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  • 1
    ISSN: 1432-1130
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A new method has been developed for the quantification of 2-hydroxyethylated cysteine resulting as adduct in blood proteins after human exposure to ethylene oxide, by reversed-phase HPLC with fluorometric detection. The specific adduct is analysed in albumin and in globin. After isolation of albumin and globin from blood, acid hydrolysis of the protein and precolumn derivatisation of the digest with 9-fluorenylmethoxycarbonylchloride, the levels of derivatised S-hydroxyethylcysteine are analysed by RP-HPLC and fluorescence detection, with a detection limit of 8 nmol/g protein. Background levels of S-hydroxyethylcysteine were quantified in both albumin and globin, under special consideration of the glutathione transferase GSTT1 and GSTM1 polymorphisms. GSTT1 polymorphism had a marked influence on the physiological background alkylation of cysteine. While S-hydroxyethylcysteine levels in “non-conjugators” were between 15 and 50 nmol/g albumin, “low conjugators” displayed levels between 8 and 21 nmol/g albumin, and “high conjugators” did not show levels above the detection limit. The human GSTM1 polymorphism had no apparent effect on background levels of blood protein 2-hydroxyethylation.
    Type of Medium: Electronic Resource
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  • 2
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    Dortmund: Universität Dortmund, Sonderforschungsbereich 475 - Komplexitätsreduktion in Multivariaten Datenstrukturen
    Publication Date: 2018-12-07
    Description: Problem: Cigarette smoking is the most important risk factor of transitional cell carcinoma of the urinary bladder. The effect of the glutathione S- transferases M1 (GSTM1) and M3 (GSTM3) on the influence of this risk factor was investigated. Methods: A total of 293 bladder cancer patients from Dortmund and Wittenberg as well as 176 surgical patients without any malignancy from Dortmund were genotyped for GSTM1 und GSTM3 according to standard PCR/RFLP methods. Smoking habits were also qualified by a standardized interview. Results: The percentage of GSTM1 negative cases was 63 % in the entire bladder cancer patient group compared to 50 % in the control group. GSTM3*A/*A genotype was 76 % in the entire group of bladder cancer cases and 74 % in controls. Smokers and ex-smokers were overrepresented in the bladder cancer patient group. A significant association between smoking status and GSTM1 or GSTM3 genotype could not be revealed. Conclusion: The elevated percentage of GSTM1 negative bladder cancer cases shows the important effect of this polymorphic enzyme on the development of bladder cancer. In contrast to some other studies, an influence of GSTM1 on the risk due to cigarette smoking could not be observed.
    Keywords: ddc:330 ; Bladder cancer ; glutathione S-transferase M1 ; glutathione S-transferase M3 ; smoking
    Repository Name: EconStor: OA server of the German National Library of Economics - Leibniz Information Centre for Economics
    Language: English
    Type: doc-type:workingPaper
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  • 3
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    Dortmund: Universität Dortmund, Sonderforschungsbereich 475 - Komplexitätsreduktion in Multivariaten Datenstrukturen
    Publication Date: 2018-12-07
    Description: N-Acetyltransferase 2 (NAT2) genotyping may result in a considerable percentage in several ambiguous allele combinations. PHASE 2.1 is a statistical program which is designed to estimate the probability of different allele combinations. We have investigated haplotypes of 2088 subjects genotyped for NAT2 according to standard PCR/RFLP methods. In 856 out of 2088 cases the genotype was clearly defined by PCR/RFLP only. In many of the remaining cases the program clearly defined the most probable allele combination: In the case of *5A/*6C, *5B/*6A the probability for *5B/*6A is 99% whereas the alternative allele combination *5A/*6C can be neglected. Other combinations cannot be allocated with a comparable high probability. For example the allele combination *5A/*5C, *5B/*5D provides for *5A/*5C a probability of 69% whereas the estimation for *5B/*5D allele is only 31%. In the two most often observed constellations in our data [(*12A/*5B, *12C/*5C); (*12A/*6A, *12B/*6B, *4/*6C)] the probability of allele combination was ascertained as follows: *12A/*5B, 98%; *12C/*5C, 1.4% and *12A/*6A, 82%; *4/*6C, 17%; *12B/*6B, 0%. The estimation of the NAT2 haplotype is important because the assignment of the NAT2 alleles *12A, *12B or *13 as a rapid or slow genotype has been discussed controversially. Otherwise the classification of alleles in subjects which are not showing a clearly allocation can result in a rapid or slow acetylation state. This assignment has an important role in survey of bladder cancer cases in the scope of occupational exposure with aromatic amines.
    Keywords: ddc:330 ; PHASE 2.1 ; NAT2 genotyping ; single nucleotide polymorphism
    Repository Name: EconStor: OA server of the German National Library of Economics - Leibniz Information Centre for Economics
    Language: English
    Type: doc-type:workingPaper
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  • 4
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    Dortmund: Universität Dortmund, Sonderforschungsbereich 475 - Komplexitätsreduktion in Multivariaten Datenstrukturen
    Publication Date: 2018-12-07
    Description: The determination of toxicokinetic parameters is an essential component in the risk assessment of potential harmful chemicals. It is a key step to analyse the processes involved in the formation of DNA adducts which are connected with the development of chemical-induced cancer. A general problem is the extrapolation of toxicological data from experimental animals to the human organism. Therefore a valid characterisation of the relevant processes for the whole species is required, i.e., of population mean parameters instead of sets of parameters for different individuals. These, again, may vary between repeated experiments at the same or at different administered doses. Nevertheless, these differences are of great importance in obtaining a more precise insight into the variability structure of process investigated within the test animal population, so that a valid basis for further research is the final result. The theory of hierarchical models, particularly the work of Racine-Poon (1985) and Racine-Poon and Smith (1990), provides a procedure which incorporates both, modelling of the variability structure and estimation of population mean parameter vectors. The present study was designed to elucidate interindividual and interoccasion variability of toxicokinetic parameters relevant for the biological transformation of one of the basic petrochemical industrial compounds, ethylene 2 (ethene), which is also a physiological body constituent, to its metabolite, ethylene oxide, which is a proven carcinogen.
    Keywords: ddc:310 ; Ethylene ; ethylene oxide ; toxicokinetics ; population model ; repeated measurements ; EM algorithm ; interindividual variability ; interoccasion variability
    Repository Name: EconStor: OA server of the German National Library of Economics - Leibniz Information Centre for Economics
    Language: English
    Type: doc-type:workingPaper
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  • 5
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Summary A reproducible method is described for the separation and simultaneous and specific quantitation of ascorbic acid and dehydroascorbic acid by ion-pairing reversed-phase HPLC with fluorometric detection. Copper sulphate and copper acetate were compared as oxidizing reagents for ascorbic acid and 1,2-diaminobenzene dihydrochloride and 1,2-diamino-3,4-dimethylbenzene dihydrochloride as derivatising reagents. The HPLC-method was applied to human plasma. The detection limit reaches 16 ng for ascorbic acid and 3 ng for dehydroascorbic acid. Sample preparation is carried out by solid phase extraction with a recovery of 98%; it is compared with conventional precipitation of plasma proteins by metaphosphoric acid.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1618-2650
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A new method has been developed for the quantitation of methylated blood proteins in persons exposed to methylating agents. Using different derivatizing agents, 9-fluorenylmethyl chloroformate was the most suitable with regard to both sensitivity and peak separation after subsequent HPLC. After optimization of the chromatographic conditions, two groups who worked with methyl bromide and a control group of non exposed persons were compared with regard to their adduct rates (S-methylcysteine) in the two blood proteins albumin and globin. Albumin and globin were isolated from whole blood samples. After total hydrolysis of the proteins with hydrochloric acid, an amino acid analysis was performed using HPLC with precolumn fluorescent derivatization. This method enabled a quantitation of methylated cysteine in the fmol range. Background levels of S-methylcysteine (15 nmol/g protein) in both albumin and globin were found in non-exposed control persons. Levels were up to 10 fold higher in exposed fumigators working with the methylating agent methyl bromide.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0009-2851
    Keywords: Chemistry ; Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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