Pyrogen에 依한 發熱에 있어서 解熱劑와 Prednisolone이 미치는 影響

本動物實驗으로 pyrogen (peptonee 사용하였음)에 依한 發熱現象에 對하여 어떤解熱劑를 使用하는 것이 適當한가에 對하여 다음과 같은 結論을 얻었다. 1) 溫熱中樞를 鎭靜시키는 effect가 있는 aminopyrine(pyranidone)을 使用하는 것이 가장 適當하며 2) aminopyrine 單獨投與時보다도 合成副腎皮質 Hormone을 倂用하는 것이 一層더 正確하게 解熱作用을 나타낸다. 3) 溫熱中樞를 鎭靜시키며 熱生産을 抑制한다는 Quinine-Ncl와 acetyl salicylate 와같은 系統의 Na-salicylate와 같은 解熱劑는 aminopyrine 에 比해 效果的이 아니었다. 4) 效果的이 아닌 Quinine-Ncl 및 Na-salicylate도 prednisolone 과 倂用한다면 臨床的 價値가 있다고 본다목차 = 0 第一章 緖論 = 1 第二章 實驗對象 및 方法 = 3 第三章 實驗 成績 = 5 第一節 豫備 實驗 = 5 第二節 本 實驗 = 13 第四章 總括 及 考察 = 26 第五章 結論(초록으로 간주하여 구축) = 2

블라인드가 이중외피의 열적 특성에 미치는 영향에 관한 연구

학위논문(석사)--서울대학교 대학원 :건축학과,2004.Maste

Regulation of acetyl CoA carboxylase mRNA in rat liver high carbohydrate diet and insulin

의학과/박사[한글] 백서를 장시간 굶기면 간장 세포막의 insulin수용체가 급격히 증가한다. 이런 쥐에 고함수탄수식이를 재투여하여 혈액내 insulin이 증가하면 insulin과 수용체가 결합하여 그 복합체가 세포내로 신속히 이동되어 세포내외 insulin농도가 증가하고, 이 증가된 insuli n이 핵막의 insulin수용체와 결합하면 핵으로부터 mRNA efflux를 증가시켜 증가된 mRNA가 lipogenic enzyme의 생합성을 증가시키는 요인이라고 보고한 바 있으며(Whang등, 1982; Yoon등, 1983), 그 중에서도 간장 세포질내 glucose-6-phosphate dehydrogenase(G-6-PDH) 를 합성하는 mRNA가 증가되어 G-6-PDH합성증가가 일어나는 기전을 일부 밝힌바 있다(Kim등, 1985). 또한 insulin과 포도당은 간장 세포질내 fatty acid synthetase(FAS)mRNA 함량을 증가시켜 FAS 생합성이 증가된다는 기전일부를 밝힌 바 있다(Suh등, 1986). 또한 백 서간장 세포에서 insulin은 lipogenic enzyme인 G-6-PDH와 FAS의 mRNA생합성 및 핵으로부터 efflux를 자극하여 세포질내에서 lipogenic enzymes생합성을 증가시키는 사실을 실험적으로 구명하였다(Lee 등, 1987). 본 연구는 지방산 생합성의 rate limiting step에 관여하는 효소인 acetyl CoA carboxylase가 장시간 굶긴 백서에 고함수탄소 식이 및 insulin을 처리하면 백서 간장 세포질내 acetyl CoAcarboxylase함량이 어떻게 조절되는지를 밝히기 위하여 이 효소를 정제 분리하 고, 이에 대한 항체를 얻어 이를 가지고 면역화학법에 의하여 이 효소를 합성하는 특이 po1ysome을 정제 분리하여, 이 효소의 합성 증가기전의 일부를 밝히기 위하여 실험에 착수하여 다음과 같은 결과를 얻었다. 백서를 3일간 굶긴다음 고함수탄소 식이를 3일간 재투 여한 후 간장세포에서 acetyl CoAcarboxylase를 polyethylene glycol 및 ammonium sulfate를 처리한 후 Sepharose 2B gelfiltration chromatography를 시행하여 1,552배 정제 분리하였으며 이 효소의 specific activity는 ㎎당 3.88units이었다. 이 효소를 사용하여 토끼에서 얻은 항혈청과 간장 세포 균등액을 20,Oeoxg로 원침하여 얻은 상층액, 3% polyethylene glycol 추출액과 작용시켜 Ouchterlony double immunodiffusion 실험을 한 결과 항혈청이 15㎕는 간장세포 균등액과 반응하여 서로 연결된 한개의 침전대가 형성된 것으로 보아 동일한 항혈청이 생성된 것을 확인하였다. 이 항혈청을 가지고 proteins Sepharose chromatography를 시행하여 얻은 IgG를 간장세포 균등액을 5% p olyethylene glycol로 추출한 용액에 IgG농도를 증가시켜 첨가하면 acetyl CoA carboxylase활성은 IgG농도에 비례하여 억제된 사실로 미루어 가토 혈청에서 분리한 IgG에는 acetyl CoA carboxylase에 대한 항체가 생성되었음을 확인하였다. 이 항체를 가지고 3일간 굶 긴 백서에 insulin과 고함수탄소 식이를 처리한 후 백서간장 세포질을 분리하여 세포질내 acetyl CoA carboxylase 함량을 면역화학 방법으로 정량한 결과 새로 합성된 이 효소에 ·삽입된 (3**H)-leucine의 활성치는 insulin(1.5 units/100g B.W.) 처리군은 대조군에 비하여 3배, 고함수탄소 식이 처리군은 10배가 증가되고, 세포질내 총 단백질 합성량에 비하여 이 효소 합성 비율은 insulin처리군에서 4배, 고함수탄소 식이 처리군에서 10배 증가하였다. 또한 이들 백서간장 세포질내 acetyl CoA carboxylase를 합성하는 특이 Polysome내 RNA는insulin 처리군은 279%, 고함수탄소 식이 처리군은 365%가 증가하였으며, polysome내 acetyl CoAcarboxylase nascent chain은 insulin 처리군은 153%, 고함수탄소 식이 처리군 은 311%가 증가하였다. 이상과 같은 실험결과로 미루어 보아 insulin과 고함수탄소 식이에 의하여 간장세포내 acetyl CoAcarboxylase 함량 증가는 이 효소를 합성하는 polysome내 mRNA 함량증가로 인한 결과로 사료된다. Regulation of Acetyl CoA Carboxylase mRNA in Rat Liver by High carbohydrate Diet and Insulin Dong Hee Choi Department of Medical Science The Graduate School Yonsei University (Directed by Professor Yoon Soo Kim, M.D.,Ph.d.) It has been reported that insulin receptors in the plasma membrane of liver cell rapidly increase in fasting rats, and that the intracellular insulin concentration could be increased by the rapid internalization of insulin-receptor complex formed from the increase of blood insulin level as rats were refed with high carbohydrate diet (Whang et al., 1982; Yoon et al.,1983). The increased intracellular insulin binds to the insulin receptor in nuclear membrane and stimulates the efflux of mRNA from nucleus, which may be a cause of the increased biosynthesis of lipogenic enzymes. It was an example to demonstrate that the increased biosynthesis of glucose-6-phosphate dehydrogenase(G-6-PDH) resulted from an increased amount of mRNA for G-6-PDH (Kim et al., 1985). It has been also demonstrated that insulin and glucose stimulated biosynthesis of fatty acid synthetase (FAS) by the increase of cytoplasmic mRNA for FAS (Suh et al., 1986). The fact that insulin stimulates the synthesis and nuclear efflux of mRNA for G-6-PDH and PAS, both lipogenic enzymes, has been proved by Lee et al (1987). In this study, the change of acetyl CoA carboxylase content in liver cytosol of rats refed with high carbohydrate diet or treated with insulin after fasting, was measured by immunoassay method in order to clarify the control mechanism for the amount of acetyl CoA carboxylase. The results are as follows. Acetyl CoA carboxylase was purified 1,552 folds with a specific activity of 3.88 units/㎎ from rat liver refed with a high carbohydrate diet for 3 days after 3 day fasting, by the precipitation with polyethylene glycol and ammoium sulfate, and followed by Sepharose 2B gel filtration. 15㎕ of rabbit antiserum obtained by immunization with purified acetyl CeA carboxylase was precipitated with the 27,000xg supernatant of rat liver homogenate in Ouchterlony double immunodiffusion and showed a single precipitin, indicating the antiserum for anti-acetyl CoA carboxylase was produced. Treatment of insulin and feeding a high carbohydrate diet of rats resulted in the increase of acetyl CoA carboxylase in liver cytosol by 3 times in the insulin treated group and 10 times in the high carbohydrate diet group as (3**H) -leucine incorporation into the enzyme was measured by immunochemical method. The synthetic ratios of this enzyme to total cytosolic proteins were 4 times higher in insulin treated group and 10 times higher in high carbohydrate diet group, compared to the control group. The polysomal RNA contents for acetyl CeA carboxylase in rat liver cytosol were 279% of the control in insulin treated group and 365% of the control in high carbohydrate diet group, and acetyl CoA carboxylase nascent chains in polysome were 158% of the control in insulin treated group and 311% of the control in high carbohydrate diet group. From these results, it is assumed that the increase of acetyl CoA carboxylase content in the rat liver cell by insulin and high carbohydrate diet resulted from the increased polysmal mRNA for the synthesis of this enzyme, which is directly related to the biosynthesis of this enzyme. [영문] It has been reported that insulin receptors in the plasma membrane of liver cell rapidly increase in fasting rats, and that the intracellular insulin concentration could be increased by the rapid internalization of insulin-receptor complex formed from the increase of blood insulin level as rats were refed with high carbohydrate diet (Whang et al., 1982; Yoon et al.,1983). The increased intracellular insulin binds to the insulin receptor in nuclear membrane and stimulates the efflux of mRNA from nucleus, which may be a cause of the increased biosynthesis of lipogenic enzymes. It was an example to demonstrate that the increased biosynthesis of glucose-6-phosphate dehydrogenase(G-6-PDH) resulted from an increased amount of mRNA for G-6-PDH (Kim et al., 1985). It has been also demonstrated that insulin and glucose stimulated biosynthesis of fatty acid synthetase (FAS) by the increase of cytoplasmic mRNA for FAS (Suh et al., 1986). The fact that insulin stimulates the synthesis and nuclear efflux of mRNA for G-6-PDH and PAS, both lipogenic enzymes, has been proved by Lee et al (1987). In this study, the change of acetyl CoA carboxylase content in liver cytosol of rats refed with high carbohydrate diet or treated with insulin after fasting, was measured by immunoassay method in order to clarify the control mechanism for the amount of acetyl CoA carboxylase. The results are as follows. Acetyl CoA carboxylase was purified 1,552 folds with a specific activity of 3.88 units/㎎ from rat liver refed with a high carbohydrate diet for 3 days after 3 day fasting, by the precipitation with polyethylene glycol and ammoium sulfate, and followed by Sepharose 2B gel filtration. 15㎕ of rabbit antiserum obtained by immunization with purified acetyl CeA carboxylase was precipitated with the 27,000xg supernatant of rat liver homogenate in Ouchterlony double immunodiffusion and showed a single precipitin, indicating the antiserum for anti-acetyl CoA carboxylase was produced. Treatment of insulin and feeding a high carbohydrate diet of rats resulted in the increase of acetyl CoA carboxylase in liver cytosol by 3 times in the insulin treated group and 10 times in the high carbohydrate diet group as (3**H) -leucine incorporation into the enzyme was measured by immunochemical method. The synthetic ratios of this enzyme to total cytosolic proteins were 4 times higher in insulin treated group and 10 times higher in high carbohydrate diet group, compared to the control group. The polysomal RNA contents for acetyl CeA carboxylase in rat liver cytosol were 279% of the control in insulin treated group and 365% of the control in high carbohydrate diet group, and acetyl CoA carboxylase nascent chains in polysome were 158% of the control in insulin treated group and 311% of the control in high carbohydrate diet group. From these results, it is assumed that the increase of acetyl CoA carboxylase content in the rat liver cell by insulin and high carbohydrate diet resulted from the increased polysmal mRNA for the synthesis of this enzyme, which is directly related to the biosynthesis of this enzyme.restrictio

(The) sociodemographic characteristics of first-trimester induced abortion acceptors

의학과/석사[한글] 임신중절은 출산력 억제의 가장 강력한 수단으로, 우리나라에서는 1962년 가족계획사업이 국가시책으로 채택되고 1973년 모자보건법으로 임신중절이 부분적으로 합법화되면서 계속 증가추세를 나타내고 있으며 인구성장억제에 기여해온 것도 사실이다(임등, 1979 ; 변등, 1979). 최근에는 개방풍조와 더불어 미혼여성의 임신중절이 사회문제화 되어 가고 있고, 기혼부인에서도 원하는 수의 자녀를 낳고난 후에는 피임에 의존하기 보다는 임신중절을 원치않는 임신의 해결책으로 이용하는 경향이 있어 도덕적, 경제적 문제와 함께 모성건강에도 해를 끼칠 것으로 생각된다. 저자는 1981년 3월부터 1983년 12월까지 연세대학교 의과대학 세브란스병원 산부인과 수태조절실과 1985년 3월, 1개월간 서울시내의 산부인과 병·의원 각 1개소, 그리고 동기간 동안 경기도 부천시의 종합병원 1개소, 산부인과의원 3개소등 총 7개 병 ·의원에서 임신 12주 이내에 임신중절술을 시행받은 1, 000예를 대상으로 그들의 사회 ·인구학적, 생리적 특성과 임신중절시의 임신기간간의 관계를 조사하여 다음과 같은 결과를 얻었다. 1. 대상자의 연령분포는 25 -29세군이 44 %로 가장 많았으며 시술당시 평균연령은 29. 7세이었다. 2. 도시에 거주하는 부인이 96.7 %이고 대상자의 80%에서 직업이 없었다. 대상자 중 무종교자가 51 %였다. 3. 기혼부인이 93.7 %, 미혼여성이 3.6 %였다. 4. 피시술자와 그 남편의 교육수준을 보면 고등학교학력 이상인 사람이 각각 78 %, 92 %이었다. 5. 피시술자의 45 %는 생존자녀수가 2명이었고 10.5 %는 자녀가 없었다. 6. 피시술자의 64 %가 반복임신중절자였고 이중에서는 1회 경험이 가장 많았다. 7. 임신중절 사유로는 단산을 목적으로 한 경우가 가장 많았고 경제적 이유가 16.2 %, 터울조절이 15.6 %였고 건강상의 이유는 3 % 미만이었다. 8. 임신 전에 피임을 시행한 대상자가 48 %였고 피임법 중에서는 콘돔, 주기법등의 재래식 방법의 이용이 많았다. 9. 임신중절 시의 임신기간은 5 - 6주가 46 %로 가장 많았고 8주까지가 72 %를 차지했다. 10. 최종 분만과 이번 임신중절까지의 간격이 54 %의 25개월 이상이었고 20 %에서는 12개월 이하였다. 11. 임신중절 피시술자의 특성 중 임신 7주까지 중절을 받을 비교위험도가 통계적으로 유의한 특성은 종교, 결혼상태, 교육수준, 현존자녀수, 마지막 분만과 임신중절까지의 간격등 이었고, 임신중절 경험유무는 자녀유무를 표준화했을 때 통계적으로 유의했으며 자녀유무는 피임실천을 표준화했을 때 통계적으로 의의가 없었다. [영문] Induced abortion has been known as one of the most powerful measures for the fertility control. In Korea, the incidence of induced abortion has increased steadily since the early 1960's, thereby it has contributed to the suppression of population growth. Recently, in addition to the emergence of premarital induced abortion as a serious social problem the trend has been noted in married women that they tend to resort to induced abortion rather than contraception to avoid unwanted pregnancy after the completion of their family. The study herein reported the relationship between the sociodemographic, reproductive and medical characteristics of abortees and the duration of gestation at the time of accepting abortion. The abortees consisted of 1000 women who obtained induced abortion within 12 weeks of gestation. Among the 1000 women, 501 received abortion at Severance Hospital from Mar. 1981 to Dec. 1983, and the remaining 499, at 2 Ob. Gyn. clinics in Seoul and 1 hospital and 3 Ob. Gyn. clinics in Buchun City in Mar. 1985. The results obtained are as follows: 1. In the age distribution of the abortees, women aged 25-29 occupied 44%. The mean age was 29.7 years. 2. 80% of the aborted women was not employed, and 51% had no religion. 3. 93.7% of the women was married. 4. In viewing of the educational attainment, 78% of the abortees had graduated high school or more. 5. 45% of the acceptors had 2 children, and 10% was childless. 6. 64% of the women was repeat aborters, and those who had one previous induced abortion took the first rank among them. 7. Regarding to the reason for abortion, 60% obtained induced abortion because they didn't want any more children, 16.2%, because of economic problem, 15.6%, for child spacing. 8. 48% of the abortees practiced some contraceptive method before this pregnancy terminated by induced abortion. And traditional methods such as condom and rhythm method were commonly used. 9. 46% of the abortions was performed within 6 weeks from LMP and 72%, within 8 weeks. 10. 20% of the accepters obtained abortion within 12 months after the last delivery, and in 54% of the women, the abortion was performed after 25 months since last delivery. 11. Of the characteristics of the abortees, those which had higher relative risk for obtaining earlier abortion (within 7 weeks)were religion, marital status, educational attainment, number of Living children and the interval since last delivery.restrictio

Evaluation of the impact of adhesive-bonded materials on indoor air quality based on VOC emission modeling

학위논문(박사) --서울대학교 대학원 :건축학과,2010.2.Docto

Ethanol 투여 흰쥐에서 간손상 지표 및 약물대사효소에 대한 인삼 Saponin의 영향

학위논문(석사)--서울대학교 보건대학원 :환경보건학과 환경보건전공,1999.Maste

Human papillomavirus type 16 and 18 DNAs a in relation to cervical intraepithelial n

의학과/박사[한글] Human papillomavirus (HPV) type 16과 type 18은 자궁경부암 및 진행성 경향이 높은자궁경부 상피내종양 조직에서 주로 숙주 세포 염색체내에 삽입된 상태로 높은 출현 빈도를 보이고 있으며(Durst등, 1983 ; Crum등, 1984, 1985 ; Syrjanen등, 1985), 이들 바이러스 genome중에서 특히 transacting factor (Schwarz등, 1985) 또는 promoter/enhancer로 작용 하는 부위(Durst등, 1987) 및 이들 부위의 세포 변형 능력에 대한 연구가 진행중이다(Tsunokawa등, 1986a). 본 연구에서는 HPV type 16, type 18 DNA와 자궁경부 상피내종양 및 침윤성 자궁경부암과의 연관성에 대해 알아보고자 하였다. 자궁경부 상피내종양 12예, 침윤성 자궁경부암 34예 자궁경부의 전이성 선암 1예 및 대조군(만성자궁경부염) 24예 등 총 71예에서 자궁경부 조직을 생검하여 세포내 DNA를 추출한 다음 (32)**P-labelled HPV type 16, type 18 DNA를 각각 probe로 사용하여 dot blotting hybridization 및 자가방사법(autoradiography)을 시행하여 자궁경부 조직에서 HPV type 16 또는 type 18 DNA의 출현 빈도를 조사한 결과 type 16/1ype 18 DNA의 출현 빈도는 침윤성 자궁경부암과 자궁경부 상피내종양군에서 각각 58.8%, 58.3%로서 대조군의 8.4%에 비해 의의있게 높았다. 자궁경부암 환자에서 병기(stage)와 자궁경부 조직의 HPV DNA출현 빈도에는 의의있는 상관 관계가 없었으며, 조직학적 세포 형태별로 볼때 편평상피암에서 HPV type 16/type 18의 출현 빈도는 56.7%였고, 선암 2예 중 1예 및 선편평상피암 1예에서는 type 16과 type 18, type 18이 각각 검출되었다. 자궁경부암 환자의 자궁경부 조직에서 dot blotting hybridization 결과 HPV type 16,type 18DNA가 단독으로 검출되었던 환자중 8예, 5예의 DNA를 각각 여러가지 제한 효소로처리하여 Southern blotting hybridization및 자가방사법을 시행하여 세포내에서 HPV type 16, type 18 genome의 존재 형태를 분석한 결과 HPV type 16 genome은 8예중 7예에서 multiple copy로 숙주세포 염색체내의 여러 부위에 삽입되어 있었고 그 삽입 양상은 다양하였지만 8예에서 모두 바이러스 genome중 PstI으로 절단되어 나타나는 1.78 kb에 해당하는 B조각이 보존되어 있었다. HPV type 18 genome은 5예에서 모두 multiple copy로 숙주세포 염색체내의 여러 부위에 다양하게 삽입되어 있었다. 이상의 연구결과를 볼때, 한국여성에서 자궁경부조직의 HPV type 16, type 18의 감염은 자궁경부의 편평상피암 뿐 아니라, 선암, 선편평상피암의 발생에도 관여할 것으로 사료되며, type 16의 경우 자궁경부 조직 세포내에서 바이러스 genome중 1.78 kb의 B조각의 존재유무가 암의 발생, 진행등에 중요할 것으로 사료된다. 따라서 HPV type 16, type 18DNA가 자궁경부암의 확실한 발암 인자임을 밝히기 위하여 앞으로 이들 바이러스 genome내에서 발암 능력을 갖는 부위를 규명하기 위한 연구가 필요할 것으로 사료된다. Human Papillomavirus Type 16 and 18 DNAs in Relation to Cervical Intraepithelial Neoplasia and Invasive Cervical Carcinoma Dong Hee Choi Deparment of Medical Science The Graduate School, Yonsei University (Directed by Professor Tchan Kyu Park, M.D., Ph.D.) Human papillomavirus (HPV) type 16 and 18 DNAs are known to be found frequently in the biopsy specimens from the lesions of both cervical intraepithelial neoplasia (CIN) with high tendency for progression and invasive cervical carcinoma (ICC), and their integration into human genome has been documented (Durst et al,1983; Crum et al,1984; Syrjanen et al,1985). It has been suggested that some regions within the viral genome may play some role as a transacting factor (Schwarz et at, 1985) or a promoter/enhancer (Durst et al, 1987, and efforts are now directed to showing the transforming activity of these regions (Tsunokawa et al, 1986a). The purpose of this study is to identify the relationship of HPV type 16 and 18 DNAs to CIN and ICC by analyzing the occurrence of their DNA sequences in the cells of the cervical tissues and their physical states in the cancerous cervical tissues. Cellular DNAs were extracted from the cervical tissues of a total of 71 cases; 21 CINs, 34 ICCs, 1 metastatic adenocarcinoma of the cervix, and 24 controls with chronic cervicitis. Using (32)**P-labelled HPV type 16 or 18 DNA as a probe, HPV DNA typing was performed by dot blotting hybridization and autoradiography. The following results were obtained: The positive rates for HPV type 16 and/or 18 DNA in the ICC and CIN cases were 58.8% and 58.3% respectively; they were significantly higher than that of the control group (8.4%). In the cases with ICC, no significant difference in positive rate for HPV DNA according to stage was noted. According to histological cell type, HPV type 16 and 18 DNAs were detected in 43.3% and 23.3% each in squamous cell carcinoma cases. HPV type 16 and 18 DNAs were detected in 1 of 2 cases of adenocarcinoma, and only HPV type 18 DNA was detected in 1 adenosquamous carcinoma case. Cellular DNAs from 8 and 5 cases of ICC each positive in HPV type 16 DNA alone and type 18 DNA alone were treated with several restriction enzymes. They were then processed with Southern blotting hybridization and autoradiography to evaluate the physical states of their viral genomes. Seven of the 8 cases haying HPV type 16 genome and all 5 cases having HPV type 18 genome had their viral genomes integrated as multiple copies at multiple sites of their host chromosomes, and the patterns of integration varied. It was noted that B band of 1.78kb of HPV type 16 genome was retained in all 8 cases. This study demonstrated that HPV type 16 and 15 DNAs in cervical tissues might be considered to be potentially important in the development of cervical cancer of various cell types including adeno-, adenosquamous as well as squamous cell carcinomas. And the role of HPV type 16 in He development or progression of cervical cancer in the presence of 1.78kb of B fragment of its viral genome in cervical tissue was suggested. It seems that further research of several specific sites having oncogenic potential within the viral genome would be desirable to determine the causative nature of HPV type 16 and 18 DNAs in cervical carcinoma. [영문] Human papillomavirus (HPV) type 16 and 18 DNAs are known to be found frequently in the biopsy specimens from the lesions of both cervical intraepithelial neoplasia (CIN) with high tendency for progression and invasive cervical carcinoma (ICC), and their integration into human genome has been documented (Durst et al,1983; Crum et al,1984; Syrjanen et al,1985). It has been suggested that some regions within the viral genome may play some role as a transacting factor (Schwarz et at, 1985) or a promoter/enhancer (Durst et al, 1987, and efforts are now directed to showing the transforming activity of these regions (Tsunokawa et al, 1986a). The purpose of this study is to identify the relationship of HPV type 16 and 18 DNAs to CIN and ICC by analyzing the occurrence of their DNA sequences in the cells of the cervical tissues and their physical states in the cancerous cervical tissues. Cellular DNAs were extracted from the cervical tissues of a total of 71 cases; 21 CINs, 34 ICCs, 1 metastatic adenocarcinoma of the cervix, and 24 controls with chronic cervicitis. Using (32)**P-labelled HPV type 16 or 18 DNA as a probe, HPV DNA typing was performed by dot blotting hybridization and autoradiography. The following results were obtained: The positive rates for HPV type 16 and/or 18 DNA in the ICC and CIN cases were 58.8% and 58.3% respectively; they were significantly higher than that of the control group (8.4%). In the cases with ICC, no significant difference in positive rate for HPV DNA according to stage was noted. According to histological cell type, HPV type 16 and 18 DNAs were detected in 43.3% and 23.3% each in squamous cell carcinoma cases. HPV type 16 and 18 DNAs were detected in 1 of 2 cases of adenocarcinoma, and only HPV type 18 DNA was detected in 1 adenosquamous carcinoma case. Cellular DNAs from 8 and 5 cases of ICC each positive in HPV type 16 DNA alone and type 18 DNA alone were treated with several restriction enzymes. They were then processed with Southern blotting hybridization and autoradiography to evaluate the physical states of their viral genomes. Seven of the 8 cases haying HPV type 16 genome and all 5 cases having HPV type 18 genome had their viral genomes integrated as multiple copies at multiple sites of their host chromosomes, and the patterns of integration varied. It was noted that B band of 1.78kb of HPV type 16 genome was retained in all 8 cases. This study demonstrated that HPV type 16 and 15 DNAs in cervical tissues might be considered to be potentially important in the development of cervical cancer of various cell types including adeno-, adenosquamous as well as squamous cell carcinomas. And the role of HPV type 16 in He development or progression of cervical cancer in the presence of 1.78kb of B fragment of its viral genome in cervical tissue was suggested. It seems that further research of several specific sites having oncogenic potential within the viral genome would be desirable to determine the causative nature of HPV type 16 and 18 DNAs in cervical carcinoma.restrictio

(The) role of chemotherapy in management of carcinoma of the cervix

의학과/석사[한글] 자궁경부암의 치료에 있어 항암화학요법은 수술이나 방사선 치료에 부적합한 재발암이나 진행된 암에 국한되어 고식적으로 사용되어왔으나, 최근에는 치료실패율이 높은 예후 인자를 가졌거나 행된 암에서 치료실패율을 감소시키고 무병생존율을 증가시키기위하여 수술이나 방사선치료와 함께 병행요법으로 이용되고 있다. 본 연구는 1977년 6월부터 약 8년간 연세의대 부속 세브란스 병원 산부인과에서 자궁경부암으로 항암화학요법을 단독 또는 방사선치료나 근치건 수술 등과 병행하여 시행했던 총 66예 (재발암17예, Ⅱ기암17예, Ⅲ기암23예, Ⅳ기암6예, I^^B 기암 3예 )를 대상으로 하여 그 치료효과 및 독성을 조사하여 다음과 같은 결과를 얻었다. 1. 항암화학요법을 시행하여 치료반응을 판정할 수 있었던 62예중 완전반응 6예(9.6%), 부분반응 36예(58.1%)로 67.7%에서 치료효과를 보였다. 2. 기왕 방사선치료 및 수술을 받았던 재발암과 이전에 치료를 받은 적이없는 일차암에서 항암화학요법의 효과를 비교해 보면 재발암에서 43.7%의 반응율을 보인반면 일차암에서는 76.1%의 높은 치료반응율을 보였다. 3. 기왕치료력이 없는 Ⅱ기 또는 Ⅲ기암의 일차치료로서 항암화학요법을 받았던 21예에서 3-15개월 추적관찰중 전 예에서 완전 관해를 보였는데 암 파급정도(stage), 병소의 크기, 연령이 동일한 방사선 치료만을 시행했던 대조군 21예에서는 16예(76.1%)만 완전관해 , 부분관해 3예(14.3%), 고정성 질환 1예 (4.8%) 및 진행성 질환 1예 (4.8%)였고, 완전관해를 보였던 16예중 1예는 7개월만에 재발하였다. 4. 병소의 크기가 클수록 항암화학요법의 치료효과는 낮아지는 경향을 보였으며 병소의 크기가 5.0㎝ 이상인 술통형의 병소에서 치료전 항암화학요법을 먼저 시행했을 경우 완전반응율100%로 방사선 치료만 시행한 경우의 55.6%에 비해 치료효과가 좋았다. 5. 자궁경암 근치술후 보조적 항암화학요법을 시행했던 I^^B기암 3예에서 6-16개월 추적관찰중 재발은 없었다. 6. DDP-5FU복합제의 주된 독성으로 오심 및 구토, 탈모증, 과립백혈구 감소등의 골수기능 저하, 신독성 및 간독성 등이 있었으며 이독정 때문에 항암제의 투여가 중단 또는 지연된 경우가 18예 (32.7%)있었지만 대개 임상 증상없이 비정상적인 검사소견을 보였었으 며 치료후 곧 정상으로 회복되었다. 또 항암화학방사선요법을 시행했던 26예중 6예 (23.1%)는 방사선치료도중 백혈구수가 감소하였으나 임상증상은 없었으며 치료를 중단할 정도로 심하지는 않았다. THE ROLE OF CHEMOTHERAPY IN MANAGEMENT OF CARCINOMA OF THE CERVIX Dong Hee Choi, M.D. Department of Medical Science The Graduate School, Yonsei University (Directed by Professor Tchan Kyu Park, M.D.) In management of the carcinoma of cervix, the chemotherapy had been used palliatively for the recurrent and the far advanced cancers that were net amenable to radiotherapy or surgery. Recently, in order to prevent or to lewer the treatment failures (recurrent or persistent cancers) and to improve the disease free survivals of the patients, the chemotherapy had been tried in combination with radiotherapy or/and surgery as primary treatment in cases with poor prognostic factors showing high treatment failure rates and in advanced cancers. In this study 66 patients with cervical cancer including 17 cases with recurrent cancers, 3 cases with stage IB, 17 cases with stave Ⅱ, 23 cases with stage Ⅲ and 6 cases with stage Ⅳ, treated with chemotherapy, alone or in combination with surgery or/and radiotherapy at the Department of Obstetrics and Gynecology, YUMC, were selected, and the response rates and toxicities were evaluated according to the therapy. The results of this study were as follows; 1. In 62 cases the response rates to chemotherapy were evaluated; complete response was seen in 6 cases (9.6%), and partial response in 30 cases (58.1%), so the total response rate to the chemotherapy was 67.7%. 2. The response rates to chemotherapy were compared between the previously irradiated recurrent cancers and the previously untreated primary cancers (stage Ⅱ, Ⅲ, Ⅳ). The response rate was 43.7% with recurrent cancers, which was lower than 76.1% of primary cancers. 3. In cases with stage Ⅱ & Ⅲ cancers, the response rate to chemoradiotherapy was compared to radiotherapy alone (control group). During the 3-L5 months follow up all of 21 cases who had received chemoradiotherapy showed complete response, while in the control group, complete responses were seen in 16 cases (76.1%) only, 3 cases (14.3%) of partial response, 1 case (4.8%) of stable disease and 1 case (7.8%) of progressive disease. In radiotherapy alone group, 1 case showing the complete response had recurrence of the cancer 7 months after the therapy. 4. In primary cancers, the response rates to chemotherapy seemed to decrease with increasing size of the lesion, and especially in cases with barrel shaped lesion with the size of 5.0cm or more complete response was better (100%) in the chromotherapy prior to radiotherapy than in the radiotherapy alone (55.6%). 5. In 3 cases with stage IB showing poor prognostic histopathologic factors of high treatment failures, who had adjuvant chemotherapy following curative surgery (radical abdominal hysterectomy with bilateral pelvic lymph node dissection), no recurrence was seen during the 6-16 months follow up period. 6. The toxicities of combination chemotherapy of DDP-5 FU in치uded nausea & vomiting (100%), alopecia (100%), bone marrow depression such as leukopenia (65.4%), granulocytopenia (63.6%), anemia (45.4%), and thrombocytopenia (5.5%), renal toxicity (10.9%), hepatotoxicity (38.2%), and hypomagnesemia (20%), therefore the delay or discontinuation of further chemotherapy was ensued in 18 cases (32.7%). Mostly they showed abnormal laboratory findings without clinical symptoms but they fully recovered after the discontinuation or completion of the chemotherapy. In 26 cases treated with chemoradiotherapy, asymptomatic leukopenia ( < 2000/㎣) was seen in 6 cases (23.1%) during the radiotherapy, but it was not so severe enough to discontinue the radiotherapy. [영문] In management of the carcinoma of cervix, the chemotherapy had been used palliatively for the recurrent and the far advanced cancers that were net amenable to radiotherapy or surgery. Recently, in order to prevent or to lewer the treatment failures (recurrent or persistent cancers) and to improve the disease free survivals of the patients, the chemotherapy had been tried in combination with radiotherapy or/and surgery as primary treatment in cases with poor prognostic factors showing high treatment failure rates and in advanced cancers. In this study 66 patients with cervical cancer including 17 cases with recurrent cancers, 3 cases with stage IB, 17 cases with stave Ⅱ, 23 cases with stage Ⅲ and 6 cases with stage Ⅳ, treated with chemotherapy, alone or in combination with surgery or/and radiotherapy at the Department of Obstetrics and Gynecology, YUMC, were selected, and the response rates and toxicities were evaluated according to the therapy. The results of this study were as follows; 1. In 62 cases the response rates to chemotherapy were evaluated; complete response was seen in 6 cases (9.6%), and partial response in 30 cases (58.1%), so the total response rate to the chemotherapy was 67.7%. 2. The response rates to chemotherapy were compared between the previously irradiated recurrent cancers and the previously untreated primary cancers (stage Ⅱ, Ⅲ, Ⅳ). The response rate was 43.7% with recurrent cancers, which was lower than 76.1% of primary cancers. 3. In cases with stage Ⅱ & Ⅲ cancers, the response rate to chemoradiotherapy was compared to radiotherapy alone (control group). During the 3-L5 months follow up all of 21 cases who had received chemoradiotherapy showedcomplete response, while in the control group, complete responses were seen in 16 cases (76.1%) only, 3 cases (14.3%) of partial response, 1 case (4.8%) of stable disease and 1 case (7.8%) of progressive disease. In radiotherapy alone group, 1 case showing the complete response had recurrence of the cancer 7 months after the therapy. 4. In primary cancers, the response rates to chemotherapy seemed to decrease with increasing size of the lesion, and especially in cases with barrel shaped lesion with the size of 5.0cm or more complete response was better (100%) in the chromotherapy prior to radiotherapy than in the radiotherapy alone (55.6%). 5. In 3 cases with stage IB showing poor prognostic histopathologic factors of high treatment failures, who had adjuvant chemotherapy following curative surgery (radical abdominal hysterectomy with bilateral pelvic lymph node dissection), no recurrence was seen during the 6-16 months follow up period. 6. The toxicities of combination chemotherapy of DDP-5 FU in치uded nausea & vomiting (100%), alopecia (100%), bone marrow depression such as leukopenia (65.4%), granulocytopenia (63.6%), anemia (45.4%), and thrombocytopenia (5.5%), renal toxicity (10.9%), hepatotoxicity (38.2%), and hypomagnesemia (20%), therefore the delay or discontinuation of further chemotherapy was ensued in 18 cases (32.7%). Mostly they showed abnormal laboratory findings without clinical symptoms but they fully recovered after the discontinuation or completion of the chemotherapy. In 26 cases treated with chemoradiotherapy, asymptomatic leukopenia ( < 2000/㎣) was seen in 6 cases (23.1%) during the radiotherapy, but it was not so severe enough to discontinue the radiotherapy.restrictio