[Acute postpartum psychoses]. / Les psychoses aiguës du post-partum.

The post-partum is a high risk period for the development of acute psychotic disorders. The frequence of post-partum psychoses is evaluated at 1 to 2 per 1,000 births. Post-partum psychosis include major affective disorders which is the most frequent diagnosis. The clinical pictures have specific characteristics: rapid change of symptomatology, liability of mood, and frequent confusional signs. The short-term prognosis is generally good but the risk of recurrence of the mental disorder, in or outside puerperal context, is high. At clinical, evolutive and genetic levels, the studies do not provide arguments for nosological autonomy of post-partum psychosis. At therapeutic level, the ECT is particularly efficient in this indication.

Mechanisms in interleukin-2 protection against glucocorticoid-induced apoptosis: regulation of AP-1 and glucocorticoid receptor transcriptional activities.

We have used the gibbon ape leukemia cell line MLA-144 and its corticoid-sensitive subclone MLA-E7T to analyze the mechanisms whereby interleukin-2 (IL-2) can protect T cells against dexamethasone-induced apoptosis. MLA cells are characterized by the constitutive expression of intermediate affinity receptors for IL-2, together with IL-4 receptors. MLA-144 cells secrete IL-2 and are insensitive to dexamethasone, whereas MLA-E7T cells do not constitutively produce significant amounts of IL-2 and undergo apoptotic cell death in the presence of dexamethasone. Exogenous IL-2 was shown to protect MLA-E7T cells against the apoptotic effect of dexamethasone and to increase both the DNA binding and transactivating functions of activator protein-1 (AP-1). The functional relationship between AP-1 and glucocorticoid receptors transcriptional activities was further investigated using transient expression of reporter gene constructs whose transcriptions are regulated by promoters containing TPA-responsive elements or glucocorticoid-responsive elements. The data reported here demonstrate that in MLA-144 cells, IL-2 or PMA stimulation antagonizes the glucocorticoid receptor, whereas in MLA-E7T, synergistic effects are observed between dexamethasone and IL-2 or PMA for transactivation of MMTV-CAT. Taken together with the finding that IL-2 but not PMA protects MLA-E7T from dexamethasone-induced apoptosis, our results indicate that IL-2 does not induce such a protection by repressing the transcriptional activity of the glucocorticoid receptor.

Regulation of interleukin-2 and interleukin-4 receptor expression in human and ape lymphoid cell lines.

In this study, we have analyzed the expression and regulation of receptors for IL-2 (alpha and beta chains) and IL-4 in four lymphoid cell lines established from leukemic cells. The gibbon ape cell line MLA 144 was the only one to express constitutively the IL-2R beta chain and IL-4R, whereas the NK-like YT cells express only IL-2R beta. The two other cell lines in this study, PEER and HSB2, are derived from T lymphocytes, and express neither IL-4R, IL-2R beta, nor IL-2R alpha unless stimulated. We report here that those receptors that are constitutively expressed, i.e., IL-2R beta on YT cells and IL-2R beta or IL-4R on MLA cells, are down-regulated by stimulation with PHA + PMA. In contrast, RNase protection experiments showed that PHA + PMA stimulation of T cell lines induces mRNA for all three receptors in PEER cells, and only IL-2R alpha and IL-4R in HSB-2. Thus each of these three receptors is subjected to a different regulation, which in addition varies depending on the lineage (or differentiation stage) of the cells. This was further supported by the finding that IL-1 alpha or TNF-alpha regulates these receptors differently. These two cytokines have no effect on IL-2R beta and IL-4R in MLA and YT, but induce IL-2R alpha in YT. In contrast, they do not induce either chains of the IL-2R in the T cell lines PEER or HSB-2, but TNF induces IL-4R mRNA in HSB2 cells, and IL-1 does so in both cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

ADP-ribosylation of the ras-related, GTP-binding protein RhoA inhibits lymphocyte-mediated cytotoxicity.

The Rho proteins are identified as a subgroup of the Ras superfamily of low molecular weight GTP-binding proteins. We have studied the expression of these proteins in human cytotoxic natural killer cells and found that RhoA is the most abundantly expressed member of the Rho family. The Rho proteins are specific substrates for ADP-ribosylation catalyzed by the C3 exoenzyme from Clostridium botulinum. We report here that introduction of recombinant C3 in electropermeabilized natural killer cells or in cytotoxic T lymphocytes resulted in a dose-dependent inhibition of their cytolytic function. Furthermore, a single substrate is efficiently ADP-ribosylated by C3 in extracts from cytotoxic cells. Biochemical analyses indicate that this substrate is RhoA, and subcellular fractionation experiments demonstrate that it is essentially present in the cytosol of the cells. Western blot analysis, however, revealed that a small proportion of the Rho protein can be found associated with the cell membrane as well as with the cytotoxic granules. These results indicate that the low molecular weight GTP-binding protein RhoA is present in cytotoxic lymphocytes and plays a critical role in cell-mediated cytotoxicity.

Cyclic AMP upregulates mRNA and surface expression of IL-2R alpha p55(Tac) in normal human NK cell clones.

The effects of cAMP upon cell proliferation, cytotoxic activity, and regulation of IL-2R expression was investigated in normal human, IL-2-dependent natural killer (NK) cell clones. We report here that addition to the cultures of Bt2cAMP, a cell permeant analogue of cAMP, results in inhibition of IL-2-dependent proliferation, as assessed by [3H]Thymidine incorporation, in both NK and T cell clones. In addition, Bt2cAMP was shown to block the cytotoxic activity of NK cell clones at the level of the lytic phase. Contrasting with these inhibitory effects, cAMP induces an upregulation of the membrane expression of the IL-2R alpha chain (p55, Tac) in normal NK cell clones, which correlates with an accumulation of Tac mRNA. This is clearly at variance with T cell clones in which no such effect of cAMP alone is observed. In both cell types however, cAMP appears to synergize with IL-2 to increase IL-2R alpha mRNA expression. In addition, we demonstrate, using a cDNA probe to the IL-2R beta, that expression of this second component of the high affinity IL-2R, does not appear to be co-regulated together with IL-2R alpha in response to cAMP or/and IL-2 in cultured NK cells. Thus the effects of cAMP on human NK cell clones are complex. cAMP is inhibitory of proliferation and cytolytic function, whereas it is stimulatory of IL-2R alpha expression in these cells.