월반성 무월경에 대한 임상적 및 세포유전학적 고찰

최욱환(Ook Hwan Choi),이규섭(Kyu Sup Lee),윤만수(Man Soo Yoon),김원희(Won Whe Kim) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.11

The purpose of this study was to determine the frequency of chromosomal or genetic causes of primary amenorrhea, and was made to assess the etiology of disorders in those patients whose chromosome appeared normal. Sixty eight patients with primary amenorrhea were evaluated clinically and cytogenetically, which were refered to our Cytogenetic Laboratory in Department of Obstetrics and Gynecology, Pusan National University Hospital, from Aug. 1988 to Dec. 1996. The results were as follows. l. Out of 68 cases with primary amenorrhea, 40 cases (58.9%) had the normal chromosome constitutions and 28 cases (41.1%) had the abnormal chromosome constitutions including 46, XY. 2. Turner's syndrome was found in 25 cases (36.7%), consisting of 11 cases (16.1%) of 45,X, 3 cases (4.3%) of 46,X,i (Xq), 1 case (1.5%) of 46,X, inv (X), 1 case (1.5%) of 46,X, del (Xq), 1 case (1.5%) of 46,X, del (Xp), 1 case (1.5%) of 46,X, tel (Xq), 1 case (1.5%) of 45,X/46,XX, 1 case (1.5%) of 45,X/46,XY, 1 case (1.5%) of 45, X/47,XXX, 2 cases (2.9%) of 45,X/46,X, del (Xq), I case (1.5%) of 45,X/46,X, del (Xq), 1 case (1.5%) of 45,X/46,X, r (X). 3. 3 cases (4.3%) had the 46,XY chromosome constitution consisting of 2 cases (2.9%) of testicular feminization syndrome and 1 case (1.5%) of pure gonadal dysgenesis. 4. Among 40 patients whose chromosome are normal, the etiologies of amenorrhea were assumed to be caused by 11 cases (27.5%) of hypogonadotropic hypogonadism (idiopathic), 10 cases (25.0%) of congenital absence of vagina, 5 cases (12.5%) of pure gonadal dysgenesis in order of frequency.

최신임상강좌 : 줄기세포 치료의 연구 현황 및 최신 지견

최욱환 ( Ook Hwan Choi ),장성규 ( Sung Kyoo Jang ) 대한산부인과학회 2007 Obstetrics & Gynecology Science Vol.50 No.4

In this 21st century which is considered as the era of biotechnology, the regenerative medicine emerging as an important medical science has been expected to provide hope to patients of incurable diseases, such as myriad of degenerative disease or terminal organ failure which can not be solved until recently. Because It is also thought to be a epochal alternative therapy in every medical part including cardiovascular disease, neurological disorder, hereditary disease, liver disease, endocrine disorder, bone or cartilage disease, and skin disease, many stem cell researches are conducted and many results are reported. Stem cells are at the center of this regenerative medicine. Although there is public debate because it is inevitably associated with ethical problems like destruction of embryo or risk of reproductive cloning, stem cell research generated much interest because the expected therapeutic effect and the derived economic value would be enormous. This review will describe the characteristics of stem cell and summarize the published research results recently.

사람 자궁의 동맥혈관 평활근의 Endothelin 에 의한 수축반응에 관한 연구

최욱환(Ook Hwan Choi),장미경(Mi Kyung Jang),임병용(Byung Yong Rhim) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.3

Objective: We examined the vasoconstricting poperties of endothelin (ET) on isolated arteries from pregnant as well as non-pregnant uterus. Methods: Arteries of the uterus were obtained from both hysterectomized uterus and during pregnany hysterectomy for control group and cesarean section for pregnant group. Rings of uterine artery were suspended on muscle chambers at their optimal length for generating tension and contractile properties were examined. Results: ET-1 and ET-2 induced concentration-dependent constriction of both isolated arterial strips from non-pregnant and pregnant uterus. The contraction to ET-1 and ET-2 were more enhanced in full-term pregnancy. Furthermore, in pregnant group, sarafotoxin S6c and IRL 1620, ET. agonists, induced a dose-dependent contraction, which was not shown in those from non-pregnant human. Pretreatment of human uterine arterial strips from pregnant uterus with BQ610, an ET. antagonist, for 10 min resulted in a dose-related rightward shift of ET-1 response curve with diminution of maximal response. Schild plot analysis yielded a pA value of 7.29 with a slope of 0.98. However, BQ788, an ET antagonist, did not produce any rightward shift. The contraction to lower concentration (10-8~3*10-7 M) of sarafotoxin S6c was not affected by BQ788, whereas that to higher concentration (10-s-8*10-7 M) was marked diminished. However, BQ610 did not exnt any efFect on sarafotoxin S6c-induced contraction in arterial staips from pregnant uterus. When the bath solution was replaced with Ca-free physiological salt solution (PSS) containing 1 mM EGTA for 10 min prior to adding sarafotoxin S6c, sarafotoxin S6c-induced contraction was completely abolished. Sarafotoxin S6c (10 nM)-induced contraction was prefetentially blocked by a protein kinase C antagonist, H-7, whereas it was less sensitive to a calmodulin antagonist, calmidazolium, Conclusion: Based on above results, we concluded that ET plays an important role in regulating uterine blood flow through the activation of ETa and ETB receptors. Furthermote, ETB receptors may predominantly contribute to the modulation of human uterine circulation in full-term pregnancy.

혈우병 A 환자에서 혈액응고인자 8 유전자의 역위 및 결실 분석

박동희(Dong Hee Park),최욱환(Ook Hwan Choi),김철민(Cheol Min Kim),김인주(In Joo Kim),한진영(Jin Yeong Han) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.12

Objective : For development of a direct analysis method for hemophilia A, mutational analysis of F8C carried out. Methods : The molecular analysis of F8C gene was done using DNA isolated from the peripheral blood of 106 Korean patients with hemophilia A. For the detection of inversions in F8C gene, the multiplex long amplification polymerase chain reaction (MLA-PCR) with four primers was performed. For the detection of gross deletions in F8C gene, PCR using exon-specific primers and multiplex electrophoresis was done. Results : As the result of MLA-PCR, the frequency of F8C inversion was 18.9%, 20 out of 106 hemophilia A cases. The deletions of one or more exons in F8C gene were detected in 2 out of 106 hemophilia A cases (1.9%). In one case, the exon 13 was deleted and in the other case both exons 24 and 25 were found to be deleted. Conclusion : The PCR-based direct analysis of F8C gene for the detection of inversions and deletions could successfully detect mutations in 20.8% of Korean patients with hemophilia A. This approach would be a very useful diagnostic tool for the direct analysis of hemophilia A and prenatal diagnosis in hemophilia A families.

임신 중기 양수천자 3,537예에 대한 세포유전학적 분석 및 임상적 고찰

장성규 ( Sung Kyoo Jang ),최욱환 ( Ook Hwan Choi ) 대한주산의학회 2007 Perinatology Vol.18 No.1

목적: 산전 유전학적 진단의 목적으로 임신 중기 양수천자술을 시행한 환자에서의 연령별 분포 및 적응증별 분포와 이에 따른 염색체 이상의 발현 빈도를 분석하였다. 방법: 1994년부터 2006년 6월까지 부산대학교병원 산전 유전 검사실에 의뢰되어 산전 유전검사 목적으로 시행된 3,537예의 임신 중기 양수천자검사의 결과를 후향적으로 분석하였다. 결과: 3,537예의 대상군의 연령별 분포는 25~29세군(32.8%), 30~34세군(32.1%), 35~39세군(24.3%)의 순이었다. 양수천자술의 적응증에서는 비정상 모체혈청 검사가 가장 많았으며(42.6%),고령임신이 31.8%, 염색체 이상의 가족력이 있는 경우가 7.0%였다. 전체 염색체 이상의 빈도는 5.0%였으며, 이중 수적이상과 구조적 이상이 각각 2.4%, 2.6%였다. 염색체의 이상은 45세 이상의 경우에 16.7%로 가장 높은 빈도를 보였고, 40~44세군에서 6.3%, 25~29세군에서 5.6%의 빈도를 보였다. 적응증에 따른 염색체 이상의 빈도는 습관성 유산(21.2%), 염색체 이상의 과거력이 있는 경우(14.3%), 비정상 초음파 소견을 보인 경우(11.5%), 고령임신(5.7%)의 순이었다. 결론: 산전 유전학적 진단을 위한 임신 중기 양수천자술에서 비정상 임신부 혈청 선별검사와 고령임신이 중요한 적응증을 차지하나, 본 연구에서와 같이 습관성 유산이나 염색체 이상의 과거력, 비정상초음파 소견 등도 임신 중기 양수천자술을 시행하는데 있어 중요한 적응증으로 고려해야 함을 알 수 있다. Objective: To analyze the incidence of chromosomal abnormalities according to age and indications in midtrimester amniocentesis performed for prenatal genetic diagnosis. Methods: We retrospectively analyzed the results of 3,537 cases of midtrimester prenatal genetic amniocentesis which were performed from 1994 to June 2006 in the cytogenetic laboratory at Pusan National University Hospital. Results: Of the 3,537 midtrimester amniocentesis cases, the most common maternal age group was 25~29 years old (32.8%), followed by 30-34 years old (32.1%) and 35~39 years old (24.3%). The indications for amniocentesis were abnormal triple test (42.6%), advanced maternal age (31.8%), family history of chromosomal abnormality (7.0%), in the respective order. The overall incidence of chromosomal abnormalities was 5.0%, of which numerical abnormalities and structural abnormalities were 2.4% and 2.6%, respectively. Chromosomal abnormalities were most frequently found in the maternal age over 45 (16.7%), followed by 40~44 years old (6.3%) and 25~29 years old (5.6%). According to the indications of amniocentesis, chromosomal abnormalities were found in patients with habitual abortion (21.2%), previous history of chromosomal abnormality (14.3%), abnormal finding on ultrasonography (11.5%) and advanced maternal age (5.7%), in the respective order. Conclusion: In this study, in addition to although abnormal triple test and advanced maternal age as important indications of midtrimester amniocentesis for prenatal diagnosis, other indications such as habitual abortion, previous history of chromosomal abnormality and abnormal finding on ultrasonography should be considered important as indications of midtrimester amniocentesis.

임상연구 : 생쥐 배아줄기세포에서 단일세포 부유 배양에 의한 apoptosis 의 기전

이병민(Byung Min Lee),최욱환(Ook Hwan Choi),정진섭(Jin Sup Jung) 대한산부인과학회 2002 Obstetrics & Gynecology Science Vol.45 No.1

Objective : Embryonic stem cells (ES cells) are pluripotential, and are therefore used to construct gene knock-out mice and to study cell differentiation and early developmental processes in mice. This study was designated to examine apoptotic processes in ES cells according to culture conditions and to study roles of extracellular matrix on the process. Methods : Apoptosis was determined by DNA fragmentation and kinase activity during apoptotic process was measured. Results : The apoptosis of mouse ES cells was induced when the cells were dispersed as single cells, whereas this process was suppressed when they proliferated in aggregates. Single cell suspension culture did not affect expression of bcl-2 and bax mRNA. Single cell suspension culture activated stress-activated protein kinase/c-jun-N-terminal kinase (SAPK/JNK), but not p38 kinase. The apoptosis of ES cells was repressed when the cells were cultured on feeders prepared from mouse embryonic fibroblasts (MEF), or on the petri dishes coated with fibronectin or laminin, but not with collagen or poly-L-lysine. Culture supernatants from MEF cells did not block the apoptosis of ES cells, which suggests that a direct interaction between ES cells and MEF cells is required for the suppression of apoptosis. Activation of SAPK/JNK by single cell suspension was protected by interaction of cells with laminin or fibronectin, but not with collagen or poly-L-lysine. Conclusion : The suspension of ES cells as single cells causes serious damage and induces apoptosis, and the apoptotic process is mediated by the activation of SAPK/JNK and is inhibited by the interaction of ES cells with extracellular matrix.

47,XXY와 46,XY 핵형을 가진 한국인 불임남성의 Y 염색체의 미세결실에 대한 비교 분석

허재원,김우영,김대수,하홍석,이자랑,최욱환,남기만,배화정,최진,김희수,Huh, Jae-Won,Kim, Woo-Young,Kim, Dae-Soo,Ha, Hong-Seok,Lee, Ja-Rang,Choi, Ook-Hwan,Nam, Ki-Man,Bae, Hwa-Jung,Choi, Jin,Kim, Heui-Soo 한국생명과학회 2007 생명과학회지 Vol.17 No.6

In the azoospermic patients, there are many of undiagnosed factors related to genetic bases. Among them, Klinefelter's syndrome (47,XXY; KS) and Y-chromosomal microdeletion with normal karyotype(46,XY; YMNK) are the most frequent causes of male infertility. This research focused on the comparative analysis of YMNK (n = 66) and K5 (n = 30) patients suffered from male infertility in Korean population. We used the polymerase chain reaction (PCR) approach including 19 pairs of sequence-tagged site (STS) primers for detecting the Y-chromosomal microdeletion on AZFa, b, c regions, indicating that Y chromosomal microdeletions were almost evenly occurred in AZF all regions in Korean population. Comparative analysis indicated that 34.9% YMNK and 73.4% KS patients harbored the microdeleted Y-chromosome. It seems to be high instability of Y-chromosome in KS patients than that of YMNK infertility patients. Taken together, genome instability containing microdeletion could bring male infertility with the disturbance of normal spermatogenesis. 무정자증 환자의 경우, 정확히 알려지지 않은 유전적인 요인들이 남성불임과 연관되어 있다. 그들 중 클라인펠트 증후군(KS)과 정상 핵형의 남성에게서 발견되는 Y염색체상의 미세결실 증상(YMNK)은 남성 불임의 가장 빈번한 원인이라고 할 수 있다. 본 연구는 한국인 집단에서 남성불임으로 고통 받고 있는 YMNK (66 개체)와 KS(30 개체) 환자들을 비교 분석 하였다. Y염색체 상의 AZFa,b,c 영역의 미세결실을 분석하기 위해 19개의 STS 프라이머를 이용해 PCR분석을 하였다. 실험 결과 YMNK의 34.9%와 KS의 73.4%가 미세결실을 포함하고 있었다. 이점으로 미루어보아 YMNK환자보다 KS환자의 경우가 Y염색체의 불안정성이 더욱 높은 것으로 사료된다. 결론적으로 미세결실을 포함하는 제놈의 불안정성은 정상적인 정자형성 과정을 방해하여 남성불임을 초래할 수 있을 것이다.

Expression analysis of RBMY1, CDY1, and VCY2 genes in Korean male infertility

허재원,김우영,김대수,하홍석,박남철,최욱환,남기만,최진,김희수,Huh, Jae-Won,Kim, Woo-Young,Kim, Dae-Soo,Ha, Hong-Seok,Park, Nam-Chul,Choi, Ook-Hwan,Nam, Ki-Man,Choi, Jin,Kim, Heui-Soo Korean Society of Life Science 2007 생명과학회지 Vol.17 No.5

무정자증에 영향을 미치는 AZFa, b, c 영역은 남성불임환자에서 잦은 미세결실이 발견됨으로써 정자형성과정에서 중요한 역할을 할 것으로 주목 받아왔다. 이들 영역에 있는 유전자중 RBMY1, CDY1 그리고 VCY2유전자는 고환에서 남성의 생식선 세포의 분화와 연관되어 있는 것으로 알려졌다. 42명의 무정자증 환자의 고환조직을 RT-PCR법으로 분석해본 결과 RBMY1, CDY1 그리고 VCY2 유전자는 각각 34%, 66%, 그리고 27%의 환자에서 발현되지 않는 것으로 조사되었다. RBMY1 과 VCY2유전자가 발현되지 않는 개체는 CDY1유전자도 역시 발현이 되지 않았다. 세르토리 세포만 가진 환자에서는 CDY1 유전자가 발현되지 않았다. 따라서, CDY1 유전자는 한국인 집단에서 정자형성과정의 필수적인 요인인 것으로 사료된다. Azoospermia factor(AZFa, b, and c) regions have been focused on their involvement in the spermatogenic process by frequent observation of microdeletion in male infertility. Among the azoospermia factors, RBMY1, CDY1, and VCY2 genes are strongly associated with the male germinal cell differentiation and development in testis. Using RT-PCR approach, expression patterns of RBMY1, CDY1, and VCY2 genes are examined in testicular biopsy specimens from 42 Korean azoospermic patients. No expression of RBMY1, CDY1, and VCY2 genes appeared as 34%, 66%, and 27% of the male infertility, respectively. Patients who had no expression of RBMY1 and VCY2 genes also showed negative expression of the CDY1 gene in their testis tissues. All Sertoli cell-only syndrome patients showed no expression of the CDY1 gene. Taken together, the CDY1 gene expression seems to be necessary factor to complete spermatogenesis in Korean population.

신생아에서 수질자궁증과 수신증의 원인이 된 처녀막 폐쇄증

백윤지 ( Yun Ji Baek ),김정태 ( Jeong Tae Kim ),장성규 ( Sung Kyoo Jang ),최욱환 ( Ook Hwan Choi ) 대한산부인과학회 2007 Obstetrics & Gynecology Science Vol.50 No.2

Imperforate hymen is a common congenital malformation, but usually remains asymptomatic and not detected until menarche. Neonatal hydrometrocolpos caused by imperforate hymen is reported to be very rare. We report a case of hydrometrocolpos in newborn presenting with pelvic mass and bulging membrane in vaginal introitus causing both hydronephrosis which is treated surgically with good result.

생식기능 장애 환자에서의 세포유전학적 이상

윤정섭 ( Jeong Sup Yun ),장성규 ( Sung Kyoo Jang ),최욱환 ( Ook Hwan Choi ) 대한산부인과학회 2007 Obstetrics & Gynecology Science Vol.50 No.5

Objective: The aim of this study was to investigate the relationship between chromosome abnormalities and male or female reproductive dysfunction and to be convinced of the role of pericentric inversion of chromosome 9 (inv (9)) on human phenotypes. Methods: Between Jan. 1995 and Dec. 2003, results of 1713 chromosomal analyses which were referred to our cytogenetic laboratory were analyzed. Study groups consisted of 658 cases of men and 18 cases of women with unexplained infertility, 65 cases of men and 109 cases of women with history of recurrent spontaneous abortion, 78 cases of women with primary amenorrhea, 61 cases of women with secondary amenorrhea and, 382 cases of men and 342 cases of women with no reproductive dysfunction (control group). The incidence of inv (9) among each group was compared with control group. Results: Chromosomal abnormalities were found in 110 cases (16.7%), 2 cases (11.1%), 3 cases (4.6%), 15 cases (13.8%), 29 cases (37.2%) and 10 cases (16.4%) in each group. The incidence of chromosomal abnormalities in male infertility was higher than previous reports, and 10 cases of inv (9) were detected in male infertility group. In cases of women with infertility and secondary amenorrhea, we couldn`t find the relevance between reproductive dysfunction and chromosomal abnormality. In cases of women with recurrent spontaneous abortion, 6 cases (5.5%) had autosomal translocation and 7 cases (6.42%) had inv (9). In cases with primary amenorrhea, most chromosomal abnormalities found were related to sex chromosome such as Turner`s syndrome, similar to other investigations. Thirty three cases of inv (9) was detected among the whole 1713 chromosomal analyses (1.93%). In cases of male infertility, 10 cases (1.52%) had inv (9), not significantly different with male control group. But 7 cases (6.42%) of inv (9) in women with recurrent spontaneous abortion were significantly higher than female control group (p<0.05). Conclusion: Because considerable proportion of patients with reproductive dysfunction had various cytogenetic abnormalities, the chromosomal analysis should be considered as a diagnostic tool in the evaluation of reproductive dysfunction such as infertility, recurrent spontaneous abortion, and amenorrhea. We also found that Inv (9) had a significantly increased incidence in female recurrent spontaneous abortion.