Apoptosis after traumatic human spinal cord injury

OBJECT: Apoptosis is a form of programmed cell death seen in a variety of developmental and disease states, including traumatic injuries. The main objective of this study was to determine whether apoptosis is observed after human spinal cord injury (SCI). The spatial and temporal expression of apoptotic cells as well as the nature of the cells involved in programmed cell death were also investigated. METHODS: The authors examined the spinal cords of 15 patients who died between 3 hours and 2 months after a traumatic SCI. Apoptotic cells were found at the edges of the lesion epicenter and in the adjacent white matter, particularly in the ascending tracts, by using histological (cresyl violet, hematoxylin and eosin) and nuclear staining (Hoechst 33342). The presence of apoptotic cells was supported by staining with the terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick-end labeling technique and confirmed by immunostaining for the processed form of caspase-3 (CPP-32), a member of the interleukin-1beta-converting enzyme/Caenorhabditis elegans D 3 (ICE/CED-3) family of proteases that plays an essential role in programmed cell death. Apoptosis in this series of human SCIs was a prominent pathological finding in 14 of the 15 spinal cords examined when compared with five uninjured control spinal cords. To determine the type of cells undergoing apoptosis, the authors immunostained specimens with a variety of antibodies, including glial fibrillary acidic protein, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), and CD45/68. Oligodendrocytes stained with CNPase and a number of apoptotic nuclei colocalized with positive staining for this antibody. CONCLUSIONS: These results support the hypothesis that apoptosis occurs in human SCIs and is accompanied by the activation of caspase-3 of the cysteine protease family. This mechanism of cell death contributes to the secondary injury processes seen after human SCI and may have important clinical implications for the further development of protease inhibitors to prevent programmed cell death.     

Non-Uniform Traffic Issues in DCA Wireless Multimedia Networks

Wireless networks that utilize dynamic channel allocation (DCA) are known to perform better than those with fixed channel allocation, in terms of the call level QoS measures such as the handoff dropping probability. On account of this, the DCA networks are usually designed without the call admission control (CAC). However, given the decrease of cell sizes, together with ever increasing mobile phone and terminal population, dynamic channel allocation policies (such as channel borrowing) may not be sufficient to cope with the hot-spot area size and its traffic intensity. This paper analyses the performance of the DCA networks, both with and without the call admission control, under the hot-spot traffic regime. In such cases, the pure DCA approach fails to ensure sufficiently low level of QoS in both the hot-spot area and the surrounding cells. We propose a CAC policy that can stabilize the QoS under non-uniform traffic, whilst being easy to integrate in the distributed DCA policies.     

Pentoxifylline attenuates neutrophil activation in experimental endotoxemia in chimpanzees

Costimulation of neutrophils and cytokines may play an important role in organ injury in sepsis. Pentoxifylline inhibits various neutrophil functions in vitro, and attenuates endotoxin-induced production of TNF in both in vitro and in vivo models. To assess the effect of pentoxifylline on neutrophil activation in endotoxemia, nine adult chimpanzees (Pan troglodytes) were i.v. injected with saline (n = 2), Escherichia coli endotoxin (4 ng/kg; n = 4), or E. coli endotoxin (4 ng/kg) in combination with pentoxifylline (500 mg/3 h, starting 30 min before the endotoxin injection; n = 3). Serial blood samples were obtained for measurements of leukocyte counts and the granulocytic proteinases elastase complexed with alpha 1-antitrypsin and lactoferrin, and cytokines during the next 5 h. No changes were observed in the saline-treated chimpanzees. Endotoxin induced a marked leukocytosis and neutrophilia, which were slightly reduced by pentoxifylline. In contrast, pentoxifylline almost completely prevented endotoxin-induced neutrophil degranulation: peak elastase-alpha 1-antitrypsin was 164 +/- 21 ng/ml (mean +/- SE) after endotoxin alone, vs 71 +/- 7 ng/ml after endotoxin with pentoxifylline (t = 3 h; p < 0.05); peak lactoferrin was 329 +/- 15 and 182 +/- 5 ng/ml, respectively (t = 5 h; p < 0.05). Pentoxifylline also inhibited the endotoxin-induced release of TNF (271 +/- 26 vs 55 +/- 23 pg/ml at t = 1.5 h; p < 0.05) and IL-6 (225 +/- 42 vs 73 +/- 25 pg/ml at t = 2 h; p < 0.05). IL-8 release was not significantly inhibited by pentoxifylline. In none of the animals activation of the C system could be detected. We conclude that pentoxifylline attenuates neutrophil activation in endotoxemia in chimpanzees, probably in part by inhibiting the release of TNF.     

Ferroxidase kinetics of human liver apoferritin, recombinant H-chain apoferritin, and site-directed mutants

A detailed study of the kinetics of iron(II) oxidation by molecular oxygen in natural and recombinant human apoferritins has been carried out using electrode oximetry to better understand the ferroxidase activity of the protein shell. A comparative study of recombinant L-chain ferritin (rLF), recombinant H-chain ferritin (rHF), and variants has shown that (1) rLF lacks a ferroxidase activity, confirming the results of previous studies; (2) the ferroxidase site of rHF involves Glu-62 and His-65, presumably as Fe2+ ligands, since mutation of these residues abolishes most of the oxidase activity, in agreement with previous studies; and (3) mutation of both the putative ferroxidase and nucleation site ligands in rHF renders the protein totally incapable of catalyzing the oxidation of Fe2+ whereas mutation of nucleation site ligands alone (Glu-61, Glu-64, and Glu-67) decreases the activity only slightly. Analysis of the kinetics of rHF and natural human liver ferritin (HLF) (4% H-chain, 96% L-chain) gave the following apparent parameters at pH 7: Km,O2 = 6 +/- 2 microM, Km,Fe = 80 +/- 10 microM, and kcat = 201 +/- 14 min-1 for rHF and Km,O2 = 60 +/- 12 microM, Km,Fe = 50 +/- 10 microM, and kcat = 31.2 +/- 0.6 min-1 for HLF. Furthermore, Zn2+ was shown to be a noncompetitive inhibitor of Fe2+ oxidation in rHF but a mixed inhibitor in HLF. These different forms of Zn2+ inhibition in the two proteins and the higher activity of HLF than expected, based on its H-chain composition as well as differences in their enzyme kinetic parameters, suggest that H- and L-chains cooperate in modulating the ferroxidase activity of the apoferritin even though the L-subunit lacks a ferroxidase site itself.     

Neural plasticity in adults with amblyopia

Amblyopia is a neuronal abnormality of vision that is often considered irreversible in adults. We found strong and significant improvement of Vernier acuity in human adults with naturally occurring amblyopia following practice. Learning was strongest at the trained orientation and did not transfer to an untrained task (detection), but it did transfer partially to the untrained eye (primarily at the trained orientation). We conclude that this perceptual learning reflects alterations in early neural processes that are localized beyond the site of convergence of the two eyes. Our results suggest a significant degree of plasticity in the visual system of adults with amblyopia.     

Morphological stability of copper-silver multilayer thin films at elevated temperatures

The kinetics of breakdown of Cu-Ag polycrystalline multilayers during aging at elevated temperatures was investigated. Microlaminates with Cu:Ag layer thicknesses of 2:2, 1:4, 4:1, and 4:0.1 μm were aged for 10 minutes to 192 hours (t), at temperatures ranging from 700 to 900 K. The asdeposited microlaminates had a fine-grained columnar microstructure with well-defined interfaces. Upon annealing, the morphology evolved over three time regimes. In the first regime, the grains in each phase grew quickly to an apparent terminal size, which depended on both the layer thickness and annealing temperature. Next, grooves formed at the intersections of grain boundaries and layer interfaces and grew with a t ^0.25 dependence. The groove growth appeared to be independent of layer thickness and was approximately equal in Cu and Ag. The microlaminates started to break down in the third regime, as grain-boundary grooves on opposite sides of a layer bridged its thickness. Models for grain growth and grooving in thin films were modified for multilayer microlaminates and were shown to fit the experimental data reasonably well. This suggests that the terminal grain size is reached when groove drag overcomes the capillary forces driving grain growth, and that grooving kinetics are dominated by interfacial diffusion.     

Influence of Precipitates Size and Distribution on Room Temperature Mechanical Properties and Accelerated Creep of X20CrMoV121

The effect of microstructure on creep resistance of the low carbon chromium steel X20CrMoV121 after 100‐hours of static‐load test at a temperature of 580 °C and constant stress of 170 MPa was investigated. The specimens for the experiments were extracted from steam pipes of a steam power plant and heat treated. The effect of isothermal annealing on the microstructure and hardness as well as the kinetics of the precipitation of the carbide particles were determined.