Comptes rendus des seances de la Societe de biologie et de ses filiales最新文献

Melatonin (N-Acetyl-5-methoxytryptamine) is a hormone secreted mainly by the pineal gland or epiphyse and in smaller amounts by the retina. It is biosynthesized from tryptophan, the critical enzymatic step depends upon N-Acetyl-transferase (NAT). The circadian rhythm of melatonin is the same in man and all the laboratory animals studied until now with nocturnal plasma concentrations 3-10 times greater than during daytime. The secretion and release of melatonin depend upon a large number of exogenous and endogenous factors as e.g. sex, age, pubertal stage, menstrual cycle, drugs, season.... Light is the major regulating factor which acts through the retino-hypothalamic tract. Melatonin is considered as a transducer of the light signal forwarding to the organism the information about day length (relative length of day and night). It is a time-clue provider used by the organism to adapt itself to its environment.

Chemokines are a large family of cytokines that act not only as immune and inflammatory regulators but also as regulators of hematopoiesis. Two major subfamilies of chemokines are distinguished on the basis of whether the first two cysteines are separated by a single residue (CXC) or three residues (CX3C) or they are adjacent (CC) or there is a single C. The Macrophage Inflammatory Protein 1 alpha (MIP-1 alpha), which belongs to CC family is a powerful inhibitor of hematopoisis in vitro and in vivo. The sub-family CXC comprises two main groups. The first sub-group includes the ELR chemokines, in which interleukin-8 (IL-8) is the most prototypic and possesses suppressive activities on hematopoiesis. Platelet Factor 4 (PF4) belongs to the sub-group of non-ELR CXC chemokines. PF4 acts as an inhibitor of hematopoiesis, particularly of the megakaryocytopoiesis. Recently, it has been shown that a peptide of PF4, 34-58 which does not contain the site of heparin binding, is able to inhibit the growth of hematopoietic progenitors in vitro, providing evidence for a model of heparin dependent and independent pathways of PF4 action on hematopoiesis. PF4 can reduce the chimiosensitivity of hematopoietic cells in mice treated by the cytotoxic drug 5-Fluorouracyl, suggesting a potential clinical application of PF4 in cancer therapy.

The human identification in forensic science is currently based upon the study of highly polymorphic systems with mendelian transmission: the STRs (Short Tandem Repeats). These genetic markers are three to seven bases repetitive sequences spread all over the genome. They are detected by using the Polymerase Chain Reaction (PCR). This analysis method makes it possible to amplify several different loci from very low quantities of genomic DNA (Desoxyribonucleic Acid) in very short periods of time without using any radioactive substances. Interpretation of the results is simple because the amplified fragments are of a known size. The alleles known in each system with discrete values allow the calibration of the revealing gel and the populations studies; moreover, they may be entered into a database. The fragility of this test implies specific precautions with the Laboratory's organization in order to avoid any kind of contamination. Both the establishment of a quality assurance responding to the ISO 9002 standard together with internal quality controls would ensure that these tests are reliable and repeatable in the opinion of the Courts. Only authorized laboratories may perform DNA testing on the occasion of legal proceedings.

Germline mutations in either the BRCA1 or the BRCA2 gene are responsible for the majority of hereditary breast cancers. The proposition that BRCA1 may play a role as a caretaker of the genome, was first put forward by the demonstration that, in mitotic and meiotic cells, BRCA1 can interact with Rad51, a major actor in repair and/or recombination processes. From there, a fair body of observations have converged to support the concept that BRCA1 and BRCA2 play a role in monitoring and/or repairing DNA lesions. The relaxation in this monitoring, due to mutations of either of these two genes, leaves unrepaired events and leads to the accumulation of mutations and ultimately to cancer. Understanding the precise biochemical function of BRCA1 and BRCA2 should provide basis for early diagnosis and prevention in women carrying a predisposition to breast cancer.

Disseminated neuroblastoma frequently show a very poor prognosis. N-myc gene amplification, 1p deletion and lack of CD44 gene expression, are all genetic factors associated with the disease's dissemination. Human neuroblastoma xenografts in nude mice has permitted to characterize, in disseminated neuroblasts, oncogenes overexpression, inactivation of tumor suppressor genes as well as detoxifying genes activation which contributes to increase cellular resistance to chemotherapy. These genetic abnormalities permit to propose a nosology of this very aggressive pediatric solid tumor. Hopefully, this genetic classification could be of great value for new therapeutic approaches.

First part: Structure, conformational behaviour and vectorization properties of a peptide (PFNLS) designed by association of a fusion peptide and a nuclear localization sequence is described. Tryptophan fluorescence quenching measurements show that ten peptide molecules bind one all trans retinol or all trans retinoic acid molecule with a strong affinity (Kd' = 40 nM). And is able to help the internalization of all-trans retinol in human fibroblasts. Stoichiometry, structure and affinity of the binding can be compared with those of cellular retinoid binding proteins (CRBP), the structure of which is an antiparallel beta barrel. Second part: Cytotoxic properties of the amphiphilic synthetic peptide are presented. Comparative analysis of proliferating, differentiated and confluent H9C2 adherent cells shows a correlation between toxicity and cell cycle stage (proliferating cells). Electrophysiological measurements on Xenopus laevi oocytes bathed in the peptide also demonstrate the induction of cationic currents, which are voltage dependent. These results allow us to hypothesize that the observed toxicity is related to membrane hyperpolarization of proliferating cells at the G1/S cell cycle phase transition. An important point is that in the case of the "peptide-retinoid" complex, no cytotoxicity is observed.

The scorpion venoms possess many neurotoxic peptides which constitute a group of molecular families with a common architecture and a high degree of polymorphism. This architecture is found also in circulating antimicrobial peptides belonging to the defensins family, which are especially structurally related to the blocking potassium channels neurotoxins. The diversification in functions with a unique architectural scheme is discussed taking in account the biophysiological characteristics of the scorpion order.

Our experiments were done to find out whether there are factors which influence the passage of the two major "risk factor proteins" LDL and fibrinogen, other than their plasma concentrations, from the blood into the arterial walls, where their accumulation is associated with atherogenesis. The results suggest that administration of a remarkable variety of pressor agents over a few days accelerate the uptake of both proteins by arterial walls, and that, in contrast, the process is no faster in rats that have been spontaneously, i.e., genetically, hypertensive for about 3 months. Considering our experimental findings in relation to human atherosclerotic disease, it is interesting that the risk of coronary heart disease and stroke is increased more than additively when both LDL or fibrinogen levels and systolic or diastolic blood pressures are high (18,46). If our work should point to some mechanistic connection between blood pressure and the accumulation of atherogenic plasma proteins in arterial walls, it would provide, at least in principle, an explanation for the epidemiological facts.