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Biomedical subjects

L Urbán

Publications and source records attributed to L Urbán.

At least 19 recordsLinked to original sources
PubMed2004

Single nucleotide polymorphisms: aging and diseases.

Differences of more than 3 million nucleotides can bee seen comparing the genomes of two individuals as a result of single nucleotide polymorphism (SNP). More and more SNPs can be identified and it seems that these alterations are behind of several biological phenomena. Personal differences in these nucleotides result for example in elevated disease susceptibilities, that is, certain nucleotides are more frequent in patients suffering from different diseases comparing to the healthy population. SNPs may cause substantial alterations in the cells, e.g. the enzyme activity of the respective gene changes, but in other cases the effects of the SNPs are not so pronounced. Later results indicate that SNPs can be rendered to individuals living a longer life than the average. Perhaps these results will not directly lead to the lengthening of the maximal life span; however, genes that play an important role in the aging process could be identified. In this respect SNPs are important factors in determining the information level of the cells of individuals which determines the maximal life span (I. Semsei On the nature of aging. Mech. Ageing Dev . 2000; 117: 93-108), in turn SNP is one of the factors that determine the aging process. Since there are certain age-related diseases, the discovery and the description of the SNPs as a function of age and diseases may result in a better understanding of the common roots of aging and those diseases.

Aging↗
PubMed2000

[Detection and diagnostic value of t(14;18) translocation in minimal residual disease of follicular lymphoma].

The minimal residual disease is important in several malignant diseases, such as in hematopoietic malignancies (e.g. in follicular lymphoma) or in solid tumors, due to the presence of a tumor burden following a treatment of these diseases. In case of t(14;18) chromosome translocation, which characterizes most of the follicular lymphomas, the bcl-2 gene translocates to the joining region of the immunoglobulin heavy chain of chromosome 14. The expression of bcl-2 gene alters due to the translocation, and this change results in the inhibition of cellular apoptotic processes, and in turn these series of events may finally lead to the development of lymphoma. It is inevitable to learn the results of radio- and/or chemotherapy, i.e. whether the translocation-bearing cells disappeared from the lymphocytes of peripheral blood as well as from that of bone marrow, or we have to take into account the minimal residual disease. Using nested-PCR one can detect the translocation in 1 out of 10(5) cells, this way the results of the treatments can be controlled: one can establish the emergence of remissions; and the relapses could also be detected earlier than by using conventional diagnostic methods. Our experience, yielded by the follow up studies of follicular lymphoma patients, shows that the results of PCR detection correlate excellently with the conclusions of other diagnostic techniques. Nevertheless, the t(14;18) translocation-bearing cells can also be detected in peripheral lymphocytes of healthy donors as well as in that of different diseases of other types than lymphoma, but not in bone marrow. Therefore we emphasize the importance of the translocation-detection in the bone marrow of the patients of follicular lymphoma. More and more advanced techniques have made it possible to detect the minimal residual disease, this way it will be easier to diagnose and to predict the outcome of different malignant diseases.

Bone Marrow Neoplasms↗
PubMed2000

Frequency and evaluation of t(14;18) translocation in Sjögren's syndrome.

In most cases of follicular lymphoma, t(14;18) chromosomal translocation can be detected in lymphocytes of peripheral blood and bone marrow. Nevertheless, certain other types of diseases can also be characterised by the presence of the translocation. Patients of Sjogren's syndrome have an increased frequency of developing non-Hodgkin's lymphoma, e.g. follicular lymphoma; in turn, they may have translocation-bearing cells. One hundred Sjögren's syndrome patients were screened using a nested polymerase chain reaction technique to identify whether they had the translocation in their peripheral blood lymphocytes. Five percent of that population revealed a temporary or long-lasting presence of the translocation, sometimes even in the lymphocytes from bone marrow. Our results indicate that in addition to the conventional diagnostic methods of lymphoma, there are certain other factors, e.g. the duration of the presence of t(14; 18) translocation and the source of lymphocytes, that should be considered for successful early diagnoses and perhaps for treatment of the lymphoma in the Sjögren's patients.

Base Sequence↗
PubMed2000

Diagnostic value of the detection of t(14;18) chromosome translocation in malignant hematological and immunopathological diseases using polymerase chain reaction.

The majority of the t(14;18) chromosome translocations that occur in non-Hodgkin centroblastic-centrocytic follicular lymphoma can be detected by various methods. During the translocation process the bcl-2 gene located on chromosome 18 (18q21) is translocated to the JH region of the immunoglobulin gene of chromosome 14 (14q32). The most frequent type of bcl-2 translocations is the mbr type, whereas the immunoglobulin gene breaks mainly at the JH1-6 exons. About one of the 10(5) cells bearing the translocation can already be detected by using nested polymerase chain reaction (PCR). Eight patients suffering from follicular lymphoma were included in this study, which considered the usefulness of the PCR method. The results are in good agreement with those obtained by conventional diagnostic methods. Translocation can be detected, however, in patients with non-malignant diseases such as Sjögren's syndrome (about 5% of the patients) and in a patient with Whipple disease. In addition, translocation was detected in lymphocytes of peripheral blood of a healthy donor. Since lymphomas are detected in patients with Sjögren's syndrome with a relative high frequency, an early diagnosis of the translocation could improve the treatment of the disease. Nevertheless, a diagnosis of lymphoma is valid only in cases of bone marrow translocation-positivity.

Aged↗
PubMed1999

Immunohistochemical localization of neurokinin-l receptor in the lumbar spinal cord of young rats: morphology and distribution.

The type and distribution of neurokinin-1 (NK-1) receptor-expressing neurones were studied in young (14-day-old) rats' lumbar spinal cord using pre-embedding immunohistochemistry. The heaviest immunoreactivity was observed in the middle part and lateral fourth of lamina I where the great majority of immunoreactive perikarya represented fusiform and multipolar cells. In lamina II the middle and medial part showed moderate immunoreactivity, most of the cells resembled stalked cells. In lamina III the labelled perikarya were evenly distributed, while those in lamina IV accumulated mainly in the lateral part. In both laminae most of the labelled neurones represented central cells, the rest of them belonged to the antenna-type cells with long dorsally directed dendrites penetrating the superficial laminae. The immunoreactivity in laminae V-VII was uniform and relatively weak. In lamina VIII the immunopositive perikarya were encountered only rarely while in lamina IX virtually all motoneurones showed weak immunoreactivity. Lamina X contained small, multipolar and fusiform labelled perikarya. In conclusion, we found that the general appearance of the NK-1 receptor immunostaining and the major type of NK-I receptor-expressing neurones were similar to that found previously in adult spinal cord. Using the same method as Brown and colleagues the number of labelled NK- 1 receptor immunoreactive cells was similar in young and adult animals except lamina I where the number of immunoreactive neurones was twice that in adults.

Age Factors↗
PubMed1998

Alterations of substance P immunoreactivity in lumbar and thoracic segments of rat spinal cord in ultraviolet irradiation induced hyperalgesia of the hindpaw.

Substance P immunostaining was quantified on sections from the 4th-5th lumbar and midthoracic spinal segments of rats at the peak of hyperalgesia following ultraviolet irradiation-induced inflammation of one hindpaw. The area of the immunostaining in the lumbar dorsal horn was significantly decreased on both sides by 50%, while in the thoracic spinal cord, it was increased by 18% on the contralateral and stayed unchanged on the ipsilateral side.

Animals↗
PubMed1996

Receptors mediating tachykinin-evoked depolarisations of neurons in the neonatal rat spinal cord.

We have examined the contribution of NK1, NK2 and NK3 receptors to the depolarisation of the neonatal rat spinal cord in vitro evoked by exogenously applied tachykinine. Potential changes were recorded extracellularly from a lumbar ventral root. The NK1 receptor selective agonists substance P methly ester (SPOMs), septide and/Sar9/-substance P-sulphone (/Sar9/-P-sulphone), perfused onto the cord for 20 s, evoked ventral root potentials (VRPs) with similar EC50 values of 7.2 nM (95% confidence limits, 4.4-10.9 nM), 4.6 nM (1.8-9.3 nM) and 3.1 nM (1.6-5.1 nM), respectively. The NK3 receptor selective agonist senktide also evoked VRPs with an EC50 of 12.0 nM (5.1-23.4 nM), whilst the NK2 receptor selective agonist/beta-AlaB/-neurokinin A(4-10) (/beta-AlaB/-NKA(4-10)) was much less potent (EC50 = 228.3 nM, 95% confidence limits 138.0-350.0 nM). The non-peptide NK1 receptor selective antagonist RP67580 inhibited responses to SPOMe, septide and/Sar9/-SP-sulphone to varying degrees with IC50 values against each of 16.0 nM (10.7-23.4 nM), 19.8 nM (8.9-37 nM) and 58.0 nM (41-89 nM), respectively. The NK1 receptor antagonist CP-96,345 similarly inhibited responses to these agonists, although with higher IC50 estimates of 0.84 microM (0.51-1.40 microM) against SPOMe, 0.79 microM (0.50-1.17 microM) against/Sar9/-SP-sulphone and 0.37 microM (0.27-0.51 microM) against septide. Further analysis of the activity of RP67580 yielded a significantly higher pKB estimate for antagonism of responses to septide (7.67 +/- 0.04) than of responses to/Sar9/-SP-sulphone (7.18 +/- 0.05). In both cases Schild analysis indicated competitive antagonism. RP67580 also reversibly inhibited responses to /beta-AlaB/-NKA(4-10). However, in this case the Schild alope was significantly different from unity (0.44 +/- 0.55; P < 0.001), although the potency of the antagonist appeared similar to that seen with the NK1 receptor agonists (pA2 = 7.52). There was no effect of RP67580 against responses to senktide or of the inactive isomer RP67581 against septide-evoked VRPs. The NK2 receptor antagonist MEN 10,376 at concentrations up to 1 microM produced a partial but reversible inhibition of responses to a submaximal concentration of /beta-AlaB/-NKA(4-10) (0.3 microM) with a maximum reduction in VRP amplitude of 25.6 +/- 7.3%. A similar inhibitory effect was seen against septide-evoked VRPs (30.2 +/- 5.6% inhibition), although there was no effect against responses to submaximal concentrations of /Sar9/-SP-sulphone or senktide. In contrast, the non-peptide NK2 receptor antagonist SR 48,968 (1 microM) produced a maximal 48.0 +/- 7.7% inhibition of/beta-AlaB/-NKA(4-10)-evoked VRP's with no effect against responses to a submaximal concentration of septide. These data show that NK1 and NK3 receptor activation mediates depolarisation of the neonatal rat spinal cord, and suggest the presence of two NK1 receptor populations showing preference for septide and/Sar9/-SP-sulphone. Depolarisations mediated by /beta-AlaB/-NKA(4-10), previously described as a selective NK2 receptor ligand, are mediated predominantly via an action at NK1 receptors with a lesser involvement of NK2 receptors.

Animals↗
PubMed1994

Cobalt accumulation in neurons expressing ionotropic excitatory amino acid receptors in young rat spinal cord: morphology and distribution.

Excitatory amino acids (EAA) acting on N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate receptors play an important role in synaptic transmission in the spinal cord. Quantitative autoradiography and physiological experiments suggest that NMDA receptors are localized mainly in lamina II while kainate and AMPA receptors are found on both dorsal and ventral horn neurons. However the cell types expressing EAA receptors and their laminar distribution is not known. We have used a cobalt uptake method to study the morphology and distribution of spinal cord neurons expressing AMPA, kainate, or NMDA excitatory amino acid receptors in the lumbar enlargement of the rat spinal cord. The technique involved superfusion of hemisected spinal cords of 14 day-old rat pups in vitro with excitatory amino acid receptor ligands in the presence of CoCl2. Cobalt has been shown to enter cells through ligand-gated ion channels in place of Ca2+. Cells which accumulated cobalt ions following activation by ionotropic excitatory amino acid receptors were visualized histochemically. The cobalt uptake generated receptor-specific labeling of cells, as the NMDA receptor antagonist D-(-)-2-amino-(5)-phosphonovaleric acid (D-AP-5) (20 microM) blocked the NMDA, but not kainate-induced cobalt uptake. The kainate-induced cobalt labeling was reduced by the non-selective excitatory amino acid receptor antagonist kynurenic acid (4 mM). Passive opening of the voltage-gated Ca(2+)-channels by KCl (50 mM) did not result in cobalt uptake, indicating that cobalt enters the cells through ligand-gated Ca(2+)-channels. AMPA (500 microM), kainate (500 microM), or NMDA (500 microM) each induced cobalt uptake with characteristic patterns and distributions of neuronal staining. Overall, kainate induced cobalt uptake in the greatest number of neuronal staining. Overall, kainate induced cobalt uptake in the greatest number of neuronal perikarya while NMDA-induced uptake was the lowest. AMPA and kainate, but not NMDA superfusion, resulted in cobalt labeling of glial cells. Our results show that the cobalt uptake technique is a useful way to study the morphology and distribution of cells expressing receptors with ligand-gated Ca2+ channels.

Animals↗
PubMed1990

Spinal dorsal horn neurons in elevated extracellular calcium: cell properties and spontaneous discharges.

Recordings were made from neurons in the dorsal horn (DH), and from dorsal and ventral roots (DRs and VRs) of isolated spinal cords of infant mice. Raising calcium concentration ([Ca2+]) in the organ bath from 1.2 to 2.4 mmol/l resulted in a slight hyperpolarization, elevation of threshold current (rheobase), and augmentation of excitatory postsynaptic potentials (EPSPs). In many cells EPSPs acquired a much prolonged late phase. Orthodromic stimulation evoked in some DH neurons an action potential that had the same threshold as, and coincided in time with, the 'dorsal horn response' (DHR) recorded from DR. In spinal cords bathed in elevated [Ca2+], DR recordings showed irregularly recurring spontaneous waves, and DH neurons generated spontaneous EPSPs, often with spikes. Some neurons fired irregularly timed spontaneous action potentials that did not appear triggered by EPSPs. In less than 50% of the neurons the spontaneous EPSPs coincided in time with the spontaneous DR waves. The action potentials that appeared without EPSP were fired independently from DR activity. These observations confirm that elevation of interstitial free calcium concentration results in strong enhancement of excitatory transmission, especially of an EPSP of much extended duration. Virtually all neurons showed increased spontaneous activity in high [Ca2+], but only a minority appeared recruited into the synchronized discharges that are detectable as spontaneous waves in DR and VR recordings.

Action Potentials↗
PubMed1990

Reversible effects of hypoxia on neurons in mouse dorsal root ganglia in vitro.

Mouse dorsal root ganglia (DRG) were isolated and maintained in a tissue chamber. Membrane potential of 'A-type' neurons was recorded with intracellular electrodes. When the supply of oxygen was reduced, cells depolarized by a few mV and then maintained a stable membrane potential or partially repolarized. During depolarization the action potential was reduced in amplitude and the hyperpolarizing afterpotential was depressed. Reoxygenation within 15-88 min was followed by a brief period of hyperpolarization and then complete recovery. In about 60% of the cells, invasion of the cell soma by impulses triggered by dorsal root (DR) stimulation failed during hypoxia while action potentials could still be evoked by stimulation of the peripheral nerve and by direct intracellular stimuli. Conduction from DR into the peripheral nerve stump was unchanged indicating that the blockade of DR-evoked impulse conduction occurred at the bifurcation of the axon. Results with paired pulse stimulation indicated that impulses passing the axon bifurcation leave a long lasting (greater than or equal to 25 ms) post-spike subnormal period. In DRG cells treated with tetraethylammonium (TEA) the calcium-mediated 'shoulder' of the action potential was curtailed during oxygen withdrawal. In contrast to CNS neurons, DRG cells did not show early hypoxic hyperpolarization, nor the delayed hypoxic spreading depression-like depolarization. The findings support the suggestion that the reversible depression of synaptic potentials in the CNS during the early phase of hypoxia is caused by a combination of conduction failure at axon branch points and curtailment of voltage calcium currents of presynaptic terminals, both effects resulting in reduced transmitter output.

Action Potentials↗
PubMed1987

Slow excitatory transmission in rat spinal dorsal horn and the effects of capsaicin.

High intensity repetitive stimulation of a dorsal root elicited slow depolarization in more than half of the dorsal horn neurons examined in the rat spinal cord slice preparation. There was a significantly smaller group of neurons showing slow hyperpolarization as well. Slow depolarization was not observed when synaptic activity was blocked by perfusing the slice with a TTX- or a low-Ca2+ high-Mg2+ solution. This result is consistent with a presynaptic origin of the slow response. Capsaicin treatment of neonatal rats significantly reduced the incidence of slow depolarization, suggesting that the slow depolarization was generated by small diameter afferent fibres, probably unmyelinated afferents. DR-evoked slow depolarization and SP-induced depolarization were similar in several important aspects: a) Both responses caused depolarization and increased the excitability of dorsal horn neurons; b) They were frequently associated with similar membrane conductance changes; c) The size of both responses varied in parallel when the membrane potential was shifted over a wide range; d) Both responses were markedly reduced or abolished by an analogue of SP having antagonist properties, and by polyclonal and monoclonal antibodies to SP; e) The depression of the DR-elicited slow depolarization during and after the SP-induced depolarization suggested that SP and the natural transmitter for the DR-elicited slow depolarization were bound to the same receptors. The results suggest that SP or, SP-like peptide, is an agonist that mimics in some aspects the action on the natural transmitter for the slow depolarizing potential.

Animals↗
PubMed1987

Application of the glycine labelling method to the cerebellum, hippocampus and spinal cord.

3H-glycine was applied to the cat cerebellar cortex under resting conditions and during inferior olive stimulation which activated the climbing fiber system on a restricted area. Electric recording was made. The autoradiograms showed, that under resting condition labelled glycine was incorporated mainly in granule, Golgi and basket cells and only a few Purkinje and stellate cells were active. Also cerebellar glomeruli remained without labelling. On climbing fiber stimulation Purkinje cells became activated singly and grouped, also Golgi and stellate cells increased in number. Granule cells were totally inhibited. 3H-glycine, when applied to the rat hippocampus, the dentate gyrus, CA1 and CA4 fields showed labelling at low frequency stimulation. When 400 Hz high frequency stimulation periods were interposed, long-term potentiation ensued. The overall labelling of each hippocampal region was intensified significantly, indicating that glycine incorporation may be a sign not only of excitation but also of long-term potentiation. 3H-glycine was applied to frog spinal cord during rest and dorsal root stimulation. Interneurons and motor neurons excited by the afferent fibers showed intensive glycine uptake. It is concluded that the glycine labelling method is suitable for detecting neural excitation in the structures dealt with in this paper.

Animals↗
PubMed1985

Interstitial potassium concentration, slow depolarization and focal potential responses in the dorsal horn of the rat spinal slice.

Extracellular potassium concentration ([K+]o) was measured, and intra- and extracellular recordings made, in the dorsal horn of rat spinal cord slices maintained in vitro during repetitive dorsal root stimulation. In about half of the dorsal horn neurons, the stimulation evoked a possibly substance P-mediated slow depolarization. [K+]o increased during stimulation, reaching its highest values approximately 150 micron from the dorsal surface. The time course of delta [K+]o was different from that of the slow depolarization. Substance P itself evoked a much smaller delta [K+]o (0.4 mM) in the dorsal horn. It is concluded that the slow depolarization is not mediated by elevated [K+]o.

Animals↗
PubMed1985

The acute and chronic effects of capsaicin on slow excitatory transmission in rat dorsal horn.

The acute and chronic effects of capsaicin on rat spinal dorsal horn neurons and the excitatory transmission in the dorsal horn were investigated by means of intracellular recording techniques in the spinal cord slice preparation. Bath application of capsaicin (1-2 X 10(-5) M) produced in a majority of cells a prolonged depolarization associated with an increase in synaptic activity and intense neuronal discharges. During and immediately following the capsaicin depolarization, repetitive stimulation of a dorsal root failed to elicit the slow depolarization. After neonatal capsaicin treatment the proportion of dorsal horn neurons exhibiting the slow excitatory transmission was markedly reduced, however, the fast excitatory postsynaptic potentials were present in all examined cells. In addition, the proportion and sensitivity of the cells responding with a slow depolarization to substance P increased.

Animals↗
PubMed1984

Slow excitatory transmission in rat dorsal horn: possible mediation by peptides.

Repetitive stimulation of a dorsal root elicited a slow depolarization in about half of the dorsal horn neurons examined in the rat spinal cord slice preparation. The response was markedly depressed or abolished in the presence of substance P, substance P antagonists and capsaicin. In some dorsal horn neurons a slow hyperpolarization was also observed.

Animals↗