Publications

Three functional mouse flavin-containing monooxygenases (mFMOs) (i.e., mFMO1, mFMO3, and mFMO5) have been reported to be the major FMOs present in mouse liver. To examine the biochemical features of these enzymes, recombinant enzymes were expressed as maltose-binding protein fusion proteins (i.e., MBP-mFMO1, MBP-mFMO3, and MBP-mFMO5) in Escherichia coli and isolated and purified with affinity chromatography. The substrate specificity of these three mouse hepatic FMO enzymes were examined using a variety of substrates, including mercaptoimidazole, trimethylamine, S-methyl esonarimod, and an analog thereof, and a series of 10-(N,N-dimethylaminoalkyl)-2-(trifluoromethyl)phenothiazine analogs. The kinetic parameters of the three mouse FMOs for these substrates were compared in an attempt to explore substrate structure--function relationships specific for each mFMO. Utilizing a common phenothiazine substrate for all three enzymes, we compared the pH dependence for the recombinant enzymes under similar conditions. In addition, thermal stability for mFMO1, mFMO3, and mFMO5 enzymes was examined in the presence and absence of NADPH. The results revealed unique features for mFMO5, suggesting possible impact on the functional significance of this abundantly expressed FMO5 isoform in both human and mouse liver.

A medical linear accelerator equipped with optical position tracking, ultrasound imaging, portal imaging, and radiographic imaging systems was installed at University of Pittsburgh Cancer Institute for the purpose of performing image-guided radiation therapy (IGRT) and image-guided radiosurgery (IGRS) in October 2005. We report the performance characteristics and quality assurance aspects of the kilovoltage cone-beam computed tomography (kV-CBCT) technique. This radiographic imaging system consists of a kilovoltage source and a large-area flat panel amorphous silicon detector mounted on the gantry of the medical linear accelerator via controlled arms. The performance characteristics and quality assurance aspects of this kV-CBCT technique involves alignment of the kilovoltage imaging system to the isocenter of the medical linear accelerator and assessment of (a) image contrast, (b) spatial accuracy of the images, (c) image uniformity, and (d) computed tomography (CT)-to-electron density conversion relationship were investigated. Using the image-guided tools, the alignment of the radiographic imaging system was assessed to be within a millimeter. The low-contrast resolution was found to be a 6-mm diameter hole at 1% contrast level and high-contrast resolution at 9 line pairs per centimeter. The spatial accuracy (50 mm +/- 1%), slice thickness (2.5 mm and 5.0 mm +/- 5%), and image uniformity (+/- 20 HU) were found to be within the manufacturer's specifications. The CT-to-electron density relationship was also determined. By using well-designed procedures and phantom, the number of parameter checks for quality assurance of the IGRT system can be carried out in a relatively short time.

Allogeneic HSCT is the most reliable, robust, and effective cell-based biotherapy currently available to pediatric and adult patients with hematologic malignancies. The central role of donor-derived lymphocytes in mediating an effective antitumor effect, preventing and controlling opportunistic infections, and causing GVHD is well documented in animal experiments and human trials. The profound lymphopenia after conditioning regimens coupled with molecular tools to distinguish host versus donor cells provides investigators a window into immune recovery after allogeneic HSCT. Serial analyses of T cell subsets linking immunophenotype with function have revealed the kinetics of donor-derived T cell recovery after allografting and provided insights into ways the immune system can be manipulated to augment the graft-versus-tumor (GVT) effect without inducing GVHD. As this review demonstrates, investigators are not limited to being passive observers of this immune reconstitution; rather, we have an opportunity to shape the allografted T cells repertoire to selectively augment immune function.

OBJECTIVE

To examine the independent effects of race or ethnicity and insurance status on use of tubal sterilization rates.

METHODS

This study used cross-sectional data collected by the 2002 National Survey of Family Growth. The survey is designed to represent women and men aged 15-44 years in the household population of the United States. Our main outcome measure was tubal sterilization at any time before interview. A multivariable logistic regression model was used to estimate the effects of race or ethnicity and insurance status on rates of tubal sterilization after adjusting for important confounders.

RESULTS

The sample consisted of 7,643 women: 66% were white, 15% were Hispanic, and 14% were African American; 68% had private insurance and 32% had public or no insurance. After adjusting for age, insurance status, parity, income, education, marital status, and religion, African-American women were more likely than white women to undergo tubal sterilization (adjusted odds ratio 1.43, 95% confidence interval 1.08-1.88). After adjusting for age, race or ethnicity, parity, income, education, marital status, and religion, women with public or no insurance were more likely to undergo sterilization compared with women with private insurance (adjusted odds ratio 1.38, 95% confidence interval 1.09-1.74).

CONCLUSION

African-American women and women with no or public insurance were more likely to have undergone tubal sterilization compared with white women and women with private insurance, respectively. Additional research to identify factors that influence women's decision to undergo sterilization is warranted.

LEVEL OF EVIDENCE

II.

OBJECTIVE

This study was undertaken to assess the acceptability of levonorgestrel emergency contraception (EC).

STUDY DESIGN

We examined attitudes and use patterns among 1950 women in a randomized trial evaluating access to EC through advance provision, pharmacies, or clinics.

RESULTS

Most women considered EC to be safe (92%) and effective (98%). Compared with women with clinic access, women with direct pharmacy access were no more likely to use EC within 24 hours (odds ratio [OR] = 1.65, 95% CI = 0.82-3.30) or to report it very convenient (OR = 1.41, 95% CI = 0.77-2.56). However, women with advance provisions were more likely to use EC promptly (OR = 2.43, 95% CI = 1.24-4.80) and report high convenience (OR = 4.25, 95% CI = 2.32-7.76). Advance provision increased use by all women, whereas pharmacy access increased use only among condom users. Inconvenience and fear of side effects were common reasons for nonuse.

CONCLUSION

Women viewed EC favorably. Advance provision improved promptness and convenience of use overall, while pharmacy access benefited specific populations.