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Biomedical subjects

C Franceschi

Publications and source records attributed to C Franceschi.

At least 217 records · Page 12Linked to original sources
PubMed1994

Relationship between corticotropin-releasing factor and interleukin-2: evolutionary evidence.

The addition of corticotropin-releasing factor (CRF) to molluscan hemocytes induces the release of biogenic amines (norepinephrine, epinephrine, dopamine), a phenomenon we have considered as an ancestral type of stress response [(1992) Gen. Comp. Endocrinol. 87, 354-360]. A similar but less significant response was observed following the addition of interleukin-2 (IL-2). Pre-incubation of hemocytes with IL-2 or anti-IL-2 monoclonal antibody significantly reduced or completely eliminated the CRF-induced release of biogenic amines. Further direct evidence of competition between CRF and IL-2 was revealed by immunocytochemical and cytofluorimetric analysis. The data are compatible with the presence of a unique (ancestral?) receptor on molluscan hemocytes, capable of binding both CRF and IL-2, two key molecules of the neuroendocrine and immune system, respectively.

Animals↗
PubMed1994

Apoptosis and spermatogenesis: evidence from an in vivo model of testosterone withdrawal in the adult rat.

The seminiferous epithelium is a highly proliferating tissue in which germ cell "degeneration" is a constant feature. Recent data based on morphological analysis have shown that spontaneously dying germ cells display some characteristics of apoptosis. In order to evaluate the molecular signals controlling the phenomenon, adult male rats were studied after in vivo treatment with ethane dimethane sulphonate, an agent which leads to testosterone withdrawal by a selective destruction of Leydig cells. DNA fragmentation by agarose gel electrophoresis and cell DNA content by flow cytometry after propidium iodide staining were used to evaluate and quantify apoptosis in the testis. Despite the simultaneous presence of cells with different ploidies, the present data suggest that testosterone withdrawal induces death by apoptosis and that this phenomenon is particularly evident in haploid germ cells. Thus, this study support the involvement of testosterone in regulating programmed cell death, beside cell proliferation and differentiation, during spermatogenesis.

Animals↗
PubMed1994

3-Aminobenzamide induces cytoskeleton rearrangement in M14 melanoma cells.

3-aminobenzamide (3-ABA) is an inhibitor of poly-ADP-ribose-polymerase, an enzyme involved in numerous subcellular processes including cell death. With the aim of contributing to clarify the mode of action of the drug, which is still poorly understood, its effects on cultured melanoma cells M14 have been assessed. In particular, an impairment of cell growth accompanied by the formation of long and numerous dendritic-like protrusions has been detected. This finding appears to be due to a specific effect of the drug on some cytoskeletal elements and could be associated with its differentiating capability. This finding, together with previous data from our group--Biochem. Biophys. Res. Commun., (1994) 199, 525-530 and 1250-1255--suggests that cytoskeleton is an important target of 3-ABA.

Benzamides↗
PubMed1994

Lack of chromosomal aberration and micronucleus induction in human lymphocytes exposed to pulsed magnetic fields.

We exposed human peripheral blood lymphocyte cultures to 50 Hz pulsed magnetic fields (PMFs) in order to evaluate a possible genotoxic effect of such non-ionizing radiation. The genotoxic effect was evaluated in terms of both micronucleus (MN) induction and classical chromosomal aberrations (CA); the mitotic index (MI) was also calculated. Khalil and Qassem (1991) found chromosomal and chromatid breaks and mitotic delay in human lymphocytes exposed for 24, 48 and 72 h to a field with characteristics similar to those used in our laboratory. These data are in contrast with our results previously reported in terms of MN induction using the cytokinesis block method (Scarfi et al., 1991). In this study lymphocytes from five healthy human donors were examined with the above mentioned tests. No genotoxic effects and increased MI were found in exposed samples compared to the control ones, in agreement with our previous results.

Cells, Cultured↗
PubMed1994

Cell death protection by 3-aminobenzamide: impairment of cytoskeleton function in human NK cell-mediated killing.

3-aminobenzamide, an inhibitor of the nuclear enzyme poly(ADP-ribose) polymerase, is capable of interfering with the tumor cell lysis induced by specialized cells from the immune system, i.e., natural killer (NK) cells. In this report we suggest that the mechanism by which the drug can exert its protective effects on target cell killing by NK effectors can also be due to its ability to impair cell-to-cell conjugate formation (binding), without affecting either the expression of cell adhesion molecules nor the features of effector-target cell contact. The mechanism of this inhibition seems to be associated with an alteration of cytoskeletal elements involved during conjugate formation, i.e., with the integrity and function of the microfilament system.

Actin Cytoskeleton↗
PubMed1994

Cell death protection by 3-aminobenzamide and other poly(ADP-ribose)polymerase inhibitors: different effects on human natural killer and lymphokine activated killer cell activities.

The death of target cells by cytotoxic effector cells is a relevant biological phenomenon, where cells are activated and a very quick apoptotic program occurs. In order to test the hypothesis that the nuclear enzyme poly(ADP-ribose)polymerase (PADPRP) plays a role in such a process, a variety of PADPRP inhibitors such as 3-aminobenzamide, nicotinamide, 4-aminobenzamide and luminol were used. All of them were able to strongly inhibit K562 target cell killing by human effector natural killer cells (NK) in a 4hr 51Cr release assay. PADPRP inhibitors were much less effective in protecting target cells when lymphokine activated killer cells (LAK) were used as effectors. These substances were active only when both target and effector cells were mixed, being ineffective on target or effector cells alone. On the whole, these data indicate that PADPRP is involved in the death of target cells. Moreover, the different sensitivity of NK and LAK activities to PADPRP inhibitors suggests that the molecular mechanisms underlying these two types of cytotoxicity are at least partially different.

4-Aminobenzoic Acid↗
PubMed1994

Mitochondrial modifications during rat thymocyte apoptosis: a study at the single cell level.

Apoptosis is an active type of cell death, occurring under several physiological and pathological conditions. The role of cellular organelles such as mitochondria in this process is still an open question. We recently described a new method to measure mitochondrial membrane potential in intact cells using flow cytometry. Using this method we studied alterations of mitochondrial membrane potential in a classical model of apoptosis, i.e., dexamethasone-treated rat thymocytes. Moreover, apoptosis induced by heat shock was also studied in the same cells. Mitochondria are functionally intact during the early phases of apoptosis, when DNA fragmentation occurs, whereas early alteration in their potential and mass takes place after DNA damage. According to flow-cytometric analysis, the presence of a hypodiploid peak, an index of nuclear DNA loss, predates depolarization of mitochondrial membrane and decrease of mitochondrial mass. Loss of plasma membrane integrity, which indicates cell death and is revealed by the permeability to propidium iodide, eventually follows. All these phenomena are more evident in dexamethasone-treated cells than in heat-shocked cells. Thus, in these types of apoptosis the involvement of mitochondria is apparently not a primary event.

Animals↗
PubMed1994

Differential modulation of invertebrate hemocyte motility by CRF, ACTH, and its fragments.

Various reports have shown that invertebrate hemocytes are responsive to mammalian neuropeptides and cytokines. In the present study, we demonstrate that corticotropin-releasing factor (CRF) and adrenocorticotropin (ACTH) fragments (1-24), (1-4), (4-9), (1-13), (1-17), and (11-24) significantly stimulate molluscan hemocyte migration, and the whole sequence (1-39) and the fragment (4-11) have an inhibitory effect. Differences between species were found with respect to the response to individual fragments. Additionally, the (4-11) fragment was able to antagonize some of the stimulatory fragments (4-9) as well as tumor necrosis factor (TNF-alpha)-induced chemotaxis. Our results suggest that invertebrate hemocytes are able to respond to CRF and ACTH fragments that in turn provide further evidence of the complexity of intercellular signaling within the immune system in relatively primitive animals. Thus, auto- and neuroimmunoregulatory activities in mammals must have had an earlier beginning than previously believed.

Adrenocorticotropic Hormone↗
PubMed1994

[Study and treatment of varicose veins. Truths and counter-truths].

Varicose veins are not the only symptomatology of chronic venous insufficiency of the lower limbs, which has other clinical manifestations: purely symptomatic problems, varicosities, edema and trophic skin lesions. The management of varicose veins is base upon thorough clinical examination. Doppler and ultrasonography are useful in cases of varicose veins in which radical treatment is envisaged. Ultrasound investigation is essential in the presence of cutaneous ulceration in order to avoid mistaking a trophic lesion due to incompetence of deep veins, most often of post-thrombotic origin, for a varicose ulcer. The treatment of varicose veins varies according to the precise nature of the preoccupations of the patient concerned. Elastic support is useful regardless of the clinical form of the disease. Vasculoprotective and venotonic drugs can be used when venous insufficiency is symptomatic. Radical treatment of varicose veins, whether by sclerosing injections or surgery, depends upon the anatomical nature of lesions, the degree of venous incompetence and the extent of signs, but also the wishes of the patient, properly informed of the advantages and limitations of each technique.

Edema↗
PubMed1993

Transcription factors DNA-binding activity in rat thymocytes undergoing apoptosis after heat-shock or dexamethasone treatment.

The onset of apoptosis is generally thought to require the induction of a novel genetic program. Accordingly, we studied the kinetic of DNA-binding activity of several transcription factors in rat thymocytes undergoing apoptosis induced by dexamethasone (DEX) or heat shock (HS) treatment. Here we report that: 1) early activation of AP-1 occurred in both models of apoptosis, even if the intensity of activation and AP-1 complex composition were different and much less evident in HS-treated thymocytes; 2) early NFkB DNA-binding activity was also observed in both types of apoptosis; 3) downregulation of other transcription factors, such as OCT-1 and CREB, with high constitutive activity, was recorded in both models of apoptosis. The fact that some TFs are up-regulated while others are down-regulated suggests that apoptosis is the result of a complex combination of positive and negative signals regulating gene expression.

Animals↗
PubMed1993

A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1).

A new method for the cytofluorimetric analysis of mitochondrial membrane potential in intact cells has been developed by using the lipophilic cationic probe 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1), whose monomer emits at 527 nm after excitation at 490 nm. Depending on the membrane potential, JC-1 is able of forming J-aggregates that are associated with a large shift in emission (590 nm). The color of the dye changes reversibly from green to greenish orange as the mitochondrial membrane becomes more polarized. In two human cell lines (K562 and U937), we have studied by flow cytometry the changes in membrane potential provoked by the K+ ionophor valinomycin, a drug known to affect mitochondrial membrane potential, while the K+/H+ ionophor nigericin, known to affect intracellular pH but not mitochondrial membrane potential, was used as control. The incubation with valinomycin for 10 min. at 37 degrees C in a low K+ medium provoked a marked and dose-dependent reduction in JC-1 greenish orange fluorescence, while nigericin had no effect.

Benzimidazoles↗
PubMed1993

Presence of several cytokine-like molecules in molluscan hemocytes.

The presence of a variety of cytokine-like molecules (IL-1 alpha, IL-1 beta, IL-2, IL-6, TNF-alpha) in the hemocytes of two molluscs, i.e., Planorbarius corneus and Viviparus ater, is reported. These molecules are present only in hemocytes with phagocytic activity. These data, together with recent reports on the presence of cytokine-like molecules in other invertebrates, suggest that cytokines are important, ancestral and functionally conserved molecules.

Animals↗
PubMed1993

Inhibition of c-fes expression by an antisense oligomer causes apoptosis of HL60 cells induced to granulocytic differentiation.

The c-fes protooncogene is expressed at high levels in the terminal stages of granulocytic differentiation, but so far no definite function has been attributed to the product of this oncogene. To tackle this problem, the c-fes protooncogene expression has been inhibited in HL60 cells, and fresh leukemic promyelocytes of acute promyelocytic leukemia have been induced to differentiate with retinoic acid (RA) and dimethylsulfoxide (DMSO). Inhibition was obtained by incubating the cells with a specific c-fes antisense oligodeoxynucleotide. It was observed that the cells, rather than differentiating, underwent premature cell death showing the morphological and molecular characteristics of apoptosis. This process was inhibited by granulocyte and granulocyte/macrophage colony-stimulating factor, but not by interleukin 3 (IL-3), IL-6, or stem cell factor. Our present results demonstrate that the loss of cell viability that occurs during the in vitro differentiation of myeloid cells, after the complete inhibition of the c-fes gene product and treatment with RA-DMSO, is due to activation of programmed cell death. It is concluded that a possible role of the c-fes gene product is to exert an antiapoptotic effect during granulocytic differentiation.

Apoptosis↗
PubMed1993

CRF provokes the release of norepinephrine by hemocytes of Viviparus ater (Gastropoda, Prosobranchia): further evidence in favour of the evolutionary hypothesis of the mobile immune-brain.

The concentration of biogenic amines (norepinephrine, epinephrine and dopamine) was determined by HPLC in serum and hemocytes of the mollusc Viviparus ater following in vitro incubation of the hemolymph with corticotropin-releasing factor (CRF) for different periods of time. CRF provoked the release of norepinephrine from hemocytes into the serum, the maximum level being observed after 15 min. incubation. Moreover, immunoreactive tyrosine hydroxylase and dopamine beta-hydroxylase, i.e., the enzymes involved in biogenic amine biosynthesis, have been demonstrated in hemocytes. These findings show that in invertebrates an ancestral type of stress response, similar to that performed by mammalian hypothalamic-pituitary-adrenal axis, occurs in phagocytic hemocytes, a cell type capable of both fundamental immune and neuroendocrine responses.

Animals↗
PubMed1993

Studies of the relationship between cell proliferation and cell death. III. AP-1 DNA-binding activity during concanavalin A-induced proliferation or dexamethasone-induced apoptosis of rat thymocytes.

In previous papers we started to investigate the possible relationship existing between cell proliferation and cell death. We reported that in rat thymocytes, undergoing cell proliferation upon stimulation with Concanavalin A or cell death following dexamethasone treatment, an induction of c-fos and c-jun occurs with different but partially overlapping kinetics (Grassilli et al., BBRC, 1992, 188, 1261-1266). To test the hypothesis that, in both processes, the early induction of these nuclear oncogenes is necessary to allow the induction of later-expressed genes regulated at the transcriptional level by AP-1 complex, AP-1 DNA-binding activity was investigated in the aforementioned model. Indeed, we found that AP-1 is activated not only in proliferating but also in apoptotic cells, with a kinetics in accord with our data about c-fos and c-jun mRNA accumulation in the same experimental model. Moreover, our findings suggest that an interaction between AP-1 and glucocorticoid receptor also occurs in our model of dexamethasone-mediated apoptosis.

Animals↗
PubMed1993

Increased cytokine production in mononuclear cells of healthy elderly people.

The production of cytokines during aging, except interleukin (IL)-2, has been neglected in humans. We measured the in vitro production of IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and IL-1 beta by peripheral mononuclear cells from selected healthy young (mean age 26.8 years) and aged (mean age 80.2 years) subjects. Significant increases of IL-6, TNF-alpha and IL-1 beta levels were found in mitogen-stimulated cultures from aged donors, occurring at 24 to 72 h after stimulation. No significant differences were observed for IFN-gamma production. Proliferative capability of cells stimulated with PHA was not impaired in aged subjects. Since the amounts of all cytokines studied were similar in unstimulated cultures from young and aged subjects, and also serum levels of TNF-alpha did not differ, these data indicate that the cellular machinery for the production of these cytokines is well preserved in aging, and also that cells from old people are able to up-regulate their production in response to appropriate stimuli. The increases in cytokine synthesis were not dependent on changes in the number of monocytes, nor were they related to the significant rise of CD45RO+, and the concomitant decrease of CD45RA+, occurring in both CD4+ and CD8+ lymphocytes from aged subjects. The increased production of pro-inflammatory cytokines by stimulated mononuclear cells of healthy aged subjects may be relevant to several aspects of age-associated pathological events, including atherosclerosis, osteoporosis, fibrosis and dementia.

Adult↗
PubMed1993

Exposure to low frequency pulsed electromagnetic fields increases interleukin-1 and interleukin-6 production by human peripheral blood mononuclear cells.

The exposure of human peripheral blood mononuclear cells to extremely low frequency pulsed electromagnetic fields (PEMFs) increased both the spontaneous and the PHA- and TPA-induced production of interleukin-1 (IL-1) and IL-6. Our results suggest that cells of the monocytic lineage, which are good producers of both IL-1 and IL-6, can be important cellular targets for PEMFs. Taking into account that these cytokines are among the most pleiotropic ones, these data can help us understand the previous reported effects of PEMFs on the proliferation of human lymphocytes and the effects exerted by such fields on cartilage and bone cells, whose physiological activity is highly dependent on IL-1 and IL-6.

Adult↗