95 research outputs found

    Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

    Get PDF
    BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

    Misbehaviour of XIST RNA in Breast Cancer Cells

    Get PDF
    A role of X chromosome inactivation process in the development of breast cancer have been suggested. In particular, the relationship between the breast cancer predisposing gene BRCA1 and XIST, the main mediator of X chromosome inactivation, has been intensely investigated, but still remains controversial. We investigated this topic by assessing XIST behaviour in different groups of breast carcinomas and in a panel of breast cancer cell lines both BRCA1 mutant and wild type. In addition, we evaluated the occurrence of broader defects of heterochromatin in relation to BRCA1 status in breast cancer cells. We provide evidence that in breast cancer cells BRCA1 is involved in XIST regulation on the active X chromosome, but not in its localization as previously suggested, and that XIST can be unusually expressed by an active X and can decorate it. This indicates that the detection of XIST cloud in cancer cell is not synonymous of the presence of an inactive X chromosome. Moreover, we show that global heterochromatin defects observed in breast tumor cells are independent of BRCA1 status. Our observations sheds light on a possible previously uncharacterized mechanism of breast carcinogenesis mediated by XIST misbehaviour, particularly in BRCA1-related cancers. Moreover, the significant higher levels of XIST-RNA detected in BRCA1-associated respect to sporadic basal-like cancers, opens the possibility to use XIST expression as a marker to discriminate between the two groups of tumors

    Atlas Floresta Americana. Bonpland. 1850: La identificación de las plantas de la Materia Médica Misionera de Pedro de Montenegro (SJ)

    Get PDF
    The manuscript bequeathed by Amado Bonpland, Atlas Floresta Americana 1850, obtained from the Library of the Casa de la Cultura Benjamín Carrión (Quito, Ecuador) after efforts made by various entities, allows us to have material of great historical-scientific value and that contributes to the study of the plants identification described in the Materia Medica Missionera of Pedro de Montenegro. In this sense, it constitutes a documentary collection that integrates valuable data pertaining to the Jesuit period, as well as the period in which Bonpland remained in the River Plate basin. The manuscript was analyzed with an interdisciplinary approach. The objectives of the present study are to present the unpublished document, characterize it historically, transcribe it, translate it into Spanish, update the phytonyms to the current Guaraní, update the identifications of the plants of the Jesuit work Pedro de Montenegro, and compare these identifications with others made on the same work. The characteristics of the manuscript and the historical context of its production are described. The botanical affiliation of the plants identified by Bonpland from the Materia Medica Misionera is presented. The importance of this unpublished document as heritage is highlighted, as well as its possible contributions to Jesuit, botanical and pharmacological studies in general.El manuscrito legado por Amado Bonpland, Atlas Floresta Americana 1850, obtenido de la Biblioteca de la Casa de la Cultura Benjamín Carrión (Quito, Ecuador) luego de gestiones realizadas por diversas entidades, nos permite contar con un material de gran valor históricocientífico y que aporta al estudio de la identificación de las plantas descriptas en la Materia Médica Misionera de Pedro de Montenegro. En tal sentido constituye un fondo documental que integra datos valiosos pertenecientes al período jesuítico, como también del período en que Bonpland permaneció en la cuenca rioplatense. El manuscrito fue analizado desde un enfoque interdisciplinario. Los objetivos del presente trabajo son: presentar el documento inédito, caracterizarlo históricamente, transcribirlo, traducirlo al español, actualizar los fitónimos al guaraní actual, actualizar las identificaciones de las plantas de la obra del jesuita Pedro de Montenegro, y comparar dichas identificaciones con otras realizadas sobre la misma obra. Se describen las características del manuscrito y el contexto histórico de su producción. Se presenta la afiliación botánica de las plantas identificadas por Bonpland a partir de la Materia Médica Misionera. Se resalta la importancia de este documento inédito como patrimonio, como también sus posibles aportes a los estudios jesuíticos, botánicos y farmacológicos en general. INFORMACION COMPLEMENTARIA 

    Atlas American Forest. Bonpland. 1850: Identification of plants from the “Materia Médica Misionera” of Pedro de Montenegro (SJ)

    Get PDF
    El manuscrito legado por Amado Bonpland, Atlas Floresta Americana 1850, obtenidode la Biblioteca de la Casa de la Cultura Benjamín Carrión (Quito, Ecuador) luego de gestionesrealizadas por diversas entidades, nos permite contar con un material de gran valor históricocientífico y que aporta al estudio de la identificación de las plantas descriptas en la Materia Médica Misionera de Pedro de Montenegro. En tal sentido constituye un fondo documentalque integra datos valiosos pertenecientes al período jesuítico, como también del período enque Bonpland permaneció en la cuenca rioplatense. El manuscrito fue analizado desde unenfoque interdisciplinario. Los objetivos del presente trabajo son: presentar el documentoinédito, caracterizarlo históricamente, transcribirlo, traducirlo al español, actualizar los fitónimosal guaraní actual, actualizar las identificaciones de las plantas de la obra del jesuita Pedro deMontenegro, y comparar dichas identificaciones con otras realizadas sobre la misma obra.Se describen las características del manuscrito y el contexto histórico de su producción. Sepresenta la afiliación botánica de las plantas identificadas por Bonpland a partir de la MateriaMédica Misionera. Se resalta la importancia de este documento inédito como patrimonio, comotambién sus posibles aportes a los estudios jesuíticos, botánicos y farmacológicos en general.The manuscript bequeathed by Amado Bonpland, Atlas Floresta Americana 1850, obtained from the Library of the Casa de la Cultura Benjamín Carrión (Quito, Ecuador) after efforts made by various entities, allows us to have material of great historical-scientific value and that contributes to the study of the plants identification described in the Materia Medica Missionera of Pedro de Montenegro. In this sense, it constitutes a documentary collection that integrates valuable data pertaining to the Jesuit period, as well as the period in which Bonpland remained in the River Plate basin. The manuscript was analyzed with an interdisciplinary approach. The objectives of the present study are to present the unpublished document, characterize it historically, transcribe it, translate it into Spanish, update the phytonyms to the current Guaraní, update the identifications of the plants of the Jesuit work Pedro de Montenegro, and compare these identifications with others made on the same work. The characteristics of the manuscript and the historical context of its production are described. The botanical affiliation of the plants identified by Bonpland from the Materia Medica Misionera is presented. The importance of this unpublished document as heritage is highlighted, as well as its possible contributions to Jesuit, botanical and pharmacological studies in general.Fil: Arbelo, Aurora. Asociación de Directores de Museos ; ArgentinaFil: Gabriela Basualdo, M.. Ministerio de Coordinación y Planificación de Corrientes; ArgentinaFil: Cerruti, Cèdric. Université de la Rochelle; FranciaFil: Valenzuela, Fatima Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Investigaciones Geohistóricas. Universidad Nacional del Nordeste. Instituto de Investigaciones Geohistóricas; ArgentinaFil: Pageau, Christian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Investigaciones Geohistóricas. Universidad Nacional del Nordeste. Instituto de Investigaciones Geohistóricas; ArgentinaFil: González, Humberto E.. No especifíca;Fil: Clarisa Godoy, M.. No especifíca;Fil: Riabis, Melina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Guevara, David N.. No especifíca;Fil: Keller, Héctor A.. Universidad Nacional de Misiones. Facultad de Ciencias Forestales; ArgentinaFil: Stampella, Pablo César. Universidad Nacional de La Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

    PI 3 Kinase Related Kinases-Independent Proteolysis of BRCA1 Regulates Rad51 Recruitment during Genotoxic Stress in Human Cells

    Get PDF
    The function of BRCA1 in response to ionizing radiation, which directly generates DNA double strand breaks, has been extensively characterized. However previous investigations have produced conflicting data on mutagens that initially induce other classes of DNA adducts. Because of the fundamental and clinical importance of understanding BRCA1 function, we sought to rigorously evaluate the role of this tumor suppressor in response to diverse forms of genotoxic stress.We investigated BRCA1 stability and localization in various human cells treated with model mutagens that trigger different DNA damage signaling pathways. We established that, unlike ionizing radiation, either UVC or methylmethanesulfonate (MMS) (generating bulky DNA adducts or alkylated bases respectively) induces a transient downregulation of BRCA1 protein which is neither prevented nor enhanced by inhibition of PIKKs. Moreover, we found that the proteasome mediates early degradation of BRCA1, BARD1, BACH1, and Rad52 implying that critical components of the homologous recombination machinery need to be functionally abrogated as part of the early response to UV or MMS. Significantly, we found that inhibition of BRCA1/BARD1 downregulation is accompanied by the unscheduled recruitment of both proteins to chromatin along with Rad51. Consistently, treatment of cells with MMS engendered complete disassembly of Rad51 from pre-formed ionizing radiation-induced foci. Following the initial phase of BRCA1/BARD1 downregulation, we found that the recovery of these proteins in foci coincides with the formation of RPA and Rad51 foci. This indicates that homologous recombination is reactivated at later stage of the cellular response to MMS, most likely to repair DSBs generated by replication blocks.Taken together our results demonstrate that (i) the stabilities of BRCA1/BARD1 complexes are regulated in a mutagen-specific manner, and (ii) indicate the existence of mechanisms that may be required to prevent the simultaneous recruitment of conflicting signaling pathways to sites of DNA damage
    corecore