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PubMed | Semmelweis University, Leiden University, University of Groningen, Organizacion Nacional de Trasplantes and 4 more.
Type: Journal Article | Journal: Transplantation proceedings | Year: 2014

Considering the growing organ demand worldwide, it is crucial to optimize organ retrieval and training of surgeons to reduce the risk of injury during the procedure and increase the quality of organs to be transplanted. In the Netherlands, a national complete trajectory from training of surgeons in procurement surgery to the quality assessment of the procured organs was implemented in 2010. This mandatory trajectory comprises training and certification modules: E-learning, training on the job, and a practical session. Thanks to the ACCORD (Achieving Comprehensive Coordination in Organ Donation) Joint Action coordinated by Spain and co-funded under the European Commission Health Programme, 3 twinning activities (led by France) were set to exchange best practices between countries. The Dutch trajectory is being adapted and implemented in Hungary as one of these twinning activities. The E-learning platform was modified, tested by a panel of Hungarian and UK surgeons, and was awarded in July 2013 by the European Accreditation Council for Continuing Medical Education of the European Union of Medical Specialists. As a pilot phase for future national training, 6 Hungarian surgeons from Semmelweis University are being trained; E-learning platform was fulfilled, and practical sessions, training-on-the-job activities, and evaluations of technical skills are ongoing. The first national practical session was recently organized in Budapest, and the new series of nationwide selected candidates completed the E-learning platform before the practical. There is great potential for sharing best practices and for direct transfer of expertise at the European level, and especially to export this standardized training in organ retrieval to other European countries and even broader. The final goal was to not only provide a national training to all countries lacking such a program but also to improve the quality and safety criteria of organs to be transplanted.


PubMed | Karolinska Institutet, Carol Davila University of Medicine and Pharmacy, Jena University Hospital, University of Turku and 53 more.
Type: Journal Article | Journal: Leukemia | Year: 2015

Serial quantification of BCR-ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR-ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.080.13 10(6), 1.080.11 10(5), 1.030.10 10(4), 1.020.09 10(3), 1.040.10 10(2) and 10.01.5 copies/l. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR-ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR-ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/; CRM code ERM-AD623a-f).


Varga K.,Hungarian Academy of Sciences | Paszty K.,Hungarian Academy of Sciences | Padanyi R.,Hungarian National Blood Transfusion Service | Hegedu;s L.,Hungarian Academy of Sciences | And 4 more authors.
Cell Calcium | Year: 2014

The expression of the plasma membrane Ca2+ ATPase (PMCA) isoforms is altered in several types of cancer cells suggesting that they are involved in cancer progression. In this study we induced differentiation of MCF-7 breast cancer cells by histone deacetylase inhibitors (HDACis) such as short chain fatty acids (SCFAs) or suberoylanilide hydroxamic acid (SAHA), and by phorbol 12-myristate 13-acetate (PMA) and found strong upregulation of PMCA4b protein expression in response to these treatments. Furthermore, combination of HDACis with PMA augmented cell differentiation and further enhanced PMCA4b expression both at mRNA and protein levels. Immunocytochemical analysis revealed that the upregulated protein was located mostly in the plasma membrane. To examine the functional consequences of elevated PMCA4b expression, the characteristics of intracellular Ca2+ signals were investigated before and after differentiation inducing treatments, and also in cells overexpressing PMCA4b. The increased PMCA4b expression - either by treatment or overexpression - led to enhanced Ca2+ clearance from the stimulated cells. We found pronounced PMCA4 protein expression in normal breast tissue samples highlighting the importance of this pump for the maintenance of mammary epithelial Ca2+ homeostasis. These results suggest that modulation of Ca2+ signaling by enhanced PMCA4b expression may contribute to normal development of breast epithelium and may be lost in cancer. © 2014 Elsevier Ltd.


Kasza I.,Hungarian Academy of Sciences | Kasza I.,CellPharma Kft | Varady G.,Hungarian Academy of Sciences | Varady G.,CellPharma Kft | And 7 more authors.
PLoS ONE | Year: 2012

We have developed a rapid, simple and reliable, antibody-based flow cytometry assay for the quantitative determination of membrane proteins in human erythrocytes. Our method reveals significant differences between the expression levels of the wild-type ABCG2 protein and the heterozygous Q141K polymorphic variant. Moreover, we find that nonsense mutations on one allele result in a 50% reduction in the erythrocyte expression of this protein. Since ABCG2 polymorphisms are known to modify essential pharmacokinetic parameters, uric acid metabolism and cancer drug resistance, a direct determination of the erythrocyte membrane ABCG2 protein expression may provide valuable information for assessing these conditions or for devising drug treatments. Our findings suggest that erythrocyte membrane protein levels may reflect genotype-dependent tissue expression patterns. Extension of this methodology to other disease-related or pharmacologically important membrane proteins may yield new protein biomarkers for personalized diagnostics. © 2012 Kasza et al.


Penniston J.T.,Hungarian Academy of Sciences | Penniston J.T.,Massachusetts General Hospital | Padanyi R.,Hungarian National Blood Transfusion Service | Paszty K.,Hungarian Academy of Sciences | And 2 more authors.
Journal of Cell Science | Year: 2014

Plasma membrane Ca2+ ATPases (PMCAs, also known as ATP2B1-ATP2B4) are known targets of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], but if and how they control the PtdIns(4,5)P2 pool has not been considered. We demonstrate here that PMCAs protect PtdIns(4,5)P2 in the plasma membrane from hydrolysis by phospholipase C (PLC). Comparison of active and inactive PMCAs indicates that the protection operates by two mechanisms; one requiring active PMCAs, the other not. It appears that the mechanism requiring activity is the removal of the Ca2+ required for sustained PLC activity, whereas the mechanism not requiring activity is PtdIns(4,5)P2 binding. We show that in PMCA overexpressing cells, PtdIns(4,5)P2 binding can lead to less inositol 1,4,5-triphosphate (InsP3) and diminished Ca2+ release from intracellular Ca2+ pools. Inspection of a homology model of PMCA suggests that PMCAs have a conserved cluster of basic residues forming a 'blue collar' at the interface between the membrane core and the cytoplasmic domains. By molecular dynamics simulation, we found that the blue collar forms four binding pockets for the phosphorylated inositol head group of PtdIns(4,5)P2; these pockets bind PtdIns(4,5)P2 strongly and frequently. Our studies suggest that by having the ability to bind PtdIns(4,5)P2, PMCAs can control the accessibility of PtdIns(4,5)P2 for PLC and other PtdIns(4,5)P2-mediated processes. © 2014. Published by The Company of Biologists Ltd.


Smudla A.,Semmelweis University | Hegedus K.,Semmelweis University | Mihaly S.,Hungarian National Blood Transfusion Service | Szabo G.,Semmelweis University | Fazakas J.,Semmelweis University
Annals of Transplantation | Year: 2012

Background: Adequate communication with donors' relatives in the intensive care unit can crucially increase the number of donations and can influence the relatives' grief reaction and depression. The aim of this quantitative investigation was to explore how communication in the ICU about brain death and consent to donation affected family members' psychological condition.Material/Methods: The self-completed questionnaire, which the donors' relatives filled in 3-6 months after donation consisted of demographic data, participants' knowledge, opinions about and attitudes toward donation, communication in the ICU regarding brain death and donation, and 2 psychometric inventories: the Hungarian-translated version of the Revised Grief Experience Inventory and the Hungarian adaptation of the Shortened Version of the Beck Depression Inventory. Results: Before organ recovery, 100% of the 29 participants supported donation, but 24.1% considered donation for transplantation to be unhelpful, and 41.4% doubted that the diagnosis was reliable after donation. Bereavement and depression did not correlate with age, marital status or degree of religiousness. Females had higher "physical distress" and more severe depression. The psychological reaction was lower amongst relatives with higher education. Depressive symptoms occurred in 72.4% of participants. Individuals who did not have confidence in the brain death diagnosis had more intense grief reaction (p=0.020) and more serious depressive symptoms (p=0.002). Conclusions: To decrease the negative psychological impact of donation, relatives need the Help Earlier in parallel with the Loss of Loved Person. The first step of the "HELLP" concept is to establish adequate communication; consequently, the physicians' education about communication is essential. © Ann Transplant, 2012.


Csuka D.,Semmelweis University | Czirjak L.,University of Pécs | Hobor R.,University of Pécs | Illes Z.,University of Pécs | And 4 more authors.
Molecular Immunology | Year: 2013

Introduction: Controversy exists about the effectiveness of vaccine-induced immune response in patients with immunoregulatory disorders. Our aim was to determine the antibody titers to diphtheria and tetanus in patients with either of two autoimmune diseases. Methods: 279 patients with SLE (205 females, aged 45.0 ± 13.8 years), 158 patients with myasthenia gravis (MG) (101 females, aged 55 ± 18.7 years) and 208 healthy subjects (122 females, aged 48 ± 14.6 years) were enrolled. Serum concentrations of diphtheria-antitoxin-IgG (A-DIPHTH) and tetanus-antitoxoid-IgG (A-TET) were determined with ELISA. Results: Equal proportions of healthy subjects, as well as patients with SLE or MG exhibited proper antibody responses and immune protection against diphtheria and tetanus. In all three test groups, serum concentration of A-DIPHTH decreased significantly (p< 0.001) with age throughout the study population, while titers of A-TET dropped only in the elderly (>60-years-old) subjects. There were no significant differences among the groups in the age-related changes of A-TET and A-DIPHTH except that in <40-years-old subjects, A-DIPHTH level was significantly (p=. 0.029) lower in SLE patients than in controls. Conclusions: Our findings suggest that the level of vaccine-induced immunity against diphtheria and tetanus infections in patients with SLE or MG is comparable to the healthy population. © 2013 Elsevier Ltd. All rights reserved.


Antalffy G.,Hungarian Academy of Sciences | Paszty K.,Hungarian Academy of Sciences | Varga K.,Hungarian Academy of Sciences | Hegedus L.,Hungarian Academy of Sciences | And 3 more authors.
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2013

Recent evidences show that the localization of different plasma membrane Ca2+ ATPases (PMCAs) is regulated in various complex, cell type-specific ways. Here we show that in low-density epithelial and endothelial cells PMCA4b localized mostly in intracellular compartments and its plasma membrane localization was enhanced upon increasing density of cells. In good correlation with the enhanced plasma membrane localization a significantly more efficient Ca2+ clearance was observed in confluent versus non-confluent HeLa cell cultures expressing mCherry-PMCA4b. We analyzed the subcellular localization and function of various C-terminally truncated PMCA4b variants and found that a truncated mutant PMCA4b-ct24 was mostly intracellular while another mutant, PMCA4b-ct48, localized more to the plasma membrane, indicating that a protein sequence corresponding to amino acid residues 1158-1181 contained a signal responsible for the intracellular retention of PMCA4b in non-confluent cultures. Alteration of three leucines to alanines at positions 1167-1169 resulted in enhanced cell surface expression and an appropriate Ca2+ transport activity of both wild type and truncated pumps, suggesting that the di-leucine-like motif 1167LLL was crucial in targeting PMCA4b. Furthermore, upon loss of cell-cell contact by extracellular Ca2+ removal, the wild-type pump was translocated to the early endosomal compartment. Targeting PMCA4b to early endosomes was diminished by the L1167-69A mutation, and the mutant pump accumulated in long tubular cytosolic structures. In summary, we report a di-leucine-like internalization signal at the C-tail of PMCA4b and suggest an internalization-mediated loss of function of the pump upon low degree of cell-cell contact. © 2013 Elsevier B.V.


PubMed | Hungarian National Blood Transfusion Service, Hungarian Medical Students International Relations Committee Local Committee and Debrecen University
Type: Journal Article | Journal: Transplantation proceedings | Year: 2015

Organ transplantation has become an organized, routine, widely used method in the treatment of several end-stage diseases. Kidney transplantation means the best life-quality and longest life expectancy for patients with end-stage renal diseases. Transplantation is the only available long-term medical treatment for patients with end-stage liver, heart, and lung diseases. Despite the number of transplantations increasing worldwide, the needs of the waiting lists remain below expectations.One of the few methods to increase the number of transplantations is public education. In cooperation with the University of Debrecen Institute for Surgery Department of Transplantation, the Hungarian National Blood Transfusion Service Organ Coordination Office, and the Local Committee Debrecen of Hungarian Medical Students International Relations Committee (HuMSIRC), the Gerundium, a new educational program, has been established to serve this target. Gerundium is a special program designed especially for youth education. Peer education means that age-related medical student volunteers educate their peers during interactive unofficial sessions.Volunteers were trained during specially designed training. Medical students were honored by HuMSIRC, depending on their activity on the basis of their own regulations. Uniform slides and brochures to share were designed. Every Hungarian secondary school was informed. The Local Committee Budapest of HuMSIRC also joined the program, which helps to expand our activity throughout Hungary. The aim of the program is public education to help disperse disapproval, if presented.As a multiple effect, our program promotes medical students to have better skills in the field of transplantation, presentation, and communication skills. Our program is a voluntary program with strong professional support and is free of charge for the community.


PubMed | Hungarian National Blood Transfusion Service, Red Cross, Hungarian Academy of Sciences and University of Lodz
Type: Journal Article | Journal: PloS one | Year: 2014

Lan is a high-incidence blood group antigen expressed in more than 99.9% of the population. Identification of the human ABC transporter ABCB6 as the molecular basis of Lan has opened the way for studies assessing the relation of ABCB6 function and expression to health and disease. To date, 34 ABCB6 sequence variants have been described in association with reduced ABCB6 expression based on the genotyping of stored blood showing weak or no reactivity with anti-Lan antibodies. In the present study we examined the red blood cell (RBC) surface expression of ABCB6 by quantitative flow cytometry in a cohort of 47 healthy individuals. Sequencing of the entire coding region of the ABCB6 gene in low RBC ABCB6 expressors identified a new allele (IVS9+1G>A, affecting a putative splice site at the boundary of exon 9) and two nonsynonymous SNPs listed in the SNP database (R192Q (rs150221689) and G588 S (rs145526996)). The R192Q mutation showed co-segregation with reduced RBC ABCB6 expression in a family, and we found the G588 S mutation in a compound heterozygous individual with undetectable ABCB6 expression, suggesting that both mutations result in weak or no expression of ABCB6 on RBCs. Analysis of the intracellular expression pattern in HeLa cells by confocal microscopy indicated that these mutations do not compromise overall expression or the endolysosomal localization of ABCB6. Genotyping of two large cohorts, containing 235 and 1039 unrelated volunteers, confirmed the high allele frequency of Lan-mutations. Our results suggest that genetic variants linked to lower or absent cell surface expression of ABCB6/Langereis may be more common than previously thought.

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