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      • 마우스피부암 발생과정에 있어서 텔로머레이저 활성에 관한 연구

        강호일,지승완,주종호,황명실,염영나,이국경,김옥희 식품의약품안전청 2000 식품의약품안전청 연보 Vol.4 No.-

        텔로머레이저는 진핵세포 염색체의 텔로미어를 합성하는 DNA 중합효소로서 정상세포에서는 발현되지 않지만 차부분의 악성종양에서 발현되고 있는 것으로 알려져 있다. 현재까지 형질변환 된 세표에서 무제한의 증식을 조절하는 효소로 알려져 있지만 텔로머레이저 활성화의 기전 및 조절인자들은 알려져 있지 않은 실정이다. 본 연구에서는 각기 다른 11전으로 발암촉진을 할 수 있는 4종류의 TPA,okadaic acid, anaralin 및 benzoyl perox겨e 발암촉진제를 사용하여 마우스 피부암을 운도한 후 이들 암 조직으로부터 텔로머레이저 활성을 측정함으로써 텔로머레이저f') 어떤 방식으로 재찰성화 되는가에 대한 단서를 추적하고 분자병리학적인 기법을 사용하여 조절기전을 찾고자 하였다. 븐 실험에서 사용 한 동물 발암모델은 다단계 발암과정을 비교적 용이하게 관찰할 수 있는 마우스 피부암 모델을 이웅하였다. 그 결과 TPA promotion 10주에서 22주까지 얻은 pap기oma 조직에서는 렐로머레이저 활성이 검출되었으며 TPA 대씬 benfoyl peroxide, okadaic acid, anthralin 으로 처리하여 얻은 papi13orna 조직(promotion 10주에서 22주까지)에서도 텔로머레이저 활성이 나타나는 것을 발견하였다. 그러나 TPA 를 포함하며 이들 발암축진제 등으로 처궈한 동일 주령의 papilloma 주위조직 및 acetone 만을 처리한 정상 피부조직아서늪 틸로머레아저 활성은 나타나지 않았다. 이상의 결과를 모두 종합하면 마우스 피부암 발생과정에사를 틸로머레이저 재활성화와 단백질 인산화와는 전혀 관련이 없는 것으로 추정되며 향후 텔로머레이저는 새로운 조기 암 진단지표로서 사용 가능성이 높다고 사료된다. Telomerase, a speciallzed RNA-directed BNA polymerase that extends telomeres of eukaryotic chromosomes, has acti)'ity in most malignant tumors and provides a mechanismfor the unlimited potential fo'S division of neoplastic celts. Although telornerase is known to hea regulated enzyme, the factors and mechanisms involved in telornerase regulation are not wellunderstood. In the present study, we compared the effect of 12-0-tetradecano?1-phorbol-13-acetate fTPA) and non-phorbol ester tumor promoters such as okadaic acid,anthralin and benzo!71 per()xide on the expression of telomerase in the mouse skincarcinogenesis system, a well characterized model for studying pre-malignant and malignantf-ogression. We found that most early papillomas harvested after 10 weeks of TPA promotionshowed telomerase activity- Other papillomas harvested after 10 weeks of okadaic acid,anthralin and benzoy3 peroxide promotion and after single treatment of DMBA only alsoshowed telomerase activity, 1-espec4ive3y. On the other hand, normal 3nd all skins surroundedby papiBlomas harvested after 10 11·eelts of these promo·ters has no telomerase activity. Takentogether these results, there .Bppears to be no clear association betwetn the level of telomeraseactivity and protein phosphor#lation in mouse skin papi31omas and telomerase may be useful asbio-markers in early detectiorl of tumors.

      • Nicotine 및 Tobacco-specific nitrosamine이 발암과정에 미치는 영향

        강호일,황명실,김은정,김윤정,이국경,정자영,원도희,김옥희 식품의약품안전청 1998 식품의약품안전청 연보 Vol.2 No.-

        Nicotine은 그동안 계암발생파정에 관여되어 있는 것으로 추정되어지고 있으나 현재 이에 대한 기전.은 밝혀진 것이 거의 없다.본 연구에서는 폐암발생과정에서 있어서 nicotine의 역할을 조사하기 위해 첫번째 실험군으로 nicotine을 Sprague-Dawley 랫드에 연속적으로 10ㅇ리간 투여한 후 암유전자 및 암억제유전자의 발현변화를 단백질과 mRNA레벨에서 검토하엿다. 그 결과 5종류의 암유전자인 ras,raf,myc,fos, jun,및 2종류의 암억제유전자인 p53,Rb 단백질의 발현변화는 거의 없는것으로 나타났다.그리고 2종류의 암유전자인 myc,fos및 암억제유전자 p53 mRNA발현변화 역시 거의 없어 단백질 발현 실험결과와 일치하는 것으로 나타났다. 두번째 실험군으로 nicotine 및 sodium nitrite그리고 NNK를 Fischer344 랫드에 투여하여 발암물질인 NNK의 생성여부를 검토한 결과 NNK를 단독투여한 실험군의 경우 8-OHdG 레벨이 1.8배에서 2.3배까진 현저하게 증가하였으나 nicotine 및 sodium nitrite를 단독 혹은 병용 투여한 경우 8-OHdG 레벨의 유의한 차이가 관찰되지 않아 NNK 생성을 확인할수 없었다. Nicotine has been implicated as a potential factor in the pathogenesis of human lung cancer, however its mechanism of action in the development of lllng cancer remains largely unknown.To explore the role of Bicotine in the developmene of lung cancer, lue first investigated the effects of nic-otine on the expression of tumor associated genes by treating Spragve-Barley rats with nirotine (10 mf/kg) by gavage once daily for 10 days. We determined the expression of proteins and rnRNAs of the raf,raf, mrt JHn, foa oncogenes and p53, ab tumor suppressor genes by Western and Northern blotting,respectively. We did not detect any changes on t31e levels of prote·ins aBO mRNAs of these tumor associ-ated genes in the lung of Sprague-Dawley rats from 3 days to 12 ·weeks after the last treatment of nico-tine, indicating that nicotine appears to have no effect on the exE)ression of these oncogenes aBd turnersuppressor genes at an early stage in multistage chemical carcinoifenesis. In a second experiment, we in-vestigated the possibility that 4-(methylnitrosamino)- t- (3-p!rridyl)-1-butaaone (NNK) could beformed eBdogenously bf treating with nicotine and sodium nitrite. We treated groups of Fischer 344 ratswith nicetiBe (60 rrnol/kg) and sodium nitrite (180 rmol/kg), nicotiae, sodiu:n-nitrite and NNK (120 #mol/kg) flfne by gavage once daily to, 7 dafs, .espectively and dete,mined the 8-hydroxy-deoByguanosine (8-OHdG), as an indicator of NNK formation, in the lungs of rats 24 hours and 48hours after the last treatmeilt by HPLC/ECD method. We detect 3ncreased level of 8-OHdG in the tungsof rats treated with NNK, but in the case of nicotine plus sodiLlra nitrite, nicotine and sodium nitritealone we could not detected any changes of 8-OHdG, respectively.

      • 이태리 포플러의 기내 클론증식

        姜鎬德,朴敎秀,Richard B. Hall 동국대학교 생명자원과학대학 연습림 1995 연습림논문집 Vol.- No.4

        교잡종 포플러 (Canada blanc, Eugenei, Ⅰ-45/51, Wisconsin #5)의 기내증식에 미치는 요인들이 조사되어졌다. 식물성장 조절물질로서 싸이토키닌류와 오옥신류와의 조합은 뿌리, 줄기, 잎의 시료로부터 기내증식의 효율 증대에 영향을 미치었다. 일반적으로 benzylaminopurine (BA)과 오옥신과의 조합은 Canada blanc 클론의 잎 시료에 매우 효과적 이었고, zeation과 오옥신류와의 조합은 Wisconsin #5 클론의 줄기 시료에 매우 중요하게 작용했다. 각 시료에서 최대의 증식되어진 줄기의 수는 BA 2.0 ㎎/l를 처리 했을때 Canada blanc의 뿌리 시료로 부터 17.60±8.96개가 생산되어졌다. 반면에, Wisconsin #5의 줄기와 Canada blanc의 잎은 zeation/ 2.0㎎/l와 IAA 0.2㎎/l의 조합과/ BA0.5㎎/l와 2.4-D 0.05㎎/l의 조합에서 각각 18.20±3.03개와 17.80±1.92개의 줄기들을 증식시켰다. 특히, 싸이토키닌의 들어있는 배지에 2.4-D의 첨가는 줄기증식을 촉진시켰다.

      • KCI우수등재

        육제품에 관한 위생학적 연구 3 . 염지첨가제가 아초산의 잔유농도에 미치는 영향

        강호조 ( Ho Jo Kang ) 한국축산학회 1979 한국축산학회지 Vol.21 No.1

        This experiment was carried out to investigate the effect of food additives on residual nitrite contents of samples treated with various food additives. The longissimus dorsi muscles of 10 month-old pig were used as meat samples. The food additives used were sorbic acid(SOA), ascorbic acid(ASA), sodium phosphate(SOP), nicotinamide(NIA), sodium nitrite (NO₂) and sodium chloride (NaCl). The samples were stored at 3℃ for 3 ∼ 7 days after preparation and residual nitrite contents were determined by the A. O. A. C. method(1970). The results obtained were summarized as follows ; 1. The residual nitrite contents of SOA(I), SOA+ASA(II), SOA+ASA+SOP(III) and SOA+ASA+SOP+NIA(IV) treated with various pickles were decreased from 150.0 ppm to 60.0, 1.5, 1.5 and 1.3ppm, respectively, after 3 days of storage and those of control group were 96.7 ppm. 2. The residual nitrite contents were decreased more at lower pH and decreased more rapidly to less than pH 6.0 in the samples. When pH was adjusted to the same value, samples that added ascorbic acid were more lowered at 50 ppm than nitrite contents of control group. 3. The residual nitrite contents of samples which added ascorbic acid to 0.02, 0.1 and 0.3% were decreased from 150.0 ppm to 80.0, 40.0 and 0.2 ppm and decreased more rapidly than 92.0ppm in control group. 4. The residual nitrite contents of samples which was added ascorbic acid to 0.02 and 0.3% were decreased from 150 ppm to 83.3 and 62.0 ppm, respectively, and control group was 92.0 ppm. 5. The residual nitrite contents of samples which added sodium chloride to 2.0, 5.0 and 10.0 were deceased from 150 ppm to 96.7, 96.7 and 75.0 ppm, respectively, and sodium phosphate and nicotinamide were not affected From the above results, it might be concluded that 0.1% of ascorbic acid was most available level to decrease the residual nitrite content.

      • 악성종양에 동반된 고칼슘혈증에 대한 연구

        姜好耕,李順男 梨花女子大學校 韓國生活科學硏究院 1990 韓國生活科學硏究院 論叢 Vol.46 No.-

        Tumor-associated hypercalcemia is a common and important clinical problem. Two major pathogenic mechanisms appear to be operative in this disorder:local osteolytic hypercalcemia and humoral hypercalcemia of malignancy. We experienced 20 cases of tumor-associated hypercalcemia from January 1987 to september 1989 and reviewed their clinical findings. The results were as follows; 1) The age ranged from 30 to 79 years with mean age of 57.5 and a male predominance was observed(M:F=3:1). 2. The frequent primary sites of tumor were lung(35%), kidney(20%), esophagus(10%), breast(10%), cervix(10%) and the pathologic findings were squamous cell carcinomas(50%) and renal cell carcinoma(20%). 3) Out of 20 cases, 18 were stage Ⅳ and 2 were Ⅲ. Bone metastasis was observed in 11 cases(55%) and out of 10 cases of squamous cell cancer, only 3 cases showed bone metastasis. 4) The most frequent earliest symptoms were anorexia(90%), constipation(50%), nausea/vomiting(40%) and abdominal pain(35%), and neurologic symptoms as muscle weakness, lethargy, confusion and coma were developed also. 5) Common laboratory findings were moderate to severe hypercalcemia(90%), normal phosphours level(80%), alkaline phosphatase elevation(50%), with 3 liver metastasis, 2 osteoblastic bone metastasis and 5 mixed bone metastasis. 6) On ECG, shortened QTc interval was noted in 35%. 7) Saline diuresis was initial therapy in all 20 cases, steroid was given concomitantly in 5 of them, calcitonin with oral phosphate were given concomitantly in 3 of them and mithramycin was given in only 1 case. 8) 14 cases were died and others were survived more than 6 months. The results suggest that squamous cell carcinoma, renal cell carcinoma, breast cancer and multiple myeloma are relatively common causes of malignancy associated hypercalcemia and hypercalcemia generally represents a late complication in the course of neoplasia as extensive tumor burden.

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