17 research outputs found

    ๋‚จ๋…€ ํ‰๋“ฑ์˜ ์‹œ๊ฐ์—์„œ ๋ณธ ์กฐ์„ธ์ œ๋„์˜ ๊ฐœ์„ ๋ฐฉํ–ฅ

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ํ–‰์ •๋Œ€ํ•™์› :ํ–‰์ •ํ•™๊ณผ ์ •์ฑ…ํ•™์ „๊ณต,1995.Maste

    ์„ธํฌํˆฌ๊ณผ์„ฑ ํŽฉํƒ€์ด๋“œ์™€ ๊ธฐ๋Šฅ์„ฑ๋‹จ๋ฐฑ์งˆ์„ ์ด์šฉํ•œ ์„ธํฌ์ „๋‹ฌ๋ฌผ์งˆ ๊ฐœ๋ฐœ

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    ํ•™์œ„๋…ผ๋ฌธ(๋ฐ•์‚ฌ) -- ์„œ์šธ๋Œ€ํ•™๊ต๋Œ€ํ•™์› : ์ž์—ฐ๊ณผํ•™๋Œ€ํ•™ ํ™”ํ•™๋ถ€, 2021.8. ์žฅ์ •์šฐ.The cell membrane is an important barrier which protects the cells from the surroundings. The cell membrane is composed of lipid bilayer containing various membrane proteins and carbohydrates. This important structure works as a semi-permeable filter that manages the exchange of materials inside and outside the cells which means cells uptake materials very precisely and selectively. For examples, ions or small hydrophilic nutrients usually use specific channels or transporter proteins to enter the cells whereas hydrophilic macromolecules are unable to go in to the cells efficiently. This selective material transportation of cell membrane works as safeguard of the cells but at the same time, the cell membrane is the most challenging hurdles in developing therapeutic drugs using large-size molecules such as peptide, proteins, antibodies, or nucleic acids. To overcome the poor permeability of drugs, various drug delivery vehicles have been developed such as viruses, polymers, and nanoparticles. Cell penetrating peptides (CPPs), or protein transduction domains (PTDs), are short peptides that facilitate cellular uptake of various molecular cargoes. Since the transactivator of transcription (TAT) was firstly found as it has remarkable ability to across cell membrane, various artificial cell penetrating sequences have been developed and they have been widely used in various biological and therapeutic applications. In our lab, a new series of Leucine and Lysine rich ฮฑ-helical cell penetrating peptides, LK peptides (LKKLLKLLKKLLKLAG), was developed. Those peptides show the cell penetrating ability in the nanomolar range which is extremely efficient compared to conventional CPPs. Furthermore, in the previous research, I found that the cell penetrating ability dramatically increases as it became multimers and the ability is saturated when the sequence is repeated four times (LK-4). However, they do not have any special functions besides high cell penetrating ability across the cell membrane. In order to give special functions to LK peptides, I proposed to introduce affibody proteins to the LK sequences. Affibody molecules, a member of antibody mimetic families, are small proteins engineered to bind to a large number of target proteins or peptides with very high affinity. The first affibody protein was found on the surface protein โ€“ the protein A - of Staphylococcus aureus and it was found that the protein A contains five different triple helix domains (E, D, A, B, C), each showing great affinity to antibody. From the domain B of protein A, scientist artificially engineered protein domain Z which can specifically bind to Fc region of immunoglobulin G without affecting Fab region. After developing the first engineered affibody domain Z, a large number of affibody has been developed from domain Z through the phage display technique. In this thesis, two types of affibody proteins โ€“ domain Z (Zwt) and ZHER2:342 โ€“ were introduced LK sequences through simple DNA recombinant technology. As already mentioned above, domain Z of protein A is known to bind to Fc region of Immunoglobulin G (IgG) with high affinity (Kd= ~50nM). The first part of the thesis started from the hypothesis that domain Z can give the Fc-binding ability to LK sequences and the recombinant protein LK-domain Z can work as an extremely efficient IgG delivery vehicle at the nanomolar concentration range. Based on various experiments, I figured out that LK-domain Z proteins bind to Fc region of IgG at specific ratio and the proteins successfully deliver IgG across the live cell membrane at nanomolar concentrations without showing any toxicity. I also revealed the penetration mechanisms and kinetics of IgG/LK-domain Z complexes. Furthermore, as a proof-of-concept, I delivered anti- NF-ฮบB IgG to regulate specific signaling pathway of cancer cells and saw the possibility of LK-domain Z protein as an efficient IgG delivery vehicle for the future therapeutics. In the second part of the thesis, I overcame the critical limitations of various drug delivery vehicles โ€“ the lack of selectivity. Here, HER2-overexpressed breast cancer targeted cell penetrating peptide and therapeutics were developed using the affibody named ZHER2:342. ZHER2:342 is one of the affibody molecules which are derived from Domain Z from the phage display. With the changes of only 13 amino acids on the surface of domain Z, a new affibody โ€“ showing totally different characteristics to domain Z โ€“ was discovered. ZHER2:342 is known to bind to HER2 receptors (Kd= ~22pM) which are usually overexpressed on the membrane of many breast cancer cells and manage the proliferation of various cancer cells. In this study, ZHER2:342 was brought into LK-2 peptides (LKKLLKLLKKLLKL GGLKKLLKLLKKLLKLAG) through DNA recombinant technology to give them the selectivity against HER2-positive breast cancers and I named this protein as LK-2-ZHER2. As I predicted, LK-2-ZHER2 showed great targeting effect against HER2-overexpressed cells both in vitro and in vivo. Furthermore, with anti-cancer therapeutic, doxorubicin, LK-2-ZHER2 selectively killed HER2-overexpressed cells in vitro. Based on those two researches in this Ph.D thesis, it is very clear that simple introduction of affibody through DNA recombinant technology is a very simple and easy way to give special function to cell penetrating peptides. Since large number of affibody proteins were developed and are being developed, I can infinitely expand the function of cell penetrating peptides in the future.์„ธํฌ๋Š” ์ธ์ง€์งˆ ์ด์ค‘์ธต์œผ๋กœ ์ด๋ฃจ์–ด์ง„ ์„ธํฌ๋ง‰์œผ๋กœ ๋‘˜๋Ÿฌ์Œ“์—ฌ ์žˆ๋‹ค. ์ด๋Ÿฌํ•œ ์„ธํฌ๋ง‰์€ ์„ธํฌ์˜ ๋‚ด๋ถ€์™€ ์™ธ๋ถ€์˜ ๋ฌผ์งˆ๊ตํ™˜์„ ์„ ํƒ์ ์ด๊ณ  ํšจ๊ณผ์ ์œผ๋กœ ์กฐ์ ˆํ•˜๋ฉฐ ์„ธํฌ ์ƒ์กด์— ๋งค์šฐ ์ค‘์š”ํ•œ ์—ญํ• ์„ ํ•œ๋‹ค. ์ด๋Ÿฌํ•œ ์„ธํฌ๋ง‰ ๋–„๋ฌธ์— ์‚ฌ์ด์ฆˆ๊ฐ€ ํฌ๊ฑฐ๋‚˜ ์„ธํฌ๋ง‰๊ณผ ์ƒํ˜ธ์ž‘์šฉ์„ ๋ชปํ•˜๋Š” ๋ฌผ์งˆ์€ ์„ธํฌ ๋‚ด๋ถ€๋กœ ์ „๋‹ฌ ๋˜์ง€ ๋ชปํ•œ๋‹ค. ์ด๋Ÿฌํ•œ ์„ธํฌ ๋น„ํˆฌ๊ณผ ๋ฌผ์งˆ ์ค‘์—๋Š” ์น˜๋ฃŒ ์•ฝ๋ฌผ๋กœ ์‚ฌ์šฉ๊ฐ€๋Šฅํ•œ ํ•ญ์•”์ œ๋‚˜ ํ•ญ์ฒด๋ฅผ ํฌํ•จํ•œ ๋‹ค์–‘ํ•œ ๋‹จ๋ฐฑ์งˆ ๋“ฑ์ด ํฌํ•จ ๋œ๋‹ค. ๋งŽ์€ ์„ธํฌ ๋น„ํˆฌ๊ณผ ์•ฝ๋ฌผ๋“ค์ด ์„ธํฌ์— ์ค‘์š”ํ•œ ์—ญํ• ์„ ํ•˜๊ธฐ ๋•Œ๋ฌธ์—, ๊ณผ๊ฑฐ๋ถ€ํ„ฐ ์ด๋Ÿฌํ•œ ์•ฝ๋ฌผ์„ ์„ธํฌ ๋‚ด๋ถ€๋กœ ์ „๋‹ฌํ•˜๊ธฐ ์œ„ํ•œ ๋‚˜๋…ธ์ž…์ž๋ฌผ์งˆ, ํ•˜์ด๋“œ๋กœ๊ฒ”, ๊ณต์ค‘ํ•ฉ์ฒด๋ฅผ ํฌํ•จํ•œ ๋งŽ์€ ์ „๋‹ฌ์ฒด๋“ค์ด ๊ฐœ๋ฐœ ๋˜์–ด ์™”๋‹ค. ์„ธํฌ ํˆฌ๊ณผ์„ฑ ํŽฉํƒ€์ด๋“œ (Cell Penetrating Peptide)๋Š” ์„ธํฌ ๋น„ํˆฌ๊ณผ ๋ฌผ์งˆ์„ ํšจ์œจ์ ์œผ๋กœ ์„ธํฌ๋‚ด๋ถ€๋กœ ์ „๋‹ฌํ•˜๋Š” ํšจ์œจ์ ์ธ ์ „๋‹ฌ์ฒด ์ค‘ ํ•˜๋‚˜์ด๋‹ค. ํŠนํžˆ ์ด ๋ฌผ์งˆ์€ ํŽฉํƒ€์ด๋“œ๋กœ ๋งŒ๋“ค์–ด์กŒ๊ธฐ ๋•Œ๋ฌธ์— ๋‹ค๋ฅธ๋ฌผ์งˆ๋“ค์— ๋น„ํ•ด ์ƒ๋Œ€์ ์œผ๋กœ ๋…์„ฑ์ด ๋‚ฎ์œผ๋ฉฐ ์ƒ์ฒด์ ํ•ฉ์„ฑ์ด ๋†’์•„ ๋„๋ฆฌ ์ด์šฉ๋˜๊ณ  ์žˆ๋‹ค. ๊ณผ๊ฑฐ HIV-1๋กœ ๋ถ€ํ„ฐ ์œ ๋ž˜๋œ Tat (Transactivator of transcription) ํŽฉํƒ€์ด๋“œ๊ฐ€ ์ฒ˜์Œ ๋ฐœ๊ฒฌ ๋œ ์ดํ›„ poly arginine, penetratin ๊ณผ ๊ฐ™์€ ๋‹ค์–‘ํ•œ ์„ธํฌํˆฌ๊ณผ์„ฑ ํŽฉํƒ€์ด๋“œ๋“ค์ด ๊ฐœ๋ฐœ๋˜์—ˆ๊ณ , ์ด๋“ค์€ ์ฃผ๋กœ ์Œ์„ฑ ์ „ํ•˜๋ฅผ ๊ฐ€์ง€๋Š” ์„ธํฌ๋ง‰๊ณผ ์ž˜ ์ƒํ˜ธ์ž‘์šฉ ํ•  ์ˆ˜ ์žˆ๋Š” ์–‘์„ฑ ์ „ํ•˜๋ฅผ ๋„๋Š” ์•„๋ฏธ๋…ธ์‚ฐ๋“ค๋กœ ์ด๋ฃจ์–ด์ ธ ์žˆ๋‹ค. ์ด๋Ÿฌํ•œ ์„ธํฌํˆฌ๊ณผ์„ฑ ํŽฉํƒ€์ด๋“œ๋“ค์€ ๋ณดํ†ต ๋น„ํˆฌ๊ณผ๋ฌผ์งˆ์„ ์ˆ˜ ๋งˆ์ดํฌ๋กœ๋ชฐ๋ž„ ๋†๋„์—์„œ ์ ์€ ๋…์„ฑ์„ ๋ณด์ด๋ฉฐ ์‚ด์•„์žˆ๋Š” ์„ธํฌ ๋‚ด๋ถ€๋กœ ์ „๋‹ฌํ•˜๋Š” ๊ฒƒ์ด ๊ฐ€๋Šฅํ–ˆ๋‹ค. ์„œ์šธ๋Œ€ํ•™๊ต ์ƒ์ฒด์žฌ๋ฃŒํ™”ํ•™์—ฐ๊ตฌ์‹ค์—์„œ๋Š” ๊ธฐ์กด์— ์กด์žฌํ•˜๋Š” ์„ธํฌํˆฌ๊ณผ์„ฑ ํŽฉํƒ€์ด๋“œ ๋ณด๋‹ค ํ›จ์”ฌ ๋†’์€ ํšจ์œจ์ ์ธ, ์ˆ˜ ๋‚˜๋…ธ๋ชฐ๋ž„ ๋†๋„์—์„œ ์ž‘๋™์ด ๊ฐ€๋Šฅํ•œ ์ƒˆ๋กœ์šด ์ข…๋ฅ˜์˜ ์–‘์นœ๋งค์„ฑ(amphipathic) ์„ฑ์งˆ์„ ์„ธํฌํˆฌ๊ณผ์„ฑ ํŽฉํƒ€์ด๋“œ๋ฅผ ๊ฐœ๋ฐœ ํ•˜๋Š”๊ฒƒ์„ ์„ฑ๊ณตํ•˜์˜€๋‹ค. ์ƒˆ๋กœ์ด ๋ฐœ๊ฒฌ๋œ ์ด ํŽฉํƒ€์ด๋“œ๋Š” ๋ฃจ์‹ ๊ณผ ๋ผ์ด์‹ ์ด ๋ฐ˜๋ณต๋˜๋Š” LK ํŽฉํƒ€์ด๋“œ ์ด๋ฉฐ ์ด๊ฒƒ์˜ ์‹œํ€€์Šค๋Š” LKKLLKLLKKLLKLAG ์ด๋‹ค. ํ›„์† ์—ฐ๊ตฌ์—์„œ ์ด ํŽฉํƒ€์ด๋“œ์˜ ์‹œํ€€์Šค๊ฐ€ ์—ฌ๋Ÿฌ๋ฒˆ ๋ฐ˜๋ณต ๋  ์ˆ˜๋ก ๋” ๋†’์€ ์„ธํฌํˆฌ๊ณผ ํšจ์œจ์„ ๋ณด์ด๋Š” ๊ฒƒ์„ ์•Œ ์ˆ˜ ์žˆ์—ˆ๋‹ค. LK๊ฐ€ ๋‘๋ฒˆ ๋ฐ˜๋ณต๋˜๋Š” LK-2 ์™€ ๊ฐ™์€ ๊ฒฝ์šฐ์—๋Š” ๊ณ ์ฒด์ƒ ํŽฉํƒ€์ด๋“œ ํ•ฉ์„ฑ๋ฒ•์œผ๋กœ ์–ป์„ ์ˆ˜ ์žˆ์ง€๋งŒ, ๊ทธ ์ด์ƒ ๋ฐ˜๋ณต๋˜๋Š” ํŽฉํƒ€์ด๋“œ๋Š” ๋„ˆ๋ฌด ๊ธธ๊ธฐ ๋•Œ๋ฌธ์— ๋Œ€์žฅ๊ท  ๋‹จ๋ฐฑ์งˆ ๋ฐœํ˜„ ๋ฐฉ๋ฒ• (E.coli protein expression)์œผ๋กœ ์–ป์„ ์ˆ˜ ์žˆ์—ˆ๊ณ  LK๊ฐ€ ๋„ค๋ฒˆ ๋ฐ˜๋ณต๋˜๋Š” LK-4์—์„œ ์„ธํฌํˆฌ๊ณผ๋„์˜ ํšจ์œจ์ด ๊ฐ€์žฅ ๋†’์•˜์Œ์„ ์•Œ ์ˆ˜ ์žˆ์—ˆ๋‹ค. ๋” ๋‚˜์•„๊ฐ€ ๋Œ€์žฅ๊ท ์—์„œ LK ์‹œํ€€์Šค๋ฅผ ๋ฐœํ˜„ ๊ฐ€๋Šฅ ํ•˜๊ฒŒ ํ•จ์œผ๋กœ์จ ๋‹ค์–‘ํ•œ ๋‹จ๋ฐฑ์งˆ ๋ฐ ํŽฉํƒ€์ด๋“œ ์‹œํ€€์Šค๋ฅผ DNA ์žฌ์กฐํ•ฉ ๊ธฐ์ˆ ์„ ์ด์šฉํ•˜์—ฌ LK์™€ ํ•จ๊ป˜ ํ•œ๋ฒˆ์— ์ •์ œ ํ•ด ๋‚ผ ์ˆ˜ ์žˆ๊ฒŒ ๋˜์–ด LK ์„ธํฌํˆฌ๊ณผ์„ฑ ํŽฉํƒ€์ด๋“œ์˜ ๋‹ค์–‘ํ•œ ํ™œ์šฉ์ด ๊ฐ€๋Šฅํ•˜๊ฒŒ ๋˜์—ˆ๋‹ค. ๋ณธ ๋ฐ•์‚ฌํ•™์œ„ ๋…ผ๋ฌธ์—์„œ๋Š” ๋Œ€์žฅ๊ท  ๋ฐœํ˜„์„ ํ†ตํ•œ LK ์‹œํ€€์Šค๋ฅผ ์ด์šฉํ•œ ๋‘๊ฐ€์ง€ ํ™œ์šฉ ์—ฐ๊ตฌ๋ฅผ ์ง„ํ–‰ํ•˜์˜€๋‹ค. ๋…ผ๋ฌธ์˜ PART I ์—์„œ๋Š” LK ์‹œํ€€์Šค์— ํ•ญ์ฒด์— ์„ ํƒ์ ์œผ๋กœ ๊ฒฐํ•ฉ์ด ๊ฐ€๋Šฅํ•˜๋‹ค๊ณ  ์•Œ๋ ค์ง„ Domain Z of Staphylococcus protein A๋ฅผ DNA ์žฌ์กฐํ•ฉ ๋ฐฉ๋ฒ•์œผ๋กœ ๋„์ž…ํ•˜์—ฌ, ๊ฑฐ๋Œ€ํ•œ ์„ธํฌ ๋น„ํˆฌ๊ณผ์„ฑ ๋‹จ๋ฐฑ์งˆ์ธ ํ•ญ์ฒด๋ฅผ ๋งค์šฐ ์ €๋†๋„์—์„œ ํšจ์œจ์ ์œผ๋กœ ์‚ด์•„์žˆ๋Š” ์„ธํฌ ๋‚ด๋ถ€๋กœ ์ „๋‹ฌ ํ•˜๋Š” ๊ฒƒ์„ ๊ฐ€๋Šฅํ•˜๊ฒŒ ํ•จ์œผ๋กœ์จ ์ƒˆ๋กœ์šด ํ•ญ์ฒด ์ „๋‹ฌ ๋ฌผ์งˆ ๊ฐœ๋ฐœ์— ์„ฑ๊ณต ํ•˜์˜€๋‹ค. ์ด ์—ฐ๊ตฌ์—์„œ ๋งŒ๋“ค์–ด์ง„ LK-Domain Z ๋‹จ๋ฐฑ์งˆ์€ domain Z ํŒŒํŠธ์˜ ์˜ํ–ฅ์œผ๋กœ ํ•ญ์ฒด์™€ ์ผ์ •ํ•œ ๋น„์œจ๋กœ ๋งค์šฐ ํšจ์œจ์ ์ธ ๋น„๊ณต์œ ์„ฑ ๊ฒฐํ•ฉ์„ ํ˜•์„ฑํ•œ๋‹ค. ๊ทธ ์ดํ›„ LK์˜ ๋†’์€ ์„ธํฌํˆฌ๊ณผ์„ฑ ๋•Œ๋ฌธ์— ํ•ญ์ฒด๊ฐ€ ์‚ด์•„์žˆ๋Š” ์„ธํฌ์˜ ์„ธํฌ์งˆ ๋‚ด๋ถ€๋กœ ํšจ๊ณผ์ ์œผ๋กœ ๋“ค์–ด๊ฐˆ ์ˆ˜ ์žˆ๋‹ค. ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” ์ด ํšจ์œจ์ ์ธ ํ•ญ์ฒด ์ „๋‹ฌ๋ฌผ์งˆ์˜ ์„ฑ์งˆ๊ณผ ๊ทธ์— ๋Œ€ํ•œ ํˆฌ๊ณผ ๊ธฐ์ „์— ๋Œ€ํ•ด ๋ฐํ˜”์œผ๋ฉฐ ์ „๋‹ฌ๋œ ํ•ญ์ฒด๊ฐ€ ์‹ค์ œ๋กœ ์„ธํฌ ๋‚ด๋ถ€์—์„œ ์ •ํ™•ํ•œ ์—ญํ• ์ด ๊ฐ€๋Šฅํ•œ์ง€์— ๋Œ€ํ•œ ์—ฐ๊ตฌ ๋˜ํ•œ ์ง„ํ–‰ ๋˜์—ˆ๋‹ค. LK-Domain Z ๋ฅผ ์ด์šฉํ•˜์—ฌ ์•”์„ธํฌ์˜ ์‹ ํ˜ธ์ „๋‹ฌ์— ๊ด€์—ฌํ•˜๋Š” NF-ฮบB ์˜ ์—ญํ• ์„ ๋ฐฉํ•ดํ•˜๋Š” anti-NF-ฮบB ํ•ญ์ฒด๋ฅผ ์ด์šฉํ•˜์—ฌ ์‹ค์ œ๋กœ ์•”์„ธํฌ์˜ ์ฆ์‹์— ํ•„์š”ํ•œ ์œ ์ „์ž์˜ ๋ฐœํ˜„์ด ์–ต์ œ๋˜๋ฉด์„œ ์„ธํฌ์‚ฌ๋ฉธ์ด ์ผ์–ด๋‚˜๋Š” ๊ฒƒ์„ ๊ด€์ฐฐ ํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. ์ด๋ฅผ ํ†ตํ•ด ์ƒˆ๋กœ์ด ๋ฐœ๊ฒฌ๋œ LK-Domain Z ๋‹จ๋ฐฑ์งˆ์ด ์„ธํฌ ๋‚ด๋ถ€์—์„œ ์ž‘์šฉํ•˜๋Š” ๋‹ค์–‘ํ•œ ํ•ญ์ฒด๋ฅผ ์ „๋‹ฌํ•˜์—ฌ ํ–ฅํ›„ ๋‹ค์–‘ํ•œ ์ƒ๋ฌผ ์„ธํฌํ•™์  ์—ฐ๊ตฌ ๋ฐ ์•ฝ๋ฌผ ์—ฐ๊ตฌ์— ์‚ฌ์šฉ ๊ฐ€๋Šฅ ํ•  ๊ฒƒ์ž„์„ ํ™•์ธ ํ•˜์˜€๋‹ค. ๋…ผ๋ฌธ์˜ PART II ์—์„œ๋Š” LK ์‹œํ€€์Šค์— ์„ธํฌ ์„ ํƒ์„ฑ์„ ๋ถ€์—ฌํ•˜์—ฌ ํ‘œ์ ์„ธํฌ์— ํšจ์œจ์ ์œผ๋กœ ์ž‘์šฉํ•˜๋Š” ์„ธํฌํˆฌ๊ณผ์„ฑ ํŽฉํƒ€์ด๋“œ ๊ฐœ๋ฐœ์— ๋Œ€ํ•ด ์„œ์ˆ  ํ•˜์˜€๋‹ค. ์ˆ˜๋งŽ์€ ์•ฝ๋ฌผ์ „๋‹ฌ์ฒด์™€ ๋งˆ์ฐฌ๊ฐ€์ง€๋กœ LK ์‹œํ€€์Šค ๋˜ํ•œ ์„ธํฌ ์„ ํƒ์„ฑ์ด ์—†๋‹ค๋Š” ๋‹จ์ ์„ ๊ฐ€์ง„๋‹ค. ์•ฝ๋ฌผ์ „๋‹ฌ์ฒด๊ฐ€ ์„ธํฌ์— ๋Œ€ํ•œ ์„ ํƒ์„ฑ์„ ๊ฐ€์ง€๋ฉด ๋‹ค์–‘ํ•œ ์•ฝ๋ฌผ์˜ ๋ณต์šฉ๋Ÿ‰์„ ๋‚ฎ์ถœ์ˆ˜ ์žˆ๊ณ  ์ •์ƒ์„ธํฌ์— ๋Œ€ํ•œ ๋ถ€์ž‘์šฉ์„ ์ค„์ผ ์ˆ˜ ์žˆ๋Š” ์žฅ์ ์„ ๊ฐ€์ง„๋‹ค. ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” LK ์‹œํ€€์Šค์— ์„ธํฌ์„ ํƒ์„ฑ์„ ๋ถ€์—ฌํ•˜๊ธฐ ์œ„ํ•ด 20~30% ์ •๋„์˜ ์œ ๋ฐฉ์•” ์„ธํฌ์— ๊ณผ๋ฐœํ˜„ ๋˜์–ด์žˆ๋Š” HER2 ๋ฆฌ์…‰ํ„ฐ์— ํŠน์ด์ ์œผ๋กœ ๊ฒฐํ•ฉ์ด ๊ฐ€๋Šฅํ•˜๋‹ค๊ณ  ์•Œ๋ ค์ง„ ZHER2:342 (ZHER2)๋‹จ๋ฐฑ์งˆ์„ DNA ์žฌ์กฐํ•ฉ ๋ฐฉ๋ฒ•์„ ํ†ตํ•ด LK์— ๋„์ž…ํ•˜์˜€๋‹ค. ์ด ์—ฐ๊ตฌ์—์„œ ๊ฐœ๋ฐœ๋œ LK-ZHER2 ๋‹จ๋ฐฑ์งˆ์€ HER2๊ฐ€ ์—†๋Š” ์„ธํฌ์—๋Š” ์•„์ฃผ ๋Š๋ฆฌ๊ณ  ๋น„ํšจ์œจ์ ์œผ๋กœ ์„ธํฌํˆฌ๊ณผ๋„๋ฅผ ๋ณด์ด๋Š” ๋ฐ˜๋ฉด, HER2๊ฐ€ ๊ณผ๋ฐœํ˜„ ๋œ ์„ธํฌ์—์„œ๋Š” ๋งค์šฐ ๋น ๋ฅด๊ณ  ํšจ์œจ์ ์ธ ์„ธํฌํˆฌ๊ณผ์„ฑ์„ ๋ณด์˜€๋‹ค. ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” LK-ZHER2์˜ ์„ธํฌํˆฌ๊ณผ์„ฑ๊ณผ HER2 ๋ฆฌ์…‰ํ„ฐ ๋ฐœํ˜„๊ณผ์˜ ๊ด€๊ณ„์— ๋Œ€ํ•ด ๋ฐํž ์ˆ˜ ์žˆ์—ˆ์œผ๋ฉฐ, LK-ZHER2 ๋‹จ๋ฐฑ์งˆ์— ํ•ญ์•”์ œ์ธ doxorubicin์„ ๊ฒฐํ•ฉํ•˜์—ฌ ์„ธํฌ๋ฅผ ์„ ํƒ์ ์œผ๋กœ ์ฃฝ์ด๋Š” ํ‘œ์ ์น˜๋ฃŒ์ œ๋กœ์„œ์˜ ์—ญํ• ์„ in vitro ์ƒ์—์„œ ํ™•์ธ ํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. ๋” ๋‚˜์•„๊ฐ€ in vivo ์—์„œ๋„ ์ด LK-ZHER2๊ฐ€ HER2 ๊ณผ๋ฐœํ˜„ ์„ธํฌ์— ๋งค์šฐ ๋†’์€ ์„ ํƒ์„ฑ์„ ๋ณด์ธ๋‹ค๋Š” ๊ฒƒ์„ ๋ฐํ˜”๋‹ค. ๋ณธ ๋ฐ•์‚ฌํ•™์œ„ ์—ฐ๊ตฌ์—์„œ๋Š” LK ์‹œํ€€์Šค์— ๋‹ค์–‘ํ•œ ์„ฑ์งˆ์„ ๊ฐ€์ง€๋Š” ๋‹จ๋ฐฑ์งˆ์€ DNA ์žฌ์กฐํ•ฉ ๋ฐฉ๋ฒ•์œผ๋กœ ๋„์ž…ํ•˜์—ฌ ์ƒˆ๋กœ์šด ๊ธฐ๋Šฅ์„ ๊ฐ€์ง€๋Š” ์„ธํฌํˆฌ๊ณผ์„ฑํŽฉํƒ€์ด๋“œ ๊ฐœ๋ฐœ์— ์„ฑ๊ณตํ•˜์˜€๋‹ค. Domain Z, ZHER2 ์™ธ์—๋„ ๊ต‰์žฅํžˆ ๋งŽ์€ ์ข…๋ฅ˜์˜ ๊ธฐ๋Šฅ์„ฑ ๋‹จ๋ฐฑ์งˆ๋“ค์ด ์กด์žฌํ•˜๊ธฐ ๋•Œ๋ฌธ์— ์œ„์™€๊ฐ™์€ ๋ฐฉ๋ฒ•์œผ๋กœ LK์— ๋„์ž…์ด ๋œ๋‹ค๋ฉด, ํ–ฅํ›„ LK๋Š” ๋”์šฑ ๋‹ค์–‘ํ•œ ๊ธฐ๋Šฅ์„ ๊ฐ€์ง€๋Š” ์„ธํฌํˆฌ๊ณผ์„ฑ ํŽฉํƒ€์ด๋“œ๋กœ ๋ฐœ์ „ํ•  ์ˆ˜ ์žˆ์„ ๊ฒƒ์ด๋ผ ๊ธฐ๋Œ€๋œ๋‹ค.Part I. Development of Immunoglobulin G Delivery Vehicle at Nanomolar Concentrations with Domain Z-fused Multimeric ฮฑ-Helical Cell Penetrating Peptides 1 Part II. Development of Targeted Drug Delivery Vehicle with Dimeric ฮฑ-Helical Cell Penetrating Peptide and HER2-Selective Affibody 70 Abstract in Korean (๊ตญ๋ฌธ์ดˆ๋ก) 129 Acknowledgement 132๋ฐ•

    C6 ์‹ ๊ฒฝ๊ต์ข… ์„ธํฌ์—์„œ ์‚ฐ์†Œ/ํฌ๋„๋‹น ๊ฒฐํ•์œผ๋กœ ์œ ๋„๋˜๋Š” ์„ธ

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    Dept. of medical science/๋ฐ•์‚ฌ[ํ•œ๊ธ€] [์˜๋ฌธ]Bcl-2 interacting cell death suppressor (Bis) has been implicated in anti-stress and anti-apoptotic pathways. Previous study showed a significant induction of Bis in the reactive astrocytes of rat hippocampus after transient forebrain ischemia. To investigate the significance of its induction in the ischemic injury, the expression of Bis was reduced by si-RNA strategy in C6 glioma cells, which were then exposed to oxygen-glucose deprivation (OGD). Bis knock-down resulted in a decrease in viability after OGD accompanied by ROS accumulation. Among the cellular antioxidants, superoxide dismutase (SOD) activity was significantly perturbed in bis si-RNA treated cells (bis-kd C6). A Subsequent analysis of in-gel reduction ability and quantification of mRNA revealed that induction of SOD1 in response to OGD was impaired at transcriptional levels as a result of bis knock-down. As a candidate for the transcription factor for sod1 gene, the activity of NF-?B was determined using a DNA binding assay and the nuclear translocation of p65 subunit, showing that activation of NF-?B was attenuated in bis si-RNA transfected C6 cells. The treatment of SOD mimetic resulted in the recovery of the viability of C6 cells upon OGD, which is more prominent in bis si-RNA treated C6 cells. Furthermore, the inhibition of NF-?B suppressed the induction of SOD1 transcription and aggravated the cell death, which was potentiated with reduction of Bis, after OGD. The constitutive levels of p65 were decreased by Bis reduction while Bis overexpression increased p65 protein levels, but not mRNA levels. These results suggest that one of the physiological function of Bis is the regulation of p65 protein stability and thereby NF-?B activity which affects the induction of SOD1 after oxidative stress and subsequent cell viability. The critical mechanisms by which Bis control the p65 stability remain to be determined.ope

    (A) case study on the psychology of women who have had a hysterectomy

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    ๊ฐ„ํ˜ธํ•™๊ณผ/์„์‚ฌ[ํ•œ๊ธ€] ์—ฌ์„ฑ์—๊ฒŒ ์žˆ์–ด์„œ ์ƒ์ง•์ ์ธ ์žฅ๊ธฐ์ธ ์ž๊ถ์„ ์ œ๊ฑฐํ•˜๋Š” ์ž๊ถ์ ์ถœ์ˆ ์€ ๋‹ค๋ฅธ ์žฅ๊ธฐ์™€๋Š” ๋‹ฌ๋ฆฌ ์ž๊ถ์ƒ์‹ค์ด๋ผ๋Š” ์‹ ์ฒด์  ์†์ƒ๋ฟ ์•„๋‹ˆ๋ผ ์‹ฌ๋ฆฌ์  ์†์ƒ์„ ๊ฐ€์ ธ์˜จ๋‹ค. ์ด๋Ÿฌํ•œ ์‹ฌ๋ฆฌ์  ์†์ƒ์€ ์ƒ๋ฆฌ์  ๊ธฐ๋Šฅ์— ์œ ํ•ดํ•œ ์˜ํ–ฅ์„ ๋ผ์ณ ์ˆ˜์ˆ ๋กœ๋ถ€ํ„ฐ์˜ ์‹ ์ฒด์ , ์‹ฌ๋ฆฌ์  ํšŒ๋ณต์„ ์ง€์—ฐ์‹œํ‚จ๋‹ค. ๋”ฐ๋ผ์„œ ์ž๊ถ์ ์ถœ์ˆ ์ด๋ผ๋Š” ์‚ฌ๊ฑด์„ ์ „ํ›„๋กœ ํ•˜์—ฌ ๋ถ€์ธ๋“ค์ด ๊ฒช๋Š” ์‹ฌ๋ฆฌ๋Š” ์ˆ˜์ˆ ํ›„ ํšŒ๋ณต๊ณผ ์ ์‘์— ์˜ํ–ฅ์„ ๋ฏธ์น˜๋‚˜ ์ด ์‹œ๊ธฐ์—๋Š” ์‹ ์ฒด์ ์ธ ์•ˆ์œ„๋ฅผ ์œ„ํ•œ ๊ฐ„ํ˜ธ์ค‘์žฌ๋งŒ์ด ์ฃผ์–ด์งˆ ๋ฟ ์ž๊ถ์ ์ถœ์ˆ ์„ ๋ฐ›์€ ๋ถ€์ธ๋“ค์ด ๊ฒช๊ฒŒ ๋˜๋Š” ์‹ฌ๋ฆฌ์˜ ๋ฌธ์ œ๋Š” ์†Œํ™€ํžˆ ๋‹ค๋ฃจ์–ด์ง€๊ณ  ์žˆ๋Š” ์‹ค์ •์ด๋‹ค. ์ด์— ๋ณธ ์—ฐ๊ตฌ๋Š” ์ž๊ถ์ ์ถœ์ˆ ์„ ๋ฐ›์€ ๋ถ€์ธ๋“ค์˜ ์‹ฌ๋ฆฌ๋ฅผ ํŒŒ์•…ํ•˜์—ฌ ์ด๋“ค์˜ ์‹ ์ฒด์ , ์‹ฌ๋ฆฌ์ ์ธ ํšŒ๋ณต๊ณผ์ •์„ ๋„์šธ ์ˆ˜ ์žˆ๋Š” ๊ฐ„ํ˜ธ๊ณ„ํš์˜ ๊ทผ๊ฑฐ๋ฅผ ์ œ์‹œํ•˜๊ณ ์ž ์‹œ๋„๋˜์—ˆ๋‹ค. ๋ณธ ์—ฐ๊ตฌ๋Š” ์‚ฌ๋ก€์—ฐ๊ตฌ๋กœ ๋ณธ์—ฐ๊ตฌ์ž๊ฐ€ ์ง์ ‘ 1992๋…„ 3์›” 29์ผ๋ถ€ํ„ฐ 5์›” 18์ผ๊นŒ์ง€ ์„œ์šธ์˜ Y๋Œ€ํ•™ ๋ถ€์†๋ณ‘์›์— ์ž…์›ํ•˜์—ฌ ์ˆ˜์ˆ ํ›„ 6-7์ผ์ด ๊ฒฝ๊ณผ๋œ 10๋ช…์˜ ๋ถ€์ธ๋“ค์„ ๋Œ€์ƒ์œผ๋กœ ์ž๋ฃŒ์ˆ˜์ง‘์„ ํ•˜์˜€๊ณ  ์ค€ํ‘œ์ค€ํ™” ๋ฉด์ ‘ํ˜•ํƒœ๋ฅผ ์‚ฌ์šฉํ•œ ์‹ฌ์ธต๋ฉด๋‹ด๊ณผ ๊ด€์ฐฐ ๊ทธ๋ฆฌ๊ณ  ์˜๋ฌด๊ธฐ๋ก์ง€ ๊ฒ€ํ†  ๋“ฑ์„ ํ†ตํ•˜์—ฌ ์ž๋ฃŒ์ˆ˜์ง‘์„ ํ•˜์˜€๋‹ค. ์ž๋ฃŒ๋ถ„์„์€ Lincoln & Guba(1985)์™€ Smith(1979)๊ฐ€ ์ œ์‹œํ•œ ์‚ฌ๋ก€์—ฐ๊ตฌ ๊ฒฐ๊ณผ๋ณด๊ณ ๋ฅผ ๊ธฐ์ดˆ๋กœ ํ•˜์˜€์œผ๋ฉฐ, ๊ด€์ฐฐ๊ณผ ๋ฉด๋‹ด์—์„œ ๋‚˜ํƒ€๋‚œ ์ž๋ฃŒ๋“ค์„ ์„œ์ˆ ํ•˜๊ณ  ์˜๋ฏธ์žˆ๋Š” ์ž๋ฃŒ๋ฅผ ๋ถ„๋ฅ˜ํ•˜์—ฌ ์œ ์‚ฌํ•œ ๋‚ด์šฉ๋ผ๋ฆฌ ๋‹จ์œ„ํ™”ํ•œ ๋‹ค์Œ ๊ณตํ†ต๋œ ์š”์†Œ๋ฅผ ํ™•์ธํ•˜์—ฌ ๊ฐœ๋…์„ ์„ค์ •ํ•˜์˜€๊ณ  ์ด๋Ÿฌํ•œ ๊ฐœ๋…๋“ค์„ ๊ด€๊ณ„๋ฌธํ—Œ์„ ์ฐธ๊ณ ํ•˜์—ฌ ํ™•์ธํ•˜๋Š” ์ˆœ์œผ๋กœ ํ•˜์˜€๋‹ค. ์—ฐ๊ตฌ๊ฒฐ๊ณผ๋Š” ๋‹ค์Œ๊ณผ ๊ฐ™๋‹ค. ์ž๊ถ์ ์ถœ์ˆ ์„ ๋ฐ›์€ ๋ถ€์ธ๋“ค์˜ ์งˆ๋ณ‘ ๋ฐœ๊ฒฌ ๊ฒฝ์œ„๋Š” ํ—ˆ๋ฆฌ์˜ ํ†ต์ฆ, ๋ถ„๋น„๋ฌผ ์ฆ๊ฐ€, ์›”๊ฒฐ๋Ÿ‰์˜ ๊ณผ๋‹ค์™€ ๋ณต๋ถ€์—์„œ ๋ญ”๊ฐ€ ๋งŒ์ ธ์ง€๋Š” ๋“ฑ ์‹ ์ฒด์  ์ฆ์ƒ์˜ ๊ฒฝํ—˜์ด ์žˆ๋Š” ๊ฒฝ์šฐ์™€ ์ฆ์ƒ์ด ์—†๋Š” ์ƒํƒœ์—์„œ ์ •๊ธฐ์  ์•”๊ฒ€์‚ฌ๋ฅผ ๋ฐ›์œผ๋Ÿฌ ๊ฐ”๋‹ค๊ฐ€ ์šฐ์—ฐํžˆ ๋ฐœ๊ฒฌํ•˜๊ฒŒ ๋˜๋Š” ๋“ฑ ๋‘๊ฐ€์ง€ ๊ฒฝ์šฐ๋กœ ๋‚˜ํƒ€๋‚ฌ๋‹ค. ์ง„๋‹จ์„ ๋ฐ›๊ณ ๋‚˜์„œ ์ˆ˜์ˆ ์ „๊นŒ์ง€๋Š” ์ ˆ๋ง๊ฐ, ์ฃ„์ฑ…๊ฐ, ๋ถˆ์•ˆ, ์—ฌ์„ฑ์ •์ฒด๊ฐ ์†์ƒ, ํšŒํ”ผ, ๋ถˆ์‹ , ์šฐ์šธ, ๊ณตํฌ, ์—ด๋“ฑ๊ฐ, ํƒœ์—ฐํ•จ, ๊ธฐ๋Œ€๊ฐ ๋“ฑ์˜ ์‹ฌ๋ฆฌ๋ฅผ ๋‚˜ํƒ€๋ƒˆ๋‹ค. ์œ„์˜ ๋‚˜ํƒ€๋‚œ ์‹ฌ๋ฆฌ๋“ค์—์„œ๋Š” ์ž๊ถ์ œ๊ฑฐ์™€ ์ˆ˜์ˆ ์ด๋ผ๋Š” ์™ธ๊ณผ์  ์†์ƒ์— ๋”ฐ๋ฅธ ๊ณตํฌ, ๋ถˆ์•ˆ, ๋„ํ”ผ ๋“ฑ์˜ ๋ฐ˜์‘์ด ๋‚˜ํƒ€๋‚ฌ์œผ๋ฉฐ ์—ฌ์„ฑ์ •์ฒด๊ฐ ์†์ƒ๊ณผ ๋”๋ถˆ์–ด ์šฐ์šธ, ์—ด๋“ฑ๊ฐ, ์ฃ„์ฑ…๊ฐ, ์ ˆ๋ง๊ฐ ๋“ฑ์„ ๊ฒฝํ—˜ํ•˜๊ณ  ์žˆ์—ˆ๋‹ค. ๋˜ํ•œ ์‹ฌํ•œ ์‹ ์ฒด์  ์ฆ์ƒ์„ ๊ฒฝํ—˜ํ–ˆ๋˜ ๋ถ€์ธ๋“ค์˜ ๊ฒฝ์šฐ์—๋Š” ์ž๊ถ์ œ๊ฑฐ๋กœ ๋” ์ด์ƒ์˜ ๊ณ ํ†ต์„ ๊ฒช์ง€ ์•Š๊ฒŒ ๋  ๊ฒƒ์ด๋ผ๋Š” ๊ธฐ๋Œ€๊ฐ์„ ๊ฐ–๊ณ  ์žˆ์—ˆ๊ณ  ๋‚จํŽธ๊ณผ ๊ฐ€์กฑ๋“ค์˜ ์ง€์ง€๋ฅผ ๋ฐ›์€ ๋ถ€์ธ๋“ค์€ ์ˆ˜์ˆ ๊ณผ ์ž๊ถ์ƒ์‹ค์— ๋Œ€ํ•œ ์ ˆ๋ง๊ฐ, ์—ฌ์„ฑ์ •์ฒด๊ฐ ์†์ƒ, ๋ถˆ์•ˆ ๋ฐ ์šฐ์šธ๋“ฑ์ด ๊ฐ์†Œ๋˜๋Š” ๊ฒฝํ–ฅ์„ ๋ณด์˜€๋‹ค. ์ˆ˜์ˆ ๋กœ ์ž๊ถ์„ ์ œ๊ฑฐํ•ด์•ผ ๋œ๋‹ค๋Š” ๋ง์„ ๋“ฃ๊ณ  ๋‚˜์„œ๋Š” ์ž๊ถ์ œ๊ฑฐ๋ฅผ ํ•ด์•ผ๋งŒ ํ•˜๋Š” ๊ฒƒ์ด๋ผ๋Š” ๋‹น์—ฐํ•จ ๋‚ด์ง€ ์˜๋ฌด๋กœ์„œ์˜ ์ˆ˜์šฉ์ž์„ธ๋ฅผ ๋ณด์˜€๊ณ  ์ถœ์‚ฐ์˜ ์—ผ๋ ค๊ฐ€ ์—†์—ˆ๋˜ ๊ฒฝ์šฐ์—๋Š” ํƒœ์—ฐํ•จ๊ณผ ๊ธฐ๋Œ€๊ฐ์„ ๋‚˜ํƒ€๋ƒˆ๋‹ค. ์ˆ˜์ˆ ํ›„ ์ž๊ถ์ด ์—†๋Š” ํ˜„์žฌ์˜ ์‹ฌ๋ฆฌ๋Š” ํ—ˆํƒˆ๊ฐ, ํ‰์˜จํ•จ, ํ•ด๋ฐฉ๊ฐ, ์•ˆ๋„, ์ฒด๋…, ์‹ค๋ง๊ฐ, ์ฃ„์ฑ…๊ฐ ๋“ฑ์ด์—ˆ๋‹ค. ์ž๊ถ์ œ๊ฑฐ๊ฐ€ ์‚ฌ์‹ค๋กœ ๋ฐ›์•„๋“ค์—ฌ์ง€๋ฉด์„œ ํ—ˆํƒˆ๊ฐ์ด ๋“ ๋‹ค๊ณ  ํ•œ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ์ ์ฐจ ์‹ ์ฒด์ ์œผ๋กœ ํšŒ๋ณต์ด ๋˜๋ฉด์„œ ํ‰์˜จํ•œ ๋งˆ์Œ์ด ๋“ ๋‹ค๊ณ  ํ•˜์˜€๊ณ  ์‹ฌํ•œ ์‹ ์ฒด์  ์ฆ์ƒ์œผ๋กœ ๊ณ ํ†ต์„ ๋ฐ›์•˜๋˜ ๊ฒฝ์šฐ์—๋Š” ์ž๊ถ์ œ๊ฑฐ๋กœ ์ธํ•˜์—ฌ ํ•ด๋ฐฉ๊ฐ์„ ๋‚˜ํƒ€๋ƒˆ์œผ๋ฉฐ ์•ž์œผ๋กœ ๋ถ€์ธ๋ณ‘์œผ๋กœ ์ธํ•ด ๊ณ ํ†ต์„ ๋ฐ›์ง€ ์•Š์•„๋„ ๋  ๊ฒƒ์ด๋ผ๋Š” ์•ˆ๋„๊ฐ์„ ๋‚˜ํƒ€๋ƒˆ๋‹ค. ๋˜ํ•œ ๋Œ€์ƒ์ž๋“ค์€ ์ž๊ถ์ œ๊ฑฐ๋กœ ์ธํ•œ ์ž๊ถ์ƒ์‹ค์„ ์—ฌ์„ฑ ๊ธฐ๋Šฅ์˜ ์ƒ์‹ค๊ณผ ๋™์ผ์‹œ ํ•˜์—ฌ ์—ฌ์„ฑ์ •์ฒด๊ฐ ์ƒ์‹ค์„ ๊ฒฝํ—˜ํ•˜๋ฉฐ ์ด์™€ ๊ด€๋ จ๋˜์–ด ์ž๋…€์ถœ์‚ฐ ๋Šฅ๋ ฅ์˜ ์ƒ์‹ค์— ๋Œ€ํ•œ ์‹ค๋ง๊ฐ, ์ฒด๋…, ์ฃ„์ฑ…๊ฐ, ๋“ฑ์„ ๋‚˜ํƒ€๋ƒˆ๋‹ค. ํšŒ๋ณต๊ณผ์ •๋™์•ˆ ์˜ˆ์ƒ๋˜๋Š” ๋ฌธ์ œ๋“ค์—์„œ๋Š” ์„ฑ์ƒํ™œ ๋ฐ ๋ถ€๋ถ€๊ด€๊ณ„์˜ ๋ณ€ํ™”, ์ž๊ธฐ์—ญํ•  ๋ณ€ํ™” ๋ฐ ๊ธฐ๋Šฅ์ €ํ•˜์— ๋Œ€ํ•œ ์—ผ๋ ค, ์ž์กด๊ฐ ์ƒ์‹ค์šฐ๋ ค, ์‹ ์ฒด์ ์ธ ๊ฑด๊ฐ•๋ฌธ์ œ๋“ฑ์œผ๋กœ ๋‚˜ํƒ€๋‚ฌ๋‹ค. ์ด์™€๊ฐ™์ด ์ž๊ถ์ ์ถœ์ˆ ์„ ๋ฐ›์€ ๋ถ€์ธ๋“ค์˜ ์‹ฌ๋ฆฌ์— ๊ด€ํ•œ ๋ณธ ์—ฐ๊ตฌ๊ฒฐ๊ณผ๋ฅผ ํ†ตํ•˜์—ฌ ์ž๊ถ์ ์ถœ์ˆ ์„ ๋ฐ›์€ ๋ถ€์ธ๋“ค์˜ ์ˆ˜์ˆ  ์ „ํ›„ ์‹ฌ๋ฆฌ์ƒํƒœ๋ฅผ ์ดํ•ดํ•˜๊ณ  ๊ฐ๊ฐ ์‚ฌ์ •ํ•จ์œผ๋กœ์จ ์‹ ์ฒด์  ์•ˆ๋…•์„ ์œ„ํ•œ ๊ฐ„ํ˜ธ๋งŒ์ด ์•„๋‹Œ ๊ทธ์— ์•Œ๋งž๋Š” ์ ์ ˆํ•˜๊ณ  ๊ฐœ๋ณ„ํ™”๋œ ์‹ฌ๋ฆฌ์  ๊ฐ„ํ˜ธ์ค‘์žฌ๊ฐ€ ์ฃผ์–ด์งˆ ์ˆ˜ ์žˆ๋„๋ก ๊ธฐ์—ฌํ•˜๋ฉฐ ์ด๋ฅผ ํ™œ์šฉํ•˜์—ฌ ์ˆ˜์ˆ ํ›„ ์‹ ์ฒด์  ์‹ฌ๋ฆฌ์  ํšŒ๋ณต๊ณผ์ •์„ ๋„์šธ ์ˆ˜ ์žˆ๋Š” ์‹ค์ œ์ ์ธ ์ž๋ฃŒ๊ฐ€ ๋  ์ˆ˜ ์žˆ๊ธฐ๋ฅผ ๊ธฐ๋Œ€ํ•œ๋‹ค. [์˜๋ฌธ] For a woman, the uterus as a symbolic organ is essential to her femininity and to her role as a complete woman. Because of the psychological importance of the uterus, women who have had a hysterectomy expericence psychological damage as well as physical in the loss of the uterus. This case study attempted to identify and explain the psychology of women who have had a hysterectomy in order to help their physical and psychological recovery. The data were collected from March 29 to May 18, 1992. The subjects were 10 women who have had a hysterectomy for benign gynecological disease. The data of this study were collected through in depth interviews, observations and reviews of the patients' charts. The results of this are as follow : Women usually became aware of their disease through the experience of physical symptoms like back pain, dysmenorrhea, palpable abdominal mass and leukorrhea, and occasionally through regular cervix cancer screening tests. The psychological status before the hysterectomy was one of despair, guilt feelings, damage to feminine identity, avoidance, disbelief, depression, fear related to death and the operation itself, displeasure, inferiority, calmness and expectation. After the hysterctomy, the psychology that women appear to have experienced was that of vacancy, calmness, liberation, a feeling of relief, resignation, discourgement and guilt feeling. In anticipating problems during the process of recovery after a hysterectomy, the women were anxious about negative changes in sexual and marital life, alteration in role and decreased function as a wife, mother and career woman as compared to life before the surgery, the loss of self-esteem and about whether they would recover physical health. It could be mentioned that there were various, inconsistant and ambivalent psychological reactions for each women. Therefore it can be concluded that nurses have to do pre-post assessment for scientific nursing care prior to do planning care. Nurses should identify and understand the psychology of women who have had a hysterectomy, in order to give appropriate nursing care and interventions for these women to recover psychologically as well as physically.restrictio

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    (A) predictive model for health risk behaviors of unmarried women in Korea.

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    ๊ฐ„ํ˜ธํ•™๊ณผ/๋ฐ•์‚ฌ[ํ•œ๊ธ€]๋ณธ ์—ฐ๊ตฌ๋Š” ๋ฏธํ˜ผ์—ฌ์„ฑ์˜ ๊ฑด๊ฐ•์œ„ํ—˜ํ–‰์œ„์— ์˜ํ–ฅ์„ ์ฃผ๋Š” ์š”์ธ๋“ค์„ ํŒŒ์•…ํ•˜์—ฌ ์ด๋ฅผ ์„ค๋ช…, ์˜ˆ์ธกํ•˜๊ธฐ ์œ„ํ•œ ๋ชจํ˜•์„ ๊ตฌ์ถ•ํ•˜๊ธฐ ์œ„ํ•˜์—ฌ ์‹œ๋„๋˜์—ˆ๋‹ค. ์—ฐ๊ตฌ์˜ ๊ฐ€์„ค์  ๋ชจํ˜•์€ ๋ฌธํ—Œ๊ณ ์ฐฐ๊ณผ ์„ ํ–‰์—ฐ๊ตฌ๋ฅผ ํ† ๋Œ€๋กœ ๊ตฌ์„ฑํ•˜์˜€๋‹ค. ์™ธ์ƒ๋ณ€์ˆ˜๋กœ๋Š” ๋‚ด์  ๊ฑด๊ฐ•ํ†ต์ œ์œ„, ํƒ€์ธ์˜์กด ๊ฑด๊ฐ•ํ†ต์ œ์œ„, ์„ฑ์—ญํ•  ์ •์ฒด์„ฑ์˜ ๋‚จ์„ฑ์„ฑ, ์—ฌ์„ฑ์„ฑ๊ณผ ์ธ์ง€๋œ ์ƒํ™œ์ŠคํŠธ๋ ˆ์Šค๊ฐ€ ์žˆ์œผ๋ฉฐ ๋‚ด์ƒ๋ณ€์ˆ˜๋กœ๋Š” ์ž์•„์กด์ค‘๊ฐ, ๊ฑด๊ฐ•๊ด€๋ จ ์ž๊ธฐํšจ๋Šฅ, ์นœ๊ตฌ์˜ํ–ฅ๊ณผ ๊ฑด๊ฐ•์œ„ํ—˜ํ–‰์œ„๋กœ ๊ตฌ์„ฑํ•˜์˜€๊ณ  ์ด 25๊ฐœ์˜ ๊ฐ€์„ค์„ ์„ค์ •ํ•˜์˜€๋‹ค. ์—ฐ๊ตฌ์˜ ์ž๋ฃŒ์ˆ˜์ง‘์€ 2000๋…„ 10์›” 9์ผ์—์„œ 2000๋…„ 10์›” 28์ผ๊นŒ์ง€ ์‹ค์‹œํ•˜์˜€์œผ๋ฉฐ, ์„œ์šธ๊ณผ ์ˆ˜๋„๊ถŒ, ์ถฉ์ฒญ์ง€์—ญ์˜ ์ง์žฅ ๋ฏธํ˜ผ์—ฌ์„ฑ์„ ๋Œ€์ƒ์œผ๋กœ ์ž๋ฃŒ๋ฅผ ์ˆ˜์ง‘ํ•˜์˜€๋‹ค. ์ž๋ฃŒ์ˆ˜์ง‘๋ฐฉ๋ฒ•์€ ์ž๊ฐ€๋ณด๊ณ ์‹ ์„ค๋ฌธ์ง€๋กœ ํ•˜์˜€์œผ๋ฉฐ ์ด 375๊ฐœ์˜ ์ž๋ฃŒ๊ฐ€ ๋ถ„์„๋˜์—ˆ๋‹ค. ๋ชจํ˜•๊ฒ€์ฆ์— ์ด์šฉ๋œ ์ด 7๊ฐœ ์—ฐ๊ตฌ๋„๊ตฌ์˜ Cronbach' Alpha ๊ฐ’์˜ ๋ฒ”์œ„๋Š” 0.64์—์„œ 0.95์˜€๋‹ค. ๋Œ€์ƒ์ž์˜ ์ผ๋ฐ˜์ ์ธ ํŠน์„ฑ๊ณผ ์—ฐ๊ตฌ๋ณ€์ˆ˜์˜ ํŠน์„ฑ์€ SPSS 9.02 Win Program์„ ์ด์šฉํ•˜์—ฌ ๋ถ„์„ํ•˜์˜€์œผ๋ฉฐ, ๊ฐ€์„ค์  ๋ชจํ˜•๊ณผ ์ˆ˜์ •๋ชจํ˜•์˜ ๊ฒ€์ฆ์€ LISREL 8.12 Win Program์„ ์ด์šฉํ•˜์—ฌ ๊ณต๋ณ€๋Ÿ‰ ๊ตฌ์กฐ๋ถ„์„์„ ํ•˜์˜€๋‹ค. ๋ณธ ์—ฐ๊ตฌ์˜ ๊ฒฐ๊ณผ๋Š” ๋‹ค์Œ๊ณผ ๊ฐ™๋‹ค. 1. ๋ชจํ˜•์˜ ๋ถ€ํ•ฉ๋„ ๋ถ„์„๊ฒฐ๊ณผ 1) ๊ฐ€์„ค์  ๋ชจํ˜•์˜ ์ „๋ฐ˜์ ์ธ ๋ถ€ํ•ฉ์ง€์ˆ˜๋Š” ๋†’๊ฒŒ ๋‚˜ํƒ€๋‚˜ ๋ชจํ˜•๊ณผ ์‹ค์ œ์ž๋ฃŒ๊ฐ€ ์ž˜ ๋ถ€ ํ•ฉํ•˜๋Š” ๊ฒƒ์œผ๋กœ ๋‚˜ํƒ€๋‚ฌ๋‹ค(ฯ‡ยฒ/df=1.46(p=.10), GFI=.98, AGFI=.94, RMR=.01, NNFI=.98, NFI=.98, CN=505). 2) ๋ชจํ˜•์˜ ๊ฐ„๋ช…ํ•จ๊ณผ ๋ถ€ํ•ฉ๋„๋ฅผ ๋†’์ด๊ธฐ ์œ„ํ•ด ์„ธ๋ถ€์ง€์ˆ˜๋ฅผ ์ด์šฉํ•˜์—ฌ 3๊ฐœ์˜ ๊ฒฝ๋กœ๋ฅผ ์ œ๊ฑฐํ•˜์—ฌ ์ˆ˜์ •๋ชจํ˜•์„ ํ™•์ •ํ•˜์˜€๋‹ค. ์ˆ˜์ •๋ชจํ˜•์˜ ๋ถ€ํ•ฉ์ง€์ˆ˜๋Š” ๊ฐ€์„ค์  ๋ชจํ˜•์˜ ๋ถ€ ํ•ฉ์ง€์ˆ˜๋ณด๋‹ค ์กฐ๊ธˆ ๋” ๋‚˜์€ ๊ฒƒ์œผ๋กœ ๋‚˜ํƒ€๋‚ฌ๋‹ค(ฯ‡ยฒ/df=1.28(p=.18), GFI=.98, AGFI=.94, RMR=.01, NNFI=.99, NFI=.98, CN=549). 2, ๊ฐ€์„ค๊ฒ€์ฆ์˜ ๊ฒฐ๊ณผ 1) ์ž์•„์กด์ค‘๊ฐ์€ ๋‚ด์  ๊ฑด๊ฐ•ํ†ต์ œ์œ„๊ฐ€ ๋†’์„์ˆ˜๋ก(ฮณ11=0.29, t=6.57), ์„ฑ์—ญํ•  ์ •์ฒด ์„ฑ์˜ ๋‚จ์„ฑ์„ฑ(ฮณ13=0.23, t=7.40)๊ณผ ์—ฌ์„ฑ์„ฑ(ฮณ14=0.12, t=4.08)์ด ๋†’์„์ˆ˜๋ก, ๊ทธ๋ฆฌ ๊ณ  ์ธ์ง€๋œ ์ƒํ™œ์ŠคํŠธ๋ ˆ์Šค๊ฐ€ ๋‚ฎ์„์ˆ˜๋ก(ฮณ15=--0.17, t=-3.08) ๋†’๊ฒŒ ๋‚˜ํƒ€๋‚ฌ๋‹ค. 2) ๊ฑด๊ฐ•๊ด€๋ จ ์ž๊ธฐํšจ๋Šฅ์€ ๋‚ด์  ๊ฑด๊ฐ•ํ†ต์ œ์œ„(ฮณ21=0.12, t=2.44)์™€ ํƒ€์ธ์˜์กด ๊ฑด๊ฐ• ํ†ต์ œ์œ„๊ฐ€ ๋†’์„์ˆ˜๋ก(ฮณ22=0.16, t=3.22), ์„ฑ์—ญํ•  ์ •์ฒด์„ฑ์˜ ์—ฌ์„ฑ์„ฑ์ด ๋†’์„์ˆ˜๋ก (ฮณ24=0.08, t=2.46), ์ž์•„์กด์ค‘๊ฐ์ด ๋†’์„์ˆ˜๋ก(ฮฒ21=0.25, t=4.54) ๋†’๊ฒŒ ๋‚˜ํƒ€ ๋‚ฌ๋‹ค. ์„ฑ์—ญํ•  ์ •์ฒด์„ฑ์˜ ๋‚จ์„ฑ์„ฑ์€ ์ง์ ‘ํšจ๊ณผ(ฮณ23=0.04, t=1.22)๋Š” ์œ ์˜ํ•˜์ง€ ์•Š ์•˜์œผ๋‚˜ ๊ฐ„์ ‘ํšจ๊ณผ(ํšจ๊ณผ๊ณ„์ˆ˜=0.06, t=3.85)๊ฐ€ ์œ ์˜ํ•˜๊ฒŒ ๋‚˜ํƒ€๋‚˜ ์ดํšจ๊ณผ(ํšจ๊ณผ๊ณ„ ์ˆ˜=0.10, t=2.84)๊ฐ€ ํ†ต๊ณ„์ ์œผ๋กœ ์œ ์˜ํ•˜๊ฒŒ ๋‚˜ํƒ€๋‚ฌ๋‹ค. ๋˜ํ•œ ์ธ์ง€๋œ ์ƒํ™œ์ŠคํŠธ ๋ ˆ์Šค๋Š” ์ง์ ‘ํšจ๊ณผ๋Š” ์—†์œผ๋‚˜ ๊ฐ„์ ‘ํšจ๊ณผ(ํšจ๊ณผ๊ณ„์ˆ˜=-0.04, t=-2.68)๊ฐ€ ์ถ”๊ฐ€๋˜์–ด ์œ ์˜ํ•˜๊ฒŒ ๋‚˜ํƒ€๋‚˜ ๊ฑด๊ฐ•๊ด€๋ จ ์ž๊ธฐํšจ๋Šฅ์— ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š” ๊ฒƒ์œผ๋กœ ๋‚˜ํƒ€๋‚ฌ๋‹ค. 3) ์นœ๊ตฌ์˜ํ–ฅ์€ ์ธ์ง€๋œ ์ƒํ™œ์ŠคํŠธ๋ ˆ์Šค๊ฐ€ ๋†’์„์ˆ˜๋ก(ฮณ35=0.22, t=3.95), ๊ฑด๊ฐ•๊ด€๋ จ ์ž๊ธฐํšจ๋Šฅ์ด ๋‚ฎ์„์ˆ˜๋ก(ฮฒ32=-0.23, t=-4.41) ๋งŽ์ด ๋ฐ›๋Š” ๊ฒƒ์œผ๋กœ ๋‚˜ํƒ€๋‚ฌ๋‹ค. ๋‚ด์  ๊ฑด๊ฐ•ํ†ต์ œ์œ„์™€๋Š” ์ง์ ‘ํšจ๊ณผ(ฮณ31=-0.05, t=-1.38)๋Š” ์œ ์˜ํ•˜์ง€ ์•Š์•˜์œผ๋‚˜ ๊ฐ„์ ‘ํšจ๊ณผ(ํšจ๊ณผ๊ณ„์ˆ˜=-0.04, t=-2.97)๊ฐ€ ์ถ”๊ฐ€๋˜์–ด ์ดํšจ๊ณผ(ํšจ๊ณผ๊ณ„์ˆ˜=-0.09, t=-2.61)๊ฐ€ ์œ ์˜ํ•˜๊ฒŒ ๋‚˜ํƒ€๋‚ฌ๋‹ค. ์„ฑ์—ญํ•  ์ •์ฒด์„ฑ์˜ ๋‚จ์„ฑ์„ฑ๊ณผ ์—ฌ์„ฑ์„ฑ์€ ์นœ๊ตฌ์˜ ํ–ฅ์— ๋Œ€ํ•œ ์ง์ ‘ํšจ๊ณผ๋Š” ์—†์œผ๋‚˜ ๊ฐ„์ ‘ํšจ๊ณผ(๋‚จ์„ฑ์„ฑ; ํšจ๊ณผ๊ณ„์ˆ˜=-0.03, t=-2.34, ์—ฌ์„ฑ์„ฑ; ํšจ๊ณผ๊ณ„์ˆ˜=-0.03, t=-2.58)๊ฐ€ ์œ ์˜ํ•˜๊ฒŒ ๋‚˜ํƒ€๋‚˜ ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š” ๊ฒƒ์œผ๋กœ ๋‚˜ํƒ€๋‚ฌ๋‹ค. 4) ๊ฑด๊ฐ•์œ„ํ—˜ํ–‰์œ„๋Š” ์„ฑ์—ญํ•  ์ •์ฒด์„ฑ์˜ ๋‚จ์„ฑ์„ฑ์ด ๋†’์„์ˆ˜๋ก(ฮณ43= 0.06, t=2.75), ์—ฌ์„ฑ์„ฑ์ด ๋‚ฎ์„์ˆ˜๋ก(ฮณ44=-0.05, t=-2.11), ๊ฑด๊ฐ•๊ด€๋ จ ์ž๊ธฐํšจ๋Šฅ์ด ๋†’์„์ˆ˜๋ก (ฮฒ42=-0.21, t=-4.37), ๊ทธ๋ฆฌ๊ณ  ์นœ๊ตฌ์˜ํ–ฅ์ด ๋งŽ์„์ˆ˜๋ก(ฮฒ43= 0.21, t=3.80) ๋†’๊ฒŒ ๋‚˜ํƒ€๋‚ฌ๋‹ค. ๊ฑด๊ฐ•์œ„ํ—˜ํ–‰์œ„์—์„œ ์ง์ ‘ํšจ๊ณผ๋Š” ์œ ์˜ํ•˜์ง€ ์•Š์•˜์œผ๋‚˜ ๊ฐ„์ ‘ํšจ๊ณผ๊ฐ€ ์ถ”๊ฐ€๋˜์–ด ์ดํšจ๊ณผ๊ฐ€ ์œ ์˜ํ•˜๊ฒŒ ๋‚˜์˜จ ๊ฒฝ๋กœ๋Š” ๋‚ด์  ๊ฑด๊ฐ•ํ†ต์ œ์œ„(ํšจ๊ณผ๊ณ„์ˆ˜=-0.10, t=-2.614), ์ธ์ง€๋œ ์ƒํ™œ์ŠคํŠธ๋ ˆ์Šค(ํšจ๊ณผ๊ณ„์ˆ˜=0.11, t=2.39)์™€ ์ž์•„์กด์ค‘๊ฐ(ํšจ๊ณผ๊ณ„ ์ˆ˜=-0.07, t=-2.12)์ด๋‹ค. ๊ฑด๊ฐ•์œ„ํ—˜ํ–‰์œ„์— ๊ฐ€์žฅ ์ดํšจ๊ณผ๊ฐ€ ํฐ ๊ฒฝ๋กœ๋Š” ๊ฑด๊ฐ•๊ด€๋ จ ์ž๊ธฐํšจ๋Šฅ์—์„œ ๊ฑด๊ฐ•์œ„ํ—˜ ํ–‰์œ„๋กœ ๊ฐ€๋Š” ๊ฒฝ๋กœ์˜€๋‹ค(ํšจ๊ณผ๊ณ„์ˆ˜=-0.26, t=-4.68). ์ด์ƒ์˜ ๋ชจํ˜•๊ฒ€์ฆ์˜ ๊ฒฐ๊ณผ ๋ณธ ์—ฐ๊ตฌ์—์„œ ๊ตฌ์ถ•ํ•œ ๋ฏธํ˜ผ์—ฌ์„ฑ์˜ ๊ฑด๊ฐ•์œ„ํ—˜ํ–‰์œ„ ์˜ˆ์ธก๋ชจํ˜•์€ ์‹ค์ œ์ž๋ฃŒ์™€ ์ž˜ ๋ถ€ํ•ฉํ•˜์—ฌ ๋ฏธํ˜ผ์—ฌ์„ฑ์˜ ๊ฑด๊ฐ•์œ„ํ—˜ํ–‰์œ„๋ฅผ ์ ์ ˆํ•˜๊ฒŒ ์˜ˆ์ธกํ•˜๋Š” ๋ชจํ˜•์ด๋ผ๊ณ  ์ƒ๊ฐ๋œ๋‹ค. ๋ณธ ์—ฐ๊ตฌ์˜ ๋ชจํ˜•๊ฒ€์ฆ ๊ฒฐ๊ณผ ๋ฏธํ˜ผ์—ฌ์„ฑ์˜ ๊ฑด๊ฐ•์œ„ํ—˜ํ–‰์œ„์— ๊ฐ€์žฅ ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š” ๋งค๊ฐœ๋ณ€์ˆ˜๋Š” ๊ฑด๊ฐ•๊ด€๋ จ ์ž๊ธฐํšจ๋Šฅ์œผ๋กœ ๋‚˜ํƒ€๋‚ฌ๋‹ค. ๊ฑด๊ฐ•๊ด€๋ จ ์ž๊ธฐํšจ๋Šฅ์€ ๋‚ด์  ๊ฑด๊ฐ•ํ†ต์ œ์œ„, ํƒ€์ธ์˜์กด ๊ฑด๊ฐ•ํ†ต์ œ์œ„, ์„ฑ์—ญํ•  ์ •์ฒด์„ฑ์˜ ์—ฌ์„ฑ์„ฑ๊ณผ ์ž์•„์กด์ค‘๊ฐ์— ์˜ํ•ด ์˜ํ–ฅ์„ ๋ฐ›๋Š”๋‹ค. ์ž์•„์กด์ค‘๊ฐ์€ ๋‚ด์  ๊ฑด๊ฐ•ํ†ต์ œ์œ„, ์„ฑ์—ญํ•  ์ •์ฒด์„ฑ์˜ ๋‚จ์„ฑ์„ฑ๊ณผ ์—ฌ์„ฑ์„ฑ ๋ฐ ์ธ์ง€๋œ ์ƒํ™œ์ŠคํŠธ๋ ˆ์Šค์˜ ์˜ํ–ฅ์„ ๋ฐ›์œผ๋‚˜, ๊ฑด๊ฐ•์œ„ํ—˜ํ–‰์œ„์— ์ง์ ‘์ ์ธ ์˜ํ–ฅ์„ ์ฃผ์ง€๋Š” ์•Š๋Š”๋‹ค. ์นœ๊ตฌ์˜ํ–ฅ์€ ์ธ์ง€๋œ ์ƒํ™œ์ŠคํŠธ๋ ˆ์Šค์™€ ๊ฑด๊ฐ•๊ด€๋ จ ์ž๊ธฐํšจ๋Šฅ์œผ๋กœ๋ถ€ํ„ฐ ์ง์ ‘์ ์ธ ์˜ํ–ฅ์„ ๋ฐ›์œผ๋ฉฐ, ๊ฑด๊ฐ•์œ„ํ—˜ํ–‰์œ„์— ์ง์ ‘์ ์ธ ์˜ํ–ฅ์„ ๋ฏธ์นœ๋‹ค. ์ด๋Ÿฌํ•œ ์—ฐ๊ตฌ๊ฒฐ๊ณผ๋ฅผ ๋ฐ”ํƒ•์œผ๋กœ ๋ฏธํ˜ผ์—ฌ์„ฑ์˜ ๊ฑด๊ฐ•์œ„ํ—˜ํ–‰์œ„๋ฅผ ์˜ˆ๋ฐฉํ•˜๊ธฐ ์œ„ํ•˜์—ฌ๋Š” ๊ฑด๊ฐ•๊ด€๋ จ ์ž๊ธฐํšจ๋Šฅ์„ ๋†’์ด๊ณ , ์ž์‹ ์˜ ์„ฑ์—ญํ•  ์ •์ฒด์„ฑ์˜ ์—ฌ์„ฑ์„ฑ์— ๋Œ€ํ•œ ์ธ์ง€๋ฅผ ํ™•๊ณ ํžˆ ํ•˜๋ฉฐ, ๊ฑด๊ฐ•์œ„ํ—˜ํ–‰์œ„์™€ ๊ด€๋ จ๋˜์–ด ์นœ๊ตฌ์˜ํ–ฅ์„ ์ ๊ฒŒ ๋ฐ›๋„๋ก ๊ฐ•์กฐํ•˜์—ฌ์•ผ ํ•  ๊ฒƒ์ด๋‹ค. ๋”ฐ๋ผ์„œ ์ด๋Ÿฌํ•œ ๋‚ด์šฉ์„ ๋ฐ”ํƒ•์œผ๋กœ ํ•œ ํ”„๋กœ๊ทธ๋žจ์˜ ๊ฐœ๋ฐœ๊ณผ ์ ์šฉ ๋ฐ ๊ต์œก ๋“ฑ์˜ ์ค‘์žฌ๋ฐฉ์•ˆ๋“ค์„ ๊ฐ•๊ตฌํ•ด์•ผ ํ•  ๊ฒƒ์œผ๋กœ ๋ณด๋ฉฐ, ๊ฑด๊ฐ•์œ„ํ—˜ํ–‰์œ„์— ์ง์ ‘์ ์ธ ์˜ํ–ฅ์€ ์—†์œผ๋‚˜ ๊ฐ„์ ‘์ ์œผ๋กœ ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š” ๋‚ด์  ๊ฑด๊ฐ•ํ†ต์ œ์œ„์™€ ์ž์•„์กด์ค‘๊ฐ์„ ์ฆ๊ฐ€์‹œํ‚ค๊ณ  ์ŠคํŠธ๋ ˆ์Šค๋ฅผ ์ค„์ด๋Š” ๊ฐ„ํ˜ธ์ค‘์žฌ ์ „๋žต์˜ ๊ฐœ๋ฐœ๋„ ๋ฏธํ˜ผ์—ฌ์„ฑ์˜ ๊ฑด๊ฐ•์œ„ํ—˜ํ–‰์œ„๋ฅผ ์ค„์ด๊ธฐ ์œ„ํ•ด ํ•„์š”ํ•˜๋‹ค๊ณ  ๋ณธ๋‹ค. _____________________________________ ํ•ต์‹ฌ๋˜๋Š” ๋ง: ๋ฏธํ˜ผ์—ฌ์„ฑ, ๊ฑด๊ฐ•์œ„ํ—˜ํ–‰์œ„ [์˜๋ฌธ]The Purpose of this study is to identify the effects of the psychological factors on health risk behaviors and to develop a predictive model that explains health risk behaviors of unmarried women in Korea. A hypothetical model was constructed on the basis of extensive review of literature on health risk behaviors. The exogenous variables of the hypohtetical model were internal health locus of control, powerful others health locus of control, masculinity and feminity of sex-role identity, and perceived life stress. The endogenous variables included self-esteem, health related self-efficacy, peer influence, and health risk behaviors such as drinking, smoking and sexual risk taking behaviors. The data was collected by self-reported questionnaire from 375 unmarried career women in Seoul, Kyunggi-Do, and Chungchung-Do from October, 9 to October, 28, 2000. Reliabilities of the seven instruments were tested Chronbach's alpha score which ranged from 0.64 to 0.95. Data analysis was done using SPSS 9.02 Win Program for descriptive and correlational statistics. LISREL 8.12 Win Program was used for covariance structural analysis to find the best fit model which assumes causal relationship among variables. The results are as follows; 1. The results of covariance structural analysis indicated: 1) The overall measure of fit of the hypothetical model to the data was shown to be good. ใ€”ฯ‡ยฒ/df=1.46(p=.10), GFI=.98, AGFI=.94, RMR=.01, NNFI=.98, NFI=.98, CN=505ใ€• 2) Paths of the model were modified by considering theoretical implication and statistical significance of parameter estimates. A modified model was constructed by deleting three paths. Compared to the hypothetical model, the revised one had a better fit to the data. ใ€”ฯ‡ยฒ/df=1.28(p=.18), GFI=.98, AGFI=.94, RMR=.01, NNFI=.99, NFI=.98, CN=549ใ€• 2. The results of hypothesis testing were as follows: 1) Internal health locus of control(ฮณ11=0.29, t=6.57), masculinity(ฮณ13=0.23, t=7.40) and feminity(ฮณ14=0.12, t=4.08) of sex-role identity, and perceived life stress(ฮณ15=-0.17, t=-3.08) had significant direct effects on self-esteem. 2) Internal health locus of control(ฮณ21=0.12, t=2.44), powerful others health locus of control(ฮณ22=0.16, t=3.22), feminity of sex-role identity(ฮณ24=0.08, t=2.46), and self-esteem(ฮฒ21=0.25, t=4.54) had significant direct effects on health related self-efficacy. The direct effects of masculinity of sex-role identity(ฮณ23=0.04, t=1.22) and perceived life stress on health related self-efficacy were insignificant but their indirect effects were significant. 3) Perceived life stress(ฮณ35=0.22, t=3.95) and health related self-efficacy(ฮฒ 32=-0.23, t=-4.41) had significant direct effects on peer influence. The direct effects of internal health locus of control(ฮณ31= -0.05, t=-1.38), and masculinity and feminity of sex-role identity on peer influence were not significant, while their indirect effects were significant on that. 4) Masculinity(ฮณ43= 0.06, t=2.75) and feminity(ฮณ44=-0.05, t=-2.11) of sex role identity, health related self-efficacy(ฮฒ42=-0.21, t=-4.37), and peer influence (ฮฒ43= 0.21, t=3.80) had significant direct effects on health risk behaviors. Internal health locus of control, perceived life stress, and self-esteem had significant both indirect and total effects statistically, but not direct effects on health risk behaviors. The above findings showed that health related self-efficacy as a mediating variable had the most significant direct effect on health risk behaviors of unmarried women. Also peer influence had a significant direct effect on them. Internal and powerful others health locus of control, feminity of sex-role identity, and self-esteem had significant direct effects on health related self-efficacy. Self-esteem had not a significant direct effect on health risk behaviors and internal health locus of control, masculinity and feminity of sex-role identity, and perceived life stress had significant direct effects on self-esteem. Peer influence had influenced on health risk behaviors directly, and perceived life stress and health related self-efficacy had significant direct effects on peer influence. Finally, to increase health related self-efficacy, to identify sex-role identity, and to reduce peer influence, an effective intervention program and education should be developed to prevent health risk behaviors of unmarried women. Also it is necessary to develop nursing intervention strategies for health risk behaviors of unmarried women by increasing internal health locus of control and self-esteem, and reducing perceived life stress which had significant indirect effects on health risk behaviors. ___________________________________ Key words: Unmarried women, Health Risk Behaviorsope

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :์˜๋ฅ˜ํ•™๊ณผ,2003.Maste
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