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        A selective cyclin-dependent kinase 4, 6 dual inhibitor, Ribociclib (LEE011) inhibits cell proliferation and induces apoptosis in aggressive thyroid cancer

        Lee, Hyun Joo,Lee, Woo Kyung,Kang, Chan Woo,Ku, Cheol Ryong,Cho, Yoon Hee,Lee, Eun Jig Elsevier 2018 Cancer letters Vol.417 No.-

        <P><B>Abstract</B></P> <P>The RB-E2F1 pathway is an important mechanism of cell-cycle control, and deregulation of this pathway is one of the key factors contributing to tumorigenesis. Cyclin-dependent kinases (CDKs) and Cyclin D have been known to increase in aggressive thyroid cancer. However, there has been no study to investigate effects of a selective CDK 4/6 inhibitor, Ribociclib (LEE011), in thyroid cancer. Performing Western blotting, we found that RB phosphorylation and the expression of Cyclin D are significantly higher in papillary thyroid cancer (PTC) cell lines as well as anaplastic thyroid cancer (ATC) cell lines, compared with normal thyroid cell line and follicular thyroid cancer cell line. LEE011 dose-dependently inhibited RB phosphorylation and also decreased the expressions of its target genes such as <I>FOXM1, Cyclin A1,</I> and <I>Myc</I> in ATC. Furthermore, LEE011 induced cell cycle arrest in G0-G1 phase and cell apoptosis, and inhibited cell proliferation in ATC. Consistently, oral administration of LEE011 to ATC xenograft models strongly inhibited tumor growth with decreased expressions of pRB, pAKT and Ki-67, and also significantly increased tumor cell apoptosis. Taken together, our data support the rationale for clinical development of the CDK4/6 inhibitor as a therapy for patients with aggressive thyroid cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> pRB and Cyclin D were expressed high in aggressive thyroid cancer. </LI> <LI> LEE011 suppressed pRB and also decreased the expressions of its target genes in ATC. </LI> <LI> LEE011 induced cell cycle G1 arrest and apoptosis, and inhibited cell proliferation. </LI> <LI> LEE011 inhibited in vivo tumor growth with decreased expressions of pRB and Ki-67. </LI> <LI> We could explain the anticancer effects with the RB-E2F pathway. </LI> </UL> </P>

      • SCOPUSKCI등재

        간호실무에서 신봉이론(Espoused theories)에 대한 탐색적 연구

        서문자,김혜숙,이은희,박영숙,조경숙,강현숙,임난영,김주현,이소우,조복희,이명하,지성애,하양숙,손영희,권성복,김희진,추진아 성인간호학회 2001 성인간호학회지 Vol.13 No.1

        As a nursing practice involves nurses' actions in a specific context of health care, this study has focused on exploring the espoused theories in nursing practice within the action science perspectives, Espoused theories are the belief, principles, and rationale expressed by the practitioner as guiding her/his actions in a situation of practice. The data were analysed qualitatively and 25 elements of espoused theories of nursing action were identified and clustered into 6 categories. The 25 elements of espoused theories are as follows: The clinical nurse worked in wholistic and individual nursing, focussed on the patient's needed, comfort and supportive nursing (5 theories of nursing goal) ; excellent skills, knowledge based, assessment and data collection, explaining, educating or a scientific basis(6 theories of nursing intervention): advocacy, value oriented, treatment, account- ability and commitment(4 theories of nursing ethics) ; human respect. partnership, trust(3 theories of patient-nurse relationship) : knowledgable, accumulated clinical experiences and personally lived experiences. positive perspectives(4 theories of nurse), role of intervention. rewarding peer relationship(3 theories of situations) The above mentioned espoused theories are similar to that of nursing textbooks which students learned through basic nursing education and almost the same as the Acts ofa Nurse in Korean. However, we are doubtful whether nurses actually do as they think. Therefore. it is recommended to review the theories-in-use in order to and any discrepancies between the espoused theories and the reality of nursing actions

      • 대학생 흡연자의 금연경험에 따른 건강신념차이

        구정일,김민정,김동희,백정희,안현실,은가희,우혜령,이명희,이수현,김수지 이화여자대학교 간호과학대학 2003 이화간호학회지 Vol.- No.37

        It has been generally known that smoking is one of the worst factor increasing disease and mortality in human health since in 1950's and nowadays. But regardless of various proofs about social or economical problems due to smoking, current smoking rate has not been decreased in our country. Until now, most of tobacco use and its addiction researches have been focused on the adolescent or adult women smokers not on the university students. Therefore, the purpose of this study was to investigate smoking cessation of university smokers and analyze the health belief-perceived sensitivity, severity, benefits and barriers- difference, then to provide basic data for effective smoking cessation strategy for university smokers. The subjects were comprised of 181 university smokers from 15 universities in Seoul. The data were collected by structured questionaires. The questionaires were designed to measure general characteristics, smoking cessation and health belief, based on Ahn(2003)'s result on the Study of Smoking attitude, Behavior and Smoking Cessation of Adult Male and Lee(1987)'s result on Relationships Between the Health Belief Model and Smoking Habits. The data were collected from May 5 to 16. The collected data were analyzed by SPSS program. The actual number, percentiles, means, standard deviation, t-test and ANOVA were done. The result of this study were as follows; 1. The general characteristics of the subjects of this study The range of age was from 18 to 34 and the averaging age was 23. The subjects of this study were 141 males and 40 females. The religions were Christianity 25.4%(46), Buddhism 12.7%(23), Catholic 23.2%(42), no religion 37.0%(67). The residential forms were living with family 59.1%(107), cooking food for oneself 28.7%(52), dormitory 5.0%(9), boarding house 1.7%(3). Smoking starting age were university 43.1 %(78), high school 29.8%(54), middle school 14.9%(27), in the army 6.1 %(11), elementary school 1.1 %(2). 2. The smoking cessation of the subjects 80% of current smokers showed quitting smoking decision and 20% have not tried. The frequency of quitting smoking decision were from 1 to above 8 and mean was 3.06. As for smoking cessation plan, 54.7%(99) current smokers answered yes, 3.9%(7) said no, 35.4%(64) had no idea and 6.1 %(11) didn't answer. As for the reason of never quitting smoking decision, 71.42%(25 among total 35) have no need to quit smoking and the others said difficulty of smoking cessation. As for the main reason of smoking cessation decision, 54.7%(99) answered for the health, 7.2%(13) family advice, 15.5%(28) girl/boy friend's advice, 1.7%(3) to save money. As for the reason to fail smoking cessation, 56.7%(68) were will-lack, 17.5%(21) stress, 15%(18) smoking mood, 10%(12) withdrawl symptom. As for the smoking cessation method, 85.0%(125) were oneself-will, 2.7%(4) way acquired by mass-media, 2%(3) doctor's prescription, 2%(3) religion's help, 0.7%(1) smoking cessation school. As for the difficulty in smoking cessation, 42.2%(62) were drinking meeting, 23.1 %(34) no alternative of stress release, 12.2%(18) withdrawl symptom, 11.6%(17) having nothing to do, 7.5%(11) friend's encouragement. As for the most difficult cigarette to quit, 67.8%(99) were all-day smoking except the first smoking in the morning, 32.2%(47) the first smoking in the morning. 3. Health belief as for general characteristics Gender - The total point in benefits showed higher in male(28.5177) than female(26.6750). There was significant difference(t=.778, p<.05). The total point in health belief showed higher in male (105.8298) than female(l00.5000). So there was significant difference(t=.345, p<.05). Age - There was significant difference in benefits between age(10's-25.83, 20's-28.39, 30's-32.00)(F=3.73, p<.05). Smoking starting age - There was significant difference in total point of sensitivity and health belief(sensitivity F=4.00, p<.Ol, health belief F=2.843, p<.05). As for sensitivity, subjects who started smoking in the army showed the highest(33.36) and ones in high school showed the lowest(26.96). The total point in health belief showed the highest in elementary school(l19.00) and the lowest in high school(100.98). 4. Health belief as for smoking cessation There was significant difference in health belief as for smoking cessation(t=0.189, p=0.OO2). Sensitivity point showed higher in smoking quitting trial smokers(29.2) than non-trial smoker (26.9). Severity point showed higher in trial smokers (30.7) than non-trial smokers(28.9). Benefit point showed higher in trial smokers(28.6) than non-trial smokers(26.2). There was no significant difference in barriers point.

      • 경연 대회를 통한 초ㆍ중고생의 창의력 신장 효과에 관한 연구

        이희복,육근철,류해일,김현섭,김희수,박달원,유병환,김선효,김여상,서광수,변두원,서명석,배성효,박종석,심규철,이성희 공주대학교 과학교육연구소 2001 과학교육연구 Vol.32 No.1

        미래 사회를 대비하기 위한 개인의 개성을 존중과 창의적인 능력을 지닌 인간을 양성을 목적으로 충청남도 지역의 초 ㆍ 중고등학생들을 대상으로 한 창의력 경연대회가 공주대학교 과학교육연구소에서 개최되었다. 충청남도 초 ㆍ중 ㆍ 고등학생들을 대상으로 실시한 창의력 경연대회는 창조적 아이디어를 내어 스스로 문제를 해결해 나갈 수 있는 교육 프로그램을 제공하는 좋은 기회였음이 확인되었으나, 일부의 팀에서만 참신하고 재미있는 아이디어들이 제안되었다. 여학생의 참가자 수가 상당히 증가하였으며, 대체적으로 입상권의 학생들의 상당 부분이 여학생이라는 것이 특이할만하다. 학년이 올라감에 따라서 창의적인 아이디어를 내는 양이나 질에 있어서 뒤떨어지는 것으로 분석되었으며, 토론 학습의 적응력이 미흡하고 발표력 및 청취력에 있어서도 떨어지는 것으로 나타났다. 따라서 중 ㆍ고등학교의 학교교육에서도 학생들에게 프로젝트형 탐구학습 프로그램의 적용은 물론 토론식 수습을 통한 학생들의 사고의 전환의 기회를 제공해야 할 것으로 사료된다. The creativity competition was held to foster the creativity of elementary and secondary school students in the Institute of Science Education, Kongju national University. It was found that the creativity competition effected on the improvement of inventing creative ideas and problem solving activities. But, only some competitors participated in semifinal and final contests, presented original and interesting ideas. More female students participated in competition than last year. More female participants were awarded a prize than males. Totally, participants were defective in discussion and communication, and presentation and listening ideas. Increasing grades correlated inversely with creativity and originality. There is need of inquiry project teaming programs and presenting opportunities of conversion of thinking by discussing instructions in school

      • 중증 재생불량성빈혈에서 타인 혹은 HLA 불일치 혈연간 골수이식을 위한 cyclophosphamide와 antithymocyte globulin전처치 요법

        이정희,이제환,김신,설미이,이정신,김우건,김상희,지현숙,박찬정,이규형 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.1

        배경: Cyclophosphamide와 ATG의 전처치 요법은 HLA가 일치하는 형제간 골수이식에서는 매우 효과적인 것으로 알려져 있으나, 타인 혹은 HLA 불일치 혈연간 골수이식에서는 전처치 요법으로서 불충분한 것으로 보고되었는데, 주요 문제는 착상 부전이었다. 우리나라를 포함하는 극동아시아 지역의 국가들에서 발표되는 보고에 의하면 타인이식을 포함하여 골수이식 후 착상 부전과 이식편대숙주질환의 발생이 서구 국가들로부터의 보고에서보다 적은 것으로 알려져 있다. 저자 등은 6예의 중증 재생불량성빈혈 환자들에서 질병 초기에 Cyclophosphamide와 ATG만을 이용하여 전처치를 한 후에 타인 혹은 HLA 불일치 혈연간 골수이식을 시행하였다. 방법: 1999년 5월부터 2000년 4월까지 서울중앙병원에서 타인 혹은 HLA 불일치 혈연간 골수이식을 시행 받은 성인 중증 재생불량성빈혈 환자들을 대상으로 하였다. 골수이식을 위한 전처치 요법으로 cyclophosphamide (50 mg/kg/d x 4)와 ATG (30 mg/kg/d x 3)를 투여하였는데, 골수이식 전에 ATG에 대하여 과민 반응을 보였던 한 예 (UPN 120)에서는 ATG 대신에 fludarabine (30 mg/m2/d x 3)을 투여하였다. 이식편대숙주질환의 예방을 위하여 cyclosporine과 methotrexate를 투여하였다. 결과: 연구 기간 중에 모두 6예가 타인 혹은 HLA 불일치 혈연간 골수이식을 시행 받았는데, 5예는 타인으로부터 골수를 공여 받았으며, 1예는 HLA의 표현형이 하나의 유전자좌에서 일치하지 않는 형제로부터 골수를 공여 받았다. 타인 골수이식을 받은 5예 중에서 3예의 공여자는 HLA의 표현형이 일치하였으며, 1예는 하나의 유전자좌가 major mismatch였고, 1예는 하나의 유전자좌가 minor mismatch였다. 추적기간의 중앙값은 406일 (범위, 328-643일)인데, 6예 모두에서 착상된 상태를 유지하면서 생존해있다. 2예에서 3도의 급성 이식편대숙주질환과 전신성 만성 이식편대숙주질환이 발생하였다. 결론: Cyclophosphamide와 ATG의 전처치 요법은 재생불량성빈혈의 초기에 타인 혹은 HLA 불일치 혈연간 골수이식을 시행 받은 한국인 환자들에서 충분히 착상을 가져올 수 있는 요법으로 생각된다. 비록 본 연구의 대상 환자 수가 적지만 결과는 매우 고무적이다. HLA가 일치하는 형제가 없는 중증 재생불량성빈혈 환자의 경우에 타인 골수 공여자에 대한 검색을 조기에 시행해야 하며, 타인 혹은 HLA 불일치 혈연간 골수이식을 질병 초기에 적극적으로 고려해야 할 것으로 생각된다. Background: Cyclophosphamide (CY) and ATG regimen was reported to be insufficient for alternative donor BMT in SAA patients due to high incidence of graft rejection. The rates of graft rejection and GVHD after allogeneic BMT including unrelated donor transplants seemed to be lower in reports from Asian countries of Far East. We applied CY/ATG regimen to six patients with early stage of SAA transplanted with marrow from alternative donors other than HLA-identical siblings. Methods: Three patients were transplanted from HLA-phenotypically identical unrelated donors, two from one-locus mismatched unrelated donors, and one from an one-locus mismatched sibling donor. Four patients received no previous therapy for SAA, and two received one course of immunosuppressive therapy with ATG. Preparative regimen was CY (200 mg/kg) plus ATG (90 mg/kg) in all patients except one who had had an anaphylactic reaction to ATG prior to BMT and received fludarabine (90 mg/m2) in place of ATG. Cyclosporine plus methotrexate were given for GVHD prophylaxis. Results: All six patients engrafted and all are alive with durable engraftment at a median follow-up of 406 days (range, 328 to 643). Two patients developed grade III acute GVHD and extensive chronic GVHD. Conclusions: CY/ATG regimen may be sufficient in Korean patients with early stage of SAA transplanted with marrow from alternative donors. Although the number of patients in present study is small, results are encouraging. Stem cell transplantation using alternative donors may be considered at early stage of aplastic anemia.

      • 평면형 Bi-Sb 다중접합 열전변환기의 특성

        이현철,유호종,김진섭,함성호,신장규,이종현,이정희,권성원,박세일 경북대학교 센서기술연구소 1997 센서技術學術大會論文集 Vol.8 No.1

        A planar Bi-Sb multijunction thermal converter for the precise measurements of ac voltage and current has been fabricated and its characteristics was discussed. In order to convert ac power into heat, a bifilar thin film Pt-heater, which could cancel its Thomson and Peltier effects, was prepared on the Si_(3)N_(4)/SiO_(2)/Si_(3)N_(4) diaphragm for the thermal isolation between heater and silicon substrate. To convert the temperature or the heat generated by the heater into dc voltage and current, hot and cold junctions of the Bi-Sb thermopile, which has a large difference in Seebeck coefficients, were formed on the dielectric diaphragm and the silicon substrate, respectively. The respective thermal sensitivity of the thermal converter with a bifilar heater was about 10.1 mV/mW and 14.8 mV/mW in the air and vacuum, which is about eight times higher than that of commercial 3-dimensional thermal converter. In the case of ac 2 V-input voltage, the ac-dc voltage transfer difference was about ±2.0 ppm, and in the case of ac 10 mA-input current, the ac-dc current transfer difference was about ± 0.6 ppm, in the frequency range from 10 Hz to 10 kHz.

      • KCI등재

        Alterations in DNA methylation patterns in regenerated Chinese cabbage (Brassica rapa ssp. pekinensis) plants derived from tissue culture

        Hyun‑Min Lee,Jee‑Soo Park1,Yun‑Hee Shin,박영두 한국원예학회 2021 Horticulture, Environment, and Biotechnology Vol.62 No.4

        Plant tissue culture is an essential tool in biotechnology. However, tissue-cultured plants often exhibit variations that are either genetic or epigenetic in origin, termed somaclonal variations. Among these variations, DNA methylation is an important heritable epigenetic modification that plays a role in a wide variety of biological processes, including gene expression. In this study, we performed bisulfite sequencing of regenerated Chinese cabbage (Brassica rapa ssp. pekinensis) lines to identify DNA alterations induced by tissue culture. Sequencing data from each regenerated line were compared with reference genome sequences, and common differentially methylated regions (DMRs) were detected in the regenerants. To determine changes in expression levels of DMR-containing genes, we performed quantitative reverse transcription-polymerase chain reaction (qRT-PCR) of the target genes and PCR amplification with bisulfite-converted DNA. We identified DMRs between a non-regenerant line and regenerant lines and selected 10 DMR-associated genes that presented annotation information in Arabidopsis or Brassica rapa. Their expression levels were verified by qRT-PCR to determine the relation between methylation state and gene expression. We observed that genes positioned in DMRs significantly correlated with differential gene expression. We also observed similar methylation patterns in the selected DMRs by PCR-based methylation analysis. The results of this study are a valuable resource for the epigenetic analysis of regenerated lines, especially for Chinese cabbage.

      • 성인에서 Haemophilus influenzae 감염증의 임상양상과 미생물학적 특성

        이종섭,황병연,정희진,김우주,박승철,이도현,이창규,신종희,황규잠,이영희 대한화학요법학회 2000 대한화학요법학회지 Vol.18 No.2

        목적 : H. influenzae는 성인에서 흔히 호흡기 감염을 일으키는 균주로, 최근 ampicillin 내성 β-lactamase 생성 균주들이 지속적인 증가를 보이고 있어, 이에 국내 성인에서 H. influenzae에 의한 감염의 임상양상과 분리된 균주들의 미생물학적 특성을 조사하고자 하였다. 방법 : 1998년 3월부터 1999년 9월까지 고려대 구로병원에 내원한 환자중에서 H. influenzae가 분리된 68명을 대상으로 임상양상을 조사하고 항균제 감수성 검사를 시행하였다. 분리된 33주에 대해서 혈청형, 생물형, 세포외막 단백분석을 시행하였고, β-lactamase 생성여부에 따른 감염 환자군간 임상상 및 예후의 차이를 비교하였다. 결과 : 환자의 평균연령은 68세였고, 지역사회 획득감염이 전체의 85%를 차지하였다. 폐렴과 기관지염과 같은 하기도 감염이 전체환자의 75%를 차지하였고 분리 검체 역시 객담이 84%로 가장 많았다. 환자의 71%가 기저질환을 가지고 있었으며, 그 중에 만성 폐쇄성 폐질환, 심혈관 질환, 악성종양, 당뇨병이 대부분이었다. 혈청형으로는 nontypeable 형이 68%로 가장 많았고 b형은 한 예도 없었다. β-lactamase 생성율은 63.2%였고, β-lactamase 양성균주의 항균제 내성율이 음성균주에 비하여 높았으나 β-lactamase 생성 여부에 관계없이 cefotaxime, azithromycin, ciprofloxacin에 대하여 100%의 감수성을 나타내었고 cefaclor, cefuroxime에 대해서는 10% 이하의 낮은 내성율을 보여 이들 항균제들이 치료에 효과적일 것으로 사료된다. 세포외막 단백분석에서는 C형과 D형이 전체의 64%로 가장 많았으며, 혈청형과의 유의한 연관성은 보이지 않았다. 결론 : 성인에서 H. influenzae는 주로 만성 기저질환자에서 급성 호흡기감염 또는 만성 폐쇄성 폐질환의 급성 악화를 유발한다. 기존의 보고에 비해 β-lactamase 양성율이 증가하였고, 이에 따른 항균제 내성율도 증가하여 항균제의 선택에 유의하여야 할 것으로 생각된다. 세포외막 단백분석상 특정한 유형의 균주에 의해 감염이 집중적으로 발생하고 있어 향후 역학 조사의 도구로 이용할 수 있겠다. Purpose : H. influenzae is one of the common causative microorganisms of respiratory tract infections in adults. Recently. β-lactamase producing, ampicillin-resistant H. infiuenzae has become worldwide problem as well as in Korea. We studied to investigate the clinical features and microbiologic characteristics of H. infiuenzae infections in adults. Materials & Methods : From March 1998 to September 1999, 68 patients were enrolled in this study. Clinical features of H. infiuenzae infections were investigated, 68 isolates were subjected to the β-lactamase test, and 33 isolates were used for serotyping. biotyping, antibiotic susceptibility and outer membrane protein (OMP) analysis. Results : Mean age of study patients was 68 years-old and the acquisition rate in community was 85%. Pneumonia and bronchitis were the most common type of infection such as 80%, sputum was the most common clinical specimen for H. mQuenzae isolation. 70% of patients had chronic underlying diseases. Non-typeable strains were 68% and β-lactamase producing rate was 63%. There was no difference in the clinical features and prognosis of H. influenzae infection between the β-lactamase positivie and -negative groups. The susceptibility of cefotaxime, azithromycin, and ciprofloxacin was 100% and that of cefaclor, cefuroxime was under 10% in spite of β-lactamase positivity. In OMP analysis, C and D types were dominant (64%). Conclusion : H. influenzae caused acute respiratory infections in adults with chronic underlying disorders. This study shows higher β-lactamase producing rate and antibiotic-resistance rate than that were reported previously. OMP analysis shows that two major types of strains cause clinical infections intensively.

      • KCI등재

        통합심리치료의 인지분화훈련이 정신분열병 환자의 기초 인지기능에 미치는 영향

        이희상,현명호,조현상,이연희,김태용,장순아,노규식,정기립,이만홍,유계준 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.5

        연구목적 : 정신분열별 환자들을 대상으로 통합심리치료의 소프로그램인 인지분화훈련을 실시하여 실행기능, 개념형성능력, 언어능력 및 추론력에 대한 훈련이 보다 더 하위단계의 인지기능인 주의력, 기억력, 반응시간 등을 호전시킬 수 있는 지를 알아보고자 하였다. 연구방법 : DSM-IV상 정신분열병으로 진단된 24명의 입원환자를 무작위로 양분하여 한 군은 인지분화훈련군으로 다른 한 군은 대조군으로 나누었다. 훈련군은 4주동안 1주일에 3회(매회 60분간)로 총 12회의 통합심리치료의 인지분화훈련을 받았으며 대조군은 동일한 시간동안 정신건강교육을 받았다. 훈련전후에 훈련군과 대조군을 대상으로 개정판 Wechsler 기억검사로 주의집중력, 장·단기 기억력을 측정하였고 Vienna test system중 결정반응시간검사로 반응시간, 반응결정시간, 반응운동시간을 평가하였다. 연구결과 : 1) 주의집중력에서는 훈련군과 대조군사이에 집단간 효과, 집단내 효과 및 상호작용 효과가 없었다. 2) 단기기억력에서는 훈련군과 대조군사이에 집단내 효과는 있었으나(F(1,24)=10.46. p〈.05). 집단간 효과, 상호작용 효과는 없었다. 3) 장기기억력에서는 훈련군과 대조군사이에 집단내 효과는 있었으나(F(1,24)=15.09. p〈.05). 집단간 효과, 상호작용 효과는 없었다. 4) 반응시간에서는 상호작용 효과(F(1,24)=5.18, p〈.05)가 있었다. 5) 반응운동시간에서는 집단간 효과, 집단내 효과 및 상호작용 효과가 없었다. 6) 반응결정시간에서는 상호작용 효과(F(1.24)=6.00, p〈.05)가 있었다. 결 론 : 통합심리치료의 인지분화훈련은 정신분열병 환자에서 하위단계의 인지기능 중 반응시간(특히 반응결정시간)을 단축시키는 효과가 있었다. Objectives : The purpose of this study was to investigate the effects of cognitive differentiation training of Integrated Psychological Therapy(a training program of executive function, concept formation, language, and abstraction) on micro-level cognitive function such as attention, memory and reaction time in patients time in patients with schizophrenia. Methods : Twenty-four inpatients diagnosed as schizophrenia using DSM-IV were randomly assigned to 2 groups. The training group went through a total of 12 sessions of cognitive differentiation training for 4 weeks. The control group received psychoeducation program during the same period. Wechsler Memory Scale-Revised and Decision-Reaction Timer of Vienna Test System were administered to all patients, both before and after the training program. Results : 1) In the attention and concentration scores of Wechsler Memory Scale-Revised, between group, within group and interaction effects of training were not significant. 2) In the short-term memory scores of Wechsler Memory Scale-Revised, within group effect of training was significant(F(1,24)=10.46, p〈0.05), but the between group and interaction effects did not reach significance. 3) In the long-term memory scores of Wechsler Memory Scale-Revised, within group effect of training was significant(F(1,24)=15.09, p〈0.05), but the between group and interaction effects did not reach significance. 4) In the reaction time scores of Decision-Reaction Timer, interaction effect of training was significant(F(1,24)=5.18, p〈0.05). 5) In the motor time scores of Decision-Reaction Timer, between group, within group and interaction effects of training were not significant. 6) In the decision time scores of Decision-Reaction Timer, interaction effect of training was significant(F(1,24)=6.00, p〈0.05). Conclusion : Our findings suggest that cognitive differentiation training of Integrated Psycho-logical Therapy is partly effective on improving micro-level cognitive functions such as reaction time(especially, decision time) in patents with schizophrenia.

      • Gilbert 증후군에서 열량 제한 시험과 Phenobarbital 자극 시험의 의의(14예)

        이헌영,채경훈,정재훈,강윤세,김연수,문희석,박기오,이엄석,김선문,김석현,성재규,이병석,이강욱 충남대학교 의학연구소 2003 충남의대잡지 Vol.30 No.2

        Gilbert 증후군은 인구의 7%에서까지 나타날 수 있는 매우 흔한 증후군으로서 비진행성인 양성의 만성적 경과를 치하며, 간질환의 증상과 징후가 없는 경한 비포합형 고빌리루빈혈증이 특징인 일종의 체질적인 증상으로서 혈장 빌리루빈 농도에 대한 사춘기의 영향 때문에 10대와 20대에 자주 진단이 된다. 따라서 임상적인 중요성은 미약하지만 높은 빈도가 예상되는 점에 그 중요성이 부여되어야 할 것이다. 따라서 적정한 임상적 진단법으로 기왕에 소개된 열량제한 시험과 phenobarbital 유도 시험을 시행하고 이들의 진단적 가치를 알아보기 위하여 본 연구를 시행하였다. 1990년 7월부터 1999년 4월까지 충남대학교병원에 내원하여 HBsAg, IgG anti-HBc 및 anti-HCV가 음성이고, 간 초음파 스캔에서 이상이 없으며, 혈청 AST, ALT 및 AP가 정상인 비음주자에서 경한 비포합형 고빌리루빈혈증이 있는 14예의 환자들을 대상으로 ^(99m)Tc-DISID 스캔을 시행하였으며, 기저 치 총빌리루빈 및 포합형 빌리루빈 치를 측정한 다음에 하루에 400Kcal로 48시간동안 제한한 열량 제한 시험을 시행하였고, phenobarbital을 하루 60mg씩 5일간 투여한 후에도 각각 총빌리루빈과 포합형 빌리루빈 치를 검사하여 비포합형을 구하였다. 대상 환자들은 모두 14예로서 남자가 11예(78.6%)였고 여자가 3예(21.4%)여서 3.7:1로 남자에서 많았으며, 20대가 6예(42.9%), 30대가 역시 6예(42.9%) 및 40대가 2예(14.2%)로서 2,30대가 대부분(85.8%)이었다. 열량 제한 시험 후의 총빌리루빈 치, 비포합형 및 포합형 빌리루빈 치들은 평균 각각 5.5±2.7, 4.2±2.3 및 1.3±10mg/dL 로서, 시험 전 치들인 3.0±0.8, 2.2±0.8 및 0.7±0.4mg/dL 보다 유의하게(p=0.001, p=0.001, p=0.023) 상승하였다. 포합형 빌리루빈 치도 유의하게 상승하였으나 비포합형의 상승보다는 훨씬 낮아서 주로 비포합형이 증가하였다. phenobarbital 투여 중 설사가 발생하여 중단한 1예를 제외한 13예에서 열량 제한 시험 후에 상승하였던 총, 비포합형 및 포합형 빌리루빈 치가 phenobarbital 유도 시험후에는 2.0±1.1, 1.5±0.8 및 0.5±0.4mg/dL로서 열량 제한 시험 결과보다 유의하게 낮아졌고(p=0.00, p=0.000, p=0.001), 열량 제한 시험 전의 기초치들인 3.0±0.8, 2.2±0.8 및 0.7±0.4mg.dL 보다도 더욱 낮아졌으며 유의한 차이(p=0.001, p=0.02, p=0.005)를 나타내었다. 14예에서 시행한 ^(99m)-Tc DISIDA 스캔에서 9예(64.3%)가 정상이었고, 5예(35.7%)에서는 심장 및 신장으로의 간외 섭취가 3예였고, 60분까지 소장 배출이 없는 배설 지연 예와 담낭 수축 불량 예가 각각 1예 씩 발견되었다. Phenobarbital 투여시험에서 민감도가 열량제한시험에 비해 더 높았다(92.3%와 50.0%). Gilbert 증후군에서 1일 400 Kcal로 48시간의 열량제한 시험과 1일 60mg의 phenobarbital을 5일간 투여하는 유도 시험은 편리하고 유용한 임상적인 진단법으로 이용할 수 있다고 생각된다. 그러나 열량 제한 시험에서는 증가 기준의 통일이 필요하다고 유추되며 phenobarbital 유도 시험이 민감도가 더 높은 것으로 생각된다. Gilbert's syndrome is very frequent and benign chronic process characterized by mild, intermittent, unconjugated hyperbilirubinemia without any symptom and sign of liver disease. Previously intoduced caloric restriction test and phenobarbital stimulation test as two appropriate clinical tests had been examined and their diagnostic values were reevaluated. Fourteen patients with mild, persistent, unconjugated hyperbilirubinemia were included. Subsequently caloric restriction has been applicated by 400 Kcal/day for 48 hours and phenobarbital has been prescribed by 60 mg/day for 5 days. Therafter serum levels of total and direct bilirubin were measured. Most of the patients were third and fourth decade(85.8%) and male predominant. Each basal serum levels of total, indirect and direct bilirubin were 3.0±0.8, 2.2±0.8 and 0.7±0.4 mg/dL. After caloric restriction test, each levels were increased significantly to 5.5±2.7, 4.2±2.3 and 1.3±1.0 mg/dL(p=0.001, p=0.001, p=0.023). After phenobarbital stimulation test for 13 patients had been practiced, increased levels of each bilirubin after caloric restriction test were decreased significantly to 2.0±1.0, 1.5±0.8 and 0.5±0.4 mg/dL(p=0.000, p=0.000, p=0.001) and these levels were significantly lower than basal levels(p=0.001, p=0.02, p=0.005). The sensitivities of caloric restriction test were 85.7%, 50.0%, and 71.4%, 35.7%(1.0, 1.5 mg increase of total bilirubin and 1.0, 1.5 mg/dL increase of indirect bilirubin). The sensitivities of phenobarbital stimulation test were 93.2% and 92.3% at criteria of 1.5 mg/dL increase of total bilirubin and indirect bilirubin. On the diagnosis of Gilbert syndrome, caloric restriction test and phenobarbital stimulation test are convenient and useful diagnostic tools in clinical face. And also phenobarbital stimulation test has higher sensitivity than caloric restriction test. Furthermore, standardization of bilirubin increment would be necessary in caloric restriction test.

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