Prolactin inhibits EGF-induced DNA synthesis in mammary epithelium via early signaling mechanisms: possible involvement of protein kinase C

Prolactin and prolactin agonists inhibited EGF-induced DNA synthesis in mammary epithelium, whereas other pituitary hormones had no effect on EGF-induced DNA synthesis. The inhibitory effect of prolactin was seen for EGF and TGF-alpha, but not for IGF-I or cholera toxin. Autoradiography indicated that prolactin decreased the ability of EGF to induce cells to progress to S phase of the cell cycle, and time course studies indicated that the effects of prolactin were not due to an altered timing of DNA synthesis induction. Prolactin addition within 30 min of adding EGF was necessary to inhibit EGF-induced DNA synthesis. Conditioned media from prolactin-treated cells from which prolactin had been neutralized with the extracellular domain of the prolactin receptor had no effect on EGF-induced DNA synthesis, suggesting that the effect was due to prolactin, not an autocrine factor induced by prolactin. Prolactin induced a rapid association of protein kinase C with the membrane fraction of NMuMG cells, as well as increased threonine phosphorylation of the EGF receptor. Protein kinase C inhibitors eliminated most of the inhibitory effect of prolactin on EGF-induced DNA synthesis. The protein kinase C inhibitor Calphostin C restored high-affinity EGF binding in prolactin-treated cells and reversed the inhibitory effect of prolactin on EGF-induced EGF receptor tyrosine phosphorylation.     

A prospective study of reproductive factors and risk of epithelial ovarian cancer

BACKGROUND: Parity and long term use of oral contraceptives have been associated consistently with a decreased risk of ovarian cancer. However, previous reports of the relationship of other reproductive factors (time since first use or last use of oral contraceptives, age at menarche or menopause, age at first birth) with ovarian cancer have been inconsistent. METHODS: The authors studied these relationships in the Nurses' Health Study, a prospective cohort study of 121,700 female registered nurses aged 30-55 years in 1976 when the study began. From 1976 to 1988, 260 cases of confirmed epithelial ovarian cancer occurred among 1.2 million person-years of follow-up. RESULTS: A statistically significant inverse association was observed between parity and ovarian cancer risk (relative risk [RR] = 0.84; 95% confidence interval [CI] = 0.77-0.91 per pregnancy); age at first birth was not associated independently with risk. In age-adjusted analyses, a significant inverse association was noted between long term use of oral contraceptives and ovarian cancer, which was no longer significant after controlling for other ovarian cancer risk factors (RR with > or = 5 years' use: 0.65; 95% CI = 0.40-1.05). After control for duration of use, a weak nonsignificant inverse association was observed with time since first oral contraceptive use and no independent effect of time since last use. Neither age at menarche nor age at menopause was associated significantly with ovarian cancer risk. CONCLUSIONS: In this large prospective study, parity was the only reproductive factor that had a substantial independent association with ovarian cancer. Long term oral contraceptive use also appeared to have an inverse relationship with ovarian cancer, although this association was of borderline significance (P = 0.11) after adjustment for other risk factors.     

Diabetic eye disease

Diabetic retinopathy accounts for most visual loss in the United States among working-age individuals. With appropriate detection, evaluation, and treatment, the risk for severe visual loss from this condition is dramatically reduced. This article details the natural history, pathophysiology, complications, grading, evaluation, and treatment for patients with diabetic retinopathy and discusses potential novel treatment modalities currently under investigation.     

A conserved 90 nucleotide element mediates translational repression of nanos RNA

Correct formation of the Drosophila body plan requires restriction of nanos activity to the posterior of the embryo. Spatial regulation of nanos is achieved by a combination of RNA localization and localization-dependent translation such that only posteriorly localized nanos RNA is translated. Cis-acting sequences that mediate both RNA localization and translational regulation lie within the nanos 3' untranslated region. We have identified a discrete translational control element within the nanos 3' untranslated region that acts independently of the localization signal to mediate translational repression of unlocalized nanos RNA. Both the translational regulatory function of the nanos 3'UTR and the sequence of the translational control element are conserved between D. melanogaster and D. virilis. Furthermore, we show that the RNA helicase Vasa, which is required for nanos RNA localization, also plays a critical role in promoting nanos translation. Our results specifically exclude models for translational regulation of nanos that rely on changes in polyadenylation.     

Results of a genome-wide genetic screen for panic disorder

There is some controversy over whether or not a discrete site that integrates vomiting activities in somatic and autonomic nerves is present in the medulla oblongata. On the basis of our previous studies, we hypothesized that the temporal patterns of muscle contractions in vomiting are generated by a central pattern generator in the retrofacial area of the rostral medulla. To investigate this hypothesis further, the effects of electrical and chemical lesions of the medullary area were observed in decerebrate paralyzed dogs. Efferent activities of the phrenic and abdominal muscle nerves were recorded to recognize fictive vomiting. The right half of the medulla oblongata was transversely severed about 3 mm rostral to the obex. Fictive vomiting responses to vagal stimulation still appeared after hemisection in all 11 dogs. In addition, stimulation of the contralateral reticular area dorsomedial to the retrofacial nucleus produced fictive vomiting even after hemisection. An electrical lesion or injection of kainic acid (0.5-1.0 microl) was applied at the point where reticular stimulation induced fictive vomiting. After this destruction, no activities that corresponded to fictive vomiting could be induced by stimulation of vagal afferents or the reticular site. Salivation was decreased by hemisection, and decreased further, but was not completely abolished, with destruction of the reticular area. Kainic acid is known to selectively destroy neural cell bodies. Therefore, we concluded that neuronal somata in the reticular formation dorsomedial to the retrofacial nucleus play an essential role in the central patterning of vomiting activities in peripheral motor nerves.     

Allograft heart valve viability and valve-processing variables

BACKGROUND: The impact of allograft valve viability on valve durability remains controversial. Analyses of our clinical results have demonstrated the superiority of the cryopreserved valve viable at the time of implantation over the 4 degrees C stored valve nonviable at the time of implantation. In this study, we quantitatively assessed the effects on viability of current and past valve-processing protocols at The Prince Charles Hospital. METHODS: The viability of pulmonary valves was quantitatively analyzed by thin-layer autoradiography to assess the effects of donor type, antibiotics, and valve storage. RESULTS: Control valve segments obtained from beating-heart donor valves had a higher initial viability (0.92+/-0.02) than nonbeating-heart donor valves (0.66+/-0.03). Cryopreservation after low-dose antibiotic sterilization significantly reduced viability to 50% to 60% of the control, and in the presence of amphotericin B, viability dropped further to 10% to 36% of the control. After 7 days' storage at 4 degrees C, viability was reduced to 2% of control and to 0% viability after 21 days. CONCLUSIONS: For maximal preimplantation viability, valves should be procured as soon as possible after cessation of heart beat and should be cryopreserved if they are not to be clinically implanted within 1 to 2 days. Amphotericin B should not be used in conjunction with cryopreservation if viability is to be maximized.