http://hdl.handle.net/2027.42/78416 Sun, 19 May 2013 03:34:53 GMT 2013-05-19T03:34:53Z http://deepblue.lib.umich.edu:80/bitstream/id/280031/216680.gif http://hdl.handle.net/2027.42/78416 http://hdl.handle.net/2027.42/78145 Change in Markers of Bone Metabolism with Chemotherapy for Advanced Prostate Cancer: Interleukin-6 Response Is a Potential Early Indicator of Response to Therapy Woods Ignatoski, Kathleen M.; Friedman, Judah; Escara-Wilke, June; Zhang, Xiaohua; Daignault, Stephanie; Dunn, Rodney L.; Smith, David C.; Keller, Evan T. Men with androgen-independent prostate cancer (AIPC) frequently have bone metastasis. The effects of chemotherapy on markers of bone metabolism have not been well characterized. We conducted a prospective study of patients with AIPC randomized in the first cycle to receive either docetaxel/estramustine or zoledronic acid, a bisphosphonate, to inhibit osteoclastic activity. Here we report the effects of therapy on markers of bone metabolism in these patients following the first cycle of therapy. Serum levels of several indices of bone remodeling were evaluated using commercial enzyme-linked immunosorbent assays. Changes in markers of bone metabolism were compared in patients receiving initial chemotherapy versus bisphosphonate. There was no significant difference in median change in any of the measured bone markers in patients given zoledronic acid when compared to chemotherapy. When comparing responders to nonresponders, overall interleukin-6 (IL-6) decreased by 35% in prostate-specific antigen responders; whereas, IL-6 levels increased by 76% in nonresponders (p = 0.03). Elevated IL-6 levels and reductions in IL-6 levels early in treatment may reflect ultimate clinical response to docetaxel-based regimens. Sun, 01 Feb 2009 00:00:00 GMT http://hdl.handle.net/2027.42/78145 2009-02-01T00:00:00Z http://hdl.handle.net/2027.42/78134 CD28/B7-Mediated Co-stimulation Is Critical for Early Control of Murine Cytomegalovirus Infection Cook, Charles H.; Chen, Li; Wen, Jin; Zimmerman, Peter; Zhang, Yingxue; Trgovcich, Joanne; Liu, Yang; Gao, Jian-xin Abstract Control of acute murine cytomegalovirus (MCMV) infection is dependent upon both innate and adaptive immune responses, relying primarily upon natural killer (NK) and T-cell responses for control. Although CD28/B7 plays a clear role in T-cell responses in many antigen systems including some viral infections, the importance of co-stimulation during MCMV infection is unconfirmed. In addition, recent data suggest that CD28/B7 co-stimulation might also be important to Ly49H+ NK-cell expansion. We therefore hypothesized that CD28/B7 co-stimulation is critical to viral control after MCMV infection, and further that CD28/B7 co-stimulation plays a role in MCMV-specific T- and NK-cell responses. To test these hypotheses, we utilized C57BL/6 mice lacking the co-stimulatory molecules B7-1 and B7-2 or CD28. After primary infection with MCMV, viral titers are significantly elevated in mice lacking CD28 or B7 compared with wild-type mice. Impaired viral control is associated with significant defects in peripheral T-cell responses to MCMV, which appear to be dependent upon CD28/B7 co-stimulation. Abnormal hepatic T-cell responses in CD28/ mice are preceded by impaired MCMV-specific Ly49H+ NK-cell responses. Cytokine evaluations confirm that CD28/B7 co-stimulation is not required for non-specific antiviral responses. We conclude that CD28-mediated co-stimulation is critical for early viral control during acute MCMV infection. Wed, 01 Apr 2009 00:00:00 GMT http://hdl.handle.net/2027.42/78134 2009-04-01T00:00:00Z http://hdl.handle.net/2027.42/78132 Differentiation of Human Embryonic Stem Cells to a Parathyroid-Like Phenotype Bingham, Eve L.; Cheng, Shih-Ping; Woods Ignatoski, Kathleen M.; Doherty, Gerard M. Iatrogenic hypoparathyroidism is the most common complication of cervical endocrine surgery. Current management is limited and palliative. As the molecular steps in parathyroid development have been defined, they may be replicable in vitro, with a goal of cellular replacement therapy. Human embryonic stem cell (hESC) lines were investigated as a model for parathyroid regeneration in vitro. BG01 was selected as a model based on expression of genes of interest in embryoid bodies (EBs). Established strategies for mouse embryonic stem cell differentiation into definitive endoderm were modified and extended to maximize the expression of definitive markers of parathyroid development. The optimal approach included the use of Activin A at 100 ng/mL with BG01 cells grown on murine embryonic fibroblasts for 5 days under conditions of increasing serum concentration. After 5 days, the cells were allowed to mature further in tissue culture without murine fibroblasts but with continuous Activin A. Our strategy produced differentiated cell cultures that expressed intermediate markers of endoderm and parathyroid development (CXCR4, EYA1, Six1, and Pax1), as well as markers of committed parathyroid precursors or developed parathyroid glands (glial cell missing-2 [Gcm2], CCL21, calcium sensing receptor [CaSR], and parathyroid hormone [PTH]). We further characterized the cells by testing conditioned medium from various time points in our differentiation scheme for the presence of PTH. We found that by keeping the cells in culture 2 weeks after the withdrawal of Activin A, the cells were able to produce PTH. Further in vivo work will be needed to demonstrate proper functionality of the cells developed in this way. Tue, 01 Sep 2009 00:00:00 GMT http://hdl.handle.net/2027.42/78132 2009-09-01T00:00:00Z http://hdl.handle.net/2027.42/75759 Pemphigoid and pemphigus antigens in cultured epidermal cells Diaz, Luis A.; Marcelo, Cynthia L. Fractions of IgG from sera of patients with pemphigoid and pemphigus added to monolayer cultures of mouse epidermal cells resulted in a sparse distribution of cells. Direct immunofluorescence studies of these monolayers revealed epidermal cell surface antigens reacting with pemphigoid and pemphigus antibodies. We suggest that these antibodies may bind to epidermal cell surface antigenic molecules which are important in maintaining epidermal cell adhesion in culture. Thu, 01 Jun 1978 00:00:00 GMT http://hdl.handle.net/2027.42/75759 1978-06-01T00:00:00Z