Mechanism of mitogen-induced stimulation of glucose transport in human peripheral blood mononuclear cells. Evidence of an intracellular reserve pool of glucose carriers and their recruitment.

The present study examines the effects of phytohemagglutinin stimulation of a population of human (h) PBMC enriched in lymphocytes (hPBMC) on D-glucose displaceable cytochalasin B binding sites or medium-affinity sites (M-sites) in relation to glucose transport. Previously we have shown that M-sites are glucose transporters in hPBMC (Mookerjee, B.K., et al. 1981. J. Biol. Chem. 256:1290-1300). Equilibrium exchange of 3-O-methyl D-glucose in unstimulated cells revealed two populations with fast and slow flux rates. Phytohemagglutinin stimulates flux rates by converting part of the slow flux population to the fast flux population. M-sites occur in two distinct pools, one in plasma membrane and the other in microsomal fraction. Phytohemagglutinin treatment increases the plasma membrane pool size of M-sites with a concomitant reduction in the microsomal pool size without affecting the binding affinities or the total number of M-sites/cell. Data presented in this paper demonstrate that there are two pools of glucose transporters in these cells and phytohemagglutinin stimulation induces an energy-dependent net translocation of glucose transporters from an intracellular reserve pool to the plasma membrane, which accounts for greater than 60% of the increment in glucose transport.     

Cefotaxime and desacetylcefotaxime in neonates and children: a review of microbiologic, pharmacokinetic, and clinical experience

Over the past 5 yr, we have conducted two clinical and two pharmacokinetic investigations of cefotaxime (CTX) and desacetylcefotaxime (dCTX) in neonates, infants, and children. A total of 50 children with culture-proven bacterial meningitis were randomized to receive either 200 mg/kg/day of CTX (n = 23, mean age 24.4 mo) or standard doses of ampicillin (AMP) and chloramphenicol succinate (CAPS; n = 27, mean age 16.6 mo). Results were similar between the CTX and Amp/CAPS groups for clinical/microbiological cures (100% versus 96%, respectively) and for survival without sequelae (78% vs. 77%, respectively). All bacterial isolates were sensitive to CTX, and the comparison of the MIC/MBC values for CTX to the CSF bactericidal titers suggested antimicrobial activity for dCTX. In a second clinical trial, 20 infants (1 wk-3 mo) were treated with 200 mg/kg/day of CTX for Gram-negative enteric bacillary meningitis. Cultures of CSF obtained 24 hr after the initiation of treatment were sterile in all subjects. Survival and complication rates of 95% and 21%, respectively, were observed. This compared favorably to previously published experiences with alternate treatment regimens for Gram-negative meningitis in the newborn. In both meningitis studies, the safety profile for CTX was excellent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial tagging in polar coordinates with use of striped tags

Regional deformation abnormalities in the heart wall provide a good indicator of ischemia. Myocardial tagging with magnetic resonance imaging is a new method of assessing heart wall motion during contraction. Current methods of myocardial tagging either do not provide two-dimensional information or lack a coordinate system well adapted to the morphology of the heart. In this article, the authors describe a new tagging method that provides a true polar coordinate system, with both radial and angular dimensions. This is accomplished with use of a section-selective version of spatially modulated magnetization resulting in striped tags (STAGs). These STAG planes are placed in the myocardium in a star pattern so that they intersect on the long axis of the heart and stripes appear through the width of the heart wall. In the short-axis view during contraction, rotation around the long axis yields angular information such as shear and twist, while separation of the stripes within the myocardium permits measurement of radial thickening. Therefore, this method provides a coordinate system for calculating two-dimensional strain that is adapted to the morphology of the left ventricle.     

Fc-gamma receptor-ligand interactions enhance macrophage GSIB4-binding activity

Activated macrophages have an increased ability to bind the lectin Griffonia simplicifolia-IB4 (GSIB4). Since macrophages readily use the Fc-receptor (FcR) during several immunologic and inflammatory processes, it is important to determine whether interactions with this moiety affect GSIB4-binding ability. Peritoneal macrophages cultured in vitro with Fc fragments of immunoglobulin G (IgG), whole IgG, or heat-aggregated IgG demonstrate an increase in this function. Conversely, treatment of macrophages with (Fab')2 fractions alone has no direct effect on this activity. Although the GSIB4-binding response is minimally expressed by normal macrophages, it is more markedly apparent on macrophages from LPS-treated animals. In both cases, however, pretrypsinization of the cells renders them refractory to IgG-mediated induction of the GSIB4-binding response. Moreover, macrophages cultured independently with IgG subclasses 1, 2a, or 3 demonstrate that the magnitude of their response to this signal is directly associated with the type of subclass used. Although each subclass enhanced the response, in this study interactions with IgG2a produced the best results. Overall, however, the greatest GSIB4-binding activity is generated when FcRs are crosslinked by aggregated IgG rather than simply bound by independent monomeric interactions at the FcRs. This suggests that the event of appropriately interacting with the FcRs amplifies the GSIB4-binding function. Such a mechanism could play a key role in coordinating the humoral, cell-mediated, and innate responses of the immune system.