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We experimentally investigated the effects of gender identity threat on men's and women's perceptions of date rape and sexual coercion. Results showed that men whose masculinity was threatened responded by blaming the victim and exonerating the perpetrator more, while threatened women respond by blaming male perpetrators more and placing less blame on female victims. Men's response to threats was more pronounced than women's, an asymmetry we attribute to the cultural devaluation of femininity. Our findings highlight the significance of masculinity concerns in perceptions of sexual violence and, more generally, the importance of perceiver context in views of violence against women.

The authors examined how ambivalence toward adult children within the same family differs between mothers and fathers and whether patterns of maternal and paternal ambivalence can be explained by the same set of predictors. Using data collected in the Within-Family Differences Study, they compared older married mothers' and fathers' (N = 129) assessments of ambivalence toward each of their adult children (N = 444). Fathers reported higher levels of ambivalence overall. Both mothers and fathers reported lower ambivalence toward children who were married, better educated, and who they perceived to hold similar values; however, the effects of marital status and education were more pronounced for fathers, whereas the effect of children's value congruence was more pronounced for mothers. Fathers reported lower ambivalence toward daughters than sons, whereas mothers reported less ambivalence toward sons than daughters.

The development of antagonists to the α4 integrin family of cell adhesion molecules has been an active area of pharmaceutical research to treat inflammatory and autoimmune diseases. Presently being tested in human clinical trials are compounds selective for α4β1 (VLA-4) as well as several dual antagonists that inhibit both α4β1 and α4β7. The value of a dual versus a selective small molecule antagonist as well as the consequences of inhibiting different affinity states of the α4 integrins have been debated in the literature. Here, we characterize TBC3486, a N,N-disubstituted amide, which represents a unique structural class of non-peptidic, small molecule VLA-4 antagonists. Using a variety of adhesion assay formats as well as flow cytometry experiments using mAbs specific for certain activation-dependent integrin epitopes we demonstrate that TBC3486 preferentially targets the high affinity conformation of α4β1 and behaves as a ligand mimetic. The antagonist is capable of blocking integrin-dependent T-cell co-activation in vitro as well as proves to be efficacious in vivo at low doses in two animal models of allergic inflammation. These data suggest that a small molecule α4 integrin antagonist selective for α4β1 over α4β7 and, specifically, selective for the high affinity conformation of α4β1 may prove to be an effective therapy for multiple inflammatory diseases in humans., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Effects of sitaxsentan (TBC11251), an orally active, highly selective antagonist of endothelin A receptors, were examined on the development and maintenance of pulmonary hypertension, pulmonary vascular remodeling, and cardiac hypertrophy in the rat. The pulmonary vasoconstrictor response to acute hypoxia (10% O(2)for 90 min) was prevented with sitaxsentan (5 mg/kg infused iv 10 min prior to the onset of hypoxia) while BQ-788 (a specific endothelin B receptor antagonist) was without effect. The same dose of sitaxsentan delivered iv 50 min after the onset of hypoxia reversed the established pulmonary vasoconstriction. In a 2-week model of hypoxia using 10% O(2), treatment with sitaxsentan (15 mg/kg per day in drinking water) attenuated pulmonary hypertension and the associated right ventricular hypertrophy, and prevented the remodeling of small pulmonary arteries (50-100 microM) without affecting systemic arterial blood pressure or heart rate. Institution of sitaxsentan treatment (15 and 30 mg/kg per day in drinking water) for 4 weeks after 2 weeks of untreated hypoxia produced a significant, dose dependent reversal of the established pulmonary hypertension, right heart hypertrophy, and pulmonary vascular remodeling despite continued hypoxic exposure. Sitaxsentan blocked increased plasma endothelin levels in the prevention protocol but did not affect the established elevated levels in the intervention study. Sitaxsentan dose dependently (10 and 50 mg/kg per day in the drinking water) attenuated right ventricular systolic pressure, right heart hypertrophy, and pulmonary vascular remodeling observed 3 weeks after a single subcutaneous injection of monocrotaline. These findings support the hypothesis that endothelin-1 plays a significant role in the development of pulmonary hypertension, pulmonary vascular remodeling, and the associated cardiac hypertrophy, and further suggest that specific endothelin-A receptor blockade may be useful in the treatment of pulmonary hypertension of diverse etiologies., (Copyright 2000 Academic Press.)

Tumor necrosis factor-alpha (TNF-alpha) and fibroblast growth factor-2 (FGF-2 or bFGF) are potent stimulators of angiogenesis. TNF- alpha, but not FGF-2, can induce the expression of vascular cell adhesion molecule-1 (VCAM-1) on the surface of endothelial cells. The soluble form of VCAM-1 has recently been demonstrated to function as an angiogenic mediator. Here we demonstrate that monoclonal antibodies directed against VCAM-1 or its alpha4 integrin counter- receptor inhibited TNF-alpha-induced endothelial cell migration in vitro. Angiogenesis induced in vivo in rat corneas by TNF-alpha was inhibited by a neutralizing antibody directed against the rat alpha4 integrin subunit. A peptide antagonist of the a4 integrins blocked TNF-alpha-induced endothelial cell migration in vitro and angiogenesis in rat corneas in vivo. No inhibition by the antibodies or peptide antagonist was observed either in vitro or in vivo when FGF-2 was used as the stimulus. The peptide antagonist did not inhibit TNF-a binding to its receptor nor did it block the function of alphavbeta3, an integrin previously implicated in TNF-a and FGF- 2 mediated angiogenesis. These results demonstrate that angiogenic processes induced by TNF-alpha are mediated in part by agr;4 integrins possibly by a mechanism involving the induction of soluble VCAM-1.