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        A human monoclonal antibody $F_{ab}$ reactive to oxidized LDL and carbamylated LDL recognizes human and mouse atherosclerotic lesions

        Jang, Young-Ju,Joo, Hee-Jae,Yang, Jeong-In,Seo, Chang-Won,Chung, Kui-Yea,Lanza, Gregory M.,Zhang, Huiying The Korean Society for Integrative Biology 2011 Animal cells and systems Vol.15 No.4

        This study was undertaken to produce a $F_{ab}$ fragment of a human monoclonal antibody reactive to oxidized and carbamylated low-density lipoprotein (oxLDL and cLDL) using phage display technology. An analysis of DNA sequences of this $F_{ab}$, termed plaque 15,16-46 $F_{ab}$, revealed that the rearranged $V_H$ was highly mutated. Complementarity-determining regions of the $V_H$ showed a very high R/S ratio and contained many positively charged amino acids. In direct binding and competitive ELISA, the $F_{ab}$ reacted strongly with both MDA-LDL and Cu-oxLDL forms of oxLDL, and also showed high affinity for cLDL. Immunofluorescence and immunohistochemical analyses showed that this $F_{ab}$ positively stained atherosclerotic aortic plaques in $ApoE^{-/-}$ mice as well as those in patients with atherosclerosis. The $F_{ab}$ also showed positive staining in placental decidua from patients with preeclampsia. It is suggested that the plaque 15,16-46 $F_{ab}$ against oxLDL and cLDL might possibly be applicable for developing a diagnostic reagent for both human and rodent animal research to detect and characterize atherosclerotic disease progression in atherosclerotic lesions as well as exploring the pathogenesis of atherogenic diseases such as preeclampsia.

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        Effects of Vitamin C on Oxidative Stress Due to Anesthesia and Surgical Trauma in Dogs

        최경하,이재연,정성목,Gregory K Joo,김명철 한국임상수의학회 2011 한국임상수의학회지 Vol.28 No.5

        The study evaluated the antioxidant effects of ascorbic acid (AA) against oxidative stress during laparotomy in dogs under general anesthesia using isoflurane. Twelve dogs were randomly assigned to either the ascorbic acid group (AAG) or the sham group (SG). AAG received intravenous dosage of 100 mg/animal of standard AA 10 minutes before anesthesia. Plasma levels of cortisol, glucose, total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were measured. Cortisol level increased significantly with time in both groups (p < 0.05). The change of glucose levels was not significantly different between both groups. TOS and OSI increased significantly with time in the SG (p < 0.05), whereas it did not significantly change with time in the AAG. The TOS and OSI of the AAG were significantly lower than in the SG (p < 0.05). However, TAS did not significantly change between both groups. The results suggest that the decrease of TOS in the AAG might be related to the conversion of antioxidants to oxidants. The decrease of OSI indicates that the decrease of reactive oxygen species (i.e., oxidative stress) produced at the site of injury is able to decrease surgical side effects of abnormal blood circulation, organ failure, and inflammation. Therefore, AA can be used to protect a surgical patient from oxidative stress in canine laparotomy.

      • Special Lecture : VEGF; Hot Track To Qualified Ulcer Healing

        ( Sang Woon Park ),( Min Ho Kim ),( Yong Seok Kim ),( Eun Jeong Jang ),( Joo Sang Park ),( Sang Jong Park ),( Hyun Wook Baik ),( Gregory Chung ),( Sung Won Cho ),( Ki Baik Hahm ) 대한소화기학회 2007 SIDDS Vol.9 No.-

        Background and Aim: Irrespective of etiologies of peptic ulcer diseases (PUD), the most ulcers develop on the lesser curvature side of stomach including incisura and anterior wall of duodenal bulb. However, still no clear explanation why ulcers are prevalent in these areas has been given except some speculations including insufficient perfusion through abnormality in blood vessel, weak structural points or host characteristics. Here, we hypothesized that VEGF polymorphism can predict the susceptibility to peptic ulcer disease through deranged angiogenic activities. Methods: Based on several single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) gene reported in literature search and their frequency studies done with Korean population, we performed the case-control study of 864 patients of chronic gastritis and gastric ulcer in 10 SNPs of VEGF gene including -2488 C/T, -634G/C, -7C/T, 3436G/C, 6112C/A, 6894C/T, 9374G/A, 9812C/T, 13128C/T, and 13553C/T, but of which results showed no statistically significant association between chronic gastritis and gastric ulcer. Results: We performed denatured high-performance liquid chromatography analysis to discover the novel SNP of VEGF gene, after which two novel SNPs of VEGF gene, -1780T/C and IVS-99 G/C, were identified, among which -1780T/C showed significant association between chronic gastritis and peptic ulcer disease, showing OR=2.93 on co-dominant analysis (p<0.001), OR=8.62 on dominant analysis (p<0.001), and OR=3.21 on recessive analysis (p<0.001). Promoter assay using site directed mutagenesis and in vitro angiogenesis assay showed repressed transcription of VEGF gene in gastric epithelial cells and defective tube formation in endothelial cells transfected with plasmid containing -1780C/C mutant of VEGF gene. Conclusion: Novel VEGF polymorphism, -1780T/C, is significantly associated with the predisposition to PUD after the exposure to etiologic risks.

      • Comparison of the anti-inflammatory effects of induced pluripotent stem cell-derived and bone marrow-derived mesenchymal stromal cells in a murine model of corneal injury

        Yun, Young In,Park, Se Yeon,Lee, Hyun Ju,Ko, Jung Hwa,Kim, Mee Kum,Wee, Won Ryang,Reger, Roxanne L.,Gregory, Carl A.,Choi, Hosoon,Fulcher, Samuel F.,Prockop, Darwin J.,Oh, Joo Youn Elsevier 2017 cytotherapy Vol.19 No.1

        <P>Background aims. Mesenchymal stromal cells (MSCs) offer tremendous potential for therapeutic applications for inflammatory diseases. However, tissue-derived MSCs, such as bone marrow derived MSCs (BM-MSCs), have considerable donor variations and limited expandability. It was recently demonstrated that MSCs derived from induced pluripotent stem cells (iPSC-MSCs) have less pro-tumor potential and greater expandability of homogenous cell population. In this study, we investigated the anti-inflammatory effects and mechanism of iPSC-MSCs in a murine model of chemical and mechanical injury to the cornea and compared the effects with those of BM-MSCs. Methods. To create an injury, ethanol was applied to the corneal surface in mice, and the corneal epithelium was removed with a blade. Immediately after injury, mice received an intravenous injection of (i) iPSC-MSCs, (ii) BM-MSCs or (iii) vehicle. Clinical, histological and molecular assays were performed in the cornea to evaluate inflammation. Results. We found that corneal opacity was significantly reduced by iPSC-MSCs or BM-MSCs. Histological examination revealed that the swelling and inflammatory infiltration in the cornea were markedly decreased in mice treated with iPSC-MSCs or BM-MSCs. Corneal levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 were lower in iPSC-MSC- and BM-MSC-treated mice, compared with vehicle-treated controls. In contrast, iPSC-MSCs with a knockdown of the TNF-alpha stimulating gene (TSG)-6 did not suppress the levels of inflammatory cytokines and failed to reduce corneal opacity. Conclusions. Together these data demonstrate that iPSC-MSCs exert therapeutic effects in the cornea by reducing inflammation in part through the expression of TSG-6, and the effects are similar to those seen with BM-MSCs.</P>

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