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  • Blackwell Science Ltd  (29)
  • 2000-2004  (23)
  • 1995-1999  (6)
  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The paired helical filament (PHF), which makes up the major fibrous component of the neurofibrillary lesions of Alzheimer's disease, is composed of hyperphosphorylated and abnormally phosphorylated microtubule-associated protein τ. Previous studies have identified serine and threonine residues phosphorylated in PHF-τ and have shown that τ can be phosphorylated at several of these sites by proline-directed protein kinases and cyclic AMP-dependent protein kinase. Here we have investigated which protein phosphatase activities can dephosphorylate recombinant τ phosphorylated with mitogen-activated protein kinase, glycogen synthase kinase-3β, neuronal cdc2-like kinase, or cyclic AMP-dependent protein kinase. We show that protein phosphatase 2A is by far the major protein phosphatase activity in brain that dephosphorylates τ phosphorylated in this manner.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The effect of selective inhibition of monoamine oxidase (MAO) subtypes A and B on striatal metabolism of DOPA to dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), and 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid; HVA) was studied in halothane-anesthetized rats 3 weeks after unilateral 6-hydroxydopamine lesion of the substantia nigra. Implantation of bilateral microdialysis probes allowed simultaneous quantitation of metabolite production on lesioned and control sides. The DOPA was administered as a 15-min bolus of 1 mM solution in the striatal microdialysate. Rats were pretreated with the selective MAO-A inhibitor clorgyline, or the selective MAO-B inhibitors deprenyl or TVP-101 [2,3-dihydro-N-2-propynyl-1H-inden-1-amine-(1R)-hydrochloride]. Intrastriatal infusion of DOPA caused an increased efflux of DA, DOPAC, and HVA, which was greater on the intact side. Clorgyline, but not deprenyl or TVP-101, increased post-DOPA DA efflux on both intact and lesioned sides. Clorgyline also caused a marked suppression of post-DOPA DOPAC and HVA effluxes, whereas only mild effects were produced by the MAO-B inhibitors. There was no evidence for a differential effect of MAO-B inhibition on efflux of DA or metabolites in the lesioned as compared with the control striatum. The results indicate a major role for MAO-A in DA metabolism both intra- and extraneuronally in the rat striatum.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Neurofilament (NF) protein [high molecular mass (NF-H)] is extensively phosphorylated in vivo. The phosphorylation occurs mainly in its characteristic KSP (Lys-Ser-Pro) repeat motifs. There are two major types of KSP motifs in the NF-H tail domain: KSPXKX and KSPXXX. Recent studies by two different laboratories have demonstrated the presence of a cdc2-like kinase [cyclin-dependent kinase-5 (cdk5)] in nervous tissue that selectively phosphorylates KSPXKX and XS/TXK motifs in NF-H and lysine-rich histone (H1). This article describes the identification of phosphatases dephosphorylating three different substrates: histone (H1), NF-H in a NF preparation, and a bacterially expressed C-terminal tail domain of NF-H, each containing KSPXKX repeats phosphorylated in vitro by cdk5. Among various phosphatases identified, protein phosphatase (PP) 2A from rabbit skeletal muscle appeared to be the most effective phosphatase in in vitro assays. Three phosphatase activity peaks—P1, P2, and P3—were partially purified from frozen rat spinal cord by ion exchange and size exclusion column chromatography and then characterized on the basis of biochemical, pharmacological, and immunochemical studies. One of the three peaks was identified as PP2A, whereas the others were mixtures of both PP2A and PP1. These three peaks could dephosphorylate cdk5-phosphorylated 32P-histone (H1), 32P-NF-H in the NF preparation, and 32P-NF-H tail fusion protein. These studies suggest the involvement of PP2A or a PP2A-like activity in the regulation of the phosphorylation state of KSPXKX motifs in NF-H.
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  • 4
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Mitochondria are recognized as modulators of neuronal viability during ischemia, hypoxia and toxic chemical exposure, wherein mitochondria dysfunction leading to ATP depletion may be a common pathway of cell death. Estrogens have been reported to be neuroprotective and proposed to play a role in the modulation of cerebral energy/glucose metabolism. To address the involvement of 17β-estradiol preservation of mitochondrial function, we examined various markers of mitochondrial activity in human SK-N-SH neuroblastoma cells exposed to 3-nitroproprionic acid (3-NPA), a succinate dehydrogenase inhibitor which uncouples oxidative phosphorylation. 3-NPA (10 mm) significantly increased ATP levels at 2 h then caused a 40% and a 50% decrease in ATP levels from baseline when treated for 12 h and 24 h, respectively. 3-NPA also induced significant increases in levels of cellular hydrogen peroxide and peroxynitrite at 2 h and a 60% decrease in mitochondrial membrane potential (MMP) at 12 h exposure. 17β-Estradiol (17β-E2) pretreatment restored the ATP level back to 80% at 12 h of that in control cells treated with 3-NPA but without E2, blunted the effect of 3-NPA on MMP and reactive oxygen species levels. The present study indicates that 17β-E2 can preserve mitochondrial function in the face of inhibition of oxidative phosphorylation.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Clinical and experimental dermatology 29 (2004), S. 0 
    ISSN: 1365-2230
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A previously undescribed missense mutation was detected in the L12 domain of keratin 5 (K5) in a Chinese family with Weber–Cockayne epidermolysis bullosa simplex. Direct sequencing of the PCR products identified a single base substitution (983A→G) that changes the aspartic acid residue at codon 328 to glycine in all affected family members, while no mutation was observed either in the healthy individual or 50 unrelated control samples. Asp328 of K5 is remarkably conserved among all type II keratins. D328G is the fourth mutation found to affect this residue in K5-related epidermolysis bullosa simplex, indicating the importance of Asp328 for K5 structure and the dramatic effect that fine changes can have on keratin intermediate filament integrity.
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of soil science 52 (2001), S. 0 
    ISSN: 1365-2389
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Geosciences , Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Summary Methods  of determining exchangeable K+ of soil by mixing extracting solutions and analysing the soil suspension with ion-selective electrodes were developed and evaluated on 30 samples of soils. From preliminary comparisons of the K+ extracted by BaCl2 and NH4OAc solutions and by batch and leaching treatments of soils, we established that suspensions of 5 g soil in 100 ml 0.5 m BaCl2 and single batch treatments of 1 h should be used. The exchangeable K+ was determined with a K-selective, valinomycin-based PVC membrane electrode and electrochemical cells that did or did not include a liquid junction (the reference electrode being a double-junction reference electrode assembly with a 10 m LiOAc salt bridge solution or a Cl-selective electrode, respectively). The Ba-exchangeable K+ values were sensibly the same whether a liquid junction was involved or not, a result that can be attributed to the beneficial effects of the salt bridge and the ionic strength of the extractant. Comparisons of these Ba-exchangeable results with those obtained by various combinations of batch or leaching treatments, BaCl2 or NH4OAc extractants and filtrate analysis by the ion-selective electrode method or atomic absorption spectrometry showed they were all highly correlated (r≥ 0.996). The selectivity of the K+-selective electrode (kpotKNH4 = 0.004) significantly reduced the interference from indigenous soil NH4+ in the BaCl2 suspensions. Overall, the results show potentiometric measurements of K+ in soil suspensions can provide a simple, rapid, and reliable means of determining exchangeable K+ in soils.
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  • 7
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In a randomised prospective cross-over study, we compared the effects of desflurane and isoflurane on arterial oxygenation, heart rate and mean arterial pressure during one-lung anaesthesia. Thirty patients scheduled for oesophagogastrectomy were randomly assigned to one of two groups. One group of 15 patients received desflurane to an end-tidal concentration of 6% in oxygen from induction until the end of 30 min of open chest one-lung ventilation in the lateral position. This was followed by isoflurane to an end-tidal concentration of 1.1% in oxygen for the next 30 min of one-lung ventilation. The other group of 15 patients received the two anaesthetic agents in the reverse order. We found no significant difference in arterial oxygenation, heart rate or mean arterial pressure between the two inhalational agents. In the subgroup of 10 patients with pulmonary artery catheters, we found no significant differences in mixed venous saturation, derived shunt or cardiac output. We conclude that during one-lung ventilation, the choice between desflurane and isoflurane does not significantly influence arterial oxygenation.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford : Blackwell Science Ltd
    Anaesthesia 54 (1999), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Anaesthesia 58 (2003), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The aim of this study was to investigate the pharmacokinetics of sevoflurane uptake into the brain and body by comparing sevoflurane concentrations in internal jugular-bulb blood (Jsev), arterial blood (Asev) and pulmonary arterial blood (PAsev) over a fixed inspired sevoflurane concentration. Ten patients (aged 51–73 years), undergoing coronary artery bypass grafting surgery were enrolled in this study. They were anaesthetised using a constant 3.5% inspired sevoflurane concentration (CIsev) during the first hour of anaesthesia. During constant volume-controlled ventilation, we measured CIsev and end-tidal sevoflurane (CEsev) using infrared analysis. The sevoflurane concentration in the blood was analysed using gas chromatography, and cardiac output was measured using an Opti-Q pulmonary artery catheter. We found that it took 40 min for the brain concentration to equilibrate with arterial blood (Asev). Both CIsev–CEsev and Asev–PAsev gradients persisted during the study period. There was no further uptake of sevoflurane into the brain after 40 min; however, there was near-constant uptake into the body.
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  • 10
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Current immunosuppressive strategies are aimed at abrogating the allospecific T-cell response against donor tissues or organs. However, little information is yet available on the potential influences of these drugs on innate immune responses. In order to address this, we have employed a whole blood model. Human whole blood was pretreated with sirolimus, cyclosporine A or tacrolimus in therapeutic as well as supra therapeutic doses, and subsequently stimulated with lipopolysaccharide (LPS), peptidoglycan (PepG) or lipoteichoic acid (LTA). Plasma cytokine analyses revealed a potent inhibitory effect of sirolimus on interleukin(IL)-10 production induced by all bacterial products tested. In contrast, cyclosporine A and tacrolimus inhibited the tumour necrosis factor (TNF)-α production in response to LPS, but not to PepG and LTA. Using a quantitative mRNA analyses, we also observed that sirolimus significantly decreased the IL-10 mRNA accumulation to sub-basal levels in peripheral blood mononuclear cells (PBMC). This suggests that the sirolimus inhibits IL-10 production by interfering with the IL-10 gene transcription. However, the molecular mechanism of this inhibition remains unclear. Based on the present study and observations by others, we postulate that the clinical use of the sirolimus may be associated with a dysregulated innate immune response to bacterial infection and thus an increased risk of hyperinflammation and sepsis.
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