Preeclampsia (PE) is associated with altered immune activation during pregnancy. We have previously shown that adoptive transfer of CD4(+) T cells from the reduced uterine perfusion pressure (RUPP) rat model of PE increases blood pressure, oxidative stress (ROS), and inflammation in normal pregnant recipient rats. The objective of this study was to determine if blockade of communication via the CD40-CD40 ligand (CD40L) interaction between placental ischemia-induced CD4(+) T cells with endogenous normal pregnant (NP) cells would improve pathophysiology that was previously observed in NP recipient rats of RUPP CD4(+) T cells. Splenic CD4(+) T lymphocytes were magnetically separated, incubated with 2.5 μg/ml anti-CD40 ligand (αCD40L) overnight, and transferred into NP rats on day 12 of gestation (NP+RUPP CD4(+) T+anti-CD40L). On day 19 of gestation, blood pressure (MAP), blood, and tissues were collected. MAP was 99 ± 2 in NP (n = 13), 116 ± 4 in NP+RUPP CD4(+) T cells (n = 7; P < 0.01); MAP only increased to 104 ± 2 in NP+RUPP CD4(+) T cells+CD40L (n = 24) (P < 0.05 vs. NP+RUPP CD4(+) T cells). Mechanisms of hypertension in response to RUPP CD4(+) T cells include endothelin-1 (ET-1), ROS, and angiotensin II type I receptor (AT1-AA) were analyzed. Inhibition of CD40L binding reduced placental ET-1 to 2.3-fold above NP rats and normalized placental ROS from 318.6 ± 89 in NP+RUPP CD4(+) T cells (P < 0.05) to 118.7 ± 24 in NP+RUPP CD4(+) T+anti-CD40L (P < 0.05). AT1-AA was also normalized with inhibition of CD40L. These data suggest that placental ischemia-induced T-cell communication via the CD40L is one important mechanism leading to much of the pathophysiology of PE.

Objective: To determine a role for endothelin (ET) in progression of uterine fibroids. Design: An in vitro model of fibroid and myometrium cultivation. Patients: A total of 32 women undergoing hysterectomies for uterine fibroids and 11 women undergoing hysterectomies for abnormal uterine bleeding (control population). Results: Women with uterine fibroids were hypertensive and displayed significantly greater circulating ET-1 compared to control patients. Secretion of ET-1 was greater from the fibroids compared to myometrium explants. Endothelin 1 secretion was attenuated with blockade of the angiotensin II type 1 or endothelin A receptors. Hypoxia stimulated ET-1 secretion from both myometrium and fibroid explants. Preproendothelin messenger RNA expression increased with hypoxia from fibroid explants compared to normoxic controls. Conclusions: These data support the hypothesis that uterine fibroids are associated with hypertension and increased ET-1, which is exacerbated with hypoxia. These data suggest a possible link between mechanisms of blood pressure regulation and development of uterine leiomyoma.

In this paper we study lattice (Riesz) homomorphisms or, more generally, disjointness preserving (Lamperti, see [2]) operators between real Banach lattices having locally compact representation spaces in the sense of Schaefer [12, III 5.4]. We recall that a Banach lattice E is said to have a locally compact representation space if E contains a copy of C k (X), the continuous real-valued functions on a locally compact space X with compact support, as a dense (order) ideal. This broad class of Banach lattices includes, for example, all Banach lattices with quasi-interior points, topological orthogonal systems or topological order partitions. Such lattices have been studied in [3,4,11,12].These Banach lattices can be represented as continuous extended real-valued functions on their locally compact representation spaces (for example see [3,4]). Theorems 1 and 2 below describe the lattice homomorphisms or disjointness preserving operators on these Banach lattices as weighted composition operators with respect to the representation spaces, generalizing results known for the function lattices of the type C(K) where K is compact (see [15]). and for quasi-interior point spaces (see [10]). These results should also be compared with those of Abramovich [1]. We show that, if T is a lattice homomorphism between Banach lattices E and F, then, given / in E, Tf is of the form r(/o ), where r is a continuous real-valued function on the representation space for F and ^ is an essentially continuous map between the appropriate representation spaces. These results permit an analysis of the principal order ideal ZT generated by a lattice homomorphism T. Corollary 1 states that 3T is equal to the orthomorphisms composed with T. It also generalizes a result of Nagel [10, 3.3], and complements Haid's Theorem 2.7 in [6]. Theorem 5 states that each positive element in the closure of ST can be expressed as the composition with T of what we call a' partial orthomorphism'. This result and Corollary 3 are analogues of a Radon-Nikodym type theorem proved by Luxemburg and Schep (see [8,9]). Corollary 4 provides sufficient conditions for the principal ideal &~ generated by T to be closed. PreliminariesGiven a Banach lattice E with a locally compact representation space X, we shall identify E with a space of continuous extended real-valued functions on X (each finite on a dense set) containing C k (X) as a dense order ideal [3]. We recall [3] that E has a locally compact representation space if and only if E contains a topological order partition (t.o.p.). A special case of a t.o.p. is a quasi-interior point, a positive element generating a dense order ideal.For a continuous function r ^ 0 on X, we let P r = {xeX: r(x) > 0}, Z r = {xeX: r(x) = 0} and we denote the interior of Z r by Z°r. We shall use the fact that P r U Z°r is dense in X.

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Mice homozygous for the autosomal recessive mutation wasted (wst/wst) undergo a progressive wasting beginning at the third week of postnatal life, when body weight declines in the mutants. The wst/wst mice do not survive past 30 days of age. The present report describes histologic and functional abnormalities in a longitudinal analysis (17 to 29 days postpartum) of wst/wst mice. In addition to a marked age-dependent decline in wst/wst body weight as well as spleen and thymus wet weight to body weight ratios, we have observed a significant decline in spleen and thymus cell number in these organs, compared with phenotypically normal (+/+ or +/wst) littermates. Histologic analysis of the wst/wst thymus revealed marked cortical pyknosis at 23 days of age and significant cortical depletion by 26 days postpartum. The wst/wst spleen at 23 days of age and later was characterized by a marked reduction in the content of red pulp. Lymphoproliferative responsiveness to Con A was markedly altered in the wst/wst thymus and spleen, in an age-dependent fashion, compared with normal littermates. The wst/wst spleen LPS responsiveness was also markedly altered in an age-dependent fashion. Hypotheses are presented concerning the possible site(s) of gene action in the wst/wst mutant which may mediate the observed morphologic and functional abnormalities.