Balazs Dezso
Research interests
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InterestsImmunoregulation, Inflammation, Macrophage, Atherosclerosis
Publications
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4.60Impact points
Carboxypeptidase-M is regulated by lipids and CSFs in macrophages and dendritic cells and expressed selectively in tissue granulomas and foam cells.
Laboratory investigation; a journal of technical methods and pathology. 12/2011; 92(3):345-61.
Granulomatous inflammations, characterized by the presence of activated macrophages (MAs) forming epithelioid cell (EPC) clusters, are usually easy to recognize. However, in ambiguous cases the use of a MA marker that expresses selectively in EPCs may be needed. Here, we report that carboxypeptidase... [more] Granulomatous inflammations, characterized by the presence of activated macrophages (MAs) forming epithelioid cell (EPC) clusters, are usually easy to recognize. However, in ambiguous cases the use of a MA marker that expresses selectively in EPCs may be needed. Here, we report that carboxypeptidase-M (CPM), a MA-differentiation marker, is preferentially induced in EPCs of all granuloma types studied, but not in resting MAs. As CPM is not expressed constitutively in MAs, this allows utilization of CPM-immunohistochemistry in diagnostics of minute granuloma detection when dense non-granulomatous MAs are also present. Despite this rule, hardly any detectable CPM was found in advanced/active tubercle caseous disease, albeit in early tuberculosis granuloma, MAs still expressed CPM. Indeed, in vitro both the CPM-protein and -mRNA became downregulated when MAs were infected with live mycobacteria. In vitro, MA-CPM transcript is neither induced remarkably by interferon-γ, known to cause classical MA activation, nor by IL-4, an alternative MA activator. Instead, CPM is selectively expressed in lipid-laden MAs, including the foam cells of atherosclerotic plaques, xanthomatous lesions and lipid pneumonias. By using serum, rich in lipids, and low-density lipoprotein (LDL) or VLDL, CPM upregulation could be reproduced in vitro in monocyte-derived MAs both at transcriptional and protein levels, and the increase is repressed under lipid-depleted conditions. The microarray analyses support the notion that CPM induction correlates with a robust progressive increase in CPM gene expression during monocyte to MA maturation and dendritic cell (DC) differentiation mediated by granulocyte-MA-colony-stimulating factor+IL-4. M-CSF alone also induced CPM. These results collectively indicate that CPM upregulation in MAs is preferentially associated with increased lipid uptake, and exposure to CSF, features of EPCs, also. Therefore, CPM-immunohistochemistry is useful for granuloma and foam MA detections in tissue sections. Furthermore, the present data offer CPM for the first time to be a novel marker and cellular player in lipid uptake and/or metabolism of MAs by promoting foam cell formation.
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5.65Impact points
Peroxisome proliferator-activated receptor γ-regulated cathepsin D is required for lipid antigen presentation by dendritic cells.
Journal of immunology (Baltimore, Md. : 1950). 07/2011; 187(1):240-7.
It is well established that dendritic cells (DCs) take up, process, and present lipid Ags in complex with CD1d molecules to invariant NKT cells. The lipid-activated transcription factor, peroxisome proliferator-activated receptor γ (PPARγ), has previously been shown to regulate CD1d expression in hu... [more] It is well established that dendritic cells (DCs) take up, process, and present lipid Ags in complex with CD1d molecules to invariant NKT cells. The lipid-activated transcription factor, peroxisome proliferator-activated receptor γ (PPARγ), has previously been shown to regulate CD1d expression in human monocyte-derived DCs, providing a link between lipid metabolism and lipid Ag presentation. We report that PPARγ regulates the expression of a lysosomal protease, cathepsin D (CatD), in human monocyte-derived DCs. Inhibition of CatD specifically reduced the expansion of invariant NKT cells and furthermore resulted in decreased maturation of saposins, a group of lipid transfer proteins required for lysosomal lipid Ag processing and loading. These results reveal a novel mechanism of lipid Ag presentation and identify CatD as a key component of this machinery and firmly place PPARγ as the transcriptional regulator linking lipid metabolism and lipid Ag processing.
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3.08Impact points
Receptors for luteinizing hormone-releasing hormone (LHRH) in benign prostatic hyperplasia (BPH) as potential molecular targets for therapy with LHRH antagonist cetrorelix.
The Prostate. 04/2011; 71(5):445-52.
The majority of men will develop symptoms of benign prostatic hyperplasia (BPH) after 70 years of age. Various studies indicate that antagonists of LHRH, such as cetrorelix, exert direct inhibitory effects on BPH mediated by specific LHRH receptors. Our aim was to investigate the mRNA for LHRH and L... [more] The majority of men will develop symptoms of benign prostatic hyperplasia (BPH) after 70 years of age. Various studies indicate that antagonists of LHRH, such as cetrorelix, exert direct inhibitory effects on BPH mediated by specific LHRH receptors. Our aim was to investigate the mRNA for LHRH and LHRH receptors and the expression of LHRH receptors in specimens of human BPH. The expression of mRNA for LHRH (n=35) and LHRH receptors (n=55) was investigated by RT-PCR in surgical specimens of BPH, using specific primers. The characteristics of binding sites for LHRH on 20 samples were determined by ligand competition assays. The LHRH receptor expression was also examined in 64 BPH specimens by immunohistochemistry. PCR products for LHRH were found in 18 of 35 (51%) BPH tissues and mRNA for LHRH receptors was detected in 39 of 55 (71%) BPH specimens. Eighteen of 20 (90%) samples showed a single class of high affinity binding sites for [D-Trp(6) ]LHRH with a mean K(d) of 4.04 nM and a mean B(max) of 527.6 fmol/mg membrane protein. LHRH antagonist cetrorelix showed high affinity binding to LHRH receptors in BPH. Positive immunohistochemical reaction for LHRH receptors was present in 42 of 64 (67%) BPH specimens. A high incidence of LHRH receptors in BPH supports the use of LHRH antagonists such as cetrorelix, for treatment of patients with lower urinary tract symptoms from BPH.
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3.54Impact points
miR-126 inhibits proliferation of small cell lung cancer cells by targeting SLC7A5.
FEBS letters. 03/2011; 585(8):1191-6.
Despite intensive efforts to improve therapies, small cell lung cancer (SCLC) still has a dismal median survival of 18 months. Since miR-126 is under-expressed in the majority of SCLC tumors, we investigated the effect of miR-126 overexpression on the proliferation and cell cycle distribution of H69... [more] Despite intensive efforts to improve therapies, small cell lung cancer (SCLC) still has a dismal median survival of 18 months. Since miR-126 is under-expressed in the majority of SCLC tumors, we investigated the effect of miR-126 overexpression on the proliferation and cell cycle distribution of H69 cells. Our results demonstrate that miR-126 inhibits proliferation of H69 cells, by delaying the cells in the G1 phase. Short interfering RNA (siRNA) mediated suppression of SLC7A5, a predicted target of mir-126, has the same effect on H69 cells. We also show for the first time that SLC7A5 is a direct target of miR-126.
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1.94Impact points
Chronic obstructive pulmonary disease-specific gene expression signatures of alveolar macrophages as well as peripheral blood monocytes overlap and correlate with lung function.
Respiration; international review of thoracic diseases. 03/2011; 81(6):499-510.
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by progressive airflow limitation and significant extrapulmonary (systemic) effects that lead to co-morbid conditions, though the pathomechanism of COPD is largely undetermined. Alveolar macrophages (AM) der... [more] Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by progressive airflow limitation and significant extrapulmonary (systemic) effects that lead to co-morbid conditions, though the pathomechanism of COPD is largely undetermined. Alveolar macrophages (AM) derived from peripheral monocytes (MO) appear to play a key role in initiating and/or sustaining disease progression. To identify disease- and cell type-specific gene expression profiles and potential overlaps in those in order to diagnose COPD, characterize its progression and determine the effect of drug treatment. Global gene expression analysis was used for primary screening in order to obtain expression signatures of AMs and circulating MOs of COPD patients and healthy controls. The results of microarray analyses of AMs (20 controls and 26 COPD patients) and MOs (16 controls and 22 COPD patients) were confirmed and validated by real-time quantitative polymerase chain reaction. We have identified gene sets specifically associated with COPD in AMs and MOs. There were overlapping genes between the two cell types. Our data also show that COPD-specific gene expression signatures in AMs and MOs correlate with percent of predicted FEV(1). Disease-specific and overlapping gene expression signatures can be defined in lung-derived macrophages and also in circulating monocytes. Some of the validated expression changes in both cell types correlate with lung function and therefore could serve as biomarkers of disease progression.
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2.84Impact points
Analyses of association between PPAR gamma and EPHX1 polymorphisms and susceptibility to COPD in a Hungarian cohort, a case-control study.
BMC medical genetics. 11/2010; 11:152.
In addition to smoking, genetic predisposition is believed to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Genetic association studies of new candidate genes in COPD may lead to improved understanding of the pathogenesis of the disease. Two proposed casual s... [more] In addition to smoking, genetic predisposition is believed to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Genetic association studies of new candidate genes in COPD may lead to improved understanding of the pathogenesis of the disease. Two proposed casual single nucleotide polymorphisms (SNP) (rs1051740, rs2234922) in microsomal epoxide hydrolase (EPHX1) and three SNPs (rs1801282, rs1800571, rs3856806) in peroxisome proliferator-activated receptor gamma (PPARG), a new candidate gene, were genotyped in a case-control study (272 COPD patients and 301 controls subjects) in Hungary. Allele frequencies and genotype distributions were compared between the two cohorts and trend test was also used to evaluate association between SNPs and COPD. To estimate the strength of association, odds ratios (OR) (with 95% CI) were calculated and potential confounding variables were tested in logistic regression analysis. Association between haplotypes and COPD outcome was also assessed. The distribution of imputed EPHX1 phenotypes was significantly different between the COPD and the control group (P = 0.041), OR for the slow activity phenotype was 1.639 (95% CI = 1.08- 2.49; P = 0.021) in our study. In logistic regression analysis adjusted for both variants, also age and pack-year, the rare allele of His447His of PPARG showed significant association with COPD outcome (OR = 1.853, 95% CI = 1.09-3.14, P = 0.0218). In haplotype analysis the GC haplotype of PPARG (OR = 0.512, 95% CI = 0.27-0.96, P = 0.035) conferred reduced risk for COPD. The "slow" activity-associated genotypes of EPHX1 were associated with increased risk of COPD. The minor His447His allele of PPARG significantly increased; and the haplotype containing the minor Pro12Ala and the major His447His polymorphisms of PPARG decreased the risk of COPD.
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20.59Impact points
STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Immunity. 11/2010; 33(5):699-712.
Peroxisome proliferator-activated receptor γ (PPARγ) is a lipid-activated transcription factor regulating lipid metabolism and inflammatory response in macrophages and dendritic cells (DCs). These immune cells exposed to distinct inflammatory milieu show cell type specification as a result of altere... [more] Peroxisome proliferator-activated receptor γ (PPARγ) is a lipid-activated transcription factor regulating lipid metabolism and inflammatory response in macrophages and dendritic cells (DCs). These immune cells exposed to distinct inflammatory milieu show cell type specification as a result of altered gene expression. We demonstrate here a mechanism how inflammatory molecules modulate PPARγ signaling in distinct subsets of cells. Proinflammatory molecules inhibited whereas interleukin-4 (IL-4) stimulated PPARγ activity in macrophages and DCs. Furthermore, IL-4 signaling augmented PPARγ activity through an interaction between PPARγ and signal transducer and activators of transcription 6 (STAT6) on promoters of PPARγ target genes, including FABP4. Thus, STAT6 acts as a facilitating factor for PPARγ by promoting DNA binding and consequently increasing the number of regulated genes and the magnitude of responses. This interaction, underpinning cell type-specific responses, represents a unique way of controlling nuclear receptor signaling by inflammatory molecules in immune cells.
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1.18Impact points
Differentially expressed microRNAs in small cell lung cancer.
Experimental lung research. 10/2009; 35(8):646-64.
Expression of microRNAs (miRNAs) is characteristically altered in cancer, and they may play a role in cancer development and progression. The authors performed microarray and real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analyses to determine the miRNA expression pr... [more] Expression of microRNAs (miRNAs) is characteristically altered in cancer, and they may play a role in cancer development and progression. The authors performed microarray and real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analyses to determine the miRNA expression profile of primary small cell lung cancer. Here we show that at least 24 miRNAs are differentially expressed between normal lung and primary small cell lung cancer (SCLC) tumors. These include miR-301, miR-183/96/182, miR-126, and miR-223, which are microRNAs deregulated in other tumor types as well; and other miRNAs, such as miR-374 and miR-210, not previously reported in association with lung cancer. The aberrant miRNA profile of SCLC may offer new insights in the biology of this aggressive tumor, and could potentially provide novel diagnostic markers.
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2.26Impact points
The presence of carboxypeptidase-M in tumour cells signifies epidermal growth factor receptor expression in lung adenocarcinomas: the coexistence predicts a poor prognosis regardless of EGFR levels.
Journal of cancer research and clinical oncology. 04/2008; 134(4):439-51.
PURPOSE: Carboxypeptidase-M (CPM) is a membrane-bound peptidase that metabolizes peptides, and is present in pneumocytes. CPM hydrolyses the C-terminal arginine of epidermal growth factor (EGF) resulting in des-Arg53-EGF which binds to the EGF receptor (EGFR) with an equal or greater affinity than n... [more] PURPOSE: Carboxypeptidase-M (CPM) is a membrane-bound peptidase that metabolizes peptides, and is present in pneumocytes. CPM hydrolyses the C-terminal arginine of epidermal growth factor (EGF) resulting in des-Arg53-EGF which binds to the EGF receptor (EGFR) with an equal or greater affinity than native EGF. Therefore, this study focused on the possible presence of CPM in human lung adenocarcinomas (ADC) and evaluated the relationship between CPM and EGFR by assessing the impact of expressions on patient clinical outcome. METHODS: This is a retrospective study of 110 patients who underwent resection of the primary tumour (92) or metastatic tissues (18) for treatment or diagnosis. Immunohistochemistry (IHC) for CPM and EGFR was made in serial sections using standard methods. RESULTS: This study demonstrates for the first time that 23.6% of ADCs express carboxypeptidase-M (26/110), mainly in membrane-bound forms. The amounts and the extent of CPM within tumours vary from low levels to obviously overexpressed forms. The immunohistochemical positivity (+) for CPM in ADCs negatively correlated with disease survival. In addition, 80% of CPM+ adenocarcinomas (21/26) showed a coexpression with EGFR suggesting a high prevalence for coexistence. The follow up data indicated a significantly shorter 5-year survival time for patients with CPM+-EGFR+ (double-positive) tumours compared to those harbouring neoplasias negative for both proteins (9.5 vs. 60.4% survivals, P < 0.001). CONCLUSION: The fact that CPM+ ADCs often co-express with EGFR suggests a functional-regulatory link between these proteins which might have therapeutical consequences. The present novel data could lead to improved IHC tests in lung adenocarcinomas for EGFR expression.
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[Successful surgical removal of adrenocortical carcinoma growing into the inferior vena cava and the right atrium]
Magyar sebészet. 03/2008; 61(1):38-41.
The authors discuss a case of a 47-year old female, who underwent a left adrenalectomy for adrenocortical carcinoma. A few months later the tumour locally recurred and spread through the inferior vena cava into the right atrium. The tumour thrombus almost completely occluded the lumen of the inferio... [more] The authors discuss a case of a 47-year old female, who underwent a left adrenalectomy for adrenocortical carcinoma. A few months later the tumour locally recurred and spread through the inferior vena cava into the right atrium. The tumour thrombus almost completely occluded the lumen of the inferior vena cava resulting in significant hepatic congestion, ascites and oedema of the lower extremities. The whole tumour thrombus was successfully removed through the right atrium under visual control using extracorporeal circulation in deep hypothermic (20 degrees C) circulatory arrest. The locally recurred tumour from the site of the left adrenal gland was also removed a month later. The histological examination revealed moderately differentiated adrenocortical carcinoma with a proliferation rate higher than 10%. Thereafter, patient underwent adjuvant oncological therapy and she has been disease free in the last one year. Clinical data suggest that tumour thrombus of various origin that grow into the inferior vena cava can be safely removed using extracorporeal circulation (with or without cardiac arrest), and in such cases, when the primary tumour is resectable, the prognosis is relatively good.
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1.94Impact points
Natural course of isolated pulmonary langerhans' cell histiocytosis in a toddler. 3-year follow-up.
Respiration; international review of thoracic diseases. 02/2008; 75(2):215-20.
Isolated pulmonary Langerhans' cell histiocytosis (LCH) is distinctly rare under the age of 15 years, since the majority of patients are young adult males with heavy smoking habits. Isolated pulmonary involvement suggests that antigens inhaled from cigarette smoke are involved. Here we present a... [more] Isolated pulmonary Langerhans' cell histiocytosis (LCH) is distinctly rare under the age of 15 years, since the majority of patients are young adult males with heavy smoking habits. Isolated pulmonary involvement suggests that antigens inhaled from cigarette smoke are involved. Here we present a case of LCH restricted to the lungs in a toddler whose parents were heavy smokers. Since LCH was not medically treated for 3 years due to parental refusal, the disease can be regarded as having followed its natural course. During the 3-year follow-up, the disease progressed to severe pulmonary fibrosis resulting in honeycomb lungs. Based on the comparative immunohistochemical analyses of the cells obtained from bronchoalveolar lavages during the disease course, it appears that the evolution of fibrosis is rather a result from the accumulating alveolar macrophages than from the persistence of the Langerhans' cells. Passive cigarette smoking may be considered a significant risk factor in both the pathogenesis and development of pulmonary LCH in a small child.
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0.90Impact points
Catastrophic antiphospholipid syndrome (Asherson's syndrome) associated with cytokeratin 7-positive endometrial cancer.
The Israel Medical Association journal : IMAJ. 01/2008; 9(12):891-3.
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10.56Impact points
Differentiation of CD1a- and CD1a+ monocyte-derived dendritic cells is biased by lipid environment and PPARgamma.
Blood. 02/2007; 109(2):643-52.
Accumulating data have shown that the microenvironment of dendritic cells modulates subtype differentiation and CD1 expression, but the mechanisms by which exogenous factors confer these effects are poorly understood. Here we describe the dependence of CD1a- monocyte-derived dendritic cell (moDC) de... [more] Accumulating data have shown that the microenvironment of dendritic cells modulates subtype differentiation and CD1 expression, but the mechanisms by which exogenous factors confer these effects are poorly understood. Here we describe the dependence of CD1a- monocyte-derived dendritic cell (moDC) development on lipids associated with the expression of peroxisome proliferator-activated receptor-gamma (PPARgamma). We also show the consecutive differentiation of immature CD1a-PPARgamma+ moDCs to CD1a+PPARgamma- cells limited by serum lipoproteins and terminated by proinflammatory cytokines. Immature CD1a- moDCs possess higher internalizing capacity than CD1a+ cells, whereas both activated subtypes have similar migratory potential but differ in their cytokine and chemokine profiles, which translates to distinct T-lymphocyte-polarizing capacities. CD1a+ moDCs stand out by their capability to secrete high amounts of IL-12p70 and CCL1. As lipoproteins skew moDC differentiation toward the generation of CD1a-PPARgamma+ cells and inhibit the development of CD1a+PPARgamma- cells, we suggest that the uptake of lipids results in endogenous PPARgamma agonists that induce a cascade of gene transcription coordinating lipid metabolism, the expression of lipid-presenting CD1 molecules, subtype dichotomy, and function. The presence of CD1a-PPARgamma+ and CD1a+PPARgamma- DCs in lymph nodes and in pulmonary Langerhans cell histiocytosis confirms the functional relevance of these DC subsets in vivo.
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14.51Impact points
PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells.
The Journal of experimental medicine. 11/2006; 203(10):2351-62.
Dendritic cells (DCs) expressing CD1d, a molecule responsible for lipid antigen presentation, are capable of enhancing natural killer T (iNKT) cell proliferation. The signals controlling CD1 expression and lipid antigen presentation are poorly defined. We have shown previously that stimulation of th... [more] Dendritic cells (DCs) expressing CD1d, a molecule responsible for lipid antigen presentation, are capable of enhancing natural killer T (iNKT) cell proliferation. The signals controlling CD1 expression and lipid antigen presentation are poorly defined. We have shown previously that stimulation of the lipid-activated transcription factor, peroxisome proliferator-activated receptor (PPAR)gamma, indirectly regulates CD1d expression. Here we demonstrate that PPARgamma, turns on retinoic acid synthesis by inducing the expression of retinol and retinal metabolizing enzymes such as retinol dehydrogenase 10 and retinaldehyde dehydrogenase type 2 (RALDH2). PPARgamma-regulated expression of these enzymes leads to an increase in the intracellular generation of all-trans retinoic acid (ATRA) from retinol. ATRA regulates gene expression via the activation of the retinoic acid receptor (RAR)alpha in human DCs, and RARalpha acutely regulates CD1d expression. The retinoic acid-induced elevated expression of CD1d is coupled to enhanced iNKT cell activation. Furthermore, in vivo relevant lipids such as oxidized low-density lipoprotein can also elicit retinoid signaling leading to CD1d up-regulation. These data show that regulation of retinoid metabolism and signaling is part of the PPARgamma-controlled transcriptional events in DCs. The uncovered mechanisms allow the DCs to respond to altered lipid homeostasis by changing CD1 gene expression.
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1.49Impact points
Pulmonary arterial hypertension in mixed connective tissue disease: successful treatment with Iloprost.
Rheumatology international. 02/2006; 26(3):264-9.
This paper describes a 61-year-old woman who presented with mixed connective tissue disease, which was complicated by the development of pulmonary arterial hypertension (PAH). Her condition worsened rapidly, with development of haemopthysis, tachypnoe and cardiac arrest. Doppler echocardiography sho... [more] This paper describes a 61-year-old woman who presented with mixed connective tissue disease, which was complicated by the development of pulmonary arterial hypertension (PAH). Her condition worsened rapidly, with development of haemopthysis, tachypnoe and cardiac arrest. Doppler echocardiography showed a high systolic pulmonary arterial pressure (98 mmHg), confirmed by the right heart catheterization. Vasculopathy of the pulmonary artery vessels was detected following open lung biopsy. No pulmonary embolism was found. Because of suspicion of flare of her underlying disease, which leads to PAH, immunosuppressive treatment was started with high doses of corticosteroid and cyclophosphamide, in combination with the prostacyclin analogue, Iloprost, and low molecular weight heparin. The therapy resulted in slow recovery over 6 weeks, with control echocardiography showing normalization of the high pulmonary pressure, and the patient being capable of returning to everyday activities.
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[Reclassification of gastrointestinal mesenchymal tumors]
Magyar onkologia. 02/2006; 50(4):287-92.
A retrospective (1985-2005) multicentric evaluation of the pathological diagnoses of GIST (gastrointestinal stromal tumor) in Hungary was performed. A large cohort of 463 patients with abdominal mesenchymal tumors was reevaluated with the help of immunohistochemistry for CD117, CD34, desmin and S100... [more] A retrospective (1985-2005) multicentric evaluation of the pathological diagnoses of GIST (gastrointestinal stromal tumor) in Hungary was performed. A large cohort of 463 patients with abdominal mesenchymal tumors was reevaluated with the help of immunohistochemistry for CD117, CD34, desmin and S100. Prognostic groups have been established based on international criteria. Two hundred fifty five GISTs have been found in 245 patients during the evaluated period. Beside GIST, 81 leiomyogenic and 25 neurogenic tumors were the primary pathological diagnosis and in 74/255 cases the primary diagnosis was a benign tumor. In our cohort high-risk GIST cases were found to be the predominant. Based on our experience, in case of abdominal tumors of uncertain localization, immunohistochemical markers of CD117, CD34, S100 and desmin provide a proper tool for precise identification of the tumor entity including GIST.
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[Interstitial lung disease in mixed connective tissue disease]
Orvosi hetilap. 12/2005; 146(48):2435-43.
INTRODUCTION: The authors analyzed the incidence of interstitial lung disease in mixed connective tissue disease. They were seeking an answer to the following problems: the nature of the pathological course of mixed connective tissue disease complicated by and the therapy to be used in interstitial ... [more] INTRODUCTION: The authors analyzed the incidence of interstitial lung disease in mixed connective tissue disease. They were seeking an answer to the following problems: the nature of the pathological course of mixed connective tissue disease complicated by and the therapy to be used in interstitial lung disease. PATIENTS AND METHODS: 179 patients were followed up during a period of 15.9 +/- 6.1 years. Interstitial lung disease was diagnosed using high resolution computed tomography. The diagnosis of interstitial lung disease was not obvious in 5 patients thus open lung biopsy was performed, which confirmed common interstitial pneumonitis. The patients were followed-up, and the data of computed tomography and respiratory function tests were detected 6 months, and then 4 years after the acute lung disease complicated by mixed connective tissue disease. RESULTS: Out of the 179 mixed connective tissue disease patients 96 (53.6%) had interstitial lung disease. The onset of interstitial lung disease was the most frequent in the 2-4 years of the disease. Four years after the first appearance of interstitial lung disease severe fibrosis was diagnosed in 24 patients (25%). A honey comb formation in the lung developed only in one patient. For the treatment of interstitial lung disease, corticosteroid treatment had to be combined with cyclophosphamide in 51 cases. In 4 patients (24%), pulmonary arterial hypertension evolved 2-4 years following interstitial lung disease. The high pulmonary arterial pressure decreased using pulsed corticosteroid treatment, cyclophosphamide, prostacyclin analogue, anticoagulants therapy and the 4 patients stay alive. The pulmonary arterial hypertension was caused by obliterative vasculopathy. CONCLUSION: Pulmonary involvement is found in more than half of the patients with mixed connective tissue disease. Early diagnosis of interstitial lung disease is possible by computed tomography. Interstitial lung disease can be treated by the combination of corticosteroids and cyclophosphamide. The authors were the first to detect the coexistence of interstitial lung disease and pulmonary arterial hypertension in mixed connective tissue disease. Subsequent respiratory alterations in these patient necessitate regular patient follow up.
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7.67Impact points
The prevalence of prostate carcinoma and its precursor in Hungary: an autopsy study.
European urology. 12/2005; 48(5):739-44.
OBJECTIVES: The prevalence of incidental prostatic adenocarcinoma (PCa) and its precursor, high grade intraepithelial neoplasia (HGPIN) in an autopsy series from Hungarians (Central European Caucasians) was assessed and compared to similar data from the United States and European countries. METHODS:... [more] OBJECTIVES: The prevalence of incidental prostatic adenocarcinoma (PCa) and its precursor, high grade intraepithelial neoplasia (HGPIN) in an autopsy series from Hungarians (Central European Caucasians) was assessed and compared to similar data from the United States and European countries. METHODS: Autopsy cases (n=139; 18-95 years) with no history of urological disease were histologically examined for prostate cancer and HGPIN. After en block removal, the prostate glands were fixed in formalin, sectioned at 3-5mm intervals and embedded in paraffin. Whole-mount serial sections were stained with Hematoxylin-eosin and examined for the presence of PCa and HGPIN. The frequency of PCa and HGPIN was compared to autopsy data obtained from other geographical areas. RESULTS: We found a 38.8% prevalence of incidental PCa with increasing age-related incidence. Both PCa and HGPIN are first detected in the 3rd decade and show a steady increase with age with respect to number of foci, tumor grade and volume. In the age group 81-95, 86.6% and 60% of men had PCa and HGPIN, respectively. CONCLUSIONS: Incidental PCa and HGPIN are very prevalent in Hungarian population, comparable with the high US and the Scandinavian epidemiological data for Caucasians.
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[In vitro examination of the influence of lipase and amylase on dog's pancreas tissue incubated with endotoxins, phospholipase A2 or cytokines]
Magyar sebészet. 05/2005; 58(2):120-4.
Proinflammatory cytokines are elevated during acute pancreatitis. The endotoxins and Phospholipase A2 (PLA2) also have important role in acute pancreatitis. The aim of this study was to determine, what factors are responsible for the tissue damage in acute pancreatitis. The examinations were perform... [more] Proinflammatory cytokines are elevated during acute pancreatitis. The endotoxins and Phospholipase A2 (PLA2) also have important role in acute pancreatitis. The aim of this study was to determine, what factors are responsible for the tissue damage in acute pancreatitis. The examinations were performed on fixed and frozen sections of healthy dog's pancreas tissue. Direct effects of endotoxins, PLA2, and proinflammatory cytokines together with pancreas enzymes were examined on pancreatic tissue. Pancreas enzymes themselves did not cause any change in the structure of pancreas. The common influence of endotoxins, PLA2 and pancreas enzymes was examined, and finally the effect of proinflammatory cytokines and enzymes was examined on pancreas tissue. Our results show, that besides enzymes many other factors are necessary to inflict tissue damage in acute pancreatitis, but for necrosis the presence of TNF alfa is a must.
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20.59Impact points
Activation of PPARgamma specifies a dendritic cell subtype capable of enhanced induction of iNKT cell expansion.
Immunity. 08/2004; 21(1):95-106.
Little is known of the transcriptional events controlling the differentiation and function of dendritic cells (DC). We found that the ligand-activated transcription factor Peroxisome Proliferator Activated Receptor gamma (PPARgamma) is immediately upregulated after the induction of monocyte-derived ... [more] Little is known of the transcriptional events controlling the differentiation and function of dendritic cells (DC). We found that the ligand-activated transcription factor Peroxisome Proliferator Activated Receptor gamma (PPARgamma) is immediately upregulated after the induction of monocyte-derived DC differentiation. Activation of PPARgamma changed the expression pattern of cell surface receptors and enhanced the internalizing activity of DC. Unexpectedly, we found that CD1 glycoproteins, a class of molecules responsible for the presentation of self and foreign modified lipids, were coordinately regulated by PPARgamma activation. CD1a levels were reduced, while CD1d expression was induced. Enhanced expression of CD1d was coupled to the selective induction of invariant natural-killer T cell (iNKT cell) proliferation in the presence of alpha-GalCer. These results suggest that PPARgamma orchestrates a transcriptional response leading to the development of a DC subtype with increased internalizing capacity, efficient lipid presentation, and the augmented potential to activate iNKT cells.
Following (6)
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András Penyige
University of Debrecen -
Eszter Csanky
MISEK, Ignac Semmelweis Medical Center andUniversity Hospital Nonprofit, Ltd, Miskolc -
Arpad Lanyi
University of Debrecen -
Iain Kilty
Pfizer -
Judit Végh
University of Debrecen
