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  • 11
    Digitale Medien
    Digitale Medien
    Family study of genetic and environmental factors determining the protein binding of propranolol (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 437-441 
    Details
    ISSN: 1432-1041
    Schlagwort(e): propranolol ; protein binding ; genetic factors ; environmental factors ; plasma orosomucoid ; plasma albumin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The unbound fraction of propranolol was found to vary from 1.9 to 13.2% in 434 plasma samples from members of 132 families. As expected, there was a linear correlation between the ratio of bound/unbound propranolol and the orosomucoid concentration (r=0.67, P〈0.001). Albumin concentration did not influence propranolol binding. The unbound fraction was negatively correlated with obesity and alcohol intake, but was not significantly influenced by age and sex. By applying path analysis, 21% of the variability in propranolol binding could be ascribed to genetic factors and 5% to common environmental factors.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00542107
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  • 12
    Digitale Medien
    Digitale Medien
    Polymorphic 2-hydroxylation of desipramine (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 445-450 
    Details
    ISSN: 1432-1041
    Schlagwort(e): Desipramine ; Genetic polymorphism ; cytochrome P450 ; debrisoquine ; drug metabolism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary We have studied desipramine hydroxylation capacity, determined as the metabolic ratio of desipramine to 2-hydroxydesipramine in the urine after a single oral dose of 10 mg of desipramine, in 340 Swedish Caucasians, including the members of 45 two-generation families. Desipramine metabolic ratios were bimodally distributed among 237 unrelated subjects and 8% were poor metabolizers. There was a strong correlation between the metabolic ratios for desipramine and debrisoquine in 337 subjects phenotyped with both drugs and there was no dissociation between their capacities to hydroxylate desipramine and debrisoquine. Complex segregation analysis in the 45 families gave evidence for a major locus with incomplete recessivity (d=0.14) controlling the 2-hydroxylation of desipramine. Simila results were obtained in segregation analysis for debrisoquine. There was evidence for linkage between the CYP2D6 gene and the gene regulating the hydroxylation of desipramine and debrisoquine. This study has provided unequivocal evidence that the capacity to 2-hydroxylate desipramine is polymorphic and under similar genetic control to the hydroxylation of debrisoquine.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00315541
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  • 13
    Digitale Medien
    Digitale Medien
    Changes in the incidence of Down syndrome in Sweden during 1968–1982 (1986)
    Springer
    Human genetics 〈Berlin〉 72 (1986), S. 133-139 
    Details
    ISSN: 1432-1203
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Notizen: Summary A continuous increase in the incidence of Down syndrome in Sweden was noted during 1979–1981. This increase mainly occurred among children of younger mothers and was more pronounced for hte males than for the females. There was no evidence of a significant seasonal variation, increased frequency of prematurely born children, or decrease in the number of cases aborted after prenatal diagnosis. An analysis of the whole 15-year period indicates that the incidence of Down syndrome has increased slowly in both sexes, and that there might have been a superimposed cyclic variation limited to the males.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00283931
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  • 14
    Digitale Medien
    Digitale Medien
    Severity of mutation in the phenylalanine hydroxylase gene influences phenylalanine metabolism in phenylketonuria and hyperphenylalaninaemia heterozygotes (1994)
    Springer
    Journal of inherited metabolic disease 17 (1994), S. 215-222 
    Details
    ISSN: 1573-2665
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary We examined whether the degree of residual activity from the mutant phenylalanine hydroxylase (PAH) allele affected phenylalanine metabolism in heterozygotes for phenylketonuria (PKU) or non-PKU hyperphenylalaninaemia (HPA). Discriminant analysis was carried out to find the function of fasting plasma concentrations of phenylalanine (PHE) and tyrosine (TYR) that best separated carriers from non-carriers. This function (0.103TYR −0.214PHECORR −4.499) was subsequently used as the dependent variable, with thein vitro activity of the expressed mutant PAH as the independent variable, in a regression analysis performed on heterozygotes for mutations that had been studied in a eukaryotic cell expression system. This analysis showed a significant correlation (r=0.40,n=140,p〈0.001), although there was a wide spread of values within each of the two major groups of carriers and a considerable overlap between the groups. We conclude that the severity of the mutation, as determined byin vitro expression analysis, in the mutant PAH gene is reflected in the biochemical phenotype of heterozygotes. This result emphasizes the relevance of the cell expression system used for establishing the relative severities of most mutations at the PAH locus. Differences in the activities from the carried mutant PAH allele on phenylalanine metabolism in heterozygotes are, however, small compared to the activity from the normal PAH allele and are easily obscured by other factors leading to inter- or intra-individual variation in phenylalanine metabolism. Fasting plasma concentrations of phenylalanine and tyrosine thus can not be used to predict the severity of the carried PAH mutation in individual PKU or HPA heterozygotes.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00711621
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