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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 66 (1996), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Exposure of cerebellar granule cells to NMDA in culture at 5 days in vitro, when cells are not yet vulnerable to NMDA, evoked a pronounced reduction in NMDA receptor activity, measured by NMDA-induced 45Ca2+ influx, and counteracted the normal developmental increase in NMDA receptors. The effect was concentration and time dependent, the half-maximal effect being reached at about 45 µM and by 4–5 h. The decrease in NMDA receptor function was accompanied by a significant reduction in the protein level of the obligatory NMDA receptor subunit (NR) NR1. Both parameters remained at a low level as long as the agonist was present. However, receptor down-regulation was reversible, as receptor protein levels and NMDA responses were restored to control values upon NMDA removal, this process requiring protein synthesis. NMDA treatment also elicited a decrease in NR1, NR2A, and NR2B subunit messenger RNA (mRNA) levels. However, in comparison with NMDA receptor proteins, the decrease was faster, and NMDA receptor mRNA content recovered to control levels within 24 h in spite of the presence of NMDA. Concerning the mechanisms of agonist-induced regulation of NMDA receptor expression, it seems that protein kinase C-mediated protein phosphorylation is not involved, whereas inhibition of Ca2+/calmodulin-dependent kinase II/IV by KN-62 does depress NMDA receptor expression even in the absence of NMDA.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 66 (1996), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The regional and developmental expression of NMDA receptors containing the NR2D subunit was analyzed on the level of the subunit mRNA and protein in rat brain. RNase protection experiments indicated that among two proposed splice variants of the NR2D subunit, only the NR2D-2 subunit is expressed. The regional distribution of the NR2D subunit protein was visualized with a newly developed NR2D-2 subunit-specific antiserum on brain sections using the histoblot technique. In adult brain, NR2D immunoreactivity was mainly restricted to diencephalic, mesencephalic, and brainstem structures. During postnatal development, the NR2D subunit was detected transiently in certain regions, such as the ventro-basal complex of the thalamus, hippocampus, inferior colliculus, and brainstem reticular formation, suggesting that NR2D subunit-containing receptors play a role in these brain areas only during development. The level of NR2D subunit mRNA and protein decreased during late postnatal development. However, significant levels of NR2D subunit mRNA and protein were present in adulthood, in particular, in the globus pallidus, thalamus, subthalamic nuclei, and superior colliculus. These results indicate a functional relevance for NMDA receptors containing the NR2D subunit in the developing and adult brain, although its expression in the adult brain is less prominent and restricted to a few brain areas.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The influence of K+-induced membrane depolarization and NMDA treatment on the regulation of NMDA receptor subunit (NR) expression was investigated during the development of granule cells in culture, as a follow-up of previous work on NMDA receptor activity. In spite of the increase in NMDA receptor activity elicited by these treatments (K25 or K10 + NMDA cultures), the main developmental changes in receptor mRNA levels were similar to those in untreated cells (K10) (a threefold increase in total NMDA receptor mRNA, quantitative dominance of NR1 mRNA, late expression of NR2C, and virtual absence of NR2D). However, high K+ and NMDA treatment resulted in a greater increase of NR2A mRNA levels and a retardation in the developmental changes in the relative amounts of NR2B and NR2C mRNAs. The correspondence between NMDA receptor activity and the amount of NR1 and NR2A subunit proteins was excellent, the rank order being K25 〉 K10 + NMDA 〉 K10 at 9 days in vitro. Because the increase in subunit mRNA was not always paralleled by an increase in subunit protein, the control of NMDA receptor expression involves critically, in addition to gene transcription, regulation of translational and/or posttranslational events.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 86 (1987), S. 5141-5145 
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: X-ray diffraction measurements have been performed on glasses of the AgX–Ag2O–B2O3 (X=Br,Cl) systems. The only meaningful structural detail of the radial distribution functions is due to Ag–X interactions. The mean numbers of Ag–X contacts has been obtained through analysis of the high-angle partial structure functions si(s), calculated by subtracting experimental structure function of the Ag2O–B2O3 glasses from that of the corresponding AgX–doped glasses. Calculations have been also performed for AgI–Ag2O–B2O3 glasses, and comparison between the results from systems containing different halides is made. The average number of Ag–X contacts is very similar in samples at equimolar composition, thus suggesting a close structural feature in AgX–doped glasses.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Anaesthesia 49 (1994), S. 0 
    ISSN: 1365-2044
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: A patient with Dupuytren 's diathesis experienced a prolonged sensory and motor block following epidural anaesthesia. It was postulated that this occurred secondary to fibrous changes within the epidural space.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    International journal of immunogenetics 17 (1990), S. 0 
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The CCGG and GCGC sites of the human HLA-DRα gene are hypermethylated in human tissues (including B-lymphocytes, T-lymphocytes, muscle, brain, sperm, skin, kidney, suprarenal and mammary glands) and three B-lymphoid cell lines. Therefore, the HLA-DRα gene can be transcribed even though extensively methylated. The only exception to the hypermethylated state of the HLA-DRα gene is represented by one or both of the two HhaI sites (H1 and H2) localized in the 5’portion of the gene. Analysis of the computer-generated secondary structure of the HLA-DRα mRNA suggests that the H1 and H2 sites belong to a region (5′-GAGCGCCCA-3′/5′-UGAGCGCUC-3′) exhibiting extensive base pairing. Therefore, unmethylation of these CG sites can contribute in preventing mCG→TG/CA changes in this region, which would lead to extensive alterations of the secondary structure of the 5’portion of the HLA-DRα MRNA.On the other hand, the selective pressure to maintain unaltered the methylated CG dinucleotides in the coding regions of the HLA-DRα gene could be due to codon restrictions, since the majority of the methylation-related CG→TG or CG→CA variations would generate aminoacid changes.Accordingly, the analysis of different HLA-DRα genomic sequences indicates that variations of the CpG dinucleotides occur only in the non-coding portions of the HLA-DRα gene.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 39 (1994), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Binding characteristics of a monovalenl bispecific monoclonal antibody (bsMoAb), which recognizes both epidermal growth factor receptor (EGF-R) and drug doxorubicin (DXR) were compared with those of the parental bivalent MoAb directed against the EGF-R binding site. Scatchard analysis indicated that both MoAbs bound to EGF-R-overexpressing A431 cells with the same affinity. In tracer amounts, both MoAbs also displayed the same capacity to be internalized after binding to the cell surface. However, when the MoAbs were used at saturating concentrations, down-modulation of the receptor was greater with the bivalent MoAb. The bivalent MoAb also inhibited proliferation of A431 cells both in vitro and in vivo whereas the bsMoAb was inhibitory only in vivo. These data suggest that MoAb bivalency is required for EGF-R down-modulation and in vitro cell growth inhibition.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    The @journal of physical chemistry 〈Washington, DC〉 95 (1991), S. 1690-1693 
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1365-2516
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary.  The provision of health care to patients with haemophilia through replacement of the deficient coagulation factor is the result of a complex interaction between patients, physicians and policy makers, each carrying their individual sets of preferences. Preferences of patients, physicians and pharmacists towards perceived viral safety, risk of inhibitor development, infusion frequency during prophylaxis, pharmaceutical dosage form, distribution modes and price were evaluated by conjoint analysis, using a discrete choice experiment. Overall 178 patients’, 69 physicians and 58 pharmacists completed the study. Patients, physicians and pharmacists displayed preferences: (i) similar in direction and strength for risk of inhibitors and frequency of prophylaxis, (ii) similar in direction, but not in strength for perceived viral safety and price, with patients showing lower strength compared with physicians and pharmacists, and (iii) dissimilar in direction and/or strength for: (i) dosage form, which tested important only for pharmacists and (ii) distribution mode, which tested important for patients and physicians only. Our study provides evidence of the differences between different stakeholders in the preferences towards haemophilia replacement therapy, indicating that different opinions should be taken into account when planning optimal care.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    European journal of neuroscience 7 (1995), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In contrast to the acute toxic effect of NMDA on mature cerebellar granule cells, chronic treatment with NMDA (140 μM from 1 to 9 days in vitro) did not compromise cell survival. Such treatment markedly suppressed NMDA receptor activity: at 8 days in vitro NMDA-induced 45Ca2+ influx was reduced by -60% and acute exposure to NMDA (highest concentration tested, 1 mM) at 9 days in vitro did not cause detectable toxicity. The reduction in NMDA receptor activity was accompanied by a significant decrease (±80% at 9 days in vitro) in the level of the NR1 and the NR2A NMDA receptor subunit protein, detected using the selective photoaffinity ligand [125I]CGP55802A. It seems, therefore, that the agonist-induced decrease in NMDA receptor activity is due to receptor down-regulation. In contrast to the marked influence of chronic NMDA exposure on the cellular content of the NMDA receptor subunit proteins, mRNA levels of the different subunits (NR1, NR2A, NR2B and NR2C) were not significantly affected. It seems, therefore, that agonist-induced down-regulation of the NMDA receptor involves critically mRNA translation and/or post-translational regulation.
    Type of Medium: Electronic Resource
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