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.     

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.     

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.     

Misconceptions of hypertension

A prospective questionnaire study of the misconceptions of hypertension by hypertensive patients was carried out in 1365 male and female hypertensive patients aged between 21-80 years. About 40% of the study population could not define hypertension, but even those who did appeared to be in denial of the disease. About 24% were unaware of the causes of hypertension; the most common cause mentioned was psychosocial stress. Between 0.6% and 14% of subjects were unaware of the effect of risk factors, like obesity, cigarette smoking, exercise, excessive alcohol and salt consumption, or hypertension. Interestingly, some feel that regular sexual intercourse worsens hypertension. Eight percent of subjects had no fear of the effect of poor compliance to antihypertensive medication, while 10% were anxious about the heavy financial burden imposed by hypertension management, Sixty-five percent of subjects feel that they will require no more medication once they achieve control of their blood pressure. Twenty-one percent of respondents are of the opinion that they will achieve a permanent cure only from alternative medical practitioners and will consider using alternative medicine in future. The study confirms the importance of medical education for patients irrespective of their level of education, as many of these patients still entertain that gross misconceptions may have negative impact on outcome.