Ethnic variation in the prevalence of echogenic intracardiac foci and the association with Down syndrome.

OBJECTIVE: To determine whether the prevalence of fetal echogenic intracardiac foci (EIF) differs according to maternal ethnicity. METHODS: We performed a retrospective cohort study of all women undergoing second-trimester diagnostic ultrasound examination and amniocentesis at a prenatal diagnosis referral center from January 1 2000 to July 1 2003. Data were collected on the presence of EIF, gestational age at time of ultrasound scan, karyotype results, maternal age and ethnicity. Univariate and multivariate analyses of EIF, ethnicity and presence of aneuploidy were conducted. RESULTS: Among the 7480 women qualifying for the study, EIF were found in 309 (4.1%). When maternal ethnicity was subdivided into Caucasian, African-American, Hispanic, Asian-American, Native American, Asian Indian, and Middle Eastern, the highest rates of EIF were found in fetuses of African-American (6.7%), Asian-American (6.9%), and Middle Eastern (8.1%) mothers compared to a rate of 3.3% in Caucasians (P < 0.001). In all ethnic groups except Hispanics, EIF was associated with an increased risk for Down syndrome (odds ratio range from 1.8 to 15.7). CONCLUSIONS: African-American, Asian-American, and Middle Eastern patients are more likely than patients of other ethnicities to have a fetus with an EIF. Even controlling for ethnicity, fetuses with an EIF still have an increased risk for Down syndrome. As more data accumulate, the prevalence of EIF and its association with Down syndrome among different ethnic groups can be incorporated into patient counseling.

Vaginally administered misoprostol for outpatient cervical ripening in pregnancies complicated by diabetes mellitus.

OBJECTIVE: To compare the use of vaginally administered misoprostol to placebo for outpatient labor induction in patients with diabetes. STUDY DESIGN: In this double-masked, controlled clinical trial, pregnant women with diabetes and gestational age of >38(1/2) weeks were randomized to receive 25 microg misoprostol or placebo vaginally on days 1 and 4 of a 7-day outpatient cervical ripening period. If necessary, inpatient labor induction was managed by using a standard protocol. RESULTS: Of 120 women included in the study, 57 received misoprostol and 63 received placebo. Most of the women had been diagnosed with gestational (Class A) diabetes. Similar numbers of misoprostol and placebo-treated women delivered within 7 days of the first dose (31/57 [54%] vs 36/63 [57%], P =.63). The mean (+/-SEM) interval from induction to delivery was similar (8530.5 minutes +/-1439.7 minutes vs 6712.5 minutes +/-606.4 minutes, P =.23). CONCLUSION: Vaginally administered misoprostol was no more effective than placebo in reducing the need for inpatient labor induction or the induction-delivery interval. Outpatient cervical ripening with use of vaginally administered misoprostol was well tolerated.

Cell cycle and hormonal control of nuclear-cytoplasmic localization of the serum- and glucocorticoid-inducible protein kinase, Sgk, in mammary tumor cells. A novel convergence point of anti-proliferative and proliferative cell signaling pathways.

The serum- and glucocorticoid-inducible kinase (sgk) is a novel serine/threonine protein kinase that is transcriptionally regulated in rat mammary tumor cells by serum under proliferative conditions or by glucocorticoids that induce a G1 cell cycle arrest. Our results establish that the subcellular distribution of Sgk is under stringent cell cycle and hormonal control. Sgk is localized to the perinuclear or cytoplasmic compartment as a 50-kDa hypophosphorylated protein in cells arrested in G1 by treatment with the synthetic glucocorticoid dexamethasone. In serum-stimulated cells, Sgk was transiently hyperphosphorylated and resided in the nucleus. Laser scanning cytometry, which monitors Sgk localization and DNA content in individual mammary tumor cells of an asynchronously growing population, revealed that Sgk actively shuttles between the nucleus (in S and G2/M) and the cytoplasm (in G1) in synchrony with the cell cycle. In cells synchronously released from the G1/S boundary, Sgk localized to the nucleus during progression through S phase. The forced retention of exogenous Sgk in either the cytoplasmic compartment, using a wild type sgk gene, or the nucleus, using a nuclear localization signal-containing sgk gene (NLS-Sgk), suppressed the growth and DNA synthesis of serum-stimulated cells. Thus, our study implicates the nuclear-cytoplasmic shuttling of sgk as a requirement for cell cycle progression and represents a novel convergence point of anti-proliferative and proliferative signaling in mammary tumor cells.

Indole-3-carbinol inhibits the expression of cyclin-dependent kinase-6 and induces a G1 cell cycle arrest of human breast cancer cells independent of estrogen receptor signaling.

Indole-3-carbinol (I3C), a naturally occurring component of Brassica vegetables such as cabbage, broccoli, and Brussels sprouts, has been shown to reduce the incidence of spontaneous and carcinogen-induced mammary tumors. Treatment of cultured human MCF7 breast cancer cells with I3C reversibly suppresses the incorporation of [3H]thymidine without affecting cell viability or estrogen receptor (ER) responsiveness. Flow cytometry of propidium iodide-stained cells revealed that I3C induces a G1 cell cycle arrest. Concurrent with the I3C-induced growth inhibition, Northern blot and Western blot analyses demonstrated that I3C selectively abolished the expression of cyclin-dependent kinase 6 (CDK6) in a dose- and time-dependent manner. Furthermore, I3C inhibited the endogenous retinoblastoma protein phosphorylation and CDK6 phosphorylation of retinoblastoma in vitro to the same extent. After the MCF7 cells reached their maximal growth arrest, the levels of the p21 and p27 CDK inhibitors increased by 50%. The antiestrogen tamoxifen also suppressed MCF7 cell DNA synthesis but had no effect on CDK6 expression, while a combination of I3C and tamoxifen inhibited MCF7 cell growth more stringently than either agent alone. The I3C-mediated cell cycle arrest and repression of CDK6 production were also observed in estrogen receptor-deficient MDA-MB-231 human breast cancer cells, which demonstrates that this indole can suppress the growth of mammary tumor cells independent of estrogen receptor signaling. Thus, our observations have uncovered a previously undefined antiproliferative pathway for I3C that implicates CDK6 as a target for cell cycle control in human breast cancer cells. Moreover, our results establish for the first time that CDK6 gene expression can be inhibited in response to an extracellular antiproliferative signal.