Frederick D. Coffman

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Alterations in the human 13q14 genomic region containing microRNAs mir-15a and mir-16-1 are present in most human chronic lymphocytic leukemia (CLL). We have previously found the development of CLL in the New Zealand Black murine model to be associated with a point mutation in the primary mir-15a/16-1 region, which correlated with a decrease in mature(More)
BACKGROUND YKL-40 has been implicated as a mediator of collagen synthesis and extracellular matrix re-modeling as well as mitogenesis. Elevated serum levels of YKL-40 have been associated with worse survival in a variety of malignancies including breast cancer. We wished to determine if immunohistochemically detected expression had prognostic implications(More)
Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). T-cell transformation is mainly due to the actions of the viral phosphoprotein Tax. Tax interacts with multiple transcriptional factors, aiding the transcription of many cellular genes. Here,(More)
Mouse models are valuable tools in the study of human chronic lymphocytic leukaemia (CLL). The New Zealand Black (NZB) strain is a naturally occurring model of late-onset CLL characterized by B-cell hyperproliferation and autoimmunity early in life, followed by progression to CLL. Other genetically engineered models of CLL that have been developed include(More)
Differentiation of mammalian cells implies cessation of DNA replication and cell proliferation; the potential controls of this coupling are examined here. It is clear that the known or proposed mechanisms of down-regulation of replicative cellular activities vary in different lineages of cell differentiation, and occur in all phases of the cell cycle. In G1(More)
Numerous studies have demonstrated that DNA replication initiates within the 30 kB non-transcribed spacer (NTS) region of the human ribosomal RNA gene (rDNA). Using a series of closely spaced primer pairs to measure nascent leading strand abundance in mid and late S phase cells isolated by centrifugal elutriation, we find evidence for one highly preferred(More)
An insulin hexamer containing one B10-bound Co(III) ion and one unoccupied B10 site has been synthesized. The properties of the monosubstituted hexamer show that occupancy of only one B10 site by Co3+ is sufficient to stabilize the hexameric form under the conditions of pH and concentration used in these studies. The experimentally determined, second-order(More)
Telomere integrity is critical for telomere function and genomic stability. We previously demonstrated that non-erythroid α-spectrin (αIISp) is present in mammalian cell nuclei where it is important in repair of DNA interstrand cross-links (ICLs) and chromosome stability. We now demonstrate that αIISp is also important for telomere maintenance after ICL(More)
The adherence of cells to microvascular endothelium is important in a number of processes, including inflammatory responses and metastasis. It has been demonstrated that in human models, cytokines such as TNF, IL-1, IFN-gamma increase the adhesiveness of endothelium for cells of the immune and inflammatory system by stimulating the expression of cell(More)
In response to exposure to the inflammatory cytokines tumor necrosis factor-alpha (TNF) and interferon-gamma (IFN-gamma), murine brain microvascular endothelial cells (MME) synthesize the cell surface molecule, vascular cell adhesion molecule-1 (VCAM-1), and the intracellular enzyme, inducible nitric oxide synthase (iNOS). However, iNOS synthesis requires(More)