Essential role for Bclaf1 in lung development and immune system function.

Bcl-2 associated factor 1 (Bclaf1) is a nuclear protein that was originally identified in a screen of proteins that interact with the adenoviral bcl-2 homolog E1B19K. Overexpression of Bclaf1 was shown to result in apoptosis and transcriptional repression that was reversible in the presence of Bcl-2 or Bcl-x(L). Furthermore, antiapoptotic members, but not proapoptotic members of the Bcl-2 protein family, were shown to interact with Bclaf1 and prevent its localization to the nucleus. Bclaf1 has also recently been identified as a binding partner for Emerin, a nuclear membrane protein that is mutated in X-linked recessive Emery-Dreifuss muscular dystrophy. To ascertain the in vivo function of Bclaf1, we have generated mice that carry a targeted mutation of the bclaf1 locus. In this study, we show that Bclaf1 is required for proper spatial and temporal organization of smooth muscle lineage during the saccular stage of lung development. We also show that Bclaf1 is dispensable for thymocyte development but is essential for peripheral T-cell homeostasis. Despite its postulated role as a proapoptotic protein, Bclaf1-deficient cells did not show any defect in cell death linked to development or after exposure to various apoptotic stimuli. Our findings show a critical role for Bclaf1 in developmental processes independent of apoptosis.

Brca1 required for T cell lineage development but not TCR loci rearrangement.

Brca1 (breast cancerl, early onset) deficiency results in early embryonic lethality. As Brca1 is highly expressed in the T cell lineage, a T cell-specific disruption of Brca1 was generated to assess the role of Brca1 in relation to T lymphocyte development. We found that thymocyte development in Brca1-/- mice was impaired not as a result of V(D)J T cell receptor (TCR) recombination but because thymocytes had increased expression of tumor protein p53. Chromosomal damage accumulation and abnormal cell death were observed in mutant cells. We found that cell death inhibitor Bcl-2 overexpression, or p53-/- backgrounds, completely restored survival and development of Brca1-/- thymocytes; peripheral T cell numbers were not totally restored in Brcal-/- p53-/- mice; and that a mutant background for p21 (cyclin-dependent kinase inhibitor 1A) did not restore Brca1-/- thymocyte development, but partially restored peripheral T cell development. Thus, the outcome of Brca1 deficiency was dependent on cellular context, with the major defects being increased apoptosis in thymocytes, and defective proliferation in peripheral T cells.

Partnering with academic institutions to improve population health.

Eager to make the most of local knowledge, hospitals, medical schools and managed care organizations are forming alliances to shape healthcare delivery in their regions. Such collaborations often involve training residents to work within managed care, but others are pursuing disease management and population health improvement.

A new resource: empowered patients.

Patients who have access to healthcare information on the Internet or elsewhere or who have learned to demand interaction with their providers can be intimidating--and also one of a provider's biggest assets. When providers take the time to talk with patients about their conditions, to involve them in decisionmaking and to give them access to information, patients can become active participants in the care process. That shift in roles can reduce inappropriate utilization, cut costs and increase satisfaction.

Health plans, providers struggle with quality in alternative medicine.

Consumer demand is pushing many healthcare providers and payers to offer complementary and alternative therapies, from chiropractic to acupuncture, even in the absence of conclusive evidence of their efficacy. To keep patients safe, and to limit costs, organizations are setting strict limits about the type and amount of alternative therapy they will provide.

Is there a PSO in your future?

A decision to form a provider-sponsored organization and go after the lucrative Medicare market depends on several variables. Chief among them are risk-management and marketing capabilities, strength of the provider network, the potential market and the competition, and availability of appropriate information systems and controls.