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Biomedical subjects

M G Boavida

Publications and source records attributed to M G Boavida.

30 records · Page 2Linked to original sources
PubMed1997

Isochromosome 14q in refractory anemia.

Trisomy 14 in hematologic disease is a rare finding and is almost exclusively associated with myeloid cell lineage. We present a case of refractory anemia (MDS-RA) with the uncommon features of marked elliptocytosis and schistocytosis in the peripheral blood and isochromosome 14q. The analysis of the clinical outcome of this case and of others of myelodysplastic (MDS)/myeloproliferative syndromes with trisomy 14 as the sole abnormality suggests that it does not confer an unfavorable prognosis.

Aged↗
PubMed1996

Insertion of a short Alu sequence into the hMSH2 gene following a double cross over next to sequences with chi homology.

Alu repeat sequences and other multiple copy repetitive elements are present throughout the human genome and are active in promoting recombination. It is believed that reverse transcription of transcribed Alu repeats followed by chromosomal integration has been responsible for the wide dispersion and high copy number of these sequences. During studies on the hMSH2 gene we have used RT-PCR to amplify from peripheral blood lymphocytes a cDNA species in which 553 base pairs of hMSH2 cDNA have been deleted to be replaced by a short 36 base pair Alu sequence as a result of a genomic insertion/deletion event. The 36 base pair Alu insert is homologous to a 26 base pair Alu sequence previously implicated in the promotion of recombination and contains the GCTGG motif which is part of the prokaryotic chi sequence. A second chi-like sequence is also located within the deleted hMSH2 region. Both chi-like sequences are located within 4 bp of the two 4-bp regions of cross over containing the insertion/deletion breakpoints. This suggest that a double recombination event has occurred, providing direct evidence for the recombinogenic activity of this Alu element. Furthermore, it suggests that chi-like sequences may define recombination hotspots as in prokaryotes.

DNA, Complementary↗
PubMed1996

Naturally occurring splicing variants of the hMSH2 gene containing nonsense codons identify possible mRNA instability motifs within the gene coding region.

We have identified certain unusually spliced cDNA species following PCR amplification of peripheral blood lymphocyte (PBL) mRNA from the hMSH2 gene. A naturally occurring transcript containing a nonsense codon due to the skipping of 5 exons was amplified from PBLs of several healthy individuals. A feature of this and another unusual splicing product was the presence of sequence motifs which bore significant similarity to mRNA instability determinants in the region immediately downstream of the stop codon. In particular, the rare tetranucleotide GAUG, previously identified in yeast as being of critical importance to the rapid degradation of nonsense-containing mRNAs was situated 23 base pairs downstream of the stop codon. Furthermore the region downstream of the stop codon was A:U rich and contained 2 copies of the AUUUA motif. As other forms of alternative splicing would not result in the same juxtaposition of stop codons and instability motifs, we suggest that the stop codons may have been deliberately introduced by the splicing process for their proximity to these destabilising motifs, and that splicing may play a role in channeling mRNAs into degradative pathways. These results are consistent with the hypothesis that nuclear factors may scan pre-mRNAs prior to splicing.

Adenosine Triphosphatases↗
PubMed1996

Sister chromatid exchange analysis in workers exposed to noise and vibration.

Workers chronically exposed to whole-body vibration and noise are known to develop pathophysiological and psychological disturbances. The frequencies of sister chromatid exchanges (SCEs) and of cells with high frequencies of SCEs (HFCs) were analyzed in lymphocytes of 50 workers occupationally exposed to vibration and noise and of 34 controls. The exposed group included: individuals operating hand-vibrating tools (group 1), 'test-cell operators' (group 2) and 'run-up' operators (group 3) from an air base and helicopter pilots (group 4). The statistical analysis of the mean SCE count per cell was carried out by multiple regression analysis, comparing various predictor variables: exposure group, duration of exposure, age and cigarette consumption. Only cigarette consumption and exposure group were found to be significantly correlated with the mean SCE frequency. After allowing for the effects of smoking, the analysis indicates that: (1) there was no significant difference between group 1 and controls (p > 0.05); (2) the differences between group 2 and group 0, group 3 and group 0 and group 4 and group 0 were all highly significant (p < 0.001); (3) there was no significant difference between groups 2 and 3 (p > 0.05), nor between groups 2 and 3 combined and group 4 (p > 0.05); (4) exposure groups 2, 3 and 4 combined, had a significantly elevated mean SCE frequency compared to the control group (p < 0.0001). Statistical analysis of the proportion of HFCs was consistent with these results. Our data suggest that chronic exposure to whole-body vibration and noise may lead to an increase in the level of SCEs in man. The observed effects may not reflect a direct action of these physical agents on DNA. Alternative explanations may include some of the whole-body vibration and noise-induced or stress-induced pathophysiological alterations which may indirectly induce SCE formation.

Adult↗
PubMed1996

Jumping translocation in a phenotypically normal female.

"Jumping translocation" jt refers to a rare type of chromosome mosaic, in which the same portion of a (donor) chromosome is translocated to different (recipient) chromosome sites. Jt have mainly been observed in lymphocyte cultures of patients with hematologic malignancies. We report a phenotypically normal female carrying a mosaic of two cell lines with the Xq26-qter segment translocated to the short arm of chromosomes 15 or 21 in peripheral blood lymphocytes. In skin fibroblasts, only the X/21 translocation was detected. We speculate that recombination between homologous repetitive sequences on non-homologous human acrocentrics may be the cause of such chromosomal rearrangements.

Abnormalities, Multiple↗
PubMed1995

Silent APC (adenomatous polyposis coli) gene polymorphism in the Portuguese population.

We describe a new, silent polymorphism in exon 15 of the APC gene on chromosome 5q in the Portuguese population. The polymorphism is located at codon 1442 and results in a CCT-->CCA (Pro) base transversion, with no amino acid change. Population analysis in unrelated healthy controls indicated that the polymorphism was present in 2 out of 50 individuals giving an allele frequency of 0.02 +/- 0.01. The polymorphism is the most common encountered in the Portuguese population in the mutation cluster region of exon 15, and has not been previously described in other populations.

Adenomatous Polyposis Coli↗
PubMed1994

Dose dependence of radiation-induced micronuclei in cytokinesis-blocked human lymphocytes.

Following selection of appropriate culture conditions, various experiments were conducted to evaluate the suitability of the micronucleus assay in cytokinesis-blocked lymphocytes for biological dosimetry purposes. A dose-effect relationship was determined, based on the frequency of micronuclei induced by various doses of 60Co gamma-rays. The data were best fitted to a linear-quadratic model. To validate the system, an attempt was made to estimate unknown dose levels from the yield of micronuclei, by inverting the derived dose-response function. It was concluded that the assay provides a valid approach for dose assessment. The size of radiation-induced micronuclei was measured in relation to the dose. A significant difference in the proportion of large micronuclei between high and low doses was observed. The chromosomal composition of micronuclei, detected by immunofluorescent staining of kinetochores, showed that only a small proportion of micronuclei contains kinetochore. The possible contribution of various mechanisms for the formation of large radiation-induced micronuclei is discussed.

Adult↗
PubMed1993

Insertional inactivation of the WT1 gene in tumour cells from a patient with WAGR syndrome.

The WT1 gene was analysed using DNA from a Wilms' tumour derived from a patient with the WAGR syndrome using single strand conformation polymorphism analysis and polymerase chain reaction sequencing. A 14-bp insertion was found in the intron part of the splice donor site of exon 7 and was a tandem duplication of an upstream exon sequence. This mutation would be expected to disrupt the correct processing of the WT1 mRNA and is predicted to result in a non-functional protein. This observation further supports the role of WT1 in Wilms' tumorigenesis in patients with constitutional 11p13 deletions.

Abnormalities, Multiple↗
PubMedDate not supplied

P73 expression in neuroblastoma: a role in the biology of advanced tumors?

p73, a recently identified gene showing high homology to p53 and mapping to 1p36.33, was presented as a candidate gene for neuroblastoma. In this study the authors evaluate the levels and allelic nature of p73 expression in primary neuroblastomas using reverse transcription-polymerase chain reaction-restriction fragment length polymorphism strategies based on intragenic polymorphisms. From 32 neuroblastoma patients, 11 were heterozygous for the p73 polymorphisms analyzed. p73 expression was found to be low in the correspondent tumors and while all 6 stages 1 and 2 tumors presented biallelic expression, 4 out of the 5 stage 4 tumors showed only one active p73 allele. Analysis of blood samples from 8 healthy donors and 4 neuroblastoma patients revealed much higher levels of p73 expression, and exclusively of biallelic nature. These results are supportive of a role for p73 in the biology of neuroblastoma, particularly in some advanced tumors. Nevertheless, the G81A/C91T polymorphism, previously implicated in regulating the expression of p73, did not show any significant association with neuroblastoma development.

Adolescent↗