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1. Perifollicular transgenic expression of human interleukin-1 receptor antagonist protein following topical application of novel liposome-plasmid dna formulations in vivo

Author

College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065., Department of Internal Medicine, Division of Rheumatology, 5520 MSRB I, Box 0608, 1150 West Medical Center Drive, University of Michigan Medical Center, Ann Arbor, MI 48109-0680., College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065. ; Department of Internal Medicine, Division of Rheumatology, 5520 MSRB I, Box 0608, 1150 West Medical Center Drive, University of Michigan Medical Center, Ann Arbor, MI 48109-0680. ; College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065., Niemiec, Susan M., Latta, Jill M., Ramachandran, Chandrasekharan, Weiner, Norman D., Roessler, Blake J., College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065., Department of Internal Medicine, Division of Rheumatology, 5520 MSRB I, Box 0608, 1150 West Medical Center Drive, University of Michigan Medical Center, Ann Arbor, MI 48109-0680., College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065. ; Department of Internal Medicine, Division of Rheumatology, 5520 MSRB I, Box 0608, 1150 West Medical Center Drive, University of Michigan Medical Center, Ann Arbor, MI 48109-0680. ; College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065., Niemiec, Susan M., Latta, Jill M., Ramachandran, Chandrasekharan, Weiner, Norman D., and Roessler, Blake J.

Abstract

Expression plasmid DNA for the human interleukin-1 receptor antagonist (IL-1ra) protein was formulated with nonionic:cationic (NC) liposomes or phosphatidylcholine:cationic (PC) liposomes and applied to the auricular skin of hamsters in single- and multiple-dose protocols. Confocal microscopy identified delivery of plasmid DNA proximal to perifollicular cells, and successful transfection of perifollicular cells was identified by immunohistochemistry and ELISA. Skin treated for 3 days with the NC liposomes had statistically significant levels of transgenic IL-1ra present for 5 days post-treatment. Expression of transgenic IL-1ra was specific to areas of skin treated with NC liposomes but not PC liposomes. The results indicate that the NC liposomes can deliver expression plasmid DNA to perifollicular cells and mediate transient transfection in vivo.

Published
2006

2. Expression of Escherichia coli [beta]-Galactosidase and Rat HPRT in the CNS of Macaca mulatta Following Adenoviral Mediated Gene Transfer

Author

Department of Internal Medicine, Division of Rheumatology, University of Michigan Medical School, Ann Arbor, Michigan, USA., Department of Surgery, Division of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan, USA., Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA., Davidson, Beverly L., Doran, Stephen E., Shewach, Donna S., Latta, Jill M., Hartman, John W., Roessler, Blake J., Department of Internal Medicine, Division of Rheumatology, University of Michigan Medical School, Ann Arbor, Michigan, USA., Department of Surgery, Division of Neurosurgery, University of Michigan Medical School, Ann Arbor, Michigan, USA., Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA., Davidson, Beverly L., Doran, Stephen E., Shewach, Donna S., Latta, Jill M., Hartman, John W., and Roessler, Blake J.

Abstract

Adenoviral-mediated gene transfer to the caudate nucleus of Macaca mulatta was accomplished using stereotactic injection of two distinct recombinant Ad5 vectors containing the gene for Escherichia coli [beta]-galactosidase and the cDNA for rat hypoxanthine-guanine phosphoribosylphosphotransferase (HPRT), respectively. Multiple analyses (including immunohistochemistry, histochemistry, transmission electron microscopy, RNA in situ hybridization, nucleotide pool analysis, and enzyme assay) confirmed efficient expression of [beta]-galactosidase and rat HPRT. Transgene expression was evident in both neurons and glia. Clinically, no evidence of meningitis or cerebritis was observed and no focal neurological deficits were detected in the animal. These preliminary studies indicate that recombinant adenovirus is capable of mediating high level transgene expression to the brains of higher order mammals.

Published
2006

4. Serum Soluble Interleukin-2 Receptor Is Associated With Clinical and Pathologic Disease Status in Hairy Cell Leukemia

Author

Richards, Jon M., Mick, Rosemarie, Latta, Jill M., Daly, Karen, Ratain, Mark J., Vardiman, James W., and Golomb, Harvey M.

Abstract

Hairy cell leukemia is a chronic lymphoproliferative disorder of B-cell lineage, whose malignant cells express the interleukin-2 (IL-2) receptor. A soluble form of the IL-2 receptor is released by these cells in culture, and the sera of patients with hairy cell leukemia contain elevated levels of this soluble receptor. Four hundred twenty-seven serum samples from 101 patients were analyzed for soluble IL-2 receptor (sIL-2R). The clinical status of patients appeared to be associated with the serum level of sIL-2R. The hairy cell index (a measure of tumor cell burden) was correlated with the square root of the serum sIL-2R level (r = .77). Improved clinical status was associated with decreasing serum sIL-2R levels, whereas disease relapse was associated with increasing levels. Notably, every patient who responded to therapy had a decline in serum sIL-2R level, and every patient with disease progression had an increase in serum sIL-2R level. This phenomenon was observed for several different treatments, including standard-dose interferon, low-dose interferon, and deoxycoformycin. The predictive reliability of this test is currently being prospectively evaluated.

Published
1990
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