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  • 1
    Electronic Resource
    Electronic Resource
    Interleukin-1β and Tumor Necrosis Factor-α Induce Expression of α1-Antichymotrypsin in Human Astrocytoma Cells by Activation of Nuclear Factor-κB (1996)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 67 (1996), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The protease inhibitor α1-antichymotrypsin (ACT) has been suggested to be involved in the etiology of Alzheimer's disease (AD). Increased levels of ACT have been found in serum and brains of AD patients, and ACT has been proposed to regulate β-amyloid fibril formation in vitro. To gain insight into the regulation of ACT in the brain, we investigated the signal transduction pathways involved in ACT gene expression and protein synthesis in the human astrocytoma cell line U373. This cell line has previously been shown to respond with strong ACT synthesis on stimulation with interleukin-1β (IL-1β) or tumor necrosis factor-α (TNFα). Here, we describe that both IL-1β and TNFα activate the transcription factor nuclear factor-κB (NF-κB) via production of reactive oxygen intermediates resulting in ACT expression. In addition, we show that neither protein kinase C nor protein kinase A is involved in IL-1β- or TNFα-induced ACT expression. These results suggest that activation of NF-κB may be one possible cause of increased ACT levels in AD and provide a basis for the development of drugs used for the modulation of inflammatory processes occurring in AD.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1996.67052039.x
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  • 2
    Electronic Resource
    Electronic Resource
    Interleukin-1β Uses Common and Distinct Signaling Pathways for Induction of the Interleukin-6 and Tumor Necrosis Factor α Genes in the Human Astrocytoma Cell Line U373 (1996)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 66 (1996), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Cytokines are involved in the etiology of different disorders of the CNS. For a better understanding of their pathogenic role, we analyzed signal transduction pathways mediating the interleukin (IL)-1β-induced synthesis of IL-6 and tumor necrosis factor α (TNFα) in the human astrocytoma cell line U373 MG. Both protein kinase C and reactive oxygen intermediates (ROIs) were involved in IL-6 and TNFα gene expression by IL-1β. In contrast, protein tyrosine kinases were only necessary for expression of the IL-6 gene. Whereas activation of protein kinase A was able to induce expression of the IL-6 gene, it did not induce TNFα gene expression and was not involved in IL-1β-induced IL-6 and TNFα gene expression. Activation of the transcription factor nuclear factor-κB by IL-1β involved ROIs, whereas the IL-1β-induced activation of the transcription factor AP-1 was mediated via protein kinase C. Our findings provide the basis for the development of specific drugs for the treatment of disorders of the CNS in which cytokines play a pathogenic role.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.1996.66041496.x
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  • 3
    Electronic Resource
    Electronic Resource
    Atomic transport and phase formation in the Sb/Al system induced by heavy-ion bombardment (1995)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 78 (1995), S. 2303-2310 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Antimony/aluminium films in bilayer and multilayer geometries were irradiated at liquid-nitrogen temperature with 50–900 keV ion beams ranging in mass from 20Ne to 208Pb. Depth profiling of the element concentrations was carried out via Rutherford backscattering spectroscopy. The formation of intermetallic phases and phase segregation was analyzed by means of x-ray diffraction, cross-section transmission electron microscopy, and scanning electron microscopy. From the low-dose irradiation data, the mixing rates k were obtained and found to depend linearly on the energy density FD deposited at the interface. The mixing efficiency of Sb/Al bilayers, k/FD=296(30) A(ring)5/eV, supports the local thermal spike model. After high-fluence irradiations of Sb/Al bilayers with 550 keV Xe++ ions, a reacted layer of crystalline SbAl (B3 phase) at the interface was observed. Sb/Al multilayers irradiated with 900 keV Xe++ ions were found to become amorphous. Phase formation was studied as a function of the ion fluence, irradiation energy, and ion mass, and was found to start at that fluence, where cracking and shrinking of the Sb top layer and an increase of the sputtering yield were also observed. © 1995 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.360148
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  • 4
    Electronic Resource
    Electronic Resource
    Ion-beam induced amorphization and dynamic epitaxial recrystallization in α-quartz (1999)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 85 (1999), S. 3120-3123 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: We report on the evaluation of ion-beam induced damage in α-quartz and its dynamic annealing behavior in the temperature range between 80 and 1050 K using Rutherford backscattering spectrometry in channeling geometry. The results illustrate that the critical temperature for inhibiting amorphization during irradiation is about Tc(approximate)940 K. The critical fluence φc for amorphization is independent of the temperature up to 550 K, but strongly increases at higher temperatures. The activation energy for the diffusion of defects in the collision cascade or at the amorphous/crystalline interface is found to be 0.28±0.02 eV. The dynamic annealing mechanism is explained by the vacancy out-diffusion model of Morehead and Crowder. © 1999 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.369650
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  • 5
    Electronic Resource
    Electronic Resource
    Ion irradiation induced atomic transport and phase formation in the system nickel–aluminum (1993)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 73 (1993), S. 3499-3509 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Nickel–aluminum bi-, multi-, and marker layers were irradiated with 80–900 keV Ar, Kr, and Xe ions at 80 and 300 K. The ion induced mass transport through the interface(s) was measured via Rutherford backscattering spectrometry. A bilayer mixing efficiency of 157 A(ring)5/eV was obtained, independent on the irradiation temperature, and the ion species. In the mixing of 0.5–5 nm Ni marker layers embedded in Al, the influence of thermodynamic driving forces was verified by varying the Ni marker thickness. The results as discussed in the light of current ion beam mixing models, are neither consistent with the ballistic nor the global thermal spike model. The phases formed after multilayer mixing were studied by means of x-ray diffraction and perturbed angular correlation spectroscopy. The latter is a novel method to investigate early stages of ion beam induced phase transformations and changes produced by single implanted (111In) tracer ions. For the RT mixing of equiatomic multilayers, the formation of crystalline NiAl was followed. By changing the multilayer composition different crystalline and amorphous Ni–Al phases were identified.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.352955
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  • 6
    Electronic Resource
    Electronic Resource
    A low-energy ion implanter for surface and materials science (1998)
    [S.l.] : American Institute of Physics (AIP)
    Review of Scientific Instruments 69 (1998), S. 2120-2126 
    Details
    ISSN: 1089-7623
    Source: AIP Digital Archive
    Topics: Physics , Electrical Engineering, Measurement and Control Technology
    Notes: A low-energy ion-beam facility for surface and materials science has been built which allows ion beam treatments of solid surfaces via single-ion impacts up to high-fluence implantations. The system offers mass-separated ion beams of 0.5–10 keV by a normal acceleration, and of 5–2000 eV by an acceleration/deceleration lens combination. Its energy spread is estimated to be as small as 2 eV in the whole range. Ion current densities are available in the range between 0.1 nA/cm2 and up to 50 μA/cm2, corresponding to a particle flux of 109–1014 ions/cm2 s. Homogeneous implantation profiles are achieved using an electrostatic x-y deflection system. First applications for ion induced defect production on highly oriented pyrolytic graphite surfaces detected via scanning tunneling microscopy are presented. Hillock shaped defect formations were detected and attributed to protusions of the atomic surface structure, which were induced by interstitials and interstitial clusters between the first atomic planes originated from recoil atoms of the collision cascade. © 1998 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.1148909
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  • 7
    Electronic Resource
    Electronic Resource
    Valproic acid inhibits substance P-induced activation of protein kinase C epsilon and expression of the substance P receptor (2003)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 86 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The neuropeptide substance P (SP) has been hypothesized to be involved in the etiopathology of affective disorders. This hypothesis is based on the findings that neurokinin-1-receptor antagonists have antidepressant effects in depressed patients and that SP may worsen mood. In this study, we investigated the effect of the mood-stabilizing agents valproic acid (VPA), carbamazepine, and lithium on SP-induced gene expression. As a model system, we used primary rat astrocytes and human astrocytoma cells, which both express functional SP-receptors and, upon stimulation with SP, synthesize interleukin-6 (IL-6), a cytokine which has been shown to be elevated during the acute depressive state. We found that VPA dose-dependently inhibited SP-induced IL-6 synthesis which was seen with pre-incubation periods of 30 min, 3, 7 and 14 days, whereas carbamazepine and lithium showed no inhibitory effect. The inhibitory effect of VPA was not mediated by inhibition of the stress-regulated kinases p38 and p42/44 (Erk1/2) but by inhibition of protein kinase C epsilon activation. Furthermore, VPA down-regulated the expression of the substance P receptor (neurokinin(NK)-1-receptor) as assessed by real-time PCR. Whether both mechanisms contribute to the mood-stabilizing properties of VPA has to be evaluated in further studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2003.01802.x
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  • 8
    Electronic Resource
    Electronic Resource
    Synergistic inhibitory effect of ascorbic acid and acetylsalicylic acid on prostaglandin E2 release in primary rat microglia (2003)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 86 (2003), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Ascorbic acid (vitamin C) has been suggested to protect cerebral tissue in a variety of pathophysiological situations such as head trauma, ischemia or Alzheimer's disease. Most of these protective actions have been attributed to the antioxidative capacity of ascorbic acid. Besides the presence of elevated levels of oxygen radicals, prostaglandins produced by neurones and microglial cells seem to play an important role in prolonged tissue damage. We investigated whether ascorbic acid alone inhibits prostaglandin E2 (PGE2) synthesis and may augment the inhibitory effect of acetylsalicylic acid on prostaglandin synthesis. Ascorbic acid dose-dependently inhibited PGE2 synthesis in lipopolysaccharide-treated primary rat microglial cells (IC50 = 3.70 µm). In combination with acetylsalicylic acid (IC50 = 1.85 µm), ascorbic acid augmented the inhibitory effect of acetylsalicylic acid on PGE2 synthesis (IC50 = 0.25 µm in combination with 100 µm ascorbic acid). Ascorbic acid alone or in combination with acetylsalicylic acid did not inhibit cyclooxygenase-2 (COX-2) protein synthesis but inhibited COX-2 enzyme activity. Our results show that ascorbic acid and acetylsalicylic acid act synergistically in inhibiting PGE2 synthesis, which may help to explain a possible protective effect of ascorbic acid in various brain diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2003.01822.x
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  • 9
    Electronic Resource
    Electronic Resource
    Serotonin via 5-HT7 receptors activates p38 mitogen-activated protein kinase and protein kinase C ɛ resulting in interleukin-6 synthesis in human U373 MG astrocytoma cells (2005)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 93 (2005), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Serotonin [5-hydroxytryptamine (5-HT)] is a widely distributed neurotransmitter which is involved in neuroimmunomodulatory processes. Previously, it has been demonstrated that 5-HT may induce interleukin (IL)-6 expression in primary rat hippocampal astrocytes. The present study was undertaken to investigate the molecular pathways underlying this induction of IL-6 synthesis. As a model system, we used the human astrocytoma cell line U373 MG, which synthesizes IL-6 upon stimulation with various inducers. 5-HT dose- and time-dependently induced IL-6 protein synthesis. We identified several 5-HT receptors to be expressed on U373 MG cells, including the 5-HT1D, 5-HT2A, 5-HT3 and 5-HT7 receptors. In this report, we show that the 5-HT-induced IL-6 release is mediated by the 5-HT7 receptor based on several agonist/antagonists that were used. 5-HT-induced IL-6 synthesis is inhibited by the partially selective 5-HT7 receptor antagonist, pimozide, and the selective antagonist SB269970. Furthermore, IL-6 synthesis was induced by the 5-HT7 receptor agonist carboxamidotryptamin. In addition, we found p38 MAPKs and protein kinase C (PKC) ɛ to be involved in 5-HT-induced IL-6 synthesis as specific inhibitors of these enzymes (SB202190 and RO-31-8425, respectively) blocked 5-HT-induced IL-6 synthesis. Furthermore, 5-HT mediated the phosphorylation of both p38 MAPK as well as the PKC ɛ isoform. The p42/44 MAPKs, however, were not involved in 5-HT-induced IL-6 synthesis. This study shows, for the first time, a central role of 5-HT7 receptor linked to p38 MAPK and PKC ɛ for the induction of cytokine synthesis in astrocytic cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.2005.03079.x
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  • 10
    Electronic Resource
    Electronic Resource
    1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline-induced apoptosis in the human neuroblastoma cell line SK-N-SH (2004)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 91 (2004), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Trichloroethylene, a common industrial solvent and a metabolic precursor of chloral hydrate, occurs widely in the environment. Chloral hydrate, which is also used as a hypnotic, has been found to condense spontaneously with tryptamine, in vivo, to give rise to a highly unpolar 1-trichloromethyl-1,2,3,4-tetrahydro-β-carboline (TaClo) that has a structural analogy to the dopaminergic neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Earlier studies have revealed the relative permeability of the molecule through the blood–brain barrier and its ability to induce Parkinson-like symptoms in rats. In this study, we report that TaClo induces an apoptotic pathway in the human neuroblastoma cell line, SK-N-SH, involving the translocation of mitochondrial cytochrome c to the cytosol and activation of caspase 3. TaClo-induced apoptosis shows considerable differences from that mediated by other Parkinson-inducing agents such as MPTP, rotenone and manganese. Although it is not clear if the clinically administered dosage of chloral hydrate or the relatively high environmental levels of trichloroethylene could lead to an onset of Parkinson's disease, the spontaneous in vivo formation of TaClo and its pro-apoptotic properties, as shown in this report, should be considered.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.2004.02710.x
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