T Otonkoski

..Here, we describe the derivation of five hESC lines (called FES 21, 22, 29, 30 and 61) from frozen-thawed human embryos and compare their individual differentiation characteristic...

..Structural analyses were performed by specific glycosidase enzymes and mass spectrometric fragmentation analyses...

..In conclusion, EIHI represents a new autosomal-dominant hyperinsulinemia syndrome that may be more common than has been realized. The pyruvate test provides a simple, safe, and specific diagnostic test for this condition...

..This unique SUR1 mutation explains the majority of PHHI cases in Finland and is strongly associated with a severe form of the disease. These findings provide diagnostic and prognostic utility for suspected PHHI patients...

..After initial excitement, it appears that much basic research is still required before this goal could be achieved...

..In conclusion, [(18)F]-DOPA PET is a promising noninvasive method for the identification and localization of the focal form of CHI...

..This information has potentially important implications for the generation of an optimal microenvironment for beta-cell function, proliferation and differentiation...

..These findings describe a novel disease mechanism based on the failure of cell-specific transcriptional silencing of a gene that is highly expressed in other tissues...

..Coxsackie B viruses cause functional impairment and beta-cell death characterized by nuclear pyknosis. Apoptosis appears to play a minor role during a productive CBV infection in beta-cells...

..In addition, we have identified betacellulin as a possible modulator of beta-cell growth...

..Based on mouse study findings, pancreatic islet cells are supposed to lack basement membrane (BM) and interact directly with vascular endothelial BM. Until now, the BM composition of human islets has remained elusive...

..We sought evidence for this through autopsy studies and by investigating known enterovirus receptors in cultured human islets...

..The islet progenitors have been thought to be ductal cells. Since previous experiments have been 'contaminated' by a number of pre-existing islet cells, we examined their involvement in islet cell neogenesis...

..Our results support the previous notion that pancreatic progenitor cells represent a subpopulation of ductal epithelial cells. No evidence was found for the development of endocrine cells from nestin-positive stem cells...

..Sirolimus and daclizumab have no adverse effects on these parameters. The immunosuppressive protocol may be an important determinant of long-term clinical islet graft function...

..In this study we investigated the role of EGFR signalling in the physiological states of beta cell mass expansion in adults during metabolic syndrome and pregnancy, as well as in regeneration after pancreatic duct ligation...

..However, we were unable to confirm the capacity of these cells to differentiate into insulin-producing cells. Our results indicate that Nkx2.2 plays a role in the transcriptional regulation of PP expression...

..Exocrine pancreatic insufficiency was diagnosed at the age of 1 year. CONCLUSION/INTERPRETATION: These observations suggests that enteroviral infections may induce beta-cell autoimmunity even in utero...

..Ductal cell differentiation into endocrine cells may be an important factor in sustaining the long-term function of islet transplants...

..In summary, our results show that even a modest attenuation of EGF-R signaling leads to a severe defect in postnatal growth of the beta-cells, which leads to the development of diabetes...

..BTC, acting through EGF-R/erbB-1, is important for the differentiation of beta-cells. This could be applied in the targeted differentiation of stem cells into insulin-producing cells...

..Family history was negative. Adrenal insufficiency is an uncommon feature in multiple malformation syndromes and may thus serve as a diagnostic handle for recognizing other possible patients with a similar syndrome...

..These data suggest that the pattern and mechanisms of coxsackievirus B5 infection induced beta-cell death depend on the MOI...

..However, restriction of viral replication shifts the mechanism of cell death from necrosis toward apoptosis. A slowly progressing subclinical infection of islets could thus lead to increased beta-cell apoptosis...

..The defence mechanisms depend heavily on glutathione, the synthesis of which is dependent on the availability of cysteine. We investigated whether an increased amount of cysteine available could protect beta cells from oxidative damage...

..These results provide consequential information of the biological role of BM in hESCs, warranting further investigation of BM biology of human pluripotent stem cells...

..Our results thus suggest that Fgfr2b-mediated signaling plays a major role in pancreatic ductal proliferation and branching morphogenesis, but has little effect on endocrine and exocrine differentiation...

..It thus appears that rAAV vectors are not compatible with the derivation of integration-free iPSC...

....

..The aim of this study was to describe the expression of nephrin mRNA and protein in human pancreas as well as identify the nephrin-expressing cell types...

..We compared the prevalence and characteristics of diabetes between Somali and Finnish children in the City of Helsinki...

..Upregulated PAI-1 production and decreased gelatinolytic activity correlated to this migration defect. An intact EGF-R pathway appears to be a prerequisite for normal pancreatic development...

..Definition of safe culture conditions for stem cells is essential for future development of cellular therapies...

..Infection with Ad-caALK7 of MIN6 insulinoma cells, in which ALK7 has previously been shown to be endogenously expressed, led to a marked increase in the phosphorylation of Smad2, a signaling molecule also used by TGF-betas and activins...

..We extended these studies to additional enterovirus serotypes including several echoviruses, some of which have been associated clinically with the development of Type I (insulin-dependent) diabetes mellitus...

..Our findings highlight the role of IL-17 immunity in the pathogenesis of human T1D and point to a potential therapeutic strategy...

..We conclude that GATA-4 is a marker of exocrine pancreatic differentiation, whereas GATA-6 is a marker of endocrine pancreatic development...

..EGFR thus plays an essential role in beta-cell mass regulation, but its mechanisms of action remain poorly understood...

..This variant represents a new subtype of autosomal dominant diabetes...

....

..However, genotyping usually takes too long to be helpful in the absence of a founder mutation...

..Limited overlap between gene expression profiles illustrates the importance of cross-validation of results between different ESC lines...

..Teratomas can also be fixed in Bouin's or cryosectioned for analysis, and they can be analyzed by immunohistochemistry for tissue markers. Methods for these procedures are included in this unit...

..We conclude that both over- and underdosage of SOX3 are associated with similar phenotypes, consisting of infundibular hypoplasia and hypopituitarism but not necessarily MR...

..This article describes the two opposing positions based largely on research in laboratory rodents and its extrapolation to humans...

..Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected...

..These findings demonstrate that the range of the clinical phenotype caused by GCK mutations varies from complete insulin deficiency to extreme hyperinsulinemia...

..The strong coherence between the datasets of the two ethnic groups studied with highly contrasting disease incidence, socioeconomic characteristics, and profoundly diverse environment emphasizes the impact of this finding...