Biomedical subjects

R Maestro

Publications and source records attributed to R Maestro.

41 records · Page 3Linked to original sources

PubMed1990

Pathogenesis of malignant lymphomas in intravenous drug-abuser, HIV-infected patients.

To study the pathogenesis of malignant lymphomas (ML) in intravenous drug-abuser HIV-infected patients, we analyzed 19 cases of reactive lymphadenopathy (LAS) and 10 cases of ML. Clonality and differences in characteristics of these lymphoproliferative disorders were investigated by immunohistochemical and Ig and TCR gene rearrangement analyses. Rearrangements at the c-myc locus and presence of HIV and EBV viral genomes were also investigated. Four out of the five non-Hodgkin's lymphomas (NHL) analyzed were high-grade extranodal ML and were found to derive from precursor B cells. Monoclonal cell expansions were also detected in 2 cases of LAS. These cell expansions also consisted of precursor B cells. HIV genome was not detected in any of the samples tested and was therefore considered not to be involved as an etiological agent in these lymphoproliferative disorders. EBV genome was present in a clonal episomal form in the five Hodgkin's disease (HD) specimens tested. This finding suggested that a clonal cell population harboring the EBV viral genome must be present in HDs, pointing to a possible etiological relationship between EBV and HD in HIV-infected patients.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1989

In K562 leukemia cells treated with doxorubicin and hemin, a decrease in c-myc mRNA expression correlates with loss of self-renewal capability but not with erythroid differentiation.

The decrease in c-myc mRNA expression occurring in leukemia cell lines induced to differentiate is supposed to be an early event of the commitment to the differentiation program. Alternatively, the decrease in c-myc mRNA expression could be simply a consequence of loss of the self-renewal capability characteristic of the terminal differentiated phenotypes. In an attempt to clarify these hypotheses, we analysed comparatively the kinetics of variations in c-myc mRNA expression, hemoglobin synthesis, DNA and RNA syntheses, cell cycle kinetics and self-renewal capability in normal and hemin-treated K562 leukemia cells exposed for different periods of time to the antitumoral antibiotic doxorubicin. Times of exposure to doxorubicin were either 2 h, which resulted in reversible induction of hemoglobin synthesis without significant cytostatic effects, or continuously for more than 5 days, which resulted in an irreversible induction of hemoglobin synthesis and in the complete and irreversible loss of self-renewal activity. Comparative analysis of the experimental data indicated that the decrease in c-myc mRNA expression correlated with the loss of replicative activity, possibly due to an irreversible cytostatic effect of the long exposure to doxorubicin, but not with the commitment to the differentiation programs.

Blotting, Northern↗

PubMed1989

N-myc activation by proviral insertion in MCF 247-induced murine T-cell lymphomas.

N-myc proto-oncogene rearrangement was found in three out of six AKR murine T-cell lymphomas induced by the highly oncogenic MCF 247 MuLV. Molecular analyses showed that structural modification of the proto-oncogene in all three lymphomas was in the consequence of MCF 247 proviral integration within the gene III exon. All integrated proviruses have the same transcriptional orientation as the N-myc gene. As a consequence of proviral insertion, the N-myc gene becomes transcriptionally active, producing an abnormal mRNA. These findings suggest a possible causative role of such an integrative event in murine T-cell lymphomagenesis.

Amino Acid Sequence↗

PubMed1988

Activation by point mutation of Ki-ras gene occurring in transfected human normal DNA.

A mutation-activated human Ki-ras gene was detected in NIH 3T3 cells transfected with high molecular weight DNA extracted from peripheral blood leukocytes of a healthy blood donor. A deoxyguanosine at position 35 of the first exon was substituted by deoxythymidine. Nevertheless, cloning and sequencing of seven independent Ki-ras first exons, isolated from the same human genomic DNA used to transfect NIH 3T3 cells, failed to reveal the expected point mutation. Since transfected DNA is susceptible to mutagenesis in mammalian cells, we hypothesize that a base substitution occurred during the transfection assay.

Animals↗

PubMedDate not supplied

Spontaneous mutation of cell oncogenes plays a minor role in neoplastic transformation of virus-induced murine T-cell lymphomas.

Mink cell focus-forming viruses (MCF) are slow-transforming retroviruses that are able to accelerate the appearance of T-cell lymphomas when injected in newborn AKR mice. Activation of proto-oncogenes by proviral insertion is thought to be the major mechanism by which these viruses exert their oncogenic potential. However, molecular phenomena not strictly virus-determined, such as mutations in cellular oncogenes/tumor suppressor genes or chromosome aberrations, have been hypothesized to contribute to the achievement of the fully neoplastic phenotype in MCF-infected mice. To evaluate the role of spontaneous mutagenesis phenomena in murine virus-induced lymphomagenesis, we analyzed a series of 18 MCF247-induced thymic lymphomas and derived cell lines for the presence of p53 and c-ras gene mutations. Only 1 mutation at the p53 gene and 1 mutation at the ki-ras gene were detected in our study. Our results suggest that spontaneous mutagenesis plays a minor role in virus-induced lymphomagenesis and support the notion that multiple proviral insertions could be the prevalent mechanism of transformation in this experimental system.

Animals↗