Search results for "TRANSCRIPTION FACTORS"
showing 10 items of 848 documents
Deficiency of the autoimmune regulator AIRE in thymomas is insufficient to elicit autoimmune polyendocrinopathy syndrome type 1 (APS‐1)
2007
Thymomas are thymic epithelial neoplasms, associated with a variety of autoimmune disorders (especially myasthenia gravis), that apparently result from aberrant intra-tumourous thymopoiesis and export of inefficiently tolerized T-cells to the periphery. The autoimmune regulator (AIRE) drives the expression of self-antigens in the thymic medulla and plays an essential role in ‘central’ tolerance in both humans and mice. However, while inactivating AIRE mutations result in the ‘autoimmune polyendocrinopathy syndrome type 1’ (APS-1), its major features are not well reproduced in AIRE-knock-out mice. Therefore, alternative human disease scenarios with concomitant AIRE deficiency may be valuable…
Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III
2000
Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III. We found 35 different mutations in 44 of 51 unrelated p…
Ten novel mutations found in Aniridia.
1998
Aniridia (AN) is a sight-threatening congenital ocular disorder characterized by iris hypoplasia, corneal pannus, foveal and optic nerve hypoplasia, cataract formation, and glaucoma. In two-thirds of the patients, AN is inherited in an autosomal dominant fashion with almost complete penetrance but variable expression. The remaining cases are sporadic. Aniridia has been shown to be associated with mutations in the PAX6 gene, located on chromosome 11p13, telomeric to the Wilms' tumor predisposition gene (WT1). This paper describes 14 mutations in the PAX6 gene in patients with AN. Among these 14 mutations, 10 have been unpublished until now. They result most probably in haploinsufficiency and…
Underexpressed Coactivators PGC1α AND SRC1 Impair Hepatocyte Nuclear Factor 4α Function and Promote Dedifferentiation in Human Hepatoma Cells
2006
Hepatocyte nuclear factor 4alpha (HNF4alpha) plays critical roles during liver development and in the transcriptional regulation of many hepatic genes in adult liver. Here we have demonstrated that in human hepatoma HepG2 cells, HNF4alpha is expressed at levels as high as in human liver but its activity on target genes is very low or absent. We have discovered that the low expression of key coactivators (PGC1alpha, SRC1, SRC2, and PCAF) might account for the lack of function of HNF4alpha in HepG2 cells. Among them, PGC1alpha and SRC1 are the two most important HNF4alpha coactivators as revealed by reporter assays with an Apo-CIII promoter construct. Moreover, the expression of these two coa…
The influence of bone marrow- and synovium-derived mesenchymal stromal cells from osteoarthritis patients on regulatory T cells in co-culture
2013
Summary There is increasing evidence that inflammation in the synovium plays a major role in the progression of osteoarthritis (OA). However, the immunogenic properties of mesenchymal stromal cells (MSCs), which are considered to regulate immunity in various diseases, remain largely unknown in OA. The purpose of this study was to determine the influence of MSCs from OA patients on regulatory T cells (Tregs) in an allogeneic co-culture model. Bone marrow (BM) and synovial membrane (SM) were harvested from hip joints of OA patients and co-cultured with lymphocytes enriched in CD4+CD25+CD127– regulatory T cells (Treg+LC) from healthy donors. Treg proportions and MSC markers were assessed by fl…
Reprogramming of Pericyte-Derived Cells of the Adult Human Brain into Induced Neuronal Cells
2012
SummaryReprogramming of somatic cells into neurons provides a new approach toward cell-based therapy of neurodegenerative diseases. A major challenge for the translation of neuronal reprogramming into therapy is whether the adult human brain contains cell populations amenable to direct somatic cell conversion. Here we show that cells from the adult human cerebral cortex expressing pericyte hallmarks can be reprogrammed into neuronal cells by retrovirus-mediated coexpression of the transcription factors Sox2 and Mash1. These induced neuronal cells acquire the ability of repetitive action potential firing and serve as synaptic targets for other neurons, indicating their capability of integrat…
The role of recent thymic emigrant-regulatory T-cell (RTE-Treg) differentiation during pregnancy.
2014
During pregnancy, regulatory T cells (Tregs) have a key role in maternal immune tolerance to the semi-allogeneic fetus. Our previous results showed that the naive CD45RA(+)-Treg pool is functionally improved in pregnant women compared with non-pregnant women. Therefore, we examined the thymic output and differentiation of CD45RA(+)CD31(+) recent thymic emigrant (RTE)-Tregs during normal pregnancy and in the presence of preeclampsia. With the onset of pregnancy, the composition of the total CD4(+)CD127(low+/-)FoxP3(+)-Treg pool changed in the way that its percentage of RTE- and CD45RA(-)CD31(+)-memory Tregs decreased strongly, whereas that of the CD45RA(+)CD31(-)-mature naive (MN)-Tregs did …
(Partial) loss of BAF250a (ARID1A) in rectovaginal deep-infiltrating endometriosis, endometriomas and involved pelvic sentinel lymph nodes
2015
study hypothesis: Loss of protein BAF250a (ARID1A) expression is present in women with rectovaginal deep-infiltrating endometriosis (DIE) and endometriosis affecting the pelvic sentinel lymph nodes (PSLN). study finding: Partial loss of protein BAF250a was found in some of our patient samples, comprising all endometriosis entities, including rectovaginal DIE and endometriosis affecting the PSLN. what is known already: Loss of BAF250a (BRG-associated factor 250a)/ARIDIA (AT-rich interactive domain 1A) protein expression was identified among endometriosis-associated ovarian carcinomas and ovarian endometriosis, and this phenomenonwas described as a possible early event in the transformation o…
The role of regulatory T cell (Treg) subsets in gestational diabetes mellitus.
2014
Physiological changes during normal pregnancy are characterized by an inflammatory immune response and insulin resistance. Therefore, we hypothesize that gestational diabetes mellitus (GDM) may be caused by an inappropriate adaption of the maternal immune system to pregnancy. In this study we examined the role of regulatory T cell (Treg) differentiation for the development of GDM during pregnancy. We used six-colour flow cytometric analysis to demonstrate that the total CD4(+) CD127(low+/-) CD25(+) forkhead box protein 3 (FoxP3(+)) T(reg) pool consists of four different T(reg) subsets: naive CD45RA(+) T(regs), HLA-DR(-) CD45RA(-) memory T(regs) (DR(-) T(regs)) and the highly differentiated …
Repair of oxidatively generated DNA damage in Cockayne syndrome
2013
Defects in the repair of endogenously (especially oxidatively) generated DNA modifications and the resulting genetic instability can potentially explain the clinical symptoms of Cockayne syndrome (CS), a hereditary disease characterized by developmental defects and neurological degeneration. In this review, we describe the evidence for the involvement of CSA and CSB proteins, which are mutated in most of the CS patients, in the repair and processing of DNA damage induced by reactive oxygen species and the implications for the induction of cell death and mutations. Taken together, the data demonstrate that CSA and CSB, in addition to their established role in transcription-coupled nucleotide…