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Christine Mitchell

Publications and source records attributed to Christine Mitchell.

14 recordsLinked to original sources

Sex assignment for newborns with ambiguous genitalia and exposure to fetal testosterone: attitudes and practices of pediatric urologists.

OBJECTIVE: Sex assignment to newborns with ambiguous genitalia is controversial. Our objective was to determine the attitudes and practices of pediatric urologists on this subject. STUDY DESIGN: A survey of fellows in the Urology Section of the American Academy of Pediatrics was completed by 185/228 (81%). The survey referred to two cases, masculinized 46XX congenital adrenal hyperplasia (CAH) and 46XY cloacal exstrophy. Questions referred to sex assignment, timing of surgery, decision making process, and respondent demographics. RESULTS: For masculinized 46XX CAH, virtually all respondents favored female sex assignment. The most important factor was potential fertility. For 46XY cloacal exstrophy, two thirds favored the male sex. The most important factor was potential androgen brain imprinting, whereas in selecting female assignment, it was difficulty creating a functional phallus. Respondent characteristics associated with assigning female sex were longer duration in practice (>15 years) and affiliation with training programs. Most respondents advocated a team approach to decision making with parental involvement and early surgery (<18 months). CONCLUSION: Pediatric urologists are in strong consensus about sex assignment for newborns with ambiguous genitalia from CAH, a team approach with parental involvement, and early reconstruction. Yet, there is striking variability in attitudes toward sex assignment for newborns with 46XY cloacal exstrophy, which should be incorporated into the decision-making process with parents.

Adrenal Hyperplasia, Congenital↗

Positive and negative cis-acting regulatory sequences control expression of leukotoxin in Actinobacillus actinomycetemcomitans 652.

Integration of IS1301 into an AT-rich inverted repeat located upstream of the ltx operon was previously shown to confer a hyperleukotoxic phenotype in Actinobacillus actinomycetemcomitans IS1 (T. He, T. Nishihara, D. R. Demuth, and I. Ishikawa, J. Periodontol. 70:1261-1268, 1999), but the mechanism leading to increased leukotoxin production was not determined. We show that an IS1 ltx promoter::lacZ reporter construct expresses 12-fold higher levels of beta-galactosidase activity than a reporter containing the ltx promoter from A. actinomycetemcomitans 652, suggesting that IS1301 increases transcription of the ltx operon. Examination of the IS1301 sequence identified a potential outwardly directed promoter. However, site-specific mutagenesis of the -35 element of the putative promoter had no effect on the transcriptional activity of the IS1 reporter construct. Furthermore, reverse transcriptase PCR and real-time PCR experiments did not detect a transcript that was initiated within IS1301. These results suggest that increased expression of leukotoxin in strain IS1 does not arise from an outwardly directed IS1301 promoter. To determine how IS1301 alters transcriptional regulation of the ltx operon, cis-acting sequences that regulate leukotoxin expression were identified. The AT-rich sequence that resides downstream from the site of IS1301 insertion was shown to function as a positive cis-acting regulator of leukotoxin expression. This sequence resembles an UP element in its location, AT-rich content, and activity and is homologous to the consensus UP element sequence. In addition, a negative cis-acting sequence was identified upstream from the site of IS1301 insertion, and deletion of this region increased promoter activity by fourfold. Mobility shift experiments showed that this region bound to a protein(s) in extracts from A. actinomycetemcomitans 652. The specific sequences required for this interaction were localized to a 26-nucleotide segment of the ltx promoter that resides 17 bp upstream from the site of IS1301 insertion. Together, these results suggest that positive and negative cis-acting sequences regulate leukotoxin expression and that IS1301 may increase transcription of the ltx operon in A. actinomycetemcomitans IS1 by displacing a negative cis-acting regulator approximately 900 bp upstream from the basal elements of the ltx promoter.

Actinobacillus Infections↗

Irene's story.

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Bioethical Issues↗