Linfoma Cutâneo Primário de Grandes Células B, Tipo Perna: Relato de Caso com Apresentação Rara

Primary cutaneous lymphomas are defined as a heterogeneous group of malignant lymphoproliferative neoplasms that attack the skin, without extracutaneous involvement at the moment of the diagnosis. The subgroup "primary cutaneous lymphoma of great cells B, leg type (PCLBCL, LT)" generally attacks one or both lower limbs, however in 10% - 15 % of the cases other areas of the skin may be affected. We present a rare case of PCLBCL, LT with a nodular lesion located in the cervical region to empathize an atypical presentation. Considering its quick growth and high proliferative rate, it is of great importance to know all its possible clinical presentations for a precocious diagnosis and efficient treatment.Linfomas cutâneos primários são definidos como um grupo heterogéneo de neoplasias malignas linfoproliferativas que acometem a pele, sem evidência de envolvimento extracutâneo no momento do diagnóstico. O subgrupo “linfoma cutâneo primário de grandes células B, tipo perna (PCLBCL, LT)” geralmente acomete um ou ambos membros inferiores, porém 10% - 15% dos casos apresentam lesões em outros locais. Apresenta-se um caso raro de PCLBCL, LT com lesão nodular na região cervical posterior, enfatizando sua apresentação atípica. Considerando o crescimento rápido da lesão e o alto índice proliferativo, é importante conhecer todas as possíveis apresentações clínicas para assim realizar o diagnóstico precoce e instituir o tratamento efetivo

Dysregulation of Gene Expression in a Lysosomal Storage Disease Varies between Brain Regions Implicating Unexpected Mechanisms of Neuropathology

The characteristic neurological feature of many neurogenetic diseases is intellectual disability. Although specific neuropathological features have been described, the mechanisms by which specific gene defects lead to cognitive impairment remain obscure. To gain insight into abnormal functions occurring secondary to a single gene defect, whole transcriptome analysis was used to identify molecular and cellular pathways that are dysregulated in the brain in a mouse model of a lysosomal storage disorder (LSD) (mucopolysaccharidosis [MPS] VII). We assayed multiple anatomical regions separately, in a large cohort of normal and diseased mice, which greatly increased the number of significant changes that could be detected compared to past studies in LSD models. We found that patterns of aberrant gene expression and involvement of multiple molecular and cellular systems varied significantly between brain regions. A number of changes revealed unexpected system and process alterations, such as up-regulation of the immune system with few inflammatory changes (a significant difference from the closely related MPS IIIb model), down-regulation of major oligodendrocyte genes even though white matter changes are not a feature histopathologically, and a plethora of developmental gene changes. The involvement of multiple neural systems indicates that the mechanisms of neuropathology in this type of disease are much broader than previously appreciated. In addition, the variation in gene dysregulation between brain regions indicates that different neuropathologic mechanisms may predominate within different regions of a diseased brain caused by a single gene mutation

The crystal structure of the Leishmania infantum Silent Information Regulator 2 related protein 1: implications to protein function and drug design.

The research leading to these results received funding from the European Community’s Seventh Framework Programme under grant agreement No.602773 (Project KINDRED).The de novo crystal structure of the Leishmania infantum Silent Information Regulator 2 related protein 1 (LiSir2rp1) has been solved at 1.99Å in complex with an acetyl-lysine peptide substrate. The structure is broadly commensurate with Hst2/SIRT2 proteins of yeast and human origin, reproducing many of the structural features common to these sirtuin deacetylases, including the characteristic small zinc-binding domain, and the larger Rossmann-fold domain involved in NAD+-binding interactions. The two domains are linked via a cofactor binding loop ordered in open conformation. The peptide substrate binds to the LiSir2rp1 protein via a cleft formed between the small and large domains, with the acetyl-lysine side chain inserting further into the resultant hydrophobic tunnel. Crystals were obtained only with recombinant LiSir2rp1 possessing an extensive internal deletion of a proteolytically-sensitive region unique to the sirtuins of kinetoplastid origin. Deletion of 51 internal amino acids (P253-E303) from LiSir2rp1 did not appear to alter peptide substrate interactions in deacetylation assays, but was indispensable to obtain crystals. Removal of this potentially flexible region, that otherwise extends from the classical structural elements of the Rossmann-fold, specifically the β8-β9 connector, appears to result in lower accumulation of the protein when expressed from episomal vectors in L. infantum SIR2rp1 single knockout promastigotes. The biological function of the large serine-rich insertion in kinetoplastid/trypanosomatid sirtuins, highlighted as a disordered region with strong potential for post-translational modification, remains unknown but may confer additional cellular functions that are distinct from their human counterparts. These unique molecular features, along with the resolution of the first kinetoplastid sirtuin deacetylase structure, present novel opportunities for drug design against a protein target previously established as essential to parasite survival and proliferation.Publisher PDFPeer reviewe