The transcription factor junB belongs to the jun family of protooncogenes. The appearence of junB... more The transcription factor junB belongs to the jun family of protooncogenes. The appearence of junB mRNA in hepatic cells is an extremely early and sensitive marker of the action of proinflammatory cytokines including interleukin-6. In this study, a competitive reverse transcription (RT)-PCR assay has been developed that is suitable for the quantitative determination of junB mRNA expression. This nonisotopic assay compared to other methods (e.g., Northern blot) is a fast and convenient way to determine the expression of the junB gene and thus the immediate concentration- and time-dependent action of interleukin-6. Because interleukin-6 and interleukin-6-type cytokines play a highly important regulatory role in various pathophysiologically important processes, such as hepatic acute-phase reaction, the quantitative assay of junB mRNA completes the scale of laboratory approaches in inflammation and among other pathological conditions.
Preeclampsia is a disease of the mother, fetus, and placenta, and the gaps in our understanding o... more Preeclampsia is a disease of the mother, fetus, and placenta, and the gaps in our understanding of the complex interactions among their respective disease pathways preclude successful treatment and prevention. The placenta has a key role in the pathogenesis of the terminal pathway characterized by exaggerated maternal systemic inflammation, generalized endothelial damage, hypertension, and proteinuria. This of preeclampsia may be triggered by distinct underlying mechanisms that occur at early stages of pregnancy and induce different phenotypes. To gain insights into these molecular pathways, we employed a systems biology approach and integrated different "omics," clinical, placental, and functional data from patients with distinct phenotypes of preeclampsia. First trimester maternal blood proteomics uncovered an altered abundance of proteins of the renin-angiotensin and immune systems, complement, and coagulation cascades in patients with term or preterm preeclampsia. More...
Incubation of purified human beta 2-microglobulin (B2-m) with tissue transglutaminase (Tgase) res... more Incubation of purified human beta 2-microglobulin (B2-m) with tissue transglutaminase (Tgase) resulted in the formation of high molecular weight polymers revealed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. In the presence of 30 mM [14C]methylamine, the polymer formation was prevented, but incorporation of methylamine into beta 2-m (equal to 1 methylamine per 1 molecule) could be observed. From the sheddings of peripheral blood mononuclear cells occurring in the presence of Tgase, it is apparent that anti-beta 2-m immunoadsorbent removed, in addition to human leukocyte antigen (HLA) and beta 2-m, some other proteins. The enzyme could incorporate [14C]methylamine into beta 2-m of the shedding cells. On addition of rabbit anti-human beta 2-m antibody, followed by fluoresceine-labeled goat anti-rabbit IgG antibody to human mononuclear blood cells, the otherwise homogeneous distribution of fluorescence turned into spots and patches on cells previously incubated with Tg...
Proceedings of the National Academy of Sciences, 2009
Limited responsiveness to IFN-α in hepatitis C virus (HCV)-infected African-Americans compared to... more Limited responsiveness to IFN-α in hepatitis C virus (HCV)-infected African-Americans compared to European Americans (AAs vs. EAs) hinders the management of HCV. Here, we studied healthy non-HCV-infected AA and EA subjects to test whether immune cell response to IFN-α is determined directly by race. We compared baseline and IFN-α-induced signal transducer and activator of transcription (STAT)-1, STAT-2, STAT-3, STAT-4, and STAT-5 protein and phosphorylation levels in purified T cells, global transcription, and a genomewide single-nucleotide polymorphism (SNP) profile of healthy AA and EA blood donors. In contrast to HCV-infected individuals, healthy AAs displayed no evidence of reduced STAT activation or IFN-α-stimulated gene expression compared to EAs. Although >200 genes reacted to IFN-α treatment, race had no impact on any of them. The only gene differentially expressed by the two races (NUDT3, P < 10 −7 ) was not affected by IFN-α and bears no known relationship to IFN-α s...
C5-deficient mice differed from C5-sufficient mice both quantitatively and qualitatively in C5 pr... more C5-deficient mice differed from C5-sufficient mice both quantitatively and qualitatively in C5 protein, C5 mRNA, and the C5 gene. C5-deficient protein was present as decreased amounts of an unprocessed, single-chain precursor. C5-deficient mRNA was decreased in amount and present in two forms, the smaller of which was the same as the single form in normal cells. Nuclei from both normal and deficient cells contained the larger form of C5 mRNA, and C5-deficient DNA demonstrated differences from the normal pattern on Southern analysis for two restriction enzymes. These data suggest that the primary transcript of the C5-deficient gene is abnormal, retarding the processing of the C5 mRNA, and that the C5-deficient mRNA codes for an abnormal protein.
The discovery of the biological relevance of non-coding RNA molecules represents one of the most ... more The discovery of the biological relevance of non-coding RNA molecules represents one of the most significant advances in contemporary molecular biology. It has turned out that a major fraction of the non-coding part of the genome is transcribed. Beside small RNAs (including microRNAs) more and more data are disclosed concerning long non-coding RNAs of 200 nucleotides to 100 kb length that are implicated in the regulation of several basic molecular processes (cell proliferation, chromatin functioning, microRNA-mediated effects, etc.). Some of these long non-coding RNAs have been associated with human tumours, including H19, HOTAIR, MALAT1, etc., the different expression of which has been noted in various neoplasms relative to healthy tissues. Long non-coding RNAs may represent novel markers of molecular diagnostics and they might even turn out to be targets of therapeutic intervention. Orv. Hetil., 2012, 153, 1494–1501.
The transcription factor junB belongs to the jun family of protooncogenes. The appearence of junB... more The transcription factor junB belongs to the jun family of protooncogenes. The appearence of junB mRNA in hepatic cells is an extremely early and sensitive marker of the action of proinflammatory cytokines including interleukin-6. In this study, a competitive reverse transcription (RT)-PCR assay has been developed that is suitable for the quantitative determination of junB mRNA expression. This nonisotopic assay compared to other methods (e.g., Northern blot) is a fast and convenient way to determine the expression of the junB gene and thus the immediate concentration- and time-dependent action of interleukin-6. Because interleukin-6 and interleukin-6-type cytokines play a highly important regulatory role in various pathophysiologically important processes, such as hepatic acute-phase reaction, the quantitative assay of junB mRNA completes the scale of laboratory approaches in inflammation and among other pathological conditions.
Preeclampsia is a disease of the mother, fetus, and placenta, and the gaps in our understanding o... more Preeclampsia is a disease of the mother, fetus, and placenta, and the gaps in our understanding of the complex interactions among their respective disease pathways preclude successful treatment and prevention. The placenta has a key role in the pathogenesis of the terminal pathway characterized by exaggerated maternal systemic inflammation, generalized endothelial damage, hypertension, and proteinuria. This of preeclampsia may be triggered by distinct underlying mechanisms that occur at early stages of pregnancy and induce different phenotypes. To gain insights into these molecular pathways, we employed a systems biology approach and integrated different "omics," clinical, placental, and functional data from patients with distinct phenotypes of preeclampsia. First trimester maternal blood proteomics uncovered an altered abundance of proteins of the renin-angiotensin and immune systems, complement, and coagulation cascades in patients with term or preterm preeclampsia. More...
Incubation of purified human beta 2-microglobulin (B2-m) with tissue transglutaminase (Tgase) res... more Incubation of purified human beta 2-microglobulin (B2-m) with tissue transglutaminase (Tgase) resulted in the formation of high molecular weight polymers revealed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. In the presence of 30 mM [14C]methylamine, the polymer formation was prevented, but incorporation of methylamine into beta 2-m (equal to 1 methylamine per 1 molecule) could be observed. From the sheddings of peripheral blood mononuclear cells occurring in the presence of Tgase, it is apparent that anti-beta 2-m immunoadsorbent removed, in addition to human leukocyte antigen (HLA) and beta 2-m, some other proteins. The enzyme could incorporate [14C]methylamine into beta 2-m of the shedding cells. On addition of rabbit anti-human beta 2-m antibody, followed by fluoresceine-labeled goat anti-rabbit IgG antibody to human mononuclear blood cells, the otherwise homogeneous distribution of fluorescence turned into spots and patches on cells previously incubated with Tg...
Proceedings of the National Academy of Sciences, 2009
Limited responsiveness to IFN-α in hepatitis C virus (HCV)-infected African-Americans compared to... more Limited responsiveness to IFN-α in hepatitis C virus (HCV)-infected African-Americans compared to European Americans (AAs vs. EAs) hinders the management of HCV. Here, we studied healthy non-HCV-infected AA and EA subjects to test whether immune cell response to IFN-α is determined directly by race. We compared baseline and IFN-α-induced signal transducer and activator of transcription (STAT)-1, STAT-2, STAT-3, STAT-4, and STAT-5 protein and phosphorylation levels in purified T cells, global transcription, and a genomewide single-nucleotide polymorphism (SNP) profile of healthy AA and EA blood donors. In contrast to HCV-infected individuals, healthy AAs displayed no evidence of reduced STAT activation or IFN-α-stimulated gene expression compared to EAs. Although >200 genes reacted to IFN-α treatment, race had no impact on any of them. The only gene differentially expressed by the two races (NUDT3, P < 10 −7 ) was not affected by IFN-α and bears no known relationship to IFN-α s...
C5-deficient mice differed from C5-sufficient mice both quantitatively and qualitatively in C5 pr... more C5-deficient mice differed from C5-sufficient mice both quantitatively and qualitatively in C5 protein, C5 mRNA, and the C5 gene. C5-deficient protein was present as decreased amounts of an unprocessed, single-chain precursor. C5-deficient mRNA was decreased in amount and present in two forms, the smaller of which was the same as the single form in normal cells. Nuclei from both normal and deficient cells contained the larger form of C5 mRNA, and C5-deficient DNA demonstrated differences from the normal pattern on Southern analysis for two restriction enzymes. These data suggest that the primary transcript of the C5-deficient gene is abnormal, retarding the processing of the C5 mRNA, and that the C5-deficient mRNA codes for an abnormal protein.
The discovery of the biological relevance of non-coding RNA molecules represents one of the most ... more The discovery of the biological relevance of non-coding RNA molecules represents one of the most significant advances in contemporary molecular biology. It has turned out that a major fraction of the non-coding part of the genome is transcribed. Beside small RNAs (including microRNAs) more and more data are disclosed concerning long non-coding RNAs of 200 nucleotides to 100 kb length that are implicated in the regulation of several basic molecular processes (cell proliferation, chromatin functioning, microRNA-mediated effects, etc.). Some of these long non-coding RNAs have been associated with human tumours, including H19, HOTAIR, MALAT1, etc., the different expression of which has been noted in various neoplasms relative to healthy tissues. Long non-coding RNAs may represent novel markers of molecular diagnostics and they might even turn out to be targets of therapeutic intervention. Orv. Hetil., 2012, 153, 1494–1501.
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