Search results for "ATP binding"

TAP-polymorphisms in juvenile onset psoriasis and psoriatic arthritis.

1996

Abstract Juvenile onset psoriasis is strongly associated with the HLA-class I genes Cw6 and B57 whereas patients with psoriatic arthritis show an increased frequency of HLA-B27. It is unclear whether additional major histocompatibility genes also increase disease susceptibility. The TAP genes (transporter associated with antigen processing) encode two membrane-spanning proteins that translocate antigenic peptides from the cytoplasm into the endoplasmic reticulum. Comparison of 60 patients with juvenile onset psoriasis, 63 psoriatic arthritis patients, and 101 caucasoid controls revealed an increase of the TAP1 ∗ 0101 allele in the psoriasis group, that could not be explained by linkage to o…

In situ kinetic modelling of intestinal efflux in rats: functional characterization of segmental differences and correlation with in vitro results.

2007

The objective was to devise and apply a novel modelling approach to combine segmental in situ rat perfusion data and in vitro cell culture data, in order to elucidate the contribution of efflux in drug absorption kinetics. The fluoroquinolone CNV97100 was used as a model P-gp substrate. In situ intestinal perfusion was performed in rat duodenum, jejunum, ileum and colon to measure the influence of P-gp expression on efflux. Inhibition studies of CNV97100 were performed in the presence of verapamil, quinidine, cyclosporin A and p-aminohippuric acid. Absorption/efflux parameters were modelled simultaneously, using data from both in situ studies as well as in vitro studies. The maximal efflux …

Profile of P-glycoprotein distribution in the rat and its possible influence on the salbutamol intestinal absorption process.

2004

8 pages, 2 figures, 2 tables.--PMID: 15124220 [PubMed]

Pharmacogenetic Study of ABCB1 and CYP3A5 Genes During the First Year Following Heart Transplantation Regarding Tacrolimus or Cyclosporine Levels

2011

Pharmacogenetics explains part of the interindividual variability in drug responses. Many published works about the effects of single nucleotide polymorphisms (SNPs) on immunosuppressive drug blood levels present contradictory results. We evaluated the SNPs in ABCB1 (glycoprotein P) and CYP3A5 (metabolic enzyme) genes, seeking correlate them with tacrolimus or cyclosporine levels during the first year after heart transplantation. One blood sample was obtained from each of 41 patients: 26 treated with cyclosporine and 15 with tacrolimus. We characterize the SNPs rs1045642, 1128503, 2032582, 2235013, 2235033, 2229109, 3213619, 9282564 in ABCB1 and rs10264272, 776746 in CYP3A5 genes using the …

The ABCB4 p.T175A variant as potential modulator of hepatic fibrosis in patients with chronic liver diseases: Looking beyond the cholestatic realm

2017

TGF-β2 silencing to target biliary-derived liver diseases

2020

ObjectiveTGF-β2 (TGF-β, transforming growth factor beta), the less-investigated sibling of TGF-β1, is deregulated in rodent and human liver diseases. Former data from bile duct ligated and MDR2 knockout (KO) mouse models for human cholestatic liver disease suggested an involvement of TGF-β2 in biliary-derived liver diseases.DesignAs we also found upregulated TGFB2 in liver tissue of patients with primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), we now fathomed the positive prospects of targeting TGF-β2 in early stage biliary liver disease using the MDR2-KO mice. Specifically, the influence of TgfB2 silencing on the fibrotic and inflammatory niche was analysed on m…

The antifibrotic potential of a sustained release formulation of a PDGF beta-receptor targeted rho kinase inhibitor

2019

Rho kinase activity in hepatic stellate cells (HSCs) is associated with activation, transformation and contraction of these cells, leading to extracellular matrix production and portal hypertension in liver cirrhosis. Inhibition of rho kinase activity can reduce these activities, but may also lead to side effects, for instance systemic hypotension. This can be circumvented by liver-specific delivery of a rho kinase inhibitor to effector cells. Therefore, we targeted the rho kinase inhibitor Y27632 to the key pathogenic cells in liver fibrosis, i.e. myofibroblasts including activated HSCs that highly express the PDGF beta-receptor, using the drug carrier pPB-MSA. This carrier consists of mou…

Acidosis induces multi-drug resistance in rat prostate cancer cells (AT1) in vitro and in vivo by increasing the activity of the p-glycoprotein via a…

2008

Because solid growing tumors often show hypoxia and pronounced extracellular acidosis, the aim of this study was to analyze the impact of an acidotic environment on the activity of the p-glycoprotein (pGP) and on the cellular content and cytotoxicity of the chemotherapeutic drug daunorubicin in the AT1 R-3327 Dunning prostate carcinoma cell line cultured in vitro and in vivo. In vitro, extracellular acidosis (pH 6.6) activated p38 and ERK1/2 and thereby induced daunorubicin resistance via a pronounced activation of pGP. De-novo protein synthesis was not necessary and analysis of transport kinetics indicated a fast and persistent pGP activation at pH 6.6 (when compared with 7.4). Intracellul…

Antigen-processing machinery breakdown and tumor growth.

2000

Defects in the major histocompatibility complex (MHC) class I antigen-processing machinery (APM) have been described in tumors of different histology. Murine data suggest that defects in the MHC class II APM might also be associated with malignant transformation of human cells. This article describes the pathophysiology of the MHC class I and II APM, reviews APM abnormalities in tumor cells and discusses their role in the escape of tumor cells from in vitro recognition by T cells.

Podoplanin discriminates distinct stromal cell populations and a novel progenitor subset in the liver

2015

Podoplanin/gp38+ stromal cells present in lymphoid organs play a central role in the formation and reorganization of the extracellular matrix and in the functional regulation of immune responses. Gp38+ cells are present during embryogenesis and in human livers of primary biliary cirrhosis. Since little is known about their function, we studied gp38+ cells during chronic liver inflammation in models of biliary and parenchymal liver fibrosis and steatohepatitis. Gp38+ cells were analyzed using flow cytometry and confocal microscopy, and the expression of their steady state and inflammation-associated genes was evaluated from healthy and inflamed livers. Gp38+ cells significantly expanded in …