PI3K Signaling in Normal B Cells and Chronic Lymphocytic Leukemia (CLL).

B cells provide immunity to extracellular pathogens by secreting a diverse repertoire of antibodies with high affinity and specificity for exposed antigens. The B cell receptor (BCR) is a transmembrane antibody, which facilitates the clonal selection of B cells producing secreted antibodies of the same specificity. The diverse antibody repertoire is generated by V(D)J recombination of heavy and light chain genes, whereas affinity maturation is mediated by activation-induced cytidine deaminase (AID)-mediated mutagenesis. These processes, which are essential for the generation of adaptive humoral immunity, also render B cells susceptible to chromosomal rearrangements and point mutations that in some cases lead to cancer. In this chapter, we will review the central role of PI3K s in mediating signals from the B cell receptor that not only facilitate the development of functional B cell repertoire, but also support the growth and survival of neoplastic B cells, focusing on chronic lymphocytic leukemia (CLL) B cells. Perhaps because of the central role played by PI3K in BCR signaling, B cell leukemia and lymphomas are the first diseases for which a PI3K inhibitor has been approved for clinical use

Parallel Implementation of a Sparse Approximate Inverse Preconditioner

. A parallel implementation of a sparse approximate inverse (spai) preconditioner for distributed memory parallel processors (dmpp) is presented. The fundamental spai algorithm is known to be a useful tool for improving the convergence of iterative solvers for ill-conditioned linear systems. The parallel implementation (parspai) exploits the inherent parallelism in the spai algorithm and the data locality on the dmpps, to solve structurally symmetric (but non-symmetric) matrices, which typically arise when solving partial differential equations (pdes). Some initial performance results are presented which suggest the usefulness of parspai for tackling such large size systems on present day dmpps in a reasonable time. The parspai preconditioner is implemented using the Message Passing Interface (mpi) and is embedded in the parallel library for unstructured mesh problems (plump). 1 Introduction We consider the linear system of equations Ax = b; x; b 2 IR n : (1) Here A is a large and..

Bilanz und Perspektiven zum Berufsschulsport in Deutschland

Arndt M, Baumgartner M, Leineweber H, Meier S, Wegener M. Bilanz und Perspektiven zum Berufsschulsport in Deutschland. In: Gogoll A, Messmer R, eds. Sportpädagogik zwischen Stillstand und Beliebigkeit. Bern & Magglingen: BASPO; 2013: 178-193

Ipilimumab-Induced Enteritis without Colitis: A New Challenge

Introduction: Ipilimumab is an immune checkpoint inhibitor targeting cytotoxic T-lymphocyte associated antigen 4 (CTLA4), approved to treat metastatic melanoma. It was the first therapy shown to prolong survival in a large, randomized clinical trial. However, immune-related adverse events are common and can be severe. Enterocolitis is a common adverse event with ipilimumab, but enteritis without colitis has not been previously described. Case Report: An 83-year-old man presented to our hospital with grade 3 diarrhea for 5 days. One month prior, he had started treatment with ipilimumab for metastatic melanoma. On presentation, he was found to have severe electrolyte disturbances, including hyponatremia, hypokalemia, and acute kidney injury. Causes of infectious diarrhea were excluded, and he was treated with corticosteroids for presumed ipilimumab-associated enterocolitis. However, colonoscopy revealed normal mucosa, both grossly and on pathology of random biopsies. Steroids were weaned but his symptoms recurred. He then underwent upper endoscopy with enteroscopy. Biopsy of the duodenum was notable for acute inflammation, villous blunting, and other changes consistent with ipilimumab-associated injury. He was restarted on high-dose steroids and his symptoms resolved. Discussion: Ipilimumab-induced enteritis is a serious and potentially life-threatening immune related adverse event that warrants prompt recognition and aggressive management. As in cases of ipilimumab-associated enterocolitis, steroids are an effective therapy. Enteritis without colitis should be suspected in patients on ipilimumab who present with severe diarrhea but have a normal colonoscopy

Facial allograft transplantation: fiction or reality? Surgical techniques in a fresh human cadaver model

The aim of this study was to describe two methods of face-harvesting techniques - a skin and soft tissue flap and a combined osteocutaneous flap - and to demonstrate the compatibility between donor and recipient in a human fresh cadaver model. In fresh human cadavers the skin and soft tissue of the face (type 1) and a combined osteocutaneous flap (including a le Fort III segment, type 2) were harvested. The faces were subsequently exchanged among the donor crania, simulating full-face transplantation. Both flaps are based on the external blood supply of the faciotemporal vessels and the external jugular vein. The end branches of the trigeminal nerve could potentially be used for restoration of sensation (type 1 flap). With type 2 flaps the facial expression may be restored with the inclusion of the facial nerve. Four morphological parameters determine the donor/recipient compatibility: skin color and texture, anthropometric head dimensions, specific soft tissue components (nose, lip, cheek, and eyebrow), and gender. Apart from ethical considerations, long-term immunosuppression will remain the limiting factor of full facial transplantation in the near future. © 2007 Springer Medizin Verlag