1,720,987 research outputs found
Possible involvement of the IL4 gene in Waldenström's macroglobulinemia
No full textWe report the results of a molecular investigation of 11 patients affected by Waldenström's macroglobulinemia, a rare B-cell malignancy characterized by an excessive proliferation of immunoglobulin(Ig)M-secreting plasmacytoid cells. In particular, we studied the interleukin-4 (IL4) gene, which codes for a B-specific growth factor capable of stimulating the proliferation and differentiation of secreting plasma cells. By Southern hybridization, in three patients we found the presence of additional bands in comparison with the expected pattern; moreover, these bands showed a different degree of intensity. © 1994
Sister chromatid exchange in Waldenström's macroglobulinemia
No full textResults on sister chromatid exchange (SCE) frequency and interchromosomal distribution in bone marrow and peripheral blood cultures from patients with Waldenström's macroglobulinemia are reported. PHA-stimulated bone marrow cultures showed increased SCE frequencies in all 12 patients examined. The increase was particularly high in two cases (17.07 and 16.77 SCE/cell, respectively) and, in one of them, a very high SCE level was found in PHA-stimulated peripheral blood culture (40.81 SCE/cell). In LPS-stimulated cultures, increased SCE levels were observed in some patients. Comparison between SCE frequency in bone marrow cell cultures with either mitogen showed a significant increase in PHA-stimulated cultures. Analysis of the interchromosomal SCE distribution revealed significant differences with respect to the control values; however, these differences were variable in the different patients. In pooled data of PHA-stimulated bone marrow cultures, there were differences between expected and observed SCEs in chromosomes 1 and 2 and in B, E, F, and G chromosome groups. Results of cell cycle modifications are also reported. © 1993
Biochemical approaches to characterize targets responsible for acrylamide-induced inhibition of topoisomerase II
No full textVinyl monomer acrylamide (AA), generally used in numerous industrial applications, has been classified by the International Agency for Research on Cancer (IARC) as “probably carcinogenic to humans” (group 2A), but the molecular mechanism underlying its genotoxicity has not fully known.
Previously, we observed that Acrylamide (AA) was able to antagonize in vivo the citotoxicity of well know poison etoposide suggesting that topoisomerase II (Topo II) activity was affected by AA.
In the current studies we investigated the inhibitory activity of acrylamide toward topoisomerase II by performing tests in vitro
Persistent dysregulation of DNA methylation in cells with arsenic-induced genomic instability
Full text linkThe mechanisms by which arsenic-induced genomic instability is initiated and maintained are poorly understood. In previous studies long-term progression of chromosomal instability was typified by increasing aneuploidy in Chinese hamster V79 and human keratinocyte cells treated with arsenite for a 24 hr exposure period followed by growth in arsenic-free medium for 40-120 cell generations. In the current study the role of progressive DNA methylation changes was evaluated in long-term cell cultures after brief arsenite treatments as above. We have found altered genomic methylation patterns in cells that were briefly exposed to arsenic with evidence for widespread dysregulation of CpG methylation that persists for many population doublings after the treatment.
In V79 cell populations, progressive aneuploidy increases were notable by 50 cell generations after a 24 hr exposure to 1-10 uM arsenite. Dicentric chromosomes and/or telomeric associations, as well as complex chromosome rearrangements, occurred by 90 cells generations post treatment; and mutator and transformed phenotypes began to appear thereafter. This increasing genomic instability correlated with modifications of global DNA methylation patterns in V79 cells evaluated by 5-methylcytosine antibody binding and MeSAP-PCR. The results show that short-term exposure to arsenite induced an apparent genome hypomethylating effect within a short time after exposure.
In identical protocols using human HaCaT keratinocytes exposed to low doses of arsenite (0.05-0.1 M) for 24 hr, genomewide methylation levels were measured by LINE1 pyrosequencing and gene-specific methylation status was assessed by Methylation-Specific-PCR for up to 40 generations post exposure. Global demethylation following treatment was supported by preliminary LINE-1 studies. Moreover, the study of gene-specific MSP and determination of expression levels by RT-PCR of several genes (p16, hMLH1, hMSH2, DNMT1, DNMT3a and DNMT3b) demonstrated that hMSH2 gene was epigenetically regulated by arsenite and that down regulation of DNMT3a and DNMT3b genes occurred in an arsenite dose-dependent manner.
The results reported here demonstrate that acute 24 hr arsenic exposure promptly induces genome wide DNA hypomethylation, and support the hypothesis that the cells continue to undergo epigenetic reprogramming both at the gene and genomic levels in the absence of further arsenite treatment; thus likely contributing to long-lasting genomic instability that manifests as aberrant chromosomal, mutator and cell transformation effects
Il PTHrP [38-94]-amide è un fattore “DNA-binding”: dati citogenetica e molecolari ed effetto biologico su cellule epiteliali mammarie immortalizzate e neoplastiche
No full textGoing Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Chromosomal abnormalities in Waldenström's macroglobulinemia
No full textWe report the results of cytogenetic studies of direct bone marrow (BM) preparations and of short-term BM and peripheral blood (PB) cultures from 17 patients with Waldenström's macroglobulinemia. We noted clonal chromosome changes in 10 patients. Abnormalities affected chromosomes X, Y, 2, 4, 5, 15, 16, 18, 19, 20, 21, and 22; in particular, chromosomes 2, 4, and 5 were involved in structural changes: a homogeneously staining region [hsr(2)], a der(4)t(4;?)(q32;?), and a 5q+. The other chromosomes were involved in numerical abnormalities, such as pseudodiploidy (a 46,X,-X,+15 clone), loss of chromosome Y, and monosomy of chromosomes 16, 18, 19, 20, 21, and 22. Nonclonal chromosome rearrangements were also observed. The results are discussed in comparison with the few data reported in the literature, and the finding of an hsr in the long arm of chromosome 2 is emphasized; indeed, this is the first report of hsr in WM. © 1992
Polimorfismi del gene CYP2A6 e dipendenza dal fumo in un gruppo di soggetti della Sicilia Occidentale
No full textE’ stato dimostrato che la diversa capacità di metabolizzare alcune sostanze è la conseguenza di differenze geneticamente determinate nelle attività di alcuni enzimi. In particolare, il citocromo P450 CYP2A6 ha diversi livelli di espressione interindividuali ed interetnici a causa di polimorfismi genetici; metabolizza circa il 70-80% della nicotina e ciò determina in alcune popolazioni una dipendenza interindividuale più o meno elevata dal fumo di sigaretta. Più in dettaglio, individui con alleli CYP2A6 con elevata attività metabolizzante (CYP2A6*1) avranno una maggiore dipendenza dalla nicotina, poiché questa, essendo metabolizzata velocemente, rimane nell’organismo per breve tempo: di conseguenza questi individui fumeranno molte sigarette per sopperire alla carenza di nicotina. Al contrario, individui con alleli CYP2A6 che codificano per un enzima con bassa attività metabolizzante (CYP2A6*2, ad esempio) avranno una minore dipendenza dalla nicotina in quanto questa, essendo metabolizzata più lentamente, rimane nell’organismo per più tempo e questa condizione indurrà il soggetto a fumare meno.
Allo scopo di verificare che la correlazione fra genotipo CYP2A6 e dipendenza dal fumo di sigaretta sia valido anche nella popolazione della Sicilia Occidentale, abbiamo analizzato la distribuzione di alcuni alleli CYP2A6 in 39 soggetti donatori abituali di sangue ai quali, dopo consenso informato, è stato somministrato un questionario sullo stile di vita con particolare riferimento all’abitudine al fumo. Il DNA, estratto da linfociti di sangue periferico mediante il sistema FASST DNA Releaser, è stato utilizzato come stampo in una Multiplex-PCR per amplificare una regione da 1717 bp comprendente gli esoni 1-4 del gene CYP2A6. Successivamente il prodotto della Multiplex-PCR è stato utilizzato come stampo per reazioni Multiplex-Nested-PCR, nelle quali sono state separatamente utilizzate coppie di oligonucleotidi innesco specifiche per l’allele selvatico CYP2A6*1 e per l’allele mutato CYP2A6*2. In queste condizioni è stato amplificato un frammento da 414 bp compreso fra gli esoni 3 e 4 del gene CYP2A6 nel quale può ricadere la trasversione TA che caratterizza l’allele mutato CYP2A6*2. In tal modo è stato possibile determinare il genotipo CYP2A6 dei soggetti esaminati visualizzando i prodotti di amplificazione su gel di poliacrilammide 12% in condizioni non denaturanti. I nostri risultati indicano che il genotipo omozigote CYP2A6*1/*1 è presente soltanto in soggetti fumatori, che tutti i soggetti non fumatori presentano il genotipo eterozigote CYP2A6*1/*2 e che nessun soggetto presenta genotipo CYP2A6*2/*2; inoltre, genotipi con delezione totale o parziale del gene CYP2A6 sono presenti tanto in fumatori che in non fumatori.
Ciò dimostra che polimorfismi del gene CYP2A6 sono in correlazione alla dipendenza dal fumo anche nella popolazione della Sicilia Occidentale e suggerisce che alla definizione di questo fenotipo concorrano fattori genetici ai quali si affiancano fattori di tipo comportamentale-sociale.
Studi più estesi sono auspicabili per definire le frequenze genotipiche del gene CYP2A6 dal momento che diverse configurazioni alleliche di questo gene, modulando la dipendenza dal fumo, indirettamente definiscono la suscettibilità individuale a contrarre alcune malattie come il cancro
Long-term exposure to submicromolar arsenite induces bypass of the spindle assembly checkpoint in mammalian cells
No full textMitosis is regulated by checkpoints that delay mitotic progression when chromosome segregation errors occur. Inaccuracy in checkpoint processes can lead to chromosome instability both in number and structure (CIN). Arsenic is reported to induce CIN by perturbing mitotic spindles and checkpoints, however, its carcinogenic mechanisms are poorly understood. We previously studied the long-term progression of chromosomal instability in V79 cells treated acutely with arsenite (10 M, 24 hr) followed by growth in arsenic-free medium for 120 cell generations, and found time-dependent increase of aneuploid cells. Here, we treated V79-derived G12 cells with sub-lethal doses (0.1-1.0 μM) of arsenite for 10 days followed by growth in arsenite-free medium for 40 cell generations. Cytogenetic analysis at the end of treatment showed concentration-dependent increases in the frequency of aneuploid cells that was even higher after 40 cell generations. Furthermore, the mitotic index (MI) of arsenite-exposed cells was higher than untreated cells at the end of the 10-day treatment or after 40 cell generations without arsenite. Surprisingly, we found that submicromolar 10-day arsenic exposure induced a large amount of cells in anaphase with premature centromere division. These aberrant mitotic figures dramatically increased after 40 cell generations. Taken together, these results raise the possibility that chronic exposure to sub-lethal arsenic doses induces bypass of the spindle assembly checkpoints and may be mechanistically involved in the induction of cell transformation
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