Children's thinking in the wake of Challenger

OBJECTIVE: The Challenger spacecraft explosion in 1986 offered an opportunity to study the thinking of normal children after a sudden and distant disaster, differences in thinking among children of different levels of emotional concern and different ages, and changes in their thinking over time. METHOD: The authors studied six thinking patterns known to characterize childhood posttraumatic stress disorder and four additional hypothesized patterns in 153 randomly selected children of Concord, N.H. (who watched the explosion on television) and Porterville, Calif. (who heard about it later). They compared the structured-interview responses of the more involved (East Coast) and less involved (West Coast) children, of the latency-age children and the adolescents, and of the children initially (5-7 weeks after the explosion) and 14 months later. RESULTS: The children exhibited the 10 predictable thinking patterns. They initially defended themselves, denying the reality of the explosion. They later fantasized about it. They tried to cope by seeking additional information on their own, at home, and at school. Most children talked about Challenger, but a minority of the latency-age youngsters avoided related talk and thoughts. The adolescents experienced more paranormal thinking, philosophical changes, and negative attitudes. Over the year, omens, paranormal experiences, and Challenger-based fantasies tended to disappear, but negative views about institutions and the world's future held steady or increased. CONCLUSIONS: The children's thinking followed predictable patterns. A higher degree of emotional involvement (East Coast children) was strongly linked to these thinking patterns, as was being an adolescent. Distant disasters appear to set up commonalities of thought that might come to characterize certain generations of children.     

Effects of pressure and duration of hyperkalemic infusions on endothelial function

Infusions of crystalloid hyperkalemic cardioplegic solutions (CHCSs) are known to impair endothelium-dependent coronary relaxation. This impairment might also be influenced by high perfusion pressure and duration of CHCS infusion. To verify this hypothesis, we designed experiments to study the influence of pressure and duration of CHCS infusion as modulating factors in CHCS-related endothelial impairment. Isolated hearts of Sprague-Dawley rats were studied in a Langendorff apparatus for coronary endothelial function. Hearts (n = 6) were exposed to four different CHCSs containing 12, 24, 40, or 100 mmol/L of potassium chloride (KCl). Endothelial and smooth muscle functions were respectively tested by infusion of 5-hydroxytryptamine (1 x 10(-6) mol/L) and sodium nitroprusside (1 x 10(-5) mol/L) before and after CHCS perfusion. In group I (n = 24), 37 degrees C CHCSs were perfused at 80 cm H2O of pressure for 30 minutes. In group II (n = 24), the same CHCSs were perfused at 160 cm H2O for 30 minutes. In group III (n = 18), CHCSs containing 24, 40, and 100 mmol/L of KCl were infused at 160 cm H2O for 10 minutes. In all groups, response to sodium nitroprusside was unaltered by CHCS infusion, indicating that smooth muscle function was preserved. However, in group II, 5-hydroxytryptamine-induced vasodilation was significantly impaired in hearts perfused with CHCS containing 24 mmol/L of KCl or more, suggesting endothelial damage. This study demonstrates that, in addition to KCl concentration, pressure and duration of infusion are two major determinants in CHCS-mediated endothelial damage.     

Long-term outcomes and life satisfaction of adults who had pediatric spinal cord injuries

OBJECTIVE: To determine long-term outcomes and life satisfaction of adults who sustained pediatric spinal cord injury (SCI). DESIGN: Structured interview of adults who were 25 years or older who had pediatric SCI. SETTING: Community. PARTICIPANTS: A convenience sample of 46 patients from a total of 81 patients who received care in an SCI program: 1 refused participation, 4 died, and 30 were lost to follow-up. MAIN OUTCOME MEASURES: A structured questionnaire including physical, psychosocial, and medical information. The Craig Handicap Assessment and Reporting Technique and two measures of life satisfaction were also administered. RESULTS: Participants were 25 to 34 years old, mean 27 years. Thirty-two had tetraplegia and 14 had paraplegia. Thirty-one were men. Mean years of education was 14. Fifty-four percent were employed, 48% lived independently, and 15% were married. Life satisfaction was associated with education, income, satisfaction with employment, and social/recreation opportunities, and was inversely associated with some medical complications. Life satisfaction was not significantly associated with level of injury, age at injury, or duration of injury. CONCLUSIONS: Individuals who had pediatric SCI, much like adult-onset SCI, have the greatest opportunity for a satisfying adult life if rehabilitation emphasizes psychosocial factors such as education, employment, and long-term health management.     

The Cbl phosphotyrosine-binding domain selects a D(N/D)XpY motif and binds to the Tyr292 negative regulatory phosphorylation site of ZAP-70

The Cbl protooncogene product has emerged as a novel negative regulator of receptor and non-receptor tyrosine kinases through currently undefined mechanisms. Therefore, determining how Cbl physically interacts with tyrosine kinases is of substantial interest. We recently identified a phosphotyrosine binding (PTB) domain residing within the N-terminal transforming region of Cbl (Cbl-N), which mediated direct binding to ZAP-70 tyrosine kinase. Here, we have screened a degenerate phosphopeptide library and show that the Cbl-PTB domain selects a D(N/D)XpY motif, reminiscent of but distinct from the NPXpY motif recognized by the PTB domains of Shc and IRS-1/2. A phosphopeptide predicted by this motif and corresponding to the in vivo negative regulatory phosphorylation site of ZAP-70 (Tyr(P)292) specifically inhibited binding of ZAP-70 to Cbl-N. A ZAP-70/Y292F mutant failed to bind to Cbl-N, whereas a D290A mutant resulted in a 64% decrease in binding, confirming the importance of the Tyr(P) and Y-2 residues in Cbl-PTB domain recognition. Finally the ZAP-70/Y292F mutant also failed to associate with Cbl-N or full-length Cbl in vivo. These results identify a potential Cbl-PTB domain-dependent role for Cbl in the negative regulation of ZAP-70 and predict potential Cbl-PTB domain binding sites on other protein tyrosine kinases known to interact with Cbl.     

Insulin availability among International Diabetes Federation member associations. Report of the Task Force on Insulin Distribution

The authors used data from the New Zealand Household Travel Survey to examine the extent to which children's pedestrian exposure varies with age, sex and household income. Pedestrian injury morbidity data were combined with pedestrian exposure data to examine age-specific pedestrian injury risk. The annual number of road crossings for girls was greater than that for boys. Pedestrian exposure increased with increasing age. Children aged 5-9 years in the lowest household income bracket crossed approximately 50% more roads than those in the middle and upper income brackets. However, for children aged 10-14 years there was little variation with household income. Sex differences in pedestrian injury rates cannot be explained by differences in exposure although increased exposure may partly explain the increased injury rates for children in lower socio-economic groups. Prevention strategies might aim to reduce pedestrian exposure for alternatively to reduce pedestrian injury risk per unit of exposure by making safer urban living environments.     

Calcium and a mitochondrial signal interact to stimulate phosphoinositide hydrolysis and insulin secretion in rat islets

Fuel metabolism generates multiple signals that interact to stimulate insulin secretion. These studies explored the mechanism by which fuels activate phosphoinositide (PI) hydrolysis and the role of this signal transduction pathway in fuel-stimulated insulin secretion. High potassium (30 mM), which depolarizes the membrane and increases Ca2+ influx, caused only a transient monophasic release of insulin. In contrast, glucose (20 mM) or monomethylsuccinate (MMSucc; 10 mM) markedly stimulated a sustained insulin secretory response, indicating that fuel metabolism generates a signal(s) in addition to Ca2+ influx that is required for a sustained secretory response. On the other hand, diazoxide, an ATP-sensitive K+ channel activator that prevents membrane depolarization and Ca2+ influx in response to fuel metabolism, reduced the secretory responses to glucose and MMSucc to baseline levels, demonstrating that Ca2+ influx was essential to fuel-stimulated insulin secretion. The further addition of high K+ bypassed the diazoxide block and restored insulin secretory rates. The insulin secretory response to glucose or MMSucc in the presence of diazoxide and K+ was inhibited by the Ca2+ channel antagonist nitrendipine and the protein kinase-C inhibitor staurosporine. Changes in PI hydrolysis paralleled those in insulin secretion. High potassium alone induced only a modest 2.5-fold increase in inositol phosphate accumulation. This response was significantly less than that to glucose or MMSucc, which increased inositol phosphate accumulation by 6.8- or 5.2-fold, respectively. Like its effect on secretion, diazoxide markedly reduced glucose- or MMSucc-stimulated PI hydrolysis, and this inhibition was reversed with high K+. In contrast, diazoxide had no effect on receptor-activated PI hydrolysis stimulated by 100 nM cholecystokinin (CCK), and the effects of CCK were not dependent on added fuel, indicating that fuel and CCK activate PI hydrolysis by distinct pathways. These findings demonstrate that mitochondrial metabolism of glucose or MMSucc generates a signal(s) that interacts with Ca2+ influx to stimulate PI hydrolysis and sustained insulin secretion. This pathway of fuel-activated PI hydrolysis is distinct from that of CCK receptor-activated PI hydrolysis. These studies suggest that fuel-activated PI hydrolysis plays an important role in fuel-stimulated insulin secretion.     

Preimplantation embryo sexing by polymerase chain reaction amplification of the sry gene on single mouse blastomeres

Accurate and rapid sex determination of preimplantation embryos has great potential both in animal breeding and in human pathology. In the past, sex determination has been accomplished by cytogenetic or immunologic means and by polymerase chain reaction amplification of Y-chromosome-specific repetitive sequences. More recently, amplification of the Y-specific single-copy ZFY gene has been used in humans for sex determination of preimplantation embryos. The experiments reported here indicate that another Y-chromosome-specific single-copy gene, the sex-determining region gene (sry) can be successfully amplified from single mouse blastomeres. Blastocysts positive for sry amplification were reimplanted to foster mothers, and six of six newborns were male. We conclude that sry gene amplification can represent a good marker for embryo sex determination.     

Structure of a sarcoplasmic calcium-binding protein from amphioxus refined at 2.4 A resolution

The three-dimensional structure of a sarcoplasmic Ca(2+)-binding protein from the protochordate amphioxus has been determined at 2.4 A resolution using multiple-isomorphous-replacement techniques. The refined model includes all 185 residues, three calcium ions, and one water molecule. The final crystallographic R-factor is 0.199. Bond lengths and bond angles in the molecules have root-mean-square deviations from ideal values of 0.015 A and 2.8 degrees, respectively. The overall structure is highly compact and globular with a predominantly hydrophobic core, unlike the extended dumbbell-shaped structures of calmodulin or troponin C. There are four distinct domains with the typical helix-loop-helix Ca(2+)-binding motif (EF hand). The conformation of the pair of EF hands in the N-terminal half of the protein is unusual due to the presence of an aspartate residue in the twelfth position of the first Ca(2+)-binding loop, rather than the usual glutamate. The C-terminal half of the molecule contains one Ca(2+)-binding domain with a novel helix-loop-helix conformation and one Ca(2+)-binding domain that is no longer functional because of amino acid changes. The overall structure is quite similar to a sarcoplasmic Ca(2+)-binding protein from sandworm, although there is only about 12% amino acid sequence identity between them. The similarity of the structures of these two proteins suggests that all sarcoplasmic Ca(2+)-binding proteins will have the same general conformation, even though there is very little conservation of primary structure among the proteins from various species.