József Balla

University of Debrecen, Debreczyn, Hajdú-Bihar, Hungary

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Publications (121)446.33 Total impact

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    ABSTRACT: Aim: The incidence of atrial fibrillation is increased during hemodialysis (HD); however, the effects of hemodiafiltration (HDF) on atrial arrhythmias have not been evaluated. The prolongation of the P wave and P dispersion (Pd) can predict atrial arrhythmias. Methods: Data from 30 patients receiving HDF over a period of 3 months were collected; the same group of patients was then evaluated during treatment with conventional HD for at least another 3 months. Electrolyte values were obtained, and surface electrocardiograms (ECG), echocardiography, and Holter ECGs were performed. Results: The duration of the P wave and Pd increased significantly during HD. The left atrial diameter decreased significantly only during HDF. During HDF, the left atrial cross diameter measured at the beginning of the session was positively correlated with the incidence of supraventricular premature beats (p = 0.011, r = 0.4556). The decrease in left atrial diameter during HDF was negatively correlated with the incidence of supraventricular premature beats (p = 0.016, r = -0.43). During HDF, the changes in sodium and Pd were significantly positively correlated (p < 0.05, r = 0.478). During HD, the changes in ionized calcium levels and Pd were positively correlated (p < 0.05, r = 0.377). Conclusion: Our results suggest that HDF has a more beneficial effect on P wave duration and Pd than HD. The alterations in the ECG markers may be the result of the simultaneous occurrence of certain electrolyte imbalances and renal replacement methods.
    International Urology and Nephrology 11/2015; DOI:10.1007/s11255-015-1144-4 · 1.52 Impact Factor
  • Mónika Nyitrai · György Balla · József Balla ·

    Orvosi Hetilap 11/2015; 156(47):1926-1931. DOI:10.1556/650.2015.30299
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    ABSTRACT: Vascular calcification is a frequent complication of atherosclerosis, diabetes and chronic kidney disease. In the latter group of patients, calcification is commonly seen in tunica media where smooth muscle cells (SMC) undergo osteoblastic transformation. Risk factors such as elevated phosphorus levels and vitamin D3 analogues have been identified. In the light of earlier observations by our group and others, we sought to inhibit SMC calcification via induction of ferritin. Human aortic SMC were cultured using β-glycerophosphate with activated vitamin D3 , or inorganic phosphate with calcium, and induction of alkaline phosphatase (ALP) and osteocalcin as well as accumulation of calcium were used to monitor osteoblastic transformation. In addition, to examine the role of vitamin D3 analogues, plasma samples from patients on haemodialysis who had received calcitriol or paricalcitol were tested for their tendency to induce calcification of SMC. Addition of exogenous ferritin mitigates the transformation of SMC into osteoblast-like cells. Importantly, pharmacological induction of heavy chain ferritin by 3H-1,2-Dithiole-3-thione was able to inhibit the SMC transition into osteoblast-like cells and calcification of extracellular matrix. Plasma samples collected from patients after the administration of activated vitamin D3 caused significantly increased ALP activity in SMC compared to the samples drawn prior to activated vitamin D3 and here, again induction of ferritin diminished the osteoblastic transformation. Our data suggests that pharmacological induction of ferritin prevents osteoblastic transformation of SMC. Hence, utilization of such agents that will cause enhanced ferritin synthesis may have important clinical applications in prevention of vascular calcification.
    Journal of Cellular and Molecular Medicine 10/2015; DOI:10.1111/jcmm.12682 · 4.01 Impact Factor
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    ABSTRACT: Intracellular free heme predisposes to oxidant-mediated tissue damage. We hypothesized that free heme causes alterations in myocardial contractility via disturbed structure and/or regulation of the contractile proteins. Isometric force production and its Ca(2+)-sensitivity (pCa50) were monitored in permeabilized human ventricular cardiomyocytes. Heme exposure altered cardiomyocyte morphology and evoked robust decreases in Ca(2+)-activated maximal active force (Fo) while increasing Ca(2+)-independent passive force (Fpassive). Heme treatments, either alone or in combination with H2O2, did not affect pCa50. The increase in Fpassive started at 3µM heme exposure and could be partially reversed by the antioxidant dithiothreitol. Protein sulfhydryl (SH) groups of thick myofilament content decreased and sulfenic acid formation increased after treatment with heme. Partial restoration in the SH group content was observed in a protein running at 140kDa after treatment with dithiothreitol, but not in other proteins, such as filamin C, myosin heavy chain, cardiac myosin binding protein C, and α-actinin. Importantly, binding of heme to hemopexin or alpha-1-microglobulin prevented its effects on cardiomyocyte contractility, suggesting an allosteric effect. In line with this, free heme directly bound to myosin light chain 1 in human cardiomyocytes. Our observations suggest that free heme modifies cardiac contractile proteins via posttranslational protein modifications and via binding to myosin light chain 1, leading to severe contractile dysfunction. This may contribute to systolic and diastolic cardiac dysfunctions in hemolytic diseases, heart failure, and myocardial ischemia-reperfusion injury.
    Free Radical Biology and Medicine 09/2015; 89. DOI:10.1016/j.freeradbiomed.2015.07.158 · 5.74 Impact Factor
  • R.P. Szabó · I Varga · J Balla · L Zsom · B Nemes ·
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    ABSTRACT: Introduction: Cardiovascular disease is a major cause of morbidity and mortality in end-stage renal disease patients on dialysis and the most common cause of death in the immediate post-transplantation period. The aim of our study was to describe a novel approach of cardiovascular screening and management of dialysis patients evaluated for the transplant waiting list. Methods: Twenty-eight patients with end-stage renal disease put on the waiting list between July 2013 and July 2014 were subjected to a prespecified cardiovascular screening protocol utilizing noninvasive and/or invasive tests. Patients were subsequently divided into 3 strata in terms of their estimated cardiovascular risk. Each of these groups were then prescribed interventions aiming to improve their cardiovascular condition. Results: According to our prespecified protocol of cardiovascular screening studies, 15 (54%) patients were identified as low, 5 (18%) as intermediate, and 8 (28%) as high risk. Four (14%) patients were current smokers. In the low-risk group, we initiated a patient education program involving counseling on regular exercise such as swimming or cycling to improve their functional capacity. In the high-risk group revascularization was done in 5 cases (63%), including 3 percutaneous transluminal coronary angioplasties (PTCA) with stents for single-vessel disease, and coronary artery bypass graft surgeries (CABG) for triple-vessel disease in 2 cases. In the medium-risk group medical management was opted for, including introduction of beta-blockers, inhibitors, statins, and ezetimibe, as well as efforts to optimize anemia management, indices of bone-mineral disease, and fluid status. Conclusion: In our regional transplant program, we introduced a comprehensive multidisciplinary approach to treat potential transplant candidates according to cardiovascular risk stratification based on a prespecified screening protocol. Further studies are needed to correlate this novel strategy with post-transplantation outcomes.
    Transplantation Proceedings 09/2015; 47(7):2192-5. DOI:10.1016/j.transproceed.2015.07.018 · 0.98 Impact Factor

  • Atherosclerosis 07/2015; 241(1):e205. DOI:10.1016/j.atherosclerosis.2015.04.979 · 3.99 Impact Factor

  • Orvosi Hetilap 05/2015; 156(22):896-900. DOI:10.1556/650.2015.30139
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    ABSTRACT: Inflammation culminating in fibrosis contributes to progressive kidney disease. Cross-talk between the tubular epithelium and interstitial cells regulates inflammation by a coordinated release of cytokines and chemokines. Here we studied the role of heme oxygenase-1 (HO-1) and the heavy subunit of ferritin (FtH) in macrophage polarization and renal inflammation. Deficiency in HO-1 was associated with increased FtH expression, accumulation of macrophages with a dysregulated polarization profile, and increased fibrosis following unilateral ureteral obstruction in mice: a model of renal inflammation and fibrosis. Macrophage polarization in vitro was predominantly dependent on FtH expression in isolated bone marrow-derived mouse monocytes. Using transgenic mice with conditional deletion of FtH in the proximal tubules (FtH(PT-/-)) or myeloid cells (FtH(LysM-/-)), we found that myeloid FtH deficiency did not affect polarization or accumulation of macrophages in the injured kidney compared with wild-type (FtH(+/+)) controls. However, tubular FtH deletion led to a marked increase in proinflammatory macrophages. Furthermore, injured kidneys from FtH(PT-/-) mice expressed significantly higher levels of inflammatory chemokines and fibrosis compared with kidneys from FtH(+/+) and FtH(LysM-/-) mice. Thus, there are differential effects of FtH in macrophages and epithelial cells, which underscore the critical role of FtH in tubular-macrophage cross-talk during kidney injury.Kidney International advance online publication, 15 April 2015; doi:10.1038/ki.2015.102.
    Kidney International 04/2015; 88(1). DOI:10.1038/ki.2015.102 · 8.56 Impact Factor
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    ABSTRACT: Various factors (hypertension [27%], diabetes mellitus [40%]) and their cardiovascular complications play an important role in the genesis of end stage renal disease. Furthermore, primary kidney diseases (glomerulonephritis, tubulointerstitial nephritis, obstructive uropathy, analgesic nephropathy, polycystic kidney disease, autoimmune diseases) have an unfavorable effect on the cardiovascular outcome of this particular population. Increased susceptibility for arrhythmias may be caused by intermittent volume overload, metabolic disturbance, renal anemia, structural and electrophysiological changes of the myocardium, inflammatory mechanisms that may worsen the mortality statistics of these patients. A novel renal replacement method, hemodiafiltration - based on a convective transport - ensures reduced mortality that may be attributed to a decreased occurrence of arrhythmias. The aim of this paper is to review the pathogenetic factors taking part in the arrhythmogenesis of end stage renal disease and to provide diagnostic and therapeutic opportunities that can help in the prediction and prevention of arrhythmias. Orv. Hetil., 2015, 156(12), 463-471.
    Orvosi Hetilap 03/2015; 156(12):463-71. DOI:10.1556/OH.2015.30111
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    ABSTRACT: The fluorinated glucocorticoid betamethasone stimulated both the extracellular phospholipase production and hypha formation of the opportunistic human pathogen Candida albicans and also decreased the efficiency of the polyene antimycotics amphotericin B and nystatin against C. albicans in a dose-dependent manner. Importantly, betamethasone increased synergistically the anti-Candida activity of the oxidative stress generating agent menadione, which may be exploited in future combination therapies to prevent or cure C. albicans infections, in the field of dermatology. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Journal of Basic Microbiology 02/2015; 55(8). DOI:10.1002/jobm.201400903 · 1.82 Impact Factor
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    ABSTRACT: Relapsing polychondritis (RP) is a rare autoimmune disease with chronic inflammatory/destructive lesions of the cartilaginous tissues. In one third of the cases it is associated with other autoimmune disorders, mostly with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). We report three cases of RP with p-ANCA positive AAV. In the first patient RP developed 1.5 years after the onset of AAV. In the others the signs of RP were present before the onset of severe crescent glomerulonephritis. Patients responded well on steroid and cyclophosphamide. In dialysis dependent cases plasmapheresis was also used successfully. During the 2 and 1.5 years of follow up, they were symptom-free, and had stable glomerular filtration rate. The first patient died after four years of follow-up due to the complications of sudden unset pancytopenia, which raises the possibility of associated hemophagocytic syndrome. In the setting of RP or AAV physicians should always be aware of the possibility of sudden or insidious appearance of the other disease.
    12/2014; 2(12):912-7. DOI:10.12998/wjcc.v2.i12.912
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    Viktória Jeney · György Balla · József Balla ·
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    ABSTRACT: For decades plaque neovascularization was considered as an innocent feature of advanced atherosclerotic lesions, but nowadays growing evidence suggest that this process triggers plaque progression and vulnerability. Neovascularization is induced mostly by hypoxia, but the involvement of oxidative stress is also established. Because of inappropriate angiogenesis, neovessels are leaky and prone to rupture, leading to the extravasation of red blood cells (RBCs) within the plaque. RBCs, in the highly oxidative environment of the atherosclerotic lesions, tend to lyse quickly. Both RBC membrane and the released hemoglobin (Hb) possess atherogenic activities. Cholesterol content of RBC membrane contributes to lipid deposition and lipid core expansion upon intraplaque hemorrhage. Cell-free Hb is prone to oxidation, and the oxidation products possess pro-oxidant and pro-inflammatory activities. Defense and adaptation mechanisms evolved to cope with the deleterious effects of cell free Hb and heme. These rely on plasma proteins haptoglobin (Hp) and hemopexin (Hx) with the ability to scavenge and eliminate free Hb and heme form the circulation. The protective strategy is completed with the cellular heme oxygenase-1/ferritin system that becomes activated when Hp and Hx fail to control free Hb and heme-mediated stress. These protective molecules have pharmacological potential in diverse pathologies including atherosclerosis.
    Frontiers in Physiology 10/2014; 5:379. DOI:10.3389/fphys.2014.00379 · 3.53 Impact Factor
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    ABSTRACT: Magnesium participates in numerous enzymatic reactions in the human body and it has essential role in the maintenance of the antioxidant system. Since several magnesium compounds have been applied in the food and pharmaceutical industry, our purpose was to investigate the antioxidant/free radical scavenging activity of some magnesium compounds in vitro. The antioxidant/prooxidant effect of inorganic salts (e.g. MgCl2) and organic complexes (e.g. Mg-gluconate) was determined with chemiluminometric method (H2O 2/•OH-microperoxidase-luminol) and heme mediated LDL oxidation (LDL-heme-H2O2 ) in vitro. It has been stated that the chemiluminescence method and LDL (low density lipoprotein) oxidation measurement is applicable in the presence of magnesium salts and complexes. Most of the compounds do not generate free radicals and the antioxidant/prooxidant effect depends on the quality of the ligand and the concentration. In the concentration range used, some representatives of the magnesium compounds (MgO, Mg-gluconate, Mg-polygalacturonate) investigated showed radical generating activity measured with chemiluminescence method, whereas the LDL oxidation has not been affected. Magnesium citrate and malate proved to be antioxidants measured with the chemiluminescence method and they slightly accelerate the LDL oxidation in the system and in the concentration applied. In vitro some of the ligands of magnesium compounds showed antioxidant activities.
    Acta Alimentaria 09/2014; 43(3):419-425. DOI:10.1556/AAlim.43.2014.3.8 · 0.27 Impact Factor

  • Atherosclerosis 08/2014; 235(2):e36-e37. DOI:10.1016/j.atherosclerosis.2014.05.076 · 3.99 Impact Factor
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    ABSTRACT: Podocytes are highly specialized, arborized epithelial cells covering the outer surface of the glomerular tuft in the kidney. Terminally differentiated podocytes are unable to go through cell division and hereby they are lacking a key property for regeneration after a toxic injury. Podocytes are long-lived cells but, to date, little is known about the mechanisms that support their stress resistance. Our aim was to investigate whether the well-known morphological changes during podocyte differentiation are accompanied by changes in oxidative resistance in a manner that could support their long-term survival. We used a conditionally immortalized human podocyte cell line to study the morphological and functional changes during differentiation. We followed the differentiation process for 14 days by time-lapse microscopy. During this period nondifferentiated podocytes gradually transformed into large, nonproliferating, frequently multinucleated cells, with enlarged nuclei and opened chromatin structure. We observed that differentiated podocytes were highly resistant to oxidants such as H 2 O 2 and heme when applied separately or in combination, whereas undifferentiated cells were prone to such challenges. Elevated oxidative resistance of differentiated podocytes was associated with increased activities of antioxidant enzymes and H-ferritin expression. Immunohistochemical analysis of normal human kidney specimens revealed that podocytes highly express H-ferritin in vivo as well.
    Oxidative medicine and cellular longevity 07/2014; 2014(25):976394. DOI:10.1155/2014/976394 · 3.36 Impact Factor
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    ABSTRACT: Iron is an essential element for all microorganisms. Bacteria and fungi produce versatile siderophores for binding and storing this essential transition metal when its availability is limited in the environment. The aim of the study was to optimize the fermentation medium of Aspergillus fumigatus for siderophore production. Triacetyl-fusarinine C and ferricrocin yields were dependent on glucose and glycine supplementations as well as the initial pH of the culture media. The optimal fermentation medium for triacetylfusarinine C production contained 8% glucose, 0.4% glycine and the initial pH was set to 5.9. Meanwhile, maximal ferricrocin yields were recorded in the presence of 10% glucose, 0.5% glycine and at an initial pH of 7.4. Under optimized fermentation conditions, the yields for triacetylfusarinine C and ferricrocin increased up to 2.9 g/l culture medium and 18.9 mg/g mycelium, respectively.
    Acta Microbiologica et Immunologica Hungarica 06/2014; 61(2):107-19. DOI:10.1556/AMicr.61.2014.2.2 · 0.78 Impact Factor
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    ABSTRACT: Iron accumulates in human atherosclerotic lesions but whether it is a cause or simply a downstream consequence of the atheroma formation has been an open question for decades. According to the so called "iron hypothesis," iron is believed to be detrimental for the cardiovascular system, thus promoting atherosclerosis development and progression. Iron, in its catalytically active form, can participate in the generation of reactive oxygen species and induce lipid-peroxidation, triggering endothelial activation, smooth muscle cell proliferation and macrophage activation; all of these processes are considered to be proatherogenic. On the other hand, the observation that hemochromatotic patients, affected by life-long iron overload, do not show any increased incidence of atherosclerosis is perceived as the most convincing evidence against the "iron hypothesis." Epidemiological studies and data from animal models provided conflicting evidences about the role of iron in atherogenesis. Therefore, more careful studies are needed in which issues like the source and the compartmentalization of iron will be addressed. This review article summarizes what we have learnt about iron and atherosclerosis from epidemiological studies, animal models and cellular systems and highlights the rather contributory than innocent role of iron in atherogenesis.
    Frontiers in Pharmacology 05/2014; 5:94. DOI:10.3389/fphar.2014.00094 · 3.80 Impact Factor
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    ABSTRACT: The prolongation of the QT interval and dispersion could predict ventricular arrhythmias. It is not yet established whether there is a difference between the effects of hemodialysis and hemodiafiltration on QT interval duration and dispersion. Data of thirty patients was investigated while they were receiving hemodiafiltration over a period of 3 months; then the same group of patients was evaluated during treatment with conventional hemodialysis for at least another 3 months. Ionic parameters and surface electrocardiograms (ECG) were analyzed five times during each session, and 2D, M-mode echocardiography and Holter ECGs were performed to acquire additional information. QT interval duration (QTmax) and dispersion (QTd) showed a significant increase during hemodialysis, but not during hemodiafiltration. QTmax was 388.66 ± 31.81 ms at the beginning of hemodialysis and increased to 400.66 ± 39.12 ms even at the 30th minute (p < 0.05). QTd was found to be 31.33 ± 10.08 ms before the commencement of hemodialysis with the largest prolongation being seen at the 240th minute (51.33 ± 14.56 ms, p < 0.05). The occurrence of ventricular premature beats was significantly higher during hemodialysis (p = 0.018). The left atrial diameter significantly decreased at the end of hemodiafiltration (at the beginning 45.1 ± 5.25 mm, at the end 40.77 ± 5.76 mm; p < 0.05). Our results suggest a beneficial effect of hemodiafiltration on the studied electrocardiographic parameters compared to hemodialysis. The larger decrease in the left atrial diameter suggests a more efficient intracardiac volume-decreasing potential of hemodiafiltration.
    Clinical and Experimental Nephrology 03/2014; 18(6). DOI:10.1007/s10157-014-0950-9 · 2.02 Impact Factor
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    ABSTRACT: Introduction: Patients with renopulmonary syndrome who have both anti-neutrophil cytoplasmic and anti-glomerular basement membrane antibodies have been described since 1989. Aim: The aim of the authors was to analyse the data of "double positive" patients diagnosed in their department, and compare these with previous studies. Method: During the last 16 years, 87 anti-neutrophil cytoplasmic antibody positive and 11 anti-glomerular basement membrane antobody positive patients were diagnosed. Four patients with anti-glomerular basement membrane antibodies (36%) had detectable anti-neutrophil cytoplasmic antibodies, 2 patients were positive for anti-myeloperoxidase and 2 patients for anti-proteinase 3. Results: In comparison with patients having anti-glomerular basement membrane antibodies, the double-positive patients were characterized by older age (median of 46 vs. 24 years), lack of male dominance (50% vs. 71%), more frequent presence of previous extrarenal symptoms (50% vs. 0%), and lower anti-glomerular basement membrane antibody levels (<100EU/ml: 100% vs. 29%). The double-positive patients had more favourable 1-year survival (100% vs. 71%), despite their older age and similar treatment regimen (immunosuppression 100% in both groups, plasmapheresis in 75% vs. 86%), but 1-year renal survival was not different (25% vs. 14%). Conclusions: In agreement with literature data, about one third of patients with anti-glomerular basement membrane antibodies had detectable anti-neutrophil cytoplasmic antibodies, and the coexistence of the two antibodies may have clinical consequences. Orv. Hetil., 154 (43), 1696-1701.
    Orvosi Hetilap 10/2013; 154(43):1696-701. DOI:10.1556/OH.2013.29735
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    ABSTRACT: Ferritin plays a central role in iron metabolism and is made of 24 subunits of 2 types: heavy chain and light chain. The ferritin heavy chain (FtH) has ferroxidase activity that is required for iron incorporation and limiting toxicity. The purpose of this study was to investigate the role of FtH in acute kidney injury (AKI) and renal iron handling by using proximal tubule-specific FtH-knockout mice (FtHPT-/- mice). FtHPT-/- mice had significant mortality, worse structural and functional renal injury, and increased levels of apoptosis in rhabdomyolysis and cisplatin-induced AKI, despite significantly higher expression of heme oxygenase-1, an antioxidant and cytoprotective enzyme. While expression of divalent metal transporter-1 was unaffected, expression of ferroportin (FPN) was significantly lower under both basal and rhabdomyolysis-induced AKI in FtHPT-/- mice. Apical localization of FPN was disrupted after AKI to a diffuse cytosolic and basolateral pattern. FtH, regardless of iron content and ferroxidase activity, induced FPN. Interestingly, urinary levels of the iron acceptor proteins neutrophil gelatinase-associated lipocalin, hemopexin, and transferrin were increased in FtHPT-/- mice after AKI. These results underscore the protective role of FtH and reveal the critical role of proximal tubule FtH in iron trafficking in AKI.
    The Journal of clinical investigation 09/2013; 123(10). DOI:10.1172/JCI67867 · 13.22 Impact Factor

Publication Stats

5k Citations
446.33 Total Impact Points


  • 1990-2015
    • University of Debrecen
      • • Department of Neurology
      • • Third Department of Internal Medicine
      • • Faculty of Medicine
      • • Department of Pharmacology and Pharmacotherapy
      • • Department of Pediatrics
      Debreczyn, Hajdú-Bihar, Hungary
  • 2013
    • Hungarian Academy of Sciences
      • Virology Research Group
      Budapeŝto, Budapest, Hungary
  • 2007-2009
    • Debreceni Egyetem, Orvos- és Egészségtudományi Centrum
      Debreczyn, Hajdú-Bihar, Hungary
  • 2004
    • Magyar Tudományos Akadémia Wigner Fizikai Kutatóközpont
      Budapeŝto, Budapest, Hungary
  • 2001
    • Beth Israel Deaconess Medical Center
      • Department of Surgery
      Boston, Massachusetts, United States
  • 1992-1996
    • University of Minnesota Duluth
      • • Medical School
      • • Laboratory Medicine and Pathology
      Duluth, Minnesota, United States