Telomere length is similar in different organs of the human fetus but variable among fetuses. During extrauterine life telomere length is highly variable among individuals and longer in women than men. In the present work we addressed the following questions: 1) Are there sex-related differences in telomere length at birth? 2) Is there synchrony (i.e. correlation in length) of telomeres in tissues within the newborn? 3) Is the variability in telomere length among newborns as large as that in adults? We studied normal male and female newborns who donated DNA samples from three sources: white blood cells, umbilical artery, and foreskin. Telomere length was measured by the mean length of the terminal restriction fragments (TRF). TRF length was not different between male and female newborns. It was highly synchronized among the DNA samples from white blood cells, umbilical artery and skin within individual donors but exhibited a high variability among donors. We conclude that there is no evidence for the effect of sex on telomere length at birth, suggesting that longer telomeres in women than men arise from a slower rate of telomeric attrition in women. The variability in telomere length among newborns and synchrony in telomere length within organs of the newborn are consistent with the concept that variations in telomere length among adults are in large part attributed to determinants (genetic and environmental) that start exerting their effect in utero. The loss of telomere repeats associated with replication of human somatic cells in culture is central to the concept that in these cells telomeres serve as a "mitotic clock" (1). In human beings, telomere length of replicating somatic cells is inversely related to donor age (2-4), highly variable among donors of the same age (2-4), highly heritable (3, 5), and longer in women than in men (5, 6). These observations suggest that in human somatic cells telomere length is a biomarker of replicative history not only in vitro but also in vivo and that it is modified by genetic factors and sex.In contrast to the considerable information available about telomere length in humans during extrauterine life, little is known about telomere length during intrauterine life. Limited information indicates that in utero, the length of human telomeres is highly synchronized in that it is similar among tissues of the same fetus, but variable among fetuses (7). The present research was undertaken to answer the following key questions about telomere length: 1) Do male and female newborns differ in the length of their telomeres? 2) At birth, is there synchrony of telomere length in cells derived from three tissues (blood, umbilical artery and foreskin)? 3) Is the variability of telomere length among newborns the same as that observed in adults? METHODS Subjects.We studied normal newborns born at two hospitals, i.e. The University Hospital of the University of Medicine and Dentistry of NJ (UMDNJ) in Newark, NJ, and the affiliated Hackensack University Medical Center in Hackensack, NJ. Gen...

Editing of the nonprotein amino acid homocysteine by certain aminoacyl-tRNA synthetases results in the formation of the thioester homocysteine thiolactone. Here we show that in the presence of physiological concentrations of homocysteine, methionine, and folic acid, human umbilical vein endothelial cells efficiently convert homocysteine to thiolactone. The extent of this conversion is directly proportional to homocysteine concentration and inversely proportional to methionine concentration, suggesting involvement of methionyl-tRNA synthetase. Folic acid inhibits the synthesis of thiolactone by lowering homocysteine and increasing methionine concentrations in endothelial cells. We also show that the extent of post-translational protein homocysteinylation increases with increasing homocysteine levels but decreases with increasing folic acid and HDL levels in endothelial cell cultures. These data support a hypothesis that metabolic conversion of homocysteine to thiolactone and protein homocysteinylation by thiolactone may play a role in homocysteine-induced vascular damage.

Background-Antiretrovirals (ARVs) are recommended for maternal health and to reduce HIV-1 mother-to-child transmission, but suboptimal adherence can counteract its benefits.

Telomere length, measured by terminal restriction fragments, was examined in tissues from human fetuses of gestational ages estimated as 15-19 weeks. The length of telomeres was similar in most fetal tissues. However, there were significant variations in telomere length among fetuses, with no apparent relationship between gestational age and telomere length. We conclude that synchrony in telomere length exists among tissues of the human fetus. This synchrony is apparently lost during extrauterine life.

Background Conflicting results have been reported among studies of protease inhibitor (PI) use during pregnancy and preterm birth. Uncontrolled confounding by indication may explain some of the differences between studies. Methods 777 HIV-infected pregnant women in a prospective cohort who were not on ARV at conception were studied. Births < 37 weeks gestation were reviewed and deliveries due to spontaneous labor and/or rupture of membranes were identified. Risk of preterm birth and low birth weight (< 2,500 grams) were evaluated using multivariable logistic regression. Results 72% of the study population received combination ARV with PI during pregnancy and a total of 130 preterm births were observed. In adjusted analyses, combination ARV with PI was not significantly associated with spontaneous preterm birth compared to ARV without PI (Odds ratio (OR): 1.22, 95% confidence interval (CI): 0.70, 2.12). Sensitivity analyses including women on ARV prior to pregnancy also did not identify a significant association (OR: 1.34, 95% CI: 0.84, 2.16). Low birth weight results were similar. Conclusions No evidence of an association between use of combination ARV with PI during pregnancy and preterm birth was found. Our study supports current guidelines which promote consideration of combination ARV for all HIV-infected pregnant women.