Biomedical subjects

Daniel E Hall

Publications and source records attributed to Daniel E Hall.

21 records · Page 2Linked to original sources

PubMed2002

Noninvasive real-time imaging of apoptosis.

Strict coordination of proliferation and programmed cell death (apoptosis) is essential for normal physiology. An imbalance in these two opposing processes results in various diseases including AIDS, neurodegenerative disorders, myelodysplastic syndromes, ischemiareperfusion injury, cancer, autoimmune disease, among others. Objective and quantitative noninvasive imaging of apoptosis would be a significant advance for rapid and dynamic screening as well as validation of experimental therapeutic agents. Here, we report the development of a recombinant luciferase reporter molecule that when expressed in mammalian cells has attenuated levels of reporter activity. In cells undergoing apoptosis, a caspase-3-specific cleavage of the recombinant product occurs, resulting in the restoration of luciferase activity that can be detected in living animals with bioluminescence imaging. The ability to image apoptosis noninvasively and dynamically over time provides an opportunity for high-throughput screening of proapoptotic and antiapoptotic compounds and for target validation in vivo in both cell lines and transgenic animals.

Animals↗

PubMedDate not supplied

Molecular imaging of gene expression and efficacy following adenoviral-mediated brain tumor gene therapy.

Cancer gene therapy is an active area of research relying upon the transfer and subsequent expression of a therapeutic transgene into tumor cells in order to provide for therapeutic selectivity. Noninvasive assessment of therapeutic response and correlation of the location, magnitude, and duration of transgene expression in vivo would be particularly useful in the development of cancer gene therapy protocols by facilitating optimization of gene transfer protocols, vector development, and prodrug dosing schedules. In this study, we developed an adenoviral vector containing both the therapeutic transgene yeast cytosine deaminase (yCD) along with an optical reporter gene (luciferase). Following intratumoral injection of the vector into orthotopic 9 L gliomas, anatomical and diffusion-weighted MR images were obtained over time in order to provide for quantitative assessment of overall therapeutic efficacy and spatial heterogeneity of cell kill, respectively. In addition, bioluminescence images were acquired to assess the duration and magnitude of gene expression. MR images revealed significant reduction in tumor growth rates associated with yCD/5-fluorocytosine (5FC) gene therapy. Significant increases in mean tumor diffusion values were also observed during treatment with 5FC. Moreover, spatial heterogeneity in tumor diffusion changes were also observed revealing that diffusion magnetic resonance imaging could detect regional therapeutic effects due to the nonuniform delivery and/or expression of the therapeutic yCD transgene within the tumor mass. In addition, in vivo bioluminescence imaging detected luciferase gene expression, which was found to decrease over time during administration of the prodrug providing a noninvasive surrogate marker for monitoring gene expression. These results demonstrate the efficacy of the yCD/5FC strategy for the treatment of brain tumors and reveal the feasibility of using multimodality molecular and functional imaging for assessment of gene expression and therapeutic efficacy.

Adenoviridae↗

PubMedDate not supplied

Religious attendance: more cost-effective than lipitor?

BACKGROUND: A recent meta-analysis demonstrates a robust but small association between weekly religious attendance and longer life. However, the practical significance of this finding remains controversial. METHODS: Age specific, actuarial death rates were modified according to published odds ratios to model the additional years of life attributable to: (1) weekly religious attendance; (2) regular physical exercise; and (3) statin-type lipid-lowering agents. Secondary analyses estimated the approximate cost for each additional year of life gained. RESULTS: Weekly attendance at religious services accounts for an additional 2 to 3 life-years compared with 3 to 5 life-years for physical exercise and 2.5 to 3.5 life-years for statin-type agents. The approximate cost per life-year gained was between 2,000 dollars and 6,000 dollars for regular exercise, 3,000 dollars and 10,000 dollars for regular religious attendance, and between 4,000 dollars and 14,000 dollars for statin-type agents. CONCLUSION: The real-world, practical significance of regular religious attendance is comparable to commonly recommended therapies, and rough estimates even suggest that religious attendance may be more cost-effective than statins. Religious attendance is not a mode of medical therapy, but these findings warrant more and better quality research designed to examine the associations between religion and health, and the potential relevance such associations might have for medical practice.

Actuarial Analysis↗