당뇨병환자에서 뇨중 Fibronection 치에 관한 연구

이인규(In Kyu Lee),박근용(Keun Young Park),조성래(Sung Rae Cho),박기락(Ki Rak Park),진선미(Sun Mi Jin),손건영(Kun Young Sohn),이병헌(Bung Heun Lee),조준승(Joon Seung Jo) 대한내과학회 1995 대한내과학회지 Vol.49 No.4

N/A Objectives: In diabetic nephropathy, thickening of basement membrane in the glomerulus and tubule is a well known finding. Therefore, we evaluated whether the excretion of urinary fibronectin, which is one of important factors of basement membrane, is related with the presence of diabetic nephropathy. Methods: We measured and compared the urinary fibronectin excretion rate(FER) and the albumin excretion rate (AER) in 20 healthy controls and 89 diabetic patients', 44patients without microalbuminuria, 26 patients with microalbuminuria, 19 patients with overt nephropathy, Urinary fibronectin levels were measured by our enzyme linked immunosorbent assay (ELISA) method and urinary microalbumin by radioimmunoassay. Results: Patients with overt proteinuria were characterized by a significantly (p<0.005) longer duration of diabetes (Mean±SD: 97.1±30.8 years, 60.5±74.4 years, 62.2±58.3 years) and by a higher systolic presure (l34.2±19,5mmHg, 120.5±5.8 mmHg, 121.8±14.2mmHg, 127.7±14.5mmHg) compared with control and diabetic patients with or with- out microabluminuria 2) The mean fibronectin excretion rate was significantly (p<0,05) higher in the group with microalbuminuria (277.9+244,6μg/min) than in normoalhuminuria patients(165.7±90.3μg/ min) or in control subjects (184.1±96.9μg/min) and also significantly (p<0.005) higher in the group with overt proteinuria (370.6±331.6μg/min) than in microalbuminuria (277.9±244.6μg/min) or in normoalbuminuria (165.7±90.3μg/min) 3) Significant (p<0.01, p<0.001) degree of correlation were found between urine fibronectin excretion rate and duration of diahetes (r=0.31) or systolic blood pressure(r=0.35), where as AKR significnatly (p<0.01) correlated with duration of disease (r=0,27). 4) Urine fibronectin excretion rate were, significantly ocrrelated with AER(r=0.13, p<0.001) Conclusion: The results of this study suggest that FER is a useful indicator for the occurrence and progression of early diabetic nephropathy.

인체 대장암에서 72kDa 제4형콜라겐 분해효소의 발현

전수한(Soo Han Jun),김정은(Jung Eun Kim),손건영(Kun Young Sohn) 대한외과학회 1997 Annals of Surgical Treatment and Research Vol.53 No.1

肝臟損傷이 肝의 Superoxide Dismutase에 미치는 影響

孫健英,曺準承 慶北大學校 醫科大學 1982 慶北醫大誌 Vol.23 No.2

간장손상시 간의 superoxide dismutase의 변화를 알아보기위하여 흰쥐에게 CCl_4를 투여하거나 또는 총담관을 결찰하고 시간경과에 따른 간장의 superoxide dismutase 변동을 관찰하여 다음과 같은 결과를 얻었다. 정상흰쥐 간세포에서의 superoxide dismutase 분포는, 세포질에는 세포 총 superoxide dismutase의 95.2%. mitochandria에는 4.8%가 분포되어 있었다. CCl_4단회 투여시에는, 세포질 superoxide dismutase는 투여후 6시간네 감소되기 시작하여 24시간에 최저치를보이다가 이후 증가하여 72시간에는 대조군의 약 82%까지 회복되는 경향이었고, mitochondrial superoxide dismutase는 투여후 12시간에 감소하기 시작하여 24시간에 최저치를 나타내고 이후 증가하여 72시간에는 대조군의 약 79%까지 회복되는 경향이었다. CCl_4간격투여시에는 세포질, mitochondrial superoxide dismutase 모두 투여후 9일까지 감소되어 회복되지 않았다. CCl_4 간격투여시에는 세포질, mitochondrial superoxide dismutase 모두 투여후 6일까지는 감소되어 있었으나 9일에는 다소 회복되는 경향이었다. 그리고 총담관 결찰시에는 의의있는 변동을 볼 수가 없었다. 이상의 결과로 보아 CCl_4에 의한 간손상시에는 간세포내 superoxide dismutase가 감소하며 세포질의 superoxide dismutase 감소가 mit-ochondrial superoxide dismutase의 감소보다 빨리 일어나나, 담관결찰시에는 이 효소의 변동이 없는 것을 알 수 있었다. To study the influence of liver injury on hepatic superoxide dismutase in rats, superoxide dismutase was determined in rat liver after either CCl_4 injection or common bile duct ligation. In normal rat liver cells, 95.2% of total cellular superoxide dismutase was distributed in cytosol and 4.8% was in mitochondria, respectively. In single injection of CCl_4, cytocolic superoxide dismutase was decreased at 6 hours after injection and revealed minimum value at 24 hours, thereafter increased to 82% of the control level at 72 hours. Mitochondrial superoxide dismutase was decreased at 12 hours after injection and revealed minimum value at 24 hours while increasing to 79% of the control level at 72 hours after injection. In 2 day-interval injection of CCl_4, both cytosolic and mitochondrial superoxide dismutase showed decreased levels until 9 days after the first injection and did not recover. In 3 dua-interval injection of CCl_4, both cytosolic and mitochondrial superoxide dimutase showed decreased levels until 6 days after the first injection and recovered to 75% and 64% of the control at 9 days, respectively. No significant changes were noted after common bile duct ligation. All of these findings are compatible with the views that cellular superoxide dismutase decreases in CCl_4-induced liver injury and decrease of cytosolic superoxide dismutase precedes that of mitochondrial superoxide dismutase. But superoxide dismutase did not change after the ligation of common bile duct.

Sarcoma 180 誘發 생쥐의 生存延長에 對한 Cyclophosphamide, Picibanil, 및 Tubercin-3의 單獨 및 倂合投與의 有效成

鄭泰浩,孫健英 慶北大學校 醫科大學 1981 慶北醫大誌 Vol.22 No.1

생쥐에 Sarcoma 180을 유발 시키고 각각 그 작용점이 상이한 면역요법제 Tubercin-3와 Picibanil의 단독 요법과 병합요법 그리고 화학요법제 Cyclophosphamide와의 병합사용의 효과를 검토 하였다. Sarcoma 180 유발후의 생쥐의 생존일수의 평균치는 대조군 11.1일 : Tubercin-3투여군 14.8일 : Picibanil 투여군 12.4일 : 그리고 Tubercin-3과 Picibanil의 병합투여군은 8.4일 이었다. Cyclophosphamide 단독투여군의 생존일수는 18.1일이었고 Cyclophosphamide와 Tubercin-3 병합군은 27.4일, Cyclophosphamide와 Picibanil 병합군 22.6일로서 상당히 연장 되었으나 Cyclophosphamide와 두가지 면역요법제를 같이 사용한 동물군의 생존일은 평균 18.7일로서 면역요법제를 사용하지 않은 군과 같았다. This study was carried out to determine the efficacy of combined treatment of cyclophosphamide with Tubercin-3 and Picibanil. One hundred sixty sarcoma 180 bearing mice were divided eight groups of 20 animals each group receiving saline, Tubercin-3, Picibanil, and Cyclophosphamide alone and Cyclophosphamide combined with Tubercin-3, with Picibanil and with both Tubercin-3 and Picibanil respectively. The treatment was initiated 48 horus after tumor cell implantation and repeated three times given once a day with following doses suspended or dissolved in 0.2㎖ of saline at the interval of every other days: 0.5 microgram Tubercin-3 0.1㎎ Picibanil; 3.O㎎ Cyclophophamide; either in alone or in combination. Immunotherapeutic agents were administered by subcutaneously and Cyclophosphamide was given abdominally. The observation of general conditions of animal took place twice a day following treatment and the time of death after tumor implantation was determined. Average survival days in each group of animals were as follows: Control, 11.1 days; Tubercin-3, 14.8 days; Picibanil, 12.4 days; Cyclophosphamide 18.1 days. In combined therapy Cyclophosphamide with Tubercin-3, 27.4 days; Cyclophosphamide with Picibanil, 22.6 day and Cyclophosphamide with both Tubercin-3 and Picibanil 18.7 days. Conclusively, the therapeutic potentiation was reflected to be extended survival in combined treatment of a chemotherapeutics Cyclophosphamide with either one of immunotherapeutics. Tubercin-3 or Picibanil. Combination of Tubercin-3 and Picibanil showed to be antagonistic each other.

인체 대장암에서 72kDa 제 4형콜라겐 분해효소의 발현

김정은,손건영,전수한 경북대학교 병원 1998 경북대학교병원의학연구소논문집 Vol.2 No.1

수술 절제한 대장암 45예에서 Northern blot analysis와 gelatin zymography를 시행하여 72kDa 제 4 형콜라겐 분해효소의 mRNA치와 활성도를 조사하였다. 대장암에서 주위 정상조직에 비해 이 효소의 mRNA치가 증가하였으며 단백질 합성단계에서 효소의 활성도와도 연관되었다. 특히 활성형인 62kDa의 활성도가 크게 증가하였다. 암진행에 따른 이 효소의 활성도 변화는 T2와 T3에서 암조직과 정상조직사이에서 mRNA치와 효소활성도에 차이가 있었으나 전반적으로 암의 침윤도, 림프절 전이, 듀크스 병기에 따른 유의한 차이는 볼 수 없었다. 암침윤과 전이에는 제 4 형콜라겐 분해효소 외에 딴 metalloproteinase들, plasminogen activator등 여러 가지 다른 단백질 분해효소도 관여하며, 암종류에 따라 이들 효소의 작용정도가 차이가 날 수 있다. 또 조직 억제제인 tissue inhiitors of metalloproteinase(TIMPs)와의 균형관계도 고려해야 한다. 그러므로 대장암에서 72kDa 제 4 형콜라겐 분해효소의 증가된 활성양상을 이들 다른 인자들과 함께 관찰하면 암의 진행정도를 나타낼 수 있는 보다 뚜렷한 지표를 만들 수 있을 것으로 생각된다. Type Ⅳ collkagenases are thought to play a role in the proteolysis of the basement membrance and the extracellular matrix by the malignant cells that occur early in the development of invasive tumors. In several human tumors, including breast, colonic, ovarian, and gepatocellular carcinomas, Type Ⅳ collagenase expression has been positively correlated with tumor invasiveness. In this study, we examined the expression and the activation of 72kDa Type Ⅳ collagenase in cancerous and normal tissues of the colon and, we attempted to clarify its clinical significance in 45 cases of human colorectal cancer by using northern blot analysis and gelatin zymography. This study showed that the level of 72kDa Type Ⅳ collagenase mRNA was increased in colorectal cancer and that this increase was associated with increased enzymatic activity. While there was a difference in the expression and the activation of this enzyme between T2 and T3, this enzyme activity did not show a definite correlation with cancer progress as measured by the depth of tumor invasion and lymph node metastasis.

家兎에 四鹽化炭素投與로 因한 血淸內 各種 酵素의 活性變動에 關하여

曺秉權,孫健英,曺準承 慶北大學校 醫科大學 1985 慶北醫大誌 Vol.26 No.2

Hepatotoxin의 하나인 CCl_4를 投與하여 急性 肝損傷을 惹起시킬 때 血淸中 여러 가지 酸素의 活性이 어떻게 變動되는가를 알아보기 위하여 體重 2.2에서 2.5kg 되는 外見上 健康한 白色家兎 10마리를 使用하여 olive油와 1:1로 混合한 CCl_4를 體重 100gm 當 0.2ml 씩 皮下로 12時間 間隔으로 2回 注射한 後 時間經過에 따라 血中의 AST, ALT, LDH, LAP 및 Ch-E의 活性을 測定하였다. CCl_4 投與 後 AST, ALT 및 LDH는 다 같이 顯著히 上昇되었으나 LAP와 Ch-E의 活性은 別다른 變動을 보이지 않았다. 特히 AST는 CCl_4 投與 後 急히 上昇하여 24時間째에는 正常値치(39單位)보다 約 40倍나 높은 最高値에 到達한 後 急히 下降하였으며, 이에 比하여 ALT는 늦게 上昇하여 48時間째에 正常値(27單位)보다 約 45倍에 澾하는 最高値를 나타낸 後 약간느리게 低下되었으며 144時間後에는 거의 正常으로 回復되었다. AST/ALT 比率은 正常値는 1.6이었으나 CCl_4 投與 後 12時間에는 11.7로 急激히 增加되었으며 그 後 減少되어 48時間에는 1.1이 되었고 72時間에는 0.4로 逆轉되어 오히려 ALT가 約2倍로 높았다. LDH의 變動樣相은 AST와 비슷하여 CCl_4 投與 後 急히 上昇하여 24時間에는 正常値(286單位/ml)보다 約 6倍나 높은 最高値를 나타낸 後 急히 下降되었다 LAP 와 Ch-E의 正常値는 各各 333單位/ml, 208 I.U./l로써 CCl_4 投與 後 有意的인 變動을 나타내지 않았다. 以上의 結果로 보아 hepatotoxin에 依한 急性 肝損傷詩에는 血淸 酵素가운데 AST, ALT 및 LDH가 銳敏하게 變動한다고 하겠다. Effect of carbon tetrachloride administration on the activity of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydaogenase (LDH) and cholinesterase (Ch-E) was studied in albino rabbits weighing between 2.2 to 2.5kg. The animals were treated under the same condition before experiment for one week, and a single dose of 0.2ml of carbon tetrachloride, mixed with the same volume of olive oil, per 100g body weight was subcutaneously injected twice in 12 hours, and then level of the enzyme activities was estimated for the following 6 days. After the administration of carbon tetrachlorides, AST, ALT and LDH were markedly elevated but the changes of LAP and Ch-E level were trivial. Especially, the activity of AST was rapidly elevated and reached to maximum level after 24 hours of administration, and then rapidly decreased. In comparison to AST, the activity of ALT was slowly elevated and reached to maximum level after 48 hours and returned to normal range after 6 days of the administration. In addition, value of AST/ALT ratio was also changed following the administration of carbon tetrachloride; normal value of the ratio was 1.6. However it was increased in 11.7 after 12 hours of the administration and ten rapidly decreased to 1.1 and 0.4 after 48 hours and 72 hours. The variation pattern of LDH activity following the administration was similar to that of AST activity. The normal level of LAP and Ch-E was 333 U/ml, 208 IU/l. The change of those levels was trivial after the administration of carbon tetrachloride. These results indicated that the estimation of serum activity of LDH with AST and ALT is much more significant than that of LAP and Ch-E to evaluate the damage of hepatic tissue with carbon tetrachloride.

대동맥 평활근세포에서 인슐린 및 포도당의 농도에 따라 Transforming Growth Factor-B와 Platelet Derived Growth Factor가 콜라겐 및 비콜라겐 단백 합성과 유전자 발현에 미치는 영향

김인산,손건영,김보완,김정국,하승우,남직화,구성모,권삼,박낭운 대한당뇨병학회 1999 Diabetes and Metabolism Journal Vol.23 No.4

혈관내피세포와 피부섬유아세포에서 Collagen 및 Fibronectin 합성에 대한 Insulin 과 Insulin-like Growth Factor-1의 작용

김인산,손건영,이인규,조병채,박낭은 대한당뇨병학회 1993 Diabetes and Metabolism Journal Vol.17 No.4

成長期間中 Superoxide Dismutase의 活性 變動

金奇山,孫健英,曺準承 慶北大學校 醫科大學 1983 慶北醫大誌 Vol.24 No.2

흰쥐의 성장기간 중의 superoxide dismutase(SOD)의 변화를 알아보기 위해 생후 즉시, 출생후 2주, 4주, 6주, 그리고8주에 체중과 간장무게의 변동, 그리고 간장 SOD의 변동을 관찰하여 다음과 같은 결과를 얻었다. 출생시부터 8주까지 체중과 간장의 무게는 모두 증가하였으나 체중에 대한 간장무게의 백분율은 각각 6.1, 5.3, 4.4, 4.2, 및 3.3%로 감소하였다. 간장에서의 SDO의 specific activity는 각각 9.21, 9.44, 12.36, 14.62, 그리고 22.48 unit/mgprotein으로 계속 증가되었다. 이상의 결과로 보아 동물은 출생후 성장이 왕성할 때는 SOD의 활성도 증가된다고 하겠다. To study the changes of hepatic superoxide dismutase(SOD) during developmental stage, body weight, liver weigh and hepatic SOD of rat were determined immediately after birth, 2,4,6 and 8 weeks after birth. Body and liver weight were increased linearly during 8 weeks after birth, but percentage of liver to body weight was decreased at rate of 6.1, 5.3, 4.4, 4.2 and 3.3%, respectively. Specific activity of hepatic SOD was 9.21, 9.44, 12.36, 14.62 and 22.48 units/mg protein at the time of birth, and 2,4,6 and 8 weeks after birth, respectively. This result means that SOD activity is increased during developing stage in rats.

당뇨병환자에서 뇨증 Fibronectin농도의 증가에 관한 연구

한승범,조준승,손건영,서성문,박근용,조성래,박규영,박정모,이인규,여준기 啓明大學校 醫科大學 1994 계명의대학술지 Vol.13 No.4

Plasma fibronectin is an α₂-glyoprotein, which is produced by vascular endothelial cells. Raised level of plasma fibronectin has been observed in diabetic patients particularly in the presence of microvascular complications. However, no available data exist about urine level of this glycoprotein in diabetic patients. We measured urine fibronectin level by ELISA methods in 54 diabetic patients who have microvascular comlications or not. The following results were obtained. 1) Urine fibronectin level(㎍/g creatinine) in diabetic group(1740.0±678.0) is increased compaired with those in normal control group(471.0±59.0). but this results were not significantly different among two groups(P>0.05). 2) Urine fibronectin level(㎍/g creatinine) was significantly increased in patients with nephropathy (6188.0±3144.0) compared with those in normal control group(471.0±59.0) and patients without nephropathy(645.0±251.0)(P<0.001). 3) There were a significant correlation between BUN, creatinine, creatinine clearance, 24hr urine total protein and urine fibronectin level in diabetic patients. Our data suggest that urine fibronectin excretion level might be used as a sensitive guide for diabectic nephropathy.