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기관지 천식 환자에서 천식 증상의 정도에 따른 $\beta_2$ 교감신경 수용체의 유전자 다형성
심재정,김제형,이승룡,권영환,이소라,이상엽,강세용,강용구,조재연,인광호,원남희,유세화,강경호,Shim, Jae-Jeong,Kim, Jei-Hyung,Lee, Seung-Yong,Kwan, Young-Hwan,Lee, So-Ra,Lee, Sang-Youb,Kang, Se-Yong,Kang, Yong-Koo,Cho, Jae-Youn,In, Kwang-Ho,Wo 대한결핵및호흡기학회 1998 Tuberculosis and Respiratory Diseases Vol.45 No.1
서 론: $\beta_2$ 교감신경 수용체 유전자에는 여러 종류의 다형성(polymorphism)가 존재하며, 천식 환자에서 $\beta_2$ 교감신경 수용체의 대표적인 변이는 $\beta_2$ 교감신경 수용체의 아미노산이 대치된 부분으로 Arg16-Gly, Gln27-Glu, Val34-Met 및 Thr164-Ile 등인 것으로 알려져 있다. 지속적인 $\beta_2$ 교감신경 유도체의 자극에 대하여 세포표면으로 부터 세포내의 전달과정이 둔화되어 점차 세포전달이 없어질 수도 있는 desensitization 또는 수용체와 수가 감소하는 downregulation이 존재하는 것으로 알려져 있다. 천식환자에서 $\beta_2$ 교감신경 수용체의 desensitization 또는 downregulation 뿐만 아니라 천식 표현형과 $\beta_2$ 교감신경 수용체 유전자 다형성의 상관 관계에 대한 연구가 이루어지고 있으나 논란이 많다. 이에 본 연구는 기관지 천식환자에서 $\beta_2$ 교감신경 수용체의 가장 흔한 16, 27, 34 및 164 의 아미노산에 해당하는 유전자의 다형성을 MASA (Mutated Allele Specific Amplification)법으로 시행하여 각각의 다형성의 발생 빈도와 천식의 심한 정도와 연관이 있는 가를 확인하였다. 대상 및 방법: 대상 환자는 천식 환자 103명이었으며, 이중 남자는 54명, 여자는 49명으로 평균 연령은 46.6세 (19~80세)였고 이환 기간은 4.7년이었다. 대상 환자는 경미하고 간헐적 증상을 보인 30명, 지속적인 경미한 천식 환자는 32명으로 경미한 천식은 모두 62명이었으며, 중등증의 천식 증상은 17명 및 중종의 천식증상을 보인 환자는 24명이었다. 이중 1년 중에 6개월 이상 전신적 스테로이드를 투여하는 환자는 39명이었으며, 투약 중에도 야간 발작이나 야간 기침이 발생되었던 환자는 44명이었다. 대상 환자로부터 10cc의 전혈구를 체취 하여 분리된 림파구에서 분리된 DNA를 이용하여 MASA 방법으로 $\beta_2$ 교감신경 수용체 16번, 27번, 34번 및 164번째 아미노산의 다형성을 검색하였고, 천식의 심한 정도 따른 $\beta_2$ 교감신경 수용체 유전자의 다형성의 분포와 야간 천식의 발작이나 증상의 유무에 따른 $\beta_2$ 교감신경 수용체 유전자의 다형성의 분포를 확인하였다. 결 과: 16 번째 Arginine이 Glycine으로 변이는 heterozygous 변이가 67명, homozygous 변이가 13명으로 heterozygous 변이가 65.1%로 가장 많았다. 27번째 Glutamine이 Glutamate로 변이는 heterozygous만 11명으로 10.7%였으며, 34번째 Valine이 Methionine으로 변이를 일으키는 100번째 핵산의 경우도 heterozygous만 6명으로 5.8%였다. 27 번째와 34번째 아미노산의 변이를 일으키는 homozygous 변이와 164번째 아미노산의 변이는 대상 환자 중에는 없었다. 천식 증상의 심한 정도를 경종 및 중등증, 중중으로 2 구분하여 $\beta_2$ 교감신경 수용체 다형성의 발생빈도를 관찰한 결과 중증의 천식환자에서 16번째 아미노산의 변이의 빈도는 많았으나 (p=0.015), 27번, 34번 및 164번째의 아미노산의 변이는 천식 증상의 정도와는 연관성이 없었다. 야간 천식 증상의 유무에 따른 $\beta_2$ 교감신경 수용체 다형성은 16, 27, 34 및 164번째 아미노산의 핵산의 변이와 연관성이 없었다. 결 론: 이상의 결과로 기관지 천식 환자에서 $\beta_2$ 교감신경 수용체 다형성은 Arg 16, Gln 27 및 Val 34의 변이가 존재하고, Arg 16이 가장 많았으며, Thr 164는 없었다. 기관지 천식 환자에서 증상이 심한 중증 천식은 $\beta_2$ 교감 신경 수용체의 다형성중 Arg 16의 변이는 중증 천 Background: Genetic and environmental factors are known to affect the incidence and severity of asthma. Stimulation of $\beta_2$-Adrenergic Receptor ($\beta_2$AR) results in smooth muscle relaxation, leading to decrease in resistance of airflow. The gene encoding the $\beta_2$AR has recently been seguenced. The $\beta_2$AR genotype at the polymorphic loci of codons 16, 27, 34, and 164 was known to cause changes in the amino acids. The relationships between the structure of the $\beta_2$AR and its functions are being elucidated. Purpose : The gene encoding the $\beta_2$AR was carried out to assess the frequency of polymorphisms in bronchial asthma, to determine wheather these polymorphisms have any relation to the severity, or nocturnal symptoms in bronchial asthma. Methods: The subjects studied were 103 patients with bronchial asthma, which consisted of 30 mild episodic, 32 mild persistent, 17 moderate, and 24 severe asthma patients. The polymorphisms of the $\beta_2$AR gene were detected by mutated allele specific amplification (MASA) method at the codons 16,27,34, and 164. Results: The most frequent polymorphism was arginine 16 to glycine. The other two polymorphisms, valine 34 to methionine and glutamine 27 to glutamic acid occured in 11 and 6 patients respectively. The polymorphism of threonine 164 to isoleucine was not found in our enrolled patients. The homozygous polymorphism of $\beta_2$AR gene was found in only arginine 16 to glycine (12.6%). The heterozygous polymorphisms of $\beta_2$AR gene were in arginine 16 to glycine, valine 34 to methionine, and glutamine 27 to glutamic acid, as 65.1 %,10.7%, and 5.8% respectively in asthma patients. The presence of agrginine 16 to glycine heterozygous or/and homozygous polymorphism was associated in severe asthma (p=0.015), but there was no association between the other three polymorphisms and the severity of asthma. The frequency of the $\beta_2$AR gene polymorphisms was no relation in nocturnal asthma as compared with non-nocturnal asthma. Conclusion: The arginine 16 to glycine polymorphism of the $\beta_2$AR gene is the most frequently found in asthma patients and association with severe asthma. But there was no association between the polymorphism of the $\beta_2$AR gene and nocturnal asthma.
기관지 천식 환자에서 천식 증상의 정도에 따른 β2 교감신경 수용체의 유전자 다형성
심재정 ( Jae Jeong Shim ),김제형 ( Jei Hyung Kim ),이승룡 ( Seung Yong Lee ),권영환 ( Young Hwan Kwan ),이소라 ( So Ra Lee ),이상엽 ( Sang Youb Lee ),강세용 ( Se Yong Kang ),강용구 ( Yong Koo Kang ),조재연 ( Jae Youn Cho ),인광호 대한결핵 및 호흡기학회 1998 Tuberculosis and Respiratory Diseases Vol.45 No.1
이민수 ( Min Su Lee ),박형서 ( Hyeong Seo Park ),박재형 ( Jae Hyeong Park ),이재환 ( Jae Hwan Lee ),최시완 ( Si Wan Choi ),정진옥 ( Jin Ok Jeong ),구본정 ( Bon Jeong Ku ),김대현 ( Dae Hyun Kim ),김제 ( Jei Kim ),이태용 ( Tae Yong 한국지질동맥경화학회(구 한국지질학회) 2006 韓國脂質學會誌 Vol.16 No.2
Objective: Increased serum ferritin concentration can be associated with elevated oxidative stress and the development of arteriosclerosis. We evaluated the relationship between increased ferritin level and arterial stiffness in a normal population without known coronary and cerebrovascular diseases. Methods: We evaluated a total of 995 subjects (578 females; mean age: 58±8 years). After excluding subjects with known cardiovascular and cerebrovascular disease, we analyzed data from 949 subjects. Risk factors of coronary arterial disease (CAD), serum cholesterol profiles, high-sensitive C-reactive protein, fasting blood sugar (FBS) level, and ferritin concentrations were recorded. Arterial stiffness was assessed by brachial to ankle pulse-wave velocity (baPWV). Results: A univariate analysis revealed the following: baPWV was correlated with conventional clinical variables, including age (R=0.389, P<0.001), sex (R=0.099, P=0.002), blood pressure (systolic (R=0.614, P<0.001), diastolic (R=0.417, P<0.001)), triglyceride concentration (R=0.151, P<0.001), and FBS level (R=0.184, P<0.001). The baPWV was also correlated with the 10-year cardiovascular risk score (R=0.419, P<0.001) and serum ferritin concentration (R=0.184, P<0.001). The multivariate analysis demonstrated that baPWV was significantly correlated with serum ferritin concentration; this was similar to other cardiovascular risk factors, including age, blood pressure, smoking, and FBS concentration. Conclusion: Elevated serum ferritin concentration was associated with increased arterial stiffness in subjects without known coronary and cerebrovascular diseases; this may contribute to increased cardiovascular risk.
김제,이애영,정진상,김재문 충남대학교 의과대학 지역사회의학연구소 1996 충남의대잡지 Vol.23 No.2
Seizures in the geriatric population are uncommon. They are more commonly associated with underlying brain lesions than seizures of other generations. We investigated type and cause in 44 patients, who experienced seizures firstly over 60 years old during last 6 years. Intracranial lesions on CT and/or MRI were also in vestigated in each type of seizure. Generalized tonic-clonic seizure was more common seizure type (26 patients, 59%) than focal seizures (18, 41%). The causes of seizures were detectable in 77% of patients. Previous stroke was the most frequent cause of seizures (18 of 44 patients, 41%), particularly in thrombotic infarcts (14 patients). Brain tumors (primary 3; metastatic 2), previous trauma history (2), alcohol withdrawal (4), neurocysticercosis (1), and viral meningoencephalitis (2) were followed. In 10 patients (23%). no causative factor was identified. Brain lesions were visualized in 72% of focal-onset seizures and in 42% of generalized seizures on CTs and/or MRIs. We concluded that generalized tonic-clonic type is common type of seizure and causes of seizures were frequently detected in first onset seizure patients over 60 years old.
중뇌동맥경색에서 조기 혈행역학적 변화와 예후와의 관계: 예비연구
김제,김종홍,이훈복,송희정,이애영,김재문 충남대학교 의과대학 지역사회의학연구소 1997 충남의대잡지 Vol.24 No.1
We evaluate transcranial Doppler findings and clinical features of middle cerebral artery (MCA) infarction patients to correlate early hemodynamic changes with clinical outcomes in the patients. We included 7 patients who were clinically diagnosed as MCA infarction. TCD was performed within 48 hours from onset of Symptoms. Clinical outcomes were divided into 1) good, 2) fair, 3) poor, and 4) bad. The TCD findings were correlated with the clinical outcomes. CT and MRI findings were reviewed to observe the intraparenchymal lesion in each patient. TCD findings could be classified into three groups: 1) normal or increased mean blood flow velocity (MBFV) in MCA of the lesion side (n=2), 2) decreased MBFV in the lesion side with increased BFV in the opposite in neighboring vessels (n=2), 3) no dectected BFV on MCA of lesion side without increased BFV on neighboring vessels (n=3). Good or fair outcomes were shown in group 1 and 2 patients, except a patient with chronic renal failure. Subcortical involvements were detected in most of patients in these groups. In group 3, poor or bad clinical outcomes were observed and parenchymal involvements were more extensive in subcortical and cortical area than in group 1 and 2. Early evaluation of hemodynamic changes may provide as a simple tool to predict the prognosis of the MCA infarction.