Blockade of RAGE ameliorates elastase-induced emphysema development and progression <i>via</i> RAGE-DAMP signaling

Lee, Hanbyeol,Park, Jeong-Ran,Kim, Woo Jin,Sundar, Isaac K.,Rahman, Irfan,Park, Sung-Min,Yang, Se-Ran The Federation of American Societies for Experimen 2017 The FASEB Journal Vol.31 No.5

<P>The receptor for advanced glycan end products (RAGE) has been identified as a susceptibility gene for chronic obstructive pulmonary disease (COPD) in genome-wide association studies (GWASs). However, less is known about how RAGE is involved in the pathogenesis of COPD. To determine the molecular mechanism by which RAGE influences COPD in experimental COPD models, we investigated the efficacy of the RAGE-specific antagonist FPS-ZM1 administration in in vivo and in vitro COPD models. We injected elastase intratracheally and the RAGE antagonist FPS-ZM1 in mice, and the infiltrated inflammatory cells and cytokines were assessed by ELISA. Cellular expression of RAGE was determined in protein, serum, and bronchoalveolar lavage fluid of mice and lungs and serum of human donors and patients with COPD. Downstream damage-associated molecular pattern (DAMP) pathway activation in vivo and in vitro and in patients with COPD was assessed by immunofluorescence staining, Western blot analysis, and ELISA. The expression of membrane RAGE in initiating the inflammatory response and of soluble RAGE acting as a decoy were associated with up-regulation of the DAMP-related signaling pathway via Nrf2. FPS-ZM1 administration significantly reversed emphysema in the lung of mice. Moreover, FPS-ZM1 treatment significantly reduced lung inflammation in Nrf2(+/+) , but not in Nrf2(-/-) mice. Thus, our data indicate for the first time that RAGE inhibition has an essential protective role in COPD. Our observation of RAGE inhibition provided novel insight into its potential as a therapeutic target in emphysema/COPD.-Lee, H., Park, J.-R., Kim, W. J., Sundar, I. K., Rahman, I., Park, S.-M., Yang. S.-R. Blockade of RAGE ameliorates elastase-induced emphysema development and progression via RAGE-DAMP signaling.</P>

임상실습 교육을 위한 임상실습지도자제도(preceptorship)의 모형개발

안양희,최상순,허혜경,임영미,신윤희,박소미,김대란,김기경,김기연 연세대학교 교육대학원 2002 연세교육과학 Vol.50 No.-

The purpose of this study was to construct a modified preceptorship model that could be used to improve the quality of clinical practice for student nurses in the Department of Nursing, Wonju College of Medicine, Yonsei University. Through a literature review, three workshops, and analysis of the preceptorship performance of new nurses, three findings were identified. First, based on the literature review and workshops, a modified preceptorship proposal for clinical practice for student nurses in the hospital setting was developed. It contained standard criteria outlining qualifications and rewards for preceptors, training for preceptors, and regulations concerning reciprocal relations among preceptors, head nurses, clinical instructors, and students. Second, results of the analysis of the preceptorship performance of new nurses in the hospital found implications for improvement of self-esteem and self-confidence and, for burden in overloading. Third, based on the literature review, the modified preceptorship proposal, and the results of the analysis of the preceptorship performance of new nurses, a modified preceptorship model was constructed. The modified preceptorship model for clinical practice for student nurses in both hospital and community settings contained standard criteria outlining qualifications and rewards for preceptors, training and education fur preceptors, and regulations concerning reciprocal relations. The standard criteria for qualification as a preceptor should be at least a BSN, at least two years experience, and leadership ability. Rewards for preceptors could be job conditions. For the training and education of preceptors, the difference between hospital and community settings was the content and duration of training. The common training content for preceptors were objectives, orientation to curriculum and preceptorship, clinical practice guidelines, communication channels between health teams and preceptors, nursing process, nursing interventions, and evaluation. In conclusion, the findings suggest a need fur further study on preceptorship when used to improve the quality of clinical practice for student nurses in the both hospital and community settings. The ultimate goal of the research on preceptorship was not only to help student nurses to enhance their ability in clinical practice, but also to maintain the quality of clinical practice in the professional nurses in any clinical setting.

급성 백혈병 환자에서 발생한 감염 양상의 분석(1986~1992)

박선양,오명돈,김양수,백경란,김병국,최강원,김성민 대한감염학회 1993 감염 Vol.25 No.3

Infection is a major complication and potentially life-threatening in patients with acute leukemia. The patients require prompt broad-spectrum antibiotics therapy when fever develops. One of the keys to successful patient management is the recognition of institutional trends of the spectrum of infections and infecting microorganisms. So we evaluated 138 patients with acute leukemia and blastic crisis of chronic myelogenous leukemia admitted to Seoul National University Hospital from July 1986 to June 1992. The results are following: 1) Total number of febrile episodes was 224 and 60% of them occurred after chemotherapy. 2) Microbiologically-defined infection, clinically-defined infection, and unexplained fever accounted for 28%, 45%, 27% of the febrile episodes respectively. 3) Fifty-eight percent of microbiologically-defined infections were caused by gram-negative bactria, and 36% were gram-positive bacteria. There was a tendency to a greater proportion of gram (+) organisms than that of the last study (p>0.1). Escherichia coli was the most common organism, and coagulase-negative staphylococci, Pseudomonas aeruginosa, Klebsiella pneumoniae were common in decreasing order. 4) Pneumonia was the most common type of infection, followed by skin and soft tissue infection, perianal infection, gingivitis and primary septicemia. 5) Seventy-two percent of total infections improved with therapy and this success rate was higher than that of the last study(p<0.001).

성견 절치에서 수직 골결손 형성후 함입이동시 치주조직의 반응

박양수,김영준,최홍란,황현식 전남대학교 치과대학 2000 전남치대논문집 Vol.12 No.1

The present study was performed to investigate the periodontal response following orthodontic intrusion of teeth with vertical bony defect produced by periodontal disease. Vertical bony defect and periodontal disease were produced adjacent to the both maxillary second lateral incisors in four adult dogs, weighing 20kg or more. Four weeks later, a flap operation was performed to eliminate inflammation and a reference notch was made on the root surface at the level of bottom of each defect. Two weeks after periodontal surgery, four weeks of intrusion and another four weeks of retention was executed on the right incisors while left incisors served as the control. Through the histologic analysis, following results were obtained. 1. The periodontal lesion which was produced by elastics and artificial bony defect was characterized by three walled infrabony pocket. 2. In the histologic section of control side, the base of the pocket was located below the level of the cemento-enamel junction. Connective tissue attachment was formed apically from the base of the pocket. 3. On the experimental side, the base of the pocket was localized close to the cemento-enamel junction. Connective tissue attachment was formed near to pocket base and extended apically. 4. New cementum was formed from the notch coronally toward the epithelial junction along the root surface in the both intruded incisors and control. 5. In the fluorescence microscopic observation, bone regeneration was began at the base of defect and the remodelling pattern characterized by a combination of coronal bone generation and resorption of the marginal crest could be detected. Although the remodelling pattern was the same in the both side, the bone remodelling in intruded incisors was continued during tooth movement. The results of the present study suggest that an orthodontic intrusion of extruded incisors with vertical bony defect can be carried out with a desirable periodontal response, provided that both the oral hygiene and the biomechanical force system are kept under control.

골결손과 치주질환 유도 후 성견 절치의 실험적 함입이동시 치주조직의 반응

황현식,박양수,최홍란 대한치과교정학회 1998 대한치과교정학회지 Vol.28 No.3

치주질환에 이환된 성인환자에서 상악전치의 치간공간과 아울러 정출이 발생된 경우 기능 및 심미의 회복을 위해서는 함입이동이 필요하다. 본 연구는 골하치주낭 즉, 수직적 골결손이 있는 절치의 함입이동시 치주조직 반응을 살펴보기 위하여 시행되었다. 상악 좌우 측절치에 골결손과 함께 치주질환을 유발시킨 성견 4마리를 실험대상으로 하여 양측 모두에 치주수술을 시행하고 결손부 최하방 치근면에 notch를 형성한 2주후 우측 제2측절치는 4주간 함입이동 후 4주간 보정을 시행한 실험측으로, 좌측 제2측절치는 구강위생관리만 시행한 대조측으로 사용한 바 조직소견을 통하여 다음과 같은 결론을 얻었다. 1. 함입이동없이 치주수술만 시행한 대조측의 조직소견은 치주낭 깊이의 감소를 보였으나 notch 부위부터 치주낭 기저부까지 긴 접합상피 상태를 보였으며 신생백악질이 형성된 일부에서만 결합조직 부착의 양상이 보였다. 2. 함입이동을 시행한 실험측은 대조측에 비하여 상피부착이 줄어든 반면 보다 넓은 신생 결합조직 부착 소견을 나타내었다. 3. 대조측과는 달리 실험측 notch 근처의 결합조직내에는 다수의 세포가 관찰되었으며, 신생 백악질 생성 역시 대조측 보다 많이 관찰되었다. 이상의 결과는 치주질환으로 인하여 정출된 치아에서도 철저한 염증조절과 구강위생이 유지되고 적절한 크기의 힘에 의하여 순수한 함입이동이 적용된다면 바람직한 치료결과가 가능함을 시사하였다. While periodontal disease results in the extrusion of upper incisors with interdental spacing in adult patient, the intrusive movement should be executed for the rehabilitation in terms of esthetics and function. The present study was performed to investigate the periodontal response following orthodontic intrusion of teeth with infrabony pocket. Bone defect and periodontal disease were produced adjacent to the both maxillary second lateral incisors in four adult dogs. Four weeks later, a flap operation was performed to eliminate inflammation and a reference notch was made on the root surface at the level of bottom of each defect. Two weeks after periodontal surgery, 4 weeks of intrusion and subsequent another 4 weeks of retention was executed on the right side of incisors while left incisors served as the control. Through the histologic analysis, following results were obtained. 1. Histologic section of control side showed the reduction of pocket depth after flap operation. However, the status of long junctional epithelium was observed while new connective tissue attachment occurred in a small area adjacent newly formed cementum. 2. Epithelial attachment was less around the intruded incisor while new connective tissue attachment was much more compared to the control side. 3. Plenty of cells were observed in the connective tissue around the reference notch of the intruded incisor and the degree of the new cementum formation was higher in the intruded incisor than the control. The results of the present study suggested that an orthodontic intrusion of periodontally involved and extruded incisors could be carried out with a desirable periodontal response, provided that inflammation is under control.

고삼투압성 비케톤성 상태의 예후인자

안성훈,김양원,김미란,진헌철,안지영,이상래,류석용,김홍용,김성준,이병권,김경환 대한응급의학회 2001 대한응급의학회지 Vol.12 No.2

Background: A hyperosmolar nonketotic state has been known to have a high mortality, and even now, despite this high mortality, only a few studies of this disease have been performed. We studied the prognostic factors for the hyperosmolar nonketotic state. Methods: We retrospectively studied the cases of 40 patients who were in a hypersomolar nonketotic state when admitted to Sanggye Paik Hospital during the 6-year Period from 1995 through 2000. We divided the hyperosmolar nonketotic patients into two groups, the complete recovery group and the incomplete recovery group, and compared the clinical features, the laboratory findings, and the precipitating factors between two groups. Results: 1) A total of 40 patients were studied: 24 in the complete recovery group and 16 patients in the incomplete recovery group. The mortality rate was 32.5%. 2) No significant statistical difference existed among the clinical features of the two groups, except for the sex(p<0.01). 3) Among the laboratory findings of both groups, analysis revealed that the effective osmolarity was significantly higher among those in the incomplete recovery group(p<0.01). Serum sodium concentration was also significantly higher among those in the incomplete recovery group(p<0.01). Serum creatinine was also significantly higher among those in the incomplete recovery group(p<0.05). Serum bicarbonate concentration, on the other hand, was significantly lower among those in that group(p<0.05).4) Infection was identified as the most common precipitating factor(62.5%). Among the precipitating factors of the two groups, there were significant statistical difference in pneumonia, UTI, and inappropriate glucose control. 5) A significant statistical difference existed among the initial level of consciousness of both groups(p<0.05). 6) The only significant independent factor responsible for prognosis of nonketotic hyperosmolar state patients was the sex. Conclusion: The sex was only significant independent prognostic factor of nonketotic hyperosmolar state patients.

재래종 콩 유전자원의 주요 형태적 특성과 변이

윤문섭,백형진,이정란,김행훈,조양희,안종웅,김창영 한국국제농업개발학회 2003 韓國國際農業開發學會誌 Vol.15 No.4

본 실험은 한국, 중국 및 일본 재래종 콩 유전자 자원의 주요형질 변이를 조사하고 이들 자원간의 지리적 유연관계를 비교하고자 수행하였으며, 그 결과를 요약하면 다음과 같다. 1. 경장은 한국(66㎝)이나 일본자원(54.9㎝)보다 중국자원(71㎝)에서 더 컸으며, 또한 변이도 중국자원에서 가장 큰 것으로 나타났다. 2. 개화일수 및 생육일수는 한국자원(65.5일, 151.4일)이 가장 길었으며 중국(57일, 120일)과 일본자원(59.9일, 122.4일)은 같은 경향을 나타냈다. 또한 한국과 중국자원은 지역에 따른 차이를 나타냈으나 일본자원에서는 확인할 수 없었다. 3. 백립중은 한국(18.8g), 일본(17.2g) 및 중국(14.7g) 순으로 무거웠다. 특히 한국자원은 9~11g과 23~25g에서 정점을 나타냈고, 변이폭도 가장 컸다. 반면 일본과 중국자원은 13~17g사이에서 정점을 나타냈다. 4. 협수는 중국(46.9개)이나 일본자원(36.5개)보다 한국자원(75.5개)에서 가장 많았으며, 변이폭도 한국자원에서 가장 컸다. 내도복성은 일본자원에서 가장 강하였다. 5. 정준판별분석결과 can 1을 경계로 하여 오른쪽 상하에 한국재래종이 주로 분포하였고 왼쪽에는 중국과 일본 재래종이 주로 분포하여 각 나라별로 고유한 영역을 가지고 분리되었다. 전체적 경향이 중국과 일본자원이 한국자원보다 가까운 경향을 나타냈다. This experiment was carried out to compare the characters of 944 Korean soybean landraces, 716 Chinese, and 170 Japanese soybean landraces introduced from USDA soybean germplasm collection. Cannonical discriminant and cluster analyses were conducted by their origins. The population from China was taller in plant height than those from Korea and Japan, also its variation was largest in Chinese population. The population from Korea was langer than those from China and Japan in terms of days to flowering and maturity. Also, Korean and Chinese accessions appeared the difference of those traits according to latitude. One hundred seeds weight was in the order of Korean(18.8g), Japanese(17.2g) and Chinese populations(14.7g), especially Korean population was distinguished into two groups; the group including accessions between 10 and 15g, and the other group including accessions between 20 and 25g. However, others showed the peak in range of 13~17g. The number of pod per plant was more in Korean accession(75.5) with the largest variation than Chinese(46.9) and Japanese accession(36.5). The distribution of Korean, Chinese and Japanese accessions reflected the origin of accessions analyzed by cannonical discriminant analysis. The relationship between their geographical origins showed the population of China and Japan are losely related.

How to Manage the Pediatric Nutritional Support Team: Updates

Yang, Hye Ran The Korean Society of Pediatric Gastroenterology 2012 Pediatric gastroenterology, hepatology & nutrition Vol.15 No.2

Pediatric patients in hospital are at risk of malnutrition at admission and even during their hospitalization. Although the concept of nutritional support team (NST) was introduced to hospitals for optimal nutritional care since 1960s and the benefits of pediatric NST have been proven by many studies and reports in terms of patient clinical outcome and cost saving, the pediatric NST is not widespread yet. The pediatric NST composed of pediatricians, dieticians, pharmacist, and nutrition support nurses as core members dedicated to nutritional care in children should be independent of central NST or other disciplines, but closely cooperate with other teams in hospitals. There is no doubt that a multidisciplinary NST is an effective way to provide appropriate nutritional support to an individual patient. Therefore, the implementation of the pediatric NST in hospitals should be recommended to provide optimum nutritional support including enteral tube feeding and parenteral nutrition and to assess pediatric patients at risk of malnutrition.

Noninvasive diagnosis of pediatric nonalcoholic fatty liver disease

Yang, Hye Ran The Korean Pediatric Society 2013 Clinical and Experimental Pediatrics (CEP) Vol.56 No.2

Because nonalcoholic steatohepatitis can progress towards cirrhosis even in children, early detection of hepatic fibrosis and accurate diagnosis of nonalcoholic fatty liver disease (NAFLD) are important. Although liver biopsy is regarded as the gold standard of diagnosis, its clinical application is somewhat limited in children due to its invasiveness. Noninvasive diagnostic methods, including imaging studies, biomarkers of inflammation, oxidative stress, hepatic apoptosis, hepatic fibrosis, and noninvasive hepatic fibrosis scores have recently been developed for diagnosing the spectrum of NAFLD, particularly the severity of hepatic fibrosis. Although data and validation are still lacking for these noninvasive modalities in the pediatric population, these methods may be applicable for pediatric NAFLD. Therefore, noninvasive imaging studies, biomarkers, and hepatic fibrosis scoring systems may be useful in the detection of hepatic steatosis and the prediction of hepatic fibrosis, even in children with NAFLD.

Distinct evolution of toll‑like receptor signaling pathway genes in cetaceans

Ran Tian,Inge Seim,Zepeng Zhang,Ying Yang,Wenhua Ren,Shixia Xu,Guang Yang 한국유전학회 2019 Genes & Genomics Vol.41 No.12

Background The relatively rapid spread and diversity of marine pathogens posed an initial and ongoing challenge for cetaceans (whales, dolphins, and porpoises), descendants of terrestrial mammals that transitioned from land to sea approximately 56 million years ago. Toll-like receptors (TLRs) play important roles in regulating immunity against pathogen infections by detecting specific molecular patterns and activating a wide range of downstream signaling pathways. The ever-increasing catalogue of mammalian genomes offers unprecedented opportunities to reveal genetic changes associated with evolutionary and ecological processes. Objective This study aimed to explore the molecular evolution of TLR signaling pathway genes in cetaceans. Methods Genes involved in the TLR signaling pathway were retrieved by BLAST searches using human coding sequences as queries. We tested each gene for positive selection along the cetacean branches using PAML and Hyphy. Physicochemical property changes of amino acids at all positively selected residues were assessed by TreeSAAP and visualized with WebLogo. Bovine and dolphin TLR4 was assessed using human embryonic kidney cell line HEK293, which lacks TLR4 and its co-receptor MD-2. Results We demonstrate that eight TLR signaling pathway genes are under positive selection in cetaceans. These include key genes in the response to Gram-negative bacteria: TLR4, CD14, and LY96 (MD-2). Moreover, 41 out of 65 positively selected sites were inferred to harbor substitution that dramatically changes the physicochemical properties of amino acids, with most of them situated in or adjacent to functional regions. We also found strong evidence that positive selection occurred in the lineage of the Yangtze finless porpoise, likely reflecting relatively recent adaptions to a freshwater milieu. Species-specific differences in TLR4 response were observed between cetacean and terrestrial species. Cetacean TLR4 was significantly less responsive to lipopolysaccharides from a terrestrial E. coli strain, possibly a reflection of the arms race of host–pathogen co-evolution faced by cetaceans in an aquatic environment. Conclusion This study provides further impetus for studies on the evolution and function of the cetacean immune system.