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  • High-Energy Phosphates  (3)
  • Breast carcinoma  (2)
  • 6-Aminonicotinamide  (1)
  • Cerebral Metabolism  (1)
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Material
Years
Keywords
  • 1
    Electronic Resource
    Electronic Resource
    Comparative study of the effects of chloral hydrate and trichloroethanol on cerebral metabolism (1973)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 277 (1973), S. 323-332 
    Details
    ISSN: 1432-1912
    Keywords: Chloral Hydrate ; Trichloroethanol ; 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 chloral hydrate and trichloroethanol on cerebral energy metabolism. After a perfusion period of 30 min the brain levels of the following substrates and metabolites were measured spectrophotometrically: P-creatine, creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6-P, fructose diphosphate, α-glycero-P, dihydroxyacetone-P, pyruvate, lactate, glutamate, α-ketoglutarate and ammonia. Furthermore, the concentration of chloral hydrate and trichloroethanol in the isolated brain and in the perfusion medium was measured colorimetrically. Little more than 10% of chloral hydrate in the isolated brain and in the perfusion medium were reduced to trichloroethanol. In intact animals there were about 70% of chloral hydrate transformed. Chloral hydrate and trichloroethanol caused an accumulation of P-creatine, no change in the lactate/pyruvate ratio, an increase of the glucose concentration and a decrease of glucose-6-P level in the isolated brain. The rise of brain glucose level was more pronounced after trichloroethanol than after chloral hydrate. The effects of chloral hydrate and trichloroethanol on brain glucose and glucose-6-P levels suggest an inhibition of brain hexokinase activity by these drugs.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00500993
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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)
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  • 3
    Electronic Resource
    Electronic Resource
    The effects of increased glucose supply and thiopental anesthesia on energy metabolism of the isolated perfused rat brain (1975)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 289 (1975), S. 399-407 
    Details
    ISSN: 1432-1912
    Keywords: Isolated Perfused Rat Brain ; High-Energy Phosphates ; Glycolytic Pathway ; Thiopental
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of glucose concentrations in the perfusion medium ranging from 5 to 15 mM and thiopental, on cerebral energy metabolism were studied using the isolated perfused rat brain. After a perfusion time of 30 min brain levels of the following substrates and metabolites were determined: P-creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6-P, fructose-6-P, pyruvate, lactate, α-ketoglytarate, glutamate, ammonia. In control experiments increasing the glucose concentration in the perfusion medium produced an increase of intracellular brain glucose concentration only, revealing a linear relationship between glucose content in brain and blood. Neither high-energy phosphates nor glycolytic intermediates were markedly affected by the changes in blood glucose. With an anesthetic dose of thiopental (0.15 mM) in the perfusion medium identical metabolic alterations occurred in all experiments: P-creatine and glucose were significantly increased whereas ADP, AMP, lactate and pyruvate were diminished. Also with thiopental brain glucose was linearly related with the glucose concentration in the perfusion medium. The calculated regression line was apparently parallel with that from control experiments; that means thiopental always caused an elevation of brain glucose by the same amount of 0.9 μmoles/g—irrespective of the initial cerebral glucose content. The results yield further evidence that glucose transport is not the rate-limiting step in glycolysis. The action of thiopental on glycolytic pathway is discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00508413
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    Paper (German National Licenses)
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  • 4
    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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  • 5
    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
  • 6
    Electronic Resource
    Electronic Resource
    Suitability of the isolated perfused rat brain for studying effects on cerebral metabolism (1972)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 275 (1972), S. 124-134 
    Details
    ISSN: 1432-1912
    Keywords: Isolated Perfused Rat Brain ; High-Energy Phosphates ; Glycolytic Pathway ; Phenobarbital ; Ischemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The concentrations of P-creatine, creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6-P, fructose diphosphate, dihydroxyacetone-P, α-glycero-P, lactate and pyruvate were measured in the isolated perfused rat brain as well as in rat brain in vivo. Similar levels were observed in the isolated brain and in intact animals, and the values measured were in good accordance with those described in the literature. Only the pyruvate and lactate content were significantly higher in the isolated brain but the lactate/pyruvate ratio remained unchanged. An anesthetic or ischemia caused just the same effects on energy metabolism of the isolated rat brain as described for intact animals. Thus, 1.5 mM phenobarbital in the perfusion medium produced a statistically significant increase in P-creatine and glucose levels as well as a decrease of pyruvate, lactate and α-glycero-P levels. After ischemia of the isolated brain the concentrations of high-energy phosphates, glycogen, glucose, and pyruvate fell considerably concomitantly with significant accumulations of creatine, AMP, α-glycero-P and lactate. The results indicate that the isolated perfused rat brain may be a useful tool for studying cerebral metabolism.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00508901
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    Paper (German National Licenses)
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  • 7
    Electronic Resource
    Electronic Resource
    Decreased glycolytic flux rate in the isolated perfused rat brain after pretreatment with 6-aminonicotinamide (1975)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 290 (1975), S. 323-327 
    Details
    ISSN: 1432-1912
    Keywords: 6-Aminonicotinamide ; Glycolytic Pathway ; Isolated Perfused Rat Brain
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cerebral energy metabolism was studied in the isolated perfused rat brain after 6-aminonicotinamide (6-AN; 35 mg/kg i.p.) administered to the intact animals 7 hrs before perfusion was started. The metabolic alterations in the isolated rat brains were such as reported for rat and mouse brain in vivo: Inhibition of 6-phosphogluconate dehydrogenase was followed by an accumulation of 6-phosphogluconate, leading to a decreased activity of glucosephosphate isomerase. This was reflected by increased levels of glucose and glucose 6-phosphate and decreased levels of fructose 6-phosphate, pyruvate and lactate. Since the concentration of lactate in the perfusate of the isolated brain was also lowered, 6-AN must have reduced the glycolytic flux rate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00510561
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    Paper (German National Licenses)
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