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Biomedical subjects

R Kroes

Publications and source records attributed to R Kroes.

At least 91 records · Page 5Linked to original sources

Demonstration of the role of prostate-specific antigen in semen liquefaction by two-dimensional electrophoresis.

Two-dimensional protein profiles of human semen, prostatic fluid, and seminal vesicle fluid were compared to demonstrate changes in the protein composition of human semen before and after liquefaction. Semen specimens were obtained from a volunteer. Prostatic fluid specimens were collected by rectal massage from patients visiting a urology clinic. Samples of seminal vesicle fluid were collected by needle aspiration from isolated seminal vesicles, which were removed at surgery. All specimens were prepared and processed according to the ISO-DALT system for separation of proteins in two-dimensional gels. Following electrophoresis, protein spots in the gels were visualized by silver staining. Prostatic fluid and seminal vesicle fluid showed their characteristic protein profiles. The protein profile of human semen contained specific proteins of both prostatic fluid and seminal vesicle fluid. One major group of proteins in seminal vesicle fluid (Mw 28,000-68,000 daltons), designated as seminal vesicle-specific antigen, was observed in freshly ejaculated human semen, but disappeared from the two-dimensional profile when the ejaculate was allowed to stand at room temperature for 30 min. When prostatic fluid or prostate-specific antigen was mixed with seminal vesicle fluid and incubated at 37C for 30 min, the seminal vesicle-specific antigen also disappeared from the two-dimensional profiles. The findings indicate that seminal vesicle-specific antigen, a group of predominant proteins in seminal vesicle fluid, is the structural component of seminal coagulum, and that prostate-specific antigen is the enzyme which digests seminal vesicle-specific antigen and liquifies semen coagulum.

Adult↗

Forestomach carcinogens: possible mechanisms of action.

A brief review indicates that a considerable number of compounds induce forestomach tumours in different species. Naturally occurring forestomach tumours are rare (an incidence of less than 1%) in rats and mice, but they do occur in hamsters with incidences up to 12%. Most forestomach carcinogens are known to be genotoxic, although a few non-genotoxic substances are also able to induce this type of tumour. The promoting and inhibiting action of substances in a two-stage forestomach tumour model is described. Morphologically the development of tumours is characterized by early lesions such as epithelial damage, hyperplasia and hyperkeratosis, which at a later stage progress to strong diffuse hyperplasia, dysplasia, papilloma and squamous-cell carcinoma. Possible mechanisms of action of non-genotoxic forestomach carcinogens are described, and the relevance to man is discussed. Since humans have no squamous epithelium in the stomach, the potential risk from non-genotoxic forestomach carcinogens involves exposure of the mouth, pharynx and oesophagus at dose levels that exert irritating action. It seems very unlikely that exposure to concentrations far below those having irritating potential is hazardous to man.

Animals↗

Assessment of intake from the diet.

Exposure assessment is one of the key parts of the risk assessment process. Only intake of toxicologically significant amounts can lead to adverse health effects even for a relatively toxic substance. In the case of chemicals in foods this is based on three major aspects: (i) how to determine quantitatively the presence of a chemical in individual foods and diets, including its fate during the processes within the food production chain; (ii) how to determine the consumption patterns of the individual foods containing the relevant chemicals; (iii) how to integrate both the likelihood of consumers eating large amounts of the given foods and of the relevant chemical being present in these foods at high levels. The techniques used for the evaluation of these three aspects have been critically reviewed in this paper to determine those areas where the current approaches provide a solid basis for assessments and those areas where improvements are needed or desirable. For those latter areas, options for improvements are being suggested, including, for example, the development of a pan-European food composition database, activities to understand better effects of processing on individual food chemicals, harmonisation of food consumption survey methods with the option of a regular pan-European survey, evaluation of probabilistic models and the development of models to assess exposure to food allergens. In all three areas, the limitations of the approaches currently used lead to uncertainties which can either cause an over- or underestimation of real intakes and thus risks. Given these imprecisions, risk assessors tend to build in additional uncertainty factors to avoid health-relevant underestimates. This is partly done by using screening methods designed to look for "worst case" situations. Such worse case assumptions lead to intake estimates that are higher than reality. These screening methods are used to screen all those chemicals with a safe intake distribution. For chemicals with a potential risk, more information is needed to allow more refined screening or even the most accurate estimation. More information and more refined methods however, require more resources. The ultimate aims are: (1) to obtain appropriate estimations for the presence and quantity of a given chemical in a food and in the diet in general; (2) to assess the consumption patterns for the foods containing these substances, including especially those parts of the population with high consumption and thus potentially high intakes; and (3) to develop and apply tools to predict reliably the likelihood of high end consumption with the presence of high levels of the relevant substances. It has thus been demonstrated that a tiered approach at all three steps can be helpful to optimise the use of the available resources: if relatively crude tools - designed to provide a "worst case" estimate - do not suggest a toxicologically significant exposure (or a relevant deficit of a particular nutrient) it may not be necessary to use more sophisticated tools. These will be needed if initially high intakes are indicated for at least parts of the population. Existing pragmatic approaches are a first crude step to model food chemical intake. It is recommended to extend, refine and validate this approach in the near future. This has to result in a cost-effective exposure assessment system to be used for existing and potential categories of chemicals. This system of knowledge (with information on sensitivities, accuracy, etc.) will guide future data collection.

Animals↗