241 research outputs found
Thymic stromal alterations and genetic disorders of immune system
No full text© 2015 Pignata, D’Assante and Sousa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
La cura dei folli nel Progetto di Stabilimento per alienati proposto da Biagio Gioacchino Miraglia
No full textThe essay is a study of the evolution of the mental institutions legislation after the Italy Unification. The author highlights the problems that Italy had to face regarding the adjustment of institutional arrangements in the healthcare, which urgently needed legislation to make uniform the mental institutions management and organization. Alienists were pressing for a primary and active role in the debate on the mental institutions legislation. Among these was certainly Biagio Gioacchino Miraglia who proposed in South Italy an important project
Beckwith-Wiedemann syndrome and twinning: case report and brief review of literature
No full textAbstract Background Beckwith-Wiedemann syndrome (BWS, OMIM #130,650) is a pediatric overgrowth disorder involving a predisposition to tumor development. Although the clinical management of affected patients is well established, it is less clear how to handle with the cases of siblings of affected patients, since the prevalence of the condition in twins (1:1000) is ten times higher than in singletones (1:10000). Case presentation We report the case of a premature twin patient who during her follow-up develops a clinical phenotype compatible with BWS, genetically confirmed in blood. However, the methylation alteration characteristic of the condition was also found in the almost phenotypically normal sibling, making it challening her management. Conclusion Through our case report we highlight how the diagnosis of BWS can be made without any prenatal suspicion and we propose a review of the literature on how to manage siblings of affected patients in twinning situation
Analisi dell’ alterazione dei meccanismi di tolleranza periferica associata ad alta variabilità fenotipica.
No full textEpigenetic Alterations in Inborn Errors of Immunity
No full textThe epigenome bridges environmental factors and the genome, fine-tuning the process of gene transcription. Physiological programs, including the development, maturation and maintenance of cellular identity and function, are modulated by intricate epigenetic changes that encompass DNA methylation, chromatin remodeling, histone modifications and RNA processing. The collection of genome-wide DNA methylation data has recently shed new light into the potential contribution of epigenetics in pathophysiology, particularly in the field of immune system and host defense. The study of patients carrying mutations in genes encoding for molecules involved in the epigenetic machinery has allowed the identification and better characterization of environment-genome interactions via epigenetics as well as paving the way for the development of new potential therapeutic options. In this review, we summarize current knowledge of the role of epigenetic modifications in the immune system and outline their potential involvement in the pathogenesis of inborn errors of immunity
Understanding the Variability of 22q11.2 Deletion Syndrome: The Role of Epigenetic Factors
No full textInitially described as a triad of immunodeficiency, congenital heart defects and hypoparathyroidism, 22q11.2 deletion syndrome (22q11.2DS) now encompasses a great amount of abnormalities involving different systems. Approximately 85% of patients share a 3 Mb 22q11.2 region of hemizygous deletion in which 46 protein-coding genes are included. However, the hemizygosity of the genes of this region cannot fully explain the clinical phenotype and the phenotypic variability observed among patients. Additional mutations in genes located outside the deleted region, leading to “dual diagnosis”, have been described in 1% of patients. In some cases, the hemizygosity of the 22q11.2 region unmasks autosomal recessive conditions due to additional mutations on the non-deleted allele. Some of the deleted genes play a crucial role in gene expression regulation pathways, involving the whole genome. Typical miRNA expression patterns have been identified in 22q11.2DS, due to an alteration in miRNA biogenesis, affecting the expression of several target genes. Also, a methylation epi-signature in CpG islands differentiating patients from controls has been defined. Herein, we summarize the evidence on the genetic and epigenetic mechanisms implicated in the pathogenesis of the clinical manifestations of 22q11.2 DS. The review of the literature confirms the hypothesis that the 22q11.2DS phenotype results from a network of interactions between deleted protein-coding genes and altered epigenetic regulation
Therapeutic Challenges for Cisplatin-Resistant Ovarian Germ Cell Tumors
No full textThe majority of patients with advanced ovarian germ cell cancer are treated by cisplatin-based chemotherapy. Despite adequate first-line treatment, nearly one third of patients relapse and almost half develop cisplatin-resistant disease, which is often fatal. The treatment of cisplatin-resistant disease is challenging and prognosis remains poor. There are limited data on the efficacy of specific chemotherapeutic regimens, high-dose chemotherapy with autologous progenitor cell support and targeted therapies. The inclusion of patients in clinical trials is strongly recommended, especially in clinical trials on the most frequent male germ cell tumors, to offer wider therapeutic opportunities. Here, we provide an overview of current and potential new treatment options including combination chemotherapy, high-dose chemotherapy and molecular targeted therapies, for patients with cisplatin-resistant ovarian germ cell tumors
Effect of chemiotherapy with 5-fluoruracil on intestinal permeability and absorption of patients with advanced colorectal cancer
No full textLa mutazione del gene FOXN1 associata al fenotipo NUDE/SCID previene completamente il differenziamento dei linfociti CD4, ma non dei CD8.
No full textThe cellular amount of the common Î3-chain influences spontaneous or induced cell proliferation
No full textMutations of the IL2RG encoding the common Î3-chain (Î3c) lead to the X-linked SCID disease. Gene correction through ex vivo retroviral transduction restored the immunological impairment in the most of treated patients, although lymphoproliferative events occurred in five of them. Even though in two cases it was clearly documented an insertional mutagenesis in LMO2, it is conceivable that Î3c could have a role per se in malignant lymphoproliferation. The Î3c is a shared cytokine receptor subunit, involved also in growth hormone (GH) receptor signaling. Through short interfering RNA or using X-linked SCID B lympho-blastoid cell lines lacking Î3c, we demonstrate that self-sufficient growth was strongly dependent on Î3c expression. Furthermore, a correlation between Î3c amount and the extent of constitutive activation of JAK3 was found. The reduction of Î3c protein expression also reduced GH-induced proliferation and STAT5 nuclear translocation in B lymphoblastoid cell lines. Hence, our data demonstrate that Î3c plays a remarkable role in either spontaneous or GH-induced cell cycle progression depending on the amount of protein expression, suggesting a potential role as enhancing cofactor in lymphoproliferation. Copyright © 2009 by The American Association of Immunologists, Inc
- …
