Myocarditis is an inflammatory disease in the heart and is mainly caused by viral infections. Viral myocarditis has been proposed to be divided into three phases; the acute viral phase, the subacute immune phase, and the chronic cardiac remodeling phase. Although individualized therapy should be applied depending on the phase, no clinical or experimental studies have found biomarkers that distinguish between the three phases of myocarditis. Theilers murine encephalomyelitis virus (TMEV) belongs to the genus Cardiovirus, and can cause myocarditis in susceptible mouse strains. Using this novel model for viral myocarditis induced with TMEV, we conducted multivariate analysis including echocardiography, serum troponin and viral RNA titration, and microarray for identifying the biomarker candidates that discriminate the three phases. Using C3H mice infected with TMEV on 4, 7, and 60 days post infection (p.i.), we conducted bioinformatics analyses, including principal component analysis (PCA) of microarray data, since our traditional cardiac and serum assays, including two-way comparison of microarray data, did not lead to the identification of a single biomarker. PCA separated heart samples clearly between the groups of 4, 7, and 60 days p.i. Representative genes contributing to the separation were as follows: 4 and 7 days p.i., innate immunity-related genes, such as Irf7, and Cxcl9; 7 and 60 days p.i., acquired immunity-related genes, such as Cd3g and H2-Aa; and cardiac remodeling-related genes, such as Mmp12 and Gpnmb. Here, sets of molecules, but not a single molecule, identified by the unsupervised PCA, were found to be useful as the phase-specific biomarkers.
Bioinformatics multivariate analysis determined a set of phase-specific biomarker candidates in a novel mouse model for viral myocarditis.
Sex, Specimen part, Time
View SamplesAnalysis of HER2-amplified NCI-N87 gastric cancer cell line exposed to 0.1 g/mL T-DM1 and subsequently cultured in the presence of gradually increasing doses, up to a maximum of 4 g/mL. The resultant cell lines that grew exponentially in the presence of T-DM1 were designated as drug resistant gastric cancer cell lines, and named N87-TDMR.
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Specimen part, Cell line
View SamplesPluripotency of mammalian stem cells is stabilized at different status depending upon the extracellular stimuli of their environment. Now, there is a consensus that mouse embryonic stem cells (mESCs) and iPSCs (miPSCs) represent undifferentiated status very close to ground-state of mammalian development when cultured in optimal condition. Since they have not been activated to commit into any lineages, they are stated as nave-state stem cells. In contrast, human ESCs (hESCs), hiPSCs, and mEpiSCs are considered to possess partially differentiated characteristics compared with mESCs and miPSCs. Thus, they are stated as primed-state stem cells. Investigation of the prerequisites for establishment of the nave-state is significantly important to fully understand mammalian development and to extrapolate the technologies developed with mouse ES/iPS cells for human.
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Specimen part
View SamplesPluripotency of mammalian stem cells is stabilized at different status depending upon the extracellular stimuli of their environment. Now, there is a consensus that mouse embryonic stem cells (mESCs) and iPSCs (miPSCs) represent undifferentiated status very close to ground-state of mammalian development when cultured in optimal condition. Since they have not been activated to commit into any lineages, they are stated as nave-state stem cells. In contrast, human ESCs (hESCs), hiPSCs, and mEpiSCs are considered to possess partially differentiated characteristics compared with mESCs and miPSCs. Thus, they are stated as primed-state stem cells. Investigation of the prerequisites for establishment of the nave-state is significantly important to fully understand mammalian development and to extrapolate the technologies developed with mouse ES/iPS cells for human.
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Cell line
View SamplesBackground: Survival and function of insulin-secreting pancreatic -cells are markedly altered by changes in nutrient availability. In vitro, culture in 10 rather than 2mM glucose improves rodent -cell survival and function whereas glucose concentrations above 10mM are deleterious. Aim-Method: To identify the mechanisms of such -cell plasticity, we tested the effects of a 18h culture at 2, 5, 10 and 30mM glucose on the transcriptome of rat islets precultured for 1 week at 10mM glucose (Affymetrix Rat 230.2 arrays). Results: Culture in either 2-5mM or 30mM instead of 10mM glucose markedly impaired -cell function without affecting islet cell survival. Of ~16000 probe sets reliably detected in islets, ~5000 were significantly regulated at least 1.4-fold by glucose. Analysis of these probe sets with GeneCluster software identified 10 mRNA profiles with unidirectional up- or down-regulation between 2 and 10, 2 and 30, 5 and 10, 5 and 30 or 10 and 30 mM glucose, and 8 complex V-shaped or inverse V-shaped profiles with a nadir or peak level of expression in 5 or 10mM glucose. Analysis of genes belonging to these various clusters with Onto-express and GenMapp software revealed several signaling and metabolic pathways that may contribute to the induction of -cell dysfunction and apoptosis after culture in low or high vs. intermediate glucose concentration. Conclusion: We have identified 18 distinct mRNA profiles of glucose-induced changes in islet gene mRNA levels that should help understanding the mechanisms by which glucose affects -cell survival and function under states of chronic hypo- or hyperglycemia.
Cluster analysis of rat pancreatic islet gene mRNA levels after culture in low-, intermediate- and high-glucose concentrations.
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View SamplesPreviously, we have shown that an AP-1 family member Fra-2, which is hardly expressed in normal mature T cells, is consistently over-expressed in adult T-cell leukemia/lymphoma (ATLL), and together with JunD, upregulates CCR4 and many other genes including proto-oncogenes c-Myb, MDM2, Bcl-6, and SOX4. SOX4 is frequently overexpressed in many solid tumors and considered to be a potential oncogene.
SOX4 is a direct target gene of FRA-2 and induces expression of HDAC8 in adult T-cell leukemia/lymphoma.
Cell line
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The human primary hepatocyte transcriptome reveals novel insights into atorvastatin and rosuvastatin action.
Specimen part, Subject, Time
View SamplesAffymetrix gene expression profiling in cumulus cells (CC) retrieved from patients undergoing GnRH agonists and GnRH antagonists IVF treatment.
Cumulus cells gene expression profiling in terms of oocyte maturity in controlled ovarian hyperstimulation using GnRH agonist or GnRH antagonist.
Subject
View SamplesWith particular emphasis on interactions between cholesterol homeostasis and drug metabolism we investigate the transcriptome of human primary hepatocytes treated by two commonly prescribed cholesterol lowering drugs atorvastatin and rosuvastatin and by rifampicin that serves as an outgroup as well as a model substance for induction of nuclear receptor PXR.
The human primary hepatocyte transcriptome reveals novel insights into atorvastatin and rosuvastatin action.
Specimen part, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
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Specimen part, Time
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