PubMed Health⌕ Search

Biomedical subjects

F Gallyas

Publications and source records attributed to F Gallyas.

At least 19 recordsLinked to original sources
PubMed2005

Pituitary adenylate cyclase activating polypeptide protects cardiomyocytes against oxidative stress-induced apoptosis.

Pituitary adenylate cyclase activating polypeptide (PACAP) has well-known neuroprotective effects, and one of the main factors leading to neuroprotection seems to be its anti-apoptotic effects. The peptide and its receptors are present also in the heart, but whether PACAP can be protective in cardiomyocytes, is not known. Therefore, the aim of the present study was to investigate the effects of PACAP on oxidative stress-induced apoptosis in cardiomyocytes. Our results show that PACAP increased cell viability by attenuating H2O2-induced apoptosis in a cardiac myocyte culture. PACAP also decreased caspase-3 activity and increased the expression of the anti-apoptotic markers Bcl-2 and phospho-Bad. These effects of PACAP were counteracted by the PACAP antagonist PACAP6-38. In summary, our results show that PACAP is able to attenuate oxidative stress-induced cardiomyocyte apoptosis.

Animals↗
PubMed2003

Recovery versus death of "dark" (compacted) neurons in non-impaired parenchymal environment: light and electron microscopic observations.

The formation of massively shrunken, hyperbasophilic, hyperargyrophilic and hyper-electron-dense but not apoptotic ("dark") neurons was initiated in rat brains by means of an electric-shock and two mechanical-injury paradigms that do not cause considerable parenchymal damage in the areas investigated. The rats were killed by perfusion fixation either immediately after these instantaneous initiating insults or after a survival period ranging from 40 min to 6 days. The formation of "dark" neurons was complete in less than a few minutes. In the somatodendritic domain of each "dark" neuron, all ultrastructural elements were remarkably preserved during the acute stage, apart from a dramatic reduction of the distances between them. This ultrastructural compaction was accompanied by a marked shift of cell fluid through seemingly intact plasma membrane, mainly into surrounding astrocytic elements. The majority of the "dark" neurons regained their normal morphology and staining properties (recovery) in 4 h. Thereafter, only solitary mitochondrion-derived membranous whorls in the cytoplasm reminded of a previous morphological disturbance. The dead "dark" neurons fell apart into membrane-bound fragments that retained their sharp outlines and compacted interior even after being engulfed by astrocytes or microglial cells. The latter sequence of morphological changes can not be harmonized with the prevailing assumption, according to which "dark" neurons die through the necrotic pathway. The fate of the "dark" neurons appeared to depend on the presence or absence of serious post-insult pathophysiological circumstances in their surroundings.

Animals↗
PubMed2002

Traumatic compaction of the axonal cytoskeleton induces argyrophilia: histological and theoretical importance.

It was earlier established that one of the primary morphopathological consequences of experimental traumatic brain injury is a dramatic reduction in the distances between the neurofilaments (cytoskeletal compaction) inside a number of axon segments that appear to be randomly distributed among normal axons in an otherwise undamaged parenchymal environment. The present results demonstrate that the cytoskeletal compaction instantly induces argyrophilia, thereby rendering possible selective visualisation of the affected axon segments for light microscopy through use of a special silver staining method. On combination of this method with electron microscopy, it was revealed that the cytoskeletal compaction is completed in much shorter times and extends to much longer axon segments than previously assumed.

Animals↗
PubMed2001

Direct effect of Taxol on free radical formation and mitochondrial permeability transition.

To elucidate the potential role of mitochondria in Taxol-induced cytotoxicity, we studied its direct mitochondrial effects. In Percoll-gradient purified liver mitochondria, Taxol induced large amplitude swelling in a concentration-dependent manner in the microM range. Opening of the permeability pore was also confirmed by the access of mitochondrial matrix enzymes for membrane impermeable substrates in Taxol-treated mitochondria. Taxol induced the dissipation of mitochondrial membrane potential (DeltaPsi) determined by Rhodamine123 release and induced the release of cytochrome c from the intermembrane space. All these effects were inhibited by 2.5 microM cyclosporine A. Taxol significantly increased the formation of reactive oxygen species (ROS) in both the aqueous and the lipid phase as determined by dihydrorhodamine123 and resorufin derivative. Cytochrome oxidase inhibitor CN(-), azide, and NO abrogated the Taxol-induced mitochondrial ROS formation while inhibitors of the other respiratory complexes and cyclosporine A had no effect. We confirmed that the Taxol-induced collapse of DeltaPsi and the induction of ROS production occurs in BRL-3A cells. In conclusion, Taxol-induced adenine nucleotide translocase-cyclophilin complex mediated permeability transition, and cytochrome oxidase mediated ROS production. Because both cytochrome c release and mitochondrial ROS production can induce suicide pathways, the direct mitochondrial effects of Taxol may contribute to its cytotoxicity.

Animals↗
PubMed2001

Granule cells are the main source of excitatory input to a subpopulation of GABAergic hippocampal neurons as revealed by electron microscopic double staining for zinc histochemistry and parvalbumin immunocytochemistry.

Immunocytochemistry was combined with a recent modification of Timm's method to evaluate semiquantitatively the mossy fiber innervation of dendrites and somata of parvalbumin-containing neurons of the hilus of the dentate gyrus and the CA3 area of Ammon's horn. Using this electron microscopic double staining technique, it was found that (1) the overwhelming majority (95%) of terminals forming asymmetric synapses with parvalbumin-positive dendrites in the dentate hilus, and the strata pyramidale and lucidum of the CA3 area of Ammon's horn, originated from granule cells; (2) two-thirds of the asymmetric axosomatic terminals of parvalbumin-positive neurons contained zinc; and (3) no zinc-containing axon terminals formed synapses with somata or main dendritic shafts of the granule cells.

Animals↗
PubMed2000

The use of a sodium tungstate developer markedly improves the electron microscopic localization of zinc by the Timm method.

The Timm's sulfide-silver method is frequently used for the demonstration of the mossy fiber bundle or sprouted mossy fibers in the normal or epileptic hippocampal dentate gyrus. Under the light microscope the results are excellent, but the ultrastructure is considerably impaired and the silver grains produced are too large as compared to the sizes of intra-synaptic structures. The present study was meant to test a series of physical developers containing, instead of gum arabic, sodium tungstate as protective colloid. One of them left the ultrastructure fairly intact and produced small, round silver grains, making it possible to precisely locate zinc in mossy terminals. With this method, it could be demonstrated that zinc is contained inside synaptic vesicles in the resting axon terminals of granule cells. As a consequence of prolonged sodium sulfide perfusion, zinc is released from synaptic vesicles and enters the synaptic cleft.

Animals↗
PubMed1999

Enhanced ADP-ribosylation and its diminution by lipoamide after ischemia-reperfusion in perfused rat heart.

Poly-ADP-ribose polymerase (PARP) is considered to play an important role in oxidative cell damage. We assumed that ischemia-reperfusion resulting from the increasing reactive oxygen species (ROS) can lead to the activation of endogenous mono- and poly-ADP-ribosylation reactions and that the reduction of ROS level by lipoamide, a less known antioxidant, can reverse these unfavorable processes. Experiments were performed on isolated Langendorff hearts subjected to 60-min ischemia followed by reperfusion. ROS, malondialdehyde, deoxyribonucleic acid (DNA) breaks, and NAD+ content were assayed in the hearts, and the ADP-ribosylation of cytoplasmic and nuclear proteins were determined by Western blot assay. Ischemia-reperfusion caused a moderate (30.2 +/- 8%) increase in ROS production determined by the dihydrorhodamine 123 method and significantly increased the malondialdehyde production (from < 1 to 23 +/- 2.7 nmol/ml), DNA damage (undamaged DNA decreased from 71 +/- 7% to 23.1 +/- 5%), and NAD+ catabolism. In addition, ischemia-reperfusion activated the mono-ADP-ribosylation of GRP78 and the self-ADP-ribosylation of the nuclear PARP. The perfusion of hearts with lipoamide significantly decreased the ischemia-reperfusion-induced cell membrane damage determined by enzyme release (LDH, CK, and GOT), decreased the ROS production, reduced the malondialdehyde production to 5.5 +/- 2.4 nmol/ml, abolished DNA damage, and reduced NAD+ catabolism. The ischemia-reperfusion-induced activation of poly- and mono-ADP-ribosylation reactions were also reverted by lipoamide. In isolated rat heart mitochondria, dihydrolipoamide was found to be a better antioxidant than dihydrolipoic acid. Ischemia-reperfusion by ROS overproduction and increasing DNA breaks activates PARP leading to accelerated NAD+ catabolism, impaired energy metabolism, and cell damage. Lipoamide by reducing ROS levels halts PARP activation and membrane damage and improves the recovery of postischemic myocardium.

ADP Ribose Transferases↗
PubMed1999

Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation.

Familial Alzheimer disease mutations of presenilin 1 (PS-1) enhance the generation of A beta1-42, indicating that PS-1 is involved in amyloidogenesis. However, PS-1 transgenic mice have failed to show amyloid plaques in their brains. Because PS-1 mutations facilitate apoptotic neuronal death in vitro, we did careful quantitative studies in PS-1 transgenic mice and found that neurodegeneration was significantly accelerated in mice older than 13 months (aged mice) with familial Alzheimer disease mutant PS-1, without amyloid plaque formation. However, there were significantly more neurons containing intracellularly deposited A beta42 in aged mutant transgenic mice. Our data indicate that the pathogenic role of the PS-1 mutation is upstream of the amyloid cascade.

Age Factors↗
PubMed1999

Initial clinical experience with a combined pulsed holmium-neodymium-YAG laser in minimally invasive neurosurgery.

Various biophysical features of the laser beam have already been utilized in clinical neurosurgery. However, the application of this therapeutic modality has by no means been overexploited. The history of laser application in neurosurgery has shown that there is no universal laser system capable of performing all surgical tasks in a suitable manner. The best results in traditional neurosurgery were achieved with instruments combining various wavelengths, such as the CO2 and neodymium-YAG lasers. A pulsed holmium-YAG and neodymium-YAG (Ho:YAG and Nd:YAG) combined laser have been recently developed to meet the special requirements of minimally invasive neurosurgery. The system consists of a compact double-crystal single-head solid-state laser system generating 2 different wavelengths (Ho:YAG 2.08 microns and Nd:YAG 1.05 microns), selected for their capabilities of efficient coagulation and ablation. The two wavelengths are coupled into a common flexible optical fiber, which allows endoscopic application. The wavelengths can act simultaneously or separately without any interchange of the instruments. The system was employed first for experimental and subsequently for clinical purposes, primarily for endoscopic operations. In this work the initial clinical experience is reported. The excellent haemostatic properties of the Nd:YAG laser and the ablative properties of the Ho:YAG laser were confirmed. It was concluded that simultaneous application of the two laser modalities within one flexible fiber offers new perspectives in tissue handling in endoscopic neurosurgery and as in open microsurgery.

Adult↗
PubMed1997

Intracranial pressure waves generated by high-energy short laser pulses can cause morphological damage in remote areas: comparison of the effects of 2.1-micron Ho:YAG and 1.06-micron Nd:YAG laser irradiations in the rat brain.

BACKGROUND AND OBJECTIVE: Histological effects of 2.1-micron Ho:YAG and 1.06-micron Nd:YAG laser pulses were compared in the rat brain, with special regard to areas remote from the irradiated site. STUDY DESIGN/MATERIALS AND METHODS: Laser pulses were delivered through a 0.6-mm glass fiber, the tip of which was either introduced into the caudate nucleus (application mode I), or held at a 2-mm distance above the exposed intact dura. In the latter case, the space between the dura and the fiber tip was filled either with physiological saline (application mode II) or with air (application mode III). RESULTS: In application modes I and II, but not in application mode III, Ho:YAG laser pulses of 1.5 J and 200 microseconds, but not Nd:YAG laser pulses with the same parameters, immediately caused morphological damage to a considerable number of neurons and axons randomly distributed among apparently normal ones in certain areas remote from the irradiated site. A decrease in the energy and an increase in the length of the pulses lowered the incidence of the remote morphological damage. CONCLUSION: This novel finding may impose limits on the application of Ho:YAG lasers in human endoscopic neurosurgery.

Animals↗
PubMed1997

Identifying monoaminergic, GABAergic, and cholinergic characteristics in immortalized neuronal cell lines.

We measured the concentration of neurotransmitters in immortalized neural cell lines of hippocampal, septal, brainstem and cerebellar origin. While in most of the cell lines, concentrations of monoamines, gamma-aminobutyric acid (GABA) and acetylcholine were low, in some they were markedly higher. This made it quite easy to identify possible monoaminergic, GABAergic or cholinergic cell lines. However all the cell lines contained glutamate and aspartate and there were no outstanding differences in levels of these amino acids differences between the cell lines. Deprivation of serum, which made the cells acquire a more differentiated morphology, caused an increase in the intracellular concentrations of some compounds and a switch from multiple to a single transmitter in the case of some cell lines. It suggested that measurement of transmitter concentrations combined with serum deprivation studies, may provide an indication of the neurochemical characteristics of immortalised neuronal cell lines.

Acetylcholine↗
PubMed1997

A common morphological response of astrocytes to various injuries: "dark" astrocytes. A light and electron microscopic analysis.

Our previous studies showed that neurons became argyrophilic following different kinds of brain injuries. In the present study we demonstrated that astrocytes could also become argyrophilic following compressive or concussive head injuries and following intraperitoneal administration of pentylenetetrazole or kainic acid. Furthermore the soma, nucleus and processes of these argyrophilic astrocytes were shown in other preparations to be hyper-basophilic with the light microscope, and hyper-electron dense and shrunken at the ultrastructural level. When the head injuries were inflicted either at the 15th min. of perfusion-fixation or at the 30th min. of transcardial perfusion with chilled physiological saline, several astrocytes also became argyrophilic, hyper-basophilic, shrunken and hyper-electron dense. These data indicate that (i) the intracellular pathological event in these astrocytes is similar to that of "dark" neurons or "dark" cells of non-neural tissues, (ii) the formation of "dark" astrocytes can be independent of the actual state of metabolism, and (iii) the "dark" morphological state of astrocytes might have a role in neuropathological processes.

Animals↗
PubMed1997

Ultrastructural pathology of degenerating "dark" granule cells in the hippocampal dentate gyrus of adrenalectomized rats.

Adrenalectomy-evoked delayed degeneration and death of granule cells in the hippocampal dentate gyrus (DG) of the rat brain were studied by means of electron microscopy and a recently elaborated silver method that selectively stains the "dark", collapsed neurons in a Golgi-like manner. At the light microscopic level, the silver technique revealed degenerating granule cells located exclusively in the dentate gyrus; other glucocorticoid receptor-containing regions of the brain were not affected. The silver-stained cell bodies were shrunken, most of the dendrites had a beaded appearance, and the stained axons could be traced along their route to the CA3 pyramidal neurons of the hippocampus. The analysis of 2.5 microns thick Epon-embedded sections stained with toluidine blue revealed hyperchromatic, dark granule neurons and their remains and a heavy glial activity in the vicinity of collapsing neuronal profiles. At the ultrastructural level, early and late stages of neuronal degeneration were observed. The early phase was characterized by markedly increased electron density, a massive shrinkage of the whole somato-dendritic domain, vacuolization of mitochondria, swelling of the nucleolus and condensation of the nuclear chromatin. In the late stage, subcellular organelles were hardly recognizable due to the extremely high electron density and dramatic shrinkage of the cytoplasm. These profiles exhibited disintegration of the cellular organelles and loss of their afferents. Concomitantly, disintegration of granule cell dendrites (clasmatodendrosis) and lifting of "dark" mossy fibers from cell bodies and dendrites of CA3 pyramidal neurons were observed. In the latter cells, this partial denervation caused no apparent signs of ultrastructural alterations. Proliferation of astrocytes and microglial cells was also obvious as they engulfed and eliminated the degenerating neuronal elements. Degenerating neurons frequently occurred adjacent neurons with normal morphology. These morphological features indicate that the delayed degeneration of hippocampal granule cells following adrenalectomy might proceed through a cytoskeletal collapse terminating in cell death.

Adrenal Glands↗
PubMed1995

Neurotransmitter synthesis by SN6 cell lines, a family of hybrid cell lines of embryonic septal origin.

Previously, we reported the presence of multiple neurotransmitters in subclones of SN6, a septal cholinergic hybrid cell line. To obtain information concerning the functionality of these transmitters, we measured transmitter contents, activities of transmitter-producing enzymes, and the effect of serum-free culture medium in two different batches (SN6.1.6 and SN6.10.2.2) and two subclones of the SN6 cell line (SN6.2a and SN6.1b). Except for SN6.1b, SN6 cell lines and subclones had basically the same neurotransmitter characteristics. Among the transmitters, only acetylcholine seemed to be functional. Monoamine oxidase was missing and activity of aromatic amino acid decarboxylase was diminished in SN6 cell lines. Even in serum-containing medium, SN6.1b had a more mature morphology than the other cell lines, and it contained choline acetyltransferase and acetylcholine but not tyrosine hydroxylase or catecholamines. Similar characteristics were acquired by the mother cell line in response to serum-free conditions. Thus, SN6.1b is the most mature of these central cholinergic neuronal cell lines, at least with regard to neurotransmitter profiles.

Animals↗
PubMed1994

Short-term and long-term changes in the postischemic hippocampus.

We have demonstrated a far more widespread and selective ischemic cell damage than previously thought. In area CA3, a distinct subpopulation of interneurons, characterized by their spiny dendrites and their calretinin content, was selectively vulnerable in the absence of any other CA3 involvement. In the dentate hilus, four different types of spiny cells were consistently damaged. The common denominator in these two cell groups is the presence of spines on their dendrites and hence the greater density of mossy fiber innervation they receive. A common mechanism of cell death may be the presence of non-NMDA receptor subtypes that are highly permeable to calcium. We speculate that they may constitute an important control mechanism in the CA3 region and the hilus, and impairment of this mechanism may be causal to delayed neuronal death in CA1. We have also shown that neuronal degeneration does not end after delayed cell death of CA1 pyramidal cells. Our results suggest that there is progressive degeneration throughout the life of the animal and degeneration of additional cell populations (e.g. CA1 interneurons and CA3 pyramidal cells) may also occur secondary to the insult.

Animals↗
PubMed1994

An immediate morphopathologic response of a subpopulation of astrocytes to electroshock: "dark" astrocytes.

Varying numbers of astrocytes lining the subarachnoid and Virchow-Robin's spaces become stainable by a special silver method in brain sections of rats subjected to a single electroshock of "suitable" parameters immediately before being sacrificed by perfusion fixation. This type of argyrophilia is considered to be induced by some electrically caused morphological damage, since the affected astrocytes are dramatically shrunken and hyperchromatic at both light- and electron-microscopic levels. Based on several points of morphopathologic similarity between the electroshock-damaged astrocytes and "dark" cells of various tissues, especially electroshock-induced "dark" neurons, it is supposed that their nature is also similar ("dark" astrocytes).

Animals↗
PubMed1993

Functional erythropoietin receptor of the cells with neural characteristics. Comparison with receptor properties of erythroid cells.

Radioiodinated erythropoietin (Epo) was bound specifically to the cells of two non-erythroid clonal lines, PC12 and SN6, which expressed neuronal characteristics. The binding was time-, cell number-, and dose-dependent and was reversible. Although the cloned Epo receptor from PC12 cells (derived from rat adrenal medulla) was identical to that from rat erythroid cells, significant differences in the ligand binding properties between two cell lineages were found; 1) PC12 cells had a single class of binding sites with very low affinity (Kd = 16 nM), whereas erythroid cells had two classes of binding sites with different affinities (Kd = 95 pM for high affinity sites and 1.9 nM for low affinity sites), and 2) cross-linking experiments revealed one cross-linked product of 105 kDa for PC12 cells and two products of 140 and 120 kDa for erythroid cells. Taken together with additional results, the presence of a putative accessory protein(s) that may alter the ligand binding affinity through interaction with Epo receptor is discussed. The binding of Epo to PC12 cells caused a rapid increase in the cytosolic concentration of free calcium. The presence of EGTA had no effect on the Epo binding but completely inhibited the calcium increase, indicating that Epo stimulated the calcium influx from outside of the cells. The addition of Epo to the culture media of PC12 cells elevated the intracellular concentrations of monoamines.

Adrenal Medulla↗