Rejoinder of: Treelets--An adaptive multi-scale basis for spare unordered data

Rejoinder of "Treelets--An adaptive multi-scale basis for spare unordered data" [arXiv:0707.0481]Comment: Published in at http://dx.doi.org/10.1214/08-AOAS137REJ the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Letters to the Editor: Correspondence re R. Lapointe et al., CD40-stimulated B Lymphocytes Pulsed with Tumor Antigens Are Effective Antigen-presenting Cells That Can Generate Specific T Cells. Cancer Res 2003;63:2836–43.

La réplique provient de Réjean Lapointe, Jacques Thibodeau et Patrick Hwu; Réjean Lapointe et Jacques Thibodeau sont affiliés à la faculté de médecine de l'Université de Montréa

Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade

Allogeneic hematopoietic stem cell transplantation (AHSCT) offers the best chance of cure for many patients with congenital and acquired hematologic diseases. Unfortunately, transplantation of alloreactive donor T cells which recognize and damage healthy patient tissues can result in Graft-versus-Host Disease (GvHD)1. One challenge to successful AHSCT is the prevention of GvHD without associated impairment of the beneficial effects of donor T cells, particularly immune reconstitution and prevention of relapse. GvHD can be prevented by non-specific depletion of donor T cells from stem cell grafts or by administration of pharmacological immunosuppression. Unfortunately these approaches increase infection and disease relapse2-4. An alternative strategy is to selectively deplete alloreactive donor T cells after allostimulation by recipient antigen presenting cells (APC) before transplant. Early clinical trials of these allodepletion strategies improved immune reconstitution after HLA-mismatched HSCT without excess GvHD5, 6. However, some allodepletion techniques require specialized recipient APC production6, 7and some approaches may have off-target effects including depletion of donor pathogen-specific T cells8and CD4 T regulatory cells9.One alternative approach is the inactivation of alloreactive donor T cells via induction of alloantigen-specific hyporesponsiveness. This is achieved by stimulating donor cells with recipient APC while providing blockade of CD28-mediated co-stimulation signals10.This "alloanergization" approach reduces alloreactivity by 1-2 logs while preserving pathogen- and tumor-associated antigen T cell responses in vitro11. The strategy has been successfully employed in 2 completed and 1 ongoing clinical pilot studies in which alloanergized donor T cells were infused during or after HLA-mismatched HSCT resulting in rapid immune reconstitution, few infections and less severe acute and chronic GvHD than historical control recipients of unmanipulated HLA-mismatched transplantation12. Here we describe our current protocol for the generation of peripheral blood mononuclear cells (PBMC) which have been alloanergized to HLA-mismatched unrelated stimulator PBMC. Alloanergization is achieved by allostimulation in the presence of monoclonal antibodies to the ligands B7.1 and B7.1 to block CD28-mediated costimulation. This technique does not require the production of specialized stimulator APC and is simple to perform, requiring only a single and relatively brief ex vivo incubation step. As such, the approach can be easily standardized for clinical use to generate donor T cells with reduced alloreactivity but retaining pathogen-specific immunity for adoptive transfer in the setting of AHSCT to improve immune reconstitution without excessive GvHD

Activation of PI3K Is Indispensable for Interleukin 7–mediated Viability, Proliferation, Glucose Use, and Growth of T Cell Acute Lymphoblastic Leukemia Cells

Interleukin (IL)-7 is essential for normal T cell development. Previously, we have shown that IL-7 increases viability and proliferation of T cell acute lymphoblastic leukemia (T-ALL) cells by up-regulating Bcl-2 and down-regulating the cyclin-dependent kinase inhibitor p27kip1. Here, we examined the signaling pathways via which IL-7 mediates these effects. We investigated mitogen-activated protein kinase (MEK)–extracellular signal-regulated kinase (Erk) and phosphatidylinositol-3-kinase (PI3K)–Akt (protein kinase B) pathways, which have active roles in T cell expansion and have been implicated in tumorigenesis. IL-7 induced activation of the MEK–Erk pathway in T-ALL cells; however, inhibition of the MEK–Erk pathway by the use of the cell-permeable inhibitor PD98059, did not affect IL-7–mediated viability or cell cycle progression of leukemic cells. IL-7 induced PI3K-dependent phosphorylation of Akt and its downstream targets GSK-3, FOXO1, and FOXO3a. PI3K activation was mandatory for IL-7–mediated Bcl-2 up-regulation, p27kip1 down-regulation, Rb hyperphosphorylation, and consequent viability and cell cycle progression of T-ALL cells. PI3K signaling was also required for cell size increase, up-regulation of CD71, expression of the glucose transporter Glut1, uptake of glucose, and maintenance of mitochondrial integrity. Our results implicate PI3K as a major effector of IL-7–induced viability, metabolic activation, growth and proliferation of T-ALL cells, and suggest that PI3K and its downstream effectors may represent molecular targets for therapeutic intervention in T-ALL

Reconstruction of a first-order phase transition from computer simulations of individual phases and subphases

We present a new method for investigating first-order phase transitions using Monte Carlo simulations. It relies on the multiple-histogram method and uses solely histograms of individual phases. In addition, we extend the method to include histograms of subphases. The free energy difference between phases, necessary for attributing the correct statistical weights to the histograms, is determined by a detour in control parameter space via auxiliary systems with short relaxation times. We apply this method to a recently introduced model for structure formation in polypeptides for which other methods fail.Comment: 13 pages in preprint mode, REVTeX, 2 Figures available from the authors ([email protected], [email protected]

A Multi-Institutional Study on the Safety and Efficacy of Specimen Morcellation After Laparoscopic Radical Nephrectomy for Clinical Stage T1 or T2 Renal Cell Carcinoma

Abstract Introduction and Objective: Specimen morcellation during laparoscopic radical nephrectomy (LRN) for renal cell carcinoma (RCC) is controversial. We seek to evaluate the safety and efficacy of specimen morcellation and LRN for treatment of presumed malignant renal lesions. Methods: We retrospectively reviewed all patients who underwent LRN at three academic institutions from 1996 to 2007. One hundred eighty-eight patients underwent specimen morcellation after LRN for enhancing solid or cystic renal masses. Results: LRN was successfully performed on all the patients. Patient age ranged from 36 to 94. One hundred sixty-seven patients were in clinical stage T1, 19 patients T2, and unknown in two. The specimen was manually morcellated within a Cook Lap Sac or Endocatch II bag under laparoscopic or direct observation. On histological review of morcellated specimens, 165 patients were confirmed to have RCC, 17 had an oncocytoma, and 2 had benign cysts. At least 13 patients with RCC were pathologically upgraded to stage T3. Mean operative time was 225 minutes (range 94-650). Mean hospital stay was 2.5 days (range 1-8). In patients with RCC, 11 developed recurrent disease with mean follow-up of 21 months (range 0.3-111). In one patient, a port site recurrence occurred in concert with renal fossa and lymph node metastases. Conclusions: Intracorporeal mechanical morcellation after LRN appears to be safe and effective in clinical stage T1 and T2 RCC. This supports the use of morcellation as an alternative for intact specimen removal in properly selected patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78157/1/end.2009.0387.pd

Retroperitoneoscopic Partial Nephrectomy in a Horseshoe Kidney

A 21-year-old woman with a 4 cm enhancing cystic renal mass in the left moiety of a horseshoe kidney was treated through a retroperitoneal laparoscopic approach. The tumor was excised completely with cold scissors, and renal parenchyma suturing with a surgical bolster was done with Vicryl 2-0 sutures. Choosing the proper approach according to the location of the lesion and the surgeon's experience with both approaches are of importance in laparoscopic surgery in horseshoe kidney cases. A preoperative kidney computed tomography angiography was helpful for understanding the complex renal vasculature

Characterization of the stretched exponential trap-time distributions in one-dimensional coupled map lattices

Stretched exponential distributions and relaxation responses are encountered in a wide range of physical systems such as glasses, polymers and spin glasses. As found recently, this type of behavior occurs also for the distribution function of certain trap time in a number of coupled dynamical systems. We analyze a one-dimensional mathematical model of coupled chaotic oscillators which reproduces an experimental set-up of coupled diode-resonators and identify the necessary ingredients for stretched exponential distributions.Comment: 8 pages, 8 figure