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Biomedical subjects

E Hutchins

Publications and source records attributed to E Hutchins.

4 recordsLinked to original sources

TNF-alpha receptor signaling and IL-10 gene therapy regulate the innate and humoral immune responses to recombinant adenovirus in the lung.

Recombinant adenovirus-mediated gene therapy has demonstrated great promise for the delivery of genes to the pulmonary epithelium. However, dose-dependent inflammation and local immune responses abbreviate transgene expression. The purpose of these studies was to determine the role of TNF-alpha and individual TNF receptor signaling to adenovirus clearance and immune responses, and whether coexpression of human IL-10 could reduce inflammation and extend the duration of transgene expression in the lung. beta-Galactosidase expression in mice receiving intratracheal instillation of Adv/beta-gal (adenovirus construct expressing beta-galactosidase) was transient (less than 14 days), but a significant early increase of beta-galactosidase expression was seen in mice lacking either or both TNF-alpha receptors. Absence of TNF-alpha or the p55 receptor significantly attenuated the Ab response to both adenovirus and beta-galactosidase. Human IL-10 expression in the lung suppressed local TNF-alpha production following AdV/hIL-10 (adenovirus construct expressing human IL-10) delivery, but did not lead to increased or prolonged transgene expression when coexpressed with beta-galactosidase. Expression of human IL-10 following AdV/hIL-10 instillation extended at least 14 days, was nonimmunogenic, and suppressed the development of neutralizing Abs against adenoviral proteins as well as against human IL-10. We conclude that TNF-alpha signaling through both the p55 and p75 receptor plays important roles in the clearance of adenoviral vectors and the magnitude of the humoral immune response. Additionally, although coexpression of human IL-10 with beta-galactosidase had only modest effects on transgene expression, we demonstrate that AdV/hIL-10 is well tolerated, has extended expression compared with beta-galactosidase, and is nonimmunogenic in the lung.

Adenoviridae↗

Reducing complications from alcohol use during pregnancy through screening.

Prenatal providers are reluctant to discuss alcohol use in the clinical setting, even though heavy alcohol use is associated with fetal alcohol syndrome (FAS) and fetal alcohol effects (FAE), sometimes known as alcohol-related neurodevelopmental disorder. Fourteen percent to 20% of pregnant women report drinking some alcohol during pregnancy. Approximately 0.2% to 1% meet the criteria for heavy drinking. Reducing drinking during pregnancy has the potential to reduce the risk for FAS and FAE. Routine screening for alcohol use during pregnancy followed by referrals for those considered to be at risk is recommended. Women are often more receptive to intervention during pregnancy, as they focus on positive health behaviors. A number of brief screening tools designed for use on a routine basis are reviewed. Physicians who learn to comfortably discuss alcohol use during pregnancy can help substantially reduce the impact of these disorders.

Adult↗

Psychosocial risk factors associated with cocaine use during pregnancy: a case-control study.

OBJECTIVE: To investigate whether psychosocial risk factors predict cocaine use during pregnancy. METHODS: We sampled 229 pregnant women from an urban prenatal clinic. Drug use ascertainment was based on self-report and urine toxicology, with 102 subjects classified as drug users and 127 as nonusers. A questionnaire measuring seven psychosocial risk factors was administered. The predictive relation between these characteristics and drug use was ascertained through multivariate analyses, controlling for potential sociodemographic confounders. RESULTS: Six of the seven psychosocial risk factors were significant predictors for this sociodemographic group. Women who used cocaine during pregnancy were more likely to have a family history of alcohol or drug problems, to have been introduced to drugs by a male partner, to be depressed, to have less social support, to have current partners who were substance users, and to have less-stable living situations. Both groups of subjects had high rates of childhood sexual abuse, but this alone was not predictive of drug use. In addition, cigarette smoking was a strong predictor of illicit drug use. CONCLUSION: Identification of multiple psychosocial risk factors has implications for the identification and treatment of substance-using pregnant women. Because cocaine users and nonusers did not differ in gestational age at entry into prenatal care, opportunities exist for intervention during pregnancy. Based on the study findings, evaluation of the following aspects of a patient's lifestyle can aid in the detection of cocaine use during pregnancy: smoking status, family history of alcohol or drug problems, and current drug use by a male partner.

Adult↗

Why the islands move.

Micronesian navigators routinely make voyages across large expanses of open ocean. To do this, a navigator must judge both the direction in which he is sailing and the distance he has travelled. The rising and setting points of the stars (and other cues) provide instantaneous information about direction, but distance can only be judged by integrating velocity-related information over time. Micronesian navigators judge distance in a way that seems odd. When they are out of sight of land, they imagine that the canoe is stationary and that the islands move back past them. For each voyage, they 'attend' to an island off to the side of the course which is out of sight over the horizon. As they sail, they imagine the island moving back along the horizon changing in bearing until it is imagined to be under the bearing it is known to have from the destination island. Then they know they are near their destination. There is good reason for using a frame of reference whose origin is defined by the boat. We show how it finesses a perceptual paradox--the rising and setting points of the stars do not exhibit motion parallax.

Cues↗