Comparison of Proliferative Activity in Each Histological Subtypes of Benign and Atypical Intracranial Meningiomas by PCNA and Ki-67 Immunolabeling

최승진,장은덕,권성오,계대곤,박춘근,이상원,강준기,Choi, Seung Jin,Chang, Eun Deok,Kwon, Seung Oh,Kye, Dae Kon,Park, Choon Keun,Lee, Sang Won,Kang, Joon Ki The Korean Neurosurgical Society 2000 Journal of Korean neurosurgical society Vol.29 No.9

목 적 : 양성 뇌수막종에 비하여 이형성 및 악성 뇌수막종이 나쁜 임상적인 예후 및 양상을 보이는 것은 잘 알려져 있으나, 양성 뇌수막종에 있어서 각각의 병리조직학적 아형에 따른 생물학적 양상의 차이에 대해서는 잘 알려지지 않거나 일부 논란이 되고있다. 본 연구에서는 이형성 뇌수막종 및 양성 뇌수막종의 각각의 병리조직학적 아형에 따른 증식능의 차이여부를 알아보고자 PCNA와 Ki-67표지지수를 분석하였다. 방 법 : 본원에서 뇌수막종으로 수술을 시행하여 얻은, 재발을 보여 재수술을 시행한 2례를 포함하여, 파라핀에 포매시킨 27개의 조직을 대상으로 병리학적인 증식능을 분석하기 위해, PCNA에 대한 단일항체 및 MIB-1 단일항체를 이용한 면역조직화학적 염색을 시행하였다. 조직학적 분류상 meningothelial type이 8례, transitional type이 9례, fibroblastic type이 5례였으며, 이형성 수막종이 5례였다. 결 과 : PCNA표지지수의 평균값은 양성 수막종에서 meningothelial type이 $4.82{\pm}5.10%$, transitional type이 $9.01{\pm}4.25%$, fibroblastic type이 $5.66{\pm}5.32%$를 보였으나 이형성 수막종에서는 $27.62{\pm}19.67%$의 높은 지수를 나타냈고, Ki-67 표지지수의 평균값은 양성 수막종의 아형에서 각각 $0.43{\pm}0.85%$, $0.44{\pm}1.08%$, $0.24{\pm}0.18%$를 보이고, 역시 이형성 수막종에서는 $0.84{\pm}0.59%$의 높은 지수를 보였다. 즉, 양성 수막종에서 각각의 아형에 따른 PCNA 및 Ki-67 표지지수는 통계학적으로 의미있는 차이는 없었으나(p>0.05), 이형성 수막종에서는 의미있는 높은 표지지수를 보여(p<0.05) 양성 수막종에서 보다 높은 증식능을 보임을 알 수 있었다. 결 론 : PCNA 및 Ki-67 표지지수를 이용한 증식능의 비교결과, 양성 뇌수막종에서는 각각의 아형에 따른 생물학적 양상이나 예후는 차이가 없을것으로 생각되나, 이형성 수막종에서는 높은 증식능을 보여 이에 대한 예후를 예상할 수 있을것으로 생각되며, 또한 이러한 표지지수가 병리조직학적으로 양성과 이형성의 감별에 많은 도움이 될것으로 사료된다. Objective : The clinical prognosis and biological behavior of atypical and especially malignant meningiomas are well known to be worse than benign meningioma, but the degree of biological aggressiveness in each classical subtypes of benign meningioma is controversy. This study was performed to see whether there is a difference in the proliferative activity between each different histological subtypes of benign meningioma as well as atypical meningioma. Methods : Paraffin-embedded surgical specimens of 27 meningiomas, including two recurrent tumors, were studied to evaluate proliferative activity by immunohistochemical method with monoclonal antibodies to proliferating cell nuclear antigen(PCNA) and MIB-1. The specimens consisted of 8 cases of meningothelial, 9 cases of transitional, 5 cases of fibroblastic subtypes and 5 cases of atypical meningiomas. Results : Mean PCNA labeling indices of meningothelial, transitional and fibroblastic meningiomas were $4.82{\pm}5.10%$, $9.01{\pm}4.25%$ and $5.66{\pm}5.32%$, but that of atypical meningiomas was $27.62{\pm}19.67%$, noting a higher value compared to all three subtypes of benign meningiomas. Mean Ki-67 labeling indices of the above 3 subtypes were $0.43{\pm}0.85%$, $0.44{\pm}1.08%$ and $0.24{\pm}0.18%$, and that of atypical meningiomas was also revealed to be of higher value ($0.84{\pm}0.59%$). PCNA and Ki-67 labeling indices were not statistically different between histological subtypes of benign meningioma(p>0.05), but the differences of both immunolabeling between benign and atypical meningiomas were statistically significant(p<0.05). Conclusion : Immunolabeling of PCNA and Ki-67 in intracranial meningiomas reveals no prognostic difference between meningothelial, transitional and fibroblastic subtypes in classical benign meningiomas by measuring expression of PCNA and Ki-67, but it seems to be helpful in differentiating benign and atypical meningioma, later showing more proliferative activity and biological aggressiveness.

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).

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

수족냉증(手足冷症) 환자(患者)에 대(對)한 컴퓨터 적외선(赤外線) 체열촬영(體熱撮影)의 의의(意義)

조유경,오수완,조남희,김동묵,김진성,류봉하,박동원,류기원,Cho, Yu-Kyung,Oh, Su-Wan,Cho, Nam-Hee,Kim, Dong-Mook,Kim, Jin-Seong,Ryu, Bong-Ha,Park, Dong-Won,Ryu, Ki-Won 대한한방내과학회 1998 大韓韓方內科學會誌 Vol.19 No.2

To make a objective diagnosis of the syndrome of cold-limbs, We investigated the 20 patients with cold limbs and GI trouble and 20 normal people as a control group. And we compared the thermal difference between Chon-jung(CV17) and Chung-wan(CV12 中脘), Chon-jung(CV17) and Ki-hae(氣海 CV6) and we compared the thermal differences of No-gung(PE8 勞宮) and Yong-chon(湧泉 KI1), too. The results were as follows. 1. All 20 patients had GI trouble and cold limbs. They had the symptom-Indigestion(16 cases-80%) with heart burn, tympanites, abdominal distention, hiccup, belching. Beside that symptom they also had constipation(6 cases-30%), diarrhea(3 cases-15%), headache & dizziness(6 cases-30%). And some had the menstrual syndrome, chronic fatigue, palpitation, insomnia, edema, arthralgia. 2. The thermal difference of the palms between the patients group and the control group were $25.70^{\circ}C,\;25.82^{\circ}C$, but they were not significant. 3. The thermal difference of the soles between the patients group and the control group were $23.58^{\circ}C,\;24.42^{\circ}C$ and the significancy was P=0.020 so it was significant(P<0.05). 4. The thermal difference of the palms and Chon-jung(CV17) between the patients group and the control group were $1.08^{\circ}C,\;0.76^{\circ}C$, but they were not significant. 5. The thermal difference of the sales and Chon-jung(CV17) between the patients group and the control group were $3.01^{\circ}C,\;1.90^{\circ}C$ and the significancy was P=0.003 so it was significant(P<0.05). 6. The thermal difference of Chon-jung(CV17) and Chung-wan(CV12 中脘) between the patients group and the control group was $0.30^{\circ}C,\;0.62^{\circ}C$ and the significancy was P=0.793 so it was significant(P<0.05). 7. The thermal difference of Chon-jung(CV17) and Ki-hae(CV6 氣海) between the patients group and the control group was $0.53^{\circ}C,\;0.68^{\circ}C$, but they were not significant. From the above, I could find the significance of D.I.T.I to diagnose the cold-feet not the cold-hands and the thermal difference between the trunk and limbs was more significant on cold-feet than on cold-hand, either.

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>

Ki-67 Expression Gives Additional Prognostic Information on St. Gallen 2007 and Adjuvant! Online Risk Categories in Early Breast Cancer

Jung, So-Youn,Han, Wonshik,Lee, Jong Won,Ko, Eunyoung,Kim, Eunkyu,Yu, Jong-Han,Moon, Hyeong-Gon,Park, In Ae,Oh, Do-Youn,Im, Seock-Ah,Kim, Tae-You,Hwang, Ki-Tae,Kim, Sung-Won,Noh, Dong-Young Springer - Society of Surgical Oncology 2009 Annals of Surgical Oncology Vol.16 No.5

신생아 간염에 동반된 Q열 1례

오세기,김흥동,정철영,이원영 인제대학교 1992 仁濟醫學 Vol.13 No.3

Q-fever is an acute or chronic febrile disease, which is transmitted by inhalation of aerosol contaminated with Coxiella burnetti or ingestion of milk from infected animals. We experienced a case of Q-fever in a 5month-old male infant with neonatal hepatitis. The abnormal laboratory findings were mild granulocytopenia, mild thrombocytopenia, elevated sGOT/sGPT and & increased serum bilirubin. Coxiella burnetii was identified in the patient's leukocytes by immunofluorescent technique. After administration of rifampin & chlorampenicol, the prolonged high spiking fever was subsided within 48hours. We report a case of Q-fever with a review of literatures

수평 2중관 열교환기내에서 R-22와 그 대체냉매의 응축 열전달 특성

오후규,박기원,문정욱,노건상,이상훈 麗水水産大學校産業技術硏究所 1997 産業基術硏究所 論文集 Vol.6 No.-

Compared experimental results for forced convection condensation of R-22 and its alternative refrigerants inside a horizontal smooth tube are presented. The pure refrigerant, azeotropic refrigerant mixtures and binary and ternary non-azeotropic refrigerant mixtures are used as the test fluids and a double pipe heat exchanger is used. The refrigerant mass flow rate and temperatures were measured. Using the data, the heat flux, quality and local and mean heat transfer coefficients for the condensation have been obtained. Local heat transfer coefficients for R-22 and its alternative refrigerants were measured at top, side and bottom of the test tube. The results indicated that the heat transfer coefficient of pure and azeotropic refrigerant mixtures was higher than at top of the tube. Non-azeotropic refrigerant mixtures, however, were higher than side and top of the tube. Mean heat transfer coefficients for non-azeotropic refrigerant mixtures increased with refrigerant mass velocity and quality, but were considerably lower that of pure refrigerant and azeotropic refrigerant mixtures.

韓半島의 周邊情勢와 統一接近에의 漸進的 摸索

吳基元 건국대학교 1987 政法論叢 Vol.22 No.1