119 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
La riunificazione in mostra. Musei ed esposizioni a Berlino dopo il 1989
No full textL’articolo analizza come i musei di Berlino presentano i temi della rivoluzione pacifica (il processo che condusse al crollo del Muro di Berlino e alla fine della DDR) e della successiva riunificazione tedesca. L’articolo concentra la sua attenzione su quattro differenti musei storici (Deutsches Historisches Museum, DDR-Museum, Mauer-Museum, Stasi-Museum) e analizza inoltre due mostre temporanee («Wir sind das Volk!» e «1990: der Weg zur Einheit»), tenutesi a Berlino nel 2009/2010, in occasione delle celebrazioni del ventennale della rivoluzione pacifica e della riunificazione. Analizzando le diverse strategie espositive e le interpretazioni storiche offerte, l’autore mette in evidenza come i musei e le esposizioni prese in esame vadano a comporre una narrazione articolata ed eterogenea degli eventi dell’89/90. A guidare l’analisi è la consapevolezza del ruolo che i musei giocano nella costruzione della memoria pubblica, aspetto che si cerca di approfondire proprio attraverso questa ricerca.The article aim is to analyze how Berlin museums display the peaceful revolution (the movement that caused the fall of the Berlin Wall and the end of GDR) and the following German reunification. The article focuses on four different historical-museums (Deutsches Historisches Museum, DDR-Museum, Mauer-Museum, Stasi-Museum). Furthermore it examines two temporary exhibitions («Wir sind das Volk!» and «1990: der Weg zur Einheit»), that took place in Berlin in 2009/2010. Looking at the different exhibition strategy and at the slightly different historical interpretations the museums offer, the author underlines how museums and exhibitions develop heterogeneous depiction of the 1989/90 events. The museums role in building the public memory is the key-concept of the article, and this inquiry wants to represent a way to analyze it
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
Introduction. Sayad and Migrants’ Descendants: A Renewed Gaze
No full textDespitebeing widely known and cited, Abdelmalek Sayad remains an author subject to divergent representations and interpretations and frequently reduced to a superficial use of some of his most famous concepts. Contrary to this simplifying reading, Sayad’s work crosses different fields of study and is characterised by a particular reflexive depth. Through migration, the author is able to analyse the dynamics of social and symbolic inclusion and exclusion, the construction and modification of social hierarchies at both local and international levels, and social change and conflict at large. In this sense, Sayad also offers important and little explored keys to understanding the experiencesand trajectories of the children of migration. This introductory contribution aims to draw attention to the way Sayad has studied migrants’descendants, highlighting how his approach is helpful for the renewal of this field of study. The contribution concludes with a presentation of the papers that are part of this Special Issue
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
Enhanced proliferative potential of hematopoietic cells expressing degradation-resistant c-Myb mutants
No full textThe c-myb gene encodes a transcription factor required for proliferation, differentiation, and survival of hematopoietic cells. Expression of c-Myb is often increased in hematological malignancies, but the underlying mechanisms are poorly understood. We show here that c-Myb has a longer half-life ( at least 2-fold) in BCR/ABL-expressing than in normal hematopoietic cells. Such enhanced stability was dependent on a phosphatidylinositol 3-kinase ( PI-3K)/Akt/GSKIII beta pathway( s) as indicated by the suppression of c-Myb expression upon treatment with PI-3K inhibitors or co-expression with dominant negative Akt or constitutively active GSKIII beta. Moreover, inhibition of GSKIII beta by LiCl enhanced cMyb expression in parental 32Dcl3 cells. Compared with wild type c-Myb, three mutants ( Delta( 358 - 452), Delta( 389 - 418), and L389A/L396A c-Myb) of the leucine zipper domain had increased stability. However, only expression of Delta( 358 - 452) was not affected by inhibition of the PI-3K/Akt pathway and was not enhanced by a proteasome inhibitor, suggesting that leucine zipper-dependent and - independent mechanisms are involved in the regulation of c-Myb stability. Indeed, Delta( 389 - 418) carrying four lysine-to-alanine substitutions ( Delta( 389 - 418) K387A/K428A/ K442A/K445A) was as stable as Delta( 358 - 452) c-Myb. Compared with full-length c-Myb, constitutive expression of Delta( 358 - 452) and Delta( 389 - 418) c-Myb in Lin-Sca-1(+) mouse marrow cells increased cytokine-dependent primary and secondary colony formation. In K562 cells, expression of Delta( 358 - 452), Delta( 389 - 418), and L389A/L396A c-Myb led to enhanced proliferation after STI571 treatment. Thus, enhanced stability of c-Myb by activation of PI-3K-dependent pathway( s) might contribute to the higher proliferative potential of BCR/ABL-expressing and, perhaps, other leukemic cells
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