-H were classified. GCs with MSI-H tended to have more variants significantly compared with GCs with MS stable (MSS) and MSI-L (standardized J-T statistic  =  3.161 for number of variants; <I>P</I>  =  .002). The mean number of all variants and hotspot mutations per tumor samples only in GCs with MSI-H were 3.9 (range, 1–6) and 1.1 (range, 0–3), respectively. Whereas, the mean number of all variants and hotspot mutations per tumor samples only in GCs with MSS/MSI-L were 1 (0–5)/0.8 (0–1) and 0.5 (0–3)/0.8 (0–1), respectively.</P><P>In conclusion, GC with MSI-H harbored more mutations in genes that act as a tumor suppressor or oncogene compared to GC with MSS/MSI-L. This finding suggests that the accumulation of MSIs contributes to the genetic diversity and complexities of GC. In addition, targeted NGS approach allows for detection of common and also rare clinically actionable mutations and profiles of comutations in multiple patients simultaneously. Because GC shows distinctive patterns related to ethnics, further studies pertaining to different racial/ethnic groups or cancer types may reinforce our investigations.</P>

      • SCISCIESCOPUS

        Molecular drug resistance profiles of <i>Mycobacterium tuberculosis</i> from sputum specimens using ion semiconductor sequencing

        Park, Joonhong,Jang, Woori,Kim, Myungshin,Kim, Yonggoo,Shin, So Youn,Park, Kuhn,Kim, Myung Sook,Shin, Soyoung Elsevier Biomedical 2018 Journal of microbiological methods Vol.145 No.-

        <P><B>Abstract</B></P> <P>The increasing burden of multidrug resistant (MDR)-TB, defined by resistance to rifampin (RFP) and isoniazid (INH), and extensively drug resistant-TB, defined by MDR-TB with additional resistance to fluoroquinolones (FQs) and more than one second-line injectable drug, is a serious impediment to global TB control. We evaluated the feasibility of full-length gene analysis including <I>inhA</I>, <I>katG</I>, <I>rpoB</I>, <I>pncA</I>, <I>rpsL embB</I>, <I>eis</I>, and <I>gyrA</I> using a semiconductor NGS with the Ion AmpliSeq TB panel to directly analyse 34 sputum specimens confirmed by phenotypic DST: INH, RFP, ethambutol (EMB), pyrazinamide (PZA), amikacin, kanamycin, streptomycin (SM), FQs including ofloxacin, moxifloxacin, and levofloxacin. The molecular drug resistance profiles showed “very good” and “substantial” strength of agreement for the phenotypic DST results of RFP and EMB, PZA, SM, FQs resistance with specificities of 96%, and 88%, 97%, 100% and sensitivities of 100%, and 88%, 60%, 67%, respectively. The strength of agreement for the detection of resistance to INH was “substantial”, compared between <I>katG</I> mutation and phenotypic INH only. Ion semiconductor NGS could make possible detection of several uncommon or novel amino acid changes in the full coding regions of these eight genes. However, molecular drug resistant profile should be complemented and validated by subsequent phenotypic DST studies at the same time.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Molecular drug susceptibility of <I>M. tuberculosis</I> from sputum is proposed using NGS. </LI> <LI> The agreement between Molecular and phenotypic drug susceptibility is “substantial”. </LI> <LI> Molecular drug resistance profiles can be used as predictors of phenotype DST. </LI> <LI> Molecular drug resistant profile should be complemented with phenotypic DST. </LI> </UL> </P>

      • KCI등재

        Wideband VHF and UHF RF Front-End Receiver for DVB-H Application

        Joonhong Park,Sunyoul Kim,Minhye Ho,Donghyun Baek 대한전기학회 2012 Journal of Electrical Engineering & Technology Vol.7 No.1

        This paper presents a wideband and low-noise direct conversion front-end receiver supporting VHF and UHFbands simultaneously. The receiver iscomposed of a low-noise amplifier (LNA), a down conversion quadrature mixer, and a frequency divider by 2. The cascode configuration with the resistor feedback is exploited in the LNA to achieve a wide operating bandwidth. Four gainstep modesare employed using a switched resistor bank and a capacitor bank in the signal path to cope with wide dynamic input power range. The verticalbipolar junction transistors are used as the switching elements in the mixer to reduce 1/f noise corner frequency. The proposed front-end receiver fabricated in 0.18 μm CMOS technology shows very low minimum noise figureof 1.8 dB and third order input intercept pointof -12dBm inthe high-gain mode of 26.5 dBmeasured at 500 MHz.The proposed receiverconsumeslow current of 20 mA from a 1.8 V power supply.

      • SCIESCOPUS

        Chromosome abnormalities in T-cell acute lymphoblastic leukemia in Korea.

        Park, Joonhong,Kim, Myungshin,Lee, Hae Kyung,Kim, Yonggoo,Han, Kyungja,Son, Jungok,Lee, Seok,Chung, Nack-Gyun,Cho, Bin Elsevier Science Publishers 2014 INTERNATIONAL JOURNAL OF HEMATOLOGY Vol.99 No.3

        <P>The aim of the present study was to analyze chromosome abnormalities in Korean patients with T-cell acute lymphoblastic leukemia (T-ALL). A total of 65 patients with newly diagnosed T-ALL were enrolled in the study from December 2004 to December 2011. Chromosome analysis was performed at diagnosis on short-term cultures of bone marrow specimens. Of these 65 patients, abnormal karyotypes were found in 50 (77 %). Numerical and structural chromosome abnormalities were identified in 16 (25 %) and 47 (72 %) patients, respectively. Deletion was the most common structural abnormality (48 %), followed by translocation (29 %). Overall survival (OS) and relapse-free survival (RFS) outcome were unaffected by the number and/or type of chromosome abnormalities in both childhood and adult T-ALL; however, the OS interval was longer for childhood patients than for adult patients in the entire cohort (P = 0.0003). Similarly, patients with first complete remission (CR) showed a better OS than those who failed to achieve first CR (P < 0.0001). There was a negative clinical impact in adult patients and patients without first CR according to multivariate analysis. This study helps to fill the gap regarding chromosome findings in T-ALL and may lead to identification of the molecular background behind phenotypic differences.</P>

      • SCOPUSKCI등재

        Genetic Characterization of Molecular Targets in Korean Patients with Gastrointestinal Stromal Tumors

        Park, Joonhong,Yoo, Han Mo,Sul, Hae Jung,Shin, Soyoung,Lee, Seung Woo,Kim, Jeong Goo The Korean Gastric Cancer Association 2020 Journal of gastric cancer Vol. No.

        Purpose: Gastrointestinal stromal tumors (GISTs) frequently harbor activating gene mutations in either KIT or platelet-derived growth factor receptor A (PDGFRA) and are highly responsive to several selective tyrosine kinase inhibitors. In this study, a targeted next-generation sequencing (NGS) assay with an Oncomine Focus Assay (OFA) panel was used for the genetic characterization of molecular targets in 30 Korean patients with GIST. Materials and Methods: Using the OFA that enables rapid and simultaneous detection of hotspots, single nucleotide variants (SNVs), insertion and deletions (Indels), copy number variants (CNVs), and gene fusions across 52 genes relevant to solid tumors, targeted NGS was performed using genomic DNA extracted from formalin-fixed and paraffin-embedded samples of 30 GISTs. Results: Forty-three hotspot/other likely pathogenic variants (33 SNVs, 8 Indels, and 2 amplifications) in 16 genes were identified in 26 of the 30 GISTs. KIT variants were most frequent (44%, 19/43), followed by 6 variants in PIK3CA, 3 in PDGFRA, 2 each in JAK1 and EGFR, and 1 each in AKT1, ALK, CCND1, CTNNB1, FGFR3, FGFR4, GNA11, GNAQ, JAK3, MET, and SMO. Based on the mutation types, majority of the variants carried missense mutations (60%, 26/43), followed by 8 frameshifts, 6 nonsense, 1 stop-loss, and 2 amplifications. Conclusions: Our study confirmed the advantage of using targeted NGS with a cancer gene panel to efficiently identify mutations associated with GISTs. These findings may provide a molecular genetic basis for developing new drugs targeting these gene mutations for GIST therapy.

      • SCIEKCI등재

        Use of Stable Isotope Probing in Selectively Isolating Target Microbial Community Genomes from Environmental Samples for Enhancing Resolution in Ecotoxicological Assessment

        Park, Joonhong,Congeevaram, Shankar,Ki, Dong-Won,Tiedje, James M. The Korean Society of Toxicogenomics and Toxicopro 2006 Molecular & cellular toxicology Vol.2 No.1

        In this study we attempted to develop a novel genomic method to selectively isolate target functional microbial genomes from environmental samples. For this purpose, stable isotope probing (SIP) was applied in selectively isolating organic pollutant-assimilating populations. When soil microbes were fed with $^{13}C-labeled $ biphenyl, biphenyl-utilizing cells were incorporated with the heavy carbon isotope. The heavy DNA portion was successfully separated by CsCl equilibrium density gradient. And the diversity in the heavy DNA was sufficiently reduced, being suitable for the current DNA microarray techniques to detect biphenyl-utilizing populations in the soil. In addition, we proposed a new way to get more genetic information by combining this SIP method with selective metagenomic approach. The increased selective power of these new DNA isolation methods will be expected to provide a good quality of new genetic information, which, in turn, will result in development of a variety of biomarkers that may be used in assessing ecotoxicology issues including the impacts of organic hazards, and antibiotic-resistant pathogens on human and ecological systems.

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