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    μ—­μ‚¬λ°œμƒμ  원리에 λ”°λ₯Έ μˆ˜μ§μ„  μ˜λ―Έμ™€ μ§€λ„λ°©μ•ˆ κ³ μ°°

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    ν•™μœ„λ…Όλ¬Έ (석사)-- μ„œμšΈλŒ€ν•™κ΅ λŒ€ν•™μ› μ‚¬λ²”λŒ€ν•™ μˆ˜ν•™κ΅μœ‘κ³Ό, 2017. 8. 졜영기.μ™œ 직선에 μ‹€μˆ˜λ₯Ό μž…νžˆκ²Œ λ˜μ—ˆλŠ”κ°€?에 λŒ€ν•œ μ˜λ¬ΈμœΌλ‘œλΆ€ν„° μ—°κ΅¬λ¬Έμ œκ°€ μ œκΈ°λ˜μ—ˆλ‹€. 였랜 μ‹œκ°„ λ§Žμ€ μˆ˜ν•™μžλ“€μ΄ λ…ΌμŸν•˜μ—¬ 얻은 결과물이 ν•™κ΅μˆ˜ν•™μ—μ„œλŠ” λ‹Ήμ—°ν•œ λŒ€μƒμœΌλ‘œ μ—¬κ²¨μ§€λŠ” κ²½μš°κ°€ μžˆλŠ”λ° κ·Έ 쀑 ν•˜λ‚˜κ°€ μˆ˜μ§μ„ μ΄λ‹€. 특히 μˆ˜μ§μ„ μ€ 음수λ₯Ό 처음 μ ‘ν•˜λŠ” 학생듀을 지도할 λ•Œ 자주 μ‚¬μš©λ˜λŠ” λͺ¨λΈμ΄λ©°, 수의 체계λ₯Ό ν™•μž₯ν•˜λŠ” κ³Όμ •μ—μ„œ 수λ₯Ό 직선에 λŒ€μ‘μ‹œν‚€λŠ” ν™œλ™μ„ 톡해 학생듀은 μ‹€μˆ˜μ˜ μ„±μ§ˆμ„ μ§κ΄€μ μœΌλ‘œ μ΄ν•΄ν•˜λŠ”λ° 도움을 주기도 ν•œλ‹€. λ³Έ μ—°κ΅¬μ—μ„œλŠ” μ—­μ‚¬λ°œμƒμ  원리에 κΈ°λ°˜ν•˜μ—¬ μˆ˜μ§μ„ μ΄ κ°–λŠ” 의미λ₯Ό νƒμƒ‰ν•˜μ—¬ ν•™κ΅μˆ˜ν•™μ— 효과적으둜 μˆ˜μ§μ„ μ„ ν™œμš©ν•˜κΈ° μœ„ν•œ λ°©μ•ˆμ„ λͺ¨μƒ‰ν•˜κ³ μž ν•˜μ˜€λ‹€. μˆ˜ν•™μ‚¬μ—μ„œ 수의 크기λ₯Ό μ„ λΆ„μ˜ 길이에 λ‚˜νƒ€λ‚΄λŠ” 것은 κ³ λŒ€μ—λΆ€ν„° μ‚΄νŽ΄λ³Ό 수 μžˆμœΌλ‚˜ μ–‘μ˜ κ°œλ…μ—μ„œ λ²—μ–΄λ‚˜ 수λ₯Ό 직선에 λŒ€μ‘μ‹œν‚¨ 것은 비ꡐ적 졜근의 μΌμ΄μ—ˆλ‹€. 즉, μˆ˜ν•™μ‚¬μ—μ„œ μˆ˜μ§μ„ μ„ μˆ˜ν•™μ  λŒ€μƒμœΌλ‘œ μΈμ‹ν•˜μ—¬ μ •μ˜λ˜κΈ°κΉŒμ§€λŠ” 였랜 μ‹œκ°„μ΄ κ±Έλ¦° 것이닀. μˆ˜ν•™μ‚¬μ˜ 흐름과 μœ μ‚¬ν•˜κ²Œ ν•™κ΅μˆ˜ν•™μ—μ„œλ„ μˆ˜μ§μ„ μ˜ ν˜•μ‹μ  μ •μ˜λ³΄λ‹€ μ‹€μš©μ  μ‚¬μš©μ΄ μ•žμ„ λ‹€. λ³Έ μ—°κ΅¬μ—μ„œλŠ” μš°λ¦¬λ‚˜λΌ 쀑학ꡐ 14μ’… κ΅κ³Όμ„œμ— λ‚˜νƒ€λ‚œ μˆ˜μ§μ„ μ˜ μ •μ˜μ™€ ν™œμš©μ„ λΆ„μ„ν•˜μ˜€μœΌλ©°, ν•™κ΅μˆ˜ν•™μ—μ„œλŠ” μˆ˜μ§μ„ μ˜ μ •μ˜λ³΄λ‹€ ν™œμš©μ— μžˆμ–΄ 더 λ§Žμ€ 비쀑을 두고 μžˆμ—ˆλ‹€. ν•™κ΅μˆ˜ν•™μ—μ„œ λŒ€μˆ˜μ™€ κΈ°ν•˜μ˜ λ§Œλ‚¨μ„ 졜초둜 μ—°κ²°ν•΄μ£ΌλŠ” 것이 μˆ˜μ§μ„ μž„μ—λ„ λΆˆκ΅¬ν•˜κ³ , μ΄λŸ¬ν•œ μˆ˜ν•™μ  κ°€μΉ˜λ³΄λ‹€λŠ” 문제λ₯Ό ν•΄κ²°ν•˜κΈ° μœ„ν•œ μˆ˜λ‹¨μ— μΉ˜μ€‘λ˜μ–΄ μžˆμŒμ„ ν™•μΈν•˜μ˜€λ‹€. 이에 κΈ°λ°˜ν•˜μ—¬ 학생듀이 μˆ˜μ§μ„ μ˜ μ •μ˜λ₯Ό 탐ꡬ할 수 μžˆλŠ” 섀문연ꡬλ₯Ό μ§„ν–‰ν•˜μ˜€λ‹€. 학생듀은 μ‹€μˆ˜λ₯Ό λ‚˜νƒ€λ‚΄λŠ” 졜적의 λͺ¨μ–‘이 μ§μ„ μž„μ„ κ°„μ ‘μ μœΌλ‘œ νƒκ΅¬ν•˜μ˜€μœΌλ©°, μˆ˜μ§μ„ μ˜ μˆ˜ν•™μ‚¬μ  κ°€μΉ˜λ₯Ό μΈμ‹ν•˜μ˜€λ‹€. 학생듀은 μ •μ˜ν•˜κΈ°λ₯Ό ν•™μŠ΅ν•˜κ³  μˆ˜μ§μ„ μ˜ λͺ¨μ–‘이 λ°”λ€Œμ—ˆμ„ λ•Œ μƒκΈ°λŠ” 상황과 κ΄€λ ¨ν•˜μ—¬ μ‹€μˆ˜μ˜ μ„±μ§ˆμ— λŒ€ν•΄ κ³ λ―Όν•΄λ³Ό 수 μžˆμ—ˆλ‹€. μˆ˜μ§μ„ μ΄ μ‹€μˆ˜μ˜ μ„±μ§ˆμ„ μ‹œκ°μ μœΌλ‘œ λ‚˜νƒ€λ‚Έλ‹€λŠ” μ μ—μ„œ μ΄λŸ¬ν•œ νƒκ΅¬ν™œλ™μ€ μœ μ˜λ―Έν•˜λ©°, λ‚˜μ•„κ°€ μˆ˜ν•™μ  κ°œλ…μ„ λ˜μ§šμ–΄λ³΄λŠ” 과정은 μ™„μ„±λœ κ²°κ³Όκ°€ μ•„λ‹Œ κ³Όμ •μœΌλ‘œμ„œμ˜ μˆ˜ν•™μ„ μ‹€ν˜„μ‹œν‚¨λ‹€λŠ” μ μ—μ„œ κ·Έ μ˜μ˜κ°€ μžˆλŠ” 것이닀. 각각 λ°œμ „ν•΄μ˜¨ λŒ€μˆ˜μ™€ κΈ°ν•˜λ₯Ό μ—°κ²°ν•΄μ£ΌλŠ” μˆ˜μ§μ„ μ€ μˆ˜ν•™μ‚¬μ  κ°€μΉ˜κ°€ μΆ©λΆ„ν•˜λ©°, λ‚˜μ•„κ°€ ν•™κ΅μˆ˜ν•™μ—μ„œλŠ” 수의 κ°œλ… 이해와 문제λ₯Ό ν•΄κ²°ν•˜λŠ” κ³Όμ •μ—μ„œ ν™œμš©κ°€μΉ˜κ°€ λ†’λ‹€. 이에 따라 μˆ˜μ§μ„ μ˜ μ§€λ„λ°©μ•ˆμ„ λͺ¨μƒ‰ν•˜μ—¬ 효과적인 κ΅μˆ˜ν•™μŠ΅μ„ λ§ˆλ ¨ν•˜κ³ μž ν•˜μ˜€λ‹€.β… . μ„œλ‘  1 1. μ—°κ΅¬μ˜ λͺ©μ  및 ν•„μš”μ„± 1 2. μ—°κ΅¬λ¬Έμ œ 4 β…‘. 이둠적 λ°°κ²½ 6 1. μ—­μ‚¬λ°œμƒμ  μˆ˜ν•™ ν•™μŠ΅-지도 원리 6 1.1. μ—­μ‚¬λ°œμƒμ  μ›λ¦¬λž€ 6 1.2. Freudenthal의 μˆ˜ν•™ ν•™μŠ΅-지도 원리 10 2. μˆ˜ν•™μ‚¬μ—μ„œ μˆ˜μ§μ„ μ˜ 의미 13 2.1. 음수의 역사 13 2.2. μŒμˆ˜μ— κ΄€ν•œ λ…ΌμŸ 20 2.3. μ‹€μˆ˜μ˜ μ™„λΉ„μ„± 26 2.4. μˆ˜μ§μ„ μ˜ 역사 29 3. ν•™κ΅μˆ˜ν•™μ—μ„œ μˆ˜μ§μ„ μ˜ 의미 31 3.1. μˆ˜μ§μ„ μ˜ μ •μ˜ 31 3.2. 음수 지도 34 3.3. μ‹€μˆ˜μ™€ μˆ˜μ§μ„  40 β…’. 연ꡬ 방법 및 절차 43 1. 연ꡬ 방법 43 1.1. 연ꡬ λŒ€μƒ 43 1.2. 연ꡬ 방법 45 2. 연ꡬ 섀계 46 2.1. 연ꡬ 섀계 λ°°κ²½ 46 2.2. 연ꡬ 진행 κ³Όμ • 49 3. 자료 μˆ˜μ§‘ 및 뢄석 50 3.1. μˆ˜μ§μ„  μ •μ˜ν•˜κΈ° 50 3.2. μˆ˜μ§μ„ μ˜ λͺ¨μ–‘이 직선이 아닐 κ²½μš°μ— λŒ€ν•œ 탐ꡬ 52 3.3. ν˜„μž¬ μ‚¬μš©ν•˜λŠ” μˆ˜μ§μ„ μ— λŒ€ν•œ 재음미 56 3.4. μˆ˜ν•™μ‚¬μ  κ΄€μ μ—μ„œ μˆ˜μ§μ„ μ˜ 의미 탐ꡬ 57 4. 연ꡬ κ²°κ³Ό 59 β…£. κ²°λ‘  및 μ œμ–Έ 61 μ°Έκ³ λ¬Έν—Œ 65 κ΅κ³Όμ„œμ—μ„œ μ œμ‹œν•˜λŠ” μˆ˜μ§μ„ μ˜ μ •μ˜ 73 μˆ˜μ§μ„  μ •μ˜ 탐ꡬ 평가 문항지 75 Abstract 79Maste

    λΉ„κ²°ν•΅ ν•­μ‚°κ·  감염과 μ•Œλ ˆλ₯΄κΈ°μ„± μ²œμ‹μ„ λ™λ°˜ν•œ λ§Œμ„± νμ§ˆν™˜μ˜ 병인 κΈ°μ „ 연ꡬ

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    κ·Ήμ‹¬ν•œ ν™˜κ²½μ˜€μ—Όκ³Ό μ„œκ΅¬ν™”λœ μƒν™œ ν™˜κ²½μ— λ”°λ₯Έ λΉ„κ²°ν•΅ ν•­μ‚°κ·  감염에 μ˜ν•œ μœ λ³‘λ₯ μ΄ μ¦κ°€ν•˜κ³  μžˆλ‹€. λΉ„κ²°ν•΅ 항산균을 μ œμ–΄ν•˜κΈ° μœ„ν•œ λ…Έλ ₯듀이 κ³„μ†λ˜κ³  μžˆμ§€λ§Œ κΈ°μ € μ§ˆν™˜κ³Ό λ™λ°˜ν•˜μ—¬ μž„μƒμ μœΌλ‘œ λ”œλ ˆλ§ˆμ— λΉ μ Έμžˆλ‹€. κ·Έ μ€‘μ—μ„œλ„ κ³΅ν†΅μ μœΌλ‘œ μ€‘λ…„μ˜ 마λ₯Έ μ—¬μ„±μ—κ²Œ μœ λ°œλ˜λ©΄μ„œ 폐에 λ§Œμ„±μ§ˆν™˜μ„ μΌμœΌν‚€λŠ” μ•Œλ ˆλ₯΄κΈ°μ„± μ²œμ‹κ³Ό λΉ„κ²°ν•΅ ν•­μ‚°κ·  κ°μ—Όμ˜ 경우, μ„œλ‘œ μƒλ°˜λ˜λŠ” 면역체계λ₯Ό 이룸에도 λΆˆκ΅¬ν•˜κ³  두가지 μ§ˆλ³‘μ„ λͺ¨λ‘ κ°–κ³ μžˆλŠ” ν™˜μžκ°€ 높은 수치둜 μ‘΄μž¬ν•œλ‹€λŠ” μž„μƒμ  톡계듀이 보고되고 μžˆλ‹€. 뿐만 μ•„λ‹ˆλΌ, 두 μ§ˆλ³‘μ΄ λ™λ°˜ 될 λ•Œ μΉ˜λ£Œκ°€ λ”μš± μ–΄λ €μ›Œ μ§€λŠ” νŠΉμ§•μ„ κ°–λŠ”λ‹€. λ”°λΌμ„œ μ•Œλ ˆλ₯΄κΈ°μ„± μ²œμ‹κ³Ό λΉ„κ²°ν•΅ ν•­μ‚°κ·  감염이 λ™λ°˜λœ 마우슀 λͺ¨λΈμ„ μƒˆλ‘­κ²Œ κ΅¬μΆ•ν•˜κ³ , 면역학적 병리학적 영ν–₯을 두가지 μ§ˆλ³‘μ˜ μΈ‘λ©΄μ—μ„œ 비ꡐ, λΆ„μ„ν•˜μ˜€λ‹€. λΉ„κ²°ν•΅ ν•­μ‚°κ·  감염과 μ•Œλ ˆλ₯΄κΈ°μ„± μ²œμ‹μ„ λ°œλ³‘ μˆœμ„œμ— 따라 λ‚˜λˆ„μ–΄ μ‹€ν—˜μ„ μ§„ν–‰ν•˜μ˜€λ‹€. κ·Έ κ²°κ³Ό, λΉ„κ²°ν•΅ ν•­μ‚°κ·  감염과 μ•Œλ ˆλ₯΄κΈ°μ„± μ²œμ‹ λ™λ°˜ μ‹œ, 감염이 진행됨에 따라 폐의 염증 μ„± λ³‘λ³€μ˜ 증가와 균의 증식 μ†λ„μ˜ 가속화가 μΌμ–΄λ‚˜λŠ” 것을 ν™•μΈν•˜μ˜€λ‹€. μ΄λŸ¬ν•œ κ²°κ³ΌλŠ” λΉ„κ²°ν•΅ ν•­μ‚°κ· κ³Ό 같은 세포 λ‚΄ 기생 μ„Έκ·  μ œμ–΄μ— μ€‘μš”ν•œ IFN-γ의 생산과, μ£Όλͺ©λ°›λŠ” λ°©μ–΄ μ „λž΅μΈ IL-17A의 생산이 κ°μ†Œν•˜λŠ” 것과 λΉ„λ‘€ν•˜μ—¬ λ°œμƒν•œλ‹€. λ°˜λŒ€λ‘œ, μ•Œλ ˆλ₯΄κΈ°μ„± μ²œμ‹μ˜ νŠΉμ§•μΈ μˆ μž”μ„Έν¬μ˜ κ³Όν˜•μ„±μ€ 감염이 진행될 수둝 κ°μ†Œν•˜λŠ” νŠΉμ§•μ„ λ³΄μ˜€λ‹€. μ΄λŸ¬ν•œ κ²°κ³ΌλŠ” 제 2ν˜• 사이토카인인 IL-5와 IL-13의 생산이 κ°μ†Œν•˜λŠ” 것과 λΉ„λ‘€ν•œλ‹€. μœ„ κ²°κ³Όλ₯Ό μ’…ν•©ν•˜μ˜€μ„ λ•Œ, 감염과 μ•Œλ ˆλ₯΄κΈ°μ„± μ²œμ‹μ΄ λ™λ°˜λ  λ•Œ 균에 λŒ€ν•œ μˆ™μ£Όμ˜ λ°©μ–΄ 체계가 λ¬΄λ„ˆμ§€λŠ” 것을 μ•Œ 수 μžˆλ‹€. 감염 ν›„ 5μ£Ό μ‹œμ μ—μ„œ, 폐 내에 μΉ¨μœ€ν•˜λŠ” λ©΄μ—­μ„Έν¬μ˜ κ΅¬μ„±μ—λŠ” 큰 차이λ₯Ό 보이지 μ•Šμ§€λ§Œ κ·  특이적인 CD4+ T μ„Έν¬μ˜ λ°©μ–΄ 체계가 μ•½ν™”λ˜λŠ” κ²ƒμœΌλ‘œ 보아 μˆ˜μ§€μƒ μ„Έν¬μ˜ κΈ°λŠ₯이 ν•­-μ—Όμ¦λ°˜μ‘μ„ μœ λ„ν•˜λ„λ‘ ν™œμ„±ν™” 될 것이라고 가섀을 μ„Έμ› λ‹€. 골수 유래 μˆ˜μ§€μƒ 세포λ₯Ό μ΄μš©ν•˜μ—¬ λΉ„κ²°ν•΅ ν•­μ‚°κ·  감염과 μ•Œλ ˆλ₯΄κΈ°μ„± μ²œμ‹μ„ μœ λ„ν•˜λŠ” 항원인 μ˜€λΈŒμ•ŒλΆ€λ―Όμ„ μ²˜λ¦¬ν•˜μ˜€μ„ λ•Œ ν•­ 염증성 사이토카인인 IL-10의 생성과 κ³΅λ™μ–΅μ œλΆ„μžμΈ PD-L1의 λ°œν˜„μ΄ 감염과 μ•Œλ ˆλ₯΄κΈ° μœ λ„ 항원 처리λ₯Ό λ™λ°˜ν•˜μ˜€μ„ λ•Œ 특이적으둜 증가함을 λ³΄μ˜€λ‹€. 이 κ²°κ³Όλ₯Ό ν†΅ν•˜μ—¬ λΉ„κ²°ν•΅ ν•­μ‚°κ·  감염과 μ•Œλ ˆλ₯΄κΈ°μ„± μ²œμ‹μ΄ λ™λ°˜λ˜μ—ˆμ„ λ•Œ 균의 μ œμ–΄κ°€ μ–΄λ €μ›Œμ§€κ³  폐의 염증성 ν‘œν˜„ν˜•μ΄ μ•…ν™”λ˜λŠ” 이유λ₯Ό 규λͺ…ν•˜μ˜€λ‹€. μ΄λŸ¬ν•œ νŠΉμ§•λ“€μ€ μ•Œλ ˆλ₯΄κΈ°μ„± μ²œμ‹μ΄ μ•½ν•˜κ²Œ λ°œμƒν•˜λŠ” C57BL/6Jκ°€ μ•„λ‹Œ μ•Œλ ˆλ₯΄κΈ°μ„± μ²œμ‹ μœ λ„μ— μ·¨μ•½ν•œ BALB/c 마우슀 μ’…μ—μ„œ 특이적으둜 λ°œμƒν•˜λŠ” 것을 ν™•μΈν•˜μ˜€λ‹€. λ³Έ 연ꡬλ₯Ό ν†΅ν•˜μ—¬ λΉ„κ²°ν•΅ ν•­μ‚°κ·  감염과 μ•Œλ ˆλ₯΄κΈ°μ„± μ²œμ‹μ˜ λ™λ°˜ μ‹œ μΌμ–΄λ‚˜λŠ” λ¬Έμ œμ λ“€μ˜ 해결을 μœ„ν•˜μ—¬ 효과적인 마우슀 λͺ¨λΈμ„ κ΅¬μΆ•ν•˜μ˜€λ‹€. λ˜ν•œ 두 μ§ˆλ³‘μ˜ λ™λ°˜ μ‹œ λ°œμƒν•˜λŠ” 증상 μ•…ν™”μ˜ 원인이 μ•½ν™”λœ μˆ™μ£Όμ˜ μ—Όμ¦λ°˜μ‘μž„μ„ 규λͺ…ν•˜μ˜€μœΌλ©° λ™λ°˜μ΄ν™˜ ν™˜μžμ˜ ν˜Έμ „μ„ μœ„ν•˜μ—¬ μˆ™μ£Όμ˜ Th 1 λ˜λŠ” Th 17 λ°˜μ‘μ„ μœ λ„ν•˜λŠ” λ°©μ•ˆμ„ μ œμ‹œν•œλ‹€. Purpose: The incidence of pulmonary disease (PD) due to nontuberculous mycobacteria (NTM) and allergic asthma is increasing globally. Comorbidity by both chronic respiratory diseases has emerged, particularly in middle-aged women. Accumulating evidence suggests that patients with NTM-PD are susceptible to the development of allergic asthma, especially poorly controlled asthma; asthmatic patients are also associated with susceptibility to NTM infection. However, there have been limited studies elucidating the association between these two diseases, particularly how they mutually affect each other in terms of disease progression and which disease can be a significant underlying disease to the other. Thus, the aim of this study was to investigate the disease phenotype and immunological characteristics of these comorbid diseases in animal models. Methods: BALB/c female mice were used to establish two animal models of comorbidity: 1) an NTM infection was established with a clinical strain of Mycobacterium avium complex (MAV), followed by ovalbumin-induced asthma, and 2) a comorbidity model was established vice versa. We then compared the disease phenotypes using common evaluation criteria for each disease, such as bacterial burden, histopathological assessment of granulomatous inflammation and goblet cell hyperplasia, and antigen-specific immune responses. Results: Airway and pulmonary inflammation were exacerbated because of the co-occurrence of NTM-PD and allergic asthma, regardless of both diseases. Moreover, the induction of allergic asthma accelerated the growth of bacteria because of the progression of NTM-PD and alleviated goblet cell hyperplasia. This phenotype resulted from inhibition of MAV-specific IFN-Ξ³ and -IL-17A. However, IL-13 and IL-5 levels were attenuated by OVA, regardless of which disease preceded the other in terms of onset. Conclusions: The co-occurrence of allergic asthma and MAV infection aggravated inflammation and bacterial growth by diminishing MAV-specific Th1 and Th17 responses. Taken together, NTM-PD was aggravated by the disruption of antigen-specific T cell response because of exposure to an allergen, whereas allergic asthma gradually improved with the reduced allergen-specific Th2 response upon MAV infection. These findings will help in improving our understanding of the pathogenesis and establishing therapeutic strategies for patients with comorbid NTM-PD and allergic asthmaopen석
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