Search tips
Search criteria

Results 1-8 (8)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  Using a Health in All Policies Approach to Address Social Determinants of Sexually Transmitted Disease Inequities in the Context of Community Change and Redevelopment 
Public Health Reports  2013;128(Suppl 3):77-86.
We used a Health in All Policies (HiAP) framework to determine what data, policy, and community efficacy opportunities exist for improving sexual health and reducing sexually transmitted diseases (STDs) in an area surrounding an Army base undergoing redevelopment in Atlanta, Georgia.
We conducted a literature review, consulted with experts, mapped social determinants in the community, conducted key informant interviews with community leaders to explore policy solutions, used Photovoice with community members to identify neighborhood assets, and shared data with all stakeholder groups to solicit engagement for next steps.
We identified the following HiAP-relevant determinants of STD inequities in the literature: education, employment, male incarceration, drug and alcohol marketing, and social capital. Quantitative data confirmed challenges in education, employment, and male incarceration in the area. Interviews identified policy opportunities such as educational funding ratios, Community Hire Agreements, code and law enforcement, addiction and mental health resources, lighting for safety, and a nonemergency public safety number. Photovoice participants identified community assets to protect including family-owned businesses, green spaces, gathering places, public transportation resources, historical sites, and architectural elements. Stakeholder feedback provided numerous opportunities for next steps.
This study contributes to the HiAP literature by providing an innovative mixed-methods design that locates social determinants of STDs within a geographic context, identifies policy solutions from local leaders, highlights community assets through the lens of place attachment, and engages stakeholders in identifying next steps. Findings from this study could inform other redevelopments, community-based studies of STDs, and HiAP efforts.
PMCID: PMC3945453  PMID: 24179283
2.  Alfentanil: Correlations Between Absence of Effect Upon Subcutaneous Mast Cells and Absence of Granuloma Formation After Intrathecal Infusion in the Dog 
We hypothesize that intrathecal (IT) granulomas arising from the IT infusion of several opiates may result from the degranulation of meningeal mast cells (MC). Given functional covariance between cutaneous and meningeal mast cells, we propose that opioids that do not degranulate cutaneous mast cells will not produce a granuloma. An opioid meeting this criteria is the phenylpiperadine Alfentanil HCl.
Three experiments were accomplished in dogs. 1) Cutaneous MC degranulation. Flare areas on the dog abdomen were measured after intradermal (ID) alfentanil, morphine or compound 48–80. 2) Dose ranging of analgesic effects of IT alfentanil infusion. Dogs with lumbar IT catheters received continuous infusion for 24 hrs of different concentrations (1–20 mg/mL/d) of alfentanil and analgesic effects were assessed. iii) Granuloma inducing effects. Dogs received IT Alfentanil (20 mg/ml/d; N = 5; 22–28 days)) or morphine (12 mg/mL/d; N=3; 22–30 days) and spinal cord harvested for histopathology after 22–30d of infusion.
1) ID Morphine (10 mg/mL) and Compound 48–80 (1mg/mL) but not alfentanil at concentrations up to 20mg/mL produced a cutaneous flare. Intrathecal Alfentanil infusion produced increases in thermal escape latency at concentrations as low as 2 mg/mL/d). A significant depression of arousal was noted in the dogs receiving 20 mg/mL. Over the 22–30 day infusion period, morphine (12 mg/mL/d) resulted in granulomas in all three animals examined whereas intrathecal alfentanil at 20 mg/mL/d failed to initiate a granuloma in any animal.
These results support the hypothesis linking mast cell degranulation and intrathecal granulomas.
PMCID: PMC3582801  PMID: 23170763
3.  Coordination of adjacent domains mediates TACC3–ch-TOG–clathrin assembly and mitotic spindle binding 
The Journal of Cell Biology  2013;202(3):463-478.
Aurora A phosphorylation-induced interaction of TACC3 and clathrin coordinates adjacent domains in each protein to create a microtubule-binding interface, whereas a distinct site in TACC3 recruits ch-TOG to mitotic spindles.
Acomplex of transforming acidic coiled-coil protein 3 (TACC3), colonic and hepatic tumor overexpressed gene (ch-TOG), and clathrin has been implicated in mitotic spindle assembly and in the stabilization of kinetochore fibers by cross-linking microtubules. It is unclear how this complex binds microtubules and how the proteins in the complex interact with one another. TACC3 and clathrin have each been proposed to be the spindle recruitment factor. We have mapped the interactions within the complex and show that TACC3 and clathrin were interdependent for spindle recruitment, having to interact in order for either to be recruited to the spindle. The N-terminal domain of clathrin and the TACC domain of TACC3 in tandem made a microtubule interaction surface, coordinated by TACC3–clathrin binding. A dileucine motif and Aurora A–phosphorylated serine 558 on TACC3 bound to the “ankle” of clathrin. The other interaction within the complex involved a stutter in the TACC3 coiled-coil and a proposed novel sixth TOG domain in ch-TOG, which was required for microtubule localization of ch-TOG but not TACC3–clathrin.
PMCID: PMC3734082  PMID: 23918938
4.  Examining the Prospective Effects of Making a Virginity Pledge Among Males Across Their 4 Years of College 
We examined prospective associations of making a virginity pledge on sexual behaviors among male college students.
A sample of 795 males was followed for 4 years (2008, 2009, 2010, 2011), with response rates ranging from 72% – 82% across the follow-up years.
Males were surveyed at the end of each of their 4 years in college about sexual behavior activities and other risky behaviors.
Multivariate regression analyses indicated that males who made private virginity pledges were significantly more likely to remain abstinent across all 4 years of college and have fewer sexual partners at the end of their third and fourth years of college, even after controlling for age, race, high-risk drinking, impulsivity, and religiosity. Making a pledge was not related to condom use.
Findings suggest that abstinence-based messages alone are not sufficient yet should be included as part of comprehensive sex education programs.
PMCID: PMC3576721  PMID: 23409861
college students; sexual behaviors; virginity pledges; prospective design
5.  Nrf2 is overexpressed in pancreatic cancer: implications for cell proliferation and therapy 
Molecular Cancer  2011;10:37.
Nrf2 is a key transcriptional regulator of a battery of genes that facilitate phase II/III drug metabolism and defence against oxidative stress. Nrf2 is largely regulated by Keap1, which directs Nrf2 for proteasomal degradation. The Nrf2/Keap1 system is dysregulated in lung, head and neck, and breast cancers and this affects cellular proliferation and response to therapy. Here, we have investigated the integrity of the Nrf2/Keap1 system in pancreatic cancer.
Keap1, Nrf2 and the Nrf2 target genes AKR1c1 and GCLC were detected in a panel of five pancreatic cancer cell lines. Mutation analysis of NRF2 exon 2 and KEAP1 exons 2-6 in these cell lines identified no mutations in NRF2 and only synonomous mutations in KEAP1. RNAi depletion of Nrf2 caused a decrease in the proliferation of Suit-2, MiaPaca-2 and FAMPAC cells and enhanced sensitivity to gemcitabine (Suit-2), 5-flurouracil (FAMPAC), cisplatin (Suit-2 and FAMPAC) and gamma radiation (Suit-2). The expression of Nrf2 and Keap1 was also analysed in pancreatic ductal adenocarcinomas (n = 66 and 57, respectively) and matching normal benign epithelium (n = 21 cases). Whilst no significant correlation was seen between the expression levels of Keap1 and Nrf2 in the tumors, interestingly, Nrf2 staining was significantly greater in the cytoplasm of tumors compared to benign ducts (P < 0.001).
Expression of Nrf2 is up-regulated in pancreatic cancer cell lines and ductal adenocarcinomas. This may reflect a greater intrinsic capacity of these cells to respond to stress signals and resist chemotherapeutic interventions. Nrf2 also appears to support proliferation in certain pancreatic adenocarinomas. Therefore, strategies to pharmacologically manipulate the levels and/or activity of Nrf2 may have the potential to reduce pancreatic tumor growth, and increase sensitivity to therapeutics.
PMCID: PMC3098205  PMID: 21489257
6.  Laminin-511 and integrin beta-1 in hair follicle development and basal cell carcinoma formation 
Initiation of the hair follicle placode and its subsequent growth, maturation and cycling in post-natal skin requires signaling interactions between epithelial cells and adjacent dermal cells and involves Shh signaling via the primary cilium. Previous reports have implicated laminins in hair follicle epithelial invagination.
Here we use a human BCC model system and mouse mutants to re-evaluate the role of laminin-511 in epithelial invagination in the skin. Blocking laminin 511 and 332 in BCCs maintains primary cilia and Shh signalling, but prevents invagination. Similarly, in laminin-511 and dermal beta-1 integrin mutants, dermal papilla development and primary cilia formation are normal. Dermal beta-1 integrin mutants have normal hair follicle development.
Our data provides support for a primary role of laminin-511 promoting hair follicle epithelial downgrowth without affecting dermal primary cilia and Shh target gene induction.
PMCID: PMC2995472  PMID: 21067603
7.  Proteomic analysis of Nrf2 deficient transgenic mice reveals cellular defence and lipid metabolism as primary Nrf2-dependent pathways in the liver 
Journal of Proteomics  2010;73(8):1612-1631.
The transcription factor Nrf2 regulates expression of multiple cellular defence proteins through the antioxidant response element (ARE). Nrf2-deficient mice (Nrf2−/−) are highly susceptible to xenobiotic-mediated toxicity, but the precise molecular basis of enhanced toxicity is unknown. Oligonucleotide array studies suggest that a wide range of gene products is altered constitutively, however no equivalent proteomics analyses have been conducted. To define the range of Nrf2-regulated proteins at the constitutive level, protein expression profiling of livers from Nrf2−/− and wild type mice was conducted using both stable isotope labelling (iTRAQ) and gel electrophoresis methods. To establish a robust reproducible list of Nrf2-dependent proteins, three independent groups of mice were analysed. Correlative network analysis (MetaCore) identified two predominant groups of Nrf2-regulated proteins. As expected, one group comprised proteins involved in phase II drug metabolism, which were down-regulated in the absence of Nrf2. Surprisingly, the most profound changes were observed amongst proteins involved in the synthesis and metabolism of fatty acids and other lipids. Importantly, we show here for the first time, that the enzyme ATP-citrate lyase, responsible for acetyl-CoA production, is negatively regulated by Nrf2. This latter finding suggests that Nrf2 is a major regulator of cellular lipid disposition in the liver.
Graphical abstract
PMCID: PMC2891861  PMID: 20399915
Nrf2; Transgenic; Liver; Protein expression; iTRAQ; Lipid metabolism
8.  Bilateral Congenital Absence of Internal Iliac Arteries, Prominent Lumbar Arteries, and a Ruptured Mycotic Aneurysm of the Abdominal Aorta 
A 46-year-old man was admitted for surgery on a ruptured mycotic abdominal aortic aneurysm. Emergency repair was performed, during which certain anomalies were noted. First, the bifurcation of the aorta was posterior to the left common iliac vein. Second there were no internal iliac arteries. Also, there were prominent lumbar arteries compensating for the absent internal iliac arteries bilaterally. This, we consider, is the first reported case of congenitally absent bilateral internal iliac arteries.
PMCID: PMC1964626  PMID: 16834843
Bilateral congenital absence of internal iliac arteries

Results 1-8 (8)