Evaluation of Biological Performance in a Newly Developed Single-use Bioreactor, the CELBIC System

Hyunwoo KIM,Rock Ki KIM,Young Hee SHIN,Yeong Ok BAIK,Sun Young KIM,Chong Myong KIM,Yong Bok LEE,Kyung Nam KIM,Duk Jae OH 한국생물공학회 2021 한국생물공학회 학술대회 Vol.2021 No.10

Since the SUB(Single-Use Bioreactor)s have several advantages compared with the conventional stainless steel-based bioreactors, such as flexibility in scale, low risk of contamination, reduced labors for cleaning/ sterilization, and validation/regulation issues, the usage of SUBs for cell culture has been increasing continuously, as the bioindustry of biopharmaceuticals (proteins, antibodies, cell therapies and gene therapies products) has expanded dramatically during recent decades. In this study, a newly developed cell culture system, the CELBIC system, driven by multi-directional rocking movement is introduced and evaluated its physical and biological performances as a cell culture device. Three recombinant cell lines, CHO DG44, CHO-S, and CHO-K1, producing proteins were used for experiments, and cell cultures were carried out in four different working volumes of 1 liter, 5 liters, 50 liters, and 250 liters. Those cell cultures as the biological evaluation were performed under the conditions chosen from the results of evaluation of physical performances of the CELBIC system. For comparison, Erlenmeyer flasks and STR bioreactors representing a conventional cell culture device were used as control groups. Productivity was analyzed through ELISA and HPLC analysis methods. In the CELBIC system, cell cultures could be carried out successfully. In addition, cell growth performances were equal or superior to those of the control groups. From the results of biological evaluation, it was found that the CELBIC system is a SUB system easy to scale-up and able to cultivate cells specialized in suspension culture for producing proteins. It is considered that the CELBIC system can be an appealing alternative as a culture device across the biopharmaceutical fields including research and industry.

Redox regulation of the tumor suppressor PTEN by glutathione

Kim, Yujeong,Song, Yong Bhum,Kim, Tae-Youl,Kim, Inyoung,Han, Seong-Jeong,Ahn, Younghee,Cho, Seung-Hyun,Choi, Cheol Yong,Chay, Kee-Oh,Yang, Sung Yeul,Ahn, Bong Whan,Huh, Won-Ki,Lee, Seung-Rock Elsevier 2010 FEBS letters Vol.584 No.16

<P><B>Abstract</B></P><P>Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expressed in <I>Saccharomyces cerevisiae</I> was reversibly oxidized by hydrogen peroxide and reduced by cellular reductants. Reduction of hPTEN was delayed in each of <I>S. cerevisiae</I> gsh1Δ and gsh2Δ mutants. Expression of γ-glutamylcysteine synthetase Gsh1 in the gsh1Δ mutant rescued regeneration rate of hPTEN. Oxidized hPTEN was reduced by glutathione in a concentration- and time-dependent manner. Glutathionylated PTEN was detected. Incubation of 293T cells with BSO and knockdown expression of GCLc in HeLa cells by siRNA resulted in the delay of reduction of oxidized PTEN. Also, in HeLa cells transfected with GCLc siRNA, stimulation with epidermal growth factor resulted in the increase of oxidized PTEN and phosphorylation of Akt. These results suggest that the reduction of oxidized hPTEN is mediated by glutathione.</P>

Characterization and Modeling of 1/<tex> $f$</tex> Noise in Si-nanowire FETs: Effects of Cylindrical Geometry and Different Processing of Oxides

Rock-Hyun Baek,Chang-Ki Baek,Hyun-Sik Choi,Jeong-Soo Lee,Yun Young Yeoh,Kyoung Hwan Yeo,Dong-Won Kim,Kinam Kim,Kim, D M,Yoon-Ha Jeong IEEE 2011 IEEE TRANSACTIONS ON NANOTECHNOLOGY Vol.10 No.3

<P>In this paper, the volume trap densities <I>Nt</I> are extracted from gate-all-around silicone-nanowire FETs with different gate oxides, using a cylindrical-coordinate-based flicker noise model developed. For extracting <I>Nt</I>, the drain-current power spectral densities were measured from a large number of identical devices and averaged over, thereby mimicking the spatial distribution of trap sites inducing 1/<I>f</I> curve. Also, effective mobility and threshold voltage were simultaneously extracted with the series resistance to characterize the 1/<I>f</I> noise in terms of intrinsic values of these two channel parameters. The volume trap densities thus extracted from different oxides (in situ steam-generated oxide/rapid thermal oxide/nitride-gated oxide) are compared and further examined using hot-carrier stress data. Finally, radius dependence of the cylindrical 1/<I>f</I> model developed is discussed.</P>

The General Public’s Awareness of Early Symptoms of and Emergency Responses to Acute Myocardial Infarction and Related Factors in South Korea: A National Public Telephone Survey

Kim, Hee-Sook,Lee, HeyJean,Kim, KeonYeop,Park, Hyeung-Keun,Park, Ki-Soo,Kang, Gil Won,Shin, Hee-Young,Kim, Rock Bum,Oh, Gyung-Jae,Seo, Jae Hee,Lee, Young-Hoon Japan Epidemiological Association 2016 Journal of epidemiology Vol.26 No.5

<P><B>Background</B></P><P>Prompt treatment affects prognosis and survival after acute myocardial infarction (AMI) onset. This study evaluated the awareness of early symptoms of AMI and knowledge of appropriate responses on symptom occurrence, along with related factors.</P><P><B>Methods</B></P><P>Participants’ knowledge of the early symptoms of and responses to AMI onset were investigated using a random digit dialing survey. We included 9600 residents of 16 metropolitan cities and provinces in Korea.</P><P><B>Results</B></P><P>The proportions of respondents who were aware of early symptoms of AMI ranged from 32.9% (arm or shoulder pain) to 79.1% (chest pain and discomfort). Of the respondents, 67.0% would call an ambulance if someone showed signs of AMI, 88.7% knew ≥1 symptom, 10.9% knew all five symptoms, and 3.1% had excellent knowledge (correct identification of all five AMI symptoms, not answering “Yes” to the trap question, and correctly identifying calling an ambulance as the appropriate response when someone is exhibiting AMI symptoms). The odds ratio (OR) for having excellent knowledge was significantly higher for those who graduated college or higher (OR 3.42; 95% confidence interval [CI], 1.09–10.76) than for those with less than a primary school education, as well as for subjects with AMI advertisement exposure (OR 1.49; 95% CI, 1.10–2.02) and with knowledge of AMI (OR 1.63; 95% CI, 1.16–2.27). The 60- to 79-year-old group had significantly lower OR for excellent knowledge than the 20- to 39-year-old group (OR 0.53; 95% CI, 0.28–0.99).</P><P><B>Conclusions</B></P><P>Awareness of AMI symptoms and the appropriate action to take after symptom onset in South Korea was poor. Therefore, educational and promotional strategies to increase the overall awareness in the general public, especially in the elderly and those with low education levels, are needed.</P>

Ka-대역 계단형 도파관 벤드 최적 설계 및 제작

김기록(Ki-Rock Kim),주병국(Byung-kook Joo),방재훈(Jae-Hoon Bang),안병철(Bierng-Chearl Ahn),전종훈(Jong-Hun Chun) 한국정보기술학회 2009 한국정보기술학회논문지 Vol.7 No.6

외과적 합병증을 동반한 십이지장 궤양의 임상적 고찰

김기영(Ki Young Kim),박용기(Young Ki Park),최창록(Chang Rock Choi) 대한외과학회 1992 Annals of Surgical Treatment and Research Vol.43 No.1

우울증상에 관련된 요인과 우울증상이 지각된 건강수준, 외래의료이용, 삶의 질에 미치는 영향

김록범(Rock Bum Kim),박기수(Ki Soo Park),이진향(Jin Hyang Lee),김봉조(Bong Jo Kim),전진호(Jin Ho Chun) 한국보건교육건강증진학회 2011 보건교육건강증진학회지 Vol.28 No.1

Objectives: The purpose of this study is to evaluate the influence of depression symptom on the self-rated health status(SRHS), the outpatient health service utilization and quality of life(QOL) also the relationship depression symptom with socio-demographic and health related factors. Methods: We selected 9,550 participants without chronic diseases from a total of 18,104 in the '2009 community health survey in Gyeongnam. They were assessed by using a Korean version of the Center for Epidemiological Studies-Depression Scale(CES-D). Those with CES-D scores of 21 or greater were defined as having probable depression. Results: A probable depression were associated in bivariate analysis with gender, age, educational status, monthly household income, marital status, current smoking status, drinking habit, physical activities and body mass index. After adjustment for covariates, probable depression groups predicted a lower status in SRHS. Likewise probable depression groups predicted a higher utilization in outpatient health service. Also probable depression groups predicted a lower score in QOL. Conclusions: Probable depression influence SRHS, outpatient health service utilization and QOL even after adjusting for the socio-demographic, health related factors and chronic medical illness. Programs for prevention and management of depression will be helpful to promote health and QOL.

Development of Indirect Enzyme-Linked Immunosorbent Assay Using Recombinant P46 Surface Antigen for Serum Antibody Against Mycoplasma hyopneumoniae

Woo Chang Kim,Rock Ki Kim,Byung Sik Chang,Kyu hyung Han,Ae ran Kim,Chun Tae Lim,Suk Chan Jung,Ji Youn Lee,Hoo Don Joo 대한수의학회 2009 대한수의학회 학술대회발표집 Vol.2009 No.-

유전성 대사질환에서의 동종조혈모세포이식 : 단일 기관에서의 경험 A single center experience

유건희,김흥렬,이지은,이호영,천정미,성기웅,구홍회,이문향,진동규,김종원,김대원,김형록 대한조혈모세포이식학회 2001 대한조혈모세포이식학회지 Vol.6 No.2

배경: 유전성 대사질환의 치료로서 효소 요법 및 유전자 치료가 제한적인 현실에서 동종 조혈모세포이식이 현재로선 가장 중요한 치료가 될 수 있다. 본 연구에서는 단일 기관에서 유전성 대사질환에 대해 동종 조혈모세포이식을 시행한 경험을 보고하고자 하였다. 방법: 삼성서울병원 유전성 대사질환 조혈모세포이식팀에서는 1999년 12월부터 2001년 3월까지 총 6례의 유전성 대사질환을 대상으로 동종 조혈모세포이식을 시행하였다. 대상 질환은 Hunter 증후군 3례, galactosialidosis 1례, 이염성 백질이영양증 1례, 부신백질이영양증 1례였으며 성별 분포는 남아가 5명, 여아가 1명이었으며 연령 분포는 2년 9개월에서 15년 9개월이었다. 5례는 HLA 일치 혈연간 골수이식이었으며 1례는 HLA 불일치 T 림프구 제거 말초혈액 조혈모세포이식이었다. 전처치는 모두 BuCy를 사용하였으며 이식편대숙주반응의 예방에는 cyclosporine을 사용하였다. 이식된 세포는 유핵세포가 4.81×10^(8)(2.40~7.01×10^(8))/kg이었으며 CD34+ 세포는 3.65×10^(6)(0.88~10.72×10^(6))/kg이었다. 결과: 이식 후 조혈기능의 회복은 모두 조기에 달성되었으며(ANC>500: 정중 9.5일, 범위 9~14일; PLT>50K: 정중 32일, 범위 23~34일) 이식과 관련된 합병증은 Gr I의 aGVHD 3례, 국한성의 cGVHD 1례, 경증의 간정맥 폐쇄성 질환이 1례이었다. 모든 환자에서 직간접적으로 이식 후 효소의 생산이 증가함이 확인되었으며 임상적인 호전을 보인 경우가 4례, 질병 진행이 중단된 경우가 1례, 질병이 진행된 경우가 1례이었다. 질병 진행이 중단되었던 1례는 면역억제제 투여 중 수두 감염에 의한 폐출혈로 사망하였다. 결론: 유전성 대사질환에서 동종 조혈모세포이식이 가장 중요한 치료법으로 사용될 수 있고 중추신경계 증상이 나타나기 전, 가능한 조기에 조혈모세포이식을 시행하는 것이 바람직할 것이며 적극적인 지지 요법이 필요하다. 향후 더 많은 임상 경험이 필요하리라 사료된다. Background: Allogeneic hematopoietic stem cell transplantation (HSCT) may be the most important treatment modality to cure a number of genetic metabolic disorders because of the limitation of enzyme replacement or gene therapy. In this study, we report our single center experience about HSCT in several genetic metabolic disorders. Methods: We performed 6 cases of HSCT for genetic metabolic disorders from December 1999 to March 2001. Patients' diagnoses were Hunter syndrome (3), galactosialidosis (1), metachromatic leukodystrophy (1), and adrenoleukodystrophy (1). Stem cell sources were bone marrow from HLA matched sibling donors in 5 patients and mother's peripheral blood stem cells in one patient who did not have HLA matched donors. Busulfan and cyclophosphamide for conditioning, and cyclosporine for the prevention of graft versus host disease were used in all patients. Transplanted total nucleated cell counts were median 4.81×10^(8)(2.40~7.01×10^(8))/kg , and CD34+ cells 3.65×10^(6)(0.88~10.72×10^(6))/kg. Results: All patients achieved early hematologic recovery (median 9.5 days, range 9~14 days for ANC>500/μL; median 32 days, range 23~34 days for PLT>50,000/μL). Transplant-related complications were 3 cases of grade 1 acute GVHD, a case of limited chronic GVHD, and a case of mild hepatic veno-occlusive disease. Enzyme levels were normalized in 4 patients evaluated and there were indirect evidences of enzyme production in the other 2 patients after HSCT. Four of the 6 patients showed symptomatic improvement, 1 patient (galactosialidosis) experienced disease stabilization without progression before he eventually died due to pulmonary hemorrhage, and the other 1 patient deteriorated progressively even after HSCT. Conclusions: Allogeneic HSCT can be done as the only curative treatment in a number of genetic metabolic disorders. It seems desirable to perform HSCT as early as possible before the onset of central nervous system symptoms. More experience and long term follow up is needed to evaluate the efficacy and to monitor the long term transplant-related complications.

The association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression in patients with rheumatoid arthritis

Cheon, Yun-Hong,Lee, Seung-Geun,Kim, Mingyo,Kim, Hyun-Ok,Sun Suh, Young,Park, Ki-Soo,Kim, Rock Bum,Yang, Hyun-Su,Kim, Ji-Min,Son, Chang-Nam,Kyoung Park, Eun,Kim, Sang-Hyon,Lee, Sang-Il Elsevier 2018 Brain, behavior, and immunity Vol.73 No.-

<P><B>Abstract</B></P> <P>Inflammation and trophic factors (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor-1) are associated with depression in the general population. Rheumatoid arthritis (RA) is a chronic representative inflammatory autoimmune disease; however, the association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression has not been sufficiently investigated. Therefore, we determined the prevalence of depression and risk factors for depression and deterioration of depressive symptoms in RA patients. In addition, we analyzed the association between disease activity, pro-inflammatory cytokines, trophic factors, and depression in RA (N = 474). Demographic and laboratory data were examined, and routine assessment of patient index data 3 (RAPID 3) and disease activity score 28-joint count C-reactive protein (DAS 28-CRP) was performed to assess disease activity of RA. Depression was measured using the Korean version of the Beck Depression Inventory-second edition (K-BDI II). A K-BDI score ≥18 was considered the cut-off for depression in accordance with a previous validation study. The serum level of pro-inflammatory cytokines and neurotrophic factors was assessed by enzyme-linked immune sorbent assay. The prevalence of depression was 32.4% in patients with RA. The severity of disease activity of RA (RAPID 3 score [OR 2.34; 95% confidence interval, CI 1.22–4.51], DAS 28-CRP [≥3.2] [OR 1.60, 95% CI 1.01–2.53]) and severity of fatigue (OR 1.26 95% CI 1.15–1.38) were associated with depression and deterioration of depressive symptoms in the multivariate analysis. Among the components of RAPID 3 and DAS 28-CRP, patient assessment for global health and abilities for daily performance were more related to depression. The level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-alpha) was not related to depression. The level of BDNF was significantly lower in RA patients with depression and was negatively correlated with K-BDI II score. Depression was related with the level of fatigue, low expression of BDNF, and high RA disease activity, which was associated with impaired ability to perform activities of daily life. Strict control of fatigue and disease activity to improve one’s capacity to perform daily life activities would be important to regulate depression. The level of BDNF might be one of the possible biomarkers to predict or monitor depression in patients with RA.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Prevalence of depression in patients with rheumatoid arthritis (RA) was analyzed. </LI> <LI> Risk factors for depression and deterioration of depressive symptoms and were analyzed. </LI> <LI> Depression was related with disease activity in RA. </LI> <LI> Depression in RA was associated with impaired ability to perform activities of daily life. </LI> <LI> Among neurotrophic factors, the level of BDNF was related with depression in RA patients. </LI> <LI> The level of pro-inflammatory cytokines were not related with depression in RA patients. </LI> </UL> </P>