Publications

Vitamin D and its analogs have been suggested to have palliative effects in the cardiovascular system. We have examined the effects of co-administration of the vitamin D receptor agonist, paricalcitol, on the hypertension, cardiac hypertrophy and interstitial fibrosis produced by chronic angiotensin II (AII) infusion. Administration of AII (800ng/kg/min) over a 14-day period resulted in increased blood pressure, myocyte hypertrophy, activation of the hypertrophic fetal gene program (atrial natriuretic peptide, B-type natriuretic peptide and alpha skeletal actin gene expression), increased expression of the pro-hypertrophic modulatory calcineurin inhibitor protein 1 (MCIP 1), and increased fibrosis with augmented procollagen 1 and 3 gene expression. In each case co-administration of paricalcitol (300ng/kg intraperitoneally every 48h) at least partially reversed the AII-dependent effect. These studies demonstrate that the liganded vitamin D receptor possesses potent anti-hypertrophic activity in this non-renin-dependent model of cardiac hypertrophy. The anti-hypertrophic activity appears to be at least partially intrinsic to the cardiac myocyte and may involve suppression of the MCIP 1 protein. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

The delivery of HIV risk assessment and behavioral counseling by clinicians in HIV clinical settings is one component in a comprehensive "positive prevention" strategy to help patients reduce their transmission risk behavior. Clinicians engage in behavioral prevention inconsistently, however, depending on whether patients are new to a practice or are established in regular care and on their attitudes and characteristics of their practices. We analyzed clinician reports of behavioral prevention delivered before and after participation in a large federal demonstration project of positive prevention interventions. The interventions that were part of this project were successful in increasing behavioral prevention among both new and returning patients. Prior to study interventions, clinicians reported counseling 69% of new patients and 52% of returning patients. In follow-up interviews 12 months after receiving training, clinicians reported delivering prevention messages to 5% more new patients and 9% of returning patients (both p<0.01). After 12 months, clinicians were more likely to engage in behavioral prevention if other providers in their sites were also involved. Clinicians agreeing that behavioral prevention was part of the clinic's mission were more likely to conduct it. The interventions were successful in mitigating the influence of provider attitudes precluding prevention delivery. Intervention strategies can help clinicians more consistently deliver behavioral prevention messages to their HIV-infected patients.

Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10(-8)) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10(-6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10(-9)), and with both ER-positive (OR = 1.09; P = 1.5 × 10(-5)) and ER-negative (OR = 1.16, P = 2.5 × 10(-7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.