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>

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.

초음파 영상 데이터를 활용한 내장기 추나요법 시술 부위 탐색 연구

이상진 ( Sang-jin Lee ),기성훈 ( Sung-hoon Ki ),고동균 ( Dong-kyun Koh ),이상훈 ( Sang-hun Lee ),임형호 ( Hyoung-ho Lim ),송윤경 ( Yun-kyung Song ) 한방재활의학과학회 2022 한방재활의학과학회지 Vol.32 No.2

Objectives This study was conducted to confirm anatomical information near the treatment areas of visceral chuna manual therapy and to secure stability and effectiveness during the treatment. Methods For 50 healthy adult men and women, a total of 13 ultrasound images were taken of the 7 treatment areas which are the representative treatment areas of visceral Chuna manual therapy. Results The treatment area of the bottom of the liver can be palpated around the right side ST19 and CV14. The treatment area of the gallbladder and the common bile duct can be palpated around the right side SP16 and ST20. The treatment area of the cardia and the pylorus can be palpated around the left side KI21, right side ST20, ST21, KI19, KI20, CV12, and CV13. The origin point of the mesentery root can be moved to the left and lower left from CV12 and can be palpated. The treatment area of the ileocecal valve and the cecum can be palpated around the right side SP14. The treatment area for the colic flexure can be palpated around the both side LR13. The treatment support point for the kidneys can be palpated around both side BL51. Conclusions It is thought that if the ultrasound image data from the meridians around the treatment site is used as an auxiliary, it will be more effective in terms of safety and effectiveness during the treatment of visceral Chuna manual therapy. (J Korean Med Rehabil 2022;32(2):139-154)

광선각화증, 보웬병, 편평상피세포암에서 Ki-67, Cyclin A, p53, p16의 발현 양상

이효진 ( Hyo Jin Lee ),신동훈 ( Dong Hoon Shin ),최종수 ( Jong Soo Choi ),김기홍 ( Ki Hong Kim ) 대한피부과학회 2012 대한피부과학회지 Vol.50 No.4

Background: Actinic keratosis (AK) and bowen`s disease (BD) are pre-cancerous diseases, and are regarded as an early squamous cell carcinoma (SCC). AK and BD can be progressed into SCC. In this process, tumor suppressor and cell proliferative proteins may play important roles. Objective: To investigate the differences of expression patterns of the immunohistochemical (IHC) staining and useful markers for differential diagnosis in AK, BD and SCC. Methods: Biopsy had proven 17 cases of AK, 20 cases of BD and 17 cases of SCC, which were all selected. IHC staining for Ki-67 and cyclin-A, as cell proliferative markers, p53 and p16 as tumor suppressor markers, were performed. Labeling index (LI) and distribution pattern of IHC expressions were measured. Results: LI of Ki-67 in AK, BD and SCC were 30.6%, 60.2% and 54.8%, respectively. LI of cyclin-A in AK, BD and SCC were 9.2%, 24.4% and 24.1%, respectively. LI of p53 in AK, BD and SCC were 20.7%, 37.9%, and 39.9%, respectively. LI of p16 in AK, BD and SCC were 10.6%, 38.3% and 39.9%, respectively. Lower 1/3 was the most frequent distribution pattern in AK in all IHC stains, full thickness lower 2/3 were the most frequent distribution pattern in BD and SCC in all IHC stains. Conclusion: LI and distribution pattern of Ki-67, cyclin-A, and p16, as well as the distribution pattern of p53 may be useful markers to differentiate AK from BD and SCC. Higher degree and full-thickness distribution pattern IHC expressions in all stains may be helpful in the diagnosis of BD, rather than AK. (Korean J Dermatol 2012;50(4):290∼298)

원발성 피부 CD30 양성/ALK 음성 퇴형성 대세포 림프종 1예

이은주,김협,서영준,서기범,이증훈,박장규,김유찬,김춘옥 대한피부과학회 2003 大韓皮膚科學會誌 Vol.41 No.5

Primary cutaneous CD3O(Ki-1) Positive anaplastic large cell Iymphoma(ALCL) is a rare subset of cutaneous Iymphoma. with a much better prognosis. ALCL is a heterogeneous process that may have a T-cell, B-cell, or indeterminant(null) phenotype and which may or may not express the anaplastic Iymphoma kinase(ALK) oncoprotein. We report a case of ALCL in a 72 year old man. About 4 months ago, multiple erythematous firm ulcerative mass and satellite nodules developed on the right lower leg. The skin lesions rapidly increased in number and size. Some lesions became painful and centrally ulcered. The histologic findings showed a diffuse infiltrate of large Iymphocytes with large nuclei, prominent and multiple nucleoli, and ample cytoplasm. Immunohistochemical stainings for CD3O, CD5 were positive but stainings for LCA, CD3, CD45RO, CD2O, cytokeratin, EMA, and ALK were negative. Therefore, we diagnosed our case as CD+/30ALK- ALCL (Korean J Dermatol 2003;41(5) : 666~669)

Differential Manifestation of Ocular Phenotypes in TALEN-mediated p19arf Knockout FVB/N and C57BL/6J mouse lines

Jin‑Sung Park,Joo‑Il Kim,Hyun‑Jin Lim,Soo‑Kyung Ryu,Euna Kwon,Kang‑Min Han,Ki‑Taek Nam,Han‑Woong Lee,Byeong‑Cheol Kang 한국유전학회 2020 Genes & Genomics Vol.42 No.9

Background p19arf, primarily known as a tumor suppressor, has also been reported to play an essential role in normal development of mouse eyes. Consistently, lack of p19arf has been associated with ocular defects, but the mixed background of the knockout (KO) mouse strain used raised a concern on the accuracy of the phenotypes observed in association with the targeted gene due to genetic heterogeneity. Object We carried out a study to investigate into the efect of genetic background on the manifestation of p19arf KO associated phenotypes. Methods We characterized the phenotypes of novel p19arf KO mouse lines generated in FVB/N and C57BL/6J using a transcription activator-like efector nuclease (TALEN) system in comparison to the reported phenotypes of three other p19arf-defcient mouse lines generated using homologous recombination. Results Ninety-fve percent of FVB/N-p19arf KO mice showed ocular opacity from week 4 after birth which worsened rapidly until week 6, while such abnormality was absent in C57BL/6J-p19arf KO mice up to the age of 26 weeks. Histopathological analysis revealed retrolental masses and dysplasia in the retinal layer in FVB/N-p19arf KO mice from week 4. Besides these, both strains developed normally from birth to week 26 without increased tumorigenesis except for a subcutaneous tumor found in a C57BL/6J-p19arf KO mouse. Conclusion Our fndings demonstrated surprisingly variable manifestation of p19arf-linked phenotypes between FVB/N and C57BL/6J mice, and furthermore between our mouse lines and the established lines, indicating a critical impact of genetic background on functional study of genes using gene targeting strategies in mice.

Toluene, Xylene, Trichloroethylene 투여가 흰쥐의 시상하부와 뇌하수체의 GnRH, GnRH Receptor, Pit-1 유전자 발현에 미치는 영향

기노석,이종태,강대성,김대환,이채관,이헌,전진호,김정호,이채언 大韓産業醫學會 1998 대한직업환경의학회지 Vol.10 No.2

The workplace exposure of chemicals has steadily increased, therefore the concern for subsequent effect on reproductive outcome has been an important issue in occupational medicine. In previous studies, higher rates of spontaneous abortion, reduced fertility and menstrual disorder among women, and an impairement of sperm quantity and quality among men have been associated with a wide variety of chemical agents. This study was conducted to evaluate the effects of toluene, xylene and trichloroethylene(TCE) injection on the mRNA levels of GnRH, GnRH receptor and Pit-1 genes in male rats hypothalamus and pituitary and the effects on the plasma levels of FSH, LH, prolactin and testosterone. Sprague-Dawley male rats were divided into five groups of five each according to concentration of toluene, xylene and TCE. The rats were injected subcutaneously to 0, 50, 100, 200, 400 mg/kg body weight/day of toluene, xylene and TCE, respectively for 6 days. Rat brains were excised and hypothalamus and pituitary were separated. Reverse transcription-polymerase chain reaction (RT-PCR) and RNase protection assay(RPA) were used to evaluate the GnRH, GnRH receptor and Pit-1 mRNA levels. Plasma concentrations of FSH, LH, prolactin and testosterone were assayed by radioimmunoassay(RIA). The results were as follows; 1. GnRH, GnRH receptor and Pit-1 mRNA levels in toluene and xylene injected groups, and GnRH receptor mRNA levels in TCE injected group were lowered dose-dependently. Especially, GnRH receptor and Pit-1 mRNA levels in 200mg/kg of toluene injected group, and GnRH, GnRH receptor and Pit-1 mRNA levels in 400mg/kg of toluene injected group were significantly lower than control group (p<0.05). GnRH receptor and Pit-1 mRNA levels in 400mg/kg of xylene injected group, and GnRH receptor mRNA levels in 400mg/kg of TCE injected group were significantly lower than control group(p<0.05). 2. The plasma levels of prolactin and testosterone in 400mg/kg of toluene injected group, and LH in 100, 200 and 400mg/kg of xylene injected group, and testosterone in 400 mg/kg of TCE injected group were significantly lower than control group(p<0.05). In conclusion, we speculated that toluene and xylene affected reproductive system secondarily through hypothalamus-pituitary axis, and TCE affected directly through steroidogenesis. And we recommended that further study for assessment of the reproductive toxicity of mixed organic solvent exposures should be conducted.

Ascorbate Peroxidase 유전자의 도입에 의한 식물의 형질전환

이인애,이효신,배은경,김기용,이병헌,손대영,조진기 Plant molecular biology and biotechnology research 2002 Plant molecular biology and biotechnology research Vol.2002 No.-

This study was conducted to obtain the transformed tobacco (Nicotiana tubacum) plants with cytosolic ascorbate peroxidase gene(ApxSC7) using Agrobacterium tumefaciens LBA4404. A cDNA encoding the cytosolic ascorbate peroxidase of strawberry, ApxSC7, was introduced into tobacco plants via Agrobacterium-mediated gene transfer system. The expression vector, pIG-AP8, harboring ApxSC7 gene was used for production of transgenic tobacco plants. A large number of transgenic plants were regenerated on a medium containing hygromycin. Integration of ApxSC7 gene was confirmed by PCR and Southern blot analyses with genomic DNA. Northern blot analyses revealed that the pIGap8 gene was constitutively expressed.

들잔디 성숙종자로부터 캘러스배양 및 식물체 재분화에 미치는 몇 가지 요인의 영향

이상훈,김범수,원성혜,조진기,김기용,박근제,성병렬,이효신,이병현 Plant molecular biology and biotechnology research 2004 Plant molecular biology and biotechnology research Vol.2004 No.-

In an effort to optimize tissue culture responses of zoysiagrass (Zoysia japonica Steud.) for genetic transformation, factors affecting callus induction and plant regeneration were investigated. MS medium containing 3 ㎎/L 2,4-D was optimal for embryogenic callus induction from mature seed. The plant regeneration frequency of 73.3% was observed when embryogenic calli induced in this medium were transferred to N6 medium supplemented with 0.1 ㎎/L 2,4-D and 5 ㎎/L BA. Among several basic media, MS and N6 medium were optimal for callus induction and plant regeneration, respectively. Regenerated plants were grown normally when shoots transplanted to the soil. A rapid and efficient plant regeneration system established in this study will be useful for molecular breeding of turfgrass through genetic transformation.