High maternal vitamin E intake by diet or supplements is associated with congenital heart defects in the offspring

Objective  To study associations between maternal dietary and supplement intake of antioxidants vitamin E, retinol and congenital heart defects (CHDs).
Design  Case–control study.
Setting  Erasmus MC, University Medical Center Rotterdam, the Netherlands.
Population  Participants were 276 case mothers of a child with CHD and 324 control mothers with their children.
Methods  Food frequency questionnaires covering the intake of the previous 4 weeks were filled out at 16 months after the index pregnancy. Data were compared between cases and controls using the Mann–Whitney U test. Risk estimates for the association between CHD and dietary intake of vitamin E and retinol were estimated in a multivariable logistic regression model.
Main outcome measures  Medians (5–95th percentile) and odds ratios with 95% CI.
Results  Dietary vitamin E intake was higher in case mothers than in controls, 13.3 (8.1–20.4) and 12.6 (8.5–19.8) mg/day ( P = 0.05). CHD risk increased with rising dietary vitamin E intakes ( P -trend = 0.01). Periconception use of vitamin E supplements in addition to a high dietary vitamin E intake above 14.9 mg/day up to nine-fold increased CHD risk. Retinol intakes were not significantly different between the groups and not associated with CHD risk.
Conclusions  High maternal vitamin E by diet and supplements is associated with an increased risk of CHD offspring.     

Expression and silencing of the microtubule-associated protein Tau in breast cancer cells

The microtubule-associated protein Tau has been reported to be a predictive factor for clinical response to taxanes in metastatic breast cancer. We generated a panel of eight taxane-resistant variants from four human breast cancer cell lines (MCF-7, T-47D, MDA-MB-231, and BT-549). Four variants had higher levels of Tau compared with their T-47D and MDA-MB-231 parental cells. Using isoform-specific primers, we found that Tau 0N, 1N, 2N, 3R, and 4R isoforms are overexpressed in the resistant variants, as is Tau exon 6 but not exons 4A or 8. To determine whether Tau overexpression produces resistance to taxanes, we derived three independent T-47D clones stably overexpressing Tau 3R and 4R isoforms. Tau overexpression did not result in taxane resistance compared with parental cells transfected with vector alone. We then knocked down Tau expression in three cell lines that expressed Tau constitutively (MCF-7 and ZR-75-1 breast cancer cells, and OVCAR-3 ovarian cancer cells). Lentivirus-mediated silencing of Tau expression in MCF-7 and OVCAR-3 cells did not result in increased taxane sensitivity compared with luciferase short hairpin RNA-infected cells and uninfected parental cells. Transient silencing using Tau-specific small interfering RNAs also did not alter taxane sensitivity relative to nontargeting controls in both MCF-7 and ZR-75-1 cells. These results show that neither overexpression nor depletion of Tau modulates cellular sensitivity to taxanes. Although Tau overexpression has been reported to be a predictive marker of taxane resistance, it is not likely to be a direct mechanism of taxane resistance in breast cancer.     

CD80 expression is decreased in hyperplastic lymph nodes of HIV+ patients

A centrofollicular hyperplasia is present within secondary lymphoid organs during all the asymptomatic phase of the HIV disease. Although this hyperplasia has been well characterized by histological studies, the nature of the phenotypic alterations in B cell populations occurring within HIV+ lymphoid organs remains to be established. By immunohistochemistry, we thus investigated whether a particular germinal center (GC) B cell population was increased during HIV-induced hyperplasia and whether any phenotypic change was specific to HIV-1 infection. As compared to normal tonsils (three cases) and HIV- hyperplastic lymph nodes (eight patients), we observed a loss of GC polarization in all HIV+ sections (11 patients), with no more delineation between dark and light zones, as shown by Ki67, CD10, CD77, CD95 and CD86 staining. In contrast to CD86 expression which remained as intensive in HIV+ as in HIV- lymph nodes, CD80 staining was strongly decreased in GC of HIV+ lymph nodes but not in their extrafollicular zones. The loss of CD80 expression from CD19+ B cells was also observed by cytometric analysis of cell suspensions of three HIV+ patients. Although we found no evidence of an increase in a particular GC B cell subset in HIV-1-induced hyperplasia, the strong GC disorganization observed may induce impaired cell-cell interactions and thus participate in the loss of CD80 antigen. In contrast to HIV- situations where CD80 and CD86 was similarly expressed on B cells, the lower level of CD80 expression in HIV+ GC may favor Th2 T cell responses through CD86-CD28 interactions.      

Changes on radiographs of wives of workers exposed to asbestos

Between January and March 1986, 117 wives of insulation workers exposed to asbestos were screened by means of chest radiography, pulmonary function testing, and a detailed questionnaire. The final study group included 93 women over 40 years of age. Eighteen of these (19.4%) demonstrated pleural changes consistent with asbestos exposure, including pleural plaque (88.9%), diaphragm plaque (27.8%), pleural calcification (16.6%), and diffuse pleural thickening (5.5%). In statistical correlation between the groups with normal and abnormal radiographs, the only factor that proved significant was the year of first exposure (the duration of the latent period). Finally, radiographs of the husbands were compared for 17 of the 18 wives with radiographic abnormalities. Fourteen of the husbands (82%) demonstrated more severe radiographic changes than their wives.     

Shape and dimensions of cardiac chambers: importance of CT section thickness and orientation

Three-dimensional (3D) computed tomography (CT) scan data were used to quantitate the geometry of all heart chambers. The Dynamic Spatial Reconstructor (DSR) was used to scan dogs with in situ casts of the cardiac chambers. Chamber volumes estimated from DSR images were accurate within 5% of water displacement volume measurements of the actual casts for chambers greater than 11 ml and within 10% of water displacement volumes for chambers less than 11 ml. Anatomic features of the actual cast correlated closely with anatomy visible in computer-generated surface images of the 3D DSR image data. The important effect of reconstructed section thickness and orientation on the fidelity of 3D cardiac geometry is demonstrated.     

ES2, a gene deleted in DiGeorge syndrome, encodes a nuclear protein and is expressed during early mouse development, where it shares an expression domain with a Goosecoid-like gene

ES2 is a gene deleted in DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS) which has homologs in species as distant as Caenorhabditis elegans and Drosophila . The function of ES2 is unknown, and the predicted protein sequence does not contain motifs which suggest a particular role in the developmental defects present in DGS and VCFS. Here we show that the mouse homolog, Es2 , is transcribed in two forms resulting from the use of alternative polyadenylation signals. Structural analysis programs predict that the Es2 -encoded peptide has a coiled-coil domain, and transfection experiments with an Es2 -green fluorescent protein (GFP) fusion construct show that the peptide is recruited into the nucleus. Es2 is highly expressed during mouse embryogenesis from E7 onwards. In situ hybridization with an RNA probe revealed that the gene is widely expressed; however, relatively higher expression was detected in the nervous system, with a particularly high area of expression in a sub-region of the pons. The Es2 expression domain in the pons is shared with a Goosecoid-like gene ( Gscl) which is located upstream of Es2 , and raises the possibility that the two genes share regulatory elements and/or interact in this region of the developing brain. This finding suggests that different genes in the deleted region may be functionally related and might explain the occurrence of the characteristic phenotype in patients with non-overlapping genetic lesions.      

RELAXATION OF RABBIT MIDDLE CEREBRAL ARTERIES IN VITRO BY H1 HISTAMINERGIC AGONISTS IS INHIBITED BY INDOMETHACIN AND TRANYLCYPROMINE

The H1-histaminergic agonists 2-pyridylethylamine (2-PEA) and 2-methylhistamine relaxed potassium-constricted, perfused, rabbit middle cerebral arteries at low concentrations (3 x 10(-11) to 3 x 10(-8) M) and constricted them at high concentrations (3 x 10(-7) to 3 x 10(-4) M). The relaxation and the contraction were not antagonized by propranolol (up to 3 x 10(-6) M) given 30 min before, suggesting that beta-adrenergic mechanisms were not involved. When 2-PEA was tested on arteries constricted with uridine triphosphate (UTP), similar results were obtained. In the UTP-constricted arteries, the 2-PEA-induced responses were competitively antagonized by 3 x 10(-9) M mepyramine. Together with previous work (Ea Kim et al., 1986), these results are compatible with the hypothesis that H1-receptors were responsible for both the relaxation and the contraction observed. When either indomethacin (10(-8), 3 x 10(-7), or 10(-5) M), dexamethasone (10(-5) M), or tranylcypromine (10(-5) or 10(-4) M) were tested on the response to 2-PEA or 2-methylhistamine, these inhibitors suppressed the relaxation or reversed it to a contraction. Furthermore, they potentiated the contraction induced by these agonists. These results favour the hypothesis that the H1-mediated relaxation in rabbit cerebral arteries may in part involve the release of prostaglandins, especially prostacyclin. The participation of such a prostanoid in histaminergic relaxation seems exclusively an H1-mediated mechanism, since the relaxation induced by the H2-agonist dimaprit (in the presence of mepyramine) was not antagonized by either indomethacin (3 x 10(-7) M) or tranylcypromine (10(-4) M).