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Wootton SK, Halbert CL, Miller AD: Sheep retrovirus structural protein induces lung tumours. Nature 43:904–907, 2005
Vascular adhesion protein-1 (VAP-1) is a glycoprotein that has both adhesive and enzymatic functions. VAP-1 is produced by endothelial cells and rapidly translocated to the cell surface during inflammation, where it is believed to mediate leukocyte binding to vascular endothelium. Finnish investigators recently developed a blocking antibody that neutralized VAP-1 function and enabled them to investigate the role of VAP-1 in inflammation. Using murine models, they showed that leukocytes recognize and use VAP-1 to migrate into sites of both acute and chronic inflammation. Acute models included proteose peptone-induced peritonitis and CCL-12-induced air pouch inflammation; chronic inflammation was studied in the non-obese diabetic model. In acute inflammation models, VAP-1 blocking antibody inhibited monocyte and granulocyte migration into sites of inflammation. Long-term administration of the antibody to non-obese diabetic mice significantly reduced the incidence of diabetes. Thus, VAP-1 is an important modulator of leukocyte trafficking during inflammation.
Merinen M, Irjala H, Salmi M, Jaakkola I, Hanninen A, Jalkanen S: Vascular adhesion protein-1 is involved in both acute and chronic inflammation in the mouse. Am J Pathol 166:793–800, 2005
Microarray analysis of mRNA expression is a valuable tool for discovering biomarkers, predicting disease outcome, assessing response to treatment, and identifying pathways activated during specific disease states. However, since mRNA expression levels may not correlate well with protein expression levels, antibody arrays have been developed to assess directly protein expression in tissues. These arrays frequently use a two-color system essentially equivalent to those used for cDNA arrays. A group of investigators at the Mayo Clinic recently published recommendations for the appropriate use of antibody arrays. These recommendations include those for 1) choosing an experimental design, 2) implementing a suitable normalization procedure, 3) assessing differential expression statistically, and 4) analyzing patterns of protein expression. These procedures are often derived from methods developed for two-color cDNA array analysis. The authors review the literature and supply appropriate references for further study.
Eckel-Passow JE, Hoering A, Therneau TM, Ghobrial I: Experimental design and analysis of antibody microarrays: applying methods from cDNA arrays. Cancer Res 65:2985–2989, 2005
Inherited lysosomal storage disorders are good candidates for gene therapy because achieving even a small increase in the amount of active enzyme could make a large difference in restoring normal metabolism. Intracerebral gene therapy experiments have been performed in the mouse, but the use of larger animal models is infrequent. Investigators at the University of Pennsylvania used an adeno-associated virus vector in a feline model of human alpha-mannosidosis. Cats received several injections of the vector in a single operative procedure. The cats showed marked improvement in clinical signs with a concomitant increase in brain myelination and reduction in storage lesions throughout the brain. The reduction in storage lesions was apparent even at large distances from the injection tracks and the immediate vicinity of gene transfer. This work demonstrates the potential utility of central nervous system gene therapy for inherited lysosomal storage disorders.
Vite CH, McGowan JC, Niogi SN, Passini MA, Drobatz KJ, Haskins ME, Wolfe JH: Effective gene therapy for an inherited CNS disease in a large animal model. Ann Neurol 57 (3):355–364, 2005[CrossRef][ISI][Medline]
Severe acute respiratory syndrome (SARS) is caused by a coronavirus. SARS is particularly deadly in the elderly, with mortality rates of up to 50% for those over 60 years old. Investigators at the National Institutes of Health Laboratory of Infectious Diseases and the Centers for Disease Control and Prevention inoculated aged BALB/c mice with the SARS virus. The aged mice supported viral replication and developed pneumonia similar to that which is seen in elderly patients. Thus, the aged BALB/c mouse appears to be a useful model to study the role of advanced age in SARS virus susceptibility, morbidity and mortality.
Roberts A, Paddock C, Vogel L, Butler E, Zaki S, Subbarao, K: Aged BALB/c mice as a model for increased severity of severe acute respiratory syndrome in elderly humans. J Virol 79 (9):5833–5838, 2005
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