Hakbae Lee

Tissue Transglutaminase Is Essential for Integrin-Mediated Survival of Bone Marrow-Derived Mesenchymal Stem Cells

Autologous mesenchymal stem cell (MSC) transplantation therapy for repair of myocardial injury has inherent limitations due to the poor viability of the stem cells after cell transplantation. Adhesion is a prerequisite for cell survival and also a key factor for the differentiation of MSCs. As a novel prosurvival modification strategy, we genetically engineered MSCs to overexpress tissue transglutaminase (tTG), with intention to enhance adhesion and ultimately cell survival after implantation. tTG‐transfected MSCs (tTG‐MSCs) showed a 2.7‐fold and greater than a twofold increase of tTG expression and surface tTG activity, respectively, leading to a 20% increased adhesion of MSCs on fibronectin (Fn). Spreading and migration of tTG‐MSCs were increased 4.75% and 2.52%, respectively. Adhesion of tTG‐MSCs on cardiogel, a cardiac fibroblast‐derived three‐dimensional matrix, showed a 33.1% increase. Downregulation of tTG by transfection of small interfering RNA specific to the tTG resulted in markedly decreased adhesion and spread of MSCs on Fn or cardiogel. tTG‐MSCs on Fn significantly increased phosphorylation of focal adhesion related kinases FAK, Src, and PI3K. tTG‐MSCs showed significant retention in infarcted myocardium by forming a focal adhesion complex and developed into cardiac myocyte‐like cells by the expression of cardiac‐specific proteins. Transplantation of 1 × 106 MSCs transduced with tTG into the ischemic rat myocardium restored normalized systolic and diastolic cardiac function. tTG‐MSCs further restored cardiac function of infarcted myocardium as compared with MSC transplantation alone. These findings suggested that tTG may play an important role in integrin‐mediated adhesion of MSCs in implanted tissues.

Calreticulin inhibits the MEK1,2-ERK1,2 pathway in α1-adrenergic receptor/Gh-stimulated hypertrophy of neonatal rat cardiomyocytes

In cardiac myocytes, stimulation of alpha(1)-adrenoceptor (AR) leads to a hypertrophic phenotype. The G(h) protein (transglutaminase II, TGII) is tissue type transglutaminase and transmits the alpha(1B)-adrenoceptor signal with GTPase activity. Recently, it has been shown that the calreticulin (CRT) down-regulates both GTP binding and transglutaminase activities of TGII. To elucidate whether G(h) mediates norepinephrine-stimulated intracellular signal transductions leading to activation of extracellular signal-regulated kinases (ERKs) and neonatal rat cardiomyocyte hypertrophy, we examined the effects of G(h) on the activation of ERKs and inhibitory effects of CRT on alpha(1)-adrenoceptor/G(h) signaling. In neonatal rat cardiomyocytes, norepinephrine-induced ERKs activation was inhibited by an alpha(1)-adrenoceptor blocker (prazosin), but not by an beta-adrenoceptor blocker (propranolol). Overexpression of the G(h) protein stimulated norepinephrine-induced ERKs activation, which was inhibited by alpha-adrenoceptor blocker (prazosin). Co-overexpression of G(h) and CRT abolished norepinephrine-induced ERKs activation. Taken together, norepinephrine induces hypertrophy in neonatal rat cardiomyocytes through alpha(1)-AR stimulation and G(h) is partly involved in norepinephrine-induced MEK1,2/ERKs activation. Activation of G(h)-mediated MEK1,2/ERKs was completely inhibited by CRT.

Using neural networks to support early warning system for financial crisis forecasting

This study deals with the construction process of a daily financial condition indicator (DFCI), which can be used as an early warning signal using neural networks and nonlinear programming. One of the characteristics in the proposed indicator is to establish an alarm zone in the DFCI, which plays a role of predicting a potential financial crisis. The previous financial condition indicators based on statistical methods are developed such that they examine whether a crisis will be break out within 24 months. In this study, however, the alarm zone makes it possible for the DFCI to forecast an unexpected crisis on a daily basis and then issue an early warning signal. Therefore, DFCI involves daily monitoring of the evolution of the stock price index, foreign exchange rate and interest rate, which tend to exhibit unusual behaviors preceding a possible crisis. Using nonlinear programming, the procedure of DFCI construction is completed by integrating three sub-DFCIs, based on each financial variable, into the final DFCI. The DFCI for Korean financial market will be established as an empirical study. This study then examines the predictability of alarm zone for the financial crisis forecasting in Korea.

Investigating SIR, DOC and SAVE for the Polychotomous Response

This paper investigates the central subspace related with SIR, DOC and SAVE when the response has more than two values. The subspaces constructed by SIR, DOC and SAVE are investigated and compared. The SAVE paradigm is the most comprehensive. In addition, the SAVE coincides with the central subspace when the conditional distribution of predictors given the response is normally distributed.

P09.02: Transabdominal embryofetoscopy: 6 cases of first trimester prenatal diagnosis for congenital anomalies

Objective: Value of ultrasonography in assessment of pathological changes in ovaries of premenopausal women in comparison with histological diagnosis after surgery. Method: Study group consisted of 46 patients age 16 to 45 with ovarian cyst diagnosed by transvaginal (44 patients) or abdominal and transperineal ultrasonography. Results: Histological diagnoses were in close correlation with ultrasound examination results. All the patients with endometrial, serous and follicular cysts were correctly diagnosed with ultrasound. Teratoma tumors were diagnosed with great accuracy (91.7%). Lower accuracy was noted with reference to paraovarian and corpus luteum cysts (50.0% and 66.7%). Hydropyosalpinx was correctly diagnosed in 75.0% cases. Conclusions: Ultrasonography performed by experienced ultrasonologist is a great diagnostic method which allow to make correct diagnosis before histopathological confirmation.

Classification Using Sliced Inverse Regression and Sliced Average Variance Estimation

We explore classification analysis using graphical methods such as sliced inverse regression and sliced average variance estimation based on dimension reduction. Some useful information about classification analysis are obtained by sliced inverse regression and sliced average variance estimation through dimension reduction. Two examples are illustrated, and classification rates by sliced inverse regression and sliced average variance estimation are compared with those by discriminant analysis and logistic regression.