Efficient Interleukin-21 Production by Optimization of Codon and Signal Peptide in Chinese Hamster Ovarian Cells

( Hee Jun Cho ),( Byung Moo Oh ),( Jong-tae Kim ),( Jeewon Lim ),( Sang Yoon Park ),( Yo Sep Hwang ),( Kyoung Eun Baek ),( Bo-yeon Kim ),( Inpyo Choi ),( Hee Gu Lee ) 한국미생물 · 생명공학회 2019 Journal of microbiology and biotechnology Vol.29 No.2

Interleukin-21 is a common γ-chain cytokine that controls the immune responses of B cells, T cells, and natural killer cells. Targeting IL-21 to strengthen the immune system is promising for the development of vaccines as well as anti-infection and anti-tumor therapies. However, the practical application of IL-21 is limited by the high production cost. In this study, we improved IL-21 production by codon optimization and selection of appropriate signal peptide in CHO-K1 cells. Codon-optimized or non-optimized human IL-21 was stably transfected into CHO-K1 cells. IL-21 expression was 10-fold higher for codon-optimized than non-optimized IL-21. We fused five different signal peptides to codon-optimized mature IL-21 and evaluated their effect on IL-21 production. The best result (a 3-fold increase) was obtained using a signal peptide derived from human azurocidin. Furthermore, codon-optimized IL-21 containing the azurocidin signal peptide promoted IFN-γ secretion and STAT3 phosphorylation in NK-92 cells similar to codon-optimized IL-21 containing original signal peptide. Collectively, these results indicate that codon optimization and azurocidin signal peptides provide an efficient approach for the high-level production of IL-21 as a biopharmaceutical.

β-Carotene과 알코올을 섭취한 쥐의 혈액 성분변화의 상관관계

고재웅,조만희,이상한,우기민,염윤기,김창세 순천향의학연구소 2000 Journal of Soonchunhyang Medical Science Vol.6 No.2

The study was carried out to investigate the effects of dietary carotenids and β-carotene on the hematological changes caused by alcohol administration into the rats. The results were analyzed using several statistical methods; SPSS computer program for measuring the mean values and standard deviations, one way ANOVA for the test of significance, Duncan method for post HOC multiple comparison, and Pearson method for measuring the correlation coefficient. The following are the conclusion from those statistical analysis. 1. ALB and TB were shown to have the most significant correlation among the blood compositions f개m the basic dietary groups. 2. BUN and CHO were shown to have the most positive correlation among those from the carrot-fed groups. 3. CA and AG were shown positively correlated, and CHO and IP negatively correlated, respectively among those from the cheese-fed groups. 4. AP was shown positively correlated among those from the alcohol-administrated groups. 5. CHO, CA and BUN were shown positively correlated, and CA was negatively correlated among those from the β-Carotene -fed groups. 6. TB and TP were not affected by the correlations between the blood composition from all the experimental groups.

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.

경피적관상동맥확장술 도중 발생한 관상동막파열과 대동맥박리 급성페색증을 경피적방법으로 치료한 1예

이내희,조윤행 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.2

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구강에 발생한 편평상피암종의 MMP-2, MMP-9, TIMP-1, TIMP-2 발현과 EGFR 및 E-cadherin 발현의 상호연관성

조성재,권창석,김용환,윤혜경,김우형,이희철 인제대학교 백병원 2002 仁濟醫學 Vol.23 No.4

Objective : Matrix metalloproteinases(MMPs) are involved in the degradation of extracellular matrix, which is related to infiltrative growth and metastasis of tumor. Positive correlation between MMPs expression and clinico-pathologic parameters were reported, and MMPs expressions were regulated by tissue inhibitor of metalloproteinases(TIMPs) or cell adhesion molecules such as E-cadherin and epidermal growth factor receptor EGFR). The aim of this study is to evaluate the relationship between MMP-2, MMP-9 expressions and clinico-pathologic factors such as clinical stage. recurrence. histologic grade and invasion pattern, and between MMP-2 and MMP-9 Expressions and TIMP-1, TIMP-2, and E-cadherin expressions. Methods and Material : The materials were 55 cases of squamous cell carcinoma of the oral cavity, and immunohisdtochemical studies for MMP-2, MMP-9, TIMP-1, TIMP-2, E-cadherin and EGFR were performed. Clinico-pathologic factors such as clinical stage, recurrence, histologic grade and invasion pattern were recorded through microscopic examination and clinical record review. Statistical analyses between MMP-2, MMP-9 expressions and clinico-pathologic factors, TIMP-1, TIMP-2 expressions and EGFR and E-cadherin expressions were done. Results : 1. MMP-2 and MMP-9 expressions were noted in 30(54.5%) and 22(40.0%) of 55 cases, respectively. TIMP-1 and TIMP-2 expressions were observed in 21(38.2%) and 33(60.0%), and E-cadherin and EGFR expressions were found in 35(63.6%) and 26(47.3%) of 55 cases, respectively. 2. MMP-2 expression rate was slightly higher in cases without recurrence, and TIMP-2 expression rate was slightly higher in cases showing more infiltrative growth pattern. However, there were no significant differences of MMP-2, MMP-9, TIMP-1, and TIMP-2 expression rates according to other clinico-pathologic parameters were noted. 3. The expression rate of EGFR was higher in cases with well differentiation (p=0.0047), but no positive relationship between the expression rate of E-cadherin and histologic grade was found. There were no significant differences of the expression rates of E-cadherin and EGFR according to other clinico-pathologic parameters. 4. Cases with positive reaction for MMP-9 showed an increasing tendency of negative reaction for TIMP-1. However, signigicant relationships between MMP-2, MMP-9 expressions and TIMP-1, TIMP-2 expressions were not noted. 5. The expression rate of MMP-2 was higher in cases with positive reaction for Ecadherin and EGFR with no statistical significance. The expression rate of MMP-9 was significantly higher in cases with positive reaction for E-cadherin(p=0.0221), but there was no significant relationship between MMP-9 and EGFR expression. Conclusion : These results suggest that MMP-2, MMP-9, TIMP-1 and TIMP-2 expressions are involved in the development of oral squamos cell carcinomas, but MMP-2, MMP-9, TIMP-1, and TIMP-2 expressions might not seem to be a sueful prognostic factors because there were no significant relationship between clinicopathologic parameters, EGFR expression showed positive correlation with low histologic grace, so EGFR expression could be regarded as a good prognostic factor. In the progression of squamous cell carcinoma of oral cavity, MMP-9 and E-cadherin might be involved with positive correlation, but there were no significant correlations between MMP-2, MMP-9 and TIMP-1, TIMP-2 and EGFR expressions rate. Further study for other factors such as cytokines or growth factors except TIMP-1, TIMP-2 and EGFR will be needed.

심환좌심실기능부전을 동반한 만성신부전환자에서 완전폐색관상동맥의 경피적관상동맥확장술

이내희,조윤행 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.2

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서울시 대기오염과 일별 사망의 상관성에 관한 시계열적 연구 (1998~2001년)

조용성,이종태,김윤신,홍승철,김호,하은희,박혜숙,이보은 한국대기환경학회 2003 한국대기환경학회지 Vol.19 No.6

This study was performed to examine the relationship between air pollution exposure and mortality in Seoul for the years of 1998~2001I. Daily counts of death were analyzed by general additive Poisson model, with adjustment for effects of seasonal trend, air temperature, humidity, and day of the week as confounders in a nonparametric approach. Daily death counts were associated with CO (current day), 0₃(current day), PM_(10) (current day), NO₂, (1 day before), SO₂, (1 day before). Increase of 41.711㎍/㎥ (interquartile range) in PM_(10) was associated with 1.3% (95% CI = 0.7~1.9%) increase in the daily number of death. 0₃concentrations resulted in an increased risk of 1.3% for 23.86 ppb in all-aged mortality [RR = 1.013 (1.004-1.023)]. This effect was greater in children (less than 15 aged) and elderly (more than 65 aged). After ozone level exceeds 25 ppb, the dose-response relationship between mortality and ozone was almost linear. We concluded that Seoul had 1~5% increase in mortality in association with IQR (interquartile range) in air pollutants. Daily variations in air pollution within the range currently occurring in Seoul might have an adverse effect on daily mortality. These findings also support the hypothesis that air pollution, at levels below the current ambient air quality standards of Korea, is harmful to sensitive subjects, such as children or elderly.

산발성 장형 위선암 환자의 Microsatellite Instability와 병리학적 양상

조창희,홍유찬,안지현,최경현,이상호,신영명,윤기영,정민정,장희경 고신대학교의과대학 2007 고신대학교 의과대학 학술지 Vol.22 No.2

Background : Through many researches, microsatellite is expected to be a good diagnositic and prognostic factor in colorectal cancer, endometrial cancer, gastric cancer, and the others. The prevalence of microsatellite instability (MSI) in gastric carcinoma has reported variously, 13~44%. Purpose : We aimed to determine the prevalence of MSI-high and the relationship between MSI and pathological characteristics of sporadic intestinal type adenocarcinoma of stomach. Material and Methods : We analyzed 106 sporadic intestinal type adenocarcinoma specimens excised from patients who were over thirty-five years old to determine the statue of microsatellite by DNA sequencing. The tissues were formalin-fixed and paraffin embedded. DNA were extracted and amplified by polymerase chain reaction (PCR). MSI was determined using five markers recommended by National Cancer Institute (NCI). Specimens were also studied with five patholical factors-differenciation of tumor cells, depth of invasion, lymph node metastasis, vessel invasion, and perineural invasion- to determine pathological state. Result : The microsatellite statue was determined as MSI-High in 5 cases (4.7%), no MSI-low, and MSS (microsatellite stable) in 101 cases (95.3%). Within the frequency, there was no large gap in the distinction of gender in MSI cases, but in MSS cases, there was three-times more cases in male. MSI cases had moderate-to-poor differenciation and trend to invade toward serosa. All MSI cases showed no perineural invasion. But we could not find any statistical significance between MSI and pathological characteristics of sporadic intestinal type adenocarcinoma. Conclusion : Results suggest that MSI can not make any certain pathological significance in sporadic intestinal type adenocarcinoma. Even though less than 5% of sporadic intestinal type adenocarcinoma patients showed MSI, it can be used as a influential prediagnostic factor of gastric cancer. Further study with large scale of cases will be followed to verify these results.

열대 지역에서 통일형 초다수성 벼 품종의 생육 및 수량성 비교

이지윤,준현,성환,손영보,송유천,한상익,박동수,권영업,이철원,이종희 忠北大學校 農業科學硏究所 2015 農業科學硏究 Vol.31 No.2

젊은 성인 남자의 흡연과 혈청 지질과의 관련성

조선,류소연,박종,강명근,김은숙,김형철,박광희,윤혜은,노희송 朝鮮大學校 附設 醫學硏究所 2007 The Medical Journal of Chosun University Vol.32 No.2

Objectives: This study was performed to find the association of cigarette smoking and blood lipid profiles in healthy young adults. Methods: The data was collected by a self-administered questionnaire and health examination in 489 professional soldiers from 6 to 12 May, 2004. The status of cigarette smoking was classified by non-smoking, ex-smoked, ≤4.9, 5-9.9, and ≥10 pack-years. The statistical analysis were used by chi-square test, analysis of variance and analysis of covariates. Results: In status of subjects cigarette smoking, current smoking, ex-smoked, and non-smoking were 71.8%, 11.2%, and 17.0%, respectively, In distribution by amount of smoking, non-smoking, ex-smoked, ≤4.9 pack-years, 5-9.9 pack-years, and ≥10 pack-years were 17.0%, 11.2%, 37.4%, 21.3%, and 13.1%, respectively. At other confounding variables were controlled, total cholesterol and LDL-cholesterol were increased significantly when amount of smoking was increased. However, triglyceride and HDL-cholesterol did not showed statistically significant differences, Conclusion: Smoking has relevant to total cholesterol and LDL-cholesterol and it is need to perform the further study for finding how blood lipid profiles are affected its level by cigarette smoking and to find an influence of cigarette smoking on cardiovascular disease.