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Article ; Online: Radioembolization Planning With Dual-Isotope Acquisition of 166 Ho-Labeled Microparticles and 99m Tc-Mebrofenin.

Czibor, Sándor / Bibok, András / Horváthy, Dénes / Fábián, Krisztián / Györke, Tamás

2023 Volume 48, Issue 8, Page(s) 719–721

Abstract: Abstract: A 76-year-old man with hepatocellular carcinoma was referred for liver radioembolization. Given a prior left hemihepatectomy, it was clinically important to consider potentially irradiated healthy liver at planning. Thus, at the SPECT/CT ... ...

Abstract	Abstract: A 76-year-old man with hepatocellular carcinoma was referred for liver radioembolization. Given a prior left hemihepatectomy, it was clinically important to consider potentially irradiated healthy liver at planning. Thus, at the SPECT/CT imaging of the scout dose 166 Ho-microparticles before injected superselectively in the right hepatic artery, 99m Tc-mebrofenin was injected intravenously, and functional volumetry SPECT was performed simultaneously. Based on the 2 image sets, the nonirradiated healthy liver was calculated as 1589 mL (functional liver reserve of 85.5% on 99m Tc-mebrofenin SPECT). Posttreatment dosimetry calculations showed optimal normal tissue and tumor absorbed doses, and the patient is clinically well after 3 months.
MeSH term(s)	Male ; Humans ; Aged ; Liver Neoplasms/diagnostic imaging ; Liver Neoplasms/radiotherapy ; Liver Neoplasms/drug therapy ; Carcinoma, Hepatocellular/diagnostic imaging ; Carcinoma, Hepatocellular/radiotherapy ; Carcinoma, Hepatocellular/drug therapy ; Tomography, Emission-Computed, Single-Photon/methods ; Yttrium Radioisotopes/therapeutic use ; Isotopes ; Embolization, Therapeutic
Chemical Substances	mebrofenin (7PV0B6ED98) ; Yttrium Radioisotopes ; Isotopes
Language	English
Publishing date	2023-06-08
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	197628-x
ISSN	1536-0229 ; 0363-9762
ISSN (online)	1536-0229
ISSN	0363-9762
DOI	10.1097/RLU.0000000000004732
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Zs.A 1276: Show issues

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Article ; Online: Preliminary study on individual radiation dose received by medical staff for dose constraint determination.

Milecz-Mitykó, Richárd / Bérczi, Viktor / Czibor, Sándor / Bánsághi, Zoltán / Taba, Gabriella / Kári, Béla / Györke, Tamás

Radiation protection dosimetry

2023 Volume 199, Issue 8-9, Page(s) 989–994

Abstract: The staff of the Radiation Protection Service of a European clinical center measured the radiation dose by type-tested thermoluminescent dosemeter systems to which the medical staff was exposed, to assess the effectiveness of current procedures and ... ...

Abstract	The staff of the Radiation Protection Service of a European clinical center measured the radiation dose by type-tested thermoluminescent dosemeter systems to which the medical staff was exposed, to assess the effectiveness of current procedures and equipment for optimalisation prompted by the requirements EU Basic Safety Standard 2013. There were three participating sites, the Site 1 was an external hospital, whereas Sites 2 and 3 are part of the same clinical center, who provided data regarding their personnel, from technologists, nurses and medical doctors. In this preliminary study, only a low number of cases were available and used to establish a new, more realistic yearly dose constraint, namely 6 (from two) mSv for whole-body effective dose, 15 (from two) mSv for eye lens dose and 300 (from 50) mSv for extremity dose. Furthermore, the state of safety culture and protection equipment was assessed. Collection of the sufficient amount of data for statistical evaluation is ongoing.
MeSH term(s)	Humans ; Medical Staff ; Extremities ; Hospitals ; Lens, Crystalline ; Radiation Dosage
Language	English
Publishing date	2023-06-01
Publishing country	England
Document type	Journal Article
ZDB-ID	225912-6
ISSN	1742-3406 ; 0144-8420
ISSN (online)	1742-3406
ISSN	0144-8420
DOI	10.1093/rpd/ncad120
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Zs.A 2009: Show issues

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Article ; Online: Prognostic parameters on baseline and interim [ 18 F]FDG-PET/computed tomography in diffuse large B-cell lymphoma patients.

Czibor, Sándor / Carr, Robert / Redondo, Francisca / Auewarakul, Chirayu U / Cerci, Juliano J / Paez, Diana / Fanti, Stefano / Györke, Tamás

Nuclear medicine communications

2023 Volume 44, Issue 4, Page(s) 291–301

Abstract: Objective: 2-[ 18 F]fluoro-2-deoxy- d -glucose PET/computed tomography ([ 18 F]FDG-PET/CT) is a widely used imaging method in the management of diffuse large B-cell lymphomas (DLBCL). Our aim was to investigate the prognostic performance of different ... ...

Abstract	Objective: 2-[ 18 F]fluoro-2-deoxy- d -glucose PET/computed tomography ([ 18 F]FDG-PET/CT) is a widely used imaging method in the management of diffuse large B-cell lymphomas (DLBCL). Our aim was to investigate the prognostic performance of different PET biomarkers in a multicenter setting. Methods: We investigated baseline volumetric values [metabolic tumor volume (MTV) and total lesion glycolysis (TLG), also normalized for body weight] segmented with three different methods [>SUV4 (glob4); 41% isocontour (41pc), and a gradient-based lesion growing algorithm (grad)] and interim parameters [Deauville score, maximal standardized uptake value (ΔSUVmax), modified qPET, and ratio PET (rPET)] alongside clinical parameters (stage, revised International Prognostic Index), using 24-month progression-free survival as the clinical endpoint. Receiver operating characteristics analyses were performed to define optimal cutoff points for the continuous PET parameters. Results: A total of 107 diffuse large B-cell lymphoma patients were included (54 women; mean age: 53.7 years). MTV and TLG calculations showed good correlation among glob4, 41pc, and grad methods; however, optimal cutoff points were markedly different.Significantly different PFS was observed between low- and high-risk groups according to baseline MTV, body weight-adjusted (bwa) MTV, TLG, bwaTLG, as well as interim parameters Deauville score, ΔSUVmax, mqPET, and rPET. Univariate Cox regression analyses showed hazard ratios (HRs) lowest for bwaMTVglob4 (HR = 2.3) and highest for rPET (HR = 9.09). In a multivariate Cox-regression model, rPET was shown to be an independent predictor of PFS ( P = 0.041; HR = 9.15). Combined analysis showed that ΔSUVmax positive patients with high MTV formed a group with distinctly poor PFS (35.3%). Conclusion: Baseline MTV and TLG values and optimal cutoff points achieved with different segmentation methods varied markedly and showed a limited prognostic impact. Interim PET/CT parameters provided more accurate prognostic information with semiquantitative 'Deauville-like' parameters performing best in the present study.
MeSH term(s)	Humans ; Female ; Middle Aged ; Fluorodeoxyglucose F18 ; Prognosis ; Positron Emission Tomography Computed Tomography ; Tomography, X-Ray Computed ; Lymphoma, Large B-Cell, Diffuse/diagnostic imaging ; Body Weight ; Retrospective Studies ; Tumor Burden
Chemical Substances	Fluorodeoxyglucose F18 (0Z5B2CJX4D)
Language	English
Publishing date	2023-01-30
Publishing country	England
Document type	Multicenter Study ; Journal Article
ZDB-ID	758141-5
ISSN	1473-5628 ; 0143-3636
ISSN (online)	1473-5628
ISSN	0143-3636
DOI	10.1097/MNM.0000000000001664
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Zs.A 1577: Show issues

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Article ; Online: Toxoplasma gondii in small mammals in Romania: the influence of host, season and sampling location.

Kalmár, Zsuzsa / Sándor, Attila D / Balea, Anamaria / Borşan, Silvia-Diana / Matei, Ioana Adriana / Ionică, Angela Monica / Gherman, Călin Mircea / Mihalca, Andrei Daniel / Cozma-Petruț, Anamaria / Mircean, Viorica / Györke, Adriana

BMC veterinary research

2023 Volume 19, Issue 1, Page(s) 177

Abstract: Background: Toxoplasma gondii is a protozoan parasite that infects a large spectrum of warm-blooded animals, including humans. Small rodents and insectivores play an important role in the epidemiology of T. gondii and may serve as a source of infection ... ...

Abstract	Background: Toxoplasma gondii is a protozoan parasite that infects a large spectrum of warm-blooded animals, including humans. Small rodents and insectivores play an important role in the epidemiology of T. gondii and may serve as a source of infection for both, domestic and wild definitive felid hosts. Factors influencing the occurrence of T. gondii in wild small mammals are unknown, despite the fact that many intermediate host species are identified. We have used small mammals (Rodentia and Lipotyphla) captured over two years in various habitats, both in urbanised and in natural landscapes. We assessed the importance of land-use, season and host ecology on T. gondii infection. Results: We examined 471 individuals belonging to 20 small mammal species, collected at 63 locations spread over wide altitude, habitat and land-use ranges from Romania. Heart tissue samples were individually analysed by PCR targeting the 529 bp repetitive DNA fragment of T. gondii. The overall prevalence of infection was 7.3%, with nine species of rodents and two species of shrews being found to carry T. gondii DNA. Five species showed high frequency of infection, with the highest prevalence found in Myodes glareolus (35.5%), followed by Spermophilus citellus (33.3%), Sorex minutus (23.1%), S. araneus (21.7%) and Micromys minutus (11.1%). Adults seemed more often infected than young, however when controlling for season, the difference was not significant, as in spring both adults and young showed higher infection rates, but more adults were sampled. Contrary to our expectations, urban/rural areas (with their implicit high density of domestic feline presence) had no effect on infection prevalence. In addition, neither habitat, nor land-use at sampling sites was important as only geographical location and host species were contributing factors to the infection risk. Conclusions: High prevalence of T. gondii infection showed a highly localised, patchy occurrence, with long living and higher mobility host species being the most common carriers, especially during autumn.
MeSH term(s)	Humans ; Animals ; Cats ; Toxoplasma/genetics ; Sciuridae/genetics ; Seasons ; Romania/epidemiology ; Shrews ; DNA, Protozoan/genetics ; Toxoplasmosis, Animal/epidemiology ; Toxoplasmosis, Animal/parasitology ; Cat Diseases ; Rodent Diseases/epidemiology
Chemical Substances	DNA, Protozoan
Language	English
Publishing date	2023-09-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2191675-5
ISSN	1746-6148 ; 1746-6148
ISSN (online)	1746-6148
ISSN	1746-6148
DOI	10.1186/s12917-023-03729-7
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Article: Acute Detubulation of Ventricular Myocytes Amplifies the Inhibitory Effect of Cholinergic Agonist on Intracellular Ca

Belevych, Andriy E / Bogdanov, Vladimir / Terentyev, Dmitry A / Gyorke, Sandor

Frontiers in physiology

2021 Volume 12, Page(s) 725798

Abstract: Muscarinic receptors expressed in cardiac myocytes play a critical role in the regulation of heart function by the parasympathetic nervous system. How the structural organization of cardiac myocytes affects the regulation of ... ...

Abstract	Muscarinic receptors expressed in cardiac myocytes play a critical role in the regulation of heart function by the parasympathetic nervous system. How the structural organization of cardiac myocytes affects the regulation of Ca
Language	English
Publishing date	2021-08-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2021.725798
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Article ; Online: Molecular basis of catecholaminergic polymorphic ventricular tachycardia.

Györke, Sandor

Heart rhythm

2009 Volume 6, Issue 1, Page(s) 123–129

Abstract: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a malignant arrhythmia syndrome linked to mutations in the cardiac ryanodine receptor (RyR2) and calsequestrin (CASQ2). RyR2 and CASQ2 are parts of the multimolecular Ca(2+) release channel ... ...

Abstract	Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a malignant arrhythmia syndrome linked to mutations in the cardiac ryanodine receptor (RyR2) and calsequestrin (CASQ2). RyR2 and CASQ2 are parts of the multimolecular Ca(2+) release channel complex that is present on the sarcoplasmic reticulum (SR) to support myocyte Ca(2+) cycling and contractile activity. Whereas RyR2 operates as a Ca(2+) release channel, the SR Ca(2+) binding protein CASQ2 plays a dual role by serving as a SR Ca(2+) buffer and by regulating RyR2 function. Essential to stable Ca(2+) cycling, SR luminal Ca(2+)-dependent control of RyR2 activity by CASQ2 contributes to RyR2 deactivation and to the development of a temporary refractory state that occurs after each Ca(2+) release. Accumulating evidence suggests that the CPVT mutations act by reducing the extent and shortening the duration of Ca(2+) signaling refractoriness, thereby promoting untimely SR Ca(2+) release and arrhythmogenic delayed afterdepolarizations in cardiac myocytes. Similar mechanisms may apply to arrhythmias during various conditions, including heart failure and ischemic heart disease, associated with acquired defects in components of the Ca(2+) release channel complex.
MeSH term(s)	Calcium/metabolism ; Calcium Channels/metabolism ; Catecholamines/metabolism ; Humans ; Intracellular Fluid/metabolism ; Myocardium/metabolism ; Signal Transduction ; Tachycardia, Ventricular/metabolism
Chemical Substances	Calcium Channels ; Catecholamines ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2009-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2229357-7
ISSN	1556-3871 ; 1547-5271
ISSN (online)	1556-3871
ISSN	1547-5271
DOI	10.1016/j.hrthm.2008.09.013
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Zs.A 6278: Show issues

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Article ; Online: Neuronal sodium channels: emerging components of the nano-machinery of cardiac calcium cycling.

Veeraraghavan, Rengasayee / Györke, Sándor / Radwański, Przemysław B

The Journal of physiology

2017 Volume 595, Issue 12, Page(s) 3823–3834

Abstract: Excitation-contraction coupling is the bridge between cardiac electrical activation and mechanical contraction. It is driven by the influx of ... ...

Abstract	Excitation-contraction coupling is the bridge between cardiac electrical activation and mechanical contraction. It is driven by the influx of Ca
MeSH term(s)	Action Potentials/physiology ; Animals ; Arrhythmias, Cardiac/metabolism ; Calcium/metabolism ; Excitation Contraction Coupling/physiology ; Humans ; Myocytes, Cardiac/metabolism ; Neurons/metabolism ; Sarcoplasmic Reticulum/metabolism ; Sodium/metabolism ; Sodium Channels/metabolism
Chemical Substances	Sodium Channels ; Sodium (9NEZ333N27) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2017-03-26
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP273058
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Uc I Zs.65: Show issues

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Article: Cardiac Arrhythmias as Manifestations of Nanopathies: An Emerging View.

Radwański, Przemysław B / Johnson, Christopher N / Györke, Sándor / Veeraraghavan, Rengasayee

Frontiers in physiology

2018 Volume 9, Page(s) 1228

Abstract: A nanodomain is a collection of proteins localized within a specialized, nanoscale structural environment, which can serve as the functional unit of macroscopic physiologic processes. We are beginning to recognize the key roles of cardiomyocyte ... ...

Abstract	A nanodomain is a collection of proteins localized within a specialized, nanoscale structural environment, which can serve as the functional unit of macroscopic physiologic processes. We are beginning to recognize the key roles of cardiomyocyte nanodomains in essential processes of cardiac physiology such as electrical impulse propagation and excitation-contraction coupling (ECC). There is growing appreciation of nanodomain dysfunction, i.e., nanopathy, as a mechanistic driver of life-threatening arrhythmias in a variety of pathologies. Here, we offer an overview of current research on the role of nanodomains in cardiac physiology with particular emphasis on: (1) sodium channel-rich nanodomains within the intercalated disk that participate in cell-to-cell electrical coupling and (2) dyadic nanodomains located along transverse tubules that participate in ECC. The beat to beat function of cardiomyocytes involves three phases: the action potential, the calcium transient, and mechanical contraction/relaxation. In all these phases, cell-wide function results from the aggregation of the stochastic function of individual proteins. While it has long been known that proteins that exist in close proximity influence each other's function, it is increasingly appreciated that there exist nanoscale structures that act as functional units of cardiac biophysical phenomena. Termed nanodomains, these structures are collections of proteins, localized within specialized nanoscale structural environments. The nano-environments enable the generation of localized electrical and/or chemical gradients, thereby conferring unique functional properties to these units. Thus, the function of a nanodomain is determined by its protein constituents as well as their local structural environment, adding an additional layer of complexity to cardiac biology and biophysics. However, with the emergence of experimental techniques that allow direct investigation of structure and function at the nanoscale, our understanding of cardiac physiology and pathophysiology at these scales is rapidly advancing. Here, we will discuss the structure and functions of multiple cardiomyocyte nanodomains, and novel strategies that target them for the treatment of cardiac arrhythmias.
Language	English
Publishing date	2018-09-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2018.01228
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Article ; Online: STIM1 ablation impairs exercise-induced physiological cardiac hypertrophy and dysregulates autophagy in mouse hearts.

Bonilla, Ingrid M / Baine, Stephen / Pokrass, Anastasia / Mariángelo, Juan Ignacio Elio / Kalyanasundaram, Anuradha / Bogdanov, Vladimir / Mezache, Louisa / Sakuta, Galina / Beard, Casey M / Belevych, Andriy / Tikunova, Svetlana / Terentyeva, Radmila / Terentyev, Dmitry / Davis, Jonathan / Veeraraghavan, Rengasayee / Carnes, Cynthia A / Györke, Sandor

Journal of applied physiology (Bethesda, Md. : 1985)

2023 Volume 134, Issue 5, Page(s) 1287–1299

Abstract: Cardiac stromal interaction molecule 1 (STIM1), a key mediator of store-operated ... ...

Abstract	Cardiac stromal interaction molecule 1 (STIM1), a key mediator of store-operated Ca
MeSH term(s)	Mice ; Animals ; Myocytes, Cardiac/metabolism ; Calcium Channels/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Stromal Interaction Molecule 1/metabolism ; Cardiomegaly/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Mice, Knockout ; Calcium/metabolism ; Calcium Signaling ; Mammals/metabolism
Chemical Substances	Calcium Channels ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Stromal Interaction Molecule 1 ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Calcium (SY7Q814VUP) ; Stim1 protein, mouse
Language	English
Publishing date	2023-03-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	219139-8
ISSN	1522-1601 ; 0021-8987 ; 0161-7567 ; 8750-7587
ISSN (online)	1522-1601
ISSN	0021-8987 ; 0161-7567 ; 8750-7587
DOI	10.1152/japplphysiol.00363.2022
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Uc I Zs.249: Show issues

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Article ; Online: NaV1.6 dysregulation within myocardial T-tubules by D96V calmodulin enhances proarrhythmic sodium and calcium mishandling.

Tarasov, Mikhail / Struckman, Heather L / Olgar, Yusuf / Miller, Alec / Demirtas, Mustafa / Bogdanov, Vladimir / Terentyeva, Radmila / Soltisz, Andrew M / Meng, Xiaolei / Min, Dennison / Sakuta, Galina / Dunlap, Izabella / Duran, Antonia D / Foster, Mark P / Davis, Jonathan P / Terentyev, Dmitry / Györke, Sándor / Veeraraghavan, Rengasayee / Radwański, Przemysław B

The Journal of clinical investigation

2023 Volume 133, Issue 7

Abstract: Calmodulin (CaM) plays critical roles in cardiomyocytes, regulating Na+ (NaV) and L-type Ca2+ channels (LTCCs). LTCC dysregulation by mutant CaMs has been implicated in action potential duration (APD) prolongation and arrhythmogenic long QT (LQT) ... ...

Abstract	Calmodulin (CaM) plays critical roles in cardiomyocytes, regulating Na+ (NaV) and L-type Ca2+ channels (LTCCs). LTCC dysregulation by mutant CaMs has been implicated in action potential duration (APD) prolongation and arrhythmogenic long QT (LQT) syndrome. Intriguingly, D96V-CaM prolongs APD more than other LQT-associated CaMs despite inducing comparable levels of LTCC dysfunction, suggesting dysregulation of other depolarizing channels. Here, we provide evidence implicating NaV dysregulation within transverse (T) tubules in D96V-CaM-associated arrhythmias. D96V-CaM induced a proarrhythmic late Na+ current (INa) by impairing inactivation of NaV1.6, but not the predominant cardiac NaV isoform NaV1.5. We investigated arrhythmia mechanisms using mice with cardiac-specific expression of D96V-CaM (cD96V). Super-resolution microscopy revealed close proximity of NaV1.6 and RyR2 within T-tubules. NaV1.6 density within these regions increased in cD96V relative to WT mice. Consistent with NaV1.6 dysregulation by D96V-CaM in these regions, we observed increased late NaV activity in T-tubules. The resulting late INa promoted aberrant Ca2+ release and prolonged APD in myocytes, leading to LQT and ventricular tachycardia in vivo. Cardiac-specific NaV1.6 KO protected cD96V mice from increased T-tubular late NaV activity and its arrhythmogenic consequences. In summary, we demonstrate that D96V-CaM promoted arrhythmias by dysregulating LTCCs and NaV1.6 within T-tubules and thereby facilitating aberrant Ca2+ release.
MeSH term(s)	Mice ; Animals ; Calmodulin/genetics ; Calmodulin/metabolism ; Calcium/metabolism ; Sodium/metabolism ; Arrhythmias, Cardiac/genetics ; Arrhythmias, Cardiac/metabolism ; Long QT Syndrome/genetics ; Myocytes, Cardiac/metabolism ; NAV1.5 Voltage-Gated Sodium Channel/genetics
Chemical Substances	Calmodulin ; Calcium (SY7Q814VUP) ; Sodium (9NEZ333N27) ; NAV1.5 Voltage-Gated Sodium Channel
Language	English
Publishing date	2023-04-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI152071
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