Follistatin (FST) and FST-like-3 (FSTL3) are activin-binding and neutralization proteins that also bind myostatin. Three FST isoforms have been described that differ in tissue distribution and cell-surface binding activity, suggesting that the FST isoforms and FSTL3 may have some nonoverlapping biological actions. We produced recombinant FST isoforms and FSTL3 and compared their biochemical and biological properties. Activin-binding affinities and kinetics were comparable between the isoforms and FSTL3, whereas cell-surface binding differed markedly (FST288 > FST303 > FST315 > FSTL3). Inhibition of endogenous activin bioactivity, whether the FST isoforms were administered endogenously or exogenously, correlated closely with surface binding activity, whereas neutralization of exogenous activin when FST and FSTL3 were also exogenous was consistent with their equivalent activin-binding affinities. This difference in activin inhibition was also evident in an in vitro bioassay because FST288 suppressed, whereas FST315 enhanced, activin-dependent TT cell proliferation. Moreover, when FSTL3, which does not associate with cell membranes, was expressed as a membrane-anchored protein, its endogenous activin inhibitory activity was dramatically increased. In competitive binding assays, myostatin was more potent than bone morphogenetic proteins (BMPs) 6 and 7, and BMPs 2 and 4 were inactive in binding to FST isoforms, whereas none of the BMPs tested competed with activin for binding to FSTL3. Neutralization of exogenous BMP or myostatin bioactivity correlated with the relative abilities of the isoforms to bind cell-surface proteoglycans. These results indicate that the differential biological actions among the FST isoforms and FSTL3 are primarily dependent on their relative cell-surface binding ability and ligand specificity.
The aim of this study was to compare the predictive value of umbilical artery Doppler velocimetry in women in the supine position with that in women in the complete left lateral position as a screening test for abnormal obstetric outcomes. Umbilical artery resistance index (RI) was measured at 27-29 weeks and 35-37 weeks in 202 pregnant women. The measurements were performed with the mother in the supine position in 100 cases (supine group), and in the complete left lateral position in 102 cases (lateral group). Predictive values of the tests for abnormal outcomes (small for gestational age, fetal distress, pregnancy-induced hypertension) were compared between both groups. When abnormal RIs were defined as being greater than the 90th centile in the supine group, the sensitivities for any of the abnormal outcomes at 27-29 weeks were 18% in the supine group and 6% in the lateral group; the positive predictive values were 30% and 25%, respectively. For measurement at 35-37 weeks, the sensitivity and positive predictive value were 29% and 45%, respectively in the supine group, and 0% in both cases in the lateral group. When abnormal RIs were defined as being greater than the 90th centile in the lateral group, the sensitivities at 27-29 weeks were 41% in the supine group and 6% in the lateral group; the positive predictive values were 44% and 8%, respectively. At 35-37 weeks, the sensitivity and positive predictive value were 53% and 43% in the supine group, and 6% and 8% in the lateral group. Umbilical artery Doppler velocimetry when the mother was in the complete left lateral position was of little value as a screening test. However, when the mother is in the supine position, it may serve as a kind of stress test and disclose latent obstetric abnormalities in certain cases.
Syphilis remains a serious cause of neonatal morbidity and mortality worldwide. In this paper, we describe a case of congenital syphilis that was fully supported by abnormal fetal heart rate patterns and placental histopathological evidence. A 24-year-old para 4 woman, who did not attend antenatal care, was admitted to our hospital with a complaint of abdominal discomfort at an estimated 31-week gestation. Fetal heart rate monitoring showed prolonged bradycardia. A neonate weighting 1,423 g with severe birth asphyxia was immediately delivered by cesarean section. Following delivery, the mother and the neonate were diagnosed with syphilis. Histopathological examination confirmed severe chorioamnionitis and necrotizing funisitis with numerous Treponema pallidum. Conclusions. Challenges in establishing the diagnosis of necrotizing funisitis are essential for optimal management of a fetus with a systemic inflammatory response in utero.
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