Interaction of ICOS - ICOS ligand is required for the germinal center formation, T-cell immune responses, and development of autoimmune diseases. Human ICOS deficiency with the identical ICOS mutation has been identified in nine patients worldwide. In vitro studies showed T-cell defect of the patients was mild, and in vivo autoimmunity was uncommon and mild. Here we report in-depth analysis of T-cell function in two siblings with novel ICOS deficiency. While the brother displayed mild skin infections, psoriasis-like skin region, and defective immunoglobulin class switching, the sister had more severe symptoms, which included immunodeficiency, rheumatoid arthritis, inflammatory bowel disease, interstitial pneumonitis, and psoriasis. Despite of normal CD3/CD28-induced proliferation and IL-2 production in vitro, peripheral blood T-cells from both patients demonstrated decreased percentage of CD4 central and effector memory T-cells and impaired production of Th1, Th2, and Th17 cytokines upon CD3/CD28 costimulation or upon PMA/ionophore stimulation. The defective polarization into effector cells were associated with impaired induction of T-bet, GATA3 and MAF and RORC. Reduced CTLA-4+CD45RO+ FoxP3+ regulatory T-cells and diminished induction of inhibitory cell surface molecules including CTLA-4 were also observed in the patients. Further analysis of the gene expression and immune functions of the patients demonstrated increased induction of RANKL, lack of IFN-g response, and loss of Itch expression upon activation in the female case with autoimmunity. Our study suggests extensive T-cell dysfunction and loss of balance between effector cells and regulatory cells in the ICOS-deficient patients may account for their immunodeficiency and/or autoimmune disorder.
Impaired CD4 and CD8 effector function and decreased memory T cell populations in ICOS-deficient patients.
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View SamplesThe dentate gyrus (DG) of the hippocampus is one of major targets for antidepressant treatments. Using electroconvulsive stimulation (ECS), a model of highly effective and fast-acting antidepressant therapy, here we show that neural stimulation via ECS induces rapid and lasting dematuration of granule neurons in DG. A single time of stimulation transiently reduced mature marker expression and mature synaptic functions. Repetitive stimulation converted this transient dematuration into a stable form lasting more than 1 month. We compared the activity-dependent neuronal responsiveness in the DG between a single ECS and repeated ECS.
Rapid and stable changes in maturation-related phenotypes of the adult hippocampal neurons by electroconvulsive treatment.
Specimen part, Disease, Treatment
View SamplesThe dentate gyrus (DG) of the hippocampus is one of major targets for antidepressant treatments. Our recent research has revealed that selective serotonin reuptake inhibitor (SSRI) treatment causes a long-lasting change in the phenotypes of mature dentate granule neurons to immature state in adult mouse DG. However, it is unknown whether this dematuration of DG is a common effect of antidepressant treatments and what mechanisms underlie it. Using electroconvulsive stimulation (ECS), a model of highly effective and fast-acting antidepressant therapy, here we show that neural stimulation via ECS induces rapid and lasting dematuration of granule neurons in DG. A single or few times of stimulation transiently reduced mature marker expression and mature synaptic functions. Repetitive stimulation converted this transient dematuration into a stable form lasting more than 1 month. Dematured granule neurons showed higher excitability, and an increase in GABA-mediated inhibition by the benzodiazepine diazepam prevented the lasting maintenance phase of dematuration without affecting the initial induction phase. Our study suggests that dematuration of DG is a common cellular mechanism underlying effects of different types of antidepressant treatments, and demonstrate a novel role for excitation/inhibition balance in bidirectional regulation of the state of neuronal maturation in the adult brain.
Rapid and stable changes in maturation-related phenotypes of the adult hippocampal neurons by electroconvulsive treatment.
Specimen part
View SamplesThe dermal papilla (DP) of the hair follicle plays crucial roles in the hair follcie morphogenesis and cycling. Thus, the elucication of human DP molecular signature is of great interest. DP cell culture by conventional method impairs intrinsic properties of DP cells.
Restoration of the intrinsic properties of human dermal papilla in vitro.
Sex, Age, Specimen part, Treatment
View SamplesTo investigate effects of intake of mulberry leaves on hyperlipidemia, we performed gene expression profiling on rat liver by microarray analysis.
Ameliorative effects of mulberry (Morus alba L.) leaves on hyperlipidemia in rats fed a high-fat diet: induction of fatty acid oxidation, inhibition of lipogenesis, and suppression of oxidative stress.
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View SamplesBACKGROUND: Lim1 is a homeobox gene that is essential for nephrogenesis. During metanephric kidney development, Lim1 is expressed in the nephric duct, ureteric buds, and the induced metanephric mesenchyme. Conditional ablation of Lim1 in the metanephric mesenchyme blocks the formation of nephrons at the nephric vesicle stage, leading to the production of small, non-functional kidneys that lack nephrons.
Gene expression profiles in developing nephrons using Lim1 metanephric mesenchyme-specific conditional mutant mice.
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View SamplesIdentification of the relationships of Kaposi sarcoma (KS), normal skin to various cell cultures. The effects of KS herpes virus, the infectious cause of KS, on infected endothelial cells are also investigated.
ARID3B induces malignant transformation of mouse embryonic fibroblasts and is strongly associated with malignant neuroblastoma.
Sex, Specimen part, Disease, Disease stage, Cell line, Subject
View SamplesIron plays a central role in the regulation of many cellular functions. Dysregulation of its metabolism leads an iron overload situation and iron depletion leads to an inhibition of cell proliferation. Recent reports demonstrated that ICL670 (Novartis) acts as a potent NF-kappa-B inhibitor and improves hematological data in a subset of MDS patients (Cilloni et al, Haematologica, s1: 238, 2007). However, the precise mechanism of anti-cancer effect of ICL670 is still uncertain.
The oral iron chelator deferasirox represses signaling through the mTOR in myeloid leukemia cells by enhancing expression of REDD1.
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View SamplesSide population (SP) cells are identified based on their capacity to efflux of the fluorescent dye Hoechst 33342, and are enriched for hematopoietic stem cells (HSCs) in mammalian bone marrow. We recently demonstrated that SP cells were present in the teleost kidney, the main hematopoietic organ in teleosts, and were enriched for HSCs. In this analysis, to identify the regulated genes in teleost HSCs, gene expression analysis of zebrafish kidney SP cells were performed using the GeneChip Zebrafish Genome Array.
Comparative gene expression analysis of zebrafish and mammals identifies common regulators in hematopoietic stem cells.
No sample metadata fields
View SamplesObjectives: Sex hormone receptors are reported to be present in human dental pulp (HDP) cells. The purpose of this study was to examine the biological significance of estrogen and androgen receptors (ER and AR, respectively) in HDP cells. Design: We isolated HDP cells expressing ER- and AR-mRNAs and investigated the expression status of the receptors and the response to sex hormones in the cells. Results: HDP cells expressing ER- and/or AR-mRNAs had the ability to form alizarin red S-positive nodules in which calcium and phosphorus were deposited in vitro and to differentiate into odontoblasts-like cells and dentin-like tissue in vivo. Individual clones isolated from HDP cells exhibited a different expression pattern of mRNA for ER and AR. Some clones expressed ER- and/or ER-mRNAs and the others coexpressed ER- and AR-mRNAs. Using the Ingenuity software, we found that 17-estradiol (E2) and dihydrotestosterone (DHT) could act directly on HDP cells through ER- or androgen signaling-mediated mechanisms. E2 or DHT stimulated the mRNA expression for genes related to odontogenesis of dentin-containing teeth and odontoblast differentiation, suggesting that ER and AR in HDP cells may be involved in dentinogenesis. Conclusions: Our findings provide new insights into the biological significance of sex hormone receptors in HDP cells.
Expression status of mRNA for sex hormone receptors in human dental pulp cells and the response to sex hormones in the cells.
Sex, Specimen part, Treatment
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