Stainable hepatic iron in 341 African American adults at coroner/medical examiner autopsy

Background  

Results of previous autopsy studies indicate that increased hepatic iron stores or hepatic iron overload is common in African Americans dying in hospitals, but there are no reports of hepatic iron content in other cohorts of African Americans.     

Age-dependent DNA methylation changes in the ITGAL (CD11a) promoter

DNA methylation patterns change with age in a complex fashion, typically with an overall decrease in genomic deoxymethylcytosine (d(m)C) content, but with local increases in some promoters that contain GC-rich sequences known as CpG islands. While the consequences of age-dependent CpG island methylation have recently been studied in organs such as the colon, less is known about the functional significance of the progressive hypomethylation of promoters lacking CpG islands, and the significance of age-dependent changes in T cell DNA methylation is completely unexplored. We asked if age-dependent DNA hypomethylation might contribute to overexpression of the T cell ITGAL gene, which encodes CD11a, a subunit of LFA-1. CD11a mRNA increased with age as well as with experimentally induced DNA hypomethylation. This increase correlated with hypomethylation of sequences flanking the ITGAL promoter in vitro and in aging. 'Patch' methylation of the region suppressed promoter function. DNA methyltransferases 1 and 3a also decreased with aging. These results indicate that hypomethylation of regions flanking the ITGAL promoter may increase CD11a expression, and suggest that age-dependent hypomethylation of promoters lacking CpG islands, perhaps due to decreased DNA methyltransferase expression, may be one mechanism contributing to increased T cell gene expression with aging.     

Locally enhanced angiogenesis promotes transplanted cell survival

A developing therapy for complete or partial loss of function in various tissues and organs involves transplanting an appropriate cell population, capable of compensating for the existing deficiencies. Clinical application of this type of strategy is currently limited by the death or dedifferentiation of the transplanted cells after delivery to the recipient. A delay in thorough vascularization of the implant area creates an environment low in oxygen and other nutrients, and likely contributes to the initial death of transplanted cells. We have addressed this problem by sustained delivery of vascular endothelial growth factor (VEGF), an initiator of angiogenesis, from a porous polymer matrix utilized simultaneously for cell delivery. As expected from previous studies, VEGF delivered from these constructs elicited an enhanced angiogenic response over a 2-week period when implanted subcutaneously in SCID mice. Hepatocytes implanted using VEGF-containing matrices demonstrated significantly greater survival after 1 week in vivo as compared with cells implanted on matrices without growth factor. The results of this study therefore indicate that enhancing vascularization in the location of transplanted cells promotes their survival. In addition, this delivery system may be used in future studies to directly promote cell survival and function by also providing growth factors specific to the transplanted cells.     

The cotton rat: an underutilized animal model for human infectious diseases can now be exploited using specific reagents to cytokines, chemokines, and interferons.

The cotton rat represents the best or only animal model for a large number of human infectious diseases, and it may be unique among small laboratory animals in its susceptibility to several potential agents of bioterrorism. Although the cotton rat is a reliable model to define pathologic changes produced during infection with human pathogens, the lack of specific reagents has precluded a more extensive analysis of the molecular basis of pathogenesis. Here, we report the cloning of 24 cotton rat genes encoding various cytokines, chemokines, and interferons (IFNs). Analysis of the expression of most of these genes was performed by RT-PCR in cotton rat macrophages during treatment with lipopolysaccharide (LPS) and in cotton rat lungs after infection with influenza virus. The availability of these reagents will provide the tools for molecular analysis of pathogenesis and immune responses to a wide variety of pathogens and set the basis for the development of new prophylactic and therapeutic strategies against human infectious diseases.     

Monitoring hemodialysis vascular access by digital phonoangiography

We are intrigued by the possibility of using digital spectral analysis to detect hemodialysis vascular access stenosis. Such a monitor could be inexpensive, noninvasive, and portable enough to allow continuous monitoring. This report suggests how individuals wishing to conduct such research can use a simple but effective transducer design we have employed, how the data so obtained can be analyzed in the time and frequency domains using inexpensive digital signal processing software available via the Internet, and how data recordings might be shared via the Internet to facilitate collaboration. © 2002 Biomedical Engineering Society. PAC2002: 8763Df, 8780Tq