Clonal Chromosome Anomalies Affecting Fli1 Mimic Inherited Thrombocytopenia Of The Paris-Trousseau Type

Introduction: The thrombocytopenia of the Paris-Trousseau (TCPT) type is a contiguous gene syndrome characterized by mild bleeding tendency, variable thrombocytopenia (THC), abnormal giant alpha-granules in platelets and dysmegakaryopoiesis: it derives from a constitutional deletion of chromosome 11 leading to the loss of FLI1, a transcription factor involved in megakaryocyte differentiation and maturation. Case report: A women with an acquired, isolated THC developing over 10 yr showed morphological features typical of TCPT in platelets and bone marrow (BM). Twenty years after the onset of THC, the other hematological parameters are still normal and the patient is well. Results: Clonal hemopoiesis was shown and chromosome analyses performed on BM revealed a clone with 45 chromosomes and a complex unbalanced translocation involving chromosomes 2, 3, and 11. The anomaly was present in the majority of bone marrow cells but only in a few peripheral blood elements. A microarray-based comparative genomic hybridization defined the deleted region of chromosome 11 including the FLI1 locus that was missing. Conclusion: Although our patient presented with nearly all the characteristics of TCPT, her illness was acquired instead of being inherited and the most appropriate diagnosis is that of the unilineage dysplasia 'refractory THC.' This observation suggests that appropriate cytogenetic investigations should be always considered in patients with acquired THC of unknown origin

Alteration of Liver Enzymes Is a Feature of the Myh9-Related Disease Syndrome

BACKGROUND: MYH9-related disease (MYH9-RD) is a rare autosomal dominant genetic syndrome characterized by congenital thrombocytopenia associated with the risk of developing progressive nephropathy, sensorineural deafness, and presenile cataract. During the collection of a large case-series of patients with MYH9-RD we noticed several cases with unexplained elevation of liver enzymes. Our aim was to evaluate if the alteration of liver tests is a feature of the MYH9-RD and to define its clinical significance. METHODS AND FINDINGS: Data concerning liver tests, prospectively recorded in the Italian Registry for MYH9-RD, were collected and compared with those of three control populations: patients with autoimmune thrombocytopenia, patients with inherited thrombocytopenias other than MYH9-RD, and the participants to a large epidemiologic survey in an Italian geographic isolate. Thirty-eight of 75 evaluable MYH9-RD patients (50.7%) showed an elevation of ALT and/or AST, and 17 of 63 (27.0%) an increase of GGT. The increases ranged from 1.9 ± 0.7 to 2.7 ± 1.6 fold the upper normal limit. The prevalence of liver test alterations was significantly higher in MYH9-RD patients than in each of the control populations, with odds ratios ranging from 8.2 (95% CIs 2.2-44.8) to 24.7 (14.8-40.8). Clinical follow-up and more detailed liver studies of a subset of patients, including ultrasound liver scan, liver elastography and liver biopsy in one case, did not show any significant structural damage or evolution towards liver insufficiency. CONCLUSIONS: Elevation of liver enzymes is a frequent and previously unrecognized feature of the MYH9-RD syndrome; however, this defect does not appear to have poor prognostic value

EP-1349: Long term results of a phase I-II study of moderate hypofractionated IGRT in prostate cancer

Pregnant women diagnosed with gestational diabetes mellitus subjected to diet (GDMd) that do not reach normal glycaemia are passed to insulin therapy (GDMi). GDMd associates with increased human cationic amino acid transporter 1 (hCAT-1)-mediated transport of L-arginine and nitric oxide synthase (NOS) activity in foetoplacental vasculature, a phenomenon reversed by exogenous insulin. Whether insulin therapy results in reversal of the GDMd effect on the foetoplacental vasculature is unknown. We assayed whether insulin therapy normalizes GDMd-associated foetoplacental endothelial dysfunction. Primary cultures of human umbilical vein endothelial cells (HUVECs) from GDMi pregnancies were used to assay L-arginine transport kinetics, NOS activity, p44/42mapk and protein kinase B/Akt activation, and umbilical vein rings reactivity. HUVECs from GDMi or GDMd show increased hCAT-1 expression and maximal transport capacity, NOS activity, and eNOS, and p44/42mapk, but not Akt activator phosphorylation. Dilation in response to insulin or calcitonin-gene related peptide was impaired in umbilical vein rings from GDMi and GDMd pregnancies. Incubation of HUVECs in vitro with insulin (1 nmol/L) restored hCAT-1 and eNOS expression and activity, and eNOS and p44/42mapk activator phosphorylation. Thus, maternal insulin therapy does not seem to reverse GDMd-associated alterations in human foetoplacental vasculature.Fondo Nacional de Desarrollo Científico y Tecnológico Chileno 1150377 , 1150344 , 11150083Servicio de Salud de Medicina Oriente de Chile 1938–2016Marie Curie International Research 295185 - EULAMDIM

An Analysis of Volatile components of the Liverworts Dumortiera hirsuta subsp. hirsuta and Dumortiera hirsuta subsp. nepalensis (Dumortieraceae) from Panama and Taxonomic Observations on the Species

We report for the first time the chemical composition of volatile components (VOCs) of two subspecies, D. hirsuta subsp. hirsuta and D. hirsuta subsp. nepalensis, of the liverwort Dumortiera hirsuta from Panama by using headspace-solid phase microextraction-gas chromatography-mass spectrometry in order to assess distinguishing markers between the two species. Forty VOCs were identified in total for both subspecies. Of these, 34 are reported for the first time in D. hirsuta. Furthermore, both subspecies showed clear differences in the type and amount of VOCs. The major compounds in D. hirsuta subsp. hirsuta were α-gurjunene, β-selinene, α-guaiene, α-humulene and β-caryophyllene; while in D. hirsuta subsp. nepalensis were ledene, α-gurjunene, β-caryophyllene and α-guaiene, respectively. Two oxygenated sesquiterpenes, globulol and nerolidol, could be considered as possible distinguishing chemical markers between these two subspecies. We conclude that both morphotypes of D. hirsuta are chemically different

Chemical profiling of volatile components of the gametophyte and sporophyte stages of the hornwort leiosporoceros dussii (Leiosporocerotaceae) from Panama by HSSPME-GC-MS

We report for the first time the chemical profiling of volatile organic compounds (VOCs) of gametophyte and sporophyte life stages of Leiosporoceros dussii, from Panama by using headspace-solid phase microextraction-gas chromatography-mass spectrometry in order to assess distinguishing chemical markers between the male and female gametophytes, and sporophytes of this hornwort. A total of 27 VOCs were identified in L. dussii. Furthermore, the gametophyte and sporophyte showed clear differences in the type and amount of VOCs. The main constituents of L. dussii female thalli were menthacamphor (17.8%), hexanol (12.3%), and menthyl acetate (12.3%), while the major compounds of the male thalli were hexanol (25.3%), β-ionone (21.1%), benzeneacetaldehyde (17.6%), and β-cyclocitral (14.0%). The main VOCs of the sporophytes were hexanal (19.3%), β-cyclocitral (17.6%), 2-nonenal (15.8%), hexanol (12.5%), and β-ionone (10.2%). Unique compounds found in the female thalli were 3-pentanone, 3-octenol, nonanol, estragole, and menthyl acetate, and in the male thalli were methyl heptenone, nonanal, neoisomenthol, and bornyl acetate. Isomenthol, thymol, isomenthol acetate, and β-methylnaphthalene were only found in the sporophyte. The characteristic VOCs identified in L. dussii suggest a difference between the chemical constituents of L. dussii and other hornworts species. The presence of simple VOCs when compared with compounds previously characterized in another hornwort genera may support the distinct genetic nature of this species

Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics

Item does not contain fulltextBACKGROUND: Mutations in complement factor H (CFH), factor I (CFI), factor B (CFB), thrombomodulin (THBD), C3 and membrane cofactor protein (MCP), and autoantibodies against factor H (alphaFH) with or without a homozygous deletion in CFH-related protein 1 and 3 (CFHR1/3) predispose development of atypical hemolytic uremic syndrome (aHUS). METHODS: Different mutations in genes encoding complement proteins in 45 pediatric aHUS patients were retrospectively linked with clinical features, treatment, and outcome. RESULTS: In 47% of the study participants, potentially pathogenic genetic anomalies were found (5xCFH, 4xMCP, and 4xC3, 3xCFI, 2xCFB, 6xalphaFH, of which five had CFHR1/3); four patients carried combined genetic defects or a mutation, together with alphaFH. In the majority (87%), disease onset was preceeded by a triggering event; in 25% of cases diarrhea was the presenting symptom. More than 50% had normal serum C3 levels at presentation. Relapses were seen in half of the patients, and there was renal graft failure in all except one case following transplant. CONCLUSIONS: Performing adequate DNA analysis is essential for treatment and positive outcome in children with aHUS. The impact of intensive initial therapy and renal replacement therapy, as well as the high risk of recurrence of aHUS in renal transplant, warrants further understanding of the pathogenesis, which will lead to better treatment options.01 augustus 201

Performance of ALICE AD modules in the CERN PS test beam

Two modules of the AD detector have been studied with the test beam at the T10 facility at CERN. The AD detector is made of scintillator pads read out by wave-length shifters (WLS) coupled to clean fibres that carry the produced light to photo-multiplier tubes (PMTs). In ALICE the AD is used to trigger and study the physics of diffractive and ultra-peripheral collisions as well as for a variety of technical tasks like beam-gas background monitoring or as a luminometer. The position dependence of the modules' efficiency has been measured and the effect of hits on the WLS or PMTs has been evaluated. The charge deposited by pions and protons has been measured at different momenta of the test beam. The time resolution is determined as a function of the deposited charge. These results are important ingredients to better understand the AD detector, to benchmark the corresponding simulations, and very importantly they served as a baseline for a similar device, the Forward Diffractive Detector (FDD), being currently built and that will be in operation in ALICE during the LHC Runs 3 and 4.Peer reviewe

Platelets of patients with chronic kidney disease demonstrate deficient platelet reactivity in vitro

<p>Abstract</p> <p>Background</p> <p>In patients with chronic kidney disease studies focusing on platelet function and properties often are non-conclusive whereas only few studies use functional platelet tests. In this study we evaluated a recently developed functional flow cytometry based assay for the analysis of platelet function in chronic kidney disease.</p> <p>Methods</p> <p>Platelet reactivity was measured using flow cytometric analysis. Platelets in whole blood were triggered with different concentrations of agonists (TRAP, ADP, CRP). Platelet activation was quantified with staining for P-selectin, measuring the mean fluorescence intensity. Area under the curve and the concentration of half-maximal response were determined.</p> <p>Results</p> <p>We studied 23 patients with chronic kidney disease (9 patients with cardiorenal failure and 14 patients with end stage renal disease) and 19 healthy controls. Expression of P-selectin on the platelet surface measured as mean fluorescence intensity was significantly less in chronic kidney disease patients compared to controls after maximal stimulation with TRAP (9.7 (7.9-10.8) vs. 11.4 (9.2-12.2), P = 0.032), ADP (1.6 (1.2-2.1) vs. 2.6 (1.9-3.5), P = 0.002) and CRP (9.2 (8.5-10.8) vs. 11.5 (9.5-12.9), P = 0.004). Also the area under the curve was significantly different. There was no significant difference in half-maximal response between both groups.</p> <p>Conclusion</p> <p>In this study we found that patients with chronic kidney disease show reduced platelet reactivity in response of ADP, TRAP and CRP compared to controls. These results contribute to our understanding of the aberrant platelet function observed in patients with chronic kidney disease and emphasize the significance of using functional whole blood platelet activation assays.</p