Medical Biology - Research Publications

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    Cytomegalovirus DNAemia and disease: natural history and management in settings other than allogeneic stem cell transplantation
    Ng, Ashley P. ; WORTH, LEON ; Chen, Luke ; Seymour, John F. ; Prince, H. Miles ; SLAVIN, MONICA ; Thursky, Karin (Ferrata Storti Foundation, 2005-12)
    Background and Objectives. Despite increasing intensity and profound immunosuppressionassociated with newer therapies for hematologic malignancies, little information exists regarding cytomegalovirus (CMV) reactivation in settings other than allogeneic stem cell transplantation (SCT).Design and Methods. We reviewed the epidemiology of CMV disease in patients who were CMV polymerase chain reaction (PCR) positive during treatment for hematologic malignancies without allogeneic SCT from June 1999 to June 2004.Results. Thirty-six patients with CMV reactivation were identified. Of these, 92% were undergoing investigation for fever. Fifteen patients with CMV DNAemia were treatedwith ganciclovir without CMV disease developing. Notably, 20 patients with untreated CMV DNAemia did not develop CMV disease during a median follow-up of 3.5 (1-19)months. The highest rates of reactivation were observed with HyperCVAD (7.8%) and alemtuzumab (50%).Interpretation and Conclusions. We recommend that screening for CMV DNAemia be instituted and pre-emptive therapy contemplated for asymptomatic CMV reactivationonly in patients receiving alemtuzumab therapy, but not routinely for other patients outside the allogeneic SCT setting. Indeed for such patients, detection of isolated CMV DNAemia does not imply the need for immediate therapy and future studies are needed to validate PCR detection of CMV DNA and CMV DNA titers as predictors for CMV disease.
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    Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells
    Gainsford, T. ; Willson, T. A. ; METCALF, DONALD ; HANDMAN, EMANUELA ; McFarlane, C. ; Ng, A. ; STOKES, NICOLA ; Alexander, W. S. ; Hilton, D. J. ( 1996)
    Many cytokines exert their biological effect through members of the hemopoietin receptor family. Using degenerate oligonucleotides to the common WSXWS motif, we have cloned from human hemopoietic cell cDNA libraries various forms of the receptor that was recently shown to bind the obesity hormone, leptin. mRNAs encoding long and short forms of the human leptin receptor were found to be coex- pressed in a range of human and murine hemopoietic organs, and a subset of cells from these tissues bound leptin at the cell surface. Ectopic expression in murine BaF3 and M1 cell lines revealed that the long, but not the short, form of the leptin receptor can signal proliferation and differentiation, respectively. In cultures of murine or human marrow cells, human leptin exhibited no capacity to stimulate cell survival or proliferation, but it enhanced cytokine production and phagocytosis of Leishmania parasites by murine peritoneal macrophages. Our data provide evidence that, in addition to its role in fat regulation, leptin may also be able to regulate aspects of hemopoiesis and macrophage function.