Publications

We have identified a novel mAb, SG31, which recognizes the mouse integrin alpha4 subunit. Unlike the epitopes recognized by other anti-alpha4 antibodies, the SG31 epitope is expressed on subpopulations of thymocytes and peripheral T cells. After manganese ion, but not phorbol myristic acetate activation, the epitope is induced and expressed on the majority of peripheral T cells. These data suggest that the SG31 epitope is an activation epitope and that manganese ions activate alpha4 integrins by inducing a conformational change. Comparative flow cytometric analyses showed that the SG31 epitope as well as the epitope detected by other anti-alpha4 antibodies is expressed on all B lineage cells. In the T lineage, expression of the alpha4 integrins is down-regulated during thymocyte development. Although mature thymocytes still express the alpha4 integrins, they lose almost entirely the activation epitope recognized by SG31. In contrast, the most immature thymocytes express high levels of this epitope. In the periphery, SG31 epitope is expressed mostly by activated T cells, in contrast to the overall population of T cells that express the alpha4 integrins at homogenous levels. These results suggest that the activation of the alpha4 integrins is parallel to that of T cells.

Sphingosine-1-phosphate (S1P) protects neonatal rat cardiac myocytes from hypoxic damage through unknown signaling pathways. We tested the hypothesis that S1P-induced cardioprotection requires activation by the epsilon-isoform of protein kinase C (PKC epsilon) by subjecting hearts isolated from PKC epsilon knockout mice and wild-type mice to 20 min of global ischemia and 30 min of reperfusion. Pretreatment with a 2-min infusion of 10 nM S1P improved recovery of left ventricular developed pressure (LVDP) in both wild-type and PKC epsilon knockout hearts and reduced the rise in LV end-diastolic pressure (LVEDP) and creatine kinase (CK) release. Pretreatment for 2 min with 10 nM of the ganglioside GM-1 also improved recovery of LVDP and suppressed CK release in wild-type hearts but not in PKC epsilon knockout hearts. Importantly, GM-1 but not S1P, increased the proportion of PKC epsilon localized to particulate fractions. Our results suggest that GM-1, which enhances endogenous S1P production, reduces cardiac injury through PKC epsilon-dependent intracellular pathways. In contrast, extracellular S1P induces equivalent cardioprotection through PKC epsilon-independent signaling pathways.

PURPOSE

To describe a pilot initiative sponsored by the Veterans Health Administration (VHA) to improve the health and community tenure of frail older veterans living in rural counties 50-100 miles from two host VHA medical centers.

DESIGN AND METHODS

Veterans aged 75 and older who scored at risk of repeated hospital admission on the PRA-Plus telephone questionnaire were targeted and visited by evaluators who administered a comprehensive health questionnaire prior to being assessed at home by the Coordination and Advocacy for Rural Elders (CARE) program clinical teams. Guided by current state-of-the-art practices, the nurse-social worker teams performed in-home standardized assessments using the MDS-HC, developed patient-specific care plans, and mobilized family, community, and VHA resources to implement plans.

RESULTS

On average, eight problems were identified for each patient, most commonly falls risk, social needs, pain, and needs related to IADL disability. As a result of initial assessment, two thirds of CARE participants received referral/linkage to formal services, more than half to medical providers.

IMPLICATIONS

Through CARE, the VHA is learning more about the unmet needs of older rural veterans. Further development and evaluation should guide the VHA toward providing efficient, effective community-based services to all frail older veterans.