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Biomedical subjects

S Bozzo

Publications and source records attributed to S Bozzo.

8 recordsLinked to original sources
PubMed2000

Defective nuclear localization of p53 protein in a Chinese hamster cell line is associated with the formation of stable cytoplasmic protein multimers in cells with gene amplification.

Many p53 functions require p53 transport into the nucleus. Mutant p53 also generally accumulates in the nucleus of transformed or neoplastic cells. However, examples of cytoplasmic accumulation of wild-type or mutant p53 have also been reported. Various explanations have been provided for defective nuclear localization. Here we propose a novel example of cytoplasmic p53 localization which occurs in cells showing gene amplification and appears to be due to the formation of stable p53 multimers. We studied a methotrexate-resistant Chinese hamster cell line (MTX M) carrying amplified dihydrofolate reductase genes and derived from a cell line with p53 nuclear accumulation. MTX M showed cytoplasmic p53 localization and, on immunoblots, several extra bands in the high molecular weight region, besides the expected 53 kDa band. p53 localization and the appearance of high molecular weight bands appeared to be correlated with the degree of DNA amplification. However, amplification of dihydrofolate reductase itself was not involved. Changing the p53 phosphorylation status quantitatively influenced the formation of high molecular weight bands. Cell fusion experiments demonstrated that p53 cytoplasmic localization in MTX M is a dominant phenotype. This result suggests that the defect causing lack of nuclear localization in this cell line does not reside in the nucleus. In the cytoplasm of MTX M and of wild-type/MTX M heterodikaryons p53 gives rise to protein complexes that are unable to re-enter the nucleus. The formation of such protein complexes is dependent on the amplification of an unknown gene product.

3T3 Cells↗
PubMed1999

Derivative chromosome 17 in a case of Burkitt lymphoma with 8;14 translocation.

A complex chromosome rearrangement present in a B-cell line established from a patient with Burkitt lymphoma was studied by using fluorescence in situ hybridization (FISH) and immunocytochemistry techniques. The rearranged chromosome (der17) was apparently composed of 17q, of a partially deleted 17p, and of other material of chromosome 17p origin that was interspersed with regions without any clear banding pattern. der(17) contained a functional ch17 centromere and two additional centromeres of unknown origin that were inactive by all evidence. By FISH analysis with a TP53 probe, a signal could be demonstrated on the normal ch17, but not on the rearranged chromosome, a finding which indicates that 17p deletion caused a concurrent loss of one of the two TP53 alleles. The marker chromosome was previously observed in some of the malignant cells obtained from the patient's peripheral blood. These observations therefore indicate that cells with this specific rearrangement were generated in vivo and subsequently selected. This rearrangement is likely to have conferred a selective growth advantage to a subclone present in the original malignant cell population.

Adult↗
PubMed1997

Heterogeneous p53 mutations in a Burkitt lymphoma from an AIDS patient with monoclonal c-myc and VDJ rearrangements.

This study investigates the timing of p53 mutations detected in the malignant cells of a Burkitt's lymphoma cell line (BRG-P) with respect to other maturation or transforming events. The BRG-P cell line, derived from an AIDS patient, was of special value since it displayed subclones that had undergone an isotype switch from IgM to IgA1 (BRG-M and BRG-A cells). BRG-M and BRG-A cells were characterized by the same monoclonal c-myc and VDJ rearrangements and by the expression of Ig receptors with specificity for a 45 kDa protein of human breast cells. Analysis of p53 mutations in the different BRG subclones showed that 1) BRG-M cells displayed 2 different p53 mutations in trans; since the original BL cells also showed the same mutations, this finding indicated that both occurred in vivo; 2) one of the p53 alleles of BRG-A cells was lost, while the other showed a mutation different from those seen in BRG-M cells; and 3) all 3 mutations observed in BRG-M or BRG-A cells resulted in the functional inactivation of the transcriptional activation function of p53. Together, our data demonstrate that p53 mutations were relatively late events during lymphomagenesis. Moreover, in view of the role of p53 in cell apoptosis, it is conceivable that BRG cells were subjected to a strong selective pressure that favored p53 inactivation. Such inactivation was possibly required to counterbalance other potentially apoptotic events, including the presence of a deregulated c-myc oncogene and signals delivered by the host environment in situ.

B-Lymphocytes↗
PubMed1995

Variations in UV radiation in Chile.

The first observations of UV global radiation in Chile with a portable multichannel radiometer are reported. Four UV wavelengths are included: 305, 320, 340 and 380 nm. Observation latitudes spanning from 18 degrees to 53 degrees S allow an estimation of latitudinal variations in daily maxima for both summer and winter. Measurements over Santiago deviate from a smooth latitudinal profile, probably as a consequence of urban air pollution. The main effect of this is to prevent UV solar radiation from reaching the ground, especially during winter. Altitudinal increments in UV radiation are estimated by comparing observations along the coast and valleys with others on the Andes and one isolated summit. Diurnal variations in the height increment support an increase from morning to evening. The results indicate that in rural areas the altitudinal increment is lower (4%-10% per kilometre) than that reported for Europe, reaching very low magnitudes (2% or less) in the Andean summits of desert regions.

Chile↗
PubMed1995

p53 expression in normal versus transformed mammalian cells.

To answer the question whether the level of p53 expression also reflects the status of a cell, with reference to transformation and genome stability, we have examined, by immunocytochemistry, the presence of p53 protein in a number of cell types including human diploid cells, Chinese hamster embryonal cells at different passages and gene amplified and/or transformed Chinese hamster cell lines. Primary human fibroblasts at early passage (LEO) and an established, non transformed, Chinese hamster cell line at early passage (CHEF/18) did not show any detectable p53 expression, either nuclear or cytoplasmic. All transformed human (Raji) and Chinese hamster cell lines (CHO, V79, V79/B7) showed a nuclear expression of p53, although at different intensities. Two cell lines selected from V79/B7 for their resistance to phosphonacetyl-L-aspartate or methotrexate and previously shown to bear gene amplification, showed p53 expression. In PALA L cells p53 expression was nuclear as in other positive cell lines tested, while in MTX M cells it was cytoplasmic. CHEF/18 cells at late passage in culture showed the typical behaviour of transformed cells and p53 was detected in several cells. Moreover, when transformed CHO cells were treated with compounds known to induce reverse transformation, both the disappearance of hallmarks of transformed phenotype and p53 reduction were observed. These results indicate a strong association within the same cell type between p53 expression and transformed status.

Animals↗
PubMed1991

Effect of chronic renal failure on Na,K-ATPase alpha 1 and alpha 2 mRNA transcription in rat skeletal muscle.

Previous studies have suggested that an alteration in the expression of the Na,K-ATPase of muscle may be an important determinant of enhanced insulin sensitivity in chronic renal failure. Therefore, in the present studies we have examined the effect of uremia on the Na,K-ATPase alpha isoforms in skeletal muscle, at the level of mRNA expression and enzymatic activity. The activity of the sodium pump, as measured ouabain-sensitive 86Rb/K uptake in soleus muscle, revealed a reduction in the activity in uremia, related to the increment in plasma creatinine values. The decrement in 86Rb uptake by the rat soleus muscle of experimental animals was associated with changes on Na,K-ATPase gene product. Northern analysis of mRNA revealed isoform-specific regulation of Na,K-ATPase by uremia in skeletal muscle: a decrease of approximately 50% in alpha 1 subunit Na,K-ATPase mRNA, as compared to controls. The decrement in alpha 1 mRNA correlates with the decreased activity of the Na,K-ATPase in uremia, under basal conditions and with the almost complete inhibition of the Na,K-ATPase, of uremic tissue by a concentration of 10(-5) M ouabain. Although the activity of the alpha 2 isoform pump was not modified by uremia, the 3.4-kb message for this enzyme was increased 2.2-fold; this discrepancy is discussed. Altogether these findings demonstrate that the defective extrarenal potassium handling in uremia is at least dependent in the expression of alpha 1 subunit of the Na,K-ATPase.

Animals↗
PubMed1991

[Computer analysis of motility of small intestine in the dog].

Prolonged recordings at different levels of the small intestine have become necessary in motility studies. This has increased the number of motor events that are registered. The direct measurement of the numerous contractions is time-consuming, monotonous and rutinary. The use of computer analysis of this activity has been small. It is our objective to report our experience with this technique. Simultaneous recordings of small intestine motility were obtained on a polygraph and in a computer with an analogue digital converse system. The following parameters were compared: frequency, amplitude, motility index, and area under the curve. Excellent correlation of results obtained by both methods was observed. Computer analysis reduced the relation recording time/analysis time from 1/1.2 to 1/0.08. In our experience, the study of intestinal motility with analogue digital technique is very efficient and exact.

Animals↗