Induction of Anti-Aquaporin 5 Autoantibody Production by Immunization with a Peptide Derived from the Aquaporin of Prevotella melaninogenica Leads to Reduced Salivary Flow in Mice
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- IMMUNE NETWORK
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- 제21권5호
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- pp.34.1-34.16
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- 2021
Sjögren's syndrome (SS) is an autoimmune disease characterized by dryness of the mouth and eyes. The glandular dysfunction in SS involves not only T cell-mediated destruction of the glands but also autoantibodies against the type 3 muscarinic acetylcholine receptor or aquaporin 5 (AQP5) that interfere with the secretion process. Studies on the breakage of tolerance and induction of autoantibodies to these autoantigens could benefit SS patients. To break tolerance, we utilized a PmE-L peptide derived from the AQP5-homologous aquaporin of Prevotella melaninogenica (PmAqp) that contained both a B cell "E" epitope and a T cell epitope. Repeated subcutaneous immunization of C57BL/6 mice with the PmE-L peptide efficiently induced the production of Abs against the "E" epitope of mouse/human AQP5 (AQP5E), and we aimed to characterize the antigen specificity, the sequences of AQP5E-specific B cell receptors, and salivary gland phenotypes of these mice. Sera containing anti-AQP5E IgG not only stained mouse Aqp5 expressed in the submandibular glands but also detected PmApq and PmE-L by immunoblotting, suggesting molecular mimicry. Characterization of the AQP5E-specific autoantibodies selected from the screening of phage display Ab libraries and mapping of the B cell receptor repertoires revealed that the AQP5E-specific B cells acquired the ability to bind to the Ag through cumulative somatic hypermutation. Importantly, animals with anti-AQP5E Abs had decreased salivary flow rates without immune cell infiltration into the salivary glands. This model will be useful for investigating the role of anti-AQP5 autoantibodies in glandular dysfunction in SS and testing new therapeutics targeting autoantibody production.
2017년 8월 미(美) 국방성 산하 DARPA(Defense Advanced Research Projects Agency)는 "모자이크전(mosaic warfare)"이라는 새로운 전투방식을 제안하였다. DARPA의 전략기술국장(Director of Strategic Technology Office) Timothy Grayson에 따르면 모자이크전이란 "지정된 위치에 딱 들어맞아야 제 역할을 할 수 있는 특정 모양의 "퍼즐조각(puzzle pieces, 특정임무가 지정된 플랫폼)"이 아니라 호환 가능한 "타일(tile, 센서 및 타격 기능)"이 복합체계로 구성된 전투방식"이다. 모자이크전 이론 및 최근 동향을 살펴보기에 앞서, 모자이크전에 대한 배경과 몇 가지 핵심전제를 분석하였다. 미 국방성은 중국 A2/AD에 대한 자국 자산의 방호가 극도로 제한된다는 점을 암묵적으로 인정하고 있다. 또한 미국은 여전히 다른 나라의 영토와 영공에서도 완전한 군사적 우위를 추구하고자 한다. 미국은 모자이크전을 통한 재빠른 전투손실 회복력, 인명피해 최소화로 대량의 물량이 필요한 소모전도 감수할 수 있을 것이다. 모자이크전의 핵심은 "의사결정 중심전(Decision Centric Warfare)"이다. 이를 구현하기 위해 아군에게는 적응력과 융통성을, 적에게는 복잡성과 불확실성을 제공하는 것으로, 인간의 "지휘(command)"와 기계의 "통제(control)"를 결합·활용하여 분산된 전력의 신속한 구성 및 재구성한다. 이를 통해 우군에게 더 많은 방책을 제공하고, 궁극적으로 상대의 의사결정 체계(OODA loop)를 붕괴시킨다. 이런 모자이크전 수행을 위한 핵심 요소는 적응형 킬웹(Adaptable kill web), 조합형 전력 패키지, 인공지능, 상황중심 C3 구조 등이 있다. 최근 CSBA(Center for Strategic and Budgetary Assessments)에서는 모자이크전의 의사결정과 관련하여 의미 있는 워게임 결과를 발표했다. 전통적인 전투수행 조직/방식(전통적 팀)과 모자이크전 수행방식의 팀(모자이크팀)간 분명한 차이점이 발견되었는데, 모자이크팀에서 더 많은 동시다발적 작전 수행 및 복잡성으로 상대의 의사결정 체계를 압도하고, 우군의 인명손실은 적었다. 또한 우군의 의사결정 속도를 증가시켜 지휘관 작전적 템포를 보다 신속하게 할 수 있었다. 한국군의 발전방향으로 우선 우리 안보환경을 고려한 '모자이크전'에 대한 연구와 발전이 필요하다. 미래전에 대비하여 영역에 상관없이 전력을 조합할 수 있는 전반적 군 구조를 검토해야 한다. 제한된 국방재원과 예산을 고려하여 선택과 집중이 필요하며, 주변국의 미래전 발전 동향에 대해 예의주시해야 한다.
Study of Animation 3-Dimensional Motion Picture국내뿐만 아니라 전 세계의 수백만의 인구가 영상을 접하고 있다. 영상은 움직이는 형상을 시각화 하는 것에서 지식, 정보 전달의 매체로서 자리 매김 하였다. 과학의 발전은 온라인(Online)시대를 열어주었고 온라인 시대의 정보습득은 지속적으로 고속화 되어, 과량의 정보 속에서 선택을 해야 하는 관객들을 함께 가속화 시키고 있다. 선택적인 측면에서 시각적인 전달 방법은 급변하는 시대의 요구에 맞게 변화하게 된다. 다량의 정보 속에서 순간의 선택을 받기 위한 일한으로, 1차적인 요건은 시선을 집중시키는 것이며, 그에 상응하는 만족감을 선사하는 것이다. 영상의 초기는 실제로 자신이 보고 있는 상황을 그대로 옮기고자 하는 욕구에서 출발한 것이다. 정지화면에서 만족하지 못한 인간은 움직이는 화면(Film)을 개발하였고 양안의 시점의 차이와 광선의 자극 반응을 감안한 실제 인지하는 시점보다 더 입체감을 만들어내는 영상을 가늠 해내는 연구를 하게 된다. 이는 컬러 필름(Color Film)에서 입체영상 개발까지 놀라운 성과를 누리게 된다. 인간의 가시적인 면에 대한 욕망의 추구 즉, 극대화된 실재감(Reality) 있는 볼거리 추구는 영상이 포함되는 모든 분야에 지속적으로 요구되고 있다. 지금 수백만의 인구가 보편적으로 보고 있는 영상들은 평면적이다. 화면의 깊이 감(Depth)과 착시현상(Optical Illusion)은 효과적으로 현실감을 주며 정보를 전달한다. 하지만, 인간의 양안 시점차이로 인식하는 입체감은 평면속에서 만들어 내는 깊이 감으로는 현실감 있게 인식하는데 한계점이 존재한다. 이러한 한계를 만족시킬 입체 영상) 입체영상은 영화에서 시작되었으나, 20c후반기에 들어서면서 애니메이션 분야와 모바일, 광고 패널, 텔레비전등의 매체를 이용한 입체 영상의 개발로 인하여 특정 분야에 한정 시킬 수 없으므로 영상으로 칭한다. 입체 영상은 21c에 들어서면서 영상매체의 한 분야로 급부상하고 있다. 1900년 무렵부터 연구된 입체영화(3-Dimensional motion Picture)는 In여 년이 지난 지금 대중화를 눈앞에 두고 있다. 국내에서는 놀이 동산이나 박물관등에서 흔히 볼 수 있다. 하지만 앞으로는 HDW등의 대중화로 화질의 발전을 이룬 텔레비전 분야 등에서 실용화 될 전망이다. 국제적인 흐름과 함께 국내에서도 입체 영화에 대한 연구가 활성화 되어 영상산업의 한 주류로서 대두되고 있다. 이러한 상황에서 입체영상에 대한 이해와 콘텐츠(Contents)의 개발은 기술적인 진보에 발맞추어 준비되어야 한다. 본 논문은 이러한 기술적인 계보에 발맞춘 영상 콘텐츠 개발에 박차를 가하고자 앞으로의 발전분야에 대한 기술적인 면과 기법적인 면을 제시하여 기술만 앞서고 내용은 수입하는 수입국이기 보다는 미리 준비하여 비전문가나 타국의 기술에 선점 당하지 않는 분야로 성장할 수 있는 진보적인 영상 인들의 관심과 지속적인 연구를 독려하고자 한다.
According as the automation of clerical work(OA ; Office Automation) develops, the use of VDT(Visual or Video Display Terminal) is increasing suddenly. But, in proportion to the spread of office automation(OA tendency), the self-conciousness syptom attendant upon the work is appearing also (Kim, Jung Tae, Lee, Young Ook, 1990). The apparatuses of office enable the clerical workers to be convenient and perform mass businesses. But, they are increasing the opportunity to be exposed to VDT syndrom, techno stress, computer terminal disease, pain by muscle strain(RSI), bradycausia of noise nature, and electromagnetic waves, etc. which are referred to as the new type of occupational diseases to the workers. It is the real situation that the workers to use VDT is complaining of the physical inconvenience sense in the recent newspaper and literature, it is the point of time that the sydrome to come from VDT use and computer terminal disease, etc. must be classified into the occupational disease(Lee, Kwang Young 1990, Lee, Kyoo Hak 1990, Lee, Won Ho 1991, Lee, Si Young 1991, Lee, Joon 1991, Choi, Young Tae 1991, Heo, Seung Ho 1989). In addition, it is the real situation that the scientifitic study result about the scope that electromagnetic waves has influence on the human body has not been suggested yet, and criticism on the stable exposure permission standard about electromagnetic waves to be emitted from VDT and on the problem in the health about electromagnetic waves is continuing. (IEEE Spectrum, 1990). In addition according to the experience of nursery business of industry field, it is the real situation that the patients who consult complaining of physical and mental inconvenience sence, among the users of apparatus of office automation, are reaching 10% of the patients coming to doctor's room. Therefore, it is necessary to confirm the self-consciousness symptom that the clerical workers complain of multilaterally with the actual state examination about the use of the apparatuses of offices automaton. Thus, this study was tried as th basic data for the cosultation and education for the maintenance and furtherance of the health of workers as the nurse of industry field, by confirming the contents of self-consciousness symptom attendant upon the use of the apparatus for office outomation making the financial institution in which the spparatus for office automation in most frequently used as the subject, and by examining whether there is the difference according to the subject of study, the data were collected, by using the questionnaire method, making 200 workers who consented to the study participation as the subject, among the persons who have spent over 3 months since they used the apparatuses for office automation and didn't receive the treatment in hospital due to the clerical disease for recent 3 years. The period of data collection was from Oct. 9, 1991 to Oct. 12. As for the measurement instrument about the complaint if self-consciousness symptom attendant upon the use of apparatuses fo office automation, the question item on the complaint symptom of health problem attendant upon the treatment of VDT that Kim(1991) developed and on CMI health problem and the question items on the fatigue degree due to industry were used by previous examination to 25 persons. Collected data were analyzed with the statistical method such as percentage, arithmetic mean, Person correlation coeffient, Kai square verfication, t-test, ANOVA, etc. by using SPSS/PC+ program, and the result is as follows : 1. The self-consciousness symptom that the clerical workers complained of most frequetly appeared high in 'My eyes are tired'(99.4%), 'I feel fatigue and weariness'(99.4%), 'I feel that my head is heavy5(90.0%), 'eyesight fell'(88.8%), 'I have a stiff neck'(88.8%), 'I fell pain in the shoulder'(85.0%), 'I feel cold and painful in the eyes'(76.9%), 'I feel the dry sense of eyeball'(76.2%), 'My nerves are edgy, and I an fretful, (75.6%), 'I feel pain in the waist'(73.2%) and 'I fell pain in the back'(72.8%). It emerged that the subject use the apparatuses for office automation complained of self-consciousness symptoms related to visual symptoms and musculoskeletal symptoms. 2. As for the general feature of examination subjects, the result to see the distribution by classifying into sex, age, school career, use career of apparatuses for office automation, skillfulness degree of the use of apparatus for office automation, use hours of the apparatuses for office automation per 1 day, type of business of the apparatus for office automation, rest hours during the use of apparatus for office automation, satifaction degree of business of office automation, and work circumstance, etc. emerged as follows : As for the sex of subjects, the distribution showed that men were 58.8% and women were 41.3%, Age was average 26.9. As the distribution of school career, the distribution showed that4below the graduation of high school' was 58.8%, 'graduation from junior college-university' was 35.0%, and 'over graduate school' was 6.3%. In the question to ask the existence or non-existence of experience of health consultation in connection with the work of office automation, the response that I had the consultation exprience and I feel the necessity emergerd as 90.1% And, the case that the subject who didn't wear the glasses or lens before using the OA apparatus wear glasses or lens after using OA apparatus emerged as 28.3% of whole. As for the existence or non-existence of use career of OA apparatus, the case under 3 years was highest as 52. 7%. As for the skillfulnness degree about the use of apparatus for office automation, most of them are skillful with the fact that 'common' was 44.4%, 'skill' was 42.5%, and 'unskillful' was 13.1% As for the use average hours of the apparatus for office automation per 1 day, the distribution showed that the case under 3-6 hours was 33.1%, the case under 6-9 hours was 28.1%, the case under 3 hours was 30.6%, and the case over 9 hours was 8.1% Main OA business and the use hours for 1 day showed in the order of keeping and retrieval, business of information transmission(162min), business of information transmission(79.3 min), business of document framing(55.5 min), and business of duplication and printing(25.4min). as for the rest during the use of apparatus for affice automation, that I take rest occasion demands the major portion, but that I take after completing the work emerged as 33.8%. Though the subiness gets to be convenient by the use of the apparatus for of office automation, respondents who showed the dissatisfaction about the present OA business emergd high as 78.1%. The work circumstances of each office was good with the fact that the temperature of office was 21.8, noise was average 42.7db, and the illumination was average 364.4 lx, in the light of ANSi/HFS 100 Standard. 3. Sight syptom, musculoskeletal symptom, skin and other symptoms showed the significant difference according to the extent of skillfulness of the apparatus for office automation. All the symptoms exept skin symptom showed the difference according to the use hours of the apparatus for office automation. All the question items exept the sytoms of digestive organs and the rest hours during the apparatus for office automation showed the signicant difference. The question item which showed the signicant difference from the satisfaction degree of present OA business showed the significant difference from all the question item classified into 6 groups. But, age and school career didn't significant difference from the complaint of any self-consciousness symptoms.