A rationally designed small molecule for identifying an <i>in vivo</i> link between metal–amyloid-β complexes and the pathogenesis of Alzheimer's disease

Beck, Michael W.,Oh, Shin Bi,Kerr, Richard A.,Lee, Hyuck Jin,Kim, So Hee,Kim, Sujeong,Jang, Milim,Ruotolo, Brandon T.,Lee, Joo-Yong,Lim, Mi Hee Royal Society of Chemistry 2015 Chemical Science Vol.6 No.3

<▼1><P>An <I>in vivo</I> chemical tool designed to target metal–Aβ complexes and modulate their activity was applied to the 5XFAD mouse model of Alzheimer’s disease (AD) demonstrating the involvement of metal–Aβ in AD pathology.</P></▼1><▼2><P>Multiple factors, including amyloid-β (Aβ), metals, and reactive oxygen species (ROS), are involved in the development of Alzheimer's disease (AD). Metal ions can interact with Aβ species generating toxic oligomers and ROS <I>in vitro</I>; however, the involvement of metal–Aβ complexes in AD pathology <I>in vivo</I> remains unclear. To solve this uncertainty, we have developed a chemical tool (<B>L2-b</B>) that specifically targets metal–Aβ complexes and modulates their reactivity (<I>i.e.</I>, metal–Aβ aggregation, toxic oligomer formation, and ROS production). Through the studies presented herein, we demonstrate that <B>L2-b</B> is able to specifically interact with metal–Aβ complexes over metal-free Aβ analogues, redirect metal–Aβ aggregation into off-pathway, nontoxic less structured Aβ aggregates, and diminish metal–Aβ-induced ROS production, overall mitigating metal–Aβ-triggered toxicity, confirmed by multidisciplinary approaches. <B>L2-b</B> is also verified to enter the brain <I>in vivo</I> with relative metabolic stability. Most importantly, upon treatment of 5XFAD AD mice with <B>L2-b</B>, (i) metal–Aβ complexes are targeted and modulated in the brain; (ii) amyloid pathology is reduced; and (iii) cognition deficits are significantly improved. To the best of our knowledge, by employing an <I>in vivo</I> chemical tool specifically prepared for investigating metal–Aβ complexes, we report for the first time experimental evidence that metal–Aβ complexes are related directly to AD pathogenesis.</P></▼2>

정화조에서 배출되는 하수관악취 저감방안 연구

조용모 ( Yong Mo Cho ),남미아 ( Mi A Nam ) 서울시정개발연구원 2009 연구보고서 Vol.2009 No.5

Outline: Recently, the urban foul odor problem is frequently happening all around Seoul area; CBD, large apartment districts, and low-lying areas where a foul water running velocity is slow. Even though a life foul odor has not been regarded as a serious problem until now, cases of civil appeal are increasing for the sewer foul odor all around Seoul along with the improvement of standard of living and frequent rise of bad smell problems especially in large buildings. The purpose of this study is deliberating the way of reducing the sewer foul odor by examining the origin and process of the urban sewer foul odor generating throughout Seoul. 2. Main results of the study The result of the survey had performed for three years, during 2006~2008, shows that the generating spot of the life sewage foul odor is increasing every year; 1,442 cases in 2006, 2,067 cases in 2007, and 2,523 cases in 2008, total 6,032 cases had been reported. 608,205 Septic tanks including polluted water purifying devices had installed in Seoul, and 11,454 tanks among them are over 500 people capacity tanks. 2) Foul odor concentration examination in Seoul The foul odor in the circumference of Yeosung Green Castle apartment was examined to find the generating characteristics of the life sewage foul odor. Yeosung Green Castle apartment is located where about 10% gradient road is continued more than 500 meters. Foul odor is severly generated at the end of this road, the entrance of a path up a mountain. The sewage foul odor of Namhyun-dong neighborhood is generated from the foul odor of Septic tanks in the houses and apartments. The result of foul odor examination showed the degree of mixed foul odor at the 1 and 2 spots of rainwater receivers are individually 144 and 208 dilution rate, and they are far over 15 that is permissible level. Hydrogen sulfide was measured 15 times higher than the permissible level, 20.0ppb, at the each spots. Methyl mercaptan also was gauged as largely exceeding 2.0ppb, the permissible level. 3) Types of life foul odor The foul odor generated in Seoul could be largely classified into five types as follows; A. the foul odor adjacent to the large buildings, B. the foul odor of small water-purifiers in single-family housing districts, C. the foul odor of sewer system in upstream hilly sections, D. the foul odor of sewer system in low-lying areas, and E. the foul odor of Storm Overflow Diverging Tanks. 4) Problems of life sewage foul odor The problems of the life sewage foul odor are as follows; A. absence of the efficient alteration of sewage foul odor prevention, B. difficulty of a origin blockade in the Septic tanks, the main source of life sewage foul odor, C. absence of a provision for prevention of life sewage foul odor in the Foul Odor Prevention Law and D. difficulty of achieving the foul odor reducing effect by resetting the quality standard of Septic thank`s discharging water. 3. Policy recommendation: 1) Basic principles for reducing ife foul odor (1) Analyzing reality of life sewage foul odor generation The foul odor is inevitably generated in most Korean buildings when discharging water of a Septic tank is influented to the sewer system. However, the foul odor prevention with improving efficiency of a Septic tank has not only much difficulty of securing effectiveness but also lack of scientific approaches. (2) Establishing basic frame for life foul odor prevention The basic frame for life foul odor prevention is as follows, Firstly, introducing the public concept, the mandatory installation and management of Septic tanks and sewer systems, to reduce the sewage foul odor. Secondly, promoting the synthesized management that focuses on a sewer pipe; moving from point control to line control Thirdly, establishing a system by adding the life sewer foul odor provision in the Foul Odor Prevention Law or legislating a new law for the preventing life sewer foul odor, Fourthly, connecting the measure for reduction of Septic tanks and sewer pipe foul odor with the sewerage maintenance, Lastly, founding the effective reduction measure with considering limited effect of a rainwater receiver for the sewer foul odor prevention. (1) Process for managing life sewer foul odor The main contents of process for the life sewer foul odor management are as follows in the order named; A. recognizing the generation spot of the life sewer foul odor, B. examining the life sewer foul odor, C. selecting sewer systems for managing the life sewer foul odor, D. requiring the reduction facility to the large buildings discharging sewage to the sewer system and water-purifying tanks over 500 people capacity by law, E. establishing the synthesized reduction plan in the selected sewer system district, and F. installing the reduction facility for the life sewer foul odor. (2) Systemic improvement for reduction of sewer foul odor Adding the sewer foul odor section in the Foul Odor Prevention Law or Sewerage Law is necessary, and legislating the municipal ordinance for the life sewer foul odor in Seoul is required. It is necessary to make installing the foul odor facility into a mandatory requirement both new construction buildings installed Septic tank over 500 people capacity or larger than 1,500 floor area, and existing buildings located within the sewer foul odor sewer system area. (3) Efficient plan for reducing foul odor in building district ① Installing plan of the foul odor reduction facility for existing buildings in the urban building districts installing vertical outlets on the building side using existing sewer pipes as an induction pipe. ② New construction buildings in single-family housing districts systemizing installing the foul odor reduction facility as mandatory requirement in the buildings both have Septic tank over 500 people capacity and larger than 1500 floor area, ③ Indistinctive source of the sewer foul odor installing the "L"type induction pipe using a street light or telephone pole as a prop. (4) Establishing a plan for sewer four odor reduction Establishing the sewer foul odor maintenance and improvement scheme is required in each district of the sewer foul odor management, On top of that, the sewer foul odor reduction study should be proceeded with the whole region of Seoul, (5) Operating sewer foul odor counterplan party under the government of Seoul The foul odor counterplan party that is consisted with professionals and public service workers should be organized, and the solutions for the foul odor should be made such as a field study, reduction programs, the allotment of facility construction in the regions where the foul odor reduction measure is urgent.

Shadows on the Rock에 나타난 미국의 꿈

이경아,하미애 慶南大學校 人文科學硏究所 1998 人文論叢 Vol.10 No.-

<ABSTRACT>The protagonists in Cather's novels written between 1920 and 1926 experience crises of self and desperately seek new avenues to personal fulfillment. In such portrayals. Cather moves farther away from any notion of success that centers on material gain or that elevates the individual, and toward an understanding the American Dream that is community-oriented and fundamentally at odds with wealth and position. Thus Cather in the early 1930's, when she wrote Shadow on the Rock, was still negotiating a position for herself on the American Dream.Published in 1931, Shadow on the Rock, seems an appropriate Depression-era novel, with its poor-but-happy, Shirley Temple type of heroine, who teaches her observers that they can find personal happiness without money or fame. And in the spirit of the Depression-era intellectual, more interested in a universal human community than in a specifically American community (Peeler 7), Cather "un-Americanizes" her setting by moving it beyond the United states to Canada. Cather at the end of this period seems especially to be reverencing communal values-represented by religion and Family-and perhaps thinking of abandoning or at least tempering the bolder individualism that early heroines such as Thea Kronborg and Marian Forrester display.At one point in the novel, Cather especially emphasizes this theme of traditions. In Shadows on the Rock, Cather clearly defines the community that more and more came to hold importance for her: the tradition-bearers who transmit values from past to present and preserve those values for future humanity. In fact, Cather in this novel uses religion as a concrete example of tradition: religion is not only a vehicle for the transmission of tradition, but it provides for those who cherish, practice, and spread it a sense of community and of belonging. For Cather, religion is a means of carrying that past to the future.Like religion, family gains importance as a symbol of community in this phase of Cather's writing. As Cather validates these two avenues to a tradition-based, self-affirming community-religion and family-she reflects a cultural shift in focus as America itself moved toward an era of economic upheaval and widespread disillusionment with the American Dream. The family community is actually elevated to the level of art and religion as a symbol of what must be preserved. The beauty and sacredness of family in this work perhaps reflects Cather's own growing awareness of how much her family meant to her. And Cather's need for family reflects not only a growing personal awareness of the importance of this initial community, but a growing national reawakening to the strength and power of the family as a unit.

DACUM 기법에 의한 병원 임상영양사의 직무기술서 개발

차진아 ( Jin A Cha ),김강은 ( Kang Eun Kim ),김은미 ( Eun Mi Kim ),박미선 ( Mi Sun Park ),박유경 ( Yoo Kyoung Park ),백희준 ( Hee Joon Baek ),이송미 ( Song Mi Lee ),최수경 ( Soo Kyong Choi ),서정숙 ( Jung Sook Seo ) 대한영양사협회 2013 대한영양사협회 학술지 Vol.19 No.3

본 연구에서는 DACUM 기법을 통해 국내 병원 임상영양사의 직무를 조사 및 분석하고 그 결과를 바탕으로 도출된 임상영양사의 직무기술서를 평가함으로써 병원 임상영양사를 위한 직무기술서를 개발하고자 하였다. 2011년 7월초에 DACUM 워크숍을 통해 1차적으로 직무기술서를 도출하고 전문가 집단의 자문회의와 Delphi 조사 방법을 적용한 표적집단 면접을 통해 수정 및 보완 작업을 거쳐 직무기 술서를 도출하였다. DACUM 위원회의 패널로는 3차 의료기관에 종사하고 있는 현직 임상영양사 9인과 임상영양학을 전공하는 교수 4인, 직무분석을 담당하는 교수 1인 등 총 14명이 참여하였다. 전문가 자문단을 별도로 구성하였으며, 의사 1인, 간호사 1인, 임상영양분야 실무자 및 교수 5인이 포함된 전문가의 의견을 추가적으로 수렴하였다. 도출된 직무기술서는 2011년 7∼8월까지 전국 500병상 이상의 종합 병원 90개 중 설문조사에 응답한 46개 병원에서 각각 임상영양 실무책임자 1인으로부터 수집한 자료를 분석하여 현장 적합성을 평가하였다. 본 연구의 결과를 요약하면 다음과 같다. 1. 본 연구에서 DACUM 기법에 의해 처음 도출된 직무는 총 8개의 직무, 33개의 과업, 114개의 과업요소였으나 수정 보완작업을 거쳐 총 7개의 직무, 27개의 과업과 93개의 과업요소로 재분류되었다. 최종적으로 병원 임상영양사의 직무는 영양판정(A), 영양진단(B), 영양중재(C), 영양모니터링ㆍ평가(D), 자문ㆍ협력(E), 영양연구(F), 자기계발(G)로 도출되었다. 2. 각 직무영역별로 세부내용을 보면, (A) 영양판정은 A1. 영양 초기평가하기, A2. 식품영양관련 자료 수집·평가하기, A3. 의학적 자료 점검하기, A4. 신체계측 자료 수집·평가하기, A5. 신체증상 자료 점검하기, A6. 개인력 및 과거력 점검하기, A7. 영양 요구량 결정하기, A8. 영양판정 기록하기의 8개의 과업으로 구분하였다. (B) 영양진단은 B1. 영양진단 도출하기, B2. 우선순위 정하기, B3. 영양진단 기록하기로 나뉘었고, (C) 영양 중재는 C1. 영양중재 계획하기, C2. 영양처방 관리하기, C3. 영양상담하기, C4. 영양교육하기, C5. 영양집중지원하기, C6. 영양중재 기록하기로 구분 하였다. (D) 영양모니터링·평가는 4개의 과업으로 D1. 영양상태 모니터하기, D2. 영양중재과정 모니터하기, D3. 영양중재 결과 평가하기, D4. 영양모니터링·평가 기록하기로 구분하였다. (E) 자문·협력은 E1. 영양자문하기, E2. 협력관계 구축 및 유지하기로 (F) 영양연구는 F1. 질 향상 활동하기, F2. 연구 활동하기로 분류하였다. 마지막으로 (G) 자기계발은 G1. 전문성 향상, G2. 자기관리가 포함되었다. 3. 도출된 임상영양 직무기술서에 대한 평가를 위해 설문조사에 참여한 대상 병원의 유형은 상급종합 병원이 65.2%를 차지하였으며, 종합병원은 34.8%였다. 병원의 재원일수는 8.0±1.5일이었으며 병원 조직에서 영양부서는 6곳을 제외한 39개의 병원에서 진료부서 또는 진료지원부서에 속하였다. 또한 병원에서 영양부서가 단독으로 편제되어 있는 경우가 93%로 높은 비율을 보였다. 병원 임상 영양사의 성별은 여자가 100%로 나타났으며, 연령별 분포는 40∼49세가 가장 높은 비율을 보였다. 근무경력은 10년 이상인 경우가 50% 이상을 차지하였고 최종학력은 석사졸업이 가장 높은 것으로 나타났다. 4. 전체 과업요소의 인지된 중요도를 비교하면 6개의 과업요소를 제외한 대부분의 과업요소들이 4.0점 이상이었고 총 7개 직무영역에 대한 중요도는 ‘영양중재’가 4.6±0.6점으로 가장 중요도가 높게 나타났으며, ‘영양진단’과 ‘영양모니터링·평가’의 직무가 4.5점 이상으로 비교적 높게 조사 되었다. 전체 과업요소 중 수행도가 4.5점 이상으로 매우 자주 수행되는 과업요소가 13개, 4.0점 이상의 자주 수행되는 과업도 29개의 과업요소로 나타났으며, 직무영역 중 ‘영양중재’가 4.2±1.0점으로 높게 나타났다. 직무영역별 난이도를 조사한 결과에서는 ‘영양연구’ 업무가 4.1±0.9점으로 가장 높게 조사되었다. ‘영양진단’과 ‘자문·협력’은 각각 3.8±1.0점, 3.7±0.9점으로 비교적 어렵게 인식되는 직무로 나타났다. 직무영역별 과업요소 전체의 중요도, 수행도, 난이도의 평균은 각각 4.5±0.8점, 3.7±1.3점, 3.5±1.0점으로 나타났으며 유의적인 차이가 나타났다(P<0.001). 5. 임상영양사 업무의 중요도와 수행도 사이의 관계를 나타낸 격자도 분석에서 영양 초기평가하기, 영양요구량 결정하기, 영양판정 기록하기, 영양진단 도출하기, 영양중재 계획하기, 영양처방 관리하기, 영양교육하기, 영양집중지원하기, 영양중재 기록하기, 영양상태 모니터하기, 영양중재 과정 모니터하기는 중요도와 수행도가 모두 높은 영역(doing great)에, 식품영양관련 자료수집·평가하기, 의학적 자료 점검하기, 신체계측 자료수집·평가하기, 신체증상 자료 점검하기, 개인력 및 과거력 자료 점검하기, 영양진단의 우선순위 정하기, 영양진단 기록하기, 영양상담하기, 영양 모니터링·평가 기록하기는 수행도는 높으나 중요도가 낮은 영역(overdone)에 속하였다. 중요도가 높으나 수행도가 낮은 영역(focus here)에는 협력관계 구축 및 유지하기, 질 향상 활동하기가 속하였고, 중요도와 수행도가 모두 낮은 영역(low priority)은 영양중재 평가하기, 영양 자문 활동하기, 연구 활동하기, 전문성 향상하기, 자기관리하기가 속하는 것으로 나타났다. 이상의 결과를 볼 때, 본 연구에서 DACUM 기법에 의해 개발된 병원 임상영양사의 직무기술서는 현장에서 임상영양서비스를 수행하는데 가이드라인으로 사용될 수 있을 것으로 여겨지며, 인지된 중요도가 평균 이상으로 높지만 그에 비해 수행도가 미흡한 과업들에 대하여는 임상영양사에 대한 교육 실시, 업무 분담, 적정인원 배치 등 제도적인 뒷받침을 마련하여 수행도를 높일 수 있는 방안이 강구 되어야 할 것이다. 또한 질병별 맞춤형 임상영양 업무에 관한 후속연구를 통하여 보다 전문적인 환자 영양치료가 가능할 것으로 여겨진다. The present study was conducted to develop a standardized job description for clinical dietitians working in hospitals. A developing curriculum (DACUM) method was used for the job analysis of clinical dietitians. Based on DACUM analysis with 14 members, including clinical dietitians and professors majoring in clinical nutrition and job analysis, information on the duties, tasks, and task elements of clinical dietitians was determined. To verify the job descriptions derived from DACUM analysis, a total of 46 tertiary and general hospitals with over 500 beds were recruited for the survey. The final developed job description for clinical dietitians included 7 duties, 27 tasks, and 93 task elements. The duties consisted of nutritional assessment, nutrition diagnosis, nutrition intervention, nutrition monitoring·evaluation, consultation·cooperation, nutrition research, and self-development. The mean scores of perceived importance, performance, and difficulty on the clinical dietitian`s task elements (out of a maximum score of 5.0) were 4.5, 3.7, and 3.5, respectively, with significant differences between the items (P<0.001). The perceived importance and performance grid of clinical dietitian`s tasks showed that “construction and maintenance of collaboration” (E2) and “activity of quality improvement” (F1) received relatively low scores for performance despite their high importance scores; thus the performance of these tasks requires significant improvement. In conclusion, the job descriptions of clinical dietitians developed from this study are useful for the qualitative improvement of clinical nutrition services in hospitals.

인간 혈장 아포지단백질 A-1 ( apo A-1 ) 에 대한 단일클론 항체 생산 및 단일클론 항체를 사용한 혈중 apo A-1 측정용 효소면역분석법 ( ELISAs ) 의 개발

이동익,남경수,한문희,김태웅,곽주원,윤미청,최성아 한국지질학회 1994 韓國脂質學會誌 Vol.4 No.1

Recently, apolipoprotein(apo) A-I has received considerable clinical attention as a better marker of inverse correlation with the presence of coronary heart disease than the customary lipid marker, high-density lipoprotein(HDL)-cholesterol. Here we report the production of marine monoclonal antibodies(Mabs) designated as MabA 12 and MabA34 against human apo A-I, recognizing the HDL in plasma. From isotyping analyses, it was found that MabA 12 and MabA34 had IgG2b and IgGI isotype, respectively. Both of the Mabs had κ light chains. The binding specificity of two Mabs was analyzed by immunoblotting and enzyme-linked immunosorbent assay(ELISA). MabA12 and MabA34 reacted well with purified apo A-I or HDL in plasma but they didn't react with low-density lipoproteins(LDL), serum albumin or lipoprotein-deficient serum(LPDS). These indicate that the two Mabs are very specific to human apo A-I in HDL. The validity of the Mabs for serum apo A-I assays was examined by two kinds of ELISA, i.e., non-competitive and competitive ELISA. Both assays revealed that MabA12 or MabA34 reacted well with apo A-I in sample in concentration-dependent manners. Standard curves and, antibody titration curves were drawn. In conclusion, two IgG-type monoclonal antibodies specific to human apo A-I in HDL were produced and applicated for ELISAs of serum apo A-I. The two Mabs would be useful not only for research purposes but also for further development of immuno-diagnostic kits for the measurement of serum apo A-I concentrations.

자궁 내 감염 관련 유전자 및 산화 스트레스 관련 유전자와 조기분만의 연관성

유시연 ( Si Yeon You ),김정명 ( Jung Myung Kim ),이경아 ( Kyung A Lee ),박미혜 ( Mi Hye Park ),김영주 ( Young Ju Kim ),전선희 ( Sun Hee Chun ) 대한산부인과학회 2010 Obstetrics & Gynecology Science Vol.53 No.7

목적: 조기 분만과 자궁 내 감염 관련 유전자 (IFN-γ, interleukin [IL]-10) 및 산화 스트레스 관련 유전자 (CYP1A1)와의 연관성을 알아보고자 한다. 연구 방법: 2007년 1월부터 2008년 12월까지 이대 목동병원 산부인과에서 산전 검사 및 분만을 시행한 산모 중 37주 이전에 분만한 조산군 164명과 37주 이후에 분만한 대조군 305명을 대상으로 하였으며, 임신 주수 24주 미만, 태아의 선천성 기형, 다태아 분만, 사산의 경우를 제외하였다. 참여자는 입원 시 키, 몸무게 측정 및 혈액 채취를 시행하였고 임신 주수는 최종 월경일 또는 초음파 측정을 통해 계산 되었다. 산모의 혈액에서 IFN-γ, IL-10, CYP1A1 유전자형을 PCR과 SNaPShot method를 사용하여 검사하였으며 카이제곱 검정과 다중 로지스틱 회귀분석을 사용하여 통계분석 하였다. 결과: 조기 분만군과 만삭 분만군 사이에 임신 주수, 태아 체중에 통계적으로 유의한 차이가 있었다(P<0.0001). IFN-γ, IL-10, CYP1A1 유전자형의 빈도와 조기 분만 사이에는 유의한 상관성이 없었다(P>0.05). 결론: 본 연구에서 IFN-γ (874A/T) 및 IL-10 (1082A/G), IL-10 (819C/T), IL-10 (592A/C)와 CYP1A1 (T6235C), CYP1A1 (Ile462val [A/G]) 유전자형의 빈도는 조산과 관련이 없었다. Objective: To investigate the association between preterm birth and cytokine genes (IFN-γ, interleukin (IL)-10) in intrauterine infection and enzyme gene (CYP1A1) in oxidative stress response. Methods: This study involved a case-control study conducted at Ewha Womans University Hospital in Seoul, Korea. Subjects with preterm deliveries (<37 weeks of gestation) and normal controls with term deliveries (≥37 weeks of gestation) were selected from gravidas who had undergone prenatal examinations in the hospital and were followed until infant delivery. The weight, height, and blood samples of each participants were obtained according to standard protocols. We included subjects who gave birth to a singleton infant and had a gestational age between 24 and 42 weeks. Mutiple births, stillbirths, and congenital anomalies were excluded. Finally, 164 gravidas with preterm births and 305 normal controls with term deliveries were enrolled in the present study. Results: Preterm delivery group and term delivery group had significant difference in gestational age and neonatal body weight (P<0.0001). There were no statistically significant association between preterm birth and IFN-γ, IL-10, CYP1A1 genes (P>0.05). Conclusion: In this study, IFN-γ (874A/T), IL-10 (1082A/G), IL-10 (819C/T), IL-10 (592A/C) and CYP1A1 (T6235C), CYP1A1 (Ile462val [A/G]) genes had no significant association with preterm birth.

Chelation-induced diradical formation as an approach to modulation of the amyloid-β aggregation pathway

Porter, Meghan R.,Kochi, Akiko,Karty, Jonathan A.,Lim, Mi Hee,Zaleski, Jeffrey M. Royal Society of Chemistry 2015 Chemical Science Vol.6 No.2

<▼1><P>We demonstrate that ligand–metal–Aβ interaction with subsequent radical generation is a relatively rapid mechanism for influencing Aβ structural integrity and thus, the aggregation pathway.</P></▼1><▼2><P>Current approaches toward modulation of metal-induced Aβ aggregation pathways involve the development of small molecules that bind metal ions, such as Cu(<SMALL>II</SMALL>) and Zn(<SMALL>II</SMALL>), and interact with Aβ. For this effort, we present the enediyne-containing ligand (<I>Z</I>)-<I>N</I>,<I>N</I>′-bis[1-pyridin-2-yl-meth(<I>E</I>)-ylidene]oct-4-ene-2,6-diyne-1,8-diamine (<B>PyED</B>), which upon chelation of Cu(<SMALL>II</SMALL>) and Zn(<SMALL>II</SMALL>) undergoes Bergman-cyclization to yield diradical formation. The ability of this chelation-triggered diradical to modulate Aβ aggregation is evaluated relative to the non-radical generating control pyridine-2-ylmethyl-(2-{[(pyridine-2-ylmethylene)-amino]-methyl}-benzyl)-amine (<B>PyBD</B>). Variable-pH, ligand UV-vis titrations reveal p<I>K</I><SUB>a</SUB> = 3.81(2) for <B>PyBD</B>, indicating it exists mainly in the neutral form at experimental pH. Lipinski's rule parameters and evaluation of blood–brain barrier (BBB) penetration potential by the PAMPA–BBB assay suggest that <B>PyED</B> may be CNS+ and penetrate the BBB. Both <B>PyED</B> and <B>PyBD</B> bind Zn(<SMALL>II</SMALL>) and Cu(<SMALL>II</SMALL>) as illustrated by bathochromic shifts of their UV-vis features. Speciation diagrams indicate that Cu(<SMALL>II</SMALL>)–<B>PyBD</B> is the major species at pH 6.6 with a nanomolar <I>K</I><SUB>d</SUB>, suggesting the ligand may be capable of interacting with Cu(<SMALL>II</SMALL>)–Aβ species. In the presence of Aβ<SUB>40/42</SUB> under hyperthermic conditions (43 °C), the radical-generating <B>PyED</B> demonstrates markedly enhanced activity (2–24 h) toward the modulation of Aβ species as determined by gel electrophoresis. Correspondingly, transmission electron microscopy images of these samples show distinct morphological changes to the fibril structure that are most prominent for Cu(<SMALL>II</SMALL>)–Aβ cases. The loss of CO<SUB>2</SUB> from the metal binding region of Aβ in MALDI-TOF mass spectra further suggests that metal–ligand–Aβ interaction with subsequent radical formation may play a role in the aggregation pathway modulation.</P></▼2>

자궁내막암 환자의 재발여부 확인에 있어 FDG-PET scan 의 유용성에 대한 고찰

홍성진 ( Hong Seong Jin ),이삼미 ( Lee Sam Mi ),박천숙 ( Park Cheon Sug ),김호아 ( Kim Ho A ),김법종 ( Kim Beob Jong ),김문홍 ( Kim Mun Hong ),최석철 ( Choe Seog Cheol ),유상영 ( Yu Sang Yeong ),이경희 ( Lee Gyeong Hui ) 대한산부인과학회 2004 Obstetrics & Gynecology Science Vol.47 No.2

목적 : Inhibin은 α-subunit와 β-subunit로 구성된 이질 이량체의 당단백으로 β-subunit의 차이에 의해 inhibin A (α-βA)와 inhibin B (α-βA)로 구분된다. 여성에서 inhibin은 주로 난소의 과립막세포 및 황체에서 생산되어 뇌하수체의 FSH 분비를 억제한다고 알려져 왔으나, 임신중 태반과 남성의 고환에서도 생산된다는 사실이 밝혀져 다양한 생리적 작용이 추정되고 있으며 최근에 inhibin A와 B를 분리 측정할 수 있는 방법이 개발되어 inhibin에 대한 연구가 활발히 진행되고 있다. 이에 저자들은 정상 월경주기를 가진 가임기 여성, 폐경이행기 여성, 폐경후기 여성에서 inhibin A와 inhibin B의 농도를 측정하여 월경주기에 따른 정상치의 변화와 노화에 따른 농도 변화를 관찰하고, 난소에서 면역조직화학적 염색법으로 inhibin A와 inhibin B의 발현 양상과 변화를 비교 관찰하여 inhibin의 정확한 생리작용, 폐경이행기에서 inhibin의 역할 및 폐경이행기와 폐경의 예측 지표의 사용 가능성을 알아보고자 하였다. 연구 방법 : 월경주기와 난소기능이 정상이면서 난소종양이 없는 정상 가임기 여성 160명, 폐경이행기 여성 60명, 폐경후기 여성 20명에서 정맥혈을 채혈하여 혈중 inhibin A와 inhibin B 농도를 ELISA로 측정하였고, 그중 정상 가임기 여성 35명, 폐경이행기 여성 20명, 폐경기 여성 5명의 난소 조직을 inhibin α, βA 및 βB subunit에 대한 단클론 항체를 이용하여 면역조직화학적 염식을 시행하였다. 결과 : 1. 정상 가임기 여성에서 혈중 inhibin A 농도는 중증식기까지 낮은 농도를 유지하다 후증식기 (16.53±1.57 pg/ml)부터 증가하기 시작하여, 중분비기 (45.85±2.08 pg/ml)에 최고치에 이른 후 서서히 감소하는 경향을 보였다. Inhibin B 농도는 전증식기 (65.40±4.08 pg/ml)부터 증가하기 시작하여 증식기 동안 계속 높은 농도를 유지하다가 배란기 (110.74±9.83 pg/ml)에 최고치에 이른 다음 분비기에 급격히 감소하였다. 2. 폐경이행기 여성에서 혈중 inhibin A 농도는 증식기에 6.68±0.53 pg/ml, 분비기에 21.78±3.61 pg/ml로 모두 정상 가임기 여성과 비교하여 유의하게 낮았다 (P<0.01). Inhibin B의 농도는 증식기에 52.16±7.46 pg/ml, 분비기에 22.41±6.73 pg/ml로 모두 정상 가임기 여성과 비교하여 유의하게 낮았다 (각각 P<0.01, P=0.025). 3. 폐경후기 여성에서 inhibin A와 inhibin B 농도는 모두 검출되어 않았다. 4. 정상 가임기 여성에서 inhibin α subunit의 면역염색반응은 과립막세포, 난포막세포 및 황체에서 강하게 발현되었다. Inhibin βA의 면역염색반응은 난포에서는 거의 발현되지 않았으나 황체에서는 관찰되었다. Inhibin βB의 면역염색반응은 일차난포에서 처음 발현되어 성장난포와 성숙난포의 과립막세포와 난포막세포에서 관찰되었으나 Inhibin α보다는 약했고 황체에서는 거의 관찰되지 않았다. 5. 폐경이행기 여성에서 inhibin subunit들의 면역염색반응은, 정상 가임기 여성과 같은 양상으로 발현되었으나, 발현정도는 약했다. 모든 면역염색반응은 과립막세포보다 난포막세포에서 더 강하게 나타났다. 6. 폐경후기 여성에서 inhibin subunit들의 면역염색반응은 전혀 관찰되지 않았다. 결론 : Inhibin A는 후증식기 성숙난포에서 처음 생산되기 시작하여 배란 후 황체에서 주로 생산되며, Inhibin B는 일차난포에서 생성되기 시작하여 배란 시까지 분비되므로 inhibin A는 황체기능을, inhibin B는 난포의 기능을 반영한다. 폐경이행기가 되면 inhibin A와 B의 분비는 급속히 감소하게 되어 폐경 후에는 난소에서 생성되지 않는다. 따라서 inhibin A와 B는 여성의 월경주기에 따라 생산과 분비가 서로 다른 호르몬으로 난자 성숙과 난포발달에 관여하며, 난소의 노화 정도를 측정하는 폐경이행기의 지표로 이용될 수 있을 것이다. Objective : To understand the physiologic effects and secretion pattern of inhibin A and inhibin B during menstrual cycle and menopausal transition, inhibin A and inhibin B levels were measured. And to detect any changes in expression of inhibins in human ovary with age, we examined immunohistochemical staining of α, βA, and βB subunits of inhibin in ovarian tissues. This study was also designed to investigate whether or not inhibin is an early marker for menopausal transition. Methods : Inhibin A and inhibin B levels were measured in 320 samples from normal reproductive women, in 60 from perimenopausal women, and in 20 from menopausal women by ELISA. And we examined the immunohistochemical staining of α, βA, and βB subunits of inhibin in ovarian tissues of 35 normal reproductive, 20 perimenopausal, and 5 menopausal women, respectively. Results : In the normal reproductive women, inhibin A begins to increase in the late proliferative phase (16.53±1.57 pg/ml), reaches the peak in the mid-secretory phase (45.85±2.08 pg/ml), reaches the peak in the ovulatory phase (110.74±9.83 pg/ml), reaches the peak in the ovulatory phase (110.74±9.83 pg/ml), and thereafter declines rapidly. In the perimenopausal women, mean inhibin A serum concentration was 6.68±0.53 pg/ml during proliferative phase and 21.78±3.61 pg/ml during secretory phase, which were significantly lower than that of the same phase in the normal reproductive women (P<0.01). Mean inhibin B serum concentration was 52.16±7.46 pg/ml during proliferative phase and 22.41±6.73 pg/ml during secretory phase, which were significantly lower than that of the same phase in the normal reproductive women (P<0.01, P=0.025). In the menopausal women, both inhibin A and inhibin B were not detected. In the normal reproductive women, we observed strong immunostaining for α subunit in granulosa cells, theca cells, and corpus luteum. Immunostaining for βA subunit was observed in corpus luteum, but not in growing follicles. Immunostaining for βB subunit was observed in primary follicle, granulosa and theca cells of growing follicle, and mature follicle, but less strong than immunostaining for α subunit. No staining for βB subunit was observed in the corpus luteum. In the perimenopausal women, immunostaining for inhibin subunits were observed in the same pattern as that of the normal reproductive women, but weaker. Stronger immunostaining was observed in theca cells than granulosa cells. In the menopausal women, none of the immunostaining of inhibin subunits were observed.

한국인에서 5,10-Methylenetetrahydrofolate Reductase 유전자 다형성 분석 및 임신의 결과에 미치는 영향

김아리 ( Ari Kim ),강은지 ( Eun Ji Kang ),이경아 ( Kyung A Lee ),박세나 ( Se Na Park ),박종순 ( Jong Soon Park ),박보현 ( Bo Hyun Park ),박혜숙 ( Hyesook Park ),박미혜 ( Mi Hye Park ),전선희 ( Sun Hee Chun ),안정자 ( Jung Ja Ahn ) 대한주산의학회 2006 大韓周産醫學會雜誌 Vol.17 No.3

목적: 본 연구는 한국인 임신 여성에서 MTHFR 유전자형 변이와 혈청내 호모시스테인 및 엽산의 농도와 이들이 임신에 미치는 영향을 알아보고자 하였다. 방법: 임신부 600명에게서 혈액을 채취하여 얻어진 DNA로 MTHFR C677T와 A1298C 유전자의 다형성을 PCR-RELP로 분석하였고 혈청내 호모시스테인은 HPLC 방법으로, 엽산은 RIA 방법으로 측정하였다. 결과: 혈청내 호모시스테인은 MTHFR C677T 유전자형이 C/C형이나 C/T인 군에 비해 T/T인 군에서 유의하게 높았으며 MTHFR A1298C 유전자형이 A/C형이나 C/C인 군에 비해 A/A인 군에서 역시 유의하게 높았다( p<0.05). 혈청 호모시스테인은 모든 MTHFR 유전자형에서 혈청 엽산농도와 역상관관계를 보였으나, 변이형 유전자형(T/T와 A/A유전자형)에서 더 큰 역 상관관계를 보였다. 15?mol/L 이상의 고호모시스테인혈증의 임신부에서 임신 주수와 출생체중이 36.1주, 3053.8 g으로 15 ?mol/L미만인 군의 38.3 주, 3215.3 g 보다 유의하게 낮았다( p<0.05). 결론: 혈청 호모시스테인의 농도는 MTHFR C677T와 A1298T 유전자의 다형성에 의해 영향을 받으며, MTHFR C677T와 A1298T 유전자의 다형성과 혈청 호모시스테인은 모두 임신주수와 신생아의 체중에 영향을 미친다. Objective: The purpose of this study was to analyze MTHFR polymorphism among the Korean population and to evaluate the relationship between serum levels of homocysteine and MTHFR polymorphism and also to investigate the effect on pregnancy outcomes. Methods: DNA was extracted from whole blood of 600 pregnant women. All samples were genotyped for the C677T and A1298C polymorphisms in MTHFR gene by PCR-RELP assay. Serum levels of homocysteine and folate were measured by high performance liquid chromatography for homocysteine and radioassay for folate. Pregnancy outcomes were estimated by gestational weeks and birth weights of newborns. Results: Serum homocysteine was higher in women with the T/T genotype than those with the C/T or C/C genotype of the MTHFR C677T polymorphism (p<0.05). And also serum homocysteine was higher in women with the A/A genotype than those with the A/C or C/C genotype of the MTHFR A1298C polymorphism (p<0.05). Serum homocysteine was negatively correlated with serum folate in all MTHFR genotypes, especially prominent in T/T genotype of MTHFR C677T polymorphism and A/A genotype of MTHFR A1298C polymorphism. Gestational age and the birth weight of infant from hyperhomocysteinemic mothers whose homocysteine levels higher than 15 μmol/L were 36.1 weeks, 3053.8 g, respectively, which were significant lower than those from normohomocysteinemic mothers (38.3 weeks, 3,215.3 g) (p<0.05). Conclusion: Serum homocysteine was influenced significantly by MTHFR C677T polymorphism and MTHFR A1298C polymorphism. MTHFR C677T and A1298C polymorphism and serum homocysteine levels affect pregnancy outcomes, although not mainly by serum folate level.

Gynecologic manifestation and identification of genetic causes of Klippel-Trenaunay syndrome

( A Mi Roh ),( Sa Ra Lee ),( Young Mee Lim ),( Kyung Ah Jeong ),( Hye Sung Moon ),( Hyewon Chung ) 대한산부인과학회 2018 대한산부인과학회 학술대회 Vol.104 No.-

Klippel-Trenaunay syndrome (KTS) is a congenital disorder characterized by malformations of the arteries, capillaries, veins and lymphatic system, surrounding soft tissue and bone hypertrophy. A. Timur et al. (2005) and others have reported that AGGF1 gene causes excessive angiogenesis in KTS. In addition, Fabio C. Vicentini (2006) and others introduced cases involving bladder and vulva. However, there has been no genetic study of KTS patients who have invaded the clitoris. In this study, whole genome sequencing of KTS patients and their families involving vulva were performed to identify KTS - related genes and to confirm genetic variants in KTS. A 26 year old woman visited OBGY clinic for protruding vaginal mass. On examination, the purplish protruding anterior vaginal wall was noted and a 1.5 x 1.5 cm sized clitoral mass was also noted. A sessile type elevated skin lesion causing itching and irritation symptom was noted on both buttock. She had suffered heavy menstrual bleeding and on pelvic MRI, a upward displacement of uterus was noted near umbilicus level. NSAIDs prescribed onthe first 3 days of menstruation decreased the menstrual blood loss upto 40percent. In this study, whole genome sequencing of a KTS patient involving vulva was performed to identify KTS - related genes and to confirm genetic variation. The patient's peripheral blood and a sessile mass around buttock was sampled and whole genome sequencing was performed. Most KTS has known to be a sporadic one, however some genetic variants has been reported.