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  • 2005-2009  (1)
  • 2000-2004  (6)
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  • 1
    Electronic Resource
    Electronic Resource
    Altered Interaction Between PSD-95 and the NMDA Receptor Following Transient Global Ischemia (2000)
    Oxford UK : Blackwell Science Ltd
    Journal of neurochemistry 74 (2000), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The postsynaptic density (PSD) is a cytoskeletal specialization involved in the anchoring of neurotransmitter receptors and in regulating the response of postsynaptic neurons to synaptic stimulation. The postsynaptic protein PSD-95 binds to NMDA receptor subunits NR2A and NR2B and to signaling molecules such as neuronal nitric oxide synthase and p135synGAP. We investigated the effects of transient cerebral ischemia on protein interactions involving PSD-95 and the NMDA receptor in the rat hippocampus. Ischemia followed by reperfusion resulted in a decrease in the solubility of the NMDA receptor and PSD-95 in 1% sodium deoxycholate, the decrease being greater in the vulnerable CA1 hippocampal subfield than in the less sensitive CA3/dentate gyrus regions. Solubilization of the kainic acid receptor GluR6/7 and the PSD-95 binding proteins, neuronal nitric oxide synthase and p135synGAP, also decreased following ischemia. The association between PSD-95 and NR2A and NR2B, as indicated by coimmunoprecipitation, was less in postischemic samples than in sham-operated controls. Ischemia also resulted in a decrease in the size of protein complexes containing PSD-95, but had only a small effect on the size distribution of complexes containing the NMDA receptor. The results indicate that molecular interactions involving PSD-95 and the NMDA receptor are modified by an ischemic challenge.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2000.0740169.x
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  • 2
    Electronic Resource
    Electronic Resource
    Increased phosphorylation of the NR1 subunit of the NMDA receptor following cerebral ischemia (2001)
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 78 (2001), S. 0 
    Details
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The effects of transient cerebral ischemia on phosphorylation of the NR1 subunit of the NMDA receptor by protein kinase C (PKC) and protein kinase A (PKA) were investigated. Adult rats received 15 min of cerebral ischemia followed by various times of recovery. Phosphorylation was examined by immunoblotting hippocampal homogenates with antibodies that recognized NR1 phosphorylated on the PKC phosphorylation sites Ser890 and Ser896, the PKA phosphorylation site Ser897, or dually phosphorylated on Ser896 and Ser897. The phosphorylation of all sites examined increased following ischemia. The increase in phosphorylation by PKC was greater than by PKA. The ischemia-induced increase in phosphorylation was predominantly associated with the population of NR1 that was insoluble in 1% deoxycholate. Enhanced phosphorylation of NR1 by PKC and PKA may contribute to alterations in NMDA receptor function in the postischemic brain.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2001.0780051179.x
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Comparison of a pasture-based system of milk production on a high rainfall, heavy-clay soil with that on a lower rainfall, free-draining soil (2004)
    Oxford, UK : Blackwell Science Ltd
    Grass and forage science 59 (2004), S. 0 
    Details
    ISSN: 1365-2494
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: The objective of this study was to compare the biological and economic efficiency of a seasonal pasture-based spring calving system of milk production on a high-rainfall, heavy-clay soil [Kilmaley (KMY)] to that on a lower-rainfall free-draining soil [Moorepark (MPN)] in Ireland. The physical performance data were obtained from a 3-year study (1998–2000) carried out at both sites. Analysis of the system of milk production at the two sites was undertaken using the Moorepark Dairy System Model. Herbage dry-matter production was greater at the MPN site with a greater proportion being produced between 1 September and 1 May. On average, over the 3 years, the system of milk production at the MPN site had a higher stocking rate (2·34 vs. 1·89 cows ha−1), higher milk production per cow (6421 vs. 5781 kg per cow), longer grazing season (250 vs. 149 d) and a higher proportion of the diet of the herd from grazed grass (0·70 vs. 0·40) than at KMY. Economic analysis showed that, in a 468 100 kg European Union milk quota scenario, the profitability at the MPN site was €28 417 greater than at the KMY site. At similar milk production per cow it was €19 138 greater. Monte Carlo simulation showed that the MPN site was stochastically dominant over the KMY site. Sensitivity analyses showed that farm profit was most sensitive to changes in milk price. The results also indicated that milk production in the future may not be sustainable economically on high-rainfall, heavy-clay soils in Ireland.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2494.2004.00415.x
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  • 4
    Electronic Resource
    Electronic Resource
    Increased phosphorylation and redistribution of NMDA receptors between synaptic lipid rafts and post-synaptic densities following transient global ischemia in the rat brain (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: Ischemia results in increased phosphorylation of NMDA receptors. To investigate the possible role of lipid rafts in this increase, lipid rafts and post-synaptic densities (PSDs) were isolated by the extraction of rat brain synaptosomes with Triton X-100 followed by sucrose density gradient centrifugation. Lipid rafts accounted for the majority of PSD-95, whereas SAP102 was predominantly located in PSDs. Between 50 and 60% of NMDA receptors were associated with lipid rafts. Greater than 85–90% of Src and Fyn were present in lipid rafts, whereas Pyk2 was mainly associated with PSDs. Lipid rafts and PSDs were isolated from animals subjected to 15 min of global ischemia followed by 6 h of recovery. Ischemia did not affect the yield, density, flotillin-1 or cholesterol content of lipid rafts. Following ischemia, the phosphorylation of NR1 by protein kinase C and tyrosine phosphorylation of NR2A and NR2B was increased in both lipid rafts and PSDs, with a greater increase in tyrosine phosphorylation occurring in the raft fraction. Following ischemia, NR1, NR2A and NR2B levels were elevated in PSDs and reduced in lipid rafts. The findings are consistent with a model involving close interaction between lipid rafts and PSDs and a role for lipid rafts in ischemia-induced signaling pathways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1471-4159.2004.03009.x
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  • 5
    Electronic Resource
    Electronic Resource
    Clinical experience of patients undergoing photodynamic therapy for Barrett's dysplasia or cancer (2004)
    Oxford, UK : Blackwell Science Ltd
    Alimentary pharmacology & therapeutics 20 (2004), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Introduction : Barrett's oesophagus is the most important risk factor in the increase in incidence of oesophageal adenocarcinoma. Photodynamic therapy using porfimer sodium is the only approved endoscopic treatment for use in patients with Barrett's high-grade dysplasia.Aim : To determine clinical characteristics, endoscopic findings and treatment complications in Barrett's high-grade dysplasia patients undergoing photodynamic therapy.Methods : We reviewed our experience using porfimer sodium photodynamic therapy to treat patients with Barrett's oesophagus and high-grade dysplasia or mucosal carcinoma. Data collected included patients characteristics, presentation symptoms, endoscopic findings, subsequent use of surveillance endoscopy and outcome after photodynamic therapy.Results : Since 1997, 102 patients with Barrett's high-grade dysplasia (69 patients) or mucosal adenocarcinoma (33 patients) have been treated with photodynamic therapy using porfimer sodium as an alternative to oesophagectomy (median series follow-up time = 1.6 years). Almost half (46%) of patients had high-grade dysplasia or carcinoma detected on their first endoscopy and the remainder (54%) were found during surveillance of known Barrett's oesophagus. Symptoms typically associated with oesophageal disease were only found in 29 of 47 (62%) patients in whom dysplasia/carcinoma was detected on the initial endoscopy – chest pain in 13 patients, dysphagia in nine patients and chronic gastro-oesophageal disease in seven patients. Comparison of endoscopic characteristics found the median Barrett's glandular segment length was significantly shorter in adenocarcinoma patients (median 3 cm; range: 1–12) vs. Barrett's high-grade dysplasia patients (median 5 cm; range: 1–16, P 〈 0.001). Overall treatment results found complete ablation of glandular epithelium with one course of photodynamic therapy in most patients (56%). Stricture requiring dilation occurred in 20 patients (20%) was the most common serious adverse event. Photodynamic therapy failed to ablate dysplasia or carcinoma in four patients and subsequent oesophagectomy was curative in three of these patients.Conclusions : Approximately 40% of newly diagnosed patients with Barrett's associated dysplasia or carcinoma had no oesophageal symptoms and had carcinoma associated with short segment (3 cm or less). Photodynamic therapy is a highly effective, safe and minimally invasive first-line treatment for patients with Barrett's dysplasia and mucosal adenocarcinoma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2036.2004.02209.x
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  • 6
    Electronic Resource
    Electronic Resource
    Inhibition of protein kinase C reduces ischemia-induced tyrosine phosphorylation of the N-methyl-d-aspartate 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 role of protein kinase C (PKC) in tyrosine phosphorylation of the N-methyl-d-aspartate receptor (NMDAR) following transient cerebral ischemia was investigated. Transient (15 min) cerebral ischemia was produced in adult rats by four-vessel occlusion and animals allowed to recover for 15 or 45 min. Following ischemia, tyrosine phosphorylation of NR2A and NR2B and activated Src-family kinases (SFKs) and Pyk2 were increased in post-synaptic densities (PSDs). Phosphorylation of NR2B on Y1472 by PSDs isolated from post-ischemic forebrains was inhibited by the SFK specific inhibitor PP2, and by the PKC inhibitors GF109203X (GF), Gö6976 and calphostin C. Intravenous injection of GF immediately following the ischemic challenge resulted in decreased phosphorylation of NR1 on PKC phosphorylation sites and reduced ischemia-induced increases in tyrosine phosphorylation of NR2A and NR2B without affecting the increase in total tyrosine phosphorylation of hippocampal proteins. Ischemia-induced increases in activated Pyk2 and SFKs in PSDs, but not the translocation of PKC, Pyk2 or Src to the PSD, were also inhibited by GF. The inactive homologue of GF, bisindolylmaleimide V, had no effect on these parameters. The results are consistent with a role for PKC in the ischemia-induced increase in tyrosine phosphorylation of the NMDAR, via a pathway involving Pyk2 and Src-family kinases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1471-4159.2003.01951.x
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  • 7
    Electronic Resource
    Electronic Resource
    Detection of preinvasive cancer cells (2000)
    [s.l.] : Macmillan Magazines Ltd.
    Nature 406 (2000), S. 35-36 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] More than 85% of all cancers originate in the epithelium that lines the internal surfaces of organs throughout the body. Although these are readily treatable provided they are diagnosed in one of the preinvasive stages, early lesions are often almost impossible to detect. Here we present a ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/35017638
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