28 research outputs found

    Risk Factors of Postoperative Hypocalcemia after Total Thyroidectomy of Papillary Thyroid Carcinoma Patients

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    Purpose : Postoperative hypocalcemia is a common complication of thyroidectomy. This study evaluated the incidence and predisposing risk factors for postoperative permanent hypocalcemia after total thyroidectomy. Methods : There were 1,247 consecutive patients undergoing total thyroidectomy and complete treatment and observation for differentiated thyroid cancer between January 2012 to December 2012 who were enrolled in this study. Patients were divided into two groups, those remaining normalcalcemic (Group I-824 pts) and those who had hypocalcemia requiring treatment (Groups II-423 pts). Group II was subdivided into a transient hypocalcemic group (Group IIA-409 pts) and a permanent hypocalcemic group (Group IIB-14 pts). Results : Female gender, thyroiditis, preserved parathyroid number, lateral lymph node metastasis, RAI treatment, preoperative parathyroid hormone and preoperative vitamin D were significantly associated with the development of postoperative hypocalcemia by multivariate analysis. Comparing patients with transient versus permanent hypocalcemia, tumor size and multiplicity were significantly related to the development of permanent hypocalcemia by multivariate analysis. RAI treatment and parathyroid hormone level on the postoperative third day were significantly related to recovery from transient hypocalcemia to normo-calcemia. Conclusion : Risk factors of postoperative hypocalcemia were associated with preoperative patient factors and advanced thyroid cancer. Advanced thyroid cancer was a risk factor for permanent hypocalcemia. To prevent postoperative hypocalcemia, we should focus on patient condition and need to preserve parathyroid gland more carefully in thyroid surgery.ope

    Hwaong eco-park master plan in consideration of environment changes after reclamation

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :์ƒํƒœ์กฐ๊ฒฝํ•™๊ณผ,2005.Maste

    ์ง‘๋‹จ๋‚ด๋‹ค์–‘์„ฑ๊ณผ๊ฐœ์ธ-์ง‘๋‹จ์ ํ•ฉ์„ฑ์ด์ง‘๋‹จ์„ฑ๊ณผ์—๋ฏธ์น˜๋Š”ํšจ๊ณผ

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    Thesis(doctors) --์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :๊ฒฝ์˜ํ•™๊ณผ,2010.2.Docto

    ์ „๋žต์  ์ธ์ ์ž์›๊ด€๋ฆฌ์™€ ๊ธฐ์—…์„ฑ๊ณผ๊ฐ„์˜ ๊ด€๊ณ„์— ๊ด€ํ•œ ์—ฐ๊ตฌ

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :๊ฒฝ์˜ํ•™๊ณผ ๊ฒฝ์˜ํ•™์ „๊ณต,2002.Maste

    PPI ์‚ฌ์—… ์˜ ๊ฑฐ์‹œ์  ํšจ๊ณผ ๋ถ„์„ : ์ค‘์ €์†Œ๋“ ๊ตญ๊ฐ€๋ฅผ ๋Œ€์ƒ์œผ๋กœ

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :๊ฒฝ์ œํ•™๋ถ€ ๊ฒฝ์ œํ•™์ „๊ณต,2007.Maste

    (A)Study on the educational effect of mulitiple intelligences theory through the hands-on exhibition

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :ํ˜‘๋™๊ณผ์ • ๋ฏธ์ˆ ๊ต์œก์ „๊ณต, 2005.Maste

    ํƒˆ๋ถ์ฒญ์†Œ๋…„์˜ ์‚ถ๊ณผ ์ •์ฒด์„ฑ์— ๊ด€ํ•œ ์˜ˆ์ˆ ๊ธฐ๋ฐ˜์—ฐ๊ตฌ

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    ํ•™์œ„๋…ผ๋ฌธ (๋ฐ•์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ์‚ฌ๋ฒ”๋Œ€ํ•™ ํ˜‘๋™๊ณผ์ •(๋ฏธ์ˆ ๊ต์œก์ „๊ณต), 2018. 8. ๊น€ํ˜•์ˆ™, ์กฐ์šฉํ™˜. ์ธ๊ฐ„์€ ์ด์ฃผํ•˜๋ฉฐ ์‚ด์•„๊ฐ„๋‹ค. ์‚ถ์˜ ํ„ฐ์ „์„ ์˜ฎ๊ธฐ๋Š” ์ด์ฃผ๋ฏผ์€ ์ธ๋ฅ˜ ์—ญ์‚ฌ์ƒ ์˜ค๋ž˜ ์ „๋ถ€ํ„ฐ ์กด์žฌํ•ด์™”๋‹ค. ํ•œ๊ตญ์‚ฌํšŒ์˜ ํƒˆ๋ถ๋ฏผ์€ ๋‚จ๋ถ ๋ถ„๋‹จ์˜ ํŠน์ˆ˜ํ•œ ์ƒํ™ฉ์—์„œ ์ด์ฃผํ•œ ๊ฒฝ์šฐ์ด๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ์ตœ๊ทผ ํ–‰๋ณตํ•™๊ต(๊ฐ€๋ช…)์˜ ํƒˆ๋ถ์ฒญ์†Œ๋…„ ์ค‘ ๋ฐ˜ ์ด์ƒ์ด ๋ถํ•œ์„ ํƒˆ์ถœํ•˜์ง€ ์•Š๊ณ  ์ค‘๊ตญ์—์„œ ํƒœ์–ด๋‚œ ํƒˆ๋ถ๋ฏผ์˜ ์ž๋…€๋“ค์ด๋‹ค. ์ด๋Ÿฌํ•œ ํƒˆ๋ถ์ฒญ์†Œ๋…„๋“ค์˜ ์ƒํ™ฉ์„ ๋‚ด๊ฐ€ ๋งˆ์Œ์œผ๋กœ ์ดํ•ดํ•˜๋Š” ๋ฐ์— 2๋…„ ์ด์ƒ์ด ๊ฑธ๋ ธ๋‹ค. ๋‚˜๋Š” ๊ทธ ๊ณผ์ •์—์„œ ํ•™์ƒ๋“ค์—๊ฒŒ ์ •์ž‘ ์ค‘์š”ํ•œ ๊ฒƒ์€ ๋ฏธ์ˆ ์ด ์•„๋‹Œ ์ •์ฒด์„ฑ ๋ฌธ์ œ๋ผ๊ณ  ์ƒ๊ฐํ•˜๊ฒŒ ๋˜์—ˆ๋‹ค. ๋”ฐ๋ผ์„œ ๋ณธ ์—ฐ๊ตฌ์˜ ๋ชฉ์ ์€ ํƒˆ๋ถ์ฒญ์†Œ๋…„๋“ค์˜ ์ •์ฒด์„ฑ์„ ์ดํ•ดํ•˜๊ณ  ๋” ๋‚˜์€ ์‚ถ์„ ์œ„ํ•œ ๋ฏธ์ˆ ๊ต์œก์„ ๋ชจ์ƒ‰ํ•˜๋Š” ๋ฐ ์žˆ๋‹ค. ์ด์— 2014๋…„๋ถ€ํ„ฐ 2015๋…„๊นŒ์ง€ ํƒˆ๋ถ๋‹ค๋ฌธํ™”์ฒญ์†Œ๋…„ ๋Œ€์•ˆํ•™๊ต์ธ ํ–‰๋ณตํ•™๊ต๋ฅผ ์ค‘์‹ฌ์œผ๋กœ ๋‚˜์™€ ํ•จ๊ป˜ ๋ฏธ์ˆ ํ•™์Šต์„ ์ฒดํ—˜ํ•œ 16๋ช… ํ•™์ƒ๋“ค์˜ ์ด์•ผ๊ธฐ์™€ ๊ทธ๋ฆผ์— ์ฃผ๋ชฉํ•˜์˜€๋‹ค. ์‚ถ์˜ ์ด์ฒด์ ์ธ ๋งฅ๋ฝ์—์„œ ํƒˆ๋ถ์ฒญ์†Œ๋…„์˜ ์ •์ฒด์„ฑ ํ˜•์„ฑ ๊ณผ์ •์„ ํŒŒ์•…ํ•˜๊ธฐ ์œ„ํ•˜์—ฌ ์ด์•ผ๊ธฐ ๊ทธ๋ฆผ ์† ์ƒ์• ์‚ฌ๋ฅผ ์‚ดํŽด๋ณด์•˜๋‹ค. ๊ทธ๋ฆฌ๊ณ  ์˜ˆ์ˆ ๊ธฐ๋ฐ˜์—ฐ๊ตฌ ๋ฐฉ๋ฒ•์œผ๋กœ ํƒˆ๋ถ์ฒญ์†Œ๋…„์˜ ๊ทธ๋ฆผ์„ ๋ถ„์„ํ•˜๊ณ  ํ•ด์„ํ•˜์˜€๋‹ค. ๋˜ํ•œ ์•„ํ† ๊ทธ๋ž˜ํ”ผ๋ฅผ ์ ์šฉํ•˜์—ฌ ์˜ˆ์ˆ ๊ฐ€-์—ฐ๊ตฌ์ž-๊ต์‚ฌ๋กœ์„œ ๋‚˜์˜ ์„ฑ์žฅ๊ณผ ๋ณ€ํ™” ๊ณผ์ •์„ ethnodrawing์œผ๋กœ ๋‚˜ํƒ€๋‚ด์—ˆ๋‹ค. ๋ฏธ์ˆ ํ•™์Šต์œผ๋กœ ์ •์ฒด์„ฑ ๋ฌธ์ œ๋ฅผ ํƒ์ƒ‰ํ•˜๊ธฐ ์œ„ํ•œ ์—ฐ๊ตฌ๋ฌธ์ œ๋Š” ๋‹ค์Œ๊ณผ ๊ฐ™๋‹ค. ์ฒซ์งธ, ํƒˆ๋ถ์ฒญ์†Œ๋…„๋“ค์˜ ์‚ถ๊ณผ ์ด์ฃผ๋Š” ์–ด๋–ป๊ฒŒ ์ „๊ฐœ๋˜์–ด ์™”๋Š”๊ฐ€? ๋‘˜์งธ, ํƒˆ๋ถ์ฒญ์†Œ๋…„์˜ ์ •์ฒด์„ฑ์€ ์–ด๋–ป๊ฒŒ ์žฌ๊ตฌ์„ฑ๋˜๋Š”๊ฐ€? ์…‹์งธ, ํƒˆ๋ถ์ฒญ์†Œ๋…„๋“ค์˜ ์‚ถ์—์„œ ๋ฏธ์ˆ ํ•™์Šต์€ ์–ด๋–ค ์˜๋ฏธ๊ฐ€ ์žˆ๋Š”๊ฐ€? ์šฐ์„  ํƒˆ๋ถ์ฒญ์†Œ๋…„๋“ค์€ ํƒœ์ƒ, ํƒˆ๋ถ ๋™๊ธฐ, ์ž…๊ตญ ๊ฒฝ๋กœ, ๊ฐ€์กฑ ๋™๋ฐ˜ ์—ฌ๋ถ€, ํƒˆ๋ถ ๊ธฐํš ์œ ํ˜• ๋“ฑ์— ๋”ฐ๋ผ ๋‹ค์–‘ํ•œ ์ƒ์• ๊ฒฝ๋กœ๋ฅผ ๊ฐ€์ง€๊ณ  ์žˆ์—ˆ๋‹ค. ํ–‰๋ณตํ•™๊ต ์•ˆ์—๋Š” ๋ถํ•œ์—์„œ ํƒœ์–ด๋‚œ ํƒˆ๋ถ์ฒญ์†Œ๋…„๊ณผ ์ค‘๊ตญ์—์„œ ํƒœ์–ด๋‚œ ์ œ3๊ตญ ์ถœ์ƒ ๋น„๋ณดํ˜ธ ํƒˆ๋ถ์ฒญ์†Œ๋…„ ์‚ฌ์ด์— ๋ณด์ด์ง€ ์•Š๋Š” ๋ฒฝ์ด ์žˆ์—ˆ๋‹ค. ํ•™์ƒ๋“ค์€ ๊ทธ ์‚ฌ์ด์—์„œ ๋ณธ์ธ์ด๋‚˜ ๋ถ€๋ชจ์˜ ์ถœ์ƒ๊ตญ๊ฐ€์— ๋”ฐ๋ผ ๋ช…ํ™•ํ•˜๊ฒŒ ๊ตฌํš๋œ ๊ตญ๊ฐ€์ •์ฒด์„ฑ์„ ํ˜•์„ฑํ•˜์ง€ ์•Š์•˜๋‹ค. ์˜คํžˆ๋ ค ๊ฑฐ์ฃผ ๊ธฐ๊ฐ„์ด๋‚˜ ์†Œ์†๊ฐ์— ๋”ฐ๋ผ ๋ณตํ•ฉ์ ์ด๊ณ  ์ค‘์ธต์ ์ธ ์ •์ฒด์„ฑ์„ ํ˜•์„ฑํ•˜์˜€๋‹ค. ์ด์™€ ๊ฐ™์€ ์ •์ฒด์„ฑ์„ ์œ ํ˜•๋ณ„๋กœ ๋ถ„๋ฅ˜ํ•˜์—ฌ ๋ณด๋ฉด ์ค‘๋„ํฌ๊ธฐํ˜•๊ณผ ์„ฑ์ทจ์ถ”๊ตฌํ˜•, ํ์‡„์ง€ํ–ฅํ˜•๊ณผ ๊ฐœ๋ฐฉ์ง€ํ–ฅํ˜•, ๊ฒฐ์ •์œ ์˜ˆํ˜•๊ณผ ์ •์ฃผ์ง€ํ–ฅํ˜•, ์ด์ฃผ์ง€์†ํ˜•์œผ๋กœ ๋‚˜๋ˆŒ ์ˆ˜ ์žˆ์—ˆ๋‹ค. ์ด ์ค‘ ๊ฒฐ์ •์œ ์˜ˆํ˜•๊ณผ ์ด์ฃผ์ง€์†ํ˜• ํ•™์ƒ๋“ค์˜ ๊ทธ๋ฆผ์—์„œ๋Š” ํ”๋“ค๋ฆผ์˜ ์ด๋ฏธ์ง€์ธ ๋ฐฐ์™€ ์ƒˆ๊ฐ€ ๋งŽ์ด ๋‚˜ํƒ€๋‚ฌ๊ณ , ์ •์ฃผ์ง€ํ–ฅํ˜• ํ•™์ƒ๋“ค์˜ ๊ทธ๋ฆผ์—๋Š” ๋ฉˆ์ถค์˜ ์ด๋ฏธ์ง€์ธ ๋‚˜๋ฌด๊ฐ€ ๋งŽ์ด ๋“ฑ์žฅํ–ˆ๋‹ค. ์„ฑ์ทจ์ถ”๊ตฌํ˜•, ์ด์ฃผ์ง€์†ํ˜•์€ ๋‚˜์•„๊ฐ์˜ ์ด๋ฏธ์ง€์ธ ๊ธธ์„ ์ข…์ข… ๊ทธ๋ ธ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ํ”๋“ค๋ฆฌ๋Š” ๋ฐฐ๋„ ํ‰ํ™”๋กญ๊ฒŒ ๋– ๊ฐ€๋ฉฐ ์•ˆ์ •๋œ ์žฅ์†Œ์— ์ •๋ฐ•ํ•˜๊ณ , ๋‚˜๋ฌด๋„ ๋น„๋ฐ”๋žŒ์— ํ”๋“ค๋ฆฌ๊ฑฐ๋‚˜ ๋ฟŒ๋ฆฌ ์ฑ„ ๋ฝ‘ํ˜€์„œ ์˜ฎ๊ฒจ์ง€๋Š” ๋“ฑ ๊ฐœ์ธ์˜ ์„ฑํ–ฅ๊ณผ ์ƒํ™ฉ์— ๋”ฐ๋ผ ๋‹ค๋ฅด๊ฒŒ ํ‘œํ˜„๋˜๊ธฐ๋„ ํ•˜์˜€๋‹ค. ๋‘ ๋ฒˆ์งธ ์—ฐ๊ตฌ๋ฌธ์ œ์ธ ํƒˆ๋ถ์ฒญ์†Œ๋…„์˜ ์ •์ฒด์„ฑ์ด ํ˜•์„ฑ๋˜๋Š” ๊ณผ์ •์„ ๋ณด๊ธฐ ์œ„ํ•ด ์ฃผ๋ณ€ ํ™˜๊ฒฝ๊ณผ ๊ด€๊ณ„ ์† ๊ฐˆ๋“ฑ๊ณผ ์ƒ์ƒ์„ ์ฃผ๋ชฉํ•˜์˜€๋‹ค. ํƒˆ๋ถ์ฒญ์†Œ๋…„๋“ค์ด ๊ด€๊ณ„ ๋งบ๋Š” ์žฅ์œผ๋กœ์„œ์˜ ์ƒํ™œ์„ธ๊ณ„๋Š” ํ•™๊ต, ๊ฐ€์ •, ์‚ฌํšŒ๊ฐ€ ์žˆ๋‹ค. ํ•™๊ต ์•ˆ์—๋Š” ๋ถํ•œ ์ถœ์ƒ ํ•™์ƒ๋“ค๊ณผ ์ค‘๊ตญ ์ถœ์ƒ ํ•™์ƒ๋“ค ์‚ฌ์ด์˜ ๋™์งˆ๊ฐ๊ณผ ์ด์งˆ๊ฐ, ์ค‘๊ตญ์ธ ๊ต์‚ฌ์™€ ๋‚จํ•œ ๊ต์‚ฌ๋ฅผ ๋ฐ”๋ผ๋ณด๋Š” ํƒˆ๋ถ๋ฏผ ํ•™๋ถ€๋ชจ์˜ ์‹œ์„  ์ฐจ์ด, ๊ต์‚ฌ๋“ค์ด ๊ฐ๊ฐ์˜ ํ•™์ƒ๋“ค์„ ๋ฐ”๋ผ๋ณด๋Š” ๋ฏธ๋ฌ˜ํ•œ ์ฐจ์ด๋“ค์ด ๋ณต์žกํ•˜๊ฒŒ ๊ต์ฐจํ•˜๊ณ  ์žˆ์—ˆ๋‹ค. ํ•™๊ต๋Š” ์ง‘์ฒ˜๋Ÿผ, ๊ต์‚ฌ๋“ค์€ ๋ถ€๋ชจ์ฒ˜๋Ÿผ ํ•™์ƒ๋“ค์—๊ฒŒ ๋Œ๋ด„์„ ์ œ๊ณตํ•˜๋Š” ์ง€์ง€๊ทธ๋ฃน์ด ๋œ๋‹ค. ํ•˜์ง€๋งŒ ๋™์‹œ์— ์ผ๋ถ€ ํ•™์ƒ์„ ์–ต์••ํ•˜๊ณ  ๋ฐฐ์ œํ•˜๊ฑฐ๋‚˜ ์ฃผ๋ณ€ํ™”ํ•˜๋Š” ํ•œ๊ณ„ ์ƒํ™ฉ์ด ๋ฐœ์ƒํ•˜๊ธฐ๋„ ํ•˜์˜€๋‹ค. ํ•™์ƒ๊ณผ์˜ ๋Œ€ํ™”๋ฅผ ํ†ตํ•ด ๋‚จํ•œ ๊ต์‚ฌ๋“ค์€ ์šฐ๋ฆฌ์—๊ฒŒ ๋‚ด์žฌ๋œ ์„ ์ž…๊ฒฌ๊ณผ ์ฐจ๋ณ„์  ์š”์†Œ๋“ค์„ ๋ฐœ๊ฒฌํ•˜๋ฉฐ ์ž์‹ ์„ ์„ฑ์ฐฐํ•ด๋ณด๊ฒŒ ๋˜์—ˆ๋‹ค. ๊ฐ€์ •๊ณผ ์‚ฌํšŒ์—์„œ๋„ ํƒˆ๋ถ์ฒญ์†Œ๋…„๋“ค์€ ํƒ€์ž์™€์˜ ์‚ฌ์ด์— ๋ณด์ด์ง€ ์•Š๋Š” ์„ ์ด ์กด์žฌํ–ˆ๋‹ค. ํ•™์ƒ๋“ค์€ ์ด๋Ÿฐ ๊ฒฝ๊ณ„๋ฅผ ๋Š์ž„์—†์ด ๋„˜๋‚˜๋“ค๋ฉฐ ๊ฒฝ๊ณ„์„  ์œ„์— ์œ„ํƒœ๋กญ๊ฒŒ ์„œ ์žˆ๊ธฐ๋„ ํ•˜์˜€๋‹ค. ๊ฒฐ๊ตญ ์ •์ฒด์„ฑ ๋ฌธ์ œ๋Š” ๊ฐœ์ธ์  ์ฐจ์›์ด ์•„๋‹Œ ์‚ฌํšŒ ๊ตฌ์กฐ์  ์ฐจ์›์˜ ๋ฌธ์ œ๋กœ ๋ณผ ํ•„์š”๊ฐ€ ์žˆ์—ˆ๋‹ค. ๋”ฐ๋ผ์„œ ์†Œ์ƒํ™ฉ-(๋งค๊ฐœ์ƒํ™ฉ)-๋Œ€์ƒํ™ฉ์˜ ์ƒํ™ฉ๋ถ„์„์„ ํ†ตํ•ด ์ •์ฒด์„ฑ ํ˜•์„ฑ์˜ ์ƒํ™ฉ์  ๊ตฌ์กฐ๋ฅผ ์„ธ ๊ฐ€์ง€๋กœ ํŒŒ์•…ํ•˜์˜€๋‹ค. ์ฒซ์งธ, ํƒˆ๋ถ์ฒญ์†Œ๋…„๋“ค์€ ํ•™๊ต ์•ˆ์—์„œ ๋Œ€ํ•™์ž…์‹œ์™€ ๊ฒ€์ •๊ณ ์‹œ๋กœ ๋‚ด๋ชฐ๋ฆฌ๋ฉฐ ๋Š์ž„์—†๋Š” ๊ฒฝ์Ÿ๊ณผ ์ŠคํŠธ๋ ˆ์Šค์— ๋…ธ์ถœ๋˜์–ด ์žˆ์—ˆ๋‹ค. ๊ทธ ์ด๋ฉด์—๋Š” ํ•œ๊ตญ์‚ฌํšŒ์˜ ํ•™๋ฒŒ์ฃผ์˜์™€ ํ•™๋ ฅ์ฃผ์˜๊ฐ€ ์žˆ์—ˆ๋‹ค. ๋‘˜์งธ, ๋‹น์žฅ์˜ ์ด์ต์„ ์œ„ํ•œ ์ „๊ณต๊ณผ ์ง„๋กœ๋ฅผ ์„ ํƒํ•˜๋Š” ํƒˆ๋ถ์ฒญ์†Œ๋…„ ์‚ถ์˜ ์ „๋ฐ˜์—๋Š” ํ›„๊ธฐ ์ž๋ณธ์ฃผ์˜๊ฐ€ ๊น”๋ ค ์žˆ์—ˆ๋‹ค. ์ด๋“ค์€ ์‹œ์žฅ ๊ฒฝ์ œ ๋…ผ๋ฆฌ ์†์—์„œ ๊ฐ์ข… ์ง€์›๊ธˆ๊ณผ ๊ฒฝ์ œ์  ํ˜œํƒ์„ ๋”ฐ๋ผ๋‹ค๋‹ˆ๋ฉฐ ๋Š์ž„์—†์ด ์ž์‹ ์˜ ์ •์ฒด์„ฑ์„ ํ˜‘์ƒํ•˜์˜€๋‹ค. ์…‹์งธ, ์„ธ๊ณ„ํ™”๋กœ ์ธํ•œ ๋‹ค๋ฌธํ™”์ฃผ์˜๋กœ ํ•™์ƒ๋“ค์˜ ๊ฐ€์ •๊ณผ ์‚ถ์— ํ™•์—ฐํ•˜๊ฒŒ ํผ์ ธ์žˆ๋Š” ๋…ธ๋งˆ๋“œ ํ˜„์ƒ์ด์—ˆ๋‹ค. ์ผ๋ถ€ ํ•™์ƒ๋“ค์€ ํ•œ๊ตญ์„ ์ค‘๊ฐ„ ๊ฒฝ์œ ์ง€๋กœ ์ธ์‹ํ•˜๋ฉฐ ๋Š์ž„์—†์ด ์ด์ฃผ๋ฅผ ์ง€์†ํ•˜๋ฉฐ ํ•œ๊ตญ์‹œ๋ฏผ์—์„œ ๋‚œ๋ฏผ์œผ๋กœ ๋‹ค์‹œ ๋Œ€ํ•™์ƒ์œผ๋กœ ๋‹ค์–‘ํ•œ ์ •์ฒด์„ฑ์„ ๋น„๊ต ์ฒดํ—˜ํ•˜๊ณ  ๋Œ์•„์™”๋‹ค. ๊ทธ ๊ณผ์ •์—์„œ ํ•™์ƒ๋“ค์˜ ์ผ์ƒ๊ณผ ์‚ฌํšŒ์˜ ๊ฑฐ๋Œ€๋‹ด๋ก ์„ ์—ฐ๊ฒฐํ•˜๋Š” ๋งค๊ฐœ์ƒํ™ฉ์€ ๊ต์‚ฌ๋‚˜ ๋จผ์ € ์˜จ ๊ฐ€์กฑ๊ณผ ์นœ๊ตฌ ๋“ฑ์˜ ์‚ฌ๋žŒ, ์ธํ„ฐ๋„ท๊ณผ ํ•ธ๋“œํฐ, TV ๋“ฑ์˜ ๋Œ€์ค‘๋งค์ฒด, ๊ทธ๋ฆฌ๊ณ  ์ค‘๊ตญ๊ณผ ํ•ด์™ธ ๊ฑฐ์ฃผ ๊ฒฝํ—˜ ๋ฐ ํ•™์Šต ๊ฒฝํ—˜ ๋“ฑ ์ฒดํ—˜์ด ์˜ํ–ฅ์„ ์ฃผ๋Š” ์ƒํ™ฉ์ด์—ˆ๋‹ค. ๊ฒฐ๋ก ์ ์œผ๋กœ ํƒˆ๋ถ์ฒญ์†Œ๋…„์€ ํƒˆ๋ถ์ฒญ์†Œ๋…„์ด๋ผ๋Š” ํ•˜๋‚˜์˜ ์ด๋ฆ„์œผ๋กœ ๋™์งˆํ™”ํ•  ์ˆ˜ ์—†๋Š” ํ˜ผ์ข…์ ์ธ ์ •์ฒด์„ฑ์„ ๊ฐ€์ง€๊ณ  ์žˆ์—ˆ๋‹ค. ๋˜ํ•œ ๊ณ ์ •๋˜์ง€ ์•Š๊ณ  ๋Š์ž„์—†์ด ํƒˆ์˜ํ† ํ™”์™€ ์žฌ์˜ํ† ํ™”๋ฅผ ์ง€์†ํ•˜๋Š” ์œ ๋™์ ์ธ ์ •์ฒด์„ฑ์„ ๋ณด์—ฌ์ฃผ์—ˆ๋‹ค. ๊ทธ ๊ณผ์ •์—์„œ ๋ถ€์กฑํ•œ ์ž์› ํš๋“์„ ์œ„ํ•ด ์ž์‹ ๋“ค์˜ ์‚ฌํšŒ์  ์œ„์น˜์™€ ์ธ์  ์—ฐ๊ฒฐ๋ง์„ ํ™œ์šฉํ•˜์—ฌ ์‚ถ์„ ๊ฐœ์ฒ™ํ•ด ๋‚˜๊ฐ€๋Š” ์ฃผ์ฒด๋กœ์„œ์˜ ํ–‰์œ„์ž์„ฑ์„ ๋ณด์—ฌ์ฃผ๊ธฐ๋„ ํ•˜์˜€๋‹ค. ๊ทธ๋ฆฌ๊ณ  ์ฐจ์ด์™€ ๋ฐ˜๋ณต์„ ํ†ตํ•ด ์ƒ๋ช…๋ ฅ ์žˆ๋Š” ์šด๋™์„ฑ์„ ์ง€๋‹Œ ๊ฒฝ๊ณ„์ธ์œผ๋กœ์„œ ์—ญ๋™์ ์ธ ์ •์ฒด์„ฑ์„ ์žฌ๊ตฌ์„ฑํ•˜๊ธฐ๋„ ํ•˜์˜€๋‹ค. ์„ธ ๋ฒˆ์งธ ์—ฐ๊ตฌ๋ฌธ์ œ์ธ ๋ฏธ์ˆ ๊ต์œก์˜ ์˜๋ฏธ๋ฅผ ์ฐพ์•„๋ณด์•˜๋‹ค. ํƒˆ๋ถ์ฒญ์†Œ๋…„๋“ค์€ ์ •์„œ์ , ์ธ์ง€์ , ์‹ค์กด์ ์ธ ์ธก๋ฉด์—์„œ ๋ฏธ์ˆ ํ•™์Šต์„ ์ฒดํ—˜ํ•˜์˜€๋‹ค. ์šฐ์„  ์ •์„œ์  ์ธก๋ฉด์—์„œ ๋ฏธ์ˆ ์„ ํ†ตํ•ด ๋งˆ์Œ์„ ๋ณด๊ณ  ๊ทธ๋ฆฌ๋ฉฐ ์ •์„œ๋ฅผ ํ‘œ์ถœํ•˜๊ณ , ์‰ผ์„ ์ฃผ๋Š” ๋ฏธ์ˆ ๋กœ ์‹ฌ๋ฆฌ์  ์ด์™„์„ ์ฒดํ—˜ํ•˜์˜€๋‹ค. ์ธ์ง€์  ์ธก๋ฉด์—์„œ ํƒˆ๋ถ์ฒญ์†Œ๋…„๋“ค์€ ์†์„ ํ†ตํ•œ ์‹ ์ฒด์  ์ง€์‹ ๋ฟ๋งŒ ์•„๋‹ˆ๋ผ ๋ณด์ด์ง€ ์•Š๋Š” ๋‚ด์žฌ์  ๊ฐ€์น˜๋ฅผ ๋ฐฐ์šฐ๋ฉด์„œ ์„ฑ์žฅํ•˜๊ฒŒ ๋˜์—ˆ๋‹ค. ์ฆ‰, ์ž์‹ ๊ณผ์˜ ๋Œ€ํ™”๋ฅผ ํ†ตํ•ด ์ž๊ธฐ๋ฅผ ์„ฑ์ฐฐํ•˜๊ณ , ๋‚จํ•œ ์ฒญ์†Œ๋…„๋“ค๊ณผ ์ฝœ๋ผ์ฃผ ์ž‘์—…์„ ํ†ตํ•ด ํƒ€์ž์™€ ์†Œํ†ตํ•  ์ˆ˜ ์žˆ๋‹ค๋Š” ์„ฑ์ทจ๊ฐ์„ ๋Š๊ผˆ๋‹ค. ๋˜ํ•œ ํƒ€์ธ์—๊ฒŒ ์ธ์ •๋ฐ›๋Š” ์ฒดํ—˜์œผ๋กœ์„œ์˜ ์ „์‹œ๋Š” ์ž์‹ ๊ฐ์„ ๊ฐ€์ง€๊ฒŒ ํ•ด์ฃผ๋Š” ๊ธฐํšŒ๊ฐ€ ๋˜์—ˆ๋‹ค. ์‹ค์กด์  ์ธก๋ฉด์—์„œ๋Š” ์ž๊ธฐ ์•ˆ์˜ ํƒ€์ž๋ฅผ ๋ฐœ๊ฒฌํ•˜๋ฉด์„œ ์ƒ์กด์ด ์•„๋‹Œ ์‹ค์กด์  ์˜๋ฏธ์—์„œ์˜ ๋ฏธ์ˆ ํ•™์Šต์„ ์ฒดํ—˜ํ•˜๊ฒŒ ๋˜์—ˆ๋‹ค. ์ด๋•Œ ๋ฏธ์ˆ ์€ ๊ฐœ์ธ์˜ ์‚ถ์˜ ์ด์•ผ๊ธฐ๋ฅผ ๋“ค๋ ค์คŒ์œผ๋กœ์จ ์ž์‹ ๊ณผ ํƒ€์ธ์„ ํƒ๊ตฌํ•˜๊ณ  ๋” ๋‚˜์•„๊ฐ€ ์‚ฌํšŒ๋ฅผ ์ดํ•ดํ•˜๊ฒŒ ํ•ด์ค€๋‹ค. ๋ฏธ์ˆ ์„ ํ†ตํ•ด ์ž์‹ ์˜ ์ •์ฒด์„ฑ์„ ํ˜•์ƒํ™”ํ•˜๊ณ  ๊ตฌ์ฒดํ™”ํ•˜๋ฉด์„œ ์„ธ์ƒ๊ณผ ์ž์‹ ์˜ ๊ด€๊ณ„๋ฅผ ์ธ์‹ํ•˜๊ฒŒ ๋˜๋Š” ๊ฒƒ์ด๋‹ค. ์ด์™€ ๊ฐ™์ด ๋ฏธ์ˆ ์€ ๊ฐœ์ธ์„ ์„ฑ์žฅ์‹œํ‚ค๊ณ  ๋” ๋‚˜์€ ์‚ฌํšŒ๋กœ ๋ณ€ํ™”์‹œํ‚ฌ ์ˆ˜ ์žˆ๋‹ค๋Š” ์ ์—์„œ ๊ต์œก์ ์ด๋‹ค. ์ฃผ์š”์–ด : ํƒˆ๋ถ์ฒญ์†Œ๋…„, ์‚ถ, ์ •์ฒด์„ฑ, ๋ฏธ์ˆ ๊ต์œก, ์˜ˆ์ˆ ๊ธฐ๋ฐ˜์—ฐ๊ตฌ, ์•„ํ† ๊ทธ๋ž˜ํ”ผ ํ•™ ๋ฒˆ : 2007-30384I. ์„œ๋ก  1 1. ์—ฐ๊ตฌ์˜ ํ•„์š”์„ฑ๊ณผ ๋ชฉ์  1 2. ์—ฐ๊ตฌ ๋ฌธ์ œ 6 3. ์—ฐ๊ตฌ ๋ฐฉ๋ฒ• 8 4. ์—ฐ๊ตฌ ๋ฒ”์œ„์™€ ํ•œ๊ณ„ 16 II. ์ด๋ก ์  ๋ฐฐ๊ฒฝ 18 1. ์˜ˆ์ˆ ๊ธฐ๋ฐ˜์—ฐ๊ตฌ 18 2. ํƒˆ๋ถ์ฒญ์†Œ๋…„์˜ ์ •์ฒด์„ฑ 25 3. ์„ ํ–‰์—ฐ๊ตฌ ๊ฐœ๊ด€ 33 III. ํƒˆ๋ถ์ฒญ์†Œ๋…„์˜ ์‚ถ๊ณผ ๋ฏธ์ˆ ํ•™์Šต ์ฒดํ—˜ 41 1. ์‚ถ์„ ๋‹ด์€ ์ด์•ผ๊ธฐ ๊ทธ๋ฆผ 42 1) ์†Œ์˜ : ๋งˆ์Œ ๋ฟŒ๋ฆฌ ์† ๊นŠ์ˆ™์ด์— 42 2) ์›๊ฒฝ : ์˜จ์ „ํžˆ ์ค‘๊ตญ ์‚ฌ๋žŒ์ด์—ˆ์œผ๋ฉด 48 3) ์ธํ™” : ์‹ค์ œ๋ก  ๋‹ค๋ฌธํ™”์ด์ง€๋งŒ ๊ณต์‹์ ์œผ๋ก  ํ•œ๊ตญ์ธ 53 4) ์ˆ™ํฌ : ๋ญ ์ž๋งค์ง€๊ฐ„์—๋„ ๋„ˆ๋ฌด ๋‹ค๋ฅธ๋ฐ 56 5) ๊ด‘์„ : ์ €๋Š” ๊ทธ๋Ÿฐ ๋…ธ๊ฐ€๋ฆฌ๋„ ๋ชป ํ„ธ์–ด์š”. 63 6) ์ค€ํ˜ : ์ œ๊ฐ€ ์ผ๋งŒ ํ•˜๋Š” ์†Œ ๊ฐ™์•„์š”. 67 7) ์†Œ๊ฒฐ : ์‚ฌ๋ก€ ๋น„๊ต 71 2. ๋ฏธ์ˆ ํ•™์Šต์„ ํ†ตํ•œ ๊ทธ๋ฆผ ์ด์•ผ๊ธฐ 75 1) ํ”๋“ค๋ฆผ : ๋ง๋งํ•œ ๋ฐ”๋‹ค์— ๋ฐฐ ํ•œ ์ฒ™ 79 2) ๋จธ๋ฌด๋ฆ„ : ์˜ฎ๊ฒจ ์‹ฌ์€ ๋‚˜๋ฌด 91 3) ๋‚˜์•„๊ฐ : ๋˜ ๋‹ค๋ฅธ ๊ธธ 101 4) ๋‚˜์˜ ์ฒดํ—˜ : ์˜ˆ์ˆ ๊ฐ€-์—ฐ๊ตฌ์ž-๊ต์‚ฌ๋กœ์„œ์˜ ์ •์ฒด์„ฑ 108 IV. ํƒˆ๋ถ์ฒญ์†Œ๋…„์˜ ์‚ถ๊ณผ ์ •์ฒด์„ฑ 124 1. ์ •์ฒด์„ฑ : ์ฃผ์ฒด-ํƒ€์ž์˜ ๊ฐˆ๋“ฑ๊ณผ ์ƒ์ƒ 124 1) ํ•™์ƒ๊ณผ์˜ ๊ด€๊ณ„ 125 2) ๊ต์‚ฌ์™€์˜ ๊ด€๊ณ„ 133 3) ๊ฐ€์กฑ๊ณผ์˜ ๊ด€๊ณ„ 148 4) ๋‚จํ•œ์‚ฌ๋žŒ๊ณผ์˜ ๊ด€๊ณ„ 164 2. ํ˜•์„ฑ ๊ณผ์ • : ์ƒํ™ฉ์  ๊ตฌ์กฐ 183 1) ์†Œ์ƒํ™ฉ 184 2) ๋Œ€์ƒํ™ฉ 201 3) ๋งค๊ฐœ์ƒํ™ฉ 205 3. ๋ฏธ์ˆ ํ•™์Šต๊ณผ์˜ ์ƒํ˜ธ์—ฐ๊ด€์„ฑ 211 1) ์ •์„œ์  ์ธก๋ฉด 212 2) ์ธ์ง€์  ์ธก๋ฉด 221 3) ์‹ค์กด์  ์ธก๋ฉด 228 V. ํ•ด์„ ๋ฐ ๋…ผ์˜ 241 1. ์ •์ฒด์„ฑ์˜ ์žฌํ•ด์„ 242 1) ํ˜ผ์ข…์ ์ธ ์ •์ฒด์„ฑ 243 2) ์œ ๋™์ ์ธ ์ •์ฒด์„ฑ 245 3) ์—ญ๋™์ ์ธ ์ •์ฒด์„ฑ 250 2. ๋ฏธ์ˆ ๊ต์œก์  ํ•จ์˜ 252 1) ๋ฏธ์ˆ ๊ณผ ์ •์ฒด์„ฑ 253 2) ๋ฏธ์ˆ ๊ต์œก์  ์ƒํ˜ธ์ž‘์šฉ 257 VI. ์š”์•ฝ ๋ฐ ๊ฒฐ๋ก  261 1. ์š”์•ฝ 263 2. ๊ฒฐ๋ก  268 ์ฐธ๊ณ ๋ฌธํ—Œ 271 Abstract 281Docto

    Role of the ฮฑ-synuclein and its mechanism in neurodegenerative disease

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    ์˜๊ณผํ•™๊ณผ/๋ฐ•์‚ฌ[ํ•œ๊ธ€] ฮฑ-Synuclein์€ ์‹ ๊ฒฝ ์„ธํฌ์˜ ์‹ ๊ฒฝ์ ‘ํ•ฉ ์ „๋ถ€์œ„์— ๋‹ค๋Ÿ‰ ์กด์žฌํ•˜๋Š” ๋น„์ •ํ˜• ๊ตฌ์กฐ ๋‹จ๋ฐฑ์งˆ๋กœ์„œ 140๊ฐœ์˜ ์•„๋ฏธ๋…ธ์‚ฐ ์ž”๊ธฐ๋กœ ๊ตฌ์„ฑ๋˜์–ด์žˆ๋‹ค. ์ด ๋‹จ๋ฐฑ์˜ 30๋ฒˆ์งธ ๋ฐ 53๋ฒˆ์งธ ์•Œ๋ผ๋‹Œ ์ž”๊ธฐ๊ฐ€ ๊ฐ๊ฐ ํ”„๋กค๋ฆฐ๊ณผ(A30P), ํŠธ๋ ˆ์˜ค๋‹Œ์œผ๋กœ(A53T) ์น˜ํ™˜๋œ ๋ณ€์ด๊ฐ€ ๊ฐ€์กฑ๋ ฅ์ด ์žˆ๋Š” ํŒŒํ‚จ์Šจ๋ณ‘ ํ™˜์ž์—์„œ ๋ฐœ๊ฒฌ๋จ์œผ๋กœ์„œ ์ด ์œ ์ „์ž์˜ ๋Œ์—ฐ ๋ณ€์ด๊ฐ€ ์œ ์ „์„ฑ ํŒŒํ‚จ์Šจ๋ณ‘์˜ ๋ณ‘์ธ์œผ๋กœ ๋ฐํ˜€์กŒ๋‹ค. ์ด๋Ÿฌํ•œ ฮฑ-synuclein ๋‹จ๋ฐฑ์€ ํŒŒํ‚จ์Šจ๋ณ‘ ํ™˜์ž์˜ ์ค‘์ถ” ์‹ ๊ฒฝ์„ธํฌ ๋‚ด์— ํ˜•์„ฑ๋˜๋Š” ๋‹จ๋ฐฑ ์นจ์ฐฉ๋ฌผ์ธ ๋ฃจ์ด ์†Œ์ฒด์˜ ์ค‘์š” ๊ตฌ์„ฑ ์„ฑ๋ถ„์ž„์ด ์•Œ๋ ค์กŒ๋‹ค. ๋ฃจ์ด ์†Œ์ฒด ํ˜•์„ฑ์€ ํŒŒํ‚จ์Šจ๋ณ‘ ๋ฟ ์•„๋‹ˆ๋ผ ๋‹ค๋ฅธ ํ‡ดํ–‰์„ฑ ์‹ ๊ฒฝ๊ณ„ ์งˆํ™˜์ธ ์•Œ์ฏ”ํ•˜์ด๋จธ๋ณ‘์ด๋‚˜, ๋ฃจ์ด์†Œ์ฒด์„ฑ ์น˜๋งค, ๋‹ค๋ฐœ์„ฑ๊ฒฝํ™”์ฆ์—์„œ๋„ ๋ฐœ๊ฒฌ๋˜๋Š” ๊ฒƒ์œผ๋กœ ๋ณด์•„ ฮฑ-synuclein์ด ๋‹ค์–‘ํ•œ ํ‡ดํ–‰์„ฑ ์‹ ๊ฒฝ๊ณ„ ์งˆํ™˜ ๋ฐœ์ƒ์— ๊นŠ์ด ๊ด€์—ฌํ•จ์„ ๋ณด์—ฌ ์ค€๋‹ค. ์ด๋Ÿฌํ•œ ๋‹จ๋ฐฑ ์‘์ถ•๋ฌผ ํ˜•์„ฑ๊ณผ ํŠน์ • ๋‡Œ ์„ธํฌ์˜ ์‚ฌ๋ฉธ๋กœ ์ธํ•œ ๋‡Œ ๊ธฐ๋Šฅ ์žฅ์• ๊ฐ€ ์‹ ๊ฒฝ์งˆํ™˜์œผ๋กœ ๋ฐœ๋ณ‘ํ•˜๋ฆฌ๋ผ ์—ฌ๊ฒจ์ง€์ง€๋งŒ ฮฑ-synuclein์— ์˜ํ•œ ๋‹จ๋ฐฑ ์‘์ถ•๋ฌผ ํ˜•์„ฑ๊ธฐ์ „์ด๋‚˜ ์„ธํฌ ์‚ฌ๋ฉธ ์œ ๋„ ๊ธฐ์ „์— ๋Œ€ํ•ด์„œ๋Š” ์•„์ง๊นŒ์ง€ ๋ช…ํ™•ํ•˜๊ฒŒ ๋ฐํ˜€์ ธ ์žˆ์ง€ ์•Š๋‹ค. ์„ธํฌ ๋‚ด๋ถ€์—์„œ ฮฑ-synuclein ๋‹จ๋ฐฑ ์‘์ถ•๋ฌผ ํ˜•์„ฑ๋ฟ๋งŒ ์•„๋‹ˆ๋ผ ๊ทธ ์ž˜๋ฆฐ ๋‹จ๋ฐฑ์ด ์„ธํฌ ๋ฐ–์—์„œ ์•Œ์ฏ”ํ•˜์ด๋จธ ํ™˜์ž์˜ ๋‡Œ ์„ธํฌ ์™ธ๋ถ€์—์„œ ๋ฐœ๊ฒฌ๋˜๋Š” Aฮฒ(amyloid ฮฒ)์™€ ํ•จ๊ป˜ senile plaque๋ฅผ ํ˜•์„ฑํ•œ๋‹ค๋Š” ๋ณด๊ณ ์™€ ๋‡Œ์ฒ™์ˆ˜ ์•ก์—์„œ๋„ ฮฑ-synuclein์ด ์กด์žฌํ•œ๋‹ค๋Š” ๋ณด๊ณ  ๋“ฑ์€ ฮฑ-synuclein์ด ์„ธํฌ ๋ฐ–์œผ๋กœ ๋ถ„๋น„๋˜์–ด ์„ธํฌ ์™ธ๋ถ€์—์„œ ์„ธํฌ ์ƒ์กด ๋ฐ ์‚ฌ๋ฉธ์— ์˜ํ–ฅ์„ ๋ฏธ์น  ์ˆ˜ ์žˆ์Œ์„ ์•”์‹œํ•œ๋‹ค. ๋˜ํ•œ ฮฑ-synuclein์˜ 61๋ฒˆ๋ถ€ํ„ฐ 95๋ฒˆ ์•„๋ฏธ๋…ธ์‚ฐ๊นŒ์ง€์˜ ์ž˜๋ฆฐ ๋ถ€๋ถ„์ด ์„ธํฌ์˜ ์™ธ๋ถ€์—์„œ ํ˜•์„ฑ๋œ plaque์— ์กด์žฌํ•œ๋‹ค๋Š” ์ด์ „์˜ ๋ณด๊ณ ๋Š” ฮฑ-synuclein์ด ์ž˜๋ฆผ ๋˜๋Š” ๋ถ„ํ•ด ๊ฐ€๋Šฅ์„ฑ์„ ๋ณด์—ฌ์ฃผ๊ณ  ์žˆ์ง€๋งŒ ๊ทธ ๋ถ„ํ•ด ๊ธฐ์ „์ด๋‚˜ ๊ด€์—ฌํ•˜๋Š” ๋ถ„ํ•ด ํšจ์†Œ์˜ ํŠน์„ฑ ๋ฐ, ์ž˜๋ฆฐ ฮฑ-synuclein์— ์˜ํ•œ ์‘์ถ•๋ฌผ ํ˜•์„ฑ์ด๋‚˜ ์„ธํฌ ์‚ฌ๋ฉธ์— ๋ฏธ์น˜๋Š” ์˜ํ–ฅ ๋“ฑ์— ๋Œ€ํ•ด์„œ ๋ช…ํ™•ํ•˜๊ฒŒ ๋ฐํ˜€์ ธ ์žˆ์ง€ ์•Š๋‹ค. ๋ณธ ๋…ผ๋ฌธ์—์„œ๋Š” ์„ธํฌ ๋ฐ–์œผ๋กœ ๋ถ„๋น„๋œ ฮฑ-synuclein์— ์˜ํ•ด ์œ ๋„๋˜๋Š” ์‹ ๊ฒฝ ์„ธํฌ ์‚ฌ๋ฉธ ๊ธฐ์ „์„ ๋ฐํžˆ๊ณ ์ž ๋Œ€์žฅ๊ท ์—์„œ ๋ฐœํ˜„ ์ •์ œํ•œ ฮฑ-synuclein ๋‹จ๋ฐฑ์„ ์‹ ๊ฒฝ ์„ธํฌ ์™ธ๋ถ€์—์„œ ์ฒ˜๋ฆฌํ•˜์˜€์„ ๋•Œ ์ผ์–ด๋‚˜๋Š” ์„ธํฌ ๋‚ด ๋ณ€ํ™”๋ฅผ ์กฐ์‚ฌํ•˜์˜€๋‹ค. ์™ธ๋ถ€์—์„œ ์ฒ˜๋ฆฌํ•œ ฮฑ-synuclein์€ ์‹ ๊ฒฝ ์„ธํฌ ์‚ฌ๋ฉธ์„ ์œ ๋„ํ•˜์˜€์œผ๋ฉฐ ์„ธํฌ ๋‚ด์—์„œ ํ™œ์„ฑ ์‚ฐ์†Œ์ข…(ROS)์„ ๋†๋„ ์˜์กด์ ์œผ๋กœ ์ƒ์„ฑํ•˜๊ณ  ์„ธํฌ ๊ณจ๊ฒฉ ๋ถ•๊ดด๋ฅผ ์•ผ๊ธฐํ•˜์˜€๋‹ค. ์ด๋Ÿฌํ•œ ์„ธํฌ ์‚ฌ๋ฉธ์€ ์„ธํฌ๋ง‰์„ ํˆฌ๊ณผ, ์„ธํฌ ๋‚ด๋ถ€๋กœ ฮฑ-synuclein์ด ์ด๋™ํ•˜์—ฌ ๋ฃจ์ด์†Œ์ฒด์™€ ์œ ์‚ฌํ•œ ๋‹จ๋ฐฑ ์‘์ถ•๋ฌผ์„ ํ˜•์„ฑํ•˜๊ธฐ ๋•Œ๋ฌธ์ด๋ฉฐ, ์ด๋Ÿฌํ•œ ฮฑ-synuclein์˜ ์„ธํฌ ๋‚ด ์œ ์ž…์€ Rab5A๋ผ๋Š” endocytosis์— ๊ด€์—ฌํ•˜๋Š” ๋‹จ๋ฐฑ์— ์˜์กด์ ์œผ๋กœ ์ผ์–ด๋‚จ์„ ๋ฐœ๊ฒฌํ•˜์˜€๋‹ค. ๋˜ํ•œ human neuroblastoma ์„ธํฌ์ฃผ์— ฮฑ-synuclein์„ ๊ณผ ๋ฐœํ˜„์‹œ์ผฐ์„ ๋•Œ ฮฑ-synuclein ๋‹จ๋ฐฑ์ด ์„ธํฌ ์™ธ๋ถ€๋กœ ๋ถ„๋น„๋˜์–ด monomer ๋‹จ๋ฐฑ์™ธ์— oligomer๊ฐ€ ํ˜•์„ฑ๋จ์„ ๊ด€์ฐฐํ•˜์˜€๋‹ค. ๋˜ํ•œ MMP-3๊ณผ MMP-9๋Š” ฮฑ-synuclein์˜ ๊ณผ๋ฐœํ˜„์œผ๋กœ ์„ธํฌ ๋‚ด ํ•ฉ์„ฑ์ด ์œ ๋„๋˜๊ณ  ์ด ์‹ ๊ฒฝ ์„ธํฌ์ฃผ์— NO ์ƒ์„ฑ์„ ์œ ๋ฐœํ•˜๋Š” ์‹œ์•ฝ์„ ์ฒจ๊ฐ€ํ•˜์˜€์„ ๋•Œ ฮฑ-synuclein์˜ ์ž˜๋ฆผ ํ˜„์ƒ์ด ๊ด€์ฐฐ๋˜์—ˆ๋‹ค. ๋˜ํ•œ MMP ์–ต์ œ์ œ๋ฅผ ์ „์ฒ˜๋ฆฌ ํ•˜๋ฉด NO donor์— ์˜ํ•œ ฮฑ-synuclein์˜ ์ž˜๋ฆผ ํ˜„์ƒ์ด ์–ต์ œ๋จ์œผ๋กœ ๋ณด์•„ ฮฑ-synuclein์˜ ์„ธํฌ ์™ธ๋ถ€์—์„œ ์ž˜๋ฆผ๋„ MMP์˜ ํ™œ์„ฑ๋„์™€ ๊ด€๋ จ ์žˆ์Œ์„ ์•”์‹œํ•œ๋‹ค. MMP-3์™€ MMP-9์— ์˜ํ•ด ์ž˜๋ฆฐ ฮฑ-synuclein์€ ์‘์ถ•๋ฌผ ํ˜•์„ฑ ์†๋„๊ฐ€ ์ž˜๋ฆฌ์ง€ ์•Š์€ ๋‹จ๋ฐฑ๊ณผ ๋น„๊ตํ•˜์—ฌ ํ›จ์”ฌ ๋น ๋ฅด๋ฉฐ ํ˜•์„ฑ๋œ ์‘์ถ•๋ฌผ์˜ ์„ธํฌ ๋…์„ฑ๋„ ์ž˜๋ฆฌ์ง€ ์•Š์€ ๋‹จ๋ฐฑ๊ณผ ๋น„๊ตํ•˜์—ฌ ๋”์šฑ ์ฆ๊ฐ€๋˜์–ด์žˆ์Œ์„ ์•Œ ์ˆ˜ ์žˆ์—ˆ๋‹ค. ์ด์ƒ์˜ ๊ฒฐ๊ณผ๋กœ ฮฑ-synuclein์ด ์‹ ๊ฒฝ ์„ธํฌ ๋‚ด๋ถ€์™€ ์™ธ๋ถ€๋กœ ์ด๋™ํ•˜์—ฌ ์„ธํฌ ์™ธ๋ถ€์—์„œ๋Š” MMP์— ์˜ํ•ด ์ž˜๋ ค์ง€๋ฉฐ ํŒŒํ‚จ์Šจ ํ™˜์ž์—๊ฒŒ์„œ ๋ณด์ด๋Š” ๋‹จ๋ฐฑ ์นจ์ฐฉ๋ฌผ์„ ํ˜•์„ฑํ•จ์„ ๋ณด์—ฌ ์ค€๋‹ค. ์ด๋Ÿฐ ์—ฐ๊ตฌ๋ฅผ ๋ฐ”ํƒ•์œผ๋กœ ๊ด€์—ฌํ•˜๋Š” ๋ถ„์ž ๊ธฐ์ „ ์—ฐ๊ตฌ ๋ฐ ๊ฒฐํ•ฉ ๋‹จ๋ฐฑ ๋™์ •์„ ํ†ตํ•ด ์„ธํฌ ์‚ฌ๋ฉธ ์กฐ์ ˆ ์ธ์ž๋ฅผ ๊ทœ๋ช…ํ•  ์ˆ˜ ์žˆ๋‹ค๋ฉด ํŒŒํ‚จ์Šจ๋ณ‘์˜ ๋ณ‘์ธ ๊ธฐ์ „ ๋ถ„์„๊ณผ ์ƒˆ๋กœ์šด ์น˜๋ฃŒ ๊ธฐ์ˆ  ๊ฐœ๋ฐœ์— ๋„์›€์„ ์ค„ ๊ฒƒ์œผ๋กœ ๊ธฐ๋Œ€ํ•œ๋‹ค. [์˜๋ฌธ] The presynaptic ฮฑ-synuclein is a prime suspect for contributing to Lewy pathology and clinical aspects of diseases, including Parkinson''s disease, dementia with Lewy bodies, and a Lewy body variant of Alzheimer''s disease. ฮฑ-synuclein is also the precursor to an intrinsic component of extracellular plaques in Alzheimer''s disease. In the present study first we examined the pathogenic mechanism to induce the neuronal cell death by extracellular ฮฑ-synuclein. The exogenous addition of ฮฑ-synuclein induced necrotic cell death in immortalized hippocampal and dopaminergic neuronal cells. Its intracellular response included the activation of c-Jun N-terminal kinase, generation of reactive oxygen species and disruption of cytoskeletal actin structures. After cell fractionation, most of ฮฑ-synucleins were localized in intracellular soluble fraction and distributed unevenly as a granular form with the similar contents of cytoplasmic Lewy body inclusions. By using metabolic labeling with [35S]-Met, we observed that de novo protein synthesis of ฮฑ-synuclein is not occurred during the cell death, indicating that ฮฑ-synuclein added exogenously are transported into the cells. We also found that Rab5 protein, a small GTPase and known to be involved in endocytosis, binds to ฮฑ-synuclein in a specific way and is co-localized with ฮฑ-synuclein at the cytosolic area. Overexpression of GTPase-mutant Rab5A proteins resulted in the significant suppression of cell toxicity of exogenous ฮฑ-synuclein due to its incomplete endocytosis. Overall theses results indicated that Rab5A-specific endocytosis of ฮฑ-synuclein caused Lewy body-like intracytoplsmic inclusions followed by cell death in neuronal hippocampal cells. Next, we examined the possible functional relationship between several forms of matrix metalloproteinases and ฮฑ-synuclein in human dopaminergic neuroblastoma cell line. When human dopaminergic neuroblastoma SK-N-BE(2) cells were transiently transfected with a plasmid encoding ฮฑ-synuclein, the cell viability decreased significantly. Interestingly, the presence of ฮฑ-synuclein was detected in the extracellular culture media and cleaved by NO-activated MMPs. In addition, the ฮฑ-synuclein has been selectively digested by MMP-3 and 9, but not by MMP-2 and 14, in vitro. When its cleavage pattern was analyzed in detail, the 62th, 67-th amino acids of ฮฑ-synuclein were cleaved by MMP-9. Furthermore, the overexpression of ฮฑ-synuclein in neuronal cells resulted in the activation of MMP-3 and -9 as well as the levels of their mRNA levels, respectively. While the aggregation rate was increased in the MMP-mediated ฮฑ-synuclein fragments, compared with that of intact ฮฑ-synuclein, the proteolytic ฮฑ-synuclein fragments showed the more toxic effect on cell viability. In addition, the levels of MMP-3 and 9 were found to be increased significantly in MPTP-injected rat brain model. Taken together, our findings suggest that the extracellular-secreted ฮฑ-synuclein could be processed via the activation of MMP-3 and 9 in a selective manner and this kind of ฮฑ-synuclein digestion could play a certain role in the pathogenesis of Parkinson''sope

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    A Review of the Studies on the Relationship between Organizational Culture and Organizational Performance

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    ์กฐ์ง๋ฌธํ™”์™€ ์„ฑ๊ณผ์˜ ๊ด€๊ณ„๋Š” ์˜ค๋žซ๋™์•ˆ ์‹ค๋ฌด์™€ ํ•™๊ณ„์˜ ๊ด€์‹ฌ์‚ฌ๊ฐ€ ๋˜์–ด ์™”๋‹ค. ๊ทธ๋Ÿผ์—๋„ ๋ถˆ๊ตฌํ•˜๊ณ , ๊ทธ ๊ฐœ๋…์˜ ๋ชจํ˜ธ์„ฑ๊ณผ ์ธก์ •์ƒ์˜ ์–ด๋ ค์›€์œผ๋กœ ์ธํ•ด, ์กฐ์ง๋ฌธํ™”์™€ ์„ฑ๊ณผ์˜ ๊ด€๊ณ„๋Š” ํ•œ๋งˆ๋”” ๊ฒฐ๋ก ์œผ๋กœ ๋‹จ์–ธํ•˜๊ธฐ ์–ด๋ ค์› ๋‹ค. ์ด์ œ๊นŒ์ง€ ์กฐ์ง๋ฌธํ™”์— ๋Œ€ํ•œ ์—ฐ๊ตฌ๋Š” ์กฐ์ง๋ฌธํ™”์˜ ๊ฐ•๋„(strength) ์ธก๋ฉด์— ์ค‘์ ์„ ๋‘์–ด์™”์œผ๋ฉฐ ์„ฑ๊ณผ ์—ญ์‹œ ์ฃผ๋กœ ์žฌ๋ฌด์  ์„ฑ๊ณผ๋ฅผ ์ค‘์‹ฌ์œผ๋กœ ์—ฐ๊ตฌ๊ฐ€ ์ด๋ฃจ์–ด์ ธ์™”๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ๋ฌธํ™”์˜ ๊ฐ•๋„๋ฟ๋งŒ ์•„๋‹ˆ๋ผ ๋…ํŠน์„ฑ๊ณผ ์•ˆ์ •์„ฑ ๋“ฑ ์กฐ์ง๋ฌธํ™”์˜ ๋‹ค์–‘ํ•œ ํŠน์„ฑ์  ์ธก๋ฉด์„ ํ•จ๊ป˜ ๊ณ ๋ คํ•  ํ•„์š”๊ฐ€ ์žˆ๋‹ค. ์„ฑ๊ณผ์˜ ๊ฒฝ์šฐ๋„ ์žฌ๋ฌด์  ์„ฑ๊ณผ ์ด์™ธ์— ์ข…์—…์› ๊ฐœ์ธ์˜ ์ธก๋ฉด์—์„œ ์ข…์—…์› ๋ชฐ์ž…์ด๋‚˜ ์ด์ง, ์กฐ์ง์˜ ํŒ€์ฐจ์›์—์„œ ์‘์ง‘์„ฑ์ด๋‚˜ ํŒ€์„ฑ๊ณผ, ์กฐ์ง์ฐจ์›์˜ ์ƒ์กด ๋“ฑ ๋ณด๋‹ค ๋‹ค์–‘ํ•œ ์ˆ˜์ค€(level)๊ณผ ๋‚ด์šฉ์˜ ์„ฑ๊ณผ๋ฅผ ์‚ดํŽด๋ณผ ํ•„์š”๊ฐ€ ์žˆ๋‹ค. ์ด์— ๋ณธ ์—ฐ๊ตฌ๋Š” ์กฐ์ง๋ฌธํ™”์™€ ์„ฑ๊ณผ ๊ฐ„์˜ ๊ด€๊ณ„๋ฅผ ์กฐ๋ช…ํ•˜๊ธฐ ์œ„ํ•ด ์กฐ์ง๋ฌธํ™”์˜ ์ œ ์ธก๋ฉด๊ณผ ์„ฑ๊ณผ์˜ ์ œ ์ธก๋ฉด์„ ๋น„๊ตํ•œ๋‹ค. ์กฐ์ง๋ฌธํ™”์™€ ์„ฑ๊ณผ์— ๋Œ€ํ•œ ๋ฌธํ—Œ๊ณ ์ฐฐ์„ ๋ฐ”ํƒ•์œผ๋กœ ์ง€์ง๋ฌธํ™”๋ฅผ ์ •์  ์ธก๋ฉด๊ณผ ๋™์  ์ธก๋ฉด์œผ๋กœ ๊ตฌ๋ถ„ํ•˜์˜€์œผ๋ฉฐ ์„ฑ๊ณผ๋Š” ์ˆ˜์ค€ ๋ฐ ๊ธฐ๊ฐ„์— ๋”ฐ๋ผ ๋ถ„๋ฅ˜ํ•˜์—ฌ ์ข…ํ•ฉ์ ์ธ ์ธก๋ฉด์˜ ๊ณ ์ฐฐ์„ ์‹œ๋„ํ•˜์˜€๋‹ค
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