Dual bio-responsive gene delivery via reducible poly(amido amine) and survivin-inducible plasmid DNA

Namgung, Ran,Brumbach, Jonathan H.,Jeong, Ji Hoon,Yockman, James W.,Kim, Sung Wan,Lin, Chao,Zhong, Zhiyuan,Feijen, Jan,Engbersen, Johan F. J.,Kim, Won Jong Springer-Verlag 2010 Biotechnology letters Vol.32 No.6

<P>A bioreducible poly(amido amine) (SS-PAA) gene carrier, known as poly (amido-butanol) (pABOL), was used to transfect a variety of cancer and non-cancer cell lines. To obtain cancer-specific transgene expression for therapeutic efficiency in cancer treatment, we constructed survivin-inducible plasmid DNA expressing the soluble VEGF receptor, sFlt-1, downstream of the survivin promoter (pSUR-sFlt-1). Cancer-specific expression of sFlt-1 was observed in the mouse renal carcinoma (RENCA) cell line. pABOL enhanced the efficiency of gene delivery compared to traditional carriers used in the past. Thus, a dual bio-responsive gene delivery system was developed by using bioreducible p(ABOL) for enhanced intracellular gene delivery and survivin-inducible gene expression system (pSUR-sFlt-1 or pSUR-Luc reporter gene) that demonstrates increased gene expression in cancer that has advantages over current gene delivery systems.</P>

The Effect of Metronidazole and Quinacrine on the Morphology and the Excystation of Giardia lamblia

Ran, Namgung,Ryu,Jae-Sook,Lee,Keun-Tae,Soh,Chin-Thack INSTITUTE OF TROPICAL MEDICINE YONSEI UNIVERSITY 1985 YONSEI REPORTS ON TROPICAL MEDICINE Vol.16 No.1

람블편모충 씨스트의 생사여부를 판정함에 있어 최근 Rice 및 Schaefer Ⅲ(1981)는 시험관내에서 씨스트를 탈낭시켜 영양형이 나오는 비율을 기준으로 하는 합리적인 방법을 개발함으로써 신빙성 있는 판정을 할 수 있게 되었다. 람블편모충의 미세구조에 대하여 Morecki 및 Parker(1967), Sheffield 및 Bjorvatn(1977)이 종래에 광학현미경으로는 밝혀지지 않았던 새로운 미세구조를 관찰하여 보고 하였으나 약제 투여후 원충자체의 형태학적 및 생물학적 변화에 대하여는 연구된바가 없다. 따라서 본 연구에서는 람블편모충 감염환자에게 약제를 투여했을 경우 배출되는 씨스트가 어떠한 영향을 받는지, 또한 시험관내 실험에서 약제를 투여했을 때 본 원충의 영양형과 씨스트가 어떤 영향을 받는지를 규명하고저 하였다. 람블편모충 씨스트를 Bingham 및 Meyer(1979), Rice 및 Schaefer Ⅲ(1981)의 방법을 수정하여 탈낭시켰고 수식에 따라 탈낭률을 산정하였다. 시험관내에서 약제노출후 씨스트의 탈낭률을 알아보기 위하여 metronidazole 10mg/ml과 quinacrine 28.5mg/ml액속에서 3∼48시간 노출시켰으며, 람블편모충증 환자에서 투약후 탈낭률을 알아보기 위하여 metronidazole과 quinacrine 치료용량을 투여하면 배출된 씨스트를 탈낭시켜 수식에 따라 탈낭률을 산정하였다. 람블편모충을 시험관내에서 약제에 노출시킨 후 미세구조를 관찰하기 위하여 metronidazole과 quinacrine의 minimal immobilizing concentration(MIC)을 Jokipii 및 Jokipii(1980)의 방법에 따라 결정하였으며, 배양 2일째 되는 영양형을 두가지 약제의 MIC에 노출시키고 24시간 배양후 전자현미경 관찰을 위한 조작과정을 거쳐 Hitachi-500투과 전자현미경으로 관찰하였다. 람블편모충 영양형의 약제노출후 효소활성을 관찰하기 위하여 metronidazole, quinacrine의 MIC에 노출된 영양형을 alkaline phosphatase와 peroxidase 기질용액에서 1시간 동안 incubation한후 고정 탈수하여 관찰하였다. 람블편모충 씨스트의 약제노출후 미세구조의 변화를 관찰하기 위하여 시험관내에서 metronidazole 10mg/ml, quinacrine 28.5mg/ml에 각각 18시간, 3시간씩 처리한 후 통상적인 방법대로 고정 탈수 염색하여 관찰하였다. 본 실험에서 얻은 결과는 다음과 같다. 1. 람블편모충 씨스트를 시험관내에서 약제노출후 탈낭률은 약제에 노출시키지 않은 대조군에 비하여 현저히 감소하였으며 metronidazole 노출후에는 48시간에, quinacrine 노출후에는 12시간에 씨스트를 사멸하였다. 2. 람블편모충증 환자에서 투약후 배출되는 씨스트의 탈낭률은 두가지 약제 모두에서 투약전에 비하여 현저히 감소하였다. 3. 람블편모충 영양형의 시험관내 약제노출 후 형태적인 변화는 metronidazole의 경우 모양이 불규칙해지고 핵막이 파괴되었으며 공포의 수가 증가하였고, quinacrine에서는 핵막과 원형질막이 파괴되고 세포질내 입자가 응집되어 있는 것이 관찰되었다. 4. 람블편모충 영양형의 약제노출후 alkaline phosphatase와 peroxidase 활성도는 두가지 약제에서 모두 대조군에 비하여 현저히 저하되었으며, 약화된 효소의 활성이 세포질, 핵막과 공포의 한계막등에서 관찰되었다. 5. 람블편모충 씨스트의 시험관내 약제노출후 형태적인 변화는 metronidazole의 경우 세포질의 전자밀도가 감소되었고 세포질이 위축되어 열공이 넓어졌고 공포의 수가 증가되었으며, quinacrine의 경우 핵이 파괴되고 공포의 수가 증가되었으며 세포질내 입자가 응집되어 있는 것이 관찰되었다. 이상의 결과로 보아 metronidazole 및 quinacrine에 노출된 람블편모충의 씨스트는 탈낭률이 현저히 감소되고 영양형과 더불어 미세구조에 현저한 변화를 초래하는 것으로 본다.

정상 신생아에서 혈청 Insulin like growth factor-Ⅰ의 계절별 차이에 관한 연구

남궁란,이철,한동관 大韓周産醫學會 1997 大韓周産醫學會雜誌 Vol.8 No.1

고위험 신생아의 예후

남궁란 대한의학협회 1990 대한의학협회지 Vol.33 No.5

최근 3년간 분리된 균주의 내성 양상 및 항균제 사용 현황

손혜란,남궁광현,오양순,김보영,조송자 한국병원약사회 1996 病院藥師會誌 Vol.13 No.3

Graphene Oxide–PolyethylenimineNanoconstructas a Gene Delivery Vector and Bioimaging Tool

Kim, Hyunwoo,Namgung, Ran,Singha, Kaushik,Oh, Il-Kwon,Kim, Won Jong American ChemicalSociety 2011 Bioconjugate chemistry Vol.22 No.12

<P>Graphene oxide (GO) has attracted an increasing amountof interestbecause of its potential applications in biomedical fields such asbiological imaging, molecular imaging, drug/gene delivery, and cancertherapy. Moreover, GO could be fabricated by modifying its functionalgroups to impart specific functional or structural attributes. Thisstudy demonstrated the development of a GO-based efficient gene deliverycarrier through installation of polyethylenimine, a cationic polymer,which has been widely used as a nonviral gene delivery vector. Itwas revealed that a hybrid gene carrier fabricated by conjugationof low-molecular weight branched polyethylenimine (BPEI) to GO increasedthe effective molecular weight of BPEI and consequently improved DNAbinding and condensation and transfection efficiency. Furthermore,this hybrid material facilitated sensing and bioimaging because ofits tunable and intrinsic electrical and optical properties. Consideringthe extremely high transfection efficiency comparable to that of high-molecularweight BPEI, high cell viability, and its application as a bioimagingagent, the BPEI–GO hybrid material could be extended to siRNAdelivery and photothermal therapy.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bcches/2011/bcches.2011.22.issue-12/bc200397j/production/images/medium/bc-2011-00397j_0008.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/bc200397j'>ACS Electronic Supporting Info</A></P>

Bioreducible Polymers for Gene Silencing and Delivery

Son, Sejin,Namgung, Ran,Kim, Jihoon,Singha, Kaushik,Kim, Won Jong American Chemical Society 2012 Accounts of chemical research Vol.45 No.7

<P>Polymeric gene delivery vectors show great potential for the construction of the ideal gene delivery system. These systems harness their ability to incorporate versatile functional traits to overcome most impediments encountered in gene delivery: from the initial complexation to their target-specific release of the therapeutic nucleic acids at the cytosol. Among the numerous multifunctional polymers that have been designed and evaluated as gene delivery vectors, polymers with redox-sensitive (or bioreducible) functional domains have gained great attention in terms of their structural and functional traits. The redox environment plays a pivotal role in sustaining cellular homeostasis and natural redox potential gradients exist between extra- and intracellular space and between the exterior and interior of subcellular organelles. In some cases, researchers have designed the polymeric delivery vectors to exploit these gradients. For example, researchers have taken advantage of the high redox potential gradient between oxidizing extracellular space and the reducing environment of cytosolic compartments by integrating disulfide bonds into the polymer structure. Such polymers retain their cargo in the extracellular space but selectively release the therapeutic nucleic acids in the reducing space within the cytosol. Furthermore, bioreducible polymers form stable complex with nucleic acids, and researchers can fabricate these structures to impart several important features such as site-, timing-, and duration period-specific gene expression. Additionally, the introduction of disulfide bonds within these polymers promotes their biodegradability and limits their cytotoxicity.</P><P>Many approaches have demonstrated the versatility of bioreducible gene delivery, but the underlying biological rationale of these systems remains poorly understood. The process of disulfide reduction depends on multiple variables in the cellular redox environment. Therefore, the quest to unravel various issues such as the site and time of disulfide bond reduction during the cellular uptake and trafficking have stimulated a number of interesting studies which have employed disulfide compounds with a variety of reducible linkers. Such studies help researchers understand not only how modifications made to disulfides can alter their thiol–disulfide exchange characteristics but also to decipher the effect of the induced changes on the dynamics of the redox environment.</P><P>This Account discusses current research trends and recent progress in the disulfide chemistry enabling novel and versatile designs of reducible polymeric gene delivery systems. We present strategies for the introduction of disulfide bonds into polymers. These representative examples and their respective outcomes elaborate the benefit and efficiency of disulfides at the individual stages of gene delivery.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/achre4/2012/achre4.2012.45.issue-7/ar200248u/production/images/medium/ar-2011-00248u_0001.gif'></P>

신생아 지속성 폐동맥 고혈압증의 임상적 경험

박국인,남궁란,이철,한동관 大韓周産醫學會 1990 Perinatology Vol.1 No.2

Effective Tidal Volume for Normocapnia in Very-Low-Birth-Weight Infants Using High-Frequency Oscillatory Ventilation

Lee, Seul Mi,Namgung, Ran,Eun, Ho Sun,Lee, Soon Min,Park, Min Soo,Park, Kook In Yonsei University College of Medicine 2018 Yonsei medical journal Vol.59 No.1

<P><B>Purpose</B></P><P>Removal of CO<SUB>2</SUB> is much efficient during high-frequency oscillatory ventilation (HFOV) for preterm infants. However, an optimal carbon dioxide diffusion coefficient (DCO<SUB>2</SUB>) and tidal volume (VT) have not yet been established due to much individual variance. This study aimed to analyze DCO<SUB>2</SUB> values, VT, and minute volume in very-low-birth-weight (VLBW) infants using HFOV and correlates with plasma CO<SUB>2</SUB> (pCO<SUB>2</SUB>).</P><P><B>Materials and Methods</B></P><P>Daily respiratory mechanics and ventilator settings from twenty VLBW infants and their two hundred seventeen results of blood gas analysis were collected. Patients were treated with the Dräger Babylog VN500 ventilator (Drägerwerk Ag & Co.) in HFOV mode. The normocapnia was indicated as pCO<SUB>2</SUB> ranging from 45 mm Hg to 55 mm Hg.</P><P><B>Results</B></P><P>The measured VT was 1.7 mL/kg, minute volume was 0.7 mL/kg, and DCO<SUB>2</SUB> was 43.5 mL<SUP>2</SUP>/s. Mean results of the blood gas test were as follows: pH, 7.31; pCO<SUB>2</SUB>, 52.6 mm Hg; and SpO<SUB>2</SUB>, 90.5%. In normocapnic state, the mean VT was significantly higher than in hypercapnic state (2.1±0.5 mL/kg vs. 1.6±0.3 mL/kg), and the mean DCO<SUB>2</SUB> showed significant difference (68.4±32.7 mL<SUP>2</SUP>/s vs. 32.4±15.7 mL<SUP>2</SUP>/s). The DCO<SUB>2</SUB> was significantly correlated with the pCO<SUB>2</SUB> (<I>p</I>=0.024). In the receiver operating curve analysis, the estimated optimal cut-off point to predict the remaining normocapnic status was a VT of 1.75 mL/kg (sensitivity 73%, specificity 80%).</P><P><B>Conclusion</B></P><P>In VLBW infants treated with HFOV, VT of 1.75 mL/kg is recommended for maintaining proper ventilation.</P>

Effect of tolazoline on persistent hypoxemia in severe hyaline membrane disease

Park, Kook-In,Namgung, Ran,Lee, Chul,Han, Dong Gwan Yonsei University, College of Medicine 1990 Yonsei medical journal Vol.31 No.2