Fonsecaea pedrosoi is an important causative agent of chromoblastomycosis (CBM) especially in humid areas of the world; however, little is known about the infective forms of this agent that cause CBM. The aim of this study was to investigate the murine tissue response to inoculation with different forms of F. pedrosoi and the morphological changes of the fungal cells in vivo. BALB/c mice were inoculated intraperitoneally with hyphae, conidia or conidiogenous cells and conidia (CCC) at a single site. In addition, the abdomen and footpads were infected subcutaneously with CCC. Fungal forms were inoculated at a final concentration of 1 × 10(6) cells. Hyphae and ungerminated conidia inocula could not be transformed into parasitic forms. In tissue, a great number of conidiogenous cells underwent transformation into sclerotic bodies, which were more resistant to phagocytes in vivo than conidia and hyphae. Clinical and mycological cure of animals infected with CCC was observed from the fourth to the sixth week of infection, while conidia and hyphae infections were faster and generally lasted 2 to 3 weeks. A high number of destructed conidia was observed intracellularly in macrophages. The migration of neutrophils to the inflammatory site seems important for microbicidal activity, particularly against hyphae. Our observations suggest that inocula with conidiogenous cells are associated with in vivo transformation into sclerotic bodies and that local immune response involved with host resistance to experimental F. pedrosoi-infection is primarily mediated by neutrophils as observed in histological sections.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Although the presence of p53 gene mutations has been considered as a bad prognostic feature in DLBCL, its clinical significance is still controversial. The aims of this study were: detect the presence of mutations in exons 5 to 9 of the p53 gene and correlate it to prognosis in DLBCL. Fifty-one DLBCL patients were enrolled in this study. Expression of p53 was evaluated by immunohistochemistry. The screening of p53 mutations was performed using PCR-SSCP methods. Cases showing a mobility shift on SSCP electrophoresis were analyzed by automatic sequencing. We could identify 8 missense mutations in 6 of 48 cases (12.5%). In addition, we found a known polymorphism at codon 213 and 2 instances of silent mutations. Of all mutations/polymorphisms found, 7 (64%) were localized in codons previously described as p53 hot spots in NHL cases. Of the remaining alterations (4 or 36%), 2 mutations were localized in codons previously described as hot spots for p53 in other tumors and 2 (codon 142 of the exon 5 and codon 195 of the exon 6), in codons not described as hot spots for p53 up to now. The presence of missense mutations in exons 5 to 9 of p53 gene had adverse impact on overall survival (P = 0.020). Cox's Regression Model identified that high-risk International Prognostic Index (IPI) and p53 gene mutations have independent negative impact on OS. Therefore, the association of IPI with cellular factors, such as p53 mutation, can be very helpful in deciding when we should indicate more aggressive therapies in patients with DLBCL, to somehow increase the chance of cure in these patients.
Our findings underline the frequent expression of VEGF in advanced-stage MM and the greater prognostic information of simple and readily available factors, namely plasmablastic morphology and elevated LDH. Moreover, despite the absence of prognostic importance in multivariate analysis, VEGF and its receptors remain promising therapeutic targets in MM.
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