[Estriol therapy of the menopause and in the post-menopausal period].
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Biomedical subjects
Publications and source records attributed to R Hooghe.
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We examined the cultured mouse melanoma cell line B16 (clone F1) and its wheat germ agglutinin-resistant variant Wa4 that suffers from abnormal protein glycosylation (a high fucose:sialic acid ratio in glycoproteins). In both cell lines the adenylate cyclase system was endowed with a functional guanine nucleotide binding protein Gs and was efficiently coupled to alpha-MSH receptors. In the B16 cell line F1 studied we also observed an efficient stimulation of adenylate cyclase activity by helodermin, VIP and the VIP analogue [acetyl-His1]VIP, and also by PGE1. In membranes from the lectin-resistant variant Wa4, the stimulations by VIP-like peptides and by PGE1 were reduced by 60% and 50%, respectively, while the stimulation by alpha-MSH remained normal. As other components of the adenylate cyclase system (Gs site, catalytical unit) appeared unchanged in the Wa4 variant, we conclude that impaired glycosylation essentially affected the number of both VIP-like peptide receptors and PGE1 receptors.
Two municipal waste incinerators in the vicinity of a residential area close to the city of Antwerp caused concern to local habitants. Risk assessment was performed combining chemical, toxicological measurements and model calculations. As the first step in risk assessment an inventory was made of historic emissions from both incinerators with emphasis on dioxins. The operational atmospheric transport and deposition model for priority substances (OPS) was used to calculate the deposition of dioxins in the vicinity of incinerators. The observed soil contamination pattern did not correspond to the calculated deposition pattern, indicating that other sources may contribute at least partly to the local PCDD/PCDF contamination of the area. Dioxin exposure of people in the Neerlandquarter as a function of the food consumption behavior was calculated using a mathematical model (VLIER-HUMAAN) combined with transfer factors. According to the results of these calculations, just residing in the impact area does not result in a meaningful risk. Only if locally produced food was consumed (milk, meat and vegetables), exposure in the Neerlandquarter was enhanced compared to the average dioxin exposure estimated for the Flemish population. Exposure in 1997 was below the exposure in 1980. As a consequence of different eating habits and lower bodyweight, children are subjected to significantly higher exposure than adults. Adverse health outcomes from dioxin exposure in the past cannot be excluded. There was no evidence for enhanced exposure to genotoxicants based on a comparison of chromosomal damage to blood cells of children from the study area to those from a control group.
The time course of recovery of beta-adrenergic and VIP/helodermin receptors after homologous and heterologous down regulation was studied in the murine lymphoma cell line BL/VL3, a neoplastic equivalent of immature T cells. The heterologous part of isoproterenol down regulation was rapidly reversed, even in the presence of cycloheximide, suggesting that down regulation was linked to ligand-receptor interaction and/or cyclic AMP increase. Homologous down regulations of beta-adrenoceptors and VIP/helodermin receptors were less rapidly reversible and depended on protein synthesis as they were inhibited by cycloheximide: beta-adrenoceptors recovered faster than VIP/helodermin receptors.
A low-metastatic, glycosylation-defective variant of the B16 murine melanoma was obtained by Tao and Burger (1977) through selection with wheat germ agglutinin. We found that variant and parental (wild-type) cell lines were equally invasive when confronted with precultured embryonic chick heart fragments in vitro. Also, a short-term in vivo arrest assay showed no significant differences. After intravenous injection, wild-type cells killed the recipient mice faster than did the variant cells. We were able to confirm the changes in glycosylation at the enzyme level. In addition, we showed that the pattern of endogenous lectins was strikingly different, at least at the quantitative level. We also looked at another set of receptor proteins, namely receptors for neurotransmitters coupled to adenylate cyclase. The response to the vasoactive intestinal peptide and prostaglandins was lower in the variant cells, which also had a delayed response to cholera toxin. Although most of the data can be explained by altered glycosylation in the variant cells, the large number of differences between variant and parent cells makes it difficult to identify the biochemical basis of altered metastatic behaviour. This might also be the case with other pairs of cells differing in metastatic activity.
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