Biomedical subjects
Publications and source records attributed to C Franceschi.
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.
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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.
To assess the relationship between cell proliferation and cell death, the mRNA accumulation of ornithine decarboxylase (ODC) and sulfated glycoprotein 2 (SGP-2) were measured in human peripheral blood lymphocytes (HPBL) 2-6 hours after stimulation with phytohemagglutinin (PHA). ODC is the rate limiting enzyme of polyamines biosynthesis and its early induction in mitogen-stimulated lymphocytes has been reported. On the other hand, SGP-2, a glycoprotein present in most mammalian tissues, is induced in classical models of apoptosis, such as dexamethasone-treated thymocytes. Indeed, a consistent amount of SGP-2 mRNA in quiescent HPBL, an early and progressive decrease of SGP-2 mRNA and a parallel increase of ODC mRNA accumulation, were observed, in PHA-stimulated HPBL, suggesting that concomitant repression of SGP-2 and induction of ODC genes contribute for the cell entering the cell cycle.
The presence of immunoreactive ACTH molecules on phagocytic cells from the freshwater snails Planorbarius corneus and Lymnaea stagnalis was shown by cytofluorimetric analysis. The role of ACTH in phagocytosis and in the release of biogenic amines, two biological responses that may be taken as ancestral types of immune response and stress, respectively, has also been evaluated. ACTH markedly increased the phagocytosis of Staphylococcus aureus by P. corneus haemocytes and caused the release of biogenic amines from such cells into the serum. These data, as well as tracing the ancestral physiological role of ACTH, favour the hypothesis that immune and neuroendocrine systems share a common evolutionary origin.
The cytokinesis block micronucleus method, a very sensitive cytogenetic assay, was used to ascertain the possible genotoxic effects of extremely low frequency pulsed magnetic fields in phytohemagglutinin-stimulated human lymphocytes cultures from 16 healthy donors. Four conditions were studied: i) lymphocytes not exposed to the field (control cultures); ii) lymphocytes exposed to the field; iii) lymphocytes treated with mitomycin-C and not exposed to the field; iv) lymphocytes treated with mitomycin-C and exposed to the field. Mitomycin-C-treated cultures were used as control for the micronucleus method, because it is known that mitomycin-C is a potent genotoxic agent, capable of inducing micronuclei. The frequency of micronuclei in field-exposed cultures was similar to the spontaneous frequency observed in control unexposed-cultures. Moreover, the exposure to pulsed magnetic fields did not affect the frequency of micronuclei induced by mitomycin-C, suggesting that, in the experimental conditions used, this kind of field neither affected the integrity of chromosomes nor interfered with the genotoxic activity of mitomycin-C.
Two hours after a single intraperitoneal injection of dexamethasone (20 micrograms/Kg b.w.) into adult male rats, a typical ladder of DNA fragments was detectable upon separation on agarose gels of DNA from thymocytes. This became maximally evident at 4 hours. Accumulation of sulfated glycoprotein-2 (SGP-2) mRNA, whose rate of expression has been associated to the processes of programmed cell death, preceded the appearance of DNA degradation, starting to increase as early as 30 min after steroid injection, and maintained higher than controls until 8 hrs; a different time course was shown by changes in the levels of beta-actin mRNA. In the spleen, under the same conditions, the SGP-2 message also increased at 30 min, prior to DNA fragmentation, but decreased thereafter below the control value.
Peripheral blood lymphocyte subsets of two groups of patients affected by Down's syndrome (DS), ie, 28 children and nine adults of relatively advanced age (greater than 34 years), were investigated and compared with those of age- and sex-matched healthy controls (13 children and 20 adults). Particular attention was devoted to cells with markers of natural killer (NK) activity. Double- and triple-color cytofluorimetric analysis was used to better characterize the phenotypic features of the different subsets. Apart from a reduced number of T lymphocytes (CD3+) in DS children and of B lymphocytes (CD19+) in both DS groups, the major alteration we found was a marked age-related increase of the percentage of cells bearing markers associated with NK activity, such as CD16, CD56, and CD57. These DS cells were apparently severely defective as far as their function was concerned, because NK activity was significantly reduced in comparison with age-matched controls, but still capable of responding to cytokines such as interleukin-2, interferon-beta, and interferon-gamma, and to the modulation of lytic activity exerted by the anti-CD16 monoclonal antibody. On the whole, our data stress the importance of studying DS subjects of different ages to fully appreciate the immunologic derangement characteristic of this syndrome.
The hypothesis that natural killer (NK) cells represent an important form of cell recognition and cytotoxicity leads to the prediction that NK-like activity should be preserved throughout phylogenetic development. This was tested in the invertebrate Planorbarius corneus. Two types of cells can be identified and separated from the hemolymph of this mollusc, i.e. glass-adherent macrophage-like spreading hemocytes (SH) and nonadherent round hemocytes (RH). Only RH are able to lyse the K-562 human target cell line in a short-term NK cytotoxicity test. This NK-like activity, severely reduced after 18 h incubation at 24 degrees C, is preserved by human recombinant interleukin 2. A further analysis of P. corneus hemocytes has been performed by using several mouse anti-human monoclonal antibodies and cytofluorimetric analysis. Unexpectedly, both SH and RH react with several monoclonal antibodies, including those directed against epitopes typical of mammalian NK cells and cell adhesion molecules. On the whole, these data support the hypothesis that a primitive NK-like activity appeared early in evolution and is not shared by phagocytic cells.
The peripheral T cell receptor repertoire is mainly controlled by the processes of positive and negative selection occurring in the thymus. Studies in normal or transgenic mice have provided compelling evidence for both negative and positive selection. Negative selection is characterized by partial or total disappearance from the periphery of T cells expressing certain C beta regions, which are normally present in the thymus. Positive selection is chiefly characterized, in the periphery, by an imbalanced ratio between CD4+ and CD8+ T cells expressing a given V domain. To date little information concerning positive and negative selection has been available in man. We studied the distribution of 4 V beta domains on CD4+ and CD8+ peripheral T cells of 34 healthy individuals with a wide age-range (0-96 years). One of the V beta domain studied, V beta 6.7, is preferentially expressed on CD4+ compared to CD8+ T cells (p greater than 0.001). No significant differences were observed using the other V beta domain-specific monoclonal antibodies (V beta 5.2-5.3, 8 or 12). These results provide evidence that a process of thymic education, similar to that described in murine animal models, may also take place in man.
We previously reported that exposure of human mitogen-stimulated peripheral blood lymphocytes (PBL) to extremely low frequency pulsed electromagnetic fields (PEMFs) could restore the defective proliferative capability of PBL from aged subjects. The effects of exposure to PEMFs were studied in PBL from 25 patients with Down's syndrome (DS), a syndrome of premature aging characterized by precocious immune system derangement, including age-related defective PBL proliferative capability. PBL were stimulated with different doses of phytohemagglutinin, and cell proliferation was assessed by measuring the incorporation of tritiated thymidine. After PEMF-exposure, a significant increase in cell proliferation was observed in cells from DS children and young adults, but it was much more evident in PBL from relatively aged DS patients. The age-related effect of PEMFs on DS lymphocytes demonstrates that age must be considered a major variable when studies on DS are performed, and confirms that DS must be regarded as a syndrome of accelerated aging.
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Inhibin and activin are referred to as gonadal glycoprotein hormones whose function is the control of FSH release from the pituitary gland. However, several observations indicate that inhibin and activin are produced in various organs and serve multiple functions. Because bone marrow and spleen produce inhibin and activin, our aim was to evaluate their possible effect on cell-mediated immune function. For this reason we studied 1) monocyte chemotaxis, 2) lymphocyte interferon-gamma production, 3) phytohemagglutinin-induced lymphocyte proliferation, and 4) nonmajor histocompatibility complex-restricted and lymphokine-activated lymphocyte cytotoxicity. All studies were performed on human peripheral blood cells in the absence or presence of various doses of inhibin, activin, or inhibin plus activin. A significant dose-related increase in monocyte chemotaxis was induced by inhibin. Activin increased the migrational activity of monocytes, but via random, not directed, migration. Inhibin significantly decreased interferon-gamma production, and its effect was reversed by activin. Inhibin and/or activin had no significant effect on either phytohemagglutinin-induced lymphocyte proliferation or lymphocyte cytotoxic capability. The present demonstration that inhibin and activin may affect some immune parameters suggests a possible involvement of these hormones in regulating cell-mediated immune function.
OBJECTIVE: analysis of Doppler Duplex (DD) contribution to renal artery percutaneous angioplasty (ATL) follow-up. METHOD: between 1983 and 1989, SO ATL were performed in 47 subjects with renovascular hypertension. Their average age was 50 +/- 12 years. The lesions were fibromuscular dysplasia (n = 20) and atherosclerosis (n = 27). The DD was performed simultaneously with arteriography (A degrees) (considered the gold standard), when the stenosis was discovered (n = 32), before (n = 32) and after (n = 39) ATL, and during the follow-up between the 6th and 12th month (n = 38). RESULTS: during the initial exploration, the concordance between DD and A degrees is 78% and the sensitivity of DD for the diagnosis of stenosis is 90%. ATL was performed once on the basis of DD alone, that showed a tight and significant stenosis with dysplasia, when A degrees failed to detect it. ATL confirmed the lesion and was successful, and hypertension cured. The concordance DD-A degrees before and after ATL is respectively 88% and 77%. At the late control, the concordance is 92%, the sensitivity 73% and the specificity 85% for all stenosis. While maintaining a good specificity, DD recognized the 3 tight found by the A degrees control. The complications encountered during ATL were diagnosed by DD most of the time: all the local complications at the site of entry (n = 5), all the dissections with obliteration (n = 2) and 5 of the 8 dissections without obliteration of the renal artery. CONCLUSION: the detection and the lesional assessment of post-ATL complications are facilitated by DD. The good sensitivity of DD combined with satisfactory specificity will allow the reduction of angiographic surveillance by taking advantage of a non-invasive method.