Association of Extracellular Cleavage of E-Cadherin Mediated by MMP-7 with HGF-Induced in vitro Invasion in Human Stomach Cancer Cells

Lee, K.H.,Choi, E.Y.,Hyun, M.S.,Jang, B.I.,Kim, T.N.,Kim, S.W.,Song, S.K.,Kim, J.H.,Kim, J.-R. S. Karger AG 2007 European surgical research Vol.39 No.4

<P><I>Background:</I> Proteolytic shedding of the ectodomain of a variety of transmembrane proteins, including cell-to-cell adhesion molecules, has been observed in solid cancers. We have investigated whether extracellular cleavage of E-cadherin mediated by matrix metalloproteinase-7 (MMP-7) is involved in hepatocyte growth factor (HGF) induced in vitro invasion in stomach cancer cells. <I>Methods:</I> The effects of HGF on the expression of E-cadherin/β-catenin and MMP-7 at both the protein and mRNA levels were assessed in stomach cancer cells, NUGC-3 and MKN-28, and in cells in which the expression of MMP-7 was downregulated by transfection with a MMP-7 short hairpin RNA plasmid. <I>Results:</I> Treatment with HGF increased the extracellular cleavage of E-cadherin and the release of MMP-7 and reduced the level of E-cadherin in a dose- and time-dependent manner. HGF treatment repressed the phosphorylation of β-catenin in a Triton-soluble fraction, but enhanced this phosphorylation in a Triton-insoluble fraction. The association of E-cadherin with β-catenin was decreased by HGF treatment in the Triton-soluble fraction. In addition, treatment of MMP-7 short hairpin RNA transfected NUGC-3 cells with HGF resulted in no extracellular cleavage of E-cadherin and also decreased the in vitro cell invasion. <I>Conclusions:</I> These results suggest that incubation with HGF mediated the release of MMP-7, resulting in extracellular cleavage of E-cadherin from stomach cancer cells. This might be a key mechanism in HGF-induced in vitro invasion and metastasis.</P><P>Copyright © 2007 S. Karger AG, Basel</P>

AFLP Marker를 이용한 한국 재래돼지의 유전적 다양성 및 품종식별

정의룡,김우태,김연수,이정구,한상기 한국동물자원과학회 2001 한국축산학회지 Vol.43 No.6

본 연구는 한국재래돼지의 순수 혈통정립 및 유전자원 보존을 목적으로 AFLP 다형성을 분석하고 이를 유전적 표지인자로 이용하여 재래돼지의 유전적 특성을 분자 수준에서 규명하고 품종 집단내 유전적 변이성과 품종 특이적인 DNA marker를 탐색하며 동시에 타품종들과의 유전적 근연관계를 추정하기 위해 수행하였다. 13종류의 selective primer 조합형을 이용하여 분석한 결과 총 band의 수는 611개로 각 조합형 당 평균 47개의 band가 확인되었으며 이 가운데 다형적 band가 152개로 다형성 수준은 약24.5%였다. 한국 재래돼지의 다형율과 유전적 다양성 값은 각각 29.8%와 2.9로 개량종에 비해서 다소 높은 경향이었다. 한편, 13종류의 primer 조합형 가운데 E35/T38 및 E38/H13 primer 조합형에서 품종간의 차이를 나타내는 DNA marker가 확인되었다. 특히, 재래돼지에서 검출된 E35/T38 primer 조합형의 0.50kb, 0.25kb 및 0.38kb의 DNA band는 개량종과 명확히 구별되어 이들 품종 특이적 DNA band는 한국 재래돼지의 품종식별에 유용한 표지인자로 이용 가능할 것으로 기대된다. 품종간 유전적 근연관계에서 한국 재래돼지는 Hampshire종과 유전적 유사성이 가장 높은 것으로 추정되었다. 본 연구에서 검출한 한국 재래돼지의 AFLP 유전자 지문은 재래돼지 집단의 유전적 변이성 및 타 품종과의 근연관계 분석뿐만 아니라 경제형질과 연관된 marker 개발에 유용한 DNA 표지인자로 활용할 수 있을 것으로 기대된다. For the purpose of genetic conversation and utilization of Korean native pig(KNP) as a valuable animal genetic resource, DNA polymorphisms of AFLP (amplified fragment length polymorphisms) as genetic markers were analyzed in KNP and foreign pig breeds (Landrace, Duroc, Hamphsire and Yorkshire). Using these AFLP markers, the genetic structure and characteristics of KNP population were analyzed at the DNA level and the genetic variability and diversity within and between breed population were evaluated. Breed-specific DNA marker for KNP was screened, and phylogenetic relationship within and among breeds were estimated. A total of 611 AFLP markers were amplified by 13 selective primer combinations, and the average number of bands per primer combination was 47.0. Among them 152 bands were polymorphic (24.5%). The rate of polymorphisms and genetic diversity values of KNP (29.8% and 2.90) was higher than these of other foregin breeds. E35/T38 and E38/H13 primer combinations produced AFLP banding patterns which clearly discriminated between KNP and other foreign pig breeds. Three bands(0.50kb, 0.25kb and 0.20kb) identified in E35/T38 and two bands(0.45kb and 0.38kb) identified in E38/H13 primer combinations were present in all of the KNP examined, but not present in the foreign pig breeds. Therefore, these two primer combinations could be used as breed-specific DNA markers for breed identification of KNP. In comparison of genetic distances among pig breeds, KNP was the most closely related to the Hampshire breed. AFLP fingerprints may be useful for genetic variability and relationships and development of breed-specific DNA markers in pig breeds.

Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1-high T cells

Kim, J.H.,Choi, Y.J.,Lee, B.H.,Song, M.Y.,Ban, C.Y.,Kim, J.,Park, J.,Kim, S.E.,Kim, T.G.,Park, S.H.,Kim, H.P.,Sung, Y.C.,Kim, S.C.,Shin, E.C. Mosby 2016 The journal of allergy and clinical immunology Vol.137 No.5

<P>Background: Psoriasis is one of the most common chronic inflammatory diseases of the skin. Recently, IL-17-producing T cells have been shown to play a critical role in psoriatic inflammation. Programmed cell death 1 (PD-1) is a coinhibitory receptor expressed on T cells in various chronic inflammatory diseases; however, the expression and function of PD-1 during psoriatic inflammation have not previously been characterized. Objective: We examined PD-1 expression on IL-17A-producing T cells from imiquimod-treated mice and patients with psoriasis. Additionally, we investigated the therapeutic effect of recombinant programmed cell death ligand 1 (PD-L1) protein on imiquimod-induced psoriatic inflammation. Methods: PD-1 expression on IL-17A-producing gamma delta T cells from imiquimod-treated mice was examined by means of multicolor flow cytometric analysis. In the psoriatic skin of patients, PD-1 and IL-17A expression was analyzed by using immunofluorescence. The therapeutic effect of PD-L1-Fc fusion protein (PD-L1-Fc) was assessed in imiquimod-treated mice ex vivo and in vivo. Results: During imiquimod-induced psoriatic inflammation, PD-1 is overexpressed on CD27(-)V gamma 1(-) gamma delta T cells. Furthermore, PD-1 expression on IL-17A(+) T cells was confirmed in psoriatic skin tissues from patients and imiquimod-treated mice. In the CD27(-)V gamma 1(-) gamma delta T-cell population, V gamma 4(-) gamma delta T cells with V gamma 6 mRNA expression showed a high level of PD-1 expression. Furthermore, these PD-1(hi)V gamma 4(-)(V gamma 6(+)) gamma delta Tcells were specialized for anti-CD3-induced IL-17A production, which was inhibited by PD-L1-Fc treatment. In imiquimod-treated mice PD-L1-Fc reduced psoriatic inflammation when given alone and enhanced the therapeutic effect of anti-p40 when given in combination. Conclusion: PD-1 is overexpressed in IL-17A-producing T cells in both imiquimod-treated mice and patients with psoriasis. Moreover, recombinant PD-L1-Fc alleviates psoriatic inflammation in imiquimod-treated mice.</P>

Growth Performance and Carcass Characteristics of Korean Native Ducks Fed Diets with Varying Levels of Limiting Amino Acids

Choo, Y.K.,Kwon, H.J.,Oh, S.T.,Kang, C.W.,Kim, H.K.,Hong, E.C.,Heo, K.N.,Lee, S.K.,An, B.K. Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.4

There are multiple experiments conducted with male Korean native ducks (KND) to evaluate the optimal levels of limiting amino acids (AA). In Exp. 1, a total of 450 one-d-old male KNDs were divided into five groups with six replicates and fed experimental diets with varying levels of lysine, total sulfur amino acids (TSAA) and threonine (T1, 0.90/0.74/0.70%; T2, 1.00/0.82/0.77%; T3, 1.10/0.90/0.85%; T4, 1.20/0.98/0.93%; T5, 1.30/1.07/1.01%) to 21 d of age. In Exp. 2, one-d-old male KND were received and fed commercial starter diet from hatching to 21 d of age, and then divided into five groups with six replicates and fed one of five diets varying levels of lysine, TSAA, and threonine (T1, 0.73/0.62/0.54%; T2, 0.80/0.68/0.60%; T3, 0.87/0.74/0.65%; T4, 0.94/0.80/0.70%; T5, 1.01/0.86/0.75%) during 22 to 56 d of age, respectively. The BW gain was linearly increased as dietary limiting AA levels increased to 1.20% lysine, 0.98% TSAA and 0.93% threonine. There were no significant differences in feed intake, gain:feed and uniformity among groups. In Exp. 2, the BW gain and gain:feed were not affected by dietary limiting AA levels. There were no significant differences in carcass characteristics and meat quality among groups. The growth performance and carcass characteristics did not show the significant response to increasing dietary limiting AA levels in KND during 22 to 56 d of age. In conclusion, the levels of lysine, TSAA and threonine necessary to maximize growth for starter phase were at least 1.20%, 0.98%, and 0.93%, respectively. On the other hands, KND require relatively low levels of limiting AA for late growth and carcass yield. The dietary levels of 0.73% lysine, 0.62% TSAA and 0.54% threonine appear to be adequate during growing phase.

소 품종별 Melanocortin Receptor 1(MC1R) 유전자의 유전자형 빈도에 관한 연구

한재용,김경남,오성종,정일정,김태헌,윤두학,박응우,이혜영,탁태영 한국동물자원과학회 2000 한국축산학회지 Vol.42 No.6

The melanocortin 1 receptor (MC1R) plays a central role in regulation of eumelanin(black/brown) and phaeomelanin (red / yellow) synthesis within the mammalian melanocyte and encoded by the classical Extension (E) coat color locus. The objectives of this study were carried out to observe the genotype frequencies of MC1R in 1,044 samples of imported beef and eight different cattle breeds including Hanwoo, Holstein, Angus, Brown-Swiss, Charolais, Limousin, Simmental and Hereford. The primers for the amplification of bovine MC1R gene were designed based on a bovine MC1R gene sequence (GenBank accession no. Y19103). A size of 350 by was amplified by polymerase chain reaction(PCR), digested with each or together of two different restriction enzyme, BsrFI and MspAII, and electrophoresed in 2.5% or 4% Metaphore agarose gel for determination of genotypes. One thousand and forty four samples including eight different cattle breeds and imported beef were determinated their genotypes by PCR-RFLP. Genotype frequencies of Hanwoo were 0.10 in E e and 0.90 in ee. Allele E^D was shown in all of Holstein and Angus breeds tested which have black coat color phenotypes. However, genotype frequencies of Limousin and Simmental breeds were 0.21 and 0.07 in E^DE^D, 0.00 and 0.03 in E^De^+ , 0.38 and 0.35 in E^De, respectively. These results of this study suggest that alleles of the bovine MC1R gene are associated strongly with coat color except for Simmental and Limousin breeds with dark brown, light yellow or mosaic coat color of red and brown. Therefore, it needs to be studied on relationship between A and E loci and coat color phenotypes. Furthermore, genotypes of the bovine MC1R gene can be used as a DNA marker for distinguishing. beef between Hanwoo and Holstein and Angus having black coat color phenotype.

원발성 종격동 종양의 임상적 고찰

이수영,강원택,송하숙,이용철,이양근,정근,정은택,유제윤,송호신,김귀완 예수병원 1992 예수병원학술지 Vol.13 No.-

An albumin nanocomplex-based endosomal pH-activatable on/off probe system

Lee, C.,Lee, S.,Thao, L.Q.,Hwang, H.S.,Kim, J.O.,Lee, E.S.,Oh, K.T.,Shin, B.S.,Choi, H.G.,Youn, Y.S. Elsevier 2016 Colloids and Surfaces B Vol.144 No.-

<P>Albumin has gained considerable interest as a material for fabricating nanoparticulate systems due to its biomedical advantages, such as biocompatibility and chemical functionality. Here, we report a new pH-sensitive albumin nanocomplex prototype with a zinc-imidazole coordination bond. Albumin was conjugated with 1-(3-aminopropyl)imidazole and mPEG(10kDa)-NHS, and the resulting albumin conjugate (PBI) was then modified with either Cy5.5 or BHQ-3. The newly formed albumin nanocomplex (C/BQ-PBI Zn NCs: similar to 116 nm) system was facilely self-assembled around pH 7.4 in the presence of Zn2+, but it quickly disassembled in an acidic environment (similar to pH 5.0). Based on this pH-sensitivity, C/BQ-PBI Zn NCs emitted strong near-infrared fluorescence and released Zn2+, turning 'off' at pH similar to 7.4 (e.g., plasma) and 'on' at pH similar to 5.0 (e.g., endo/lysosomes in tumor cells) on account of fluorescence resonance energy transfer. C/BQ-PBI Zn NCs displayed significant cytotoxicity due to an increase in cellular. Zn2+ in response to endosomal pH (similar to 5.0) in breast cancer MCF-7 cells and lung adenocarcinoma A549 cells. Particularly, confocal laser scanning microscopic images showed a strong fluorescence signal caused by the disassembly of C/BQ-PBI Zn NCs in the endosomal region of MCF-7 cells. Based on these results, we believe that this albumin nanocomplex is an attractive biocompatible tumor targeting probe carrier for the theranostic purpose. (C) 2016 Elsevier B.V. All rights reserved.</P>

Hautmann and Studer orthotopic neobladders : the Michigan experience 미시간 대학병원 경험

Lee, Kyung Seop,Montie, James E.,Dunn, Rodney L.,Lee, Cheryl T. 東國大學校醫學硏究所 2002 東國醫學 Vol.9 No.2

연구목적 : 요로전환술의 치료에 있어서 Hautmann과 Studer 정위방광대치술은 획기적인 방법이다. 이에 저자들은 Hautmann과 Studer 정위방광대치술을 시행했던 환자들을 대상으로 임상적 결과를 후향적으로 분석하였다. 대상 및 방법 : 1995년 3월 1일부터 2000년 9월 30일까지 미시간 대학 병원 비뇨기과에서 방광종양으로 방광절제술 후 Hautmann과 Studer 정위방광대치술을 시행받았던 130명(Hautmann 37명, Studer 93명)을 대상으로 하였다. 이 환자들을 대상으로 두 술식에 대한 환자의 나이, 성, 수술 소요 시간, 입원 기간, 수술 중 출혈 양, 병리학적 병기와 합병증율, 요자제율 및 재수술률을 비교분석해 보았다. 통계적 분석은 Fishers exact test, T-test와 Wilcoxon rank-sum 분석을 이용하였다. 결과 : Hautmann과 Studer 정위방광대치술에 걸린 수술 시간은 각각 5.9, 5.3시간이었다(p=0.003). 입원 기간은 7일과 8.3일로 Hautmann 정위방광대치술이 짧았다(p=0.02). 그 외 나이, 성, 수술 중 출혈 양, 병리학적 병기와 합병증률 및 재수술률은 차이를 보이지 않았다. 요 자제율은 Hautmann과 Studer 정위방광대치술 각각에서 낮 시간은 67%로 같았으며 밤 시간에는 47%와 40%로 비슷하였다. 결론 : Hautmann과 Studer 정위방광대치술 두 술식 모두 안전하고 쉽게 시행할 수 있는 좋은 방법이며 요 자제율 면에서 Hautmann 정위방광대치술이 좀 더 나은 것 같으나 통계적으로 유의하지는 않았다. 또한 Hautmann 정위방광대치술이 수술 시간이 좀 덜 걸리는 것은 요관문합에서의 차이로 생각되며 입원 기간 역시 좀 더 빨리 퇴원을 종용한 결과로 생각된다. Objectives: The development of Studer and Hautmann orthotopic neobladders has revolutionized the management of urinary diversion. Several series have promoted one technique over the other This study examines the clinical outcome of a contemporary cohort of bladder cancer patients who underwent either Hautmann or Studer orthotopic reconstruction. Materials and Methods: Retrospective analysis was performed on 130 patients (93 Studer and 37 Hautmann) who underwent cystectomy and orthotopic diversion between 1st march. 1995 and 30th September 2000. Clinical parameters evaluated were age, gender, procedure time, length of hospital stay, blood loss, pathologic stage, and rate of complication, continence, and reoperation. Diversion type was compared with clinical parameters using the Fishers exact Test, t-test, and Wilcoxon rank-sum analysis. Results: Studer and Hautmann techniques had mean procedure times of 5.9 and 5.3 hours, respectively (p=0.003); Hautmann patients also had a shorter mean length of hospital stay (LOS) (7.0 vs 8.3 days, respectively; p=0.02). When comparing both populations, there was no difference in age, gender, estimated blood loss (EBL), pathologic stage, or rate of complication or reoperation. Total continence was similar in the Hautmann and Studer cohorts, whether during daytime (67% vs 67%) or nighttime (47% vs 40%) hours, respectively. Conclusions: The data suggests that both orthotopic techniques can be performed in men and women in a safe and timely fashion. Continence rates appear better with the Hautmann technique, though the limited cohort size did not offer sufficient power to detect a statistical difference. The shortened procedure time in Hautmann patients likely relates to variations in th ureteral anastomosis. Decreased LOS may reflect recent trends of early patient discharge.

전치태반의 임상적 고찰

이병주,이명재,이태헌,김용봉,이응수,박성관 인제대학교 1995 仁濟醫學 Vol.16 No.4

전치태반은 임신의 산전시 태반의 박리현상이 초래되어 심한 출혈이 일어남으로써, 산모뿐만아니라 태아에서도 매우 치명적인 위험을 초래할 수도 있다. 저자는 인제대학교 서울백병원 산부인과학교실에서 5년간 경험했던 52례의 전치태반 환자를 대상으로 그 임상적 소견을 조사, 분석하였다. During the period from January 1, 1990 to December 31, 1994, 52 cases which diagnosed and treated as placenta previa among the total delivery of 3,802 in Inje University, Seoul Paik Hospital were reviewed. 1.The incidence of placenta previa was 1:73.1 deliveries(1.37%) and types of placenta previa were totalis in 29 cases(55.8%), low lying in 13 cases(25.0%), partialis in 6 cases(11.5%) and marginalis in 4 cases(7.7%). 2.The placenta previa has occured more often in multiparous(55.8%) than primigravida(44.2%). 3.The first episode of vaginal bleeding occured after 29 weeks in 42 cases(80.8%). 4.The fetal presentation in placenta previa was vertex in 40 cases(76.9%), breech in 10 cases(19.2%), and transverse lie in 2 cases(3.9%). 5.The method of delivery included vaginal delivery in 7 cases(13.5%), Cesarean section in 40 cases(76.9%), and Cesarean hysterectomy in 5 cases(9.6%). 6.Blood loss at delivery was over 500ml in 44 cases(84.6%) and blood transfusion was needed in 27 cases(51.9%). 7.The perinatal mortality rate was 76.9 per 1,000 births, and preterm delivery occurred in 31 cases (59.6%), low birthweight babies were born in 19 cases (36.5%). 8.In 22 cases(42.3%), there were maternal complications including placenta accreta, puerpural fever, wound infection, and preeclampsia.

Magnetic resonance imaging of macrophage activity in atherosclerotic plaques of apolipoprotein E-deficient mice by using polyethylene glycolated magnetic fluorescent silica-coated nanoparticles

Lee, K.,Moon, H.Y.,Park, C.,Kim, O.R.,Ahn, E.,Lee, S.Y.,Park, H.E.,Ihm, S.H.,Seung, K.B.,Chang, K.,Yoon, T.J.,Lee, C.,Cheong, C.,Hong, K.S. Elsevier 2009 Current Applied Physics Vol.9 No.1

We have recently synthesized organic dye-incorporated silica-coated core-shell magnetic nanoparticles (MFSNs) that enable the detection of both fluorescence and magnetic properties in cells and tissues by using magnetic resonance imaging (MRI). Furthermore, polyethylene glycolation of the surface of these MFSNs would render them more stable and biocompatible, and thus allow their in vivo use as a circulating agent with a long half-life. Atherosclerotic vascular diseases are the leading cause of death worldwide. A noninvasive diagnostic imaging method is required to identify vulnerable plaques prior to the occurrence of a clinical event. Macrophages are the key cellular mediators in the pathogenesis of plaque inflammation and vulnerability. We evaluated whether the use of polyethylene glycolated (PEGylated) MFSNs could help in effectively detecting the macrophage activity in the aorta of apolipoprotein E (apoE)-deficient mice. PEGylated MFSNs (Fe, 30mg/kg) were injected via the tail vein in 1.2% cholesterol-fed 30-week-old apoE-deficient mice. After 24h, ex vivo MRI was carried out. The atheromas were then observed by confocal laser scanning microscopy (CLSM), and immunohistochemical staining targeted toward the macrophages was performed. Ex vivo MRI demonstrated robust enhancement of the atherosclerotic plaques along the aortic wall. CLSM images showed accumulation of PEGylated MFSNs in the atherosclerotic plaques, and histological examination revealed the localization of MFSNs in the macrophages present in the lesion. Therefore, PEGylated MFSNs could function as an effective multimodal imaging agent in the identification of macrophage activity in atherosclerotic plaques.