Direct effects of luteinizing hormone-releasing hormone agonists and antagonists on MCF-7 mammary cancer cells.

The binding of luteinizing hormone-releasing hormone (LH-RH) analogues to the human mammary tumor cell line MCF-7 and their effect on the cell proliferation was studied to elucidate their direct action on estrogen-dependent mammary tumors. The growth rate of these cells was doubled by the addition of 1 nM estradiol to cells maintained in an estrogen-deficient medium. Although the basal growth rate was only slightly inhibited by the LH-RH antagonist [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,D-Cit6,D-Ala10]LH-RH (SB-75), the estrogen-stimulated growth was completely abolished by the antagonist. In contrast, the LH-RH agonist buserelin stimulated cell growth in estrogen-deficient medium, whereas it had no effect in the presence of estrogen. 125I-labeled buserelin was used for the measurement of LH-RH receptors on MCF-7 cells. A Scatchard plot analysis of buserelin-specific binding revealed a nonlinear plot, which suggested the presence of one high-affinity binding site with a Kd of 1.4 +/- 1.0 nM and the remaining sites with low affinity (Kd = 1.3 +/- 1.0 microM). The binding of 125I-labeled buserelin was displaced equally well by unlabeled buserelin and by the LH-RH antagonist SB-75, suggesting that both analogues are bound to the same receptor. When parallel experiments were performed with 125I-labeled SB-75, the binding was displaced by unlabeled SB-75 and other antagonists, but only partially displaced by unlabeled buserelin. The results suggest that in these mammary tumor cells there is a LH-RH antagonist binding site that is not recognizable by LH-RH agonists. This hypothesis was tested by measuring cell growth in the presence of both agonists and antagonists. It was found that SB-75 inhibited the stimulation of growth by buserelin, but buserelin did not prevent the inhibition by the antagonist of the estrogen-dependent growth. These results suggest that antagonists directly inhibit mammary tumor growth, not only by competing with LH-RH high-affinity receptors, but also by other mechanisms mediated by low-affinity antagonist binding sites

Incorporating an ambient agent to support people with a cognitive vulnerability

This article presents the design of an intelligent agent application aimed at supporting people with a cognitive vulnerability to prevent the onset of a depression. For this, a computational model of the cognitive processes around depression is used. The agent application uses the principles of Rational Emotive Behavioural Therapy (RBET). The effect of the application is studied using software simulation.The simulation shows that a person that responds to REBT therapy develops less cognitive vulnerability than people that are not supported

Sociotropic and autonomous personality and stressful life events as predictors of depressive symptoms in the postpartum period

Measures of stressful life events, sociotropic and autonomous personality, and depressive symptoms were completed by 76 women in the last trimester of pregnancy and 8-weeks postpartum. During pregnancy, women with strong sociotropic or autonomous personality style, or high levels of negative life events (or perceived loss resulting from events) in sociotropic or autonomous domains, tended to report higher levels of depressive symptoms. Cross-sectionally, there was some support for the cognitive diathesis-stress model, but not a congruency model, of depression. Longitudinal results indicated that high levels of sociotropic personality style, sociotropic loss, or autonomous loss resulting from events significantly predicted increases in depressive symptoms from pregnancy to the postpartum period. The interaction between personality styles and life events did not predict depressive symptoms longitudinally, either congruently or incongruently. Negative automatic thoughts mediated the direct effects of personality and life events upon depressive symptoms