Philip J Smith — Page 2

PubMed2002

An exonic splicing enhancer in human IGF-I pre-mRNA mediates recognition of alternative exon 5 by the serine-arginine protein splicing factor-2/alternative splicing factor.

The human IGF-I gene has six exons, four of which are alternatively spliced. Variations in splicing involving exon 5 may occur, depending on the tissue type and hormonal environment. To study the regulation of splicing to IGF-I exon 5, we established an in vitro splicing assay, using a model pre-mRNA containing IGF-I exons 4 and 5 and part of the intervening intron. Using a series of deletion mutants, we identified an 18-nucleotide purine-rich splicing enhancer in exon 5 that increases the splicing efficiency of the upstream intron from 6 to 35%. We show that the serine-arginine protein splicing factor-2/alternative splicing factor specifically promotes splicing in cultured cells and in vitro and is recruited to the spliceosome in an enhancer-specific manner. Our findings are consistent with a role for splicing factor-2/alternative splicing factor in the regulation of splicing of IGF-I alternative exon 5 via a purine-rich exonic splicing enhancer.

Alternative Splicing↗

PubMedDate not supplied

The first oral rotavirus vaccine, 1998-1999: estimates of uptake from the National Immunization Survey.

OBJECTIVE: On August 31, 1998, the rhesus-human reassortant rotavirus vaccine (RRV-TV) was licensed for use in the U.S. During the next nine months, 15 cases of intussusception were reported among infants who received the vaccine. Case-control and cohort studies showed a significantly increased risk of developing intussusception within one week of receiving the vaccine; subsequent ecologic studies did not. In this study, the authors used data on RRV-TV vaccination rates from the National Immunization Survey (NIS) to estimate state and national RRV-TV uptake rates and factors associated with receiving RRV-TV. These estimates are a key component in evaluating published ecologic studies designed to investigate the relationship between receipt of the vaccine and intussusception. METHODS: The authors analyzed NIS data for children ages 19 to 35 months who were eligible to receive RRV-TV between September 1998 and July 1999. The authors estimated vaccine coverage and the number of doses administered by state, NIS sampling quarter, and birth cohort, and analyzed demographic and socioeconomic variables to evaluate their relationship with receiving RRV-TV. RESULTS: It was estimated that approximately 1 million doses of RRV-TV were administered to 504,585 (+/-61,854) children, 13.4% (+/-1.6%) of children who were eligible. The estimated number of doses administered and the vaccination coverage rate varied greatly from state to state. Children living in households with higher socioeconomic conditions were more likely to receive the vaccine. CONCLUSION: Ecologic studies had a limited ability to detect a significant increase in the population incidence rate of intussusception that could be attributed to RRV-TV because populations in these studies consisted primarily of children who did not receive the vaccine. The example from RRV-TV demonstrates some of the challenges of assessing the magnitude of the association between a vaccine and an uncommon or rare adverse event.

Administration, Oral↗