The protein tyrosine phosphatases (PTPs) PTP-SL, STEP and HePTP are mitogen-activated kinase (MAPK) substrates regulators that bind to MAPKs through a kinase-interaction motif (KIM) located in their non-catalytic regulatory domains. We have found the binding of these PTPs extracellular-signal-regulated 1 2 (ERK1/2), p38alpha is differentially determined by KIM-adjacent C-terminal regions PTPs, which been termed kinase-specificity sequences, influenced reducing agents. Under control...

Abstract In the present work, we have demonstrated in vivo an altered maturation of thymic epithelium that results defective T cell development which increases with age, thymus Eph A4-deficient mice. The deficient thymi are hypocellular and show decreased proportions double-positive (CD4+CD8+) cells reach minimal numbers 4-wk-old thymi. EphA4 −/− phenotype correlates early block precursor differentiation accumulation CD44−CD25+ triple-negative and, sometimes, CD44+CD25− thymocytes as well...

Abstract Recruitment of lymphoid progenitors to the thymus is compromised by lack Eph/ephrin signaling in both T-cell and thymic microenvironmental cells The ephrin-Eph ligand receptor pair known control repulsion/adhesion process different tissues, including immune system. Herein, we evaluated role EphB2 receptors T cell progenitor migration during vitro colonization ECM or chemokine stimuli. their ligands, ephrin-B1 ephrin-B2, are expressed BM-derived progenitors, EphB2−/− had diminished...

Abstract Thymus development and function are dependent on the definition of different graded microenvironments that provide maturing T cell with signals drive its maturation to a functional lymphocyte. In these processes, cell-cell interactions, migration, positioning clues for correct functioning organ. The Eph family receptor tyrosine kinases their ligands, ephrins, has been implicated in all processes by regulating cytoskeleton adhesion functioning, but systemic analysis presence possible...

The Eph and ephrin families are involved in numerous developmental processes. Recently, an increasing body of evidence has related these with some aspects T cell development. In the present study, we show that addition either EphB2-Fc or ephrinB1-Fc fusion proteins to fetal thymus organ cultures established from 17-day-old mice decreases numbers both double-positive (CD4(+)CD8(+)) single-positive (both CD4(+)CD8(-) CD4(-)CD8(+)) thymocytes, correlation increased apoptosis. By using...

In the present study, we have analysed phenotype of EphB2 and/or EphB3 deficient thymocytes confirming and extending previous studies on role this family molecules in T-cell differentiation. all mutant thymuses statistically significant reduced cell contents were observed. This reduction thymic cellularity correlated with increased proportions apoptotic cells, largely both double negative (DN; CD4- CD8-) positive (CD4+ CD8+) decreased DN cycling cells. Adult also showed cells but not...

The protective effects of immunosuppressants against ischemia/reperfusion (I/R) injury have been attributed to their non-specific anti-inflammatory effect. However, these may also depend on effect T lymphocytes, which are increasingly considered be key players in I/R. Here, we studied the tacrolimus and sirolimus lymphocyte subpopulations an I/R rat model. animals were treated with tacrolimus, or vehicle, before undergoing a 60-min ischemia event right hepatic lobe, followed by excision...

Abstract In adult life, the high CD4:CD8 cell ratio observed in peripheral lymphoid organs originates thymus. Our results show that low seen during fetal life also has an intrathymic origin. This distinct production of CD4+CD8− and CD4−CD8+ thymocytes is regulated by developmental age thymic stroma. The differential expression Notch receptors their ligands, especially Jagged1, throughout thymus development plays a key role generation different ratios. We sharply changes from to values around...

In order to carry out an in‐depth study of the roles EphB receptors in T‐cell development and determine specific relevance forward reverse signals process, we established severe combined immunodeficient (SCID) mice chimeras with wild‐type (WT) or EphB‐deficient bone marrow cells. The obtained results demonstrate that EphB2 contributes more significantly than EphB3 control CD4 − CD8 (DN)–CD4 + (DP) progression, generated SCID receiving EphB2LacZ precursors, which express extracellular domain,...

Regulated function of mitogen-activated protein (MAP) kinases involves their selective association through docking sites with both activating MAP kinase and inactivating phosphatases, including dual specificity protein-tyrosine phosphatases (PTP). Site-directed mutagenesis on the mammalian ERK2 p38alpha identified within C-terminal grooves two clusters residues important for regulatory PTPs, PTP-SL STEP. mutations that resembled sevenmaker gain-of-function mutation in Rolled D. melanogaster...

Hepatic acetylator phenotype has been determined, using sulfamethazine, in 81 white Spanish women with histologically proven breast cancer and 75 adequate female controls. No differences were detected the distribution of between two groups slow acetylators, 49 patients (60.5%) 45 controls (60%). The percentage acetylated sulfamethazine plasma for each was not different either. Our results suggest that there is no relationship hepatic polymorphism risk developing women.

Previous analysis on the thymus of erythropoietin-producing hepatocyte kinases (Eph) B knockout mice and chimeras revealed that Eph-Eph receptor-interacting proteins (ephrins) are expressed both T cells thymic epithelial (TECs) play a role in defining microenvironments. In current study, we have used Cre-LoxP system to selectively delete ephrin-B1 and/or ephrin-B2 either thymocytes (EfnB1(thy/thy), EfnB2(thy/thy), EfnB1(thy/thy)EfnB2(thy/thy) mice) or TECs (EfnB1(tec/tec), EfnB2(tec/tec),...

Oxidative polymorphism of debrisoquine (DBQ) was determined in 98 women with breast cancer (mean age 59.2 years, SD 10.7; 18 were premenopausal when diagnosed), and 446 healthy control 25.4 9.15). All them free drug interactions oxidation DBQ. Ten patients (10.2%), all postmenopausal diagnosed, 423 controls (5.2%), values for metabolic ratio DBQ > 12.6, classified as poor metabolizers (PM) (p = 0.006). Relative risk developing among PM phenotype 2.09 (95% confidence limits 0.97–4.48). The...

The role of EphB2 and EphB3 in the organization thymic epithelial cells has been studied EphB-deficient fetal thymus lobes grafted under kidney capsule WT mice. deficient lobes, as compared with ones, showed altered distribution medullary areas, shortening cell processes presence K5(-)K8(-) areas. expressed on play an autonomous their organization. relevance Eph/ephrinB forward reverse signals for this process was evaluated from mice expressing a truncated receptor capable activating...

Background Oral administration of glucocorticoid alters serum cystatin C ( sC ysC) concentration in humans. Objective To determine if oral prednisone ysC dogs without pre‐existing renal disease. Animals Forty six were included: 10 diagnosed with steroid responsive meningitis arteritis SRMA ; group A), 20 pituitary‐dependent hyperadrenocorticism PDH B), and 16 healthy control (group C). Methods Retrospective observational study. administered 4 mg/kg/24 h PO 7 days, reducing the dose to 2 days...