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1.  Community-Based Participatory Approach to Reduce Breast Cancer Disparities in South Dallas 
South Dallas experiences significant disparities in breast cancer mortality, with a high proportion of stage III and IV diagnoses. To address these rates, the Dallas Cancer Disparities Community Research Coalition created an educational intervention to promote breast health and early detection efforts.
The goals of the intervention were to increase (a) knowledge regarding the chief contributing factors for breast cancer, (b) awareness of the importance of screening for early detection, and (c) the proportion of women who have engaged in appropriate breast cancer screening practices.
Eligibility criteria for this nonrandomized, controlled trial included women age 40 and older, English-speaking, and having no personal history of cancer. Control participants received written breast health educational materials. Intervention participants attended 8 weekly sessions that included interactive educational materials, cooking demonstrations, and discussions emphasizing primary and secondary breast cancer prevention. All study participants completed a 1-hour survey at baseline and 4 months later.
There were 59 women were enrolled in the intervention and 60 in the control group. At follow-up, after controlling for baseline mammography status, women in the intervention group were 10.4 times more likely (95% confidence interval [CI], 2.9–36.4) to have received a screening mammogram in the last year compared with the control group. Intervention participants demonstrated statistically significantly higher rates of breast self-examination (odds ratio [OR], 3.0; 95% CI, 1.0–8.6) and breast cancer knowledge (p = .003).
Lessons learned from this community-based participatory research (CBPR) study can be used to create sustainable cancer disparity reduction models that can be replicated in similar communities.
PMCID: PMC4238068  PMID: 22616205
Breast neoplasms; community-based participatory research; health status disparities; health promotion; women's health
2.  5-HT2 Receptors Facilitate JC Polyomavirus Entry 
Journal of Virology  2013;87(24):13490-13498.
The human JC polyomavirus (JCPyV) causes the rapidly progressing demyelinating disease progressive multifocal leukoencephalopathy (PML). The disease occurs most often in individuals with AIDS but also occurs in individuals receiving immunomodulatory therapies for immune-related diseases such as multiple sclerosis. JCPyV infection of host cells requires the pentasaccharide lactoseries tetrasaccharide c (LSTc) and the serotonin receptor 5-hydroxytryptamine (5-HT) receptor 5-HT2AR. While LSTc is involved in the initial attachment of virus to cells via interactions with VP1, the mechanism by which 5-HT2AR contributes to infection is not clear. To further define the roles of serotonin receptors in infection, HEK293A cells, which are poorly permissive to JCPyV, were transfected with 14 different isoforms of serotonin receptor. Only 5-HT2 receptors were found to support infection by JCPyV. None of the other 11 isoforms of serotonin receptor supported JCPyV infection. Expression of 5-HT2 receptors did not increase binding of JCPyV to cells, but this was not unexpected, given that the cells uniformly expressed the major attachment receptor, LSTc. Infection of these cells remained sensitive to inhibition with soluble LSTc, confirming that LSTc recognition is required for JCPyV infection. Virus internalization into HEK293A cells was significantly and specifically enhanced when 5HT2 receptors were expressed. Taken together, these data confirm that the carbohydrate LSTc is the attachment receptor for JCPyV and that the type 2 serotonin receptors contribute to JCPyV infection by facilitating entry.
PMCID: PMC3838264  PMID: 24089568
3.  The Effects Of Fas-Ligand Overexpression On Alveolar Type II Cell Growth Kinetics In Perinatal Murine Lungs 
Pediatric research  2010;68(1):57-62.
We determined the time-specific effects of FasL overexpression on perinatal alveolar type II cell growth kinetics. To achieve temporal overexpression of respiratory epithelium-specific FasL expression, tetracycline inducible CCSP-rtTA/FasL-TetOp transgenic mice were given doxycycline (Dox) either from gestational day 14 (E14) to E19 (‘antenatal’ treatment group), from postnatal day 1 (P1) to P7 (‘postnatal’ group) or from E14 to P7 (‘combined’ antenatal and postnatal group). Antenatal Dox administration induced an increase of pulmonary FasL mRNA levels in double transgenic animals up to >300-fold over single transgenic littermate controls, associated with massive fetal respiratory epithelial apoptosis and excessive postnatal lethality. While animals from the combined antenatal/postnatal Dox treatment group continued to display evidence of increased apoptosis, there was a paradoxical increase in alveolar type II cell proliferation, resulting in a net increase in type II cell density, elevated pulmonary surfactant protein C levels and improved postnatal survival. Postnatal Dox administration was also associated with increased type II cell density, although FasL upregulation was more variable. In conclusion, these results, and our previous studies, suggest that FasL signaling has dual timing-dependent proapoptotic and proproliferative effects on postcanalicular type II cell kinetics.
PMCID: PMC2888646  PMID: 20375852
4.  Role of N-Linked Glycosylation of the 5-HT2A Receptor in JC Virus Infection▿  
Journal of Virology  2010;84(19):9677-9684.
JC virus (JCV) is a human polyomavirus and the causative agent of the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV infection of host cells is dependent on interactions with cell surface asparagine (N)-linked sialic acids and the serotonin 5-hydroxytryptamine2A receptor (5-HT2AR). The 5-HT2AR contains five potential N-linked glycosylation sites on the extracellular N terminus. Glycosylation of other serotonin receptors is essential for expression, ligand binding, and receptor function. Also, glycosylation of cellular receptors has been reported to be important for JCV infection. Therefore, we hypothesized that the 5-HT2AR N-linked glycosylation sites are required for JCV infection. Treatment of 5-HT2AR-expressing cells with tunicamycin, an inhibitor of N-linked glycosylation, reduced JCV infection. Individual mutation of each of the five N-linked glycosylation sites did not affect the capacity of 5-HT2AR to support JCV infection and did not alter the cell surface expression of the receptor. However, mutation of all five N-linked glycosylation sites simultaneously reduced the capacity of 5-HT2AR to support infection and altered the cell surface expression. Similarly, tunicamycin treatment reduced the cell surface expression of 5-HT2AR. Mutation of all five N-linked glycosylation sites or tunicamycin treatment of cells expressing wild-type 5-HT2AR resulted in an altered electrophoretic mobility profile of the receptor. Treatment of cells with PNGase F, to remove N-linked oligosaccharides from the cell surface, did not affect JCV infection in 5-HT2AR-expressing cells. These data affirm the importance of 5-HT2AR as a JCV receptor and demonstrate that the sialic acid component of the receptor is not directly linked to 5-HT2AR.
PMCID: PMC2937807  PMID: 20660194
5.  Forced expression of the cell cycle inhibitor p57Kip2 in cardiomyocytes attenuates ischemia-reperfusion injury in the mouse heart 
BMC Physiology  2008;8:4.
Myocardial hypoxic-ischemic injury is the cause of significant morbidity and mortality worldwide. The cardiomyocyte response to hypoxic-ischemic injury is known to include changes in cell cycle regulators. The cyclin-dependent kinase inhibitor p57Kip2 is involved in cell cycle control, differentiation, stress signaling and apoptosis. In contrast to other cyclin-dependent kinase inhibitors, p57Kip2 expression diminishes during postnatal life and is reactivated in the adult heart under conditions of cardiac stress. Overexpression of p57Kip2 has been previously shown to prevent apoptotic cell death in vitro by inhibiting stress-activated kinases. Therefore, we hypothesized that p57Kip2 has a protective role in cardiomyocytes under hypoxic conditions. To investigate this hypothesis, we created a transgenic mouse (R26loxpTA-p57k/+) that expresses p57Kip2 specifically in cardiac tissue under the ventricular cardiomyocyte promoter Mlc2v.
Transgenic mice with cardiac specific overexpression of p57Kip2 are viable, fertile and normally active and their hearts are morphologically indistinguishable from the control hearts and have similar heart weight/body weight ratio. The baseline functional parameters, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), LVdp/dtmax, heart rate (HR) and rate pressure product (RPR) were not significantly different between the different groups as assessed by the Langendorff perfused heart preparation. However, after subjecting the heart ex vivo to 30 minutes of ischemia-reperfusion injury, the p57Kip2 overexpressing hearts demonstrated preserved cardiac function compared to control mice with higher left ventricular developed pressure (63 ± 15 vs 30 ± 6 mmHg, p = 0.05), rate pressure product (22.8 ± 4.86 vs 10.4 ± 2.1 × 103bpm × mmHg, p < 0.05) and coronary flow (3.5 ± 0.5 vs 2.38 ± 0.24 ml/min, p <0.05).
These data suggest that forced cardiac expression of p57Kip2 does not affect myocardial growth, differentiation and baseline function but attenuates injury from ischemia-reperfusion in the adult mouse heart.
PMCID: PMC2268709  PMID: 18312674
6.  Regulated Proteolysis by Cortical Granule Serine Protease 1 at Fertilization 
Molecular Biology of the Cell  2004;15(5):2084-2092.
Cortical granules are specialized organelles whose contents interact with the extracellular matrix of the fertilized egg to form the block to polyspermy. In sea urchins, the granule contents form a fertilization envelope (FE), and this construction is critically dependent upon protease activity. An autocatalytic serine protease, cortical granule serine protease 1 (CGSP1), has been identified in the cortical granules of Strongylocentrotus purpuratus eggs, and here we examined the regulation of the protease activity and tested potential target substrates of CGSP1. We found that CGSP1 is stored in its full-length, enzymatically quiescent form in the granule, and is inactive at pH 6.5 or below. We determined the pH of the cortical granule by fluorescent indicators and micro-pH probe measurements and found the granules to be pH 5.5, a condition inhibitory to CGSP1 activity. Exposure of the protease to the pH of seawater (pH 8.0) at exocytosis immediately activates the protease. Activation of eggs at pH 6.5 or lower blocks activation of the protease and the resultant FE phenotypes are indistinguishable from a protease-null phenotype. We find that native cortical granule targets of the protease are β-1,3 glucanase, ovoperoxidase, and the protease itself, but the structural proteins of the granule are not proteolyzed by CGSP1. Whole mount immunolocalization experiments demonstrate that inhibition of CGSP1 activity affects the localization of ovoperoxidase but does not alter targeting of structural proteins to the FE. The mistargeting of ovoperoxidase may lead to spurious peroxidative cross-linking activity and contribute to the lethality observed in protease-null cells. Thus, CGSP1 is proteolytically active only when secreted, due to the low pH of the cortical granules, and it has a small population of targets for cleavage within the cortical granules.
PMCID: PMC404006  PMID: 14978210

Results 1-6 (6)