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Biomedical subjects

D W Emery

Publications and source records attributed to D W Emery.

42 records · Page 3Linked to original sources
PubMed1990

Slow response variant of the B lymphoma 70Z/3 defective in LPS activation of NF-kappa B.

The mouse B cell lymphoma 70Z/3 is membrane immunoglobulin M (mIgM) negative, but treatment of the cells with bacterial lipopolysaccharide (LPS) induces the expression of kappa (kappa) light chain synthesis, and the cells become mIgM+. In wild type cells, this reaction is maximal after 24 h; we have isolated a variant, 1B8, which becomes mIgM+ only after a more prolonged incubation with LPS. This delayed response results from a reduced rate of accumulation of (kappa) mRNA and protein. The transcription factor, NF-kappa B is present in the cytoplasm of both the wild type and the variant cells in its inactive form. The delay in kappa expression is correlated with the failure of NF-kappa B to be activated and translocated to the nucleus. Although NF-kappa B cannot be activated by LPS, it can be activated by treatment with phorbol ester (PMA). In contrast to the clear defect in NF-kappa B, LPS treatment of 1B8 cells causes the octamer-binding factor OTF-2 to increase normally. We conclude that the defect in 1B8 cells is in an early part of the LPS activation pathway, prior to the activation of NF-kappa B, but after the signal for OTF-2 induction. The phenotype of 1B8 demonstrates that an increase in OTF-2 alone is sufficient to cause a large increase in kappa transcription in 70Z/3 cells, but that without NF-kappa B, the response is slow to develop. In this view, NF-kappa B functions to facilitate kappa transcription and to speed its rate of increase, but is not required for the long-term response of 70Z/3 cells to LPS.

Animals↗
PubMed1990

1.3E2, a variant of the B lymphoma 70Z/3, defective in activation of NF-kappa B and OTF-2.

The mouse B-cell cell lymphoma 70Z/3 is a convenient model system in which to study the regulation of immunoglobulin synthesis. Three transcriptional activators of kappa (kappa) light chain synthesis have been identified for these cells: bacterial lipopolysaccharide (LPS), interferon-gamma (IFN), and interleukin-1 (IL-1). The response of the kappa gene in 70Z/3 cells to LPS is mediated by increases in two transcription factors: NF-kappa B and OTF-2. In contrast, IFN has no effect on either of these factors in 70Z/3 cells. We have isolated by immunoselection an LPS- IFN+ variant of 70Z/3 called 1.3E2. We show here that LPS treatment of these cells causes no increase in nuclear localization of either NF-kappa B or OTF-2. Although they have normal levels of cytoplasmic NF-kappa B, it cannot be activated by LPS or by phorbol 12-myristate 13-acetate (PMA) treatment of the cells. These experiments expand the genetic dissection of the molecular pathways of activation of kappa transcription in 70Z/3 cells.

Animals↗
PubMedDate not supplied

Global theory and the nature of risk, Part I. How orthodox managed care stifles innovation.

The growing awareness that managed care is rapidly unraveling has not only produced a good deal of alarm, but also a call for prognostications regarding the future. Unfortunately, old habits die hard, and wedded ideologies die even harder. Instead of paving the way for innovation, most managed care pundits refuse to read the tea leaves properly and acknowledge that the orthodox regime is irretrievably comatose. Not understanding the fundamental flaws inherent in the old model, many persevere with rehashed predictions that only echo the very non-starters that got us in the present jam in the first place. Managed care has so far focused its energies on integrating the wrong objects, insurance and care, with all the predictably bad effects. Part 2 of this article will explore what this means and introduce the global theory of managed care as an alternative vision. Global theory lays a new foundation based on a more sound microeconomic model of risk, bifurcated markets, global fees for integrated episodes of care, and most important of all, patient/physician sovereignty.

Capitation Fee↗
PubMedDate not supplied

Global theory and the nature of risk, Part 2. Towards a choice-based model of managed care.

Orthodox managed care depends on top-down, command and control techniques to squeeze efficiency out of the system. But for every unit of economic good this approach produces, two or three bad units come as result. The key to moving to an environment where value and efficiency become self-sustaining is to structurally recognize the medicoeconomic reality of medicine: the episode of care. The episode forms a natural unit of analysis that not only renders costs and outcomes information translucent and accessible, but it also forms the natural conduit through which premium dollars can find their optimal value. By bifurcating probability risk from technical risk and allocating them in the ex ante and ex post markets, respectively, health care insurers and providers return to their rightful economic roles, and to their appropriate fiduciary duties. And patients regain some semblance of reasonable sovereignty in managing their own medical affairs.

Consumer Behavior↗
PubMedDate not supplied

Induction of specific tolerance to MHC-disparate allografts through genetic engineering.

The potential for induction of transplantation tolerance through genetic engineering of allogeneic MHC genes is being studied in two animal models. The first system involves a congenic mouse strain combination differing by a single class I locus. Using a retroviral vector, cDNA encoding one allele of this locus was introduced into bone marrow of the congenic partner strain, and the transduced bone marrow was used to reconstitute autologous animals. Skin-grafting data indicate that this reconstitution led to tolerance for the allelic products of this class I locus. The second system involves similar manipulations of miniature swine bone marrow, with the goal of inducing tolerance to class II antigens, since these antigens have been shown to be of overwhelming importance in determining the fate of vascularized allografts in this model. In vitro data in a bone marrow culture system indicate that an appropriate vector for this purpose has been produced.

Animals↗