Nucleophosmin (NPM, also known as B23, numatrin or NO38) is a ubiquitously expressed phosphoprotein belonging to the nucleoplasmin family of chaperones. NPM is mainly localized in the nucleolus where ...it exerts many of its functions, but a proportion of the protein continuously shuttles between the nucleus and the cytoplasm. A growing number of cellular proteins have been described as physical interactors of NPM, and consequently, NPM is thought to have a relevant role in diverse cellular functions, including ribosome biogenesis, centrosome duplication, DNA repair and response to stress. NPM has been implicated in the pathogenesis of several human malignancies and intriguingly, it has been described both as an activating oncogene and a tumor suppressor, depending on cell type and protein levels. In fact, increased NPM expression is associated with different types of solid tumors whereas an impairment of NPM function is characteristic of a subgroup of hematolologic malignancies. A large body of experimental evidence links the deregulation of specific NPM functions to cellular transformation, yet the molecular mechanisms through which NPM contributes to tumorigenesis remain elusive. In this review, we have summarized current knowledge concerning NPM functions, and attempted to interpret its multifaceted and sometimes apparently contradictory activities in the context of both normal cellular homeostasis and neoplastic transformation.
The t(12;21) translocation is the most common genetic rearrangement in childhood acute lymphoblastic leukemia (ALL) and gives rise to the TEL-AML1 fusion gene. Many studies on TEL-AML1 describe ...specific properties of the fusion protein, but a thorough understanding of its function is lacking. We exploited a pluripotent hematopoietic stem/progenitor cell line, EML1, and generated a cell line (EML-TA) stably expressing the TEL-AML1 fusion protein. EML1 cells differentiate to mature B-cells following treatment with IL7; whereas EML-TA display an impaired differentiation capacity and remain blocked at an early stage of maturation. Global gene expression profiling of EML1 cells at different stages of B-lymphoid differentiation, compared with EML-TA, identified the interferon (IFN)α/β pathway as a primary target of repression by TEL-AML1. In particular, expression and phosphorylation of interferon-regulatory factor 3 (IRF3) was decreased in EML-TA cells; strikingly, stable expression of IRF3 restored the capacity of EML-TA cells to differentiate into mature B-cells. Similarly, IRF3 silencing in EML1 cells by siRNA was sufficient to block B-lymphoid differentiation. The ability of TEL-AML1 to block B-cell differentiation and downregulate the IRF3-IFNα/β pathway was confirmed in mouse and human primary hematopoietic precursor cells (Lin- and CD34+ cells, respectively), and in a patient-derived cell line expressing TEL-AML1 (REH). Furthermore, treatment of TEL-AML1 expressing cells with IFNα/β was sufficient to overcome the maturation block. Our data provide new insight on TEL-AML1 function and may offer a new therapeutic opportunity for B-ALL.
Background
X-ray defecography or magnetic resonance defecography (MRD) and high-resolution anorectal manometry (HR-ARM) are essential for the diagnosis of pelvic floor disorders (PFD). However, there ...is only scarce information available about the accuracy of MRD in the functional assessment of the pelvic floor. The aim of this study was to examine the accuracy of MRD in the diagnosis of pelvic floor disorders by examining the intra-test agreement with x-ray defecography and HR-ARM in patients with PFD.
Methods
The study population included adults referred to our institution in January 2018–February 2020 for MRD as part of their evaluation of PFD. The MRD results were compared with X-ray defecography and HR-ARM.
Results
Forty-two patients were included in the study (36 female, 86%, mean age 56.9 years ± 15.8, range 19–86 years). When compared to X-ray defecography, the sensitivity of MRD for the evaluation of normal rest and squeeze pressures was high (0.83 and 1, respectively). High sensitivity rates were observed for the detection of pelvic organ prolapse and pelvic floor dyssynergia (0.84–1). When compared to HR-ARM, the sensitivity of MRD for the evaluation of squeeze and dyssynergia was very good (0.92and 1, respectively), and good for the evaluation of rest pressure (0.6). Inter-test agreement was high (0.5, 0.6, 0.6 for rest, squeeze and dyssynergia). Excellent rates of sensitivity as well as almost perfect intra-test agreement was found between abnormal balloon expulsion test and the diagnosis of dyssynergia and pelvic organ prolapse on MRD (1, 0.81).
Conclusions
This study demonstrated substantial diagnostic agreement between HR-ARM and MRD in the diagnosis of pathological etiologies for functional pelvic floor disorders, mainly obstructed defecation syndrome.
Aim
The aim was to evaluate the influence of a half day, hands‐on, workshop on the detection and repair of obstetric anal sphincter injuries (OASIs).
Method
Starting in February 2011, hands‐on ...workshops for the diagnosis and repair of OASIs were delivered by trained urogynaecologists in departments of tertiary medical centres in Israel. The structure of the hands‐on workshop resembles the workshop organized at the International Urogynecological Association annual conferences. Participants included medical staff, midwives and surgical residents from each medical centre. We collected data regarding the rate of OASIs, 1 year before and 1 year following the workshop, in 11 medical centres. The study population was composed of parturients with the following inclusion criteria: singleton pregnancy, vertex presentation and vaginal delivery. Pre‐viable preterm gestations (< 24 weeks), birth weight < 500 g, stillborn, and those with major congenital anomalies, multifoetal pregnancies, breech presentations and caesarean deliveries were excluded from the analysis.
Results
In the reviewed centres, 70 663 (49.3%) women delivered prior to the workshop (pre‐workshop group) and 72 616 (50.7%) women delivered following the workshop (post‐workshop group). Third‐ or fourth‐degree perineal tears occurred in 248 women (0.35%) before the workshop, and in 328 (0.45%) following the workshop, a significant increase of 28.7% (P = 0.002). The increase in diagnosis was significant also in women with third‐degree tears alone, 226 women (0.32%) before the workshop and 298 (0.41%) following the workshop, an increase of 28.3% (P = 0.005).
Conclusion
The detection rate of OASIs has significantly increased following the hands‐on workshop. The implementation of such programmes is crucial for increasing awareness and detection rates of OASI following vaginal deliveries.
Complications musculaires de l’hémophilie Alcalay, M.
Archives de pédiatrie : organe officiel de la Société française de pédiatrie,
2/2009, Letnik:
16, Številka:
2
Journal Article
Recenzirano
L’hémophilie s’exprime principalement par des hémorragies dans les muscles et les articulations. Le traitement est actuellement purement palliatif, basé sur les injections de facteur ...antihémophilique. Les hématomes musculaires sont les manifestations les plus précoces, généralement post-traumatiques. S’ils ne mettent que très rarement en jeu le pronostic vital, ils ont volontiers un retentissement fonctionnel important et parfois durable, en l’absence d’un traitement précoce et énergique. Celui-ci doit associer, aux injections du facteur antihémophilique manquant, la kinésithérapie faisant contracter le muscle atteint et, pour les membres inférieurs, la mise en décharge jusqu’à disparition du flessum ou retour au
statu quo ante.
Haemophilia causes principally bleedings in muscles and joints. Therapy is purely palliative, based on injections of antihemophilic factor. Muscular hematomas represent the most precocious complication and generally happen after a trauma. Though they scarcely threaten the life of the patients, they often may generate an important functional disability if not treated quickly, and vigorously. Treatment should associate injections of the defective clotting factor to physiotherapy and contractions of the involved muscle. When hematomas involve lower limbs, standing up and walking should not be authorized before the end of the flessum or recovering of the statu quo ante.
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