38 research outputs found

    ์ถœ์‚ฐ์žฅ๋ ค๊ธˆ ์ •์ฑ…์˜ ํšจ๊ณผ์— ๊ด€ํ•œ ์—ฐ๊ตฌ

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ํ–‰์ •ํ•™๊ณผ, 2017. 2. ๋ฐ•์ƒ์ธ.๊ตญ๋ฌธ์ดˆ๋ก ์šฐ๋ฆฌ๋‚˜๋ผ๋Š” ํ˜„์žฌ ์„ธ๊ณ„์ ์œผ๋กœ ์œ ๋ก€์—†๋Š” ๊ธ‰๊ฒฉํ•œ ์ €์ถœ์‚ฐ ๋ฐ ๊ณ ๋ นํ™”์‚ฌํšŒ๋กœ์˜ ์ „ํ™˜ ์‹œ๊ธฐ์— ์ง๋ฉดํ•ด์žˆ๋‹ค. ์ •๋ถ€๋Š” ์ด๋Ÿฌํ•œ ๋ฌธ์ œ์— ๋ณธ๊ฒฉ์ ์œผ๋กœ ๋Œ€์‘ํ•˜๊ธฐ ์œ„ํ•ด์„œ ์ €์ถœ์‚ฐ์„ ๊ทน๋ณตํ•˜๊ธฐ ์œ„ํ•œ ๋‹ค์–‘ํ•œ ์ •์ฑ…์„ ์ง‘ํ–‰ํ•˜๊ณ  ์žˆ๋‹ค. ์ถœ์‚ฐ์„ ์žฅ๋ คํ•˜๊ธฐ ์œ„ํ•œ ์ •์ฑ…์˜ ํ•˜๋‚˜์ธ ์ถœ์‚ฐ์žฅ๋ ค๊ธˆ ์ง€๊ธ‰์€ 2000๋…„์— ์ฒ˜์Œ์œผ๋กœ ์‹œํ–‰๋˜์–ด 2004๋…„๋ถ€ํ„ฐ ๋ณธ๊ฒฉ์ ์œผ๋กœ ๋„์ž…๋œ ์ •์ฑ…์œผ๋กœ ํ˜„ ์‹œ์ ์—์„œ๋Š” ๊ฑฐ์˜ ๋ชจ๋“  ์ง€๋ฐฉ์ž์น˜๋‹จ์ฒด๊ฐ€ ์ถœ์‚ฐ ์‚ฐ๋ชจ์—๊ฒŒ ์ถœ์‚ฐ์žฅ๋ ค๊ธˆ์„ ์ง€๊ธ‰ํ•˜๊ณ  ์žˆ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ์ด๋Ÿฌํ•œ ์ •๋ถ€ ์ •์ฑ… ์ง‘ํ–‰์—๋„ ๋ถˆ๊ตฌํ•˜๊ณ  2004๋…„๋ถ€ํ„ฐ ํ˜„์žฌ๊นŒ์ง€์˜ ์ถœ์‚ฐ์œจ ์ง€ํ‘œ๋Š” ๊ทธ๋ฆฌ ๋†’์•„์ง€์ง€ ์•Š์•˜๋‹ค. ๋”ฐ๋ผ์„œ ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” ์ถœ์‚ฐ์žฅ๋ ค๊ธˆ์˜ ์ง€๊ธ‰์ด ์‹ค์ œ๋กœ ์ถœ์‚ฐ์œจ ํ–ฅ์ƒ์— ์–ด๋–ค ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š”์ง€์— ๋Œ€ํ•ด์„œ ์—ฐ๊ตฌํ•˜๊ณ ์ž ํ•œ๋‹ค. 2004๋…„๋ถ€ํ„ฐ 2014๋…„๊นŒ์ง€ ์ „๊ตญ ์ง€๋ฐฉ์ž์น˜๋‹จ์ฒด์—์„œ ์ž๋ฃŒ์ˆ˜์ง‘์ด ๊ฐ€๋Šฅํ•œ 179๊ฐœ์˜ ์ž์น˜๋‹จ์ฒด๋ฅผ ์„ ์ •ํ•˜์—ฌ ํŒจ๋„์ž๋ฃŒ๋ฅผ ๊ตฌ์ถ•ํ•˜๊ณ  ์ถœ์‚ฐ์œจ์— ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š” ๋‹ค์–‘ํ•œ ๋ณ€์ˆ˜๋ฅผ ์ธ๊ตฌํ•™์  ์š”์ธ, ๊ฒฝ์ œ์  ์š”์ธ, ์‚ฌํšŒ์  ์š”์ธ ๋“ฑ์œผ๋กœ ๊ตฌ๋ถ„ํ•˜์—ฌ ๊ทธ ์˜ํ–ฅ์„ ๊ฒ€์ฆํ•˜์˜€๋‹ค. ํŒจ๋„ ํšŒ๊ท€๋ถ„์„์„ ํ†ตํ•ด ํ•ฉ๊ณ„์ถœ์‚ฐ์œจ model 1, ์ด ์ถœ์ƒ์•„์ˆ˜ model 2, ์—ฐ๋ น๋ณ„ ์ถœ์‚ฐ์œจ model 3, ์ถœ์ƒ์ˆœ์œ„๋ณ„ ์ถœ์ƒ์•„์ˆ˜ model 4์˜ ๋ชจํ˜•์œผ๋กœ ๋‚˜๋ˆ  ์ถœ์‚ฐ์žฅ๋ ค๊ธˆ์ด ํ•ด๋‹น ์ข…์†๋ณ€์ˆ˜์— ๋ฏธ์น˜๋Š” ์˜ํ–ฅ์„ ๊ฒ€์ฆํ•˜์˜€๊ณ , ๊ทธ ๊ฒฐ๊ณผ ์ถœ์‚ฐ์žฅ๋ ค๊ธˆ์˜ ์•ก์ˆ˜๊ฐ€ ๋น„๊ต์  ํฐ ์ „๋ผ๋„, ๊ฒฝ์ƒ๋„์—์„œ๋Š” ์ถœ์‚ฐ์œจ์— ์œ ์˜๋ฏธํ•œ ์–‘์˜ ๊ด€๊ณ„๊ฐ€ ์žˆ์Œ์„ ํ™•์ธํ•˜์˜€์œผ๋‚˜, ์ถœ์‚ฐ์žฅ๋ ค๊ธˆ์˜ ์•ก์ˆ˜๊ฐ€ ์ ๊ณ  ํ˜œํƒ์„ ๋ฐ›๋Š” ๋Œ€์ƒ์ด ๋‹ค์ˆ˜์ธ ์ˆ˜๋„๊ถŒ์—์„œ๋Š” ์ถœ์‚ฐ์žฅ๋ ค๊ธˆ์˜ ํ˜œํƒ์ด ๋ฏธ๋ฏธํ•จ์„ ๋ฐํ˜€๋ƒˆ๋‹ค. ๋”ฐ๋ผ์„œ ๋ณธ ์—ฐ๊ตฌ์˜ ๊ฒฐ๋ก ์œผ๋กœ ์ถœ์‚ฐ์žฅ๋ ค๊ธˆ ์ •์ฑ…์˜ ์ ‘๊ทผ ๋ฐฉ์‹์„ ๋‹ค์Œ๊ณผ ๊ฐ™์ด ์ œ์•ˆํ•˜์˜€๋‹ค. ์ „์ฒด ์˜ˆ์‚ฐ๊ทœ๋ชจ๊ฐ€ ํฌ์ง€๋งŒ ์ •์ฑ…์ˆ˜ํ˜œ์ž๊ฐ€ ๋งŽ์•„ ์ƒ๋Œ€์ ์œผ๋กœ ์ ์€ ์ถœ์‚ฐ์žฅ๋ ค๊ธˆ์„ ์ง€๊ธ‰๋ฐ›๋Š” ์ˆ˜๋„๊ถŒ์˜ ๊ฒฝ์šฐ, ๋ณด์œก์‹œ์„ค ํ™•๋Œ€๋ฅผ ์œ„ํ•œ ํˆฌ์ž, ์ถœ์‚ฐ ์ดํ›„ ์œก์•„ ์„œ๋น„์Šค ์ฆ๋Œ€ ์ง€์›์„ ํ†ตํ•ด ์ถœ์‚ฐ์— ๋Œ€ํ•œ ๋ฐฉ๋ฒ•์„ ์ „ํ™˜ํ•  ํ•„์š”๊ฐ€ ์žˆ์œผ๋ฉฐ, ์ง€๋ฐฉ์˜ ๊ฒฝ์šฐ ํ˜„์žฌ์˜ ๋ฐฉ์‹๋Œ€๋กœ ์ˆ˜๋„๊ถŒ๋ณด๋‹ค ๋งŽ์€ ์ถœ์‚ฐ์žฅ๋ ค๊ธˆ ์ง€๊ธ‰์„ ํ†ตํ•ด ์ถœ์‚ฐ์œจ์„ ํ–ฅ์ƒ์‹œํ‚ค๋Š” ๋…ธ๋ ฅ์ด ํ•„์š”ํ•˜๋‹ค๋Š” ์ ์„ ๊ฐ•์กฐํ•˜์˜€๋‹ค. ์ฃผ์š”์–ด : ์ถœ์‚ฐ์žฅ๋ ค๊ธˆ, ํ•ฉ๊ณ„์ถœ์‚ฐ์œจ, ์ด ์ถœ์ƒ์•„์ˆ˜, ์—ฐ๋ น๋ณ„ ์ถœ์‚ฐ์œจ, ์ถœ์ƒ์ˆœ์œ„๋ณ„ ์ถœ์ƒ์•„์ˆ˜, ํŒจ๋„ํšŒ๊ท€๋ถ„์„ ํ•™ ๋ฒˆ : 2013-23609์ œ 1 ์žฅ ์„œ ๋ก  1 ์ œ 2 ์žฅ ํ•œ๊ตญ์˜ ์ €์ถœ์‚ฐ ํ˜„ํ™ฉ๊ณผ ์ถœ์‚ฐ์žฅ๋ ค์ •์ฑ… 3 1. ํ•œ๊ตญ์˜ ์ €์ถœ์‚ฐ ํ˜„ํ™ฉ 3 2. ํ•œ๊ตญ ์ง€๋ฐฉ์ž์น˜๋‹จ์ฒด์˜ ์ถœ์‚ฐ์žฅ๋ ค์ •์ฑ… 6 ์ œ 3 ์žฅ ์„ ํ–‰์—ฐ๊ตฌ์˜ ๊ฒ€ํ†  10 1. ํ•ด์™ธ ์„ ํ–‰์—ฐ๊ตฌ 10 2. ๊ตญ๋‚ด ์„ ํ–‰์—ฐ๊ตฌ 11 3. ์„ ํ–‰์—ฐ๊ตฌ ์ •๋ฆฌ์™€ ํ•œ๊ณ„ 17 ์ œ 4 ์žฅ ๋ถ„์„๋‹จ์œ„์™€ ๋ณ€์ˆ˜์˜ ์„ค์ • 19 1. ๋ถ„์„ ๋‹จ์œ„ 19 1) ์—ฐ๊ตฌ๋Œ€์ƒ 19 2) ๋ถ„์„๋ฐฉ๋ฒ• 21 2. ๋ณ€์ˆ˜์˜ ์„ค์ • 21 1) ์ข…์†๋ณ€์ˆ˜ 21 2) ๋…๋ฆฝ๋ณ€์ˆ˜ 23 3) ํ†ต์ œ๋ณ€์ˆ˜ 24 3. ๊ฐ€์„ค ์„ค์ • 26 4. ๋ถ„์„๋ชจํ˜• 28 ์ œ 5 ์žฅ ๋ถ„์„ ๊ฒฐ๊ณผ 29 1. ๊ธฐ์ดˆํ†ต๊ณ„๋ฅผ ํ†ตํ•œ ๋น„๊ต๋ถ„์„ 29 1) ์ „๊ตญ ์ถœ์‚ฐ์žฅ๋ ค๊ธˆ ๊ธฐ์ดˆ ํ†ต๊ณ„ 29 2) ์ „๊ตญ ์—ฐ๋ น๋ณ„ ์ถœ์‚ฐ์œจ 30 3) ์ „๊ตญ ์ถœ์ƒ์ˆœ์œ„๋ณ„ ์ถœ์‚ฐ์žฅ๋ ค๊ธˆ 30 4) ์ง€์—ญ๋ณ„ ์ถœ์‚ฐ์žฅ๋ ค๊ธˆ ๊ธฐ์ดˆํ†ต๊ณ„ 31 (1) ์„œ์šธ 32 (2) ๊ฒฝ๊ธฐ 34 (3) ์ถฉ์ฒญ 36 (4) ๊ฒฝ์ƒ 38 (5) ์ „๋ผ 40 (6) ๊ฐ•์› 42 2. ์ „๊ตญ ์ถœ์‚ฐ์žฅ๋ ค๊ธˆ, ํ•ฉ๊ณ„์ถœ์‚ฐ์œจ, ์ด ์ถœ์ƒ์•„์ˆ˜ ๊ธฐ์ดˆํ†ต๊ณ„ 44 3. ์ „๊ตญ ์—ฐ๋ น๋ณ„ ์ถœ์‚ฐ์œจ ๊ธฐ์ดˆํ†ต๊ณ„ 45 4. ์ „๊ตญ ์ถœ์ƒ์ˆœ์œ„๋ณ„ ์ถœ์‚ฐ๊ธˆ ๋ฐ ์ถœ์ƒ์•„์ˆ˜ ๊ธฐ์ดˆํ†ต๊ณ„ 45 5. ์ƒ๊ด€๊ด€๊ณ„ ๋ถ„์„ 47 ์ œ 6 ์žฅ ๋ถ„์„๊ฒฐ๊ณผ 49 1. ํ•˜์šฐ์Šค๋งŒ ๊ฒ€์ • 49 2. ์ „๊ตญ ๋ถ„์„๊ฒฐ๊ณผ 51 3. ์„œ์šธ์‹œ ๋ถ„์„๊ฒฐ๊ณผ 52 4. ๊ฒฝ๊ธฐ๋„ ๋ถ„์„๊ฒฐ๊ณผ 54 5. ์ถฉ์ฒญ๋„ ๋ถ„์„๊ฒฐ๊ณผ 56 6. ๊ฐ•์›๋„ ๋ถ„์„๊ฒฐ๊ณผ 58 7. ์ „๋ผ๋„ ๋ถ„์„๊ฒฐ๊ณผ 60 8. ๊ฒฝ์ƒ๋„ ๋ถ„์„๊ฒฐ๊ณผ 62 ์ œ 7 ์žฅ ๊ฒฐ๋ก  64 1. ์—ฐ๊ตฌ์˜ ๊ฒฐ๊ณผ 64 2. ์—ฐ๊ตฌ์˜ ์‹œ์‚ฌ์  65 3. ์—ฐ๊ตฌ์˜ ํ•œ๊ณ„ 68 ์ฐธ๊ณ ๋ฌธํ—Œ 69 Abstract 73Maste

    Prognoses and Clinical Outcomes of Primary and Recurrent Uveal Melanoma.

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    PURPOSE: Uveal melanoma has a very poor prognosis despite successful local primary tumor treatment. In this study, we investigated prognostic factors that more accurately reflected the likelihood ofrecurrence and survival and delineated a prognostic model that could effectively identify different risk groups based on initial clinical parameters. Materials and Methods: Prognostic factors associated with distant recurrence, recurrence-free survival (RFS), progression-free survival, and overall survival from distant recurrence to death (OS2) were analyzed in 226 patients with stage I-III uveal melanoma who underwent primary local therapy. RESULTS: Forty-nine patients (21.7%) had distant recurrences, which occurred most frequently in the liver (87.7%). In a multivariate analysis, local radiotherapy improved RFS among patients with multiple recurrence risk factors relative to excision (not reached vs. 19.0 months, p=0.004). Patients with BRCA1-associated protein-1 (BAP1)โ€’negative primary tumors showed a longer RFS duration after primary treatments, while those with BAP1-negative metastatic tissues had a shorter OS2 compared to those with BAP1-positive tumors, both not statistically insignificance (RFS: not reached vs. 82.0 months, p=0.258; OS2: 15.7 vs. 24.4 months, p=0.216). Male sex (hazard ratio [HR], 3.79; p=0.012), a short RFS (HR, 4.89; p=0.014), and a largest metastatic tumor linear diameter โ‰ฅ 45 mm (HR, 5.48; p=0.017) were found to correlate with worse post-recurrence survival. CONCLUSION: Risk factors could be used to classify uveal melanoma cases and subsequently direct individual treatment strategies. Furthermore, metastasectomy appears to contribute to improved survival outcomes.ope

    Tropomyosin-Related Kinase Fusions in Gastrointestinal Stromal Tumors

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    The canonical mutations in gastrointestinal stromal tumors (GISTs) are typically activating mutations in KIT and platelet-derived growth factor receptor alpha (PDGFRA). GISTs with non-canonical mutations are a heterogeneous group. Here, we examined tropomyosin-related kinase (TRK) fusion in GIST cases without KIT/PDGFRA mutations (KIT/PDGFRA wild-type (WT) GISTs). We retrospectively analyzed patients who were diagnosed with GISTs at the Yonsei Cancer Center, Severance Hospital, between January 1998 and December 2016. Thirty-one patients with KIT/PDGFRA WT GISTs were included in the analysis. TRK expression in tumor samples was assessed by pan-TRK immunohistochemistry (IHC), and the neurotrophic tyrosine receptor kinase (NTRK: the gene encoding TRK) rearrangement was analyzed by fluorescence in situ hybridization (FISH). IHC analyses revealed that five cases in this cohort exhibited a weak to moderate TRK expression. NTRK1 fusions were detected in three tumor samples, and two samples harbored NTRK3 fusions. The remaining 26 samples did not harbor NTRK fusions. Two types of NTRK fusions were detected, and the overall NTRK fusion frequency in KIT/PDGFRA WT GIST cases was 16% (5/31). Our data provide insights into the molecular alterations underpinning KIT/PDGFRA WT GISTs. More effort should be devoted to improve methods to identify this distinct disease subtype within the KIT/PDGFRA WT GIST group.ope

    Detection of asymptomatic recurrence improves survival of gastric cancer patients

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    Background: The effect of long-term surveillance for asymptomatic patients after curative resection of gastric cancer is being debated. We compared the prognosis of Korean patients with recurrent gastric cancer according to the presence or absence of cancer-related symptoms at the time of recurrence detection. Methods: We retrospectively reviewed the medical records of 305 Korean patients who experienced recurrence after curative resection of primary gastric cancer between March 2002 and February 2017 at Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Results: The median follow-up duration was 169.8 months (1-267.2), and the median age at first recurrence was 58.1 years (23.4-81.9). Among 305 patients with recurrence, 97 of 231 (42.0%) patients with early recurrence (โ‰ค5 years after curative surgical resection) and 47 of 74 (63.5%) patients with late recurrence (>5 years after curative surgical resection) had cancer-related symptoms at recurrence (p = 0.001). For survival after recurrence, detection of asymptomatic recurrence was an independent favorable factor (hazard ratio, 0.527; 95% confidence interval, 0.409-0.681; p < 0.001) accompanied with the possibility of subsequent treatment, targeted-, or immunotherapy for recurrent disease, and locoregional recurrence only. In the late-recurrence group, the patients with asymptomatic detection of recurrence showed favorable post-recurrence survival (median, 33.3 months vs. 14.7 months; p = 0.002), overall survival (median, 136.3 months vs. 106.1 months; p = 0.010), and cancer-specific survival (median, 177.5 months vs. 106.1 months; p = 0.005) than the patients with symptomatic detection. Conclusion: The detection of gastric cancer recurrence in patients without cancer-related symptoms may be related to improved survival, suggesting the potential benefit of long-term surveillance.ope

    Role of adjuvant chemotherapy in locally advanced rectal cancer with ypT0-3N0 after preoperative chemoradiation therapy and surgery

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    BACKGROUND: We aimed to explore the clinical benefit of adjuvant chemotherapy (AC) with fluoropyrimidine in patients with ypT0-3N0 rectal cancer after preoperative chemoradiation therapy (CRT) followed by total mesorectal excision (TME). METHODS: Patients with ypT0-3N0 rectal cancer after preoperative CRT and TME were included using prospectively collected tumor registry cohort between January 2001 and December 2013. Patients were categorized into two groups according to the receipt of AC. Disease-free survival (DFS) and overall survival (OS) were compared between the adjuvant and observation groups. To control for potential confounding factors, we also calculated propensity scores and performed propensity score-matched analysis for DFS and OS. RESULTS: Of the 339 evaluated patients, 87 patients (25.7%) did not receive AC. There were no differences in DFS (hazard ratio [HR], 0.921; 95% confidence interval [CI], 0.562-1.507; Pโ€‰=โ€‰0.742) and OS (HR, 0.835; 95% CI, 0.423-1.648; Pโ€‰=โ€‰0.603) between the adjuvant and observation groups. After propensity score matching, DFS (HR, 1.129; 95% CI, 0.626-2.035; Pโ€‰=โ€‰0.688) and OS (HR, 1.200; 95% CI, 0.539-2.669; Pโ€‰=โ€‰0.655) did not differ between the adjuvant and observation groups. Advanced T stage and positive resection margin were independently associated with inferior DFS and OS on multivariate analysis. CONCLUSIONS: AC did not improve DFS and OS for patients with ypT0-3N0 rectal cancer after preoperative CRT followed by TME in this cohort study. The confirmative role of AC in locally advanced rectal cancer should be evaluated in prospective randomized trials with a larger sample size.ope

    ๋ฃจ์ด์†Œ์ฒด ์น˜๋งค ํ™˜์ž์—์„œ ํœด์ง€๊ธฐ ๋‡Œ ๋Œ€์‚ฌ ์—ฐ๊ฒฐ์„ฑ์˜ ๋ณ€ํ™”

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ์ž์—ฐ๊ณผํ•™๋Œ€ํ•™ ๋‡Œ์ธ์ง€๊ณผํ•™๊ณผ, 2019. 2. ๊น€๊ธฐ์›….Objective: Although Dementia with Lewy bodies (DLB) have Parkinsonism in common with Parkinsons disease (PD) or PD dementia (PDD), they have different neuropathology that underlie Parkinsonism. Altered brain functional connectivity that may correspond to neuropathology has been reported in PD while never been studied in DLB. We compared the resting state metabolic connectivity in striato-thalamo-cortical (STC) circuit, nigrostriatal pathway, and cerebello-thalamo-cortical motor (CTC) circuit in 27 drug-naรฏve DLB patients and 27 age- and sex-matched normal controls using 18F-fluoro-2-deoxyglucose positron emission tomography. Methods: We derived 118 regions of interest (ROIs) using the Automated Anatomical Labeling templates and the Wake Forest University Pick Atlas Tailarach Daemon. We applied the sparse inverse covariance estimation method to construct the metabolic connectivity matrix. Results: DLB patients, with or without Parkinsonism, showed lower inter-regional connectivity between the areas included in the STC circuit (motor cortex โ€“ striatum, midbrain โ€“ striatum, striatum โ€“ globus pallidus, and globus pallidus โ€“ thalamus) than the controls. DLB patients with Parkinsonism showed less reduced inter-regional connectivity between midbrain and striatum than those without Parkinsonism, and higher inter-regional connectivity between the areas included in the CTC circuit (motor cortex โ€“ pons, pons โ€“ cerebellum, and cerebellum โ€“ thalamus) than those without Parkinsonism and the controls. Interpretation: Resting state metabolic connectivity in the STC circuit may be reduced in DLB. In DLB with Parkinsonism, CTC circuit and nigrostriatal pathway may be activated to mitigate Parkinsonism. This difference in the brain connectivity may be a candidate biomarker for differentiating DLB from PD or PDD.๋ฐฐ๊ฒฝ : ๋ฃจ์ด์†Œ์ฒด ์น˜๋งค (DLB)๋Š” ํŒŒํ‚จ์Šจ๋ณ‘ (PD)์ด๋‚˜ ํŒŒํ‚จ์Šจ ์น˜๋งค (PDD)์™€ ๊ณตํ†ต์œผ๋กœ ํŒŒํ‚จ์Šจ ์ฆ์ƒ์„ ๊ฐ€์ง€์ง€๋งŒ, ์ด๋“ค์€ ํŒŒํ‚จ์Šจ ์ฆ์ƒ์˜ ๊ธฐ์ดˆ๊ฐ€ ๋˜๋Š” ์‹ ๊ฒฝ ๋ณ‘๋ฆฌํ•™์€ ๋‹ค๋ฅด๋‹ค. ํŒŒํ‚จ์Šจ ์ฆ์ƒ์˜ ์‹ ๊ฒฝ ๋ณ‘๋ฆฌํ•™์— ํ•ด๋‹นํ•˜๋Š” ๋‡Œ์˜ ๊ธฐ๋Šฅ์  ์—ฐ๊ฒฐ์„ฑ ๋ณ€ํ™”๋Š” ํŒŒํ‚จ์Šจ๋ณ‘์—์„œ๋Š” ๋ณด๊ณ ๋˜์—ˆ์ง€๋งŒ, ๋ฃจ์ด์†Œ์ฒด ์น˜๋งค์—์„œ๋Š” ์•Œ๋ ค์ง„ ๋ฐ” ์—†๋‹ค. ์šฐ๋ฆฌ๋Š” ์•ฝ๋ฌผ์„ ๋ณต์šฉ ์ด๋ ฅ์ด ์—†๋Š” ๋ฃจ์ด์†Œ์ฒด ํ™˜์ž 27๋ช…๊ณผ ๋‚˜์ด์™€ ์„ฑ๋ณ„์„ ๊ณ ๋ คํ•œ ์ •์ƒ ๋Œ€์กฐ๊ตฐ 27๋ช…์„ ๋Œ€์ƒ์œผ๋กœ ์–‘์ „์ž ๋ฐฉ์ถœ ๋‹จ์ธต ์ดฌ์˜ (18F-FDG-PET) ์„ ์ด์šฉํ•˜์—ฌ ์„ ์กฐ์ฒด-์‹œ์ƒ-ํ”ผ์งˆ ์šด๋™ํšŒ๋กœ ์™€ ํ‘์งˆ-์„ ์กฐ์ฒด ๊ฒฝ๋กœ, ์†Œ๋‡Œ-์‹œ์ƒ-ํ”ผ์งˆ ํšŒ๋กœ์˜ ํœด์ง€๊ธฐ ๋‡Œ ๋Œ€์‚ฌ ์—ฐ๊ฒฐ์„ฑ์„ ๋น„๊ตํ–ˆ๋‹ค. ๋ฐฉ๋ฒ• : Automated Anatomical Labeling templates์™€ the Wake Forest University Pick Atlas Tailarach Daemon์„ ์‚ฌ์šฉํ•˜์—ฌ 118๊ฐœ์˜ ๊ด€์‹ฌ ์˜์—ญ (ROI)์„ ์ถ”์ถœํ–ˆ๋‹ค. ์šฐ๋ฆฌ๋Š” sparse inverse covariance estimation (SICE) ๋ฐฉ๋ฒ•์„ ์ ์šฉํ•˜์—ฌ ๋Œ€์‚ฌ ์—ฐ๊ฒฐ ํ–‰๋ ฌ์„ ๊ตฌ์„ฑํ–ˆ๋‹ค. ๊ฒฐ๊ณผ : ํŒŒํ‚จ์Šจ์ฆ์ƒ ์œ ๋ฌด์— ๊ด€๊ณ„์—†์ด DLB ํ™˜์ž๋Š” ์ •์ƒ๊ตฐ๋ณด๋‹ค ์„ ์กฐ์ฒด-์‹œ์ƒ-ํ”ผ์งˆ ์šด๋™ํšŒ๋กœ (์šด๋™ํ”ผ์งˆ โ€“ ์„ ์กฐ์ฒด, ์ค‘๋‡Œ โ€“ ์„ ์กฐ์ฒด, ์„ ์กฐ์ฒด - ๋‹ด์ฐฝ๊ตฌ, ๋‹ด์ฐฝ๊ตฌ - ์‹œ์ƒ)์—์„œ ๋‚ฎ์€ ์ง€์—ญ๊ฐ„ ์—ฐ๊ฒฐ์„ฑ์ด ๋‚˜ํƒ€๋‚ฌ๋‹ค. ํŒŒํ‚จ์Šจ ์ฆ์ƒ์ด ์žˆ๋Š” DLB ํ™˜์ž๋“ค์€ ํŒŒํ‚จ์Šจ ์ฆ์ƒ์ด ์—†๋Š” DLBํ™˜์ž๋“ค๋ณด๋‹ค ์ค‘๋‡Œ-์„ ์กฐ์ฒด ์‚ฌ์ด์˜ ์ง€์—ญ๊ฐ„ ์—ฐ๊ฒฐ์„ฑ์ด ๋‚ฎ์•˜๊ณ , ์†Œ๋‡Œ-์‹œ์ƒ-ํ”ผ์งˆ ์šด๋™ํšŒ๋กœ (์šด๋™ํ”ผ์งˆ โ€“ ๊ต๋‡Œ, ๊ต๋‡Œ-์†Œ๋‡Œ, ์†Œ๋‡Œ-์‹œ์ƒ)์˜ ์—ฐ๊ฒฐ์„ฑ์ด ๋†’์•˜๋‹ค. ํ•ด์„: DLB์—์„œ ์„ ์กฐ์ฒด-์‹œ์ƒ-ํ”ผ์งˆ ์šด๋™ํšŒ๋กœ์˜ ํœด์ง€๊ธฐ ๋‡Œ ๋Œ€์‚ฌ ์—ฐ๊ฒฐ์„ฑ์ด ๊ฐ์†Œํ–ˆ๋‹ค. ํŒŒํ‚จ์Šจ ์ฆ์ƒ์ด ์žˆ๋Š” DLB ํ™˜์ž์—์„œ ํŒŒํ‚จ์Šจ ์ฆ์ƒ์„ ์™„ํ™”ํ•˜๊ธฐ ์œ„ํ•ด ์†Œ๋‡Œ-์‹œ์ƒ-ํ”ผ์งˆ ์šด๋™ํšŒ๋กœ์™€ ํ‘์งˆ-์„ ์กฐ์ฒด ๊ฒฝ๋กœ๊ฐ€ ํ™œ์„ฑํ™” ๋˜์—ˆ์„ ๊ฒƒ์ด๋‹ค. ์ด๋Ÿฌํ•œ ํœด์ง€๊ธฐ ๋‡Œ ๋Œ€์‚ฌ ์—ฐ๊ฒฐ์„ฑ์˜ ์ฐจ์ด๋Š” DLB์™€ PD ๋˜๋Š” DLB์™€ PDD๋ฅผ ๊ตฌ๋ณ„ํ•˜๊ธฐ ์œ„ํ•œ ์ž ์žฌ์ ์ธ ๋ฐ”์ด์˜ค๋งˆ์ปค์˜ ๊ฐ€๋Šฅ์„ฑ์ด ์žˆ๋‹ค.1. Introduction 1 2. Methods 3 3. Results 8 4. Discussion 10 References 13 List of Tables 19 List of Figures 21 ๊ตญ๋ฌธ ์ดˆ๋ก 28Maste

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    ์˜๊ณผํ•™๊ณผ/์„์‚ฌ[ํ•œ๊ธ€] ํ˜„์žฌ๊นŒ์ง€ TRAIL์„ ์ด์šฉํ•œ ์œ ์ „์ž ์น˜๋ฃŒ๋Š” CMV promoter๋ฅผ ์ด์šฉํ•œ adenovirus๋กœ๋ถ€ํ„ฐ TRAIL์„ ๊ณผ๋ฐœํ˜„ํ•˜๊ฑฐ๋‚˜ telomerase promoter์— ์˜ ํ•ด TRAIL ๋ฐœํ˜„์ด ์กฐ์ ˆ ๋ฐ›๋Š” adenovirus๋ฅผ ์ œ์กฐํ•˜์—ฌ ๊ทธ ์—ฐ๊ตฌ๊ฐ€ ์ง„ํ–‰ ๋˜์—ˆ์œผ๋‚˜, ์ด ๊ฒฝ์šฐ์—๋Š” TRAIL์— ๋ฏผ๊ฐํ•œ ์„ธํฌ์—์„œ๋งŒ ๊ทธ ํšจ๊ณผ๋ฅผ ๊ด€์ฐฐํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” ์•”์„ธํฌ์—์„œ๋งŒ ์„ธํฌ ์‚ฌ๋ฉธ์„ ์œ ๋ฐœํ•˜๋Š” ๋ฌผ์งˆ๋กœ ์•Œ๋ ค์ง„ TRAIL์— ๋Œ€ํ•œ ์„ธํฌ๋ง‰ ์ˆ˜์šฉ์ฒด DR4๋ฅผ ์‚ฌ๋žŒ telomerase promoter๋ฅผ ์ด์šฉํ•˜์—ฌ ์•”์„ธํฌ์—์„œ๋งŒ ์„ ํƒ์ ์œผ๋กœ ๋ฐœํ˜„ํ•  ์ˆ˜ ์žˆ๋„๋ก ํ•˜๋Š” ์žฌ์กฐํ•ฉ adenovirus๋ฅผ ์ œ์กฐํ•˜๊ณ , ์žฌ์กฐํ•ฉ adenovirus ๋‹จ๋… ๋˜๋Š” ์žฌ์กฐํ•ฉ TRAIL ๋‹จ๋ฐฑ์งˆ ๋˜๋Š” TRAIL์„ ๊ณผ๋ฐœํ˜„ํ•  ์ˆ˜ ์žˆ๋Š” adenovirus์™€ ํ•จ๊ป˜ ์ฒ˜๋ฆฌํ•˜์—ฌ TRAIL์— ๋Œ€ํ•œ ๋‚ด์„ฑ์ด ์•Œ๋ ค์ง„ ์•”์„ธํฌ์— ๋Œ€ํ•œ ์„ธํฌ ์‚ฌ๋ฉธ ํšจ๊ณผ๋ฅผ ๊ฒ€์ฆํ•˜์—ฌ ํ–ฅํ›„ ์ธ๊ฐ„์„ ๋Œ€์ƒ์œผ๋กœ ํ•˜๋Š” ์œ ์ „์ž ์น˜๋ฃŒ ๊ธฐ์ˆ ์˜ ๊ทผ๊ฐ„์„ ๋งˆ๋ จํ•˜๊ณ ์ž ํ•˜์˜€๋‹ค. ์ด๋ฅผ ์œ„ํ•˜์—ฌ human genomic DNA๋กœ๋ถ€ํ„ฐ human telomerase promoter ๋ถ€์œ„๋ฅผ cloningํ•˜๊ณ  ํ‘œ์  ์„ธํฌ๋กœ ์‚ฌ์šฉํ•  ์•”์„ธํฌ์—์„œ์˜ telomerase ํ™œ์„ฑ๋„๋ฅผ luciferase assay๋ฅผ ํ†ตํ•ด ์ธก์ •ํ•œ ๊ฒฐ๊ณผ ์ž๊ถ ๊ฒฝ๋ถ€์•”์„ธํฌ์ธ Caski์™€ ์‹๋„ ์ƒํ”ผ ์„ธํฌ์•”์ธ HCE4์—์„œ ์ •์ƒ ์ž๊ถ ๊ฒฝ๋ถ€ ์ƒํ”ผ ์„ธํฌ๋ณด๋‹ค ๋†’์€ ํ™œ์„ฑ์„ ๊ด€์ฐฐํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. Ubiquitin E3 ligase ํ™œ์„ฑ์„ ๊ฐ€์ง„ E6AP ๋‹จ๋ฐฑ์งˆ๊ณผ ํ•จ๊ป˜ p53 ์ข…์–‘ ์–ต์ œ ๋‹จ๋ฐฑ์งˆ์„ ํŒŒ๊ดดํ•œ๋‹ค๊ณ  ์•Œ๋ ค์ ธ ์žˆ๋Š” HPV 16, 18ํ˜•์œผ๋กœ๋ถ€ํ„ฐ ๋ฐœํ˜„๋˜๋ฉฐ telomerase promoter์˜ ํ™œ์„ฑ์„ ์ฆ๊ฐ€์‹œํ‚ค๋Š” ๊ฒƒ์œผ๋กœ ์•Œ๋ ค์ง„ ์ข…์–‘ ๋‹จ๋ฐฑ์งˆ์ค‘์˜ ํ•˜๋‚˜์ธ E6 ๋‹จ๋ฐฑ์งˆ์„ ๊ณผ๋ฐœํ˜„์‹œํ‚จ ๊ฒฝ์šฐ ๊ทธ๋ ‡์ง€ ์•Š์€ ๊ฒฝ์šฐ๋ณด๋‹ค telomerase promoter ํ™œ์„ฑ์ด ์ฆ๊ฐ€๋˜๋Š” ๊ฒƒ์„ ํ™•์ธํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. ์ด๋Ÿฌํ•œ ์•”์„ธํฌ ํŠน์ด์  ํ™œ์„ฑ์ด ํ™•์ธ๋œ telomerase promoter์™€ full length DR4 ์œ ์ „์ž๊ฐ€ ํ•จ๊ป˜ ํฌํ•จ๋œ shuttle plasmid construct๋ฅผ ์ œ์กฐํ•œ ๋’ค, pAd-Easy I system์„ ์ด์šฉํ•˜์—ฌ ์žฌ์กฐํ•ฉ adenovirus Ad-hTERT-DR4๋ฅผ 293์„ธํฌ์—์„œ ์ƒ์„ฑ ๋ฐ ์ฆํญํ•˜์˜€์œผ๋ฉฐ, TRAIL์— ๋‚ด์„ฑ์„ ๊ฐ€์ง€๋Š” ์•”์„ธํฌ CasKi์™€ HCE4์— ๊ฐ์—ผ์‹œ์ผœ DR4๋ฅผ ๊ณผ๋ฐœํ˜„์‹œํ‚ค๊ณ  TRAIL๊ณผ ๋ณ‘ํ•ฉ ์ฒ˜๋ฆฌ ์‹œ์— ์„ธํฌ ์‚ฌ๋ฉธ ํšจ๊ณผ๋ฅผ western blot immunostaining๊ณผ flow cytometry๋ฅผ ํ†ตํ•ด ์„ธํฌ ๋ฐฐ์–‘ ๋ชจ๋ธ์—์„œ ํ™•์ธํ•˜์˜€๋‹ค. ๊ทธ ๊ฒฐ๊ณผ ๋‹จ๋… ์ฒ˜๋ฆฌ์‹œ ๋ณด๋‹ค๋Š” ๋ณ‘ํ•ฉ ์ฒ˜๋ฆฌ์‹œ ์„ธํฌ ์‚ฌ๋ฉธ์˜ ์ •๋„๋ฅผ ๋ณด์—ฌ์ฃผ๋Š” ๋‹จ๋ฐฑ์งˆ์ธ PARP๋‚˜ pro-caspase 3์˜ ์ ˆ๋‹จ์ด ํ™•์ธ๋˜์—ˆ๊ณ , flow cytometry์—์„œ sub-G1 fraction์ด ์ฆ๊ฐ€ํ•˜๋Š” ๊ฒƒ์œผ๋กœ ๋ณด์•„ Ad-hTERT-DR4์™€ Ad-ILZ-TRAIL ๋˜๋Š” ์žฌ์กฐํ•ฉ TRAIL ๋‹จ๋ฐฑ์งˆ์˜ ๋ณ‘ํ•ฉ ์ฒ˜๋ฆฌ ์‹œ ์•”์„ธํฌ์˜ ์„ฑ์žฅ ์–ต์ œ ๋ฐ ์„ธํฌ ์‚ฌ๋ฉธ ํšจ๊ณผ๋ฅผ ํ™•์ธํ•  ์ˆ˜ ์žˆ์—ˆ๋‹ค. TRAIL์— ๋Œ€ํ•œ ๋‚ด์„ฑ์„ ๊ฐ€์ง„ ์„ธํฌ์ธ HCE4์™€ HCE7์— Ad-hTERT-DR4์™€ Ad-ILZ-TRAIL์„ ๊ฐ๊ฐ infection ์‹œํ‚ค๊ณ  ๋‚œ ํ›„ ๋‹ค์‹œ ๋‘ ์„ธํฌ๋ฅผ ๊ฐ™์ด ๋ฐฐ์–‘ํ•˜์˜€์„ ๋•Œ HCE4์˜ ์„ธํฌ ์‚ฌ๋ฉธ์„ ํ™•์ธํ•จ์œผ๋กœ์จ TRAIL๊ณผ DR4๋ฅผ ๋ณ‘ํ–‰ ์‚ฌ์šฉ ํ•˜์˜€์„ ๊ฒฝ์šฐ TRAIL์— ๋‚ด์„ฑ์„ ๊ฐ€์ง„ ์•”์„ธํฌ ์น˜๋ฃŒ์— ์œ ์šฉํ•œ ์น˜๋ฃŒ๋ฒ•์ด ๋  ์ˆ˜ ์žˆ์Œ์„ ์ฆ๋ช…ํ•˜์˜€๋‹ค. ์ด๋Ÿฌํ•œ TRAIL๊ณผ DR4๋ฅผ ์ด์šฉํ•œ TRAIL ๋‚ด์„ฑ์„ ๊ฐ€์ง„ ์•”์„ธํฌ ์‚ฌ๋ฉธ ํšจ๊ณผ๊ฐ€ ์•”์„ธํฌ ์„ ํƒ์  ํ˜„์ƒ์ด๋ผ๋Š” ๊ฒƒ์„ ํ™•์ธํ•˜๊ธฐ ์œ„ํ•ด ์ •์ƒ ์ž๊ถ ๊ฒฝ๋ถ€ ์ƒํ”ผ ์„ธํฌ์— Ad-GFP, Ad-hTERT-DR4, Ad-ILZ-TRAIL, Ad-E6๋ฅผ infection ํ•œ ํ›„ PARP์™€ pro-caspase 3์˜ ์ ˆ๋‹จ ์—ฌ๋ถ€๋ฅผ ํ™•์ธํ•œ ๊ฒฐ๊ณผ ์ ˆ๋‹จ ์ •๋„๊ฐ€ ๊ฑฐ์˜ ๋‚˜ํƒ€๋‚˜์ง€ ์•Š์•˜์œผ๋ฉฐ sub-G1 fraction๋„ ๊ฑฐ์˜ ์ฆ๊ฐ€ํ•˜์ง€ ์•Š์€ ๊ฒƒ์œผ๋กœ ๋ณด์•„ TRAIL๊ณผ hTERT-DR4๋ฅผ ์ด์šฉํ•œ ์•”์„ธํฌ ์‚ฌ๋ฉธ์€ ์•”์„ธํฌ ์„ ํƒ์ ์ธ ๊ฒƒ์œผ๋กœ ํ™•์ธํ•˜์˜€๋‹ค. ์ด์ƒ์˜ ๊ฒฐ๊ณผ๋กœ ์•”์„ธํฌ์—์„œ๋งŒ ์„ ํƒ์ ์œผ๋กœ TRAIL์˜ ์ˆ˜์šฉ์ฒด์ธ DR4์˜ ๋ฐœํ˜„์„ ์œ ๋„ํ•˜๊ณ  TRAIL์„ ๋ณ‘ํ•ฉ ์ฒ˜๋ฆฌํ•˜์—ฌ TRAIL์— ๋Œ€ํ•œ ๋‚ด์„ฑ์„ ๊ฐ€์ง„ ์•”์„ธํฌ์˜ ์„ธํฌ ์‚ฌ๋ฉธ์„ ์œ ๋„ํ•˜๋Š” ๊ฒƒ์€ ์•”์„ธํฌ ์„ ํƒ์ ์ธ ๊ฒƒ์ด๋ฉฐ ํ–ฅํ›„ ์•”์˜ ์น˜๋ฃŒ์— ์žˆ์–ด ์ด์šฉ ๊ฐ€๋Šฅํ•  ๊ฒƒ์œผ๋กœ ์ƒ๊ฐ๋œ๋‹ค. [์˜๋ฌธ]Telomerase activity is detected in more than 90% of immortalized and cancer cells but absent in most normal somatic cells and HPV E6 oncoprotein could activate telomerase. In this experiment, we hypothesized that the hTERT promoter can be used for tumor-specific expression of transgenes to induce selective cancer cell death in TRAIL-resisitant or HPV E6 positive cancer cells. First, we tested whether hTERT core promoter is active only in cancer cells and whether the presence of HPV E6 protein could potentiate the activation of the promoter by using luciferase constructs and we found that hTERT promoter is active only in cancer cells, and the presence of E6 protein could agument hTERT promoter activity. Then, we generated adenoviruses to express TRAIL-death receptor (DR) 4 driven by hTERT promoter to test whether the expression of DR4 is induced by the promoter in cancer cell lines in the presence or absence of E6 oncoprotein and we found that DR4 expression was induced. Finally, we tested whether TRAIL treatment and the induction of DR4 could contribute to selective cancer cell death by observing caspase 3 activation and PARP cleavage, and we found that death of Ad-hTERT-DR4 infected cells were increased in the presence of TRAIL. Taken together, our results reveal that the proper use of hTERT promoter could be useful and powerful for inducing selective cancer cell death with effective death inducing transgenes such as DR4.ope

    17รŸ-estradiol์— ์˜ํ•ด C28I2์—ฐ๊ณจ์„ธํฌ์—์„œ ์ฐจ๋“ฑ์ ์œผ๋กœ ๋ฐœํ˜„๋˜๋Š” ๋‹จ๋ฐฑ์งˆ

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    Thesis(doctoral)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :์น˜์˜ํ•™๊ณผ ์น˜๊ณผ๊ต์ •ํ•™์ „๊ณต,2006.Docto

    Neurose und Gewalt : anhand von Fontanes Cรฉcile und StrauรŸ Die Hypochonder

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    Im allgemeinen versteht man unter dem Begriff Macht die Fรคhigkeit, seinen Willen gegenรผber dem Anderen mit Zwang durchzusetzen. Bei dieser Erklรคrung nรคhert sich die Macht der Gewalt. Jedoch betont Byung-Chul Han den kommunikativen Aspekt der Macht, wodurch sich die Macht von der Gewalt unterscheidet. Die Machtbeziehung zwischen dem Ich und dem Anderen wird durch den Diskurs gefiltert, der den kommunikativen Aspekt der Macht bestimmt und sich im zeitlichen Kontext wandelt. In der vorliegenden Arbeit werde ich vor allem die Beziehung zwischen Macht und Neurose im oben erwรคhnten Zusammenhang betrachten. Dabei werden die Begriffsbestimmungen der Macht von Byung-Chul Han, Niklas Luhman sowie Hannah Arendt und Paul Tillich dazu dienen, verschiedene Typen der Neourose aus ihrer jeweiligen Beziehung zum zeitgenรถssischen Machtverhรคltnis und โ€“diskurs heraus zu erklรคren. In unserem Zusammenhang werde ich Cรฉcile von Theodor Fontane aus dem 19. Jahrhundert und Die Hypchonder von Botho StrauรŸ aus dem 20. Jahrhundert als Textbeispiele analysieren. In Cรฉcile werden die Frauenfiguren aus dem Erscheinungsraum im Sinne von Arendt, also aus dem Machtraum ausgeschlossen. Die Existenz der neurotischen Frauen, die durch diesen Ausschluss aus dem Machtraum das Gefรผhl des Ich verlieren, wird durch den aus der mรคnnlichen Perspektive erfundenen Diskurs gerechtfertigt und als schรถn bewertet. Dahinter steckt jedoch die disziplinรคre Macht, die diesen Diskurs erzeugt und die Frauen der mรคnnlichen Herrschaft unterwirft. In Die Hypchonder tritt ein anderer Neurotikertypus auf. Der an Krankheit leidende Mensch hat Angt vor dem Verlust des sozialen, kommunikativen Feldes, woraus sich seine Zwangsvorstellung zur Gesundheit ergibt. Die Hypochonder hรคngen an dieser Vorstellung und erleben die Ich-Spaltung. D.h. sie zerstรถren das einheitliche Ich und erzeugen verschiedene Ichs, welche besonders zum Machtgefรผhl des Ich beitragen. Aufgrund dieser Beziehung zwischen Macht und Neurose erklรคre ich die komplizierte Figurenkonstellation und die phantastische, widerspruchsvolle Struktur im Stรผck Die Hypchonder
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