비소세포폐암에서 Microsatellite Instability

전효성,김정란,손지웅,박선하,박태인,김창호,김인산,정태훈,박재용 경북대학교 병원 2001 경북대학교병원의학연구소논문집 Vol.5 No.1

연구베경:MMR 유전자의 불활성화에 의해 야기되는 뮤전적 불안정성은 발암기전의 한 부류로 인정되고 있다.저자들은 비소세포폐암의 발암과정에서의 MSI의 역할을 규명하기 위해 비소세포폐암에서 MSI의 빈도 및 MSI 유무에 따른 임상상의 차이를 조사하였다. 대상 및 방법:근치적 절제술을 받은 비소세포폐암 20예를 대상으로 하였다.동결된 폐암조직과 환자의 림프구에서 DNA를 추출한 후 3P와 9p의 15개의 marker들을 대상으로 PCR을 시행하고 7% polyacrylamide gel에서 전기영동한 후 silver 염색을 시행하였다. 암조직과 림프구 DNA의 PCR product의 band를 비교하여 MSI와 LOH를 판정하였다. 결과:1)대상환자들은 남자 19예,여자 1예였으며 모두 흡연자였고 평균 흠연력은 47 갑년이었다. 폐암의 조직형은 편평상피암 15예, 선암 4예,대세포암 1예였고, 술 후 병리학적 병기는 Ⅰ기 6예,Ⅱ기 5예, ⅢA기 7예,ⅢB기 2예였다. 2)20예 가운데 8예(40%)에서 MSI가 관찰되었으며 3예는 한 개의 marker에서,5예는 2개 이상의 marker에서 MSI가 관찰되었다. 3)LOH는 10예(50%)에서 있었으며,LOH유무에 따른 병가 및 흡연력의 차이가 없었다. 4)분석한 marker의 10% 이상에서 MSI가 관찰된 MSI-L종양은 5예였으며, 대부분의 marker에서 MSI양성인 MSI-H종양은 없었다.MSS종양과 MSI-L종양은 흡연력, 병기, 폐암 조직형 및 LOH 빈도의 유의한 차이가 없었다. 결론:비소세포폐암에서 MSI는 비교적 흔히 관찰되지만 MMR 유전자의 불활성화에 의한 MMP pathway 는 비소세포폐암의 주요 발생기전은 아닐 것으로 생각된다.향 후 비소세포폐암의 발암과정에 있어서 MMP pathway의 역할을 규명하기 위해서는 보다 많은 예를 대상으로 한 연구가 필요할 것으로 생각되며, MSI 발생기전에 관한 추가적인 연구가 필요할 것으로 생각된다. Purpose: Microsatellite instability(MSI) is frequently used as an indicator of microsatellite mutator phenotype (MMP) tumors.MSI has been observed in a percentage of non-small cell lung cancer(NSCLC).However, its role in tumorigenesis of NSCLC remains unknown.The frequency and partten of MSI in NSCLC were evaluted and clinical parameters of MSI-positive tumors with those of MSS(microsatellite stable) tumors were compared. Materials and Methods: Twenty surgically resected NSCLCs were analyzed for 15 microsatellite markers located at chromosomes 3p and 9p.The peripheral blood lymphocytes of patients were used as the source of the normal DNA. Results:1) of 20 cases, 8(40%) demonstrated MSI. 2) Instability was observed more frequently in tri- and tetra-nucleotide repeats that in dinucleotide repeats. In all cases, instability appeared as a shift of individual allelic bands. 3) LOH was observed in 10(50%) of 20 tumors analyzed. 4) Of 20 cases, MSI-H tumor(showing MSI in the majority of markers) was absent. There were 5 MSI-L tumors( showing MSI in a greater than 10% of markers). 5) No significant difference was observed between MSI-L tumors and MSI negative tumors in terms of clinicopathologic features such as pack-year history of smoking, histologic subtype, and (delete) stage of disease.There was also no significant difference in the incidence of LOH in relation to the status of MSI. Conclusion: These data strongly suggest that MSI plays different roles in lung and colon cancer.MMP pathway appears to be far less important in the tumorigenesis of NSCLC, caused mainly by cigarette smoke, with little familial tendency.(tuberculosis and Respiratory Diseases 2000,48:24-32)

金體乾과 武藝圖譜通志에 실린 倭劍

허인욱,김산 한국체육사학회 2003 체육사학회지 Vol.11 No.-

The Wae-geom(倭劍) transmitted in the Joeseon(朝鮮) army as training curriculum after the Japanese Invasion of Korea in 1592(壬辰倭亂). Kim Che-geon lerand the Wae-geom in the trading center for the Japanese located in Dongnae(東萊)) by General Yoo Hyuk-yun(柳赫然) from the Sookjong(肅宗, the 19th King of Joeseon)'s accession year to 5th year. and then he had been gained some book which are recoded swordmanship when he had accompanied with the Joeseon Official envoys to Japan in the Sookjong 8th year. and he had added in his own version to the Wae-geom. and taught it to a solider. The Wae-geom maybe had been changed and recreated little by little in the Joeseon martial area.

흰쥐의 Bleomycin 誘發 肺纖維化 過程에서의 Collagen과 Glycosaminoglycan의 變動

金仁山,鄭泰浩,曺準承 慶北大學校 醫科大學 1990 慶北醫大誌 Vol.31 No.3

폐섬유화 과정에서 collagen과 GAG의 변동을 조사하기 위하여 bleomycin을 기관지를 통하여 흰쥐에 투여하여 폐섬유증을 유발한 후 경시적으로 collagen과 GAG의 변동을 조사하였다. 총 collagen량은 7일군에서는 변화가 없었으며 15일군에서부터 증가하여 계속 증가를 나타내었다. 총 GAG량은 7일군에서부터 유의성있게 증가하여 15일군에서는 약 100%의 증가율을 보였으며 30일군에서는 50%의 증가율을 나타냄으로써 감소경향을 보였다. 총 GAG에 대한 HA의 백분률은 전실험기간 동안 별다른 변화가 없었으며 Chs-A와 Chs-C의 백분률은 초기에 증가하였고 DS는 15일군부터 유의성있는 증가를 나타내어 폐섬유화 과정에서 collagen 증가시기와 비슷함을 보여줬다. H/HS의 백분률은 초기부터 감소하였다. 이상의 결과로써 폐섬유화 과정중 collagen과 GAG는 현저한 변화를 보였으나 그 의미와 상호관계는 알 수 없었으며 단지 GAG의 증가가 collagen의 증가보다 선행하는 것으로 보아 GAG가 collagen의 침착에 영향을 끼칠 것으로 사료되며 특히 DS는 collagen의 증가 시기와 비슷한 것으로 미루어 collagen과 밀접한 관계를 가질 것으로 사료된다. In order to determine the changes of collagen and glycosaminoglycans during the course of development of interstitial pulmonary fibrosis, a single intratracheal injection of 1.5 unit of bleomycin was given in rats. Total lung collagen contents were increased at 15 days after bleomycin administration and this increase was continued to 60 days. Total lung glycosaminoglycan contents were significantly increased at 7 days, maximally increased at 15 days and then declined. Chondroitin sulfate A and C fractions and dermatan sulfate fraction were both increased in fibrotic lungs but the former at an early stage and the latter at a later stage. On the contrary, heparin/heparan sulafe fraction was decreased in fibrotic lungs at an early stage, and hyaluronic acid fraction remained unchanged during the fibrotic changes of lung. The results indicate that the changes of glycosaminoglycans precede those of collagen, so glycosaminoglycans may ffect the accummulation of collagen fibrils.

유연하고 신속한 표면미세가공기술을 이용한 Micro-fluidic Channel 제작

김진산,성인하,김대은 한국공작기계학회 2002 한국생산제조학회지 Vol.11 No.4

Recently, the need for transporting and manipulating minute amount of fluids in microscale channels (so-called micro-fluidics) has been increasing, especially in biotechnology and biochemical processing. This work demonstrates that the so-called mechano-chemical process which consists of mechanical abrasive action combined with chemical process can be used to fabricate micro-fluidic channels more rapidly and cost effectively than other methods. In this work, capillary filling of fluids in micro-channels was investigated by theoretical approaches and experiments. From the experimental results, it is expected that a complex micro-fluidic system can be fabricated using the micro-fabrication technique and microsystem packaging method described in this work.

肺纖維化 過程中 Collagen 및 Fibronectin의 遺傳子 發現과 Collagen 分劃의 變動

조준찬,김인산,조준승 慶北大學校 醫科大學 1990 慶北醫大誌 Vol.31 No.3

Bleomycin-induced lung damage is a well-characterized experimental model for studying pulmonary fibrosis. This model was used to examine α1(Ⅰ), α1(Ⅲ) procollagen and fibronectin mRNA levels and changes of collagen fractions during the development of pulmonary fibrosis. Rats were given 1 unit of bleomycin intratracheally and sacrificed at 4 days, 8 days, and then every week for 4 weeks. The lung tissue was assayed for collagen content by measuring total hydroxyproline content. Characteristics and specific increase of procollagen mRNAs and fibronectin mRNA were determined by northern blot and dot blot hybridization. There was a significant increase of hydroxyproline content of lung tissue following 2 weeks of bleomycin treatment. Northern blot analysis identified a major(5.3kb) and a minor (7.1kb) α1(Ⅰ) procollagen mRNA species and a single fibronectin mRNA species of 8.8kb in size. There was a significant difference among the three mRNAs in the relative increase and the time of maximum accumulation. While the accumulation of procollagen mRNAs was maximum between the 8 days and 14 days, that of fibronectin mRNA peaked in the first week after bleomycin treatment. The procollagen α1(Ⅰ) mRNA accumulated most dramatically(tenfold above the levels in the control lungs) compared with fourfold increases of mRNAs coding α1(Ⅲ) procollagen and fibronectin. In conclusion, specific increases in procollagen mRNAs in lung fibrosis precede increase of tissue collagen content. Type Ⅰ collagen may accumulate much more than type Ⅲ collagen, and the metabolism of tissue fibronectin may be perturbed during pulmonary fibrosis.

Liver‐Specific and Echogenic Hyaluronic Acid Nanoparticles Facilitating Liver Cancer Discrimination

Min, Hyun Su,Son, Sejin,Lee, Tae Woong,Koo, Heebeom,Yoon, Hong Yeol,Na, Jin Hee,Choi, Yongseok,Park, Jae Hyung,Lee, Jaeyoung,Han, Moon Hee,Park, Rang‐,Woon,Kim, In‐,San,Jeong, Seo Young,Rh WILEY‐VCH Verlag 2013 Advanced Functional Materials Vol.23 No.44

<P><B>Abstract</B></P><P>With the increasing demand for instant real‐time ultrasound (US) imaging of a specific organ, target‐specific and long‐circulating ultrasound contrast agents are of special interest. A new species of echogenic hyaluronic acid nanoparticles is presented as an ultralong‐acting, liver‐specific, US contrast agent that is distinct from conventional gas‐filled microbubbles. Using an oil‐in‐water (O/W) emulsification method, bioinert and hydrophobic perfluoropentane (PFP) is encapsulated as an ultrasound gas precursor into hyaluronic acid nanoparticles (HANPs) using hydrophobic interactions. HANPs are formulated by self‐assembly, with amphiphilic hyaluronic acid‐5β‐cholanic acid (HA‐CA) conjugating in aqueous conditions. The resulting echogenic PFP‐encapsulated HANPs (Echo‐NPs) show solid nanostructures, differentiated from core‐empty conventional microbubbles, and exhibiting outstanding physical properties as an ultrasound contrast agent. They are more stable and robust echogenic solid bodies with an in vivo favorable hydrodynamic size and because PFPs vaporize gradually, their expansion process is very slow in body conditions. After several systemic circulations, echo‐NPs generated intense and ultralong echo signals for US imaging at the target site. The echogenic properties of Echo‐NPs show a significantly increased half‐life and echo persistence, compared with conventional microbubbles. The results clearly show that echo‐NPs outperform conventional microbubbles in terms of both physical and echogenic in vitro and in vivo properties.</P>

택견의 어원에 대한 小考

김산,허인욱 한국체육사학회 2002 체육사학회지 Vol.9 No.-

The purpose of this study was to trace a word(Taek-kyon) to its origin. Teak-Kyon is being called Tak-Kyon · Tae-Kyon · D?k-Kyon and so on. So That makes us confused a lot Which is the origin. It has 4 prerequisite what had been debated by scholar, I describe the prerequisite as follows. ① It. existed in Seoul and around Kyung-ki(京畿) Province only. ② It's original pronunciation similar at Tak-Kyon. ③ It means a weapon-free martial art. ④ It derived from Chinese character. I admitted these prerequisite. so I searched for Chos?n(朝鮮) period's document and founded some words written in Chinese characters which means a weapon-free martial art. For example, Kwon-bup(拳法) · Su-bak(手搏) · Byun(卞)· Baek-ta(白打) · Kwon-to(拳鬪) · Ta-Kwon(打拳) etc. Ta-kwon's pronunciation is similar with Tak-kyon's among examples. and It used only 1 or 2 years officially, After government used Kwan-bup(拳法) as official term but Ta-Kwon used among an illiterate people in Seoul. They maybe mentioned Ta-Kwon without Chines character. As it result, they forget the original pronunciation and the word. Finally, Taek-kyon's pronunciation originated from Ta-kwon(打拳).

다양한 복합레진 시스템의 변연 누출도

김인수,민경산,신동훈 大韓齒科保存學會 2003 Restorative Dentistry & Endodontics Vol.28 No.2

The object of this study was to compare the microleakage between various composite resin systems of multistep, one-bottle, and self-etching systems using electrical conductivity. After making class V cavities (4×3×1.5 mm around CEH), they were bulk filled with three kinds of resins of A3. Teeth were storaged in a saline solution for one day, after then, they were finished and polished using Sof-Lex system. Another stress of thermocycling was made for 500 times from 5° to 55 ℃ with each dwelling time of 10 seconds. Electrical conductivity (microamphere, ㎂) was checked four times: before and after cavity preparation, after filling, after thermocycling. One-way ANOVA and 95% Scheffe Post Hoc test was used for checking any statistical difference among groups. Another 95% Paired Samples T-test was also used for estimating any significant difference within group after cavity filling or thermocycling. The results were as follows: 1. Every specimen showed various range of microleakage after filling. There was, however, no difference between composite resin systems. 2. All composite resin systems showed marked increase in microleakage with a thermocycling (p<0.05). there was, however, no difference between composite resin systems. 3. Although there was no significant difference between groups (p=0.078), one-bottle and self-etching systems seemed to be unstable than multistep system. Within the limits of this study, it was concluded that much more consideration should be needed when using thermally unstable one-bottle and self-etching systems that have multi-advantages from simplified step. More studies will be needed to solve these kinds of problems.

한국인의 각막에 관한 연구

강현식,김대년,김상연,강인산,박은규,서용원 대구보건대학 1999 대구보건대학 論文集 Vol.19 No.-

As the results of measurement of the radius of corneal curvature by keratometry for the right eye of 100 subjects, the steep meridian radius is 7.21㎜ to 8.27㎜ and flat meridian is 7.45㎜ to 8.65㎜, for the left eye the steep meridian radius is 7.30㎜ to 8.35㎜, and flat meridian is 7.45㎜ to 8.72㎜. The mean value of radius of corneal curvature is 7.8㎜ for night eye, 7.8㎜ for left eye. The results of measurement of P-value by topography, it is ranged from 0.45 to 0.91 for the night eye, 0.55 to 0.90 for the left eye, mean value is 0.756 for right eye, 0.735 for left eye respectively. That means the corneal shape is ellipses. The corneal thickness is measured 0.69㎜ 10°degree to the nasal, 0.76㎜ 20°degree to the nasal, 0.66㎜ 10°degree to the temporal, 0.72㎜ 20° degree to the temporal from the visual axis and 0.60㎜ at the central position. The horizontal size of corneal is 11.34㎜ for the night eye, 11.373㎜ for left eye. Those data can be used for contact lens design and fitting.

Four novel RUNX2 mutations including a splice donor site result in the cleidocranial dysplasia phenotype

Kim, Hyo-Jin,Nam, Soon-Hyeun,Kim, Hyun-Jung,Park, Hyo-Sang,Ryoo, Hyun-Mo,Kim, Shin-Yoon,Cho, Tae-Joon,Kim, Seung-Gon,Bae, Suk-Chul,Kim, In-San,Stein, Janet L.,van Wijnen, Andre J.,Stein, Gary S.,Lian, Liss 2006 Journal of Cellular Physiology Vol.207 No.1

<P>Cleidocranial dysplasia (CCD) is an autosomal dominant disorder caused by haploinsufficiency of the RUNX2 gene. In this study, we analyzed by direct sequencing RUNX2 mutations from eleven CCD patients. Four of seven mutations were novel: two nonsense mutations resulted in a translational stop at codon 50 (Q50X) and 112 (E112X); a missense mutation converted arginine to glycine at codon 131 (R131G); and an exon 1 splice donor site mutation (donor splice site GT/AT, IVS1 + 1G > A) at exon 1–intron junction resulted in the deletion of QA stretch contained in exon 1 of RUNX2. We focused on the functional analysis of the IVS1 + 1G > A mutation. A full-length cDNA of this mutation was cloned (RUNX2Δe1) and expressed in Chinese hamster ovary (CHO) and HeLa cells. Functional analysis of RUNX2Δe1 was performed with respect to protein stability, nuclear localization, DNA binding, and transactivation activity of a downstream RUNX2 target gene. Protein stability of RUNX2Δe1 is similar to wild-type RUNX2 as determined by Western blot analysis. Subcellular localization of RUNX2Δe1, assessed by in situ immunofluorescent staining, was observed with partial retention in both the nucleus and cytoplasm. This finding is in contrast to RUNX2 wild-type, which is detected exclusively in the nucleus. DNA binding activity was also compromised by the RUNX2Δe1 in gel shift assay. Finally, RUNX2Δe1 blocked transactivation of the osteocalcin gene determined by transient transfection assay. Our findings demonstrate for the first time that the CCD phenotype can be caused by a splice site mutation, which results in the deletion of N-terminus amino acids containing the QA stretch in RUNX2 that contains a previously unidentified second nuclear localization signal (NLS). We postulate that the QA sequence unique to RUNX2 contributes to a competent structure of RUNX2 that is required for nuclear localization, DNA binding, and transactivation function. J. Cell. Physiol. 207: 114–122, 2006. © 2005 Wiley-Liss, Inc.</P>