The effect of (2'-5') and (3'-5') phosphodiester linkages on conformational and stacking properties of cytidylyl-cytidine in aqueous solution

Conformational properties of (2'-5') and (3'-5') CpC have been determined by proton magnetic resonance spectroscopy at 220 MHz. The ribose ring structures are predominantly 3E with the exception of the ring from the 2'-phosphate fragment of C(2'-5')pC which exhibits an 2E pucker. Bases are oriented anti with respect to the ribose and the conformations about C4'-C5', C5'-O5', C3'-O3' (C2'-O2') are gg, g'g', and g+ in equilibrium g-, respectively. The dimers exist as mixtures of stacked (g+g+ and g-g- about the P-O(C) bonds) and unstacked species at 20 degrees C. Stacking is estimated to be 35% in both dimers.     

Reproductive efficiency as a social indicator

An index of reproductive effiency (RE) is proposed as a social indicator that will meet the need to consider various forms of pregnancy wastage, to compare their relative costs, and to guide reproductive health policy accordingly. This article discusses conceptual and measurement aspects of RE. Conversion of wanted to unwanted pregnancies and the reverse, interpretation of abortion in relation to other pregnancy outcomes, defining the end point for the reproductive process and criteria for the events to be included as significant outcomes are conceptual issues. Measurement problems include: whether aggregation is justified, prospective and retrospective tracking of outcomes, record limitations, duplication of adversities in a single pregnancy, and selection of optimal rate for comparison. A measurement of RE for the entire United States based on the National Natality Survey of 1964-1966 is presented, showing 74.5 percent of pregnancies resulting in healthy liveborn infants. For those years, data on abortions could not be included. Within the group of reported pregnancy losses, the importance of congenital abnormalities and low-birth-weight babies is enhanced by application of economic weights based on associated medical care costs. Changing opportunities for birth timing, prenatal and infant care, and control of family size are social means of reducing adverse outcomes associated with teenage pregnancy and high-parity births, often found together with poverty. Successive increments in RE may be progressively more expensive to achieve, and cost effectiveness comparison will be necessary.     

T cells of patients with the Wiskott-Aldrich syndrome have a restricted defect in proliferative responses

The Wiskott-Aldrich syndrome (WAS) is a disease of profound thrombocytopenia and severe immune defects caused by an unidentified defective X chromosome gene. In this study, T lymphocyte function is examined using a panel of allospecific WAS patient T cell lines, previously found to express the abnormal disease gene and the cytoarchitectural defect characteristic of the disease. Although T cell lines from normal individuals proliferate vigorously in response to immobilized anti-CD3 mAb OKT3 and SPV-T3b, five of seven WAS patient T cell lines failed to proliferate and two lines showed significantly decreased proliferation when challenged with the immobilized anti-CD3 mAb. The deficient responsiveness of the WAS T cell lines to immobilized anti-CD3 mAb is a restricted defect, because the cells proliferate normally when challenged with allospecific Ag, PHA, or PMA plus ionomycin. Addition of anti-CD28 mAb did not correct the deficient proliferation of the WAS cells challenged with immobilized anti-CD3. Deficient response of the WAS T cell lines to immobilized anti-CD3 was detected also when earlier events of the proliferation process, IL-2 production and up-regulation of activation Ag CD69 and CD28, were measured. On the other hand, WAS cell lines did not differ from normal cell lines in binding of anti-CD3 mAb, mobilization of Ca2+ in response to soluble OKT3, and tyrosine phosphorylation and GTP binding of the CD3 zeta-chain in response to OKT3. Cumulatively, these findings demonstrate a striking restricted defect in the proliferative response of WAS T cells, which because it is found in cell lines free of secondary changes that occur in the patient circulation must be a reflection of the inherited defective disease gene product.