• Journal of Preventive Medicine and Public Health
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• 제38권3호
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• pp.345-350
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• 2005

Objectives : Polycyclic aromatic hydrocarbons (PAHs), which are risk factors for lung cancer, have been reported to induce oxidative DNA damage. The paraoxonase (PON) plays a significant role in the detoxification of a variety of organophosphorous compounds, with paraoxonase-1 (PON1) being one of the endogenous free-radical scavenging systems in the human body. The aim of this case-control study was to investigate the effects of PAH exposure, oxidative stress and the Q192R polymorphism of PON1 genes, and their interactions in the carcinogenesis of lung cancer. Methods : One hundred and seventy seven lung cancer patients and 177 age- and sex-matched controls were enrolled in this study. Each subject was asked to complete a questionnaire concerning their smoking habits and environmental exposure to PAHs. The Q192R genotypes of the PON1 gene was examined, and the concentrations of urinary 1-hydroxypyrene (1-OHP), 2-naphthol and 8-hydroxydeoxyguanosine (8-OH-dG) measured. Results : Cigarette smoking was found to be a significant risk factor for lung cancer. The urinary 8-OH-dG level was higher in the patients, whereas the urinary 1-OHP and 2-naphthol levels were higher in the controls. There was a significant correlation between the urinary levels of 8-OHdG and 1-OHP in both the cases and controls. The PON1 polymorphism was associated with an increased risk of lung cancer. Individuals carrying the Q/Q genotype of the PON1 gene were found to be at higher risk of developing lung cancer. There was a significant correlation between the urinary levels of 8-OH-dG and 1-OHP in those with the PON1 Q/Q genotype. Conclusions : These results lead to the conclusion that PAHs would induce oxidative DNA damage, especially in individuals with the PON1 Q/Q genotype. Therefore, people with the PON1 Q/Q genotype would be more susceptible to lung cancer than those with the R/R or Q/R genotypes of the PON1 gene.

• 한국가축번식학회지
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• 제20권4호
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• pp.379-384
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• 1997

외인성 성선자극 호르몬에 의한 과배란처리는 난모세포의 질, 수정, 배발달, 착상, 임신유지 등에 해로운 영향을 수반하는 광범위한 배란전후의 호르몬 분비이상을 야기한다. 최근 본 연구에서 흰쥐에서의 IGF-1이 착상전 및 자궁의 환경적 조절에 미치는 잠재적 역할을 확인하였다. 그 결과는 IGF-1이 아마도 탈락막의 조절과 배발달에 적합한 자궁환경유지에 중요한 역할을 수행한다는 것을 보여주었다. 과배란후 배의 손실과 착상의 실패는, 본 연구에서 관찰되었듯이 부분적인 자궁내 IGF-1의 작용저해에 기인하리라 사료된다. 또한 본 연구진들은 생쥐의 배에서 염색체 이상빈도에 대한 과배란을 유도하는 성선자극 호르몬의 영향에 대한 연구를 수행하였다. PMSG 5, 10 및 15 I.U.를 투여하여 과배란된 생쥐에서 생쥐의 수정란과 8-16 세포기 배의 염색체 분석을 실시하였다. 이수체(aneuploidy), 다배체(polyploidy) 또한 염색체의 구조적 이상은 4개군에서 관찰되었따. 그러나 다배체만이 과배란과 상관관계가 있엇따. PMSG 10, 15 I.U. 처리군에서 다배체 발생율은 각각 2.9%와 10.5%였다. 더욱이 PMSG 용량에 따른 배의 다배체 발생빈도 사이에는 투여량에 따른 상관관계가 확인되었다(P<0.0001). 과배란과 성선자극호르몬은 양의 상관관계가 있었으며 염색체와 과배란의 정도에는 투여량에 따른 상관관계가 있었다. 과배란된 난모세포의 발달 잠재력은 모축의 내분비적 환경뿐만 아니라 생존에 필요한 내인성 요인들 즉 유전적 상태 그리고 난자의 전체적 성숙등에 연관되어 있다고 사료된다.

• 생명과학회지
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• 제16권3호
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• pp.454-458
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• 2006

출아효모인 Sacharomyces cerevisiae S288C균주를 이용한 효모의 게놈이 완성된 후 S. cerevisiae는 다양한 연구 모델로 이용되어져 왔다. 현재까지 효모를 이용한 기능 유전체학 측면에서의 연구는 laboratory strainin인 S288C 균주 또는 그 유래의 균주들이다. 그러나 자연에서 분리된 효모 또는 산업적으로 이용되어지고 있는 S. cerevisiae의 유전학 측면에서의 연구는 낮은 포자형성률 및 형질전환률, 그리고 S288C 균주와의 게놈상의 상이성 때문에 거의 이루어지지 않고 있다. 여기서 우리 연구진은 자연에서 분리된 Saccharomyces cerevisiae KNU5377 균주를 이용하여 random spore analysis를 통해 MATa 및 $MAT{\alpha}$ 타입의 각각의 haploid cell을 분리 후 이미 보고된 KanMX module를 가지고 round PCR기법에 의한 short flanking homology 기법을 이용하여 전사조절인자인 HSF1 유전자가 치환된 변이주를 구축할 수 있었다. 덧붙여, 모든 유전자에 이 기법을 적용할 수는 없다는 것을 확인하였다. 앞으로 이 변이주를 통해 기능 유전체학적인 측면에서 이 유전자의 스트레스와의 관련성을 연구하고자 한다.

• International Journal of Oral Biology
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• 제32권3호
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• pp.85-91
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• 2007

Dlx3 is a homeodomain protein and is known to playa role in development and differentiation of many tissues. Deletion of four base pairs in DLX3 (NT3198) is causally related to tricho-dento-osseous (TDO) syndrome (OMIM # 190320), a genetic disorder manifested by taurodontism, hair abnormalities, and increased bone density in the cranium. Although the observed defects of TDO syndrome involves bone, little is known about the role of Dlx3 in bone remodeling process. In this study, we examined the effect of wild type DLX3 (wtDlx3) expression on osteoclast differentiation and compared it with that of 4-BP DEL DLX3 (TDO mtDlx3). To examine whether Dlx3 is expressed during RANKL-induced osteoclast differentiation, RAW264.7 cells were cultured in the presence of receptor activator of nuclear factor-B ligand (RANKL). Dlx3 protein level increased slightly after RANKL treatment for 1 day and peaked when the fusion of prefusion osteoclasts actively progressed. When wtDlx3 and TDO mtDlx3 were overexpressed in RAW264.7 cells, they enhanced RANKL-induced osteoclastogenesis and the expression of osteoclast differentiation marker genes such as calcitonin receptor, vitronectin receptor and cathepsin K. Since osteoclast differentiation is critically regulated by the balance between RANKL and osteoprotegerin (OPG), we examined the effect of Dlx3 overexpression on expression of RANKL and OPG in C2C12 cells in the presence of bone morphogenetic protein 2. Overexpression of wtDlx3 enhanced RANKL mRNA expression while slightly suppressed OPG expression. However, TDO mtDlx3 did not exert significant effects. This result suggests that inability of TDO mtDlx3 to regulate expression of RANKL and OPG may contribute to increased bone density in TDO syndrome patients. Taken together, it is suggested that Dlx3 playa role as a positive regulator of osteoclast differentiation via up-regulation of osteoclast differentiation-associated genes in osteoclasts, as well as via increasing the ratio of RANKL to OPG in osteoblastic cells.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제36권6호
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• pp.460-465
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• 2010

Introduction: A cleft palate is a common birth defect in humans with an incidence of 1/500 to 1/1,000 births. It appears to be caused by multiple genetic and environmental factors during palatogenesis. Many molecules are involved in palate formation but the biological mechanisms underlying the normal palate formation and cleft palate are unclear. Accumulating evidence suggests that transforming growth factor $\beta$/bone morphogenetic proteins (TGF-$\beta$/BMP) family members mediate the epithelial-mesenchymal interactions during palate formation. However, their roles in palatal morphogenesis are not completely understood. Materials and Methods: To understand the roles of TGF-$\beta$/BMP signaling in vivo during palatogenesis, mice with a palatal mesenchyme- specific deletion of Smad4, a key intracellular mediator of TGF-$\beta$/BMP signaling, were generated and analyzed using the Osr2Ires-Cre mice. Results: The mutant mice were alive at the time of birth with open eyelids and complete cleft palate but died within 24 hours after birth. In skeletal preparation, the horizontal processes of the palatine bones in mutants were not formed and resulted in a complete cleft palate. At E13.5, the palatal shelves of the mutants were growing as normally as those of theirwild type littermates. However, the palatal shelves of the mutants were not elevated at E14.5 in contrast to the elevated palatal shelves of the wild type mice. At E15.5, the palatal shelves of the mutants were elevated over the tongue but did not come in contact with each other, resulting in a cleft palate. Conclusion: These results suggest that mesenchymal Smad4 mediated signaling is essential for the growth of palatal processes and suggests that TGF-$\beta$/BMP family members are essential regulators during palate development.

• Tuberculosis and Respiratory Diseases
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• 제76권5호
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• pp.226-232
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• 2014

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and results from environmental factors and genetic factors. Although cigarette smoking is a major risk factor, other environmental exposures can influence COPD. The purpose of this study is to investigate the clinical characteristics of COPD according to the history of environmental exposure. Methods: The study population comprised of 347 subjects with COPD who were recruited from the pulmonary clinics of 14 hospitals within the Korean Obstructive Lung Disease Study Group. We classified environmental exposures according to history of living near factory, and direct exposure history to firewood or briquette. According to living environmental exposures, we compared the frequency of respiratory symptoms, pulmonary function, quality of life, exercise capacity, and computed tomography phenotypes. Results: Thirty-one subjects (8.9%) had history of living near factory, 271 (78.3%) had exposure history to briquette, and 184 (53.3%) had exposure history to firewood. Patients with history of living near a factory had a significantly longer duration of sputum, while patients with exposure to firewood tended to have lower forced expiratory volume in one second, and patients with exposure to briquette tended to have lower six minute walk distance. Conclusion: COPD subjects with the history of living near factory had more frequent respiratory symptoms such as sputum. Our data suggest that environmental exposure may influence clinical phenotype of COPD.

• 동의생리병리학회지
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• 제18권4호
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• pp.1192-1198
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• 2004

Sasang Constitutional Medicine is a major branch of Korean Traditional Medicine. The differences of disease susceptibility to be shown in Sasang constitution may be due to genetic factors. Therefore, I examined interrelationship among cerebral infarction (CI), apolipoprotein E (apo E) gene polymorphism, and Sasang constitutional classification. Apo E is a key protein modulating the highly atherogenic apoB containing lipoproteins and is a candidate gene for the development of coronary artery disease (CAD). The ε2 and/or ε4 alleles were the first to be implicated in premature CAD, which resulted in this polymorphism being extensively studied. I investigated the association between apo E genotype and CI by case-control study in a Korean population. I also classified CI patients and control group into groups according to Sasang Constitutional Medicine. 218 CI patients and 379 controls without CI were examined. Apo E genotype was determined by 8% polyacrylamide gel separation after DNA amplification. A frequency of apo E ε3/ε3 in the apo E genotype distribution was higher in the CI patients compared with that in controls. Also, it was widely known that Taeumin was easily attacked with CI, but there was no association between apo E polymorphim and Taeumin. However, the Taeumin constitution did not enhance the relative risk for CI in the subjects with apo E ε2 and/or ε4 alleles. No differences in the apo E genotypes frequencies were observed in the Taeumin compared with that in the other constitutions. In addition, I investigated whether the DD(deletion/deletion) or ID(insertion/deletion) genotype of angiotensin converting enzyme (ACE) gene, a candidate gene for CI, was associated with CI, Taeumin constitution, and apo E polymorphism. As a result, the frequency of Taeumin constitution was significantly higher in CI patients with both apo E ε3/ε4 and ACE ID/DD genotypes than in the remaining Sasang constitutions. In summary, it was concluded that the apo E polymorphism is a major risk factor for CI in Koreans and the ACE ID/DD genotype enhanced the relative risk for CI in the subjects with apo E ε3/ε4 genotype and Taeumin constitution.

• KSBB Journal
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• 제24권6호
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• pp.591-597
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• 2009

심장이상증상의 상태에서 분비되는 심장혈관호르몬인 BNP의 혈중 농도측정은 심장기능부전환자의 진단에 유용하게 이용 되고 있다. 혈청 또는 혈장에서의 BNP 농도측정은 샌드위치형태의 면역학적 검정법을 이용할 수 있으며, 이때에 항 BNP 항체를 BNP 탐지 인자로 사용할 수 있다. 특히, 탐지 인자로의 사용을 위해서는 항원항체 반응부분을 링커로 연결하여 전체 항체에 비해서 경제적이며 효율 면에서도 뛰어난 scFv의 사용이 용이하다고 판단하였고, 이에 scFv의 취약점인 대장균에서의 불용성 형태의 발현을 최소화 시키고 기능적 발현을 극대화하여 심장질환 진단용 센서의 센서 칩 항체로 사용할 수 있도록 항 BNP scFv 항체의 발현을 대장균 세포질 내에서 유도 하였다. 대장균 세포질내에서의 scFv 제작을 위하여 항 BNP scFv 항체 유전자를 pColdⅣ 벡터와 pET22b (+)벡터에 각각 클로닝한 후 발현 하였으며, 그 결과 대량 생산의 장점이 있는 강력한 T7 promoter를 지닌 pET22b (+) 벡터를 이용하여 낮은 온도에서 단백질의 발현을 느리게 유도할 때 적절한 단백질 접힘 현상이 일어나 기능적인 scFv의 발현이 극대화됨을 확인하였다. 또한 IPTG의 투여에 있어서 그 농도가 높아지면 빠른 단백질 유전자의 전사를 도와 발현율이 증가하지만 과도한 농도의 IPTG 투여는 세포내의 독성을 일으켜 단백질의 생산을 저해할 수 있다는 결론에 도달하였으며, 연구를 통하여 개발한 항 BNP scFv 항체가 오직 BNP 항원과의 결합특이성을 가진다는 사실도 확인 가능 하였다.

• The Korean Journal of Ecology
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• 제27권3호
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• pp.147-153
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• 2004

본 연구는 카드뮴 처리에 대한 박달나무 유묘의 가계간 생장 차이와 광합성 특성을 구명하고자 실시하였다. 카드뮴 처리는 3가계의 박달나무 1년생 묘목에 0, 0.4, 0.8mM의 CdSO4 · H2O 용액을 이용하여 3수준으로 2개월간 실시하였다. 박달나무의 가계간 및 처리간 생장과 생리적 반응은 건중량, 상대생장율, 순양자수율 및 탄소고정효율을 이용하여 결정하였다. 0.4 mM과 0.8mM 카드뮴이 처리된 박달나무 유묘는 대조구와 비교해서 건중량과 상대생장율이 크게 감소하였으며, 박달나무 유묘의 생장 감소는 광합성 능력의 감소에 큰 영향을 받은 것으로 나타났다. 또한 순양자수율과 탄소고정효율은 카드뮴 처리로 감소하였으며, 모든 가계에서 카드뮴 농도가 증가함에 따라 감소 폭이 커졌다. 한편 카드뮴 처리에 의한 생장과 광합성 반응은 박달나무 가계간 뚜렷한 차이를 보여 카드뮴 내성은 가계간 유전적 요인이 작용하고 있음을 확인하였다.

• 식물병연구
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• 제21권4호
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• pp.326-329
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• 2015

후자린산은 Fusarium이 생성하는 독소로서 다른 Fusarium 독소와 함께 독성을 증진시킬 수 있다. 후자린산 독소를 특이적으로 검출하기 위해 후자린산의 생합성유전자 중 전사인자인 FUB10을 증폭하는 프라이머를 제작하였다. Fub10-f와 Fub10-r 프라이머쌍으로 PCR을 수행했을 때, F. oxysporum, F. proliferatum, F. verticillioides, F. anthophilum, F. bulbicola, F. circinatum, F. fujikuroi, F. redolens, F. sacchari, F. subglutinans, F. thapsinum에서 약 550 bp의 단일밴드가 증폭되었으며 이들은 모두 후자린산을 생성하는 것으로 알려졌다. 반면 트라이코쎄신을 생성하는 종에서는 FUB10 특이 밴드가 증폭되지 않았다. 후자린산은 푸모니신을 생성하는 종에서 함께 생성될 수 있기 때문에 FUB10 프라이머와 푸모니신 생합성유전자인 FUM1 프라이머를 이용한 multiplex PCR을 수행하였다. 그 결과 푸모니신 생성종인 F. proliferatum과 F. verticillioides에서 밴드가 모두 증폭되었으며 이는 두 가지 독소를 생성할 수 있는 종에서 동시 검출이 가능함을 시사하였다.