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Aberrant Methylation of p16 Tumor Suppressor Gene and Death-Associated Protein Kinase in Non-Small Cell Lung Carcinoma (비소세포폐암 조직에서 p16 종양억제유전자와 Death-Associated Protein Kinase의 Aberrant Methylation의 양상)

  • Kim, Yun-Seong;Lee, Min-Ki;Jung, Kyung-Sik;Kim, Ki-Uk;Kim, Young-Dae;Lee, Hyung-Ryul;Lee, Chang-Hoon;Seok, Ju-Won;Kim, Yong-Ki;Jun, Eun-Sook;Choi, Young-Min;Rha, Seo-Hee;Park, Soon-Kew
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.2
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    • pp.108-121
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    • 2001
  • Background : The $p16^{INK4a}$ (p16) twnor suppressor gene is frequently inactivated in hwnan non-small cell lung cancers (NSCLCs), predominantly through homozygous deletion or in association with aberrant promotor hypermethylation. Death-associated protein kinase (DAPK) gene influences interferon $\gamma$-induced apoptotic cell death and has important role in metastasis of lung cancer in animal model. Hypermethylation of promoter region of DAP kinase gene may suppress the expression of this gene. Methods : This study was performed to investigate the aberrant methylation of p16 or DAP kinase in 35 resected primary NSCLCs by methylation-specific PCR (MSP), and demonstrated frequency, diagnostic value and clinical implication of aberrant methylation of two genes. Results : Thirty-two cases were male patients, and 3 cases were female patients with an average age was 57. $8{\pm}10.5$ years. The histologic types of lung cancer were 22 of squamous cell carcinoma, 12 of adenocarcinoma, 1 of large cell carcinoma. Pathologic stages were 11 cases of stage I (1 IA, 10 IB), 13 cases of stage II (1 IIA, 12 IIB), and 11 cases of stage III (9 IIIA, 2 IIIB). Regarding for the cancer tissue, p16 aberrant methylation was noted in 13 case of 33 cases (39.4%), DAP kinase in 21 cases of 35 cases (60%). Age over 55 year was associated with p16 aberrant methylation significantly (p<0.05). Methylation status of two genes was not different by smoking history, histologic type, size of tumor, lymph node metastasis and disease progression of lung cancer. There was no correlation between p16 and DAP kinase hypermethylation. Conclusion: This investigation demonstrates that aberrant methylation of p16 tumor suppressor gene or DAP kinase showed relatively high frequency (74.3%) in NSCLCs, and that these genes could be a biologic marker for early detection of lung cancer.

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Signal Transduction of MUC5AC Expression in Airway Mucus Hypersecretory Disease (기도의 점액 과분비 질환에서 MUC5AC의 발현의 신호 전달 경로에 관한 연구)

  • Shim, Jae Jeong
    • Tuberculosis and Respiratory Diseases
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    • v.55 no.1
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    • pp.21-30
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    • 2003
  • Background : Mucin synthesis in airways has been reported to be regulated by the epidermal growth factor receptor (EGFR) system. Epidermal growth factor receptor transactivation was identified as a critical element in G-protein-coupled receptors (GPCRs)-induced mitogenic signaling. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. This study was hypothesized that lipopolysaccharide (LPS)-induced mucin production associates with epidermal growth factor receptor transactivation, and MUC5AC production associates with epidermal growth factor receptor transactivation by G-protein-coupled receptors that regulates by metalloproteinase. Method : MUC5AC mucin production was examined in NCI-H292 cells and MUC5AC protein synthesis was assessed using ELISA. For the evaluation of mechanism of LPS-induced MUC5AC production, $TNF{\alpha}$ was measured using ELISA with or without pretreatment of heterotrimeric G-protein inhibitor, mastoparan. MUC5AC protein was measure with pretreatment of polyclonal $TNF{\alpha}$ antibody or mastoparan on LPS-induced MUC5AC production. For the evaluation of relation of G-protein and MUC5AC production, G-protein stimulant, mastopara-7, or matrix metalloproteinase, ADAM10, was added to NCI-H292 cells. MUC5AC protein was measure with pretreatment of polyclonal EGF antibody on mastoparan-7-induced MUC5AC production. Results : LPS alone did not increase significantly MUC5AC production. LPS with $TNF{\alpha}$ induced dose-dependently MUC5AC production in NCI-H292 cells. LPS increased dose-dependently $TNF{\alpha}$ secretion, which was inhibited by mastoparan. LPS with $TNF{\alpha}$-induced MUC5AC production was inhibited by neutralizing polyclonal $TNF{\alpha}$ antibody, mastoparan or AG 1472. Mastoparan-7 or ADAM10 increased dose-dependently MUC5AC production, which was inhibited by polyclonal neutralizing EGF antibody. Conclusion : In LPS-induced MUC5AC synthesis, LPS causes $TNF{\alpha}$ secretion, which induces EGFR expression. EGFR tyrosine kinase phosphorylation result in MUC5AC production. EGF-R transactivation by G-protein-coupled receptors requires matrix metalloproteinase cleavage of proHB-EGF.

Prevalence and Clinical Outcome of Penicillin-resistant Pneumococcal Pneumonia (폐렴구균에 의한 지역사회 획득 폐렴에서 페니실린 내성률과 내성에 따른 임상경과에 관한 연구)

  • Hong, Ji Hyun;Lee, Hyung Seok;Jung, Seung Hyun;Kim, Gyu Won;Eom, Kwang-Seok;Lee, Jae Myung;Jang, Seung Hun;Kim, Dong Gyu;Hyoen, In Gyou;Lee, Myoung Koo;Park, Yong Bum;Jung, Ki-Suck;Lee, Young Kyoung
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.3
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    • pp.295-303
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    • 2003
  • Backgroung : The incidence of penicillin-resistant streptococcus pneumoniae(PRSP) accounts for almost 70% of all pneumococcal pneumonia cases in Korea. It is still unclear as to whether the efficacy of penicillin or equally active beta-lactam agents is compromised in PRSP pneumonia. This study investigated the prevalence of PRSP in community-acquired pneumonia and its clinical course. Methods : A total of 42 patients with community-acquired pneumococcal pneumonia were evaluated from July 1999 to May 2001. The cultured strains of Streptococcus pneumoniae were divided into susceptible, intermediately resistant, and resistant strains by an E-test, and the effect of the clinical course was investigated. Results : From a total of 42 patients, 22 (52.4%) patients had an intermediate resistance (MIC $0.1-1{\mu}g/m{\ell}$) and six (14.3%) showed a high resistance ($MIC{\geq}2.0{\mu}g/m{\ell}$) with current penicillin susceptibility categories. However, according to the classification of the DRSPTWG (Drug Resistant Streptococcus pneumoniae Therapeutic Working Group), there were 11 cases (26.2%) of intermediate resistance and no case of high resistance. Under empirical antimicrobial treatment, there was no difference in the clinical outcome between the penicillin susceptible and resistant group. Conclusion : The clinical outcome of PRSP pneumonia with empirical therapy was acceptable. These results suggest that the current MIC breakpoint for penicillin resistance in Streptococcus pneumoniae has been set at a very low level and penicillin resistance according to the NCCLS classification does not significantly influence the outcome of the empirical treatment for pneumococcal pneumonia.

The Effect of Platelet-Rich Plasma on Allograft Transplantation after Curettage in Benign Bone Tumor (양성 골 종양의 소파술 후 실시한 동종골 이식에서 혈소판 풍부 혈장 투여의 효과)

  • Kim, Jae-Do;Kim, Ji-Youn;Jang, Su-Jin;Chung, So-Hak;Jung, Gu-Hee
    • The Journal of the Korean bone and joint tumor society
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    • v.16 no.1
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    • pp.8-13
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    • 2010
  • Purpose: This study was performed to evaluate the effi ciency of Platelet-rich plasma (PRP) for acceleration of bone healing process on allograft transplantation after curettage in benign bone tumor. Materials and Methods: From December 2007 to February 2009, twenty-one patients who had benign bone tumor and underwent allograft transplantation after curettage were evaluated. Mean follow-up period was 14.6 months (range, 12-26 months). We compared with 13 cases of PRP group and 8 cases of non-PRP group in terms of size of lesion, bone resorption, amount of applied PRP and complications. The mean age at surgery was 23.6 years (range, 4-73 years). The most common diagnosis was simple bone cyst (7) followed by enchondroma (4), giant cell tumor (3), undifferentiated benign bone tumor (3) and so on. Results: The mean size of lesion was 33.5 $cm^3$ (range, 2.3-181.9 $cm^3$) (29.4 $cm^3$ in PRP group and 40.2 $cm^3$ in non-PRP group). The mean volume of injected PRP was 7.4 cc (range, 3-12 cc). Bone union started at 3.0 months (range, 1.5-5.8 months) in PRP group and 5.3 months (range, 4-8 months) in non-PRP group. Three cases for each group were excluded due to recurrence and pathologic fracture. One patient had febrile episode 3 weeks later after surgery which subsided with antibiotics. Conclusion: The PRP could accelerate bone union in allograft transplantation after curettage of benign bone tumor. Furthermore, we expect that PRP can accelerate bone union in fracture or non-union.

Functional Outcomes of Internal Pelvectomy without Reconstruction for Periacetabular Maligmant Tumors (비구주변 골반골 악성 골종양에서 재건술을 시행하지 않은 내골반골 절제술의 기능적 결과)

  • Chung, Yang-Guk;Kang, Yong-Koo;Lee, Seung-Koo;Bahk, Won-Jong;Lee, An-Hi;Park, Jung-Mi;Lee, Kyo-Sun;Lee, Hyung-Ju
    • The Journal of the Korean bone and joint tumor society
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    • v.13 no.1
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    • pp.60-66
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    • 2007
  • Purpose: The purpose of this study was to evaluate the functional outcomes of periacetabular malignant bone tumors treated by internal pelvectomy without reconstruction. Materials and methods: Between January 1996 and December 2005, eight patients with primary malignant or metastatic periacetabular bone tumors were treated by internal pelvectomy without reconstruction. There were 6 men and 2 women. Mean age was 42 years old. There were 3 osteosarcomas, 3 chondrosarcomas and 2 metastatic carcinomas. The type of pelvic resections were 6 type I+II+III, 1 type I+II and 1 type II+II resection. The functional outcomes were evaluated with ISOLS revised criteria. The follow up period ranged from 6 to 84 months. Results: At last follow up, 5 patients showed CDF, 2 patients, AWD and the remained 1, DOD. The mean functional score for pain, functional activity, emotional acceptance, use of external support, walking ability and gait were 4.9, 2.9, 2.9, 1.5, 2.3 and 2.5 respectively. The total functional score ranged from 37% to 70%(average: 56%). There were three temporary nerve palsies. Conclusion: The internal pelvectomy without reconstruction for selective difficult periacetabular malignant tumors could be a viable option with fewer complications and fair functional outcomes.

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Polymorphisms of 5, 10-Methylentetrahydrofolate Reductase (MTHFR C677T) and Methionine Synthase Reductase (MTRR A66G) as Maternal Risk Factors for Fetal Aneuploidy (태아의 염색체의 수적 이상을 유발하는 모계 위험인자로서 5, 10-Methylentetrahydrofolate Reductase (MTHFR C677T)와 Methionine Synthase Reductase (MTRR A66G) 유전자의 다형성 연구)

  • Kim, Do-Jin;Kim, Shin-Young;Park, So-Yeon;Kim, Jin-Woo;Kim, Moon-Young;Han, Joung-Yeol;Yang, Jae-Hyug;Ahn, Hyun-Kyong;Choi, Jun-Seek;Chung, Jin-Hoon;Ryu, Hyun-Mee
    • Journal of Genetic Medicine
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    • v.5 no.2
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    • pp.119-124
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    • 2008
  • Purpose: Aneuploidy is the cause of diseases such as Down syndrome or Edward syndrome and, more generally, is a major cause of mental retardation and fetal loss. The purpose of this study was to evaluate the association between MTHFR (C677T) or MTRR (A66G) polymorphisms and fetal aneuploidy. Materials and Methods: Data was collected from 37 women who had a fetus with aneuploidy (cases) and 78 women who had previously delivered at least two healthy children without aneuploidy and did not have a history of miscarriage or abnormal pregnancy (controls). The MTHFR (C677T) or MTRR (A66G) polymorphisms were analyzed by PCR-restriction fragment length polymorphism assay. Results: The frequencies of the MTHFR 677 CC, CT, and TT genotypes were 30.7%, 48.7%, and 20.6% in the control group and 37.8%, 48.6%, and 13.5% in the case group, respectively. There were no significant differences in genotype frequencies between the two groups. For the MTRR A66G polymorphism, the frequencies of the AA, AG and GG genotypes were 50%, 46.1%, and 3.9% in the control group and 13.5%, 81.1%, and 5.4% in case group, respectively. The frequency of the MTRR AG mutant was significantly increased in the case group, with an odds ratio of 6.5 (95% CI: 2.3-18.6, P<0.05). Conclusion: The results of this study suggest that mother carriers with the MTRR G allele have an increased risk of fetal aneuploidy, while the MTHFR T allele is not associated with increased risk of fetal aneuploidy. The MTRR A66G polymorphism may be a risk factor for producing a child with chromosomal aneuploidy.

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The Evaluation of Reliability for the Combined Refractive Power of Overlapping Trial Lenses (중첩된 시험렌즈의 합성굴절력에 대한 신뢰도 평가)

  • Lee, Hyung Kyun;Kim, So Ra;Park, Mijung
    • Journal of Korean Ophthalmic Optics Society
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    • v.20 no.3
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    • pp.263-276
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    • 2015
  • Purpose: The current study aimed to evaluate the reliability for the combined refractive power when a spherical lens and a cylindrical lens were overlapped in a trial frame. Methods: The refractive powers, central thickness and peripheral thickness of spherical trial lenses and cylindrical lenses with negative power were measured. The combined refractive power of the spherical and cylindrical lenses was measured by auto lens meter. Measurement was repeated by changing the insertion order, and their results were further compared with the calculated combined refractive power. Results: There was no correlation between the variation of central and peripheral thickness in trial lenses and that of the lens power. Among 79 trial lenses, 3 trial lenses wasn't met the international standard. The refractive power calculated by Gullstrand's formula that could compensate vertex distance had smaller difference with the estimated power when compared with that calculated by thin lens formula however, it was significantly different from the estimated power. The refractive powers were generally apparent regardless of the insertion order of a spherical lens and a cylindrical lens: thin lens formula > actual measurements > Gullstrand's formula. The error was only found in cylindrical power calculated by Gullstrand's formula when inserted a spherical lens inside and a cylindrical lens outside however, the error was found in both of cylindrical and spherical powers calculated by Gullstrand's formula when inserted as a opposite order. By comparing actual measurements of equivalent spherical power, the accuracy was higher and the possibility of over-correction was lower when inserted a spherical lens inside and a cylindrical lens outside. Conclusions: From the results, those were revealed that the combined refractive power is influenced by the factors other than the vertex distance and the refractive power varies in accordance with the insertion order of a spherical lens and a cylindrical lens. Thus, it can be suggested that the establishment of standard for these is neccesaty.

Comparative study on effects of volume-controlled ventilation and pressure-limited ventilation for neonatal respiratory distress syndrome (신생아 호흡곤란 증후군에서 volume-controlled ventilation과 pressure-limited ventilation의 효과에 관한 비교연구)

  • Kim, Jae Jin;Hwang, Mun Jung;Lee, Sang Geel
    • Clinical and Experimental Pediatrics
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    • v.53 no.1
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    • pp.21-27
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    • 2010
  • Purpose : In contrast with traditional time-cycled, pressure-limited ventilation, during volume-controlled ventilation, a nearly constant tidal volume is delivered with reducing volutrauma and the episodes of hypoxemia. The aim of this study was to compare the efficacy of pressure-regulated, volume controlled ventilation (PRVC) to Synchronized intermittent mandatory ventilation (SIMV) in VLBW infants with respiratory distress syndrome (RDS).Methods : 34 very low birth weight (VLBW) infants who had RDS were randomized to receive either PRVC or SIMV with surfactant administration : PRVC group (n=14) and SIMV group (n=20). We compared peak inspiratory pressure (PIP), duration of mechanical ventilation, and complications associated with ventilation, respectively with medical records. Results : There were no statistical differences in clinical characteristics between the groups. After surfactant administration, PIP was significantly lower during PRVC ventilation for 48hrs and accumulatevive value of decreased PIP was higher during PRVC ventilation for 24hrs (P<0.05). Duration of ventilation and incidence of complications was no significant difference. Conclusion : PRVC is the mode in which the smallest level of PIP required to deliver the preset tidal volume in VLBW infants with RDS, adaptively responding to compliance change in lung after surfactant replacement.

A study of the Patent-related Activities affecting the Early Stage Company Performance of Technology-based Start-ups (기술창업기업의 특허활동이 초기기업 성과에 미치는 영향에 대한 연구)

  • Lee, Hyeong-Mo;Kim, Myeong-Sook;Kim, Eung-Kyu
    • Asia-Pacific Journal of Business Venturing and Entrepreneurship
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    • v.7 no.3
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    • pp.45-53
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    • 2012
  • This study is about the impact of a technology-based start-ups' patent-related activities on early stage company performance. Technology-based start-ups are closely related to the intellectual property rights, particularly patents that they aim the pursuit of new products or production methods and pioneer the introduction of market based on innovative technology, and that is a key role in such companies established and operating, hence the research of patent-related activities in technology-based start-ups has important implications. In most previous studies, the impact of the company's patent related activities on the performance of corporate management is determined by using quantitative patent indicators. Therefore, through this study, causal relationships leading to business performance through the development of new products, which includes technology performance and product performance, and the patent-related activities including the company's patented technology support activities, creating the right activities, infringement response activities, base activities validated as follows. First, the patent-related activities have a positive impact on technological and products achievements. In other words, the various activities involved in the acquisition and utilization of the patent have a positive impact on the performance of company's new product development, particularly developing new technologies or patent acquisition rate. Second, the technology have a positive impact on the performance of the products, not on the business performance. However, the empirical results shows that it has indirectly impacts on business performance through the product performance. Third, product performance have a positive impact on business performance. In conclusion, patent-related activities affects the performance of the company's management, and the maintenance of the company's business performance depends on the developing and selling product based on the customers needs, besides the technology performance such as the patents and the development of technology.

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Current status of sweetpotato genomics research (고구마 유전체 연구현황 및 전망)

  • Yoon, Ung-Han;Jeong, Jae Cheol;Kwak, Sang-Soo;Yang, Jung-Wook;Kim, Tae-Ho;Lee, Hyeong-Un;Nam, Sang-Sik;Hahn, Jang-Ho
    • Journal of Plant Biotechnology
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    • v.42 no.3
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    • pp.161-167
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    • 2015
  • Sweetpotato [Ipomoea batatas (L.) Lam] grows well in harsh environmental conditions, and is cultivated as one of the top seven food crops in the world. Recently, sweetpotato is drawing interest from people as a healthy food because it is high in dietary fiber, vitamins, carotenoids and overall nutrition value. However, few studies have been conducted on sweetpotato genome sequencing in spite of its importance. This review is aimed at increasing the efficiency of sweetpotato genome sequencing research as well as establishing a base for gene utilization in order to control useful traits. Recently, animal and plant genome sequencing projects increased significantly. However, sweetpotato genome sequencing has not been performed due to polyploidy and heterogeneity problems in its genome. Meanwhile research on its transcriptome has been conducted actively. Recently, a draft of the diploid sweetpotato genome was reported in 2015 by Japanese researchers. In addition, the Korea-China-Japan Trilateral Research Association of Sweetpotato (TRAS) has conducted research on gene map construction and genome sequencing of the hexaploid sweetpotato Xushu 18 since 2014. The Bill & Melinda Gates Foundation launched the 'sweetpotato genomic sequencing to develop genomic tools for Sub-Sahara Africa breeding program'. The chloroplast genome sequence acquired during sweetpotato genome sequencing is used in evolutionary analyses. In this review, the trend of research in the sweetpotato genome sequencing was analyzed. Research trend analysis like this will provide researchers working toward sweetpotato productivity and nutrient improvement with information on the status of sweetpotato genome research. This will contribute to solving world food, energy and environmental problems.