Zsolt Nagy

Semmelweis University, Budapeŝto, Budapest, Hungary

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Publications (93)194.1 Total impact

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    ABSTRACT: Endogenous glucocorticoids exert a diverse array of physiological processes including immune-modulatory or anti-inflammatory responses and play an important role in the pathogenesis of inflammatory and autoimmune diseases. Regulation of inflammatory processes by glucocorticoids is controlled in a cytokine-hypothalamo-pituitary-adrenal axis feedback circuit and on the local, cell-type and context-specific local regulatory system. At the tissue level the sensitivity and response to glucocorticoids are determined by multiple factors: including the local availability to glucocorticoids transported by blood, the locally-formed bioactive glucocorticoids (synthesized and metabolized 11β-hydroxysteroid dehydrogenase enzymes), the number and function of the glucocorticoid receptor (GR) and the GR affinity to its ligands. Numerous molecular factors are known to influence the sensitivity of glucocorticoid response through the GR. Cytokines are one of the major components that can inhibit GR function and can potentiate the resistance against glucocorticoids. GR isoforms, generated by alternative splicing, alternative translation and post-translation modification are further mechanisms which modulate glucocorticoid signaling. Genetic variants within the GR encoding gene are other potential factors that may influence the susceptibility and severity of autoimmune disorders and may play a key role in individual response to medication. In this review our aim was to summarize our knowledge about the connections between the cell type-specific glucocorticoid signaling and the local immune system. Prediction of individual sensitivity to steroids and identification of key players in development of glucocorticoid resistance are essential in individualized therapies. The local, tissue-specific glucocorticoid signaling and its influence by cytokines may be important in determining the magnitude of inflammatory reactions, and may also be related to the success of glucocorticoid-containing therapeutic strategies.
    Current medicinal chemistry. 12/2014;
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    ABSTRACT: The mechanical behaviour of zonular fibres greatly affects the accommodation process in mammalian eyes. This paper introduces a detailed measurement procedure for the purpose of obtaining the force-displacement diagram necessary to evaluate the mechanical properties of porcine zonular fibres in situ. It is a complex technique, keeping the integrity of the zonular bundles between the crystalline lens and the ciliary muscle cells. We present a brief description of the measurement procedure both in theory and in practice, along with the force-displacement diagrams acquired from a porcine sample group. The strengths of this newly developed method are the unequivocal force transmission between the sample and the transducer, and the intact connection between the ciliary body and the crystalline lens via zonular fibres. With the aid of these measurements, we define an estimated material model for the zonular apparatus both analytically and using the finite element method. The two different evaluation methods show close agreement in the calculated Young׳s modulus for the zonular fibres. The range of the calculated elastic modulus is 200-250kPa. This new measuring method is adaptable to human specimens. Despite its complexity, the entire procedure and the evaluation part are reproducible. The constitutive model aims to shed light on the mechanics of the accommodation process.
    Journal of Biomechanics 09/2014; · 2.50 Impact Factor
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    ABSTRACT: To describe femtosecond laser cataract surgery and discuss the published peer-reviewed articles to have a fair evaluation of this new technology and its comparisons to conventional phacoemulsification surgery.
    Journal of refractive surgery (Thorofare, N.J.: 1995) 06/2014; 30(6):420-427. · 2.78 Impact Factor
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    ABSTRACT: BRCA1 and BRCA2 are two well-known genes in the background of hereditary breast and ovarian cancer. There is also evidence that several other genes play an important role in the pathogenesis of these two malignancies. Latest population-scaled studies showed that certain mutations in different genes could cause similar risk elevation like BRCA2 mutations. In this study we present a new method to analyse the risk assessment of women to breast and ovarian cancer. Using Haloplex, a novel sequence capture method combined with next-generation sequencing we were able to perform rapid and cost-effective screening of 16 genes that could be associated with an increased risk of breast and ovarian cancer. The rapid and cost effective analysis of this 16-gene cohort can reveal the genetic background of approximately 30 % of hereditary and familiar cases of breast and ovarian cancers. Thus, it opens up a new and high-throughput approach with fast turnaround time to the genetic diagnostics of these disorders and may be helpful to investigate other familial genetic disorders as well.
    Familial Cancer 05/2014; · 1.94 Impact Factor
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    ABSTRACT: According to previous studies, aortic diameter alone seems to be insufficient to predict the event of aortic dissection in Marfan syndrome (MFS). Determining the optimal schedule for preventive aortic root replacement (ARR) aortic growth rate is of importance, as well as family history, however, none of them appear to be decisive. Thus, the aim of this study was to search for potential predictors of aortic dissection in MFS. A Marfan Biobank consisting of 79 MFS patients was established. Thirty-nine MFS patients who underwent ARR were assigned into three groups based on the indication for surgery (dissection, annuloaortic ectasia and prophylactic surgery). The prophylactic surgery group was excluded from the study. Transforming growth factor-beta (TGF-beta) serum levels were measured by ELISA, relative expression of c-Fos, matrix metalloproteinase 3 and 9 (MMP-3 and -9) were assessed by RT-PCR. Clinical parameters, including anthropometric variables - based on the original Ghent criteria were also analyzed. Among patients with aortic dissection, TGF-beta serum level was elevated (43.78 +/- 6.51 vs. 31.64 +/- 4.99 ng/l, p < 0.0001), MMP-3 was up-regulated (Ln2alpha = 1.87, p = 0.062) and striae atrophicae were more common (92% vs. 41% p = 0.027) compared to the annuloaortic ectasia group. We found three easily measurable parameters (striae atrophicae, TGF-beta serum level, MMP-3) that may help to predict the risk of aortic dissection in MFS. Based on these findings a new classification of MFS, that is benign or malignant is also proposed, which could be taken into consideration in determining the timing of prophylactic ARR.
    BMC Cardiovascular Disorders 04/2014; 14(1):47. · 1.50 Impact Factor
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    ABSTRACT: Neurofibromatosis type 1 (NF1) gene exhibits one of the highest spontaneous mutation rates in the human genome. Identification of the NF1 mutation is challenging because the NF1 gene is very large and complex, lacking mutational "hot spots." There is no clustering of mutations, there are several pseudogenes, and a wide spectrum of different types of mutation has been recognized. To date, NF1 mutations or deleted regions have been detected with a number of techniques. With the appearance of next-generation sequencing (NGS) machines, molecular biology is in a new revolutionary phase. Our aim was to work out a method to use the high-throughput NGS machine, Ion Torrent PGM, in diagnostic settings for neurofibromatosis type 1. In our examination, we could reveal 21 distinct variations in NF1 gene in seven patients. This is an absolutely new method for exploring the genetic background of neurofibromatosis type 1 exhibiting the extremely high throughput of NGS in a diagnostic setting.
    Journal of Molecular Neuroscience 03/2014; · 2.76 Impact Factor
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    ABSTRACT: To analyze complications of femtosecond lasers used for cataract surgery. Department of Ophthalmology Semmelweis University, Budapest, Hungary. Retrospective analysis. Intraoperative complications of the first 100 femtosecond laser-assisted (Alcon-Lensx, Inc.) cataract surgeries were collected. Possible complications of femtosecond capsulotomies and their management were also assessed. The complications were as follows: suction break (2%), conjunctival redness or hemorrhage (34%), capsule tags and bridges (20%), anterior tear (4%), miosis (32%), and endothelial damage due to cut within the endothelial layer (3%). There were no cases of capsule blockage or posterior capsule tear. During the learning curve, there was no complication that would require vitrectomy. All complications occurred during the first 100 cases. Femtosecond laser cataract surgery had a learning curve during the first 100 cases. With cautious surgical technique, the complications can be avoided. The femtosecond laser-assisted method was efficient and safe for cataract surgery. Drs. Nagy, T. Juhász, and Slade are consultants to Alcon-Lensx, Inc. No other author has a financial or proprietary interest in any material or method mentioned.
    Journal of Cataract and Refractive Surgery 01/2014; 40(1):20-8. · 2.75 Impact Factor
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    ABSTRACT: Differential diagnosis of adrenocortical adenoma (ACA) and carcinoma is of pivotal clinical relevance, as the prognosis and clinical management of benign and malignant adrenocortical tumors (ACTs) is entirely different. Circulating microRNAs (miRNAs) are promising biomarker candidates of malignancy in several tumors; however, there are still numerous technical problems associated with their analysis. The objective of our study was to investigate circulating miRNAs in ACTs and to evaluate their potential applicability as biomarkers of malignancy. We have also addressed technical questions including the choice of profiling and reference gene used. A total of 25 preoperative plasma samples obtained from patients with ACAs and carcinomas were studied by microarray and quantitative real-time PCR. None of the three miRNAs (hsa-miR-192, hsa-mir-197 and hsa-miR-1281) found as differentially expressed in plasma samples in our microarray screening could be validated by quantitative real-time PCR. In contrast, of the selected eight miRNAs reported in the literature as differentially expressed in ACT tissues, five (hsa-miR-100, hsa-miR-181b, hsa-miR-184, hsa-miR-210 and hsa-miR-483-5p) showed a statistically significant overexpression in adrenocortical cancer vs adenoma when normalized on hsa-miR-16 as a reference gene. Receiver operator characteristic analysis of data revealed that the combination of dCThsa-miR-210 - dCThsa-miR-181b and dCThsa-miR-100/dCThsa-miR-181b showed the highest diagnostic accuracy (area under curve 0.87 and 0.85, respectively). In conclusion, we have found significant differences in expression of circulating miRNAs between ACAs and carcinomas, but their diagnostic accuracy is not yet high enough for clinical application. Further studies on larger cohorts of patients are needed to assess the diagnostic and prognostic potential application of circulating miRNA markers.Laboratory Investigation advance online publication, 16 December 2013; doi:10.1038/labinvest.2013.148.
    Laboratory Investigation 12/2013; · 3.96 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the balance and changes of corneal higher order aberrations (HOAs) after photorefractive keratectomy (PRK). Myopic and myopic-astigmatic patients (89 eyes of 48 patients) were enrolled in this study. A PRK was performed using an Asclepion Meditec MEL 80 G flying-spot excimer laser. The mean ablation depth and diameter were 76.78 μm (±19.40 μm) and 6.0 mm (±0.06 mm), respectively. Before and 1 year after the surgery, uncorrected and best spectacle-corrected visual acuities were determined. Wavefront aberrations of the anterior [root mean square (RMS)-HOA anterior], posterior (RMS-HOA posterior), and total cornea (RMS-HOA total) were measured using a Scheimpflug Camera. Linear piecewise regression analysis was used for correlations between the ablation depth and aberration of the anterior corneal surface. The follow-up time was 1 year. At baseline, RMS-HOA anterior proved to be significantly higher compared with RMS-HOA total (P < 0.001). After the PRK was performed, the RMS-HOA anterior (P < 0.001) and RMS-HOA total values (P < 0.001) increased significantly; however, RMS-HOA posterior values (P = 0.12) remained stable. Above an ablation depth of 76.78 μm, the RMS-HOA anterior increased 2.4-fold. Uncorrected and best spectacle-corrected visual acuities were 1.0 (20/20) in 95.5% and 98.8% of the patients 1 year postoperatively. Aberrations of the posterior corneal surface seem to compensate for wavefront alterations of the anterior cornea, decreasing the amount of wavefront error regarding the total cornea in myopic patients. PRK induced increased HOAs with respect to the anterior corneal surface; however, the posterior surface remained stable. The increase in the HOAs was measured to be significantly larger above 76.78 μm photoablation depth.
    Cornea 12/2013; · 1.75 Impact Factor
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    ABSTRACT: Analysis of the femtosecond laser refractive lens surgery corneal incision configuration and corneal higher-order aberration (HOA) effect from the first postoperative day. High-resolution anterior segment optical coherence tomography was used to assess 20 eyes undergoing femtosecond laser refractive lens surgery with 2.2-mm minimal incision. The primary incision (tri-planar) actual length, cord length, surface angle, surface irregularity, and regional pachymetry values and the secondary incision (uni-planar) length, angle, surface irregularity, and pachymetry values were analyzed. Hartmann-Shack aberrometer was used to assess corneal HOAs to correlate the effect. Assessment was done preoperatively and 1 month postoperatively. The actual length, cord length, and surface angle means for the primary incision in the first postoperative day and month were 1.50 ± 0.1 and 1.47 ± 0.2 mm (P = .5), 1.41 ± 0.1 and 1.42 ± 0.2 mm (P = .8), and 27° ± 4° and 23° ± 5° (P = .07), respectively. The length and surface angle for the secondary incision in the first postoperative day and month were 1.17 ± 0.01 and 1.04 ± 0.1 mm (P = .05) and 52° ± 3° and 42° ± 5° (P = .007). The regional pachymetry values for the primary and secondary incisions were significantly increased in the first postoperative day and then significantly decreased after 1 month. All irregularities occurred in the posterior surface (endothelium): 2 cases of posterior gap (first day) and 1 case of posterior retraction (first month). The HOAs had not significantly changed preoperatively and after 1 month. The femtosecond laser refractive lens surgery incision is stable and does not significantly change the HOA. [J Refract Surg. 2013;29(9):590-595.].
    Journal of refractive surgery (Thorofare, N.J.: 1995) 09/2013; 29(9):590-5. · 2.78 Impact Factor
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    ABSTRACT: Background: MicroRNAs are involved in the pathogenesis of several tumors, and several studies have been performed on the microRNA profile of adrenocortical tumors to date. The pathways affected by these microRNAs, however, have not been analyzed yet by a systematic approach. Aim: To perform an in silico bioinformatics analysis of microRNAs commonly altered in at least two studies and to decipher the pathways affected by microRNAs in adrenocortical tumors. Methods: Datasets on microRNA and mRNA expression have been retrieved from five and three studies, respectively. MicroRNA mRNA targets have been identified by our tissue specific target prediction pipeline, and mRNAs have been subjected to Ingenuity Pathway Analysis. Results: 39 microRNAs were identified as commonly altered in two studies. Altogether 49817 mRNA targets have been found for these microRNAs. 178 significant pathways associating with these have been identified that were found in all studies. We have selected 12 pathways involving retinoic acid signaling (LPS/IL-1 mediated inhibition of RXR function, PPARα/RXRα activation, RAR activation and PPAR signaling pathways) and cell cycle alterations (aryl hydrocarbon receptor signaling, GADD45 signaling, integrin signaling, G2/M DNA damage checkpoint regulation, cyclins and cell cycle regulation and cell cycle control of chromosomal replication pathways) as these have been also established in our previous study on the functional genomics meta-analysis of adrenocortical tumors. Several microRNAs have been identified that could affect these pathways. Conclusions: MicroRNAs might affect several pathogenic pathways in adrenocortical tumors. Validation studies are required to confirm the biological relevance of these findings.
    Journal of endocrinological investigation 07/2013; · 1.65 Impact Factor
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    ABSTRACT: The currently available medical treatment options of adrenocortical cancer (ACC) are limited. In our previous meta-analysis of adrenocortical tumor genomics data, ACC was associated with reduced retinoic acid production and retinoid X receptor-mediated signaling. Our objective has been to study the potential antitumoral effects of 9-cis retinoic acid (9-cisRA) on the ACC cell line NCI-H295R and in a xenograft model. Cell proliferation, hormone secretion, and gene expression have been studied in the NCI-H295R cell line. A complex bioinformatics approach involving pathway and network analysis has been performed. Selected genes have been validated by real-time qRT-PCR. Athymic nude mice xenografted with NCI-H295R have been used in a pilot in vivo xenograft model. 9-cisRA significantly decreased cell viability and steroid hormone secretion in a concentration- and time-dependent manner in the NCI-H295R cell line. Four major molecular pathways have been identified by the analysis of gene expression data. Ten genes have been successfully validated involved in: (1) steroid hormone secretion (HSD3B1, HSD3B2), (2) retinoic acid signaling (ABCA1, ABCG1, HMGCR), (3) cell-cycle damage (GADD45A, CCNE2, UHRF1), and the (4) immune response (MAP2K6, IL1R2). 9-cisRA appears to directly regulate the cell cycle by network analysis. 9-cisRA also reduced tumor growth in the in vivo xenograft model. In conclusion, 9-cisRA might represent a promising new candidate in the treatment of hormone-secreting adrenal tumors and adrenocortical cancer.
    Cellular and Molecular Life Sciences CMLS 06/2013; · 5.86 Impact Factor
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    Rheumatology International 05/2013; · 1.63 Impact Factor
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    ABSTRACT: AIM: The effects of vitamin D3 have been investigated on various tumors, including colorectal cancer (CRC). 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1), the enzyme that inactivates the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25-D3), is considered to be the main enzyme determining the biological half-life of 1,25-D3. During colorectal carcinogenesis, the expression and concentration of CYP24A1 increases significantly, suggesting that this phenomenon could be responsible for the proposed efficacy of 1,25-D3 in the treatment of CRC. The aim of this study was to investigate the anti-tumor effects of vitamin D3 on the human CRC cell line Caco-2 after inhibition of the cytochrome P450 component of CYP24A1 activity. METHODS: We examined the expression of CYP24A1 mRNA and the effects of 1,25-D3 on the cell line Caco-2 after inhibition of CYP24A1. Cell viability and proliferation were determined by means of sulforhodamine-B staining and bromodeoxyuridine incorporation, respectively, while cytotoxicity was estimated via the lactate dehydrogenase content of the cell culture supernatant. CYP24A1 expression was measured by real-time reverse transcription polymerase chain reaction. A number of tetralone compounds were synthesized to investigate their CP24A1 inhibitory activity. RESULTS: In response to 1,25-D3, CYP24A1 mRNA expression was enhanced significantly, in a time- and dose-dependent manner. Caco-2 cell viability and proliferation were not influenced by the administration of 1,25-D3 alone, but were markedly reduced by co-administration of 1,25-D3 and KD-35, a CYP24A1-inhibiting tetralone. Our data suggest that the mechanism of action of co-administered KD-35 and 1,25-D3 does not involve a direct cytotoxic effect, but rather the inhibition of cell proliferation. CONCLUSION: These findings demonstrate that the selective inhibition of CYP24A1 by compounds such as KD-35 may be a new approach for enhancement of the anti-tumor effect of 1,25-D3 on CRC.
    World Journal of Gastroenterology 05/2013; 19(17):2621-2628. · 2.43 Impact Factor
  • Journal of Cataract and Refractive Surgery 04/2013; 39(4):657-9. · 2.75 Impact Factor
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    ABSTRACT: Carcinoids are rare tumors originating from neuroendocrine cells. A large proportion of these tumors produce serotonin and other biologically active hormones which may produce carcinoid syndrome characterized by flushing, diarrhoea and bronchospasm. Carcinoid heart disease, a rare complication of carcinoid syndrome, may itself have a great impact on life expectancy of patients with carcinoid syndrome. The authors present a case history of a patients with carcinoid heart disease and they review the symptoms, diagnosis and therapeutic options of this rare complication of carcinoid syndrome. Orv. Hetil., 2013, 154, 546-550.
    Orvosi Hetilap 04/2013; 154(14):546-50.
  • Endocrine Abstracts. 03/2013;
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    ABSTRACT: Glucocorticoids play an important role in the regulation of carbohydrate and amino acid metabolism, they modulate the function of the immune system, and contribute to stress response. Increased and decreased production of glucocorticoids causes specific diseases. In addition to systemic hypo- or hypercortisolism, alteration of local synthesis and metabolism of cortisol may result in tissue-specific hypo- or hypercortisolism. One of the key enzymes participating in the local synthesis and metabolism of cortisol is the 11β-hydroxysteroid dehydrogenase enzyme. Two isoforms, type 1 and type 2 enzymes are located in the endoplasmic reticulum and catalyze the interconversion of hormonally active cortisol and inactive cortisone. The type 1 enzyme mainly works as an activator, and it is responsible for the generation of cortisol from cortisone in liver, adipose tissue, brain and bone. The gene encoding this enzyme is located on chromosome 1. The authors review the physiological and pathophysiological processes related to the function of the type 1 11β-hydroxysteroid dehydrogenase enzyme. They summarize the potential significance of polymorphic variants of the enzyme in clinical diseases as well as knowledge related to inhibitors of enzyme activity. Although further studies are still needed, inhibition of the enzyme activity may prove to be an effective tool for the treatment of several diseases such as obesity, osteoporosis and type 2 diabetes. Orv. Hetil., 2013, 154, 283-293.
    Orvosi Hetilap 02/2013; 154(8):283-93.
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    ABSTRACT: To report the anterior segment imaging characteristics after femtosecond laser assisted cataract surgery. Cataract surgery was performed with the LenSx femtosecond laser (Alcon-LenSx Inc., Aliso Viejo, CA) in 40 eyes of 40 patients. The laser was programmed to perform a 4.5-mm capsulorhexis, a cross-pattern fragmentation of the nucleus, a 2.8-mm main incision, and a 1.0-mm side-port incision. The anterior segment was then analyzed using the Visante OCT anterior segment program (Zeiss-Meditec AG, Jena, Germany). The preoperatively set treatment parameters correlated well with the achieved results. For the capsulorhexis, the femtosecond laser cut was programmed to start 350 μm behind the anterior lens capsule and OCT measured 377 ± 55.3 μm. Nucleus fragmentation was programmed to start 750 μm in front of the posterior capsule and end 550 μm behind the anterior capsule, and OCT measured 794 ± 111 and 568 ± 147 μm, respectively. The diameter of the capsulorhexis measured by OCT was 4.54 ± 0.2 mm, compared to the 4.5 mm programmed. Anterior segment OCT imaging was able to detect the tissue changes within the lens after femtosecond laser capsulorhexis and nucleus fragmentation. The measured values correlated well with the planned treatment parameters.
    Journal of refractive surgery (Thorofare, N.J.: 1995) 02/2013; 29(2):110-2. · 2.78 Impact Factor
  • Journal of refractive surgery (Thorofare, N.J.: 1995) 01/2013; 29(1):8. · 2.78 Impact Factor

Publication Stats

597 Citations
194.10 Total Impact Points

Institutions

  • 2001–2014
    • Semmelweis University
      • • Department of Ophthalmology
      • • First Department of Internal Medicine
      Budapeŝto, Budapest, Hungary
  • 2007
    • Hungarian Academy of Sciences
      Budapeŝto, Budapest, Hungary