Diagnostic yield of chromosomal microarray analysis in fetuses with isolated increased nuchal translucency: a French multicenter study.

OBJECTIVE: To determine the frequency and nature of copy number variants (CNVs) identified by chromosomal microarray analysis (CMA) in a large cohort of fetuses with isolated increased nuchal translucency thickness (NT) ≥ 3.5 mm. METHODS: This was a retrospective, multicenter study, including 11 French hospitals, of data from the period between April 2012 and December 2015. In total, 720 fetuses were analyzed by rapid aneuploidy test and the fetuses identified as euploid underwent CMA. CNVs detected were evaluated for clinical significance and classified into five groups: pathogenic CNVs; benign CNVs; CNVs predisposing to neurodevelopmental disorders; variants of uncertain significance (VOUS); and CNVs not related to the phenotype (i.e. incidental findings). RESULTS: In 121 (16.8%) fetuses, an aneuploidy involving chromosome 13, 18 or 21 was detected by rapid aneuploidy test and the remaining 599 fetuses were euploid. Among these, 53 (8.8%) had a CNV detected by CMA: 16/599 (2.7%) were considered to be pathogenic, including 11/599 (1.8%) that were cryptic (not visible by karyotyping); 7/599 (1.2%) were CNVs predisposing to neurodevelopmental disorders; and 8/599 (1.3%) were VOUS. Additionally, there was one (0.2%) CNV that was unrelated to the reason for referral diagnosis (i.e. an incidental finding) and the remaining 21 were benign CNVs, without clinical consequence. Interestingly, we identified five genomic imbalances of the 1q21.1 or 15q11.2 regions known to be associated with congenital heart defects. CONCLUSION: Our study demonstrates the benefit of CMA in the etiological diagnosis of fetuses with isolated increased NT. It is worth noting that most (69%) of the detected pathogenic CNVs were cryptic. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Risk of falls and bleeding in elderly patients with acute venous thromboembolism.

OBJECTIVE: Whether or not a high risk of falls increases the risk of bleeding in patients receiving anticoagulants remains a matter of debate. METHODS: We conducted a prospective cohort study involving 991 patients ≥ 65 years of age who received anticoagulants for acute venous thromboembolism (VTE) at nine Swiss hospitals between September 2009 and September 2012. The study outcomes were as follows: the time to a first major episode of bleeding; and clinically relevant nonmajor bleeding. We determined the associations between the risk of falls and the time to a first episode of bleeding using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. RESULTS: Four hundred fifty-eight of 991 patients (46%) were at high risk of falls. The mean duration of follow-up was 16.7 months. Patients at high risk of falls had a higher incidence of major bleeding (9.6 vs. 6.6 events/100 patient-years; P = 0.05) and a significantly higher incidence of clinically relevant nonmajor bleeding (16.7 vs. 8.3 events/100 patient-years; P < 0.001) than patients at low risk of falls. After adjustment, a high risk of falls was associated with clinically relevant nonmajor bleeding [subhazard ratio (SHR) = 1.74, 95% confidence interval (CI) = 1.23-2.46], but not with major bleeding (SHR = 1.24, 95% CI = 0.83-1.86). CONCLUSION: In elderly patients who receive anticoagulants because of VTE, a high risk of falls is significantly associated with clinically relevant nonmajor bleeding, but not with major bleeding. Whether or not a high risk of falls is a reason against providing anticoagulation beyond 3 months should be based on patient preferences and the risk of VTE recurrence.

[Dengue virus: viral targets and antiviral drugs]. / Le virus de la dengue : cibles virales et antiviraux.

This work reviews the opportunities and scientific bases in the development of anti-dengue drugs. The timeliness of anti-dengue drug development is addressed in the context of the growing impact of dengueworldwide and existing strategies to fight the virus. The antiviral approach in therapy or prophylaxis during an epidemic as well as the impact of recent technological advances in drug-discovery and antiviral chemotherapy on the development of anti-dengue drugs are discussed. An analysis of current sources of synthetic or natural drugs is provided. Finally, we summarize the current knowledge on dengue virus proteins, which are currently considered the most viable as drug targets, as the envelop protein E and non-structural proteins NS3 and NS5 carrying protease, helicase, RNA triphosphatase, methyltransferase and RNA-dependent RNA polymerase activities. Other viral proteins proposed to be part of the replication complex and the complex itself are considered as potential targets of anti-dengue drugs. State-of-the-art methods are listed, that are expected to allow the discovery, design, and characterisation of anti-dengue drugs effective against the four serotypes.

Omega-3 fatty acids predict recurrent venous thromboembolism or total mortality in elderly patients with acute venous thromboembolism.

Essentials The role of omega-3 fatty acids (n-3 FAs) in recurrent venous thromboembolism (VTE) is unknown. Association of n-3 FAs with recurrent VTE or total mortality was investigated in 826 patients. Whole blood n-3 FAs were inversely correlated with recurrent VTE or total mortality. Major and non-major bleeding was not increased in patients with higher levels of n-3 FAs. SUMMARY: Background The role of omega-3 fatty acids (n-3 FAs) in recurrent venous thromboembolism (VTE) remains unknown. Objectives To investigate the association of n-3 FAs with recurrent VTE or total mortality at 6 months and 3 years. Methods N-3 FAs were assessed in 826 patients aged ≥ 65 years, categorized into low, medium and high based on the 25th and 75th percentile. Mean follow-up was 29 months. Results At 6 months, subjects with medium (adjusted hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.22-0.62) and high n-3 FA levels (adjusted HR, 0.36; 95% CI, 0.20-0.67) were less likely to develop recurrent VTE or total mortality, compared with those with low n-3 FAs. At 3 years, medium levels (adjusted HR, 0.67; 95% CI, 0.47-0.96) were associated with lower risk of recurrent VTE or total mortality. As compared with low n-3 FAs, the adjusted sub-hazard ratio [SHR] of recurrent VTE was 0.39 (95% CI, 0.15-0.99) in patients with medium and 0.17 (95% CI, 0.03-0.82) in patients with high n-3 FAs. The cumulative incidence of recurrent VTE was lower in the medium and high n-3 FA groups as compared with the low n-3 FA groups, but seems to have worn off after 3 years. The incidence of major and non-major bleeding was not greater in the high n-3 FA group. Conclusion Higher levels of n-3 FAs were associated with a lower risk of recurrent VTE or total mortality in elderly patients with VTE, but not with greater bleeding risk.

Crystal structure of maltose phosphorylase from Lactobacillus brevis: unexpected evolutionary relationship with glucoamylases.

BACKGROUND: Maltose phosphorylase (MP) is a dimeric enzyme that catalyzes the conversion of maltose and inorganic phosphate into beta-D-glucose-1-phosphate and glucose without requiring any cofactors, such as pyridoxal phosphate. The enzyme is part of operons that are involved in maltose/malto-oligosaccharide metabolism. Maltose phosphorylases have been classified in family 65 of the glycoside hydrolases. No structure is available for any member of this family. RESULTS: We report here the 2.15 A resolution crystal structure of the MP from Lactobacillus brevis in complex with the cosubstrate phosphate. This represents the first structure of a disaccharide phosphorylase. The structure consists of an N-terminal complex beta sandwich domain, a helical linker, an (alpha/alpha)6 barrel catalytic domain, and a C-terminal beta sheet domain. The (alpha/alpha)6 barrel has an unexpected strong structural and functional analogy with the catalytic domain of glucoamylase from Aspergillus awamori. The only conserved glutamate of MP (Glu487) superposes onto the catalytic residue Glu179 of glucoamylase and likely represents the general acid catalyst. The phosphate ion is bound in a pocket facing the carboxylate of Glu487 and is ideally positioned for nucleophilic attack of the anomeric carbon atom. This site is occupied by the catalytic base carboxylate in glucoamylase. CONCLUSIONS: These observations strongly suggest that maltose phosphorylase has evolved from glucoamylase. MP has probably conserved one carboxylate group for acid catalysis and has exchanged the catalytic base for a phosphate binding pocket. The relative positions of the acid catalytic group and the bound phosphate are compatible with a direct-attack mechanism of a glycosidic bond by phosphate, in accordance with inversion of configuration at the anomeric carbon as observed for this enzyme.

Association between thyroid dysfunction and venous thromboembolism in the elderly: a prospective cohort study.

BACKGROUND: Venous thromboembolism (VTE) and subclinical thyroid dysfunction (SCTD) are both common in elderly patients. SCTD has been related to a hypercoagulable state and an increased thromboembolic risk. However, prospective data on the relationship between SCTD and VTE are lacking. OBJECTIVES: To investigate the relationship between SCTD and recurrent VTE (rVTE), all-cause mortality, and thrombophilic biomarkers. Patients Elderly patients with VTE were studied. METHODS: In a prospective multicenter cohort, thyroid hormones and thrombophilic biomarkers were measured 1 year after acute VTE, as both may be influenced by acute thrombosis. We defined subclinical hypothyroidism (SHypo) as elevated thyroid-stimulating hormone (TSH) levels (4.50-19.99 mIU L(-1) ), and subclinical hyperthyroidism (SHyper) as TSH levels of < 0.45 mIU L(-1) , both with normal free thyroxine levels. Outcomes were incidence of rVTE and overall mortality during follow-up starting after the 1-year blood sampling. RESULTS: Of 561 participants (58% with anticoagulation), 6% had SHypo and 5% had SHyper. After 20.8 months of mean follow-up, 9% developed rVTE and 10% died. The rVTE incidence rate was 7.2 (95% confidence interval [CI] 2.7-19.2) per 100 patient-years in SHypo participants, 0.0 (95% CI 0.0-7.6) in SHyper participants, and 5.9 (95% CI 4.4-7.8) in euthyroid participants. In multivariate analyses, the sub-hazard ratio for rVTE was 0.00 (95% CI 0.00-0.58) in SHyper participants and 1.50 (95% CI 0.52-4.34) in SHypo participants as compared with euthyroid participants, without increased levels of thrombophilic biomarkers. SHyper (hazard ratio [HR] 0.80, 95% CI 0.23-2.81) and SHypo (HR 0.99, 95% CI 0.30-3.29) were not associated with mortality. CONCLUSION: In elderly patients, SHyper may be associated with lower rVTE risks. SHypo showed a non-statistically significant pattern of an association with rVTE, without increased mortality or differences in thrombophilic biomarkers.

Crystal structure of the catalytic subunit of human protein phosphatase 1 and its complex with tungstate.

Protein phosphatase 1 (PP1) is a serine/threonine protein phosphatase that is essential in regulating diverse cellular processes. Here we report the crystal structure of the catalytic subunit of human PP1 gamma 1 and its complex with tungstate at 2.5 A resolution. The anomalous scattering from tungstate was used in a multiple wavelength anomalous dispersion experiment to derive crystallographic phase information. The protein adopts a single domain with a novel fold, distinct from that of the protein tyrosine phosphatases. A di-nuclear ion centre consisting of Mn2+ and Fe2+ is situated at the catalytic site that binds the phosphate moiety of the substrate. Proton-induced X-ray emission spectroscopy was used to identify the nature of the ions bound to the enzyme. The structural data indicate that dephosphorylation is catalysed in a single step by a metal-activated water molecule. This contrasts with other phosphatases, including protein tyrosine phosphatases, acid and alkaline phosphatases which form phosphoryl-enzyme intermediates. The structure of PP1 provides insight into the molecular mechanism for substrate recognition, enzyme regulation and inhibition of this enzyme by toxins and tumour promoters and a basis for understanding the expanding family of related phosphatases which include PP2A and PP2B (calcineurin).

Crystallization of pancreatic procolipase and of its complex with pancreatic lipase.

The human pancreatic lipase-porcine procolipase complex has been crystallized in space group P3(2)21 (a = b = 80.3 A and c = 251 A) from a solution containing polyethylene glycol, NaCl and beta-octyl glucoside. The crystals diffract to 2.6 A on a synchrotron beam. The complex in the presence of bile salts and phospholipids crystallizes in a tetragonal space group P4(2)2(1)2 (a = b = 133.4 A, c = 92.6 A). Crystals of procolipase alone were obtained under slightly different experimental conditions (space group I432, a = b = c = 164.3 A).

[Multicenter evaluation of four homogenous LDL-cholesterol assays]. / Evaluation multicentrique de quatre méthodes de dosage direct du cholestérol-LDL.

International guidelines emphasize the importance of LDL cholesterol (LDL-C) assay in the care and follow-up of patients with cardiovascular risk. Most studies and common practice use Friedewald's formula for LDL-C calculation. The accuracy of the result depends closely on the precision of the input parameters (total cholesterol, triglycerides (TG) and HDL cholesterol), and discrepancies between calculated LDL-C and measurement by reference methods appear when TG exceed 4.5 mmol/L, or in the presence of abnormal lipoproteins. These restrictions and uncertainties in calculations have prompted the recent development of direct and homogeneous methods that fit all analyzers. A multicenter evaluation of four direct assays of LDL-C (Daiichi, Denka Seiken, Kyowa, Wako) was carried out on 45 serum samples (TG below 3.1 mmol/L) in eight laboratories using different analyzers. For three methods (Daiichi, Kyowa, Wako), the interlaboratory reproducibility was markedly improved relative to that of calculation. A strong correlation was found for all new methods when compared with a beta-quantification assay. Average bias in Denka Seiken assays was greater than Kyowa's and Daiichi's (although less dispersed for the latter) and for Wako all bias were positive. The relationship between bias variations and the lipid parameters of the samples was studied. Three methods, Daiichi, Kyowa and Wako, revealed a significant positive correlation between bias and serum VLDL-C/TG ratio, clearly indicating that cholesterol enrichment of VLDL was a source of variability in these assays. Specificity of the four methods was tested in situation of dyslipidemia by spiking isolated lipoproteins (chylomicrons, VLDL and HDL). This experiment revealed differences in behavior, most evidently upon addition of VLDL. No method was truly specific, but up to 8 mmol/L of TG the variations were acceptable. In the presence of type III hyperlipoproteinemia, however, only the Denka Seiken method was reliable. Linearity up to 20 mmol/L (Daiichi, Denka Seiken) or 14 mmol/L (Kyowa, Wako) of LDL-C allows these tests to be used in main routine cases. New direct assays are an obvious technological advance in terms of analytical performance and conveniency. Their use for the diagnosis and follow-up of hyperlipidemic patients offers an alternative that overcomes the limitations of the Friedewald calculation.

Test-retest reliability of pain extent and pain location using a novel method for pain drawing analysis.

BACKGROUND: Pain drawings (PDs) are an important component of the assessment of a patient with pain. The aim of this work is to present the test-retest reliability of a novel method of quantifying the extent and location of pain. Additionally, the association between PD variables and clinical features in patients with chronic neck pain (CNP) and chronic low back pain (CLBP) was explored. METHODS: Fifty-one patients with CLBP and 56 patients with CNP participated. Each patient shaded two consecutive PDs using a digital tablet. Software was developed to quantify the pain extent, to analyse the pain overlap between PDs and to produce pain frequency maps. Correlations were obtained between pain extent and clinical features including the level of pain intensity, disability, and psychological distress and cognitive function. RESULTS: The intraclass correlation coefficients for pain extent in CLBP and CNP were very high: 0.97 (95% CI: 0.95-0.98) and 0.92 (95% CI: 0.87-0.98), respectively. The Bland Altman showed a mean difference close to zero: 5.4% pixels in CNP group and 3% pixels in the CLBP group. Significant correlations were observed between pain extent and pain intensity in CLBP and CNP and pain extent and disability in CNP. There was no relation between pain extent and the level of distress or cognitive function. CONCLUSIONS: A novel method for the acquisition of PD was presented. Test-retest reliability of reporting pain extent and pain location was supported in people with CNP and CLBP. Future research is needed to establish psychometric properties of PD.

Physical activity and risk of bleeding in elderly patients taking anticoagulants.

BACKGROUND: Although the possibility of bleeding during anticoagulant treatment may limit patients from taking part in physical activity, the association between physical activity and anticoagulation-related bleeding is uncertain. OBJECTIVES: To determine whether physical activity is associated with bleeding in elderly patients taking anticoagulants. PATIENTS/METHODS: In a prospective multicenter cohort study of 988 patients aged ≥ 65 years receiving anticoagulants for venous thromboembolism, we assessed patients' self-reported physical activity level. The primary outcome was the time to a first major bleeding, defined as fatal bleeding, symptomatic bleeding in a critical site, or bleeding causing a fall in hemoglobin or leading to transfusions. The secondary outcome was the time to a first clinically relevant non-major bleeding. We examined the association between physical activity level and time to a first bleeding by using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. RESULTS: During a mean follow-up of 22 months, patients with a low, moderate, and high physical activity level had an incidence of major bleeding of 11.6, 6.3, and 3.1 events per 100 patient-years and an incidence of clinically relevant non-major bleeding of 14.0, 10.3, and 7.7 events per 100 patient-years, respectively. A high physical activity level was significantly associated with a lower risk of major bleeding (adjusted sub-hazard ratio 0.40, 95% confidence interval 0.22-0.72). There was no association between physical activity and non-major bleeding. CONCLUSIONS: A high level of physical activity is associated with a decreased risk of major bleeding in elderly patients receiving anticoagulant therapy.

Crystallographic study of the structure of colipase and of the interaction with pancreatic lipase.

Colipase (Mr 10 kDa) confers catalytic activity to pancreatic lipase under physiological conditions (high bile salt concentrations). Previously determined 3-A-resolution X-ray structures of lipase-colipase complexes have shown that, in the absence of substrate, colipase binds to the noncatalytic C-terminal domain of pancreatic lipase (van Tilbeurgh H, Sarda L, Verger R, Cambillau C, 1992, Nature 359:159-162; van Tilbeurgh et al., 1993a, Nature 362:814-820). Upon lipid binding, conformational changes at the active site of pancreatic lipase bring a surface loop (the lid) in contact with colipase, creating a second binding site for this cofactor. Covalent inhibition of the pancreatic lipase by a phosphonate inhibitor yields better diffracting crystals of the lipase-colipase complex. From the 2.4-A-resolution structure of this complex, we give an accurate description of the colipase. It confirms the previous proposed disulfide connections (van Tilbeurgh H, Sarda L, Verger R, Cambillau C, 1992, Nature 359:159-162; van Tilbeurgh et al., 1993a, Nature 362:814-820) that were in disagreement with the biochemical assignment (Chaillan C, Kerfelec B, Foglizzo E, Chapus C, 1992, Biochem Biophys Res Commun 184:206-211). Colipase lacks well-defined secondary structure elements. This small protein seems to be stabilized mainly by an extended network of five disulfide bridges that runs throughout the flatly shaped molecule, reticulating its four finger-like loops. The colipase surface can be divided into a rather hydrophilic part, interacting with lipase, and a more hydrophobic part, formed by the tips of the fingers. The interaction between colipase and the C-terminal domain of lipase is stabilized by eight hydrogen bonds and about 80 van der Waals contacts. Upon opening of the lid, three more hydrogen bonds and about 28 van der Waals contacts are added, explaining the higher apparent affinity in the presence of a lipid/water interface. The tips of the fingers are very mobile and constitute the lipid interaction surface. Two detergent molecules that interact with colipase were observed in the crystal, covering part of the hydrophobic surface.

Hormonal influences on the relationships between body fatness, body fat distribution, lipids, lipoproteins, glucose and blood pressure in French working women.

The independent associations between overall obesity, body fat distribution, lipids, lipoproteins, glucose, blood pressure and some hormonal factors (sex hormone-binding globulin (SHBG), corticosteroid binding globulin (CBG) and fasting insulin) were cross-sectionally examined in 205 French working women. After adjustment for age, overall adiposity assessed by body mass index (BMI) was significantly associated with most metabolic parameters, whereas regional adiposity assessed by the waist-hip ratio (WHR) was significantly associated only with triglyceride, systolic and diastolic blood pressure. Blood pressure, glucose but not triglyceride, were also negatively and significantly correlated with SHBG and positively with fasting insulin. Negative independent associations were found between SHBG and both BMI and WHR, whereas CBG was positively associated only with WHR. Fasting insulin was no longer related to WHR after adjustment for BMI. After controlling for the effect of SHBG or insulin, the associations between triglyceride, blood pressure and both BMI and WHR were not substantially modified. After adjustment for BMI and WHR, fasting insulin was independently associated with both HDL cholesterol and diastolic blood pressure. In conclusion, in these French women, hormonal factors under study appeared to have little influence on the relationships between body fatness, body fat distribution, metabolic variables and blood pressure.

Internalization of human sex steroid-binding protein in the monkey epididymis.

Human sex steroid-binding protein (hSBP) has been purified from late-pregnancy serum and labelled either by iodination (125I) or by photoaffinity with [3H]delta 6-testosterone. Using a micromanipulator, each labelled protein was separately injected into the lumen of epididymal tubules isolated from the head epididymis of the cynomologus monkey (Macaca fascicularis). Tubules were sampled from 3 to 90 min after the injection and processed for electron microscope autoradiography. Localization of the label occurred over the epididymal epithelium whichever tracer was used. The labelling was not randomly distributed over the different cell types constituting the epithelium, since only the 'principal cells' exhibited a silver grain count significantly greater than the background count. In these cells, labelled protein was found over endocytic organelles (coated structures, endosomes, multivesicular bodies and the trans Golgi network) and nuclei (including the nuclear envelope). Quantitative analysis demonstrated the same pattern of cellular and subcellular distribution for each tracer. Pretreatment with excess unlabelled protein significantly reduced the uptake of radioactivity by the principal cells, demonstrating the specificity of this phenomenon. This is the first study to show direct histological evidence for the internalization of hSBP in the primate epididymis, consistent with earlier immunohistochemical or biochemical localization of this protein. It is concluded that head epididymal cells are able to take up labelled hSBP across their apical membrane. The mechanism of internalization seems to involve endocytosis by the principal cells and leads to labelling of the nuclear compartment. This is strikingly similar to the pattern of uptake of rat androgen-binding protein (rABP) by rat epididymal cells previously demonstrated by our group. To what extent the chemical and structural homology between hSBP and rABP can be held responsible for the common cytophysiological behaviour of these sex steroid-binding proteins remains to be determined.

Skinfold and body circumferences as measures of body fat patterning in a French female active population: relationships with the metabolic risk profile.

Body mass index (BMI), various anthropometric indices of abdominal fat distribution and some metabolic variables (blood lipids, fasting glucose, blood pressure) were measured in 408 French-born women from an occupational population who volunteered for the study. The aim of the study was to determine the best index for describing the relationships between the body fat pattern and the metabolic risk profile. The four age-adjusted circumference ratios (waist/hip, waist/thigh, xiphoid/hip, xiphoid/thigh) showed similar associations with the metabolic variables whereas the three age-adjusted skinfold ratios (epigastric/thigh, mesogastric/thigh, hypogastric/thigh) tended to be more weakly associated with the metabolic variables, particularly with apolipoprotein (Apo) B and fasting glucose. Multiple regression analyses showed that age-adjusted BMI was significantly related to high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, Apo A and Apo B, and blood pressure, independently of abdominal fat distribution. After controlling for the effects of BMI, the waist/thigh ratio remained significantly associated to triglyceride, Apo B, fasting glucose, and systolic blood pressure, whereas the waist/hip ratio and the mesogastric/thigh skinfold ratio were significantly related only to triglyceride and systolic blood pressure independently of BMI. With the exception of triglyceride and fasting glucose, the degree of association between the metabolic variables and the abdominal fat distribution tended to be weaker than that observed with the BMI. These results emphasize the importance of the global corpulence in the levels of metabolic variables. However, all indices of abdominal fat distribution were, to varying degrees, independently associated with an unfavorable metabolic profile. Among them, the waist/thigh circumference ratio seems to be a useful indicator of the body fat pattern in women.

Stacked inspiratory spirometry reduces pulmonary shunt in patients after coronary artery bypass.

Atelectasis is a major factor in postoperative morbidity for patients undergoing cardiopulmonary surgery. We evaluated the effectiveness of stacked inspiratory spirometry (STIS) in 17 patients status postcoronary artery bypass graft in a nonrandomized fashion. We measured pulmonary shunt as an endpoint, and compared the magnitudes before and after the STIS maneuver. Our results showed an 8.66 percent reduction in pulmonary shunt (p < 0.05). The reduction in shunt was modest; however, repetitive maneuvers might result in greater improvement.

The plasma membrane of epididymal epithelial cells has a specific receptor which binds to androgen-binding protein and sex steroid-binding protein.

The binding of [3H] delta 6-testosterone photoaffinity-labelled rat androgen-binding protein (rABP) has been studied in an enriched fraction of plasma membranes of epithelial epididymal cells in immature (15 days) and adult rats (40 days). The binding was maximal in less than 30 min and more rapid at 4 degrees C than at 34 degrees C. It was calcium and pH dependent. Scatchard plots of the binding data gave curvilinear plots with two types of binding sites corresponding to a K(ass1) of 18.2 nM-1 and K(ass2) of 1.6 nM-1 (2.2 x 10(11) sites/mg protein and 5.4 x 10(11) sites/mg protein, respectively). In adult rats, only one type of binding site was found, with a K(ass) of 3.7 nM-1 (4.5 x 10(11) sites/mg protein). The number of receptors was 5-fold lower in the cauda than in the caput of the epididymis. The pretreatment of the isolated intact cells with streptozotocin induced a 45% reduction of the binding. Only unlabelled rABP and hSBP (human sex steroid-binding protein) but not other proteins (lactotransferrin, serotransferrin, asialofetuine, fetuine and bovine serum albumin) competed with the labelled ligand to bind plasma membranes. The membrane fraction was solubilized by triton X-100. Its incubation with labelled rABP and hSBP provoked the elution of the tracer as an aggregate into the void volume fraction of superose 6B mini-gel filtration columns. Structural homology between hSBP and rABP could be responsible for the common behaviour of the steroid-carrier molecules for the ABP receptor of rat epididymal epithelial cells.