331 research outputs found
Is there need for intravascular ultrasound after high-pressure dilatations of Palmaz-Schatz stents
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Identification of rare Epstein-Barr virus infected memory B cells and plasma cells in non-monomorphic post-transplant lymphoproliferative disorders and the signature of viral signaling
Background and Objectives. In early and polymorphic post-transplant lymphoprolifera- tive disorders (PTLD) Epstein-Barr virus (EBV), through its latency proteins, drives the proliferation of B lymphocytes, a process which in immunocompetent individuals leads to the establishment of latently infected memory B cells.
Design and Methods. We analyzed 11 cases, which included early and polymorphic PTLD, and 12 controls for latency of EBV infection and their antigenic profile.
Results. We identified a minority of terminally differentiated EBER+ IRTA1+ memory B cells and EBER+ CD138+ PRDM1+ plasma cells in these samples. These elements were identified both in PTLD and in tumor-free tonsils from post-transplant patients but not in EBV– control tonsils. The expression of EBV latency proteins is heterogeneous, and is associated with activation of the NF-κB pathway. EBV signaling (through EBNA2, LMP1 and LMP2A) and NF-κB activation correlated with upregulation of target proteins: cMYC, JunB, CCL22, TRAF1 and IRF4. EBV-infected lymphocytes in early and polymor- phic PTLDs represent a mixture of latencies II, III and, in at least 1/3 of infected cells, of latency 0.
Interpretation and conclusions. EBV infection correlates with NF-ÎşB activation, with EBV-dependent cell signaling, and lastly, with the presence of EBV-infected plasma cells and memory cells.
Key words: post-transplant lymphoproliferative disorder, Epstein-Barr virus, viral latency, NF-ÎşB signaling, plasma cell, memory B cell
Design Equation: A Novel Approach to Heteropolymer Design
A novel approach to heteropolymer design is proposed. It is based on the
criterion by Kurosky and Deutsch, with which the probability of a target
conformation in a conformation space is maximized at low but finite
temperature. The key feature of the proposed approach is the use of soft spins
(fuzzy monomers) that leads to a design equation, which is an analog of the
Boltzmann machine learning equation in the design problem. We implement an
algorithm based on the design equation for the generalized HP model on the
3x3x3 cubic lattice and check its performance.Comment: 7 pages, 3 tables, 1 figures, uses jpsj.sty, jpsjbs1.sty, epsf.sty,
Submitted to J. Phys. Soc. Jp
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Aberration in DNA Methylation in B-Cell Lymphomas Has a Complex Origin and Increases with Disease Severity
Despite mounting evidence that epigenetic abnormalities play a key role in cancer biology, their contributions to the malignant phenotype remain poorly understood. Here we studied genome-wide DNA methylation in normal B-cell populations and subtypes of B-cell non-Hodgkin lymphoma: follicular lymphoma and diffuse large B-cell lymphomas. These lymphomas display striking and progressive intra-tumor heterogeneity and also inter-patient heterogeneity in their cytosine methylation patterns. Epigenetic heterogeneity is initiated in normal germinal center B-cells, increases markedly with disease aggressiveness, and is associated with unfavorable clinical outcome. Moreover, patterns of abnormal methylation vary depending upon chromosomal regions, gene density and the status of neighboring genes. DNA methylation abnormalities arise via two distinct processes: i) lymphomagenic transcriptional regulators perturb promoter DNA methylation in a target gene-specific manner, and ii) aberrant epigenetic states tend to spread to neighboring promoters in the absence of CTCF insulator binding sites
A hierarchical model for aging
We present a one dimensional model for diffusion on a hierarchical tree
structure. It is shown that this model exhibits aging phenomena although no
disorder is present. The origin of aging in this model is therefore the
hierarchical structure of phase space.Comment: 10 pages LaTeX, 4 postscript-figures include
Early Stages of Homopolymer Collapse
Interest in the protein folding problem has motivated a wide range of
theoretical and experimental studies of the kinetics of the collapse of
flexible homopolymers. In this Paper a phenomenological model is proposed for
the kinetics of the early stages of homopolymer collapse following a quench
from temperatures above to below the theta temperature. In the first stage,
nascent droplets of the dense phase are formed, with little effect on the
configurations of the bridges that join them. The droplets then grow by
accreting monomers from the bridges, thus causing the bridges to stretch.
During these two stages the overall dimensions of the chain decrease only
weakly. Further growth of the droplets is accomplished by the shortening of the
bridges, which causes the shrinking of the overall dimensions of the chain. The
characteristic times of the three stages respectively scale as the zeroth, 1/5
and 6/5 power of the the degree of polymerization of the chain.Comment: 11 pages, 3 figure
MALT1 Small Molecule Inhibitors Specifically Suppress ABC-DLBCL In Vitro and In Vivo
SummaryMALT1 cleavage activity is linked to the pathogenesis of activated B cell-like diffuse large B cell lymphoma (ABC-DLBCL), a chemoresistant form of DLBCL. We developed a MALT1 activity assay and identified chemically diverse MALT1 inhibitors. A selected lead compound, MI-2, featured direct binding to MALT1 and suppression of its protease function. MI-2 concentrated within human ABC-DLBCL cells and irreversibly inhibited cleavage of MALT1 substrates. This was accompanied by NF-κB reporter activity suppression, c-REL nuclear localization inhibition, and NF-κB target gene downregulation. Most notably, MI-2 was nontoxic to mice, and displayed selective activity against ABC-DLBCL cell lines in vitro and xenotransplanted ABC-DLBCL tumors in vivo. The compound was also effective against primary human non-germinal center B cell-like DLBCLs ex vivo
Combinatorial epigenetic therapy in diffuse large B cell lymphoma pre-clinical models and patients
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