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Biomedical subjects

G Szabó

Publications and source records attributed to G Szabó.

At least 19 recordsLinked to original sources

Evaluation of three different measurement methods for dural ectasia in Marfan syndrome.

AIM: Dural ectasia is a major diagnostic criterion for Marfan syndrome using the Ghent nosology. Our aim was to evaluate the efficacy of three different radiological methods previously proposed for the assessment of dural sac diameter in Marfan syndrome. METHODS: Marfan syndrome was diagnosed in our study using the Ghent criteria, disregarding dural ectasia as a criterion. Three proposed radiological methods were applied to measure dural sac diameter, examined for 41 patients (18 patients with and 23 without Marfan syndrome) by computed tomography or magnetic resonance imaging. RESULTS: Using Oosterhof's method, 94% of the patients with and 44% of the patients without Marfan syndrome fulfilled the criteria of dural ectasia. According to Villeirs, dural ectasia was diagnosed in 18% of the patients with and in none of the patients without Marfan syndrome. With Ahn's method, dural ectasia was found in 72% of the patients with and in 44% of the patients without Marfan syndrome. In only two patients with Marfan syndrome was dural ectasia diagnosed by all three methods. CONCLUSION: Our results reveal overt discrepancy between the three methods of assessing dural ectasia. Considering the key role played by dural ectasia in reinforcing the diagnosis of Marfan syndrome according to the Ghent nosology, a standardized and reliable method should be sought.

Adolescent↗

Synthesis of the pyrazole isostere of valdecoxib.

4-(5-methyl-3-phenyl-1H-pyrazole-4-yl)-benzenesulfonamide, the pyrazole isostere of valdecoxib was synthesised. The title compound was prepared by a six-step procedure starting from commercially available deoxybenzoin 1. The pyrazole isostere 13 showed slight anti-inflammatory and analgesic activities.

Animals↗

P boutons in lamina IX of the rodent spinal cord express high levels of glutamic acid decarboxylase-65 and originate from cells in deep medial dorsal horn.

Presynaptic inhibition of primary muscle spindle (group Ia) afferent terminals in motor nuclei of the spinal cord plays an important role in regulating motor output and is produced by a population of GABAergic axon terminals known as P boutons. Despite extensive investigation, the cells that mediate this control have not yet been identified. In this work, we use immunocytochemistry with confocal microscopy and EM to demonstrate that P boutons can be distinguished from other GABAergic terminals in the ventral horn of rat and mouse spinal cord by their high level of the glutamic acid decarboxylase (GAD) 65 isoform of GAD. By carrying out retrograde labeling from lamina IX in mice that express green fluorescent protein under the control of the GAD65 promoter, we provide evidence that the cells of origin of the P boutons are located in the medial part of laminae V and VI. Our results suggest that P boutons represent the major output of these cells within the ventral horn and are consistent with the view that presynaptic inhibition of proprioceptive afferents is mediated by specific populations of interneurons. They also provide a means of identifying P boutons that will be important in studies of the organization of presynaptic control of Ia afferents.

Afferent Pathways↗

Properties of external plexiform layer interneurons in mouse olfactory bulb slices.

In the external plexiform layer (EPL) of the main olfactory bulb, apical dendrites of inhibitory granule cells form large numbers of synapses with mitral and tufted (M/T) cells, which regulate the spread of activity along the M/T cell dendrites. The EPL also contains intrinsic interneurons, the functions of which are unknown. In the present study, recordings were obtained from cell bodies in the EPL of mouse olfactory bulb slices. Biocytin-filling confirmed that the recorded cells included interneurons, tufted cells, and astrocytes. The interneurons had fine, varicose dendrites, and those located superficially bridged the EPL space below several adjacent glomeruli. Interneuron activity was characterized by high frequency spontaneous excitatory postsynaptic potential/currents that were blocked by the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and largely eliminated by the voltage-sensitive Na+ channel blocker, tetrodotoxin. Interneuron activity differed markedly from that of tufted cells, which usually exhibited spontaneous action potential bursts. The interneurons produced few action potentials spontaneously, but often produced them in response to depolarization and/or olfactory nerve (ON) stimulation. The responses to depolarization resembled responses of late- and fast-spiking interneurons found in other cortical regions. The latency and variability of the ON-evoked responses were indicative of polysynaptic input. Interneurons expressing green fluorescent protein under control of the mouse glutamic acid decarboxylase 65 promoter exhibited identical properties, providing evidence that the EPL interneurons are GABAergic. Together, these results suggest that EPL interneurons are excited by M/T cells via AMPA/kainate receptors and may in turn inhibit M/T cells within spatial domains that are topographically related to several adjacent glomeruli.

Action Potentials↗

Gastrointestinal phenotype of GAD67lacZ transgenic mice with early postnatal lethality.

It has been proposed that gamma-aminobutyric acid (GABA) in the gut may function as a neurotransmitter, hormone and/or paracrine agent. Our aim was to examine transgenic mice of the GAD67-lacZ line with impaired postnatal growth and early postnatal lethality for gastrointestinal abnormalities. The gastrointestinal tract was dissected and processed for histology, immunohistochemistry, electron microscopy, western blotting and measurement of GAD activity. Homozygous mice of both sexes displayed an intestinal phenotype characterized by a fragile and haemorrhagic intestinal wall, a reduced number of villi, epithelial lesions and the occasional appearance of pseudostratified epithelium. The number of GABA-immunoreactive enteroendocrine cells and mucin-secreting goblet cells increased significantly relative to wild-type epithelium. The appearance of GABA-immunopositive neuronal perikarya and the lack of GABA-immunoreactive varicose fibres were observed in the enteric plexuses of transgenic mice. Tissue homogenates of transgenic mice showed higher levels of expression of GAD67 and GAD65 as compared with wild-type mice. Our results suggest that the possible reason underlying the growth impairment and postnatal lethality observed in GAD67 transgenic mice is a functional impairment of GABAergic enteric neurons and disintegration of intestinal epithelium.

Animals↗

Cryopreservation of European eel (Anguilla anguilla) sperm using different extenders and cryoprotectants. Short communication.

Experiments were carried out on the sperm cryopreservation of artificially induced eels. The effects of several extenders and two cryoprotectants on the motility of spermatozoa were investigated. The highest post-thaw motility was observed with the combination of Tanaka's extender and DMSO as cryoprotectant. Further dilution after thawing resulted in complete loss of motility in samples frozen in presence of DMSO while sperm frozen with methanol as cryoprotectant retained its motility after further dilution.

Anguilla↗

The prognostic role of clinical, morphological and molecular markers in oral squamous cell tumors.

Despite of considerable advances in the diagnostic and therapeutic possibilities, the prognosis of epithelial tumors in the oral cavity is still very poor. A knowledge of the prognostic factors at the beginning of treatment is therefore indispensable for determination of the appropriate therapy for the given patient. These factors may be linked to the patient (e.g. age, sex, general condition and immunological parameters) or to the tumor localization. A survey of the literature reveals that the TNM stage, the grade, the mode of invasion and the depth of the tumor infiltration are generally the most important factors influencing the fate of the patient. The prognosis depends primarily on the clinicopathological parameters, though even if they are known, it is not possible to screen out those patients who are at particular risk of a relapse. During the past 10 years, study of the DNA content distribution, the proliferation markers and certain oncogenes has come into the focus of attention; great interest is also shown in the extracellular matrix components and the metalloproteinases, which play key roles in the invasion and metastasis formation.

Biomarkers, Tumor↗

Poly-ADP-ribose polymerase inhibition reduces mesenteric injury after cardiopulmonary bypass.

BACKGROUND: We investigated the effects of PARS inhibition on intestinal injury in a canine model of cardiopulmonary bypass (CPB). METHODS: Twelve dogs underwent 90 minutes of hypothermic CPB. 6 dogs received 5 mg/kg PJ34, a selective PARP inhibitor during CPB, 6 vehicle-treated animals served as controls. Mesenteric blood flow (MBF) and mesenteric vascular resistance (MVR) were measured before and 60 minutes after weaning from CPB. Endothelium-dependent vasorelaxation to acetylcholine (ACH) and endothelium-independent vasorelaxation to sodium-nitroprusside (SNP) were expressed as percent change of MVR. In addition, mesenteric creatine kinase (CK) and lactate release were determined. RESULTS: Baseline hemodynamics, MBF, response to ACH (- 41 +/- 3 vs. - 55 +/- 6 %) and SNP (- 60 +/- 2 vs. - 56 +/- 4 %) did not differ significantly between the groups. The response to ACH decreased significantly in the control group while it remained unchanged in the PJ34 group (- 29 +/- 5 vs. - 46 +/- 9 %, p < 0.05). The response to SNP did not change. Mesenteric CK release (325 +/- 99 vs. 16 +/- 10 U/l, p < 0.05) and lactate production (0.96 +/- 0.17 vs. 0.4 +/- 0.2 mmol/l, p < 0.05) were significantly lower in the PJ34 group. CONCLUSION: PARP inhibition prevents CPB-induced mesenteric endothelial dysfunction and tissue damage.

Acetylcholine↗

The effect of leukocyte interleukin injection (Multikine) treatment on the peritumoral and intratumoral subpopulation of mononuclear cells and on tumor epithelia: a possible new approach to augmenting sensitivity to radiation therapy and chemotherapy in oral cancer--a multicenter phase I/II clinical Trial.

OBJECTIVES/HYPOTHESIS: The main objective of this study was to investigate the effect of the administration of a novel immunoadjuvant, leukocyte interleukin injection, as part of an immuno-augmenting treatment regimen on the peritumoral and intratumoral subpopulations of the tumor infiltrating mononuclear cells and on the epithelial and stromal components, when administered to patients with advanced primary oral squamous cell carcinoma classified as T2-3N0-2M0, as compared with disease-matched control patients (not treated with leukocyte interleukin injection). STUDY DESIGN: Multicenter Phase I/II clinical trial. Fifty-four patients from four clinical centers were included in the dose-escalating study (27 in each group [leukocyte interleukin injection-treated and control groups]). Cumulative leukocyte inter-leukin injection doses were 2400, 4800, and 8000 IU (as interleukin-2 equivalent). METHODS: Paraffin-embedded tumor samples obtained at surgical resection of the residual tumor (between days 21 and 28 after treatment initiation) were used. Histological analysis, necrosis evaluation, and American Joint Committee on Cancer grading were performed from H&E-stained sections. Immunohistochemical analysis was performed on three different tumor regions (surface, zone 1; center, zone 2; and tumor-stroma interface, zone 3). Trichrome staining was used to evaluate connective tissue, and morphometric measurements were made using ImagePro analysis software. Cell cycling was determined by the use of Ki-67 marker. RESULTS: Leukocyte interleukin injection treatment induced a shift from stromal infiltrating T cells toward intraepithelial T cells and posted a significant (P <.05) increase in intraepithelial CD3-positive T cells independent of the leukocyte interleukin injection dose, whereas the increase in CD25 (interleukin-2 receptor alpha [IL-2Ralpha])-positive lymphoid cells was significant only at the lowest leukocyte interleukin injection dose (P <.05). Furthermore, both low- and medium-dose leukocyte interleukin injection treatment induced a significant (P <.05) increase in the number of cycling tumor cells, as compared with control values. CONCLUSION: The results could be highly beneficial for patients with oral squamous cell carcinoma. First, leukocyte interleukin injection treatment induces T-cell migration into cancer nests and, second, noncycling cancer cells may enter cell cycling on administration of leukocyte interleukin injection. This latter effect may modulate the susceptibility of cancer cells to radiation therapy and chemotherapy. The findings may indicate a need to re-evaluate the way in which follow-up treatment (with radiation therapy and chemotherapy) of patients with head and neck cancer is currently approached.

Adjuvants, Immunologic↗

Comparative study of beta-tricalcium phosphate mixed with platelet-rich plasma versus beta-tricalcium phosphate, a bone substitute material in dentistry.

Animal experiments were carried out with osteoconductive bone substitute beta-tricalcium phosphate (beta-TCP), with the aim of assessing the effects of the growth factors synthesised by thrombocytes on the speed of beta-TCP incorporation and on the quality of newly formed bone. The question to be answered was the extent to which platelet-rich plasma (PRP) accelerated the resorption of beta-TCP and the formation of new bone. Two teeth were removed symmetrically from each side of the mandible of 12 Beagle dogs; the resulting cavities were filled on one side with beta-TCP alone, and on the other side with a mixture of beta-TCP + PRP (obtained from autologous blood). The quality of the newly formed bone and the effects of this PRP were studied by histological and histomorphometric methods. In week 6, bone formation was already more effective when PRP was applied in comparison with beta-TCP alone, and in week 12 the growth was significantly greater. The results demonstrate that the use of PRP accelerates the remodelling of new bone created by beta-TCP.

Animals↗

Perfusion-contractility matching during Fontan circulation.

We investigated the relationship between coronary perfusion pressure (CPP) and myocardial contractility and the effects of an acute elevation of right atrial pressure (RAP) on this relationship in an experimental model of Fontan circulation in 6 anesthetized open-chest dogs with isolated perfused coronary arteries. The relationship between CPP and Ees could be described by biphasic J-shaped curves which were nearly identical before and under Fontan circulation. While above a "critical" CPP (72 +/- 9 mmHg vs. 81 +/- 8 mmHg, n.s.) the changes of CPP did not affect Ees, below this level the decrease of CPP resulted in a progressive decrease of Ees. Under Fontan circulation, the progressive increase of RAP did not influence Ees at CPP = 100 mmHg, led to a moderate decrease of Ees at CPP = 75 mmHg and severe decrease at CPP = 60 mmHg. Thus, both coronary arterial and venous pressure affect myocardial contractility after Fontan procedure.

Animals↗

Kinetics of ochratoxin A production in different Aspergillus species.

Kinetics of ochratoxin A production was examined in a number of ochratoxin producing isolates representing different sections of the Aspergillus genus. Both weak and high ochratoxin producers were tested using immunochemical or high-performance liquid chromatograhic methods. All isolates were found to produce the highest amounts of ochratoxin A after 7-10 days of incubation. Ochratoxin production varied between 30 - 5 x l0(5) ng ml(-1) among the Aspergillus isolates tested. The A. albertensis and A. melleus isolates examined were found to produce ochratoxin A constitutively. A. albertensis produced the highest amounts of ochratoxin A at 30 degrees C after 7 days' incubation in YES liquid medium. Ergosterol content and ochratoxin production of A. albertensis cultures were in good correlation.

Aspergillus↗

Quadruple cancer, including triple cancers in the head and neck region.

Multiple primary tumors are not rare: they are encountered in 3-5% of malignant tumors. They are particularly frequent in the head and neck [20]. They are most often met with secondary malignant tumors; triple tumors occur in only 0.5%, quadruple tumors in 0.3% of malignant tumors. The possibility of developing a second metachronous cancer 5 years after undergoing treatment of the initial head and neck cancer is approximately 22%. Multiple metachronous tumors often appear 3-4 years after the observation of the primary tumor, or even after 5-10 years in the case of laryngeal tumors. The frequency of multiple primary tumors in the head and neck region supports the "field cancerization" theory, according to which the inducing agents (primarily smoking and alcohol consumption) can initiate the tumorous degeneration at a number of sites in the oropharyngeal region. The authors report on a case in whom surgery for bladder tumor was followed 101 months later by tumor development in the region of the head and neck: 3 such tumors were treated within a period of 21 months. The histologic result on the bladder tumor was transitiocellular carcinoma, while the latter ones were squamous cell carcinomas. Three of the tumors were treated effectively (no local recurrence or metastasis developed), but the fourth led to the death of the patient. The literature on multiple tumors of the head and neck is reviewed, and possible etiologic factors are discussed. It is pointed out that, besides primary and secondary prevention, close observation of these patients is required, repeated panendoscopy of the upper aerodigestive tract and genetic examinations are recommended.

Carcinoma, Squamous Cell↗

[Anti-Saccharomyces cerevisiae antibodies in patients with Crohn's disease].

Inflammatory Bowel Diseases are a group of diseases with chronic inflammation of the gastrointestinal tract, but without proven etiology. Immunologic, environmental, infective and genetic factors equally can play role in their development. Antibodies to an oligomannose epitope of the Saccharomyces cerevisiae demonstrated in 60-70% of the patients with Crohn's disease. The origin and the clinicopathological role are not clarified. It is important that there are no surveys with patients suffering in gluten sensitive enteropathy in the literature. As there are no ASCA survey in Hungary, the aim of this study was to determine the prevalence of the ASCA. The authors examined at their patients the ASCA's occurrence and compared with the clinical picture of the Crohn's disease. The results supported the theory that ASCA positivity correlates with small intestines' Crohn's disease and in these cases both the IgG and IgA type antibodies proved. The antibodies in the sera at the analyzed ASCA positive cases prove a systemic immune response against Saccharomyces cerevisiae and the authors suggest the end of the oral tolerance against the yeast's antigens. The diet restriction (elemental diet, total parenteral nutrition, and fecal diversion) may ameliorate the status of the patients with Crohn's disease. It is speculated that the yeast-free diet as a part of the therapy for the ASCA positive patients can be reasonable: moreover the permanent "forbidding" of the yeast can be an acceptable alternative in case of getting well.

Adult↗

Defensive alliances in spatial models of cyclical population interactions.

As a generalization of the three-strategy Rock-Scissors-Paper game dynamics in space, cyclical interaction models of six mutating species are studied on a square lattice, in which each species is supposed to have two dominant, two subordinated, and a neutral interacting partner. Depending on their interaction topologies, all imaginable systems can be classified into four (isomorphic) groups exhibiting significantly different behaviors as a function of mutation rate. In three out of four cases three (or four) species form defensive alliances that maintain themselves in a self-organizing polydomain structure via cyclic invasions. Varying the mutation rate, this mechanism results in an ordering phenomenon analogous to that of magnetic Ising systems. The model explains a very basic mechanism of community organization, which might gain important applications in biology, economics, and sociology.

Ecology↗

Influence of degradation on binding properties and biological activity of endomorphin 1.

The recently-isolated endogenous peptide endomorphin 1 has high affinity for the mu opioid receptor and plays an important role in analgesia. Several of its degradation products have been isolated from the central nervous system. Degradation products present structural similarities and may influence the receptor binding properties and biological activity of the parent compound. Therefore, we investigated how degradation of endomorphin 1 might influence ligand binding to the mu opioid receptor, the consequent activation of G proteins and its antinociceptive effect. Both N- and C-terminal truncation of endomorphin 1 resulted in peptides presenting considerably lower opioid receptor binding potency. None of these peptides had an effect on GTP binding, nor was able to produce analgesia, suggesting that degradation destroys the biological activity of endomorphin 1.

Analgesia↗

Phase transition in a spatial Lotka-Volterra model.

Spatial evolution is investigated in a simulated system of nine competing and mutating bacterium strains, which mimics the biochemical war among bacteria capable of producing two different bacteriocins (toxins) at most. Random sequential dynamics on a square lattice is governed by very symmetrical transition rules for neighborhood invasions of sensitive strains by killers, killers by resistants, and resistants by sensitives. The community of the nine possible toxicity/resistance types undergoes a critical phase transition as the uniform transmutation rates between the types decreases below a critical value P(c) above that all the nine types of strains coexist with equal frequencies. Passing the critical mutation rate from above, the system collapses into one of three topologically identical (degenerated) states, each consisting of three strain types. Of the three possible final states each accrues with equal probability and all three maintain themselves in a self-organizing polydomain structure via cyclic invasions. Our Monte Carlo simulations support that this symmetry-breaking transition belongs to the universality class of the three-state Potts model.

Bacterial Physiological Phenomena↗

The influence of intraoperative complications on adhesion formation during laparoscopic and conventional cholecystectomy in an animal model.

BACKGROUND: The aim of this study was to evaluate the extent of postoperative adhesion formation after laparoscopic and open cholecystectomy. MATERIALS AND METHODS: Qualified surgeons performed 60 experimental laparoscopic cholecystectomies (LC) in dogs with the aim to acquire the laparoscopic technique. To assess the relation between the complications during the operation (bleeding, laceration of the liver bed, or gallbladder perforation) and the formation of adhesions, surviving animals were divided into four groups according to the type of complication occurred. Assessment of the results was made by second-look laparoscopy 4 weeks after LC using the adhesion index (AI; score range, 0-4). The animals then were killed so the extent of adhesion formation could be measured. As a control, open cholecystectomy was performed in 15 dogs without intraoperative complications. The Mann-Whitney rank-sum test and Dunn's method were used for statistical analysis. RESULTS: No adhesion formation or intraoperative complications were registered in the laparoscopic group I. In all the cases wherein bleeding or laceration of the liver bed occurred and was managed with electrocoagulation, adhesions formed. Adhesion formation in these groups was significantly higher than in "ideal LC" or cases of gallbladder perforation alone (p < 0.01). All the animals in the control group developed significantly more adhesions than those in the experimental group (p < 0.05). CONCLUSIONS: It seems that LC has a lower rate of adhesion formation than the conventional open technique. Complications such as bleeding or laceration of the liver bed during LC can enhance adhesion formation. No adhesion formation can be mentioned in relation to gallbladder perforation during LC.

Animals↗