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        신이식 환자의 말초혈액 림프구에서 Perforin , Fas - ligand 와 Granzyme B 의 발현

        신규태(Gyu Tae Shin),김승정(Seung Jung Kim),마경애(Kyung Ai Ma),김정은(Jung Eun Kim),이종우(Jong Woo Lee),김흥수(Heung Soo Kim),이태승(Tae Seung Lee),오창권(Chang Kwon Oh),최영일(Young Il Choi),김도헌(Do Hun Kim) 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.3

        배 경 : 최근의 여러 연구를 통하여 신이식 환자의 급성거부반응 시에 세포독성 물질들의 발현이 증가한다고 알려져 있다. 본 연구에서 저자 등은 신이식 환자의 말초 혈액 림프구에서 perforin, granzyme B와 Fas ligand(FasL)의 mRNA 발현을 순차적으로 검사하여, 이들이 급성 거부반응을 진단할 수 있는 지표로서 유용한지 평가하고자 하였다. 방 법 : 말초혈액 림프구를 신이식후 2, 4, 6, 8, 10, 12일에 환자의 혈액으로부터 분리하여, perforin, granzyme B, FasL의 mRNA에 대한 발현 정도를 competitive polymerase chain reaction으로 평가하였다. 결과는 β-Actin의 값으로 나누어 보정하였다(fg/pg). 대조군에서 perforin, granzyme B, FasL 각각의 평균값+2×표준편차를 기준상한치로 설정하였다. 결 과 : Perforin mRNA 발현의 평균치는 대조군(8명, 47개)에 비해 급성거부반응 군(7명, 41 개) 에서 현저히 높게 나타났다(1.84±3.01 vs 0.71±0.48, p=0.01). 기준상한치(1.67)를 초과하는 perforin mRNA 발현의 수도 급성거부반응군에서 현저히 높았다(12/41 vs. 1/47, p=0.0003). 급성거부반응 군에서 5명이 기준상한치를 초과하는 perforin mRNA 발현을 보인 반면(5명/7명, 71.4%), 대조군에서는 한 명만이 이러한 결과를 보였다(1명/8명, 12.5%, p=0.02). 거부반응 0-1 일째의 perforin mRNA 발현이 연구 기간 중 가장 높게 나타났다. Granzyme B와 FasL mRNA 발현은 급성거부반응 시기와 일정한 연관성을 보이지 않았다. 결 론: 본 연구에서 말초혈액 림프구의 perforin mRNA 발현이 급성거부반응시에 유의하게 증가되었으며, perforin mRNA 발현을 급성거부반응의 진단에 이용할 가능성을 제시하였다. Background : Previous findings demonstrated that the expression of cytotoxic effector molecules is increased in acute rejection of renal allografts. In the present study, we serially examined the gene expression of perforin, granzyme B and Fas ligand(FasL) in peripheral blood lymphocytes(PBLs) of renal allograft recipients to assess the potential of their expression as a marker of acute rejection. Methods : PBLs were isolated from blood samples taken on days 2, 4, 6, 8, 10 and 12 after transplantation. Competitive PCR was performed to evaluate the abundance of mRNA of perforin, granzyme B and FasL. The mean value of each molecule plus 2 SD for the control group was set as a discriminatory level. Results : When all measured samples were compared, perforin expression was significantly higher in patients with acute rejection than in the control group(1.84±3.01 versus 0.71±0.48, p=0.01). The percentage of perforin expression exceeding the discriminatory level was also significantly higher in patients with acute rejection(p=0.0003). Five patients in the rejection group(5/7, 71.4%) showed perforin expression exceeding the discriminatory level, while only 1 patient in the control group did so(1/8, 12.5%)(p=0.02). Perforin expression of days 0 and 1 of rejection crisis was the highest over the study period. No consistent pattern of granzyme B and FasL expression was identified in relation to rejection crisis. Conclusion : Gene expression of perforin by PBLs was upregulated in accordance with acute rejection, thus offering the possibility that it may be utilized as a marker of acute rejection.

      • SCOPUSKCI등재
      • KCI등재후보

        Wegener`s granulomatosis 환자에서 발생한 cyclophosphamide 에 의한 폐독성 1 예

        김흥수,이진호,박경주,최영일,임현이,최영인,김도헌,엄철,마경애,한명호,신규태 대한내과학회 2001 대한내과학회지 Vol.61 No.4

        $quot;Lung toxicity associated with cyclophosphamide use is a rare but serious side effect, that may result in a fatal course. However no such cases have been reported in Korea, so clinicians would not be alert to this adverse effect. We recently experienced a woman with Wegener's granulomatosis and idiopathic pulmonary fibrosis. This patient had been administered 12 grams of cyclophosphamide for 4 months. At that time of admission, She felt aggravating dyspnea on exertion for 2 weeks. Her chest X-ray and high resolution CT revealed aggravated reticular opacities and ground glass appearances. Dyspnea was improved and ground glass appearances on HRCT was disappeared after discontinuation of cyclophosphamide. We diagnosed this case as cyclophosphamide-induced pneumonitis and report it with a brief review of the liter ature. (Korean J Med 61:439-443, 2001)$quot; Background: A number of theories have been proposed to explain the nature of aging process. Unfortunately, there is so far no theory that can completely explain all aging processes. In the present study, to investigate roles of inducibility of defense mechanisms by oxidative stress, cellular mRNA level of super oxide dismutases (SODs) and metallothionein (MT) as well as their inducibility by paraquat, an intracellular super oxide generator , was examined in the liver and kidney of the mice of aging process. Methods: The steady-state levels of SODs and MT mRNA and their induction by paraquat were determined by the RT-PCR assay in male mice of 4 ages, 1, 4, 8, and 12 months. Results: In the liver, the steady-state levels of Mn-SOD, Cu/Zn-SOD and MT mRNA increased until 8 months with age and decreased significantly at 12 months. Cu/Zn- SOD and MT mRNA were induced well by paraquat at all ages but Mn-SOD mRNA not at 12 months. In the kidney, their mRNA levels of Mn-SOD, Cu/Zn-SOD and MT increased with age. Mn-SOD mRNA was induced by paraquat only at 1 month but Cu/Zn-SOD mRNA not at all ages. On the other hand, MT mRNA was significantly induced by paraquat at all ages. Conclusion: These results suggest that SODs and MT are differentially expressed and induced according to the age and organs . In addition, it is thought that the lack of induction of Mn-SOD by oxidative stress in both the liver and kidney may be one of causative factors in the aging process while Cu/Zn-SOD and MT in the liver and MT in the kidney may play protective roles in the aging process. It is therefore implicated that the tissue antioxidant/prooxidant balance could be one of determinants of mean life span. (Korean J Med 61:430-438, 2001)

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