Distinct p53/56lyn and p59fyn domains associate with nonphosphorylated and phosphorylated Ig-alpha.

Among the earliest detectable events in B-cell antigen receptor-mediated signal transduction are the activation of receptor-associated Src-family tyrosine kinases and the tyrosine phosphorylation of Ig-alpha and Ig-beta receptor subunits. These kinases appear to interact with resting B-cell antigen receptor complexes primarily through the Ig-alpha chain antigen receptor homology 1 (ARH1) motif. Recent studies showed a dramatic increase in the amount of Src-family kinase p59fyn bound to Ig-alpha when ARH1 motif tyrosines were phosphorylated. To explore the submolecular basis of these interactions, we conducted mutational analysis to localize sites in p53/56lyn and p59fyn that bind nonphosphorylated and phosphorylated Ig-alpha. Here we report that distinct regions within these kinases bind nonphosphorylated and phosphorylated Ig-alpha ARH1 motifs. The N-terminal 10 residues mediate binding to the nonphosphorylated Ig-alpha ARH1 motif. Association with the phosphorylated Ig-alpha ARH1 motif is mediated by Src homology 2 domains. These findings suggest a mechanism whereby ligand-induced Ig-alpha tyrosine phosphorylation initiates a change in the orientation of an associated kinase that may alter its activity and/or access to substrates and other effectors.     

cAMP production via the adenylyl cyclase pathway is reduced in RCS rat RPE.

cAMP production was investigated in retinal pigment epithelium (RPE) cells isolated from normal rats and from rats with an inherited retinal dystrophy (Rdy/p+). In normal RPE cells, 5'-[N-Ethylcarboxamido]-adenosine (A2 receptors) produced a fivefold increase in the level of cyclic adenosine monophosphate (cAMP) over basal levels. However, only a onefold increase in cAMP was observed in dystrophic cells. cAMP production by prostaglandins E1 and E2 (prostaglandin receptors) in dystrophic RPE cells was only 29-38% of the level observed in normal cells. Direct stimulation of adenylyl cyclase by 10 mumol/l forskolin increased cAMP levels in normal RPE cells by 90 fold over basal, but only by sixfold in the dystrophic cells. These data suggest there may be a defect in the adenylyl cyclase signaling pathway in dystrophic RPE cells.     

Self-efficacy in weight management

Self-efficacy is an important mediating mechanism in advancing understanding of the treatment of obesity. This study developed and validated the Weight Efficacy Life-Style Questionnaire (WEL), improving on previous studies by the use of clinical populations, cross-validation of the initial factor analysis, exploration of the best fitting theoretical model of self-efficacy, and examination of change in treatment. The resulting 20-item WEL consists of five situational factors: Negative Emotions, Availability, Social Pressure, Physical Discomfort, and Positive Activities. A hierarchical model was found to provide the best fit to the data. Results from two separate clinical treatment studies (total N = 382) show that the WEL is sensitive to changes in global scores as well as to a subset of the five situational factor scores. Treatment programs may be incomplete if they change only a subset of the situational dimensions of self-efficacy. Theoretical and clinical implications are discussed.     

Complications of endodrainage retinotomies created during vitreous surgery for complicated retinal detachment

The authors report nine cases of endodrainage retinotomy site complications that occurred after vitreous surgery for complicated retinal detachments (RDs). Postoperative subretinal neovascularization developed in four eyes at the retinotomy drainage site. In two eyes, postoperative proliferation at a posteriorly placed endodrainage site created traction macular detachments. Redetachment due to retinotomy opening caused by postoperative drainage site proliferation developed in three eyes. The retinas of all nine eyes were eventually reattached, and vision improved from the preoperative level. These complications are related to retinal pigment epithelium and/or Bruch's membrane damage during internal subretinal fluid drainage and retinotomy endolaser photocoagulation. Careful evaluation of extrusion instruments, drainage techniques, retinotomy placement, and subsequent endolaser treatment is necessary to minimize these complications.     

Lateralized Hemispheric Mechanisms and the Antidepressant Effects of Right and Left Unilateral ECT

This article critically reviews the six controlled studies of the antidepressant effects of right unilateral versus left unilateral ECT (R-ECT, L-ECT), contrasting them with results recently obtained in double-blind, random assignment comparison of the two methods, using a square-wave stimulus, widely spaced temporoparietal electrode placement, and markedly supra-threshold stimulus charge. The author challenges the prevalent belief in a therapeutic advantage of R-ECT versus L-ECT, proposing instead the contrary case for a therapeutic advantage of L-ECT, based on the interaction of a hypothesized interhemispheric seizure threshold difference and a maximally efficient method of stimulus delivery.