Michelle Nijs

Cross-border reproductive care in Belgium

BACKGROUNDnCross-border reproductive care indicates the cross-border movements made by patients to obtain infertility treatment they cannot obtain at home. The problem at present is that empirical data on the extent of the phenomenon are lacking. This article presents the data on infertility patients going to Belgium for treatment.nnnMETHODSnA survey was conducted among the centres for reproductive medicine that are allowed to handle oocytes and create embryos (B-centres). Data were collected on the nationality of patients and the type of treatment for which they attended during the period 2000-2007.nnnRESULTSnSixteen of 18 centres responded to the questionnaire. The flow of foreign patients has stabilized since 2006 at approximately 2100 patients per year. The majority of foreign nationals seeking treatment in Belgium were French women for sperm donation. The next highest group was patients entering the country to obtain ICSI with ejaculated sperm.nnnCONCLUSIONSnThere are clear indications that numerous movements are motivated by the wish to evade legal restrictions in ones home country, either because the technology is prohibited or because the patients have characteristics, which exclude them from treatment in their own countries.

Steroid receptors in the human prostate: 1. Estradiol — 17β binding in benign prostatic hypertrophy

Agar gel electrophoresis and ultracentrifugation on continuous sucrose gradients revealed the presence of a 4S estradiol receptor in cytosols of samples of human benign hyperplastic prostate tissue. High affinity (charcoal stability) and saturability (disappearance with excess competitor) binding characteristics of the molecular species concerned facilitated its clear distinction from similarly migrating serum albumin-steroid complexes. Our data, obtained with human serum, purified human albumin and albumin-enriched cytosol strongly suggest that agar gel electrophoresis, when used alone, may lack specificity for the quantification of estrogen receptors. Radioligand binding to these molecules may be obscured by similarly migrating albumin-steroid complexes which fail to dissociate during electrophoresis. We advocate the inclusion of competitor experiments to improve the specificity of the method.

Steroid receptors in the human prostate. 2. Some properties of the estrophilic molecule of benign prostatic hypertrophy.

Abstract Some physicochemical properties of the estrophilic ‘receptor’ of human benign prostatic hypertrophy were examined by agar gel electrophoresis. 1) Competition analyses revealed the high selectivity of the molecule for the naturally occurring estrogens but not for representatives of other classes of steroid hormones (androgens, corticosteroids, progesterone). This, coupled with the failure of an estrogen ‘receptor’-rich extract to exhibit detectable tissue specific binding of ( 3 H) 5α-dihydrotestosterone suggests that prostatic androgen and estrogen receptors may have separate identities. 2) The molecule proved highly resistant to enzyme attack, a stability conferred by estradiol-17β rather than by the thiol reagent dithiothreitol. Its proteinaceous nature was finally demonstrated when extract was exposed to enzymes at 0°C prior to steroid addition. 3) Initial complex formation between estrogen and its ‘receptor’ protein was rapid and reached a plateau after 4 hours. Binding was greater at 0°C than 37°C.

Steroid receptors in the human prostate. Detection of tissue-specific androgen binding in prostate cancer

We have searched for tissue-specific binding of 5alpha-androstan-17beta-ol-3-one (5alpha-dihydrotestosterone; 5alpha-DHT) in cytosols prepared from 25 surgically obtained benign prostatic hypertrophy (BPH) samples and in 3 tissue specimens containing prostate cancer cells. The distinction between steroid-receptor complexes and ligand binding to serum sex hormone-binding globulin (SHBG) was facilitated by combination experiments involving both sucrose gradient ultracentrifugation and agar gel electrophoresis. Gradient analysis of a cytosol prepared from a cervical lymph node (CLN) containing metastatic prostate tissue, revealed both 8-S and 4-S forms of high affinity (charcoal stable) 5alpha-[3H]DHT binding. When electrophoresis was performed on gradient fractions from these zones, anodally migrating steroid-receptor complexes were found only in the 8-S peak, the 4-S region containing radioligand bound to cathodally directed SHBG. In similar experiments with two BPH samples heavily invaded with prostate cancer cells only a single 4-S peak of radioligand binding was detected. Its multicomponent nature was uncovered electrophoretically when, in addition to SHBG, saturable, androgen binding molecules appeared anodally. Their incomplete resolution from SHBG on a gradient might have prevented their identification had this been the only method used. In contrast to the cancer-containing tissues, no saturable 5alpha-[3H]-DHT binding, other than that to SHBG, was detected in any of the BPH samples analysed. It is considered that, of the methods currently available, agar gel electrophoresis may be particularly useful for further investigations into the possible multicomponent nature of androgen binding of tissue origin in the human prostate.

Direct fibrinogenolytic and fibrinolytic activity in the human prostate

Abstract Previous work had demonstrated a direct proteolytic activity of human prostatic extract on a substrate of casein but not of fibrinogen or fibrin. In the experiments reported here, with a substrate of fibrin or fibrinogen having a higher concentration and specific activity than in previous experiments, it became possible to demonstrate such a direct proteolytic activity on these substrates. In addition, the presence of a trypsin and plasmin inhibitor in prostatic extract could be demonstrated. By ammonium sulphate fractionation, a fraction can be separated from the extract, containing the factor responsible for the direct proteolytic activity and the inhibitor.

Characterization of two direct fibrinogenolytic activities and of one proteolytic inhibitor activity in the human prostate

Abstract The gel filtration of a fraction prepared by precipitation of a crude extract of human benign hyperplastic prostate tissue resulted in two separated peaks of direct proteolytic activity (DPA1 and DPA2) devoid of any kinase or plasminogen activator activity. A third peak showing proteolytic inhibitory activity (PIf) was also obtained. DPA1 was active on fibrinogen as well as on casein, although the proteolysis of fibrinogen was limited as shown by the electrophoretic pattern of breakdown products. This peak had an esterase activity on p-tosyl-Larginine methyl ester (TAME) but not on L-lysine methyl ester (LME). DPA2 was devoid of esterase activity and was much more active on fibrinogen than on casein, releasing large fragments of fibrinogen. DPA1 and DPA2 appeared to be different from plasmin, to have an active serine center and not to be dependent on thiol groups for their activity. Their possible role in the pathogenesis of the hemorrhagic diathesis associated with some prostatic disorders should be envisaged. Although the human prostate crude extract contained an antiplasmin and an antitrypsin activity, PIf was ineffective against plasmin and did not inhibit either one of the two DPAs. PIf had identical antigenic determinants as plasma α 1 -antitrypsin