Tumor suppressor fumarate hydratase is phosphorylated and regulated by AMP-activated protein kinase

International audienc

Prenatal diagnosis of urinary malformations: results in a series of 93 consecutive cases.

OBJECTIVE: To evaluate the pertinence of prenatal diagnosis in cases of congenital uropathy. STUDY DESIGN: Retrospective evaluation over a period of 6.5 years. METHOD: 93 cases were involved in the comparison of prenatal ultrasonographic diagnosis with neonatal findings, autopsy results, and follow-up data. RESULTS: 33 fetuses had renal parenchymal lesions, 44 had excretory system lesions, and 6 had bladder and/or urethral lesions. Seventy-three pregnancies lead to live births. Eighteen terminations of pregnancy were performed on the parents' request for extremely severe malformations. Two intrauterine deaths were observed, and two infants died in the postnatal period. Prenatal diagnosis was obtained at an average of 27 weeks gestation. Diagnostic concordance was excellent in 82% and partial in 12% of cases with renal parenchymal lesions; the false-positive rate was 6%. For excretory system lesions, concordance was excellent in 87% and partial in 7.4% of cases, with a false-positive rate of 5.6%. Finally, concordance was excellent in 100% of cases of bladder and/or urethral lesions. The overall rate of total concordance was 86%. Partial concordance cases consisted of malformations different from those previously diagnosed, but prenatal diagnosis nevertheless lead to further investigations in the neonatal period and to proper management. The false-positive diagnoses (5.4%) never lead to termination of pregnancy. CONCLUSION: Prenatal diagnosis of congenital uropathy is effective. A third-trimester ultrasonographic examination is necessary to ensure proper neonatal management, considering that the majority of cases are diagnosed at this gestational age

Stage IV ovarian cancer: a retrospective study on patient's management and outcome in a single institution.

The management of stage IV epithelial ovarian carcinoma remains controversial. The aim of this study was to evaluate and compare our results to other published series. A retrospective database and casenote review was performed on all patients diagnosed with stage IV disease over a ten-year period (1992-2002). Survival analysis was performed using the Kaplan-Meier and Mantel-Haenszel methods. The study group comprised 23 women. Nine had positive pleural effusions (39.1%), and 14 had other sites of metastases (60.9%). Nine patients underwent interval debulking (39.1%), and 14 were operated on primarily (60.9%). We had six postoperative complications (26.1%) but no perioperative deaths. Optimal cytoreduction (inferior or equal to 2 cm residual disease) was obtained in 18 patients (78.3%). The overall median survival was 22.6 months. There was no statistically significant difference in overall or disease-free survival between primary surgery and interval debulking. Patients with positive pleural effusions had significantly reduced survival compared to those with distant metastases in other sites. Interestingly, there was no difference in survival between optimally and suboptimally cytoreduced patients. Debulking surgery can be performed in patients with stage IV ovarian cancer, with an acceptable level of morbidity. Optimal cytoreduction is achievable in the majority of these patients. Interval debulking should be considered in selected patients

Novel candidate substrates of AMP-activated protein kinase identified in red blood cell lysates

AMPK is a metabolic stress-sensing kinase with important functions for red blood cell (RBC) survival. By using a proteomic approach, we identified putative AMPK targets in hemoglobin-depleted lysates of RBC, including metabolic enzymes, cytoskeletal proteins and enzymes involved in the oxidative stress response. These data tie in with the phenotypic observations of AMPKalpha1-deficient RBC and provide reference for future studies

Chirurgie [Visceral surgery].

Visceral surgery has benefited from several significant therapeutical improvements in 2005. They involve more specifically endocrine surgery, obesity, ovarian cancer, rectocele and cystic pancreatic neoplasia. Minimal invasive surgery is increasingly used, for example in endocrine conditions and obesity treatment. New techniques also emerge, such as electrical gastric stimulation for obesity or Stapled Trans Anal Rectal Resection (STARR) for anterior rectocele. Accurate diagnosis criteria allow better management of cystic pancreatic neoplasia, especially to choose the best treatment of this condition

Tracking and quantification of 32P-labeled phosphopeptides in liquid chromatography matrix-assisted laser desorption/ionization mass spectrometry

Phosphoamino acid modifications on substrate proteins are critical components of protein kinase signaling pathways. Thus, diverse methodologies have been developed and applied to identify the sites of phosphorylated amino acids within proteins. Despite significant progress in the field, even the determination of phosphorylated residues in a given highly purified protein is not a matter of routine and can be difficult and time-consuming. Here we present a practicable approach that integrates into a liquid chromatography matrix-assisted laser desorption/ionization mass spectrometry (LC-MALDI MS) workflow and allows localization and quantification of phosphorylated peptides on the MALDI target plate prior to MS analysis. Tryptic digests of radiolabeled proteins are fractionated by reversed-phase LC directly onto disposable MALDI target plates, followed by autoradiographic imaging. Visualization of the radiolabel enables focused analysis of selected spots, thereby accelerating the process of phosphorylation site mapping by decreasing the number of spectra to be acquired. Moreover, absolute quantification of the phosphorylated peptides is permitted by the use of appropriate standards. Finally, the manual sample handling is minimal, and consequently the risk of adsorptive sample loss is very low. Application of the procedure allowed the targeted identification of six novel autophosphorylation sites of AMP-activated protein kinase (AMPK) and displayed additional unknown phosphorylated peptide species not amenable to detection by MS. Furthermore, autoradiography revealed topologically inhomogeneous distribution of phosphorylated peptides within individual spots. However, accurate analysis of defined areas within single spots suggests that, rather than such quantitative differences, mainly the manner of matrix crystallization significantly affects ionization of phosphopeptides