Abstract The p53 gene is rarely mutated in neuroblastoma, but codon 72 polymorphism that modulates its proapoptotic activity might influence cancer risk and clinical outcome. We investigated whether ...this polymorphism affects neuroblastoma risk and disease outcome and assessed the biologic effects of the p53-72R and p53-72P isoforms in p53-null cells. Comparison of 288 healthy subjects and 286 neuroblastoma patients revealed that the p53-72 polymorphism had no significant impact on the risk of developing neuroblastoma; however, patients with the Pro/Pro genotype had a shorter survival than those with the Arg/Arg or the Arg/Pro genotypes even in the stage 3 and 4 subgroup without MYCN amplification. By Cox regression analysis, the p53 Pro/Pro genotype seems to be an independent marker of poor prognosis (hazard ratio = 2.74; 95% confidence interval = 1.14–6.55, P = .014) together with clinical stage, MYCN status, and age at diagnosis. In vitro , p53-72P was less effective than p53-72R in inducing apoptosis and inhibiting survival of p53-null LAN-1 cells treated with etoposide, topotecan, or ionizing radiation but not taxol. By contrast, p53-72P was more effective in promoting p21-dependent accelerated senescence, alone or in the presence of etoposide. Thus, the p53-72 Pro/Pro genotype might be a marker of poor outcome independent of MYCN amplification, possibly improving risk stratification. Moreover, the lower apoptosis and the enhanced accelerated senescence by the p53-72P isoform in response to DNA damage suggest that patients with neuroblastoma with the p53-72 Pro/Pro genotype may benefit from therapeutic protocols that do not rely only on cytotoxic drugs that function, in part, through p53 activation.
We describe an unusual case of hepatosplenic T-cell lymphoma in a 61-year-old man who presented with fever, hepatosplenomegaly, anemia, and thrombocytopenia. A spleen biopsy was consistent with ...T-cell lymphoma. Cytogenetic studies did not reveal chromosome abnormalities. Using the polymerase chain reaction approach, clonality of the T-cell receptor gamma-chain gene rearrangement could be demonstrated, while Southern blot analysis disclosed only a germline configuration of the T-cell receptor beta chain genes. Of interest, an immune-mediated mechanism was demonstrated and was most likely responsible for erythrocyte and platelet destruction; this is, therefore, the first report of gamma T-cell lymphoma in association with Evans' syndrome. Initial steroid treatment was efficacious in limiting autoimmunity but constitutional symptoms did not subside. Chemotherapy (MACOP-B) was successful in obtaining complete clinical remission. Finally, thrombocytopenia in gammadelta T-cell lymphoma patients should be routinely evaluated for platelet autoantibodies.
Patients infected with HIV-1 are at high risk of developing Epstein-Barr virus (EBV)-associated lymphoproliferative disorders. This study evaluated the impact of highly active antiretroviral therapy ...(HAART) on EBV infection.
To measure EBV content in peripheral blood lymphocytes (PBL) and in plasma, we set up a quantitative analysis using the real-time PCR. EBV latent membrane protein 1 (LMP1) expression was determined by reverse transcriptase-PCR.
EBV levels were determined in 33 HIV-1- and EBV-coinfected patients at the start of HAART, and during therapy. At baseline, EBV content in PBL samples ranged from 8 to 14 532 copies/microg DNA. EBV levels transiently increased in nine out of 17 patients in whom HIV-1 plasmaviraemia declined to undetectable levels (virological response) and CD4 cell counts increased (immunological response), while they remained fairly stable or decreased in the other eight virological and immunological responders, and in seven patients who showed a virological response only. Of interest, a significant increase in EBV load was observed in five out of nine patients who showed an increase in CD4 cell counts but lack of HIV-1 suppression during HAART. This EBV increase was accompanied by the detection of both LMP1 transcripts in PBL and EBV DNA in plasma, and was paralleled by an increase in immunoglobulin levels, a marker of B-cell stimulation.
These findings suggest that peripheral immune reconstitution during HAART without a reduction in HIV-1 replication may increase B-cell stimulation and the number of EBV-infected B cells.
RESUMO A espécie Solidago chilensis Meyen, Asteraceae é conhecida como erva-lanceta ou arnica-brasileira, sendo utilizada popularmente como antimicrobiana e para o tratamento de inflamações tópicas. ...No entanto, estudos fitoquímicos e farmacológicos para as partes aéreas são escassos. Neste trabalho, realizou-se a determinação de flavonoides por espectrofotometria de UV/Vis, prospecção fitoquímica da fração acetato de etila visando o isolamento do constituinte químico majoritário e validação analítica por cromatografia líquida de alta eficiência (CLAE). O teor de flavonoides totais foi de 5,42%, representados como hiperosídeo. O fracionamento químico utilizando métodos cromatográficos (cromatografia líquida em coluna gel de sílica; CHCl3:EtOH; 8:2 v/v) e espectroscópicos (1H RMN,13C RMN e ESI-MS) revelou o isolamento de quercetina-3-O-α-L-ramnosídeo(quercitrina). A sensibilidade e a linearidade (r = 0,999) da validação analítica, utilizando a quercitrina isolada do extrato hidroalcoólico da planta, revelaram um rendimento de 5,29% do analito em relação à droga vegetal. Precisão, recuperação e robustez, além dos valores estabelecidos para os limites de detecção (LOD) e de quantificação (LOQ), poderão ser utilizados como parâmetros de qualidade para extratos à base de S. chilensis.
ABSTRACT The species Solidago chilensis Meyen Asteraceae, known as “erva-lanceta” or “Brazilian arnica”, is popularly used as an antimicrobial and topical treatment for inflammations. However, phytochemical and pharmacological studies of its aerial parts are scarce. In this study, flavonoids were determined by UV/Vis spectrophotometry and phytochemical screening of the ethyl acetate fraction with the goal of isolating the major chemical constituent and analytically validating it through high performance liquid chromatography (HPLC). The total flavonoid content was 5.42%, represented as hyperoside. Chemical fractionation using chromatographic (liquid chromatography in column of silica gel, CHCl3:EtOH, 8:2 v/v) and spectroscopic methods (1H RMN, 13C RMN, and ESI-MS) revealed the isolation of quercetin-3-O-α-L-rhamnoside (quercitrin). The sensitivity and linearity (r = 0.999) using the isolated quercitrin of the hydroalcoholic extract of the plant revealed a yield of 5.29% of analyte in relation to the plant. Precision, recovery, and robustness, as well as values set for the limits of detection (LOD) and quantitation (LOQ) can be used as quality parameters for extracts based on S. chilensis.
Most of the hereditary breast cancers are attributed to constitutive alterations of either BRCA1 or BRCA2 genes; nonetheless, germline mutations of these genes in 'high risk' families are found less ...frequently than expected from linkage data. Recent findings suggest that major genomic rearrangements of the BRCA1 gene might account for at least some of the apparently mutation negative cases. We studied 60 affected probands belonging to families with a strong history of breast and/or ovarian cancer who scored negative for BRCA1 gene mutations by PTT and SSCP analysis. DNA was analysed by the Southern blotting procedure using three different restriction enzymes, and two probes obtained by RT-PCR of the 5' and 3' BRCA1 coding sequence. A 3 kb deletion encompassing exon 17 and causing a frameshift mutation was identified in two independently ascertained families. RT-PCR and long-range DNA PCR were employed to characterize the rearrangement that was finally shown to be the result of a recombination between two very similar Alu repeats. This type of mutation is not identified by the conventional methods of mutation detection which are based on PCR amplification of single exons. Therefore, further search for gene rearrangements is needed to better define the proportion of 'high risk' families that might be explained by gross genomic alterations of the BRCA1 gene.
Ao propor o título para esta comunicação, veio-me à mente a discussão histórica sobre a avaliação e os rumos que este processo vem tomando, no espaço ─ Escola ─ onde deveria encontrar ambiente ...favorável para fundar seus alicerces e firmar-se como uma nova ciência.
Contudo, e contrariamente ao que se esperava, é justamente na escola que o processo avaliativo encontra seus maiores entraves. Tais percepções vêm promovendo no interior do grupo de pesquisa coordenado por mim, reunindo alunos da graduação, da pós-graduação, meus orientados, ex-orientados (mestres) e professores do ensino fundamental e médio uma discussão profícua sobre os instrumentos utilizados para avaliar os alunos e os usos de seus resultados com vistas a garantir uma aprendizagem significativa e um ensino de qualidade. Discute-se e investiga-se ainda, a prática da avaliação em cursos de formação de professores que visam a preparar profissionais para atuarem junto ao ensino fundamental de 1ª a 4ª séries.
Correction to: Oncogene (2008) 27, 2929–2933; doi:10.1038/sj.onc.1210947; published online 19 November 2007 Since the publication of the above manuscript, the authors have identified an error in the ...author list; the name of the seventh author was misspelt. The corrected author list is shown above. In addition to the published affiliation, B Calabretta is affiliated with Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson Medical College, Philadelphia, PA, USA.
We report a patient with myasthenic syndrome who, 2 years after diagnosis, developed an oligoclonal lymphocytosis. This disorder was sustained by both kappa+ and lambda+ CD5+ B-cell clones; over the ...following year, the white blood cell count increased and phenotypic characterization revealed a clear imbalance in the immunoglobulin light chain ratio (84% kappa+). Accordingly, persistence of a kappa+ B-cell clone was disclosed by molecular analysis of immunoglobulin heavy chain gene rearrangements. Our results may suggest that prolonged immune system stimulation due to an autoimmune disease can drive a benign lymphoproliferation into a B-cell neoplastic process.
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