PubMed Health⌕ Search

Biomedical subjects

Szabolcs Tóth

Publications and source records attributed to Szabolcs Tóth.

6 recordsLinked to original sources

Ca2+ oscillatory pattern in fertilized mouse eggs affects gene expression and development to term.

The Ca2+ oscillations initiated by the fertilizing sperm (but terminating concomitant with pronucleus formation) apparently ensure that the events constituting egg activation occur in the correct temporal order; early events (e.g., cortical granule exocytosis) require fewer oscillations than later events (e.g., recruitment of maternal mRNA). Whether the Ca2+ signaling events impact long-term development, in particular development to term, is unknown. Using fertilized eggs that have undergone the first few Ca2+ oscillations, we developed procedures that result either in inhibiting or stimulating the natural pattern of Ca2+ signaling of inseminated eggs. Although the incidence of development to the blastocyst stage is unaltered by these procedures, fewer offspring are born following embryo transfer, indicating that developmental competence of the blastocysts is reduced. Interestingly, embryo transfer experiments reveal that when the natural regime of Ca2+ oscillations is precociously interrupted, the incidence of implantation is compromised whereas hyper-stimulation of Ca2+ signaling events compromises post-implantation development. Moreover, although there was no major difference in the overall growth rates of the offspring, those obtained following hyper-stimulation exhibited a far greater variability in their weight. Analysis of global patterns of gene expression by microarray analysis revealed that approximately 20% of the transcripts are mis-regulated when too few oscillations are experienced by the embryo and EASE analysis indicates that genes preferentially involved in RNA processing and polymerase II transcription are differentially affected. In addition, a set of genes involved in cell adhesion is also mis-expressed and could thus be mechanistically linked to the observed reduced implantation. Only about 3% of the transcripts were mis-regulated following hyper-stimulation, and EASE analysis indicates that genes preferentially involved in metabolism are differentially affected. In toto, these results indicate that a range Ca2+ signaling events following fertilization (an excess or reduction) has long-term effects on both gene expression and development to term.

Animals↗

Egg activation is the result of calcium signal summation in the mouse.

Egg activation in mammals is caused by cytosolic Ca(2+) oscillations that are essential for development. However, despite increasing knowledge about signal transduction mechanisms, the functional linkage between frequency number, amplitude and duration of the Ca(2+) signal and the kinetics of pronucleus formation has not yet been defined. While a wide range of Ca(2+) signal parameters are efficient in causing egg activation, the basic rules governing how the egg integrates these signalling events are not yet clear. Thus, in the perspective of better understanding how the egg processes Ca(2+) signalling events, the objective of this study was to determine experimentally whether the efficiency of egg activation and the subsequent early developmental stages rely on Ca(2+) signalling summation. Non-fertilized, but freshly ovulated mouse eggs, were subjected to a series of repetitive Ca(2+) influxes of various patterns modulated by a non-invasive membrane electropermeabilization method. Using a combination of two suboptimal treatments we have shown that mouse eggs can sum up the effects caused by various patterns of intracellular Ca(2+) concentrations transient during the period of egg activation. In addition, overloading the intracellular milieu by repetitive Ca(2+) influxes did not seem to inhibit the process of activation. The kinetics of pronuclear formation among a population of eggs treated in the same conditions became accelerated when the total dose of Ca(2+) signal 'experienced' by the eggs was increased. The results suggested that summation of the biological effects of all Ca(2+) signals constitutes an important mode of Ca(2+) signal integration.

Animals↗

[Supplementary sensory-motor seizures--symptomatology, etiology, and surgical management with illustrative case reports].

In the past decade, owing to the advance of epilepsy surgery, growing knowledge has accumulated on the role of the supplementary motor area, described by Penfield and coworkers in the early fifties, in movement regulation and on the characteristics of seizures involving this area. In the Hungarian neurological literature this topic--despite its neurophysiological and practical clinical importance--has been hardly touched. The authors, based on their own experience obtained from surgeries performed within the framework of the "Co-operative Epilepsy Surgery Program", describe the electrophysiological features of this area, its role in movement regulation and the symptoms of epileptic seizures stemmed from or spread onto this area. Using cases as illustrations, they demonstrate the reasoning and various algorithms of the multidisciplinary examination necessary to explore the seizure onset zone and the pathways of seizure spread. Details of the surgical solution are also described.

Adolescent↗

[Prevalence of patellofemoral pain syndrome. Evaluation of the role of biomechanical malalignments and the role of sport activity].

INTRODUCTION: Disorders around the patella are the most frequent knee complaints seen in adolescents. In the literature many intrinsic and extrinsic risk factors have been linked to Patellofemoral Pain Syndrome (PFPS), but the role of these risk factors is controversial. AIM: The goal of this study was to evaluate the prevalence of PFPS in a group of adolescents aged 12-20 years in Hungary, and to gain more information on the relationship between the biomechanical anomalies of the lower extremity and the PFPS. MATERIAL AND METHODS: In this epidemiological study the authors investigated the effect of sporting activity in the maturation of symptoms among 586 randomly selected students. Different physical examinations, anthropometric measurements, stability tests, footscan analysis were performed. RESULTS: Concerning the prevalence of this syndrome they could not find any differences between males (n = 60, 20.41%) and females (n = 61, 20.89%). The authors could not identify any statistically significant intrinsic risk factors, although changes in the Q angle may be linked to increased prevalence of PFPS. The study supports the theory of the importance of "overload", for there was a significant correlation between the prevalence of PFPS and the different levels of sporting activities (competitive, recreational and non-athletes). CONCLUSION: The authors concluded that the prevalence of PFPS among Hungarian students is 20.65%.

Adolescent↗

In vivo laminar electrophysiology co-registered with histology in the hippocampus of patients with temporal lobe epilepsy.

Laminar multiple microelectrodes have been developed to sample cortical and hippocampal activity in animals. If these measurements are adequately co-registered with the anatomy of the region, they can yield important information about its function and structure. In vivo laminar electrophysiological recordings from the human epileptic hippocampus are rare. However, histological and immunohistochemical analyses are widely used to determine the structural changes associated with temporal lobe epilepsy (TLE). Here we present data obtained by a combined approach: intraoperative recording of laminar field potentials, single and multiple unit activity under anesthesia, accompanied by histology and immunohistochemistry from the same hippocampal region of epileptic patients undergoing temporal lobectomy for drug-resistant TLE. The stability of the electrophysiology and the accuracy of its co-registration with histology were tested successfully. We have found large field potential spikes associated with bursting single units in CA1. Intracortical and subdural strip recordings from the lateral temporal cortex showed similar field potential activation patterns. A prominent oscillatory activity was present in the dentate gyrus with highly localized field potential gradient and multiple unit activity. This pattern could be used as a landmark defining the position of the electrode in the hippocampus. Our findings indicate that some aspects of the local and network epileptiform activity in the hippocampal formation are likely preserved under anesthesia. Electrophysiological identification of the functional state of the hippocampus together with its local structural correlates could further enhance our understanding of this disease.

Action Potentials↗

Paradoxical methylation of the tyrosine hydroxylase gene in mouse preimplantation embryos.

The mouse tyrosine hydroxylase (Th) gene is located in an evolutionarily conserved imprinted gene cluster on distal chromosome 7. It is associated with a CpG island that spans the promoter of the gene. Using a bisulfite sequencing method we show that the Th promoter is fully methylated in both male and female mouse germ cells and in human spermatozoa, suggesting that it belongs to the newly identified category of CpG islands, the similarly methylated regions (SMRs). Contrary to other tissue-specific gene sequences, the mouse Th promoter escapes the initial wave of genome demethylation during the first few cell cycles, but becomes demethylated between the morula and the blastocyst stages. This unusual methylation ontogeny may be a characteristic of the SMRs and/or related to the localization of the Th gene in an imprinted gene cluster.

Animals↗