• Journal of Microbiology
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• 제44권1호
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• pp.64-71
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• 2006

To investigate the effects of the nucleotide sequences in Shine-Dalgarno (SD) and the spacer region (SD-ATG) on bovine growth hormone (bGH) gene expression, the expression vectors under the control of the T7 promoter (pT7-7 vector) were constructed using bGH derivatives (bGH1 & bGH14) which have different 5'-coding regions and were induced in E. coli BL21 (DE3). Oligonucleotides containing random SD sequences and a spacer region were chemically synthesized and the distance between the SD region and the initiation codon were fixed to nine bases in length. The oligonucleotides were annealed and fused to the bGH1 and bGH14 cDNA, respectively. When the bGH gene was induced with IPTG in E. coli BL21(DE3), some clones containing only bGH14 cDNA produced considerable levels of bGH in the range of $6.9\%\;to\;8.5\%$ of total cell proteins by SDS-PAGE and Western blot. Otherwise, the bGH was not detected in any clones with bGH1 cDNA. Accordingly, the nucleotide sequences of SD and the spacer region affect on bGH expression indicates that the sequences sufficiently destabilize the mRNA secondary structure of the bGH14 gene. When the free energy was calculated from the transcription initiation site to the +51 nucleotide of bGH cDNA using a program of nucleic acid folding and hybridization prediction, the constructs with values below -26.3 kcal/mole (toward minus direction) were not expressed. The constructs with the original sequence of bGH cDNA also did not show any expression, regardless of the free energy values. Thus, the disruption of the mRNA secondary structure may be a major factor regulating bGH expression in the translation initiation process. Accordingly, the first stem-loop among two secondary structures present in the 5'-end region of the bGH gene should be disrupted for the effective expression of bGH.

• 대한골관절종양학회지
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• 제17권2호
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• pp.65-72
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• 2011

목적: 골종양을 절제한 후 동종골을 이용한 재건술 후 발생한 합병증을 평가하고 그 합병증에 대한 문헌고찰을 하고자 한다. 대상 및 방법: 골종양 절제 후 동종골을 이용한 재건술을 시행한 15예에 대하여 임상적 및 방사선학적 자료를 통해 후향적으로 연구를 시행하였다. 결과: 남자가 8예, 여자가 7예이었으며 평균 나이는 27.1세(1-56세), 평균 추시 기간은 89.5개월(33-146개월)였다. 21예(80.0%)에서 평균 8.35개월(4-12개월)에 방사선학적 골유합 소견을 보였다. Musculoskeletal Tumor Society 점수 평균은 73.5%(46.6-93.0%)였다. 동종골 이식과 관련된 술 후 합병증을 모두 기록하였다. 추시 기간 동안 9예(60.6%)에서 한 가지의 합병증이 발생하였고 3예(20.0%)에서 두 가지 이상의 합병증이 발생하였다. 합병증으로는 감염 3예, 골절 2예, 불유합 2예, 하지 부동 2예, 내반 변형이 2예였다. 합병증이 발생하지 않은 평균 기간은 60.8개월(6-144개월)이었다. 동종골의 평균 생존기간은 80.2개월이었고 5년 생존률은 83.0%였다. 결론: 동종골의 합병증을 줄이기 위하여 동종골을 이용한 재건술시 자가비골을 추가하는 것이 추천된다. 더나아가 조직 공학 기술과 줄기 세포 및 혈소판 풍부 혈장의 적용이 동종골의 재흡수나 불유합 등의 합병증을 줄일 수 있을 것으로 생각된다.

• Journal of Chest Surgery
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• 제25권3호
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• pp.247-257
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• 1992

Bronchial adenoma, firstly described by Muller[1882] had been reported on the subject stressed their benign nature prior to 1940`s, but these tumors including carcinoid tumor, mucoepidermoid carcinoma, adenoid cystic carcinoma, pleomorphic adenoma are now known to possess the various degree of malignant natures from benign course, low grade malignant potential to distant lymphatic or hematogenous metastasis or combination. Although histologically diffeerent, four varieties except carcinoid tumor which is a spectrum of neu-roendocrine tumor originating Kulchitsky cell of the bronchial epithelium and form the part of the APUD tumor spectrum, are morphologically and in many respects clinically similar to the corresponding tumor of the salivary gland is a specific varient of adenocarcinoma that occurs most commonly in the major and minor salivary gland and less frequently tra-cheobronchial tree, esophagus etc. To better understand the clinical characteristics and assess more precisely the malignat nature of bronchial adenoma, we studied 17 cases of bronchial adenoma, which had been experienced at the Department of Thoracic and Cardiovascular surgery of Catholic University Medical College from April 1977 to september 1991. Seventeen cases of bronchial adenoma consist of 2 carcinoid tumors, 6 adenoid cystic carcinomas, 8 mucoepidermoid carcinomas and one pleomorphic adenoma. There is a slight predominace of male patients[10/17] and the age of pt studied varied with a higher incidence occurring between the ages of 40 years and 60 years[mean age, 46.5 years]; the youngest being 15 years and oldest 69 years. Their leading complaints were hemoptysis[4], exertional dyspnea[8], fever & chilness [4], and symptoms mimicking the bronchial asthma[4]. Diagnosis was aided by the radiologic studies such as chest X-ray, polytomography, CT scan, brochography and bronchoscopy. The preferred locations of fumor were in the trachea[4], main stem bronchus[3], bronchus intermedius[3], bronchus of RUL[2], LUL[1], RLL[1], LLL[3] with no peripheral location. Modalities of treatments were single or combination of surgical resection, radiation therapy, chemotherapy. Complete resections were permitted in 12 cases with late recurrences of 4 cases ranging from 6 months to 10 years: pneumonectomy[4], lobectomy[4], bil-obectomy[2], sleeve resection[2]. Gross findings of resected specimens in 14 cases showed that 4 cases were polyp-like pedunculated mass[entirely intraluminal mass] with intact mucosa, 8 cases were broad-bas-ed sessile mass[predominatly intraluminal] and the main portions were located below the mucosa similar to tip of iceburg[predominantly extraluminal] in 2 cases. Follow-up information was availble in all 17 cases ; eight were alive without evidence of disese ranging from 1 month to 13 years. But seven cases died of the causes related to tumor[6 cases within 12 months, one case 10 years after pneumonectomy]. We concluded that 8 cases[47%] of 17 cases were metastasizing bronchial adenoma and precise survival rate cannot be answered by the scanty materials available for study.

• 한국발생생물학회지:발생과생식
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• 제14권2호
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• pp.123-129
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• 2010

배아 줄기세포는 미분화상태에서 자가 재생을 유지할 수 있다. 자가 재생은 OCT4, SOX2와 NANOG와 같은 많은 인자들이 작용한다. 생쥐 배아 줄기세포에서 OCT4와 SOX2가 Nanog 프로모터에 결합하여 Nanog 유전자의 발현을 촉진한다는 사실은 생쥐 promoter에 관한 정밀분석으로 알려져 있다. 본 연구에서는 인간 Nanog promoter를 정밀 분석하기 위해 연속적인 결손 돌연변이를 가진 promoter-reporter construct를 제조하였다. Promoter의 최대 활성은 0.6 kb(-253/+365) promoter-reporter construct에서 발견되었으며, 이 construct에는 OCT4 및 SOX2의 결합부위가 포함된다. OCT4와 SOX2의 기여도를 확인하기 위하여 OCT4 및 SOX2의 결합부위에 자리 특이적 돌연변이를 유도하고 promoter 활성에 미치는 영향을 조사한 결과, OCT4나 SOX2 어느 한 군데라도 돌연변이가 존재하면 promoter 활성이 현저히 저해되었다. 본 연구 결과를 통해 인간 Nanog 유전자 발현에 있어 OCT4 및 SOX2가 필수적임을 직접적으로 확인할 수 있었다.

• 대한두경부종양학회지
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• 제16권2호
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• pp.228-234
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• 2000

Objectives: Esthesioneuroblastoma is a rare malignant neoplasm that originates from the olfactory sensory cells. This tumor grows from the upper nasal cavity and ethmoid sinus and invades surrounding structures through the cribriform plate into intracranium or orbit in advanced stage. Even though there has been some controversies in determining standard treatment due to rarity of this tumor, the combination treatment of surgery and adjuvant radiation has been recommended for the locally advanced esthesioneuroblastomas. However, the recent clinical experiences of advanced cases showed that combination chemotherapy is highly effective to reduce tumor mass and improve clinical outcomes. Materials and Methods: The authors conducted a retrospective analysis of 6 esthesioneuroblastoma patients who were treated in our hospital from 1986. Results: The age of these patients was between 19 and 86 year-old. Among the 6 cases, 2 were diagnosed at stage B and 4 at stage C, according to Kadish classification. Anti-tumor treatments were performed in 5 patients. One patient refused active treatment and was lost to follow-up. Better survival outcome were observed in 3 patients who were treated with combination chemotherapy alone or combined modality treatment including chemotherapy. Conclusion: Based on our retrospective study, the combined treatment consisting of surgery, radiotherapy, and combination chemotherapy should be used to improve treatment results. And furthermore, innovative clinical approaches such as neoadjuvant chemotherapy, high-dose chemotherapy and autologous peripheral stem cell transplantation, which have been reported to have good therapeutic results, should be considered and applied actively.

• 보험의학회지
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• 제25권
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• pp.49-62
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• 2006

생명공학의 시대로 일컬어 지고 있는 오늘날, 재생의학 분야에서는 난치성 질환 치료를 목적으로 활발한 연구가 진행되고 있다. 특히, 줄기세포를 이용한 세포 대체치료 관련 연구는 최근 국내 황우석 박사의 체세포 핵이식 배아세포주 확립에 이르기 까지 괄목할 만한 발전을 보여 주고 있다. 이와 관련해 생명보험산업에 적잖은 파장이 예상되며, 생명보험사 내부적으로 기존에 판매된 상품의 사차손 관리와 함께 급속도로 발전하는 줄기세포 연구에 직접적으로 대응하는 상품개발, 언더라이팅, 지급 심사 등 보험사 내외에서의 전방위적인 변화가 필요하다는 문제 제기가 있다. 줄기세포란 조직 분화 과정에서 볼 수 있는 세포이며 근육 뼈 뇌 피부 등 신체의 어떤 기관으로도 전환할 수 있는 만능세포로서, 간 폐 심장 등 구체적 장기를 형성하기 이전에 분화를 멈출 배아 단계의 세포를 말한다. 한편, 성체줄기세포는 조직이나 기관의 분화된 세포들 사이에서 발견되는 미분화 세포로써, 자기 스스로 증식할 수 있으며, 조직이나 기관의 특수한 기능을 가지고 있는 세포로 분화할 수 있는 능력을 가진 신체줄기세포를 말한다. 배아줄기세포와 생체줄기세포를 통한 장기이식 등 난치병 정복은 윤리적, 사회적으로 많은 논란이 예상되며, 기술적으로도 해결해야 할 문제점들이 산적해 있기 때문에 아직은 요원한 것이 사실이다. 현재 유럽 대부분의 나라와 미국에서는 인간 배아의 복제가 금지되어 있으며, 일본 정부는 연구용 배아 복제를 제한적으로 허용하고 있다. 하지만, 우리 나라의 경우 2005년 1월에 '생명윤리 및 안전에 관한 법'이 발효되었지만 정부는 관련 부작용에 대한 깊은 고찰 없이 전폭적인 지원들 약속하고 있는 실정이다. 줄기세포 연구의 발달로 인해 인류가 난치병 치료의 첫 장을 열었다고 하더라도 그 영향이 당장 보험사에 미친다고 할 수는 없다. 왜냐하면 앞으로 이러한 신기술이 실제 의료행위에 적용되기 위해서는 여러 단계의 안정화 작업과 임상시험이 필요한데 이러한 작업이 기술적으로 어렵고 그 시간도 만만치 않게 걸리기 때문이다. 또한, 보험사의 보장은 크게 사망/수술/입원/암/기타보장으로 구별할 수 있는데, 줄기세포 연구의 발달과 관련이 있는 보장이 제한되어 있어 보험사에 미치는 영향이 당장 우려할 만한 수준이라 할 수 없다. 하지만 만약 치료용 줄기세포 배양으로 인한 장기 기관의 이식이나 손상세포의 대체 등과 같은 의학신기술의 예상 외로 급격하게 발전한다면 보험사의 Risk 관리에 상당한 저해요인으로 작용할 것으로 판단된다. 특히 진단 입원 수술로 대표되는 생존보장에 대한 사차 Risk 및 사차손의 급증이나 역선택 증가는 보험사의 경영수지 악화를 유발하여 보험산업 전반에 위험으로 작용할 수도 있다. 따라서, 장기적인 안목으로 업계 공동의 대응이 필요하고, 각 사에서도 상품개발, 언더라이팅, 지급심사 간의 긴밀한 협조가 요구된다. 생명보험산업의 Risk 관리는 기존의 시장환경에 영향을 받는 비차, 이차중심에서 보험회사가 어느 정도 관리를 통해 적정규모를 유지할 수 있는 사차로 그 중심축이 이동하고 있다. 보험산업이 계속 활력을 갖고 성장하기 위해서는 체계적인 Risk나 관리가 핵심일 것이며, 보험사의 사차 Risk의 중요성이 더욱 커져 가고 있는 현실에서 거시적으로 의학신기술 발달 등 위험요인에 대해 미리 분석하고 이에 대한 대비책 마련이 필요할 것으로 판단된다.

• The Korean Journal of Physiology and Pharmacology
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• 제16권4호
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• pp.273-279
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• 2012

Busulfan is an antineoplastic agent with a narrow therapeutic window. A post-hoc population pharmacokinetic analysis of a prospective randomized trial for comparison of four-times daily versus once-daily intravenous busulfan was carried out to search for predictive factors of intravenous busulfan (iBu) pharmacokinetics (PK). In this study the population PK of iBu was characterized to provide suitable dosing recommendations. Patients were randomized to receive iBu, either as 0.8 mg/kg every 6 h or 3.2 mg/kg daily over 4 days prior to hematopoietic stem cell transplantation. In total, 295 busulfan concentrations were analyzed with NONMEM. Actual body weight and sex were significant covariates affecting the PK of iBu. Sixty patients were included in the study (all Korean; 23 women, 37 men; mean [SD] age, 36.5 [10.9] years; weight, 66.5 [11.3] kg). Population estimates for a typical patient weighing 65 kg were: clearance (CL) 7.6 l/h and volume of distribution (Vd) 32.2 l for men and 29.1 L for women. Inter-individual random variabilities of CL and $V_d$ were 16% and 9%. Based on a CL estimate from the final PK model, a simple dosage scheme to achieve the target $AUC_{0-inf}$ (defined as median AUC0-inf with a once-daily dosage) of 26.18 $mg/l{\cdot}hr$, was proposed: $24.79{\cdot}ABW^{0.5}mg$ q24h, where ABW represents the actual body weight in kilograms. The dosing scheme reduced the unexplained interindividual variabilities of CL and Vd of iBu with ABW being a significant covariate affecting clearance of iBU. We propose a new simple dosing scheme for iBu based only on ABW.

• Journal of Korean Neurosurgical Society
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• 제29권10호
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• pp.1289-1295
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• 2000

Purpose : Recent evidence suggests a possible role for leukocytes in brain injury following ischemia and reperfusion. This study examined the temporal profile of ischemic tissue damage and leukocyte response after transient middle cerebral artery occlusion(MCAO) with reperfusion in the mouse. Methods : Focal cerebral ischemia was made by temporary occluding of the stem of the proximal MCA. Two groups of the mouse were investigated : (1) sham operation(n＝10), and (2)those having the arterial occlusion released after 90 minute(n＝20). By 4 hours(n＝10) and 24 hours(n＝10) after the onset of ischemia-reperfusion, fluorescein videoimages were under-taken in the pial venules of the mouse using a closed cranial window technique. Rhodamine 6G was administered as a $80-100{\mu}l/min$ i.v. loading dose and a $30-40{\mu}l/min$ i.v. maintenance dose in saline to selectively label circulating leukocytes. Neuropathologic evaluation for brain injury was accomplished using the histochemical stain 2,3,5-triphen-yltetrazolium chloride(TTC) and hematoxylin and eosin(H & E) stain. Results : The mean number of adherent leukocytes to cerebral venules in the 90 minutes MCAO and 24 hours reperfusion group were $306{\pm}24$ compared with $72{\pm}8$ in the sham operation group. In the TTC staining method, the cortical infarct affecting 34.8% of hemispheric volume were created in all of animals (n＝10) undergoing 90 minute MCAO with 24 hours reperfusion, but the infarcted area were not found in the other(sham operation and 90 minute MCAO with 4 hours reperfusion)groups. In the H & E stain, the brain tissue following 90 minute MCAO with 4 hours reperfusion revealed only a pyknosis of the nuclei with shrunken cytoplasm, but infiltrated leukocytes were not observed. After 24 hours of reperfusion, a many leukocytes were infiltrated within parenchyma and blood vessles. Conclusions : These findings demonstrate the feasiblity of continous in vivo monitoring of leukocyte adherence in cerebral venules and suggest that reperfusion induced leukocyte adherence to venular endothelium may contribute to tissue injury following focal cerebral ischemia.

• 한국약용작물학회지
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• 제28권1호
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• pp.1-8
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• 2020

Background: This study was conducted to investigate the effects of NaCl concentration on the photosynthetic parameters, chlorophyll fluorescence and growth characteristics of Crepidiastrum sonchifolium. Methods and Results: As treatments, we subjected C. sonchifolium plants to four different concentrations of NaCl (0, 50, 100 and 200 mM). We found that the photosynthetic parameters maximum photosynthesis rate (P_{N max}), net apparent quantum yield (Φ), maximum carboxylation rate (V_cmax), and maximum electron transport rate (J_max) were significantly reduced at an NaCl concentration greater than 100 mM. In contrast, there was an increase in water-use efficiency with increasing NaCl concentration, although in terms of growth performances, leaf dry weight, root dry weight, stem length, and total dry weight all decreased with increasing NaCl concentration. Furthermore, leakage of electrolytes, as a consequence of cell membrane damage, clearly increased in response to an increase in NaCl concentration. Analysis of the polyphasic elevation of chlorophyll a fluorescence transients (OKJIP) revealed marked decrease in flux ratios (Φ_PO, Ψ_O and Φ_EO) and the PI_abs, performance index in response to treatment with 200 mM NaCl, thereby reflectings the relatively reduced state of photosystem II. This increase in fluorescence could be due to a reduction in electron transport beyond Q^-_A. We thus found that the photosynthetic parameters, chlorophyll fluorescence and growth characteristics of C. sonchifolium significantly increased in response to treatment with 200 mM NaCl. Conclusions: Collectively, the findings of this study indicate that C. sonchifolium shows relatively low sensitivity to NaCl stress, although photosynthetic activity was markedly reduced in plants exposed to 200 mM NaCl.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.443-449
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• 2015

Background: Myeloproliferative disorders (MPDs) are clonal hematologic malignancies originating at the level of the pluripotent hematopoietic stem cell. Matrix metalloproteases (MMPs) are proteolytic enzymes that contribute to all stages of malignancy progression. Genetic variants in the MMP genes may influence the biological function of these enzymes and change their role in carcinogenesis and progression. To our knowledge, this is the first investigation of associations between the -735 C/T and -1562 C/T polymorphisms in the MMP2 and MMP9 genes, respectively, and the risk of essential thrombocytosis (ET), and polycythemia vera (PV). Materials and Methods: The case-control study included JAK2V617F mutation positive 102 ET and PV patients and 111 controls. Polymorphisms were determined by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and electrophoresis. Results: No statistically significant differences were detected between patient (ET+PV) and control groups regarding genotype distribution for MMP2 gene-735 C/T and MMP9 gene -1562 C/T polymorphisms and C/T allele frequency (p>0.050). Statistically borderline significance was observed between PV and control groups regarding genotype distribution for the MMP9 gene -1562 C/T polymorphism (p=0.050, OR=2.26, 95%Cl=0.99-5.16). Conclusions: Consequently this study supported that CC genotype of MMP9 gene -1562 C/T polymorphism may be related with PV even if with borderline significance.