Papers by Ágnes Nemeskéri
Experimental and Clinical Endocrinology & Diabetes, Jul 16, 2009
The ontogeny of hypothalamic GnRH, of pituitary and gonadal receptors and of pituitary LH and FSH... more The ontogeny of hypothalamic GnRH, of pituitary and gonadal receptors and of pituitary LH and FSH was studied in the fetal and neonatal rat. Hypothalamic, hypophyseal and gonadal primordia were dissected from animals ranging in age from postconceptual day 12 to birth. Immunoreactive GnRH was detectable in the hypothalamus from fetal day 12 onwards at a low level until day 17, whereafter hypothalamic GnRH content and concentration increased until birth. GnRH receptors were reliably detectable in the pituitary anlage from fetal day 16 onwards and increased progressively with advancing age whether expressed as content or concentration. Signs of pituitary LH synthesis were evident as early as fetal day 12 but intrapituitary LH levels remained low until fetal day 17 when levels increased progressively until the end of gestation. Pituitary FSH was undetectable until fetal day 19, thereafter rising dramatically until the end of gestation. GnRH binding to testicular and ovarian tissues was undetectable throughout the period of fetal development. The possible relations among the developmental changes in hypothalamic GnRH, pituitary GnRH receptors and gonadotrophins are discussed.
EP Europace, 2018
Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with... more Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased mortality, morbidity and impaired quality of life. Maintenance of sinus rhythm is the primary therapeutic goal for symptomatic AF patients but remains difficult to achieve because of suboptimal treatment options. While being effective in detecting and terminating AF, the use of implantable atrial defibrillators is limited due to patients intolerance to repeated shocks. The negative adverse effects of electroshock therapy can hypothetically be overcome by allowing the heart itself to produce the electric current required for arrhythmia termination. As a result, the effector function of an electrical defibrillator would be provided by the heart itself, and therefore no longer rely on electronics, but on bioelectricity instead. Purpose: The purpose of this study was to evaluate the feasibility of autogenous AF termination through light-controlled generation of atrial currents following local optogenetic gene delivery. Methods: Adeno-associated virus (AAV) vectors encoding red-activatable channelrhodopsin (ReaChR) under control of an atrial specific promoter were delivered locally to the right atrium (RA) of adult Wistar rats by gene painting (n¼8). Four to six weeks later, episodes of AF were induced in vivo by electrical burst pacing during carbachol infusion, followed by programmed and local epicardial illumination of the RA through a small opening of the 4th right intercostal space. Results: Gene painting of the RA encoding ReaChR resulted in transmural transduction of right-atrial myocytes with minimal transgene expression of the left atrium and ventricular myocytes. Electrophysiological assessments by ECG and optical mapping, 4-6 weeks following the gene paint procedure, revealed no significant differences in heart rate, P-wave duration, PR-interval, action potential duration and conduction velocity when compared to baseline. Following in vivo induction of sustained AF (>10 s), a single brief 470-nm light pulse (1000ms, 3.5 mW/mm 2) targeting 20 mm 2 of the RA, terminated AF in all rats tested (n¼8), with an average termination efficiency of 9265% vs 0% when no light was applied (p < 0.01). No bradycardias were observed following autogenous AF termination as the average R-R interval prior AF induction and following autogenous AF termination were similar (p¼0.454). Conclusions: Our study delivers proof that the heart can be enabled to autogenously terminate AF with high efficiency by adding light-gated ion channels to its bioelectric capacity. This way, the heart relies on endogenous cardiac electrochemical gradients for arrhythmia termination rather than high-voltage shocks used in conventional electrical cardioversion. These findings may lay the foundation for the design and development of pain-free device therapy for atrial arrhythmias through biomedical engineering.
European Journal of Surgical Oncology, 2019
colorectal cancer (CRC) and to evaluate their potential as an immunotherapeutic modality. Materia... more colorectal cancer (CRC) and to evaluate their potential as an immunotherapeutic modality. Material and Methods: Samples of resected colorectal cancers were collected from 20 patients. Tumors were minced into fragments and cultured in media containing high dose interleukin-2 (IL-2) for up to 5 weeks. T cell phenotype, activation markers, and reactivity were measured. Results: TILs were successfully isolated from at least one plated fragment in all of the 20 patient tumors (100 %) in the presence of high dose IL-2 (6000 IU/mL) after 2 to 3 weeks of culture. TILs yield varied between patient samples with an average yield of 1.37 x 10 6 TILs from an average of just over 20 fragments per patient. 18 samples of the 20 (90 %) measured gave rise to at least 10 million TIL, the minimum number required for initiation of a clinical scale rapid expansion protocol (REP). Extrapolated to the 48 fragments typically set up during a clinical scale expansion, the average yield increased to over 65.8 million TILs. The majority of these expanded TIL were CD8+ T cells and CD4+ T cells. Especially, greater than 80 % of CD8+ T cells were producing IFN-g and CD107a. Conclusion: In this study, we successfully expanded TILs from CRC tissue and showed that the ex vivo expanded TILs contained mostly effector memory T cells and they were found the functional potential to elicit an anti-tumor response. These results together indicate that TILs could be an alternative medicine for patients with refractory CRC. Conflict of interest: No conflict of interest.
European Journal of Surgical Oncology, 2019
Introduction: Hilar cholangiocarcinoma (Klatskin-tumor) accounts for 60-80% of bile duct cancers.... more Introduction: Hilar cholangiocarcinoma (Klatskin-tumor) accounts for 60-80% of bile duct cancers. Hilar resection in combination with extended liver resection and radical hilar lymphadenectomy has resulted in a higher rate of R0 resections and increased survival in patients with Klatskin-tumor. This aggressive surgical approach could however be associated with higher rates of operative morbidity and mortality largely due to postsectorial liver failure. To optimize the liver function and to improve the mortality rate after extended liver resections preserving of the functional liver parenchyma is crucial. Little is known about exact bile drainage of Segment I. Aim of our study was to analyse the anatomical variations in bile duct drainage of caudate lobe or Segment I in order to help hepatobiliary surgeons operating on Klatskin-tumours and extended liver resections. Materials and methods: A modified corrosion technique was worked out and applied in a total of 106 cadaveric livers: the main bile duct was cannulated with polyethylene tubing, then a special synthetic resin mixture was injected into it. Parenchyma was removed by KOH solution and the different variations of bile drainage of Segment I were analyzed. Results: On the 106 preparations Segment I drained directly just into the left hepatic duct (LHD) in 41.5%, directly just into the right hepatic duct (RHD) in 14.2%. Drained directly just into the right posterior hepatic duct (RPHD) in 14.2%, however it was affected in a total of 33.95%. Segment I. duct joined into Segment II. duct in a total of 4.7%. A combined drainage of Segment I. was observed in a total of 20.65% (RHD+LHD: 7.5%, RPHD+S.II duct: 3.75%, RPHD+LHD: 6.6%, RPHD+RHD: 2.8%). Conclusions: Our results could contribute to preoperative and intraoperative decision making during extended liver resections due to hilar cholangiocarcinoma and other liver tumors. Preserving viable liver parenchyma during extended resections could decrease the rate of postoperative liver failure as "small for size syndrome" and could reduce the postoperative morbidity. Conflict of interest: No conflict of interest.
HPB, 2016
arterial branch thrombosis (1 early, 1 late) requiring anticoagulation. Other morbidity included ... more arterial branch thrombosis (1 early, 1 late) requiring anticoagulation. Other morbidity included collection (n = 2) and graft pancreatitis (n = 1). All grafts were functioning at a median follow up of 15 months (range 10e21) and all patients were insulin independent. Conclusions: Our data suggests luminal narrowing of all arteries associated with the pancreatic allograft without any corresponding changes in the renal arteries. This does not appear to impact on short term graft function. It is difficult to determine whether this remodelling process directly contributes to the development of vascular pathology. Therefore further studies should be performed to discover whether this phenomenon is detrimental in the long-term, and to determine if therapeutic intervention is required.
HPB, 2016
to the individual risk. Results: Between 2008 and 2014, 98 patients were candidates to IAT. 54 pa... more to the individual risk. Results: Between 2008 and 2014, 98 patients were candidates to IAT. 54 patients finally received IAT, while the remaining patients did not for a variety of factors (unmet intraoperative requirements, isolation failure/contamination, unstable patients, refusal or other). Control group was made of the remaining patients + further 17 patients with predicted high-risk anastomosis who entered a randomized study but were not randomized to IAT. Early IAT-related complications occurred in 8 patients (14.8%), four of these in case of completion pancreatectomy for POPF. 26/54 patients receiving IAT and 35/61 patients of the control group had malignancy. At a median follow-up of 557d, in the IAT group, relapse was observed in 4/22 patients that were disease-free after surgery (18.2%), and only 2 patients developed new liver metastases (9.1%). In the control group, relapse was observed in 13 patients (40.6%) of whom 7 developed new liver metastases (21.9%). At last follow-up, insulin independency was present in 45% of patients undergoing IAT and further 35% showed partial graft function. Conclusions: IAT can be performed with acceptable safety profile in selected patients with malignancy.
Interventional Medicine and Applied Science, 2009
In recent years, post mortem multi-slice computed tomography (MSCT) is increasingly applied for f... more In recent years, post mortem multi-slice computed tomography (MSCT) is increasingly applied for forensic and pathologic examination. However, classical dissection remains dominant in everyday practice. Lack of quantifiable data on the coronary system has become a disadvantageous attribute of traditional autopsy. Therefore, post mortem MSCT angiography was performed in 80 ex corpo hearts with the aim of improving the accuracy and quantitative documentation of pathologic and forensic diagnoses of coronary artery disease (CAD). Hearts were perfused by introducing a new oily or synthetic resin, or using both contrast materials successively. Then the perfused organs were processed for imaging. Detailed angiographic analysis enabled us to localize, map and quantify coronary calcifications, stenoses, and to characterize the types of atherosclerotic plaques. Significant early or late complications of widely used percutaneous coronary interventions (PCI) and coronary bypass surgery (CABS) co...
Pancreatology, 2012
Objectives: To evaluate the ability of contrast-enhanced computerized tomography (CECT) to diagno... more Objectives: To evaluate the ability of contrast-enhanced computerized tomography (CECT) to diagnose acute postnecrotic collections (APNC) over course of the disease. Patients and methods: Retrospective observation double centre study: performed to our patients with acute pancreatitis (AP) admitted in Gomel Regional Clinical and Mozyr City Hospitals in 2011. We studied the CT characteristics of APNC in various stages of the disease. Accuracy of CT differentiation we controlled by drainage and operation data. Results: From 59 patients with AP collections were present in 23 (39%) cases and 9 (15%) of them were detected as APNC. CECT was performed within the first 10 days after admission and later on 20-71 day of necessity. In 5 patients collections were drained on mean 16,4 day and 3 of these were operated on mean 29,7 day. Necrotic masses in collection content detected by CECT were proved to be present perioperatively in all drained/operated patients and none of them had walls. We reexamined the density of APNC on preoperative CT scans and subjected obtained data to statistical analysis. The Hounsfield units' analysis of CT images (Me [25%-75%]): early APNC HU¼12,35 [9-16,2]; late APNC HU¼18,4 [11,7-23,6]. According to Mann-Whitney analysis, the difference is statistically significant (p<0,001). Conclusion: 1. Over the course of AP APNC becomes more homogenous, but the density increases.
Anaesthesia, 2017
SummaryWe assessed the suitability of human cadavers preserved using Thiel's method for teach... more SummaryWe assessed the suitability of human cadavers preserved using Thiel's method for teaching flexible fibreoptic tracheal intubation. Thirty‐one anaesthetists unacquainted with this technique received didactic teaching followed by handling of the fibrescope on the Oxford teaching box. They then carried out fibreoptic intubations in two cadavers to establish a baseline sample of their intubation skills. Thereafter, we randomly assigned the trainees to two groups to practice fibreoptic intubation either on two distinct cadavers or on two airway manikins. After 7 days we re‐assessed procedural skills using the same cadavers as at baseline. Intubation time was the primary outcome and secondary outcomes included the incidence of failed intubations. We also evaluated trainee satisfaction. The mean (SD) intubation time decreased from a baseline value of 74 (20) s to 35 (6) s in the cadaver group and to 56 (16) s in the manikin group. The effect of ‘time’ was significant (p = 0.002)...
Neuro endocrinology letters
Endocrinologia experimentalis, 1990
Rathke's pouches of 12- and 13-day-old rat embryos were implanted beneath the kidney capsule ... more Rathke's pouches of 12- and 13-day-old rat embryos were implanted beneath the kidney capsule of adult male rats subjected to the removal of median eminence or to sham-operation. Host animals were sacrificed 28 days after grafting and the implanted pituitaries were processed for immunohistological examination. ACTH, LH-beta, FSH-beta, TSH-beta, GH and PRL immunopositive cells could be observed in fetal grafts of all experimental groups. However, the number and staining intensity of different hormone containing cells largely varied and presumably depended on the hormonal state of host animals. The results indicate that undifferentiated fetal pituitary does not require hypothalamic hypophysiotrophic neurohormones for proliferation and cytodifferentiation and that its development might be modulated by circulating trophic hormones of host animals.
Neuro endocrinology letters
Acta paediatrica Academiae Scientiarum Hungaricae, 1972
Endocrinologia experimentalis, 1990
Rathke's pouches of 12- and 13-day-old rat embryos were implanted beneath the kidney capsule ... more Rathke's pouches of 12- and 13-day-old rat embryos were implanted beneath the kidney capsule of adult male rats subjected to the removal of median eminence or to sham-operation. Host animals were sacrificed 28 days after grafting and the implanted pituitaries were processed for immunohistological examination. ACTH, LH-beta, FSH-beta, TSH-beta, GH and PRL immunopositive cells could be observed in fetal grafts of all experimental groups. However, the number and staining intensity of different hormone containing cells largely varied and presumably depended on the hormonal state of host animals. The results indicate that undifferentiated fetal pituitary does not require hypothalamic hypophysiotrophic neurohormones for proliferation and cytodifferentiation and that its development might be modulated by circulating trophic hormones of host animals.
Acta physiologica Hungarica, 1986
The effect of unilateral vagotomy on compensatory renal growth that follows unilateral nephrectom... more The effect of unilateral vagotomy on compensatory renal growth that follows unilateral nephrectomy was studied. Unilateral vagotomy inhibited the usual compensatory growth of the remaining kidney. Unilateral vagotomy did not effect kidney weight in animals with two kidneys. Data indicate that the vagus nerve is involved in the development of compensatory kidney hypertrophy.
Annales d'endocrinologie, 1987
Specific differentiation of the hypothalamus and that of hypophysis has been followed. From day 1... more Specific differentiation of the hypothalamus and that of hypophysis has been followed. From day 12 of fetal life the synthesis of hypothalamic LHRH could be demonstrated by radioimmunoassay. The presence of adenohypophyseal LHRH receptors was also evident from day 16 of gestation. Studies on gonadotroph hormone synthesis have revealed that production of LH starts on fetal day 12, while that of FSH appears later, on fetal day 19. In order to study the capacity of hypophysis to differentiate, Rathke's pouches removed on fetal days 11-12 were maintained in organ culture. It has been demonstrated by immunocytochemistry and RIA that hormone production occurs also in cultures pituitaries kept in chemically defined medium (M 199). In sum, these results suggest that hypothalamus factors do not seem to play a determining role in the cytodifferentiation of hypophyseal cells.
Medical science monitor : international medical journal of experimental and clinical research, 2002
The presence of PACAP and VIP was demonstrated in all the four levels of the photoneuroendocrine ... more The presence of PACAP and VIP was demonstrated in all the four levels of the photoneuroendocrine system (PNES) with the use of immunohistochemistry (IHC), radioimmunoassay (RIA), anterograde and retrograde tracing techniques, and cell immunoblot assay (CIBA). Both peptides play a physiological role in the PNES. According to our results both PACAP and VIP are involved in the regulation of the gonadotrop hormone secretion and their inhibitory role may be mediated through the neuronal chain of the PNES.
Acta paediatrica Academiae Scientiarum Hungaricae, 1972
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Papers by Ágnes Nemeskéri