라미부딘 장기투여 중 발생한 B 형 간염 바이러스 YMDD 영역의 유전자변이

이종훈(Jong Hun Lee),신우원(Woo Won Shin),안현숙(Hyun Sook Ahn),성명식(Myung Sik Seong),조정환(Jeong Hwan Cho),정동엽(Dong Yup Jung),강기태(Ki Tae Kang),김병희(Byung Hee Kim),노명환(Myung Hwan Roh),한상영(Sang Young Han),최석렬(Seok 대한내과학회 2001 대한내과학회지 Vol.61 No.4

N/A Background: The emergence of YIDD or YVDD mutant hepatitis B virus (HBV), with point mutation in the YMDD motif of DNA polymerase gene, has been reported in patient s with lamivudine treatment group. The aims of this study was to investigate the emergence of mutant HBV during long-term lamivudine therapy using nested polymerase chain reaction (PCR) method and direct DNA sequencing. Methods: Twenty-one chronic hepatitis B patients with HBeAg and HBV DNA positive were evaluated. During lamivudine therapy, there were reported breakthroughs of HBV DNA (over 50pg/mL) when investigated the emergence of YMDD mutants by nested PCR method using restriction fragment length polymorphism (RFLP) in all patients. Direct DNA sequencing of HBV DNA polymerase gene including YMDD motif was also performed. Results: There were 13 patients (61.9%) with YIDD mutant and 8 patients (38.1%) with YVDD mutant. The result s of direct DNA sequencing were consistent with those of nested PCR data based on RFLP. The breakthrough was occurred at 15 to 106 weeks (57.9±23.6). At the point of breakthrough, the level of ALT was 74.8±117.7 (14-546) IU/L, and it was lower than the level of ALT before the therapy. Conclusion: In the long-term therapy of lamivudine, the emergence of YMDD motif mutant HBV was related to the breakthrough of HBV DNA and YIDD mutant was frequent. The nested PCR method using RFLP may be simple and sensitive to detect the YMDD motif mutant HBV. (Korean J Med 61:374-383, 2001)

사람 암세포주 K562 , U937 및 쥐 암세포주 P388 , FM3A 에서의 항암제 다제내성 기전 및 내성극복

도현국(Hyun Kuk Doh),김재석(Jae Seok Kim),손지원(Ji Weon Son),성명식(Myung Sik Sung),김종성(Jong Seong Kim),김선희(Sun Hee Kim),정병선(Byung Sun Jung) 대한내과학회 1992 대한내과학회지 Vol.43 No.3

N/A Background: To study the mechanism of multidrug resistnce (MDR) and overcome MDR in cancer cells, we investigated the combination effects of anticancer agents with calmodulin inhibitors (e,g trifluoroperazine (TFP) and W-7), calcium function modifiers (e.g., quinidine and verapamil) and a protein kinase-C activator (e.g., phorbol ester) in chronic myelogenous leukemic cells, histiocytic lymphoma cells and breast cancer cells. Methods: Some MDR mutant sublines which had cross-resistance to colchicine, actinomycm D, adriamycin and vinblastine were isolated from K562, U937 and FM3A cell lines. MTT analysis was used to measure the level of the cytotoxicity, The cytotoxicity and the combination effects were compared by IC50 (1nhibition concentration50) to control group. Results: In case of U937/MDR, TFP increased the combination effect to tenfold in colchicine (COL), eightfold in vinblastine (VLB) and thirteenfold in actinomycin D (ACT-D). Quinidine increased the effect to threefold in COL, fourfold in VLB and sevenfold in ACT-D. Verapamil also increased the effect to sevenfold in COL, sixfold in VLB fivefold in ACT-D. In case of K562/MDR, TFP, quinidine and verapamil each increased the combination effect to sixfold, twelvefold and thirteenfold in COL and sixfold, fivefold and fivefold in adriamycin (ADM). W-7 in concentration of 20uM increased the combination effect to six point sevenfold in ACT-D, twofold in COL and two point threefold in ADM. In the combination of COL with 0.48uM TPA, the cytotoxicity was reduced to two point eightfold in case of FM3A/MDR. TPA (12-0-tetradecanoyl phorbol 13-acetate), in concentration of 0.48uM, a phorbol ester, reduced the cytotoxicity to two point eightfold in case of FM3A/ MDR. Conclusion: When the combination effects of anticancer agents with calmodulin inhibitors (e.g TFP and W -7) and calcium function modifiers (e.g., quinidine and verapamil) were examined, the cytotoxicity changes of anticancer agents were small in drug sensitive cells. But in MDR cells, the combination effects were prominent. The reduced cytotoxicity of anticancer agents by TPA suggested that protein kinase-C might be related with the mechanism of acquiring drug resistance on cancer cells.

관동맥 조영술로서의 상완 접근법

손지원(Ji Won Son),김무현(Moo Hyun Kim),이주일(Ju Il Lee),김문범(Moon Beom Kim),성명식(Myung Sik Sung),도현국(Hyun Kuk Do),김종성(Jong Seoung Kim) 대한내과학회 1995 대한내과학회지 Vol.48 No.5

N/A Objectives: There are two approach methods in the coronary angiography, which are femoral and brachial approaches. In Korea, femoral approach has been used routinely, but brachial approach is not used widely compared to America, Europe and Japan, where the brachial approach is used more than 30% among the diagnostic coronary angiography. Recently, we had experienced coronary angiography by brachial artery puncture, so we will discuss about its usefulness. Methods: Coronary angiography was done in 149 cases by femoral approach, and 39 cases by brachial approach, from Nov. 1992 to Oct. 1993. Unpaired t-test, x2-test and ANOVA were used for comparison of each method about the duration of procedure time, the total dose of the contrast media, numbers of the used catheter and the learning effect. Results: 1) In brachial approach group, mean procedure time was 25±12 min, and the mean dose of contrast media was 147±37ml, which were not statistically significant compared with femoral approach group, 22±9 min and 138±37ml respectively. Mean numbers of the used catheter were 1.6 in brachial group and 3.6 in femoral group(p<0.05). 6 cases of brachial approach(6/39) were done by outpatient basis. 2) The percentage of incomplete engagement was 7.8(3/39) in brachial group and 2.7% (4/149) in femoral group, which was significantly higher in brachial group(p<0.05). By the way, all 3 cases of in- complete engagement were left coronary artery in brachial group, but there was same incidence between left and right coronary artery in femoral group. 3) Complications occurred 10.2%(4/39) in brachial group, 3.3%(5/149) in femoral group(p<0.01), but most of them were minor. 4) We compared the total dose of contrast media and procedure time by 3 month, 6 month interval. The duration of procedure time was relatively constant in femoral group, but decreased in brachial group with time course(p<0.05). By 6 month interval, it was significantly shorter in femoral group compared with brachial group in the first half(p<0.05), but there were no statistical significance between 2 groups in the 2nd half. Also there were no significant differences in the total dose of contrast media between two groups. Conclusion: Coronary angiography via brachial artery puncture has similar result in the duration of procedure time, the total dose of contrast media, compared with femoral approach. Brachial approach is useful method especially in the patient with obstructive vascular lesions and outpatient basis. We think it requires experience and discipline.

원발성 중복암 4예에 대한 보고

한상영,최석렬,신우원,성명식 대한소화기내시경학회 1993 Clinical Endoscopy Vol.13 No.1

Double primary cancer is defined as the case of primary malignant tumors in one person, which must be arisen in different sites and have a different histologic appearances in each other. The number of reported cases of multiple primary malignant tumors has increased in recent years, because of more developed diagnostic procedure and long survival of cancer patients, We have experienced 4 cases of double primary malignant tumors which were stomach cancer with colon, bronchus and esophagus cancer, and report these cases with review of literatures.

B형 간염바이러스 동반성 막성신병증 및 막성증식성사구체신염의 임상상

이성원,김성은,문성훈,김기현,신우원,성명식,안원석,장채령,우영석,장광열 대한신장학회 2000 Kidney Research and Clinical Practice Vol.19 No.6

Chronic hepatitis B viral infection causes membranous nephropathy and membranoproliferative glomerulonephritis. Patients with positive serum HBsAg with membranous nephropathy or membranoproliferative are considered as hepatitis B virus associated glomerulonephritis(HBV-GN) in epidemic areas of hepatitis B viral infection. To elucidate the clinical difference between hepatitis B virus-associated membranous nephropathy and membranoproliferative glomerulonephritis, and idiopathic membranous nephropathy and membranoproliferative glomerulonephritis, the authors conducted a clinical study including 71 cases of patients with renal biopsy proven diagnoses. Among the patients with hepatitis B virus antigenemia, the pathologic diagnoses were 7 membranous nephropathy(HBV-MN), 13 membranoproliferative glomerulonephritis(HBV-MPGN) but patients with mixed pattern of both membranous nephropathy and membranoproliferative glomerulonephritis were excluded. For the patients with idiopathic glomerulonephritis, 35 of membranous nephropahty(MN) and 16 cases of membranoproliferative glomerulonephritis (MPGN) were enrolled in this study. The patients of HBV-GN groups had more than 80% of HRe antigenemia. The nephrotic range proteinuria presented more frequently in HBV-MN(86%) than in MN group(54%). The cases of HBV-MPGN group(4 cases, 31%) showed nephrotic range proteinuria less frequently than those with MPGN(69%, p$lt;0.05) and significant discrepancy existed in HBV-MN vs HBV-MPGN and HBV-MPGN vs MPGN. The cases with decreased serum C3 level below normal were over 50% of HBV-GN and MPGN group except MN group. Serum levels of SGOT and SGPT were significantly elevated in HBV-MN and HBV-MPGN groups than those of MN and MPGN groups, respectively(p$lt;0.05). The number of cases with increased SGOT, SGPT and γ-GTP were 4(57%), 2 (29%) and 1(16%) in HBV-MN and 15(83%), 12(67%) and 9(75%) cases in HBV-MPGN group, in respectively. The cases developed progressive renal functional impairment during follow-up period of at least one year were 3 of 5(60) in HBV-MN, 2 of 8 (25%) in MPGN and 3 of 9(33%) in HBV-MPGN groups which were significantly more than 2 of 22 cases(9%) in MN group(respectively p$lt;0.05, not in HBV-MPGN vs MN). The renal functional impairment rate defined by the ratio of patients with their serum creatinine elevated above 2mg/dL over 3 months in each group was more rapidly increased in HBV-MPGN & HBV-MN than the idiopathic groups by Kaplan-Meier statistic analysis. We suggest that the patients with HBV-associated glomerulonephropathy seem to have worse prognosis in terms of renal functional impairment than those with idiopathic types of glomerulonephropathy with same pathology.

B형 간염바이러스 동반성 막성신병증 및 막성증식성사구체신염의 임상상

우영석,김기현,안원석,장광열,이성원,장채령,문성훈,성명식,김성은,신우원 대한신장학회 2000 대한신장학회잡지 Vol.19 No.6

췌장의 점액성 낭선종 1예

김종성,김재석,손지원,최석렬,신우원,성명식 대한소화기내시경학회 1992 Clinical Endoscopy Vol.12 No.1

The majority of the cysts developed in pancreas are inflammatory pseudocyst but neoplastic cysts are rarely encountered Especially, mucinous cystadenoma which was begun and originated from epithelial cell of pancreatic duct is difficult to differentiate from pseudocysts by preoperative clinical, laboratory and radiologic findings. Mucinous cystadenoma has a malignant potentiality, so complete excision of cystadenoma is the treatment of choice. Recently, we experienced one case of mucionus cystadenoma in 37 year-old female, we report it with a review of the literature.