Directed evolution of the periodic table: probing the electronic structure of late actinides.

Recent investigations of the coordination chemistry and physical properties of berkelium (Z = 97) and californium (Z = 98) have revealed fundamental differences between post-curium elements and lighter members of the actinide series. This review highlights these developments and chronicles key findings and concepts from the last half-century that have helped usher in a new understanding of the evolution of electronic structure in the periodic table.

Reliability of the rating of perceived exertion at ventilatory threshold in children.

The purpose of this study was to examine the reliability of the rating of perceived exertion (RPE), using the Borg 6-20 scale, at ventilatory threshold (VT) in children. Thirty children (19 male, 11 female) with a mean +/- SD age of 10.4 +/- 1.1 yrs performed two graded exercise tests for the assessment of VT and VO2max. RPE was recorded throughout each exercise test. There were no significant (p > 0.05) differences between the mean VO2max (50.9 +/- 6.0 vs 51.0 +/- 5.7 ml.kg-1.min-1; r = 0.95) or the mean VO2 at VT (36.2 +/- 4.4 vs 36.7 +/- 4.5 ml.kg-1.min-1; r = 0.87) between trials. The mean RPE at VT during trial 1 (12.4 +/- 2.7) was significantly higher than during trial 2 (11.4 +/- 3.3; p < 0.05). The test-retest reliability correlation for the RPE at VT was r = 0.78. The lower RPE in the second trial may have been due to a greater comfort and familiarity with the testing procedures. The reliability analysis indicates that the RPE at VT within a given child is fairly consistent from trial to trial. However, large inter-individual variability in the RPE at VT (range = 6 to 19) was noted and was not related to variations in the onset of VT. This raises some concern over the use of a given RPE value or range of RPE values in the regulation of exercise intensity for this age group. The test-retest reliability of VT and VO2max in this age group is similar to previous reports.

Pertussis toxin as a probe of neutrophil activation.

In reviewing our own and other work, it is clear that pertussis toxin treatment of neutrophils causes a time- and concentration-dependent inhibition of granule enzyme secretion induced by formylmethionylleucylphenylalanine (fMet-Leu-Phe), C5a, leukotriene (LT) B4 and platelet-activating factor (PAF). Chemotaxis, O2- generation, aggregation, and arachidonic acid production induced by fMet-Leu-Phe are also inhibited by pertussis toxin. Granule enzyme release caused by A23187 or phorbol 12-myristate 13-acetate is not inhibited. The inhibition of neutrophil function correlates closely with the NAD-ribosylation of a 41,000-dalton protein in the neutrophil plasma membrane, presumably the GTP-binding regulatory protein Ni. Pertussis toxin treatment prevents or obtunds the increased influx of Ca2+ induced by fMet-Leu-phe and LTB4, but not that caused by stimulation of neutrophils with PAF. Pertussis toxin prevents the receptor-induced breakdown of polyphosphoinositides in intact neutrophils and isolated membrane and prevents or decreases the production of inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol. The hypothesis advanced by us and others is that pertussis toxin interacts with a GTP-binding regulatory protein identical or similar to Ni, which couples receptor-chemotactic factor interaction to phospholipase C activation. Inhibition of the activation prevents the production of IP3 and the resulting release of Ca2+ from intracellular stores and of 1,2-diacylglycerol and thus, the activation of protein kinase C. The lack of these two mediators is the immediate cause of the depression of neutrophil activation resulting from pertussis toxin. Some of the limitations and uncertainties of our present knowledge with respect to this hypothesis are discussed.

The inhibition of neutrophil granule enzyme secretion and chemotaxis by pertussis toxin.

Pertussis toxin treatment of rabbit peritoneal neutrophils causes a concentration-dependent inhibition of granule enzyme secretion induced by formylmethionyl-leucyl-phenylalanine, C5a, and leukotriene B4. It also inhibits chemotaxis induced by formylmethionyl-leucyl-phenylalanine. The same toxin treatment, however, has no effect on granule enzyme secretion induced by the calcium ionophore A23187 or phorbol 12-myristate 13-acetate. Moreover, pertussis toxin treatment does not affect either the number or affinity of the formylpeptide receptors on the neutrophil nor does it have any effect on the unstimulated levels of cyclic AMP (cAMP) or the transient rise in cAMP induced by chemotactic factor stimulation in these cells. We hypothesize that pertussis toxin, as in other cells, interacts with a GTP binding regulatory protein identical with or analogous to either Ni or transducin which mediates the receptor-induced inhibition or activation of a target protein or proteins required in neutrophil activation. The nature of the target protein is unknown, but it is not the catalytic unit of adenylate cyclase. The target protein acts after binding of chemotactic factor to its receptor in the sequence that leads to the receptor-induced rise in intracellular Ca2+. It does not affect the responses elicited by the direct introduction of calcium into the cells or the activity of protein kinase C.

Pertussis toxin inhibits fMet-Leu-Phe- but not phorbol ester-stimulated changes in rabbit neutrophils: role of G proteins in excitation response coupling.

Addition of pertussis toxin to rabbit neutrophils inhibits the fMet-Leu-Phe- induced increases in Na+ influx and in intracellular pH. In addition, pretreatment of the cells with the toxin inhibits the decrease in the levels of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-phosphate and the enhanced production of phosphatidic acid produced by the chemotactic factor fMet-Leu-Phe. Furthermore, the fMet-Leu-Phe-induced changes in the phosphorylation of a 46-kDa protein and of several other proteins are also inhibited by the toxin. On the other hand, the phorbol 12-myristate 13-acetate (PMA)-induced increases in the phosphorylation of several proteins are not inhibited by the toxin. PMA, but not its inactive analogue 4 alpha-phorbol 12,13-didecanoate, was also found to stimulate Na+ influx and to increase the intracellular pH in rabbit neutrophils. These ionic effects, like those produced by fMet-Leu-Phe, are inhibited by amiloride. The stimulated Na+ influx and H+ efflux produced by the phorbol ester, on the other hand, are not inhibited by pertussis toxin. The results reported here suggest that the activity of the Na+/H+ antiport in neutrophils is regulated by protein kinase C; that the G-protein system, either directly or indirectly, is involved in the stimulus-response coupling sequence in these cells; and that the toxin acts at, or prior to, the steps responsible for the activation of phospholipase C, and it does not affect the sequence of reactions initiated by the activation of the protein kinase C.

Pertussis toxin inhibits the rise in the intracellular concentration of free calcium that is induced by chemotactic factors in rabbit neutrophils: possible role of the "G proteins" in calcium mobilization.

The addition of pertussis toxin to rabbit neutrophils inhibits the rise in the intracellular concentration of free calcium induced by the chemotactic factors fMet-Leu-Phe and leukotriene B4. At high concentrations of fMet-Leu-Phe, the inhibitory effect of the toxin is more on the stimulus-induced increase in membrane permeability to calcium than on calcium mobilization from internal stores. These results suggest that the "G protein" system either directly or indirectly is involved in the regulation of the stimulus-induced changes in the calcium mobilization and/or gating systems.

Fluctuating intracranial hypertension due to Cheyne-Stokes respiration.

Cyclically fluctuating intracranial pressure (ICP) with periodic breathing was first described by Nils Lundberg in 1960. While Cheyne-Stokes respiration (CSR) frequently accompanies severe cerebrovascular accidents, it is not commonly appreciated that cycles of severe intracranial hypertension can complicate this abnormal ventilation pattern. We recently treated a patient with a hemorrhagic stroke in whom episodes of elevated ICP were synchronously associated with CSR.