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Selected AbstractsChanges in gene expression and morphology of mouse embryonic stem cells on differentiation into insulin-producing cells in vitro and in vivoDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2009Ortwin Naujok Abstract Background Embryonic stem (ES) cells have the potential to produce unlimited numbers of surrogate insulin-producing cells for cell replacement therapy of type 1 diabetes mellitus. The impact of the in vivo environment on mouse ES cell differentiation towards insulin-producing cells was analysed morphologically after implantation. Methods ES cells differentiated in vitro into insulin-producing cells according to the Lumelsky protocol or a new four-stage differentiation protocol were analysed morphologically before and after implantation for gene expression by in situ reverse transcription polymerase chain reaction and protein expression by immunohistochemistry and ultrastructural analysis. Results In comparison with nestin positive ES cells developed according to the reference protocol, the number of ES cells differentiated with the four-stage protocol increased under in vivo conditions upon morphological analysis. The cells exhibited, in comparison to the in vitro situation, increased gene and protein expression of Pdx1, insulin, islet amyloid polypeptide (IAPP), the GLUT2 glucose transporter and glucokinase, which are functional markers for glucose-induced insulin secretion of pancreatic beta cells. Renal sub-capsular implantation of ES cells with a higher degree of differentiation achieved by in vitro differentiation with a four-stage protocol enabled further significant maturation for the beta-cell-specific markers, insulin and the co-stored IAPP as well as the glucose recognition structures. In contrast, further in vivo differentiation was not achieved with cells differentiated in vitro by the reference protocol. Conclusions A sufficient degree of in vitro differentiation is an essential prerequisite for further substantial maturation in a beta-cell-specific way in vivo, supported by cell-cell contacts and vascularisation. Copyright © 2009 John Wiley & Sons, Ltd. [source] WORKINGS OF THE MELTING POT: SOCIAL NETWORKS AND THE EVOLUTION OF POPULATION ATTRIBUTES,JOURNAL OF REGIONAL SCIENCE, Issue 2 2007Jan K. Brueckner ABSTRACT This paper links the two nascent economic literatures on social networks and cultural assimilation by investigating the evolution of population attributes in a simple model where agents are influenced by their acquaintances. The main conclusion of the analysis is that attributes converge to a melting-pot equilibrium, where everyone is identical, provided the social network exhibits a sufficient degree of interconnectedness. When the model is extended to allow an expanding acquaintance set, convergence is guaranteed provided a weaker interconnectedness condition is satisfied, and convergence is rapid. If the intensity of interactions with acquaintances becomes endogenous, convergence (when it occurs) is slowed when agents prefer to interact with people like themselves and hastened when interaction with dissimilar agents is preferred. [source] Management of retinoblastoma with proximal optic nerve enhancement on MRI at diagnosisPEDIATRIC BLOOD & CANCER, Issue 4 2008Saro H. Armenian DO Abstract Background In North America, retinoblastoma rarely presents with gross clinical evidence of tumor involving the optic nerve. Extent of microscopic tumor infiltration into the postlaminar optic nerve is a significant risk factor for metastasis, especially if there is tumor at the cut end. Due to poor outcomes in patients with metastatic disease, historical treatment for patients with clinical evidence of extraocular optic nerve involvement has included upfront enucleation followed by aggressive adjuvant chemotherapy. Additional orbital irradiation is advocated for individuals with optic nerve involvement at the surgical margin. Little is known about the role of neoadjuvant therapy in the setting of orbital optic nerve enhancement on magnetic resonance imaging (MRI) at diagnosis. Methods A retrospective review of consecutive retinoblastoma cases at Childrens Hospital Los Angeles over a 3-year period (2004,2006) found to have gadolinium contrast enhancement in the proximal portion of optic nerve on MRI at diagnosis. Results Nine patients fit the inclusion criteria. Two had secondary glaucoma of a sufficient degree to cause an enlarged eye (buphthalmos). Median age at presentation was 17 months (2,36 months). All patients received neoadjuvant chemotherapy prior to enucleation. Only two received external beam radiation. All are disease-free with a median follow-up of 22 months (12,41 months). Conclusions Neoadjuvant chemotherapy is well tolerated prior to enucleation of retinoblastoma-containing eyes associated with contrast enhancement of the proximal optic nerve on MRI at diagnosis. Such an approach may be used to decrease intensity or duration of chemotherapy and need for external beam radiation. Pediatr Blood Cancer 2008;51:479,484. © 2008 Wiley-Liss, Inc. [source] Increased plasma levels of natriuretic peptide type B and A in children with congenital heart defects with left compared with right ventricular volume overload or pressure overloadCLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, Issue 5 2005Daniel Holmgren Summary Aim:, Natriuretic peptide levels B (BNP) and A (ANP) have been described in children with congenital heart defects (CHD) with pressure and volume overload. However, the impact of ventricular morphology per se on natriuretic peptide levels has not been reported. The aim of the present study was to evaluate plasma BNP and ANP in children with CHD with left or right ventricular volume or pressure overload. Methods and results:, Plasma BNP and ANP were analysed in 61 children, median age 3·1 (0·3,16·2) years. Haemodynamic load was evaluated by echo-Doppler and/or catheterization measurements and classified as: pressure overload of the right (RV pressure) or left (LV pressure) ventricle, or volume overload of the right (RV volume) or left (LV volume) ventricle, of a sufficient degree to indicate surgery/catheter intervention. Twenty-three children, with a median age of 1·1 (0·1,8·3) years, without heart disease, served as controls for the natriuretic peptide measurements. Children in the LV volume group had significantly higher BNP and ANP values, 55·4 ng l,1 (10·7,352) and 164 (31·8,346), than children in the RV volume, 15·6 (0·0,105·1) and 57·2 (11·3,234·1), LV pressure, 6·8 (0·7,170) and 40·8 (12·6,210), and RV pressure, 18·0 (5·0,29·1) and 69·3 (8·7,182), groups respectively (P<0·0001). The values in the LV pressure group were close to the values in the Control group, 4·7 (0·0,17·7) and 32·9 (11·7,212·1), respectively (P = 0·051 and P = 0·378, respectively). Conclusions:, Plasma concentrations of BNP and ANP were higher in children with CHD with left ventricular volume overload compared with right ventricular volume overload or pressure overload. [source] A semi-Markov model for binary longitudinal responses subject to misclassificationTHE CANADIAN JOURNAL OF STATISTICS, Issue 3 2001Rhonda J. Rosychuk Abstract The authors propose a two-state continuous-time semi-Markov model for an unobservable alternating binary process. Another process is observed at discrete time points that may misclassify the true state of the process of interest. To estimate the model's parameters, the authors propose a minimum Pearson chi-square type estimating approach based on approximated joint probabilities when the true process is in equilibrium. Three consecutive observations are required to have sufficient degrees of freedom to perform estimation. The methodology is demonstrated on parasitic infection data with exponential and gamma sojourn time distributions. Un modèle semi-markovien pour données longitudinales binaires sujettes à des erreurs de classification Les auteures proposent un modèle semi-markovien à temps continu et à deux états pour un processus binaire alternant non-observable. Un processus auxiliaire observé en temps discret renseigne toutefois de façon imparfaite quant à l'état réel du processus d'intér,t. Pour estimer les paramètres du modèle, les auteures proposent la minimisation d'un critère de type khi-deux de Pearson en s'appuyant sur une approximation des probabilités conjointes du processus en équilibre. Trois observations consécutives fournissent suffisamment de degrés de liberté aux fins d'estimation. La méthodologie est illustrée au moyen de données sur une infection parasitaire avec temps de séjour exponentiel et gamma. [source] | ||||||||||