Enhanced expression of Fas-associated proteins in decidual and trophoblastic tissues in pregnancy-induced hypertension

PROBLEM: To determine if feto-placental tissues from gestations complicated by pregnancy-induced hypertension (PIH) have altered expression of Fas-associated proteins. METHOD OF STUDY: The expression of several Fas-related proteins was determined in fetal membranes, decidua, and placentas obtained from PIH-affected (n = 12, age range 32-36 weeks) and normal (n = 6, age range 37-41 weeks) gestations. Paraffin-embedded tissue sections were stained with specific monoclonal antibodies to Fas, Fas ligand (FasL), caspase-3, and bax. RESULTS: We observed greater expression of Fas and FasL in amnion and decidua from PIH-affected gestations than in normal controls. Intense staining was observed only in the perivascular endothelium (caspase-3) and in decidual cells (bax) from PIH gestations. CONCLUSION: Differential expression of Fas-related proteins in fetal membranes, decidua, and placentas from PIH-affected gestations is consistent with increased apoptosis, and suggests activation of the Fas/FasL pathway in a tissue-specific manner.     

1141610241Altered expression of HuR, an mRNA stabilizing protein, mediates aberrant Placenta Growth Factor (PlGF) expression in preeclampsia

Background:  Control of mRNA stability is an essential regulatory process in eukaryotic gene expression. HuR, a 3'UTR mRNA binding protein, can protect AU-rich mRNA from degradation in response to stresses. PlGF, an angiogenic growth factor, contains two consensus AU-rich sites suggesting that under normal conditions HuR may protect PlGF mRNA from degradation. Trophoblast expression of PlGF is significantly decreased in preeclampsia and by hypoxia in vitro . We hypothesize that decreased levels of cytoplasmic HuR may contribute to decreased PlGF expression in hypoxic and preeclamptic trophoblast.
Methods:  Western blots were used to determine relative effects of in vitro hypoxia on HuR protein expression and subcellular localization in trophoblast. Immunohistochemistry was used to compare HuR expression patterns in trophoblast of preeclamptic and normal placentae.
Results:  Cytoplasmic expression of HuR was decreased 1.4 fold in the cytoplasm and 1.2 fold in the nucleus of JEG3 cells. A shift in HuR was more apparent in primary trophoblast with a greater than 2-fold decrease in the cytoplasm and a 1.4 fold decrease in the nucleus following 24 hr of hypoxia. Immunohistochemical analyses detected HuR expression in near term trophoblast in situ . However, this technical approach did not detect a significant change in HuR expression between normal and preeclamptic trophoblast.
Conclusions:  HuR expression is decreased in hypoxic trophoblast, at least in vitro , which may provide a causal link to decreased PlGF mRNA expression. Down regulation of trophoblast PlGF expression is thought to contribute to the pathophysiology associated with preeclampsia including the relative lack of perfusion of the placenta and systemic renal effects.     

Blood-brain barrier breakdown by cold injury. Polyamine signals mediate acute stimulation of endocytosis, vesicular transport, and microvillus formation in rat cerebral capillaries

Polyamines have been previously implicated in the mediation of blood-brain barrier breakdown induced by cryogenic injury (H Koenig, AD Goldstone, CY Lu, Biochem Biophys Res Commun 116:1039, 1983). We studied acute (less than 5 minute) changes in capillary ultrastructure, microvascular permeability, and the levels of polyamines and their rate regulating synthetic enzyme ornithine decarboxylase (ODC) in rat cerebral cortex after focal cold injury. Microvascular permeability was measured by relative transport of intravenously administered fluorescein. Capillary ultrastructure was studied by quantitative stereology and morphometry after intravenous administration of horseradish peroxidase. Focal cold injury induced a 2.5-, 3.8-, 1.7-, and 1.4-fold increase in the levels of ODC, putrescine, spermidine and spermine, and a 46-fold increase in fluorescein uptake in perilesional cortex. Few capillaries in control cortex contained endocytic pits or horseradish peroxidase-positive vesicles, whereas most capillaries near lesions showed these structures. Cryoinjury induced a 5-fold increase in the relative volume of microvilli and horseradish peroxidase vesicles, a 2.3-fold increase in area of luminal endocytic pits, and a 6.3-fold increase in area of abluminal exocytic pits. The ODC inhibitor alpha-difluoromethylornithine blocked the cryoinjury-induced changes in ODC, polyamines, fluorescein uptake, and capillary ultrastructure. Putrescine negated the effect of alpha-difluoromethylornithine or capillary ultrastructure, and was previously shown to nullify the alpha-difluoromethylornithine effects on polyamines and fluorescein permeability (cited above). These data link rapid changes in ODC and polyamines to blood-brain barrier breakdown, and suggest that the abnormal permeability is associated with an acute, polyamine-mediated stimulation of microvillus formation, endocytosis, and vesicular transport in capillary endothelium.     

Comparison of active and cancer registry-based follow-up for breast cancer in a prospective cohort study

The authors compared the relative effectiveness of two distinct follow-up designs in prospective cohort studies--the active approach, based on direct contact with study subjects, and the passive approach, based on record linkages with population-based cancer registries--utilizing available information from the New York University Women's Health Study (WHS) and the New York State Cancer Registry (NYSCR). The analyses were limited to breast cancer cases identified during the period 1985-1992, for which follow-up was considered reasonably complete by both the WHS and the NYSCR. Among 12,947 cohort members who reported a New York State address, 303 pathologically confirmed cases were identified through active follow-up and 284 through record linkage. Sixty-three percent of cancers were identified by both sources, 21% by the WHS only, and 16% by the NYSCR only. The agreement was appreciably better for invasive cancers. The percentage of cases identified only by the NYSCR was increased among subjects whose active follow-up was incomplete, as well as among nonwhites, obese patients, and parous patients. This suggests that relying on either type of follow-up alone may introduce certain biases in evaluating risk factors for breast cancer. Combining both approaches appears to be a better strategy in prospective cohort studies.     

A method for identifying comparison counties: application to a rural telemedicine evaluation project

The evaluation of telemedicine activity in rural communities is complicated by the fact that most telemedicine sites are chosen because of their existing telecommunications infrastructure and institutional relationships, not by a random selection process. In addition, it is difficult to draw conclusions about the effects of telemedicine without a careful analysis of parallel changes in communities which do not have access to telemedicine services. We have developed a method of identifying comparable counties based on an aggregate measure of health status. A set of 66 variables was collected in a previous project to develop a model to evaluate the relative health status of the population in Missouri. A stepwise regression was used to identify a subset of 15 variables that had the highest predictive value for the health status of a county. Distance measures were then used to identify six counties which were most similar to three telemedicine counties. The method can be used with any study set chosen non-randomly, to identify similar objects that can be used for comparative purposes.     

Intraoperative assessment of acute hemodynamic changes after partial left ventriculectomy

Partial left ventriculectomy (PLV) has been introduced as an alternative surgical therapy for patients with end-stage dilated cardiomyopathy. The physiological benefits of PLV are relatively unknown. Therefore, the objective of this study was to determine the acute effects of PLV by measuring cardiac function before and after PLV. Aortic and left ventricular pressures and aortic flow were measured in eight patients. Continuous, beat-to-beat data were recorded and compared pre-PLV and post-PLV with and without inferior vena cava (IVC) occlusions. PLV increased cardiac output (0.93+/-0.5, p = 0.01) as a result of increased stroke volume (5.12+/-4.24, p = 0.06) and heart rate (14.5+/-8.44, p = 0.02). Contractility (+/- dP/dt, 240.33+/-74.28, p = 0.001) and external work (650.8+/-320.4, p = 0.01) were also improved. Left ventricular end-diastolic elastance (0.15+/-0.14, p = 0.10) nearly doubled after PLV. Our results indicated an improved cardiac function as measured by increased cardiac output, stroke volume, ejection fraction (EF), and contractility.