Comparative study of the binding of prolactin and growth hormone by rabbit and human lung cell membrane fractions.

The specific binding capacities for human prolactin (hPRL) and human growth hormone (hGH) were examined in human lung membrane preparations at different developmental stages. A parallel study was carried out on rabbit lung preparations to compare binding parameters. Lung tissues were obtained from 15 fetuses of 16-38 weeks after spontaneous or therapeutic abortion and from 7 adults (lobar resection surgery). A histological study was systematically performed with a radial alveolar count in the fetuses with suspected hypoplasia. Binding analysis was performed on both intact membrane preparations and MgCl2-treated membranes, using [125I]hGH and [125I]hPRL as tracers. In the rabbit lung, specific [125I]hGH binding was found. Scatchard analysis revealed a single class of binding sites (affinity constant: 2.6 +/- 0.8 x 10(9) l/nmol and number of binding sites: 9.5 +/- 4.3 fmol/mg protein for adult rabbit; 1.85 +/- 0.5 x 10(9) l/nmol and 27.6 +/- 3.0 fmol/mg protein for 25-day-old rabbit fetuses, respectively). In contrast, [125I]hPRL did not specifically bind to lung membrane preparations. In the human lung, no consistent specific binding sites for [125I]hPRL or [125I]hGH (less than 0.5%/mg protein) were detected in adults and in 11 of the 15 fetuses. In 4 fetuses, little specific binding was observed (0.59-1.9%/mg protein) for [125I]hGH and (1.5%/mg protein) for [125I]hPRL. There was no correlation with histological lung structure. Our findings confirm the presence of specific binding sites for GH in the adult rabbit lung and demonstrate such binding in the fetal rabbit lung. In contrast, our results showed no significant binding for PRL and GH in the human lung, suggesting that these hormones do not play a direct physiological role in human lung growth and maturation.     

BRCA1, BRCA2, AR and IGF-I expression in prostate cancer: correlation between RT-qPCR and immunohistochemical detection

Identification and characterization of biomarkers in prostate cancer are important for improving the diagnosis. The aim of this study was to determine differences in the expression of 4 genes according to the stage of malignancy in prostate cancer. We analyzed BRCA1, BRCA2, androgen receptor (AR) and IGF-I gene expression in a cohort of 98 prostate biopsies. We used TaqMan RT-qPCR for mRNA detection, and correlation with proteins was performed using immunohistochemistry. Among the 98 studied prostate biopsies, high heterogeneity in the expression of the 4 genes was detected among the different histological types. However, down-regulation of BRCA1 and BRCA2 mRNA was detected, particularly in the normal tissues. The expression of AR was dependent on the stage of the tumor. The IGF-I gene was specifically expressed in the tumor tissues. Upon comparison between protein and mRNA expression for BRCA1, BRCA2 and AR, we obtained a trend; however, this did not achieve statistical significance. Regarding IGF-I, a correlation between mRNA expression and staining intensity of the protein was found to be significant (p<0.012). The AR biomarker was found to be slightly correlated with the prostate cancer diagnosis (p=0.013). AR was found to be decreased in the tumors with a 43% sensitivity and 90% specificity. The relative risk of 2.05 (1.13-3.69) indicated a 2?fold higher chance of cancer occurrence when AR was ≤0.206.     

Cachexie cancéreuse : bases physiopathologiquesCancer cachexia: physiopathology

Cachexia is a complex syndrome characterized by a decrease in nutritional intake and specific metabolic abnormalities in the host. Anorexia is a multifactorial phenomenon mainly of unknown origin which is not related to an increase in leptin level. Metabolic alterations in the host include an inconstant and weak hypermetabolism and specific perturbations in carbohydrate and lipid metabolism. Skeletal muscle wasting is the main feature of cachexia. There is a consensus on the view that muscle wasting is related not only to muscle catabolism but also to a decrease in the synthesis of new myofibrils and muscle proteins. Muscle protein catabolism is mainly related to an increase in ubiquitin-proteasom pathway by the cachectic factor PIF (Proteolysis inducing factor). Better understanding of the mechanisms of cachexia offers new targets for the development of specific therapeutic approach of cachexia.     

Recurrence of multiple chorio-angiomas: a case-report

Diffuse chorioangiomatosis is a rare placental pathology characterized by multiple chorioangiomas, inducing a high risk of fetal complications, especially cardiovascular, with a risk of fetal death. The physiopathology is not clearly established but seems to be related with an over-expression of vascular growth factors related to hypobaric-hypoxia. Here, we describe a case of recurrent chorioangiomatosis with fetal demise. No risk factors were identified (high altitude, genetic disease like Beckwith-Wiedemann, diabetes). Intra-amniotic, plasmatic values of alphafetoprotein and plasmatic beta gonadotrophin chorionic hormone remained low. Ultrasonographic assessment of placental thickness was in the normal range, at 22 and 32 weeks of gestation. In case of previous chorioangiomatosis, we recommend a weekly sonographic monitoring to diagnose fetal complications associated with an early inpatient hospitalization for daily surveillance at the age of previous accidents. Labor will be induced in case of fetal intolerance or systematically after 37-38 weeks of gestation.