The Dok-3/Grb2 adaptor module promotes inducible association of the lipid phosphatase SHIP with the BCR in a coreceptor-independent manner.

The SH2 domain-containing inositol 5'-phosphatase (SHIP) plays a key role in preventing autoimmune phenomena by limiting antigen-mediated B cell activation. SHIP function is thought to require the dual engagement of the BCR and negative regulatory coreceptors as only the latter appear capable of recruiting SHIP from the cytosol to the plasma membrane by the virtue of phosphorylated immunoreceptor tyrosine-based inhibitory motifs. Here, we demonstrate a coreceptor-independent membrane recruitment and function of SHIP in B cells.

The Dok-3/Grb2 protein signal module attenuates Lyn kinase-dependent activation of Syk kinase in B cell antigen receptor microclusters.

Recruitment of the growth factor receptor-bound protein 2 (Grb2) by the plasma membrane-associated adapter protein downstream of kinase 3 (Dok-3) attenuates signals transduced by the B cell antigen receptor (BCR). Here we describe molecular details of Dok-3/Grb2 signal integration and function, showing that the Lyn-dependent activation of the BCR transducer kinase Syk is attenuated by Dok-3/Grb2 in a site-specific manner. This process is associated with the SH3 domain-dependent translocation of Dok-3/Grb2 complexes into BCR microsignalosomes and augmented phosphorylation of the inhibitory Lyn target SH2 domain-containing inositol 5' phosphatase.

Acute marihuana (THC) exposure produces a "transient" topographic quantitative EEG profile identical to the "persistent" profile seen in chronic heavy users.

In two published pilot studies and a controlled replication using screened normals, chronic marihuana (THC) use was associated with a unique topographic quantitative EEG profile, consisting of significant elevations of Absolute and Relative Power and Coherence of alpha activity over the bilateral frontal cortex as well as a significant decrease in alpha frequency. This report attempts to establish the causal influence of THC in the above findings by the transient production of this exact quantitative EEG profile in subjects who did not display it at the beginning. Using paced smoking of marihuana with high and low dose THC content and placebo marihuana in a counterbalanced design under double blind conditions, all four of the topographic features of chronic THC exposure were produced as transient effects by THC but not by placebo.

Paradoxical embolism to the left main coronary artery: visualization by transesophageal echocardiography.

A case of myocardial infarction is described with transesophageal echocardiography visualization of left main coronary artery thrombus arising from paradoxical embolism of mobile venous thrombus by patent foramen ovale.