Vav3 modulates B cell receptor responses by regulating phosphoinositide 3-kinase activation.

To elucidate the mechanism(s) by which Vav3, a new member of the Vav family proteins, participates in B cell antigen receptor (BCR) signaling, we have generated a B cell line deficient in Vav3. Here we report that Vav3 influences phosphoinositide 3-kinase (PI3K) function through Rac1 in that phosphatidylinositol-3,4,5-trisphosphate (PIP3) generation was attenuated by loss of Vav3 or by expression of a dominant negative form of Rac1. The functional interaction between PI3K and Rac1 was also demonstrated by increased PI3K activity in the presence of GTP-bound Rac1. In addition, we show that defects of calcium mobilization and c-Jun NH2-terminal kinase (JNK) activation in Vav3-deficient cells are relieved by deletion of a PIP3 hydrolyzing enzyme, SH2 domain-containing inositol polyphosphate 5'-phosphatase (SHIP). Hence, our results suggest a role for Vav3 in regulating the B cell responses by promoting the sustained production of PIP3 and thereby calcium flux.     

Periodic lateralized epileptiform discharges: etiology, clinical aspects, seizures, and evolution in 130 patients.

The purpose of this study was to analyze the clinical aspects in 130 patients presenting periodic lateralized epileptiform discharges (PLEDs) in their EEG and to compare these results with those found in the literature. Etiology, neurologic deficit, seizure occurrence, and evolution were studied in each patient by historical review. The recordings were obtained on 8- or 16-channel EEGs with electrode placement according to the International 10-20 System. Recordings containing PLEDs were selected. PLEDs were defined as repetitive periodic, focal, or hemispheric epileptiform discharges (spikes, spike and waves, polyspikes, sharp waves) usually recurring every 1 to 2 seconds. The statistical study was carried out via the chi(2) test using the computer program SPSS. The main etiology found in this group of patients was stroke (61 of 130 patients). Other processes found were brain infections, tumors, hematomas, and several other entities grouped together as miscellaneous (anoxic encephalopathy, subarachnoid hemorrhage, craniocerebral trauma, Creutzfeldt-Jacob disease, migraine, multiple sclerosis, and aminophylline intoxication). Half of these patients (65 of 130) developed seizures, mostly partial motor seizures. No significant relation between etiology and seizures was found (chi(2) = 2.81, P = 0.4222). Seizures recurred in 14 of 130 patients during a follow-up of 14.5 months. PLEDs were not recorded in any EEG at the time of seizure recurrence. PLEDs constitute a distinctive but uncommon EEG phenomenon of repetitive, periodic, and stereotyped lateralized complexes. In agreement with the literature, PLEDs were associated with an acute process and occurred early during the course of the illness in all patients studied and were usually associated with structural lesions, with stroke being the main etiology. Traditionally, seizures occur with PLEDs but it is also accepted that they can exist in patients who never develop epileptic activity, either clinically or electrically, as demonstrated in 50% of the patients studied. No significant association between seizures and any etiology could be found. It was not demonstrated that the occurrence of seizures may influence the outcome in any way.     

Intensive versus standard blood glucose awareness training (BGAT) with insulin-dependent diabetes: mechanisms and ancillary effects

Insulin-dependent diabetes mellitus (IDDM) patients make critical daily self-care decisions on the basis of what they estimate their blood glucose (BG) levels to be. This study: a) replicated efficacy of Standard Blood Glucose Awareness Training (BGAT), b) evaluated the relative efficacy of an Intensive Blood Glucose Awareness Training (BGAT) to enhance patient accuracy of BG estimation, and c) evaluated the mechanisms and ancillary effects of BGAT. Thirty-nine subjects were randomly assigned to one of three groups. Compared with Control, both Standard and Intensive BGAT improved accuracy (p less than 0.001). Intensive BGAT post-treatment accuracy relative to Standard BGAT did not reach statistical significance (p = 0.177). Greater improvement in accuracy was associated with poorer pretreatment accuracy. Only Intensive BGAT improved metabolic control (glycosylated hemoglobin), and this improvement was associated with poorer pretreatment control. The effects of BGAT were highly specific, affecting only accuracy and metabolic control, and not affecting fear of hypoglycemia, diabetes knowledge, of frequency of blood glucose monitoring.     

Manipulating prefabricated flaps: An experimental study examining flap viability

As flap prefabrication becomes a more commonly used clinical tool, it is necessary to investigate the limitations of this technique. Reconstructive procedures of the face often require “custom fitted” flaps to satisfy esthetic demands. This study examines and compares the safety of manipulating thin prefabricated skin flaps versus established axial pattern skin flaps. Twenty-seven New Zealand white rabbits were used to determine if prefabricated flaps can be folded 180° around the edge of the rabbits' ears. The survival of these folded prefabricated flaps was compared with the survival of axial pattern flaps sutured into an identically recipient site. In addition, flaps prefabricated in the same manner were sutured onto a straight recipient bed to evaluate the viability of the newly vascularized tissue. The folded prefabricated flaps had reduced survival (56%) compared to equivalent folded axial pattern flaps (85%), P<0.005. The nonmanipulated prefabricated flaps and axial pattern flaps survived completely. © 1994 Wiley-Liss, Inc.