Are hypertensive disorders in pregnancy associated with congenital malformations in offspring? Evidence from the WHO Multicountry cross sectional survey on maternal and newborn health.

BACKGROUND: Annually, around 7.9 million children are born with birth defects and the contribution of congenital malformations to neonatal mortality is generally high. Congenital malformations in children born to mothers with hypertensive disorders during pregnancy has marginally been explored. METHODS: Country incidence of congenital malformations was estimated using data on the 310 401 livebirths of the WHO Multicountry Survey which reported information from 359 facilities across 29 countries. A random-effect logistic regression model was utilized to explore the associations between six broad categories of congenital malformations and the four maternal hypertensive disorders "Chronic Hypertension", "Preeclampsia" and "Eclampsia" and "Chronic hypertension with superimposed preeclampsia". RESULTS: The occupied territories of Palestine presented the highest rates in all groups of malformation except for the "Lip/Cleft/Palate" category. Newborns of women with chronic maternal hypertension were associated with a 3.7 (95 % CI 1.3-10.7), 3.9 (95 % CI 1.7-9.0) and 4.2 (95 % CI 1.5-11.6) times increase in odds of renal, limb and lip/cleft/palate malformations respectively. Chronic hypertension with superimposed preeclampsia was associated with a 4.3 (95 % CI 1.3-14.4), 8.7 (95 % CI 2.5-30.2), 7.1 (95 % CI 2.1-23.5) and 8.2 (95 % CI 2.0-34.3) times increase in odds of neural tube/central nervous system, renal, limb and Lip/Cleft/Palate malformations. CONCLUSIONS: This study shows that chronic hypertension in the maternal period exposes newborns to a significant risk of developing renal, limb and lip/cleft/palate congenital malformations, and the risk is further exacerbate by superimposing eclampsia. Additional research is needed to identify shared pathways of maternal hypertensive disorders and congenital malformations.

Higher-plant plasma membrane cytochrome b561: a protein in search of a function.

During the past twenty years evidence has accumulated on the presence of a specific high-potential, ascorbate-reducible b-type cytochrome in the plasma membrane (PM) of higher plants. This cytochrome is named cytochrome b561 (cyt b561) according to the wavelength maximum of its alpha-band in the reduced form. More recent evidence suggests that this protein is homologous to a b-type cytochrome present in chromaffin granules of animal cells. The plant and animal cytochromes share a number of strikingly similar features, including the high redox potential, the ascorbate reducibility, and most importantly the capacity to transport electrons across the membrane they are located in. The PM cyt b561 is found in all plant species and in a variety of tissues tested so far. It thus appears to be a ubiquitous electron transport component of the PM. The cytochromes b561 probably constitute a novel class of transmembrane electron transport proteins present in a large variety of eukaryotic cells. Of particular interest is the recent discovery of a number of plant genes that show striking homologies to the genes coding for the mammalian cytochromes b561. A number of highly relevant structural features, including hydrophobic domains, heme ligation sites, and possible ascorbate and monodehydroascorbate binding sites are almost perfectly conserved in all these proteins. At the same time the plant gene products show interesting differences related to their specific location at the PM, such as potentially N-linked glycosylation sites. It is also clear that at least in several plants cyt b561 is represented by a multigene family. The current paper presents the first overview focusing exclusively on the plant PM cyt b561, compares it to the animal cyt b561, and discusses the possible physiological function of these proteins in plants.

High level accumulation of single-chain variable fragments in the cytosol of transgenic Petunia hybrida.

The accumulation of five murine single-chain variable fragments, binding to dihydroflavonol 4-reductase, was analyzed in transgenic Petunia hybrida plants. The five scFv-encoding sequences were cloned in an optimized plant transformation vector for expression in the cytosol under control of the 35S promoter. In a transient expression assay we found that the scFv expression levels were reproducible and correlated with those in stably transformed petunia. Our results show that accumulation in the cytosol strongly depends on the intrinsic properties of the scFv fragment. Three of the five scFv fragments accumulated to unexpectedly high levels in the cytosol of the primary transformants, but no phenotypic effect could be detected. Experimental results indicate that one of the scFv fragments accumulated in the cytosol to 1% of the total soluble protein as a functional antigen-binding protein in the absence of disulphide bonds. This observation supports the idea that certain antibody fragments do not need disulphide bonds to be stable and functional. Such scFv scaffolds provide new opportunities to design scFv fragments for immunomodulation in the cytosol.