Search results for "MT"
showing 10 items of 2759 documents
Latvijas Vēstures Institūta Žurnāls. 2016, Nr. 2 (99)
2016
Valsts kultūrkapitāla fonds
Buerger`s Disease and Hyperhomocysteinemia: Is there a Relationship?
2009
Thromboangiitis obliterans, also known as Buerger's disease, is a cause of juvenile lower limb ischaemia. Buerger's disease is idiopathic and one of diagnostic criteria is the absence of atherosclerotic risk factors other than smok- ing. A possible involvement of thrombophilia has been investigated and the role of hyperhomocysteinemia is still matter of discussion. We describe 9 patients with Buerger's disease followed-up for the past 3 years. We found a significant in- crease in circulating homocysteine levels (mean: 31.6 in patients vs 8.2 μmol/L in control subjects). We also analyzed the C677T mutation of MTHFR; 5/9 Buerger's patients were heterozygotes and 4/9 homozygotes for the mutati…
Rapamycin stimulates arginine influx through CAT2 transporters in human endothelial cells
2007
In endothelial cells Tumor Necrosis Factor-alpha (TNFalpha) stimulates arginine transport through the increased expression of SLC7A2/CAT2 transcripts. Here we show that also rapamycin, an inhibitor of mTOR kinase, stimulates system y(+)-mediated arginine uptake in human endothelial cells derived from either saphenous (HSVECs) or umbilical veins (HUVECs). When used together with TNFalpha, rapamycin produces an additive stimulation of arginine transport in both cell models. These effects are observed also upon incubation with AICAR, a stimulator of Adenosine-Monophosphate-dependent-Protein Kinase (AMPK) that produces a rapamycin-independent inhibition of the mTOR pathway. Rapamycin increases …
Luminal Lipid Regulates CD36 Levels and Downstream Signaling to Stimulate Chylomicron Synthesis
2011
International audience; The membrane glycoprotein CD36 binds nanomolar concentrations of long chain fatty acids (LCFA) and is highly expressed on the luminal surface of enterocytes. CD36 deficiency reduces chylomicron production through unknown mechanisms. In this report, we provide novel insights into some of the underlying mechanisms. Our in vivo data demonstrate that CD36 gene deletion in mice does not affect LCFA uptake and subsequent esterification into triglycerides by the intestinal mucosa exposed to the micellar LCFA concentrations prevailing in the intestine. In rodents, the CD36 protein disappears early from the luminal side of intestinal villi during the postprandial period, but …
Quercetin ameliorates dysregulation of lipid metabolism genes via the PI3K/AKT pathway in a diet-induced mouse model of nonalcoholic fatty liver dise…
2015
Scope Flavonoids and related compounds seem to have favorable effects on nonalcoholic fatty liver disease (NAFLD) progression, although the exact mechanisms implicated are poorly understood. In this study, we aimed to investigate the effect of the flanovol quercetin on gene expression deregulation involved in the development of NAFLD, as well as the possible implication of phosphatidylinositol 3-kinase (PI3K)/AKT pathway modulation. Methods and results We used an in vivo model based on methionine- and choline-deficient (MCD) diet-fed mice and an in vitro model consisting of Huh7 cells incubated with MCD medium. MCD-fed mice showed classical pathophysiological characteristics of nonalcoholic…
A miRNA181a/NFAT5 axis links impaired T cell tolerance induction with autoimmune type 1 diabetes.
2018
Molecular checkpoints that trigger the onset of islet autoimmunity or progression to human type 1 diabetes (T1D) are incompletely understood. Using T cells from children at an early stage of islet autoimmunity without clinical T1D, we find that a microRNA181a (miRNA181a)-mediated increase in signal strength of stimulation and costimulation links nuclear factor of activated T cells 5 (NFAT5) with impaired tolerance induction and autoimmune activation. We show that enhancing miRNA181a activity increases NFAT5 expression while inhibiting FOXP3+ regulatory T cell (Treg) induction in vitro. Accordingly, Treg induction is improved using T cells from NFAT5 knockout (NFAT5ko) animals, whereas alter…
Donor CD4 T cells convert mixed to full donor T-cell chimerism and replenish the CD52-positive T-cell pool after alemtuzumab-based T-cell-depleted al…
2009
Donor lymphocyte infusions (DLI) are used to resolve mixed T-cell chimerism (TCC) after allo-SCT despite a substantial risk of GVHD. We analyzed the impact of prophylactic CD8-depleted (CD8(depl)) DLI in 20 recipients of anti-CD52 alemtuzumab in vivo T-cell-depleted allografts with declining donor TCC after day +60. A total of 13 patients received CD8(depl) DLI and 7 patients did not. All but one of the DLI patients converted to complete donor T-cell chimeras, whereas only one non-DLI patient converted spontaneously. DLI induced transient acute GVHD in five and extensive chronic GVHD in two patients. These data suggest the use of CD8(depl) DLI as an effective treatment for mixed TCC, partic…
Reconstitution of CD52-Negative CD4 T Cells after Alemtuzumab-Based T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation
2008
Abstract The human CD52 molecule is the target of the monoclonal antibody Alemtuzumab, which is used for treating patients with chemo-refractory chronic lymphocytic leukemia as well as for T cell depletion (TCD) in the context of allogeneic hematopoietic stem cell transplantation (HSCT). The molecule is expressed on the surface of lymphocytes, dendritic cells and to a lesser extent on blood-derived monocytes. Previously, investigators have demonstrated that the surface expression of CD52 on T cells is down-regulated after in vitro incubation with Alemtuzumab. By treating purified human CD4 T cells over 4 hours with 10 μg/mL Alemtuzumab in medium supplemented with 10% human AB serum in vitro…
Functionally Altered GPI-Anchor Negative Treg Following Alemtuzumab-Based T-Cell Depletion Are Associated with Acute Gvhd.
2012
Abstract Abstract 3059 Introduction: The monoclonal anti-CD52antibody Alemtuzumab is frequently used for T-cell depletion (TCD) in the context of allogeneic hematopoietic stem cell transplantation (HSCT) to prevent graft versus host disease (GVHD). We previously demonstrated the long term persistence of functionally impaired glycosylphosphatidylinositol (GPI)-anchor negative effector T-cells in patients receiving high dose (100mg) Alemtuzumab in combination with a dose reduced conditioning regimen (Fludarabin + Melpahlan) (Meyer, Wagner et al. BMT 2010). Despite of Alemtuzumab-mediated TCD, half of our patients developed acute GVHD. Since regulatory T cells (Treg) play a major role for cont…
CISPLATIN (C) AND ALIMTA (A) WITH PANITUMUMAB FOR ADVANCED NON-SQUAMOUS NON-SMALL CELL LUNG CANCER (NS-NSCLC): A PHASE I-DOSE FINDING STUDY.
2012
Background The treatment of NSCLC is rapidly changing since new drugs are becoming available. Recently, CA has become a standard for the first line treatment of NS-NSCLC. Previous clinical studies have shown that anti-EGFR MoAb may be added to chemotherapy, but the identification of a molecular signature can predict their activity and better define their true role. Aims In absence of data about the MTD of Panitumumab (a MoAb targeting the EGFR, potentially active in NS-NSCLC) when associated to chemotherapy, we decided to assess the optimal dose of panitumumab in combination with CA. Moreover, in view of a future phase II study, all pts will be studied for the following molecular characteri…