Characterization of a membrane-associated estrogen receptor in a rat hypothalamic cell line (D12)

The ability of estrogens to produce rapid changes in cellular function has been firmly established. The question remains whether these changes are mediated by a modified form of the nuclear estrogen receptor (ER) that is associated with the plasma membrane (mER) or by a completely novel membrane receptor. Therefore, we characterized the biochemical properties of the nuclear and membrane-associated ERs expressed endogenously in a rat hypothalamic endothelial cell line (D12). Radioligand binding experiments using D12 membrane fractions showed that these cells exhibit properties consistent with a binding site specific for estrogens (mER). Equilibrium binding assays using [¹²⁵I]16-α-iodo-3,17-β-estradiol revealed saturable binding to mER, an affinity value similar to nuclear ER, with differing receptor expression levels. Competition assays revealed that 9 of 12 ER ligands tested had comparable affinities for mER and ER. For example, 17-α-estradiol and estrone had similar binding characteristics for both receptors while differences were noted for raloxifene, 17β-estradiol (E2), and genistein. Western blot and immunocytochemical analyses using antibodies specific for ERα confirmed that D12 cells expressed a membrane-associated protein with a molecular mass (67 kDa) similar to that of ERα that colocalized with caveolae-enriched membranes. A rapid increase in intracellar Ca²⁺ levels in the presence of E2 suggests that mER can mediate physiologic changes through calcium mobilization. These data support the expression of mER in these brain-derived endothelial cells that is similar to, but biochemically distinguishable from, nuclear ERα.     

Measurement of the interleukin family member ST2 in patients with acute dyspnea: results from the PRIDE (Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department) study.

OBJECTIVES: The aim of this study was to examine the value of measurement of the interleukin-1 receptor family member ST2 in patients with dyspnea. BACKGROUND: Concentrations of ST2 have been reported to be elevated in patients with heart failure (HF). METHODS: Five hundred ninety-three dyspneic patients with and without acute destabilized HF presenting to an urban emergency department were evaluated with measurements of ST2 concentrations. Independent predictors of death at 1 year were identified. RESULTS: Concentrations of ST2 were higher among those with acute HF compared with those without (0.50 vs. 0.15 ng/ml; p < 0.001), although amino-terminal pro-brain natriuretic peptide (NT-proBNP) was superior to ST2 for diagnosis of acute HF. Median concentrations of ST2 at presentation to the emergency department were higher among decedents than survivors at 1 year (1.08 vs. 0.18 ng/ml; p < 0.001), and in multivariable analyses, an ST2 concentration > or =0.20 ng/ml strongly predicted death at 1 year in dyspneic patients as a whole (HR = 5.6, 95% confidence interval [CI] 2.2 to 14.2; p < 0.001) as well as those with acute HF (hazard ratio [HR] = 9.3, 95% CI 1.3 to 17.8; p = 0.03). This risk associated with an elevated ST2 in dyspneic patients with and without HF appeared early and was sustained at 1 year after presentation (log-rank p value <0.001). A multi-marker approach with both ST2 and NT-proBNP levels identified subjects with the highest risk for death. CONCLUSIONS: Among dyspneic patients with and without acute HF, ST2 concentrations are strongly predictive of mortality at 1 year and might be useful for prognostication when used alone or together with NT-proBNP.     

Improvement in glucose tolerance after one year of follow-up in a Hindu community in Africa

Oral glucose tolerance was studied following a 75 g glucose load in 108 (82.4%) of 131 male and 110 (79.1%) of 139 female members of a Hindu subcommunity aged 15 years and over in Dar es Salaam. One year later, the glucose tolerance tests were repeated in 93 (86.1%) and 93 (84.5%) of the 108 male, and 110 of the female subjects, respectively. In the first survey, 25 (26.9%) of the 93 male and 24 (25.8%) of the 93 female subjects had impaired glucose tolerance (IGT), 6 (6.4%) and 15 (16.1%), respectively, had diabetes mellitus; and 62 (66.7%) and 54 (58.1%), respectively, had normal glucose tolerance. In the repeat survey, of the 93 male and 93 female subjects, 8 (8.6%) and 7 (7.5%) had IGT, 4 (4.3%) and 10 (10.8%) had diabetes; and 81 (87.1%) and 76 (81.7%) were normal, respectively. Of the 21 subjects diagnosed as having diabetes in the first survey, 13 (61.9%) continued to show diabetic glucose tolerance; 4 (19%) IGT and 4 (19%) had normal glucose tolerance with no gender difference. One (1.6%) of the 62 male subjects and none of the 54 females with normal glucose tolerance in the first survey progressed to IGT, while the remainder retained normal glucose tolerance. Diabetes and IGT rates in both surveys were higher for the older than the younger persons. A significant fall in mean fasting and post-75 g blood glucose levels, and in mean systolic and diastolic pressure levels was observed between the first and second surveys in both genders. There was, however, no significant difference in body mass index (BMI), serum total cholesterol and triglyceride levels between surveys, suggesting that major dietary changes had not taken place. Male subjects who showed persistent IGT had significantly lower mean level of body mass index (kg/m²) than subjects who reverted to normal, whilst for the whole group those who had persistent IGT were older. It is tempting to speculate that these changes were due to community action. However, in view of the lack of change in weight and lipids and similar results in other communities in Tanzania when retested at 1 week, further studies are needed to establish the significance of the findings.     

HIV gp120 receptors on human dendritic cells

Dendritic cells (DCs) are important targets for human immunodeficiency virus (HIV) because of their roles during transmission and also maintenance of immune competence. Furthermore, DCs are a key cell in the development of HIV vaccines. In both these settings the mechanism of binding of the HIV envelope protein gp120 to DCs is of importance. Recently a single C-type lectin receptor (CLR), DC-SIGN, has been reported to be the predominant receptor on monocyte-derived DCs (MDDCs) rather than CD4. In this study a novel biotinylated gp120 assay was used to determine whether CLR or CD4 were predominant receptors on MDDCs and ex vivo blood DCs. CLR bound more than 80% of gp120 on MDDCs, with residual binding attributable to CD4, reconfirming that CLRs were the major receptors for gp120 on MDDCs. However, in contrast to recent reports, gp120 binding to at least 3 CLRs was observed: DC-SIGN, mannose receptor, and unidentified trypsin resistant CLR(s). In marked contrast, freshly isolated and cultured CD11c(+ve) and CD11c(-ve) blood DCs only bound gp120 via CD4. In view of these marked differences between MDDCs and blood DCs, HIV capture by DCs and transfer mechanisms to T cells as well as potential antigenic processing pathways will need to be determined for each DC phenotype.     

Parent–Adolescent Relationship Quality and Nondisclosure as Mediators of the Association Between Exposure to Community Violence and Psychological Distress

Background

African American youth residing in urban poverty have been shown to be at increased risk for exposure to violence and for psychological symptoms, but there has been little investigation of mediating processes that might explain this association.

Objectives

This study tested the quality of parent–adolescent relationships and adolescent nondisclosure to adults as mediating mechanisms through which exposure to community violence may lead to psychological symptoms.

Methods

The current study surveyed a sample of 152 low-income urban African American early adolescents (aged 12–14). Participants completed self-report questionnaires assessing exposure to community violence, nondisclosure, parent–adolescent relationship, and psychological symptoms (i.e., internalizing and externalizing symptoms).

Results

Path analyses revealed that parent–adolescent relationship quality and nondisclosure both functioned as mediators of the relation between exposure to community violence and both internalizing and externalizing symptoms, though significant direct effects for violence exposure on externalizing symptoms remained. Decomposition of effects revealed that nondisclosure was a stronger mediator than parent–adolescent relationship quality. Results also indicated that exposure to violence can lead to externalizing (but not internalizing) symptoms first by way of parent–adolescent relationship quality and then nondisclosure.

Conclusions

Combined, these findings suggest that the development of preventive interventions designed to assist adults and parents improve communication and strengthen relationships with adolescents might reduce the negative effects of exposure to community violence on adolescent mental health.

     

Characteristics of Overweight and Obesity at Age Two and the Association with Breastfeeding in Hawai’i Women,Infants, and Children (WIC) Participants

Childhood obesity is associated with many adverse health effects during childhood and is linked to an increased risk for obesity in adulthood. The objective of this study was to determine the characteristics of early childhood overweight and obesity and assess the impact of breastfeeding. Data from Hawai’i’s Special Supplemental Nutrition Program for Women, Infants and Children (WIC) were analyzed for children 2 years of age born between 2005 and 2009 and their mothers. Childhood overweight and obesity was examined using a log-binomial regression model to estimate prevalence ratios. In the sample population, 12.5 % of children were overweight and 8.5 % of children were obese. Significant differences in childhood overweight and obesity were seen between breastfeeding duration and other socio-demographic groups. Children who were breastfed for 6 months or more had a lower risk of childhood obesity at age two compared to those who were never breastfed (APR 0.79, 95 % CI 0.69–0.91) with adjustment for child race/ethnicity, maternal age, trimester of prenatal care entry, maternal smoking status, and child birth weight. The prevalence of early childhood overweight and obesity is associated with shorter durations of breastfeeding. Early and continued breastfeeding support and education for mothers in the WIC program that improves duration of breastfeeding may help reduce the risk of early childhood obesity.     

Maternal Health Literacy Progression Among Rural Perinatal Women

This research examined changes in maternal health literacy progression among 106 low income, high risk, rural perinatal African American and White women who received home visits by Registered Nurse Case Managers through the Enterprise Community Healthy Start Program. Maternal health literacy progression would enable women to better address intermediate factors in their lives that impacted birth outcomes, and ultimately infant mortality (Lu and Halfon in Mater Child Health J 7(1):13–30, 2003; Sharma et al. in J Natl Med Assoc 86(11):857–860, 1994). The Life Skills Progression Instrument (LSP) (Wollesen and Peifer, in Life skills progression. An outcome and intervention planning instrument for use with families at risk. Paul H. Brookes Publishing Co., Baltimore, 2006) measured changes in behaviors that represented intermediate factors in birth outcomes. Maternal Health Care Literacy (LSP/M-HCL) was a woman’s use of information, critical thinking and health care services; Maternal Self Care Literacy (LSP/M-SCL) was a woman’s management of personal and child health at home (Smith and Moore in Health literacy and depression in the context of home visitation. Mater Child Health J, 2011). Adequacy was set at a score of (≥4). Among 106 women in the study initial scores were inadequate (<4) on LSP/M-HCL (83 %), and on LSP/M-SCL (30 %). Significant positive changes were noted in maternal health literacy progression from the initial prenatal assessment to the first (p < .01) postpartum assessment and to the final (p < .01) postpartum assessment using McNemar’s test of gain scores. Numeric comparison of first and last gain scores indicated women’s scores progressed (LSP/M-HCL; p < .0001) and (LSP/M-SCL; p < .0001). Elevated depression scores were most frequent among women with <4 LSP/M-HCL and/or <4 LSP/M-SCL. Visit notes indicated lack or loss of relationship with the father of the baby and intimate partner discord contributed to higher depression scores.