Maternal diet but not gestational weight gain predicts central adiposity accretion in utero among pregnant adolescents.

BACKGROUND: Modifiable risk factors during pregnancy, such as diet and weight gain, are associated with fetal birth weight but little is known about how these factors influence fetal fat acquisition in utero among pregnant adolescents. OBJECTIVE: To determine whether maternal pre-pregnancy BMI (ppBMI), gestational weight gain (GWG) and dietary intake during pregnancy influence fetal fat accretion in utero. METHODS: Longitudinal data were obtained from 121 pregnant adolescents enrolled in a study designed to identify determinants of maternal and fetal bone changes across gestation. Adolescents (ages 13-18 years) completed up to three study visits during early, mid- and late gestation. Maternal anthropometrics, 24 h dietary recalls and measures of fetal biometry were obtained at each visit. Fetal abdominal wall thickness (abdominal subcutaneous fat thickness, AbFat), a measure of fetal subcutaneous fat, was calculated by sonography at each visit. Statistical determinants of AbFat during late pregnancy were explored using simple and multiple regression. RESULTS: During late pregnancy (34.8±2.0 weeks; range 31.0-40.6 weeks of gestation), the median (inter-quartile range) fetal AbFat and GWG were 0.44 (0.39, 0.55) cm and 14.6 (9.5, 18.3) kg, respectively. After adjusting for infant birth weight, variables significantly associated with fetal AbFat included gestational age (P<0.0001, 95% confidence interval, CI: 0.01, 0.03), maternal race (P=0.029, 95% CI: -0.04, -0.002) and dietary intake of added sugar (P=0.025, 95% CI: 1.42e-6, 2.06e-5). Fetal AbFat had a significant positive quadratic relationship with total maternal dietary sugar intake such that both low and high extremes of sugar consumption were associated with significantly higher fetal AbFat. Birth weight was not significantly associated with maternal intake of added sugars. CONCLUSION: Extreme sugar intakes among pregnant adolescents may lead to increased accumulation of fetal abdominal fat with little net effect on birth weight. This finding suggests that increased sugar consumption during pregnancy promotes shifts in fetal body composition.

Analysis of the flame retardant metabolites bis(1,3-dichloro-2-propyl) phosphate (BDCPP) and diphenyl phosphate (DPP) in urine using liquid chromatography-tandem mass spectrometry.

Organophosphate triesters tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate are widely used flame retardants (FRs) present in many products common to human environments, yet understanding of human exposure and health effects of these compounds is limited. Monitoring urinary metabolites as biomarkers of exposure can be a valuable aid for improving this understanding; however, no previously published method exists for the analysis of the primary TDCPP metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP), in human urine. Here, we present a method to extract the metabolites BDCPP and diphenyl phosphate (DPP) in human urine using mixed-mode anion exchange solid phase extraction and mass-labeled internal standards with analysis by atmospheric pressure chemical ionization liquid chromatography tandem mass spectrometry. The method detection limit was 8 pg mL(-1) urine for BDCPP and 204 pg mL(-1) for DPP. Recoveries of analytes spiked into urine ranged from 82 ± 10% to 91 ± 4% for BDCPP and from 72 ± 12% to 76 ± 8% for DPP. Analysis of a small number of urine samples (n=9) randomly collected from non-occupationally exposed adults revealed the presence of both BDCPP and DPP in all samples. Non-normalized urinary concentrations ranged from 46-1,662 pg BDCPP mL(-1) to 287-7,443 pg DPP mL(-1), with geometric means of 147 pg BDCPP mL(-1) and 1,074 pg DPP mL(-1). Levels of DPP were higher than those of BDCPP in 89% of samples. The presented method is simple and sufficiently sensitive to detect these FR metabolites in humans and may be applied to future studies to increase our understanding of exposure to and potential health effects from FRs.

Ubiquitin-mediated degradation of active Src tyrosine kinase.

Src family tyrosine kinases are involved in modulating various signal transduction pathways leading to the induction of DNA synthesis and cytoskeletal reorganization in response to cell-cell or cell-matrix adhesion. The critical role of these kinases in regulating cellular signaling pathways requires that their activity be tightly controlled. Src family proteins are regulated through reversible phosphorylation and dephosphorylation events that alter the conformation of the kinase. We have found evidence that Src also is regulated by ubiquitination. Activated forms of Src are less stable than either wild-type or kinase-inactive Src mutants and can be stabilized by proteasome inhibitors. In addition, poly-ubiquitinated forms of active Src have been detected in vivo. Taken together, our results establish ubiquitin-mediated proteolysis as a previously unidentified mechanism for irreversibly attenuating the effects of active Src kinase.

Genetic engineering of insulin expression in nonislet cells: implications for beta-cell replacement therapy for insulin-dependent diabetes mellitus.

Insulin-dependent diabetes mellitus (IDDM) occurs as a consequence of autoimmune destruction of the insulin-producing pancreatic beta-cells. Although progress has been made in the field of islet transplantation, an appealing alternative strategy for beta-cell replacement therapy for IDDM is to target insulin expression to non-islet cells. We have recently generated transgenic nonobese diabetic (NOD) mice in which insulin gene expression was targeted to proopiomelanocortin (POMC)-expressing cells of the intermediate lobe (IL) of the pituitary. We have shown that POMC-expressing IL pituitary cells secreted large amounts of mature insulin, similar to islet beta-cells. However, in contrast to the insulin-producing islet beta-cells, the insulin-producing IL pituitary cells were not attacked by the immune system. Remarkably, transplantation of small amounts of the transgenic IL tissues into diabetic NOD mice resulted in the restoration of near-normogylcemia and the complete reversal of diabetic symptoms. In separate experiments, IL allografts showed enhanced viability and were highly vascularized, compared with similarly transplanted islet allografts. These features are highly advantageous in the transplantation setting and demonstrate the considerable potential of these non-islet cell types for insulin-gene delivery in IDDM.

Insulin-secreting non-islet cells are resistant to autoimmune destruction.

Transgenic nonobese diabetic mice were created in which insulin expression was targeted to proopiomelanocortin-expressing pituitary cells. Proopiomelanocortin-expressing intermediate lobe pituitary cells efficiently secrete fully processed, mature insulin via a regulated secretory pathway, similar to islet beta cells. However, in contrast to the insulin-producing islet beta cells, the insulin-producing intermediate lobe pituitaries are not targeted or destroyed by cells of the immune system. Transplantation of the transgenic intermediate lobe tissues into diabetic nonobese diabetic mice resulted in the restoration of near-normoglycemia and the reversal of diabetic symptoms. The absence of autoimmunity in intermediate lobe pituitary cells engineered to secrete bona fide insulin raises the potential of these cell types for beta-cell replacement therapy for the treatment of insulin-dependent diabetes mellitus.

Chronic pain and disease conviction.

OBJECTIVE: The results of cross-sectional and prospective studies suggest that the disease conviction scale of the Illness Behavior Questionnaire (IBQ) provides important information about chronic pain. To examine further the characteristics and correlates of this scale, the relationships between disease conviction and average pain intensity and interference of pain with daily activities were examined in a sample of chronic pain patients. DESIGN: The disease conviction scale and measures of hypochondriasis, psychological distress, pain intensity, and pain interference were administered to a sample of 127 chronic pain patients. RESULTS: The results suggested that pain intensity and interference were more strongly associated with disease conviction than with measures of psychological distress and hypochondriasis. In an analysis in which the relationships between the individual items of the disease conviction scale and pain intensity and interference were examined, disease conviction scale items that reflect consequences of pain and illness were significantly associated with both pain intensity and pain interference, whereas items that reflect disease conviction were in general not associated with either pain intensity or interference. CONCLUSION: These results suggest that items included in the disease conviction scale that reflect consequences of pain and illness, rather than disease conviction, may have contributed to the relationships that have been reported between disease conviction and other aspects of the chronic pain experience.

Resolution of marked intrapartum fetal tachycardia following intravenous nalbuphine hydrochloride.

We report a case of a patient who received nalbuphine during labor. The fetus was in an awake state, but when exposed to intravenous nalbuphine manifested quiet sleep. This suggest a physiological response and not a sign of fetal compromise.

Systematic mutational analysis of the yeast beta-tubulin gene.

A systematic strategy was used to create a synoptic set of mutations that are distributed throughout the single beta-tubulin gene of Saccharomyces cerevisiae. Clusters of charged amino acids were targeted for mutagenesis and converted to alanine to maximize alterations on the protein's surface and minimize alterations that affect protein folding. Of the 55 mutations we constructed, three confer dominant-lethality, 11 confer recessive-lethality, 10 confer cold-sensitivity, one confers heat-sensitivity, and 27 confer altered resistance to benomyl. Only 11 alleles give no discernible phenotype. In spite of the fact that beta-tubulin is a highly conserved protein, three-fourths of the mutations do not destroy the ability of the protein to support the growth of yeast at 30 degrees C. The lethal substitutions are primarily located in three regions of the protein and presumably identify domains most critical for beta-tubulin function. Interestingly, most of the conditional-lethal alleles produce specific defects in spindle assembly at their restrictive temperature; cytoplasmic microtubules are relatively unaffected. The exceptions are two mutants that contain abnormally long cytoplasmic microtubules. Mutants with specific spindle defects were not observed in our previous collection of beta-tubulin mutants and should be valuable in dissecting spindle function.