Association of prostate-specific antigen promoter genotype with clinical and histopathologic features of prostate cancer

The serum test for the secreted protease prostate-specific antigen (PSA) is the most widely used screening tool for prostate cancer. The PSA gene contains multiple functional and nonfunctional single nucleotide polymorphisms (SNP) in its promoter. We showed previously that the rs925013 G/A SNP, but not the rs266882 G/A SNP, was significantly associated with serum PSA in healthy men. In this study, we evaluated the association of the PSA promoter genotype with clinical data in a cohort of 1,224 men with prostate cancer. Previous work with a subset of this cohort has shown that percent high-grade (Gleason grades 4 and 5) cancer was the strongest predictor of biochemical recurrence (PSA relapse). We found a statistically significant association (P < 0.05) of the rs925013 SNP with several clinical and histomorphologic variables. The G allele was associated with higher serum PSA at diagnosis, higher percent Gleason grade 3 cancer, and lower percent high-grade and Gleason grade 4 cancer. The rs266882 SNP was modestly associated with PSA at diagnosis in a dominant model but was not associated with cancer grade. Neither SNP was associated with biochemical recurrence. The statistically significant predictors of biochemical recurrence were tumor location in the peripheral zone [odds ratio (OR), 10.71; 95% confidence interval (95% CI), 3.15-36.49], presence of any Gleason grade 4/5 cancer (OR, 4.26; 95% CI, 1.30-14.00), presence of any intraductal cancer (OR, 1.03; 95% CI, 1.00-1.04), and serum PSA at diagnosis (OR, 2.04; 95% CI, 1.50-2.77).     

Acceptability of cognitive—behavioral and behavioral interventions among teachers

Teachers' decisions regarding acceptability ultimately affect the implementation and thus the efficacy of classroom interventions. While programmatic research on acceptability of behavioral interventions exists, acceptability of cognitive—behavioral techniques among those who would ultimately implement them has not been examined. In the present study 203 practicing teachers evaluated two cognitive—behavioral (self-instructional strategy training and self-monitoring) and two behavioral (token economy and social reinforcement) interventions for a student with either a mild or severe problem. In addition, reliability and factor structure of the intervention Rating Profile-15 (IRP-15) was examined. The IRP-15 was found to be highly reliable and unidimensional. While teachers found all four interventions to be acceptable, at the mild problem level both social reinforcement and self-monitoring were significantly more acceptable than self-instructional strategy training and token economy. Self-instructional strategy training was significantly more acceptable at the severe problem level as compared to the mild problem level, while social reinforcement was rated as significantly more acceptable at the mild problem level as compared with the severe problem level. Directions for further research are noted.Support for this study was provided by the Division of Human and Community Resources, University of Maryland. We would like to thank Dr. Richard Mainzer and the Maryland State Department of Education for their assistance.     

Differential activation of the c-Jun N-terminal kinase pathway in arsenite-induced apoptosis and sensitization of chemically resistant compared to susceptible B-lymphoma cell lines.

Various forms of inorganic arsenic are significant environmental contaminants that have multiple effects on cells, including the induction of apoptotic cell death. Induction of apoptosis in lymphoid cells can mediate immunotoxicity following exposure to chemicals. However, the mechanisms regulating the sensitivity of B-lymphocytes to arsenic-induced apoptosis are not understood. Therefore, we investigated the involvement of key mitogen-activated protein kinase pathways and apoptosis induction by sodium arsenite in a model system of chemically resistant and susceptible B-lymphoma cell lines. These studies revealed a differential requirement for the c-Jun N-terminal kinase (JNK) pathway for apoptosis induction by sodium arsenite in the resistant EW36 versus sensitive ST486 cell lines. Specifically, activation of the JNK pathway was not required for arsenite-induced apoptosis in ST486 cells, whereas JNK pathway activation was always associated with apoptosis induction in EW36 cells. Importantly, we found that EW36 cells, which overexpress the Bcl-2 protein, can be substantially sensitized to arsenite-induced apoptosis by prior exposure to nonlethal hyperthermia. Moreover, pretreatment with an inhibitor of p38 kinase acted synergistically with hyperthermia to further sensitize EW36 cells. The inhibition of p38 prolonged a transient period of JNK phosphorylation that occurred immediately after heat shock treatment and involved the persistent activation of SEK1, one of the kinases upstream of JNK. Significantly, the sensitization of resistant cells is characterized by a lowering of the threshold concentration of arsenite required to activate the JNK pathway and induce apoptosis.     

A theoretical and experimental model of ventricular interdependence

Summary Because of the close anatomical association between the ventricles, the volume of one ventricle can directly affect the volume and pressure within the other ventricle. To study the mechanical coupling between the ventricles, we modeled the right and left ventricles as a two-compartment model with right wall (C_iw), septal (C_s), and left wall (C_lw) compliances. Based on the balances of forces across the septum, four equations were obtained to predict the transfer of pressure (P) and volume (V) information from one ventricle to another. The validity of the theoretical analysis was tested first in a physical model and then in a post-mortem heart preparation. The standard errors of estimate comparing the predicted to measured values were low for both the physical model and the post-mortem heart data. All values were significantly related (P<0.05) with r>0.89. The results show excellent correlation between predicted and measured values. This model provides a better understanding of ventricular interdependence and may help to predict effects of hypertrophy and/or myocardial ischemia on ventricular interdependence.This study was supported in part by PHS NIH Grant Nos. HL31644 and HL22843. Dr. Santamore is a recipient of an NIH Research Carrer Development Award No. H101026     

Age at first episode of venereal syphilis in an Aboriginal population: an application of survival analysis

Objective: To identify the age at which screening for syphilis could be ceased in Kimberley Aboriginal people who had remained seronegative and whether this age was the same for people with and without a past history of gonorrhea.
Design: Retrospective cohort study.
Setting: The Kimberley region in the far north of Western Australia.
Participants: Kimberley Aboriginal residents.
Main Outcome Measure: Age at seroconversion.
Results: Survival analysis showed that seroconversion due to venereal syphilis occurred largely during the years between the late teens and early 20s. The probability of seroconverting by a given age was related to the time at which the subject's last gonorrhea infection occurred.
Conclusions: As a result of this study, annual periodic screening for syphilis is now offered to Kimberley Aboriginal people only between the ages of 15 and 25 years, allowing for the redistribution of resources to other activities that have greater potential to decrease the incidence of all STDs.