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Small Animal PET Imaging with [$^{124}I$]FIAU for Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression in a Hepatoma Model (간암 동물 모델에서 2'-fluoro-2'-deoxy-1-${\beta}$-D-arabinofuranosyl-5-[$^{124}I$iodo-uracil ($[^{124}I]FIAU$) 소동물 PET 영상 연구)

  • Chae, Min-Jeong;Lee, Tae-Sup;Kim, June-Youp;Woo, Gwang-Sun;Jumg, Wee-Sup;Chun, Kwon-Soo;Kim, Jae-Hong;Lee, Ji-Sup;Ryu, Jin-Sook;Cheon, Gi-Jeong;Choi, Chang-Woon;Lim, Sang-Moo
    • Nuclear Medicine and Molecular Imaging
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    • v.42 no.3
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    • pp.235-245
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    • 2008
  • Purpose: The HSV1-tk gene has been extensively studied as a type of reporter gene. In hepatocellular carcinoma (HCC), only a small proportion of patients are eligible for surgical resection and there is limitation in palliative options. Therefore, there is a need for the development of new treatment modalities and gene therapy is a leading candidate. In the present study, we investigated the usefulness of substrate, 2'-fluoro-2'-deoxy-1-${\beta}$-D-arabino-furanosyi-5-[$^{124/125}I$]iodo- uracil ([$I^{124/125}I$]FIAU) as a non-invasive imaging agent for HSV1-tk gene therapy in hepatoma model using small animal PET. Material and Methods: With the Morris hepatoma MCA cell line and MCA-tk cell line which was transduced with the HSV1-tk gene, in vitro uptake and correlation study between [$^{125}I$]FIAU uptake according to increasing numeric count of percentage of MCA-tk cell were performed. The biodistribution data and small animal PET images with [$^{124}I$]FIAU were obtained with Balb/c-nude mice bearing both MCA and MCA-tk tumors. Results:, Specific accumulation of [[$^{125}I$]FIAU was observed in MCA-tk cells but uptake was low in MCA cells. Uptake in MCA-tk cells was 15 times higher than that of MCA cells at 480 min. [$^{125}I$]FIAU uptake was linearly correlated (R2 =0.964, p =0.01) with increasing percentage of MCA-tk numeric cell count. Biodistribution results showed that [$^{125}I$]FIAU was mainly excreted via the renal system in the early phase. Ratios of MCA-tk tumor to blood acting were 10, 41, and 641 at 1 h, 4 h, and 24 h post-injection, respectively. The maximum ratio of MCA-tk to MCA tumor was 192.7 at 24 h. Ratios of MCA-tk tumor to liver were 13.8, 66.8, and 588.3 at 1 h, 4 h, and 24 h, respectively. On small animal PET, [$^{124}I$]FIAU accumulated in substantial higher levels in MCA-tk tumor and liver than MCA tumor. Conclusion: FIAU shows selective accumulation to HSV1-tk expressing hepatoma cell tumors with minimal uptake in normal liver. Therefore, radiolabelled FIAU is expected to be a useful substrate for non-invasive imaging of HSV1-tk gene therapy and therapeutic response monitoring of HCC.

Steroid Effect on the Brain Protection During OPen Heart Surgery Using Hypothermic Circulatory Arrest in the Rabbit Cardiopulmonary bypass Model (저체온순환정지법을 이용한 개심술시 스테로이드의 뇌보호 효과 - 토끼를 이용한 심폐바이패스 실험모델에서 -)

  • Kim, Won-Gon;Lim, Cheong;Moon, Hyun-Jong;Chun, Eui-Kyung;Chi, Je-Geun;Won, Tae-Hee;Lee, Young-Tak;Chee, Hyun-Keun;Kim, Jun-Woo
    • Journal of Chest Surgery
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    • v.30 no.5
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    • pp.471-478
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    • 1997
  • Introduction: The use of rabbits as a cardiopulmonary bypass(CPB) animal model is extremely dif%cult mainly due to technical problems. On the other hand, deep hypothermic circulatory arrest(CA) is used to facilitate surgical repair in a variety of cardiac diseases. Although steroids are generally known to be effective in the treatment of cerebral edema, the protective effects of steroids on the brain during CA are not conclusively established. Objectives of this study are twofold: the establishment of CPB technique in rabbits and the evaluation of preventive effect of steroid on the development of brain edema during CA. Material '||'&'||' Methods: Fifteen New Zealan white rabbits(average body weight 3.5kg) were divided into three experimental groups; control CA group(n=5), CA with Trendelenberg position group(n=5), and CA with Trendelenberg position + steroid(methylprednisolone 30 mglkg) administration group(n=5). After anesthetic induction and tracheostomy, a median sternotomy was performed. An aortic cannula(3.3mm) and a venous ncannula(14 Fr) were inserted, respectively in the ascending aorta and the right atrium. The CPB circuit consisted of a roller pump and a bubble oxygenator. Priming volume of the circuit was approximately 450m1 with 120" 150ml of blood. CPB was initiated at a flow rate of 80~85ml/kg/min, Ten min after the start of CPB, CA was established with duration of 40min at $20^{\circ}C$ of rectal temperature. After CA, CPB was restarted with 20min period of rewarming. Ten min after weaning, the animal was sacrif;cod. One-to-2g portions of the following tissues were rapidly d:ssected and water contents were examined and compared among gr ups: brain, cervical spinal cord, kidney, duodenum, lung, heart, liver, spleen, pancreas. stomach. Statistical significances were analyzed by Kruskal-Wallis nonparametric test. Results: CPB with CA was successfully performed in all cases. Flow rate of 60-100 mlfkgfmin was able to be maintained throughout CPB. During CPB, no significant metabolic acidosis was detected and aortic pressure ranged between 35-55 mmHg. After weaning from CPB, all hearts resumed normal beating spontaneously. There were no statistically significant differences in the water contents of tissues including brain among the three experimental groups. Conclusion: These results indicate (1) CPB can be reliably administered in rabbits if proper technique is used, (2) the effect of steroid on the protection of brain edema related to Trendelenburg position during CA is not established within the scope of this experiment.

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The Effect of Retailer-Self Image Congruence on Retailer Equity and Repatronage Intention (자아이미지 일치성이 소매점자산과 고객의 재이용의도에 미치는 영향)

  • Han, Sang-Lin;Hong, Sung-Tai;Lee, Seong-Ho
    • Journal of Distribution Research
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    • v.17 no.2
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    • pp.29-62
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    • 2012
  • As distribution environment is changing rapidly and competition is more intensive in the channel of distribution, the importance of retailer image and retailer equity is increasing as a different competitive advantages. Also, consumers are not functionally oriented and that their behavior is significantly affected by the symbols such as retailer image which identify retailer in the market place. That is, consumers do not choose products or retailers for their material utilities but consume the symbolic meaning of those products or retailers as expressed in their self images. The concept of self-image congruence has been utilized by marketers and researchers as an aid in better understanding how consumers identify themselves with the brands they buy and the retailer they patronize. Although self-image congruity theory has been tested across many product categories, the theory has not been tested extensively in the retailing. Therefore, this study attempts to investigate the impact of self image congruence between retailer image and self image of consumer on retailer equity such as retailer awareness, retailer association, perceived retailer quality, and retailer loyalty. The purpose of this study is to find out whether retailer-self image congruence can be a new antecedent of retailer equity. In addition, this study tries to examine how four-dimensional retailer equity constructs (retailer awareness, retailer association, perceived retailer quality, and retailer loyalty) affect customers' repatronage intention. For this study, data were gathered by survey and analyzed by structural equation modeling. The sample size in the present study was 254. The reliability of the all seven dimensions was estimated with Cronbach's alpha, composite reliability values and average variance extracted values. We determined whether the measurement model supports the convergent validity and discriminant validity by Exploratory factor analysis and Confirmatory Factor Analysis. For each pair of constructs, the square root of the average variance extracted values exceeded their correlations, thus supporting the discriminant validity of the constructs. Hypotheses were tested using the AMOS 18.0. As expected, the image congruence hypotheses were supported. The greater the degree of congruence between retailer image and self-image, the more favorable were consumers' retailer evaluations. The all two retailer-self image congruence (actual self-image congruence and ideal self-image congruence) affected customer based retailer equity. This result means that retailer-self image congruence is important cue for customers to estimate retailer equity. In other words, consumers are often more likely to prefer products and retail stores that have images similar to their own self-image. Especially, it appeared that effect for the ideal self-image congruence was consistently larger than the actual self-image congruence on the retailer equity. The results mean that consumers prefer or search for stores that have images compatible with consumer's perception of ideal-self. In addition, this study revealed that customers' estimations toward customer based retailer equity affected the repatronage intention. The results showed that all four dimensions (retailer awareness, retailer association, perceived retailer quality, and retailer loyalty) had positive effect on the repatronage intention. That is, management and investment to improve image congruence between retailer and consumers' self make customers' positive evaluation of retailer equity, and then the positive customer based retailer equity can enhance the repatonage intention. And to conclude, retailer's image management is an important part of successful retailer performance management, and the retailer-self image congruence is an important antecedent of retailer equity. Therefore, it is more important to develop and improve retailer's image similar to consumers' image. Given the pressure to provide increased image congruence, it is not surprising that retailers have made significant investments in enhancing the fit between retailer image and self image of consumer. The enhancing such self-image congruence may allow marketers to target customers who may be influenced by image appeals in advertising.

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Ischemic Preconditioning and Its Relation to Glycogen Depletion (허혈성 전처치와 당원 결핍과의 관계)

  • 장대영;김대중;원경준;조대윤;손동섭;양기민;라봉진;김호덕
    • Journal of Chest Surgery
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    • v.33 no.7
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    • pp.531-540
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    • 2000
  • Baclgrpimd; Recent studies have suggested that the cardioprotective effect of ischemic preconditioning(IP) is closely related to glycogen depletion and attenuation of intracellular acidosis. In the present study, the authors tested this hypothesis by perfusion isolated rabbit hearts with glucose(G) is closely related to glycogen depletion and attenuation of intracellular acidosis. In the present study, the authors tested this hypothesis by perfusion isolated rabbit hearts with glucose(G)-free perfusate. Material and Method; Hearts isolated from New Zealand white rabbits(1.5~2.0 kg body weight) were perfused with Tyrode solution by Langendorff technique. After stabilization of baseline hemodynamics, the hearts were subjected to 45 min global ischemia followed by 120 min reperfusion with IP(IP group, n=13) or without IP(ischemic control group, n=10). IP was induced by single episode of 5 min global ischemia and 10 min reperfusion. In the G-free preconditioned group(n=12), G depletion was induced by perfusionwith G-free Tyrode solution for 5 min and then perfused with G-containing Tyrode solution for 10 min; and 45 min ischemia and 120 min reperfusion. Left ventricular functionincluding developed pressure(LVDP), dP/dt, heart rate, left ventricular end-distolic pressure(LVEDP) and coronary flow (CF) were measured. Myocardial cytosolic and membrane PKC activities were measured by 32P-${\gamma}$-ATP incorporation into PKC-specific peptide and PKC isozymes were analyzed by Western blot with monoclonal antibodies. Infarct size was determined by staining with TTC(tetrazolium salt) and planimetry. Data were analyzed by one-way analysis of variance (ANOVA) and Turkey's post-hoc test. Result ; In comparison with the ischemic control group, IP significantly enhanced functional recovery of the left ventricle; in contrast, functional significantly enhanced functional recovery of the left ventricle; in contrast, functional recovery were not significantly different between the G-free preconditioned and the ischemic control groups. However, the infarct size was significantly reduced by IP or G-free preconditioning(39$\pm$2.7% in the ischemic control, 19$\pm$1.2% in the IP, and 15$\pm$3.9% in the G-free preconditioned, p<0.05). Membrane PKC activities were increased significantly after IP (119%), IP and 45 min ischemia(145%), G-free [recpmdotopmomg (150%), and G-free preconditioning and 45 min ischemia(127%); expression of membrane PKC isozymes, $\alpha$ and $\varepsilon$, tended to be increased after IP or G-free preconditioning. Conclusion; These results suggest that in isolated Langendorff-perfused rabbit heart model, G-free preconditioning (induced by single episode of 5 min G depletion and 10 min repletion) colud not improve post-ischemic contractile dysfunction(after 45-minute global ischemia); however, it has an infarct size-limiting effect.

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Neuroprotective Effect of Cyclosporin A on Spinal Cord Ischemic Injury in Rabbits (토끼를 이용한 척수 허혈 손상 모델에서 Cyclosporin A의 척수 손상에 대한 보호 효과)

  • Shin Yoon-Cheol;Choe Ghee-Young;Kim Won-Gon
    • Journal of Chest Surgery
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    • v.39 no.10 s.267
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    • pp.739-748
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    • 2006
  • Background: The purpose of this study is to ascertain the neuroprotective effect of cyclosporin A on the 25-min surgical ischemia model in the spinal cords of rabbits with neuropathological correlation and histoimmunochemical analyses, Material and Method: Thirty-two New Zealand white rabbits were randomly divided into four groups: Rabbits were randomly divided into four groups: the control 12 group (n=8), the control 17 group (n=8), the cyclosporin Cs2 group (n=8), and the cyclosporin Cs7 group (n=8). The 12 group underwent a 25-min aortic cross- clamp without intervention and were sacrificed on the 2nd day postoperatively, while the 17 group underwent a 25- min of aortic cross-clamp without intervention and were sacrificed on the 7th day postoperatively. The Cs2 group received cyclosporin A (25 mg/kg) intravenously 15 min after the 25-min cross-clamp and were sacrificed on the End day postoperatively, while the Cs7 group received cyclosporin A (25 mg/kg) intravenously 15 min after the 25-min cross-clamp and were sacrificed on the 7th day postoperatively. The rabbits underwent 25-min surgical aortic cross-clamp. Neurologic functions were evaluated on the 2nd day and 7th postoperative day using Tarlov scoring system. After scoring neurologic function, all rabbits were sacrificed for histopathologic observation. Result: All rabbits survived the experimental procedure. The values of Tarlov score did not show any differences between the control and cyclosporin groups on the 2nd day. The scores of group Cs7 ($2.75{\pm}0.89$) were significantly higher than those of group 17 ($1.25{\pm}1.39$) on the 7th day (p<0,05). On the histologic exanminations, specimens of the spinal cord showed necrosis and apoptosis. The pathologic scores of group Cs7 ($1,0{\pm}0.53$) was less than those of group 17 ($2.13{\pm}1.36$, p<0.05). TUNEL staing showed apoptosis of the specimen in group 12 and Cs2 but there was no stastically significant difference between groups on the score. There were more overexpression of HSP70 and nNOS in cyclosporine group than in control group. Conclusion: We think that cyclosporin A may decrease neuronal cell death with induced upregulation of HSP70 against 25-min ischemia of the spiral cord in the rabbit.