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      • SCOPUSKCI등재

        Glucose와 Phosphate가 제거된 M-TALP 배지에서의 난구세포 공배양에 의한 임신율 향상에 관한 연구

        정범식,장우현,이문희,김지연,방지호,김규현,서태광,Chung, B.S.,Chang, W.H.,Lee, M.H.,Kim, J.Y.,Bang, J.H.,Kim, K.H.,Suh, T.K. 대한생식의학회 1999 Clinical and Experimental Reproductive Medicine Vol.26 No.1

        The beneficial effect of glucose and phosphate ions in culture medium on the development of human embryos in vitro has not been fully elucidated. The purpose of this study was to evaluate the influence of fertilization and culture of embryos in glucose/phosphate-free m-TALP medium on pregnancy rates in IVF-ET program. The patients in 244 IVF-ET cycles received GnRH agonist + HMG regimens. A does of 10,000 IU HCG was administered when two or more dominent follicles reached 18mm in diameter. Thirty-six hours after HCG, oocytes were recovered transvaginally using ultrasound guidance. Aspirated oocytes were matured for 4 to 6 h in TCM-199 supplemented with 10% follicular fluid (FF). Insemination was carried out with 50,000 motile spermatozoa in TCM-199 + 10% FF or m-TALP + 5% FF + 5% fetal cord serum (FCS) according to experimental design. After 6 h, oocytes were washed 3 to 4 times and cultured in each fresh medium. After 20 h, oocytes were freed from cumulus/corona cells and examined for the presence of pronuclei. Fertilized oocytes were transferred into each co-culture drops and cultured for further incubation. On day 3, embryo transfer was performed with grade 1 and 2 embryos. Monolayers for co-culture of embryos were prepared by plating $1{\times}10^5$ cumulus cells/ml in 10ul drop of TCM-199 + 10% FF or m-TALP + 5% FF + 5% FCS media 24 h prior to the onset of co-culture. Development to 4 to 16 cell stage was observed at 70x magnification following two days of incubation. Pregnancy was confirmed by detecting increasing serum ${\beta}$-hCG concentrations for 11 days following embryo transfer. Data were analyzed by ${\chi}^2$-test. Oocytes from 244 IVF-ET cycles were randomized. The number of cycles and mean age of patients were 97 and 147, 31.3 yrs and 31.2 yrs for TCM-199 (control) and m-TALP groups, respectively. The mean number of retrieved oocytes/cycle, fertilization rates, number of embryos transferred/ET and pregnancy rates were 11.1 and 10.3, 65.1% and 67.3%, 4.1 and 4.7, 28.9% and 43.8% for TCM-199 and m-TALP groups, respectively. Differences in the pregnancy rates were found between control and m-TALP groups (p<0.05). The pregnancy rate of patients divided according to maternal age groups of ${\leq}30$, 31-35, $36{\leq}$ were 44.4% and 49.0%, 26.1% and 41.3%, 29.2% and 41.2% for control and m-TALP groups, respectively. These data indicate that culture of human embryos in glucose/phosphate-free m-TALP medium improves pregnancy rates.

      • Structural basis for differential activities of enantiomeric PPARγ agonists: Binding of S35 to the alternate site

        Jang, J.Y.,Koh, M.,Bae, H.,An, D.R.,Im, H.N.,Kim, H.S.,Yoon, J.Y.,Yoon, H.J.,Han, B.W.,Park, S.B.,Suh, S.W. Elsevier Science 2017 Biochimica et biophysica acta. Proteins and proteo Vol.1865 No.6

        <P>Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a member of the nuclear receptor superfamily. It functions as a ligand-activated transcription factor and plays important roles in the regulation of adipocyte differentiation, type 2 diabetes mellitus, and inflammation. Many PPAR gamma agonists bind to the canonical ligand-binding pocket near the activation function-2 (AF-2) helix (i.e., helix H12) of the ligand-binding domain (LBD). More recently, an alternate ligand-binding site was identified in PPAR gamma LBD; it is located beside the 52 loop between the helices H2 ' and H3. We reported previously that the chirality of two optimized enantiomeric PPAR gamma ligands (S35 and R35) differentiates their PPAR gamma transcriptional activity, binding affinity, and inhibitory activity toward Cdk5 (cyclin-dependent kinase 5)-mediated phosphorylation of PPAR gamma at Ser245 (in PPAR gamma 1 numbering; Ser273 in PPAR gamma 2 numbering). S35 is a PPAR gamma phosphorylation inhibitor with promising glucose uptake potential, whereas R35 behaves as a potent conventional PPAR gamma agonist. To provide a structural basis for understanding the differential activities of these enantiomeric ligands, we have determined crystal structures of the PPAR gamma LBD in complex with either S35 or R35. S35 and R35 bind to the PPAR gamma LBD in significantly different manners. The partial agonist S35 occupies the alternate site near the Omega loop, whereas the full agonist R35 binds entirely to the canonical LBP. Alternate site binding of S35 affects the PPAR gamma transactivation and the inhibitory effect on PPAR gamma Ser245 phosphorylation. This study provides a useful platform for the development of a new generation of PPAR gamma ligands as anti-diabetic drug candidates.</P>

      • SCISCIESCOPUS

        A novel chimeric promoter that is highly responsive to hypoxia and metals

        Lee, J-Y,Lee, Y-S,Kim, J-M,Kim, K L,Lee, J-S,Jang, H-S,Shin, I-S,Suh, W,Jeon, E-S,Byun, J,Kim, D-K Nature Publishing Group 2006 Gene Therapy Vol.13 No.10

        To develop a potent hypoxia-inducible promoter, we evaluated the usefulness of chimeric combinations of the (Egr-1)-binding site (EBS) from the Egr-1 gene, the metal-response element (MRE) from the metallothionein gene, and the hypoxia-response element (HRE) from the phosphoglycerate kinase 1 gene. In transient transfection assays, combining three copies of HRE (3 × HRE) with either EBS or MRE significantly increased hypoxia responsiveness. When a three-enhancer combination was tested, the EBS–MRE-3 × HRE (E–M–H) gave a hypoxia induction ratio of 69. The expression induced from E–M–H-pGL3 was 2.4-fold higher than that induced from H-pGL3 and even surpassed the expression from a human cytomegalovirus promoter-driven vector. The high inducibility of E–M–H was confirmed by validation studies in different cells and by expressing other cDNAs. Gel shift assays together with functional overexpression studies suggested that increased levels of hypoxia-inducible factor 1α, metal transcription factor-1 and Egr-1 may be associated with the high inducibility of the E–M–H chimeric promoter. E–M–H was also induced by hypoxia mimetics such as Co<SUP>2+</SUP> and deferoxamine (DFX) and by hydrogen peroxide. Gene expression from the E–M–H was reversible as shown by the reduced expression of the transgene upon removal of inducers such as hypoxia and DFX. In vivo evaluation of the E–M–H in ischemic muscle revealed that erythropoietin secretion and luciferase and LacZ expression were significantly higher in the E–M–H group than in a control or H group. With its high induction capacity and versatile means of modulation, this novel chimeric promoter should find wide application in the treatment of ischemic diseases and cancer.Gene Therapy (2006) 13, 857–868. doi:10.1038/sj.gt.3302728; published online 9 February 2006

      • Phenol content, antioxidant and tyrosinase inhibitory activity of mangrove plants in Micronesia

        Suh, S.S.,Hwang, J.,Park, M.,Park, H.S.,Lee, T.K. Elsevier 2014 Asian Pacific journal of tropical medicine Vol.7 No.7

        Objective: To find out and compare the in vitro antioxidant and tyrosinase inhibitory activities of two species of mangrove plants. Methods: Mangrove samples were harvested at the shoreline on the island of Weno, Chuuk State in Micronesia. The phenol content, antioxidant activity (based on DPPH-free radical scavenging) and tyrosinase inhibitory activity in different tissues (leaves, barks and roots) of Rhizophora stylosa (R. stylosa) and Sonneratia alba (S. alba), collected from the island of Weno. Results: Total phenol content ranged from 4.87 to 11.96 mg per g of freeze dried samples. The highest antioxidant activity was observed in R. stylosa bark (85.5%). The highest tyrosinase inhibitory activity was found in S. alba bark. Also, total phenol content and antioxidant activity were higher in methanol extracts than in aqueous extracts. Conclusions: Taken together, the results of this study proved that mangroves can be excellent sources of antioxidant compounds.

      • SCISCIESCOPUSKCI등재
      • SCISCIESCOPUS

        A phase II study of everolimus (RAD001), an mTOR inhibitor plus CHOP for newly diagnosed peripheral T-cell lymphomas

        Kim, S. J.,Shin, D.-Y.,Kim, J. S.,Yoon, D. H.,Lee, W. S.,Lee, H.,Do, Y. R.,Kang, H. J.,Eom, H. S.,Ko, Y. H.,Lee, S. H.,Yoo, H. Y.,Hong, M.,Suh, C.,Kim, W. S. Oxford University Press 2016 ANNALS OF ONCOLOGY Vol.27 No.4

        <P>Everolimus plus CHOP is effective for newly diagnosed, chemotherapy-naive peripheral T-cell lymphoma patients with acceptable toxicity.Everolimus, an oral mTOR inhibitor, has single-agent activity against relapsed lymphomas. Thus, we carried out a phase II study of everolimus in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) as a first-line treatment for patients with peripheral T-cell lymphoma (PTCL) based on our phase I study results. Participants (n = 30) received CHOP with 5 mg everolimus per day from day 1 to 14 every 21 days for a total of six cycles. The primary end point was the overall response rate (ORR), which included complete response (CR) and partial response (PR) to this regimen. Immunohistochemistry was used to evaluate the expression of phosphatase and tensin homology (PTEN) and phosphorylated S6 kinase (pS6K) as a response. The objective response rate was 90% with CR (n = 17) and PR (n = 10). The CR rate was different among subtypes; angioimmunoblastic T-cell lymphoma (AITL, n = 3) had a CR whereas PTCL-not-otherwise specified and ALK-negative anaplastic large-cell lymphoma (ALCL) patients showed 63% (12/19) and 29% (2/7) of CR rate, respectively. This difference in CR rate among subtypes was associated with PTEN loss because PTEN loss was not seen in AITL but 33% of ALCL patients. The most common toxicity was hematological, with 80% of patients experiencing at least one event of grade 3/4 neutropenia, and 60% of patients had grade 3/4 thrombocytopenia. The everolimus plus CHOP was effective for PTCL patients, and its efficacy might be related with the preservation of PTEN.</P>

      • 雄性不稔을 利用한 水稻 雜種品種 開發 : I. Hybrids utilized chinese CGMS I. 中共의 CGMS를 利用하는 雜種品種

        許文會,S.S. Virmani,徐學洙 서울大學校農科大學 1984 서울대농학연구지 Vol.9 No.1

        中共의 CGMS(細胞質-遺傳子的雄性不稔)을 利用한 雜種品種을 開發하기 爲하여 1982, 1983 兩年間 雜種品種의 收量性을 檢討하는 한편 韓國品種을 中共의 CGMS母本에 交配하여 그 F₁의 稔性을 檢定하고 MS維持系統을 2~4回 backcross하여 CGMS系統을 育成하였다. 그 結果를 要約하면 다음과 같다. 1. 雜種의 收量은 多收性標準品種에 比하여 4.6~24.3% 增收되며 組合에 따라 年次에 따라 環境에 따라 變異가 甚하였다. 收量의 雜種强勢現象은 主로 穗當粒數와 千粒重의 雜種强勢로 表現되었으며 穗數와 稔實率은 雜種에서 減收의 方向으로 作用하였다. 2. 稔性回復親의 收量性으로 그 回復親과의 雜種의 收量性을 推測할 수 없었으며 이러한 組合別 特異性은 出穗日數에서도 認定할 수 있었다. 3. V20A, V41A, Z97A 3個의 CGMS系統을 써서 24個의 維持系統과 30個의 稔性回復系統을 檢定하였다. 4. 本 硏究에서 供試된 中共의 CGMS系統 V20A, V41A 및 Z97A는 同一品種이 共通으로 維持系統 또는 稔性回復系統으로 될 수 있었음에 비추어 보아 3가지 MS系統이 다같은 體系의 MS라고 判斷된다. 5. 6個의 찰벼系統과 7個의 메벼系統을 2~4回 backcross해서 CGMS系統을 育成하였다. This paper reports the results of the studies on (1) the scope of the yield heterosis of the hybrids facilitated by the Chinese Cytoplasmic-Genetic Male Sterility (CGMS), (2) the fertility responses of the Korean cultivars and breeding materials in the hybrids crossed with Chinese CGMS and (3) the progress of breeding CGMS lines utilized by the Chinese CGMS. The results are summarized as follows: 1. Though the variations were significant depending on the cross combinations, years and environments, the hybrids showed 4.6%-24.3% higher yield over the highest yielding check variety. Their yield heterosis were expressed through the increased number of grains per panicle and grain weight. 2. The yield and heading data of a hybrid were not able to directly estimate through its parents, implying the manifestation of specific combining ability. 3. Among the 86 cultivars and breeding lines tested for the grain fertility of their hybrids with the Chinese CGMS lines, V20A, V41A and Z97A, 24 of them showed nearly complete sterility and 30 of them showed nearly complete fertility. These will be utilized as a MS maintainer or as a fertility restorer. 4. Many cultivars and breeding lines tested here responded as a MS maintainer or as a fertility restorer common to all of three CGMS lines, implying that they belong to the same MS system. 5. Six of waxy and seven of non-waxy CGMS lines are being bred through the back-crosses 2-4 times to the Chinese CGMS lines.

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