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      • 경부 림프절 및 비강의 양성 림프조직에서 Epstein-Barr Virus 유전자의 검출

        고영혜,박찬금,이중달 한양대학교 의과대학 1995 한양의대 학술지 Vol.15 No.2

        Recent studies have suggested that nasal NK/T cell lymphoma have strong association with Epstein-Barr virus(EBV). This study was performed to determine whether the association of EBV with NK/T cell lyphomas was ascribed to the immunophenotype and location or not. A sensitive in situ hybridization technique was used to detect EBV encoded RNA (EBER) in paraffin sections from 38 benign lymph nodes, 10 nasal mucosa and 12 adenoids and tonsils. Among 60 cases, 7(11.7%) were EBER-positive and their distribution was lymph node in 6 cases, adenoid in 1 case but none in the nasal cavity. Double in situ hybridization and immunhistochemistry revealed EBER-positive lymphocytes were B-lineage in 4 cases and T-lineage in 2 case. In one case, determination of lineage was failed. From these results, we concluded that high association between nasal NK/T cell lymphomas with EBV might not be simply ascribed to location or immunophenotype of the lymphoma.

      • 2-Acetylaminofluorene으로 유발된 실험적 간암의 세포 동태학적 연구

        금주섭,고영혜,이중달 한양대학교 의과대학 1995 한양의대 학술지 Vol.15 No.2

        Kinetics of hepatocytes in various precancerous and cancer iesions during hepatocarcinorenesis was evaluated in 38 Sprague-Dawley rats fed with 0.075% 2-acetylaminofluorene diet. The rats were sacrificed after 4, 7, 10 days. 2, 3, 4, 6, 8 weeks, and 3, 4, 5, 6, 7, 8 months of the experiment. The lesions were divided as altered cell lesions (clear cell focus, acidophilic cell focus, and basophilic cell focus). regenerating nodules. neoplastic nodules, and hepatocellular carcinomas. Cell kinetics was studied by intraperitoneal bromodexyuridine(BrdU) injection 2 hours before sacrifice. After detection of the BrdU-incorporated nuclei with monoclonal antibody kit, the BrdU labelling index(BLI) was measured as percentage of BrdU labelled cells among about 1000 cells. The liver cells in the altered cell lesions showed significantly increased BLI(clear cell 1.66: acidophilic 2.39: basophilic 2.41) in comparion with normal control(0. 18) or non-lesional hepatocytic lobules (0. 47), and lower BLI than hepatocellular carcinoma(8.61∼27.07) (P<0.05). Regenerating and neoplastic nodules did not differ in their BLI (1.54 and 1.70), and were significantly lower in their proliferating kinetics than acidophilic or basophilic cell foci (P<0.05). It was suggested from this study that the altered cell lesion should be true premalignant lesion, which was composed of at least initiated cells by the chemical carcinogen. The basophilic and acidophilic foci in altered cell lesions were suggestive of close correlation with the hepatocellular carcinoma in that they had greatest proliferative cell kinetics of all the lesions occurred before cancer developed.

      • 2-Acetylaminofluorene으로 유발된 실험적 간암의 TGF-a 및 EGF발혈에 관한 연구

        박정희,고영혜,이중달 한양대학교 의과대학 1995 한양의대 학술지 Vol.15 No.2

        Transforming growth factor-α(TgF-α) and epidermal growth factor (EGF) are growth factors acting on proliferation and differentiation of cells and expressed in various types of cancer. TGF-αmay be a physiological regulaor during liver development and liver regeneration in injured liver and known as increased in hepatocellular carcinoma. To investigate the role of TGF-αand EGF in hapatocarcinogenesis, author had undertaken an experimental study of hepatic carcinogenesis induced in 50 rats by feeding 2-acetylaminofluorene(2-AAF) in diet. The animals were sacrificed periodically after 2-AAF administration, and each liver was examined grossly and microscopically and immunostained with monoclonal antibody for TGF-αpolyclonal antibody for EGF. 1. At the third week of the experiment, the oval cells were markedly proli ferated and extended from the periphery to central areas of hepatic lobules. The altered hepatic foci, including acidophilic cell area on the fourth week and clear cell area on the second month were noted. At the third month, hype rplastic nodules developed. At the seventh month, one case of hepatocellular carcinoma and angiosarcoma were noted. At the eighth month, four cases of hepatocellular carcinoma of trabecular type were noted. Among these, three cases of squamous cell carcinoma on the neck skin occurred. 2. The control livers expressed only a few scattered hepatocytes positive for TGF-αin hepatic lobule. At the third week after 2-AAF administration, the hepatocytes exihibiting positive reaction were more widely distributed along the portal areas and around central veins. At the third month, several of the hyperplastic nodules showed strong to moderate positive reaction for TGF-α. The relationship between the TGF-αexpression and cytomorphologic changes in nodular hepatocytes was not present. All of the hepatocellular carcinoma cells and cells in the neighboring nodules at the seventh and eighth months expressed TGF-α. Oval cells were negative for TGF-αand bile ductular cells showed only focal positivity. 3. EGF was negative in cells of the centrol livers and most experimental livers. At the eighth month, one case of hepatocellular carcinoma and tree cases of squamous cell carconoma showed positive reaction for EGF. Above results suggest that TGF-α, may play a role in hepatocarcinogenesis by the mechanism that TGF-αacts as promotor for the transformation of initiated hepatocytes by 2-AAF in multistep of hepatocarcinogenesis.

      • KCI등재
      • 실험적 간암의 전암병변에 관한 면역 조직화학적 및 유세포 계측 연구 : C-ras, C-erb B2, Proliferating Cell Nuclear Antigen 및 C-myc의 변동 Expression of C-ras, C-erb B2, PCNA, and C-myc

        이중달,김종만,고영혜,김재영 한양대학교 의과대학 1994 한양의대 학술지 Vol.14 No.1

        To investigate the role of oncogenes in the hepatocarcinogenesis, author had undertaken an experimental study of hepatic carcinogenesis induced in 50 rats by feeding 2-acetylaminofluorene(2-AAF) in diet. The animals were sacrificed at 2, 4, 6, 8, 12, 16, 27, and 36 weeks after 2-AAF administration, and each liver was immunostained with monoclonal antibodies for c-ras, c-erb B2, and proliferating cell nuclear antigen(PCNA), and analysed by flow cytometry for c-myc oncoprotein. 1.The control livers were negative for expression of c-ras, c-erb B2, and c-myc oncoprotein, and positive for PCNA in 0.2% of hepatic cells. 2.The oval cells were markedly proliferated at 4 weeks after 2-AAF administration. They eventually became differentialted into bile ductular cells and small hepatocytes. 3.The oval cells and small hepatocytes showed high positive rate for PCNA with strong reaction for c=ras, c-erb B2, and c-myc oncoprotein whereas bile ductular cells failed to react for c-ras and c-erb B2. 4.Most hepatocytes in regenerative nodules lost the expression for c-myc, c-ras, and c-erb B2, although the oncoproteins persisted in some hepatocytes in the nodules. 5.Hepatocellular carcinoma of trabecular type and undifferentiated carcinoma were induced by 36 weeks after 2-AAF administration. The undifferentiated carcinoma cells expressed both PCNA and c-erb B2 oncoprotein rather strongly. Above results suggested that in the early phase of the experiment, c-ras, c-erb B2, and c-myc oncogenes were activated and stimulated to proliferation makes the oval cells to e transformed into malignant cells. However, the findings that most oval cells were differented into reversible cells in regenerating nodules suggested that overexpression of these oncogenes might not be sufficient to obtain irreversible phenotype of malignant cells. Also strong expression of oncoproteins and high PCNA positive rate in small hepatocytes and in a few cells of the hyperplastic nodules suggested that the pathway of the cancer might go through the development of oval cells to small hepatocytes to nodules and eventually to cancer. However, the results that most hepatocytes in the nodules lost oncoproteins and development of undifferentiated carcinoma in the absence of nodule formation suggested that the hepatocellular carcinoma arose from oval cells directly without a morphologic intermediate.

      • KCI등재
      • KCI등재
      • 비혈연간 동종골수이식에 의해 치료된 중증 재생불량성빈혈 1예

        김현중,이홍기,이방훈,이창근,이종태,정현식,김원석,윤성수,강원기,박근칠,김대식,고영혜,박찬형 대한조혈모세포이식학회 1997 대한조혈모세포이식학회지 Vol.2 No.1

        비혈연간 동종골수이식은 혈연간 동종골수이식이 불가능한 환자에서 기존의 면역역제요법으로 효과가 없었던 경우나 재발한 경우에 적응증이 될수 있다. 이식 거부와 이식편대숙주병의 발생이 골수 이식의 성공률을 감소시키므로, 보다 강력한 conditioning regimen의 사용과 T cell이 제거된 골수를 사용하는 것이 필요하다. 기존의 high dose corticosteroid나 cyclosporine에 대하여 불응성인 이식편대숙주병의 치료를 위해서 ATG와 Mycophenolate mofetil (Cellcept®) 의 사용이나 Tacrolimus, Methotrexate와 같은 다른 면역억제제치료를 고려해 볼 수 있다. It is known that allogenic bone marrow transplantation is the most effective treatment for aplastic anemia. However, this treatment is only applicable to a minority of patients because the proportion of patients who have HLA-matched siblings about 25% to 30% of all the aplastic anemia patients. In the case of the absence of HLA-matched donor, unrelated allogenic bone marrow transplantation is considered. However, (because of severe acute and chronic GVHD and graft failure) the success rate of this approach is only 20~30%. Recently, it was reported that increased immunosuppressive condition combined with T cell depletion of the marrow graft would result in greater success. There was no case of successfully treated aplastic anemia patient by unrelated allogenic bone marrow transplantation in Korea. Here, we report a case of severe aplastic anemia successfully treated with unrelated allogenic bone marrow transplantation.

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