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  • p53 gene mutation  (2)
  • 13.10.+q  (1)
  • Antidepressants  (1)
  • Cerebral Metabolism  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Influence of therapeutic and toxic doses of neuroleptics and antidepressants on energy metabolism of the isolated perfused rat brain (1973)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 279 (1973), S. 243-254 
    Details
    ISSN: 1432-1912
    Keywords: Neuroleptics ; Antidepressants ; Isolated Perfused Rat Brain ; High Energy Phosphates ; Glycolytic Pathway
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The isolated perfused rat brain was used for a comparative study of the effects of promazine, imipramine, monodesmethyl promazine and desipramine on cerebral energy metabolism. After perfusion for 30 min or 1 h the brain levels of the following substrates and metabolites were estimated: P-creatine, creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6-P, fructose diphosphate, dihydroxyacetone-P, pyruvate, lactate, α-ketoglutarate, and ammonia. Drug concentrations of 5·10−6 M and 10−5 M in the perfusion medium caused a significant decrease of glucose-6-P alone. When the drug concentration was raised to a toxic range (10−4 M), reflected in the EEG by the pattern of secondary discharges, an accumulation of P-creatine and glucose and a decrease of glycogen, glucose-6-P and ammonia occurred; the lactate/pyruvate ratios remained unchanged. As there were no qualitative differences between the effects of the investigated neuroleptics and antidepressants on cerebral metabolism, these effects might be unspecific and not correlated with the pharmacological action of the drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00500604
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    p53 gene mutations and expression of p53 and mdm2 proteins in invasive breast carcinoma (1997)
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 388-394 
    Details
    ISSN: 1432-1335
    Keywords: Key words p53 ; mdm2 ; p53 gene mutation ; Breast carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the study was to analyze p53 gene mutations and the expression of p53 and mdm2 proteins in 31 randomly selected invasive breast carcinomas. The results were then correlated with tumor grade, stage, estrogen receptor status, nodal status, and DNA ploidy. The expression of the proteins p53 and mdm2 was determined immunohistochemically using formalin-fixed, paraffin-embedded material. Screening for p53 mutation involved analysis of the highly conserved regions of the p53 gene (exons 5–9) by the polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) technique. PCR products with band shifts were directly sequenced. Immunohistochemical staining of p53 was positive in 9 cases (29.0 %), only 2 of which showed a p53 gene mutation. These were identified as a C→G transversion at the second position of codon 278 in exon 8 and an A→G transition at the second position of codon 205 in exon 6. A third case with a mutation was observed (C→T transition, position 1 of codon 250 in exon 7) that did not show p53 immunohistochemically. Of the 9 p53-positive tumors, 2 were moderately differentiated (grade II). The remaining tumors were poorly differentiated (7/9). By contrast, p53-negative carcinomas were well differentiated (grade I) in most cases (P = 0.02). DNA cytometry in 8 of the 9 p53-positive carcinomas revealed an aneuploid stem line. The majority of the p53-negative tumors were diploid (P = 0.01). Mdm2 oncoprotein was detected in 10 tumors (32.2 %), 4 of which were p53-positive, including the 3 with mutations. The grading of the mdm2-positive tumors was moderate or poor, G1 carcinomas were always noted to be mdm2-negative (P = 0.04). Overexpression of p53 protein is a complex mechanism and does not merely indicate the detection of mutations in the p53 gene. This study has shown that p53 expression correlates with tumor grade and DNA ploidy. Mdm2 expression was also associated with the tumor grade. Immunohistological demonstration of the p53 protein alone is insufficient as a basis for comment on the functional state of the p53 gene and gene product. The interrelation between recognition of the p53 protein and gene mutation needs more careful assessment to define their roles in the control of neoplasia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01240122
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    The isolated perfused rat brain as a model for studying drugs acting on the CNS (1974)
    Springer
    Psychopharmacology 35 (1974), S. 169-177 
    Details
    ISSN: 1432-2072
    Keywords: Isolated Rat Brain ; Methods ; Perfusion ; Cerebral Metabolism ; Animal EEG
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An isolated perfused brain preparation is regarded as offering some important advantages over intact animals or tissue slices for studying drug effects on the CNS. The rat is by far the most suitable laboratory animal for this technique because of low cost, ease of preparation and extensive literature available for comparative purposes. In this paper various preparation techniques and perfusion systems for an isolated rat brain are reported. Investigations are presented proving the viability of the isolated perfused rat brain for more than seven hours and its suitability for studies on cerebral metabolism. Until now this preparation has been successfully used for pharmacological investigations concerning the drug effects on cerebral energy metabolism, on the EEG and on the biogenic amines in the CNS. The results further demonstrate that the use of an isolated perfused rat brain affords the possibility of clarifying pharmacological problems which has not been possible using conventional methods. In addition, this preparation should become a very useful tool for studies on pharmacokinetics, on brain circulation or on brain oxygen consumption.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00429583
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    p53 gene mutations and expression of p53 and mdm2 proteins in invasive breast carcinoma (1997)
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 388-394 
    Details
    ISSN: 1432-1335
    Keywords: p53 ; mdm2 ; p53 gene mutation ; Breast carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the study was to analyzep53 gene mutations and the expression of p53 and mdm2 proteins in 31 randomly selected invasive breast carcinomas. The results were then correlated with tumor grade, stage, estrogen receptor status, nodal status, and DNA ploidy. The expression of the proteins p53 and mdm2 was determined immunohistochemically using formalin-fixed, paraffin-embedded material. Screening for p53 mutation involved analysis of the highly conserved regions of thep53 gene (exons 5–9) by the polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) technique. PCR products with band shifts were directly sequenced. Immunohistochemical staining of p53 was positive in 9 cases (29.0%), only 2 of which showed ap53 gene mutation. These were identified as a C→G transversion at the second position of codon 278 in exon 8 and an A→G transition at the second position of codon 205 in exon 6. A third case with a mutation was observed (C→T transition, position 1 of codon 250 in exon 7) that did not show p53 immunohistochemically. Of the 9 p53-positive tumors, 2 were moderately differentiated (grade II). The remaining tumors were poorly differentiated (7/9). By contrast, p53-negative carcinomas were well differentiated (grade I) in most cases (P=0.02). DNA cytometry in 8 of the 9 p53-positive carcinomas revealed an aneuploid stem line. The majority of the p53-negative tumors were diploid (P=0.01). Mdm2 oncoprotein was detected in 10 tumors (32.2%), 4 of which were p53-positive, including the 3 with mutations. The grading of the mdm2-positive tumors was moderate or poor, G1 carcinomas were always noted to be mdm2-negative (P=0.04). Overexpression of p53 protein is a complex mechanism and does not merely indicate the detection of mutations in thep53 gene. This study has shown that p53 expression correlates with tumor grade and DNA ploidy. Mdm2 expression was also associated with the tumor grade. Immunohistological demonstration of the p53 protein alone is insufficient as a basis for comment on the functional state of thep53 gene and gene product. The interrelation between recognition of the p53 protein and gene mutation needs more careful assessment to define their roles in the control of neoplasia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01240122
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    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Bhabha to Møller cross section ratios in the energy range 2.15–2.45 MeV (1993)
    Springer
    The European physical journal 345 (1993), S. 79-88 
    Details
    ISSN: 1434-601X
    Keywords: 12.20.Fv ; 13.10.+q ; 14.80.Pb
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract The cross sections for Bhabha and Møller scattering have been investigated in the energy range 2.1–2.4 MeV using monoenergetic positrons and electrons to search for hypothetical resonances superimposed to the continuum predicted by quantum electro dynamics. Bhabba-to-Mott, Møller-to-Mott and Møller-to-Bhabha cross section ratios were measured. The Bhabha-to-Mott ratios could be determined with statistical errors of typically 1% and remaining systematic errors not exceeding the statistical ones. No resonances in Bhabha scattering were observed. Limits for the intrinsic widths of hypothetical resonances are given. For the first time upper limits are deduced from our data for hypothetical resonances in the Møller scattering cross section in the MeV range. Additionally, Møller-to-Bhabha cross section ratios could be determined with good precision. A good agreement between the experimental and theoretical Møller-to-Bhabha ratios can be stated calling in question the recently predicted existence of series of narrow, unresolvable resonances in the Bhabha scattering cross section.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01290343
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    Paper (German National Licenses)
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