Modification of the L1-CAM carboxy-terminus in pancreatic adenocarcinoma cells

The neural cell adhesion molecule L1 has recently been shown to be expressed in pancreatic adenocarcinoma (PDAC) cells. In this report, we demonstrate that L1 is expressed by moderately- to poorly-differentiated PDAC cells in situ, and that L1 expression is a predictor of poor patient survival. In vitro, reduced reactivity of an anti-L1 carboxy-terminus-specific antibody was observed in the more poorly differentiated fast-growing (FG) variant of the COLO357 population, versus its well-differentiated slow-growing (SG) counterpart, even though they express equivalent total L1. The carboxy-terminus of L1 mediates binding to the MAP kinase-regulating protein RanBPM and mutation of T1247/S1248 within this region attenuates the expression of malignancy associated proteins and L1-induced tumorigenicity in mice. Therefore, we reasoned that the differential epitope exposure observed might be indicative of modifications responsible for regulating these events. However, epitope mapping demonstrated that the major determinant of binding was actually N1251; mutation of T1247 and S1248, alone or together, had little effect on C20 binding. Moreover, cluster assays using CD25 ectodomain/L1 cytoplasmic domain chimeras demonstrated the N1251-dependent, RanBPM-independent stimulation of erk phosphorylation in these cells. Reactivity of this antibody also reflects the differential exposure of extracellular epitopes in these COLO357 sublines, consistent with the previous demonstration of L1 ectodomain conformation modulation by intracellular modifications. These data further support a central role for L1 in PDAC, and define a specific role for carboxy-terminal residues including N1251 in the regulation of L1 activity in PDAC cells

Pulmonary paracoccidoidomycosis: radiology and clinical-epidemiological evaluation Paracoccidioidomicose pulmonar: radiologia e avaliação clínico-epidemiológica

INTRODUCTION: The purpose of this study was to compare respiratory signs and symptoms between patients with and without chest X-ray abnormalities in order to establish the meaning of radiographic findings in pulmonary PCM diagnosis. METHODS: The epidemiological, clinical and radiological lung findings of 44 patients with paracoccidiodomycosis (PCM) were evaluated. Patients were divided into two groups of 23 and 21 individuals according to the presence (group 1) or absence (group 2) of chest X-ray abnormalities, respectively, and their clinical data was analyzed with the aid of statistical tools. RESULTS: As a general rule, patients were rural workers, young adult males and smokers - group 1 and 2, respectively: males (91.3% and 66.7%); mean age (44.4 and 27.9 year-old); smoking (34.7% and 71.4 %); acute/subacute presentation (38.1% and 21.7%); chronic presentation (61.9% and 78.3%). The most frequent respiratory manifestations were - group 1 and 2, respectively: cough (25% and 11.4%) and dyspnea (22.7% and 6.8%). No statistical difference was observed in pulmonary signs and symptoms between patients with or without radiographic abnormalities. The most frequent radiological finding was nodular (23.8%) or nodular-fibrous (19%), bilateral (90.5%) and diffuse infiltrates (85.7%). CONCLUSIONS: Absence of statistical difference in pulmonary signs and symptoms between these two groups of patients with PCM indicates clinical-radiological dissociation. A simplified classification of radiological lung PCM findings is suggested, based on correlation of these data and current literature review.<br>INTRODUÇÃO: Comparar sinais e sintomas respiratórios entre pacientes com e sem alterações à radiografia de tórax para se estabelecer o significado dos achados radiográficos no diagnóstico da paracoccidioidomicose pulmonar. MÉTODOS: Os achados epidemiológicos, clínicos e radiológicos de 44 pacientes com paracoccidioidomicose (PCM) foram avaliados. Os pacientes foram divididos em dois grupos de 23 e 21 indivíduos de acordo com a presença (grupo 1) ou ausência (grupo 2) de anormalidades à radiografia de tórax, respectivamente, e seus dados clínicos foram analisados com auxílio de ferramentas estatísticas. RESULTADOS: Como regra geral, os pacientes eram trabalhadores rurais do sexo masculino, tabagistas e em idade adulta jovem - grupo 1 e 2, respectivamente: homens (91,3% e 66,7%); média de idade (44,4 e 27,9 anos); tabagismo (34,7% e 71,4 %); forma aguda/subaguda (38,1% e 21,7%); forma crônica (61,9% e 78,3%). As manifestações respiratórias mais frequentes foram - grupo 1 e 2, respectivamente: tosse (25% e 11,4%) e dispnéia (22,7% e 6,8%). Nenhuma diferença estatística foi observada nos sinais e sintomas respiratórios entre pacientes com ou sem anormalidades radiográficas. Os achados radiológicos mais frequentes foram o padrão nodular (23,8%) ou nodular-fibrótico (19%), bilateral (90,5%) e infiltrado difuso (85,7%). CONCLUSÕES: A ausência de diferença estatística nos sinais e sintomas pulmonares entre estes dois grupos de pacientes com PCM sugere dissociação clínico-radiológica. Uma classificação simplificada dos achados radiológicos pulmonares da PCM é sugerida, com base na correlação destes dados e revisão da literatura atual