Soyoung Choi

Systemic immune response after open versus laparoscopic cholecystectomy in acute cholecystitis : A prospective randomized study

Objective. Laparoscopic surgery is thought to reduce the postoperative immunologic effects of surgical trauma. The aim of this study is to evaluate the influence of surgical trauma on systemic inflammation and the immune response in acute cholecystitis. Material and methods. Thirty‐three patients with acute calculous cholecystitis were assigned to laparoscopic cholecystectomy (LC, n = 18) or open cholecystectomy (OC, n = 15). Blood samples were obtained preoperatively and on postoperative day 1 (24 h after surgery) and day 3 (72 h after surgery), and blood concentration of C‐reactive protein (CRP), leukocyte subpopulations, as well as levels of tumor necrosis factor‐α (TNF‐α) ex vivo secretion by peripheral blood mononuclear cells (PBMCs) were measured in both groups. Results. Hospitalization was significantly shorter in the LC group than in the OC group (LC group: 3.7±1.2 days versus OC group: 6.3±2.7 days, p = 0.010). There was no postoperative morbidity in the LC group, but two patients in the OC group had postoperative complications. Postoperative TNF‐α ex vivo secretion by PBMCs and PBMC counts in the OC group were significantly lower than those in the LC group (p = 0.002). The CRP level declined by postoperative day 3, but was significantly less in the OC group than in the LC group (p<0.001). Postoperative monocyte counts significantly decreased in the OC group compared with those in the LC group (p = 0.001). Conclusions. A laparoscopic approach appears to cause less surgical trauma and immunosuppression than open surgery in patients with acute cholecystitis.

Albumin mediates PPAR-γ or C/EBP-α-induced phenotypic changes in pancreatic stellate cells

Activation of quiescent hepatic stellate cells (HSCs) into myofibroblast-like cells is a key event of liver fibrosis, and adipogenic transcription factors, PPAR-gamma and C/EBP-alpha, reverse HSC activation. As albumin was reported to maintain the quiescent phenotype of stellate cells, we examined whether it plays a role in PPAR-gamma and C/EBP-alpha-mediated effects. Pancreatic stellate cells (PSCs) were isolated from rat pancreas and used in their culture-activated phenotype. Forced expression of PPAR-gamma or C/EBP-alpha in PSCs increased albumin mRNA and protein levels by >2.5-fold, which is accompanied with increased C/EBP-beta binding to albumin promoter. PPAR-gamma and C/EBP-alpha also induced a phenotypic switch from activated to quiescent cells and, interestingly, suppression of albumin using short-hairpin RNA (shRNA) blocked their effects. Therefore, our findings suggest that albumin may be a downstream effector of PPAR-gamma and C/EBP-alpha in PSCs and that it can be an attractive molecular target for anti-fibrotic therapies.

Fusion protein of retinol-binding protein and albumin domain III reduces liver fibrosis

Activated hepatic stellate cells (HSCs) play a key role in liver fibrosis, and inactivating HSCs has been considered a promising therapeutic approach. We previously showed that albumin and its derivative designed for stellate cell‐targeting, retinol‐binding protein–albumin domain III fusion protein (referred to as R‐III), inactivate cultured HSCs. Here, we investigated the mechanism of action of albumin/R‐III in HSCs and examined the anti‐fibrotic potential of R‐III in vivo. R‐III treatment and albumin expression downregulated retinoic acid (RA) signaling which was involved in HSC activation. RA receptor agonist and retinaldehyde dehydrogenase overexpression abolished the anti‐fibrotic effect of R‐III and albumin, respectively. R‐III uptake into cultured HSCs was significantly decreased by siRNA‐STRA6, and injected R‐III was localized predominantly in HSCs in liver. Importantly, R‐III administration reduced CCl4‐ and bile duct ligation‐induced liver fibrosis. R‐III also exhibited a preventive effect against CCl4‐inducd liver fibrosis. These findings suggest that the anti‐fibrotic effect of albumin/R‐III is, at least in part, mediated by downregulation of RA signaling and that R‐III is a good candidate as a novel anti‐fibrotic drug.

Retinol binding protein-albumin domain III fusion protein deactivates hepatic stellate cells

Liver fibrosis is characterized by accumulation of extracellular matrix, and activated hepatic stellate cells (HSCs) are the primary source of the fibrotic neomatrix and considered as therapeutic target cells. We previously showed that albumin in pancreatic stellate cells (PSCs), the key cell type for pancreatic fibrogenesis, is directly involved in the formation of vitamin A-containing lipid droplets, inhibiting PSC activation. In this study, we evaluated the anti-fibrotic activity of both albumin and retinol binding protein-albumin domain III fusion protein (R-III), designed for stellate cell-targeted delivery of albumin III, in rat primary HSCs and investigated the underlying mechanism. Forced expression of albumin or R-III in HSCs after passage 2 (activated HSCs) induced lipid droplet formation and deactivated HSCs, whereas point mutations in high-affinity fatty acid binding sites of albumin domain III abolished their activities. Exogenous R-III, but not albumin, was successfully internalized into and deactivated HSC-P2. When HSCs at day 3 after plating (pre-activated HSCs) were cultured in the presence of purified R-III, spontaneous activation of HSCs was inhibited even after passage 2, suggestive of a potential for preventive effect. Furthermore, treatment of HSCs-P2 with R-III led to a significant reduction in both cytoplasmic levels of all-trans retinoic acid and the subsequent retinoic acid signaling. Therefore, our data suggest that albumin deactivates HSCs with reduced retinoic acid levels and that R-III may have therapeutic and preventive potentials on liver fibrosis.

Recombinant fusion protein of albumin-retinol binding protein inactivates stellate cells.

Quiescent pancreatic- (PSCs) and hepatic- (HSCs) stellate cells store vitamin A (retinol) in lipid droplets via retinol binding protein (RBP) receptor and, when activated by profibrogenic stimuli, they transform into myofibroblast-like cells which play a key role in the fibrogenesis. Despite extensive investigations, there is, however, currently no appropriate therapy available for tissue fibrosis. We previously showed that the expression of albumin, composed of three homologous domains (I-III), inhibits stellate cell activation, which requires its high-affinity fatty acid-binding sites asymmetrically distributed in domain I and III. To attain stellate cell-specific uptake, albumin (domain I/III) was coupled to RBP; RBP-albumin(domain III) (R-III) and albumin(domain I)-RBP-albumin(III) (I-R-III). To assess the biological activity of fusion proteins, cultured PSCs were used. Like wild type albumin, expression of R-III or I-R-III in PSCs after passage 2 (activated PSCs) induced phenotypic reversal from activated to fat-storing cells. On the other hand, R-III and I-R-III, but not albumin, secreted from transfected 293 cells were successfully internalized into and inactivated PSCs. FPLC-purified R-III was found to be internalized into PSCs via caveolae-mediated endocytosis, and its efficient cellular uptake was also observed in HSCs and podocytes among several cell lines tested. Moreover, tissue distribution of intravenously injected R-III was closely similar to that of RBP. Therefore, our data suggest that albumin-RBP fusion protein comprises of stellate cell inactivation-inducing moiety and targeting moiety, which may lead to the development of effective anti-fibrotic drug.

Design of the Travel Agency System based on Service Oriented Architecture for business models

As industrial structure of OECD has change from the manufacturing industry to service industry rapidly, the proportion of the service industries have become nearly 70 percent. The service science is the newest science that searches intrinsic qualities of the service industry, innovates service levels, and includes knowledge of the service management, the service marketing and the service engineering, therefore develops related fields. Framework of the service science, service oriented architecture (SOA) has been making sure of its position rapidly. This paper proposed a plan that SOA could be applied to the service industry through a prototype design of the Travel Agency System based on SOA for Business Models. The analysis of requirements is proceeded by Unified Modeling Language and SOA delivery strategy is selected the top-down strategy. service candidates and operations can be derived through analyzing detailed process of each use case, these can be abstracted at two service layers for effective implementation. Travel Agency System was designed by means of WSDL, XML-based language that describes Business Service and provides a approaching means between Businesses electrically.

An assessment model for PL-product companies based on the Analytic Hierarchy Process

This paper addresses an assessment model for selecting PL(Private Level) product companies. The proposed model extracts the weights of evaluation elements based on AHP(Analytic Hierarchy Process). These evaluation elements are from real-world instances in a domestic hyper market. Especially, the model points at food products which constitute a large portion of entire profits in the market. In this model, we first classify the 54 evaluation elements into 4 layers and secondly carry out a survey with relevant specialists based on them. We also estimate the weights of evaluation elements according to pairwise comparisons from the survey, and propose them as a quantitative alternative which can be applied in real-world problems. Finally, the pilot-study is conducted to compare the proposed model with the existing simple summation method. From this study, HACCP system assessment and Review(0.279281), Transportation(0.117706) and Fundamental law observance(0.066392) are presented as the key evaluation elements for selecting PL product companies. The proposed model facilitates the company selection among those candidate companies which is not easy to determine the superiority by reflecting the importance of evaluation elements.