뇌혈관 조영에서 320-MDCT와 64-MDCT의 영상과 방사선량 비교

한아람(Aram Han),정봉재(Bongjae Jung),박지군(Jikoon Park),강상식(Sangsik Kang),최일홍(Ilhong Choi),정형진(Hyungjin Jung),노시철(Sicheol Noh) 한국방사선학회 2014 한국방사선학회 학술대회 논문집 Vol.2014 No.춘계

본 연구에서는 뇌혈관 조영CT(CTA)에 있어 320-MDCT의 Volume scan과 64-MDCT의 Helical scan의 영상과 방사선량을 비교하여 320-MDCT의 유용성을 평가하였다. 동일 증상으로 두 가지 장비를 이용하여 뇌혈관 CTA를 시행한 환자 21명의 검사 결과를 이용하여 평가하였다. 비교 결과 320-MDCT의 영상이 64-MDCT영상에 비해 대조도 및 선예도가 높고 혈관 부근에서 Noise도 적은 것을 확인 할 수 있었으며, 유효선량도 64-MDCT 보다320-MDCT가 약 15% 정도 낮게 측정되었다. In this study, the image quality and effective dose were analysed and compared of 320-MDCT Volume scan and 64-MDCT Helical scan in cerebrovascular CT angiography. Using these comparison, we evaluated the usefulness of 320-MDCT. We analysed the 21 patient’s cerebrovascular CTA results who examined using both devices to the same symptoms. With the results of comparison, the images of 320-MDCT represented higher contrast and sharpness and less noise in the vicinity of blood vessels than the images of 64-MDCT. Moreover, the effective dose of 320-MDCT was about 15% lower than 64-MDCT.

반려동물에 대한 태도와 성인의 주관적 행복감에 관한 연구

한아람 ( Aram Han ) 아시아문화학술원 2018 인문사회 21 Vol.9 No.4

본 연구는 국내 반려동물 산업에 대한 관심이 증가되는 시점에서 대전과 청주지역에 거주하는 반려동물을 소유한 성인을 대상으로 반려동물에 대한 태도가 성인의 주관적 행복감에 미치는 영향을 규명하는데 있다. 연구결과는 다음과 같다. 첫째, 반려동물에 대한 태도는 성인의 성별, 연령별, 반려동물의 소유 수, 소유 기간에 따라 유의한 차이가 있음을 확인할 수 있었다. 둘째, 성인의 주관적 행복감은 성별, 연령별, 반려동물의 소유 기간에 따라 유의한 차이가 있었다. 특히, 10년 이상의 반려동물을 소유한 집단에서 주관적 행복감이 가장 낮은 것을 확인할 수 있었다. 셋째, 반려동물에 대한 태도는 성인의 주관적 행복감 전체 변량의 9% 정도 유의한 영향을 주고 있음을 확인할 수 있었다. 또한, 성인의 주관적 행복감에 반려동물 소유에 대한 즐거움이 가장 큰 긍정적인 영향을 주었고, 반면에 가정에서의 반려동물 사육은 부정적인 영향을 주는 것을 확인할 수 있었다. 본 연구결과는 반려동물과의 상호작용은 성인의 반려동물에 대한 태도와 주관적 행복감에 대체로 긍정적인 영향을 미치지만, 부정적인 영향을 주는 요인에 대한 대책을 통해 반려동물을 소유한 성인의 주관적 행복감을 향상시키기 위한 노력이 필요함을 시사한다. With the increased interest in the domestic companion animal industry, the objective of this study is to examine the effects of attitude to companion animals on the adults’ subjective well-being, targeting the adults with companion animals in Daejeon and Cheongju region. The results of this study are as follows. First, The attitude to companion animals showed significant differences in accordance with sex, age, the number of companion animal, and the period of possession. Second, the adults’ subjective well-being showed significant differences in accordance with sex, age, and the period of possession. Especially, the group of possessing companion animals for ten years or up showed the lowest subjective well-being. Third, the attitude to companion animals had significant effects on the 9% of the whole subjective well-being variable. Also, the pleasure of possessing companion animals had the most positive effects on the adults’ subjective well-being while the breeding of companion animals at home had negative effects on it. The results of this study imply that the interaction with companion animals would have mostly positive effects on the adults’ attitude to companion animals and subjective well-being, and it would be still needed to put efforts to improve the subjective well-being of adults who possess companion animals by establishing the measures for the factors having negative effects.

Oncogene-induced senescence mediated by c-Myc requires USP10 dependent deubiquitination and stabilization of p14ARF

Ko, Aram,Han, Su Yeon,Choi, Chel Hun,Cho, Hanbyoul,Lee, Min-Sik,Kim, Soo-Youl,Song, Joon Seon,Hong, Kyeong-Man,Lee, Han-Woong,Hewitt, Stephen M.,Chung, Joon-Yong,Song, Jaewhan Nature Publishing Group UK 2018 Cell death and differentiation Vol.25 No.6

<P>Oncogene-induced senescence (OIS) is a critical tumor-suppressor mechanism, which prevents hyper-proliferation and transformation of cells. c-Myc promotes OIS through the transcriptional activation of p14ARF followed by p53 activation. Although the oncogene-mediated transcriptional regulation of p14ARF has been well addressed, the post-translational modification of p14ARF regulated by oncogenic stress has yet to be investigated. Here, we found that c-Myc increased p14ARF protein stability by inducing the transcription of ubiquitin-specific protease 10 (USP10). USP10, in turn, mediated the deubiquitination of p14ARF, preventing its proteasome-dependent degradation. USP10-null mouse embryonic fibroblasts and human primary cells depleted of USP10 bypassed c-Myc-induced senescence via the destabilization of p14ARF, and these cells displayed accelerated hyper-proliferation and transformation. Clinically the c-Myc-USP10-p14ARF axis was disrupted in non-small cell lung cancer patients, resulting in significantly worse overall survival. Our studies indicate that USP10 induced by c-Myc has a crucial role in OIS by maintaining the stability of key tumor suppressor p14ARF.</P>

Alterations in the brainstem volume of patients with major depressive disorder and their relationship with antidepressant treatment

Han, Kyu-Man,Kim, Daseul,Sim, Youngbo,Kang, June,Kim, Aram,Won, Eunsoo,Tae, Woo-Suk,Ham, Byung-Joo Elsevier 2017 Journal of affective disorders Vol.208 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Morphologic changes of the brainstem in major depressive disorder (MDD) have rarely been reported in neuroimaging studies, even though, monoaminergic neurotransmitters are synthesized in several brainstem regions. We aimed to investigate volume changes in each region of the brainstem and their association with antidepressant use or the remission status of MDD.</P> <P><B>Methods</B></P> <P>A total of 126 patients with MDD and 101 healthy controls underwent T1-weighted structural magnetic resonance imaging. We analyzed volumes of each brainstem region, including the medulla oblongata, pons, midbrain, and superior cerebellar peduncle, and the volume of the whole brainstem using the FreeSurfer.</P> <P><B>Results</B></P> <P>The patients with MDD had significantly greater midbrain volumes (<I>P</I>=0.013) compared to healthy controls. In particular, drug-naïve patients with MDD had significantly greater brainstem volumes compared to healthy controls (<I>P</I>=0.007), while no significant findings were observed between the antidepressant treatment group and healthy controls. The remitted patient group had reduced pons (<I>P</I>=0.002) and midbrain (<I>P</I>=0.005) volumes compared to healthy controls, while the non-remitted MDD patient group had significantly greater midbrain volumes compared to the healthy controls (<I>P</I>=0.017).</P> <P><B>Limitations</B></P> <P>We could not distinguish gray versus white matter volumes changes in our analysis.</P> <P><B>Conclusions</B></P> <P>We observed that the midbrain is enlarged in patients with a current depressive episode, who are not undergoing antidepressant treatment. This volume then returns to normal after antidepressant treatment, and is even reduced, when the patient is in remission. Further studies are needed to confirm our observations.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We investigate the volume changes of brainstem regions in MDD using the FreeSurfer. </LI> <LI> Medulla oblongata, pons, midbrain, and superior cerebellar peduncle were included. </LI> <LI> Drug-naïve patients had greater brainstem volumes compared to healthy controls. </LI> <LI> Remitted patients had reduced pons and midbrain volumes compared to healthy controls. </LI> </UL> </P>

Molecular Chaperone HSP90 Is Necessary to Prevent Cellular Senescence via Lysosomal Degradation of p14ARF

Han, Su Yeon,Ko, Aram,Kitano, Haruhisa,Choi, Chel Hun,Lee, Min-Sik,Seo, Jinho,Fukuoka, Junya,Kim, Soo-Youl,Hewitt, Stephen M.,Chung, Joon-Yong,Song, Jaewhan American Association for Cancer Research 2017 Cancer research Vol.77 No.2

<P>In elucidating how the tumor suppressor p14ARF is degraded, this study has implications for prognosis and treatment or p14ARF-expressing lung cancers.</P><P>The tumor suppressor function of p14ARF is regulated at a posttranslational level via mechanisms yet to be fully understood. Here, we report the identification of an unconventional p14ARF degradation pathway induced by the chaperone HSP90 in association with the E3 ubiquitin ligase C-terminus of HSP70-interacting protein (CHIP). The ternary complex of HSP90, CHIP, and p14ARF was required to induce the lysosomal degradation of p14ARF by an ubiquitination-independent but LAMP2A-dependent mechanism. Depletion of HSP90 or CHIP induced p14ARF-dependent senescence in human fibroblasts. Premature senescence observed in cells genetically deficient in CHIP was rescued in cells that were doubly deficient in CHIP and p14ARF. Notably, non–small cell lung cancer cells (NSCLC) positive for p14ARF were sensitive to treatment with the HSP90 inhibitor geldanamycin. Furthermore, overexpression of HSP90 and CHIP with a concomitant loss of p14ARF correlated with poor prognosis in patients with NSCLC. Our findings identify a relationship between p14ARF and its chaperones that suggest new therapeutic strategies in cancers that overexpress HSP90. <I>Cancer Res; 77(2); 343–54. ©2016 AACR</I>.</P>

Dynamics of ARF regulation that control senescence and cancer

( Aram Ko ),( Su Yeon Han ),( Jaewhan Song ) 생화학분자생물학회 2016 BMB Reports Vol.49 No.11

ARF is an alternative reading frame product of the INK4a/ARF locus, inactivated in numerous human cancers. ARF is a key regulator of cellular senescence, an irreversible cell growth arrest that suppresses tumor cell growth. It functions by sequestering MDM2 (a p53 E3 ligase) in the nucleolus, thus activating p53. Besides MDM2, ARF has numerous other interacting partners that induce either cellular senescence or apoptosis in a p53-independent manner. This further complicates the dynamics of the ARF network. Expression of ARF is frequently disrupted in human cancers, mainly due to epigenetic and transcriptional regulation. Vigorous studies on various transcription factors that either positively or negatively regulate ARF transcription have been carried out. However, recent focus on posttranslational modifications, particularly ubiquitination, indicates wider dynamic controls of ARF than previously known. In this review, we discuss the role and dynamic regulation of ARF in senescence and cancer. [BMB Reports 2016; 49(11): 598-606]

Atypical cystic hepatocellular carcinoma in a Himalayan cat

Aram Jang,Changhoon Han,Hyejin Jung,Jiyeon Lee,Jihun Park,Sangwoo Bae,Nahyun Kim,Jaehoon Lee 한국예방수의학회 2019 예방수의학회지 Vol.43 No.4

A liver mass was incidentally revealed in a 10-year-old male neutered Himalayan cat on radiographic examination conducted in a local animal hospital. The abdominal distention had worsened over the past five months, along with intermittent vomiting and nausea for two weeks. Serum chemistry was unremarkable, except for elevated alkaline phosphatase and gamma-glutamyl transferase levels. Radiography revealed a round-shaped soft mass in the cranial abdomen. Abdominal ultrasonography showed a well defined, massive, fluid-filled cyst with multiple lobes, and heterogeneous echogenicity in the pancreas. Computed tomography examination revealed hypoplasia of the left lobes of the liver, but the vascular changes and enhancement of the mass were not observed on contrast computed tomography images. The herniation of the abdominal fat through the diaphragm was incidentally observed on sonography and computed tomography scan. The patient was tentatively diagnosed with pancreatic cyst. The laparotomy revealed that the origin was not related to the pancreas, but was suspended from the liver. The mass was multilobular and filled with approximately 120 ml of fluid containing a few white blood cells. The patient recovered from anesthesia, but showed postoperative respiratory depression and died of cardiac arrest 15 hours later. Histopathologically, the mass was definitively diagnosed to be hepatic cellular carcinoma.

The effects of <i>5-HTTLPR</i> and <i>BDNF Val66Met</i> polymorphisms on neurostructural changes in major depressive disorder

Han, Kyu-Man,Choi, Sunyoung,Kim, Aram,Kang, June,Won, Eunsoo,Tae, Woo-Suk,Kim, Yong-Ku,Lee, Min-Soo,Ham, Byung-Joo Elsevier 2018 Psychiatry research, Neuroimaging Vol.273 No.-

<P><B>Abstract</B></P> <P>The serotonin-transporter-linked polymorphic region (<I>5-HTTLPR</I>) and brain-derived neurotrophic factor (<I>BDNF</I>) <I>Val66Met</I> polymorphism have been implicated in the pathophysiology of major depressive disorder (MDD). We aimed to investigate the effects of genetic variants of the <I>5-HTTLPR</I> and <I>BDNF Val66Met</I> polymorphisms and their interactions with MDD on cortical volume and white matter integrity. Ninety-five patients with MDD and 65 healthy participants aged 20–65 years were recruited. The subjects were genotyped for the <I>5-HTTLPR</I> and <I>BDNF Val66Met</I> polymorphisms and scanned with T1-weighted and diffusion tensor imaging. The gray matter volumes of 24 gyri in the prefrontal and anterior cingulate cortices and the fractional anisotropy values of nine white matter tracts in both hemispheres were determined. In the pooled sample of subjects from both groups, <I>5-HTTLPR</I> L-allele carriers had significantly decreased cortical volume in the right anterior midcingulate gyrus compared to S-allele homozygotes. A significant effect of the interaction of the <I>BDNF Val66Met</I> polymorphism and MDD on the fractional anisotropy values of the right uncinate fasciculus was observed. Our results suggested that these genetic polymorphisms play important roles in the neurostructural changes of emotion-processing regions in subjects with MDD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> 95 patients with major depressive disorder (MDD) and 65 controls recruited. </LI> <LI> Subjects genotyped for <I>5-HTTLPR</I> and <I>BDNF Val66</I>Met polymorphism. </LI> <LI> <I>5-HTTLPR</I> associated with volume of right anterior midcingulate gyrus. </LI> <LI> Interactive effect of <I>BDNF Val66Met</I> and MDD on right uncinate fasciculus integrity. </LI> <LI> Interactive effect of both genotypes on left transverse frontopolar gyrus volume. </LI> </UL> </P>

통합보고: 노보 노르디스크 사례 연구

홍아람 ( Aram Hong ),한종수 ( Jongsoo Han ) 한국회계학회 2016 회계저널 Vol.25 No.4

최근 기업 가치 산정시 비재무적 요소가 중요하게 인식되고 있다. 이에 따라 투자자들을 비롯한 이해관계자들은 비재무 정보를 기업이 책임감 있게 공개하도록 요구하기 시작하였다. 2010년 발족된 국제통합보고위원회(IIRC)는 2013년 <IR>프레임워크를 발표하여 국제적으로 통합보고의 개념을 체계화하였다. 이에 따르면 통합보고서는 비재무 정보 포함하여 기업의 가치창출 프로세스를 설명하는 것이다. 가치창출 프로세스는 기업이 제품 및 서비스를 생산하기 위해 사용한 자본이 결과적으로 어떻게 변형되는지의 과정을 의미한다. 여기서 자본이란 재무 자본, 제조 자본, 지적 자본, 인적 자본, 사회·관계 자본, 자연 자본의 여섯 가지 형태로 구분된다. 그러나 국내에서는 아직까지 표본이라고 할 수 있는 통합보고서를 작성하는 기업이 없다. 따라서 본 논문은 노보 노르디스크의 최근 보고서 사례를 분석하고 시사점을 제시하였다. 노보 노르디스크는 <IR>프레임워크가 발표되기 오래전부터자체적인 통합보고 형식을 갖추어 보고서를 발간해온 통합보고의 표본이라 할 수 있는 기업이다. 일관된 형태의 정보 공개를 위해서는 국제적인 통합보고 논의와 더불어 개별 국가의 통합보고 제도화 노력이 진행되어야 한다. 이에 국내 기업의 인식 변화 및 국내 공시제도의 개정이 진지하게 논의될 필요가 있다. In corporate valuation, the importance of non-financial information has greatly increased in recent years. As a result, investors and other stakeholders have started to request companies to responsibly disclose such non-financial information. This is precisely the reason that integrated reporting has started to appear in the mainstream. The International Integrated Reporting Committee (IIRC), established in 2010, has published the International <IR> Framework (hereafter, the Framework) in 2013, which codified the concept for the first time in the world. According to the Framework, integrated reporting is the means by which an organization communicates its value creation process. The value creation process explains mechanisms of how capitals are transformed into value over the short, medium and long term period. The capital referred in the Framework consists of six different categories: financial, manufactured, intellectual, human, social and relationship, and natural capital. To provide a better understanding of integrated reporting, this paper introduces Novo Nordisk’s recent report, which has achieved many awards and received praises from many academic articles as one of the best integrated reporting practices. While existing financial reports usually identify values in terms of financial capital, Novo Nordisk’s report has attempted to present how diverse categories of capital create impact on society by reporting non-financial performances such as ‘new patent families (intellectual capital),’ ‘least developed countries where they sells insulin according to the differential pricing policy (social and relationship capital).’ Through the report, Novo Nordisk was able to inform meaningful information as well as financial information of stakeholders . Currently, each jurisdiction is developing their own version of integrated reporting standards: notable examples include the Directive on disclosure of non-financial and diversity information of EU, the Integrated Reporting Committee of South Africa, and the Sustainability Accounting Standards Board (SASB) of the United States. More specifically, SASB has produced accounting standards in the non-financial dimensions with ten sectors, and aimed for mandatory disclosures. Compared to Novo Nordisk’s report on the non-financial performances, SASB’s Standard in Biotechnology includes more specific material issues of the industry. This trend of developing integrated reporting in each jurisdiction is expected to affect Korea as well in the near future. However, the current integrated reporting practice, particularly in Korea, seems to need significant improvement so that it can provide meaningful information regarding corporate valuation. For instance, the sustainability report of SK Chemical, a Korean company which is in a similar industry to Novo Nordisk, does not seem to fully satisfy the information user``s requests on non-financial information. We should start in-depth discussions on the integrated reporting in Korea. The materiality process (of selecting reporting contents) and the assurance process should be discussed by the accounting professionals and regulators who set up, implement and oversee the accounting standards, relevant laws, and its processes. While it is important to maintain universality based on foreign case studies, it is equally important to seek independent efforts to find reporting items that fit domestic needs. Efforts of corporations, continuous research and publications by professionals, followed by codification of relevant concepts should precede legislation in Korea. Along this line, corporations should recognize the need for better communication. As can be seen in Novo Nordisk``s recent report, corporations should recognize changes in the external environment and be ready to the changes with a corresponding strategy. In Korea, financial statements have traditionally been treated as more or less the same as financial reports. Stakeholders focus only on how to calculate the numbers and how to satisfy the minimum legal standards involved. This type of passive communication pushes shareholders and investors away from the information they need. For example, there were some notable legislative changes last year, which required the disclosure of registered directors’ compensation amount. However, most information users want to know whether the payment was made based on the directors’ performance or what is the rationale behind the compensation, rather than simply how much they earn. Such information can be of importance in analyzing the value of firms and deciding whether or not to make investments on those firms. In this regard, corporations should approach the ESG dimensions (or the six capitals of the Framework) in a strategic manner instead of focusing on simple collection of data. Corporations should focus on recognizing its fundamental competitive advantage and analyzing the information needs of stakeholders, rather than dwelling on what disclosure should be made in its integrated reports. Lastly, whether it be financial, manufacturing, intellectual, human, social and relationship, and natural capitals, or ESG, perceptional changes are necessary especially to areas that have previously been neglected in capital markets, beyond the boundary of reporting. Capital markets can only last when it reflects values created in the industry and society without distortion.

Acceleration of Gastric Tumorigenesis Through MKRN1-Mediated Posttranslational Regulation of p14ARF

Ko, Aram,Shin, Ji-Young,Seo, Jinho,Lee, Kang-Duck,Lee, Eun-Woo,Lee, Min-Sik,Lee, Han-Woong,Choi, Il-Ju,Jeong, Jin Sook,Chun, Kyung-Hee,Song, Jaewhan U.S. Dept. of Health, Education, and Welfare, Publ 2012 Journal of the National Cancer Institute Vol.104 No.21

<P><B>Background</B></P><P>We investigated whether Makorin ring finger protein 1 (MKRN1), an E3 ligase, affects p14ARF-associated cellular senescence and tumorigenesis by posttranslational modification in gastric tumorigenesis.</P><P><B>Methods</B></P><P>A link between MKRN1 and ARF was examined in MKRN1 null mouse embryonic fibroblasts (MEFs) and in human fibroblasts and gastric cancer cells by silencing MKRN1 using small interfering RNA (siRNA) and short hairpin RNA (shRNA). Ubiquitination and proteasomal degradation assays were used to assess p14ARF degradation associated with MKRN1. MKRN1 and p14ARF expression levels were analyzed with immunohistochemistry in malignant and normal tissues from gastric cancer patients and with χ<SUP>2</SUP> tests. The tumor growth of gastric cancer cells stably expressing MKRN1 shRNA, p14ARF shRNA, or both was examined in mouse xenograft models (n = 4–6) and analyzed with unpaired <I>t</I> tests. All statistical tests were two-sided.</P><P><B>Results</B></P><P>MKRN1 knockout MEFs exhibited premature senescence and growth retardation with increased p19ARF protein expression. Similar results were obtained for human fibroblasts or gastric cancer cell lines by MKRN1 knockdown. Biochemical analyses confirmed that MKRN1 targets p14ARF for ubiquitination and subsequent proteasome-dependent degradation. A statistically significant association was shown between MKRN1 overexpression and p14ARF underexpression (<I>P</I> = .016). Xenograft analyses using p53-functional AGS or -dysfunctional SNU601 cells displayed statistically significant tumor growth retardation by silencing MKRN1, which was reversed under depletion of p14ARF (AGS cells, MKRN1 knockdown tumors vs MKRN1 and p14ARF knockdown tumors: 164.6 vs 464.8mm<SUP>3</SUP>, difference = 300.2mm<SUP>3</SUP>, 95% CI = 189.1 to 411.3mm<SUP>3</SUP>, <I>P</I> < .001).</P><P><B>Conclusions</B></P><P>We demonstrated that MKRN1 functions as a novel E3 ligase of p14ARF and that it potentially regulates cellular senescence and tumorigenesis in gastric cancer.</P>