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An antiserum against turosteride (code name FCE 26073), a potent testosterone 5 alpha-reductase inhibitor, has been raised in rabbits by immunization with an immunogen produced by conjugation of a derivative of FCE 26073 (FCE 27424) to bovine serum albumin. The antiserum was able to distinguish FCE 26073 from its derivatives modified at the 17 beta position and from all the endogenous steroids tested. A radioimmunoassay for the determination of FCE 26073 in human plasma and urine was developed using this antiserum and tritium labeled turosteride. FCE 26073 was extracted from 50 microliters of plasma or 25 microliters of urine using ethyl-ether with a recovery greater than 90%. Using this procedure it was possible to achieve a final limit of quantitation of 142 pg/ml in plasma and 284 pg/ml in urine. The assay was validated in terms of reproducibility, accuracy and precision in the range 3.9-250 pg/50 microliters of plasma and 25 microliters of urine. The plasma concentration of FCE 26073 in a healthy male volunteer who received 0.2 mg of the drug was measured using the radioimmunoassay.

The suppressive effect of dexamethasone (Dex) on plasma cortisol and beta-lipotrophin (beta LPH) was investigated in patients with anorexia nervosa. Dex was given either orally, 1 mg at 2400 h, with blood sampling at 0800 h on the days before and after Dex, or by i.v. infusion starting at 1100 h (1 mg/h) for 4 h with sampling at 0800, 1100, 1500, 2000 and 2400 h and at 0800 h the following day. The plasma cortisol and beta LPH levels during oral or i.v. Dex administration were compared between patients and normally menstruating women of normal weight. The results showed that Dex administration depressed cortisol significantly (P less than 0.0001) during oral or i.v. infusion in most patients, without, however, suppressing it entirely as is the case in normal women. Moreover, during i.v. Dex infusion, the concentrations of cortisol escaped suppression and were higher than in normal women (less than 50 nmol/l) by 0800 h on the day following infusion. In the patients who were reinvestigated after re-feeding and weight gain (n = 9), a normal suppression of cortisol in response to i.v. Dex infusion was observed in only five cases and a slight failure to suppress, although concentrations were lower than before refeeding, was still evident in four. We concluded that, in anorexia nervosa, cortisol concentration rapidly escapes suppression by Dex administration, and that this escape is not related to the degree of starvation.

In most of our membranous glomerulonephritis (MGN) patients, we have studied the HLA-A, B, DR phenotype, the clearance of anti-D rhesus coated 51Cr-labelled autologous erythrocytes, and T-lymphocyte subpopulations with monoclonal antibodies (OKT3, T4, T8). The frequency of B8 antigen in 28 patients with MGN (five cases associated with lupus excluded) is 57.14 per cent versus 14.42 per cent in controls (Pc = 0.0002). In 26 patients the frequency of DR3 antigen is 65.38 per cent versus 20.27 per cent in controls (Pc = 0.00008). The half-life of sensitised erythrocytes is respectively 35.36 +/- 8.50 minutes in nine controls and 67.05 +/- 69.64 min in 18 patients with MGN. The half-life is significantly prolonged in one-third of the patients at time of exacerbation. The peripheral blood T-lymphocyte subsets study showed a significant decrease of OKT3 and OKT4 positive cell subsets. T4/T8 ratio is high during exacerbation of disease and diminishes in remission. Our data are consistent with a latent subtle genetic immunodeficiency, only expressed during acute phases of the disease.

In most of our patients with idiopathic membranous nephritis (MGN), we have studied the HLA-A, B, DR phenotype, the clearance of anti Rhesus D coated-51 Cr-labeled-autologous erythrocytes, and the peripheral blood T-lymphocyte subpopulations as ascertained by monoclonal antibodies (OKT3, OKT4, OKT8). The frequency of HLA-B8 antigen is 57.14% in 28 primary MGN versus 14.4% in 104 local controls (Pc less than 0.00018). The frequency of HLA-DR3 antigen is 65.38% in 26 primary MGN patients versus 20.27% in 74 local control individuals (Pc less than 0.00008). The half-life of sensitized erythrocytes is 37.30 +/- 9.55 min in 10 controls, 1963 min and 1601 min in 2 splenectomized controls, 12 min in a patient with hypersplenism, and 67.05 +/- 69.64 min in 18 idiopathic MGN patients respectively. The half-life is significantly prolonged in 6 out of 18 MGN patients. This prolongation correlates with exacerbation of the disease while normal values are obtained with remission. The OKT3 positive subpopulation (total T-lymphocytes) is 63.77 +/- 10.37% in 31 controls versus 53.74 +/- 13.81% in 22 MGN (P less than 0.002). The OKT4 positive subpopulation (helper T-cells) is 37.90 +/- 8.21% in controls versus 32.79 +/- 10.89% in MGN (P less than 0.03). The OKT8 positive subpopulation (suppressor T-cells) is 21.60 +/- 5.28% versus 20.03 +/- 5.76% respectively. The OKT4/OKT8 ratio is 1.85 +/- 0.58 in controls versus 1.74 +/- 0.69 in MGN. During exacerbation, the T-lymphocyte subset fractions are normal, whereas OKT3 and OKT4 are decreased during remission. MGN is a strongly HLA-linked disease.(ABSTRACT TRUNCATED AT 250 WORDS)