흰쥐에서 Chloramphenicol에 의해 유도된 불면에 대한 전기경련충격의 효과

추일한,김정수,홍승철,한진희,이성필 大韓神經精神醫學會 1999 신경정신의학 Vol.38 No.5

연구목적 : 수면인자의 하나로 밝혀진 muramyl peptide가 사람을 포함하여 여러 포유동물종에서 분리되었는데 이는 박테리아의 세포벽을 형성하고 있는 peptidoglycans의 구성성분으로 macrophage의 작용으로 생체에서 형성되어 수면을 유도한다고 알려져 있다. 이를 뒷받침하는 근거로는 사람과 쥐에서 항생제를 사용하면 수면이 감소한다는 연구결과가 있었으며 이는 장내 세균의 감소로 인한 결과로 생각되고 있다. 또한 전기경련충격(ECS)는 동물실험에서 서파수면(slow wave sleep)의 증가와 역설수면(paradoxical sleep)을 감소시킨다고 보고되었다. 저자들은 이제까지 연구되지 않았던 항생제 투여로 야기된 동물의 불면증에 대한 ECS의 효과를 조사하고자 한다. 방 법 : Sprague-Dawley 수컷 흰쥐 12마리에 뇌파(EEG)를 측정할 수 있는 장치를 단 다음 제1일째 baseline EEG를 측정하고 다음날을 chloramphenicol을 투여하여 불면을 유발시켰으며 제3일째는 6마리는 대조군으로 사용하고 나머지 6마리는 실험군으로 사용하여 전기경련충격을 시행함으로써 이에 대한 수면인자들을 통계적으로 비교 분석하였다. 결 과 : Chloramphenicol 투여 후 총 수면시간(t=3.757, p=0.003)이 감소하였고 수면인자별로는 주간 서파수면(t=4.944, p=0.000)과 주간 역설수면(t=3.887, p=0.003)도 감소하였다. 또한 불면상태에서 전기경련충격 후 실험군의 경우 대조군에 비해 전체 수면(t=-0.830, p=0.426)은 증가하는 경향을 보이고 야간 서파수면(t=-3.863, p=0.003)과 야간 역설수면(t=-2.458, p=0.034)이 유의하게 증가하였다. 결 론 : 이상의 결과로 볼 때 항생제에 의하여 유도된 불면이 전기경련충격에 의하여 향상됨을 확인할 수 있었고 대부분의 정신과 환자들이 호소하고 있는 불면증에 대한 기전을 알아내는 기초적 역할을 할 수 있을 것으로 기대되며 정신과 영역에서 흔히 사용되는 전기경련충격의 수면에 대한 관계를 이해하는데 도움을 줄 수 있을 것으로 기대된다. Objectives : Muramyl peptide derived from bacterial cell wall has been identified as one of several endogenous sleep-promoting factors. Several studies have shown that the administration of antibiotics decreased sleep amount as well as bacterial colony numbers in rats. Electroconvulsive shock(ECS) has been widely used in the treatment of many psychiatric disorders, including depression, bipolar disorder, and some cases of schizophrenia. However exact mechanism of ECS on the normal or psychiatric condition is not well understood so far. Previous studies indicated that ECS has diverse effects on sleep parameters both in the human and animal subjects. However, there was no report to examine the relationship between effects of ECS and sleep in the antibiotic imposed animal subjects. Therefore the author studied the effects of ECS on chloramphenicol-induced insomnia in rats. Methods : Twelve Sprague-Dawley strain rats were divided into control(N=6) and experimental group(N=6). The sleep-wake activity was recorded continuously for consecutive three days(baseline, day 1 and day 2). On day 1, both groups were intraperitoneally injected with chloramphenicol 150mg/kg. On day 2, the control group was intraperitoneally injected with chloramphenicol 150mg/kg only, whereas experimental group received ECS an hour after they were injected with chloramphenicol 150mg/kg. Results : 1) Chloramphenicol administration decreased light period slow wave sleep(SWS)(t=4.944, p=0.000) and paradoxical sleep(PS)(t=3.887, p=0.003) as well as total SWS(t=2.98, p=0.012) and total PS(t=4.391, p=0.001). 2) ECS increased dark period SWS(t=-3.863, p=0.003) and dark period Ps(t=-2.458, p=0.034) as well as total dark period sleep(t=-4.302, p=0.002). Conclusion : These results suggest that ECS may be effective to reverse chloramphenicol-induced insomnia in rats. Furthermore, chloramphenicol-induced insomnia in rats could be a useful animal model for the future sleep research.

소아 동종 조혈모세포이식 200예의 분석 : Single Center Study

김학기,조빈,정낙균,정대철,장필상,김선영,김춘추 대한조혈모세포이식학회 2002 대한조혈모세포이식학회지 Vol.7 No.1

연구배경: 1983년 11월부터 2000년 9월까지 시행한 동종 조혈모세포이식의 성적을 분석하여 소아 골수이식의 발전 방향을 모색하고자 하였다. 방법: 1983년 11월부터 2000년 9월까지 가톨릭의대 조혈모세포이식센터, 성모병원 소아과에서 동종 조혈모세포이식을 시행한 200예를 대상으로 조혈모세포이식의 유형 및 대상질환, 이식 당시의 상태 및 전처치에 따른 치료 성적을 후향적으로 분석하였다. 결과: 200예 중 HLA-일치 형제간 골수이식이 146예(73%), HLA-일치 형제간 골수이식 이외의 이식이 54예(27%)였다. 1) HLA-일치 형제간 골수이식: 146예 중 남아와 여아가 각각 78명과 68명이었으며 SAA 50예의 5년 무병 생존율은 95.8±2.9%였고 AML 45예의 5년 무병 생존율은 71.7±7.0%로 일차 및 이차 관해기에 이식 받은 40예와 5예의 5년 무병 생존율은 각각 73.6±7.2%와 60.0±21.9%였다. AML에서 전처치로 Bu/Cy를 사용한 28예와 TBI/Cy를 사용하였던 9예의 5년 무병 생존율은 각각 81.9±7.4%와 33.3±15.7%였으며 Bu/Cu/TBI를 시행한 8예의 무병 생존율은 80.0±17.9%였다. ALL 33예의 5년 이상 무병 생존율은 75.5±7.5%였고 일차 및 이차 관해기에 이식을 시행하였던 18예와 14예의 무병 생존율은 각각 83.0±9.0%와 71.4±12.1%였다. CML 및 MDS 11예의 5년 무병 생존율은 72.7±13.4%였다. 기타 질환으로는 Fanconi 빈혈 2예, 혈구탐식성 조직구증식증 2예, 순적혈구 빈혈 2예, Kostmann 증후군이 1예로 이들의 전체 무병 생존율은 85.7±13.2%였다. 2) HLA-일치 형제간 골수이식 이외의 이식을 시행하였던 54예의 3년 이상 무병 생존율은 45.3±11.6%였으며 HLA-일치 UBMT 26예, CBSCT 15예, 형제 이외의 혈연에 의한 골수이식이 13예로 이들의 무병 생존율은 각각 56.2±10.8%, 58.2±13.1%, 35.9±17.3%였다. 결론: 소아 난치성 혈액질환의 완치요법으로 동종 골수이식의 치료효과를 확인할 수 있었으며, 동종 조혈모세포의 공여원으로 비혈연간 골수나 제대혈의 이용이 점차 증가하고 있음을 알 수 있었다. Background: Bone marrow transplantation was first introduced to Korean children in 1983. Since then the number of children receiving transplants has increased steadily. Methods: We analyzed two hundred pediatric cases of allogeneic hematopoietic stem cell transplantation between Nov. 1983 and Sep. 2000 in Catholic Hematopoietic Stem Cell Transplantation Center of Korea. Results: HLA-matched sibling transplantations were performed in 146 cases (78 males, 68 females, median age; 10 years) with median follow-up of 47 months. The 3-year estimated event-free survival (EFS) of ALL and AML was 76% and 72% respectively. The 5-year estimated EFS of severe aplastic anemia and CML/MDS was 96% and 73% respectively. The 2-year estimated EFS of nonmalignant rare disease was 86%. Twenty-six children underwent unrelated bone marrow transplantation (UBMT), 15 cord blood stem cell transplanta-tion (CBSCT) and 13 familial haploidentical transplantation (FHT). There were 35 males and 19 females with a median age of 6.5 years and median follow-up of 18.5 months. The estimated 2-year EFS of UBMT, CBSCT and FHT were 56%, 58% and 34% respectively. Conclusion: HLA-matched sibling allogeneic BMT showed better survival in children with hematopoietic stem cell disorder compared to UBMT and CBSCT. Recently, transplants using alternative stem cell source are increasing due to lack of suitable matched sibling donor and continuous efforts for reducing transplant-related complications are warranted for improving survival.

Transcriptomic patterns in early-secretory and mid-secretory endometrium in a natural menstrual cycle immediately before in vitro fertilization and embryo transfer

Sung Pil Choo,Inha Lee,Jae-Hoon Lee,Dowon Lee,Hyemin Park,Joo Hyun Park,SiHyun Cho,Young Sik Choi 대한산부인과학회 2023 Obstetrics & Gynecology Science Vol.66 No.5

Objective This study aimed to evaluate the endometrial transcriptomic patterns in the early secretory phase (ESP) and mid-secretory phase (MSP) of the natural menstrual cycle before in vitro fertilization and embryo transfer (IVF-ET). Methods Thirty patients whose endometrial tissues were obtained from the ESP or MSP of a natural menstrual cycle immediately before IVF-ET were included. Endometrial dating was histologically confirmed as ESP (cycle days 16-18) or MSP (cycle days 19-21), according to the noyes criteria. The patients were divided into two groups depending on the IVF-ET outcome: pregnant (n=14; 7 in ESP and 7 in MSP) or non-pregnant (n=16; 8 in ESP and 8 in MSP). Differentially expressed genes (DEGs) in the MSP, compared to the ESP, were identified using NanoString nCounter (NanoString Technologies, Seattle, WA, USA) data for both the pregnant and non-pregnant groups. Results Thirteen DEGs in the pregnant group and 11 DEGs in the non-pregnant group were identified in the MSP compared to those in the ESP. In both groups, adrenoceptor alpha 2A, interleukin 1 receptor-associated kinase 2, a disintegrin and metalloproteinase with thrombospondin repeats 15 (ADAMTS15), serpin family E member 1, integrin subunit beta 3, transmembrane protein 252 (TMEM252), huntingtin associated protein 1, C2 calcium-dependent domain containing 4A, and integrin subunit alpha 2 were upregulated in the MSP, compared to the ESP. TMEM37, galactosidase beta 1 like 2, Rho family GTPase 3, and cytochrome P450 family 24 subfamily A member 1 were upregulated in the MSP only in the pregnant group. ADAMTS8 was downregulated and monoamine oxidase A was upregulated in the MSP only in the non-pregnant group. Conclusion Transcriptomic patterns in the endometrium immediately before IVF-ET appear to differ according to the IVF-ET outcome. These novel DEGs, which have not been previously studied, may have functional significance during the window of implantation and serve as potential biomarkers of endometrial receptivity.

Particulate matter(PM) exposures induce adverse effects on endometrium via aberrant apoptotic pathways in vitro and in vivo

( Sung Pil Choo ),( Min Jung Lee ),( Inha Lee ),( Jae Hoon Lee ),( Heeyon Kim ),( Gee Soo Jung ),( Sehee Kim ),( Wooseok Im ),( Young Sik Choi ),( Sihyun Cho ) 대한산부인과학회 2022 대한산부인과학회 학술대회 Vol.108 No.-

Objective: Particulate matter (PM) has broad toxic effects and numerous studies have suggested possible links between the recent decline in female fertility and increased PM exposure. However, the effects of PM exposures on female reproductive function are not fully understood yet. This study aimed to evaluate adverse effects of PM on endometrium and identify possible underlying mechanisms. Methods: Endometrial cells from the patients who underwent surgeries for benign conditions were obtained, cultured, and treated with 50~200 ug/ml of PM for 4, 8, and 12 hours, respectively. In vivo model, female C57BL/6 mice were exposed to urban particulate matter (low and high dose) via intranasal inhalation for four weeks. Primary cultured endometrial cells and mouse endometrium were harvested, and the expression levels of pro-inflammatory cytokines involved in mitogen-activated protein kinase (MAPK) signaling and apoptotic pathways were evaluated using qRT-PCR and western blot. Results: The expression levels of Bax/Bcl-2 ratio, Cas-3, and p53 were significantly higher in primary cultured human normal endometrial cells upon 12 hours of PM exposure. Furthermore, the mRNA levels of IL-1 were significantly upregulated after PM exposure (30.68 folds). A similar trend was observed in the endometrium of PM-exposed mice. A marked increase in the mRNA levels of IL-1 was observed in low dose(7.41 folds) and high dose (26.98 folds) PM exposed mice compared with that in the control group. Subsequently, we found that NF-kB activation leads to pro-inflammatory cytokine upregulation. In addition, Massons Trichrome staining showed increased intensity of collagen fiber content in PM exposed endometrium in a dose-dependent manner, which implies increased fibrosis of endometrium. Conclusion: In this study, we identified that exposure to PM induced adverse effects on endometrium via alteration of apoptotic and inflammatory pathways. Further, PM exposure may be associated with endometrium fibrogenesis (fibrosis).

Effects of Alpha-Ketoglutarate on mTOR pathway in endometriotic cells in Vitro

( Sung Pil Choo ),( Yunjeong Park ),( Heeyon Kim ),( Inha Lee ),( Jae Hoon Lee ),( Young Sik Choi ),( Si Hyun Cho ) 대한산부인과학회 2021 대한산부인과학회 학술대회 Vol.107 No.-

The relation ship between dienogest (VISANNE) and depressive symptoms

( Sung Pil Choo ),( So Hyun Ahn ),( Nayoung Bae ),( Young Sik Choi ),( Si Hyun Cho ),( Jung-ho Shin ) 대한산부인과학회 2021 대한산부인과학회 학술대회 Vol.107 No.-

The effect of maternal age on Cesarean delivery, maternal and perinatal outcomes following induction of labor in uncomplicated nulliparous women

( Sung Pil Choo ),( Yeo Jin Rhee ),( Jisun Yun ),( Eui Hyeok Kim ) 대한산부인과학회 2019 대한산부인과학회 학술대회 Vol.105 No.-

Objective: Women who give birth at 35 years of age or older are generally referred to advanced maternal age (AMA), which is risk factors for various kinds of complication besides genetic changes in fetus. The primary outcome is to determine if AMA is associated with emergent cesarean delivery (CD) following induction of labor (IOL). The secondary outcomes were a composite of adverse maternal and perinatal events following IOL. Methods: This was a retrospective observational study of singleton, vertex-presenting non-anomalous pregnancy from 37 0/7 to 41 6/7 weeks of gestation who were delivered following IOL in uncomplicated nulliparous women. After IOL, outcomes in women with AMA were compared with women < 35 years. Results: A total of 314 nulliparous women were attempted IOL (≥ 35 years n=73, 23.2%; < 35 years n=257, 81.8%) and among them, 257 (81.8%) delivered vaginally. The rate of CD was significantly higher in women with AMA (31.5% vs. 14.1%, p=0.001). Multivariable analysis showed that AMA was an independently associated with CD (OR 2.98, 95% CI 1.56-5.71, p=0.001). The rate of instrumental deliveries and the blood loss during the delivery were similar between the two groups (13.7% vs. 7.9%, 1.97±1.32 vs. 1.86±1.25 mg/dl, respectively, all p > 0.05). Regarding neonatal outcomes, there was no different between the two groups in NICU admission rate and Apgar score < 7 at 5 minute (38.4% vs. 31.5%, 12.3% vs. 7.6%, respectively, all p > 0.005). Conclusion: Following IOL, AMA was associated with a more than three-fold increased likelihood of birth by CD in nulliparous women. We found, however, no evidence that induced labor in elderly primigravida increases adverse maternal and neonatal outcomes as compared with women < 35 years.

The effect of Diagnosis-Related Group payment system on the quaility of medical care, among the patient diagnosed with pelvic organ prolapse in Korean Tertiary Hospitals

( Sung Pil Choo ),( Eui Hyeok Kim ),( Myung Jae Jeon ) 대한산부인과학회 2018 대한산부인과학회 학술대회 Vol.104 No.-

Objective: To examine changes in clinical practice patterns including the number of simultaneous surgeries for patients diagnosed with pelvic organ prolapse (POP) following the introduction of diagnosis-related groups (DRGs) payment system of the Fee-for-service (FFS) in July 2013 in Korean tertiary hospitals and to evaluate its effect on the quality of hospital care. Methods: Using the 20112016 administrative database from National Health Insurance Service claim data, we reviewed medical information for 8115 patients who underwent hysterectomy with the diagnosis POP in 43 tertiary hospitals. We compared changes in the number of simultaneous operations during hysterectomy and several variables in length of stay (LOS), spillover, readmission rate from before to after introduction of the DRGs for 2 and a half years respectively. Results: DRGs significantly reduced the number of simultaneous surgeries, such as colpopexies and transobturator-tape procedures using expensive mesh or tape, during hysterectomy (9.37% vs. 6.64%, 9.66% vs. 3.16% respectively, all p<0.001) while there was no significant difference in the number of colporrhaphy using simple absorbable suture materials during hysterectomy (21.35% vs. 23.09%, p=0.199). Readmission rate increased after DRGs (3.01% vs. 4.51% p< 0.001) and spillover rate did not change. LOS was reduced (7.4 ± 3.5 vs. 6.4 ± 2.7, p < 0.001) after DRGs. Conclusion: Implementation of DRGs in the field of urogynecology in Korean tertiary hospitals led to reduce the number of co-surgeries requiring expensive medical operative equipment while the number of those that did not remained the same. DRGs also led to increase the readmission rate and reduction the LOS without increasing outpatient visits.

M1 Macrophage-Derived Nanovesicles Potentiate the Anticancer Efficacy of Immune Checkpoint Inhibitors

Choo, Yeon Woong,Kang, Mikyung,Kim, Han Young,Han, Jin,Kang, Seokyung,Lee, Ju-Ro,Jeong, Gun-Jae,Kwon, Sung Pil,Song, Seuk Young,Go, Seokhyeong,Jung, Mungyo,Hong, Jihye,Kim, Byung-Soo American Chemical Society 2018 ACS NANO Vol.12 No.9

<P>Cancer immunotherapy modulates immune cells to induce antitumor immune responses. Tumors employ immune checkpoints to evade immune cell attacks. Immune checkpoint inhibitors such as anti-PD-L1 antibody (aPD-L1), which is being used clinically for cancer treatments, can block immune checkpoints so that the immune system can attack tumors. However, immune checkpoint inhibitor therapy may be hampered by polarization of macrophages within the tumor microenvironment (TME) into M2 tumor-associated macrophages (TAMs), which suppress antitumor immune responses and promote tumor growth by releasing anti-inflammatory cytokines and angiogenic factors. In this study, we used exosome-mimetic nanovesicles derived from M1 macrophages (M1NVs) to repolarize M2 TAMs to M1 macrophages that release pro-inflammatory cytokines and induce antitumor immune responses and investigated whether the macrophage repolarization can potentiate the anticancer efficacy of aPD-L1. M1NV treatment induced successful polarization of M2 macrophages to M1 macrophages <I>in vitro</I> and <I>in vivo</I>. Intravenous injection of M1NVs into tumor-bearing mice suppressed tumor growth. Importantly, injection of a combination of M1NVs and aPD-L1 further reduced the tumor size, compared to the injection of either M1NVs or aPD-L1 alone. Thus, our study indicates that M1NV injection can repolarize M2 TAMs to M1 macrophages and potentiate antitumor efficacy of the checkpoint inhibitor therapy.</P> [FIG OMISSION]</BR>

16열 CT angiography를 이용한 뇌내동맥 stent의 개통성 및 재협착 평가

Choo, Ki Seok,Lee, Tae Hong,kim, Hak Jin,Choi, Chang Hwa,Park, Kyung Pil,Lee, Sang Won,Kim, Chang Won,Kim, Suk,Jeonu, Yean Joo,Kang, Dong Won 부산대학교 병원 암연구소 2006 부산대병원학술지 Vol.- No.20

목적: 16열 CT를 이용한 CT angiography 가 뇌내동맥내 스텐트의 개통성가 재협착 여부를 평가하는데 유용한지를 평가하고자 하였다. 대상 및 방법: 7개의 뇌내동맥내에 스텐트를 설치한 총 7명의 환자에서 16열 CT를 스텐트를 설치한 후 6개월 후에 시행하였으며, MIP를 이용한 curved MPR기법을 최적의 window setting를 이용하여 재구성하였다. 두 명의 방사선과 의사가 CT촬영 후 이틀 후 시행한 고식적 혈관촬영술의 결과를 모른 채 stent의 개통성과 재협착여부를 평가하였다. 결과: CT의 결과는 모든 스텐트에 개통성이 있고, 재협착이 없는 것이었으며, 이것은 고식적 혈관촬영술에서 확인되었다. 또한 스텐트 내부는 최적의 kernel 값을 적용했을 때 잘 평가할 수 있었다. 결론: 최적의 kernel 값으로 측정 한 16열 CT angiography는 뇌내 동맥내 스텐트의 개통성과 재협착 여부를 평가하는데 도움을 줄 수 있다. Purpose: To determine whether 16-slice CT angiography is suitable for the evaluation of luminal patency and visibility of intracranial stents in comparison with conventional angiography as the standard of reference. Methods: Seven stents (5 middle cerebral arteries, 1 intracranial vertebral arteries, and 1 intracranial internal carotid arteries) of two different types were evaluated in 7 patients. CT was performed on a 16-slice scanner (Simens Medical Solutions, Forchheim, Germany, detector collimation 16x0.75 mm; table feed 2.8 mm/rotation, 370 mAs; 120 kVp; reconstruction with standard and optimized sharp kernel), following implantation of intracranial stents at least in 6 months and conventional angiography was performed in 2 days as a standard reference. Curved multiplanar reformations with maximal intensity projection (MIP) with optimal window settings for assessment of lumen of intracranial stents were evaluated for stent patency (contrast distal to the stent as an indirect sign) and visible lumen diameter by two experienced radiologists who blinded to the reports from the conventional angiography. Results: All stents were correctly classified as patent and no in-stent stenosis, which was correctly correlated with results of conventional angiography. Parts of the stent lumen could be visualized in all cases. On average, 57% of the stent lumen diameter was visible using optimized sharp kernel. Significant improvement of lumen visualization (22%, P<0.01) was observed using the optimized sharp kernel compared with the standard sharp kernel. Conclusion: 16-slice CT using the dedicated sharp kernel might provide the useful information for evaluation of patency and lumen diameter of intracranial stents.