Genomic instability and aging. Studies in centenarians (successful aging) and in patients with Down's syndrome (accelerated aging).
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to C Franceschi.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Several data in the literature suggest that an intriguing relationship exists between cell proliferation and cell death. Accordingly, we studied the early expression of different genes in the same cells, i.e. rat thymocytes, undergoing cell proliferation upon stimulation with Concanavalin A or cell death following dexamethasone treatment. We showed that an early accumulation of c-fos, c-jun and c-myc mRNA occurred in both phenomena but with different kinetics. It can be speculated that the early induction of nuclear oncogenes is necessary to allow the later induction of other genes probably regulated at the transcriptional level by the AP-1 complex and/or by Myc protein. The accumulation of the transcript for another gene, i.e. poly(ADP-ribose)polymerase, an enzyme responsible for posttranslational modifications of several nuclear proteins, could instead be related to chromatin modifications occurring in both processes.
Apoptosis--or programmed cell death--is an active type of cell death, occurring in several pathophysiological conditions. One of the most important characteristics of apoptosis is that cell death is preceded by DNA fragmentation, consequent to the activation of nuclear calcium- and magnesium-dependent endonuclease(s). DNA fragmentation can be inhibited by zinc ions. By using several techniques, such as DNA agarose gel electrophoresis, cytofluorimetric analysis of DNA content and of cell cycle, 3H-thymidine incorporation and trypan blue dye exclusion test, we show that zinc, despite completely inhibiting DNA fragmentation and the consequent loss of nuclear DNA content, does not protect rat thymocytes from spontaneous or dexamethasone-induced death. Our data also suggest that DNA fragmentation, although characteristic, is not a critical event for thymocyte death of apoptotic type.
Previous studies reported that ACTH molecules influence chemotactic and phagocytic activities of hemocytes in the freshwater snail, Planorbarius corneus. The present study reveals that ACTH and CRF affect the release of biogenic amines. Hemocytes from P. corneus hemolymph incubated in vitro with ACTH for 15, 30, and 45 min released epinephrine, norepinephrine, and dopamine. The greatest release occurred after 15 min, while after 45 min the values were similar to those of the controls. Similar incubations with CRF also provoked a release of biogenic amines, this being mainly mediated by the release of endogenous ACTH. These data suggest that (i) ACTH and CRF provoke the release of biogenic amines; (ii) there is a direct relationship between CRF, ACTH, and biogenic amines, with the hemocytes as the target; (iii) exogenous ACTH can mimic an ancestral type of stress response; (iv) the major pathway of the stress response in P. corneus is mediated by a CRF-ACTH-biogenic amine axis. These data should help to unravel part of the complex molecular signaling mechanisms involved in the physiological/endocrinological reaction of invertebrate organisms to stress, and suggest that a stress response unexpectedly similar to that present in mammalian cells is detectable in invertebrates.
Cells continuously exposed to genotoxic agents, such as oxygen free radicals (OFRs), deeply involved in the aging process use a variety of cellular defense mechanisms. These defense mechanisms include DNA repair enzymes, antioxidants, poly(ADP-ribosyl)polymerase (pADPRP), and stress proteins and they constitute an integrated network. An age-related failure of the efficiency of this network can affect cell proliferation and cell death, two phenomena tightly linked and regulated. Recent data from our laboratory on the role of DNA damage and pADPRP activation and on the type of cell death induced by OFRs in human lymphocytes are reviewed. In vitro and in vivo data on possible strategies to reduce oxidative stress in lymphocytes from normal and Down syndrome subjects, by using natural compounds and trace elements, are presented. They indicate that nicotinamide and L-carnitine protect human cells from OFR-induced damage and suggest that they are possible candidates as antiaging substances.
Human lymphocytes have been used by several researchers to investigate the biological effect of electromagnetic fields (EMF). EMF modulate the response by lymphocytes to lectin stimulation. The size and direction of the effect depends both on the lymphocyte physiology and on the physical parameters characterizing the EMF. Lymphocytes have also been used to investigate the genotoxicity of EMF exposure.
In a previous study we demonstrated the presence of NK-like activity in the mollusc Planorbarius corneus. This activity can be ascribed to round hemocytes that have a morphology similar to that of vertebrate lymphocytes. We show here that this NK-like cytotoxicity is evident in serum-free culture medium. Moreover, the type of death induced by molluscan effector cells on their targets is probably similar to that induced by vertebrate effector cells, i.e. apoptosis or programmed cell death, as assessed by the protective effect exerted by 3-aminobenzamide when both types of effector cells were used.
Using a variety of techniques we found the presence of ACTH and opioid-like molecules in the phagocytic spreading hemocytes (SH) and the serum of the mollusc Planorbarius corneus. In vitro experiments have shown that ACTH and beta-endorphin exert chemotactic activity on SH, while ACTH, but not beta-endorphin increases the phagocytic activity of SH. Moreover, ACTH and CRF provoked the release of biogenic amines from the hemocytes, mimicking a proto-stress type of response. Thus, the same mobile cell is capable of immune and proto-stress responses by using as mediators neuropeptides which remained fundamentally similar throughout evolution.
From January 1987 to December 1988, 100 conservative and hemodynamic treatments of superficial venous insufficiency in great saphenous vein territory, have been done on 86 patients. They were 32 men, whose mean age was 53.7 years, and 54 women, whose mean age was 44.5 years. Indication for surgery was mainly functional in 28 cases, esthetic in 26 cases, both in 25 cases and trophic problems in 21 cases. Ligation of the sapheno-femoral junction has been done in 91 cases (62 clips, 9 clips and ligations, 11 ligations, 9 sutures). Distal interruption has been done above knee in 24 cases, below knee in 50 cases, and both in 16 cases. Early postoperative complications have been one septic collection of the groin, one hematoma of the groin, one durable contusion of the saphenous nerve, and 21 superficial venous thrombosis. There were six thrombosis of excluded branches, seven subtotal thrombosis of the saphenous and height partial thrombosis of the saphenous vein. Subtotal thrombosis of the saphenous vein were due either to a mistake in position of distal ligation in three cases, either to a too large saphenous vein in four cases. Five out of height partial thrombosis occurred on saphenous veins larger than ten millimeters. Follow up was obtained, in 1990, so that all patients had at least one year of follow-up. Seven patients have been lost for follow-up. Three patients had recurrence because of failure of the clip. An additional procedure was necessary in 30 patients. Functional results were correct in 89% of patients, and esthetical results in 68% of patients.
Contrasting with the destructive methods of treating varicose veins, the CHIVA cure (Cure Conservatrice et Hémodynamique de l'Insuffisance Veineuse en Ambulatoire) technique is a conservative and hemodynamic approach of this problem. Based on coherent physiological principles, it proposes rigorous analysis followed by effective correction of the hemodynamic disorders, resulting in lasting benefits on the esthetic, functional and tropic changes associated with varicose veins. The results of the CHIVA technique in several french and european-centers, including over 10,000 procedures performed between 1987 and 1991, confirm the value of the method first described by the author in 1988. They confirm the necessity of respecting the strategic and tactical rules of this new approach and the need for specific theorical and practical training.
Explore the source record for details and available documents.
Tamm-Horsfall (TH) glycoprotein, the major protein of human urine, is, in vitro, a powerful immunosuppressive agent and the activity resides in its oligosaccharide chains. In this study we investigated structural features required for the inhibitory activity of TH glycoprotein oligosaccharides in the one-way mixed lymphocyte reaction (MLR). We found that both high-mannose and complex-type TH glycopeptides, fractionated from Pronase-digested TH glycoprotein, behaved as inhibitors. Sequential exoglycosidase digestion of complex-type TH glycopeptide results in a slight increase of the inhibitory activity, with a maximum after desialylation and beta-galactosidase treatment. These results suggest that the immunosuppressive activity resides in the central portion of TH glycoprotein N-linked oligosaccharides. The conjugation of complex-type TH glycopeptides to a protein carrier, such as bovine serum albumin, greatly enhanced the inhibitory activity. This effect occurred if the TH-glycopeptide conjugate was added to MLR within the first 24 hr. These results indicate that (i) the immunosuppressive activity is strongly dependent on a multivalent interaction between TH oligosaccharides and ligand(s) at the lymphocyte surface; (ii) an early step of cell-cell recognition is the target of the immunosuppressive conjugate; (iii) TH oligosaccharides compete with a carbohydrate recognition system between effector and stimulator cells which contributes to the MLR-induced blastogenesis.