Loop와 HPLC Purification 방법보다 더 높은 비방사능을 보여주는 카트리지 Methylation과 Purification을 이용한 손쉬운 [ ¹¹C]PIB 합성

이용석,조용현,이홍재,이윤상,정재민,Lee, Yong-Seok,Cho, Yong-Hyun,Lee, Hong-Jae,Lee, Yun-Sang,Jeong, Jae Min 대한핵의학기술학회 2018 핵의학 기술 Vol.22 No.2

$[^{11}C]PIB$는 베타아밀로이드($A{\beta}\;plague$)라는 변성 단백질에 결합하여 뇌의 기능과 기억력을 서서히 감퇴시키는 비가역적인 질환인 치매를 조기에 감별할 수 있는 대표적인 방사성의약품이다. 지금까지 많은 실험실에서 $[^{11}C]PIB$는 자동화합성장치에서 $[^{11}C]methyl\;iodide$나 $[^{11}C]methyl\;triflate$를 만든 다음 loop나 vial 방법을 사용하여 methylation을 한 다음 HPLC로 정제를 하는 것이다. 하지만 기존의 보고된 방법은 시간이 오래 걸리며, HPLC와 같은 복잡한 시스템을 필요로 하여 소규모 실험실에서 합성하기에 적합하지 않으며, 최종 product에서 에탄올 함량이 높다는 단점이 있었다. 이러한 단점을 보완하기 위하여 카트리지만을 사용하여 카트리지에서 methylation과 purification을 동시에 실시함으로써 합성 시간을 단축하고, 비방사능이 높고, 낮은 에탄올 함량을 가진 $[^{11}C]PIB$를 합성 가능한지 확인하고자 하였다. 가장 널리 사용하는 카트리지 6종(CM, HLB, Alumina, C18, tC18, tC18 environmental을 선택하여 screening test를 실시하였다. 6-OH-BTA-0 1 mg을 c-HXO에 녹인 다음 6개의 카트리지에 loading를 한 다음 0.5 M MSP(pH 5.1) 20 mL로 정제를 한 다음 최종 fraction을 받아서 analytical HPLC로 전구체 잔류량을 측정한 결과 hydrophobicity가 낮은 계열(CM, HLB, Alumina)의 카트리지에서는 완충액으로 정제를 하였을 때 잔류전구체의 양이 많았으나, 탄소함량이 많은 계열의 카트리지(C18, tC18, tC18 environmental)에서는 잔류전구체의 양이 CM, HLB, Alumina 카트리지에 비하여 상대적으로 적었다. 완충액의 정제 농도와 부피를 최적화 하기 위하여 screening test에서 가장 좋은 결과를 나타낸 C18 series cartridge를 가지고 추가 실험을 진행하였다. 인산완충액 농도를 10 mM, 20 mM, 30 mM, 40 mM, 50 mM, 250 mM, 500 mM로 변화시켰으며, 에탄올 함량은 20%와 30%로 하여 용출액을 분석하여서, $[^{11}C]PIB$를 카트리지로 합성하기 위한 최적의 조합은 tC18 environmental cartridge와 0.5 M MSP 20 mL인 것을 알 수 있었다. 기존에 보고된 방법과 cartridge를 비교한 결과, 합성시간에서는 각각 15 ~ 18min, 8 ~ 9 min이 소요되었으며, product activity는 각각 $4.1{\pm}1.4\;GBq$ (n=41), $3.8{\pm}0.9\;GBq$ (n=3), 방사화학적 수율(based on HPLC analysis of the crude product)에서는 $13.9{\pm}4.4%$ (n=41), $12.3{\pm}2.2%$ (n=3)로 별다른 차이가 없었으며, 비방사능에 있어서는 HPLC purification method가 $78.7{\pm}39.7\;GBq/{\mu}mol$ (n=41), cartridge method가 $420.6{\pm}20.4\;GBq/{\mu}mol$ (n=3)로 카트리지 방법이 기존 방법보다 더 좋은 결과를 나타내었다. 또한, 잔류 용매(c-HXO)도 vial or loop method와 별다른 차이가 없었으며, 에탄올 함량에 있어서는 70%(기존 방법)에서 30%(카트리지 방법)로 두 배 이상 함량이 적다는 사실을 알 수 있었다. 지금까지 알아본바와 같이 cartridge method는 reported method(HPLC purification)에 비하여 더 향상된 결과를 보여준다는 사실을 확인하였다. $[^{11}C]PIB$ synthesis has been performed by a loop-methylation and HPLC purification in our lab. However, this method is time-consuming and requires complicated systems. Thus, we developed an on-cartridge method which simplified the synthetic procedure and reduced time greatly by removing HPLC purification step. We compared 6 different cartridges and evaluated the $[^{11}C]PIB$ production yields and specific activities. $[^{11}C]MeOTf$ was synthesized by using TRACERlab FXC Pro and was transferred into the cartridge by blowing with helium gas for 3 min. To remove byproducts and impurities, cartridges were washed out by 20 mL of 30% EtOH in 0.5 M $NaH_2PO_4$ solution (pH 5.1) and 10 mL of distilled water. And then, $[^{11}C]PIB$ was eluted by 5 mL of 30% EtOH in 0.5 M $NaH_2PO_4$ into the collecting vial containing 10 mL saline. Among the 6 cartridges, only tC18 environmental cartridge could remove impurities and byproducts from $[^{11}C]PIB$ completely and showed higher specific activity than traditional HPLC purification method. This method took only 8 ~ 9 min from methylation to formulation. For the tC18 environmental cartridge and conventional HPLC loop methods, the radiochemical yields were $12.3{\pm}2.2%$ and $13.9{\pm}4.4%$, respectively, and the molar activities were $420.6{\pm}20.4GBq/{\mu}mol$ (n=3) and $78.7{\pm}39.7GBq/{\mu}mol$ (n=41), respectively. We successfully developed a facile on-cartridge methylation method for $[^{11}C]PIB$ synthesis which enabled the procedure more simple and rapid, and showed higher molar radio-activity than HPLC purification method.

비만 관련인자와 ALT 증가와의 관련성

민홍기,이정규,이하린,박현지,김윤진,이상엽 부산대학교 병원 암연구소 2009 부산대병원학술지 Vol.- No.25

흰쥐에서 Cumambrin A의 대동맥 이완작용

홍용근,양민석,박윤배 Plant molecular biology and biotechnology research 2005 Plant molecular biology and biotechnology research Vol.2005 No.

We previously reported that the exogenous administration of cumambrin A, a sesquiterpene lactone from the dried flowers of Chrysanthemum boreale Makino has a pharmacological effect on normalization of blood pressure in the spontaneously hypertensive rats (SHR). In the present study, we further investigated the effect of cumambrin A on the relaxation of phenylephrine-induced precontracted rat aortic artery rings. The potency of cumambrin A was then compared to verapamil, a well known Ca^(2+)-channel blocker. The results demonstrate that the isolated rat aortic arteries are relaxed to basal tension at a concentration of 5X10^(-5)M cumambrin A treatment. The results also show that the phenylephrine-induced contraction is inhibited by a pretreatment of cumambrin A. Co-treatment of cumambrin A and verapamil showed a strong synergetic effect on the relaxation of rat aortic artery rings. Thus, these data demonstrate that cumambrin A is a potent relaxant of rat aortic smooth muscle and suggest that cumambrin A modulates intracellular or extracellular Ca^(2+) mobilization.

공공정보자원의 상업화 모델 개발 및 적용방안

홍필기,윤상오,방민석 한국정보사회진흥원 2007 정보화정책 Vol.14 No.3

본 논문의 목적은 공공정보자원의 활용도 제고 및 지식정보산업 육성을 통한 국가경쟁력 강화의 기반으로서, 공공정보자원의 상업화 모델을 개발하고 이를 적용하기 위한 주요 이슈를 점검하고 정책적 시사점을 제공하는 것이다. 이를 위하여 미국∙EU∙영국∙캐나다의 공공정보자원 활용 제고를 위한 상업화 정책과 상업화 모델로서 자금조달(Funding Model), 비용회수(Cost Recovery Model), 수익창출(Revenue Generation) 모델을 검토하였다. 이를 토대로 공공정보자원의 생명주기와 가치사슬 모델을 활용하여 ⅰ) 공공기관 직접 상업화, ⅱ) 민간계약 상업화, ⅲ) 민∙관 공동생산 상업화, ⅳ) 민간완전위탁 상업화라는 네가지 모델을 개발하고 장단점을 살펴보았다. 그리고 이러한 모델을 우리나라의 공공정보자원 상업화에 적용하기 위해서 선결되어야 할 주요 이슈로서 공공정보 상업화의 비전과 목표, 상업화의 대상 및 범위, 상업화의 주체, 공공정보 저작권, 요금부과 방식과 이윤배분∙활용 및 예산지원, 관련 법제도 정비 등을 검토하였다. This study formulates a strategy for commercial utilization of the public sector information(PSI) to promote efficient provision and effective utilization of information. Models for commercialization of the PSI are suggested in consideration of the life cycle perspectives and the commercial arrangements of the PSI. As to the life cycle perspectives, three stages of commercialization - Funding, Cost Recovery, and Revenue Generation - are proposed based on the analysis of cost structure and the economic viability of the public sector information. This paper also considers various types of commercialization scheme and suggests four types of business arrangement for commercialization of the PSI as a sustainable mechanism. Reviewing the literature on the major countries and organizations relevant to commercialization of the PSI, we examine each of four types of commercialization arrangement in the context of an information resource life cycle along a value chain of the PSI. The study also identifies key issues such as copyright and suggests relevant policies for PSI commercialization such as pricing scheme, related legal and institutional requirements. The suggestions in this study can be the foundation for further detailed researches and practical policies regarding the PSI commercialization.

밀링작업에서 보조장치를 이용한 자유곡면의 표면거칠기 향상에 관한 연구

홍민성,윤병운 한국공작기계학회 1996 한국생산제조학회지 Vol.5 No.3

The applicability of a new method, termed the whirling motion concept, for the improvement of the surface finish in milling three-dimensional sculptured surfaces has been investigated. A method for implementing this concept on conventional NC machines that utilize a suitably configured attachment has been proposed. The tool path equation for the ball-end milling process, based on the surface-shaping system, has been obtained. Both results of the computer simulation and the experiment verified the proposed approach.

혐오자극과 모델링 및 언어적 지시가 발달지체 아동의 상동행동에 미치는 효과 : 사례연구

한현민,함소희,김윤선,지지영,홍희영 대진대학교 교육연구소 2000 교육연구 Vol.2 No.1

The experiment was undertaken to determine the combined effects of aversive, modeling, and verbal instruction on the self-stimulatory stereotyped benavior exhibited by a three-year two-month old with developmental delay, The behavioral interventions were consisted of lemon juice(aversive), behavioral rehearsal(moleling), verbal instruction(prompting), and defferential reinforcement of incompatible behavior (DRI), and continued over 73 sessions. The data gathered across multitreatments design (A-BCD-A-BD-DE) were visually analyzed. The results revealed that all the treatments reduced the occurrences of stereotyped behavior, the significant differences among any interventions were not found, and more importantly, the behavior effects were maintained.

간세포암종에 대한 간동맥 화학색전술 후 발생한 급성호흡곤란증후군

조윤원,이정미,최자윤,유동훈,차라리,오혜원,김홍준,민현주,김현진,정운태,이옥재,하창윤,이선영 이화여자대학교 의과학연구소 2013 EMJ (Ewha medical journal) Vol.36 No.1

Transcatheter arterial chemoembolization (TACE) has become an effective alternative treatment strategy for patients with inoperable hepatocellular carcinoma (HCC). Although TACE is relatively safe, acute respiratory distress syndrome associated with pulmonary lipiodol embolism is a rare and potentially fatal complication. We report a rare case of acute respiratory distress syndrome after TACE for inoperable HCC. A 75-year-old man, with huge HCC in right lobe, was treated by TACE for the first time. Seven hours after uneventful TACE procedure, he felt dyspneic and his oxygen saturation recorded by pulse oximetry (SpO2) fell to 80% despite of applying non-rebreathing mask. He underwent mechanical ventilation with a protective ventilatory strategy. We experienced a case of acute respiratory distress syndrome after TACE for HCC.

다량의 하부위장관출혈이 병발된 Vibrio vulnificus 패혈증 1예

최주연,유진홍,한석원,이대훈,최민호,박순민,김연식,김선우,신완식,강문원,강성구 대한화학요법학회 1996 대한화학요법학회지 Vol.14 No.2

최근 저자들은 Vibrio vulnificus 감염에 의해 패혈증 및 이차성 피부 병변을 보인 42세의 남자 환자의 치료중 하부 위장관 출혈이 병발된 1예를 경험하였기에 보고하는 바이다. We experienced a case of Vibrop vulnificus septicemia which showed an unusual manifestation such as hematochezia. The patient was a 42-year-old man with chronic liver disease. The blood and wound culture revealed the organism. During intensive care, he suffered from massive hematochezi for several days. Colonoscopy and abdominal CT showed findings suspicious of ischemic colitis. To our knowledge, this is the first unusual case of V.vulnificus infection which showed massive lower gastrointestinal bleeding.

견비통의 한·양방 진료 및 협진의 경제성 평가

장혜정,홍상민,박유선,남동우,이두익,이재동,이윤호,임사비나 WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2007 東西醫學硏究所 論文集 Vol.2007 No.-

Objectives : The purpose of this study was to evaluate and compare the cost-effectiveness of Eastern, Western and collaborative treatments and suggest a cost-effective approach for patients with frozen shoulder pain. Methods : Using the data of fifty-two patients, treatment effectiveness was measured by CSA, SPADI, and ROM scales and changes from the baseline score were evaluated. Data source for cost estimation was based on the national health insurance (NHI) payment system. Because the price in NHI was differentiated by health care institutions, five collaborative types were considered in assessing costs. Cost-effective ratios were computed tor economic evaluation. Results : Compared with Eastem treatinent, collaborative and Westerm treatments showed better effects on CSA scale after 4 weeks' treatment. The collaborative approach was also the most effective treatment on SPADI and ROM scales The direct cost per patient receiving Eastern treatment was less than other treatments. In general, collaborative treatment dominated Eastern and Western treatments in cost-effectiveness analysis However, the cost-effectiveness ratio of Eastern treatment resulted in \9,0OO compared to W29,OOO of collaborative treatment on SPADI Four different indicators of ROM scales resulted in different approaches as the cost-effective treatment. Conclusiuns : Considering cost-effectiveness ratios, collaborative treatment was the best treatment on CSA and SPADl scales after 4 weeks' treatment As for ROM scales, the recommended altematives were Eastern treatment for patients with abduction and adduction disabilities, Western treatment for those with flexion disability, and collab-orative approach for those with extension disability.

Structural and biochemical basis for the inhibition of cell death by APIP, a methionine salvage enzyme

Kang, Wonchull,Hong, Se Hoon,Lee, Hye Min,Kim, Na Yeon,Lim, Yun Chan,Le, Le Thi My,Lim, Bitna,Kim, Hyun Chul,Kim, Tae Yeon,Ashida, Hiroki,Yokota, Akiho,Hah, Sang Soo,Chun, Keun Ho,Jung, Yong-Keun,Yang National Academy of Sciences 2014 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.111 No.1

<P>APIP, Apaf-1 interacting protein, has been known to inhibit two main types of programmed cell death, apoptosis and pyroptosis, and was recently found to be associated with cancers and inflammatory diseases. Distinct from its inhibitory role in cell death, APIP was also shown to act as a 5-methylthioribulose-1-phosphate dehydratase, or MtnB, in the methionine salvage pathway. Here we report the structural and enzymatic characterization of human APIP as an MtnB enzyme with a <I>K</I><SUB><I>m</I></SUB> of 9.32 μM and a <I>V</I><SUB><I>max</I></SUB> of 1.39 μmol min<SUP>−1</SUP> mg<SUP>−1</SUP>. The crystal structure was determined at 2.0-Å resolution, revealing an overall fold similar to members of the zinc-dependent class II aldolase family. APIP/MtnB exists as a tetramer in solution and exhibits an assembly with <I>C4</I> symmetry in the crystal lattice. The pocket-shaped active site is located at the end of a long cleft between two adjacent subunits. We propose an enzymatic reaction mechanism involving Glu139* as a catalytic acid/base, as supported by enzymatic assay, substrate-docking study, and sequence conservation analysis. We explored the relationship between two distinct functions of APIP/MtnB, cell death inhibition, and methionine salvage, by measuring the ability of enzymatic mutants to inhibit cell death, and determined that APIP/MtnB functions as a cell death inhibitor independently of its MtnB enzyme activity for apoptosis induced by either hypoxia or etoposide, but dependently for caspase-1-induced pyroptosis. Our results establish the structural and biochemical groundwork for future mechanistic studies of the role of APIP/MtnB in modulating cell death and inflammation and in the development of related diseases.</P>