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    ๋งˆ์šฐ์Šค ๋Œ€์žฅ์—ผ์—์„œ ๋Œ€์‹์„ธํฌ Ninjurin1์˜ ๊ธฐ๋Šฅ ์—ฐ๊ตฌ

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    ํ•™์œ„๋…ผ๋ฌธ (๋ฐ•์‚ฌ) -- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ์˜๊ณผ๋Œ€ํ•™ ํ˜‘๋™๊ณผ์ • ์ข…์–‘์ƒ๋ฌผํ•™์ „๊ณต, 2020. 8. ์„ฑ์ œ๊ฒฝ.The incidence of inflammatory bowel disease (IBD) has been increasing, and IBD has become an emerging disease that requires greater elucidation of its pathogenesis. In common, IBD leads to complications like colon cancer, which is a life-threatening problem. IBD was considered as a growing disease only in western world in the past. However, recent studies report a significance rise in the number of cases of IBD in Asian countries. Especially, there has been a twentyfold increase in the number of patients with IBD over the last fourteen years in Korea. IBD is characterized by the dysregulated immune system, which means that it is an immune-mediated disease. Immune cells in the gut including macrophages, T cells, B cells, and dendritic cells are involved in contributing IBD. These immune cells induce inflammation via secreting pro-inflammatory cytokines and chemokines. Especially, macrophages are able to regulate IBD development by changing their polarized phenotype. Nerve injury-induced protein 1 (Ninjurin1, Ninj1) is a cell-surface adhesion molecule that regulates cell migration and attachment. Several studies revealed that Ninjurin1 promoted macrophage migration capacity. However, the precise function of Ninjurin1 has not yet been clearly defined. Herein, I demonstrate that Ninjurin1 protein expression is increased in a dextran sodium sulfate (DSS)-induced colitis model, which is confirmed in IBD patients. To directly assess whether Ninjurin1 plays an important role in colitis, I introduced WT and Ninjurin1-deficient mice (KO) mice to 1.5% and 2.5% DSS and evaluated colitis incidence. Ninjurin1 KO mice showed significantly less body weight loss and longer colon length when compared with WT mice. I also performed hematoxylin and eosin staining of colon tissue sections, which revealed that less crypt destruction, surface epithelial erosion, and reduced submucosal edema in DSS-treated Ninjurin1 KO mice compared to DSS-treated WT mice. No such differences in colon tissue histology were shown in control mice of either genotype. Likewise, relatively intact mucosa and larger number of mucin-containing goblet cells were remained in DSS-treated Ninjurin1 KO mice compared to WT mice, which were assessed by Ki-67 and Alcian blue staining, respectively. Various immune cells infiltrate into the site of inflammation during the development of colitis. To study what type of immune cell made a difference in colitis incidence according to Ninjurin1 expression, I investigated Ninjurin1 expression pattern on lymphocytes and myeloid cells. Myeloid cells showed the highest expression of Ninjurin1 among the various immune cells. Interestingly, Ninjurin1 does not regulate migration capacity of macrophages during development of experimental colitis. Next, I examined activation of macrophages under inflammatory conditions. Cytokines and chemokines secreted by activated macrophages play critical roles at the site of inflammation. I evaluated gene and protein expression of cytokines and chemokines in the presence or absence of Ninjurin1 in macrophages. Compared to WT cells, Ninjurin1 KO macrophages expressed less amount of cytokines and chemokines. To validate that Ninjurin1 on macrophages affects the intestinal inflammation, I generated mice with a conditional deletion of Ninjurin1 in macrophages (Ninjurin1fl/fl ; Lyz2-Cre+). Myeloid specific Ninjurin1-deficient mice exhibited significantly attenuated body weight loss, shortening of colon length, intestinal inflammation, and lesser pathological lesions than WT mice. Furthermore, DSS-treated myeloid specific Ninjurin1-deficient mice expressed less amount of pro-inflammatory cytokines compared to DSS-treated WT mice. During the development of colitis, the Ninjurin1 expressing macrophages secrete more cytokines and chemokines by regulating PKCฮด/ฮธ-STAT1 activation. Colon tissues from DSS-treated WT mice expressed activated PKCฮด/ฮธ compared with those from DSS-treated Ninjurin1 KO mice. Pharmacological and genetic inhibition of PKCฮด/ฮธ-STAT1 pathway led to reduced production of pro-inflammatory cytokines in WT macrophages. In summary, I suggest that Ninjurin1 in macrophages has a pivotal function in colon inflammation.Nerve injury-induced protein 1 (Ninjurin1)์€ ์†์ƒ๋œ ์‹ ๊ฒฝ ์ฃผ์œ„ ์Šˆ๋ฐ˜์„ธํฌ์—์„œ์˜ ๋ฐœํ˜„์ด ์ฒ˜์Œ์œผ๋กœ ์•Œ๋ ค์ง„ ์„ธํฌ๋ง‰ ๋‹จ๋ฐฑ์งˆ์ด๋‹ค. Ninjurin1์€ ์—ผ์ฆ๋ฐ˜์‘์—์„œ ๋Œ€์‹์„ธํฌ์˜ ์ด๋™๊ณผ ๋ถ€์ฐฉ์— ๊ด€์—ฌํ•˜์—ฌ ์—ผ์ฆ๋ฐ˜์‘์„ ์กฐ์ ˆํ•œ๋‹ค๊ณ  ์•Œ๋ ค์ ธ ์žˆ๋‹ค. ๋˜ํ•œ Ninjurin1์€ ๋Œ€์‹์„ธํฌ, ๋‹จํ•ต๊ตฌ, ๊ทธ๋ฆฌ๊ณ  ํ˜ธ์ค‘๊ตฌ์™€ ๊ฐ™์€ ํ˜ˆ์•ก ์œ ๋ž˜ ๋ฉด์—ญ์„ธํฌ์—์„œ ๊ฐ•๋ ฅํ•˜๊ฒŒ ๋ฐœํ˜„๋œ๋‹ค๊ณ  ๋ณด๊ณ ๋˜์—ˆ๋‹ค. ํ˜„์žฌ๊นŒ์ง€ ๋งŽ์€ ์—ฐ๊ตฌ๊ฐ€ ๋Œ€์‹์„ธํฌ์—์„œ ๋Œ€ํ•ด ์ด๋ฃจ์–ด์ ธ ์žˆ์ง€๋งŒ ์ƒ๋ฆฌํ•™์  ํ˜„์ƒ์— ๋Œ€ํ•œ ๋ณด๊ณ ๋Š” ์ œํ•œ์ ์ด๋ฉฐ ์ž์„ธํ•œ ์—ผ์ฆ์กฐ์ ˆ๊ธฐ์ „์ด ์•Œ๋ ค์ง€์ง€ ์•Š์•„ ์—ผ์ฆ์„ฑ ์งˆํ™˜์—์„œ์˜ Ninjurin1์˜ ์ž‘์šฉ ๊ธฐ์ „์„ ๋ฐํžˆ๋Š” ์—ฐ๊ตฌ๊ฐ€ ํ•„์š”ํ•  ๊ฒƒ์œผ๋กœ ์ƒ๊ฐ๋˜์—ˆ๋‹ค. ์—ผ์ฆ์„ฑ ๋Œ€์žฅ์งˆํ™˜์€ ์œ„์žฅ๊ด€์˜ ๋งŒ์„ฑ ์—ผ์ฆ ์ƒํƒœ๋ฅผ ๋‚˜ํƒ€๋‚ด๋Š” ์šฉ์–ด๋กœ์„œ ํฌ๋ก ๋ณ‘๊ณผ ๊ถค์–‘์„ฑ ์žฅ์—ผ์œผ๋กœ ๊ตฌ๋ถ„๋˜๋ฉฐ ์ด๋“ค ๋ชจ๋‘ ์—ผ์ฆ์˜ ๋ฐœ์ƒ๊ณผ ์™„ํ™”๊ฐ€ ๋ฐ˜๋ณต๋˜๋Š” ๊ฒƒ์ด ํŠน์ง•์ด๋‹ค. ๋Œ€์žฅ์—ผ ๋ฐœ์ƒ ์‹œ, ์—ฌ๋Ÿฌ ๋ฉด์—ญ ์„ธํฌ๋“ค ์ค‘ ์„ ์ฒœ ๋ฉด์—ญ์„ ๋‹ด๋‹นํ•˜๋Š” ๋Œ€์‹์„ธํฌ์˜ ํ™œ์„ฑํ™”๊ฐ€ ์ฃผ๋œ ์—ญํ• ์„ ํ•˜๋Š” ๊ฒƒ์œผ๋กœ ์•Œ๋ ค์ ธ ์žˆ๋‹ค. ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” Ninjurin1์˜ ์—ผ์ฆ ์กฐ์ ˆ ๊ธฐ์ „์„ ๋Œ€์žฅ์—ผ ๋ฐœ์ƒ๊ณผ์ •์—์„œ ํ™•์ธํ•˜๊ณ ์ž ํ•˜์˜€๋‹ค. ๊ณต๊ฐœ๋œ ์œ ์ „์ฒด ๋น…๋ฐ์ดํ„ฐ์ธ Gene Expression Omnibus์—์„œ Ninjurin1๊ณผ ๋Œ€์žฅ์—ผ์˜ ์ƒ๊ด€๊ด€๊ณ„๋ฅผ ๋ถ„์„ํ•œ ๊ฒฐ๊ณผ ๋Œ€์žฅ์—ผ ํ™˜์ž๋“ค์˜ ๋Œ€์žฅ ์กฐ์ง ์ƒ˜ํ”Œ ๋‚ด Ninjurin1 ๋ฐœํ˜„ ์–‘์ด ์ •์ƒ ๋Œ€์žฅ ์กฐ์ง์— ๋น„ํ•˜์—ฌ ์œ ์˜์ ์œผ๋กœ ์ฆ๊ฐ€ํ•จ์„ ํ™•์ธํ•˜์˜€๋‹ค. ๋˜ํ•œ ๋Œ€์žฅ์—ผ ํ™˜์ž๋“ค์˜ ๋ฆผํ”„๊ตฌ ๋ฐ ๋‹จํ•ต๊ตฌ์—์„œ Ninjurin1์˜ mRNA ๋ฐœํ˜„ ์–‘์ด ์œ ์˜์ ์œผ๋กœ ์ฆ๊ฐ€ํ•˜๋Š” ๊ฒƒ์„ ํ™•์ธํ•˜์˜€๋‹ค. ๋”ฐ๋ผ์„œ ๋Œ€์žฅ์—ผ ๋ฐœ์ƒ ๊ณผ์ •์—์„œ Ninjurin1์ด ์ค‘์š”ํ•œ ์—ญํ• ์„ ํ•  ๊ฒƒ์œผ๋กœ ์ƒ๊ฐํ•˜์˜€๋‹ค. ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” ๋Œ€์กฐ๊ตฐ๊ณผ Ninjurin1 ์œ ์ „์ž ๊ฒฐ์† ๋งˆ์šฐ์Šค(Ninjurin1 KO)์— dextran sodium sulfate (DSS)๋ฅผ 8์ผ ๋™์•ˆ ์ฒ˜๋ฆฌํ•˜์—ฌ ๋Œ€์žฅ์—ผ์„ ์œ ๋ฐœํ•˜์˜€๋‹ค. Ninjurin1 KO ๋งˆ์šฐ์Šค์—์„œ๋Š” ๋Œ€์กฐ๊ตฐ ๋งˆ์šฐ์Šค์— ๋น„ํ•ด ๋Œ€์žฅ์—ผ ๋ณ‘๋ณ€์ด ๋ฏธ์•ฝํ•˜์˜€๊ณ  ๋Œ€์žฅ์—ผ ์œ ๋„์— ๋”ฐ๋ผ ๋Œ€์‹์„ธํฌ์—์„œ Ninjurin1์˜ ๋ฐœํ˜„์ด ํ˜„์ €ํ•˜๊ฒŒ ์ฆ๊ฐ€ํ•˜๋Š” ๊ฒƒ์ด ๊ด€์ฐฐ๋˜์—ˆ๋‹ค. ๋Œ€์žฅ์—ผ ๋ถ€์œ„์˜ ๋Œ€์‹์„ธํฌ ์ˆ˜๋ฅผ ๋ถ„์„ํ•œ ๊ฒฐ๊ณผ Ninjurin1์˜ ๋ฐœํ˜„์€ ๋Œ€์‹์„ธํฌ์˜ ์ด๋™์„ฑ์—๋Š” ๊ด€์—ฌ๋ฅผ ํ•˜์ง€ ์•Š๋Š”๋‹ค๋Š” ๊ฒƒ์„ ํ™•์ธํ•˜์˜€๋‹ค. Microarray๋ฅผ ์ˆ˜ํ–‰ํ•˜์—ฌ ๋Œ€์‹์„ธํฌ์—์„œ Ninjurin1์ด ๊ฒฐ์† ๋จ์— ๋”ฐ๋ผ ๋Œ€๋ถ€๋ถ„์˜ ์—ผ์ฆ ๊ด€๋ จ ์œ ์ „์ž์˜ ๋ฐœํ˜„์ด ํ˜„์ €ํ•˜๊ฒŒ ์ €ํ•˜๋˜์—ˆ์Œ์„ ํ™•์ธํ•˜์˜€๋‹ค. LPS์— ์˜ํ•œ ๋งˆ์šฐ์Šค ๋Œ€์‹์„ธํฌ์ฃผ์˜ ์—ผ์ฆ ํ™œ์„ฑํ™” ๊ณผ์ •์—์„œ Ninjurin1 ์œ ์ „์ž์˜ ๋ฐœํ˜„์„ ์–ต์ œํ•˜๋ฉด ์—ผ์ฆ์„ฑ ์‚ฌ์ดํ† ์นด์ธ ์œ ์ „์ž๊ฐ€ ๋Œ€์กฐ๊ตฐ์— ๋น„ํ•ด ์ ๊ฒŒ ์ฆ๊ฐ€ํ•˜์˜€๋‹ค. ๋˜ํ•œ ๋Œ€์กฐ๊ตฐ ๋งˆ์šฐ์Šค ๋Œ€์žฅ์กฐ์ง์— ๋น„ํ•ด Ninjurin1 KO ๋งˆ์šฐ์Šค ๋Œ€์žฅ์กฐ์ง์—์„œ ์‚ฌ์ดํ† ์นด์ธ ๋ฐœํ˜„์ด ๋‚ฎ์•˜๋‹ค. ๋Œ€์žฅ์—ผ ๋ฐœ์ƒ์—์„œ ๋Œ€์‹์„ธํฌ์˜ Ninjurin1์ด ์ค‘์š”ํ•œ ์—ญํ• ์„ ํ•˜๊ณ  ์žˆ์Œ์„ ํ™•์ธํ•˜๊ธฐ ์œ„ํ•˜์—ฌ ๋Œ€์‹์„ธํฌ ํŠน์ด์ ์œผ๋กœ Ninjurin1์˜ ๋ฐœํ˜„์„ ์–ต์ œํ•œ ๋งˆ์šฐ์Šค์— ๋Œ€์žฅ์—ผ์„ ์œ ๋ฐœํ•˜์˜€๋‹ค. Ninjurin1์ด ๋Œ€์‹์„ธํฌ์—์„œ ๊ฒฐ์† ๋จ์— ๋”ฐ๋ผ ๋Œ€์กฐ๊ตฐ์— ๋น„ํ•ด ๋” ๋ฏธ์•ฝํ•œ ๋ณ‘๋ณ€์ด ๊ด€์ฐฐ๋˜์—ˆ๊ณ , ๋Œ€์žฅ ์กฐ์ง์œผ๋กœ๋ถ€ํ„ฐ ๋ถ„๋น„๋œ ์‚ฌ์ดํ† ์นด์ธ์„ ์ธก์ •ํ•œ ์‹คํ—˜์—์„œ๋„ ๋Œ€์กฐ๊ตฐ์— ๋น„ํ•ด ์‚ฌ์ดํ† ์นด์ธ์˜ ๋ถ„๋น„๊ฐ€ ๊ฐ์†Œ๋˜์–ด ์žˆ์Œ์„ ํ™•์ธํ•˜์˜€๋‹ค. ๋Œ€์‹์„ธํฌ์—์„œ Ninjurin1์ด ์—ผ์ฆ ์‹ ํ˜ธ๋ฅผ ์ „๋‹ฌํ•˜๋Š” ๊ธฐ์ „์„ ํ™•์ธํ•œ ๊ฒฐ๊ณผ, ๋Œ€์กฐ๊ตฐ์— ๋น„ํ•ด Ninjurin1 KO ๋งˆ์šฐ์Šค์˜ ๋Œ€์žฅ ์กฐ์ง์—์„œ Protein Kinase C (PKC) ฮด/ฮธ์˜ ํ™œ์„ฑํ™”๊ฐ€ ๊ฐ์†Œ๋˜์–ด ์žˆ์Œ์„ ๊ด€์ฐฐํ•˜์˜€๋‹ค. ๋งˆ์šฐ์Šค ์œ ๋ž˜ ๋Œ€์‹์„ธํฌ์ฃผ์—์„œ LPS๋ฅผ ์ฒ˜๋ฆฌํ•œ ์‹คํ—˜์—๋„ ์ผ๊ด€๋œ ๊ฒฐ๊ณผ๋ฅผ ์–ป์—ˆ๋‹ค. ๋ณธ ์‹คํ—˜์—์„œ๋Š” ์œ„ ์ผ๋ จ์˜ ์‹คํ—˜๋“ค์„ ํ†ตํ•˜์—ฌ ๋‹ค์Œ๊ณผ ๊ฐ™์€ ๋ช‡ ๊ฐ€์ง€ ํ˜„์ƒ ๋ฐ ๊ธฐ์ „์„ ๋ฐํ˜”๋‹ค. (1) ๋Œ€์žฅ์—ผ ์œ ๋„์‹œ ๋Œ€์กฐ๊ตฐ ๋งˆ์šฐ์Šค์— ๋น„ํ•ด Ninjurin1 KO ๋งˆ์šฐ์Šค์—์„œ ๋Œ€์žฅ์—ผ ๋ณ‘๋ณ€์ด ๋ฏธ์•ฝํ•˜๊ฒŒ ๊ด€์ฐฐ๋˜์—ˆ๋‹ค. (2) Ninjurin1์ด ๋Œ€์‹์„ธํฌ ํŠน์ด์ ์œผ๋กœ ์–ต์ œ๋œ ๋งˆ์šฐ์Šค์—์„œ๋„ ๋Œ€์กฐ๊ตฐ ๋งˆ์šฐ์Šค์— ๋น„ํ•ด ๋ณ‘๋ณ€์ด ๋œ ์ฆ๊ฐ€ํ•˜์˜€๋‹ค. (3) ๋Œ€์‹์„ธํฌ์—์„œ Ninjurin1 ๋ฐœํ˜„์˜ ์–ต์ œ๋Š” IL1ฮฒ์™€ ๊ฐ™์€ ์—ผ์ฆ์„ฑ ์‚ฌ์ดํ† ์นด์ธ์˜ ๋ถ„๋น„๋ฅผ ๊ฐ์†Œ์‹œ์ผฐ๋‹ค. (4) Ninjurin1์€ PKCฮด/ฮธ ๋‹จ๋ฐฑ์งˆ์˜ ํ™œ์„ฑํ™”๋ฅผ ์กฐ์ ˆํ•˜์—ฌ ์—ผ์ฆ์„ฑ ์‚ฌ์ดํ† ์นด์ธ์˜ ๋ถ„๋น„๋ฅผ ์œ ๋„ํ•˜์˜€๋‹ค. ๋”ฐ๋ผ์„œ ๋ณธ ์—ฐ๊ตฌ๋Š” ๋Œ€์‹์„ธํฌ์—์„œ Ninjurin1์ด PKCฮด/ฮธ ํ™œ์„ฑํ™”๋ฅผ ์œ ๋„ํ•˜๊ณ  ์—ผ์ฆ์„ฑ ์‚ฌ์ดํ† ์นด์ธ์˜ ๋ถ„๋น„๋ฅผ ์ฆ๊ฐ€์‹œ์ผœ ๊ฒฐ๊ณผ์ ์œผ๋กœ ๋Œ€์žฅ์—ผ ๋ฐœ์ƒ์„ ์ผ์œผํ‚ค๋Š” ์ž‘์šฉ ๊ธฐ์ „์„ ๊ทœ๋ช…ํ•˜์˜€์œผ๋ฉฐ ์ด๋กœ ์ธํ•ด ๋Œ€์žฅ์—ผ ์œ ๋ฐœ์˜ ์›์ธ์œผ๋กœ์„œ Ninjurin1์˜ ๊ฐ€๋Šฅ์„ฑ์„ ์ œ์‹œํ•œ๋‹ค.I. Introduction 1 Ninjurin1 in inflammatory conditions 5 Ninjurin1 in cancers 7 Inflammatory bowel disease 9 Macrophages in inflammatory conditions 13 Ninjurin1 and inflammatory signals 15 The purpose of this study 17 II. Materials and Methods 19 1. Mice and experimental colitis 19 2. Cell lines 21 3. Immunoblotting 22 4. Assessment of inflammation in colon 22 5. Immunofluorescence 23 6. Immunohistochemistry 23 7. Purification and activation of lymphocytes 24 8. RNA isolation and reverse transcriptionpolymerase chain reaction (RT-PCR)/real-time quantitative PCR (qRT-PCR) analysis 24 9. Cell isolation from colons 27 10. Flow cytometry analysis 27 11. Peritoneal macrophage isolation 27 12. Bone marrow-derived macrophage (BMDM) isolation and culture 28 13. Analysis of tight junction protein complex in vitro 28 14. Microarray analysis 29 15. Mouse cytokine array 29 16. Colon explant and ELISA 30 17. Human NF-kB Pathway Array 31 18. RNA interference 31 19. Statistical analysis 32 III. Results 33 1. Ninjurin1 expression increases under intestinal inflammatory conditions 33 2. Ninjurin1 expression increases in colon tissues of DSS-treated mice 36 3. Ninjurin1 deficiency alleviates experimental colitis 39 4. Ninjurin1 is highly expressed on cells of myeloid lineage 46 5. Macrophages during colitis development show increased expression of Ninjurin1 48 6. Intestinal barrier is not affected by Ninjurin1 54 7. Migration capacity of macrophages is not influenced by Ninjurin1 expression during colitis development 56 8. Ninjurin1 in macrophages enhances production of cytokines modulating colon inflammation 61 9. Ninjurin1 inhibition in macrophages reduces production of cytokines 70 10. Ninjurin1 deficiency in myeloid cells decreases susceptibility to experimental colitis 73 11. STAT1 is activated in macrophages under inflammatory conditions. 79 12. Ninjurin1 modulates PKCฮด/ฮธ activation 81 13. Ninjurin1 does not regulate M2 polarization 87 IV. Discussion 89 V. References 94 ๊ตญ๋ฌธ ์ดˆ๋ก 105Docto

    Renal abscesses measuring 5 cm or less: outcome of medical treatment without therapeutic drainage

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    PURPOSE: Diagnosis and proper treatment of renal abscesses remains a challenge for physicians. We investigated the characteristics and comorbidity factors of renal abscesses measuring 5 cm or less and critically examined the effectiveness of conservative treatment. MATERIALS AND METHODS: Between February 2001 and March 2009 the records of 63 patients initially diagnosed at our hospital with renal or perirenal abscesses were retrospectively reviewed. In 63 patients with renal and perirenal abscesses, 51 abscesses measured 5 cm or less, and 49 abscesses were treated with intravenous antibiotics alone. RESULTS: Most patients were women (91.8%), and their mean age was 42.3 years. The mean size of renal abscesses was 3.6 cm. The most common predisposing condition was diabetes mellitus (DM) (46.9%). Common clinical features were fever (83.7%) and flank pain (53.1%). On urinalysis, 31 (64.6%) cases had positive bacterial cultures with Escherichia coli (50.0%) being the most common pathogen. All 49 patients were treated with broad-spectrum intravenous antibiotics alone. All patients showed complete clinical regression and resolution of the renal lesions shown by CT between 3 and 14 weeks. The average hospital stay was 15.3 days (range, 5-31 days). Significant predictors of a long hospital stay were age, abscess size, and DM. CONCLUSION: Medium-sized as well as small-sized renal abscesses were treated successfully with intravenous antibiotics alone. DM was a significant predictor of prolonged hospital stay. If therapeutic drainage is believed to involve considerable risk, then intravenous antimicrobial therapy may be a good alternative treatmentope

    Function of the Cold Receptor (TRPM8) Associated with Voiding Dysfunction in Bladder Outlet Obstruction in Rats.

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    PURPOSE: Bladder outlet obstruction (BOO) causes storage and voiding dysfunction in the lower urinary tract. We investigated the expression of transient receptor potential cation channel subfamily M member 8 (TRPM8) to evaluate the relationship between TRPM8 expression and overactive bladder (OAB) in a rat model of BOO. METHODS: Fifty female Sprague-Dawley rats were divided into 4 groups; normal (n=10), normal-menthol (n=10), BOO (n=15), BOO-menthol (n=15). After 3 weeks, cystometry was performed by infusing physiological saline and menthol (3 mM) into the bladder at a slow infusion rate. The histological changes and expression of TRPM8 in the bladder were investigated by Masson's trichrome staining, immunofluorescence and reverse transcription-polymerase chain reaction. RESULTS: Cystometry showed that the intercontraction interval (ICI; 428.2ยฑ23.4 vs. 880.4ยฑ51.2, P<0.001), micturition pressure (MP; 25.7ยฑ1.01 vs. 71.80ยฑ3.01, P<0.001), and threshold pressure (2.9ยฑ0.25 vs. 9.2ยฑ1.58, P<0.01) were significantly increased in BOO rats. The bladder wall was significantly dilated compared with the control. Detrusor muscle hypertrophy and a thick mucosa layer were observed in BOO bladder. After menthol treatment, ICIs were decreased and MPs were increased in the menthol treatment groups. TRPM8-positive cells and mRNA were predominantly increased in the bladder and dorsal root ganglia of all groups compared with the normal group. CONCLUSIONS: Increased bladder wall thickness and proportion of collagen probably affect voiding dysfunction. Furthermore, an increase of TRPM8 expression in BOO may induce entry of Ca(2+) from the extracellular space or stores. The increase of Ca(2+) probably causes contraction of smooth muscle in BOO. However, OAB symptoms were not observed after menthol treatment although the expression of TRPM8 was abundant in the bladder epithelium after menthol treatment. Although OAB in BOO models may be caused by complex pathways, regulation of TRPM8 presents possibilities for OAB treatment.ope

    Comparison Analysis Between Public and Private Industrial Complex Regeneration Project Type of the Clustering Effect

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ๋„์‹œ์„ค๊ณ„ํ•™์ „๊ณต, 2017. 2. ๊ถŒ์˜์ƒ.๊ณผ๊ฑฐ ๋ฒ ๋ฒ„์˜ ๊ณต์—…์ž…์ง€๋ก  ๋“ฑ์—์„œ ๋‹ค๋ฃจ์—ˆ๋“ฏ ๊ณต์—…์‹œ์„ค, ์‚ฐ์—…์‹œ์„ค ๋“ฑ์€ ์ง‘์ , ์ง‘๋‹จํ™” ๋˜์–ด ๋งŽ์€ ๊ฒฝ์ œ์  ์ด์ต์„ ์–ป์„ ์ˆ˜ ์žˆ๊ณ , ์ด์— ๋”ฐ๋ผ ์šฐ๋ฆฌ๋‚˜๋ผ ์‚ฐ์—…๋‹จ์ง€๊ฐ€ ์กฐ์„ฑ๋˜์–ด์™”๋‹ค. ํ•˜์ง€๋งŒ IMF ๊ฒฝ์ œ์œ„๊ธฐ๋ฅผ ๊ฒช์Œ๊ณผ ๋™์‹œ์— ๊ฐ์ข… ์ œ๋„๋ณ€ํ™” ๋“ฑ์„ ํ†ตํ•ด ์‚ฐ์—…์˜ ์ง‘์  ๋ฐ ์ง‘๋‹จํ™”๋ผ๋Š” ํ‹€์ด ๊นจ์ง€๊ณ  ์ด์— ๋”ฐ๋ผ ์ฃผ๋ณ€ ์—…์ข…์„ ๊ณ ๋ คํ•˜์ง€ ์•Š๋Š” ๊ฐœ๋ณ„์  ๊ฐœ๋ฐœ์ด ์ด๋ฃจ์–ด์ ธ ์™”๋‹ค. ์ด๋Ÿฌํ•œ ์‚ฐ์—…๋‹จ์ง€์˜ ํ™˜๊ฒฝ์„ ๊ฐœ์„ ํ•˜๊ณ ์ž ๊ตญ๊ฐ€์ฃผ๋„์˜ ์‚ฐ์—…๋‹จ์ง€ ์žฌ์ƒ์‚ฌ์—…์ด ์ด๋ฃจ์–ด์ง€๊ณ  ์žˆ๋‹ค. ํ•˜์ง€๋งŒ ๊ตญ๊ฐ€์ฃผ๋„์˜ ์‚ฌ์—…๋“ค์€ ๊ธฐ์กด์˜ ์‚ฐ์—…๋‹จ์ง€๋ฅผ ์ด๋ฃจ๋Š” ์ œ์กฐ์—… ๊ธฐ๋ฐ˜์˜ ์—…์ข…๊ณผ ์ƒ๊ด€์—†๋Š” ์˜คํ”ผ์Šคํ…”, ํ˜ธํ…”๋ถ„์–‘ ๋“ฑ์˜ ์ˆ˜์ต์„ฑ์œ„์ฃผ์˜ ์‚ฌ์—…๋“ค์ด ์ฃผ๋ฅผ ์ด๋ฃจ๊ณ  ์žˆ๊ณ  ์ด๋Š” ์‚ฐ์—…๋‹จ์ง€๊ฐ€ ์ฒ˜ํ•ด์žˆ๋Š” ๊ธฐ๋ณธ์ ์ธ ๋ฌธ์ œ์ ์„ ํ•ด๊ฒฐํ•˜์ง€ ๋ชปํ•˜๊ณ  ์žˆ๋‹ค. ๋”ฐ๋ผ์„œ ๋ฏผ๊ฐ„์ฐจ์›์—์„œ ์ด๋ฃจ์–ด์ง€๊ณ  ์žˆ๋Š” ์ œ์กฐ์—… ๊ธฐ๋ฐ˜์˜ ์‚ฐ์—…์‹œ์„ค์˜ ์ง‘๋‹จํ™” ์‚ฌ๋ก€๋ฅผ ๋ถ„์„ํ•˜๊ณ  ๊ฒฝ์ œ์ , ๊ณต๊ฐ„์ , ํ™˜๊ฒฝ์  ์ฐจ์›์—์„œ์˜ ์ด์ ์„ ๋„์ถœํ•˜์—ฌ ์ง‘๋‹จํ™”์˜ ํ•„์š”์„ฑ์„ ๋„์ถœํ•œ๋‹ค. ๋˜ํ•œ ๊ฐœ๋ณ„์  ๊ฐœ๋ฐœ๋ณด๋‹ค ์ง‘๋‹จํ™”๋ฅผ ํ†ตํ•œ ๊ฐœ๋ฐœ์˜ ํ•„์š”์„ฑ์„ ์ œ์‹œํ•œ ํ›„ ์–ด๋–ป๊ฒŒ ์„ฑ๊ณต์  ์ง‘๋‹จํ™”๋ฅผ ์ด๋ฅผ ์ˆ˜ ์žˆ์—ˆ๋Š”์ง€ ์š”์ธ์„ ๋ถ„์„ํ•˜์—ฌ ์‹œ์‚ฌ์ ์„ ๋„์ถœ ํ•˜์˜€๋‹ค. ๋จผ์ € ๊ณผ๊ฑฐ ๋ฒ ๋ฒ„์˜ ๊ณต์—…์ž…์ง€๋ก ์—์„œ๋Š” ์‚ฐ์—…์‹œ์„ค ์ง‘์ ์ด์ต์ด ์ฃผ๋กœ ๊ฒฝ์ œ์  ๋ถ€๋ถ„์—๋งŒ ํ•œ์ •๋˜์–ด ์žˆ์—ˆ๋‹ค. ํ•˜์ง€๋งŒ ๋ฏผ๊ฐ„์ฐจ์›์˜ ์„ธ ์‚ฌ๋ก€๋ฅผ ๋ถ„์„ํ•จ์œผ๋กœ ํ˜„์žฌ๋Š” ๊ฒฝ์ œ์ , ๊ณต๊ฐ„์ , ํ™˜๊ฒฝ์  ์ฐจ์›์—์„œ์˜ ์ด์ ์ด ์žˆ์Œ์„ ํ™•์ธํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. ๋”ฐ๋ผ์„œ ํ˜„ ์‹œ์ ์—์„œ ์‚ฐ์—…์‹œ์„ค์˜ ์ง‘๋‹จํ™”์— ๋Œ€ํ•œ ์žฌ๊ฒ€ํ† ๊ฐ€ ํ•„์š”ํ•จ์„ ํ™•์ธํ•˜์˜€๋‹ค. ๋˜ํ•œ ์‚ฐ์—…๋‹จ์ง€ ์žฌ์ƒ์—์„œ ๊ณต๊ณต์ฃผ๋„์™€ ๋ฏผ๊ฐ„์ฃผ๋„์˜ ์‚ฌ๋ก€๋ฅผ ๋น„๊ตํ•˜์—ฌ ๋ฏผ๊ฐ„์ฃผ๋„์—์„œ ์„ฑ๊ณต์  ์ง‘๋‹จํ™”๋ฅผ ์ด๋ฃฐ ์ˆ˜ ์žˆ์—ˆ๋˜ ์š”์ธ์„ ๋น„๊ต ๋ถ„์„ํ•˜์—ฌ ์‹œ์‚ฌ์ ์„ ๋„์ถœ ํ•˜์˜€๋‹ค. ์ฒซ ๋ฒˆ์งธ, ๋šœ๋ ทํ•œ ๋ชฉํ‘œ์ด๋‹ค. ๊ฐœ์ธ ๋ฐ ์ง‘๋‹จ์ด ์ง‘๋‹จํ™”์— ๋Œ€ํ•œ ๋šœ๋ ทํ•œ ๋ชฉํ‘œ๋ฅผ ๊ฐ€์ง€๊ณ  ์ถ”์ง„ํ•˜์˜€๊ณ , ์ฃผ์ธ์˜์‹์„ ๊ฐ€์ง€๊ณ  ์ง„ํ–‰ํ•˜์˜€๋‹ค๋Š” ์ ์ด ์„ฑ๊ณต์  ์ง‘๋‹จํ™”๋ฅผ ์ด๋ฃฐ ์ˆ˜ ์žˆ๋Š” ๊ฐ€์žฅ ์ค‘์š”ํ•œ ์š”์†Œ์˜€๋‹ค. ๋‘ ๋ฒˆ์งธ, ๊ตฌ์ฒด์  ๊ธฐ์ˆ ์ด๋‹ค. ์„ธ ๊ฐ€์ง€ ์‚ฌ๋ก€๋ฅผ ๋ถ„์„ํ•จ์— ๋”ฐ๋ผ ๋ชจ๋‘ ๋šœ๋ ทํ•œ ๋ชฉํ‘œ๋ฅผ ๋‹ฌ์„ฑํ•˜๊ธฐ ์œ„ํ•œ ๊ตฌ์ฒด์  ๊ธฐ์ˆ ์ด ๋’ท ๋ฐ›์นจ ๋˜์—ˆ์Œ์„ ํ™•์ธํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. ๊ฐ ์—…์ข…๋ณ„๋กœ ๊ตฌ์ฒด์  ๊ธฐ์ˆ ์„ ๊ฐ€์ง€๊ณ  ์žˆ์—ˆ๊ธฐ์— ์ฐธ์—ฌ์—…์ฒด ๋ชจ์ง‘ ๋ฐ ์šด์˜์— ์žˆ์–ด ํšจ์œจ์ ์œผ๋กœ ์ง„ํ–‰๋  ์ˆ˜ ์žˆ์—ˆ๋‹ค. ๋”ฐ๋ผ์„œ ์–ด๋–ค ๊ธฐ์ˆ ์„ ๋„์ž…ํ•˜์—ฌ ์ง‘๋‹จํ™” ํ•˜์˜€์„ ๋•Œ ์–ด๋–ค ๋ฐฉ์‹์œผ๋กœ ์›๊ฐ€์ ˆ๊ฐ ๋ฐ ์ˆ˜์ต์ฐฝ์ถœ์„ ์ด๋ฃฐ ๊ฒƒ์ธ๊ฐ€์— ๋Œ€ํ•œ ๊ตฌ์ฒด์  ๊ธฐ์ˆ ์ด ์ค‘์š”ํ•œ ์š”์ธ์ž„์„ ํ™•์ธํ•˜์˜€๋‹ค. ์„ธ ๋ฒˆ์งธ, ์ปค๋ฎค๋‹ˆ์ผ€์ด์…˜์ด๋‹ค. ์ฐธ์—ฌ ์—…์ฒด ๊ฐ„ ์ ๊ทน์  ์ปค๋ฎค๋‹ˆ์ผ€์ด์…˜์ด ์ž˜ ์ด๋ฃจ์–ด ์กŒ๋‹ค๋Š” ์ ์ด์—ˆ๋‹ค. ์ด๋Š” ์กฐ์„ฑ๊ณผ์ • ๋ฟ๋งŒ ์•„๋‹ˆ๋ผ ์กฐ์„ฑ ํ›„์—๋„ ์ง€์†์ ์œผ๋กœ ์ด๋ฃจ์–ด์ง€๋Š” ๊ฒƒ์„ ์˜๋ฏธํ•œ๋‹ค. ํŠนํžˆ ์ง‘๋‹จํ™”๋ผ๋Š” ๊ฒƒ์ด ๊ธฐ์ˆ , ์žฅ๋น„ ๋ฟ๋งŒ ์•„๋‹ˆ๋ผ ๊ณต๊ฐ„์„ ๊ณต์œ ํ•˜๊ฒŒ ๋˜๊ณ , ์ด๋Š” ๊ณต์ƒ์˜ ์ฐจ์›์—์„œ ์ค‘์š”ํ•จ์„ ํ™•์ธํ•  ์ˆ˜ ์žˆ๋‹ค.1. ์„œ๋ก  1 1.1 ์—ฐ๊ตฌ์˜ ๋ฐฐ๊ฒฝ ๋ฐ ๋ชฉ์  1 1.2 ์—ฐ๊ตฌ์˜ ๋ฐฉ๋ฒ• 3 1.3 ๊ด€๋ จ์„ ํ–‰์—ฐ๊ตฌ ๋ฐ ์ฐจ๋ณ„์„ฑ 4 1.4 ์—ฐ๊ตฌ์˜ ํ๋ฆ„ 5 2. ์ด๋ก ์  ๊ณ ์ฐฐ 6 2.1 ์‚ฐ์—…๋‹จ์ง€์ด๋ก  ๊ณ ์ฐฐ 6 2.2 ์ „๊ตญ์‚ฐ์—…๋‹จ์ง€ ํ˜„ํ™ฉ 8 2.3 ๋…ธํ›„์‚ฐ์—…๋‹จ์ง€ ํ˜„ํ™ฉ 10 3. ๊ณต๊ณต์ฃผ๋„ ์‚ฐ์—…๋‹จ์ง€ ์žฌ์ƒ์‚ฌ์—…์˜ ์ง‘๋‹จํ™” 12 3.1 ๊ณต๊ณต์ฃผ๋„ ์‚ฐ์—…๋‹จ์ง€ ์žฌ์ƒ์‚ฌ์—… ๊ฐœ์š” 12 3.1.1 ๊ณต๊ณต์ฃผ๋„ ์‚ฐ์—…๋‹จ์ง€ ์žฌ์ƒ์‚ฌ์—… ๊ตฌ๋ถ„ 12 3.1.2 ๊ณต๊ณต์ฃผ๋„ ์‚ฐ์—…๋‹จ์ง€ ์žฌ์ƒ์‚ฌ์—… ์œ ํ˜•๋ณ„ ๊ฐœ์š” 14 3.1.3 ๊ณต๊ณต์ฃผ๋„ ์‚ฐ์—…๋‹จ์ง€ ์žฌ์ƒ์‚ฌ์—… ํ˜„ํ™ฉ 19 3.2 ๊ณต๊ณต์ฃผ๋„ ์‚ฐ์—…๋‹จ์ง€ ์žฌ์ƒ์‚ฌ์—… ํŠน์„ฑ 21 3.2.1 ๋ฐ˜์›”์‹œํ™”์‚ฐ์—…๋‹จ์ง€ 21 3.2.2 ๋‚จ๋™๊ตญ๊ฐ€์‚ฐ์—…๋‹จ์ง€ 23 3.2.3 ๊ตฌ๋ฏธ๊ตญ๊ฐ€์‚ฐ์—…๋‹จ์ง€ 25 3.2.4 ์†Œ๊ฒฐ 27 3.3 ๊ณต๊ณต์ฃผ๋„ ์‚ฐ์—…๋‹จ์ง€ ์žฌ์ƒ์‚ฌ์—… ๋ฌธ์ œ์  28 4. ๋ฏผ๊ฐ„์ฃผ๋„ ์‚ฐ์—…๋‹จ์ง€ ์žฌ์ƒ์‚ฌ์—…์˜ ์ง‘๋‹จํ™” 30 4.1 ๋ฏผ๊ฐ„์ฃผ๋„ ์‚ฐ์—…๋‹จ์ง€ ์žฌ์ƒ์‚ฌ์—… ๊ฐœ์š” 30 4.2 ๋ฏผ๊ฐ„์ฃผ๋„ ์‚ฐ์—…๋‹จ์ง€ ์žฌ์ƒ์‚ฌ์—… ํŠน์„ฑ 31 4.2.1 ์•ˆ์‚ฐ์—์ฝ”๊ทธ๋ฆฐ์„ผํ„ฐ 31 4.2.2 ๋ถ€์‚ฐํŒจ์…˜์นผ๋ผ์‚ฐ์—… 39 4.2.3 ๋ถ€์‚ฐ์กฐ์„ ํ•ด์–‘๊ธฐ์ž์žฌ ์กฐํ•ฉ 43 4.2.4 ์†Œ๊ฒฐ 47 4.3 ๊ณต๊ณต์ฃผ๋„ ๋ฐ ๋ฏผ๊ฐ„์ฃผ๋„ ์ง‘๋‹จํ™” ํšจ๊ณผ ๋น„๊ต 49 4.3.1 ์ง‘๋‹จํ™” ํšจ๊ณผ๋น„๊ต 49 4.3.2 ์‹œ์‚ฌ์  ๋„์ถœ 52 5. ๊ฒฐ๋ก  53 5.1 ์—ฐ๊ตฌ์˜ ์š”์•ฝ 53 5.2 ์—ฐ๊ตฌ์˜ ์˜์˜ ๋ฐ ํ•œ๊ณ„ 55 ์ฐธ๊ณ ๋ฌธํ—Œ 56 ๋ถ€๋ก 58 Abstract 60Maste

    Is it necessary to repeat videourodynamic studies on children?

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    ์˜ํ•™๊ณผ/์„์‚ฌ์š”์—ญ๋™ํ•™๊ฒ€์‚ฌ์˜ ๊ธฐ๋ณธ ๋ชฉ์ ์€ ๊ฒ€์‚ฌํ•˜๋Š” ๋™์•ˆ ํ™˜์ž์˜ ์ฆ์ƒ์„ ์žฌํ˜„ํ•˜๊ณ , ํ™˜์ž์˜ ์ฆ์ƒ๊ณผ ์š”์—ญ๋™ํ•™๊ฒ€์‚ฌ ๊ฒฐ๊ณผ๋ฅผ ์—ฐ๊ด€์‹œ์ผœ ์„ค๋ช…ํ•˜๋Š”๋ฐ ์žˆ๋‹ค. ํ•˜๋ถ€์š”๋กœ์ฆ์ƒ์„ ํ˜ธ์†Œํ•˜๋Š” ํ™˜์ž์—์„œ ์ฆ์ƒ์€ ๋Œ€๋‹จํžˆ ์ค‘์š”ํ•˜์ง€๋งŒ ์ฆ์ƒ๋“ค์ด ์ข…์ข… ์ž˜๋ชป ํ•ด์„๋˜๋Š” ๊ฒฝ์šฐ๊ฐ€ ๋งŽ๊ธฐ ๋•Œ๋ฌธ์— ์ฃผ์˜๋ฅผ ๊ธฐ์šธ์—ฌ์•ผ ํ•œ๋‹ค. ํŠนํžˆ ์†Œ์•„ ํ™˜์ž์˜ ๊ฒฝ์šฐ ํ˜‘์กฐ๊ฐ€ ์•ˆ๋˜๊ณ  ์ฆ์ƒ ํ‘œํ˜„์— ์–ด๋ ค์›€์ด ์žˆ์–ด ๋”์šฑ ๋” ์ฃผ์˜๋ฅผ ๊ธฐ์šธ์—ฌ์•ผ ํ•œ๋‹ค. ์ •ํ™•ํ•œ ๊ฒ€์‚ฌ ๊ฒฐ๊ณผ๋ฅผ ์–ป๊ธฐ ์œ„ํ•ด์„œ๋Š” International Childrenโ€™s Continence Society (ICCS)์—์„œ๋Š” ๋‘ ๋ฒˆ์˜ ๊ฒ€์‚ฌ๋ฅผ ๊ถŒ์œ ํ•˜๊ณ  ์žˆ๋‹ค. ๋น„๋””์˜ค์š”์—ญ๋™ํ•™๊ฒ€์‚ฌ๋Š” ๋ฐฉ์‚ฌ์„  ํˆฌ์‹œ์™€ ํ•จ๊ป˜ ์š”์—ญ๋™ํ•™๊ฒ€์‚ฌ๋ฅผ ์‹œํ–‰ํ•˜๋Š” ๊ฒƒ์œผ๋กœ ํ•˜๋ถ€์š”๋กœ๊ธฐ๋Šฅ์„ ์ดํ•ดํ•˜๋Š”๋ฐ ๋„์›€์„ ์ค€๋‹ค. ๋ณธ ์—ฐ๊ตฌ๋Š” ์‹ ๊ฒฝํƒ“๋ฐฉ๊ด‘, ๋น„์‹ ๊ฒฝํƒ“๋ฐฉ๊ด‘ ํ™˜์ž๊ตฐ์œผ๋กœ ๋‚˜๋ˆ„์–ด ๋น„๋””์˜ค์š”์—ญ๋™ํ•™๊ฒ€์‚ฌ์˜ ๋ฐ˜๋ณต ๊ฒ€์‚ฌ๊ฐ€ ํ•„์š”ํ•œ์ง€ ์•Œ์•„๋ณด๊ณ ์ž ํ•˜์˜€๋‹ค. ์ด 126๋ช…์˜ ํ™˜์•„๋ฅผ ๋Œ€์ƒ์œผ๋กœ ํ•˜์˜€์œผ๋ฉฐ ๊ธฐ์ €์งˆํ™˜์— ๋”ฐ๋ผ ์ด๋ถ„์ฒ™์ถ”์ฆ 48๋ช…, ์•ผ๋‡จ์ฆ 38๋ช…, ๋ฐฉ๊ด‘์š”๊ด€์—ญ๋ฅ˜ 40๋ช…์ด ์—ฐ๊ตฌ์— ํฌํ•จ๋˜์—ˆ๋‹ค. ๋ฐ˜๋ณต ๊ฒ€์‚ฌ ๊ฐ„ ๋ฐฉ๊ด‘์šฉ์ , ์ตœ๋Œ€๋ฐฉ๊ด‘์ˆ˜์ถ•๋ ฅ, ์ž”๋‡จ๋Ÿ‰์—์„œ๋Š” ํ†ต๊ณ„ํ•™์ ์œผ๋กœ ์œ ์˜ํ•œ ์ฐจ์ด๋ฅผ ๋ณด์ด์ง€ ์•Š์•˜๋‹ค. ๋ถˆ์ˆ˜์˜๋ฐฐ๋‡จ๊ทผ์ˆ˜์ถ•์€ ์ฒซ ๋ฒˆ์งธ ๊ฒ€์‚ฌ์™€ ๋‘ ๋ฒˆ์งธ ๊ฒ€์‚ฌ์—์„œ ๋ชจ๋‘ ๊ด€์ฐฐ๋˜์ง€ ์•Š๋Š” ๊ฒฝ์šฐ๊ฐ€ 60๋ก€ (47.6%), ๋ฐ˜๋ณต ๊ฒ€์‚ฌ์—์„œ ๋ชจ๋‘ ๊ด€์ฐฐ๋œ ๊ฒฝ์šฐ๊ฐ€ 36๋ก€ (28.6%)์˜€๋‹ค. ๋ถˆ์ˆ˜์˜๋ฐฐ๋‡จ๊ทผ์ˆ˜์ถ•์ด ์ฒซ ๋ฒˆ์งธ ๊ฒ€์‚ฌ์—์„œ ๊ด€์ฐฐ๋˜์—ˆ์œผ๋‚˜ ๋‘ ๋ฒˆ์งธ ๊ฒ€์‚ฌ์—์„œ ๊ด€์ฐฐ๋˜์ง€ ์•Š์€ ๊ฒฝ์šฐ๊ฐ€ 21๋ก€ (16.7%)๋กœ ์ด๋ถ„์ฒ™์ถ”์ฆ ํ™˜์ž 9๋ก€, ์•ผ๋‡จ์ฆ 9๋ก€, ๋ฐฉ๊ด‘์š”๊ด€์—ญ๋ฅ˜ 3๋ก€์˜€๋‹ค. ๋‘ ๋ฒˆ์งธ ๊ฒ€์‚ฌ์—์„œ ์ƒˆ๋กœ ๊ด€์ฐฐ๋œ ๋ถˆ์ˆ˜์˜๋ฐฐ๋‡จ๊ทผ์ˆ˜์ถ•์€ ์•ผ๋‡จ์ฆ 6๋ก€, ๋ฐฉ๊ด‘์š”๊ด€์—ญ๋ฅ˜ 3๋ก€์˜€์œผ๋ฉฐ ์ด๋ถ„์ฒ™์ถ”์ฆ ํ™˜์•„๋Š” ์—†์—ˆ๋‹ค. 1๋…„ ์ด์ƒ ์ถ”์ ๊ด€์ฐฐ์ด ๊ฐ€๋Šฅํ•œ ํ™˜์ž ์ค‘ ์ฒซ ๋ฒˆ์งธ ๋ถˆ์ˆ˜์˜๋ฐฐ๋‡จ๊ทผ์ˆ˜์ถ•์ด ๊ด€์ฐฐ๋˜๊ณ  ๋‘ ๋ฒˆ์งธ ๊ด€์ฐฐ๋˜์ง€ ์•Š์€ ์ด๋ถ„์ฒ™์ถ”์ฆ ํ™˜์•„ 9๋ก€ ์ค‘ 6๋ก€์—์„œ ์—ฌ์ „ํžˆ ๋ถˆ์ˆ˜์˜๋ฐฐ๋‡จ๊ทผ์ˆ˜์ถ•์ด ๊ด€์ฐฐ๋˜์—ˆ๊ณ  ๋ฐฉ๊ด‘์š”๊ด€์—ญ๋ฅ˜ ํ™˜์•„ 3๋ก€ ์ค‘ 2๋ก€์—์„œ ๊ณผ๋ฏผ์„ฑ๋ฐฉ๊ด‘ ์ฆ์ƒ์œผ๋กœ ์น˜๋ฃŒ์ค‘์ด๋‹ค. ๋‘ ๋ฒˆ์งธ ๊ฒ€์‚ฌ์—์„œ ๋ถˆ์ˆ˜์˜๋ฐฐ๋‡จ๊ทผ์ˆ˜์ถ•์ด ์ƒˆ๋กœ ๊ด€์ฐฐ๋œ ๊ฒฝ์šฐ๋Š” ๋ชจ๋‘ ๋ฐฉ๊ด‘์„ฑ์ˆ™์ด ์™„์„ฑ๋œ 5์„ธ ์ด์ƒ์˜ ๋น„์‹ ๊ฒฝํƒ“๋ฐฉ๊ด‘ ํ™˜์•„์—์„œ ๊ด€์ฐฐ๋œ ๊ฒฝ์šฐ๋กœ ์ด๋Š” ๊ฒ€์‚ฌ๋กœ ์œ ๋ฐœ๋˜์—ˆ์„ ๊ฒƒ์œผ๋กœ ์‚ฌ๋ฃŒ๋œ๋‹ค. ์ด์ƒ ์—ฐ๊ตฌ๋ฅผ ํ† ๋Œ€๋กœ ์†Œ์•„ ๋น„๋””์˜ค์š”์—ญ๋™ํ•™๊ฒ€์‚ฌ์—์„œ ๋ฐ˜๋ณต ๊ฒ€์‚ฌ๋Š” ์ด๋ถ„์ฒ™์ถ”์ฆ ํ™˜์•„์—์„œ๋Š” ์˜๋ฏธ๊ฐ€ ์—†์„ ๊ฒƒ์œผ๋กœ ์ƒ๊ฐ๋˜๋ฉฐ 5์„ธ์ด์ƒ์˜ ๋น„์‹ ๊ฒฝํƒ“๋ฐฉ๊ด‘ ํ™˜์•„์—์„œ๋Š” ์ถ”๊ฐ€์ ์œผ๋กœ ์—ฐ๊ตฌ๊ฐ€ ํ•„์š”ํ•  ๊ฒƒ์œผ๋กœ ์ƒ๊ฐ๋œ๋‹ค.ope

    ํ•™์ƒ๋“ค์˜ ํ”ผ๋“œ๋ฐฑ์ด ์˜์–ด ๊ต์‚ฌ๋“ค์˜ ์‹œํ—˜ ์ค€๋น„์™€ ์‹œํ–‰์— ๋ฏธ์น˜๋Š” ์˜ํ–ฅ

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ์™ธ๊ตญ์–ด๊ต์œก๊ณผ(์˜์–ด์ „๊ณต), 2012. 8. ๊ถŒ์˜ค๋Ÿ‰.๋ณธ ์—ฐ๊ตฌ๋Š” ํŠน์ •ํ•™๊ต์—์„œ ๊ต์‚ฌ๋“ค์ด ์ง‘ํ•„ํ•œ ์‹œํ—˜๋ฌธ์ œ์˜ ์งˆ์„ ํ‰๊ฐ€ํ•˜๊ณ  ์‹œํ—˜ ๋ฌธ์ œ์˜ ์งˆ์ด ํ•™์ƒ๋“ค์˜ ์‹œํ—˜์— ๋Œ€ํ•œ ํ”ผ๋“œ๋ฐฑ์— ์˜ํ•ด ์–ผ๋งˆ๋‚˜ ํ–ฅ์ƒ๋  ์ˆ˜ ์žˆ๋Š”๊ฐ€๋ฅผ ์‚ดํŽด๋ณด์•˜๋‹ค. ํŠนํžˆ ๋ณธ ์—ฐ๊ตฌ๋Š” 1) ํ•™์ƒ๋“ค์ด ๊ต์‚ฌ๋“ค์˜ ์‹œํ—˜์— ์–ด๋–ป๊ฒŒ ๋ฐ˜์‘ํ•˜๋Š”์ง€, 2) ํ•™์ƒ๋“ค์˜ ํ”ผ๋“œ๋ฐฑ์ด ๊ต์‚ฌ๋“ค์˜ ์‹œํ—˜์— ๋Œ€ํ•œ ์ธ์‹๊ณผ ์‹œํ—˜ ์ถœ์ œ ๊ณผ์ •์— ์–ด๋–ค ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š”์ง€, 3) ์‹œํ—˜ ๋ฌธ์ œ์˜ ์งˆ์ด ํ•™์ƒ๋“ค์˜ ํ”ผ๋“œ๋ฐฑ์— ์˜ํ–ฅ์„ ๋ฐ›์•„ ์‹ค์ œ๋กœ ๋” ๋‚˜์•„์ง€๋Š”์ง€๋ฅผ ์—ฐ๊ตฌํ•˜์˜€๋‹ค. ์•ฝ 760๋ช…์˜ ๊ณ ๋“ฑํ•™๊ต 1ํ•™๋…„ ํ•™์ƒ๋“ค์ด ์ค‘๊ฐ„๊ณ ์‚ฌ์™€ ๊ธฐ๋ง๊ณ ์‚ฌ ์‹œํ—˜์— ์‘์‹œํ•˜์˜€์œผ๋ฉฐ, ๊ทธ ์ค‘ 115๋ช…์˜ ํ•™์ƒ๋“ค์ด ์‹œํ—˜ ํ›„ ํ”ผ๋“œ๋ฐฑ ์„ค๋ฌธ์ง€๋ฅผ ์ž‘์„ฑํ•˜์˜€๋‹ค. ๋„ค ๋ช…์˜ ๊ณ ๋“ฑํ•™๊ต ์˜์–ด ๊ต์‚ฌ๋“ค์ด ์—ฐ๊ตฌ์— ์ฐธ์—ฌํ•˜์˜€์œผ๋ฉฐ ๊ทธ๋“ค์€ ์‹œํ—˜ ํ›„์— ๋‘ ๋ฒˆ์˜ ํ”ผ๋“œ๋ฐฑ ๋ชจ์ž„์„ ๊ฐ€์ง€๊ณ  ํ•™์ƒ๋“ค์˜ ํ”ผ๋“œ๋ฐฑ๊ณผ ์‹œํ—˜ ๊ฒฐ๊ณผ๋ฅผ ์‚ดํŽด๋ณด์•˜๋‹ค. ๋ณธ ์—ฐ๊ตฌ์˜ ์ฃผ์š” ๋ชฉ์ ์€ ๊ต์‚ฌ๋“ค์˜ ์‹œํ—˜์— ๋Œ€ํ•œ ์ธ์‹๊ณผ ๊ด€์Šต์ด ํ•™์ƒ๋“ค์˜ ํ”ผ๋“œ๋ฐฑ์— ์˜ํ–ฅ์„ ๋ฐ›์•„ ๋ณ€ํ•˜๋Š”๊ฐ€๋ฅผ ์‚ดํŽด๋ณด๋Š” ๊ฒƒ์ด์—ˆ๋‹ค. ์ „๋ฐ˜์ ์ธ ๊ฒฐ๊ณผ๋Š” ๋‹ค์Œ๊ณผ ๊ฐ™๋‹ค. 1. ํ•™์ƒ๋“ค์˜ ํ•™๊ต ์‹œํ—˜ ๊ณต์ •์„ฑ(test fairness)์— ๋Œ€ํ•œ ํƒœ๋„๋Š” ๊ธฐ๋ง๊ณ ์‚ฌ์—์„œ ๋‚˜์•„์กŒ์Œ์—๋„ ๋ถˆ๊ตฌํ•˜๊ณ  ๊ธ์ •์ ์ด์ง€ ์•Š์•˜๋‹ค. ํ•™์ƒ๋“ค์ด ์ธ์‹ํ•œ ๊ฐ ๋ฌธ์ œ์— ๋Œ€ํ•œ ๋‚œ์ด๋„, ๋ณ€๋ณ„๋„, ํ˜•์‹์ ํ•ฉ๋„ ๋ฐ ๋…ผํ‰์€ ๊ต์‚ฌ๋“ค์ด ๊ทธ๋“ค์˜ ์‹œํ—˜์„ ๊ฐœ์„ ํ•  ์ˆ˜ ์žˆ๋Š” ์œ ์šฉํ•œ ํ†ต์ฐฐ๋ ฅ์„ ์ œ๊ณตํ•˜์˜€๋‹ค. ํ•™์ƒ๋“ค์€ ๊ฐ๊ด€์‹ ๋ฌธ์ œ๋ณด๋‹ค ์„œ์ˆ ํ˜• ๋ฌธ์ œ์— ๋” ๋งŽ์€ ๋…ผํ‰์„ ํ•˜์˜€๋Š”๋ฐ, ์ด๋Š” ์„œ์ˆ ํ˜• ๋ฌธ์ œ๊ฐ€ ๋” ๋งŽ์€ ๋ณด์™„๊ณผ ์ˆ˜์ •์„ ํ•„์š”๋กœ ํ•จ์„ ์•”์‹œํ•œ๋‹ค. 2. ๊ต์‚ฌ๋“ค์˜ ์‹œํ—˜์— ๋Œ€ํ•œ ์ธ์‹๊ณผ ๊ด€์Šต์€ ์—ฐ๊ตฌ๋ฅผ ํ†ตํ•ด ๋งŽ์€ ๋ณ€ํ™”๋ฅผ ๋ณด์—ฌ์ฃผ์—ˆ๋‹ค. ํ•™์ƒ๋“ค์˜ ์ค‘๊ฐ„๊ณ ์‚ฌ์— ๋Œ€ํ•œ ํ”ผ๋“œ๋ฐฑ์„ ํ†ตํ•ด ๊ต์‚ฌ๋“ค์€ ์‹œํ—˜์˜ ์•ฝ์ ์„ ์•Œ์•„๋‚ด๊ณ  ์–ด๋–ป๊ฒŒ ๊ณ ์น ์ง€๋ฅผ ์˜๋…ผํ•˜์˜€๋‹ค. ๊ทธ๋“ค์ด ๋…ผ์˜ํ•œ ์ ์„ ๊ธฐ๋ง๊ณ ์‚ฌ ์ถœ์ œ์— ์‹คํ–‰ํ•จ์œผ๋กœ์จ, ๊ธฐ๋ง๊ณ ์‚ฌ์˜ ์งˆ์ด ์‹ค์ œ๋กœ ํ–ฅ์ƒ๋˜์—ˆ๋‹ค. ๊ต์‚ฌ๋“ค์€ ํ”ผ๋“œ๋ฐฑ ํšŒ์˜๊ฐ€ ๊ทธ๋“ค์˜ ์‹œํ—˜์ด ์–ด๋– ํ•œ์ง€, ์–ด๋–ป๊ฒŒ ๊ณ ์น ์ง€, ๋‚˜์•„๊ฐ€ ๊ทธ๋“ค์˜ ๋…ธ๋ ฅ์ด ์–ด๋–ค ๊ฒฐ๊ณผ๋ฅผ ๊ฐ€์ ธ์˜ฌ์ง€๋ฅผ ๊นจ๋‹ซ๊ฒŒ ํ•ด์ค€๋‹ค๋Š” ์ ์—์„œ ๋งค์šฐ ๊ธ์ •์ ์ธ ํƒœ๋„๋ฅผ ๋ณด์˜€๋‹ค. 3. ์‹œํ—˜ ๊ฒฐ๊ณผ์— ๋Œ€ํ•œ ๋ถ„์„์€ ๊ธฐ๋ง๊ณ ์‚ฌ์˜ ๊ฐ๊ด€์‹ ๋ฌธ์ œ๊ฐ€ ์งˆ์ ์œผ๋กœ ํ–ฅ์ƒ๋˜์—ˆ์Œ์„ ๋ณด์—ฌ์ฃผ์—ˆ๋‹ค. ์ด๊ฒƒ์€ ํ•™์ƒ๋“ค์˜ ํ”ผ๋“œ๋ฐฑ์ด ์‹ค์ œ๋กœ ๊ต์‚ฌ๋“ค์ด ๊ทธ๋“ค์˜ ์‹œํ—˜์„ ๊ฐœ์„ ํ•˜๋Š” ๊ฒƒ์„ ๋„์™”๋‹ค๋Š” ๊ฒƒ์„ ์˜๋ฏธํ•œ๋‹ค. ๋ฐ˜๋ฉด, ๊ต์‚ฌ๋“ค์˜ ์„œ์ˆ ํ˜• ๋ฌธ์ œ ์ •๋‹ต๋ฅ ์„ ๋†’์ด๊ณ ์ž ํ•œ ๋…ธ๋ ฅ์€ ์›ํ•˜๋Š” ๊ฒฐ๊ณผ๋ฅผ ์–ป์ง€ ๋ชปํ•˜์˜€๋‹ค. ์ „๋ฐ˜์ ์œผ๋กœ, ๊ต์‚ฌ๋“ค์ด ์ถœ์ œํ•œ ๋งŽ์€ ๋ฌธ์ œ๋“ค์ด ๋„ˆ๋ฌด ์‰ฝ๊ฑฐ๋‚˜ ๋„ˆ๋ฌด ์–ด๋ ค์› ๋˜ ๊ฒƒ์œผ๋กœ ๋ฐํ˜€์ ธ ๊ต์‚ฌ๋“ค์˜ ์‹œํ—˜ ๋ฌธ์ œ ๊ฐœ์„ ์— ๋Œ€ํ•œ ๋” ๋งŽ์€ ๋…ธ๋ ฅ์ด ํ•„์š”ํ•จ์ด ๋“œ๋Ÿฌ๋‚ฌ๋‹ค. ์ด๋Ÿฌํ•œ ๊ฒฐ๊ณผ๋“ค์€ ํ•™์ƒ๋“ค์˜ ํ”ผ๋“œ๋ฐฑ์ด ๊ต์‚ฌ๋“ค์˜ ์‹œํ—˜์„ ๊ฐœ์„ ํ•˜๋Š”๋ฐ ์œ ์šฉํ•œ ๋„๊ตฌ๊ฐ€ ๋  ์ˆ˜ ์žˆ์Œ์„ ๋ณด์—ฌ์ค€๋‹ค. ๋”ฐ๋ผ์„œ ์˜์–ด ๊ต์‚ฌ๋“ค ์‚ฌ์ด์—์„œ ํ•™์ƒ๋“ค์˜ ํ”ผ๋“œ๋ฐฑ์„ ์–ป์–ด, ์ด์šฉํ•˜๊ณ ์ž ํ•˜๋Š” ๋” ๋งŽ์€ ๋…ธ๋ ฅ์ด ํ•„์š”ํ•˜๋‹ค. ๊ต์‚ฌ๋“ค์˜ ์‹œํ—˜์˜ ์ค‘์š”์„ฑ ์ธ์‹๊ณผ ํ‰๊ฐ€์— ๋Œ€ํ•œ ๊พธ์ค€ํ•œ ๋งž์ถค์‹ ๊ต์‚ฌ ์—ฐ์ˆ˜ ๋ฐ ํ›ˆ๋ จ์ด ๋˜ํ•œ ์ด๋ฃจ์–ด์ ธ์•ผ ํ•˜๊ฒ ๋‹ค.The present study investigated the quality of teacher-made tests in one specific school and explored how it could be improved with the students feedback on the test. Specifically, the study attempted to examine 1) how students react to the quality of teacher-made tests, 2) how the students feedback influences their teachers awareness and practice on testing, and 3) how the teacher-made tests improve after the students feedback. About 760 students in the tenth grade took midterm and final exams, and among them, 115 students answered the questionnaires on both tests. Four Korean high school English teachers produced the exams and they had two feedback sessions in which they discussed the test results and students feedback. The primary purpose of this study was to investigate whether the teachers testing awareness levels and practices had changed affected by the students feedback. The overall findings from the study are as follows: 1. Students attitudes to the test fairness in both tests were not positive despite the significant improvement in the final exam. Perceived item difficulty, validity, form appropriacy and written comments by students gave useful insights for teachers to revise their tests. Compared to the multiple-choice items, students commented more on the supply-type items, which indicates that the supply-type items needed more revision and improvement. 2. Teachers awareness and practices on testing showed significant changes throughout the study. Due to the students feedback on the midterm exam, they found the weak points of their test and discussed how to change them. By practicing what they discovered on the midterm exam, they saw some improvement in the quality of the final exam. Teachers attitudes towards the feedback sessions were very positive in that they realized how their tests were perceived, understood how to change them, and recognized the results that can be brought forth by their efforts. 3. There were some improvements in the quality of the multiple-choice items in the item analyses of the final exam. This indicated that the students feedback indeed helped the teachers improve their test. On the other hand, teachers efforts to raise students scores on the supply-type items did not bring forth the expected results. Overall, many items constructed by the teachers were too easy or too difficult, indicating the necessity for more revision and modification by the teachers. These findings suggest that student feedback can be a useful tool for teachers to improve their tests. Thus, there should be more efforts among English teachers to obtain students feedback on exams and utilize it. The need for teachers to recognize the importance of testing and continuous and tailored teacher training on assessments is also suggested.ABSTRACT i TABLE OF CONTENTS iii LIST OF TABLES vii CHAPTER 1. INTRODUCTION 1 1.1. The Purpose of the Study 1 1.2. The Significance of the Study 3 1.3. Research Questions 4 1.4. Organization of the Thesis 5 CHAPTER 2. LITERATURE REVIEW 6 2.1. Theoretical Background 6 2.2. Research on Teacher-made Test 10 2.3. Research on Test-taker Feedback 14 CHAPTER 3. METHODOLOGY 18 3.1. Context of the School 18 3.2. Participants 21 3.2.1. Test Writers 21 3.2.2. Test Takers 22 3.3. Materials 23 3.3.1. The School Exam Papers 23 3.3.2. The Logs of the Feedback Sessions by the Teachers 25 3.3.3. Questionnaire for the Students 25 3.3.4. Questionnaire for the Teachers 27 3.4. Procedures 28 3.4.1. The Miderm Exam Preparation and Administration 28 3.4.2. Survey of the Students' Feedback on the Midterm Exam 29 3.4.3. The First Feedback Session by the Teachers . 29 3.4.4. The Final Exam Preparation and Administration 30 3.4.5. Survey of the Students' Feedback on the Final Exam 30 3.4.6. The Second Feedback Session by the Teachers 31 3.5. Data Analysis 31 CHAPTER 4. RESULTS AND DISCUSSION 33 4.1. The Teachers' Initial Stages of Testing Beliefs and Practices ................33 4.1.1. The Teachers' Eveluation of Themselves as Test Writers 34 4.1.2. Problems and Concersns about Test Writing 35 4.1.3. Experience in Teacher Training on Test Development 36 4.2. The Midterm Exam 37 4.2.1. The Teachers' Views on the Quality of the Midterm Exam 37 4.2.2. The Students' Feedback on the Midterm Exam 38 4.2.3. The First Feedback Session 46 4.3. The Final Exam 49 4.3.1. The Teachers' Views on the Quality of the Final Exam . 50 4.3.2. The Students' Feedback on the Final Exam 51 4.3.3. The Second Feedback Session . 59 4.3.4. The Teachers' Views on the Effects of the Feedback Sessions . 62 4.4. Results of the Statistical Analyses of the Exams 63 4.4.1. Descriptive Statistics of the Exam Scores 64 4.4.2. The Difficulty Indices of the Midterm and Final Exams 65 4.4.3. The Discrimination Indices of the Midterm and Final Exams 67 4.4.4. Distracter Analysis of the Midterm and Final Exams 70 4.4.5. Summary of the Findings 74 CHAPTER 5. CONCLUSION 76 5.1. Summary of the Research Findings and Implications 76 5.2. Limitations of the Study and Suggestions for Future Research 81 REFERENCES 83 APPENDICES 88 ABSTRACT IN KOREAN 112Maste

    ๊น€์˜์‚ผ ์ •๋ถ€์˜ ๊ด€์ฒญํ˜•์„ฑ์— ๊ด€ํ•œ ์—ฐ๊ตฌ : ์ „๋‹ฌยท์ด์ „ยทํ†ต์ œ๊ธฐ๊ด€์˜ ์ƒ๋Œ€์  ๋ณ€ํ™”

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ํ–‰์ •๋Œ€ํ•™์› :ํ–‰์ •ํ•™๊ณผ ํ–‰์ •ํ•™์ „๊ณต,1998.Maste

    ๊ฐ„ํ˜ธ์‚ฌ ๋…ธ๋™์‹œ์žฅ์˜ ์ˆ˜์š”๋…์ ์— ๋Œ€ํ•œ ์—ฐ๊ตฌ

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ๋ณด๊ฑด๋Œ€ํ•™์› :๋ณด๊ฑดํ•™๊ณผ,2000.Maste
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