Cytokine Gene Polymorphisms in Italian Preterm Infants: Association Between Interleukin-10 –1082 G/A Polymorphism and Respiratory Distress Syndrome

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Proteomic approach to hereditary stomatocytosis

La stomatocitosi ereditaria (HSt) rappresenta un gruppo di anemie emolitiche molto rare con ereditariet\ue0 per lo pi\uf9 dominante, dovuta a perdita di ioni monovalenti (Na+ e K+) attraverso la membrana. Questa forma di anemia emolitica \ue8 clinicamente eterogenea e comprende la stomatocitosi ereditaria con emazie iperidratate (Overhydratated Hereditary Stomatocytosis), la stomatocitosi ereditaria con emazie disidratare (Dehydrated Hereditary Stomatocytosis), la pseudoipercaliemia familiare (Familial Pseudohyperkalaemia FP) e la crioidrocitosi ereditaria (Hereditary Cryohydrocytosis CHC). Lo scopo del nostro progetto \ue8 quello di valutare differenze nell\u2019espressione delle proteine di membrana eritrocitaria di 5 pazienti affetti da DHSt (appartenenti a 2 famiglie diverse) provenienti dal sud Italia quando confrontati con 10 soggetti sani tramite 2D-DIGE. Attraverso questo approccio abbiamo ottenuto 1000 spots ed in seguito ad un\u2019accurata analisi statistica nella quale abbiamo isolato tutti gli spots con un p-value inferiore a 0.075 (Student\u2019s paired t test) e un AV.RATIO compreso tra +1,35 e -1.35, abbiamo focalizzato la nostra attenzione su 65 spots ritenuti significativi (36 risultano maggiormente espressi nei pazienti mentre 29 risultano meno espressi). Di questi spots \ue8 stato possibile isolare su gel bidimensionale solo 51 spots dei quali 33 risultano maggiormente espressi nei pazienti e 18 meno espressi. L'analisi dei peptidi estratti da ciascuno spot \ue8 stata effettuata mediante analisi LC/MS/MS che \ue8 riuscita ad identificare 24 proteine differenzialmente espresse ma solo le seguenti proteine sono risultati interessanti ai fini del nostro studio: Peptide C-Band3, Flotillina 1 and 2, Stomatina, perossiredoxina 1 e 2, Catalase, Annexina A1, Citovillina 2, RAP2B e RAP1A che risultano pi\uf9 espresse nei pazienti; Gliceraldeide-3-fosfatodeidroganasi, Aldolase A, proteina G subunit\ue0 beta che risultano meno espresse. Questi risultati, ed in particolare l\u2019aumento delle perossiredoxine e della catalase A1 suggeriscono che nei pazienti affetti da DHSt vi \ue8 un maggiore stress ossidativo, incentivato anche dalla diminuzione di alcuni enzimi della glicolisi importanti per la produzione di NADH e quindi di potenziali riducenti. Un altro dato importante \ue8 l\u2019aumento della proteolisi della porzione N-terminale della Banda3 e l\u2019aumento di proteine coinvolte nella formazione di zattere lipidiche (Flotillina 1 and 2, Stomatina e Citovillina 2), nell\u2019adesione cellulare (Annexina A1) e nella vescicolazione (RAP1A e RAP2B). Attualmente sono in corso studi per valutare se vi \ue8 un incremento della fosforilazione della banda 3 e un aumento della vescicolazione.Hereditary stomatocytosis (HSt) describes a wide spectrum of autosomal dominantly inherited disorders in which the basal red cell membrane cation permeability is increased. The cation leak results in the regulations of cellular volume, which can lead to morphological abnormality. Clinically HSt is very heterogeneous and we can identify four principal form: Overhydrated Hereditary Stomatocytosis (OHSt), Dehydrated Hereditary Stomatocytosis (DHSt), Familial Pseudohyperkalemia (FP) and Hereditary Cryohydrocytosis (CHC). Since, the DHSt pathogenesis is linked to a defect or a decreased in a membrane protein, we studied the red blood cells membrane proteome by 2D-DIGE. In fact we selected 2 DHSt family, for a total of 5 patients to isolate the membrane proteins and compare they with membrane proteins of 10 healthy controls. Approximately, 1000 protein spots were detected, the protein spots were then filtered for the statistically relevant trend of regulation: p-value 0.075 (Student\u2019s paired t test) and +1,35 65AV.RATIO 64 -1.35. We compared all the spots derived from healthy controls versus all the spots derived from patients and found 65 spots of interest, of these 36 spots were upregulated in the DHSt patients and 29 downregulated. To identify the differentially expressed proteins we performed two preparative gel, but unfortunately the reproducibility of this gel was not 100% and of 65 spots of interest we identified and excised only 51 spots (33 upregulated in the DHSt patients and 18 downregulated). The analysis of peptides extracted from each spot was performed by analysis LC/MS/MS. Mass spectrometric analysis identified 24 proteins. We select 14 protein that could be involved in DHSt, and grouped them on based of their expression: Peptide C-Band3, Flotillin 1 and 2, Stomatin, Peroxiredoxin 1 and 2, Catalase, Annexin A1, Cytovillin 2, RAP2B e RAP1A that resulted up-regulated and G3PD, Aldo A, G protein beta subunit that resulted down-regulated. These data, in particular the discovery of high levels of Peroxiredoxin 1 and 2 and Catalase A1, suggest an increased oxidative stress in patients whit DHSt, also promoted by the decrease of some enzymes of glycolysis are important for the production of NADH and thus reducing potential. Another important data is the increase of Peptice c-Band3 and some proteins involved in the formation of lipid raft (Flotillin 1 and 2, Stomatin and Cytovillin 2) and in the vesciculation (RAP1A and RAP2B). Studies are currently underway to assess phosphorylation of band 3 in DHST patients and red blood cell vesciculation

A novel erythroid anion exchange variant (Gly796Arg) of hereditary stomatocytosis associated with dyserythropoiesis

Stomatocytoses are a group of inherited autosomal dominant hemolytic anemias and include overhydrated hereditary stomatocytosis, dehydrated hereditary stomatocytosis, hereditary cryohydrocytosis and familial pseudohyperkalemia. This article describes a novel variant of hereditary stomatocytosis due to a de novo band 3 mutation associated with signs of dyserythropoiesis. See related perspective article on page 1039

β-spectrinBari: a truncated β-chain responsible for dominant hereditary spherocytosis

This report describes a β-spectrin variant, named β-spectrinBari, characterized by a truncated chain and associated with hereditary spherocytosis

Bortezomib-thalidomide-dexamethasone is superior to thalidomide- dexamethasone as consolidation therapy after autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma

In a randomized, phase 3 study, superior complete/near-complete response (CR/nCR) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone (VTD) versus thalidomide-dexamethasone (TD) as induction therapy before, and consolidation after, double autologous stem cell transplantation for newly diagnosed myeloma patients (intention-to-treat analysis; VTD, n = 236; TD, n = 238). This per-protocol analysis (VTD, n = 160; TD, n = 161) specifically assessed the efficacy and safety of consolidation with VTD or TD. Before starting consolidation, CR/nCR rates were not significantly different in the VTD (63.1%) and TD arms (54.7%). After consolidation, CR (60.6% vs 46.6%) and CR/nCR (73.1% vs 60.9%) rates were significantly higher for VTD-treated versus TD-treated patients. VTD consolidation significantly increased CR and CR/nCR rates, but TD did not (McNemar test). With a median follow-up of 30.4 months from start of consolidation, 3-year progression-free survival was significantly longer for the VTD group (60% vs 48% for TD). Grade 2 or 3 peripheral neuropathy (8.1% vs 2.4%) was more frequent with VTD (grade 3, 0.6%) versus TD consolidation. The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation. VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients randomly assigned to the VTD arm of the study. The study is registered at www.clinicaltrials.gov as #NCT01134484. \ua9 2012 by The American Society of Hematology