Autologous Peripheral Blood Hematopoietic Cell Transplantation in Dogs with T-Cell Lymphoma

BACKGROUND: Peripheral blood hematopoietic cell transplantation (PBHCT) is a feasible treatment option for dogs with B-cell lymphoma. OBJECTIVE: To examine apheresis and PBHCT outcomes in dogs diagnosed with T-cell lymphoma (TCL). ANIMALS: Fifteen client-owned dogs diagnosed with high-grade TCL. METHODS: After high-dose cyclophosphamide and rhG-colony-stimulating (rhG-CSF) factor treatment, peripheral blood mononuclear cells were collected using cell separators. The harvested cells then were infused after varying doses of total body irradiation (TBI). Postirradiation adverse effects were managed symptomatically and dogs were discharged upon evidence of hematopoietic engraftment. RESULTS: More than 2 × 10(6) CD34+ cells/kg were harvested from 15/15 dogs. Thirteen of 15 (87%) dogs engrafted appropriately, whereas 2 (13%) of the dogs died in the hospital. One dog developed cutaneous B-cell lymphoma 120 days post-PBHCT. The median disease-free interval and overall survival (OS) of the 13 dogs transplanted in first remission from the time of PBHCT were 184 and 240 days, respectively. Stage and substage of disease at diagnosis had no effect on OS. Two of 13 (15%) dogs were alive 741 and 772 days post-PBHCT. CONCLUSIONS AND CLINICAL IMPORTANCE: PBHCT may be considered as a treatment option for dogs with TCL

Comparison of some Reduced Representation Approximations

In the field of numerical approximation, specialists considering highly complex problems have recently proposed various ways to simplify their underlying problems. In this field, depending on the problem they were tackling and the community that are at work, different approaches have been developed with some success and have even gained some maturity, the applications can now be applied to information analysis or for numerical simulation of PDE's. At this point, a crossed analysis and effort for understanding the similarities and the differences between these approaches that found their starting points in different backgrounds is of interest. It is the purpose of this paper to contribute to this effort by comparing some constructive reduced representations of complex functions. We present here in full details the Adaptive Cross Approximation (ACA) and the Empirical Interpolation Method (EIM) together with other approaches that enter in the same category

A Two-Step Certified Reduced Basis Method

In this paper we introduce a two-step Certified Reduced Basis (RB) method. In the first step we construct from an expensive finite element “truth” discretization of dimension N an intermediate RB model of dimension N≪N . In the second step we construct from this intermediate RB model a derived RB (DRB) model of dimension M≤N. The construction of the DRB model is effected at cost O(N) and in particular at cost independent of N ; subsequent evaluation of the DRB model may then be effected at cost O(M) . The DRB model comprises both the DRB output and a rigorous a posteriori error bound for the error in the DRB output with respect to the truth discretization. The new approach is of particular interest in two contexts: focus calculations and hp-RB approximations. In the former the new approach serves to reduce online cost, M≪N: the DRB model is restricted to a slice or subregion of a larger parameter domain associated with the intermediate RB model. In the latter the new approach enlarges the class of problems amenable to hp-RB treatment by a significant reduction in offline (precomputation) cost: in the development of the hp parameter domain partition and associated “local” (now derived) RB models the finite element truth is replaced by the intermediate RB model. We present numerical results to illustrate the new approach.United States. Air Force Office of Scientific Research (AFOSR Grant number FA9550-07-1-0425)United States. Department of Defense. Office of the Secretary of Defense (OSD/AFOSR Grant number FA9550-09-1-0613)Norwegian University of Science and Technolog

Scenarios for autoimmunization of T and B cells in myasthenia gravis

We have studied responses in thymoma patients to interferon-α and to the acetylcholine receptor (AChR) in early-onset myasthenia gravis (EOMG), seeking clues to autoimmunizing mechanisms. Our new evidence implicates a two-step process: (step 1) professional antigen-presenting cells and thymic epithelial cells prime AChR-specific T cells; then (step 2) thymic myoid cells subsequently provoke germinal center formation in EOMG. Our unifying hypothesis proposes that AChR epitopes expressed by neoplastic or hyperplastic thymic epithelial cells aberrantly prime helper T cells, whether generated locally or infiltrating from the circulation. These helper T cells then induce antibody responses against linear epitopes that cross-react with whole AChR and attack myoid cells in the EOMG thymus. The resulting antigen-antibody complexes and the recruitment of professional antigen-presenting cells increase the exposure of thymic cells to the infiltrates and provoke local germinal center formation and determinant spreading. Both these and the consequently enhanced heterogeneity and pathogenicity of the autoantibodies should be minimized by early thymectomy