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Biomedical subjects

T Szabo

Publications and source records attributed to T Szabo.

At least 55 records · Page 3Linked to original sources

Effects of kainic acid on synaptic transmission in electroreceptors (the ampullae of Lorenzini) of skates.

1. Effects of kainic acid (KA) on resting and evoked activities of the ampullary electroreceptor were studied in marine skates (Raja clavata). 2. Perfusion of the basal membrane with 10(-6)-10(-9) M KA produced significant and reversible changes in impulse activity depending on initial firing rate. 3. When synaptic transmission was blocked by perfusion with elevated Mg2+, the resting and evoked activities were restored if KA was added. 4. The results are consistent with the view that KA is a potent excitant of the ampullae receptors and its effects appear to be presynaptic.

Animals↗

Adrenergic effects on internal cardiac defibrillation threshold.

Autonomic neural tone modulates arrhythmias and could affect the efficacy of an implantable defibrillator if defibrillation threshold is also altered by changes in neural activity. We determined the effects of alpha- and beta-adrenoceptor agonists and antagonists on the energy requirement for defibrillation using a sequential-pulse technique in anesthetized pigs. The doses for each drug were selected based on the results of dose-response curves. The mean defibrillation threshold was 10.2 +/- 0.65 J (mean +/- SE) in control and 10.0 +/- 0.84, 9.4 +/- 0.87 and 8.9 +/- 0.89 J during phenylephrine infusions of 0.7, 1.35, and 2.0-4.0 micrograms X kg-1 X min-1 [n = 8, P = not significant (NS)]. Phenylephrine at all infusion rates increased the ventricular fibrillation threshold, indicating that effects on the ventricular fibrillation threshold may occur independent of changes in defibrillation threshold. No significant change was observed in the defibrillation threshold before and after administration of isoproterenol (6.5 +/- 0.72 and 6.7 +/- 0.93 J, n = 8, P = NS). Similarly, no change in defibrillation thresholds was observed after 1.5-2.0 mg/kg phentolamine (8.5 +/- 0.85 and 7.9 +/- 0.93 J, n = 8, P = NS) or 3.0-6.0 mg/kg atenolol (10.0 +/- 1.7 and 10.3 +/- 2.6 J, n = 8, P = NS). However, when defibrillation threshold was determined using a single-pulse method, isoproterenol infusion produced a significant decrease (17.3 +/- 1.5 vs. 14.6 +/- 1.9 J, n = 7, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Differential growth in the brain of the weakly electric fish, Apteronotus leptorhynchus (Gymnotiformes), during ontogenesis.

Growth characteristics of the total brain and of several individual brain regions are described in Apteronotus leptorhynchus. The increase of brain volume relative to total length growth results in a sigmoid growth curve, in which three phases--proportional growth, positive-allometric and negative-allometric growth--could be distinguished. This type of enlargement of the total brain is due to the differential volume increase of individual brain regions and to the increase in the volume of the rhombencephalic structures in particular. Pros- and mesencephalic regions mainly grow in accordance with the overall enlargement of the total brain throughout development, whereas rhombencephalic and certain nuclear structures show such isometric growth only with the onset of the juvenile period. The results are interpreted in the view of functionality of the individual brain regions.

Animals↗

Retinal projections in gymnotid fishes.

Retinal projections were studied in four species of gymnotid fishes, Gymnotus carapo, Hypopomus artedi, Eigenmannia virescens and Sternopygus sp. with the aid of cobalt or HRP labelling and autoradiographic techniques. The optic tract gives off a small branch, the axial optic tract and then, after crossing in the midline, splits into a dorsomedial, dorsal and ventral fascicle. E. virescens and Sternopygus sp. display in addition an accessory optic tract. In all four species retinal projections are bilateral; ipsilateral projections, however, are extremely sparse. In all four species, the retinal fibres terminate bilaterally in the suprachiasmatic nucleus, dorsolateral optic nucleus of the thalamus and the optic nucleus of the posterior commissure; a bilateral retinotectal projection was only found in E. virescens and G. carapo. Retinal projections are only contralateral to the ventromedial nucleus of the thalamus, the central pretectal nucleus and the accessory optic nucleus. The contralateral retinotectal fibres terminate in the stratum fibrosum and griseum superficiale, and in the stratum album centrale and stratum periventriculare. A small accessory optic tract and nucleus were detected in E. virescens and Sternopygus sp. but not in G. carapo and H. artedi. The results indicate that the visual system of gymnotid fish is as simple as that of mormyrids. The poor visibility in the environment where these animals live and the additional sensory system which these animals possess may explain the poor development of the visual system.

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Synaptology of the medullary command (pacemaker) nucleus of the weakly electric fish (Apteronotus leptorhynchus) with particular reference to comparative aspects.

The general organization and synaptology of the medullary command (pacemaker) nucleus (MCN) was investigated in the high frequency weakly electric fish, Apteronotus leptorhynchus. This study was undertaken in order to establish differences and similarities between the MCN of A. leptorhynchus and that of the closely related species, Apteronotus albifrons which has been studied previously. The basic morphology and synaptology of the MCN in A. leptorhynchus is similar to that of A. albifrons. The MCN of A. leptorhynchus consists of large (relay) and small (pacemaker) cells; both cell types receive synaptic input or large club endings with electrotonic gap junctions and bouton-like terminals with polarized chemical synapses. Club endings originate from thick meyelinated fibres belonging to the small (pacemaker) cells, whereas the bouton-like terminals issue from thin myelinated fibers of extranuclear origin. Via their club endings, the small (pacemaker) cells are connected both to each other and to the large (relay) cells. Besides the similarities, there are distinct and characteristic differences between the MCN of the two species, which mainly concern the synaptology of the nucleus. In A. leptorhynchus, the large (relay) cells possess long dendritic processes, covered exclusively with bouton-like terminals; the axon initial segment of large (relay) cells receives boutons, in addition to club endings. Small (pacemaker) cells have short dendritic protrusions receiving input from club endings and boutons; furthermore, the small pacemaker cells axon initial segment receives both club endings and bouton-like terminals. These differences are discussed in terms of the functional organization of the MCN in certain gymnotoids and draw attention to the fact that the morphological and ultrastructural aspects of the central command of the electric organ discharge reveal several differences not only between different gymnotoid fish (Apteronotus and Eigenmannia) but also between closely related species such as A. albifrons and A. leptorhynchus.

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The mormyrid brainstem--II. The medullary electromotor relay nucleus: an ultrastructural horseradish peroxidase study.

The medullary relay nucleus of the mormyrid weakly electric fish Gnathonemus petersii is a stage in the command pathway for the electric organ discharge. It receives input from the presumed command or pacemaker nucleus and projects to the electromotoneurons in the spinal cord. Its fine structure and synaptology were investigated by electron microscopy. The origin of the terminals contacting the cell membrane of the neurons of this nucleus was determined by horseradish peroxidase (HRP) injections into different brain structures, namely into the bulbar command- and mesencephalic command-associated nuclei. Twenty-five to thirty large cells of about 45 micron in diameter constitute the medullary electromotor relay. Each cell has a kidney-shaped, lobulated nucleus, a large myelinated axon with a short initial segment and several long, richly arborizing primary dendrites. Many, if not all, cells are interconnected with large somatosomatic or dendrosomatic, dendrodendritic and dendroaxonic gap junctions. These junctions often occur in serial or triadic arrangements. The relay cells receive large club endings as well as small boutons. The club endings are found mainly on the soma and primary dendrites and are morphologically mixed synapses. The boutons are characterized by synapses which are only chemical and are distributed all over the cell membrane, but with a definitely higher frequency on secondary dendrites and more distal parts of dendritic processes. Horseradish peroxidase injections into the mesencephalic command-associated nucleus reveal a large number of labelled boutons on the secondary dendrites of the relay cells. Injections into the bulbar command-associated nucleus label the same type of boutons as mesencephalic injections, but also label club endings on relay cell soma and primary dendrites. The results support the conclusion made on the basis of previous light microscopical observations that boutons originate from the bulbar command-associated nucleus, whereas the club endings issue from the presumed pacemaker nucleus (nucleus c). The club endings of the bifurcating axons of this nucleus are labelled by retro- and anterograde transport of horseradish peroxidase; the bifurcating axons project simultaneously to the bulbar command-associated nucleus and the medullary relay nucleus.

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The mormyrid brainstem--III. Ultrastructure and synaptic organization of the medullary "pacemaker" nucleus.

The ultrastructure and synaptic organization of the presumed medullary pacemaker nucleus, nucleus c of the weakly electric mormyrid fish, Gnathonemus petersii has been investigated. Nucleus c consists of about 12-15 small (20-25 micron) neurones (P-cells), which form a group situated ventrally to the medullary relay nucleus and embedded in a neuropil of myelinated fibres and dendritic processes. The P-cells often exhibit an enhanced electron density of their cytoplasm and dendroplasm. They possess several dendrites of different diameter, a short, thin axon initial segment and a thickly myelinated axon running in dorsal direction. The pacemaker neurons are interconnected by complex electronic coupling, established by somatosomatic, dendrosomatic and dendrodendritic gap junctions. Perikarya and dendrites are frequently interconnected serially by gap junctions; dendrites showed sometimes triadic gap-junction arrangement. It is suggested that this high degree of electrotonic coupling amongst the pacemaker cells represents the first level of the highly ordered synchronization processes which characterize the electric discharge command system of Gnathonemus. Pacemaker cells receive synaptic input from club endings with mixed synapses and from bouton-like terminals with chemical synapses, both of them originating from medium-sized myelinated fibres and contacting mainly neuronal perikarya and dendritic processes. The axon initial segment receives only few synaptic inputs. Bouton-like terminals were found to be of two types according to their vesicle content, namely, boutons with ovoid, clear synaptic vesicles forming Gray type-1 synapses and boutons with pleomorphic clear synaptic vesicles forming Gray type-2 synapses. Different functional roles for the two types of boutons in modulating pacemaker cell activity are suggested.

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The mormyrid mesencephalon. III. Retinal projections in a weakly electric fish, Gnathonemus petersii.

The optic nerve and the retinal projections were studied in a mormyrid fish, Gnathonemus petersii, by using Fink-Heimer, HRP, cobalt labeling, and autoradiographic tracing techniques. The retinal fibers terminate bilaterally in the following places: suprachiasmatic nucleus, dorsolateral optic nucleus, optic nucleus of the posterior commissure, cortical nucleus, ventral pretectal area, optic tectum, and the accessory optic terminal field. The number of uncrossed fibers is relatively high in the suprachiasmatic nucleus, but negligibly small in the other retinal terminal fields. In the lateral geniculate nucleus and pretectal nucleus only crossed retinal fibers could be detected. The visual system of Gnathonemus is compared to that of other fishes, amphibians, and reptiles and the possible homologies are proposed. The comparison points to the conclusion that the visual system is less developed in Gnathonemus. This nocturnal species lives in turbid waters and has a special electric sense which may permit compensation for the reduced visual capacity.

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The mormyrid brainstem. I. Distribution of brainstem neurones projecting to the spinal cord in Gnathonemus petersii. An HRP study.

The sources of the descending spinal tracts were identified in the teleost fish Gnathonemus petersii by retrograde HRP transport. HRP injections were made at two spinal levels, either at level of the caudal end of the dorsal fin, anterior to the electric organ, or at the pectoral fin. In both cases all labeled cells were found in the rhombencephalon and the mesencephalic tegmentum. No labeled cells were observed either in the cerebellum and lateral line lobes or in the dorsal mesencephalon i.e. torus semicircularis and mesencephalic tectum or in the telencephalon. Following caudal spinal injections, the majority of the labeled cells were grouped in a median and a ventrolateral column of the rhombencephalic reticular formation. The latter is composed of three parts corresponding to the nucleus reticularis inferior, medius and superior. Both Mauthner cells, all the cells in the medullary relay nucleus controlling the electric organ discharge and a few cells in the posterior part of the magnocellular octaval nucleus were labeled. In the mesencephalon, four nuclei were identified by HRP labeling: the nucleus of the medial longitudinal fasciculus, the nucleus reticularis mesencephali and the anterior and posterior tegmental mesodiencephalic nuclei. The rostral injections revealed several additional spinal projections from the descending vestibular and tangential nuclei, from the medial part of the magnocellular nucleus and, finally, from the rostral periventricular gray of the mesencephalon. Also, after such injections, a greater number of cells were labeled in the reticular formation, especially in the median column and in the inferior reticular nucleus. The results suggest that the rostral spinal cord has a larger connection with the acoustico-vestibular area and the medullary reticular formation than the caudal spinal cord. In contrast, the mesencephalic nuclei, probably linked to the mesencephalic tectum and the pretectal area, appears to be a coordinating apparatus between the visual system and the trunk/tail musculature. Thus, it appears that teleost fish possess the same basic equipment of descending spinal pathways as higher vertebrates.

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Pathways of the electric organ discharge command and its corollary discharges in mormyrid fish.

The motoneurons which innervate the mormyrid electric organ are driven by a descending volley from the medullary relay nucleus. This nucleus does not initiate the electric organ discharge (EOD) but is driven in an obligatory manner by another center, a command nucleus. One goal of the present study was to identify this command nucleus anatomically. A second goal was to determine the pathways by which corollary discharges of the EOD motor command exert their effects on sensory input to the electroreceptive lateral line lobe. Horseradish peroxidase (HRP) was injected into the medullary relay nucleus and other EOD command-related centers. Placement was guided by recording the electrical activity preceding the EOD. A nucleus of smaller cells is found immediately beneath the large cells of the medullary relay nucleus. This nucleus, nucleus C, projects densely to the medullary relay nucleus and is hypothesized here to be the command nucleus. Nucleus C appears to receive input from the mesencephalon and from unspecified sources of input to the nearby reticular formation. Nucleus C projects to the medullary relay nucleus and to a lateral nucleus, the bulbar command-associated nucleus. This nucleus is probably the source of the corollary discharge signals. It projects to the medullary relay nucleus and to the paratrigeminal and mesencephalic command-associated nuclei. The latter two nuclei project to separate regions which in turn project to the electroreceptive lateral line lobe. There are thus at least two different paths by which the presumed EOD command nucleus, nucleus C, can affect the electroreceptive lateral line lobe.

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The mormyrid rhombencephalon: I. Light and EM investigations on the structure and connections of the lateral line lobe nucleus with HRP labelling.

The rhombencephalic posterior lateral line lobe nucleus (nLLL) and its connections were investigated in the mormyrid fish Gnathonemus petersii, at light and electron microscopical levels using HRP tracing. The nLLL, constituted on each side of about 1500 large, round shaped, adendritic cells, is located in the intermediate cell and fibre layer exclusively, in the ventrolateral zone of the posterior lateral line lobe. The cells show a complex synaptology: boutons with chemical synapses cover the largest part of the soma and the long initial segment of the axons. In addition each nLLL cell bears generally two club endings which form gap junctions with the postsynaptic membrane. On the unmyelinated portion of the club ending, a particular synaptic complex (= serial synaptic connections) was observed; large endings, bearing boutons with chemical synapses, contact the club ending with gap junctions. HRP injection into either lateral line nerve showed that the club endings represent the peripheral input of the nLLL. This input is exclusively ipsilateral; the anterior and posterior lateral line nerve projection does not seem to overlay at this level. Retrograde labelling of nLLL cells after HRP injection into the anterior mesencephalic exterolateral nucleus (nELa) confirms the electrophysiological results according to which the nLLL projects directly and bilaterally to the nELa. This rhombo-mesencephalic connection is established through club endings of the nLLL axons which form gap junctions with the large cells of the nELa. About two thirds of the nLLL axons form a crossed and one third an uncrossed bundle within the lateral lemniscal pathway. Anterograde transport in the axon collaterals shows that some of the nLLL cells project simultaneously to the ipsi- and to the contralateral nELa permitting this system a high degree of electrosensory information processing.

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Anatomical study and HRP identification of electromotoneurons and motoneurons in the spinal cord of Gymnarchus niloticus.

Two types of neurons were identified by light and electron microscopy in the spinal cord of Gymnarchus niloticus following HRP injections at different peripheral sites: one, situated in the mediodorsal region, is labelled after injection into the electric organ; the other, situated in the lateroventral region, is labelled in addition after injections extending beyond to the lateral muscle. The cells of the first type, thus shown to be electromotoneurons (EMNs), are spherical and do not have dendritic processes; some of them are connected by somato-somatic gap junctions. The EMNs are surrounded by dense glial processes and embedded in a network of myelinated axons of large diameter. Synaptic contacts with the EMNs are of axosomatic type, exhibiting mostly gap junctions and, less frequently, mixed or chemical junctions. Some endings establish gap junctions simultaneously, with two electromotoneurons, the somatic membrane of which may be joined. The initial segment does not bear any endings. The second type of cells, identified as motoneurons, are pyriform and have large dendritic processes. The motoneurons are surrounded by myelinated axons of small diameter. They receive axosomatic endings with chemical synapses.

Afferent Pathways↗

Synaptic organization in the pacemaker nucleus of a medium-frequency weakly electric fish, Eigenmannia sp.

The medullary command nucleus (MCN) of the medium-frequency weakly electric fish, Eigenmannia sp., contains two types of neurones, namely large and small cells, which are embedded in a neuropile of large and small myelinated fibers. Using serial semi-thin and ultra-thin sectioning, combined with HRP labelling it has been established that both cell types possess rich dendritic arborization and large myelinated axons. Only the axons of the large cells leave the nucleus and these constitute the unique output of the MCN. Axon branching has been observed only in the axons of small cells and their collaterals show an exclusively intranuclear course. Two types of synaptic terminals have been found on large as well as on small cells: (1) large club endings forming both gap (electrotonic) junctions and polarized chemical synapses, which often appear at the same junction constituting morphologically mixed synapses; and (2) small bouton-like terminals forming exclusively chemical synaptic contacts. No differences between the two neuron types could be detected with respect to the arrangement of the synaptic contacts: club endings and small bouton-like terminals synapse on dendritic processes as well as on perikarya, while the unmyelinated initial segments were always found to be free of synaptic contacts. Large and small cells were found to be simultaneously connected by the same club ending or small bouton-like terminal: in the case of club endings by means of gap junctions and chemical synapses, whereas in the case of boutons by chemical synapses only. Club endings sometimes form gap junctions with each other. The possible role of these unusual synaptic connections in local synchronization is suggested. Club endings originate from the large axons of small cells, while small bouton-like terminals originate from the fine myelinated fibers of extranuclear origin. In Eigenmannia, small cells, being connected to large cells as well as to each other by axo-somatic and axodendritic synapses, can be considered as the pacemaker cells of the MCN whereas large cells are relay cells. Small bouton-like terminals may convey exogeneous impulses towards the MCN exerting modulatory effects at both pacemaker and relay cell levels. The greater variety of ultrastructural correlates established in the MCN of Eigenmannia, in comparison with Sternarchus (see also ref. 16), suggests increased modulation possibilities in the former fish's EOD behaviour.

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Increased cytotoxic sensitivity of YPC-1 tumor cells from mice treated with nitrosoureas.

The relative cytotoxic sensitivity of the YPC-1 tumor target cells from untreated mice and from animals treated with nitrosoureas was determined. The amount of 51Cr released from target cells increased significantly when the cells were obtained from treated mice. On the basis of the results of cold-target cytotoxicity inhibition assay, this enhancement was shown to be haplotype specific. The amount of 51Cr released from target cells of mice treated with N,N'-bis(chloroethyl)-N-nitrosourea decreased significantly when the tumor cells were first incubated with fibrinogen and transglutaminase. Based on these results and other published data, a model system is suggested. The model is based on the observation that tumors, and thus tumor antigens, at the cell surface are partly or completely covered by fibrinogen or fibrin. The enzyme transglutaminase is involved in the binding of the fibrinogen or fibrin to the cell surface. Accordingly, it is hypothesized that the nitrosoureas have a dual mode of immunotherapeutic activity. The carbamoylating properties inhibit the fibrin-binding activity of transglutaminase, thus preventing fibrin from covering up or coating the tumor cells and preventing the ability of sensitized effector cells to recognize the tumor-specific antigens in association with self H-2 antigens. The alkylating property of the nitrosoureas mainly concerns reactivity with the DNA of the tumor cells.

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