Elevated levels of homologous DNA recombination activity in the regenerating rat liver

We have characterized homologous DNA recombination activity in nuclear protein extracts prepared from quiescent and regenerating rat livers. Activity measured in regenerating liver extracts was elevated approximately 35-fold above control, and its appearance closely mirrored the first wave of DNA synthesis, peaking 24 hours after a regenerative stimulus, and returning fairly rapidly to basal levels. We also identified a strand-transferase protein of approximately 100 kDa whose presence in these extracts correlates with homologous recombination activity. Recent evidence suggests that mammalian somatic cells possess a recombinational DNA repair mechanism analogous to that described in the yeastSaccharomyces cerevisiae. Our results indicate that this recombinational repair process may be regulated in vivo by, or play a role in, progression through the cell division cycle.     

Nucleolin Promotes Homologous DNA Pairing in vitro

We purified to near homogeneity a previously identified 100 kDa mammalian homologous DNA pairing protein. The purified 100 kDa protein also catalyzed high levels of cell-free homologous DNA recombination activity. This ATP-dependent activity was capable of forming conservative recombinant products between two circular, double-stranded DNA molecules. We were unable to detect any DNA polymerase, DNA ligase, or 5' or 3' exonuclease activity associated with this purified material. The purified 100 kDa protein bound silver nitrate as well as a monoclonal antibody specific for nucleolin. A recombinant protein comprised of the Escherichia coli maltos-ebinding protein fused to the carboxyl-terminal two-thirds of human nucleolin possessed homologous DNA pairing activity. These data indicate that the 100 kDa homologous DNA pairing protein is nucleolin. The observation that nucleolin can carry out homologous DNA strand pairing in vitro raises the prospect that it may function similarly in vivo.     

Surgical treatment of aortic arch hypoplasia in infants and children with biventricular hearts

Background. Results of aortic arch reconstruction in the setting of biventricular physiology are well documented in the adult population, however, in children, surgical outcome of this subgroup of patients is less clear.

Methods. We studied the clinical outcomes of 37 children aged 8 days to 15 years (median 26 months), who underwent aortic arch reconstruction for arch hypoplasia from 1982 to 1997. The children were divided into three groups: Group 1 (20 patients) had isolated aortic arch lesions, Group 2 (13 patients) had associated intra-cardiac pathology yet conserving a biventricular physiology, Group 3 (4 patients) had Williams Syndrome. Previous interventions for coarctation had been performed in 30 patients (81%). Arch repair consisted of a patch aortoplasty in the majority of patients (35 of 37 children).

Results. Operative mortality occurred in 5 children, 4 in Group 2 (31%), 1 in Group 3 (25%) and none in Group 1. Permanent neurological complications occurred in 2 children (5 %). During the follow-up, which ranged from 1 month to 8 years, balloon angioplasty for arch obstruction was required in 1 child. There was one late death, associated with a subsequent intra-cardiac repair.

Conclusions. Aortic arch surgery in children with isolated arch hypoplasia, is associated with excellent early and late survival in addition to a low reintervention rate. Alternative perfusion and operative strategies must be implemented in infants with associated intra-cardiac anomalies to improve results.     

Transmission of "a" determinant variants of hepatitis B virus in immunized babies born to HBsAg carrier mothers

Hepatitis B virus (HBV) surface antigen mutations may lead to immune escape and eventually cause failure of immunization. In this report, we identified immune escape variants in immunized babies born to hepatitis B surface antigen (HBsAg) carrier mothers. A total of 68 babies were followed up for 2 years after the full course of vaccination; 2.9% (2/68) of babies were found to be infected with the variant HBV in spite of preexisting antibody to surface antigen (anti-HBs) at 24 months post immunization. Both infants were positive for HBV-DNA; sequencing results of the "a" determinant region of the surface gene revealed that both babies had point mutations at a different nucleotide position resulting in various amino acid substitutions. In addition, an intriguing variant having an addition-deletion mutation was observed in one of the babies. This is the first report to show the addition-deletion variant of HBV in India. However, the immunological significance of the above HBV variants needs to be further elucidated.