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Biomedical subjects

L Lunsford

Publications and source records attributed to L Lunsford.

6 recordsLinked to original sources

Fractionation of radiation treatment in acoustics. Rationale and evidence in comparison to radiosurgery.

Stereotactic fractionated radiotherapy has been proposed as a strategy to improve upon the results of single-fraction radiosurgery. The rationale for the strategy is that fractionation will allow complciations to be reduced while maintaining the same degree of long-term tumor control. This paper reviews the radiobiological arguements for fractionating radiation treatment of acoustic neuromas and examines claims for improvement in outcome.

Dose Fractionation, Radiation↗

Protective immune responses elicited in mice by immunization with formulations of poly(lactide-co-glycolide) microparticles.

Parenteral administration of microparticle encapsulated DNA elicits immune responses to the encoded antigens. Experiments were performed to test whether the addition of certain lipophilic agents to such formulations enhanced the activity of a beta-galactosidase (beta-gal) DNA vaccine. Addition of either taurocholic acid (TA) or monomethoxy polyethylene-glycol-distearoylphosphatidylehanolamine (PEG-DSPE) increased the efficiency of DNA encapsulation. Immunization of mice with encapsulated DNA formulations containing either compound significantly increased the number of antibody positive responders over that achieved with non-lipid containing particles. Moreover, responding animals demonstrated trends towards higher antibody titers and increased T cell responses. Tumor protection against the CT26.CL25 tumor cell line was demonstrated with lipid and non-lipid containing formulations. These results are the first demonstration of protection obtained by parenteral administration of PLG encapsulated DNA vaccines.

Animals↗

Two methods for quantifying DNA extracted from poly(lactide-co-glycolide) microspheres.

DNA can be formulated with synthetic polymers such as poly(lactide-co-glycolide) (PLG) to generate microparticles. Researchers have used either UV spectroscopy or fluorometry with PicoGreen((R)) dye to quantify PLG-encapsulated DNA. While the sensitivity of DNA detection and quantification by PicoGreen is higher ( approximately 12 pg/ml) compared to UV ( approximately 0.5 microg/ml), each method as an analytical tool has limitations. The premise of this work addresses the usefulness and limitations of each method to determine encapsulation efficiencies in PLG microspheres post-process, and to quantify release of DNA from microspheres during in vitro release experiments. In addition, assay conditions for accurate and reproducible extraction of DNA from PLG microspheres using a biphasic (aqueous/organic) solvent system are described. It was also determined that residual poly(vinyl alcohol) and DNA isoforms (linear, nicked, supercoiled) affected PicoGreen/DNA fluorescence values.

DNA↗

Tissue distribution and persistence in mice of plasmid DNA encapsulated in a PLGA-based microsphere delivery vehicle.

Information regarding the distribution and persistence of DNA encapsulated in poly-(lactide co-glycolide) microspheres was collected to provide additional information regarding the safety of DNA vaccines and to support the clinical testing of this new delivery system for DNA. Plasmid DNA was encapsulated in poly(lactide co-glycolide) microspheres and the distribution and persistence of plasmid in murine tissues resulting from parenteral administration were examined by a sensitive PCR assay. Encapsulated DNA delivered by intramuscular or subcutaneous injection can be detected for 100 days post-injection and is distributed primarily at the site of injection and the lymphoid organs. Intravenous administration results in more widespread dissemination with long term persistence limited to the lymphoid organs and those of the reticuloendothelial system. Specific cellular uptake of DNA by professional antigen presenting cells (APCs) following injection suggests the utility of microspheres as DNA delivery agents. Distribution and persistence studies support the safety of encapsulated DNA and the specific cellular uptake of DNA by professional APCs following injection suggests the utility of microspheres as DNA delivery agents.

Animals↗

A conserved 90 nucleotide element mediates translational repression of nanos RNA.

Correct formation of the Drosophila body plan requires restriction of nanos activity to the posterior of the embryo. Spatial regulation of nanos is achieved by a combination of RNA localization and localization-dependent translation such that only posteriorly localized nanos RNA is translated. Cis-acting sequences that mediate both RNA localization and translational regulation lie within the nanos 3' untranslated region. We have identified a discrete translational control element within the nanos 3' untranslated region that acts independently of the localization signal to mediate translational repression of unlocalized nanos RNA. Both the translational regulatory function of the nanos 3'UTR and the sequence of the translational control element are conserved between D. melanogaster and D. virilis. Furthermore, we show that the RNA helicase Vasa, which is required for nanos RNA localization, also plays a critical role in promoting nanos translation. Our results specifically exclude models for translational regulation of nanos that rely on changes in polyadenylation.

Animals↗

Human lymphocyte-specific pp52 gene is a member of a highly conserved dispersed family.

For a better understanding of genes that potentially function in B lymphocyte cell signaling, we isolated the human genomic counterpart of the murine pp52 or LSP1 gene. We unexpectedly found that the human pp52 gene is one of four closely related loci. Representative cosmids from each of the four family members were isolated and chromosomally localized by fluorescence in situ hybridization. Nucleotide sequence was obtained from an exon common to each locus and demonstrated very close similarity among all four loci. Two of the four loci harbored dysfunctional frameshift mutations or premature translation stop sites. The exon of one locus was flanked by an 80-bp perfect inverted repeat, suggesting that it may have originated through a looped intermediate DNA structure. Through a series of cDNA hybridization studies and nucleotide sequence analyses we were able to unambiguously link the lymphocyte-expressed gene to the locus mapped to chromosome 11p15.5. This same chromosomal band has been involved in tumor-related chromosomal translocations found in chronic lymphocytic leukemia.

Animals↗