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Biomedical subjects

K Tóth

Publications and source records attributed to K Tóth.

At least 55 records · Page 3Linked to original sources

Stratum radiatum giant cells: a type of principal cell in the rat hippocampus.

Neurons of a distinct type in CA1 area stratum radiatum of the rat hippocampus have been found to express a direct cellular form of long-term potentiation (LTP, Maccaferri & McBain, 1996, J. Neurosci. 16, 5334), but their functional identity, i.e. whether interneuron or principal cell, remained unknown. Whole cell recording from hippocampal slices in vitro was combined with light and electron microscopy to answer this question. LTP was robustly induced by a pairing protocol and physiological properties were measured in radiatum giant cells (RGCs) using biocytin containing pipettes. Reconstruction of the cells' dendritic and axonal arbor revealed morphological properties similar to CA1 pyramidal cells with some characteristic differences. They typically had two large diameter apical dendrites, or when only one dendrite arose, it soon bifurcated. Apical dendrites formed a dendritic tuft in stratum lacunosum-moleculare and the dendrites, but not the somata, were densely covered with conventional spines. The axon arose from the basal pole of the soma, descended to stratum oriens and emitted several axon terminals bearing collaterals that travelled horizontally, remaining in stratum oriens. The main, myelinated axon trunks turned towards the fimbria. In the electron microscope axon terminals were found to form asymmetrical synapses on postsynaptic dendritic shafts and dendritic spines in stratum oriens. The dendrites received asymmetrical synapses, mostly on their spines. The axon initial segments also received several synapses, a feature never observed on interneurons. All the above characteristics support the conclusion that RGCs are excitatory principal neurons.

Animals↗

[Comparative study of verapamil and bisoprolol in the secondary prevention of myocardial infarction].

The effect of Ca-antagonist, long-acting verapamil and the selective beta-1 blocking bisoprolol were investigated and compared in the secondary prevention after myocardial infarction. Eighty-seven patients were enrolled, 27 patients were not included because of the exclusion criteria, 30 patients were treated with verapamil and 30 patients with bisoprolol. During the 540 days of follow up period treadmill ergometry and dobutamine stress-test with SPECT investigation were performed two times. Both clinically and the data of our investigations the effect of the two drugs in the secondary prevention was good, and even at the 540th day the protective effect was still excellent.

Adrenergic beta-Antagonists↗

[Determination of dihydropyrimidine dehydrogenase in the prediction of toxic side effects of 5-fluorouracil].

In the chemotherapy of colorectal cancers the most frequently given drug is 5-fluorouracil, which in certain cases reduces or delays the appearance of the local recurrence or metastasis. It is well known that the patient's response to 5-fluorouracil is very different concerning both, effects and side effects. More than 80% of the infused drug is catabolised in the first 20 minutes after the treatment. The first and rate limiting enzyme of the catabolism is dihydropyrimidine dehydrogenase, which has the highest activity in the liver and lymphocytes. The activity of this enzyme shows correlation with the blood level of 5-fluorouracil. The deficiency of this enzyme caused severe, in some cases lethal toxicity, its congenital deficiency is responsible for familial pyrimidinaemia. Authors intended to collect data about the dihydropyrimidine dehydrogenase activity of colorectal cancer patients, in order to screen enzyme deficiency or very low enzyme activity, which might be in connection with the appearance of severe side effects, moreover to determine the optimal dose of 5-fluorouracil before the treatment. Dihydropyrimidine dehydrogenase activity was determined in the lymphocytes of 48 colorectal cancer patients, treated by 5-fluorouracil, at the beginning of each cytostatic cycle. The enzyme activity of the patients was between 1.2 and 24.4 pmol/min/10(6) lymphocyte. The value of the enzyme activity fluctuated in a range, characteristic for the individual patients and this value was not modified by the 5-fluorouracil treatment. Dividing the patients in two groups, low (lower than 5 pmol/min 10(6) lymphocyte) and high (higher than 15 pmol/min 10(6) lymphocyte) dihydropirimidine dehydrogenase activity, we found that decrease in the white blood cell number and appearance of the side effects occurred with much higher frequency in the low activity group which resulted in the reduction of the dose or in more serious cases interruption of the treatment. Authors conclude that the determination of the dihydropyrimidine dehydrogenase activity in the lymphocytes is a valuable method in the prediction of the toxic side effects of 5-fluorouracil, in the screening of the congenital enzyme deficiency and in the individualization of the 5-fluorouracil dosage.

Adjuvants, Pharmaceutic↗

Disinhibition of rat hippocampal pyramidal cells by GABAergic afferents from the septum.

1. Slices were prepared from rat forebrain to include both the septum and the hippocampus in order to examine the effects of septal stimulation on hippocampal inhibitory circuits. 2. Repetitive stimulation of septo-hippocampal fibres caused a maintained decrease in the frequency of spontaneous IPSPs recorded from CA3 pyramidal cells in the presence of antagonists of excitatory amino acid receptors and of muscarine receptors. 3. In records made from pyramidal cells with CsCl-filled electrodes, IPSPs were examined at potentials both more positive and more negative than their reversal potential. Single septal stimuli hyperpolarized pyramidal cells when IPSPs were depolarizing events and depolarized them when IPSPs were hyperpolarizing. The GABAA receptor antagonist picrotoxin abolished the effects of septal stimulation. 4. Activation of septal afferents initiated an IPSP in hippocampal inhibitory cells but not in pyramidal cells. Septal IPSPs had similar kinetics to those initiated by local hippocampal stimulation and could suppress inhibitory cell discharge. 5. In pyramidal cells recorded with potassium acetate-filled electrodes, septal stimuli initiated a depolarization that increased with the driving force for Cl- and that could cause firing. 6. Rhythmic stimulation of septo-hippocampal fibres at 5 Hz initiated, in the hippocampus, a maintained out-of-phase oscillation of pyramidal cell discharge and inhibitory cell firing, as detected by the occurrence of spontaneous IPSPs. 7. These results suggest that GABAergic septo-hippocampal afferents selectively inhibit hippocampal inhibitory cells and so disinhibit pyramidal cells. This disinhibition could contribute to the transmission of the theta rhythm from the septum to the hippocampus.

Afferent Pathways↗

Epidemiology of congenital coronary artery anomalies: a coronary arteriography study on a central European population.

The anatomical patterns and frequency of occurrence of congenital coronary anomalies (CCA) in a Central European cohort has not yet been studied. The angiographic data of 7,694 consecutive patients undergoing coronary arteriography at the Albert Szent-Györgyi Medical University, Szeged, Hungary, from 1984 to 1994 were analyzed. CCA were found in 103 patients (1.34% incidence). Ninety-eight of them (95.2%) had anomalies of origin and distribution, and five (4.8%) had coronary artery fistulae. The incidence was the highest for the separate origin of left descending artery and left circumflex from the left sinus of Valsalva (52.42%). Anomalous origin of the left circumflex coronary artery from the right coronary was 8.7% while from the right sinus of Valsalva 18.4%. CCA, which may be associated with potentially serious events, such as ectopic coronary origin from the opposite aortic sinus (1.9%) and single coronary arteries (3.88%), were not frequent. The incidence of CCA in the Central European cohort under study was similar to that of the largest North American study. The anatomic classification presented can be useful from both clinical and surgical standpoints.

Adult↗

Clinical and gait analysis of 171 unilateral calcaneal fractures.

INTRODUCTION:: Reviewing the management of calcaneus fractures, conservative and operative treatment are known without a generally accepted, well proven therapeutical strategy or tactics compared to other types of fractures. The purpose of this study is to define the parameters of the differences between the fractured calcaneus and the intact one, as well as the two types of treatments using the gait analysis method. MATERIALS AND METHODS:: Retrospective clinical investigation and gait analysis have been performed on 217 patients with calcaneus fractures. An analysis of the X-rays was also included. The Novel 101 B pedobarography analyser with platform 102H (4 sensor/cm(2)) was used for pressure distribution analysis. The region of the foot was divided into four masks, Mask 1 (M1) the area of the heel, Mask 2 (M2), the mid-foot, Mask 3 (M3), metatarsal region, and Mask 4 (M4) the region of the toes. The total area of the foot (TOT) included all four masks. Eighteen bilateral fractured calcanei have been omitted from the evaluation, owing to the lack of control foot, and 28 patients were excluded for the other complications of the fractures foot, complications of the control foot or complications extending to both feet. The data on the 171 fractures (68 patients treated conservatively and 103 patients treated operatively) of the calcaneus were compared with their control feet. The average age was 52.0 years (+/- 2.7) and the average follow up time was 49.9 months (+/- 17.5). The statistical analysis was performed using SPSS for Windows. Examination of correlation, repeated measurement analysis of variance, ANOVA, and multiple comparisons were performed by Bonferoni. Linear discriminating analysis was also performed. Significance level was defined as p<0.05 in each case. RESULTS:: All investigated parameters (area, max.F, max.P, absolute and relative contact time, FTI, PTI.) of M2 were significantly higher on the fractured side than on the intact one. The investigation of the whole foot showed significant increase concerning the area, and significant decrease in the max. force, FTI and PTI values. The differences between the conservatively treated and the intact foot values, as well as the differences between operatively treated foot and the intact one, demonstrated a significant decrease in the FTI TOT and the PTI TOT in both groups. A significantly higher difference was also demonstrated when the difference in the value of PTI TOT in the operative group was compared to the conservative one. Therefore, the values of the fractured side of the operative group were significantly lower than the values of the intact one, but significantly higher than the values of the conservative group. CONCLUSIONS:: The gait analysis parameters for the calcaneus fractured and the intact sides allowed for separation of the data according to significant differences. The results of the gait analysis comparing the conservative and operative method of the treatment showed that the surgical method was the better choice.

Journal Article↗

Differences between somatic and dendritic inhibition in the hippocampus.

Hippocampal synaptic inhibition is mediated by distinct groups of inhibitory cells. Some contact pyramidal cells perisomatically, while others terminate exclusively on their dendrites. We examined perisomatic and dendritic inhibition by recording from CA3 inhibitory and pyramidal cells and injecting biocytin to visualize both cells in light and electron microscopy. Single perisomatic inhibitory cells made 2-6 terminals clustered around the soma and proximal pyramidal cell processes. Dendritic cells established 5-17 terminals, usually on different dendrites of a pyramidal cells. Perisomatic terminals were larger than those facing dendritic membrane. Perisomatic inhibitory cells initiated the majority of simultaneous IPSPs seen in nearby pyramidal cells. Single IPSPs initiated by perisomatic sodium-dependent action potentials. Activation of inhibitory fibers terminating on dendrites could suppress calcium-dependent spikes. Thus, distinct inhibitory cells may differentially control dendritic electrogenesis and axonal output of hippocampal pyramidal cells.

Action Potentials↗

MDR1 P-glycoprotein is expressed by endothelial cells of newly formed capillaries in human gliomas but is not expressed in the neovasculature of other primary tumors.

The expression of human MDR1 P-glycoprotein (Pgp) in the capillary endothelial cells of the central nervous system has been demonstrated. The brain capillary endothelial cells maintain the structure and function of the blood-brain barrier. Recently, the human MDR1 Pgp (and its mouse homologue MDR1a Pgp) has been shown to function as an important part of this barrier, pumping out xenobiotics from endothelial cells into the lumen of capillaries resulting in the protection of the brain parenchyma. To examine whether the endothelial cells of the newly formed capillaries during neoangiogenesis within malignant human brain tumors express MDR1 Pgp, 35 adult surgical brain tumor specimens (29 gliomas and 6 tumors metastatic to the brain) were obtained from previously untreated patients and studied by a new immunohistochemical sandwich method developed in our laboratory using the JSB-1 monoclonal antibody. JSB-1 is specific for the Pgp product of the human MDR1 (and not MDR3) gene. This sensitive method allows the detection of Pgp in capillary endothelial cells of normal brain in conventional paraffin sections after formalin fixation. The endothelial cells of the newly formed capillaries in 25 of 29 gliomas (86%) and 3 of 6 metastatic tumors, immunostained positive for MDR1 Pgp. The tumor cells in 7 of 35 cases were also positive for Pgp. In the 35 brain tumor cases investigated, the endothelial cells were Pgp positive in the tumor-brain border and in the brain further from the tumor. Capillary endothelial cells of neovasculature in 137 malignant tumors (non-brain) obtained from previously untreated patients showed no MDR1 Pgp expression. These results demonstrated that MDR1 Pgp is expressed not only in the capillaries of normal brain but also in the majority of the newly formed capillaries of brain tumors. Multidrug resistance of brain tumors may result not only from the expression of resistance markers in neoplastic cells but also from the MDR1 Pgp expression in endothelial cells of tumor capillaries. Pgp in this special localization can exclude chemotherapeutic agents from tumor cells that are located around the capillaries. The therapeutic benefit and selectivity of chemotherapeutic agents in combination with a Pgp-reversing agent should be evaluated.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Efficacy and tolerance of 400 MG bezafibrate in diabetic and hyperlipidaemic patients.

The authors report the results of an open clinical study using 400 mg Bezafibrate once a day. Among 25 diabetic patients (type II.) underwent a 4 weeks period with nutritional advice. Average changes from inclusion levels were -24% for total cholesterol, -56% for triglicerides, +11.9% for HDL-cholesterol, -19% for plama fibrinogen. In conclusion, bezafibrate at a daily dose of 400 mg had significant lipid-modifying properties but also exhibited a beneficial effect on other related risk factors such as fibrinogen reduction.

Adolescent↗

PAK-104P, a pyridine analogue, reverses paclitaxel and doxorubicin resistance in cell lines and nude mice bearing xenografts that overexpress the multidrug resistance protein.

Multidrug resistance (MDR) is considered multifactorial and has been associated with overexpression of the multidrug resistance protein (MRP). However, effective compounds for reversal of MRP-related MDR are limited. In the present study, the modulatory activity of the novel pyridine analogue PAK-104P on MRP-mediated resistance to doxorubicin and paclitaxel was investigated in two doxorubicin-selected human tumor cell lines [HT1080/DR4 (sarcoma) and HL60/ADR (leukemia)] and compared with the nonimmunosuppressive cyclosporine analogue PSC-833. In cell lines HT1080/DR4 (MRP/lung resistance-related protein phenotype) and HL60/ADR (MRP phenotype), doxorubicin resistance was significantly higher (250-fold and 180-fold, respectively) than that to paclitaxel (6-fold and 9-fold, respectively). With noncytotoxic concentrations of PAK-104P (1 and 5 microM), the reversal of doxorubicin resistance was significant but partial in HT1080/DR4 and HL60/ADR cells (dose-modifying factor for 5.0 microM PAK-104P, 25.0 and 31.2, respectively), whereas complete reversal of paclitaxel resistance was achieved in HL60/ADR cells. In contrast, PSC-833 modulation of doxorubicin and paclitaxel resistance was modest. Cellular drug uptake and retention studies by flow cytometry analysis demonstrated that PAK-104P was effective in restoring cellular doxorubicin concentrations in resistant cells to levels comparable to those obtained in parental cells. In athymic nude mice, PAK-104P significantly potentiated the therapeutic efficacy of doxorubicin and paclitaxel against resistant HT1080/DR4 xenografts. Of significance is that the maximum tolerated doses of doxorubicin and paclitaxel were administered in combination with PAK-104P, documenting improvement in the therapeutic index of these agents. In addition to reversing P-glycoprotein-mediated MDR, the pyridine analogue PAK-104P provides an example of an effective in vivo modulator of MRP-mediated MDR.

ATP-Binding Cassette Transporters↗

A branching dendritic model of a rodent CA3 pyramidal neurone.

1. We constructed a branching dendritic compartmental model of a CA3 pyramidal neurone, using experimental data from guinea-pig and rat cells obtained in vitro. The goal was to understand interactions between synaptic events impinging on dendritic branches and voltage- and calcium-dependent currents. The model contained sixty-four soma-dendrite (SD) compartments, an axon initial segment (IS), and four axonal compartments. There were six active conductances in the SD membrane, including a sodium conductance (gNa) and a high-threshold calcium conductance (gCa), with kinetic properties similar to those reported in a previous study. 2. The distribution of conductance densities across the IS and SD was adjusted by testing the model response to antidromic stimulation and current pulses or sustained currents injected into the soma or apical dendrites. As before, gNa was concentrated on and near the soma with lower density in the dendrites, while gCa had a higher density in apical dendrites than at the soma. 3. The model predicts that CA3 pyramidal neurones in media blocking synaptic transmission should fire a burst of action potentials following antidromic stimulation. This was confirmed experimentally in hippocampal slices. 4. Both in the model and in guinea-pig neurones, dendritic IPSCs can delay the onset of bursting. If an IPSC begins soon enough after the first fast action potential, the later burst envelope is attenuated. This effect results from suppression of dendritic Ca2+ electrogenesis. 5. The model predicts that an appropriately timed dendritic IPSC (after the first somatic spike but before the dendritic Ca2+ spike) may suppress the transient local [Ca2+] signal, while having a negligible effect on the electrical output of the neurone. This phenomenon has been reported in guinea-pig Purkinje cells. 6. We conclude that active dendritic currents are critical for regulation of the electrical output of CA3 pyramidal neurones. We suggest also that dendritic [Ca2+] signals might be controlled in individual dendrites independently of action potential outputs, an effect of possible importance for synaptic plasticity.

Action Potentials↗

[The value of detecting eosinophil cationic protein in various dermatoses].

Recent data have proved that eosinophil cells actively contribute to the pathogenesis of numerous inflammations, including that of atopic dermatitis. The expression of the activated secreted forms of eosinophil cationic protein (ECP) as well as the determination of the rise and fluctuation of the ECP level of the serum make it very easy to follow their activity. Influencing the activation of the eosinophil cell may lead to important alterations in the treatment of these diseases.

Blood Proteins↗

[Unrecognised acute myocardial infarct in a nine-year autopsy material].

The authors analysed in a retrospective study the clinical features, ECG and enzyme examinations of 97 patients who died in acute myocardial infarction proved by autopsy during 9 years in their department. They found the recognition rate of the acute myocardial infarction 73%, compared to the data of the literature good. There occurred 26 unrecognized myocardial infarctions, among which atypical clinical features were more frequent and typical ECG signs and enzyme values were less frequent, than among the recognized cases. In their earlier study 57% of the recognized acute myocardial infarctions occurred on the posterior wall, in the present one the rate of anterior and posterior cases was the same. In the earlier study from 95 posterior acute myocardial infarctions 35 (41%) were unrecognized, in present from 41 cases only 11 (27%). This 14% improvement in the recognition rate of the posterior myocardial infarctions should be attributed to the routine application of paravertebral ECG leads, but statistically was not significant.

Aged↗

[Ergometric, hemorheologic and myocardial perfusion studies and their evaluation by pattern recognition method in ischemic heart disease].

A large number of noninvasive and invasive methods are used in establishing the diagnosis of ischemic heart disease. Coronary angiography is an expensive method and a restricted capacity exists in Hungary. The aim was to elaborate an optimal combination of different noninvasive methods which can select the real positive cases for coronary angiography with maximal efficiency. Besides routine examinations, dobutamine pharmacological test was carried out and hemorheological parameters were also determined. After evaluating the results, patients were divided into three groups: absence of IHD, probable IHD and IHD. The clustering of patients into these groups was made by using their multivariable classifier algorithm (PRIMA) and 27 different parameters of 44 patients were taken into account. The groups were well separable as the class-distances indicated. The maximal ST segment depression during exercise, pharmacological test and hemorheological parameters were found to be the most powerful discriminating factors. Though the validation of the results is still in progress, based on their previous data they feel that the examination of hemorheological parameters and the application of pattern recognition method can be useful in the diagnosis of ischemic heart disease.

Algorithms↗

New immunohistochemical "sandwich" staining method for mdr1 P-glycoprotein detection with JSB-1 monoclonal antibody in formalin-fixed, paraffin-embedded human tissues.

We have developed a new immunoperoxidase "sandwich" staining method for amplified detection of P-glycoprotein (Pgp) that is suitable for use on formalin-fixed, paraffin-embedded (conventional) tissue sections. This was accomplished by substantially changing the procedure described by Chan (1988) so as to increase specific staining intensity and to decrease nonspecific background staining. To determine the most appropriate primary antibody for the assay, we compared the immunoreactivity of JSB-1, C494, and C219 monoclonal antibodies recognizing internal epitopes of Pgp, and MRK16 and 4E3 monoclonal antibodies recognizing external epitopes of Pgp. Paraffin sections of Pgp-positive normal human tissues (adrenal, liver, kidney, and brain), of renal tumors, and of cell pellets of sensitive and multidrug resistant human tumor cell lines (MCF-7, KB) were used for comparisons. Immunostaining was excellent with JSB-1, moderate with C494, and very weak with C219. MRK16 and 4E3 showed no reaction. Nonspecific background staining was reduced by 1) omitting immunoglobulin G from secondary antibodies; 2) decreasing the concentration of peroxidase-antiperoxidase complex; and 3) utilizing casein solution for blocking and washing. Pretreatment of sections before immunostaining was also simplified. Using JSB-1, the threshold for detection of elevated Pgp corresponded to less than two-fold relative resistance to doxorubicin. Applying this method, we found two of 26 non-small cell lung cancers were positive for Pgp, consistent with previous results of others using frozen sections. This new immunoperoxidase sandwich staining method using JSB-1 now allows reliable Pgp detection in sections of formalin-fixed, paraffin-embedded (archived) surgical specimens and small biopsy materials commonly used for diagnostic purposes.

ATP Binding Cassette Transporter, Subfamily B, Mem↗