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Lee Janie M.,Ichikawa Laura E.,Wernli Karen J.,Bowles Erin J. A.,Specht Jennifer M.,Kerlikowske Karla,Miglioretti Diana L.,Lowry Kathryn P.,Tosteson Anna N. A.,Stout Natasha K.,Houssami Nehmat,Onega T 대한영상의학회 2023 Korean Journal of Radiology Vol.24 No.8
Objective: When multiple surveillance mammograms are performed within an annual interval, the current guidance for oneyear follow-up to determine breast cancer status results in shared follow-up periods in which a single breast cancer diagnosis can be attributed to multiple preceding examinations, posing a challenge for standardized performance assessment. We assessed the impact of using follow-up periods that eliminate the artifactual inflation of second breast cancer diagnoses. Materials and Methods: We evaluated surveillance mammograms from 2007–2016 in women with treated breast cancer linked with tumor registry and pathology outcomes. Second breast cancers included ductal carcinoma in situ or invasive breast cancer diagnosed during one-year follow-up. The cancer detection rate, interval cancer rate, sensitivity, and specificity were compared using different follow-up periods: standard one-year follow-up per the American College of Radiology versus follow-up that was shortened at the next surveillance mammogram if less than one year (truncated follow-up). Performance measures were calculated overall and by indication (screening, evaluation for breast problem, and short interval follow-up). Results: Of 117971 surveillance mammograms, 20% (n = 23533) were followed by another surveillance mammogram within one year. Standard follow-up identified 1597 mammograms that were associated with second breast cancers. With truncated follow-up, the breast cancer status of 179 mammograms (11.2%) was revised, resulting in 1418 mammograms associated with unique second breast cancers. The interval cancer rate decreased with truncated versus standard follow-up (3.6 versus 4.9 per 1000 mammograms, respectively), with a difference (95% confidence interval [CI]) of -1.3 (-1.6, -1.1). The overall sensitivity increased to 70.4% from 63.7%, for the truncated versus standard follow-up, with a difference (95% CI) of 6.6% (5.6%, 7.7%). The specificity remained stable at 98.1%. Conclusion: Truncated follow-up, if less than one year to the next surveillance mammogram, enabled second breast cancers to be associated with a single preceding mammogram and resulted in more accurate estimates of diagnostic performance for national benchmarks.
Korean guidelines for the management of gout
( Jennifer Jooha Lee ),( Ji Soo Lee ),( Min Kyung Chung ),( Joong Kyong Ahn ),( Hyo-jin Choi ),( Seung-jae Hong ),( Chong-hyeon Yoon ),( Su-hyun Kim ),( Kyung-hwan Jeong ),( Jong-woo Kim ),( Bo-yeon K 대한내과학회 2023 The Korean Journal of Internal Medicine Vol.38 No.5
Gout is the most common form of arthritis, with the prevalence increasing worldwide. The present treatment guidelines provide recommendations for the appropriate treatment of acute gout, management during the inter-critical period, and prevention of chronic complications. The guidelines were developed based on evidence-based medicine and draft recommendations finalized after expert consensus. These guidelines are designed to provide clinicians with clinical evidence to enable efficient treatment of gout.
Lee, Hyung Chul,Jung, Seung Hee,Hwang, Hyun Jung,Kang, Donghee,De, Supriyo,Dudekula, Dawood B.,Martindale, Jennifer L.,Park, Byungkyu,Park, Seung Kuk,Lee, Eun Kyung,Lee, Jeong-Hwa,Jeong, Sunjoo,Han, K Oxford University Press 2017 Nucleic acids research Vol.45 No.11
<P><B>Abstract</B></P><P>RNA-binding proteins (RBPs) are involved in mRNA splicing, maturation, transport, translation, storage and turnover. Here, we identified <I>ACOT7</I> mRNA as a novel target of human WIG1. <I>ACOT7</I> mRNA decay was triggered by the microRNA miR-9 in a WIG1-dependent manner via classic recruitment of Argonaute 2 (AGO2). Interestingly, AGO2 was also recruited to <I>ACOT7</I> mRNA in a WIG1-dependent manner in the absence of miR-9, which indicates an alternative model whereby WIG1 controls AGO2-mediated gene silencing. The WIG1–AGO2 complex attenuated translation initiation via an interaction with translation initiation factor 5B (eIF5B). These results were confirmed using a WIG1 tethering system based on the MS2 bacteriophage coat protein and a reporter construct containing an MS2-binding site, and by immunoprecipitation of WIG1 and detection of WIG1-associated proteins using liquid chromatography-tandem mass spectrometry. We also identified WIG1-binding motifs using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation analyses. Altogether, our data indicate that WIG1 governs the miRNA-dependent and the miRNA-independent recruitment of AGO2 to lower the stability of and suppress the translation of <I>ACOT7</I> mRNA.</P>
Song, Jennifer K.,Lee, Chang Hoon,Hwang, So-Min,Joo, Bo Sun,Lee, Sun Young,Jung, Jin Sup The Korean Society of Pharmacology 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.4
Human adipose-tissue-derived stromal cells (hADSCs) are abundant in adipose tissue and can differentiate into multi-lineage cell types, including adipocytes, osteoblasts, and chondrocytes. In order to define the optimal harvest site of adipose tissue harvest site, we solated hADSCs from different subcutaneous sites (upper abdomen, lower abdomen, and thigh) and compared their proliferation and potential to differentiate into adipocytes and osteoblasts. In addition, this study examined the effect of phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, on proliferation and differentiation of hADSCs to adipocytes or osteoblasts. hADSCs isolated from different subcutaneous depots have a similar growth rate. Fluorescence-activated cell sorting (FACS) analysis showed that the expression levels of CD73 and CD90 were similar between hADSCs from abdomen and thigh regions. However, the expression of CD105 was lower in hADSCs from the thigh than in those from the abdomen. Although the adipogenic differentiation potential of hADSCs from both tissue regions was similar, the osteogenic differentiation potential of hADSCs from the thigh was greater than that of hADSCs from the abdomen. Phorbol 12-myristate 13-acetate (PMA) treatment increased osteogenic differentiation and suppressed adipogenic differentiation of all hADSCs without affecting their growth rate and the treatment of Go6983, a general inhibitor of protein kinase C (PKC) blocked the PMA effect. These findings indicate that the thigh region might be a suitable source of hADSCs for bone regeneration and that the PKC signaling pathway may be involved in the adipogenic and osteogenic differentiation of hADSCs.
Ji-Su Lee,Jennifer K. Lee,Jae-Joon Lee,Seohyun Park,Sunyoon Jung,Hyun-Joo Lee,Jung-Heun Ha 한국식품영양과학회 2022 Journal of medicinal food Vol.25 No.6
High-fat diet (HFD) consumption is closely associated with an increased risk of metabolic syndromes (MetS), such as obesity, type 2 diabetes, and cardiovascular diseases (CVDs). Therefore, the consumption of alternative and functional fatty acids to replace saturated fatty acids and/or trans-fatty acids with polyunsaturated fatty acids has become an important dietary strategy for the prevention of MetS. Consumption of omega-3 fatty acids (n-3) reduces various physiological complications, including CVDs, nonalcoholic fatty liver disease, and insulin resistance, related to inflammatory responses. In this study, we investigated the partial replacement effects of HFD with beef tallow (BT) on dyslipidemia and endoplasmic reticulum (ER) stress in male db/db mice. The animals were grouped to one of four dietary intervention groups (n = 16 per group): (1) normal diet, (2) HFD, (3) HFD partially replaced with regular beef tallow (HFD+BT1), or (4) HFD partially replaced with beef tallow containing a relatively reduced omega-6 fatty acid (n-6)/n-3 ratio (HFD+BT2) than HFD+BT1. After 6 weeks of dietary intervention, 1 mg/kg of phosphate-buffered saline or tunicamycin (TM) was injected intraperitoneally. HFD+BT2 significantly suppressed the serum total cholesterol and non-high-density lipoprotein cholesterol levels more than HFD and HFD+BT1, and triglyceride levels in the epididymal adipose tissue (EAT) were remarkably decreased. Mice that received HFD+BT2 had elevated protein expressions of phospho-AMP-activated protein kinase (p-AMPK). Moreover, HFD+BT2 effectively inhibited ER stress in the liver and EAT. Consistent with our hypothesis, HFD+BT2 remarkably alleviated dyslipidemia and TM-inducible ER stress, while activating p-AMPK.
Predisposition to Cancer Caused by Genetic and Functional Defects of Mammalian <i>Atad5</i>
Bell, Daphne W.,Sikdar, Nilabja,Lee, Kyoo-young,Price, Jessica C.,Chatterjee, Raghunath,Park, Hee-Dong,Fox, Jennifer,Ishiai, Masamichi,Rudd, Meghan L.,Pollock, Lana M.,Fogoros, Sarah K.,Mohamed, Hassa Public Library of Science 2011 PLoS genetics Vol.7 No.8
<▼1><P>ATAD5, the human ortholog of yeast Elg1, plays a role in PCNA deubiquitination. Since PCNA modification is important to regulate DNA damage bypass, ATAD5 may be important for suppression of genomic instability in mammals <I>in vivo</I>. To test this hypothesis, we generated heterozygous (<I>Atad5<SUP>+/m</SUP></I>) mice that were haploinsuffficient for Atad5. <I>Atad5<SUP>+/m</SUP></I> mice displayed high levels of genomic instability <I>in vivo</I>, and <I>Atad5<SUP>+/m</SUP></I> mouse embryonic fibroblasts (MEFs) exhibited molecular defects in PCNA deubiquitination in response to DNA damage, as well as DNA damage hypersensitivity and high levels of genomic instability, apoptosis, and aneuploidy. Importantly, 90% of haploinsufficient <I>Atad5<SUP>+/m</SUP></I> mice developed tumors, including sarcomas, carcinomas, and adenocarcinomas, between 11 and 20 months of age. High levels of genomic alterations were evident in tumors that arose in the <I>Atad5<SUP>+/m</SUP></I> mice. Consistent with a role for <I>Atad5</I> in suppressing tumorigenesis, we also identified somatic mutations of <I>ATAD5</I> in 4.6% of sporadic human endometrial tumors, including two nonsense mutations that resulted in loss of proper ATAD5 function. Taken together, our findings indicate that loss-of-function mutations in mammalian <I>Atad5</I> are sufficient to cause genomic instability and tumorigenesis.</P></▼1><▼2><P><B>Author Summary</B></P><P>Genomic instability is a hallmark of tumorigenesis, suggesting that mutations in genes suppressing genomic instability contribute to this phenotype. In this study, we demonstrate for the first time that haploinsufficiency for Atad5, a protein that is important in stabilizing stalled DNA replication forks by regulating PCNA ubiquitination during DNA damage bypass, predisposes >90% of mice to tumorigenesis in multiple organs. In heterozygous <I>Atad5</I> mice, both somatic cells and the spontaneous tumors showed high levels of genomic instability. In a subset of sporadic human endometrial tumors, we identified heterozygous loss-of-function somatic mutations in the <I>ATAD5</I> gene, consistent with the role of mouse <I>Atad5</I> in suppressing tumorigenesis. Collectively, our findings suggest that <I>ATAD5</I> may be a novel tumor suppressor gene.</P></▼2>
A missense variant in NCF1 is associated with susceptibility to multiple autoimmune diseases
Zhao, Jian,Ma, Jianyang,Deng, Yun,Kelly, Jennifer A,Kim, Kwangwoo,Bang, So-Young,Lee, Hye-Soon,Li, Quan-Zhen,Wakeland, Edward K,Qiu, Rong,Liu, Mengru,Guo, Jianping,Li, Zhanguo,Tan, Wenfeng,Rasmussen, Nature Pub. Co 2017 Nature genetics Vol.49 No.3
<P>Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a strong genetic component characterized by autoantibody production and a type 1 interferon signatures. Here we report a missense variant (g.74779296G>A; p.Arg90His) in NCF1, encoding the p47phox subunit of the phagocyte NADPH oxidase (NOX2), as the putative underlying causal variant that drives a strong SLE-associated signal detected by the lmmunochip in the GTF2IRD1-GTF2I region at 7q11.23 with a complex genomic structure. We show that the p.Arg90His substitution, which is reported to cause reduced reactive oxygen species (ROS) production(2), predisposes to SLE (odds ratio (OR) = 3.47 in Asians (P-meta = 3.1 x 10(-104)), OR = 2.61 in European Americans, OR = 2.02 in African Americans) and other autoimmune diseases, including primary Sjogren's syndrome (OR = 2.45 in Chinese, OR = 2.35 in European Americans) and rheumatoid arthritis (OR = 1.65 in Koreans). Additionally, decreased and increased copy numbers of NCF1 predispose to and protect against SLE, respectively. Our data highlight the pathogenic role of reduced NOX2-derived ROS levels in autoimmune diseases.</P>
Tidal Dwarf Galaxies around a Post-Merger Galaxy, NGC 4922
Sheen, Yun-Kyeong,Jeong, Hyun-Jin,Yi, Suk-Young K,Ferreras, Ignacio,Lotz, Jennifer M.,Olsen, Knut A.G.,Dickinson, Mark,Barnes, Sydney,Lee, Young-Wook,Park, Jang-Hyun,Ree, Chang-H. 한국우주과학회 2009 한국우주과학회보 Vol.18 No.2
One possible channel for the formation of dwarf galaxies involves birth in the tidal tails of interacting galaxies. We report the detection of a bright UV tidal tail and several young tidal dwarf galaxy candidates in the post-merger galaxy NGC 4922 in the