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Biomedical subjects

I Kovacs

Publications and source records attributed to I Kovacs.

At least 19 recordsLinked to original sources

Assessment of the results of glottis-dilating operations using lung function tests.

Our aim was to obtain an objective evaluation of the airway before and after glottis-dilating operations utilizing lung function tests. The charts of 109 patients who underwent either reversible or irreversible glottis-dilating operations by Lichtenberger were reviewed. 64 nonselected cases of these patients, all with irreversible glottis-dilating operations, were studied. Lung function tests that were performed were body-pletysmography, forced inspiratory volume (FIV1), forced expiratory volume (FEV1), peak inspiratory flow rate (PIF), peak expiratory flow rate (PEF) and resistance of the airways (RAW). The FEV1, FIV1, PEF and PIF all improved following irreversible glottis-dilating operations. The RAW was remarkably decreased post-operatively as compared to pre-operatively. In conclusion, the airways of patients undergoing irreversible glottis-dilation operations improved moderately to well following such surgeries. Lung function tests are an objective means of evaluating the airway before and after surgery.

Glottis↗

Synthesis and anti-HIV activity of thymidine analogues bearing a 4'-cyanovinyl group and some derivatives thereof.

Treatment of 3'-O-tert-butyldimethylsilyl-2',5'-dideoxy-5'-oxothymidine (4) with potassium or magnesium nitromethanide afforded in good yield the resolvable epimeric mixture of the expected blocked nitronucleosides 5 which upon dehydration led to the corresponding E-nitroenofuranosylthymidine 6. Nucleophilic attack of cyanide onto the nitrovinyl group led to a nucleoside analogue bearing a terminal 1-cyanovinyl group (7), a soft electrophilic group which, upon reaction with benzeneselenol, underwent a conjugate addition to the phenylselenonucleoside derivative 9. All these compounds, eventually de-O-silylated, were subject of in vitro biological testing, some exhibiting interesting cytotoxic or antiviral properties.

Animals↗

Human amyloid-beta1-42 applied in vivo inhibits the fast axonal transport of proteins in the sciatic nerve of rat.

Human amyloid-beta1-42 has been suggested to be a pathogenetic factor in Alzheimer's disease. The precise mechanism by which this peptide causes the degeneration of neurons in the affected brain is not yet fully understood. By using immunohistochemistry we explored the inhibitory effects of human amyloid-beta1-42 applied in vivo on the fast axonal transport of acetylcholinesterase, the amyloid precursor protein, the vesicular acetylcholine transporter and synaptophysin in the sciatic nerve of rat. Our findings provide evidence for the in vivo neurotoxic effect of human amyloid-beta peptide.

Alzheimer Disease↗

Expressions of amyloid precursor protein, synaptophysin and presenilin-1 in the different areas of the developing cerebellum of rat.

This study reveals the expressions of Alzheimer's disease-related amyloid precursor protein, presenilin-1, and a presynaptic marker protein, synaptophysin, in the archi-, paleo- and neocerebellum during the postnatal development of the rat. The Western blot results demonstrate a gradual increase in the soluble amyloid precursor protein level in the archicerebellum during the first 3 weeks, while in the neo- and paleocerebellum the levels reach a plateau as early as the 1st week. Immunohistochemically, the protein is present in the deep part of the external granule cell layer and the internal granule cell layer in the newborn animal, while in 3-week-old animals the staining appears mainly in the perikarya and dendrites of the Purkinje cells. The level of synaptophysin increases progressively from postnatal day 7 up to 3 weeks in the archi- and paleocerebellum, and up to 6 weeks in the neocerebellum. Immunohistochemically, the amyloid precursor protein staining appears first in the inner part of the molecular layer and in the internal granule cell layer. In a 3-week-old animal, synaptophysin staining is present in all areas of the cerebellar molecular layer and in the internal granule cell layer. The presenilin-1 immunohistochemical reaction appeared equally in the archi-, paleo- and neocerebellum. Much of the staining is present in the glial cells and Purkinje cells. Less immunoreactivity is observed in the Golgi cells and granule cells. It is concluded that the postnatal expressions of soluble and membrane-bound amyloid precursor protein, synaptophysin and presenilin-1 are regulated differently during the ontogenetical development of the archi-, paleo- and neocerebellum of rat. Further, the amyloid precursor protein and presenilin-1 may be present in cells which do not degenerate in Alzheimer's disease.

Aging↗

Highly stereoselective synthesis and biological properties of nucleoside analogues bearing a spiro inserted oxirane ring.

Starting from 2',5'-di-O-TBDMS-3'-ketouridine 1 or its thymine analogue 2, both xylo (3-10) and ribo (20) epimers of a series of 3"-substituted 3'-spironucleosides have been obtained in good yields and with a total stereoselectivity. Most new compounds were moderately cytotoxic with in some cases slightly selective antiproliferative activities. None of these compounds was active against HIV, but some other antiviral activities against HSV-2, CMV, EBV, or VZV, in the micromolar range, were noted in specific cases.

Antibody-Dependent Cell Cytotoxicity↗

Contour detection threshold: repeatability and learning with 'contour cards'.

Human observers are able to locate contours that are defined solely on the basis of long-range, orientation-domain correlations. The integrity of the mechanisms responsible for second-order contour detection is disrupted by amblyopia (Kovacs et al., 1996; Hess et al., 1997) and it is therefore of interest to develop methods for assessing pediatric patients undergoing treatment for amblyopia. In this study, we have determined the inter-observer and test-retest reliability of a card-based test of second-order contour integration. The magnitude of practice effects was also assessed in both adult and pediatric patient groups. Contour detection thresholds were measured for a closed contour, defined by Gabor patches, embedded in a randomly oriented Gabor-patch background. The visibility of the contour was controlled by varying the density of the background elements. Thresholds, defined in terms of the ratio of contour element spacing to average background spacing were measured with a clinical staircase procedure. Thresholds measured by two observers differed on average by 0.023 +/- 0.075 or about one half the increment between cards. Children and adults showed only small practice effects (0.022 +/- 0.051 vs 0.053 +/- 0.077, respectively) and average unsigned differences between repeated measures were equivalent to approximately 1 card across groups. A card-based test of second-order contour integration produces reliable estimates of contour integration performance in normal and amblyopic observers, including children.

Adult↗

Cholinergic structures and neuropathologic alterations in the olfactory bulb of Alzheimer's disease brain samples.

This report describes the laminar distribution of acetylcholinesterase-positive structures and the neuropathologic alterations in the human olfactory bulb of control and Alzheimer's disease brain samples. The results suggests that no correlation exists between the distribution of cholinergic axons and the neuropathological alterations in the different layers in Alzheimer's disease.

Acetylcholinesterase↗

Glutamate receptor subunits GluR1 and GluR2/3 distribution shows reorganization in the human epileptogenic hippocampus.

The AMPA-type glutamate receptor subunits GluR1 and GluR2/3 were localized by immunohistochemistry with subunit-specific antibodies in hippocampi removed surgically from patients with temporal lobe epilepsy for the control of seizures. The flip and flop splice variants of the subunits were localized by in situ hybridization histochemistry with specific oligoprobes. In patient hippocampi that were not the seizure focus, the GluR1 subunit proteins were diffusely expressed on the dendrites of neurons in all regions. In contrast, in these same hippocampi, the GluR2/3 subunit proteins were expressed strongly on the soma and proximal dendrites of principal neurons in all regions. The flip variant of these subunits was localized in the hilus and fields of Ammon's Horn (CA), while the flop variants were prominent on the dentate granule cells. In the epileptogenic hippocampus, while immunoreactivity was decreased in all fields that showed neuronal loss, there was an increased expression of GluR1 on the dendritic excrescences on the proximal dendrites of hilar neurons and CA3 pyramidal neurons, as well as expression of GluR2/3 in hilar neuron excrescences. Electron microscopic examination confirmed that the GluR1 immunoreactivity was only in dendritic processes, particularly dense at the postsynaptic membranes. Such expression of GluR1 may provide for an enhanced glutamatergic response by these neurons. GluR2/3 was also significantly increased on the dendrites of dentate granule cells in the epileptogenic hippocampus and may provide some protection against excitotoxic injury by reducing calcium flux into neurons.

Dentate Gyrus↗

Pharmacological comparison of the cloned human and rat M2 muscarinic receptor genes expressed in the murine fibroblast (B82) cell line.

The coding sequence of the human m2 receptor gene was amplified by polymerase chain reaction and stably transfected into a murine fibroblast cell line (B82). We have compared the human M2 clonal cell line (HM2-B10) with the previously established B82 cell line (M2LKB2-2) expressing the rat M2 receptor to assess drug specificity, drug selectivity and effector coupling. Both transfected cell lines showed a high level of specific, saturable [3H](-)-N-methyl-3-quinuclidinyl benzilate binding with Kd values of 243 pM (155-352 pM) and 345 pM (234-539 pM) and Bmax values of 97 +/- 4 and 338 +/- 16 fmol/10(6) cells, respectively. Inhibition of [3H](-)-N-methyl-3-quinuclidinyl benzilate binding to HM2-B10 cells and M2LKB2-2 cells showed the same rank order of potency for the antagonists: atropine > dexetimide > 4-diphenylacetoxy-N-methylpiperidine methiodide > himbacine > methoctramine > 11-[[2-[(diethylamino) methyl]-1-piperidinyl]acetyl]-5,11-dihidro-6H-pyrido-[2,3-b](1, 4)-benzodiazepine-6-one > hexahydro-sila-difenidol hydro-chloride > pirenzepine. Correlation analysis of the pKi values indicate that the expressed human and rat M2 receptors have nearly identical ligand-binding characteristics. Carbachol inhibited forskolin-stimulated cAMP formation with similar potency in both cell lines [EC50 = 2.4 microM (0.2-2.8) and 1.1 microM (0.2-5.3) for the human and rat M2 receptor, respectively]. In the M2LKB2-2 cells, carbachol slightly stimulated the [3H]inositol monophosphate formation but had no significant effect in HM2-B10 cells. In conclusion, the human and rat M2 receptors expressed in the B82 cell line have very similar binding properties but exhibit slight differences in effector coupling mechanisms.

Amino Acid Sequence↗

Experimental immune-mediated damage of septal cholinergic neurons.

Degeneration of cholinergic neurons in the medial septum and the diagonal band of Broca is a frequent neuropathological feature of Alzheimer's disease. To determine whether an immune process can injure these basal forebrain cholinergic neurons, we serially immunized guinea pigs with septal cholinergic hybrid cells (SN-56). Following immunization, a relatively selective damage of septal cholinergic neurons, reduction in septal choline acetyltransferase (ChAT) activity and decrease in acetylcholine release in hippocampus were detected. Serum IgG from guinea pigs immunized with SN-56 cells and stereotactically injected into the medial septal region of rats produced a loss of ChAT activity in the medial septum, frontal cortex and hippocampus, together with impairment of learning and long term spatial memory. These data suggest that relatively selective damage to septal cholinergic neurons can be caused by an immune-mediated process in experimental animals.

Alzheimer Disease↗

Effect of oral creatine supplementation on jumping and running performance.

The study was designed to investigate the effect of creatine monohydrate ingestion (20 g daily for 5 days) on performance in 45 s maximal continuous jumping and in all-out treadmill running at 20 km x h(-1), (inclination 5 degrees, duration approximately 60s). The participants were qualified sprinters and jumpers. The effect of creatine was compared with placebo in a double-blind design. Creatine (Cr) supplementation led to a significant enhancement of performance capacity in the jumping test by 7% during the first 15 s and by 12% during the second 15 s of the exercise. The positive effect of Cr supplementation was not observed in the last third of the continuous jumping exercise, when the contribution of anaerobic metabolism was decreasing. The time of intensive running up to exhaustion improved by 13%. The results show that Cr supplementation helps to prolong the time during which the maximal rate of power output could be maintained.

Adult↗

Cholinoceptive neurons without acetylcholinesterase activity and enzyme-positive neurons without cholinergic synaptic innervation are present in the main olfactory bulb of adult rat.

Light and electron microscopic histochemistry revealed acetylcholinesterase-positive and acetylcholinesterase-negative neurons in the main olfactory bulb of adult rat. Their distribution patterns on various neuron types have been analysed in detail. (1) No acetylcholinesterase staining could be demonstrated in the granule cells which receive a large number of the cholinergic synapses. (2) In contrast, enzyme activity was present in the soma and dendrites in most of the non-cholinergic and non-cholinoceptive relay cells (mitral cells and tufted cells) and in a subset of short-axon interneurons, where cholinergic synapses could not be detected. (3) Within the neuropil of glomeruli, two compartments were present, one of which was free of acetylcholinesterase-positive structures, while many enzyme-positive neuronal elements were seen in the other. (4) Characteristically, cholinergic and non-cholinergic neuronal structures showed triadic arrangements. (5) The axonal release of acetylcholinesterase from cholinergic axons is probable. It is suggested that, in the olfactory bulb, acetylcholinesterase is release by cholinergic afferent axons, and it is the cholinergic synapses that determine which postsynaptic neurons are cholinoceptive rather than the intraneuronal presence of acetylcholinesterase. In the main olfactory bulb, the acetylcholinesterase present in the relay cells therefore appears to have functions other than the hydrolysis of acetylcholine.

Acetylcholinesterase↗

The aminoglycoside G418 suppresses muscarinic receptor-activated calcium release in stably transfected murine N1E-115 neuroblastoma cells.

The aminoglycoside G418 inhibited the release of calcium (Ca2+) from internal stores coupled to muscarinic receptors in murine N1E-115 neuroblastoma cells carrying the aminoglycoside resistance gene neomycin phosphotransferase (NPT). No significant effect was observed on responses coupled to histamine or bradykinin receptors. Cells were transfected using the eukaryotic expression vector pH beta APr-1-neo and selected using G418. Two groups were differentiated either in the continued presence of G418 or in the absence of G418. Carbachol (1 mM), histamine (200 microM) and bradykinin (100 nM) were administered to cells for thirty seconds and changes in [Ca2+]i were measured with fluorescence video microscopy of single cells loaded with the Ca2+ indicator fura-2. The effects of G418 on carbachol evoked Ca2+ release included a 73% reduction in the number of cells responding, a two fold increase in the time to reach half-maximal response, a 35% reduction of the peak [Ca2+]i in response to agonist and an elevation of resting [Ca2+]i from 99 +/- 14 nM (mean +/- S.E.M.) to 155 +/- 27 nM. Acute application (20 min) of G418 to transfected cells differentiated without G418 also reduced the percentage of cells responding to carbachol. This effect was less pronounced in non-transfected parent cells. Thus, the mechanism might involve a metabolite of G418 produced in cells expressing NPT. These results indicate that G418 attenuates Ca2+ release coupled to muscarinic receptors.

Animals↗

Two motion systems with common and separate pathways for color and luminance.

We present psychological experiments that reveal two motion systems, a specific and an unspecific one. The specific system prevails at medium to high temporal frequencies. It comprises at least two separate motion pathways that are selective for color and for luminance and that do not interact until after the motion signal is extracted separately in each. By contrast, the unspecific system prevails at low temporal frequencies and it combines color and luminance signals at an earlier stage, before motion extraction. The successful implementation of an efficient and accurate technique for assessing equiluminance corroborates further the main findings. These results offer a general framework for understanding the nature of interactions between color and luminance signals in motion perception and suggest that previously proposed dichotomies in motion processing may be encompassed by the specific/unspecific dichotomy proposed here.

Color Perception↗

Motion perception with spatiotemporally matched chromatic and achromatic information reveals a "slow" and a "fast" motion system.

Recent reports dealing with apparent motion challenged the standard view according to which motion processing should be impossible if the visual attributes matched across space and time are processed in independent channels (the similarity principle). The present work examines this possibility insofar as it relates to the spatiotemporal combination of pure chromatic and pure luminance information. The data indicate that the "similarity principle" is indeed infringed at low (< or = 2.5 Hz, i.e. velocities of 2.5 deg/sec for spatial modulations of 1 c/deg, in this study) but not at high (> or = 7.5 Hz) temporal frequencies. The fact that colour and luminance may or may not combine to yield motion perception depending on their temporal modulation reconciliates contradictory results in the literature and supports the idea of two motion systems, a "fast"/specific one, integrating information only from similar subunits, and a "slow"/unspecific one, integrating information across dissimilar subunits (in the present case, across the chromatic and achromatic "domains"). This dichotomy is also supported by the finding that chromatic reverse-phi (i.e. with equiluminant, red and green stimuli) can be observed at medium temporal frequencies but is replaced by direct motion at low temporal frequencies, presumably within the range of the "slow"/unspecific system. Using a modified "minimum motion" technique (referred to as the Reverse-Phi equiluminance method) we present data allowing to assess the relative weights of the two systems as a function of temporal frequency.

Color Perception↗

Binding interaction of gamma aminobutyric acid A and B receptors in cell culture.

We have examined the effects of 0.1 mM baclofen and pertussis toxin treatment on gamma aminobutyric acid A (GABAA) receptor binding in whole cells and in membrane of cells from cerebellar primary culture. Baclofen, a GABAB receptor ligand, caused a marked decrease in the bicuculline sensitive (GABAA) binding of [3H]muscimol on the whole cells, but failed to inhibit specific [3H]muscimol binding to cells pretreated with pertussis toxin. The effect of baclofen was only seen in whole cells and not in cell membranes. These findings suggest that activation of GABAB receptor reduces GABAA binding sites through a GTP binding protein.

Animals↗