TWEAK Appears as a Modulator of Endometrial IL-18 Related Cytotoxic Activity of Uterine Natural Killers

BACKGROUND: TWEAK (Tumor necrosis factor like WEAK inducer of apoptosis) is highly expressed by different immune cells and triggers multiple cellular responses, including control of angiogenesis. Our objective was to investigate its role in the human endometrium during the implantation window, using an ex-vivo endometrial microhistoculture model. Indeed, previous results suggested that basic TWEAK expression influences the IL-18 related uNK recruitment and local cytotoxicity. METHODOLOGY/PRINCIPAL FINDINGS: Endometrial biopsies were performed 7 to 9 days after the ovulation surge of women in monitored natural cycles. Biopsies were cut in micro-pieces and cultured on collagen sponge with appropriate medium. Morphology, functionality and cell death were analysed at different time of the culture. We used this ex vivo model to study mRNA expressions of NKp46 (a uNK cytotoxic receptor) and TGF-beta1 (protein which regulates uNK cytokine production) after adjunction of excess of recombinant IL-18 and either recombinant TWEAK or its antibody. NKp46 protein expression was also detailed by immunohistochemistry in selected patients with high basic mRNA level of IL-18 and either low or high mRNA level of TWEAK. The NKp46 immunostaining was stronger in patients with an IL-18 over-expression and a low TWEAK expression, when compared with patients with both IL-18 and TWEAK high expressions. We did not observe any difference for TWEAK expression when recombinant protein IL-18 or its antibody was added, or conversely, for IL-18 expression when TWEAK or its antibody was added in the culture medium. In a pro-inflammatory environment (obtained by an excess of IL-18), inhibition of TWEAK was able to increase significantly NKp46 and TGF-beta1 mRNA expressions. CONCLUSIONS/SIGNIFICANCE: TWEAK doesn't act on IL-18 expression but seems to control IL-18 related cytotoxicity on uNK cells when IL-18 is over-expressed. Thus, TWEAK appears as a crucial physiological modulator to prevent endometrial uNK cytotoxicity in human

EFFECTIVE MATCHMAKING (RECURSION THEORETIC ASPECTS OF A THEOREM OF Philip Hall)

Given a set B of boys and a set 0 of girls, we call a subset S of BxO a society and we say that b knows g when (b,gy e S. The marriage problem for the society S is said to be solvable if it is possible to marry, in the traditional one-to-one manner, each boy to a girl whom he knows. We are concerned here with the computable analogues of these notions. Thus a society is recursive if there exists an algorithm which, when presented with a boy 6 and a girl g, effectively determines whether 6 knows g. Similarly, the marriage problem for the society S is said to be recursively solvable if there exists a one-to-one algorithm which, when presented with a boy 6, effectively marries him to a girl whom he knows. We first show that, even if (the marriage problem for) a recursive society is solvable, it need not be recursively solvable. We then consider several conditions on solvable recursive societies; for each we determine whether such a society must be recursively solvable and, if not, how computationally complex its solutions need be. We also discuss some sociological variations of the marriage problem and indicate how our results can be applied to them. We have drawn upon ideas from two branches of mathematics— combinatorics and recursive function theory. The combinatorial motivation has its source in a famous theorem of Philip Hall ([4]) which implies that if there are only a finite number of boys, then the society S is solvable if and only if, for each natural number k, any k distinct boys know among them at least k different girls. Using a compactness argument one can show that this same condition is necessary and sufficient even if there are an infinite number of boys, so long as no boy knows infinitely many girls. (See either [5] for a combinatorial argument or [1], p. 47, for a proof based on the propositional calculus. This generalization was first proved by M. Hall ([3]). L. Mirsky's new book ([10]) contains an exhaustiv

Mode of action of chemotherapy in vivo on human acute leukemia. II. Vincristine

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Factors influencing the release of leukemic blast cells from the marrow into the blood in human acute leukemia

The number of blood leukemic blast cells in human leukemias at the time of diagnosis has a prognostic value in terms of survival. In 5 patients studied, the blood blast count was found to be positively correlated with the number of blasts in the bone marrow and other proliferating and blast releasing sites. The present work indicates also that marrow blood cells in S, G2 and M are not released into the blood. This was shown by blocking them in these phases of the cell cycle by different antileukemic agents. The larger size of the blasts in S, G2 and mitosis as compared to the size in G1 could partly explain the inability of S, G2 and mitotic cells to egress from the marrow. Leukapheresis in one patient caused rapid recruitment of blasts in the blood. This recruitment was not due to release of blasts from the marrow. © 1977.SCOPUS: ar.jinfo:eu-repo/semantics/publishe