한국인 갑상선 수질암 환자에서 RET 원종양유전자 점돌연변이 양상

김형훈,김현진,정윤재,민용기,이명식,이문규,김광원,기창석,김종원,정재훈 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.4

연구배경: 갑상선 수질암의 25∼30%는 유전성으로 발현되는데, MEN 2A, MEN 2B 또는 가족성 수질암의 형태로 나타난다. RET 원종양유전자의 점돌연변이가 유전성 갑상선 수질암의 발생에 중요한 역할을 하므로, 진단 당시의 연령이나 가족력 유무에 관계없이 모든 갑상선 수질암 환자나 또는 RET 변이가 발견된 수질암 환자의 가족 구성원들에서 RET 변이 검색을 하여야 한다. 또한 일부 문헌에서 RET 변이의 양상에따라 임상상이 다르게 표현됨이 보고된 바 있다. 이에 저자들은 한국인 갑상선 수질암 환자에서 RET 원종양유전자의 점돌연변이의 양성률을 알아보고, 변이 양상에 따른 임상상의 차이가 있는지를 알아보고자 본 연구를 시행하였다. 방법: 치근 7년간 본원에서 갑상선절제술을 통해 갑상선 수질암으로 진단받은 29예에서 RET 원종양유전자의 점돌연변이 검사를 시행하였다. 29예의 평균연령은 39세(20∼60세)이었고, 남자 7예, 여자 22예 이었다. 이들의 말초혈액에서 genomic DNA를 분리하고, 특이 시발차를 이용하여 RET 원종양유전자의 exon10, 11, 13, 14, 16부위를 증폭하였다. 증폭된 부위를 자동염기서열분석기를 이용하여 직접 분석하였다. 양성으로 나온 경우는 모든 가족 구성원을 대상으로 RET 변이 유무를 검색하였다. 결과: 대상 환자 29예 중 9예 (31%)에서 RET 원종양유전자 점돌연변이가 발견되었다 RET 변이가 발견된 9예 (남자 3예, 여자 6예)의 평균 연령은 33세 (20∼51세)로 RET 변이가 발견되지 않은 20예의 평균연령 42세(24∼60세)보다 의미 있게 적었다. RET 변이가 발견된 9예 중 MEN 2A가 5예, 가족성 수질암이 1예, 그리고 산발성 수질암이 3예이었고, MEN 2B는단 1예도 진단되지 않았다. MEN 2A 5예 중 4예는 exon 11의 codon 634번(C634R 2예, C634Y 2예)에서, 그리고 나머지 1예는exon 10의 codon 618번 (C618R)에서 변이가 각각 발견되었다. 가족성 수질암 1아는 codon 634번(C634W)에서, 산발성 수질암 3예도 모두 codon 634번 (C634y 2예, C634s 1예)에서 각각 변이가 발견되었다. RET변이 양상 또는 위치에 따른 임상상의 차이는 발견할 수 없었다. 결론: 갑상선 수질암 환자 31%에서 RET 원종양유전자의 점돌연변이를 발견할 수 있었다. 유전성 수질암 중 가족성 수질암 1예를 제외하고 나머지 5예는MEN 2A이었다. 저자들의 5예와 지금까지 국내에서 보고 된 7예를 합친 국내 MEN 2A 12예 중 75% (9/12)는 exon 11의codon 634번(C634R 4예, C634y 4예, C634w 1예)에서, 그리고 나머지 25% (3/12)는 exon 10의 codon618번(C618R 2예, C618s 1예)에서 변이가 발견되었다. 국내에서는 codon 634과 codon 618 두 곳에만 국한된 양상이었고, codon 634에서의 C634R 변이는 1/3에서만 나타났다. 비록 본 연구에서는 제한된 환자 수 때문에 변이 양상과 임상상의 관계를 규명할 수 없었지만, 향후 많은 수의 환자를 대상으로 전향적인 연구를 시행하여 genotype-phenotype 관계 규명을 하는 것이 필요하다. Background: Medullary thyroid carcinomas (MTC) have been reported as hereditary in about 25 -30% of cases. The identification of germline mutation in RET proto-oncogene is important in the diagnosis of hereditary MTC, and occurs in three forms: MEN 2A, MEN 2B and familial MTC (FMTC). To evaluate the prevalence of the relationship of RET proto-oncogene mutation and genotype-phenotype was studied in Korean patients with MTC. Methods: Genomic DNA was obtained from 29 patients, with MTC, who underwent a total thyroidectomy, between 1997 and 2003, at the Samsung Medical Center. There were 7 male and 22 female patients, with an average age of 39, ranging from 20 to 60 years. Exon 10, 11, 13, 14 and 16 of the RET proto-oncogene were amplified, with specific primers, using PCR. A sequencing analysis was performed on the PCR product using an automatic sequencing analyzer. Results: Nine of the 29 patients (31%) were identified as having RET mutations. The average age of these 9 patients was 33 years, ranging from 20 to 51, with a female to male ratio of 2. Five patients had MEN 2A and one had FMTC, with the other 3 thought to have non-hereditary (sporadic) MTC. The 4 patients with MEN 2A had RET mutations on codon 634 of exon 11 (2 patients, C634R; 2 patients, C634Y) and the other patient on codon 618 of exon 10 (C618R). One patient with FMTC had a mutation on codon 634 (C634W). Three patients with sporadic MTC had RET mutations on codon 634 (2 patients, C634Y; 1 patient, C634S). However, no genotype- phenotype relationship could be found, due to the limited number of patients. Conclusion: Thirty-one percent (9/29) of the patients with MTC had RET proto-oncogene mutations. Three-quarters (9/12) of the Korean patients with MEN 2A, including another 7 patients reported in 3 papers in Korea, had RET mutations on codon 634 of exon 11 (4 patients, C634R; 4 patients, C634Y; 1 patient, C634W), but a quarter (3/12) had mutations on codon 618 of exon 10 (2 patients, C618R; 1 patient, C618S). Although no relations could be found between the genotypes and phenotypes, extensive prospective studies will be required to verify this (J Kor SOC Endocrinol 18:360-370, 2003).

당뇨병성 합병증을 가진 환자에서 혈중 Erythropoietin 농도

김동규,유기동,허광식,김상용,윤성호,조영신,권용은,김태원,김건영,정종훈,배학연 朝鮮大學校 附設 醫學硏究所 1998 The Medical Journal of Chosun University Vol.23 No.1

연구 배경 : 고혈당성에 의한 산화환원반응 이상(가저산소증)이 조절 되지않는 당뇨병의 특징으로 혈관과 신경 기능에 대한 진성 저산소증의 효과와 유사하며, 당뇨 합병증의 병태생리에 중요한 역할을 한다. 고혈당이 있는 인슐린 비의존형 당뇨병 환자에서 인슐린 수준이 정상이듯이, 빈혈이 있는 당뇨병 환자에서 EPO의 농도는 실제 혈색소 농도의 감소비율과 차이가 있을 것이라 추측된다. Friedman 등은 당뇨병성 합병증 원인 인자로 가저산소증(pseudohypoxia) 또는 저산소증(hypoxia)을 제기하였고 이런 인자들이 EPO의 상대적 또는 절대적 결핍에 의한 것임을 보고하였다. 방법 : EPO-Trac^(TM 125)I RIA kit을 이용하여 방사면역측정법으로 EPO 수준을 검사하였다. 전혈 3㎖을 5-10㎖ 시험관에 정맥 채혈하였으며, 용혈과 장기간의 보존을 위하여 원심분리를 즉시 시행하여 혈청을 영하 200C에서 냉동 보관 후 일괄적으로 검사 결과를 얻었다. 결과 : 1996년 9월부터 1997년 2월까지 조선대학교 부속병원 내과에 입원한 2형 당뇨병 환자 63례를 대상으로 하여 다음과 같은 결과를 얻었다. 1) 당뇨병성 합병증이 없는 군과 있는 군간의 혈색소, 혈중 EPO농도의 차이는 유의한 차이가 있었으며 혈색소의 감소율보다 혈중 EPO의 감소율이 더 높았다. 2) 당뇨병성 망막증의 유무에 따른 혈색소 농도의 차이는 유의한 차이가 없었으나 혈중 EPO농도는 유의한 차이가 있었다. 증식성군에서만 혈중 EPO의 감소비율이 혈색소에 비해 높았다. 3) 당뇨병성 신증의 유무에 따른 혈색소, 혈중 EPO농도는 유의한 차이가 있었고 혈색소 감소율에 비해 EPO농도의 감소율이 높았다. 신증의 중증도에 따른 혈색소, EPO의 차이는 미세알부민뇨군을 제외하고는 유의한 차이를 보였고 혈색소 감소율에 비해 EPO의 감소율이 더높았다. 4) 당뇨병성 신경병증의 유무에 따른 혈색소 농도의 차이는 유의한 차이가 없었으며 EPO농도는 유의한 차이를 보였다. 혈색소와 EPO의 감소비율은 비슷하였다. 신경병증의 중등도에 따른 혈색소와 EPO농도의 변화는 유의한 차이가 없었으나 stage 3에서는 혈색소감소율보다 EPO감소율이 더높았다. 결론 : 당뇨병성 합병증을 가진 환자에서 빈혈의 정도는 대부분 혈청 EPO치의 절대적 감소에 의함을 간접적으로 밝혀낼 수 있었으며 차후 더 많은 대상으로 비교 분석이 필요하리라 사료된다. Background: Hyperglycemic-induced redox(pseudohypoxia) imbalance is a characteristic feature of poorly controlled diabetes that mimics the effects of true hypoxia on vascular and neural functions and plays an important role on the pathogenesis of diabetic complications. As is true for apparently "normal" insulin levels typically found in NIDDM even in the presence of hyperglycemia, a "normal" erythropoietin level in an anemic diabetic subject may be disproportionally low for the actual red cell mass. Therefore, Friedman et al suggested that pseudohypoxia or hypoxia as an etiological factor of diabetic complications are due to absolute or relative erythropoietin deficiency Method: EPO-TracTM 125I RIA kit was used for the quantitative determination of erythropoietin(EPO) in serum by radioimmunoassay. An adequate sample of blood (3ml whole blood) was collected aseptically by venipuncture in a 5~10ml glass tube to yield a minimum of 400 L of serum per assay. The serum was promptly removed from the clot by centrifugation in order to avoid hemolysis. Then to increase its storage time it was frozen at -200C in a nonself defrosting freezer. Finally, tests were undertaken simultaneously Results We studied 63 cases with diabetes mellitus, who were admitted to Chosun University Hospital from September, 1996 to February, 1997 at the Department of Internal Medicine. We defined the control group, as diabetic patients who did not have anemia(<13mg/dl), diabetic complications(retinopathy, nephropathy, neuropathy) and the remainders were defined as the experimental group(we excluded anemic patients, who had secondary causes of anemia and diabetic patients with end stage renal disease)Data were as follow 1) The relationship of Hb and the 24hr urine protein between diabetic patients with and without complications significantly differed(p=0.02, < 0.001 respectively), but the Hb level was poorly related between diabetic patients with and without retinopathy(except in preproliferative, proliferative subgroups) and neuropathy. 2) Subgroups of patients with diabetic complications had higher 24hr urine protein than patients without diabetic complications, except stage I diabetic neuropathy 3) The EPO level was significantly different between diabetic patients with and without complications. 4) The correlation between EPO and Hb was significantly different, especially in diabetic patients with retinopathy and nephropathy according to severity of diabetic complications, compared with patients who did not have diabetic complications such as retinopathy and nephropathy. Conclusion: We know that anemia induced by diabetic complications is due to relative EPO deficiency than absolute EPO deficiency, and further evaluation and studies are needed on many cases in the future

알데히드탈수소효소 2(ALDH2) 및 CYP2E1 유전자 다형성에 따른 요중 뮤콘산 농도와 요중 8-hydroxydeoxyguanosine과의 관련성

김용대,강종원,엄상용,장연위,김성훈,김은영,이철호,문재동,김헌 대한산업의학회 2007 대한직업환경의학회지 Vol.19 No.2

만성 승모판 패쇄부전증 환자에서의 안지오텐신 전환효소 억제제의 장기 투여 효과

김대희,이명묵,이해영,조현재,박승정,서재빈,서정원,양한모,윤창환,조상호,이준희,김용진,김명아,손대원,오병희,박영배 대한순환기학회 2004 Korean Circulation Journal Vol.34 No.2

알루미늄 합금과 고장력 강판 접합을 위한 헬리컬 SPR의 단조공정 설계

김원영, 김동범, 김기호, 김도훈, 이인환, 조해용 충북대학교 산업과학기술연구소 2013 산업과학기술연구 논문집 Vol.27 No.2

A self-piercing rivet(SPR) is a mechanical component for joining dissimilar materials. It is used for joining dissimilar material sheets such as aluminum alloy and steel. The self-piercing rivet directly pierces into sheets without drilling sheets beforehand unlike conventional rivets. However, the self-piercing rivet occurs buckling when piercing high strength steel. Therefore, a helical SPR which can pierce high strength steel sheet was designed. In this study, forging process was designed for manufacturing the helical SPR and simulated by using commercial FEM code DEFORM-3D. In the simulation of forging process for manufacturing rivet, process sequence, formability, forging load were investigated. The suitable forging process could be designed by comparisons of simulated results. Experimental trials have been carried out for same conditions as simulated ones. The simulated results agreed with the experimental ones. So, the analytic approach in this thesis is useful to save cost and time in the forging industry

Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 as biomarkers of patients with established acute kidney injury

( Won Yong Cho ),( Sung Yoon Lim ),( Ji Hyun Yang ),( Se Won Oh ),( Myung-gyu Kim ),( Sang-kyung Jo ) 대한내과학회 2020 The Korean Journal of Internal Medicine Vol.35 No.3

Background/Aims: Urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been recently discovered and validated as sensitive biomarkers that can predict stage 2 or 3 acute kidney injury (AKI) development in high-risk patients. We aimed to assess whether these biomarkers could predict adverse outcomes and renal recovery in established AKI patients. Methods: This was a single-center study prospectively enrolling 124 patients diagnosed with AKI. TIMP-2, IGFBP7, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule 1 (KIM-1) levels were measured at the time of diagnosis and the predictive performance of short-term outcomes and renal recovery was assessed. Results: Patients were divided into 4 quartiles according to the initial urinary TIMP-2/IGFBP7 levels. Stage 3 AKI (odds ratio [OR], 17.86), classified by the Kidney Disease Improving Global Outcomes (KDIGO), as well as the third and fourth quartiles of TIMP-2/IGFBP7 (OR, 5.75 and 44.98, respectively), were found to be independent predictors of renal replacement therapy at the time of AKI diagnosis. In addition, KDIGO stage 3 AKI (OR, 2.468) or the third of fourth quartiles of urinary TIMP-2/IGFBP7 (OR, 1.896 and 3.622, respectively) were also found to be useful in predicting nonrecovery of renal function. In a separate analysis of patients with renal recovery at discharge, initial urinary TIMP-2/IGFBP7 or urinary IGFBP7 at discharge could also predict new-onset or progressive chronic kidney disease (CKD). Conclusions: In AKI patients, urine TIMP-2/IGFBP7 could serve as a biomarker for predicting adverse outcomes, renal recovery, or the development and progression of CKD.

Fibrous Dysplasia Associated with Primary Hyperparathyroidism Absent of McCune-Albright Syndrome : Tc-99m MIBI and Tc-99m MDP Findings

김승장,석주원,김인주,김영기,김동수 대한핵의학회 2003 핵의학 분자영상 Vol.37 No.2

섬유성 골이형성증은 비정상적인 섬유성 골조직으로 대체되며 느리게 진행하는 골병변이다. 섬유성 골이형성증과 부갑상선기능항진증은 흔하게 관찰되는 질환이나 McCune-Albright 증후군 없이 일차성 부갑상선기능항진증에 동반된 섬유성 골 이형성증은 거의 보고된바가 없다. Tc-99m MDP 골스캔이 섬유성 골이형성증의 진단에 유용하다고 알려져 있으나, Tc-99m MIBI 영상은 아직 보고된 바가 없다. 저자들은 McCune-Albright 증후군이 없이 부갑상선기능항진증에 동반된 섬유성 골 이행성증의 Tc-99m MIBI 스캔과 Tc-99m MDP 골스캔의 영상을 비교하였다. Tc-99m MDP 골스캔상 병변 부위에서 증가된 섭취 소견을 보였으며, Tc-99m MIBI 조기영상에서도 동일한 위치에서 섭취증가가 관찰되었다. 2시간 지연 Tc-99m MIBI 영상에서는 Tc-99m MIBI의 섭취가 배출되는 소견을 보였다. 섬유성 골이형성증 병변에서 Tc-99m MIBI 스캔이 유용할 것이라고 생각하며, 섬유성 골이형성증 병변에서 Tc-99m MIBI의 섭취를 증가시키는 인자에 대한 더 많은 연구가 필요할 것으로 생각한다.

생리식염수 및 포도당수액 정액 투여가 에탄올 농도에 미치는 효과에 관한 연구

김원율,이상래,안지영,안성훈,류석용,김경환,김홍용 대한응급의학회 2000 대한응급의학회지 Vol.11 No.3

Background: In emergency department, there are many drunken patients with various emergency medical situations. In these patients, evaluation and management of the medical problems are delayed from time to time because of the uncooperative nature of the patients and because of consciousness and sensory changes. A precise evaluation can only be obtained when the patients become sober. For this purpose, most clinicians start IV fluid loading. This study was carried out to evaluate the effect of IV fluid(normal saline and glucose solution) on the rate of ethanol clearance in such patients Methods: Ten volunteers(healthy males in their twenties and with a Michigan alcohol screening test below 4) were enrolled in this study. Alcohol intake was restricted to at least 48 hours before the test and food intake to at least 4 hours. For the test, A predetermined dose of ethanol(1 gm/kg) was given to the volunteers. Each volunteer was tested on three consecutive times with 3 or more days interval for alcohol wash out period . On the lst day, the volunteers received ethanol only per os. On the second day, they received ethanol and a liter of IV 10% dextrose solution. Each day, blood was drawn from the antecubital vein to measure the ethanol level at the time of ethanol ingestion and at 0.5, 1, 1.5, 2, 3, 4, 5 and 6 hours after ingestion. The repeated measure ANOVA test was used for the statistical analysis. Results: The difference in the blood ethanol level between the 3 test was F=1.7, p=0.184 and the difference corrected by the time factor was F=0.32, and p=0.985. Conclusion: There was no significant difference in the blood ethanol level between the tests. In conclusion, the IV normal saline or glucose solution does not accelerate ethanol clearance in suffering

중추성 요붕증으로 발현된 랑거한스세포 조직구증식증 1례

김준성,윤원상,김근모,최영권,박기원,김병희,유용상 대한소아내분비학회 2004 Annals of Pediatirc Endocrinology & Metabolism Vol.9 No.1

면양에서 개량된 제1위 누관 형성술 1례

김명철,김종만,김용국,김덕환,이영원 충남대학교 수의과대학 동물의과학연구소 1999 動物醫科學硏究誌 Vol.7 No.-

We performed rumen fistula operation in a sheep. In sheep, the procedure for a rumen fistula is quite successful, but choice of an appropriate cannula is of prime importance. The sheep was anesthetized by xylazine(0.1 ㎎/㎏ IM) administration 5 minutes after administration of atropine sulfate(0.1 ㎎/㎏ IM). We inserted rubber cannula in rumen incised and put rubber ring after employing purse-string suture in rumen. We marked the area for the puncture incision in the body wall through which the cannula is drawn. We drew the cannula as near the transverse process of the lumbar vertebrae as possible to minimize leakage. We isolated the cannula by fixing the stainless washer which has small holes. The sheep was given postoperative penicillin(20,000 IU/㎏ IM) to prevent secondary infection for 3 days. There were not observed the leakage of rumen contents, the entering of rubber cannula into abdominal cavity, and necrosis on incision site and skin, over months after surgery.