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L Paulesu

Publications and source records attributed to L Paulesu.

65 records · Page 4Linked to original sources

Cytokines in mammalian reproduction and speculation about their possible involvement in nonmammalian viviparity.

In recent years, the secretion of immunoregulatory factors (cytokines) at the maternofetal interface in mammals has been widely documented. Although cytokine production seems to be a specific phenomenon in mammalian reproduction, the specific roles of these substances in different species are still not clear. However, a balance of different cytokine activities appears to be crucial for regulation of the establishment and survival of the semiallogeneic embryo in maternal tissues. The apparent immunological role of placental cytokines in the mechanisms of implantation and embryonic development in mammals has raised the question of whether cytokines are also involved in the reproduction of nonmammalian vertebrates. Our studies have shown that the production of cytokines by the maternofetal unit is not limited to mammalian species, but that interleukin-1 (IL-1)alpha, IL-1beta, and transforming growth factor-beta (TGF-beta) are secreted by the placenta of a viviparous squamate reptile, Chalcides chalcides. Our finding of this parallelism between reptilian and mammalian reproduction suggests that immunological mechanisms, possibly mediated by the secretion of cytokines, played an important role in the evolution of viviparity.

Animals↗

Studies on the biological effects of ozone: 5. Evaluation of immunological parameters and tolerability in normal volunteers receiving ambulatory autohaemotherapy.

Autohaemotherapy, after a bland treatment ex vivo of blood with ozone, is a fairly unknown medical procedure claimed to have therapeutic value in viral diseases and neoplasms. Having already shown that ozone acts as a mild inducer of cytokines, we have undertaken an investigation in normal rabbits and in normal volunteers aiming to evaluate eventual changes of some cytokine levels in plasma as well as of immunological parameters such as the Mx protein, neopterin, beta 2-microglobulin and of some acute-phase proteins after single or repeated autohaemotherapy. We have also evaluated the potential development of of side-effects. This study is the first one to show that autohaemotherapy can activate an immunological marker in normal subjects without procuring any toxic effects.

Animals↗

Evidence of H beta 58, a gene involved in mammalian placental development, in the three-toed skink, Chalcides chalcides (Squamata: Scincidae), a viviparous placentotrophic reptile.

The H beta 58 gene, whose disruption in mice causes reabsorption of the embryo at 9.5 days post-conception, is believed to be essential for development of the placenta. Although the H beta 58 gene is well conserved in some Amniota, nothing is known about its presence in reptiles, some species of which have developed a chorioallantoic placenta. In this work, we investigated the expression of H beta 58 mRNA and protein in the three-toed skink, Chalcides chalcides. H beta 58 protein expression was found in the uterine epithelium beginning from the peri-ovulatory stage. However, it increased strongly at the moment of placental formation, when a high level of expression of mRNA and protein was also observed in the extra-embryonic membranes. The expression of H beta 58 mRNA and protein was maintained, although to a lesser degree, in the placenta during late pregnancy. It was also present in the early embryo. Finally, cloning and sequencing of a gene fragment revealed strong homology of the reptile gene with that of mammals. The high degree of conservation of the gene in amniote vertebrates and its presence in a viviparous squamate reptile (as in mammals) indicates an important role of this gene in the chorioallantoic placenta formation and development.

Allantois↗

Immunocytochemical localization of interferons in human trophoblast populations.

It is known that Interferon (IFN) is present in normal body fluids and tissues during pregnancy. Using an immunohistochemical technique and a panel of monoclonal antibodies we have localized IFN-alpha, -beta and -gamma directly on formalin-fixed paraffin-embedded normal human placentae at different stages of pregnancy and in the hydatidiform mole. The results show that IFNs is mostly localized in villous syncytiotrophoblast and in extravillous interstitial-trophoblast. No reactivity was observed in villous cytotrophoblast or in cytotrophoblast cell columns. The most intense staining was observed for IFN-alpha and -beta, while IFN-gamma was rather weak. There is then a gradual diminution in IFN reactivity with increasing gestation age being almost imperceptible at term. These results suggest that IFN may deploy antiviral, immunomodulator and differentiation activities during normal human pregnancy.

Antibodies, Monoclonal↗

What is the role of cytokines in human colostrum?

No one has ever doubted that maternal milk, in comparison to formula milk, has a far superior nutritional value. Colostrum has a well acknowledge crucial value for the survival of the animal species that cannot receive immunoglobulins through the placenta. Until recently the presence of cytokines in colostrum was unsuspected but it has been now clarified that normally there are at least four cytokines, namely interleukin 1 and 6, tumor necrosis factor and interferon gamma, that may exert an important immunostimulatory role particularly on the oropharyngeal-associated lymphoid tissue. As a corollary, physiological concentration of cytokines administered per os may exert a useful adjuvant activity in aged or immunodeficient people.

Adult↗

Studies on the biological effects of ozone 1. Induction of interferon gamma on human leucocytes.

In this study we have investigated the effects of ozone on human blood, as well as on resuspended buffy coats and Ficoll-purified mononuclear cells. Samples were exposed at different ozone concentrations (from 2.2 micrograms to 108 micrograms/ml) for 30 sec and then incubated for different times at 37 degrees C in a 95% air-5% CO2 humidified atmosphere. Supernatants were collected and frozen at-20 degrees C until tested for interferon (IFN) activity. We have determined that the ozone concentration is critical for lymphokine induction. In fact, while low concentrations (2.2 micrograms/ml) are effective in lymphocytes, they do not induce IFN in either whole or diluted (1:1) human blood, or resuspended buffy coats. In such cases levels as high as 42 micrograms/ml are required. On the other hand, a very high ozone concentration (108 micrograms/ml) is not effective and probably toxic. Maximal IFN production occurs 72-96 h after ozone exposure, and the kinetics of IFN release is similar to that after Staphylococcal Enterotoxin B addition. Because ozonization of blood is a medical procedure followed in several countries for treatment of viral diseases, this study can open a new field of investigation that may yield useful results both in biological and practical terms.

Adult↗

The lymphatic route. VII. Distribution of recombinant human interleukin-2 in rabbit plasma and lymph.

Human recombinant (R) interleukin-2 (IL-2) has been administered through intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) routes and its distribution in lymph and plasma has been evaluated in rabbits. It has been shown that after i.m. administration of RIL-2 in saline, the lymphokine is preferentially absorbed via lymphatics. A similar result has been obtained after s.c. administration when RIL-2 was injected with a high concentration (12.5%) of human albumin, which acts as a retarder and a promoter of lymphatic absorption. These routes may be valid alternatives to i.v. administration.

Animals↗

Enhanced induction of plasma interferon after subcutaneous administration in rabbits of poly ICLC with albumin.

Intravenous administration of poly ICLC in rabbits yields very high plasma interferon (IFN) levels; dosages from 250 to 1000 micrograms/kg body weight are very toxic. Subcutaneous administration of poly ICLC together with a high concentration of human serum albumin potentiates the inducer activity in comparison to poly ICLC in saline. Finally, a dosage of 50 micrograms of poly ICLC in 12% serum albumin is more effective as an IFN inducer than other dosages.

Albumins↗

Studies on the biological effects of ozone: 4. Cytokine production and glutathione levels in human erythrocytes.

We have investigated the effect of various concentrations of ozone on human blood aiming to correlate the production of cytokines with depletion of reduced glutathione and hemolysis. As erythrocytes constitute the bulk of blood cells and represent the main target of ozone they have been taken as a useful marker of its oxidative activity. It appears that a transient exposure (30 sec) of blood of up to 78 micrograms ozone per ml of blood does not depress the production of cytokines even though there is a slight increase of hemolysis and a small decrease of intracellular reduced glutathione. In contrast either a constant (up to 30 sec) exposure to an ozone flux or a high ozone concentration (108 micrograms/ml) markedly decreases reduced glutathione levels and depresses cytokine production.

Adult↗