Adrenergic receptors have been shown to be involved in uterine contractility. alpha-Adrenergic receptors cause uterine contraction, whereas beta-adrenergic receptors induce relaxation. In animals, myometrial alpha-adrenergic receptors are regulated by gonadal steroids. We have identified alpha 1- and alpha 2-adrenergic receptors in myometrial membranes using the newly developed radiolabeled specific antagonists [3H]prazosin and [3H]rauwolscine. This allowed characterization of both receptor subclasses individually and study of them in various physiological and pharmacological conditions in the human, i.e. during different phases of the menstrual cycle, in postmenopausal women, term pregnancy, and during depo-progestin (medroxyprogesterone acetate) therapy. The affinity and number of alpha 1-adrenergic receptors were unchanged in all conditions, whereas the number of alpha 2-adrenergic receptors increased concomitantly with circulating plasma estradiol levels. However, this latter effect was counteracted by progesterone. These results are an example of the heteroregulation of membrane receptors by estrogens and progesterone and throw new light on the regulatory mechanisms involved in uterine contractility in the human.
Mouse fibroblasts transformed by simian virus 40 (SV3T3 cells) are characterized by cyclic AMP and cyclic GMP levels, respectively, about half and twice those found in growing untransformed 3T3 cells. Densitydependent inhibition of growth is correlated with reduced cyclic GMP concentrations in 3T3 and four different density-restricted revertant lines derived from SV3T3. The levels of cyclic AMP are not increased at confluence. Upon serum restriction, serum-dependent cell lines show a greater increase in intracellular cAMP than seruminsensitive lines. Cyclic GMP levels are greatly reduced, even in serum-insensitive density revertants, but not in SV3T3. Serum readdition to all serum-dependent lines is followed by a rapid decrease in cyclic AMP and increase in cyclic GMP concentrations. The magnitude of these responses is decreased in SV3T3 and density revertants.The growth of nontransformed fibroblasts, such as the mouse 3T3 line, is regulated by serum factors and cell-to-cell contact (1-3). Transition from a growing state to a resting state occurs upon depletion or deprivation of serum and upon cell confluence. Simian virus 40 (SV40) virus-transformed 3T3 clones often lose sensitivity to these environmental factors (3). Using negative selection pressures on SV40-transformed 3T3 fibroblasts, one can isolate revertant cell lines; they have regained growth control by serum or cell density or by both signals (4-6).Recent work from various laboratories has implicated 3': 5'-cyclic AMP (cANIP) and 3': 5'-cyclic GMIP (cGMP) in the regulation of proliferation in fibroblast cultures.On one hand, the induction of fibroblast proliferation, by a variety of mitogenic signals, is associated with early decreases in intracellular cAMP (7-15) and increases in the cGMP content (14,15).On the other hand, the addition of dibutyryl cyclic AMP to the culture medium partially prevents the stimulation of cell growth (12, 13), whereas exogenous addition of cyclic GMP counteracts the inhibitory effects of dibutyryl cyclic AMP upon a number of biochemical processes activated early in the mitogenic response (16 We report here that density-dependent inhibition of growth is correlated with decreased cGMP concentrations in 3T3 and four different lines of density-dependent revertant cell lines. In contrast, the cGMMP levels remain almost unaffected over the same range of cell densities, in the non "contact-inhibited" clone SV101 of SV40-transformed 3T3 fibroblasts.
MATERIALS AND METHODSCell Lines. The cell lines used in this study are Swiss 3T3, clone SV101 of SV40-transformed 3T3, and four revertant lines derived from SV101 by Pollack and coworkers (4-6). The density-dependent revertant clones FlSV101 and BuSV2 were obtained by negative selection with fluorodeoxyuridine and bromodeoxyuridine, respectively (4, 5). The serum-dependent clones (LsSV2 and AySV5) were selected for their inability to grow at low serum concentrations (1%) and in gammadepleted (= agamma) 10% calf serum, respectively (6). The density revertants have regained den...
Objective To assess the accuracy of a single cervical fetal fibronectin test to predict spontaneous preterm Design A prospective blind cohort study.Setting Antenatal clinic of a teaching hospital in a Brussels semiurban area.Participants An unselected group of 170 women followed at the antenatal clinic.Methods A single cervical sample was obtained between 24 and 33 completed weeks of pregnancy. The fibronectin test was compared with clinical evaluation and their predictive properties were assessed.Results Fifteen women were excluded from the analysis because of elective preterm delivery for medical indications or loss to follow up. Of the 155 remaining women, nine (7%) had a spontaneous preterm delivery. For a single fetal fibronectin test, the sensitivity was 26.7%, the specificity 95.7%, and the positive and negative predictive values 40.0% and 92*4%, respectively. The likelihood ratio of a positive was similar to that of clinical predictors of preterm birth (LR = 6.2; 95% CI 2.0-19.6). Sensitivities were low for both clinical criteria and the fetal fibronectin test.Conclusions Because of low sensitivity in a low risk population, screening for preterm delivery should not be based on the result of a single fetal fibronectin test alone. However, due to its high specificity the test might be useful in avoiding unnecessary medical intervention.delivery in an unselected antenatal population.
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