Characterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrier

A human tumor xenograft (L56Br-X1) was established from a breast cancer axillary lymph node metastasis of a 53-year-old woman with a BRCA1 germ-line nonsense mutation (1806C>T; Q563X), and a cell line (L56Br-C1) was subsequently derived from the xenograft. The xenograft carries only the mutant BRCA1 allele and expresses mutant BRCA1 mRNA but no BRCA1 protein as determined by immunoprecipitation or Western blotting. The primary tumor, lymph node metastasis, and xenograft were hypodiploid by DNA flow cytometry, whereas the cell line displayed an aneuploidy apparently developed via polyploidization. Cytogenetic analysis, spectral karyotyping, and comparative genomic hybridization of the cell line revealed a highly complex karyotype with numerous unbalanced translocations. The xenograft and cell line had retained a somatic TP53 missense mutation (S215I) originating from the primary tumors, as well as a lack of immunohistochemically detectable expression of steroid hormone receptors, epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER-2), and keratin 8. Global gene expression analysis by cDNA microarrays supported a correlation between the expression profiles of the primary tumor, lymph node metastasis, xenograft, and cell line. We conclude that L56Br-X1 and L56Br-C1 are useful model systems for studies of the pathogenesis and new therapeutic modalities of BRCA1-induced human breast cancer.     

Misoprostol for induction of labour: a survey of attitude and practice in southwestern Nigeria

BACKGROUND: Although supported by research evidence, misoprostol for induction of labour remains contentious. OBJECTIVE: To assess perception and practice of obstetricians regarding use of misoprostol for labour induction. METHODOLOGY: Cross-sectional questionnaire-based survey of Senior Registrars and Consultant Obstetricians in southwestern Nigeria. RESULTS: One hundred and six questionnaires were completed (52.8% Consultants; 47.2% Senior Registrars). Most respondents (96, 90.6%) employ misoprostol for induction in both live and dead fetuses with majority having personally prescribed misoprostol for cervical ripening or induction of labour (97.2 and 79.3%, respectively). Fetal tachycardia, hyperstimulation and ruptured uterus were the commonly reported complications. Twenty-six respondents (24.5%) reported being aware of maternal death in relation to misoprostol use. Only 52.9% of the respondents have protocols guiding misoprostol use in their hospitals. More than half of respondents administer misoprostol 50 mug or higher 6 hourly. Most (92, 87.6%) believe that research evidence backs use of misoprostol for the indication; 89.5% of respondents support use of misoprostol. Most respondents (90, 86.5%) disagree with the notion that misoprostol is too dangerous for induction; only 26 respondents (25.1%) considered oxytocin a better choice for induction; 93 respondents (88.6%) agreed that, given cautious use, misoprostol is safe for induction, while 86 respondents (81.9%) considered misoprostol a cost-effective intervention for labour induction in developing countries. Though senior registrars and younger consultants tended to report side effects more frequently than older consultants, they were more likely to support misoprostol for induction of labour than older consultants. This differences were however not statistically significant (P > 0.05). CONCLUSION: Misoprostol is widely utilized by obstetricians for induction of labour in southwestern Nigeria. Fetal and maternal side effects are commonly experienced. We recommend urgent adoption of evidence-based guidelines in every unit using the drug to prevent complications.     

Application of the Attitude-Social Influence-Efficacy Model to Condom Use Among African-American STD Clinic Patients: Implications for Tailored Health Communication

The purpose of the current investigation was to apply the attitude-social influence-efficacy (ASE) model to achieve a theory-based understanding of condom use among low income, heterosexually active African-American STD clinic patients. N = 293 participants were recruited from a large, publicly-funded metropolitan STD clinic in the Southeastern United States and surveyed using an ACASI computer program. Results indicated that several ASE variables exhibited meaningful relationships with condom stages of change in univariate analyses, replicating patterns found in previous research. Fewer variables remained significant in multivariate analyses, however. There was also some support for the proposition that early stage movement (e.g., Precontemplation to Contemplation) is based more upon perceptions of condom use (e.g., pros, perceived norms), whereas later stage movement (e.g., Preparation to Action/Maintenance) is based more upon perceived and actual skills acquisition (e.g., condom self-efficacy, negotiation strategies). Results varied with regard to main and casual condom stage of change. Implications for developing tailored HIV prevention interventions with heterosexual African-Americans are discussed.     

Cisplatin‐induced testicular dysfunction and its amelioration by Launaea taraxacifolia leaf extract

This study investigates the ameliorative potential of Launea taraxacifolia (LT) aqueous leaf extract on cisplatin‐induced testicular dysfunction in Wistar rats. Thirty rats were randomly divided into six groups (A–F) of 5 rats each: Group A which served as control received water; Group B was intraperitoneally (ip) injected 10 mg kg^?1 body wt cisplatin on day 21; Groups C and D were given 100 and 400 mg of LT via oral administration, respectively, for 21 days while Groups E and F received similar treatment as Groups C and D, respectively, and then exposed to ip administration of 10 mg kg^?1 body weight cisplatin on the 21st day. Exclusively, Cisplatin‐exposed Group B rats showed reduced sperm characteristics and increased sperm morphological abnormalities; distorted histological architecture of seminiferous tubules; significantly increased lipid peroxidation (LPO) and decreased activities of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH)levels in the testes. These parameters in LT alone treated Groups C and D were not markedly different compared with the control group. The rats with the combined treatment in Groups E and F showed significantly improved sperm parameters, testicular histo‐architecture and antioxidant enzymatic activities. Conclusively, aqueous extract of L. taraxacifolia has protective potential against cisplatin damage.     

Information‐based sample size re‐estimation in group sequential design for longitudinal trials

Group sequential design has become more popular in clinical trials because it allows for trials to stop early for futility or efficacy to save time and resources. However, this approach is less well‐known for longitudinal analysis. We have observed repeated cases of studies with longitudinal data where there is an interest in early stopping for a lack of treatment effect or in adapting sample size to correct for inappropriate variance assumptions. We propose an information‐based group sequential design as a method to deal with both of these issues. Updating the sample size at each interim analysis makes it possible to maintain the target power while controlling the type I error rate. We will illustrate our strategy with examples and simulations and compare the results with those obtained using fixed design and group sequential design without sample size re‐estimation. Copyright © 2014 John Wiley & Sons, Ltd.     

Circular dichroism for secondary structure determination of proteins with unfolded domains using a self-organising map algorithm SOMSpec

Many proteins and peptides are increasingly being recognised to contain unfolded domains or populations that are key to their function, whether it is in ligand binding or material assembly. We report an approach to determine the secondary structure for proteins with suspected significant unfolded domains or populations using our neural network approach SOMSpec. We proceed by derandomizing spectra by removing fractions of random coil (RC) spectra prior to secondary structure fitting and then regenerating α-helical and β-sheet contents for the experimental proteins. Application to bovine serum albumin spectra as a function of temperature proved to be straightforward, whereas lysozyme and insulin have hidden challenges. The importance of being able to interrogate the SOMSpec output to understand the best matching units used in the predictions is illustrated with lysozyme and insulin whose partially melted proteins proved to have significant β_II content and their CD spectrum looks the same as that for a random coil.

Circular dichroism secondary structure fitting by analysing derandomized spectra using the SOMSpec approach then regenerating data for the original spectrum.