Regulation of Hepatic Gluconeogenesis by an ER-Bound Transcription Factor, CREBH

Lee, Min-Woo,Chanda, Dipanjan,Yang, Jianqi,Oh, Hyunhee,Kim, Su Sung,Yoon, Young-Sil,Hong, Sungpyo,Park, Keun-Gyu,Lee, In-Kyu,Choi, Cheol Soo,Hanson, Richard W.,Choi, Hueng-Sik,Koo, Seung-Hoi Elsevier 2010 Cell metabolism Vol.11 No.4

<P><B>Summary</B></P><P>Endoplasmic reticulum (ER)-bound transcription factor families are shown to be involved in the control of various metabolic pathways. Here, we report a critical function of ER-bound transcription factor, CREBH, in the regulation of hepatic gluconeogenesis. Expression of CREBH is markedly induced by fasting or in the insulin-resistant state in rodents in a dexamethasone- and PGC-1α-dependent manner, which results in the accumulation of active nuclear form of CREBH (CREBH-N). Overexpression of constitutively active CREBH activates transcription of <I>PEPCK-C</I> or <I>G6Pase</I> by binding to its enhancer site that is distinct from the well-characterized CREB/CRTC2 regulatory sequences in vivo. Of interest, knockdown of CREBH in liver significantly reduces blood glucose levels without altering expression of genes involved in the ER stress signaling cascades in mice. These data suggest a crucial role for CREBH in the regulation of hepatic glucose metabolism in mammals.</P> <P><B>Highlights</B></P><P>► PGC-1α/GR activates CREBH expression under fasting or insulin-resistant conditions ► CREBH enhances hepatic gluconeogenesis via a CRTC2-dependent manner ► Depletion of CREBH in the liver ameliorates fasting hyperglycemia in diabetic mice</P>

Comprehensive Evaluation of the NeoBase 2 Non-derivatized MSMS Assay and Exploration of Analytes With Significantly Different Concentrations Between Term and Preterm Neonates

Lee Beomki,Heo Won Young,Kim Jee Ah,Lee Hyun-Seung,Hwang Narae,Park Hyung-Doo,Sung Se In,Chang Yun Sil,Park Won Soon,Lee Soo-Youn 대한진단검사의학회 2023 Annals of Laboratory Medicine Vol.43 No.2

Background: Despite the popularity of the NeoBase 2 Non-derivatized MSMS assay (PerkinElmer, Turku, Finland), there are no reports of its comprehensive evaluation, including the ability to distinguish transient tyrosinemia of the newborn (TTN) from tyrosinemia type 1 (TYR 1) using succinylacetone (SUAC). No newborn screening (NBS) cutoffs for preterm neonates in the Korean population have been suggested. We evaluated the NeoBase 2 assay and identified analytes requiring different cutoffs in preterm neonates. Methods: Residual NBS dried blood spot samples and proficiency testing (PT) materials of the Newborn Screening Quality Assurance Program and the Korean Association of External Quality Assessment Service were used. Precision, accuracy, limit of detection (LOD), lower limit of quantification (LLOQ), linearity, recovery, carryover, and performance of SUAC were evaluated. Cutoffs were determined, and analytes requiring different cutoffs in preterm neonates were investigated. Results: Mean CVs for within-run and between-day precision were within 15%. Accuracy analysis indicated high agreement with in-house derivatized assay results and results of other PT participants. All analytes demonstrated acceptable LOD, LLOQ, and linearity. Recoveries were acceptable, except for SUAC. Carryover was negligible. Cutoffs were established for all analytes; Tyr, adenosine, and C20:0-lysophosphatidylcholine required different cutoffs in preterm neonates. Differential diagnosis of TYR 1 and TTN was successful with simultaneous Tyr and SUAC measurement. Conclusions: The NeoBase 2 assay demonstrated satisfactory performance. The additional analytes provide a wider diagnostic coverage, and the simultaneous measurement of Tyr and SUAC is efficient in excluding TYR 1. The new cutoffs for preterm neonates may decrease false-positive rates, without compromising diagnostic sensitivity.

용접공들의 면역능에 관한 연구

이수일,조봉수,김영욱,고광욱,조원근,김영실,강수용,황인경,조병만,김돈균 大韓産業醫學會 1997 대한직업환경의학회지 Vol.9 No.1

The authors examined human immunity indicators such as CD4, CD8, Natural Killer(NK) cell, IgG, IgA, and IgM, and heavy metals such as Pb, Cr, Cd to evaluate the health hazard of welders. We selected total 126 male subjects, 60 welders who had more than 5 year working history as an exposure group, and 66 office workers and medical college students as a control group. This immunity evaluation approach is the first newly designed study that has never been tried in past studies on welder's heath evaluation. And the results were as follows. 1. Total lymphocyte count of peripheral blood was significantly higher in welder group, 2,615±650 ea/㎕ compared with 2,368±681 ea/㎕ in control group(p>0.05). 2. The proportion of CD4, CD8, NK cell in welder group was 37.5±9.4%, 24.0±8.8%, and 21.0±9.5%, respectively, and 35.5±6.5%, 25.0±6.9%, and 19.6±8.8% in control group. CD4 and NK cell were slightly higher, and CD8 was slightly lower in welder group. but there was no statistical significance between two groups(p≥0.05). 3. IgG, IgA, and IgM in welder group were 15.9㎎/㎗, 2.7㎎/㎗ and 1.5㎎/㎗, respectively, and 15.6㎎/㎗, 2.9㎎/㎗ and 1.7㎎/㎗ in control group. There was no statistical significance between two groups(p≥0.05). 4. Blood lead, cadmium and chromium concentrations were 4.2±1.8㎍/㎗, 0.4±0.38㎍/㎗, 1.2±0.6㎍/㎗ in welder group and 3.2±1.7㎍/㎗, 0.44±0.29㎍/㎗, 1.1±0.6㎍/㎗ in control group, respectively, and these value were within normal ranges.

Natural products used as a chemical library for protein–protein interaction targeted drug discovery

Jin, Xuemei,Lee, Kyungro,Kim, Nam Hee,Kim, Hyun Sil,Yook, Jong In,Choi, Jiwon,No, Kyoung Tai Elsevier 2018 Journal of molecular graphics & modelling Vol.79 No.-

<P><B>Abstract</B></P> <P>Protein–protein interactions (PPIs), which are essential for cellular processes, have been recognized as attractive therapeutic targets. Therefore, the construction of a PPI-focused chemical library is an inevitable necessity for future drug discovery. Natural products have been used as traditional medicines to treat human diseases for millennia; in addition, their molecular scaffolds have been used in diverse approved drugs and drug candidates. The recent discovery of the ability of natural products to inhibit PPIs led us to use natural products as a chemical library for PPI-targeted drug discovery. In this study, we collected natural products (NPDB) from non-commercial and in-house databases to analyze their similarities to small-molecule PPI inhibitors (iPPIs) and FDA-approved drugs by using eight molecular descriptors. Then, we evaluated the distribution of NPDB and iPPIs in the chemical space, represented by the molecular fingerprint and molecular scaffolds, to identify the promising scaffolds, which could interfere with PPIs. To investigate the ability of natural products to inhibit PPI targets, molecular docking was used. Then, we predicted a set of high-potency natural products by using the iPPI-likeness score based on a docking score-weighted model. These selected natural products showed high binding affinities to the PPI target, namely XIAP, which were validated in an <I>in vitro</I> experiment. In addition, the natural products with novel scaffolds might provide a promising starting point for further medicinal chemistry developments. Overall, our study shows the potency of natural products in targeting PPIs, which might help in the design of a PPI-focused chemical library for future drug discovery.</P> <P><B>Highlights</B></P> <P> <UL> <LI> This paper provides <I>in silico</I> drug discovery strategy to identify natural products capable to inhibit the protein–protein interactions. </LI> <LI> The predicted PPI inhibitor-like natural products were validated in an in vitro experiment. </LI> <LI> The XIAP inhibitor LENP0044 could be used as a potent template for further chemical optimization. </LI> <LI> Natural products can be used as potent candidates in the design of a PPI-focused chemical library for drug discovery. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

대학생의 노인복지에 대한 인식도

차병준,김무룡,김기열,차경미,김귀희,김현실,서인선,임상규,이순자,위광복,남철현 慶山大學校 保健福祉硏究所 1999 保健福祉硏究 Vol.2 No.-

The purpose of this study is to grasp the change of consciousness of young people in order to seek new approach of policy for aged era. 1,200 students attending collages and universities in three small or medium sized cities were inquired for 2 months, from October 1 to November 30, 1996. The result is as follows. 1. The characteristic of the respondents of this survey is that they include 72.1% of women, 40.4% of people aged between 20 to 21, and 49.1% of people who do not have any religion. Those who are from big cities and those who are form farming villages or fishing village occupy equally 40.2%, those who reside in that cities for a long period 49.0%, and those who live with their family 60.9%. 2. The family feature of the subject is that 31.5% of them are those whose father is the age of 55 and more than 55, 10% of them are those whose mothers age is so, 33.1% of them have 5 family members, 29.5% of them have the family income of 1,000,000 to 1,490,000 won, 83.9% of them are from middle class, 47.7% of them are the people whose grand parents have passed away, 70.4% of them live apart from their grand parents, and 60.9% of them are second child. 3. 64.0% of males, 70% of respondents who are aged over 24, 58.1% of respondents who are from rural communities, 62.4% of respondents who live in rural area, and 58.3% of respondents who live alone, prefer to live with grand parents, marked higher rate than other groups. The groups whose father and mother are the age of more than 55 marked higher rate of 55.9% and 58% each than any other groups(p<0.05). The groups whose family member is less than three, whose grand parents both have passed away in middle class, who live with their grand parents, and who are second children, give more positive answers than any other groups. 4. Those who are older, who are buddhists, who are from rural area or live in rural area, whose family is small, whose family income is small, who are from lower class and whose grand parents are still alive, shows preference to support their parents after marriage. 5. Females(89.4%), those who are from small or medium sized cities(89%), who live with their family(85.6%), whose father is the age of 55 and more than 55, whose mother is the age of 54 and less than 54, whose family member is 6, who are from middle class, whose grandparents are still alive and who are the eldest child in their family, give more response that they prefer to live apart from their children in their old age than any other groups. 6. What elderly people need most right now is past time(42.3%), and the respondents whose age is 20 to 21, who are buddhists, who are from middle sized cities and live alone, whose parents are the age of more than 55, who have small family income, who live with their grand parents and who are second children show higher level than any other groups. 7. 76.8% of respondents answer that they do not need their parent's fortune, marked still higher rate than the opposite answer. Those who are older, who are buddhists, who are from big cities, who reside in rural area, who live alone and have smaller family, who are in bad family economic conditions and who live with grand parents present higher rate of positive response. 8. 59.3% of respondents reply that they think about death from time to time, and those who are female, who are in the age of 20 to 21, who are christian, who live with their family, whose siblings or other family members offer their education expenses show higher rate than any other groups. 9. 92.3% of respondents answer that the budget for welfare facility for elderly people is very small. The younger the respondents are and the worse economic condition they have among those who live in big cities, the more answered that. 10. 50% of respondents think social security should provide for their old age, and 42.8% of them believe they themselves provide against it. The respondence that social security ought provide for it appeared more among those whose age are over 24, who are female, who reside in rural area, who are christian, who are in bad economic condition, and who ever used medical institutions in recent one month, marked higher level than other groups. 11. The adequate time of retirement is 59.97±5.60 for public officers, the highest and 59.28±6.35 for teachers, the next. 12. 35.2% of respondents reply that the adequate budget for the old age after their retirement at the age of 60 is 220 million won, showed the highest level of respondence. 13. The factors which affect on the old people in the charged welfare facilities are sex(p<0.01), the type of housing(p<0.05) and whole family income(p<0.05). 14. The factors which affect on remarriage are sex(p<0.05) and religion(p<0.05). For varying old population and expanded welfare service for them, government and relevant authority should give more attention to secure the budget, establish effective plans to expand various program and the facilities for elderly people in order that elderly people spend the rest of life time more happily and more fruitfully. To do that, each college and university should open Health courses, and educate and inform about health and welfare.

노인에서 정서 인식의 저하

이경욱,채정호,최인철,이해국,권용실,이정태 大韓神經精神醫學會 2005 신경정신의학 Vol.44 No.2

Objectives : The purpose of this study was to investigate whether elderly and young adults differ in their recognition of facial expressions of emotion. Methods : A total of 120 (elderly group 53, young group 67) subjects participated in this study. Korean facial expressions of emotion including happiness, sadness, fear, anger, disgust, surprise and neutral were used as stimuli for facial affect recognition test. Computerized facial affect recognition test that consists of facial affect discrimination test and facial affect intensity test was performed. Results : For facial affect discrimination test, there was a significant difference between two groups (F==3.986, P<.01) after controlling the effect of education. Elderly participants showed significantly less correct recognition rate with sadness, anger and disgust (p<.05). For facial affect intensity test, there was no significant difference between the groups in recognition of emotional intensity. Chi-square test or t-test was done according to the clinical variables. Multivariate analysis of covahance was done to test group differences of correct recognition rate and emotional intensity. Conclusion : This is the first report of differential decrease of facial affect recognition in elderly using Korean facial expressions. This study suggests that the decrement of facial affect recognition maye be a part of normal aging process.

시스템 다이내믹스를 이용한 간호단위별 간호인력 산정에 관한 연구

김문실,성영희,권경자,김도형,김정아,신덕신,유인자,유재국,이현숙 병원간호사회 2006 임상간호연구 Vol.11 No.2

Purpose: The purpose of the study was to forecast manpower by building the nursing manpower-staffing model(surgical-medical nursing unite). Method: The system dynamics approach was adapted to build a simulation model for calculating medical-surgical nursing manpower-staffing. The model was built up on Venism 5.0b DSS. Result: The results in the basic circumstance are in following. The level of nursing service quality, patientsatisfaction, and nurse job satisfaction maintains higher at medical-surgical nursing unit of the tertiary hospitals with the ratio of bed to nurse 2.5:1-3.0:1 than at any other situations. The level of nursing service quality, patient satisfaction, and nurse job satisfaction maintains higher at madical nursing unit of the secontary hospotals with the ratio of bed to nurse 3.0:1 and at surgical nursing unit of the secondary hospitals with the ratio of bed to nurse 3.0:1-3.5:1 than at any other situations in the fundamental from. The results in the simulation circumstance are in following, As author raises the operating rate of bed into 95-100%, and cut skilled nursing staff down, the level of nursing-service quality, patient satisfaction, and nurse job satisfaction drops slightly. Conclusion: In terms of economic efficiency on tertiary hospotals, the ratio of bed to nurse for the best reasonable medical-surgical nursing manpower-staffing is 3.0:1. In terms of economic efficiency on secondary hospitals, the ratio of bed to nurse for the best reasonable medical nursing manpower-staffing is 3.0:1 and surgical nursing manpower-staffing is 3.5:1

남성화를 보이는 여성에서 발견된 난소의 Steroid Cell Tumor 1예

조인호,정대훈,박영미,서영진,손영실,정철회,강영미,정수전,김영남,이경복,성문수,김기태 인제대학교 2006 仁濟醫學 Vol.27 No.-

Steroid cell tumor is a rare ovarian sex cord-stromal tumor which accounts for 0.1% of all ovarian tumors. Until now, only 4 cases have been reported in domestic literatures. Steroid cell tumor often secrets testosterone and presents virilization in adult women or precocious puberty in children. Treatment is often performed by surgical removal, adjuvant chemotherapy and radiation, but completely accepted treatment was not existed. We experienced a case of steroid cell tumor, which was manifested by typical virilization in a 43-year old patient, who was previously performed hysterectomy and unilateral oophorectomy. So, we present with a brief review of the literatures.

p63 Expression in the Gerbil Hippocampus Following Transient Ischemia and Effect of Ischemic Preconditioning on p63 Expression in the Ischemic Hippocampus.

Lee, Jae-Chul,Cho, Geum-Sil,Kim, In Hye,Park, Joon Ha,Cho, Jeong-Hwi,Ahn, Ji Hyeon,Bae, Eun Joo,Ahn, Ji Yun,Park, Chan Woo,Cho, Jun Hwi,Kim, Young-Myeong,Won, Moo-Ho,Lee, Hui Young Kluwer Academic/Plenum Publishers 2015 Neurochem Res Vol.40 No.5

<P>p63 is a transcription factor of p53 gene family, which are involved in development, differentiation and cell response to stress; however, its roles in ischemic preconditioning (IPC) in the brain are not clear. In the present study, we investigated the effect of IPC on p63 immunoreactivity caused by 5 min of transient cerebral ischemia in gerbils. IPC was induced by subjecting the gerbils to 2 min of transie ischemia 1 day prior to 5 min of transient ischemia. The animals were randomly assigned to four groups (sham-operated-group, ischemia-operated-group, IPC plus (+)-sham-operated-group and IPC + ischemia-operated-group). The number of viable neurons in the stratum pyramidale of the hippocampal CA1 region (CA1) was significantly increased by IPC + ischemia-operated-group compared with that in the ischemia-operated-group 5 days after ischemic insult. We found that strong p63 immunoreactivity was detected in the CA1 pyramidal neurons in the sham-operated-group, and the immunoreactivity was decreased with time after ischemia-reperfusion. In addition, strong p63 immunoreactivity was newly expressed in microglial cells of the CA1 region from 2 days after ischemia-reperfusion. In all the IPC + sham-operated-groups, p63 immunoreactivity in the CA1 pyramidal neurons was similar to that in the sham-operated-group, and the immunoreactivity was well maintained in the IPC + ischemia-operated-groups after cerebral ischemia. In brief, our present findings show that IPC dramatically protected the reduction of p63 immunoreactivity in the pyramidal neurons of the CA1 region after ischemia-reperfusion, and this result suggests that the expression of p63 may be necessary for neurons to survive after transient cerebral ischemia.</P>

2003년 국내 중증급성호흡기증후군 진료 현황 및 문제점 분석

이진수,김은실,정문현,백제중,정선화,안주희,최영화,이선희,고철우,김성범,김민자,박승철,기현균,송재훈,최상호,김양수,이상오,조용균,박영훈,정숙인,김연숙,이흥범,손창희,장성희,정희진,김우주 대한감염학회 2004 감염과 화학요법 Vol.36 No.3

목적 : 2002년 말 중국에서 SARS가 발생한 이후 국내에서도 2003년 10월까지 총 3명의 추정환자, 17명의 의심환자가 보고되었다. 향후 추가적인 SARS의 유행이 우려되는 상황에서, 그간의 SARS 환자 진료에 있어서의 실질적인 준비사항, 진료 현황 등에 대한 조사를 통해 문제점을 파악하여, 향후 더 나은 대비가 될 수 있도록 개선점을 제시하고자 하였다. 재료 및 방법 : SARS로 의심되는 환자를 진료 경험이 있는 병원의료진을 대상으로 2003년 10월에 설문조사를 실시하였다. 설문에는 SARS 환자 진료 시의 실질적인 조치, 진료 현황, 병실, 응급실 및 외래에서의 격리 시설과 준비사항, 보건당국의 관리와 지원에 관한 사항을 포함하였다. 결과 : 대상이 되는 22개 병원 중 17개(17/22, 77.2%) 병원이 설문에 응하였다. SARS 환자를 위한 격리실은 응급실, 외래, 일반병실 및 중환자실에서 각각 9개(9/17, 52.9%), 5개(5/17, 29.4%), 15개(15/16, 93.7%), 4개(4/16, 25%) 병원에서 음압처리가 되어있지 않은 일인실 혹은 다인실이 사용되었고, 1개(1/16, 6.3%) 병원에서만 일반병실에서 음압격리실이 운영되었다. 입원환자의 진찰 시 개인보호구의 착용은 거의 모든 의료기관에서 이루어졌다. 보건당국에서 SARS지정병원의 시설 등을 사전에 확인한 곳은 1곳(1/12, 8.3%)이였고, 14개 병원(14/15, 93.3%)에서는 보건당국에 의뢰한 검사결과를 통하 받지 못하였다. 결론 : 의료기관에서 SARS 환자용 격리실뿐만 아니라 기존의 격리실 설비 등이 미흡하였으며, 특히 중환자실 및 외래의 준비가 더욱 부족하였다. 보건당국의 의료기관에 대한 종합적인 지원이 부족하였고, 병원과의 원활한 연계가 잘 이루어지지 않았다. SARS 만이 아닌 격리를 필요로 하는 질환의 적절한 진료를 위해 향후 병원 시설의 정비와 정부차원에서의 보다 구체적이고 실질적인 대책마련이 필요하다. Background : There was an worldwide outbreak of the Severe Acute Respiratory Syndrome (SARS) originated from China in late 2002. During that period three cases of suspected SARS and 17 cases of probable SARS were reported in Korea. With the concerns about the reemergence of SARS-coV transmission, it is important to be prepared for any possibility. So, this study is aimed to analysis the past measures in managing SARS and propose the amendatory plans to improve the preparedness. Materials & Methods : Questionnaires were collected among clinicians with any experience in managing the probable or suspected SARS cases in Oct. 2003. 17 out of 22 hospitals responded to the questionnaire. The contents in the questionnaire were practical activities, personal equipments, response plans, isolation facilities in emergency centers, outpatient clinics, general wards and intensive care units, and relationship with the public health department. Results : The dedicated isolation rooms in emergency centers, outpatient clinics, general wards, and intensive care units were prepared in 9 (9/17, 52.9%), 5 (5/17, 29.4%), 15 (15/16, 93.7%), and 4 (4/16, 25.0%) hospitals, respectively. Except for one hospital that newly made negative pressure room for SARS, single or multi-bed rooms without airborne infection control were used in all the other hospitals. The personal precaution principles were kept quite well in general wards. Before the designation of SARS hospital by the public health department prior evalution to see if the hospital was suitable for managing SARS was conducted in only 1 (1/12, 8.3%) hospital. The results of laboratory diagnosis were reported back in 1 (1/15, 6.6%) hospital. Conclusions : The isolation facilities which can control airborne infection were almost deficient not only for SARS but also for other respiratory transmissible diseases. For the infection control of transmissible diseases including SARS, more investment is needed on medical facilities and comprehensive support from the public health department required.