Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie最新文献

Bernard-Soulier syndrome involves a multicomponent adhesion receptor on the surface of human platelets. Patients with this disorder bleed excessively from the skin and mucous membranes; and in occasional cases, the bleeding is fatal. At a molecular level, the Bernard-Soulier defect affects the structure and/or function of a receptor that mediates platelet adhesion in the arterial circulation. This receptor, termed glycoprotein (GP) Ib-IX-V, consists of 4 distinct polypeptides (GPs: Ib alpha-143 kDa, Ib beta-22 kDa, IX-20 kDa, V-83 kDa) that share features such as physical associations and leucine-rich glycoprotein (LRG) repeats. All 4 genes and cDNAs have now been cloned and characterized, and the genes have been localized to distinct chromosomal sites. A number of Bernard-Soulier syndrome kindreds have been defined at the molecular genetic level; and in most instances, the defect proved to be a point mutation in either the GP Ib alpha or the GP IX gene. Study of the genetic defects provides insight into both the expression and the function of the receptor. Expression requires the co-ordinated synthesis of the Ib-IX polypeptides with a contribution from GPV. Function of the receptor entails the effect of shear forces generated by blood flow in the artificial circulation. The current challenge in this field is to understand the structure-function relationships within the receptor and its cognate adhesive ligand, von Willebrand factor (vWf).

A variety of cells - fibroblasts, vascular smooth muscle cells, endothelial cells, monocytes and polymorphonuclear leukocytes (PMNs) - carry the elastin-laminin receptor. The activation of this receptor by elastin peptides triggers a variety of reactions as chemotactic movements to an elastin peptide gradient, release of lytic enzymes and oxygen-free radicals, modifications of ion fluxes. We now show that human lymphocytes also express this receptor. Membrane labelling of the receptor by specific antibodies shows capping. In the presence of elastin peptides lymphocytes show increased proliferation and increased production of an elastase type serine protease apparently identical to PMN-elastase, inhibited by cycloheximide and by anti-PMN elastase antibodies. T-lymphocytes are present in atherosclerotic plaques where elastin degradation occurs and could contribute to the chronicity of the lesion by the above mechanism.

In a honeybee colony, brood stimulates development of hypopharyngeal glands of nurse bees. A chemical signal, a blend of 10 fatty acid esters, has been identified on larval cuticle. We demonstrate that the blend of 10 esters, ethyl oleate, and methyl palmitate stimulates the protein synthesis of hypopharyngeal glands of nurses. Thus, in Apis mellifera the chemical signal from the brood acts as a primer pheromone in addition to its previously shown role as a releaser pheromone.

The bare lymphocyte syndrome (BLS) consists of an association between a combined immunodeficiency disease and a significantly reduced expression of either human histocompatibility leukocyte antigens (HLA) class I (HLA-A, -B, -C) or HLA class II (HLA-DP, -DQ, -DR) at the cell surface. BLS type III, the more frequent form of this syndrome, is characterized by impaired expression of both class I and class II antigens on patients' cells, in particular on leukocytes. We describe herein the demonstration that expression of HLA class I molecules was reduced by approximately half on Epstein-Barr virus-transformed B cells (LCL) derived from type III BLS patients. HLA class I mRNA level was also decreased to the same extent. Expression of HLA class I molecules was also very significantly reduced at the surface of these fibroblasts as was mRNA specific for HLA class I. Simultaneously, the expression of HLA-DR molecules on LCL was even more greatly decreased, and the expression of HLA-DQ antigens was virtually abolished. Molecular analysis demonstrated an absence of mRNA for the alpha- and beta-chains of HLA-DQ and HLA-DR in the patients' lymphocytes. In general, such patients present with an association of an absence of expression of HLA class II antigens and a significantly reduced expression of HLA class I antigens. The mechanism of this association is still uncertain.

Our objectives are to define and characterize molecular events of megakaryocytopoiesis and platelet production by analyzing the in vivo expression of platelet glycoprotein (GP) receptors. Our studies target the platelet GP Ib-IX-V complex since the congenital absence of the receptor results in the Bernard-Soulier syndrome, a condition linking the expression of the complex to normal platelet morphogenesis. We have previously described the generation of a transgenic mouse colony expressing the alpha-subunit (GP Ib alpha) of the human platelet GP Ib-IX-V complex. These studies established methodologies to manipulate GP Ib-IX-V on the platelet surface and examine unique aspects of hemostasis, megakaryocytopoiesis, platelet structure and platelet release. Our recent studies have defined the genetic elements supporting the megakaryocytic-expression of GP Ib alpha. These results are defining essential cis-acting elements responsible for the expression of GP Ib alpha and are providing insights into molecular events coinciding with the release of normal platelets into the bloodstream.

In biological systems, obviously dissipative, some injection of muscle force is required in order to sustain rhythmic movement. As the movement frequency increases, the way the muscle-force-to-movement relationship evolves (in timing and amplitude) can be used to characterize some fundamental control properties, including whether the observed system is autonomous or forced. In the case of a simple rhythmic, biological movement (single-joint horizontal forearm movement), this question can be addressed by assuming that the processed electromyographic activity (EMG) is related to the muscle torques. In this case, 2 interesting phenomena can be observed as the frequency increases. The first is that the phase lag between the force and movement remains constant (40 degrees), and the second is that the co-contraction of the agonist and antagonist muscle groups increases with the square of the frequency. These results showed that the contribution of muscle forces to movement organization cannot be regarded in terms of an escapement in an autonomous system, nor in terms of a forcing function in a forced system.

Synthesis of A, B, H, Lewis and related histo-blood group antigens is catalyzed by different fucosyltransferases. Enzymatic acceptor specificity and tissue expression permit the definition of 2 types of alpha-2-fucosyltransferases and 5 types of alpha-3-fucosyltransferases encoded by specific genes registered as FUT1 to FUT7. We have previously assigned FUT4 to 11q21, the cluster FUT1-FUT2 to 19q13.3 and the cluster FUT6-FUT3-FUT5 to 19p13.3. The last gene cloned (FUT7) encodes an alpha-3-fucosyltransferase expressed in leukocytes which synthesizes the sialyl Lĕ antigen, a selectin ligand. We have localized this gene by PCR assay using somatic cell hybrids, which retain rearrangements of chromosome 9 characterized in respect with the genetic microsatellite map, and then by screening a cosmid library. We assign FUT7 to chromosome band 9q34.3 telomeric to D9S1830 and close to the genes ABC2 and C8G.

Over the past few years there have been 2 radiation-related accidents involving a large number of individuals: the April 1986 accident in Chernobyl nuclear power station in the Ukraine and the September 1987 accident in Goiania, Brazil. These 2 radiation-related accidents highlight the major question raised by radiation-induced injury to the haematopoietic system, that is: does a given patient suffer from a reversible or an irreversible haematopoietic stem cell damage? Although about 350 radiation accidents involving several thousand people are known from the literature, in-depth haematopoiesis analyses of individuals after a radiation-related accident have rarely been reported. In this paper we present the case of a young man with radiation-induced aplasia and compare some biological data to those of 16 normal individuals and of 17 patients with acquired aplastic anaemia. Our patient was clinically and biologically (as assessed by long-term bone marrow culture) indistinguishable from patients with idiopathic acquired aplastic anaemia. Furthermore, therapeutic attitudes in this patient are discussed. In-depth study of such radiation-induced aplastic anaemia cases can shed some light in the understanding of this disease and may help in therapeutic decisions.