Bulletin et memoires de l'Academie royale de medecine de Belgique最新文献

The reference method for detecting and quantifying hepatic steatosis and fibrosis is the histopathological analysis of liver biopsies. Studies performed in animals and humans have shown that magnetic resonance imaging (MRI) is useful for the accurate and non-invasive quantification of these lesions. For fibrosis quantification, functional MRI methods have to be used, including perfusion MRI, diffusion MRI, and more particularly MR elastography. Modifications of the visco-elastic parameters of the liver can also be observed with MR elastography in hepatic diseases without fibrosis, such as the early stages ofnon-alcoholi steatohepatitis. Finally, accurate quantification of liver steatosis can be performed by observing the difference of resonance frequencies between the protons of fat and water at spectroscopy or chemical shift MRI. In conclusion, combined quantification of liver steatosis and fibrosis can be performed with MRI.

At birth a number of children suffer from hepatic enzyme deficiencies or from biliary malformations. These diseases can be better understood, and in some instances better treated, with the help of knowledge gained from developmental biology studies. Here we review the key steps of liver development and illustrate how developmental biology can contribute to improve diagnosis and treatment of hepatic diseases, and at the same, time benefits from the input from clinical sciences.

E.D. Carosella was the pioneer who demonstrated the protective role of the HLA-G molecule on trophoblasts, which form a shield protecting the fetus from the immune reaction of its mother and subsequent reject. This non-classical HLA class I molecule is first expressed on the fertilized ovocyte, thus enabling a uterine implantation and then on the surface of the placenta trophoblast where the classical class I and II antigens are absent. He brought the first demonstration ex vivo of the protector role of HLA-G molecule present on the surface of fetal cytotrophoblast cells versus the lysis carried out by maternal decidual uterine NK cells, in both semi-allogenic combinations (maternal uterine NK cells and their own fetal cytotropohoblast counterparts) and allogenic combinations (different maternal uterine NK cells and cytotrophoblasts from different fetuses). The blockage of this protein triggers off an important cytotoxicity towards the fetal cells. Furthermore, he showed that HLA-G molecules act as an inhibitor of the T-lymphocytes, NK cells and antigen presenting cells (APC). Through his discovery Carosella also shows for the first time the three major clinical consequences: I) HLA-G molecules are crucial, as an altered expression of these molecules would lead to abortion and failed pregnancies, i.e. recurrent spontaneous abortions and preeclamptic disease. The embryo expression of soluble HLA-G molecules is a mandatory prerequisite to implantation. II) In allogenic transplantation (heart, kidney and liver-kidney graft) the expression of HLA-G protein significantly reduces acute rejection and showed an absence of chronic rejections. III) Finally, this expression on the malignant cells has a negative functional impact in the anti-tumour response. So the expression of HLA-G molecule constitutes an escape mechanism from immunosurveillance, just as the fetal cells protect themselves from the aggression of maternal immune cells.

Epithelial ion transport in various organs has long been known to be controlled by extracellular agonists acting via membrane receptors or by intracellular messengers. Evidence is mounting for regulation of transport by direct interaction among membrane proteins or between a membrane transport protein and membrane-attached proteins. The membrane protein CFTR (Cystic Fibrosis Transmembrane Regulator) is widely expressed along the length of the nephron, but its role as a chloride channel does not appear to be critical for renal handling of salt and water. It is well established that the inward rectifying K channels (ROMK = Kir 1.1) in the thick ascending limb of Henle and in principal cells of the collecting duct are inhibited by millimolar concentrations of cytosolic Mg-ATP. However, the mechanism of this inhibition has been an enigma. We propose that the ATP-Binding Cassette (ABC) protein CFTR is a cofactor for Kir 1.1 regulation. Indeed, Mg-ATP sensitivity of Kir 1.1 is completely absent in two different mouse models of cystic fibrosis. In addition, the open-closed state of CFTR appears to provide a molecular gating switch that prevents or facilitates the ATP sensing of Kir 1.1. Does Mg-ATP sensing by the CFTR- Kir 1.1 complex play a role in coupling metabolism to ion transport? Physiological intracellular ATP concentrations in tubule cells are in the millimolar range, a saturating concentration for the gating of Kir 1.1 by Mg-ATP. Therefore, Kir 1.1 channels would be closed and unable to contribute to regulation of potassium secretion unless some other process modulated the CFTR-dependent ATP-sensitivity of Kir 1.1. The third component of the metabolic sensor-effector complex for Kir 1.1 regulation is most likely the AMP-regulated serine-threonine kinase, AMP kinase (AMPK). Changing levels in AMP rather than in ATP constitute the metabolic signal "sensed" by tubule cells. Because AMPK inhibits CFTR by modulating CFTR channel gating, we propose that renal K secretion is physiologically regulated by tri-molecular interactions between Kir 1.1, CFTR and AMPK.

The outer membrane of Gram negative bacteria such as Escherichia coli is a permeability barrier that is essential for the viability of Gram-negative bacteria and protects them against antimicrobial drugs, including hydrophobic antibiotics. Outer membrane components, including phospholipids, lipopolysaccharids and proteins are synthesized in the cytoplasm and the cytoplasmic membrane. The mechanisms by which unfolded proteins and lipids are then transported through the hydrophilic periplasm and are inserted in the outer membrane are essentially unknown. Our overall goal is to solve the fascinating problem of how such a complex macromolecular structure is assembled in a compartment devoid of obvious energy sources. Moreover, the proteins that are involved in OM biogenesis are also attractive targets for the design of new antibiotics and anti-inflammatory drugs. Developing new antibiotics active against E. coli and other Gram negative bacteria is criticial because the number of E. coli strains that are resistant to antibiotics is rapidly rising. We will describe results obtained recently in our laboratory that allowed us to characterize several periplasmic chaperones involved in the folding of envelope proteins.

After recalling that maternal and paternal fertility, and in particular the first birth, are occurring later and later in life in all developed countries, the paper examines the relation between parental ages at childbearing on the one hand and morbidity and mortality of the child on the other hand. Age of mother at childbearing has an impact on child mortality and morbidity. Similarly, a late paternal age at childbearing, controlling for mother's age, has a statistically significant impact on neonatal mortality and on late foetal mortality, as well as on the risk for the child of suffering from various congenital anomalies.

Regenerative medicine aims to restore the function of a deficient organ without replacing it, i.e. without resection-transplantation, but by the use of healthy cells which will transfer the deficient function inside the diseased organ. Cells can be mature, harvested directly from the source tissue, or be instead produced from stem cells, which can be manipulated in vitro, expanded and/or differentiated to render them functional. Liver cell therapy has brought the proof of concept that a deficient metabolic activity can be transferred via transfusion of heterologous liver cells via the portal vein. The main limitations of the technique include organ shortage, poor renewal capacity of mature cells and poor resistance to cryopreservation. A liver derived progenitor cell has recently been identified in the adult human liver. The cell is selected by a culture process, can be expanded in vitro and differentiated into mature human hepatocytes when transplanted in rodent livers. The cell displays all the essential hepatocyte function, and may replace the mature hepatocyte for regenerative medicine of the liver.

General medicine is the main pivot of our healthcare system. General practitioners' tasks are numerous: front line responsibility, networking coordination, long-term patient care, community medicine and also primary care research. In the framework of general medicine that has been undergoing profound change for many years, we have chosen to develop three of these facets: general practitioners' knowledge of family, psychological, social or environmental factors and their capacity to coordinate with other health workers will help them in their primary and secondary prevention and also quaternary work by sparing patients unnecessary treatment and examinations. General medicine will increasingly become a discipline, one of which specific expertise will be to manage bio-psycho-societal complexity. Multidisciplinary action will be the rule: general practitioners will no longer be able to claim they can deal with all the curative, preventive and health education tasks. And the research in general medicine is essential because general practitioners can deal with over 80% of the health problems identified by patients and because the symptoms leading to the treatment cannot only be studied by laboratory or hospital research.

The family of the Medici has dominated the city of Florence from the 15th to the 18th century. With the fortune accumulated by their bank, their trade and industry, they made Florence the European capital of the Renaissance and one of the world centres of culture. However, the Medici got a lot of health problems that have often influenced the destiny of the city and its citizens. During the 15th century, the Medici of Cafaggiolo branch of the family were the uncrowned masters of the Florence republic. All got major "rheumatic" complaints, who often interfered with a normal professional activity. The tradition called their disease "gout" and one of the Medici even received the nickname "the gouty" (Piero il Gottoso). Radiological and pathological exploration of the bones, the study of documents from ocular witnesses and the icon pathological study of paintings of the family could however not confirm this diagnosis. On the contrary, 2 other osteo-articular syndromes could be disclosed in the family. During the 16th century, the Medici became Grandukes of Tuscany with absolute political power, abandoning their classical jobs as bankers and traders. Their luxurious life with feasts and lewdness induces their progressive fall that will be accelerated by illness. Malaria, the plague, venereal diseases, madness and cardiovascular disease decimate the family as well as murders, poisonings and other criminal acts. Moreover, the physical resistance of the family decreased due to some underlying, hereditary pathologies that were recently discovered. In 1737, the last Granduke died in a state of complete marasmus and Florence is taken over by the house of Lorraine.