2,159 research outputs found
Unraveling new forms of inherited thrombocytopenias: from molecular to phenotypic characterization and back
No full textVenous thromboembolism in chronic gastrointestinal disorders
No full textChronic gastrointestinal disorders (including autoimmune gastritis, celiac disease, inflammatory bowel disease, and diverticular disease) are highly prevalent disorders, that may be associated with unpredictable, life-threatening complications, such as thromboembolic events. Venous thromboembolism (VTE) is one of the major causes of morbidity and mortality worldwide. Several conditions, including cancer, major trauma, surgery, prolonged immobilization, are well-established risk factors for VTE. Over the past decade, chronic inflammation has also been identified as an independent risk factor for VTE due to the prothrombotic effects of inflammatory cytokines and oxidative stress on the coagulation cascade. Other several mechanisms were shown to be associated with a higher incidence of VTE in patients with gastrointestinal disorders
The transcription activation function of C/EBPalpha is required for induction of granulocytic differentiation
No full textThe CCAAT/enhancer binding protein-a. (C/EBPalpha) is a transcription factor required for differentiation of myeloid progenitors. In addition to specific DNA binding, C/EBPa is also involved in protein-protein interactions, some of which (p21, Cdk2/Cdk4, E2F) appear to be required for inhibition of proliferation and possibly differentiation. To investigate the mechanisms of C/EBPalpha-induced granulocytic differentiation, we generated C/EBPalpha mutants reportedly defective in DNA binding, transactivation, and Cdk2/Cdk4 and E2F interaction and assessed their effects in a myeloid precursor cell line, primary bone marrow and C/EBPalpha knockout fetal liver precursor cells. We show here that the DNA binding-deficient Lys298Glu mutant, the E2F binding-deficient basic region mutant 2 (BRM-2) carrying the IIe294AIa and Arg 47AIa substitutions, and the transactivation-deficient N-terminus truncated p30 mutant all fall to promote differentiation on ectopic expression in myeloid precursor cells. By contrast, ectopic expression of the Cdk2/ Cdk4 interaction-deficient Delta177-191 mutant promotes differentiation and induces gene expression as effectively as wildtype C/EBPa. Thus, the integrity of the transactivation and DNA binding domains, but not of the Cdk2/Cdk4 interaction region, is necessary for C/EBPalpha-induced differentiation. Since the E2F binding-deficient BRM-2 mutant interacted with E2F-1 but failed to activate gene expression, our results lend support to the hypothesis that activation of gene transcription is the determining factor in C/EBPalpha-dependent differentiation
"The love that made hell, paradise." Ouida re-writing the Paolo and Francesca theme in Held in Bondage
No full textThe bestselling Victorian author Ouida reveals in her novels, and, in particular, Held in Bondage, an extraordinary knowledge od Dante, by using characters and themes from the Commedia. The Paolo and Francesca theme actually constitutes part of the plot of the novel and is to be found in many of her other works, short stories and non-fiction writing
A degradation-resistant c-Myb mutant cooperates with Bcl-2 in enhancing proliferative potential and survival of hematopoietic cells
No full textThe c-myb gene is preferentially expressed in primitive hematopoietic cell and plays a central role in the control of cell proliferation, differentiation and survival by regulating the transcription of several genes implicated in these processes including the antiapoptotic Bcl-2. We show here that, compared to wild-type c-Myb, overexpression of a degradation resistant c-Myb mutant [Delta(358-452) c-Myb] enhances the clonogenic potential of hematopoietic progenitors as indicated by increased cytokine-dependent primary and secondary colony formation of Lin(-) Sca-1(+) Kit(+) mouse marrow cells. Moreover, proliferation assays of IL-3 dependent myeloid precursor 32Dcl3 cells co-expressing Bcl-2 and c-Myb indicate that these cells continue to proliferate in the absence of IL-3 and this effect is more apparent in cells expressing the degradation resistant Delta(358-452) c-Myb. Interestingly, overexpression of Delta(358-452) c-Myb is by itself sufficient to protect 32Dcl3 cells from apoptosis induced by IL-3 deprivation; moreover, these cells are also increased in number which most likely reflects the enhanced proliferative potential conferred by Delta(358-452) c-Myb to apoptosis-resistant cell
Requirement of c-Myb for p210(BCR/ABL)-dependent transformation of hematopoietic progenitors and leukemogenesis
No full textThe c-Myb gene encodes a transcription factor required for proliferation and survival of normal myeloid progenitors and leukemic blast cells. Targeting of c-Myb by antisense oligodeoxynucleotides has suggested that myeloid leukemia blasts (including chronic myelogenous leukemia [CML]-blast crisis cells) rely on c-Myb expression more than normal progenitors, but a genetic approach to assess the requirement of c-Myb by p210(BCR/ABL)-transformed hematopoietic progenitors has not been taken. We show here that loss of a c-Myb allele had modest effects (20%-28% decrease) on colony formation of nontransduced progenitors, while the effect on p210(BCR/ABL)-expressing Lin(-) Sca-1(+) and Lin(-) Sca-1(+)Kit(+) cells was more pronounced (50%-80% decrease). Using a model of CML-blast crisis, mice (n = 14) injected with p210(BCR/ABL)-transduced p53(-/-)c-Myb(w/w) marrow cells developed leukemia rapidly and had a median survival of 26 days, while only 67% of mice (n = 12) injected with p210(BCR/ABL)-transduced p53(-/-)c-Myb(w/d) marrow cells died of leukemia with a median survival of 96 days. p210(BCR/ABL)-transduced c-Myb(w/w) and c-Myb(w/d) marrow progenitors expressed similar levels of the c-Myb-regulated genes c-Myc and cyclin B1, while those of Bcl-2 were reduced. However, ectopic Bcl-2 expression did not enhance colony formation of p210(BCR/ABL)-transduced c-Myb(w/d) Lin(-)Sca-1(+)Kit(+) cells. Together, these studies support the requirement of c-Myb for p210(BCR/ABL)-dependent leukemogenesi
HERStory Makers 2023: Francesca Fotheringham
No full textFrancesca Fotheringham is a postdoctoral research associate at the University of Edinburgh studying educational psychology with a focus on neurodiversity. She took part in HERStory Makers 2023.What is HERStory Makers?HERStory Makers is a social media competition for female-identifying early career researchers to share their research, their career journeys, and to inspire the next generation. Winners are selected by public vote. HERStory Makers is also part of EXPLORATHON, Scotland's contribution to European Researchers' Night.In 2022-23, EXPLORATHON Francescasupported by the Engineering & Physical Sciences Research Council [grant number EP/X020762/1].Author contributions to contentFrancesca conceived, planned, and recorded the video content. Kirsty Ross edited the video content to insert HERStory Maker credits, added subtitles, and reduce video length to below Twitter/X limit of 2 mins and 20 secs.</p
Medicina illuminata. La Biblioteca Lancisiana di Roma
No full textL'articolo presenta i codici miniati della Biblioteca Lancisiana di Roma. La prima parte, del coautore, è dedicata alla Biblioteca. La seconda parte, di F. Manzari, tratta dei manoscritti miniati, costituiti da due codici con le opere di Avicenna e dal Liber fraternitatis della Confraternita dell'Ospedale di Santo Spirito in Sassia a Roma.The article introduces the illuminated manuscripts of the Biblioteca Lancisiana in Rome. The first part of the article, by the co-author, is dedicated to the Library. The second part, by Francesca Manzari, illustrates the manuscipts; these are two manuscripts with the works of Avicenna and the Liber fraternitatis of the Confraternity of the Hospital of Santo Spirito in Sassia in Rome
Rivoluzione pacifica e Unità. Celebrazioni pubbliche nella Germania riunificata (1990-2014)
No full textIl lavoro copre un arco cronologico che va dal 1989-90 al 2014. Analizza come la Germania riunificata celebri la sua festa nazionale del 3 ottobre, giorno della riunificazione statale nel 1990, la caduta del Muro del 9 novembre 1989 e la Montagsdemo di Lipsia del 9 ottobre 1989. Lo sviluppo di un nuovo calendario civile è indagato guardando alla prassi delle celebrazioni, agli enti organizzatori, ai discorsi ufficiali tenuti nelle diverse occasioni
REAZIONI AVVERSE CUTANEE DEGLI INIBITORI DEL RECETTORE DELL’EPIDERMAL GROWTH FACTOR (EGFR): DESCRIZIONE DI UN CASO E REVISIONE DELLA LETTERATURA
No full textGli inibitori del recettore dell’epidermal growth factor
(EGFRs) sono associati a peculiari e severe reazioni
dermatologiche avverse. Cetuximab, gentifib e soprattutto
erlotinib sono farmaci utilizzati nel trattamento
di pazienti affetti da carcinoma del colon-retto e nel
non small cell carcinoma (NSCC) del polmone, refrattari
o intolleranti alla chemioterapia convenzionale.
Descriviamo il caso di un paziente caucasico di 46
anni, affetto da carcinoma NSC del polmone
(T3N2M0) in terapia da circa 8 mesi con erlotinib, che
presentava lesioni acneiformi diffuse su viso, tronco,
arti superiori e inferiori e paronichia. Il paziente veniva
trattato con macrolidi sistemici e steroidi topici con
miglioramento del quadro clinico. L’evento avverso
cutaneo secondario a trattamento con gli EGFRs più
frequentemente osservato è un’eruzione il cui quadro
istologico è caratterizzato da una pustola follicolare
sterile. Generalmente non è richiesta la sospensione
della chemioterapia ma spesso viene pregiudicata la
vita di relazione di tali pazienti. Sebbene il preciso
meccanismo etiopatogenetico di questa manifestazione
non sia ben definito, esso è correlato all’inibizione
dell’EGFR nella cute e può essere considerato un marker
visibile dell’attività anti-tumorale e dell’efficacia terapeutica
di tale classe di farmaci. È necessario individuare
schemi terapeutici mirati per il trattamento della
sintomatologia cutanea al fine di migliorare la qualità
di vita di tali pazienti
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