Biomedical subjects

Ernesto de Meis

Publications and source records attributed to Ernesto de Meis.

4 recordsLinked to original sources

PubMed2006

Contrasting features of MDR phenotype in leukemias by using two fluorochromes: implications for clinical practice.

The expression and activity of P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP1) were analyzed in 178 leukemia samples. Rhodamine-123 (Rho-123) and DiOC(2) were used as substrate to evaluate efflux pump activity. Chronic myeloid leukemia (CML) exhibited a higher percentage of positivity using Rho-123 than DiOC(2) (p=0.000) as compared to other types of leukemia. Moreover, Rho-123 was able to detected Pgp positive cells in a higher proportion of samples than DiOC(2) samples (p=0.004). Similarly, MRP1 positive cells were best detected by Rho-123 as opposed to DiOC(2) (p=0.003). The co-functionality of Rho-123 and DiOC(2) was observed in 26 out of 105 (24.8%) leukemic samples. Co-expression between Pgp and MRP1 was detected in 30 out of 56 (53.6%) samples. As a whole, when the same samples were analyzed, Rho-123 was able to detect Pgp positive cells in a higher proportion of samples than DiOC(2) (p=0.000). Similarly, MRP1 positive cells were best detected by Rho-123 as opposed to DiOC(2) (p=0.007). Our results support the idea that Rho-123 is the substrate of choice for leukemic cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2004

An adapted ELISA method for differentiating pathogenic from nonpathogenic aPL by a beta 2 glycoprotein I dependency anticardiolipin assay.

With the currently available commercial kits, as well as homemade assays for detecting anticardiolipin antibodies (aCL), it is not possible to discriminate nonpathogenic, beta 2 glycoprotein (GPI)-independent, infection-related antibodies from those of patients with the true autoimmune thrombotic syndrome, known as antiphospholipid syndrome (APS). We devised an assay that is able to differentiate these two types of antibodies by determining the beta 2 GPI requirements to bind in a cardiolipin ELISA. Beta 2 GPI was purified by perchloric acid precipitation, and fixed amounts were used in the dilution solutions of the tested samples that were also tested with no source of beta 2 GPI. The ELISA plates were coated with cardiolipin, as usual, and blocked with a chicken ovalbumin solution. The serum samples had to be highly diluted in order not to have beta 2 GPI from the patient serum. The reaction was detected with alkaline phosphate tablets and developed with pNp in diethanolamine buffer. The adapted ELISA aCL assay described here was able to discriminate infectious [syphilis, hepatitis C virus (HCV), dengue fever, human immunodeficiency virus (HIV) and leprosy] and autoimmune [primary APS and systemic lupus erythematosus (SLE) related APS]. Further testing should be performed to demonstrate that this method consistently differentiates pathogenic antibodies that bind in an aCL ELISA only in the presence of beta 2 GPI.

Animals↗

PubMed2004

Treatment of children with B-cell non-Hodgkin's lymphoma in developing countries: the experience of a single center in Brazil.

PURPOSE: To treat non-Hodgkin's B-cell lymphoma (B-NHL) in children with manageable toxicity-related morbidity and without any decrease in survival. PATIENTS AND METHODS: Between January 1998 and April 2003, 53 consecutive patients (age 16 years or less) from a single institution were enrolled. The patients were stratified by risk factors (stage and LDH level) and treated with a BFM 86/90 (Berlin-Frankfurt-Münster)-based protocol with reduction of the methotrexate dose from 5 mg/m to 2 mg/m. RESULTS: The mean age of the patients was 6 years (range 1-16 years). Seventy-two percent of the patients had lymphomas classified as Burkitt type, 11% as diffuse large cell lymphoma, and 6% as Burkitt-like lymphoma, and 11% were not classified. At a median follow-up of 35 months, 44 patients (83%) survived in complete remission. The event-free survival rate for all patients was 78% (SE = 0.07): 100% (SE = 0.0) for stage I/II patients and 74% (SE = 0.08) for stage III/IV patients. Six patients suffered initial treatment failure and one patient relapsed, all of whom died. There was only one death from sepsis related to treatment. CONCLUSIONS: This strategy was very effective for treating B-NHL in a developing country. The results were comparable to those of the BFM 90 study and other contemporary groups and represented an increase in the cure rates in childhood B-NHL in Brazil.

Adolescent↗

PubMed2003

DNA sequence profile of TP53 gene mutations in childhood B-cell non-Hodgkin's lymphomas: prognostic implications.

OBJECTIVES: The TP53 gene encodes a nuclear protein implicated in the regulation of the cell cycle, DNA repair, and apoptosis. TP53 mutations and other alterations have been described in numerous types of tumors, and some of these have been associated with poor prognosis. The aim of this study was to characterize TP53 mutations in childhood B non-Hodgkin's lymphoma, their correlation with clinical prognostic factors and response to therapy. PATIENTS AND METHODS: Samples from 49 children with B non-Hodgkin's lymphoma were examined for TP53 alterations by single-strand conformation polymorphism analysis (SSCP) of exons 5-9, direct sequencing and by p53 immunohistochemistry. RESULTS: Mutations of TP53 were detected in 11 of 49 (22.5%) patients and more specifically in 20% of Burkitt's lymphoma. The sequence analysis showed missense mutations in 10 cases and an insertion mutation in one case. Mutations of the transition type occurred more frequently than transversions (seven of 11). Analysis of the spectrum of single-nucleotide substitutions showed a 30% frequency of transition mutations in CpG dinucleotide sequences. The overall frequency of p53 immunostaining positivity was 36% (15 of 41). There was a very good agreement between protein expression and the presence of TP53 mutation (P=0.0005). No significant correlation was found regarding age, gender, clinical stage and LDH level and TP53 mutations. Comparison of EFS curves using the log-rank test were also not significant. However, the analysis of the effects of mutations on the core p53 structure identified biological and biochemical mutants with phenotypes probably related to different response to chemotherapy. CONCLUSIONS: Our data suggest that some types of mutants can alter the protein distinctly and may be associated with a more aggressive phenotype. In addition, the impact of TP53 mutations on response to therapy may also be influenced by disruption of other genes.

Adolescent↗