Combination of the best pacing configuration and atrioventricular and interventricular delays optimization in cardiac resynchronization therapy.

Background: Cardiac resynchronization therapy optimization can be pursued by left ventricular pacing vector selection and atrioventricular (AV) and interventricular (VV) delays optimization. The combination of these methods and its comparison with multipoint pacing (MPP) is scarcely studied.

Methods: Using noninvasive cardiac output (CO) measurement, the best of five left ventricular pacing vectors was determined, then AV and VV delays optimization was applied on top of the best vector.

Long-term outcome of implantable cardioverter-defibrillator implantation in secondary prevention of sudden cardiac death.

Background: Little is known about the long-term outcomes of patients who receive an implantable cardioverter-defibrillator (ICD) for purely secondary prevention indications.

Aims: To assess the rates and predictors of appropriate therapies over a very long-term follow-up period in this population.

Methods: Between June 2003 and August 2006, 239 consecutive patients with structural left ventricular disease and a secondary prophylaxis indication for ICD therapy (survivors of life-threatening ventricular tachyarrhythmias) were prospectively enrolled.

Quantitative assessment of primary mitral regurgitation using left ventricular volumes: a three-dimensional transthoracic echocardiographic pilot study.

Aims: To investigate the value of assessment of mitral regurgitant fraction (RF) using left ventricular (LV) volumes obtained by three-dimensional echocardiography (3DE) to quantify primary mitral regurgitation (MR).

Methods And Results: Sixty patients with primary MR in sinus rhythm were prospectively enrolled. RF was calculated using either 2DE or 3DE LV volumes obtained as follows: (LV total stroke volume - LV forward stroke volume by Doppler)/LV total stroke volume.

Relationship between two-dimensional speckle-tracking septal strain and response to cardiac resynchronization therapy in patients with left ventricular dysfunction and left bundle branch block: a prospective pilot study.

Background: Previous studies have demonstrated variable patterns of longitudinal septal deformation in patients with left ventricular (LV) dysfunction and left bundle branch block. This prospective single center study was designed to assess the relationship between septal deformation patterns obtained by two-dimensional speckle-tracking echocardiography and response to cardiac resynchronization therapy (CRT).

Methods: One hundred one patients with New York Heart Association class II to IV heart failure, LV ejection fractions ≤ 35%, and left bundle branch block underwent echocardiography before CRT.

FOXO1 regulates L-Selectin and a network of human T cell homing molecules downstream of phosphatidylinositol 3-kinase.

In T cells, the PI3K pathway promotes proliferation and survival induced by Ag or growth factors, in part by inactivating the FOXO transcription factor 1. We now report that FOXO1 controls the expression of L-selectin, an essential homing molecule, in human T lymphocytes. This control is already operational in unprimed T cells and involves a transcriptional regulation process that requires the FOXO1 DNA-binding domain.

ERM proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation.

During activation, T cells associate with antigen-presenting cells, a dynamic process that involves the formation of a broad area of intimate membrane contact known as the immunological synapse. The molecular intermediates that link initial antigen recognition to the cytoskeletal changes involved in this phenomenon have not yet been defined. Here we demonstrate that ezrin-radixin-moesin proteins are rapidly inactivated after antigen recognition through a Vav1-Rac1 pathway.

CD5 inhibits signaling at the immunological synapse without impairing its formation.

Physiologically, Ag detection by T cells occurs at the immunological synapse (IS) formed at the interface with an APC. CD5 is considered as an inhibitory molecule for Ag receptor-mediated signals in T cells. However, the influence of CD5 at the IS on synapse formation and functioning has not yet been reported.

The distinct capacity of Fyn and Lck to phosphorylate Sam68 in T cells is essentially governed by SH3/SH2-catalytic domain linker interactions.

Sam68 phosphorylation correlates with Fyn but not Lck expression in T cells. This substrate has been used here to explore the possible basis of the specificity of Fyn versus Lck. We show that this specificity is not based on a spatial segregation of the two kinases, since a chimeric Lck molecule containing the membrane anchoring domain of Fyn does not phosphorylate Sam68.

Fyn membrane localization is necessary to induce the constitutive tyrosine phosphorylation of Sam68 in the nucleus of T lymphocytes.

A close relationship between Sam68, a tyrosine and proline-rich RNA-binding protein, and Src protein tyrosine kinases (PTK) has already been established, also in T lymphocytes. A constitutive phosphorylation of the molecule has also been documented in various transformed T cells, which probably reflects an increased expression of PTK of the Src family. Using the hybridoma T cell line, T8.

A dual participation of ZAP-70 and scr protein tyrosine kinases is required for TCR-induced tyrosine phosphorylation of Sam68 in Jurkat T cells.

Sam68 has been initially described as a substrate of src kinases during mitosis in fibroblasts. Recent evidence suggests that in T lymphocytes Sam68 may act as an adaptor protein and participate in the early biochemical cascade triggered after CD3 stimulation. A direct interaction between Sam68 and the two src kinases involved in T cell activation, p59(fyn) and p56(lck), as well as a partnership of Sam68 with various key downstream signaling molecules, like phospholipase Cgamma-1 and Grb2, has been shown.

Normal Syk protein level but abnormal tyrosine phosphorylation in B-CLL cells.

One characteristic of B cells that accumulate during chronic lymphocytic leukemia (CLL) is their highly heterogeneous functional responses to B cell receptor (BCR) stimulation. Leukemic B cells with very poor responses have defective rapid tyrosine phosphorylation of numerous substrates, especially phospholipase C (PLC)gamma, as well as a defective calcium elevation on BCR stimulation. This points to a defect in BCR-associated protein tyrosine kinase (PTK).

Theophylline synergizes with chlorambucil in inducing apoptosis of B-chronic lymphocytic leukemia cells.

We tested the effects of theophylline, a phosphodiesterase inhibitor inducing intracellular accumulation of cyclic adenosine monophosphate (cAMP), on malignant B cells from 15 patients with B-chronic lymphocytic leukemia (B-CLL). We observed a large increase in apoptotic cell numbers (mean, 90% v 20% in medium alone) in the presence of theophylline (100 micrograms/mL) or chlorambucil (10 mumol/L) after 72 hours of incubation. Maximal apoptosis (90%) was reached after 36 hours when the two drugs were used together at fourfold lower concentrations, indicating a synergistic effect; no effect was observed with normal B cells, suggesting that the combination might have therapeutic interest.

B cell superstimulatory influenza virus (H2-subtype) induces B cell proliferation by a PKC-activating, Ca(2+)-independent mechanism.

The influenza virus hemagglutinin glycoprotein (HA) induces a vigorous B cell proliferation and Ig-synthesis by an unknown activation mechanism, which is susceptible to the inhibitory effects of anti-Ig and anti-class II mAbs. To gain further insight into the activation mode of this T cell-independent, B cell "superstimulatory" virus, we analyzed the sensitivity of H2-subtype virus-mediated B cell activation to the inhibitory effects of various signal transduction-blocking agents and compared it to the well characterized anti-mu-mediated and the LPS-employed pathway. Cyclic-AMP agonists (cAMP-analogues, pentoxifylline, cholera toxin, and forskolin) blocked HA-mediated activation of B cells only at concentrations at least 50-fold higher than required for blocking of anti-mu-induced activation.

Effects of long-term treatment with D-penicillamine on antigen-induced arthritis in rabbits: studies on in vivo articular chondrocyte damage and in vitro collagen biosynthesis by cultured chondrocytes.

The effects of a long-term (120 days) treatment with D-penicillamine (DP) (50 mg/kg/day; i.v.) on antigen-induced arthritis were studied in rabbit.