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    ์–ธ์–ด

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    ๊น€์ง„์šฐ, ํƒ‘์ถœํŒ์‚ฌ, 1986, iii+405๋ฉด์ด ์ฑ…์€ 4 ๋ถ€๋กœ ๋‚˜๋‰˜์–ด์ ธ ์žˆ๋Š”๋ฐ ์ œ 1๋ถ€์—์„œ๋Š” ์–ธ์–ด์™€ ์–ธ์–ดํ•™์˜ ์ดํ•ด๋ฅผ ์œ„ํ•œ ๊ธฐ์ดˆ ์ด๋ก ์„ ์„ค๋ช…ํ•˜์˜€๊ณ  ์ œ 2๋ถ€์—์„œ๋Š” ์–ธ์–ดํ•™์˜ ์ด๋ก ์„ ํ•˜์œ„ ๋ถ„์•ผ๋ณ„๋กœ ๊ณต์‹œ์  ๊ด€์ ์—์„œ ์„ค๋ช…ํ•˜์˜€๋‹ค. ์ œ 3๋ถ€์—์„œ๋Š” ํ†ต์‹œ์  ๊ด€์ ์—์„œ์˜ ์–ธ์–ด ์ด๋ก ๋“ค์„ ์„ค๋ช…ํ•˜๊ณ  ๊ทธ ์—ฐ๊ตฌ ์„ฑ๊ณผ๋“ค์ด ์ œ์‹œ๋˜์—ˆ๋‹ค. ์ œ 4 ๋ถ€์—์„œ๋Š” ์–ธ์–ด์™€ ์ธ์ฒฉ๊ณผํ•™ ๊ณผ์˜ ๊ด€๊ณ„๋ฅผ ๋‹ค๋ฃจ์—ˆ๋‹ค. ์—ฌ๊ธฐ์—์„œ ์•Œ ์ˆ˜ ์žˆ๋Š” ๋ฐ”์™€ ๊ฐ™์ด ์ด ์ฑ…์€ ์–ธ์–ด ์—ฐ๊ตฌ ์— ๋Œ€ํ•œ ์ด๋ก  ์ „๋ฐ˜์„ ํฌ๊ด„ํ•˜๊ณ  ์žˆ์œผ๋ฉฐ ์–ธ์–ด ์ด๋ก ์˜ ๊ธฐ์ดˆ๋ฅผ ์†Œ๊ฐœํ•˜๊ธฐ ์œ„ํ•œ ์–ธ์–ดํ•™ ๊ฐœ๋ก ์„œ์ด๋‹ค

    ์–ธ์–ดํ•™ ๊ฐœ๋ก 

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    1986, iii+405๋ฉด๋ฒ•์—์„œ ๋…ผ์˜๋œ ์ค‘์š”ํ•œ ์„ฑ๊ณผ๋“ค์„ ์ค‘์šฉ์˜ ์ž…์žฅ์—์„œ ์†Œ๊ฐœํ•˜์—ฌ ํ˜„๋Œ€์–ธ์–ดํ•™์„ ์กฐ๊ฐํ•˜์˜€๊ณ  ์—ฌ๋Ÿฌ ํ•™๋ฌธ ๋ถ„์•ผ์—์„œ์˜ ์–ธ์–ด์— ๊ด€ํ•œ ์ด๋ก ์„ ํฌ๊ด„ํ•˜์—ฌ ์–ธ์–ด์˜ ์—ฌ๋Ÿฌ ๋ฉด์„ ํฅ๋ฏธ์žˆ๊ฒŒ ์„œ์ˆ ํ•˜์˜€๋‹ค. ์–ธ์–ดํ•™๋„๋Š” ๋ฌผ๋ก  ์–ธ์–ด์™€ ๊ด€๋ จ๋œ ํ•™๋ฌธ์— ์ข…์‚ฌํ•˜๋Š” ์ด๋“ค์—๊ฒŒ ์–ธ์–ด์˜ ์ดํ•ด๋ฅผ ์œ„ํ•œ ์ข‹์€ ์•ˆ๋‚ด์„œ๊ฐ€ ๋  ๊ฒƒ์œผ๋กœ ์ƒ๊ฐ๋œ๋‹ค. ์–ธ์–ด ์—ฐ๊ตฌ์‚ฌ์™€ ์˜๋ฏธ๋ก  ๋ถ€๋ถ„์ด ๋‹ค์†Œ ์†Œ๋žตํ•˜๊ฒŒ ์†Œ๊ฐœ๋˜์–ด ์žˆ๋‹ค. ์–ธ์–ด ์—ฐ๊ตฌ์‚ฌ ๋Š” ์ œ 7์žฅ์˜ ๋๋ถ€๋ถ„์—์„œ 19์„ธ๊ธฐ ํ›„๋ฐ˜์˜ ์—ญ์‚ฌ โ€ข ๋น„๊ต์–ธ์–ดํ•™๊ณผ ๋ฏธ๊ตญ์˜ ๊ตฌ์กฐ์ฃผ์˜ ์–ธ์–ดํ•™์„ ๊ฐ„๋žตํ•˜๊ฒŒ ์†Œ๊ฐœํ•˜์—ฌ ์ƒ์„ฑ๋ฌธ๋ฒ•์ด ํƒ„์ƒ๋˜๊ธฐ ์ง์ „์˜ ๋ฐฐ๊ฒฝ์„ ๋ฐํžˆ๋Š” ๋ฐ์— ๊ทธ์น˜๊ณ  ์žˆ๋‹ค. ์ธ๋ฅ˜์˜ ์–ธ์–ด์— ๋Œ€ํ•œ ์˜ค๋žœ ์—ฐ๊ตฌ์‚ฌ์™€ ํŠนํžˆ Saussure์˜ ์—…์ ๊ณผ ๊ทธ๋ฅผ ๊ธฐ์ ์œผ๋กœ ํ•œ ๊ตฌ๋ผํŒŒ์˜ ๊ตฌ์กฐ์ฃผ์˜ ์–ธ์–ดํ•™์ด ์†Œ๊ฐœ๋˜์ง€ ์•Š์€ ์ฒจ์ด ์•„ ์‰ฝ๋‹ค

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    ์‚ฌํšŒ: ์ˆ˜๊ณ ํ•˜์…จ์Šต๋‹ˆ๋‹ค. ์„ธ๋ถ€๋ถ„์œผ๋กœ ๋‚˜๋ˆ„์–ด ์ž์„ธํžˆ ๋ง์”€ํ•ด์ฃผ์…จ์Šต๋‹ˆ๋‹ค. ํ† ๋ก ํšŒ ์ˆœ์„œ๋Š” ์ฃผ์ œ ๋…ผ๋ฌธ์ด ์ง„ํ–‰๋œ ๊ฒƒ๊ณผ๋Š” ๊ฑฐ๊พธ๋กœ๏ผŒ processing, ๋ฒ”์ฃผํ™”๏ผŒ ์–ธ์–ด์Šต๋“์˜ ์ˆœ์œผ๋กœ ๋‹ค๋ฃจ๊ฒ ์Šต๋‹ˆ๋‹ค. ์ž์„ธํžˆ ๋ง์”€ํ•ด์ฃผ์…จ์ง€๋งŒ ๋จผ์ € ์‹ฌ๋ฆฌํ•™์„ ํ•˜์‹œ๋Š” ๊น€์ •์˜ค ์„ ์ƒ๋‹˜๊ป˜์„œ ์–ธ์–ด ์ฒ˜๋ฆฌ ๋ฌธ์ œ์— ์žˆ์–ด์„œ ์ „๋‹จ๊ณ„๊ฐ€ ๋˜๋Š” ์ง€๊ฐ์ธก๋ฉด๊ณผ ๊ด€๋ จํ•˜์—ฌ processing์— ๋Œ€ํ•˜์—ฌ ์ƒ์„ธํžˆ ๋ง์”€ํ•ด์ฃผ์‹œ๊ณ  ์กฐ์„ ์ƒ๋‹˜์˜ ๋ง์”€์— ๋Œ€ํ•ด์„œ ์˜๊ฒฌ์„ ์ œ์‹œํ•ด ์ฃผ์‹œ๊ฒ ์Šต๋‹ˆ๋‹ค

    ์ƒˆ๋กœ์šด ์น˜๋ฃŒ๊ธฐ์ˆ  ๊ฐœ๋ฐœ์„ ์œ„ํ•œ ์ด์ข…๊ฐ„ ์ฒด์„ธํฌ ํ•ต์ด์‹ ๊ธฐ์ˆ  ํ™•๋ฆฝ

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    Thesis (master`s)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :๋†์ƒ๋ช…๊ณตํ•™๋ถ€,2003.Recently, cell and tissue therapies with employing somatic cell nuclear transfer (SCNT) have been suggested to develop innovative medical technology, which greatly contributes to overcome degenerative diseases. After the successful birth of cloned sheep, ยกยฐDollyยกยฑ, SCNT is of significantly greater commercial and research importance. However, various concerns on human SCNT, which might cause human cloning, have been made. The objective of my master thesis was to develop an efficient SCNT, which could develop an alternative therapeutic cloning technology without sacrificing human oocytes. To achieve this purpose, I attempted to establish an interspecies nuclear transfer of human somatic cell into enucleated bovine oocytes. In the first series of experiment, I attempted to select the most efficient somatic cell type and preparation, fusion medium and culture strategy for interspecies clone embryos. As results, SCNT of fetal cord fibroblasts yielded more (P=0.0006) 2-cell embryos than SCNT of adult fibroblasts. A significant (P<0.05) batch effect of cord fibroblast on preimplantation development after SCNT was found and serum starvation greatly improved preimplantation development, regardless of the batches. No significant effect was observed after change of fusion medium (Ca2+- free mannitol solution) to Ca2+-containing mannitol or sorbitol solution, while embryo culture system greatly influenced the development. A continuous culture in modified synthetic oviduct fluid medium used in bovine embryo culture only supported blastocyst formation of interspecies clone embryos. In the second series of experiment, I further optimized the interspecies SCNT developed in my previous experiment by changing cord fibroblast cell batches and reconstruction method. Total 1,742 bovine oocytes were provided for SCNT. Reconstruction of a fibroblast by single DC pulse of 1.9 to 2.1 kV/cm for 20 ยฅรฌsecond yielded better rate of fusion (30 to 56%) and, development to the 2- cell (27 to 36%), 8-cell (7 to 14%), 16-cell (5 to 7%) and morula to blastocyst (3 to 5%) stages. Results from karyotyping and mitochondrial DNA analysis demonstrated that 56% of karyotyped embryos had presumptively normal human chromosome complements consisting of 23 pairs of autosomes with sex chromosome, while only bovine mtDNA was detected.Maste

    P53 immunoexpression in gastric adenocarcinoma with Helicobacter pylori infection

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    ์˜ํ•™๊ณผ/์„์‚ฌ[ํ•œ๊ธ€] ์œ„์•”์˜ ๋ฐœ์•” ๊ธฐ์ „์€ ์‹์ƒํ™œ, ์œ„๋‚ด ๋ฏธ์„ธํ™˜๊ฒฝ, ์œ ์ „ ๋“ฑ ๋‹ค์–‘ํ•œ ๋ถ„์•ผ์—์„œ ์—ฐ๊ตฌ๋˜์–ด ์™”๋‹ค. Helicobacter pylori(์ดํ•˜ Hp)๊ฐ์—ผ๊ณผ p53 ์•”์–ต์ œ ์œ ์ „์ž์˜ ๋Œ์—ฐ๋ณ€์ด๋Š” ๊ฐ๊ฐ ์œ„์•” ๋ฐœ๋ณ‘์— ์ผ๋ถ€ ๊ด€์—ฌํ•˜๋Š” ์ค‘์š”ํ•œ ์ธ์ž๋กœ ๊ฑฐ๋ก ๋˜๊ณ  ์žˆ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ Hp๊ฐ€ ์–ด๋–ค ์ž‘์šฉ์œผ๋กœ ์œ„์•”๊ณผ ๊ด€๋ จ๋  ์ˆ˜ ์žˆ๋Š”๊ฐ€์— ๋Œ€ํ•ด์„œ๋Š” ๊ทธ ๊ธฐ์ „์ด ์•„์ง ๋ฐํ˜€์ง€์ง€ ์•Š์•˜์œผ๋ฉฐ ์‚ฐ๋ฐœ์ ์œผ๋กœ ์ผ๋ถ€ ์‹œ๋„๊ฐ€ ์žˆ์–ด์™”๋‹ค. ์ด์— ์—ฐ๊ตฌ์ž๋Š” ์œ„์•” ํ™˜์ž์—์„œ Hp ๊ฐ์—ผ๊ณผ p53 ๋‹จ๋ฐฑ ํ‘œํ˜„์ด ์–ด๋–ค ์—ฐ๊ด€์„ ๊ฐ€์ง€๋Š”์ง€ ์กฐ์‚ฌํ•˜๊ณ  ์œ„์„ ์•”์ข…์˜ ๋ฐœ๋ณ‘์œ„์น˜, ์œก์•ˆ์†Œ๊ฒฌ, ๋ถ„ํ™”๋„, ๋ณ‘๊ธฐ, ๋‚˜์ด ๋“ฑ ์—ฌ๋Ÿฌ ์ž„์ƒ๋ณ‘๋ฆฌ์  ํŠน์„ฑ๋“ค๊ณผ ์–ด๋–ค ์œ ์˜์„ฑ์ด ์žˆ๋Š”์ง€ ๋ฐํžˆ๊ณ ์ž ํ•˜์˜€๋‹ค. 1995๋…„ 11์›”๋ถ€ํ„ฐ 1996๋…„ 3์›”๊นŒ์ง€ ์—ฐ์„ธ๋Œ€ํ•™๊ต ์˜๊ณผ๋Œ€ํ•™ ์„ธ๋ธŒ๋ž€์Šค๋ณ‘์›์—์„œ ์œ„์„ ์•”์ข…์œผ๋กœ ์ง„๋‹จ๋œ ํ™˜์ž 96๋ช…๊ณผ ๋Œ€์กฐ๊ตฐ์œผ๋กœ Non ulcer dyspepsia(NUD) ํ™˜์ž 96๋ช…์„ ๋Œ€์ƒ์œผ๋กœ ์ •์ƒ ์ ๋ง‰๊ณผ ์œ„์•” ์ฃผ๋ณ€์ ๋ง‰์˜ ์กฐ์ง๊ฒ€์‚ฌ ๋ฐ CLO**(R) (Delta West, Melbourne, Western Australia) ๊ฒ€์‚ฌ๋กœ Hp ์–‘์„ฑ๋ฅ ์„ ์กฐ์‚ฌํ•˜์˜€๊ณ  ์œ„์•”๋ณ‘๋ณ€ ๋ถ€์œ„์—์„œ p53 ๋ฉด์—ญํ™”ํ•™์—ผ์ƒ‰์„ ์‹œํ–‰ํ•˜์—ฌ ์—ฌ๋Ÿฌ ์ž„์ƒ๋ณ‘๋ฆฌ์  ์ธ์ž์™€ ๋น„๊ต๋ถ„์„ ํ•˜์˜€๋‹ค. 1. ๋Œ€์ƒํ™˜์ž 96๋ช…์˜ ์„ฑ๋ณ„๋ถ„ํฌ๋Š” ๋‚จ์ž 59๋ช…, ์—ฌ์ž 37๋ช…์ด์—ˆ์œผ๋ฉฐ ํ‰๊ท ์—ฐ๋ น 56.1์„ธ์˜€๊ณ , ๋Œ€์กฐ๊ตฐ์˜ ์„ฑ๋ณ„๊ณผ ๋‚˜์ด์™€๋Š” ํ†ต๊ณ„์ ์œผ๋กœ ์œ ์˜ํ•œ ์ฐจ์ด๊ฐ€ ์—†์—ˆ๋‹ค. 2. ์œ„์•”ํ™˜์ž์™€ ๋Œ€์กฐ๊ตฐ์˜ HP ์–‘์„ฑ๋ฅ ์€ ๊ฐ๊ฐ 78.1%์™€ 67.7%์ด์—ˆ๋‹ค(p<0.05). 3. ์œ„์•”ํ™˜์ž ์ „์ฒด์˜ p53 ๋‹จ๋ฐฑ ํ‘œํ˜„์œจ์€ 46.9%์ด์—ˆ์œผ๋ฉฐ Hp ์–‘์„ฑ์ธ ๊ตฐ์— 50.7%, Hp ์Œ์„ฑ์ธ ๊ตฐ์—์„œ๋Š” 33.3%๋กœ์„œ p53 ๋‹จ๋ฐฑ ํ‘œํ˜„์œจ์€ Hp ์–‘์„ฑ์ธ ๊ตฐ์—์„œ ์˜๋ฏธ์žˆ๊ฒŒ ๋†’์•˜๋‹ค(p<0.05). 4. ์œ„์•”ํ™˜์ž ์ค‘์—์„œ ์ง„ํ–‰์œ„์•” ํ™˜์ž๋Š” 54๋ช…, ์กฐ๊ธฐ์œ„์•” ํ™˜์ž๋Š” 42๋ช…์ด์—ˆ์œผ๋ฉฐ ์ง„ํ–‰์œ„์•”๊ณผ ์กฐ๊ธฐ์œ„์•”์˜ Hp ์–‘์„ฑ๋ฅ ์€ ๊ฐ๊ฐ 72.2%์™€ 85.7%๋กœ ์กฐ๊ธฐ์œ„์•”๋งŒ ๋Œ€์กฐ๊ตฐ์— ๋น„ํ•ด์„œ ์˜๋ฏธ์žˆ๊ฒŒ ๋†’์•˜์œผ๋ฉฐ (p<0.05), p53 ๋‹จ๋ฐฑ ํ‘œํ˜„์œจ์€ ์ง„ํ–‰์œ„์•”์ด 46.3%, ์กฐ๊ธฐ์œ„์•”์ด 47.6%๋กœ์„œ Hp ๊ฐ์—ผ๊ณผ๋Š” ์˜์˜์žˆ๋Š” ์—ฐ๊ด€์„ฑ์ด ์—†์—ˆ๋‹ค. 5. ์กฐ์ง๋ถ„ํ™”๋„์ƒ ๋ถ„ํ™”ํ˜•๊ตฐ (differentiated group)๊ณผ ๋ฏธ๋ถ„ํ™”ํ˜•๊ตฐ (differentiated group)์˜ Hp ์–‘์„ฑ๋ฅ ์€ ๊ฐ๊ฐ 90.6%์™€ 71.9%๋กœ์„œ ๋ถ„ํ™”ํ˜•๊ตฐ๋งŒ ๋Œ€์กฐ๊ตฐ์— ๋น„ํ•ด์„œ ์˜๋ฏธ์žˆ๊ฒŒ ๋†’์•˜์œผ๋ฉฐ (p<0.05), p53 ๋‹จ๋ฐฑ ํ‘œํ˜„์œจ์€ ๋ถ„ํ™”ํ˜•๊ตฐ์ด 71.9%๋กœ์„œ ๋ฏธ๋ถ„ํ™”ํ˜•๊ตฐ์˜ 34.4%์— ๋น„ํ•ด์„œ ์˜๋ฏธ์žˆ๊ฒŒ ๋†’์•˜๋‹ค(p<0.005). Hp ์–‘์„ฑ๋ฅ ๊ณผ p53 ๋‹จ๋ฐฑ ํ‘œํ˜„์œจ์ด ๋ชจ๋‘ ์˜๋ฏธ์žˆ๊ฒŒ ๋†’์•˜๋˜ ๊ฒฝ์šฐ๋Š” ๋ถ„ํ™”ํ˜•๊ตฐ์—์„œ์˜€๋‹ค(p<0.05). 6. ์œ„์•”ํ™˜์ž๊ตฐ์˜ ๋†’์€ ์—ฐ๋ น์—์„œ Hp ์–‘์„ฑ๋ฅ ์€ ๋‚ฎ์•˜์œผ๋‚˜(p<0.05), p53 ๋‹จ๋ฐฑํ‘œํ˜„๊ณผ๋Š” ๋ฌด๊ด€ํ•˜์˜€๋‹ค. Borrmann type, ๋ณ‘๊ธฐ์™€ ๋ฐœ๋ณ‘์œ„์น˜์— ๋Œ€ํ•œ Hp ์–‘์„ฑ๋ฅ ๊ณผ p53 ๋‹จ๋ฐฑ ํ‘œํ˜„์€ ๋ชจ๋‘ ์—ฐ๊ด€์„ฑ์ด ์—†์—ˆ๋‹ค. ์ด์ƒ์˜ ๊ฒฐ๊ณผ๋กœ p53 ๋‹จ๋ฐฑ ํ‘œํ˜„์œจ์€ Hp ์Œ์„ฑ์ธ ์œ„์•”ํ™˜์ž๋“ค์— ๋น„ํ•ด์„œ Hp ์–‘์„ฑ์ธ ์œ„์•”ํ™˜์ž๋“ค์—์„œ ์˜๋ฏธ์žˆ๊ฒŒ ๋†’์•˜์œผ๋ฉฐ, Hp ์–‘์„ฑ๋ฅ ๊ณผ p53 ๋‹จ๋ฐฑ ํ‘œํ˜„์œจ์ด ๋ชจ๋‘ ์˜๋ฏธ์žˆ๊ฒŒ ๋†’์•˜๋˜ ๊ฒฝ์šฐ๋Š” ์กฐ์ง๋ถ„ํ™”๋„์ƒ ๋ถ„ํ™”ํ˜•๊ตฐ์—์„œ์˜€๋‹ค. ์ด๋Ÿฌํ•œ ๊ตฐ์—์„œ๋Š” Hp ๊ฐ์—ผ์ด p53 ์–ต์ œ์œ ์ „์ž์˜ ๋ณ€์ด์™€ ์˜์˜์žˆ๋Š” ์ƒ๊ด€๊ด€๊ณ„๋ฅผ ๋ณด์—ฌ์„œ ์œ„์•”์„ ์œ ๋ฐœํ•  ๊ฐ€๋Šฅ์„ฑ์ด ์žˆ๊ฒ ์ง€๋งŒ ์ด์— ๋Œ€ํ•ด์„œ๋Š” ์•ž์œผ๋กœ ๋ณด๋‹ค ์—ฐ๊ด€์„ฑ์„ ์ฐพ๊ธฐ ์œ„ํ•œ ์—ฐ๊ตฌ๊ฐ€ ์š”๊ตฌ๋œ๋‹ค๊ณ  ์ƒ๊ฐํ•œ๋‹ค. [์˜๋ฌธ] Gastric carcinogenesis has been studied in various aspects. Helicobacter pylori(Hp) infection and mutation of p53 tumor suppressor gene has recently been debated to be important factors of gastric carcinogenesis. There have been many studies to uncover the precise mechanism of how Hp is related to gastric cancer, but it is still unknown until now, I have studied the relationship of Hp infection and p53 overexpression and tried to discover some significance in clinicopathologic factors such as age, sex, stage, site, differentiation and gross morphology. 96 patients who were diagnosed as gastric cancer in the Severance Hospital, Yonsei University Medical College from November, 1995 to March, 1996, and 96 control patients of non-ulcer dyspepsia (NUD) were studied by endoscopic biopsy of normal gastric tissue and cancer tissue and also the CLO**(R) (Delta West, Melbourne, Western Australia) test for Hp positivity and p53 immuilohistochemical stain for p53 positivity. These data were analyzed for the comparison with the clinicopathologic characteristics of the gastric cancers. 1. The sex distribution of 96 patients were 59 males and 37 females, and the mean age was 56.1. The sex and age of control patients had no significant difference. 2. Hp positivity of gastric cancer patients and the control patients was 78.1% and 67.7% (p<0.05). 3. P53 positivity of gastric cancer patients was 46.9%, and p53 positivity was significantly higher in the Hp positive patients(50.7%) compared with the Hp negative patients(33.3%) (p<0.05). 4. Among the patients with gastric cancer, 54 cases were AGC (advanced gastric cancer) and 42 cases were EGC (early gastric cancer). Hp positivity was 72.2% and 85.7% respectively and Hp positivity was significantly high in the EGC patients(p<0.05). P53 positivity was 46.3% in AGC and 47.6% in EGC, and there was no significant relationship with Hp positivity. 5. According to cellular differentiation, Hp positivity in the differentiated group and undifferentiated group was 90.6% and 71.9% respectively and Hp positivity in the differentiated group was significantly high compared with the undifferentiated group(p<0.05). P53 positivity in the differentiated group(71.7%) was significantly high compared with the undifferentiated group(34.4%) (p<0.005). Hp positivity and p53 positivity were both significantly high(p<0.05) in the differentiated group cancer. 6. Hp positivity of gastric cancer patients significantly decreased with increasing age(p<0.05), but they were not related to p53 positivity. The gross morphology, stage and site of cancer had no relationship with either Hp positivity or p53 positivity. In conclusion, p53 overexpression was more frequent in the Hp positive group than the Hp negative group, and the differentiated group cancer had a significantly high Hp positivity and p53 positivity. There is a possibility that Hp infection and p53 tumor suppressor gene mutation might be significantly related in the gastric carcinogenic process, but further study is necessary for more direct clues on the carcinogenic roles of these factors.restrictio

    Effect of interleukin-15 on natural killer cells of human immunodeficiency virus-infected persons

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    ์˜ํ•™๊ณผ/๋ฐ•์‚ฌ[ํ•œ๊ธ€] Human immunodeficiency virus (์ดํ•˜ HIV) ๊ฐ์—ผ์—์„œ๋Š” ๊ด‘๋ฒ”์œ„ํ•œ ๋ฉด์—ญ์ฒด๊ณ„์˜ ์ด์ƒ์ด ๋™๋ฐ˜๋˜๋ฉฐ ๊ทธ ์ค‘์˜ ํ•˜๋‚˜๊ฐ€ ์ž์—ฐ์‚ดํ•ด์ž‘๋™์˜ ๊ฐ์†Œ์ด๋‹ค. ์ธํ„ฐ๋ฃจํ‚จ-15(Interleukin-15; ์ดํ•˜ IL-15)์€ HIV์˜ ๋ฉด์—ญ์น˜๋ฃŒ๋กœ ํ™œ๋ฐœํžˆ ์—ฐ๊ตฌ๋˜๊ณ  ์žˆ๋Š” cytokine์ด๋‹ค. IL-15์€ HIV ๊ฐ์—ผ์ž์˜ ์ž์—ฐ์‚ดํ•ด์„ธํฌ๋ฅผ ์ž๊ทนํ•˜์—ฌ ์ž์—ฐ์‚ดํ•ด์ž‘์šฉ์„ ์ฆ๊ฐ€์‹œํ‚ค๋ฉฐ ์—ฌ๋Ÿฌ ๊ฐ€์ง€ ๋ฉด์—ญ์„ธํฌ๋กœ๋ถ€ํ„ฐ CC-chemokine์„ ๋ถ„๋น„์‹œ์ผœ์„œ ๊ฐ์ข… ๋ฉด์—ญ์„ธํฌ๋ฅผ ์ง‘๊ฒฐ์‹œํ‚ค๋Š” ๊ฒƒ์œผ๋กœ ์•Œ๋ ค์ ธ ์žˆ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ IL-15์ด HIV ๊ฐ์—ผ์ž์˜ ์ž์—ฐ์‚ดํ•ด์„ธํฌ์—์„œ ์–ด๋– ํ•œ ๊ธฐ์ „์œผ๋กœ ์ž์—ฐ์‚ดํ•ด์ž‘์šฉ์„ ์ฆ๊ฐ€์‹œํ‚ค๋Š”์ง€๋Š” ์•Œ๋ ค์ง„ ๋ฐ” ์—†์œผ๋ฉฐ, IL-15์ด ์ฆ๊ฐ€์‹œํ‚ค๋Š” CC-chemokine๊ณผ ์ž์—ฐ์‚ดํ•ด์„ธํฌ์ž‘์šฉ์˜ ์—ฐ๊ด€์„ฑ์ด ๋ถˆ๋ถ„๋ช…ํ•œ ์‹ค์ •์ด๋‹ค. IL-15์„ HIV ๊ฐ์—ผ์—์„œ ๋ฉด์—ญ์น˜๋ฃŒ๋กœ ๊ณ ๋ คํ•˜๊ธฐ ์ „์— ์ด๋Ÿฌํ•œ ์ƒ๊ด€๊ด€๊ณ„๋ฅผ ์ดํ•ดํ•˜๋Š” ๊ฒƒ์ด ํ•„์š”ํ•˜๋‹ค. ์ด์— ์ €์ž๋Š” IL-15์ด HIV ๊ฐ์—ผ์ž ์ž์—ฐ์‚ดํ•ด์„ธํฌ์˜ ์ž์—ฐ์‚ดํ•ด์ž‘์šฉ์— ๋ฏธ์น˜๋Š” ์˜ํ–ฅ๊ณผ ๊ธฐ์ „์„ ์—ฐ๊ตฌํ•˜๊ธฐ ์œ„ํ•ด์„œ HIV์— ๊ฐ์—ผ๋œ ํ™˜์ž 8๋ช…๊ณผ ์ •์ƒ์ธ 10๋ช…์˜ ๋ง์ดˆํ˜ˆ์•ก ๋‹จํ•ต์„ธํฌ(peripheral blood mononuclear cell; PBMC)์—์„œ ์ž์—ฐ์‚ดํ•ด์„ธํฌ๋ฅผ ๋ถ„๋ฆฌํ•œ ํ›„ IL-15์„ ํˆฌ์—ฌํ•˜์—ฌ ์ž์—ฐ์‚ดํ•ด์ž‘์šฉ์˜ ๋ณ€ํ™”๋ฅผ K562์„ธํฌ๋ฅผ ํ‘œ์ ์„ธํฌ๋กœ ํ•˜์—ฌ 4์‹œ๊ฐ„ (51)**Cr ๋ฐฉ์ถœ๋ฒ•์œผ๋กœ ์ธก์ •ํ•˜์˜€๋‹ค. ์ด๋•Œ ์ž์—ฐ์‚ดํ•ด์„ธํฌ๋กœ๋ถ€ํ„ฐ ๋ถ„๋น„๋˜๋Š” macrophage inflammatory protein-1ฮฑ(MIP-1ฮฑ), macrophage chemotactic protein-1(MCP-1) ๊ทธ๋ฆฌ๊ณ  regulatedupon activation, normal T cell expressed and secreted(RANTES) ๋“ฑ์˜ CC-chemokine ๋†๋„๋ฅผ enzyme-linked immunosorbent assay(ELISA)๋กœ ์ธก์ •ํ•˜์—ฌ IL-15์ด ์ž์—ฐ์‚ดํ•ด์„ธํฌ์—์„œ์˜ CC-chemokine์˜ ํ‘œํ˜„์— ๋ฏธ์น˜๋Š” ์˜ํ–ฅ์„ ์กฐ์‚ฌํ•˜์˜€๋‹ค. ๋˜ํ•œ RANTES์™€ ์ž์—ฐ์‚ดํ•ด์ž‘์šฉ์˜ ์ง์ ‘์ ์ธ ์—ฐ๊ด€์„ฑ์„ ๋ณด๊ธฐ ์œ„ํ•ด์„œ RANTES์˜ ์ค‘๋Ÿ‰ํˆฌ์—ฌ์™€ anti-RANTES antibody๋ฅผ ์ฒจ๊ฐ€ํ•œ ํ›„์˜ ์ž์—ฐ์‚ดํ•ด์ž‘์šฉ์˜ ๋ณ€ํ™”๋ฅผ ๋ณด์•˜๋‹ค. IL-15์ด ์ž์—ฐ์‚ดํ•ด์„ธํฌ๋ฅผ ์ž๊ทนํ•œ ํ›„์— ์ž์—ฐ์‚ดํ•ด์ž‘์šฉ์ด ์ฆ๊ฐ€ํ•˜๋Š” ๊ณผ์ •์—์„œ ์„ธํฌ๋‚ด์˜ ๋ณ€ํ™”๋ฅผ ์กฐ์‚ฌํ•˜๊ธฐ ์œ„ํ•ด, ์„ธํฌ์šฉํ•ด ํšจ์†Œ์˜ ํ‘œํ˜„ ์ •๋„๋ฅผ granzyme B์™€ perform์˜ Westem blot์œผ๋กœ ํ™•์ธํ•˜์˜€๊ณ , ์„ธํฌ์˜ P-glycoprotein ํ‘œํ˜„๊ณผ P-glycoprotein์˜ ๊ธฐ๋Šฅ์„ ๋Œ€๋ณ€ํ•˜๋Š” rhodamine123 efflux๋ฅผ flow cytometry๋กœ ๋ถ„์„ํ•˜์—ฌ ๋‹ค์Œ๊ณผ ๊ฐ™์€ ๊ฒฐ๊ณผ๋ฅผ ์–ป์—ˆ๋‹ค. 1. ์ •์ƒ์ธ์˜ ์ž์—ฐ์‚ดํ•ด์„ธํฌ์—์„œ๋Š” ์ฃผํšจ์„ธํฌ์™€ ํ‘œ์ ์„ธํฌ ๋น„์œจ์˜ ์ฆ๊ฐ€์— ๋”ฐ๋ผ ์ž์—ฐ์‚ดํ•ด์ž‘์šฉ์ด ์ฆ๊ฐ€ํ•œ ๋ฐ˜๋ฉด, HIV ๊ฐ์—ผ์ž์˜ ์ž์—ฐ์‚ดํ•ด์„ธํฌ์—์„œ๋Š” ์ฃผํšจ์„ธํฌ๋ฅผ ๋Š˜๋ ค๋„ ์ž์—ฐ์‚ดํ•ด์ž‘์šฉ์€ ์ฆ๊ฐ€ํ•˜์ง€ ์•Š์•˜๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ IL-15 ํˆฌ์—ฌ ์‹œ ์ž์—ฐ์‚ดํ•ด์ž‘์šฉ์ด ์ฆ๊ฐ€ํ•˜์˜€๋‹ค. 2. IL-15์„ 0, 10, 100, 1000 ng/ml์œผ๋กœ ์ฆ๋Ÿ‰ํ•  ๋•Œ ์ž์—ฐ์‚ดํ•ด์ž‘์šฉ์€ ์ •์ƒ์ธ์˜ ์ž์—ฐ์‚ดํ•ด์„ธํฌ์™€ HIV๊ฐ์—ผ์ž์˜ ์ž์—ฐ์‚ดํ•ด์„ธํฌ ๋ชจ๋‘์—์„œ ์šฉ๋Ÿ‰์˜์กด์ ์œผ๋กœ ์ฆ๊ฐ€ํ•˜์˜€๋‹ค. 3. IL-15์œผ๋กœ ์ž๊ทนํ•  ๋•Œ ๋ถ„๋น„๋˜๋Š” MIP1-ฮฑ, MCP-1, RANTES์˜ ๋†๋„๋Š” ์ •์ƒ์ธ์˜ ์ž์—ฐ์‚ดํ•ด์„ธํฌ์™€ HIV๊ฐ์—ผ์ž์˜ ์ž์—ฐ์‚ดํ•ด์„ธํฌ์—์„œ ์ฐจ์ด๊ฐ€ ์—†์—ˆ๋‹ค. 4.์ •์ƒ์ธ์˜ ์ž์—ฐ์‚ดํ•ด์„ธํฌ์™€ HIV๊ฐ์—ผ์ž์˜ ์ž์—ฐ์‚ดํ•ด์„ธํฌ์—์„œ ์ธก์ •ํ•œ ์ž์—ฐ์‚ดํ•ด์ž‘์šฉ์€ RANTES ํˆฌ์—ฌ ์–‘์— ๋น„๋ก€์ ์œผ๋กœ ์ฆ๊ฐ€ํ•˜์˜€์œผ๋ฉฐ, ์ด๋Š” anti-RANTES antibody์— ์˜ํ•ด ์ฐจ๋‹จ๋˜์—ˆ๋‹ค. 5. IL-15์œผ๋กœ ์ž๊ทนํ•œ ์ž์—ฐ์‚ดํ•ด์„ธํฌ์˜ ์„ธํฌ ๋‚ด granzyme B์™€ perforin์˜ ํ‘œํ˜„์ •๋„๋Š” ์ •์ƒ์ธ์˜ ์„ธํฌ์™€ HIV ๊ฐ์—ผ์ž์˜ ์„ธํฌ ๋ชจ๋‘์—์„œ ์ฆ๊ฐ€ํ•˜์˜€์œผ๋ฉฐ ๋‘ ๊ตฐ๊ฐ„์— ์ฐจ์ด๋Š” ์—†์—ˆ๋‹ค. 6. p-glycoprotein์˜ ํ‘œํ˜„์€ ์ •์ƒ์ธ์˜ ์„ธํฌ์— ๋น„ํ•ด HIV ๊ฐ์—ผ์ž์˜ ์„ธํฌ์—์„œ ๋‚ฎ์€ ๊ฒฝํ–ฅ์„ ๋ณด์˜€์œผ๋ฉฐ, IL-15 ํˆฌ์—ฌ ํ›„์—๋Š” HIV ๊ฐ์—ผ์ž์˜ ์„ธํฌ์—์„œ ์ฆ๊ฐ€ํ•˜๋Š” ๊ฒฝํ–ฅ์„ ๋ณด์˜€๋‹ค. 7. Rhodamine123์ด ์ž์—ฐ์‚ดํ•ด์„ธํฌ์— ์œ ์ž…๋œ ํ›„ ์„ธํฌ ๋ฐ–์œผ๋กœ ๋ฐฐ์ถœ๋˜๋Š” ์–‘์€ ์ •์ƒ์ธ์˜ ์„ธํฌ์— ๋น„ํ•ด์„œ HIV ๊ฐ์—ผ์ž์˜ ์„ธํฌ์—์„œ ์˜์˜์žˆ๊ฒŒ ๋‚ฎ์•˜์œผ๋ฉฐ, IL-15 ํˆฌ์—ฌ ํ›„์—๋Š” HIV ๊ฐ์—ผ์ž์˜ ์„ธํฌ์—์„œ ์˜์˜์žˆ๊ฒŒ ์ฆ๊ฐ€๋˜์—ˆ๋‹ค. ๋ณธ ์—ฐ๊ตฌ์˜ ๊ฒฐ๊ณผ๋กœ HIV ๊ฐ์—ผ์ž์˜ ์ž์—ฐ์‚ดํ•ด์„ธํฌ๋Š” ์ •์ƒ์ธ์˜ ์ž์—ฐ์‚ดํ•ด์„ธํฌ์™€ ๋งˆ์ฐฌ๊ฐ€์ง€๋กœ IL-15์œผ๋กœ ์ž์—ฐ์‚ดํ•ด์ž‘์šฉ์ด ์ฆ๊ฐ€ํ•˜๊ณ , ์ด ๊ณผ์ •์—์„œ IL-15์€ ์ž์—ฐ์‚ดํ•ด์„ธํฌ๋ฅผ ์ž๊ทนํ•˜์—ฌ MIP1-ฮฑ, MCP-1, RANTES ๋“ฑ๊ณผ ๊ฐ™์€ CC-chemokine ๋ถ„๋น„๋ฅผ ์œ ๋„ํ•˜๋ฉฐ, CC-chemokine ์ค‘์—์„œ ํŠนํžˆ RANTES๋Š” ์ž์—ฐ์‚ดํ•ด์„ธํฌ์— ์ง์ ‘์ ์œผ๋กœ ์ž‘์šฉํ•˜์—ฌ ์ž์—ฐ์‚ดํ•ด์ž‘์šฉ์„ ์ฆ๊ฐ€์‹œํ‚ด์„ ํ™•์ธํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. IL-15์ด ์ž์—ฐ์‚ดํ•ด์„ธํฌ๋ฅผ ์ž๊ทนํ•˜์—ฌ ์ •์ƒ์ธ์˜ ์„ธํฌ์™€ HIV ๊ฐ์—ผ์ž์˜ ์„ธํฌ ๋ชจ๋‘์—์„œ perforin๊ณผ granzyme B ํ‘œํ˜„์„ ์ฆ๊ฐ€์‹œํ‚ค์ง€๋งŒ, p-glycoprotein์˜ ํ‘œํ˜„๊ณผ ์ž‘์šฉ์€ HIV ๊ฐ์—ผ์ž์˜ ์„ธํฌ์—์„œ๋งŒ ์ฆ๊ฐ€ํ•˜๋ฏ€๋กœ IL-15์ด HIV ๊ฐ์—ผ์ž์˜ ์ž์—ฐ์‚ดํ•ด์„ธํฌ์—์„œ ์ž์—ฐ์‚ดํ•ด์ž‘์šฉ์„ ์ฆ๊ฐ€์‹œํ‚ค๋Š” ๊ธฐ์ „ ์ค‘์— P-glycoprotein์˜ ํšŒ๋ณต์ด ๊ด€์—ฌํ•  ๊ฒƒ์œผ๋กœ ์ƒ๊ฐ๋œ๋‹ค. [์˜๋ฌธ] Depressed levels of natural killer (NK) cell activity is one of the various immunologic abnormalities observed in human immunodeficiency virus (HIV) infection. Interleukin-15 (IL-15) is a cytokine considered as an immunotherapeutic candidate in HIV infection. IL-15 is known to increase NK cell activity and excrete CC-chemokines from divergent immune cells for their chemotaxis. The mechanism of enhancement of NK cell activity by IL-15 in HIV infection is indefinite and the relationship between CC-chemokines and NK cell activity after IL-15 stimulation is not clearly established. These obscure relations need to be elucidated before IL-15 is further studied as an immunotherapeutic cytokine. The present study was carried out to examine the effects of IL-15 on NK cells of HIV-infected persons and investigate the mechanism of their effects. NK cells were isolated from peripheral blood mononuclear cells of eight patients confirmed as HIV infection and 10 healthy blood donors. IL-15 was dose escalated and NK cell activity was measured by (51)**Cr release assay-Concentrations of MIP1-ฮฑ, MCP-1, and RANTES excreted from NK cells with IL-15 stimulation were quantitated by ELISA. The relationship between CC-chemokines and NK cell activity was revealed by dose escalation of RANTES, addition of anti-RANTES antibody and control isotype antibody and measuring subsequent NK cell activities. to observe intracellular changes of NK cells when NK cell activity is increased after IL-15 stimulation, cytolytic enzyme content such as granzyme B and perforin were analyzed by Westem blot, and the transmembrane P-glycoprotein expression and rhodamine 123 efflux assay were analyzed by flow cytometry. The following results were obtained. 1. While NK cell activity of healthy donors increased as the effector to target cell ratio increased, NK cell activity of HIV infected persons showed no change. With IL-15 stimulation, NK cell activity increased as the effector to target cell ratio increased in NK cells of both HIV-infected persons and healthy donors. 2. With dose escalation of IL-15 (0, 10, 1OO, 1000 ng/ml), NK cell activity increased dose dependently in both HIV -infected persons and healthy donors. 3. Concentrations of MIP1-ฮฑ, MCP-1, and RANTES excreted from NK cells with IL-15 stimulation showed no difference between HIV-infected persons and healthy donors. 4. NK cell activity increased proportionally with dose escalation of RANTES and was blocked with anti-RANTES antibody in NK cells of both HIV-infected persons and healthy donors. 5. Granzyme B and perform contents were increased after IL-15 stimulation in NK cells of both HIV-infected persons and Healthy donors and no significant difference was observed. 6. P-glycoprotein expression showed a tendency to be decreased in NK cells of HIV-infected persons compared to healthy donors, and after IL-15 stimulation, was increased in NK cells of HIV-infected persons. 7. Percentage of effluxed rhodamine 123 was significantly lower in NK cells of HIV-infected persons compared to healthy donors. After IL-15 stimulation, rhodamine 123 efflux increased in NK cells of HIV-infected persons. In conclusion, NK cell activity increased with IL-15 stimulation in NK cells of HIV-infected persons as is in normal NK cells. IL-15 stimulates NK cells to secrete CC-chemokines such as MIP1-ฮฑ, MCP-1, and RANTES, and RANTES itself eventually increases NK cell activity. IL-15 stimulation of NK cells increases perforin and granzyme B in NK cells of both HIV-infected persons and healthy donors. However, decreased P-glycoprotein expression and function is restored only in NK cells of HIV-infected persons after IL-15 stimulation. Therefore, P-glycoprotein may play a role in the mechanism of increased NK cell activity in NK cells of HIV-infected persons after IL-15 stimulation.ope

    Syntactic and Semantic Composition in LPSG

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    LPSG(Linear.Phrase Structure Grammar) is a grammar model which aims at binary and strictly linear parsing of natural languages. For binarism LPSG adopted binary rules. For linear parsing we introduced some principles such as DCAP, DCIP and CCP: Default Category Assignment Principle(DCAP) If Xโ†’Y, Z is an ID rule, Y=X[-Z] and Z=X[-Y]. Default Category Inheritance Principle(DCAP) If Xโ†’Y, Z is an ID rule, Y[U]=X[U,-Z] and Z[U] = X[U, -Y], where U is a set of default categories. Category Composition Principle(CCP) (1) A default category [-X] is cancelled, if it hits X node with no default category. (2) If a default category [-X] hits an X node with default categories, [-X] is replaced by the default categories of X
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