Search

In animal models, middle-aged females sustain greater ischemia-induced infarction as compared to adult females. This age difference in infarct severity is associated with reduced functional capacity of astrocytes, a critical neural support cell. The impaired response of astrocytes following stroke in middle-aged females may be related to epigenetic alterations, including histone acetylation or methylation. The present study measured the activity of enzymes that regulate histone acetylation and methylation in cerebral cortical astrocytes of adult (6 month) and middle-aged (11+ month) female rats 48 h following middle cerebral artery occlusion. H3K4 histone methyltransferase activity was decreased in astrocytes from middle-aged females. The next experiment therefore examined H3K4me3 (transcriptional enhancer) and H3K9me3 (transcriptional repressor) in astrocytes from adult and middle-aged females using ChIP-seq analysis. Adult females had more enriched H3K4me3 peaks (304 vs. 26) at transcriptional start sites and fewer H3K9me3 enriched peaks than middle-aged females (4 vs. 22), indicating a pattern of less active chromatin in astrocytes in the older group following ischemia. DAVID clustering analysis of H3K4me3 enriched genes found several functional categories, including cell motility, regulation of apoptosis and the vascular endothelial growth factor (VEGF) pathway. H3K4me3 was enriched at the miR-17-20 cluster and VEGFa, and analysis of a separate set of astrocytes confirmed that VEGF protein expression and miR-20 mRNA expression were significantly greater following ischemia in adult females compared to middle-aged females. These data indicate that astrocytes display less active chromatin with aging and provide new insight into possible mechanisms for differences in stroke severity observed during aging.

Summary Objective To test the hypothesis that the spondyloepiphyseal dysplasia congenita ( sedc ) heterozygous ( sedc /+) mouse, a COL2A1 mutant, is a model for the study of osteoarthritis (OA) in the absence of dwarfism and to investigate the presence of HtrA1, Ddr2, and Mmp-13 and their possible involvement in a universal mechanism leading to OA. Design Whole mount skeletons of adult animals were analyzed to determine whether sedc /+ mice exhibit dwarfism. To characterize progression of osteoarthritic degeneration over time, knee and temporomandibular joints from sedc /+ and wild-type mice were analyzed histologically, and severity of articular cartilage degradation was graded using the Osteoarthritis Research Society International (OARSI) scoring system. Immunohistochemistry was used to detect changes in expression of HtrA1, Ddr2, and Mmp-13 in articular cartilage of knees. Results As previously reported, the sedc /+ skeleton morphology was indistinguishable from wild type, and skeletal measurements revealed no significant differences. The sedc /+ mouse did, however, show significantly higher OARSI scores in knee (9, 12 and 18 months) and temporomandibular joints at all ages examined. Histological staining showed regions of proteoglycan degradation as early as 2 months in both temporomandibular and knee joints of the mutant. Cartilage fissuring and erosion were observed to begin between 2 and 6 months in temporomandibular joints and 9 months in knee joints from sedc /+ mice. Immunohistochemistry of mutant knee articular cartilage showed increased expression of HtrA1, Ddr2, and Mmp-13 compared to wild type, which upregulation preceded fibrillation and fissuring of the articular surfaces. Conclusions With regard to skeletal morphology, the sedc /+ mouse appears phenotypically normal but develops premature OA as hypothesized. We conclude that the sedc /+ mouse is a useful model for the study of OA in individuals with overtly normal skeletal structure and a predisposition for articular cartilage degeneration.

As part of its patient care mission, the U.S. Veterans Health Administration performs diagnostic imaging procedures at 141 medical centers and 850 outpatient clinics. VHA's VistA Imaging Package provides a full archival, display, and communications infrastructure and interfaces to radiology and other HIS modules as well as modalities and a worklist provider In addition, various medical center entities within VHA have elected to install commercial picture archiving and communications systems to enable image organization and interpretation. To evaluate interfaces between commercial PACS, the VistA hospital information system, and imaging modalities, VHA has built a fully constrained specification that is based on the Radiology Technical Framework (Rad-TF) Integrating the Healthcare Enterprise. The Health Level Seven normative conformance mechanism was applied to the IHE Rad-TF and agency requirements to arrive at a baseline set of message specifications. VHA provides a thorough implementation and testing process to promote the adoption of standards-based interoperability by all PACS vendors that want to interface with VistA Imaging.

27 two-yr.-old infants and their mothers were studied in their homes to analyze the relationship between infants' development and their home environment, mothers' attitudes as parents, mothers' marital adjustment, and families' socioeconomic status. Bayley Mental Development Indexes correlated with the infants' home environment, families' socioeconomic status, and maternal attitudes. Bayley Psychomotor Development Indexes related to home environment and socioeconomic status. Home environment, maternal attitude, and marital adjustment scores correlated with socioeconomic status. The implications of these ecological factors on infants' mental and motor development are discussed.