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Biomedical subjects

I Kaufmann

Publications and source records attributed to I Kaufmann.

10 recordsLinked to original sources
PubMed1987

7-Ethoxyresorufin-O-deethylase activity in human hair roots: a potential marker for toxifying species of cytochrome P-450 isozymes.

Assay systems for the evaluation of carcinogen interaction with human tissues are essential for assessing cancer risk. Human hair roots (HHR) are a readily obtainable epithelial tissue source that have been employed for investigating inherited enzyme activities. In this study HHR were found to possess cytochrome P-450-dependent 7-ethoxyresorufin-O-deethylase (ERD) activity which measures cytochrome P-450 isoenzymes that are highly specific (in the order of greater than 95%) markers for the metabolic activation of many environmental carcinogenic substances such as the polycyclic aromatic hydrocarbons (PAHs). Topical application of PAHs (in liquor carbonis detergens) to the scalp of human volunteers was found to enhance the activity of this enzyme in freshly plucked hair roots. Oral and topical administration of ketoconazole to the same subjects resulted in an appreciable (up to 73%) inhibition of detectable enzyme activity. Our data suggest that measurement of ERD in HHR may be a useful marker for the study of toxifying species of cytochrome P-450 isozymes in human populations.

Carcinogens↗
PubMed1987

Modulation of melanoma-associated antigens by monoclonal antibodies as visualized by radioimmunoelectron microscopy and radioantibody binding assay.

There is a wealth of information about monoclonal antibody (MAb) specificity and function on fixed tissues, yet little is known about formation and release of antigen-antibody complexes and their functional behavior in vivo. We analyzed the pathway of radiolabeled MAbs directed against melanoma-associated antigens by radioimmunoelectron microscopy (RIEM) on metabolically active cells of the melanoma cell lines SK-MEL-28, MeWo and Colo 38 at different time intervals. In parallel, binding and release of MAbs were investigated by the radioantibody binding assay (RBA). Both procedures gave essentially concordant results. Preferentially stable binding of immune complexes (ICs) to the cell surface after 30 and 120 min was shown for the MAb L10. Internalization was demonstrated for the MAb M.2.9.4. At the ultrastructural level, direct evidence of this phenomenon was obtained by visualization of radioactivity within the cytoplasm after 120 min. In the RBA this process was indicated by resistance of bound MAbs to acid buffer desorption. RIEM pointed to different transport mechanisms: constitutive internalization by endocytotic vesicles, or receptor-mediated endocytosis by coated vesicles. Shedding was indicated for the MAb R24 by release of the ICs from the cell membrane. It was demonstrated that stable fixation of ICs on the cell surface or modulation by internalization led to high accumulation rates, while shedding of antigen-antibody complexes resulted in a low accumulation of the MAb in tumor cells. Assuming that the potential of MAbs for clinical application is determined by the biological behavior of antigen-antibody complexes, these methods are suitable for demonstration of antigenic modulation by MAbs and eventually enable us to predict the localization, penetration and distribution pattern of individual MAbs in the melanoma patient.

Antibodies, Monoclonal↗
PubMed1987

[Development of cancer (vulvar cancer) in the Netherton syndrome (ichthyosis, hair anomalies, atopic diathesis)].

So far there has been only one incidence of a malignant tumour associated with Netherton's syndrome, a rare skin disease consisting of congenital ichthyosiform erythroderma, atopic dermatitis and trichorrhexis nodosa (bamboo hair). The aetiology and clinical consequences are discussed on the occasion of a carcinoma of the vulva occurring in a case of a patient with Netherton's syndrome, both phenomena being interlinked.

Biopsy↗
PubMed1987

Human hair follicle benzo[a]pyrene and benzo[a]pyrene 7,8-diol metabolism: effect of exposure to a coal tar-containing shampoo.

Assay systems for the evaluation of carcinogen interaction with human tissues are essential for assessing cancer risk. Hair follicles are a readily available source of human epithelial tissue and offer an excellent system with which to study carcinogen metabolism in human populations. In this study freshly plucked human hair follicles were employed to measure the metabolism of benzo[a]pyrene (BP), benzo[a]pyrene-7,8-diol (BP 7,8-diol), and the enzyme-mediated binding of [3H]-BP to DNA. The effect of human exposure to a crude coal tar (CCT)-containing shampoo, a preparation rich in polycyclic aromatic hydrocarbons (PAHs), on these parameters was also evaluated. Twelve healthy volunteers were studied before and after shampooing their hair daily for 4 days with the CCT-containing shampoo. Wide interindividual variation was observed in basal cytochrome P-450-dependent aryl hydrocarbon hydroxylase (AHH) activity which ranged from 0.6-17.6 fmol water-soluble BP metabolites/h/hair follicle (mean +/- SE of 32 individuals was 9.7 +/- 0.9). After use of the shampoo for 4 days AHH activity increased in 10 of the 12 volunteers (50-148%) and enhancement of enzyme-mediated binding of BP to DNA was detected in most subjects. Hair follicles were shown to convert BP to several metabolic species including BP 7,8-diol, a major precursor of the ultimate carcinogenic metabolite of BP. Benzo[a]pyrene-7,8-diol itself was also metabolized by the human hair follicles in this system. Clotrimazole, a known inhibitor of the metabolism of BP as well as the carcinogenicity of the hydrocarbon in rodent skin, was found to inhibit AHH and the in vitro metabolism of BP and BP 7,8-diol in human hair follicles. Oral administration of a similar antifungal imidazole, ketoconazole at a dose of 200 mg daily for 5 days, to healthy volunteers also resulted in greater than 90% inhibition of hair follicle AHH activity. These studies indicate that hair follicles represent an accessible tissue suitable for assessing the extent of PAH carcinogen metabolism in human subjects. Furthermore, enzyme activity critical to cancer induction by PAHs was shown to be inducible following the use of a CCT-containing shampoo. This carcinogen-activating enzyme system was substantially inhibited by imidazole compounds, suggesting that they may prove effective as anticarcinogens in human populations.

Aryl Hydrocarbon Hydroxylases↗
PubMed1977

Genetics of carbon catabolite repression in Saccharomycess cerevisiae: genes involved in the derepression process.

A recessive mutant cat1-1, wild type CAT1, was isolated in Saccharomyces cerevisiae. It did not grow on glycerol nor ferment maltose even with fully constitutive, glucose resistant maltase synthesis. It prevented derepression of isocitrate lyase, fructose-1,6-diphosphatase and maltase in a constitutive but glucose sensitive maltase mutant. Derepression of malate dehydrogenase was retarded and slowed down. Sucrose fermentation and invertase synthesis was not affected. Respiration was normal. From this mutant, two reverse mutants were isolated. One was recessive, acted as a suppressor of cat1-1 and was called cat2-1, wild type CAT2; the other was dominant and allelic to CAT1 and designated CAT1-2d and cat2-1 caused an earlier derepression of enzymes studied but did not affect the repressed nor the fully derepressed enzyme levels. CAT1-2d and cat2-1 did not show any additive effects. It is proposed that carbon catabolite repression acts in two ways. The direct way represses synthesis of sensitive enzymes, during growth on repressing carbon sources whereas the other way regulates the derepression process. After alleviation of carbon catabolite repression, gene CAT1 becomes active and prevents the activity of CAT2 which functions as a repressor of sensitive enzyme synthesis. The CAT2 gene product has to be eliminated before derepression can actually occur. The time required for this causes a delay in derepression after the depletion of a repressible carbon source. cat1-1 cannot block CAT2 activity and therefore, derepression is blocked. cat2-1 is inactive and derepression can start after carbon catabolite repression has ceased. CAT1-2d permanently active as a repressor of CAT2 and eliminates the delay in derepression.

Carbon↗