The effects of mesenchymal stem cells injected via different routes on modified IL-12-mediated antitumor activity

Seo, S H,Kim, K S,Park, S H,Suh, Y S,Kim, S J,Jeun, S-S,Sung, Y C Nature Publishing Group 2011 Gene Therapy Vol.18 No.5

<P>Owing to its tumor tropism and prolonged transgene expression, mesenchymal stem cell (MSC) has been considered as an ideal delivery vehicle for cancer gene therapies or therapeutic vaccines. In this study, we demonstrated that intratumoral (i.t.) injection of MSCs expressing modified interleukin-12 (MSCs/IL-12M) exhibited stronger tumor-specific T-cell responses and antitumor effects as well as more sustained expressions of IL-12 and interferon (IFN)-γ in both sera and tumor sites than did IL-12M-expressing adenovirus (rAd/IL-12M) in mice bearing both solid and metastatic tumors. Subcutaneous (s.c.) injection of MSCs/IL-12M at contralateral site of tumor exhibited similar levels of serum IL-12 and IFN-γ as i.t. injection, but much weaker antitumor effects in both B16F10 melanoma and TC-1 cervical cancer models than i.t. injection. Although intravenous (i.v.) injection elicited earlier peak serum levels of cytokines, it induced weaker tumor-specific T-cell responses and antitumor effects than i.t. injection, indicating that serum cytokine levels are not surrogate indicators of antitumor effects. Taken together, these results indicated that MSC is more efficient than adenovirus as a cytokine gene delivery vehicle and that i.t. injection of MSCs/IL-12M is the best approach to induce strong tumor-specific T-cell responses that correlate with anti-metastatic effects as well as inhibition of solid tumor growth, although MSCs themselves have an ability to migrate into the tumor site. In addition, MSCs/IL-12M embedded in Matrigel (MSCs/IL-12M/Matrigel) exhibited significant antitumor effects even in immunodeficient mice such as SCID and BNX mice lacking T, B and natural killer (NK) cells, but not in IFN-γ knockout mice. Our findings provide an optimal approach for designing an efficient clinical protocol of MSC-based cytokine gene therapy to induce strong tumor-specific T-cell responses and therapeutic anticancer efficacy.</P>

Electrical Properties of ZrO2 and YSZ Films Deposited by Pulsed Laser Deposition

S.H. Kim,B.H. Park,D.H. Seo,D.-S. Suh,I.K. Yoo,I.R. Hwang,I.S. Byun,J.E. Lee,J.H. Lee,J.S. Choi,J.S. Kim,M.J. Lee,S. Seo,S.H. Hong,S.H. Jeon,S.-H. Kim,Y.S. Joung 한국물리학회 2005 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.47 No.2

Polycrystalline ZrO2 and yttria-stabilized ZrO2 thin films have been deposited on Pt/Ti/SiO2/Si substrates by pulsed-laser-deposition methods. Pt/ZrO2/Pt and Pt/YSZ/Pt capacitor structures show giant conductivity switching behaviors which can be utilized for nonvolatile memory devices. Maximum on/off ratio of 106 and good endurance even after 105 times conductivity switching are observed in a typical Pt/ZrO2/Pt whose ZrO2 film has been deposited at 100C and at an oxygen pressure of 50 mTorr. The Pt/ZrO2/Pt structure exhibits two ohmic behaviors in the low-voltage region (V < 1.4 V), depending on the value of previously applied high voltage, and Schottky-type conduction in the high-voltage region (1.4 V < V < 8.9 V). It seems that conductivity switching behaviors in our Pt/ZrO2/Pt structure result from changes in both the Schottky barrier and the bulk conductivity controlled by applied voltages. A Pt/YSZ/Pt capacitor structure has more stable reset voltage and current state than a Pt/ZrO2/Pt capacitor structure. Moreover, a Pt/YSZ/Pt capacitor structure shows higher conductivity than a Pt/ZrO2/Pt capacitor structure, which may result from substitution of Y3+ ions for Zr4+ ions.

Preparation and characterization of sulfonated amine-poly(ether sulfone)s for proton exchange membrane fuel cell

Seo, D.W.,Lim, Y.D.,Lee, S.H.,Jeong, Y.G.,Hong, T.W.,Kim, W.G. Pergamon Press ; Elsevier Science Ltd 2010 International journal of hydrogen energy Vol.35 No.23

Sulfonated amine-poly(ether sulfone)s (S-APES)s were prepared by nitration, reduction and sulfonation of poly(ether sulfone) (ultrason<SUP>(</SUP>R)-S6010). Poly(ether sulfone) was reacted with ammonium nitrate and trifluoroacetic anhydride to produce the nitrated poly(ether sulfone), and was followed by reduction using tin(II)chloride and sodium iodide as reducing agents to give the amino-poly(ether sulfone). The S-APES was obtained by reaction of 1,3-propanesultone and the amino-poly(ether sulfone) (NH<SUB>2</SUB>-PES) with sodium methoxide. The different degrees of nitration and reduction of poly(ether sulfone) were successfully synthesized by an optimized process. The reduction of nitro group to amino was done quantitatively, and this controlled the contents of the sulfonic acid group. The films were converted from salt to acid forms with dilute hydrochloric acid. Different contents of sulfonated unit of the S-APES were studied by FT-IR, <SUP>1</SUP>H NMR spectroscopy, differential scanning calorimetry (DSC), and thermo gravimetric analysis (TGA). Sorption experiments were conducted to observe the interaction of sulfonated polymers with water and methanol. The ion exchange capacity (IEC), a measure of proton conductivity, was evaluated. The S-APES membranes exhibit conductivities (25 <SUP>o</SUP>C) from 1.05 x 10<SUP>-3</SUP> to 4.83 x 10<SUP>-3</SUP> S/cm, water swell from 30.25 to 66.50%, IEC from 0.38 to 0.82 meq/g, and methanol diffusion coefficients from 3.10 x 10<SUP>-7</SUP> to 4.82 x 10<SUP>-7</SUP> cm<SUP>2</SUP>/S at 25 <SUP>o</SUP>C.

Characteristics of the antimicrobial resistance of Staphylococcus aureus isolated from chicken meat produced by different integrated broiler operations in Korea

Kim, Y. B.,Seo, K. W.,Jeon, H. Y.,Lim, S. K.,Lee, Y. J. Oxford University Press 2018 Poultry science Vol.97 No.3

<P>Vertical integration of the broiler industry allows producers to combine different biosecurity and sanitation practices, housing technologies, and feeding regimens to improve food safety. The purpose of this study was to investigate the prevalence of Staphylococcus aureus (S. aureus) and to characterize the antimicrobial-resistant isolates recovered from 7 different integrated broiler operation systems in Korea. Among 200 chicken meat samples, 94 were observed to be positive for S. aureus. However, the prevalence varied from 25.0 to 58.3% in chicken meats, indicating variation in S. aureus occurrence among the operations. Four methicillin-resistant S. aureus isolates (MRSA) were recovered from 3 different operations. A high proportion of the S. aureus isolates were resistant to penicillins (51.2%), tetracycline (38.8%), and ciprofloxacin (CIP; 33.9%). Especially, 3 different operations showed a high number of CIP resistance (45.5 similar to 100%) and multidrug resistance (50.0 similar to 100%). Among 41 CIP-resistant S. aureus isolates, 75.6% showed a double amino-acid exchange of both gyrA and parC, with CIP minimum inhibitory concentrations (MIC) of >= 32 mu g/mL. Four MRSA isolates showed resistance to 5 or 7 classes of antimicrobial agents, exhibiting oxacillin, CIP, and enrofloxacin MIC ranges of 16 to 128, 32 to 64, and 8 to 128 mu g/mL, respectively, and had double mutations of S84L/S80F in gyrA/parC. Our findings suggest that S. aureus with resistance to important antimicrobial compounds can now be found in association with integrated broiler operations, providing the data to support the development of a monitoring and prevention program in integrated operations.</P>

Synergistic antibacterial effect of curcumin against methicillin-resistant Staphylococcus aureus

Mun, S.H.,Joung, D.K.,Kim, Y.S.,Kang, O.H.,Kim, S.B.,Seo, Y.S.,Kim, Y.C.,Lee, D.S.,Shin, D.W.,Kweon, K.T.,Kwon, D.Y. G. Fischer 2013 Phytomedicine Vol.20 No.8

<P>Methicillin-resistant Staphylococcus aureus (MRSA) are spread among infected patients, with infection rates increasing at an alarming rate. Furthermore, increased resistance to antibiotics has resulted in serious challenges in the treatment of infectious diseases worldwide. Under the selection pressure of exposure to antibiotics, microorganisms evolve to survive against the new conditions imposed by therapy. Therefore, there exists a need to develop alternative natural or combination drug therapies. Curcumin (CCM), a natural polyphenolic flavonoid isolated from the rhizome of a plant, Curcuma longa Linne., has been found to possess many beneficial biological activities. The aim of this study was to investigate the synergistic effect of curcumin and antibiotics as well as to determine the antibacterial activity of CCM against specific MRSA strains. The antibacterial activity of CCM was assessed by the broth microdilution method (by calculating the minimal inhibitory concentration [MIC]), checkerboard dilution test, and time-kill assay. Antimicrobial activity of CCM was observed against all tested strains. The MICs of CCM against 10 strains of S. aureus ranged from 125 to 250 mu g/ml. In the checkerboard test, CCM markedly reduced the MICs of the antibiotics oxacillin (OXI), ampicillin (AMP), ciprofloxacin (CIP), and norfloxacin (NOR) used against MRSA. The time-kill curves showed that a combined CCM and OXI treatment reduced the bacterial counts below the lowest detectable limit after 24 h. This study suggested that CCM reduced the MICs of several antibiotics tested, notably of OXI, AMP, CIP, and NOR, and that CCM in combination with antibiotics could lead to the development of new combination of antibiotics against MRSA infection. (C) 2013 Published by Elsevier GmbH.</P>

유전질환 등록 시스템 운영, 유전자 정보 Database 구축 및 유전자 진단 시스템 확립

구수경,이환석,손용규,김성수,이광수,김지인,서일선,진수정,정동기,오범석,정성철,이진성 국립보건연구원 2000 국립보건원보 Vol.37 No.-

Lactoferrin causes IgA and IgG2b isotype switching through betaglycan binding and activation of canonical TGF-β signaling

Jang, Y-S,Seo, G-Y,Lee, J-M,Seo, H-Y,Han, H-J,Kim, S-J,Jin, B-R,Kim, H-J,Park, S-R,Rhee, K-J,Kim, W-S,Kim, P-H Society for Mucosal Immunology 2015 Mucosal immunology Vol.8 No.4

<P>Lactoferrin (LF), a pleiotropic iron-binding glycoprotein, is known to modulate the humoral immune response. However, its exact role in Ig synthesis has yet to be elucidated. In this study, we investigated the effect of LF on Ig production by mouse B cells and its underlying mechanisms. LF, like transforming growth factor (TGF)-beta 1, stimulated B cells to produce IgA and IgG2b, while downregulating other isotypes. Using limiting dilution analysis, LF was shown to increase the frequency of IgA-secreting B-cell clones. This was paralleled by an increase in Ig germ-line alpha (GL alpha) transcripts, indicating that LF plays a role as an IgA switch factor. Interestingly, LF directly interacted with betaglycan (TGF-beta receptor III, T beta RIII) and in turn induced phosphorylation of T beta RI and Smad3 through formation of the T beta RIII/T beta RII/T beta RI complex, leading to IgA isotype switching. Peroral administration of LF increased intestinal/serum IgA production as well as number of IgA plasma cells in lamina propria. Finally, we found that LF has an adjuvant activity when nontoxigenic Salmonella typhimurium was inoculated perorally, conferring protection against intragastrical infection of toxigenic S. typhimurium. These results suggest that LF has an important effect on the mucosal/systemic IgA response and can contribute to protection against intestinal pathogens.</P>

Purification and characterization of a novel fibrinolytic α chymotrypsin like serine metalloprotease from the edible mushroom, Lyophyllum shimeji

Moon, S.M.,Kim, J.S.,Kim, H.J.,Choi, M.S.,Park, B.R.,Kim, S.G.,Ahn, H.,Chun, H.S.,Shin, Y.K.,Kim, J.J.,Kim, D.K.,Lee, S.Y.,Seo, Y.W.,Kim, Y.H.,Kim, C.S. Society for Bioscience and Bioengineering, Japan ; 2014 Journal of bioscience and bioengineering Vol.117 No.5

A novel fibrinolytic enzyme was purified from Lyophyllum shimeji, a popular edible mushroom in Asia. The enzyme was purified using combination of anion exchange chromatography on a Mono Q 5/5 column and size exclusion gel filtration chromatography on Superdex 200 100/300 column. This purification protocol resulted 80.9-fold purification of the enzyme and a final yield of 5.7%. The molecular weight of the purified enzyme was estimated to be 21 kDa by SDS-PAGE and size exclusion gel filtration. The N-terminal amino acid sequence was found to be ITFQSASP, which is dissimilar from that of known fibrinolytic enzymes. The purified enzyme was a neutral protease with an optimal reaction pH and temperature of 8.0 and 37<SUP>o</SUP>C, respectively. Enzymatic activity was inhibited by Cu<SUP>2+</SUP> and Co<SUP>2+</SUP>. It was also significantly inhibited by PMSF and TPCK. Furthermore, it was found to exhibit a higher specificity for S-7388, a well-known chymotrypsin chromogenic substrate, indicating chymotrypsin like serine metalloprotease. The relative fibrinolytic activity of 5 μg purified enzyme have two fold more activity than 1 unit/ml of plasmin on fibrin plate. Furthermore, purified enzyme preferentially hydrolyzed the Aα-chain followed by the Bβ- and γ-chain of fibrinogen, which is precursor of fibrin. Therefore, these data suggests that the fibrinolytic enzyme derived from edible mushroom, L. shimeji, might be useful for thrombolytic therapy and preventing thrombotic disease.

여호와 증인 환자에서 산부인과적 무혈 수술의 임상적 고찰

이성욱,오일영,서상기,반태학,박윤희,박성철,한광수 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.5

목적 : 여호와의 증인은 자신들의 교리에 따라 혈액이나 기타 혈액제재의 사용을 거부하는 종파이다. 이들에 대한 산부인과적 무혈 수술의 임상상 및 수술후 결과를 후향적으로 검토하였다. 연구방법 : 1995년 2월부터 1999년 8월까지 세종병원에서 입원 기간 중 어떠한 혈액이나 혈액제재를 투여 받지 않았던 여호와의 증인 환자 50예에 대해 무혈 수술의 성적을 후향적으로 조사하였다. 결과 : 환자의 연령 분포는 9세와 58세 사이로 평균 36.7 ± 8.7세 이었다. 무혈 수술의 가장 흔한 사례는 제왕 절개술이었다. 인간 조혈촉진인자(EPO)를 제왕 절개술 5예, 전자궁 적출술 2예, 난소 종양 2예에 투여하였다. EPO를 투여 받은 9예에서는 평균 혈색소 수치가 수술 전에 비해 수술 후 오히려 의미있게 증가하였다. 조직학적 결과로는 자궁 선근증 9예, 평활근종 8예, 생식 세포종 3예, 자궁외 임신 2예, 자궁 상피내 종양 1예, 상피성 난소 종양 1예, 출혈성 황체 낭종 1예, 성기삭 간질성 종양 1예로 총 27예이었다. 무혈 수술로 인한 술 후 사망은 없었으며 이환율도 적었다. 결론 : 여호와의 증인 환자에 대한 산부인과적 수술이 요구될 때 세심한 수술 기법과 다양한 혈액 보존법 등을 이용한다면 비교적 양호한 무혈 수술의 결과를 얻을 수 있었다. 그러나 향후 여호와의 증인 환자에 대한 특수화된 프로그램의 개발이 필요하다고 사료되었다. Objective : Jehovah's Witnesses are members of a religious denomination whose beliefs prohibit the use of blood or blood products. Plasma volume expanders and extracorporeal hemodilution of the patients's own blood are theologically acceptiable. And so we evaluated effectiveness of major operative procedures carried out on Jehovas's Witnesses patients without blood transfusions or blood products. Methods : We retrospectively studied 50 cases of Jehovas's Witnesses who underwent obstetric and gynecologic bloodless surgery from February 1995 to August 1999. No patients recieved any blood or blood products during hospitalizaion. Results : The age distribution of patients was between 9 years and 58 year, average 36.7±8.7 years old. The most common cases for bloodless surgery was Cesarean section. The recombinant human erythropoietin(EPO) was treated in 5 cases of Cesarean section, 2 cases of TAH and 2 cases of ovarian tumor perioperatively. EPO-treated 9 cases were increased postoperative mean Hb levels compared with preoperative mean Hb levels. Histology revealed 9 cases of adenomyosis, 8 cases of leiomyoma, 3 cases of germ cell tumor, 2 cases of ectopic pregnancy, 1 case of CIS, 1 case of Krukenberg tumor, 1 case of epithelial cell tumor, 1 case of hemorrhagic corpus tumor and 1 case of sexcord stromal tumor, total 27 cases. There was no operative death and postoperative morbidities were few. Conclusions : We concluded that if we preformed the surgeries with careful operative techniques and various blood conserving procedures we could do the bloodless surgery of Jehovah's Witnesses with relative safety. But the establishment of a well programmed special medical supports for the Jehovah's Witnesses community will be needed in future.

Effects of Trx2p and Sec23p expression on stable production of hepatitis B surface antigen S domain in recombinant Saccharomyces cerevisiae

Park, Y.K.,Jung, S.M.,Lim, H.K.,Son, Y.J.,Park, Y.C.,Seo, J.H. Elsevier Science Publishers 2012 Journal of biotechnology Vol.160 No.3

The S domain of hepatitis B virus surface antigen (sHBsAg) is the primary component for vaccine development against virus infection. For stable expression of sHBsAg in recombinant Saccharomyces cerevisiae, new accessory genes necessary for foreign protein expression were screened by DNA microarray. Among 600 genes of interest, genes coding for an activating protein of ATPase in Hsp90 (Aha1p), S. cerevisiae DnaJ (Scj1p), thioredoxin 2 (Trx2p) and a GTPase-activator specific for Sar1 (Sec23p) as well as Pdi1p were selected in transcriptome analysis, which are known to facilitate disulfide bond formation or induce protein transport in the secretion pathway. Individual and combinatorial expression of SEC23, TRX2 and PDI1 increased total sHBsAg concentration by 1.9-6.5-fold, relative to the control strain expressing sHBsAg only. Additionally, moderate expression of Kex2p protease able to cut off the signal peptide enhanced the portion of the authentic sHBsAg to total sHBsAg. Fed-batch fermentation of the S. cerevisiae 2805 strain coexpressing the sHBsAg, SEC23, PDI1 and KEX2 genes resulted in 70.6mg/L final sHBsAg concentration which was 5.6 times higher than that of the control. Transmission electron microscopic analysis of the yeast cells elucidated the effects of the accessory gene coexpression on the intracellular localization of sHBsAg. Like PDI1, coexpression of both SEC23 and/or TRX2 newly isolated in this study is expected to improve the target protein expression in S. cerevisiae.