Preeclampsia is a heterogeneous syndrome affecting 3–5% of all pregnancies. An imbalance of the anti and pro-angiogenic factors, soluble receptor fms-like tyrosine kinase 1 (sFLT1) and placental growth factor (PGF), are thought to contribute to the pathophysiology of preeclampsia. Maternal plasma PGF and sFLT1 were quantified by specific immunoassays in cross-sectional samples from 130 preeclamptic subjects and 342 normotensive controls at delivery, and longitudinally in samples from 50 women who developed preeclampsia and 250 normotensive controls. Among women who developed preeclampsia, 46% (n=23) evidenced a pattern of consistently low maternal PGF across pregnancy below the lower 95%CI of controls from 15 weeks gestation to term. In contrast, the remaining 54% (n=27) women who developed preeclampsia had maternal PGF concentrations similar to or above (n=7) those of normotensive controls. Subjects with low PGF across pregnancy who developed preeclampsia evidenced significantly higher blood pressure in early pregnancy (p<0.05), and after diagnosis, earlier gestational age at delivery (p<0.05), and more preterm birth (p<0.05) compared to preeclamptic patients with high PGF. A significant subset of women who develop preeclampsia evidence consistently low PGF across pregnancy. Low PGF with preeclampsia was associated with preterm delivery compared to preeclamptic patients with high PGF. Identifying women with consistently low plasma PGF during pregnancy may provide a greater understanding of preeclampsia pathophysiology, and may provide more focused research and clinical activities.

The structure of an intermediate in the initiation to elongation transition of Escherichia coli RNA polymerase has been visualized through region-specific DNA cleavage by the hydroxyl radical reagent FeBABE. FeBABE was tethered to specific sites of the 70 subunit and incorporated into two specialized paused elongation complexes that obligatorily retain the 70 recognizes the Ϫ10 element as both dsDNA and single-stranded (ss)DNA (2-6). At certain promoters that depend on positive activation, such as those targeted by the transcription activators AdaA (7), cI (8, 9), PhoB (10), and FNR (11), 70 region 4 also is required for the function of the activator, almost certainly through a direct contact that facilitates binding or function of holoenzyme.In a role somewhat reminiscent of its function in transcription activation, 70 is required for a unique regulatory pathway directed by a transcription antiterminator, the bacteriophage gene Q protein (Q ), as well as Q proteins of related phages (12). Like some activators, Q binds to DNA just upstream or overlapping the upstream portion of RNAP (13), positioning Q and RNAP for contact. However, Q acts not on RNAP at the promoter but instead on a paused elongation complex containing (for ) 16-17 nucleotides of RNA transcript (14). Pausing is induced by an analogue of the Ϫ10 element, displaced (for ) 12 bp downstream from the Ϫ10 element of the promoter and recognized as nontemplate ssDNA by region 2 of 70 (3,15,16 is an essential component of the paused complex, it could be a target for recognition by Q, in addition to its role in recognizing the pause-inducing sequence. For Q , there is evidence for this interaction.

BACKGROUND: Myeloperoxidase (MPO) has shown potential as a marker for cardiovascular disease. Limited studies have been published with a variety of sample types, resulting in a wide range of MPO values. Little is known or understood about the impact of collection tube type and preanalytical handling of specimens for MPO determination.

Objective-Soluble fms-like tyrosine kinase 1 (sFlt1) is involved in the pathophysiology of preeclampsia and coronary artery disease.Because sFlt1 has a heparin-binding site, we investigated whether or not heparin releases sFlt1 from the extracellular matrix. Methods and Results-We measured sFlt1 before and after heparin administration in 135 patients undergoing coronary angiography, percutanous coronary intervention, or both. sFlt1 was increased directly after heparin administration (from 254 to 13 440 pg/mL) and returned to baseline within 10 hours. Umbilical veins and endothelial cells treated with heparin released sFlt1. Heparinase I and III also increased sFlt1. Mice treated with heparin had elevated sFlt1 serum levels. Their serum inhibited endothelial tube formation. The time point showing values directly after CA/PCI is divided into CA only (single-dose heparin) and PCI (second dose). nϭ135, Pϭ0.0009. In patients with high sFlt1 values before PCI, blood was drawn after heparin administration. B, Placental growth factor (PLGF) and vascular endothelial growth factor (VEGF) before and after heparin and sFlt1/PLGF and sFlt1/VEGF ratios. nϭ20, *PϽ0.0001 and †PϽ0.05 vs at admission. Conclusion-Heparin