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).

Luria-Nebraska 神經心理檢査의 韓國版 標準化硏究(Ⅱ)

金在煥,南正鉉,金光日,金二泳,黃淳澤,김지혜,金南奎,朴康圭,林東洙,金圭泰 漢陽大學校 精神健康硏究 1990 精神健康硏究 Vol.9 No.-

안면에 발생한 신경섬유종의 치험례

김희광,윤규호,전인성,김태열,김기엽,김현우 大韓顎顔面成形再建外科學會 2003 Maxillofacial Plastic Reconstructive Surgery Vol.25 No.1

Neurofibroma is benign neurogenic tumor originated from nerve tissue-Schwann cell, fibroblast, perineural cell. They have no sexual predirection and generally no symptom. Neurofibroma is classified to solitary type and multiple type and is rare in oral resion. They located in soft tissue of tongue, lip, palate and oral mucosa in form of sessile and pedunculated mass and are rare intraosseous region. In solitary type, complete excision is the choice of treatment due to their rare recurrence rate. In multiple type, the same is choice of treatment but bas some difficulty of plastic problem, bleeding

유도 '되치기 본'의 개선 방안에 관한 연구

김의환,김도준,김규수,김관현,김종달,최종삼,조용철,박순진,윤익선,안병근,정 훈,김미정,한성철 龍仁大學校 武道硏究所 1999 武道硏究所誌 Vol.10 No.1

The purpose of this study was to reform practically a Korean Judo's Doechigi-Bon(Forms of Counterattack, judo's Gaeshi no Kata, Judo's Uradori no Kata, Judo's Gonosen no Kata) that was established in 1955 Korea, according to changing of techniques by Judo's modernization, in order to have Judo's carefulness and systematic diffusion. Reform procedure of Judo's Doechigi-Bon was 1st stage, Questionnaire survey 303 judokas, 2nd stage, Technical seminar by judo experts(12 judo professor) 4 times, 3rd stage, wording report for reform, 4rd stage, Discussion and judgement of Teaching and Judgement commission of Korean judo Association(KJA), 5th stage, Public hearing for reform in KJA, 6th stage, Report and decision of board of directors in KJA, 7th stage, public publication of Judo News(No.53) in KJA. Basic principle of reform of Judo's Doechigi-Bon were as table 1. Table 1. Basic principle of reform of Judo's Doechigi-Bon ------------------------------------------------------------------------------- Items Reformed Key Points of Judo's Doechigi-Bon ------------------------------------------------------------------------------- 1. Structure 1) Grand classification : Classified by 3 parts(1,2,3Gyo) 2)Medium classification : Te waza, Goshi waza, Ashi waza devided per each part(Gyo) 3)Sub-classification : Classified five techniques per each part(Gyo) 2. Contents 1) Selected established techniques as possible 2) Considered rationalty and overlapping of counterattack techniques 3. Decision of Conterattack techniques 1) Refered to results of Basic Questionnaire survey 2) Priority to decisions of Judo expert technical seminar -------------------------------------------------------------------------------- Reformed Korean Judo's Doechigi-Bon(Forms of Counterattack techniques-KJA, 1999) are as follows: 1. Gyo; ① Uki otoshi -> Uchi mata ② Harai goshi -> Harai goshi gaeshi ③ O soto gari -> O soto gake ④ Ko uchi gari -> Sasae tsurikomi ashi ⑤ O uchi gari -> Ko soto gari 2. Gyo; ① Ippon seoi nage -> Okuri eri jime ② Tsuri domi goshi -> Uki waza ③ Okuri ashi harai -> Okuri ashi harai ④ Ko soto gari -> Tai otoshi ⑤ Hiza guruma -> Hiza guruma 3. Gyo; ① Kata guruma -> Sumi gaeshi ② Tai otoshi -> Ko soto gari ③ Hane goshi -> Harai tsurikomi ashi ④ Uchi mata -> Tai otoshi ⑤ Tomoe nage -> O uchi gari

Poems by Kwang-kyu Kim (Ⅱ)

Kwang-kyu Kim,Kim Uchang(번역자) The Academy of Korean Studies 1980 Korea Journal Vol.20 No.10

Poems by Kwang-kyu Kim (Ⅰ)

Kwang-kyu Kim,Kim Uchang(번역자) The Academy of Korean Studies 1980 Korea Journal Vol.20 No.9

트레드밀 걷기 운동 시 무게부하의 차이가 호흡순환기능 및 대사기능에 미치는 영향

김용규,이채산,김자영,박미숙,김광중,이광호 한국스포츠리서치 2003 한국 스포츠 리서치 Vol.20 No.1

The purpose of this study was to compare on cadiopulmonary and metabolism function of 10㎏ weight loading group(10 females) and W university students with non weight loading group(10 females. Each group did treadmill walking exercise for twenty minutes by the modified balke protocol. Heart rate(HR), systolic(SBP), MVO₂, and VO₂max were analyzed using 2×2(groups×during) repeated measures analysis of variance (MANOVA). And peak blood velocity(PBV) and MBV were analyzed by using 2×2(groups×during) repeated measures analysis of variance (MANOVA). Lactate and glucose were amalyed by separate 2×2 (groupxduring) analysis of variance(ANOVA). Results of this study suggest that: The change of HR, SBP and MVO₂ in experience and control group showed the significant(p<.05) increase during walking exercise. Variables between experience and control group showed not significant level. But VO₂ in each group showed the significant(p<.001) increase during walking exercise. Differenc among each group showed significant(p<.001) level. Lactate and glucose level in each group showed significant(p<.001, p<.05) increase during walking exercise. Differences among each group showed not significant level. PBV and MBV in each group significant(p<.001) increase during walking exercise. Difference among each group showed significant(p<.05) level. According to these results, weight loading walking exercise considering safety promotes to cardiovascular function and it is expected to be an effective exercise methods able to improve the physical inefficiency of long time walking type.

Shaphylococcus enterotoxin B와 lipopolysaccharide를 작용시킨 사람 섬유아 세포에서 생성된 Transforming Growth Factor-β₁의 정량적 분석

이성근,김광혁,김욱규,김종렬,정인교,양동규 대한악안면성형재건외과학회 2000 Maxillofacial Plastic Reconstructive Surgery Vol.22 No.2

TGF-β1 is a potent chemotactic factor for inflammatory cells and fibroblasts. It also stimulates the celluar source and components of extracellular matrix and the production of proteinase inhibitors. Collectively, these biologic activities lead to the accumulation and stabilization of the nascent matrix, which is vital to infection control. The objective of this study is to investigate production of TGF-β in vitro fibroblast culture in the presence of Staphylococcus enterotoxin B(SEB) and/or lipopolysaccharide(LPS) and to elucidate the role of TGF-β1 which may be responsible for infection control. The fibroblasts were originated from gingiva and facial dermis in 26 year-old male patient. In the presence of LPS(0.01㎍, 0.1㎍, 1.0㎍), SEB(0.01㎍, 0.l㎍, 1.0㎍) respectively, cells(5×103ml) were cultivated in vitro. At 1, 3, and 5 days after incubation, cells were counted. Also, cells(2.5×105ml) were cultivated in EMEM with LPS(0.01, 0.1 and 1.0㎍), SEB(0.01, 0.1 and 1.0㎍) respectively and LPS(0.1㎍) and SEB (0.1㎍) in combination for 24,48, and 72 hours respectively. Culture supernatants were harvested at 1, 2, and 3 days after incubation period and triplicate culture supernatants were pooled and TGF-β1 was assayed in duplicate. The results were as follows. 1.In gingival fibroblast induced with SEB and LPS respectively or in combination, the suppression of cell Proliferation occurred very significantly since 3 days after incubation, compared with the control and the production of TGF-β1 occurred very significantly at 1 day after incubation, compared with the control. 2.In facial dermal fibroblast induced with SEB and LPS respectively or in combination. the suppression of cell proliferation occurred very significantly at 1 day after incubation, compared with the control. In SEB exposure, the production of TGF-β1 was decreased very significantly at 1 day after incubation, compared with the control. However, in LPS, SEB and LPS exposure, the production of TGF-β1 was increased very significantly at 1 day after incubation, compared with the control. In conclusion, the concentration of bacterial toxins and the incubation period correlated with cell proliferation and production of TGF-β1 very significantly. The gingival and facial dermal fibroblasts have different phenotype each other The orchestrated understanding of fibroblast proliferation and TGF-β1 production play an important part in host defense against the bacterial Infection and may prevent tissue necrosis such as necrotizing fasciitis and life-threatening syndrome such as multiple organ failure.

쿠싱증후군 환자에서 당 대사 이상 정도에 따른 인슐린 감수성과 인슐린 저항성의 변화

정인경,김성훈,정재훈,민용기,이명식,이문규,유형준,안규정,노정현,김동준,김광원 대한내분비학회 2003 Endocrinology and metabolism Vol.18 No.4

연구배경 당질 코르티코이드는 당 대사에 매우 중요한 호르몬으로 내인성 당질 코르티코이드 과다상태인 쿠싱증후군에서는 말초조직에서 인슐린 저항이 증가하고 이를 보상하고자 인슐린 분비의 증가로 고인슐린혈증이 동반된다고 보고되고 있다. 하지만 생체 내에서와 달리 시험관내에서는 췌도세포에 당질 코르티코이드를 장시간 처리하면, 인슐린 분비 및 생합성이직접적으로 억제됨이 확인된 바 있어 쿠싱증후군 환자에서 당뇨병의 원인으로는 아마도 말초조직에서 증가된 인슐린 저항성 뿐 아니라 이를 충분히 보상하지 못하는 췌장에서의 인슐린 분비 저하가 같이 동반되어있지 않을까 하는 가설을 세우게 되었고, 아직까지 당질코르티코이드가 당대사 이상을 일으키는 기전에 대해 쿠싱증후군을 당대사 정도에 따라 인슐린 감수성과 분비능을 분석한 연구는 없었기에 이를 알아보고자 하였다. 방법: 삼성서울병원에서 쿠싱증후군으로 진단 받은 환자 15명을 대상으로 하였다. 이에 대한 대조군으로는 쿠싱증후군 환자와 같은 성별 그리고 체질량지수를 갖은 15명의 건강한 성인을 대상으로 비교 하였다 쿠싱증후군 환자를 대상으로 경구당부하 검사를 통해 당대사 정도를 정상군, 내당능장애군, 그리고 당뇨병군으로 나눈 후 정맥 당부하 검사를 시행하여 각군의 인슐린 저항성과 인슐린 분비능의 지표를 비교하고, 수술 후 쿠싱증후군이 완치된 상태에서 수술 전후의 당대사 지표의 변화를 조사하였다. 결과: 1) 쿠싱증후군 환자 중 정상인은 20%, 내당능 장애는 27%, 그리고 당뇨병은 53%였다. 체질량지수, 나이, 그리고 발병 기간은 세 군간에 의미 있는 차이가 없었으나, 24시간 소변검사의 코르티솔 농도는 당뇨병군에서 의미있게 높았다. 2) 정맥당부하 검사 결과, 인슐린 감수성 지표인 Sl는쿠싱증추린」서 1.58±0.10[×10^(-4)(min^(-1)(μU/mL)^(-1)]로 정상 대조군의 3.37±0.49[×10^(-4)(min^(-1)(μU/mL)^(-1)]에 비해 의미있게 낮았으나(P=0.024), 쿠싱증후군 환자 중 NGT, IGT, DM 군간에 서로 통계적인 차이는 없었다. 3) SG는 정상 대조군과 쿠싱증후군 환자간에는 의미있는 차이가 없었고, 쿠싱 증후군에 있어서 당대사가 악화될수록 감소하는 경향을 보였으나 의미있는 차이는 없었다. 4) 인슐린 분비능의 지표인 AIRg는 정상인에 비해 전체 쿠싱증후군 환자의 경우 증가하는 경향을 보였으나 의미있는 차이는 없었다. 하지만 쿠싱증후군 환자중에서 당대사 상태에 따라 NGT군은 1299 (1297∼1310)(mu/g/min ×10^(-2))로 정상 대조군(368.9±98.6[mu/g/min ×10^(-2)]) 보다도 의미있게 높았고, DM군{202.2 (91.1~371.4) [mu/g/min ×10^(-2)}은 NGT군에 비해 의미있게 낮았다(P=0.0031). 5) 15명중 현재 완치 상태에 있는 6명에 대해 수술전과 후로 비교하였다. 수술 전 당대사 상태가 1명은정상, 1명은 내당능 장애, 그리고 4명은 당뇨병이었으나 수술 후 시행한 경구 당부하 검사상 모두 정상 당대사 상태를 보였다. 6) 수술 후 완치된 환자 6명에 있어 인슐린 감수성지표인 Sl는 수술전에 중앙값이 1.22[×10^(-4)(min^(-1)(μU/mL)^(-1)]로 대조군에 비해 의미있게 감고』어 있었으나(p.0.05), 수술후 10.95 [×10^(-4)(min^(-1)(μU/mL)^(-1)]로 정상 수준으로 회복되었고(P=0.0022), 인슐린 분비능을 나타내는 AIRg [mu/g/min ×10^(-2)] 값도 정상수준으로 회복되었다. 특히 인슐린 분비능의 회복양상은 혈당농도에 따라 판이하게 나타나서, 정상과 내당능장애 상태에 있던 2명은 수술전에 1201 [mu/g/min ×10^(-2)]로 증가되어 있던 AIRg 값이 수술 후 정상 수준으로 감소하였고, 수술 전에 당뇨병 상태에 있던 4명의 경우 245.9 [mu/g/min ×10^(-2)]로 인슐린 분비능이 감고il어 있었는데 이들은 수술 후 모두 정상 수준으로 증가되었다 (P=0.0286). 결론: 쿠싱증후군 환자에서 당대사 이상은 80%로 높은 유병률을 보였다. 모든 쿠싱증후군환자에서 인슐린 감수성은 정상인에 비해 저하되어 있어 말초조직의 인슐린 저항이 선행됨을 시사하며, 인슐린 분비능은 당대사의 정도에 따라 다르게 나타났는데, 정상 당대사군에서는 인슐린의 저항성을 극복할 만큼 정상 대조군보다 더 많은 양의 인슐린 분비를 하다가 고코르티솔혈증이 심할수록 인슐린 분비능의 감소로 당뇨병으로 진행됨을 확인할 수 있었고, 이런 인슐린 저항성과 인슐린 분비장애는 수술 후 다시 회복되는 가역적인변화를 보였다. Background: Glucocorticoid plays an important role in the control of carbohydrate metabolism. Patients with Cushing's syndrome have been reported to have an increased incidence of carbohydrate intolerance due to peripheral insulin resistance and hyperinsulinemia, although the exact incidence and nature of this disorder have remained unclear. Few results have been published about insulin resistance and insulin secretion according to the level of glucose concentration, or about the reversibility of such defects in patients with Cushing's syndrome. Methods: To assess the effect of glucocorticoid on the insulin sensitivity and insulin secretion in Cushing's syndrome, 15 patients with Cushing's syndrome were classified into 3 groups (normal glucose tolerance: NGT, impaired glucose tolerance: IGT, diabetes: DM) according to the degree of glucose tolerance based on the oral glucose tolerance test (OGTT). Insulin modified, frequently sampled, intravenous glucose tolerance test (FSIGT) was performed before and after curative surgery on these patients and on 15 healthy control subjects. Data were evaluated by non-parametric statistical analysis. Results: 1) Among the 15 patients with Cushing's syndrome, 3 (20%) were NGT, 4 (27%) IGT, and 8 (53%) DM, based on OGTT. Twenty-four hour urinary free cortisol (UFC) was significantly higher in the DM group. 2) Insulin sensitivity index (SI) of Cushing's syndrome was significantly lower than that of the control group p=0.0024), but was not significantly different among the three Cushing's syndrome groups of NGT, IGT and DM. 3) Glucose mediated glucose disposal (SG) (Ed- confirm this abbreviation; it does not seem to match the definition) of Cushing's syndrome was not significantly different from that of the control group. 4) Insulin secretion (AIRg) of Cushing's syndrome tended to be high, but it was not significantly different from that of control. However, according to the level of glucose concentration there was significant difference in AlRg among the three Cushing's syndrome groups p=0.0031); AIRg of DM was significantly lower than that of NGT. 5) After surgical treatment, parameters of insulin sensitivity and insulin secretion were normalized in 6 cured patients; 1 with NGT, 1 with IGT, and 4 with DM, preoperatively. Median SI of all 6 patients was significantly improved up to the normal range postoperatively p=0.0022). Median AIRg of these 6 patients was balanced around that of normal control postoperatively p=0.0286). Conclusion: Eighty percent of patients with Cushing's syndrome had abnormality of carbohydrate metabolism. Insulin sensitivity was significantly decreased in Cushing's syndrome. Insulin secretion was significantly higher only in the NGT and IGT groups of Cushing's syndrome. As the hypercortisolemia is exacerbated, insulin secretion is significantly decreased and causes DM, suggesting that glucocorticoid has a direct or indirect toxic effect on the pancreatic beta cell (J Kor SOC Endocrinol 18:392-403, 2003).

구개부에 발생한 다형성선종의 치험례

이창진,김태열,김효언,김희광,전인성,윤규호 대한악안면성형재건외과학회 2000 Maxillofacial Plastic Reconstructive Surgery Vol.22 No.2

Pleomorphic adenoma is the most common of all salivary gland tumors, constituting over 50 per cent of all cases of tumors, and approximately 90 per cent of all benign salivary gland tumors. Since the term mixed tumor' was introduced by Broca for its dual origin of epithelial and mesenchymal elements, the term plemorphic adenoma suggested by Willis characterizes closely the unusual histologic pattern of the lesion. The parotid gland is the most common site but it may occur in any of the salivary glands. It is somewhat more frequent in women and in the fourth to sixth decades, but they are also relatively common in young adult and have been known to occur in children. Treatment of choice is surgical excision. Adequate surgery with safe margin reduce its recurrence rate. We represent a case of pleomorphic adenoma with literature review in 65-year old male occured in the palate. The lesion was successfully treated by surgical excision.