Micose fungóide precedendo papulose linfomatóide

A papulose linfomatóide (LyP) é definida como uma doença cutânea papulonecrótica ou papulonodular crônica, recorrente, com características histológicas sugestivas de linfoma maligno (CD30-positivo). Em até 20% dos pacientes, o LyP é precedido por, associado ou seguido por outro tipo de linfoma cutâneo ou sistêmico, geralmente micose fungóide (MF), linfoma cutâneo primário de células grandes anaplásicas (C-ALCL). Neste caso, descrevemos um caso de MF que precedeu e continuou a coexistir com LyP tipo C.Lymphomatoid papulosis (LyP) is defined as a chronic, recurrent, self-healing papulonecrotic or papulonodular skin disease with histologic features suggestive of a (CD30-positive) malignant lymphoma. In up to 20% of patients, LyP are preceded by, associated with, or followed by another type of cutaneous or systemic lymphoma, generally mycosis fungoides (MF), primary cutaneous anaplastic large cell lymphoma (C-ALCL). In this case, we describe a case of MF that preceded and continued to coexist with LyP type C

Autoimmunity-Associated LYP-W620 Does Not Impair Thymic Negative Selection of Autoreactive T Cells.

A C1858T (R620W) variation in the PTPN22 gene encoding the tyrosine phosphatase LYP is a major risk factor for human autoimmunity. LYP is a known negative regulator of signaling through the T cell receptor (TCR), and murine Ptpn22 plays a role in thymic selection. However, the mechanism of action of the R620W variant in autoimmunity remains unclear. One model holds that LYP-W620 is a gain-of-function phosphatase that causes alterations in thymic negative selection and/or thymic output of regulatory T cells (Treg) through inhibition of thymic TCR signaling. To test this model, we generated mice in which the human LYP-W620 variant or its phosphatase-inactive mutant are expressed in developing thymocytes under control of the proximal Lck promoter. We found that LYP-W620 expression results in diminished thymocyte TCR signaling, thus modeling a "gain-of-function" of LYP at the signaling level. However, LYP-W620 transgenic mice display no alterations of thymic negative selection and no anomalies in thymic output of CD4(+)Foxp3(+) Treg were detected in these mice. Lck promoter-directed expression of the human transgene also causes no alteration in thymic repertoire or increase in disease severity in a model of rheumatoid arthritis, which depends on skewed thymic selection of CD4(+) T cells. Our data suggest that a gain-of-function of LYP is unlikely to increase risk of autoimmunity through alterations of thymic selection and that LYP likely acts in the periphery perhaps selectively in regulatory T cells or in another cell type to increase risk of autoimmunity

Differential Expression of TRAF1 Aids in the Distinction of Cutaneous CD30-Positive Lymphoproliferations

Lymphomatoid papulosis (LyP), primary cutaneous anaplastic large T-cell lymphoma (cALCL), and cutaneous infiltrates of systemic anaplastic large cell lymphoma (sALCL) are CD30-positive lymphoproliferative disorders of the skin that overlap clinically, histopathologically, immunophenotypically, and genetically but differ considerably in their prognosis. In particular, lesions of LyP regress spontaneously, whereas those of cALCL and sALCL persist and may progress and spread to extracutaneous sites. In contrast to patients with cALCL, LyP patients do not benefit from an aggressive radio- and/or chemotherapeutic approach. We generated a novel tumor necrosis factor receptor (TNFR)-associated factor 1 (TRAF1) antibody that recognizes a formalin-resistant epitope (Ber-TRAF1A) and investigated the expression of TRAF1, an intracellular component of TNFR signaling, in LyP and ALCL. We could show a strong TRAF1 expression in the tumor cells of most LyP cases (42/49, 84%). In contrast, tumor cells of primary and secondary cALCL revealed TRAF1 expression in only a few cases (3/41, 7%) as shown for sALCL without skin manifestation. The data indicate that TRAF1 expression reliably distinguishes LyP from primary or secondary cALCL. This might be of crucial diagnostic importance and has a strong impact on the treatment decision for patients with cALCL and LyP

Density Functional Calculations On First-Row Transition Metals

The excitation energies and ionization potentials of the atoms in the first transition series are notoriously difficult to compute accurately. Errors in calculated excitation energies can range from 1--4 eV at the Hartree-Fock level, and errors as high as 1.5eV are encountered for ionization energies. In the current work we present and discuss the results of a systematic study of the first transition series using a spin-restricted Kohn-Sham density-functional method with the gradient-corrected functionals of Becke and Lee, Yang and Parr. Ionization energies are observed to be in good agreement with experiment, with a mean absolute error of approximately 0.15eV; these results are comparable to the most accurate calculations to date, the Quadratic Configuration Interaction (QCISD(T)) calculations of Raghavachari and Trucks. Excitation energies are calculated with a mean error of approximately 0.5eV, compared with \sim 1\mbox{eV} for the local density approximation and 0.1eV for QCISD(T). These gradient-corrected functionals appear to offer an attractive compromise between accuracy and computational effort.Comment: Journal of Chemical Physics, 29, LA-UR-93-425

Spin-dependent localized Hartree-Fock density-functional approach for the accurate treatment of inner-shell excitation of close-shell atoms

We present a spin-dependent localized Hartree-Fock (SLHF) density-functional approach for the treatment of the inner-shell excited-state calculation of atomic systems. In this approach, the electron spin-orbitals in an electronic configuration are obtained first by solving Kohn-Sham (KS) equation with SLHF exchange potential. Then a single-Slater-determinant energy of the electronic configuration is calculated by using these electron spin-orbitals. Finally, a multiplet energy of an inner-shell excited state is evaluated from the single-Slater-determinant energies of the electronic configurations involved in terms of Slater's diagonal sum rule. This procedure has been used to calculate the total and excitation energies of inner-shell excited states of close-shell atomic systems: Be, B^+, Ne, and Mg. The correlation effect is taken into account by incorporating the correlation potentials and energy functionals of Perdew and Wang's (PW) or Lee, Yang, and Parr's (LYP) into calculation. The calculated results with the PW and LYP energy functionals are in overall good agreement with each other and also with available experimental and other ab initio theoretical data. In addition, we present some new results for highly excited inner-shell states.Comment: 8 pages and 9 table

Primary cutaneous CD30+ lymphoproliferative disorder : a 10-year follow-up : a case report and differential diagnosis

Primary cutaneous CD30+ lymphoproliferative disorders (LPDs) are the second most common group of primary cutaneous T-cell lymphomas (CTCLs). The spectrum of LPDs includes lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (C-ALCL) and borderline cases. The term “borderline lesions” refers to cases where histological features are similar to LyP, but clinically behave as C-ALCL, or to cases where histological features are typical for C-ALCL, but clinically behave as LyP. We present a clinical and morphological picture of LPD in a 57-year old patient treated in the Department of Oncology and of a relapse after ten years of follow-up and discuss clinical and morphological differential diagnosis and the significance of such diagnosis

BB rat Gimap gene expression in sorted lymphoid T and B cells

Aims: The Gimap gene family has been shown to be integral to T cell survival and development. A frameshift mutation in Gimap5, one of seven members of the Gimap family, results in lymphopenia and is a prerequisite for spontaneous type 1 diabetes (T1D) in the BioBreeding (BB) rat. While not contributing to lymphopenia, the Gimap family members proximal to Gimap5, encompassed within the Iddm39 quantitative trait locus (QTL), have been implicated in T1D. We hypothesized that expression of the Gimap family members within the Iddm39 QTL, during thymocyte development as well as in peripheral T and B cells contribute to T1D. Main methods: Cell sorted subpopulations were analyzed by quantitative real time (qRT) PCR. Key findings: Gimap4 expression was reduced in DR.(lyp/lyp) rat double negative, double positive and CD8 single positive (SP) thymocytes while expression of Gimap8, Gimap6, and Gimap7 was reduced only in CD8 SP thymocytes. Interestingly, expression of the entire Gimap gene family was reduced in DR.(lyp/lyp) rat peripheral T cells compared to non-lymphopenic, non-diabetic DR.(+/+) rats. With the exception of Gimap6. the Gimap family genes were not expressed in B cells from spleen and mesenteric lymph node (MLN). Expression of Gimap9 was only detected in hematopoietic cells of non B cell lineage such as macrophage, dendritic or NK cells. Significance: These results suggest that lack of the Gimap5 protein in the DR.(lyp/lyp) congenic rat was associated with impaired expression of the entire family of Gimap genes and may regulate T cell homeostasis in the peripheral lymphoid organs. (C) 2011 Elsevier Inc. All rights reserved

Assessment of the TCA functional in computational chemistry and solid-state physics

We assess the Tognetti-Cortona-Adamo (TCA) generalized gradient approximation correlation functional [J. Chem. Phys. 128:034101 (2008)] for a variety of electronic systems. We find that, even if the TCA functional is not exact for the uniform electron gas, it is very accurate for the jellium surface correlation energies and it gives a realistic description of the quantum oscillations and surface effects of various jellium clusters, that are important model systems in computational chemistry and solid-state physics. When the TCA correlation is combined with the non-empirical PBEint, Wu-Cohen, and PBEsol$_b$ exchange functionals, the resulting exchange-correlation approximations provide good performances for a broad palette of systems and properties, being reasonably accurate for thermochemistry and geometry of molecules, transition metal complexes, non-covalent interactions,equilibrium lattice constants, bulk moduli, and cohesive energies of solids.Comment: 14 pages, 6 figure