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Biomedical subjects

J Takács

Publications and source records attributed to J Takács.

At least 37 records · Page 2Linked to original sources

Distribution of metabotropic glutamate receptor type 1a in Purkinje cell dendritic spines is independent of the presence of presynaptic parallel fibers.

The metabotropic glutamate receptor type 1a (mGluR1a) is expressed at a high level in the molecular layer of the cerebellar cortex, where it is localized mostly in dendritic spines of Purkinje cells, innervated by parallel fibers. Treatment with methylazoxymethanol (MAM) of mouse pups at postnatal days (PND) 0 + 1 or 5 + 6 results in the partial loss of granule cells, the extent of which depends on the age of the animal at the time of injection. As a consequence of hypogranularity, the number of parallel fibers is decreased to such an amount that many of the postsynaptic Purkinje cell dendritic spines are devoid of axonal input, and only a limited number of spines participate in the formation of parallel fiber synapses, or, infrequently, in heterologous or heterotopic synapses with other presynaptic partners. At PND 30, 50% of the spines in the cerebella of mice treated with MAM at PND 0 + 1 was not contacted by any presynaptic element, compared to 5% in controls or 15% in the cerebella of mice treated with MAM at PND 5 + 6. The localization of mGluR1a was visualized by immunocytochemistry on ultrathin sections: approximately 80% of all Purkinje cell dendritic spines were immunopositive in controls and in both groups of MAM-treated mice, indicating that mGluR1a was present in Purkinje dendritic spines even when the corresponding synaptic input was absent. This observation indicates that the expression and subcellular distribution of mGluR1a are inherent, genetically determined properties of Purkinje cells.

Aging↗

[Diagnosis of chronic massive pulmonary thromboembolism in elderly patients].

Chronic massive thromboembolism of the pulmonary artery is an occlusion of the major branches of the pulmonary artery which develops as a result of repeated embolisms, as a result of non-dissolution and organizing of a thrombus or retrograde growth of a thrombus. The authors observed four elderly patients with chronic massive pulmonary embolization. In their clinical picture dominated progressing dyspnoea and signs of right heart failure. In the diagnosis perfusion scan of the lungs and pulmoangiographic examination plays an important part as they revealed even unilateral absence of pulmonary circulation. This examination was stimulated by weaker respiration at the site of the lacking perfusion in a portion of the lungs.

Age Factors↗

[N2O-induced acute funicular myelosis in latent vitamin B 12 deficiency].

The neurotoxicity of nitrous oxide ("laughing gas") had already been observed in 1956 when using N2O in the long-term sedation of tetanus patients. In 1967 Parbrook described leukopenic effects during long-term exposure to N2O. It was only in 1978 that further studies were conducted on myeloneuropathies and myelodepression under the influence of N2O. The basic cause is vitamin B12 deficiency and the irreversible oxidation of coenzyme B12 by N2O. Between 1986 and 1995 eight cases of acute funicular myelosis associated with latent vitamin B12 deficiency subsequent to nitrous oxide anaesthesia were reported. In our hospital, two further patients now have this disease. Two observations must be emphasised when assessing the 10 patients mentioned above: 1. There was no long-term exposure to N2O (> 6 hrs); the periods of anaesthesia were between 1.5 and 3.5 hrs. 2. Vitamin B12 deficiency was not known preoperatively, and there was no marked pernicious anaemia, so that the only pointers to the risk patients were supplied by the mean corpuscular haemoglobin (MCH) and the mean corpuscular volume (MCV) of the blood picture.

Anesthesia, Inhalation↗

Immunocytochemical localization of mGluR1a metabotropic glutamate receptor in inhibitory interneurons of the cerebellar cortex.

Immunocytochemical investigation of metabotrop glutamate receptor la in the cerebellar cortex of rat revealed a presence of this receptor in all cortical inhibitory nerve cells (Purkinje, basket, stellate, Lugaro and Golgi). In addition to the previously described localization of this receptor in Purkinje dendritic spines supplied by parallel and climbing fibres and considered to be responsible for cerebellar long-term depression, we have observed metabotropic glutamate receptor la immunopositivity also in the synapses between parallel fibres and dendrites of basket, stellate and Golgi neurons. The postsynaptic receptor was also present occasionally in inhibitory synapses between stellate cell axons and Purkinje cells as well as between Purkinje axon collaterals and Lugaro cell dendrites. The possibility, that mGluR1a receptors in basket, Golgi and stellate cells might directly or indirectly contribute to cerebellar LTD, is discussed.

Animals↗

Postsynaptic and extrasynaptic localization of kappa-opioid receptor in selected brain areas of young rat and chick using an anti-receptor monoclonal antibody.

kappa-opioid receptors were visualized by light and electron microscopical immunohistochemistry in young rat and chick brains, using a monoclonal antibody KA8 (IgG1, kappa) raised against a kappa-opioid receptor preparation from frog brain, which recognizes selectively the kappa-type receptor with preference for the kappa-2 subtype. The most pronounced kappa-opioid receptor-like immunoreactivity was observed in the hypothalamic nuclei of the rat brain and in the chick optic tectum, in regions where the functional significance of kappa-opioid receptors is well documented. Both neurons and glia were stained, the former on both somata and dendrites. At the ultrastructural level, the receptor-like immunoreactivity was similar in both species. Immunoprecipitate decorated the inner surface of the plasma membrane of glial cells, neuronal somata and dendrites, in a discontinuous arrangement. In the cytoplasm, labelling was associated with ribosomes, polyribosomes and rough endoplasmic reticulum membranes but not with Golgi cisternae. In the neuropil, the immunoprecipitate was observed along the dendritic microtubules and was also associated with postsynaptic sites. Nuclei and axons were devoid of label and immunoreactivity was never visible presynaptically. Our findings indicate that the antibody used in the present study marks various forms of the kappa-opioid receptor protein including those synthesised in ribosomes, transported along dendritic microtubules and incorporated into postsynaptic and non-synaptic membranes. The antibody also recognizes glial opioid receptors. The observed subcellular distribution appears to be conserved in phylogenetically distant species.

Age Factors↗

Similar fine structural localization of immunoreactive glutamate in the frog pineal complex and retina.

The distribution of immunoreactive glutamate was compared in the pineal complex (pineal and frontal organs) and retina of frogs (Rana esculenta, R. arvalis, R. ridibunda, R. catesbeiana, Bufo viridis, Bombinator igneus) by postembedding immuno-electron microscopy. Similar to retinal photoreceptors (rods and cones), bipolars and ganglion cells, the rod- and cone-like photoreceptors and the neurons of the pineal and frontal organs exhibited glutamate immunoreactivity. Synaptic terminals of photoreceptor cells on secondary neurons of the pineal complex and retina were strongly immunoreactive. The pineal tract and the fibers of the frontal nerve also displayed glutamate immunoreactivity. There was no essential difference in the immunoreactivity of the retinal and pineal elements among the species studied. The similar histology of the pineal complex and retina of the frog and the high correlation of their binding sites of antiglutamate immunosera allow us to assume that glutamate performs a similar role in the pineal complex as is already known for the retina. The high immunoreactivity of the presynaptic region of pinealocytic processes and axons of secondary neurons suggests the role of a neurotransmitter for this excitatory amino acid in the efferent pathways of the pineal complex.

Animals↗

Synaptic reorganisation of the mediodorsal thalamic nucleus in adult rat following chronic prefrontal cortical lesions.

Chronic changes in the thalamic mediodorsal nucleus (MD) after unilateral lesions of the prefrontal cortex were studied with the aid of quantitative light, and electron microscopic immunohistochemistry. Three months after the lesions, although the size of MD ipsilateral to the lesion did not change considerably, the neuronal density was significantly reduced. Conversely, as demonstrated by quantitative electron microscopy, the density of GABA immunostained axon terminals significantly increased in the lesioned side. It is suggested, that as MD does not contain GABA cells, the reactive hyperinnervation of the MD by GABA-containing axons is of extrinsic origin. This finding is also the morphological evidence of the potential of GABA-ergic nerve cells for reactive (induced) axonal sprouting.

Animals↗

Developmental dynamics of Purkinje cells and dendritic spines in rat cerebellar cortex.

Quantitative morphological changes of the developing Purkinje cells were studied from 6 to 90 postnatal (PN) days in the IVth lobule of vermis in the cerebellum of rats. The soma size (mean diameter) of Purkinje cells increased rapidly between 6 PN (on average 10 microns) and 18 PN (about 17 microns) days; it did not change between 18 and 25 PN days, but increased moderately again between 25 and 48 PN days (22-23 microns) and stabilized on the same value. In contrast, the number of Purkinje cells/100 microns (the "linear density") decreased rapidly from 6 to 18 PN days. The molecular layer area belonging to 1 Purkinje cell increased rapidly from 6 to 25 PN days (from about 370 to 6,200 microns 2) and less rapidly between PN days 30 to 48 (up to 9,300 microns 2), followed by a moderate decrease at PN day 90 (about 6,600 microns 2). The volume belonging to 1 Purkinje cell dendritic arbor was about 5,500 microns 3 at PN day 6, 93,000 microns 3 at PN day 25, and 100,000 microns 3 at PN day 90. The numerical density of dendritic spines in the molecular layer showed a biphasic curve: a rapid increase from PN days 6 to 21 followed by a significant but short decrease at PN day 25, moderate rise from PN days 25 to 48, and a subsequent decline between PN days 48 and 90. The number of spines belonging to 1 Purkinje cell showed two developmental "peaks": the first peak at 21 PN days was moderate (5.6 x 10(4) spines/Purkinje cell) while the second maximum at 48 PN days was more significant (1.2 x 10(5) spines/Purkinje cell), which then declined to 6.3 x 10(4) spines/Purkinje cell at PN day 90. It is suggested that the temporary overproduction and the following decline in the number of Purkinje dendritic spines during the development of the cerebellar cortex may be the morphological indicator of the dynamics of synaptogenetic and of synaptic stabilization processes.

Animals↗

A Combined golgi and postembedding GABA and glutamate electron microscopic study of the nucleus dorsomedialis thalami of the rat.

The synaptic organisation of neurons in the nucleus medialis dorsalis (MD) was investigate by combined Golgi, and post-embedding gamma-aminobutyric acid (GABA) and/or glutamate (GLU) immunogold methods. The morphological features of the impregnated neurons in the MD (detailed by Kuroda et al. 1992a) were similar to thalamocortical relay cells present in other thalamic nuclei. GABAergic cell bodies could not be found. Distal dendritic branches of gold toned neurons established synaptic contacts with small and medium size glutamate as well as GABA-immunoreactive axonal endings. Large glutamate and GABA-positive axon terminals formed synaptic contacts with proximal dendrites. GABAergic axon terminals exhibited symmetric synaptic contacts and contained pleomorphic vesicles. Glutamate immunoreactive terminals formed asymmetric synapses and contained spheroid vesicles, although, some large glutamate immunoreactive endings contained pleomorphic vesicles. Synaptic glomerulus-like complexes could also be observed with the participation of glutamate-, and GABA-positive large axon terminals synapsing with Golgi impregnated proximal dendrites.

Animals↗

[C-peptide levels in secondary sulfonylurea resistant diabetics].

In the presence of clinical features of secondary drug failure--even after reeducation on diet and intensive control of patients--is difficult to make a decision to switch on insulin. Therefore the serum C-peptide concentrations were assessed in order to get supporting data. From 35 patients with suspected secondary drug failure the therapy of 11 patients was continued with insulin, 24 patients remained on glibenclamide therapy. The decision based on clinical criteria. All of the patients were studied in i.v. glucagon test and with a test meal to evaluate their basal and stimulated serum C-peptide concentrations. There were only three patients with subnormal basal C-peptide (< or = 0.30 nmol/l), on the other hand nine patients had lower post-glucagon serum C-peptide level than 0.60 nmol/l. The basal and stimulated C-peptide concentrations from i.v. glucagon test and test-meal indicated the need of insulin therapy with a sensitivity of 81.8 percent and with specificity of 70.8 percent. The further glibenclamide treatment on the basis of C-peptide concentrations in 89.5 percent of cases could be accurately established. The statistical analysis showed that the glucagon-stimulated C-peptide concentration was the most characteristic feature to discriminate the patients in order to make a decision on the further diabetes therapy.

Aged↗

[Experience with using a myocutaneous flap, obtained from the gluteus maximus, in covering sacral decubitus wounds].

Nonsurgical treatment of pressure sores of the sacral region showed in long term poor results. After a short review of surgical procedures the method of gluteus maximus myocutaneous flaps is described. The results suggest that the method offers a well vascularised and resistant soft tissue cover of the pressure sore and it can be performed in any surgical department. Stay in hospital may decrease significantly and the hope for a complete rehabilitation increases.

Buttocks↗

Effect of dark rearing on the volume of visual cortex (areas 17 and 18) and number of visual cortical cells in young kittens.

The surface area, total volume, and total number of neurons of areas 17 and 18 in one hemisphere of dark-reared (DR), dark-reared and light-exposed (DRL), and normally reared (NR) kittens were studied at the age of 6 weeks. The thickness of the visual cortex was lower by 13% and 11% (area 17) and by 17% and 16% (area 18) in DR and DRL groups, respectively, when compared with similar cortical areas in NR kittens. The surface area values of area 17 were nearly the same in DR and DRL kittens, both being, however, 37% smaller than in NR animals. The surface area of area 18 was significantly smaller than that of area 17 in each group, and was also lower in DR (by 27%) and DRL (by 21%) groups when compared with the NR group. As a consequence of dark rearing, the numerical density of cortical neurons in area 17 amounted to about double of the value observed in normally reared kittens and was also significantly higher in area 18. The numerical density of nerve cells of DRL kittens fell between the DR and NR groups. The total cortical volume of area 17 was similar in DR and DRL groups but it was by 46% (DR) and by 44% (DRL) smaller than in NR kittens. In each experimental group, the total volume of area 18 was significantly smaller than that of area 17. The cortical volume of area 18 was also smaller than in the NR group by 39% and 34% in DR and DRL groups, respectively. In DR and NR kittens, the total numbers of neurons in areas 17 (DR = 26.4 million, NR = 25.7 million) and 18 (DR = 8.5 million, NR = 9.0 million) were essentially similar. In the DRL groups a significantly smaller number of cortical neurons was found both in area 17 (21.5 million) and in area 18 (6.8 million). It is concluded that, in spite of considerable differences in the cortical thickness, surface area, numerical density, and total cortical volume, the absolute numbers of neurons in area 17 and 18 of visually deprived (DR) and NR kittens do not differ at 6 weeks of age. The main deficit in cortical organization following dark rearing, therefore, appears to be confined mainly to the neuropil, as a result of an underdevelopment of neuronal processes and of depressed synaptic organization.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

GABA-containing neuronal processes in normal and cortically deafferented dorsal lateral geniculate nucleus of the cat: an immunogold and quantitative EM study.

The qualitative and quantitative synaptology of flat synaptic vesicle containing "F" type terminals was analysed in normal and in chronically cortically deafferented dorsal Lateral Geniculate Nucleus (dLGN) of the cat using an electron microscopic immunogold technique for visualization of GABA. A direct correlation was found between the density (number of gold particles) of GABA immunostaining and the number of synaptic vesicles in different F terminals. This suggested a quantitative relationship between transmitter content and the number of vesicles in the labeled terminals. Not only the number but also the size of synaptic vesicles was found to be different in the two main groups of F profiles, i.e. the axonal F1 and dendritic F2 terminals. Measurement of the size of synaptic vesicles in F1 axon terminals revealed two subpopulations of these endings: "F11" and "F12" terminals with vesicle diameters of 31.56 +/- 0.08 nm and 33.73 +/- 0.12 nm (P less than 0.01; Chi2 test) respectively. The size of synaptic vesicles in axonal F12 terminals was identical to that found in F2 dendritic profiles, suggesting that both processes belonged to the same, intrageniculate (interneuronal) cell population. F11 terminals, however, appeared to be axonal endings of extrageniculate (most probably of perigeniculate) neurons. Quantitative analysis of the two types of GABAergic axon terminals revealed the geniculocortical relay cells to be the main postsynaptic targets for F11 (extrageniculate) terminals while F12 axons terminated equally on both interneurons and relay cells. Following chronic decortication of the dLGN, the distribution pattern of both GABAergic axonal types had changed considerably. As a result of a severe loss in relay cells, more F11 and F12 axon terminals were found on GABA-containing interneuronal processes than on relay cells. An increase in the number of F1 axonal terminals per neuron was also revealed, (particularly on GABAergic interneurons), suggesting a compensatory reactive synaptogenesis by both F axonal types following decortication.

Afferent Pathways↗

Number of GABA-immunopositive and GABA-immunonegative neurons in various types of neocortical transplants.

Quantitative investigation of GABA-immunopositive and GABA-immunonegative neurons was performed in grafts of embryonic tissue of somatosensory cortex, (1) injected intraparenchymally into the barrel field of adult rats (n = 5); (2) placed in an acute cavity in the same area (n = 9); or (3) implanted into the anterior eye chamber (n = 5). Analysis of initial embryonic tissue at the age of grafting (E17) demonstrated high numerical density of neurons both GABA-positive and other. Six months after grafting the total neuronal density was higher than in normal cortex in both groups of intracortical grafts, but was lower than normal in the intraocular grafts. The numerical density of GABA-positive somata, however, decreased in all types of the grafts, and their ratio to GABA-negative neurons was significantly lower than in normal neocortical tissue. The total numerical density of the neurons in the grafts had strong positive correlation to the degree of morphological graft/host integration, which was evaluated as a ratio of extent of area of direct graft/host neuropil confluence versus the total extent of the border. The mean diameters of nuclei of GABA-negative cells in both groups of intracortical grafts did not differ from those of the intact neocortex, but in the isolated grafts they were substantially larger. Nuclei and somata of the GABA-positive cells, however, were hypertrophic in all groups of grafts, and especially in the intraocular ones. Measurements of the diameters of host neocortical neurons adjacent to the grafts also exhibited a less marked but still significant hypertrophy. The possible role of various factors (synaptic, trophic, functional), determining the described alterations in neuronal populations within the grafts is discussed.

Animals↗

Quantitative estimation of the ratio of GABA-immunoreactive cells in neocortical grafts.

Somatosensory anlage from 17-18 day old rat embryos were transplanted in place of the removed barrel cortex in adult rats. Six to eight months after transplantation, the grafts were either completely separated by glial scar or partly separated and partly confluent with the host neocortex. Each was studied histologically and immunostained for GABA. It was found that in partly confluent grafts the neuronal density was similar or even higher than in the host cortex, while the cell number in the separate grafts was much lower than in the nearby host cortex. The number of GABA-positive cells, however, was in all grafts significantly lower (2.9% on average) than in the normal cortex (11.8% on average). The decline in GABA-stained nerve cells was highest in separated grafts, but was somewhat less marked in transplants partly confluent with the host tissue. The possible role of partial or total deafferentation as well as the relative vulnerability of the transplanted tissue by temporary hypoxia and other metabolic disturbances are discussed as the probable factors in selective decline of GABA-ergic cells in the transplanted somatosensory cortex.

Animals↗

Plasticity of GABA- and glutamate-containing terminals in the mouse thalamic ventrobasal complex deprived of vibrissal afferents: an immunogold-electron microscopic study.

GABA and glutamate immunogold staining demonstrated that nerve cells of the thalamic ventrobasal complex (VB) of mice were positive exclusively for glutamate. None of the neuronal perikarya reacted the GABA antibody. By using alternate thin sections of the normal VB, it was also shown that large "specific" somatosensory and small corticothalamic terminals, both of which contained spherical synaptic vesicles, exhibited only glutamate-like immunoreactivity. A third axonal type, containing flat-ovoid synaptic vesicles, stained only for GABA. Seventy-five days after coagulation of the vibrissal follicles in newborn mice, a characteristic multiplication of GABA positive axon terminals was observed. In addition, it was demonstrated that, similarly to modified cortical endings (Hámori et al., J. Comp. Neurol. 254:166-183, '86), many GABA positive terminals appeared as specific afferent endings, replacing the missing "specific" vibrissal afferents. This finding shows a remarkable plasticity of inhibitory GABA axons during developmental synaptogenesis and provides further evidence that the size, location, and the type of attachment of presynaptic terminals are dependent on their postsynaptic target.

Afferent Pathways↗

Immunogold electron microscopic demonstration of glutamate and GABA in normal and deafferented cerebellar cortex: correlation between transmitter content and synaptic vesicle size.

Selective labeling of mossy fiber terminals and parallel fibers was obtained in rat cerebellar cortex by a glutamate antibody produced and characterized by Hepler et al. The high-resolution electron microscopic immunogold demonstration of this amino acid offered the possibility of determining the size and shape of synaptic vesicles in glutamate-positive mossy endings. Mossy terminals that stained with the glutamate antibody formed two distinct populations, one with spherical synaptic vesicles with an average diameter of 34.0 nm (more than 90% of all mossy fiber endings) and one with pleomorphic and smaller synaptic vesicles which had an average diameter of 28.5 nm. We present experimental evidence that the mossy terminals with large round vesicles are of extracerebellar origin, whereas those with small pleomorphic synaptic vesicles are endings of nucleocortical fibers. The presence of two distinct classes of gamma-aminobutyric acid (GABA)-containing axon terminals within cerebellar glomeruli has also been demonstrated; those originating from the cerebellar nuclei contain large (36.2 nm) synaptic vesicles, whereas the majority of GABA-stained axon terminals that are of local (cortical) origin contain small (29.1 nm) synaptic vesicles. It therefore appears that, at least in the case of glutamate and GABA, morphological characterization of the axon terminals based on the size and shape of synaptic vesicles is not a reliable indicator of their functional nature (i.e., whether they are excitatory or inhibitory); convincing evidence for the identity of the transmitter can be obtained only by electron microscopic immunostaining procedures. Our results also suggest the existence of both inhibitory and excitatory feedback from cerebellar nuclei to cerebellar cortex.

Animals↗

[Hepatobiliary gammagraphy in the diagnosis of Dubin-Johnson syndrome in children].

Using hepatobiliary gammagraphy (99mTc-EHIDA), the authors made 26 examinations in six families with Dubin-Johnson's syndrome. From a series of gammagrams they evaluated the hepatobiliary kinetics and from measurements of the activity of series of blood samples they assessed the half-time of decline of the rapid (Tk1) and slow (Tk2) phase of the curve and the percentage of retention in blood during the 45th minute (R45). The values in a group of normal subjects were 3.4 +/- 0.6 min., 49.1 +/- 8.5 min. and 9.9 +/- 1.7%. In 12 patients with a fully developed clinical picture the liver was visualized intensively and homogeneously within 10 min., in 10 it was enlarged. The intrahepatic biliary pathways were not visualized the passage of activity into the intestinal lumen was delayed above 60 to 120 min., and the increased retention in the liver persisted for more than 120 min. The gallbladder was visualized in six but late and with low intensity. Tk1 was 4.3 to 10.0 min., R45 16.7 to 30.0%. In 9 subjects with the clinically inapparent form the visualization of the intrahepatic pathways was only indicated, the gallbladder was not visualized only in one patient. A protracted retention in the liver was in seven subjects above 60 min., in 2 above 90 min. and in 1 above 120 min. Tk1 was 4.0 to 9.0 min. and R45 12.0 to 27.1%. Hepatobiliary gammagraphy with evaluation of blood clearance of the pharmaceutical preparation is a non-invasive method which helps in the diagnosis of Dubin-Johnson's syndrome.

Adolescent↗