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Roubalova K.,Vidia Ltd | Strunecky O.,National Institute of Public Health | Vitek A.,Institute of Haematology and Blood Transfusion | Zufanova S.,National Institute of Public Health | Prochazka B.,National Institute of Public Health
Transplant Infectious Disease | Year: 2011

Genetic variation of cytomegalovirus (CMV) strains can correlate with their pathogenicity for immunocompromised patients. Glycoprotein O (gO), together with glycoprotein L and glycoprotein H, mediate the fusion of the viral envelope with the cell membrane and promotes virus penetration, envelopment, and release. The variability of gO might play a role in CMV cell tropism. The goal was a retrospective analysis of gO variability in a cohort of hematopoietic stem cell transplant (HSCT) recipients to determine the distribution of gO genotypes and to investigate their impact on clinical outcome and manifestation of CMV infection. Methods. In archived blood samples from 51 adult allogeneic HSCT recipients with active CMV infection, gO was analyzed by sequencing the N-terminal domain of the UL74 gene using the dye deoxy termination method. Results. The gO1 and gO2 clades were most common (39% and 20%, respectively, and gO3 was associated with higher risk of symptomatic infection (P=0.026 in multivariant analysis). Despite being associated with higher antigenemia levels (P=0.02), gO4 had the best survival and lower rate of CMV recurrence. No significant differences were found in clinical manifestation and outcome of CMV disease between patients with various gO clades. Because CMV strains sharing an identical gO sequence differed in glycoprotein B genotypes, sequencing the N-terminal part of the gO gene does not seem to be optimal for the identification of strains. Conclusions. gO genotyping may contribute to the biological characterization of CMV strains in HSCT recipients. © 2011 John Wiley & Sons A/S. Source


Smetana K.,Institute of Haematology and Blood Transfusion | Zapotocky M.,Charles University
Folia Biologica | Year: 2010

The present study was undertaken to provide more information on nucleolar changes induced by a histone deacetylase inhibitor such as valproic acid in leukaemic myeloblasts at the single-cell level. For this study, RNA in nucleoli was visualized by a simple but sensitive cytochemical procedure in unfixed cytospins of short-term bone marrow cultures from patients suffering from acute myeloid leukaemia. Valproic acid in leukaemic myeloblasts markedly reduced the nucleolar size and also produced significant transformation of "active" to "resting" and "inactive" nucleoli that reflected the alteration of the nucleolar transcription in sensitive myeloblasts. On this occasion it should be added that valproic acid significantly increased the incidence of altered myeloblasts that changed to apoptotic cells or apoptotic bodies and cell ghosts. In contrast to the above-mentioned decreased nucleolar size, the nucleolar RNA concentration, expressed by computer-assisted RNA image densitometry in valproic acid-treated myeloblasts, was not significantly changed. The results of the present study clearly indicated that the nucleolar size and transformation of "active" to "sleeping" or "inactive" nucleoli are convenient markers of the sensitivity and alteration of leukaemic myeloblasts produced by a histone deacetylase inhibitor, valproic acid, at the single-cell level. Source


Juchimiuk M.,Polish Academy of Sciences | Pasikowska M.,Polish Academy of Sciences | Zatorska E.,Polish Academy of Sciences | Laudy A.E.,Medical University of Warsaw | And 2 more authors.
Yeast | Year: 2010

Two temperature-sensitive Saccharomyces cerevisiae mutants, sec59-1 and dpm1-6, impaired, respectively, in dolichol kinase (Sec59p) and dolichyl phosphate mannose (DolPMan) synthase (Dpm1p), have an aberrant cell wall structure and composition. We tested their sensitivity to four classes of antifungal drugs used in clinical practice: 5-fluorocytosine, amphotericin B, caspofungin and itraconasole. The strains were resistant to itraconazole and sensitive to the other drugs used. The minimal inhibitory concentration (MIC) of caspofungin and amphotericin B was two-fold lower for sec59-1 and dpm1-6 than for the respective wild-type strains. The sensitivity of both mutants could be brought back to the wild-type level by a multicopy suppressor of the thermosensitive phenotype, the RER2 gene, encoding cis-prenyltransferase involved in dolichol biosynthesis. Biochemical analysis revealed slight changes of the cell wall composition, different in the mutants as compared to the wild-type in response to the drugs. Our data strongly support a relationship between dolichol phosphate level, protein glycosylation and antifungal sensitivity. Copyright © 2010 John Wiley & Sons, Ltd. Source


Mansouri Taleghani M.,University of Bern | von Krogh A.-S.,Norwegian University of Science and Technology | Fujimura Y.,Nara Medical University | George J.N.,The University of Oklahoma Health Sciences Center | And 6 more authors.
Hamostaseologie | Year: 2013

Hereditary thrombotic thrombocytopenic purpura (TTP), also known as Upshaw-Schulman syndrome, is a rare recessively inherited disease. Underlying is a severe constitutional deficiency of the von Willebrand factor-cleaving protease, ADAMTS13, due to compound heterozygous or homozygous mutations in the ADAMTS13 gene. The clinical picture is variable and more and more patients with an adult-onset are diagnosed. In the majority of countries the only available treatment is plasma, which when administered regularly can efficiently prevent acute disease bouts. The decision to initiate regular prophylaxis is often not easy, as evidence based guidelines and long term outcome data are lacking. Through the hereditary TTP registry (www.ttpregistry.net, ClinicalTrials.gov identifier: NCT01257269), which was initiated in 2006 and is open to all patients diagnosed with Upshaw-Schulman syndrome and their family members, we aim to gain further information and insights into this rare disease, which eventually will help to improve clinical management of affected patients. © Schattauer 2013. Source


Mojzikova R.,Palacky University | Koralkova P.,Palacky University | Holub D.,Palacky University | Zidova Z.,Palacky University | And 9 more authors.
British Journal of Haematology | Year: 2014

Pyruvate kinase (PK) deficiency is an iron-loading anaemia characterized by chronic haemolysis, ineffective erythropoiesis and a requirement for blood transfusion in most cases. We studied 11 patients from 10 unrelated families and found nine different disease-causing PKLR mutations. Two of these mutations - the point mutation c.878A>T (p.Asp293Val) and the frameshift deletion c.1553delG (p.(Arg518Leufs*12)) - have not been previously described in the literature. This frameshift deletion was associated with an unusually severe phenotype involving neonatal hyperferritinaemia that is not typical of PK deficiency. No disease-causing mutations in genes associated with haemochromatosis could be found. Inappropriately low levels of hepcidin with respect to iron loading were detected in all PK-deficient patients with increased ferritin, confirming the predominant effect of accelerated erythropoiesis on hepcidin production. Although the levels of a putative hepcidin suppressor, growth differentiation factor-15, were increased in PK-deficient patients, no negative correlation with hepcidin was found. This result indicates the existence of another as-yet unidentified erythroid regulator of hepcidin synthesis in PK deficiency. © 2014 John Wiley & Sons Ltd. Source

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