| 1. |
- Gáll, Tamás, et al.
(författare)
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Heme induces endoplasmic reticulum stress (Hier stress) in human aortic smooth muscle cells
- 2018
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:NOV
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Tidskriftsartikel (refereegranskat)abstract
- Accumulation of damaged or misfolded proteins resulted from oxidative protein modification induces endoplasmic reticulum (ER) stress by activating the pathways of unfolded protein response. In pathologic hemolytic conditions, extracellular free hemoglobin is submitted to rapid oxidation causing heme release. Resident cells of atherosclerotic lesions, after intraplaque hemorrhage, are exposed to heme leading to oxidative injury. Therefore, we raised the question whether heme can also provoke ER stress. Smooth muscle cells are one of the key players of atherogenesis; thus, human aortic smooth muscle cells (HAoSMCs) were selected as a model cell to reveal the possible link between heme and ER stress. Using immunoblotting, quantitative polymerase chain reaction and immunocytochemistry, we quantitated the markers of ER stress. These were: phosphorylated eIF2α, Activating transcription factor-4 (ATF4), DNA-damage-inducible transcript 3 (also known as C/EBP homology protein, termed CHOP), X-box binding protein-1 (XBP1), Activating transcription factor-6 (ATF6), GRP78 (glucose-regulated protein, 78kDa) and heme responsive genes heme oxygenase-1 and ferritin. In addition, immunohistochemistry was performed on human carotid artery specimens from patients who had undergone carotid endarterectomy. We demonstrate that heme increases the phosphorylation of eiF2α in HAoSMCs and the expression of ATF4. Heme also enhances the splicing of XBP1 and the proteolytic cleavage of ATF6. Consequently, there is up-regulation of target genes increasing both mRNA and protein levels of CHOP and GRP78. However, TGFβ and collagen type I decreased. When the heme binding proteins, alpha-1-microglobulin (A1M) and hemopexin (Hpx) are present in cell media, the ER stress provoked by heme is inhibited. ER stress pathways are also retarded by the antioxidant N-acetyl cysteine (NAC) indicating that reactive oxygen species are involved in heme-induced ER stress. Consistent with these findings, elevated expression of the ER stress marker GRP78 and CHOP were observed in smooth muscle cells of complicated lesions with hemorrhage compared to either atheromas or healthy arteries. In conclusion, heme triggers ER stress in a time- and dose-dependent manner in HAoSMCs. A1M and Hpx as well as NAC effectively hamper heme-induced ER stress, supporting their use as a potential therapeutic approach to reverse such a deleterious effects of heme toxicity.
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| 2. |
- Kalmár, Péter János, et al.
(författare)
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A MECHANIKUS THROMBECTOMIÁT MEGELÔZÔ INTRAVÉNÁS THROMBOLYSIS SZEREPE AZ AKUT AGYI NAGYÉRELZÁRÓDÁSOK KEZELÉSÉBEN : [The role of intravenous thrombolysis before mechanical thrombectomy in the treatment of large vessel occlusion strokes]
- 2022
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Ingår i: Ideggyógyászati szemle. - : Literatura Medica Kiado. - 0019-1442 .- 2498-6208. ; 75:1-2, s. 23-29
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: The efficacy of intravenous thrombolysis (IVT) is moderate in the proximal vascular segments of intracranial arteries, as opposed to mecha-nical thrombectomy (MT). In the management of acute ischemic stroke (AIS) caused by large vessel occlusions (LVO), IVT prior to MT is highly recommended based on the latest guidelines, but the necessity of IVT has been questioned by the latest studies of the past years. The aim of our study was to investigate and compare the efficacy and safety of direct mechanical thrombectomy (dMT) and combined therapy (CT) for patients who suffered an AIS with LVO and were treated in our department.Methods: We investigated patients with AIS caused by LVO who were admitted up to 4.5 hours after symptom onset and underwent MT in our department between November 2017 and August 2019. Patients' data were collected in our stroke register. Patients enrolled in our study were divided into two groups depending on whether dMT or CT was used. Our primary outcome was the 30- and 90- day functional outcome measured by modified Rankin Scale (mRS). Mortality at 30- and 90- day, successful recanalization rates, and symptomatic intracranial hemorrhage were considered as secondary outcomes.Results: A total of 142 patients (age: 68.3 ± 12.6 years, 53.5% female) were enrolled in our study, including 81 (57.0%) dMT cases, and 61 (43.0%) patients who received CT. The vascular risk factors and comorbidities were significantly higher in the dMT-treated group. At day 30, the rate of favorable functional outcomes was 34.7% in dMT vs. 43.6% among those who received CT (p = 0.307), by day 90 this ratio changed to 40.8% vs. 46.3% (p = 0.542). Mortality rates at day 30 were 22.2% and 23.6% (p = 0.851), and at day 90 33.8% and 25.9% (p = 0.343). The rate of effective recanalization was 94.2% for dMT-treated patients and 98.0% for CT-treated patients (p = 0.318). Symptomatic intracranial hemorrhage was detected in 2.5% of dMT-treated patients and 3.4% of CT-treated group (p = 0.757).Conclusion: Our results suggest that CT is associated with a moderately better outcome compared to dMT. IVT prior to MT did not increase the risk of symptomatic intracranial hemorrhages.
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| 3. |
- Kalmar, Peter Janos, et al.
(författare)
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Comparing endovascular treatment methods in acute ischemic stroke Due to tandem occlusion focusing on clinical aspects
- 2021
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Ingår i: Life. - : MDPI. - 2075-1729. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Acute ischemic strokes (AIS) due to tandem occlusion (TO) of intracranial anterior large vessel and concomitant extracranial internal carotid artery (EICA) are represent in 15-20% of all ischemic strokes. The endovascular treatment (EVT) strategy for those patients is still unclear. Although the intracranial mechanical thrombectomy (MT) is considered as a standard treatment approach, the EICA lesion stent necessity remains a matter of debate. We sought to assess the efficacy and safety of EVT in tandem lesions, particularly the EICA stenting management.Methods: We retrospectively analyzed all patients with anterior circulation stroke associated with EICA lesion and receiving EVT in the three participated stroke centers between November 2017 and December 2020. Patients' data were collected from our prospective stroke registry (STAY ALIVE). Patients enrolled in our study were divided into two groups depending on whether acute carotid stenting (ACS) or balloon angioplasty only (BAO) technique was used. Our primary outcome was the 90-day functional outcome assessed by modified Rankin scale (mRS). Mortality at 90 days and symptomatic intracranial hemorrhage (sICH) were considered as secondary outcomes.Results: A total of 101 patients (age: 67 ± 10 years, 38.6% female) were enrolled in our study, including 29 (28.3%) BAO cases, and 72 (71.3%) patients treated with ACS. Patients in the BAO group were slightly older (70 ± 9 years vs. 66 ± 10 years, p = 0.054), and had higher prevalence of comorbidities such as hypertension (100.0% vs. 59.4%, p < 0.001). There was no significant difference in favorable outcomes (51.7% vs. 54.4%, p = 0.808) between the groups. However, we observed a trend towards higher rates of sICH (8.3% vs. 3.4%, p = 0.382) and 90-day mortality (23.5% vs. 13.8%, p = 0.278) with significantly higher frequency of distal embolization (39.1% vs. 17.9%, p = 0.043) in patients with ACS. In the overall population age (p = 0.013), atrial fibrillation (AF) (p = 0.008), National Institutes of Health Stroke Scale (NIHSS) baseline (p = 0.029), and successful recanalization (p = 0.023) were associated with favorable outcome.Conclusion: Endovascular approach of EICA in addition to MT was safe and effective in tandem occlusion of anterior circulation. Furthermore, our results suggest that balloon angioplasty technique without acute stenting shows a comparable favorable outcome rate to ACS with moderately less hemorrhagic events and mortality rates.
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| 4. |
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| 5. |
- Malina, Tamás, et al.
(författare)
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Individual variability of venom from the European adder (Vipera berus berus) from one locality in Eastern Hungary
- 2017
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101 .- 1879-3150. ; 135, s. 59-70
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Tidskriftsartikel (refereegranskat)abstract
- We have revealed intra-population variability among venom samples from several individual European adders (Vipera berus berus) within a defined population in Eastern Hungary. Individual differences in venom pattern were noticed, both gender-specific and age-related, by one-dimensional electrophoresis. Gelatin zymography demonstrated that these individual venoms have different degradation profiles indicating varying protease activity in the specimens from adders of different ages and genders. Some specimens shared a conserved region of substrate degradation, while others had lower or extremely low protease activity. Phospholipase A(2) activity of venoms was similar but not identical. Interspecimen diversity of the venom phospholipase A(2)-spectra (based on the components' molecular masses) was detected by MALDI-TOF MS. The lethal toxicity of venoms (LD50) also showed differences among individual snakes. Extracted venom samples had varying neuromuscular paralysing effect on chick biventer cervicis nerve-muscle preparations. The paralysing effect of venom was lost when calcium in the physiological salt solution was replaced by strontium; indicating that the block of twitch responses to nerve stimulation is associated with the activity of a phospholipase-dependent neurotoxin. In contrast to the studied V.b. berus venoms from different geographical regions so far, this is the first V.b berus population discovered to have predominantly neurotoxic neuromuscular activity. The relevance of varying venom yields is also discussed. This study demonstrates that individual venom variation among V.b. berus living in particular area of Eastern Hungary might contribute to a wider range of clinical manifestations of V.b. hems envenoming than elsewhere in Europe.
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| 6. |
- Zamora, Juan Carlos, et al.
(författare)
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Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
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Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
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Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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| 7. |
- Bonroy, Carolien, et al.
(författare)
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Detection of antinuclear antibodies : recommendations from EFLM, EASI and ICAP
- 2023
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 61:7, s. 1167-1198
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Antinuclear antibodies (ANA) are important for the diagnosis of various autoimmune diseases. ANA are usually detected by indirect immunofluorescence assay (IFA) using HEp-2 cells (HEp-2 IFA). There are many variables influencing HEp-2 IFA results, such as subjective visual reading, serum screening dilution, substrate manufacturing, microscope components and conjugate. Newer developments on ANA testing that offer novel features adopted by some clinical laboratories include automated computer-assisted diagnosis (CAD) systems and solid phase assays (SPA).Methods: A group of experts reviewed current literature and established recommendations on methodological aspects of ANA testing. This process was supported by a two round Delphi exercise. International expert groups that participated in this initiative included (i) the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group “Autoimmunity Testing”; (ii) the European Autoimmune Standardization Initiative (EASI); and (iii) the International Consensus on ANA Patterns (ICAP).Results: In total, 35 recommendations/statements related to (i) ANA testing and reporting by HEp-2 IFA; (ii) HEp-2 IFA methodological aspects including substrate/conjugate selection and the application of CAD systems; (iii) quality assurance; (iv) HEp-2 IFA validation/verification approaches and (v) SPA were formulated. Globally, 95% of all submitted scores in the final Delphi round were above 6 (moderately agree, agree or strongly agree) and 85% above 7 (agree and strongly agree), indicating strong international support for the proposed recommendations.Conclusions: These recommendations are an important step to achieve high quality ANA testing.
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| 8. |
- Brasko, Csilla, et al.
(författare)
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Intelligent image-based in situ single-cell isolation
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying heterogeneities within cell populations is important for many fields including cancer research and neurobiology; however, techniques to isolate individual cells are limited. Here, we describe a high-throughput, non-disruptive, and cost-effective isolation method that is capable of capturing individually targeted cells using widely available techniques. Using high-resolution microscopy, laser microcapture microscopy, image analysis, and machine learning, our technology enables scalable molecular genetic analysis of single cells, targetable by morphology or location within the sample.
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| 9. |
- Cinege, Gyöngyi, et al.
(författare)
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Distinctive features of Zaprionus indianus hemocyte differentiation and function revealed by transcriptomic analysis
- 2023
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Insects have specialized cell types that participate in the elimination of parasites, for instance, the lamellocytes of the broadly studied species Drosophila melanogaster. Other drosophilids, such as Drosophila ananassae and the invasive Zaprionus indianus, have multinucleated giant hemocytes, a syncytium of blood cells that participate in the encapsulation of the eggs or larvae of parasitoid wasps. These cells can be formed by the fusion of hemocytes in circulation or originate from the lymph gland. Their ultrastructure highly resembles that of the mammalian megakaryocytes.Methods: Morphological, protein expressional, and functional features of blood cells were revealed using epifluorescence and confocal microscopy. The respective hemocyte subpopulations were identified using monoclonal antibodies in indirect immunofluorescence assays. Fluorescein isothiocyanate (FITC)-labeled Escherichia coli bacteria were used in phagocytosis tests. Gene expression analysis was performed following mRNA sequencing of blood cells.Results: D. ananassae and Z. indianus encapsulate foreign particles with the involvement of multinucleated giant hemocytes and mount a highly efficient immune response against parasitoid wasps. Morphological, protein expressional, and functional assays of Z. indianus blood cells suggested that these cells could be derived from large plasmatocytes, a unique cell type developing specifically after parasitoid wasp infection. Transcriptomic analysis of blood cells, isolated from naïve and wasp-infected Z. indianus larvae, revealed several differentially expressed genes involved in signal transduction, cell movements, encapsulation of foreign targets, energy production, and melanization, suggesting their role in the anti-parasitoid response. A large number of genes that encode proteins associated with coagulation and wound healing, such as phenoloxidase activity factor-like proteins, fibrinogen-related proteins, lectins, and proteins involved in the differentiation and function of platelets, were constitutively expressed. The remarkable ultrastructural similarities between giant hemocytes and mammalian megakaryocytes, and presence of platelets, and giant cell-derived anucleated fragments at wound sites hint at the involvement of this cell subpopulation in wound healing processes, in addition to participation in the encapsulation reaction.Conclusion: Our observations provide insights into the broad repertoire of blood cell functions required for efficient defense reactions to maintain the homeostasis of the organism. The analysis of the differentiation and function of multinucleated giant hemocytes gives an insight into the diversification of the immune mechanisms.
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| 10. |
- Dévai, Gergely, et al.
(författare)
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Efficient Code Generation from the High-level Domain-specific Language Feldspar for DSPs
- 2010
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Ingår i: ODES-8: 8th Workshop on Optimizations for DSP and Embedded Systems, workshop associated with IEEE/ACM International Symposium on Code Generation and Optimization (CGO).
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Konferensbidrag (refereegranskat)abstract
- Software for digital signal processors (DSPs) is traditionally highly hardware-dependent and hence porting it to new processors usually requires significant design effort. In this paper we present Feldspar (Functional Embedded Language for DSP and Parallelism), an embedded, high-level, domain-specific language for DSP algorithm design and the compilation techniques we developed for generating C code from specifications written in Feldspar. While Feldspar allows description of algorithms on specification level, we show that with the right set of abstractions and transformations this high level, functional specification can be transformed into C code that is comparable or better than reference, hand-crafted C language implementations. The Feldspar compiler is highly modular and plugin-based, hence future hardware-specific plugins will enable automatic generation of efficient, hardware-specific code. This approach enables the encapsulation of knowledge of hardware completely in the compiler and thus allows description of algorithms in completely hardware-independent, portable manner.
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