[show abstract][hide abstract] ABSTRACT: Tuberculosis (TB) is the worldwide leading cause of death among HIV-infected individuals, accounting for more than half of AIDS-related deaths. A high risk of tuberculosis (TB) has been shown in early stages of the HIV disease, even in the presence of normal CD4(+) cell counts. Moreover, the factors that determine protective immunity vs. susceptibility to Mycobacterium tuberculosis cannot be fully explained by simple changes in IFNγ levels or a shift from Th1 to Th2 cytokines. This work investigated the relationship between cytokine expression profiles in peripheral blood mononuclear cells (PBMC) and susceptibility to M. tuberculosis in 10 HIV+ women who went onto develop TB. RNA transcripts for IL-4, IL-4δ2, IL-10, IL-12(p35), IL-13, IL-17A, IFNγ and TNFα were measured by real-time quantitative PCR in unstimulated or TB peptide antigen-stimulated PBMCs from 10 HIV+ women with positive tuberculin skin tests (TST) and compared with HIV-seropositive and seronegative women without previous TB and negative TST. Stimulated PBMC cultures showed significantly lower expression of IL-12p35 (p=0.004) and IL-10 (p=0.026) in the HIV+TB+ group 6-12months before onset of TB compared to HIV+TB- women. Unstimulated PBMC from HIV+TB+ women also had lower expression of Th2 cytokines [IL-4 (p=0.056) and IL-13 (p=0.050)] compared to HIV+TB- women. These results suggest that lower IL-12 production by PBMC in response to TB antigens and lower levels of both Th1 and Th2 cytokines by PBMC correlate with future development of TB in HIV-infected women and may be responsible for their increased susceptibility.
[show abstract][hide abstract] ABSTRACT: Neurulation requires precise, spatio-temporal expression of numerous genes and coordinated interaction of signal transduction and gene regulatory networks, disruption of which may contribute to the etiology of neural tube defects (NTDs). MicroRNAs (miRNAs) are key modulators of cell and tissue differentiation. To define potential roles of miRNAs in development of the murine neural tube (NT), miRNA microarray analysis was conducted to establish expression profiles, and identify miRNA target genes and functional gene networks.
The miRNA expression profiles in murine embryonic NTs derived from gestational days 8.5, 9.0, and 9.5 were defined and compared utilizing miRXplore microarrays from Miltenyi Biotec GmbH, Bergisch Gladbach, Germany. Gene expression changes were verified by TaqMan quantitative Real-Time PCR. The clValid R package and the UPGMA (hierarchical) clustering method were utilized for cluster analysis of the microarray data. Functional associations among selected miRNAs were examined via Ingenuity Pathway Analysis.
The miRXplore chips enabled examination of 609 murine miRNAs. Expression of approximately 12% of these was detected in murine embryonic NTs. Clustering analysis revealed several developmentally regulated expression clusters among these expressed genes. Target analysis of differentially expressed miRNAs enabled identification of numerous target genes associated with cellular processes essential for normal NT development. Utilization of Ingenuity Pathway Analysis revealed interactive biologic networks which connected differentially expressed miRNAs with their target genes, and highlighted functional relationships.
The present study defined unique gene expression signatures of a range of miRNAs in the developing NT during the critical period of NT morphogenesis. Analysis of miRNA target genes and gene interaction pathways revealed that specific miRNAs might direct expression of numerous genes encoding proteins, which have been shown to be indispensable for normal neurulation. This study is the first to identify miRNA expression profiles and their potential regulatory networks in the developing mammalian NT.
Birth Defects Research Part A Clinical and Molecular Teratology 08/2011; 91(8):744-62. · 2.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: High-level occupational exposures to some industrial chemicals have been associated with liver diseases, including nonalcoholic fatty liver disease (NAFLD). However, the potential role of low-level environmental pollution on liver disease in the general population has not been evaluated.
We determined whether environmental pollutants are associated with an elevation in serum alanine aminotransferase (ALT) activity and suspected NAFLD in U.S. adults.
This cross-sectional cohort study evaluated adult participants without viral hepatitis, hemochromatosis, or alcoholic liver disease from the National Health and Nutrition Examination Survey (NHANES) for 2003-2004. ALT elevation was defined in men as ≥ 37 IU/L (age 18-20 years) and ≥ 48 IU/L (age ≥ 21 years) and in women as ≥ 30 IU/L (age 18-20 years) and ≥ 31 IU/L (age ≥ 21 years). Adjusted odds ratios (ORs) for ALT elevation were determined across exposure quartiles for 17 pollutant subclasses comprising 111 individual pollutants present with at least a 60% detection rate. Adjustments were made for age, race/ethnicity, sex, body mass index, poverty income ratio, and insulin resistance. Individual pollutants from subclasses associated with ALT elevation were subsequently analyzed.
The overall prevalence of ALT elevation was 10.6%. Heavy metals and polychlorinated biphenyls (PCBs) were associated with dose-dependent increased adjusted ORs for ALT elevation. Within these subclasses, increasing whole-blood levels of lead and mercury and increasing lipid-adjusted serum levels of 20 PCBs were individually associated with ALT elevation.
PCB, lead, and mercury exposures were associated with unexplained ALT elevation, a proxy marker of NAFLD, in NHANES 2003-2004 adult participants.
Environmental Health Perspectives 12/2010; 118(12):1735-42. · 7.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: In the US the suicide rate on a population basis has risen and fallen over time between approximately 10 and 12 per 100,000 population. The recent trend toward an increased rate has been paralleled by an increase in emergency department visits for attempted suicide. The purpose of this study was to examine trends in suspected suicide (SS) cases reported to the National Poison Data System (NPDS), over a 9-year period (2000–2008).
[show abstract][hide abstract] ABSTRACT: The American College of Cardiology, the American Heart Association, and the Society for Cardiovascular Angiography and Interventions strongly recommend that primary Percutaneous Coronary Intervention (PCI) should be performed in facilities that have an experienced cardiovascular surgical team available as emergency backup for all procedures. The current study investigates the medical soundness of allowing select facilities in Kentucky to perform primary PCI despite being devoid of onsite emergency backup capabilities.
Two hospitals in the state of Kentucky, currently without emergency backup capabilities, have been allowed to perform primary PCIs for more than three years (beginning in April 2005) by the Kentucky Cabinet for Health and Family Services. The two hospitals selected were of similar size (approximately 200 beds) and similar distances from hospitals with onsite emergency backup capabilities (approximately one hour). We performed an analysis evaluating if hospitals without backup surgical capability have similar outcomes when compared to hospitals with backup surgical capabilities. Outcome variables included: (1) mortality, (2) cardiac arrest as result of PCI, (3) emergency surgery performed as a result of PCI, and (4) door-to-balloon time.
Our results suggest that there is no significant difference in any of the outcome variables studied between facilities with and without onsite emergency backup capabilities.
Recommendations concerning primary PCI may need to be revisited. The principal outcomes associated with primary PCI were not significantly affected by whether a facility has onsite emergency backup capabilities. Therefore, we recommend that hospitals without backup surgical capabilities be allowed to perform primary PCI (with restrictions based on surgeon experience and the facilities' volume).
The Journal of the Kentucky Medical Association 11/2009; 107(11):451-8.