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C Paxson

Publications and source records attributed to C Paxson.

5 recordsLinked to original sources
PubMed2001

Insight into the catalytic mechanism of DNA polymerase beta: structures of intermediate complexes.

The catalytic reaction mediated by DNA polymerases is known to require two Mg(II) ions, one associated with dNTP binding and the other involved in metal ion catalysis of the chemical step. Here we report a functional intermediate structure of a DNA polymerase with only one metal ion bound, the DNA polymerase beta-DNA template-primer-chromium(III).2'-deoxythymidine 5'-beta,gamma-methylenetriphosphate [Cr(III).dTMPPCP] complex, at 2.6 A resolution. The complex is distinct from the structures of other polymerase-DNA-ddNTP complexes in that the 3'-terminus of the primer has a free hydroxyl group. Hence, this structure represents a fully functional intermediate state. Support for this contention is provided by the observation of turnover in biochemical assays of crystallized protein as well as from the determination that soaking Pol beta crystals with Mn(II) ions leads to formation of the product complex, Pol beta-DNA-Cr(III).PCP, whose structure is also reported. An important feature of both structures is that the fingers subdomain is closed, similar to structures of other ternary complexes in which both metal ion sites are occupied. These results suggest that closing of the fingers subdomain is induced specifically by binding of the metal-dNTP complex prior to binding of the catalytic Mg(2+) ion. This has led us to reevaluate our previous evidence regarding the existence of a rate-limiting conformational change in Pol beta's reaction pathway. The results of stopped-flow studies suggest that there is no detectable rate-limiting conformational change step.

Animals↗
PubMed2001

Mothers and others: who invests in children's health?

We estimate the impact of family structure on investments made in children's health, using data from the 1988 National Health Interview Survey Child Health Supplement. Controlling for household size, income and characteristics, we find that children living with step-mothers are significantly less likely to have routine doctor and dentist visits, or to have a place for usual medical care, or for sick care. Who invests in children's health? It appears these investments are made, largely, by a child's mother, and that step-mothers are not substitutes for birth-mothers in this domain.

Adolescent↗
PubMed1996

Surfactant therapy prior to the interhospital transport of preterm infants.

The risk-to-benefit ratio of surfactant treatment of outborn preterm infants prior, as opposed to after, transportation to a perinatal center is not known. The objective of this study was to document current practice and to examine clinical outcomes in North America. In phase I (December, 1991 to January, 1992) questionnaires were distributed to 114 perinatal centers in the United States and Canada. The centers returned 98 surveys. Over half (50.5%) of the centers report giving surfactant rescue prior to infant transport, but only a minority (9.5%) of the centers report doing so for prophylaxis. In phase II (January, 1992 to December, 1992), clinical outcomes of surfactant-eligible babies requiring interhospital transport at a university hospital were evaluated to determine which infants ultimately received surfactant and when. The infants were compared between groups and did not differ significantly in gestational age, birthweight, sex type, number of multiple births, five-minute Apgar scores, or whether antenatal steroids were used. In phase II, the 66 consecutive, ventilator-dependent, outborn infants with average, and median, gestational age of 28 weeks were compared. The infants receiving surfactant prior to transport, when compared to the infants that got it after transport (9 hours later), did not do any better. There was 6% more survival without bronchopulmonary dysplasia in the group receiving surfactant after transport (65.2% versus 59.3%, p = 0.665). The infants receiving surfactant after transport were off the ventilator sooner (95% C.I. 6.0-28.7 versus 11.8-25.9 days) and discharged from the perinatal center earlier (95% C.I. 37.8-70.8 versus 47.9-69.0 days). Furthermore, arterial blood gases before and after transport reveals that there were no short-term advantages in administering surfactant prior to transport when compared to waiting for reevaluation at the perinatal center. These findings suggest that surfactant can be used safely prior to the interhospital transport of preterm infants, but this treatment does not seem to confer benefit over waiting for reevaluation, and possible surfactant treatment, at the tertiary perinatal center.

Administration, Inhalation↗