Proteins of human placental microvilli: II. Identification and topology of the plasma membrane proteins

We have investigated the location of proteins in the transverse plane of the plasma membrane of microvilli isolated from the syncytiotrophoblast layer of the human term placenta. Microvillous proteins were labelled with 125I under reaction conditions where those proteins exposed on the maternal-facing surface of the microvilli were most heavily labelled. The proteins were then solubilized and subjected to one- and two-dimensional electrophoresis followed by protein staining and autoradiography. More than 65 proteins, differing in molecular weight or isoelectric point or both, were identified, and these were classified into three groups: weakly, moderately heavily, and heavily labelled. The microvilli were in the form of intact vesicles that were correctly orientated ('right-side out'). Thus the extent of labelling of each protein could be used as an indication of the extent of its exposure on the maternal-facing surface of the microvilli. Human serum albumin was present on the surface of the isolated, washed microvilli, but was probably a contaminant originating from maternal blood.     

Cellular pharmacology of P-ethoxy antisense oligonucleotides targeted to Bcl-2 in a follicular lymphoma cell line

A P-ethoxy oligonucleotide (oligo), 20 bases long and specific for the translation initiation site of human Bcl-2 mRNA, was incorporated into liposomes to increase its intracellular delivery. This oligo selectively inhibited Bcl-2 protein expression and induced growth inhibition in t(14;18)-positive transformed follicular lymphoma (FL) cell lines. We studied the inhibitory effects of shorter liposomal P-ethoxy oligos (7, 9, 11 or 15 mer) in order to determine the activity of different oligo chain lengths targeted to the same Bcl-2 mRNA. At 12 μM, all the oligos inhibited the growth of a FL cell line. We compared the 7-mer oligo with the 20-mer oligo. The two oligos inhibited Bcl-2 protein expression similarly: 66% and 60% for the 7- and 20-mer, respectively. The uptake and retention of both oligos were also very similar. Our results indicate that the Bcl-2 inhibitory activity is maintained with P-ethoxy antisense oligos ranging from 7 to 20 bases.     

A Catholic ethical approach to human reproductive technology

This article presents the Catholic Christian tradition and teaching on the moral respect due to human life from conception, supported by natural law moral philosophical reasoning. This approach contrasts with the ethical views of secular philosophers on human embryo research for therapeutic purposes. The challenges for Catholic healthcare institutions is to find ethical ways of using suitable pluripotent stem cells for therapies without creating or destroying human embryos. Catholic teaching on infertility treatment and reproductive technology are presented with emphasis given to the ethical need for children to be conceived and born of the marriage union compared with alterative ethical approaches for the use of infertility treatment and reproductive technology.     

Prenatal origins of adult disease

PURPOSE OF REVIEW: Human epidemiological and animal studies show that many chronic adult conditions have their antecedents in compromised fetal and early postnatal development. Developmental programming is defined as the response by the developing mammalian organism to a specific challenge during a critical time window that alters the trajectory of development with resulting persistent effects on phenotype. Mammals pass more biological milestones before birth than any other time in their lives. Each individual's phenotype is influenced by the developmental environment as much as their genes. A better understanding is required of gene-environment interactions leading to adult disease. RECENT FINDINGS: During development, there are critical periods of vulnerability to suboptimal conditions when programming may permanently modify disease susceptibility. Programming involves structural changes in important organs; altered cell number, imbalance in distribution of different cell types within the organ, and altered blood supply or receptor numbers. Compensatory efforts by the fetus may carry a price. Effects of programming may pass across generations by mechanisms that do not necessarily involve structural gene changes. Programming often has different effects in males and females. SUMMARY: Developmental programming shows that epigenetic factors play major roles in development of phenotype and predisposition to disease in later life.     

Late event-related potential changes in alcoholics

The P3 component of the event-related potential (ERP) was recorded during a Go/No-Go task from 42 alcoholic subjects, abstinent for 11-63 days, and 66 normal adult volunteers. In two different tasks, ERPs were elicited by visually presented words which provided explicit response instructions to Go (PUSH) or No-Go (WAIT). In the Noise Task, half of both Go and No-Go stimuli were degraded with ampersands (&P&U&S&H&, &W&A&I&T&). In the Probability Task, the probability of the Go stimulus was 25% and No-Go 75% on one run and the proportion reversed on another run. For both tasks, the amplitude of alcoholics' P3 was smaller than that of controls to the Go but not to the No-Go stimulus. There was a similar, but less pronounced trend for P3 latency to be delayed in alcoholic subjects for the Go, but not No-Go stimuli for the Noise Task. The P3 changes in alcoholics are consistent with those seen in several disease states which produce cognitive impairment.