Defective FoxP3+ Treg cell differentiation in the gut of Type 1 Diabetic patients

Environmental factors that act at the intestinal level such as diet, drugs, and microflora have a high impact on the pathogenesis of autoimmune Type 1 Diabetes (T1D), but it is still unclear how the gut milieu affects autoimmunity outside the intestine. Here we show that peripheral FoxP3+ Treg cell differentiation, a mechanism that takes place in the gut and is crucial to maintain systemic immune tolerance, is impaired in T1D patients. These results provide the first evidence that gut mucosa alteration could predispose to autoimmune T1D by affecting systemic immune regulation

THE ASMATIC CHILD IN THE FAMILY: A STUDY ON A REPRESENTATION

The aim of this work, based on the Theory of Social Representations, commected to the Psychoanalytical Theory, was to apprehend the social representation of the family concerning asthmatic children. Five families collaborated. The study matenal was obtained ffirough semistructured home interviews and amalysed ffirough the content amalysis method. Questions were raised regarding the knowledge about ffie disease and the impact that its diagnosis produces on the family relations. Other emerging points were analysed, such as ffie questions of heredity amd blame, negation and fear, feelmgs of ambivaience amd impotence ffiat pervade ffie moffier-child relationship, besides using the disease as a mask to hide a conflicting family structure.O presente trabalho, que teve por fio condutor a Teoria das Representações Sociais, articulada à Teoria Psicanalítica, buscou apreender a representação social da família acerca da criança asmática. Para tanto, contou-se com a colaboração de cinco famílias. O material de estudo foi obtido por meio de entrevistas domiciliares, semi-estruturadas, sendo utilizado o método de análise de conteúdo. Foram levantadas questões concernentes ao conhecimento da doença e ao impacto que o seu diagnóstico produz no ambito das relações familiares. Foram analisados alguns pontos emergentes, como a questão da hereditariedade e da culpabilidade, a negação e o medo, os sentimentos de ambivalência e impotência que permeiam as relações mães-filhos, além do uso da doença como máscara para ocultar uma possível estrutura familiar conflituosa

A sensitive detection method for MPLW515L or MPLW515K mutation in chronic myeloproliferative disorders with locked nucleic acid-modified probes and real-time polymerase chain reaction.

Acquired mutations in the juxtamembrane region of MPL (W515K or W515L), the receptor for thrombopoietin, have been described in patients with primary myelofibrosis or essential thrombocythemia, which are chronic myeloproliferative disorders. We have developed a real-time polymerase chain reaction assay for the detection and quantification of MPL mutations that is based on locked nucleic acid fluorescent probes. Mutational analysis was performed using DNA from granulocytes. Reference curves were obtained using cloned fragments of MPL containing either the wild-type or mutated sequence; the predicted sensitivity level was at least 0.1% mutant allele in a wild-type background. None of the 60 control subjects presented with a MPLW515L/K mutation. Of 217 patients with myelofibrosis, 19 (8.7%) harbored the MPLW515 mutation, 10 (52.6%) with the W515L allele. In one case, both the W515L and W515K alleles were detected by real-time polymerase chain reaction. By comparing results obtained with conventional sequencing, no erroneous genotype attribution using real-time polymerase chain reaction was found, whereas one patient considered wild type according to sequence analysis actually harbored a low W515L allele burden. This is a simple, sensitive, and cost-effective procedure for large-scale screening of the MPLW515L/K mutation in patients suspected to have a myeloproliferative disorder. It can also provide a quantitative estimate of mutant allele burden that might be useful for both patient prognosis and monitoring response to therapy

Single dose palonosetron and dexamethasone in preventing nausea and vomiting induced by high emetogenic ABVD regimen in Hodgkin Lymphoma patients

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The JAK2V617 mutation induces constitutive activation and agonist hypersensitivity in basophils of polycythemia vera.

BACKGROUND: The JAK2V617F mutation has been associated with constitutive and enhanced activation of neutrophils, while no information is available concerning other leukocyte subtypes. DESIGN AND METHODS: We evaluated correlations between JAK2V617F mutation and the count of circulating basophils, the number of activated CD63(+) basophils, their response in vitro to agonists as well as the effects of a JAK2 inhibitor. RESULTS: We found that basophil count was increased in patients with JAK2V617F -positive myeloproliferative neoplasms, particularly in those with polycythemia vera, and was correlated with the V617F burden. The burden of V617F allele was similar in neutrophils and basophils from patients with polycythemia vera, while total JAK2 mRNA content was remarkably greater in the basophils; however, the content of JAK2 protein in basophils was not increased. The number of CD63(+) basophils was higher in patients with polycythemia vera than in healthy subjects or patients with essential thrombocythemia or primary myelofibrosis and was correlated with the V617F burden. Ultrastructurally, basophils from patients with polycythemia vera contained an increased number of granules, most of which were empty suggesting cell degranulation in vivo. Ex vivo experiments revealed that basophils from patients with polycythemia vera were hypersensitive to the priming effect of interleukin-3 and to f-MLP-induced activation; pre-treatment with a JAK2 inhibitor reduced polycythemia vera basophil activation. Finally, we found that the number of circulating CD63(+) basophils was significantly greater in patients suffering from aquagenic pruritus, who also showed a higher V617F allele burden. CONCLUSIONS: These data indicate that the number of constitutively activated and hypersensitive circulating basophils is increased in polycythemia vera, underscoring a role of JAK2V617F in these cells’ abnormal function and, putatively, in the pathogenesis of pruritus

Inorganic nanoparticles as potential regulators of immune response in dendritic cells

Aim: The spontaneous adsorption of proteins on nanoparticles (NPs) in biological media is exploited to prepare complexes of NPs and proteins from cancer cells’ lysates for application in cancer immunotherapy. Materials &amp; methods: Gold (Au) and silica NPs were synthesized, incubated with cancer cells’ lysates and characterized. Dendritic cells (DCs) were challenged with protein-coated NPs, their maturation, viability and morphology were evaluated and lymphocytes T proliferation was determined. Results: Silica and Au NPs bound different pools of biomolecules from lysates, and are therefore promising selective carriers for antigens. When incubated with immature DCs, NPs were efficiently endocytosed without cytotoxicity. Finally, protein-coated AuNPs promoted DC maturation and DC-mediated lymphocyte proliferation, at variance with lysate alone and protein-coated silica NPs, that did not promote DCs maturation. Conclusion: These results demonstrate that the spontaneous formation of protein coronas on NPs represents a possible approach to fast, easy, cost-effective DCs stimulation. </jats:p

Risk of second cancers in chronic myeloproliferative neoplasms

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Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia

Key Points CALR mutations occur in half of JAK2 and MPL wt patients with ET and associate with some distinctive phenotypic traits. Patients with ET harboring CALR mutations are at significantly lower risk of thrombosis compared with JAK2- and MPL-mutated patients