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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>

      • 폐내 기관지 낭종

        이석열,이숭진,박형주,이철세,이길노,김윤정,나주옥 순천향의학연구소;Soonchunhyang Medical Research Institute 2004 Journal of Soonchunhyang Medical Science Vol.10 No.2

        A 33-year-old female was admitted to our hospital due to removal of lung mass which indicentally detected Chest radiography. Chest computerized tomography revealed lung parenchymal cystic lesion. Open thoracotomy was done for diagnosis and therapy. Cystic lesion was communicated to bronchus and wedge resection including cystic lesion was done. Bronchogenic cyst is congenital disease and mainly locate in mediastinum. It is rare in lung parenchyme. Herein we report a case of intrapulmonary bronchogenic cyst.

      • KCI등재

        공기청정기의 일부 실내공기 오염물질 제거효율에 관한 연구

        이태형,김윤신,홍승철,이철민,김종철,전형진,김중호 한국환경과학회 2005 한국환경과학회지 Vol.14 No.5

        In this study, we investigated PM_(10), NO₂, and 1-hydroxypyrene(1-OHP) in urine at indoor environments which are 35 houses and 20 hospitals for using air cleaner and non-using air cleaner in Seoul metropolitan area and Kyoung-gi province from April, 2003 to February, 2004. Moreover, we examined effect of improvement for indoor air quality and health effect by concentration of 1-OHP also we investigated removal efficiency by air cleaner for PM_(10), NO₂, and 1-OHP that were 28.5%, 27.4%, and 42.1% respectively. Concentration of PM_(10), NO₂, and 1-OHP were 19.02±18.14μg/m³, 8.66±3.06ppb, and 0.19±0.18μg/g creatinine when air cleaner was no worked. The concentration for PM_(10), NO₂ and 1-OHP were 13.60+10.79μg/m³, 6.29±2.71ppb, and 0.11±0.10μg/g creatinine, respectively. It was significant statistically. Therefore, it is considered using the air cleaner to remove the partial pollutants in indoor environment and is positive effect for health.

      • GO-62 : Lower extremity edema in patients with endometrial cancer

        ( Myong Cheol Lim ),( Jeong Seon Lee ),( Jung Nam Joo ),( Sang Soo Seo ),( Sok Bom Kang ),( Sang Yoon Park ) 대한산부인과학회 2012 대한산부인과학회 학술대회 Vol.99 No.-

        The objective of this study was to investigate clinical manifestations of lower extremity edema (LEE) in endometrial cancer Medical records for LEE and/or responses to the Gynecologic Cancer Lymphedema Questionnaire (GCLQ) were evaluated in 177 patients with endometrial cancer Patients had a median age of 53 years. Sixty-seven patients (37.9%) had past (9 patients, 13.4%) and/or current patient-reported LEE (58 patients, 86.6%). Symptoms reported on the GCLQ in over 20% of respondents were swelling, numbness, aching , and heaviness. GCLQ total symptoms score was significantly higher in patients with current LEE. Most of the LEE (43/67, 64.2%) developed within 12 months after surgery and LEE lasted more than 6 months in most patients (56/59, 94.9%) Prospective clinical trials are needed to know the clinical significance, impact on quality of life, and preventive strategy of LEE in patients with endometrial cancer

      • KCI등재

        일 도농복합지역 저소득층 노인의 건강문제 분석 : 보건소 방문간호사업 대상자 중심으로

        고일선,,이태화,이경자,이정렬,임미혜,천의영,주윤미,이계철 노인간호학회 2005 노인간호학회지 Vol.7 No.2

        Purpose: The purpose of this study was to analyze the health problems of low-income aged with chronic illness living in urban-rural composite area. Method: The sample consisted of 440 aged who were receiving home care services from a public health center. MDS-HC was applied to analyze the health problems of the aged. Data were collected through a face- to-face interview by six trained interviewers from June 28 to July 15, 2004. Result: Subjects had average number of 8 health problems in both urban and rural area. Lack of preventive health care measure, pain, and visual function were the most frequent health problem. The rural aged had more pain, bowel management problems, compared to the urban aged having more urinary incontinence and indwelling catheter. There were many health problems related to falls and pressure ulcers with middle-old aged in urban, and old-old aged in rural area. Conclusion: The results of this study showed strategies for care intervention of low-income elderly to put in practice. Therefore, tailored-service for each subject should be provided.

      • KCI등재

        광원 및 광조사 방법에 따른 심미충전재의 중합수축

        이용근,윤태호,임범순,김철위 대한치과기재학회 2000 대한치과재료학회지 Vol.27 No.4

        The polymerization shrinkage of dental esthetic filling materials of five kinds of resin composite and three kinds of compomer was measured with a thermal dilatometer (Thermal Dilatometer, DIL 402C, TASC 414/3A Controller, Netzche, Germany) during polymerization with a halogen lamp curing unit (VIP, Bisco, U.S.A.) or a plasma arc curing unit (Flipo, Serial No. P03G02221, Lokki, France). The irradiation time of the halogen lamp was 40, 80 and 120 s with the intensity of 400 ㎽/㎠, and that of the plasma arc was 9 s. The pulse-cure mode with a halogen lamp was 5 s pre-polymerization at 200 ㎽/㎠, 3 minutes wait and then 120 s irradiation at 400 ㎽/㎠. From this experiment, the following results were obtained : 1.Depending on the irradiation source and mode, the amount of polymerization shrinkage after 14 minutes from the start of irradiation was significantly different in some materials. However, there was no significant difference in most of materials (p>0.05). 2.Most of the polymerization shrinkage occurred within two minutes from the start of irradiation except for pulse-cure. 3.In all the materials studied, the amount of polymerization shrinkage after 14 minutes from the start of irradiation was not different between the results from 120 seconds irradiation with the halogen lamp and these from pulse-cure (p> 0.05), and the amounts of shrinkage from a plasma arc was generally lower than those from other curing modes. 4.The amount of polymerization shrinkage after 14 minutes from the start of irradiation was not different between the results from 120 seconds irradiation with a halogen lamp and those from plasma arc (p>0.05) in all the eight materials studied.

      • 2-Fluorenyl chalcone 유도체의 합성과 가수분해반응에 관한 연구

        이기창,황성규,윤철훈,오세영 명지대학교 자연과학연구소 1995 자연과학논문집 Vol.12 No.-

        Fluorenyl chalcone 유도체를 합성하였고 25 ±1℃의 20% dioxane-H?O 혼합용매 중에서 자외선 분광광도법을 이용하여 pH 1.0~13.0까지의 넓은 pH범위에서 가수분해 반응속도를 측정하였다. 또한 Fluoreny chalcone 유도체의 pH변화에 따른 반응속도로 측정하고, 일반염기효과, 치환기효과 및 가수 분해 생성물 확인 등으로부터 Fluorenyl chalcone 유도체에 대한 가수분해 반응속도상수를 구하였다. 이들 유도체들은 pH와 무관한 부분과 수산화 이온농도에 비례하며, pH와 무관한 부분에서는 중성의 물분자가 첨가된다. 반응속도 상수 측정으로부터 Fluorency chalcon 유도체의 가수분해 반응은 비가역 1차 반응임을 확인하였고, 치환기효과로부터 전자유인성기에 의해 반응이 촉진되는 것을 알 수 있었다. 또한, 가수분해 최종 생성물은 확인 결과 2 ~acetyl fluorene과 벤즈알데히드였다. 이러한 실험결과를 토대로 하여 Fluorenyl chalcone 유도체에 대한 가수분해 반응 메카니즘을 제안하였다. Fluorenyl chalcone derivatives were synthesis, it was measured that hydrolysis made use of ultraviolet spectrophotometry at a wide pH 1.0 ~ 13.0 range in 20% dioxane-H?O solution, 25±1℃. On the basis of general base catalysis, substitutent effect and confirmation of hydrolysis product, it was measured the reaction rate of fluorenyl chalcone derivatives for the pH change. It maybe concluded that a part was unrelated to pH and another part was in proportion to concentration of hydroxide ion: Above pH 10.0, It was in propotion to concentration of hydroxide ion, a part having no concern with pH was added to the neutral H?O molecule. From the result of measurement the reaction rate, hydrolysis of fluorenyl chalcone derivatives confirmed to the irreversible first order through measurement the substituent effect, It was found that reaction rate was accelerated first order through measurement the substituent effect, It was found that reaction rate was accelerated by electron attracting group. Also, from the result of final product, there were 2-acetyl fluorene benzaldehyde.On the basis of these findings, Hydrolysis for the fluorenyl chalcone derivative was proposed a fitting mechanism.

      • KCI등재

        수완진동 증후군에서 신경장해의 조기진단을 위한 객관화된 방법

        윤재국,이헌,최나리,김석환,박형욱,이지호,유철인 大韓産業醫學會 2009 대한직업환경의학회지 Vol.21 No.2

        목적: 통각과 진동감각 역치검사 및 수부와 수지의 악력, 그리고 수지의 운동기능검사(태평) 등과 근로자들이 호소했던 증상에 대한 HAVS의 스톡홀름 워크샵 분류와의 관련성을 통해 좀 더 객관화된 신경학적 조기검사 방법을 찾고 타당성을 검증하고자 하였다. 방법: 2000년 1월부터 2007년 12월까지 수부진동에 폭로되고 수부의 불편함을 호소하여 진동 장해에 대한 검사를 시행한 497명의 근로자를 대상으로 하였다. 일차적으로 문진을 통해 직업력에 대해 알아보고 과거력을 조사했다. 대상자들의 스톡홀름 워크샵 분류에 따른 소견을 확인하고 수부의 말초 순환기능 검사(손톱압박, 수지피부 온도), 신경기능 검사(통각과 진동각 역치), 운동기능 검사(악력, 태평) 등을 시행하였다. 다른 질환의 감별을 위한 몇 가지 이학적 검사를 실시하고 스톡홀름 워크샵 분류에 따른 검사 결과들을 분석하였다. 결과: 사용 도구는 그라인더 단독 사용이 265명 (67.3%)으로 가장 많았으며 평균 노출 연수는 14.8년이었다. 통각과 진동감각에서 스톡홀름 워크샵 분류 단계에 따른 역치가 증가하는 경향을 보였으나 통각은 양측 모두 통계적인 유의성이 없었고, 진동감각은 125와 250 Hz에서 양측 모두 유의했다(p=0.006-0.038). 수부와 수지의 악력은 단계가 올라갈수록 감소하는 경향을 보였지만 수부와 수지 모두 우측에서만 통계적으로 유의했다 (p=0.041, p<0.01, p=0.034). 태평 첫수는 단계가 올라 가면서 전반적으로 태핑 첫수가 감소하였으며 좌측에서만 통계적으로 유의했다(p=0.002-0.019). 결론: 본 연구는 수부 진동 노출자들의 수부 불편함에 대한 신경계통을 초기에 정량적으로 객관화하여 진단할 수 있는 단일 방법은 아직 없으며 일상생활의 불편함과 스톡홀름 워크샵 분류 등을 통한 주관적인 증상에 더하여 수지 통각과 진동감각 역치검사, 수부와 수지 악력검사, 운동기능검사(태핑) 등을 통합하면 초기에 객관적으로 진단하는 것이 가능할 것으로 판단된다. Objectives: In order to determine find out the best methods for a more objective detection of neurologic abnormality in early hand ann vibration syndrome(HAVS), early with analyzing the validity of each of the detection methods was analyzed. We evaluated the relationships between the sensorineural stage of Stockholm-revised vibration syndrome classification and the results of several tests. Methods: 497 workers were investigated for symptom, exposure duration, the types of tools used, and medical history from January 2000 to December 2007. Pain sense threshold, vibrotactile threshold, hand grasp force, finger grasp force, and a finger tapping frequency test were performed by the workers. Results: The grinder(67.3%) was the most commonly used tool and the mean exposure duration was 14.8 years. Although the pain sense and vibrotactile threshold level tended to increase according to sensorineural stage of the Stockholm classification, there was statistically significant difference in the vibrotactile threshold of 125, 250 Hz (P=0.006~0.038) but not in the pain sense threshold. Hand and finger grasp force tended to decrease according to the sensorineural stage of Stockholm classification and there was statistically significant difference(P=0.041, <0.001, 0.034) only on the right hand side. The tapping frequency also generally decreased according to the sensorineural stage of the Stockholm classification and there was statistically significant difference (P=0.002~0.019) only on the left hand side. Conclusions: Although there is no single standardized method that can objectively diagnose the Sensorineural component of early HAVS early, the combination of subjective symptoms, the sensorineural stage of Stockholm classification, the pain and vibrotactile threshold test, the hand and finger grasp force, and the finger agility (tapping) test can objectively detect sensorineural component of HAVS early.

      • KCI등재

        광원의 종류에 따른 콤포짓트레진의 중합도

        윤태호,이용근,임범순,김철위 대한치과기재학회 2001 대한치과재료학회지 Vol.28 No.1

        콤포짓트레진의 중합도와 속도는 광원의 종류와 광조사 시간에 따라 영향을 받는다. 현재 할로겐 램프를 중합에 많이 사용하고 있으나 전구의 수명이 짧고, 시간경과에 따라 광선의 출력이 감소하므로 중합도는 낮아져 물성이 감소하고 수복물이 실패할 가능성도 높다. 이를 개선하기 위하여 콤포짓트레진 중합에 사용할 수 있는 LED (blue light emitting diode) 와 플라즈마 아크 기술이 소개되었다. 이 실험에서는 3 종의 광원(할로겐 램프, LED 및 플라즈마 아크) 에서 광조사시간을 달리하여 광에너지의 총량을 변화하는 조건으로 점주도가 서로 다른 3 종의 콤포짓트레진에서 깊이에 따른 중합도를 측정하여 각 광원의 효율성을 상호 비교하였다. 할로겐 램프, LED 및 플라즈마 아크 조사기로 광에너지 총량이 각각 8J/㎤와 16J/㎤ 이 되도록 중합하고 표면에서 1, 2, 3 및 4mm 위치에서 100㎛ 의 두께로 절단하였다. 시편 두께가 50~70㎛ 가 되도록 연마하고 FT-IR 로 표준기선법에 따라 중합직후의 중합도를 측정하였다. 중합방법 및 광조사 부위에서 깊이에 따른 평균 중합도를 계산하여 3 원 분산분석 및 Scheffe 의 방법에 따라 유의수준 0.05 에서 검정하였다. 이 실험에서 다음과 같은 결과를 얻었다. 재료, 깊이 및 광조사 시간 모두 전환율에 유의한 영향을 주었다(p〈0.01). 3 종 광원의 표층에서 1mm 깊이에서의 중합도는 저점도(RVN) 〉중점도(Z25) 〉응축형 콤포짓트레진(SRF) 순이었다(p〈0.05). 3종 광원의 중합도는 유의한 차이를 볼 수 없었다(p〉0.05). 3종의 조사광원 모두에서 광에너지 총량을 2배로 증가한 경우, 중합도는 2mm 깊이까지는 유의한 차이가 없었으나(p〉0.05), 3mm 부터는 광에너지 총량 증가에 따라 유의하게 증가하였다(p〈0.05).

      • 한국인에서 혈소판 당단백 Ⅱb/Ⅲa 유전자 다형성과 관동맥 성형술 후 재 협착과의 관계

        이민수,이정우,김보영,임대승,강정아,김정희,김윤철,성보영,최성준,성인환,전은석 충남대학교 의과대학 지역사회의학연구소 2000 충남의대잡지 Vol.27 No.2

        Platelet aggregation is the final pathway of acute coronary syndrome such as acute myocardial infarction and unstable angina. Platelet glycoprotein IIb/IIIa is a membrane receptor for fibrinogen and yon Willebrand factor and it plays an important role in platelet aggregation and in the pathogenesis of acute coronary syndrome. It is known that polymorphism of the gene that encoding platelet glycoprotein IIb/IIIa(PI^A1/A2) is strongly related to acute coronary syndrome in Caucasian, but not in Koreans. We investigated relationship between platelet glycoprotein llb/Illa gene polymorphism and restenosis of coronary artery after angioplasty in Koreans. Total 371 patients(M=251. F=120) were enrolled. Angioplasty group comprised 143 patients who underwent coronary angioplasty, and in the angioplasty group, restenosis group comprised with the 65 patients who had restenotic lesion over 50% of luminal diameter in follow-up coronary angiography. Normal group comprised 153 patients who had no significant angiographic lesion and variant angina group comprised 75 patients who were positive in ergonovine test. Genomic DNA was extracted from peripheral arterial blood. To determine the frequency of P1^A1/A2 genotype, polymerase chain reaction(PCR) was done and the product was restricted with Mspl. 3%. agarrose gel electrophoresis showed restriction fragment length polymorphism. Clinical profile and risk factor were also reviewed. Among all 371 patients of study group, genotype of only one patients in restenosis group if is proven to be PI^A1/A2 heterozygote. All patients of normal study group, no restenosis group, and the other patients in restenosis group have an PI^A1 homozygote genotype. In our study, platelet glycoprotein IIb/Illa polymorphism has no relationship with restenosis of the coronary artery after angioplasty in Koreans. But the genotypic frequency of platelet glycoprotein IIb/IIIa gene polymorphism in Koreans is concordant with that of previous studies.

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