Six years' experience with rapid karyotyping in prenatal diagnosis: Correlations between phenotype detected by ultrasound and fetal karyotype

From September 1985 to March 1992, 804 amniotic fluid samples from 64 different diagnostic centres of the Federal Republic of Germany were sent to our laboratory exclusively for rapid karyotyping. The average time needed for notification of the analysed karyotype was 4·65 days when the ‘pipette method’ was used for chromosome harvesting and 5·97 days when the ‘in situ’ technique was used. The overall incidence of chromosome aberrations was 15·3 per cent. Data are presented about the likelihood of abnormal ultrasound findings being caused by chromosome aberrations. These findings include polyhydramnios, oligohydramnios, growth retardation, fetal effusions, neural tube defects, craniofacial defects, heart defects, gastroschisis and omphalocele, gastrointestinal tract defects, urinogenital defects, and limb defects. In future, such data need to contain larger numbers of cases for each week of gestation. This will improve the risk evaluation for each case with abnormal ultrasound findings, which should lead to better management during pregnancy, delivery, and postnatal care for those who require rapid karyotyping.     

Designing environmental campaigns by using agent-based simulations: strategies for changing environmental attitudes

Agent-based computer simulation was used to create artificial communities in which each individual was constructed according to the principles of the elaboration likelihood model of Petty and Cacioppo [1986. The elaboration likelihood model of persuasion. In: Berkowitz, L. (Ed.), Advances in Experimental Social Psychology. Academic Press, New York, NY, pp. 123-205]. Campaigning strategies and community characteristics were varied systematically to understand and test their impact on attitudes towards environmental protection. The results show that strong arguments influence a green (environmentally concerned) population with many contacts most effectively, while peripheral cues have the greatest impact on a non-green population with fewer contacts. Overall, deeper information scrutiny increases the impact of strong arguments but is especially important for convincing green populations. Campaigns involving person-to-person communication are superior to mass-media campaigns because they can be adapted to recipients' characteristics.     

Atropisomers of 2,2′,3,3′,6,6′-hexachlorobiphenyl (PCB 136) exhibit stereoselective effects on activation of nuclear receptors in vitro

PCB 136 is an environmentally relevant chiral PCB congener, which has been found in vivo to be present in form of rotational isomers (atropisomers). Its atropselective biotransformation or neurotoxic effects linked with sensitization of ryanodine receptor suggest that it might interact also with other intracellular receptors in a stereospecific manner. However, possible atropselective effects of PCB 136 on nuclear receptor transactivation remain unknown. Therefore, in this study, atropselective effects of PCB 136 on nuclear receptors controlling endocrine signaling and/or expression of xenobiotic and steroid hormone catabolism were investigated. PCB136 atropisomers were found to exert differential effects on estrogen receptor (ER) activation; (+)-PCB 136 was estrogenic, while (?)-PCB 136 was antiestrogenic. In contrast, inhibition of androgen receptor (AR) activity was not stereospecific. Both PCB136 stereoisomers induced the constitutive androgen receptor (CAR)-dependent gene expression; however, no significant stereospecificity of PCB 136 atropisomers was observed. PCB136 was a partial inducer of the pregnane X receptor (PXR)-dependent gene expression. Here, (?)-PCB 136 was a significantly more potent inducer of PXR activity than (+)-PCB 136. Taken together, the present results indicate that at least two nuclear receptors participating in endocrine regulation or metabolism, ER and PXR, could be regulated in an atropselective manner by chiral PCB 136. The enantioselective enrichment of PCB atropisomers in animal and human tissues may thus have significant consequences for endocrine-disrupting effects of chiral ortho-substituted PCB congeners.     

Chiral polychlorinated biphenyls: absorption,metabolism and excretion—a review

Seventy eight out of the 209 possible polychlorinated biphenyl (PCB) congeners are chiral, 19 of which exist under ambient conditions as stable rotational isomers that are non-superimposable mirror images of each other. These congeners (C-PCBs) represent up to 6 % by weight of technical PCB mixtures and undergo considerable atropisomeric enrichment in wildlife, laboratory animals, and humans. The objective of this review is to summarize our current knowledge of the processes involved in the absorption, metabolism, and excretion of C-PCBs and their metabolites in laboratory animals and humans. C-PCBs are absorbed and excreted by passive diffusion, a process that, like other physicochemical processes, is inherently not atropselective. In mammals, metabolism by cytochrome P450 (P450) enzymes represents a major route of elimination for many C-PCBs. In vitro studies demonstrate that C-PCBs with a 2,3,6-trichlorosubstitution pattern in one phenyl ring are readily oxidized to hydroxylated PCB metabolites (HO-PCBs) by P450 enzymes, such as rat CYP2B1, human CYP2B6, and dog CYP2B11. The oxidation of C-PCBs is atropselective, thus resulting in a species- and congener-dependent atropisomeric enrichment of C-PCBs and their metabolites. This atropisomeric enrichment of C-PCBs and their metabolites likely plays a poorly understood role in the atropselective toxicity of C-PCBs and, therefore, warrants further investigation.