관동맥질환에서 저밀도 지단백 입자 크기의 분포

임효영,김인숙,승기배,강동헌,전두수,장기육,박준철,이수영,홍순조,최규보 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.8

노화가 인체 중간엽 줄기세포로부터 조골세포로의 증식 및 분화에 미치는 영향

백기현,태현정,오기원,이원영,조정기,권순용,강무일,차봉연,이광우,손호영,강성구,김춘추 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.3

연구배경: 일반적으로 골다공증과 연관된 위험인자로는 연령, 폐경, 약물, 불충분한 칼슘섭취, 만성질환 및 운동부족 등이 있는데, 특히 노화가 진행할수록 골밀도가 감소하는 것은 잘 알려져 있다. 노화와 관련하여 진행되는 골소실은 조골세포 및 전구조골세포의 기능적 결핍에 의한 골형성의 감소가 주요한 요인으로 여겨지고 있다. 그 동안 연령이 조골모 세포의 양과 조골모 세포로부터 성숙조골세포로의 분화 및 증식에 미치는 영향에 대한 일부 보고들이 있었으나 아직 일치된 견해는 없는 형편이다. 방법: 다양한 연령의 사람으로부터 골수를 채취, 중간엽 줄기세포가 포함된 단핵세포를 분리한 후 조골세포로 분화하기 좋은 조건하에서 배양하였다. 대상군은다시 젊은군과 노령군으로 구분하여 다양한 변수를 비교 분석하였다. 일차배양에서는 CFU-F를 계수하여 골수내 중간엽 줄기세포의 수를 추산하였고, 칼슘측정을 통하여 기질의 무기화 정도를 비교하였다. 계대배양후 이차배양에서는 시기별로 알카리성 포스파타제 활성도를 측정하고 오스테오칼신 mRNA의 발현을 관찰하여 젊은군과 노령군 사이의 증식능 차이를 비교하였다. 또한 이차배양 시기별로 MTT 측정을 하여 양군간에 증식능 차이가 있는지 알아보았다. 결과: 1. 일차배양 15일째에 평균 CFU-F의 수는 젊은군에서 유의하게 많았다(젊은군 148.3±28.9, 노령군 54.3±9.1, p=0.02). CFU-F의 평균면적은 젊은군에서 넓은 경향을 보였으나 통계적으로 유의하지는 않았다. 2. 일차배양 17일 경과 후 양군간에 기질 칼슘 침착정도는 유의한 차이를 보이지 않았다(젊은군 103.6±50.6, 노령군: 114.0±56.5, p=NS). 3. 이차배양 10일째에 젊은군에서 알카리성 포스파타제 활성도가 고령군에 비해 유의하게 높았다(젊은군: 935.5±115.0 U/mg, 노령군: 578.4±115.7U/mg,p.0.05). 고령군에서는 시간 경과에 따른 변화가 미약했으며 전반적으로 알카리성 포스파타제의 활성도가 젊은군에 비해 낮았다. 4. 이차배양도중 오스테오칼신 mRNA의 발현은 배양시기별로 젊은군에 비해 고령군에서 더 낮은 경향을 관찰할 수 있었다. 5. 이차배양 10일과 15일에 젊은군에서 노령군보다세포증식이 유의하게 증가된 양상을 보였다(10앓 젊은군 0.73±0.05, 노령군 0.58±0.04, p=0.05, 15일; 젊은군 0.80±0.05, 노령군 0.70±0.03, p=0.05).결론: 이상의 연구에서 저자들은 노령군에서 젊은군보다 골수 내 중간엽줄기세포의 수가 적고, 노령군에서 유래한 전구조골세포의 성숙조골세포로의 증식 및 분화가 젊은군 보다 감소해 있는 것을 관찰할 수 있었다. Background: Osteoblasts originate from osteoprogenitor cells in bone marrow stroma, termed mesenchymal stem cells (MSCs) or bone marrow stromal cells. Each MSC forms colonies (colony forming units-fibroblasts [CFL-Fs]) when cultured ex vivo. There are some reports about the age-related changes of the number and osteogenic potential of osteoprogenitor cells, but any relationship has not been clearly established in humans. In this study, we counted MSCs using CFU-Fs count and examined the proliferative capacity and differentiation potential of osteoprogenitor cells. Finally, we analyzed how these parameters varied with donor age. Methods: Bone marrow was obtained from the iliac crest of young (n=6, 27.2±8.6 years old) and old (n= 10, 57.4k6.7 years old) healthy donors. Mononuclear cells, including MSCs, were isolated and cultured in osteogenic medium. In primary culture, we compared the colony-forming efficiency of MSCs between the two groups and determined the matrix calcification. When primary culture showed near confluence, the cells were subcultured. Alkaline phosphatase activity, osteocalcin expression by RT-PCR and proliferative potential by MTT assay were examined by the time course of secondary culture. Results: At the 15th day of primary culture, the mean number of CFU-Fs was significantly higher in the younger donors (young: 148.3±28.9, old: 54.3±9.1, p=0.02) and the mean size of CFL-Fs was also larger in the younger donors than the older donors. However, matrix calcification was not different between the two groups (young: 103.6±50.6, old: 114.0±56.5, p=NS). In secondary culture, alkaline phosphatase activities were significantly lower in the older donors. The younger donors showed peak alkaline phosphatase activity at day 10, while the older donors didn't showed a remarkable peak (young: 935.5±115.OU/mg, old: 578.4±115.7U/mg, p<0.05). Total cell number as a proliferative index increased progressively during the secondary culture and a significantly greater cell number was noted in the younger donors. Osteocalcin expression was generally upregulated in the younger donors, but this was not statistically significant. Conclusion: Our study shows that the number of osteoprogenitor cells is decreased during aging and that the proliferative capacity and differentiation potential of osteoprogenitor cells seem to be reduced during aging (J Kor SOC Endocrinol 18:296-305, 2003).

정신분열병에 대한 리스페리돈의 효과 및 안정성

이민수,김용구,김영훈,연병길,오병훈,윤도준,윤진상,이철,정희연,강병조,김광수,김동언,김명정,김상훈,김희철,나철,노승호,민경준,박기창,박두병,백기청,백인호,손봉기,손진욱,양병환,양창국,우행원,이정호,이종범,이홍식,임기영,전태연,정영조,정영철,정인과,정인원,지익성,채정호,한상익,한선호,한진희,서광윤 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.1

연구목적 : 본 시험의 목적은 임상시험 시작전에 연구자들을 대상으로 PANSS Workshop을 통하여 PANSS, ESRS에 대한 국내에서의 표준화 작업을 구축하고 새로운 정신병 치료제인 리스페리돈의 효과와 안정성을 재확인하여 리스페리돈 사용에 대한 적정화를 이루는데 있다. 연구방법 : 1996년 4월부터 1996년 9월까지 국내 39개 대학병원 정신과에 입원중인 혹은 증상이 악화되어 입원하는 정신분열병 환자 377명을 대상으로 다시설 개방 연구를 시행하였다. 1주일간의 약물 배설기간을 가진후, 리스페리돈을 8주간 투여하였고, 기준점, 1주, 2주, 4주, 그리고 8주후에 평가되었다. 용량은 제1일에는 리스페리돈 1mg씩 1일 2회, 제2일에는 2mg씩 1일 2회, 제3∼7일에는 3mg씩 1일 2회 투여하였다. 이후 환자의 임상상태에 따라 임의로 증량할 수 있으며, 최대 일일 16mg을 초과하지 않도록 하였다. 추체외로 증상을 조절하기 위한 투약을 허용하였다. 임상증상 및 부작용의 평가는 PANSS(Positive and Negative Syndrome Scale), CGI(Clinical Global Impression) 그리고 ESRS(Extrapyramidal Symptom Rating Scale)을 사용하였다. 연구결과 : 377명중 343명(91%)이 8주간의 연구를 완결하였다. 치료 종결시점인 8주후 PANSS 총점수가 20% 이상 호전된 경우를 약물 반응군으로 정의할때, 약물반응군은 81.3%였다. 리스페리돈에 반응하는 예측인자로는 발병연령, 이전의 입원 횟수, 유병기간이 관련 있었다. 리스페리돈은 1주후부터 PANSS양성, 음성, 및 일반정신병리 점수상에 유의한 호전을 보여 효과가 빨랐다. CGI의 경우도 기준점에 비해 1주후부터 유의한 감소를 나타내었다. ESRS의 경우, 파킨슨 평가점수는 기준점과 비교해 투여 1주, 2주, 4주후 유의하게 증가되었다가 8주후 기준점과 차이가 없었다. Dystonia 평가점수는 1주후만 유의한 증가를 보였으며, dyskinesia 평가점수는 유의한 차이가 없었다. 혈압, 맥박수의 생명징후 및 일반 혈액학 검사, 생화학적 검사, 심전도 검사에서 유의한 변화는 없었다. 결 론 : 이상의 다시설 개방 임상 연구를 통해 리스페리돈은 정신분열병 환자에서 양성증상뿐만 아니라 음성증상 및 전반적인 증상에도 효과적인 것으로 사료된다. 보다 명확한 평가를 위해서는 다른 항정신병약물과의 이중맹검 연구가 필요할 것으로 생각되며, 또한 장기적 치료에 대한 평가도 함께 이루어져야 하겠다. Objective : The purpose of this study was to investigate the efficacy and safety of risperidone in the treatment of Korean schizophrenic patients. Method : This multicenter open study included 377 schizophrenic patients drawn from 39 university hospitals. After a wash-out period of 1 week, the schizophrenic patients were treated with risperidone for 8 weeks and evaluated at 5 points ; at baseline, and 1, 2, 4 and 8 weeks of treatment. The dose was increased from 2mg/day(1mg twice daily) to 6mg/day(3mg twice daily) during the first week and adjusted to a maximum of 16mg/day over the next 7 weeks according to the patient's clinical response. Medication to control extrapyramidal symptoms was permitted. The psychiatric and neurological status of the patients was assessed by PANSS, CGI, and ESRS scales. Results : 343(91%) of 377 patients completed the 8-week trial period. Clinical improvement, as defined by a 20% or more reduction in total PANSS score at end point, was shown by 81.3% of patients. The predictors of response to risperidone were associated older age, shorter duration of illness, fewer previous hospitalization. Risperidone had rapid onset of action ; a significant decrease of the total PANSS and three PANSS factor(positive, negative, general), and CGI was already noticed at the end of first week. For the ESRS, parkinsonism rating scores were significantly increased until week 4 comparing with baseline. Dystonia rating scores were significantly increased until week 1, and dyskinesia rating scores were not significantly changed during the study. Laboratory parameters including vital sign, EKG, hematological, and biochemical values showed no significant changes during the trial. Conclusions : This study suggests that risperidone is generally safe and effective against both the positive and negative symptoms in our group of patients.

The impact of pathologic differentiation (well/ poorly) and the degree of Ki-67 index in patients with metastatic WHO grade 3 GEP-NECs.

Kim, Seung Tae,Lee, Su Jin,Lee, Jeeyun,Park, Joon Oh,Park, Young Suk,Lim, Ho Yeong,Kang, Won Ki Grune & Stratton 2017 Journal of clinical oncology Vol.35 No._suppl15

<P> e15686 </P><P> Background: Herein, we investigated the impact of pathologic differentiation (well or poorly differentiated) in metastatic grade 3 GEP-NEC patients receiving etoposide and platinum-based therapy. Simultaneously, we evaluated a more exact Ki67 index cut-off point to select patients with grade 3 GEP-NEC who might benefit from etoposide plus platinum (EP)-based therapy. Methods: Among patients pathologically diagnosed with metastatic grade 3 GEP-NECs at Samsung Medical Center between June 2013 and March 2016, 31 GEP-NEC patients receiving etoposide and platinum-based therapy were included in this study. Results: Primary sites included 13 foregut-derived GEP-NECs [stomach (n = 4), duodenum (n = 4), and pancreas (n = 5)] and 2 hindgut-derived GEP-NECs of the rectum. Sixteen unclassified GEP-NECs originated from 7 gall-bladder (GB), 6 liver and 3 unknown primary sites. According to pathologic differentiation, 14 patients had well differentiated and 17 had poorly differentiated grade 3 GEP-NECs. Between well differentiated and poorly differentiated grade 3 GEP-NECs, there was a significant difference in the distribution of Ki67 index. There was no significant difference of treatment efficacy between well and poorly differentiated grade 3 GEP-NECs (RR; 35.7% vs. 41.2%, p = 0.525). Tumor response to EP occurred in 5 of 7 patients with Ki67 > 60% and 7 of 24 with Ki67≤60%, which was significantly different (RR; 71.4% vs. 29.2%, P = 0.043). There was no significant difference in PFS according to pathologic differentiation (well differentiated vs. poorly differentiated) and Ki67 index ( > 60% vs ≤60%). Conclusions: Grade 3 GEP-NECs could be morphologically classified into well and poorly differentiated NETs. Additionally, among grade 3 GEP-NECs, there was a significant difference in ranges of Ki67 index between well and poorly differentiated NECs. Higher levels ( > 60%) of Ki67 index might be a predictive marker for efficacy of EP as a standard regimen in grade 3 GEP-NECs. </P>

A Re-evaluation of the Concept of Topic

( Kang¸ Sun Young ),( Chang¸ Kyung Ki ) 현대영미어문학회 1983 현대영미어문학 Vol.1 No.-

담낭암의 발생에서 담췌관합류이상의 역할 규명과 암화과정에 관한 연구

한기준,송시영,정재복,이세준,김호근,강진경 大韓消化器病學會 1998 大韓消化器病學會誌 Vol.32 No.4

Hair growth promoting effects of different alternating- current parameter settings are mediated by the activation of Wnt/β-catenin and MAPK pathway

( Ki Min Sohn ),( Kwan Ho Jeong ),( Jung Eun Kim ),( Young Min Park ),( Hoon Kang ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: There are clinical studies demonstrating the positive effect of electrical stimuli on hair regrowth. However, the underlying mechanism and optimal parameter settings are not clarified. Objectives: To investigate the effects of different parameter settings of electrical stimuli on hair growth by examining changes in human dermal papilla cells (hDPCs) in vitro and by observing molecular changes in animal tissue. Methods: In vitro, cultured hDPCs were electrically stimulated with different parameter settings. Cell proliferation was measured by MTT assay. The Ki67 expression was measured by immunofluorescence. Hair growth-related gene expressions were measured by RT-PCR. In animal model, different parameter settings were applied to the shaved dorsal skin of rabbit for 8 weeks. Expression of hair-related genes in the skin of rabbit was examined by RT-PCR.Results: At low voltage power (3.5V) and low frequency (1MHz or 2MHz) alterating current, in vitro proliferation of hDPCs was successfully induced. A significant increase in Wnt/モ-catenin, Ki67, p-ERK and p-AKT expression was observed. In animal model, hair regrowth was observed in the entire stimulated areas and expression of hair-related genes in the skin significantly increased. Conclusion: There are optimal conditions for electric stimulated hair growth and they might be different in the cells, animal, and human tissue. Electric stimuli induces mechanisms such as activation of Wnt/モ-catenin and MAPK pathway in hair follicles.

상아질에 적용된 재 습윤제가 미세인장 결합강도에 미치는 영향

강희영,조영곤,김종욱,박병철,유상훈,진철희,최희영,기영재 大韓齒科保存學會 2004 Restorative Dentistry & Endodontics Vol.29 No.2

This study investigated that the effect of rewetting agent on dentinal microtensile bond strength (μTBS). Human molars were sectioned to expose the superficial dentin surfaces. Samples were divided into two groups according to type of adhesives-Single Bond (S) and One-Step (0)], and again subdivided into five groups by different dentin surface treatment-dry for 15s (D) , blot dry (BD) or dry for 15s, and rewet with different rewetting agents[distil1ed water (DW), Gluma Desensitizer (GD) and Aqua-Prep (AP)]for 30s. After application of adhesive, composite resin was built up on the bonding surface. Each tooth was sectioned to obtain stick with 1mm^(2) cross sectional area and the μTBS was determined by EZ test. In the S group, the mean μTBS of GD, AP and BD group was significantly higher than that of DW and D group (p < 0.05). In the 0 group, the mean μTBS of AP, GD, BD and DW group was significantly higher than that of D group (p < 0.05). The data suggested that Gluma Desensitizer and Aqua-Prep could be successfully used as rewetting agents, and Distilled water could be acceptable in aceton based adhesive system only.

조혈모세포이식술이 골수기질세포의 기원 및 조골세포로의 증식 및 분화에 미치는 효과

강무일,조성원,오은숙,백기현,이원영,오기원,김혜수,한제호,윤건호,차봉연,이광우,손호영,강성구,김춘추 대한내분비학회 2000 Endocrinology and metabolism Vol.15 No.4·5

조혈모세포이식 후 골성장인자의 변화 및 골대사에 미치는 영향 : Impact on Bone Mineral Metabolism

백기현,오은숙,오기원,이원영,김혜수,권순용,한제호,강무일,차봉연,이광우,손호영,강성구,김춘추 대한내분비학회 2002 Endocrinology and metabolism Vol.17 No.5

연구배경: 각종 장기이식의 시행이 많아지고 이식 후 생존율이 증가함에 따라 이식 후 합병증에 대한 관심 또한 높아지고 있다. 조혈모세포이식 후에도 다양한 내분비적 합병증이 발생할 수 있으며 골격에 대한 합병증도 문제점으로 대두되고 있다. 조혈모세포 이식 후 발생하는 골소실에는 이식 후 초기의 골형성 저하와 골흡수 증가가 중요한 역할을 담당하리라고 추측되는데 이러한 골재형성불일치(biochemical uncoupling)에 골 성장인자들이 미치는 영향에 대해서는 알려진 바가 없다. 본 연구에서는 조혈모세포이식 전, 후로 말초 혈액에서 IGF-I, FGF-2, M-CSF같은 성장인자의 변화를 알아보고, 이들 성장인자의 변화가 조혈모세포이식 후의 골형과 골흡수에 미치는 영향 및 이식 후 발생되는 골량 소실과의 연관성을 확인해 보고자 하였다. 방법: 여러 가지 혈액질환으로 인해 동종 골수이식을 시행 받은 환자들을 전향적으로 관찰하였으며 이식 전 및 이식 후 1주, 2주, 3주, 4주 및 3개월, 6개월 1년에 말초 혈액에서 골교체표지자를 측정하였다. 이식 전 및 이식1년 후에 요추골 및 대퇴골 골밀도를 측정할 수 있었던 36명의 환자들을 대상으로 냉동 보관되어 있던 혈청을 이용하여 IGF-I, FGF-2 및 M-CSF를 시기별로 측정하였으며 이들 성장인자와 골교체표지자의 변화 및 골밀도 변화 사이의 상관관계를 확인하였다. 결과: 골흡수 표지자인 혈청 ICTP는 이식 전에 비해 이식 후 4주까지 점차 의의 있게 증가하다가 이후 6개월까지 더욱 증가한 후 감소하였다. 골형성 표지자인 osteocalcin은 이식 후 3주까지는 점차 감소하다가 이후 증가하여 이식 후 3개월 및 6개월에 기저치보다 통계적으로 유의하게 증가한 후 감소하였다. 혈청 IGF-I과 FGF-2는 각각 이식 후 3주 및 1주까지 의미있게 감소하다가 이후 증가하였으며 혈청 M-CSF는 이식 후 1주째에 기저치에 비해 의미 있게 증가하였다가 이후 기저치로 회복되었다. 이식 1년 후 평균 요추부 골밀도는 5.2% 감소하였고 평균 근위대퇴골 골밀도는 11.6% 감소하였다. 이식 전 및 이식 후 3주에 측정한 IGF-I과 같은 시기에 측정한 오스테오칼신 사이에 유의한 상관관계가 관찰되었으며 이식 후 3주째의 M-CSF와 골흡수표지자인 M-CSF 사이에서 의미 있는 양의 상관관계를 관찰할 수 있었다. 이식 후 3주 및 3개월에 IGF-I이 낮은 환자일수록 이식 1년 후 근위대퇴골에서의 골소실이 많은 것으로 분석되었다. 결론: 조혈모세포이식 후 발생하는 골소실에는 기존에 알려진 기저질환의 영향, 성호르몬의 감소, 면역억제의 투여, 골수기질세포와 조골세포의 손상 및 이식초기 사이토카인의 변화이외에도 골성장인자가 관련이 있음을 확인하였고, 이는 이식 후 발생되는 골량소실에 중요한 역할을 할 것이라고 사료된다. Background: A loss of bone mass is usually detected after a bone marrow transplantation (BMT), especially during the early post-transplant period. We recently reported that enhanced bone resorption following a BMT was related to both the steroid dose and the increase in IL-6. We also suggested damage to the marrow stromal microenvironment, by myoablation, partly explains the impaired bone formation following a BMT. It is well known that some growth factor play important role in bone growth and osteogenesis. However, the pathogenetic role of bone growth factors in post-BMT bone loss is unknown and data on the changes in the growth factors, in accordance with bone turnover markers and bone mineral density (BMD) changes are scarce. We investigated changes in bone growth factors such as IGF-I (Insulin-like growth factor-I), fibroblast growth factor-2 (FGF-2) and Macrophage colony stimulating factor (M-CSF), during the post-BMT period, and assessed whether the growth factor changes influenced the bone turnover and post-BMT bone loss. The present study is the first prospective study to describe the changes in bone growth factors following a BMT. Methods: We prospectively investigated 110 patients undergoing a BMT, and analyzed 36 patients (32.4±1.3 years, 17 men and 19 women) whose BMDs were measured before, and 1 year after, the BMT. The serum biochemical markers of bone turnover were measured before, 1, 2, 3 and 4 weeks, 3 and 6 months, and 1 year, after the BMT. The serum, FGF-2, IGF-I and M-CSF levels were measured before and 1 and 3 weeks, and 3 months after the BMT. The correlation between the changes of growth factors and various bone parameters was analyzed. Results: The mean bone losses in the lumbar spine and total proximal femur, calculated as the percentage change from the baseline to the level at 1 year, were 5.2(p<0.05) and 11.6%(p<0.01), respectively. the serum type I carboxyterminal telopeptide(ICTP), a bone resorption marker, increased progressively until 6 months after the BMT, but thereafter decreased, to the base value after 1 year. Serum osteocalcin, a bone formation marker, decreased progressively, until 3 weeks after the BMT but then increased transiently, and finally returned to the base level at 1 year. The serum IGF-I and FGF-2 also decreased progressively until 3 weeks 1 week after the BMT, respectively, then increased to the base values at 3 months. The serum M-CSF increased briskly at 1 week post-BMT, then decreased to the base level. There were positive correlations between the percentage changes from the baseline proximal femur BMD and the IGF-I levels 3 weeks and 3 months (r=0.52, p<0.01, r=0.41, p<0.05) post BMT. A significant correlation was found between the IGF-I and osteocalcin levels pre-BMT, and 3 weeks after the BMT. Another positive correlation was found between the M-CSF and the ICTP levels at 3 weeks post BMT (r=0.54, p<0.05). Conclusion: In conclusion, there were significant changes in the serum IGF-I, FGF-2 and M-CSF levels in the immediate post-BMT period, which were related to a decrease in bone formation and loss in the proximal femoral BMD during the year following the BMT (J Kor Soc Endocrinol 17:664∼674, 2002).