Biomedical subjects

Gábor Tóth

Publications and source records attributed to Gábor Tóth.

At least 19 recordsLinked to original sources

PubMed2006

The neuroprotective effects of PACAP in monosodium glutamate-induced retinal lesion involve inhibition of proapoptotic signaling pathways.

Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors are present in the retina and exert several distinct functions. PACAP has well-known neuroprotective effects in neuronal cultures in vitro and against different insults in vivo. Recently we have shown that PACAP is neuroprotective against monosodium glutamate (MSG)-induced retinal degeneration. In the present study we investigated the possible signal transduction pathways involved in the protective effect of intravitreal PACAP administration against apoptotic retinal degeneration induced by neonatal MSG treatment. MSG induced activation of proapoptotic signaling proteins and reduced the levels of antiapoptotic molecules in neonatal retinas. Co-treatment with PACAP attenuated the MSG-induced activation of caspase-3 and JNK, inhibited the MSG-induced cytosolic translocation of apoptosis inducing factor (AIF) and cytochrome c, and increased the level of phospho-Bad. Furthermore, PACAP treatment alone decreased cytosolic AIF and cytochrome c levels, while PACAP6-38 increased cytochrome c release, caspase-3 and JNK activity and decreased phospho-Bad activity. In summary, our results show that PACAP treatment attenuated the MSG-induced changes in apoptotic signaling molecules in vivo and suggest that also endogenously present PACAP has neuroprotective effects. These results may have further clinical implications in reducing glutamate-induced excitotoxicity in several ophthalmic diseases.

Animals↗

PubMed2006

alpha4-Tubulin is involved in rapid formation of long microtubules to push apart the daughter centrosomes during earlyx Drosophila embryogenesis.

Although alpha4-tubulin comprises only about one-fifth of the alpha-tubulin pool in every Drosophila egg, in the absence of alpha4-tubulin - in eggs of the kavar(0)/- hemizygous females - only a tassel of short microtubules forms with two barely separated daughter centrosomes. We report that alpha4-tubulin is enriched in the long microtubules that embrace the nuclear envelope and suggest that they push apart daughter centrosomes along the nuclear perimeter during the initial cleavage divisions. In vitro tubulin polymerization showed that alpha4-tubulin is required for rapid tubulin polymerization. Since tubulin polymerization is slow inside eggs of the kavar(0)/- females, only short microtubules can form within the 4 to 5 minutes allowed for the process. A tassel of short microtubules with two barely separated centrosomes forms in every egg of the Kavar(18c)/+ females, in which the cytoplasm contains both wild-type and Kavar(18c)-encoded alpha4-tubulin with an E82K amino acid substitution (E82K-alpha4-tubulin). E82K-alpha4-tubulin is incorporated into the microtubules and renders them unstable. When injected into wild-type early cleavage embryos E82K-alpha4-tubulin slows down the formation of long microtubules and the separation of the daughter centrosomes. Surprisingly, when injected into late cleavage embryos E82K-alpha4-tubulin is non-toxic. Similarly, in the neuroblasts, ectopically expressed E82K-alpha4-tubulin becomes incorporated into the microtubules that grow sufficiently long and function normally.

Animals↗

PubMed2006

PLOTREP: a web tool for defragmentation and visual analysis of dispersed genomic repeats.

Identification of dispersed or interspersed repeats, most of which are derived from transposons, retrotransposons or retrovirus-like elements, is an important step in genome annotation. Software tools that compare genomic sequences with precompiled repeat reference libraries using sensitive similarity-based methods provide reliable means of finding the positions of fragments homologous to known repeats. However, their output is often incomplete and fragmented owing to the mutations (nucleotide substitutions, deletions or insertions) that can result in considerable divergence from the reference sequence. Merging these fragments to identify the whole region that represents an ancient copy of a mobile element is challenging, particularly if the element is large and suffered multiple deletions or insertions. Here we report PLOTREP, a tool designed to post-process results obtained by sequence similarity search and merge fragments belonging to the same copy of a repeat. The software allows rapid visual inspection of the results using a dot-plot like graphical output. The web implementation of PLOTREP is available at http://bioinformatics.abc.hu/PLOTREP/.

Computer Graphics↗

PubMed2006

NMR spectroscopic structure elucidation of the products of the reaction of 3-(3-aryl-3-oxopropenyl)- chromen-4-ones with 1,2-phenylenediamine.

The reaction of 3-(3-aryl-3-oxopropenyl)chromen-4-ones with 1,2-phenylenediamine resulted in the unexpected formation of 10a-aryl-1,2,10,10a-tetrahydrobenzo-[4,5]-imidazo[1,2-a]pyridin-3-yl(2-hydroxyphenyl)-1-methanones. Their structure elucidation and complete 1H and 13C assignments have been performed by a combination of various one- and two-dimensional NMR experiments.

Benzodiazepines↗

PubMed2006

Iridoid and lignan glycosides from Citharexylum spinosum L.

From the aerial parts of Citharexylum spinosum L., one new iridoid glucoside, the 7-ss-O-acetate (1) of lamiide, along with four known iridoid glucosides, lamiide (2), lamiidoside (3), duranterectoside C (4), 8-epiloganin (5) and one known lignan glucoside (+)-lyonirenisol-3a-O-ss-D-glucopyranoside (6) were isolated. The compound structures were established by one- and two-dimensional 1H- and 13C-NMR as well as by ESI-MS spectra.

Glycosides↗

PubMed2006

Glycosides from Bougainvillea glabra.

Three glycosides were isolated from Bougainvillea glabra and their structures were determined by extensive use of 1D and 2D NMR spectroscopy ((1)H and (13)C). First compound was identical to momordin IIc (quinoside D) [beta-D-glucopyranosyl 3-O-[beta-D-xylopyranosyl-(1 --> 3)-O-(beta-D-glucopyranosyluronic acid)] oleanolate], second compound was quercetin 3-O-alpha-L-(rhamnopyranosyl)(1 --> 6)-[alpha-L-rhamnopy-ranosyl(1 --> 2)]-beta-D-galactopyranoside and third compound was its derivative quercetin 3-O-alpha-L-(4-caffeoylrhamnopyranosyl)(1 --> 6)-[alpha-L-rhamnopyranosyl (1 --> 2)]-beta-D-galactopyranoside, a new natural product.

Glycosides↗

PubMed2006

Genetic variability of gag and env regions of HIV type 1 strains circulating in Slovenia.

The aim of this study was to investigate the genetic diversity of HIV-1 strains circulating in Slovenia. Proviral DNA isolated from peripheral blood mononuclear cells (PBMCs) of 20 randomly selected HIV-1-infected individuals was classified into subtypes by sequence-based phylogenetic analysis of the env (C2V3) and gag (p24) regions of the viral genome. The phylogenetic tree based on env C2V3 sequences showed that 15 of the 20 samples were subtype B, two A1, one F1, one CRF01_AE, and one CRF02_AG. The phylogenetic analysis of the gag gene yielded identical results expect for one sample that had a discordant subtype; it was identified as subtype A1 in the env and AE in the gag region. Our study confirmed that although subtype B predominates, other subtypes and circulating recombinant forms (CRFs) are also present in Slovenia. The high intrasubtype genetic diversity of subtype B sequences suggests a multiple introduction of subtype B strains into Slovenia.

Amino Acid Sequence↗

PubMed2005

Significant microsynteny with new evolutionary highlights is detected between Arabidopsis and legume model plants despite the lack of macrosynteny.

The increased amount of data produced by large genome sequencing projects allows scientists to carry out important syntenic studies to a great extent. Detailed genetic maps and entirely or partially sequenced genomes are compared, and macro- and microsyntenic relations can be determined for different species. In our study, the syntenic relationships between key legume plants and two model plants, Arabidopsis thaliana and Populus trichocarpa were investigated. The comparison of the map position of 172 gene-based Medicago sativa markers to the organization of homologous A. thaliana genes could not identify any sign of macrosynteny between the two genomes. A 276 kb long section of chromosome 5 of the model legume Medicago truncatula was used to investigate potential microsynteny with the other legume Lotus japonicus, as well as with Arabidopsis and Populus. Besides the overall correlation found between the legume plants, the comparison revealed several microsyntenic regions in the two more distant plants with significant resemblance. Despite the large phylogenetic distance, clear microsyntenic regions between Medicago and Arabidopsis or Populus were detected unraveling new intragenomic evolutionary relations in Arabidopsis.

Arabidopsis↗

PubMed2005

The beta subunit of the type I Fcepsilon receptor is a target for peptides inhibiting IgE-mediated secretory response of mast cells.

Peptides originally derived from complement component C3a were earlier shown to inhibit the type I FcepsilonR (FcepsilonRI)-mediated degranulation of mucosal type mast cells. In the present study, we show that C3a7, a peptide with a natural sequence, and its modified derivative, C3a9, are powerful inhibitors of the above response of both serosal and mucosal type mastocytes. We demonstrate that these peptides inhibit FcepsilonRI-induced membrane proximal events, suppress phosphorylation of the FcepsilonRI beta subunit, the protein tyrosine kinase Lyn, as well as the transient rise in free cytosolic Ca2+ level. The late phase of cellular response was also inhibited, as demonstrated by the reduced TNF-alpha secretion. Experiments using two independent methods provided evidence that the interaction site of complement-derived peptides is the FcepsilonRI beta-chain. This was further supported by fluorescence confocal microscopic colocalization and resonance energy transfer measurements. Taken together, these results suggest the presence of distinct "activating" and "inhibitory" motifs in the C3a sequence. Response to both is in balance under physiologic conditions. Furthermore, present data predict that such inhibitory peptides may serve as potent agents for future therapeutic intervention.

Animals↗

PubMed2005

Pituitary adenylate cyclase activating polypeptide plays a role in olfactory memory formation in chicken.

PACAP plays an important role during development of the nervous system and is also involved in memory processing. The aim of the present study was to investigate the function of PACAP in chicken embryonic olfactory memory formation by blocking PACAP at a sensitive period in ovo. Chicken were exposed daily to strawberry scent in ovo from embryonic day 15. Control eggs were treated only with saline, while other eggs received a single injection of the PACAP antagonist PACAP6-38 at day 15. The consumption of scented and unscented water was measured daily after hatching. Animals exposed to strawberry scent in ovo showed no preference. However, chickens exposed to PACAP6-38, showed a clear preference for plain water, similarly to unexposed chicken. Our present study points to PACAP's possible importance in embryonic olfactory memory formation.

Animals↗

PubMed2005

Comparison of low-order multireference many-body perturbation theories.

Tests have been made to benchmark and assess the relative accuracies of low-order multireference perturbation theories as compared to coupled cluster (CC) and full configuration interaction (FCI) methods. Test calculations include the ground and some excited states of the Be, H(2), BeH(2), CH(2), and SiH(2) systems. Comparisons with FCI and CC calculations show that in most cases the effective valence shell Hamiltonian (H(v)) method is more accurate than other low-order multireference perturbation theories, although none of the perturbative methods is as accurate as the CC approximations. We also briefly discuss some of the basic differences among the multireference perturbation theories considered in this work.

Journal Article↗

PubMed2005

Multiconfiguration perturbation theory: size consistency at second order.

A modified version of a previously elaborated multiconfiguration perturbation theory (MCPT) [Rolik et al. J. Chem. Phys. 119, 1922 (2003)] is presented. In the modified formulation size consistency is ensured at second order in energy, by omitting projectors from the zero order Hamiltonian operator. This MCPT formulation is abbreviated as SC2-MCPT (size consistent at second order). To ensure proper separability, we also require that energy denominators are constructed as differences of some one-particle energies. A similar choice for energy denominators also renders the well-known multireference Moller-Plesset (MRMP) energy size consistent at second order. The same thing applies to the related multireference perturbation theory by Witek, Nakano, and Hirao.

Journal Article↗

PubMed2005

DoOP: Databases of Orthologous Promoters, collections of clusters of orthologous upstream sequences from chordates and plants.

DoOP (http://doop.abc.hu/) is a database of eukaryotic promoter sequences (upstream regions) aiming to facilitate the recognition of regulatory sites conserved between species. The annotated first exons of human and Arabidopsis thaliana genes were used as queries in BLAST searches to collect the most closely related orthologous first exon sequences from Chordata and Viridiplantae species. Up to 3000 bp DNA segments upstream from these first exons constitute the clusters in the chordate and plant sections of the Database of Orthologous Promoters. Release 1.0 of DoOP contains 21,061 chordate clusters from 284 different species and 7548 plant clusters from 269 different species. The database can be used to find and retrieve promoter sequences of a given gene from various species and it is also suitable to see the most trivial conserved sequence blocks in the orthologous upstream regions. Users can search DoOP with either sequence or text (annotation) to find promoter clusters of various genes. In addition to the sequence data, the positions of the conserved sequence blocks derived from multiple alignments, the positions of repetitive elements and the positions of transcription start sites known from the Eukaryotic Promoter Database (EPD) can be viewed graphically.

Animals↗

PubMed2005

Effective enantiodifferentiation of spirochalcogenuranes by the dirhodium method: towards the determination of absolute configurations?

The properties of chiral spirochalcogenuranes acting as ligands in adducts with a chiral dirhodium tetracarboxylate complex is explored, and the individual adduct species are characterized by low-temperature NMR spectroscopy. Chiral recognition and the determination of enantiomeric composition of the chiral spirochalcogenuranes is easy by evaluating NMR signal dispersions both at low and at room- or slightly elevated temperatures. The uniformity in the signs of 1H dispersion effects and taking reference to the spiroselenurane with known absolute configuration [(S)-(-)-2] indicates that a convenient rule for the determination of absolute configuration in the spirochalcogenurane system can be established on the basis of 1H chemical shift dispersions.

Journal Article↗

PubMed2005

Degree of damage compensation by various PACAP treatments in monosodium glutamate-induced retinal degeneration.

Pituitary adenylate cyclase activating polypeptide (PACAP) has been shown to be neuroprotective in retinal ischemia and monosodium L-glutamate (MSG)-induced retinal degeneration. Here we describe how different MSG treatments (1x and 3x application) cause retinal damage and finally lead to the destruction of the entire inner retina and how PACAP attenuates this effect. Newborn rats from both sexes were injected subcutaneously with 2 mg/g bodyweight MSG on postnatal days 1, 5 and 9. The left eye was left intact while we injected 5 microl PACAP38 solution (100 pmol) into the vitreous of the right eye with a Hamilton syringe at the time of (i) the first, (ii) the first two or (iii) all three MSG injections. Histological analysis has shown that the above described MSG treatment caused the entire inner plexiform layer (IPL) to degenerate, and the inner nuclear (INL) and ganglion cell layers (GCL) seemed fused. One time PACAP38 treatment at the first MSG application did not change the degenerative capacity of MSG. However, if animals received PACAP38 into the vitreous of the eye at the first 2 or all 3 times, a substantial protective effect could be observed. The IPL remained well discernible, the INL retained 2-3 cell rows and the number of cells in the GCL was substantially higher than in the MSG-treated retinas, and was not significantly different from that observed in the control tissue. We conclude that (i) 2 or 3 times PACAP treatment attenuates retinal degeneration; (ii) one PACAP treatment does not provide protection against repeated excitotoxic insults, and (iii) repeated application of PACAP under these experimental conditions may lead to a primed state in which further neurotoxic insults are ineffective.

Animals↗

PubMed2005

International anthropometric study of facial morphology in various ethnic groups/races.

When anthropometric methods were introduced into clinical practice to quantify changes in the craniofacial framework, features distinguishing various races/ethnic groups were discovered. To treat congenital or post-traumatic facial disfigurements in members of these groups successfully, surgeons require access to craniofacial databases based on accurate anthropometric measurements. Normative data of facial measurements are indispensable to precise determination of the degree of deviations from the normal. The set of anthropometric measurements of the face in the population studied was gathered by an international team of scientists. Investigators in the country of the given ethnic group, experienced and/or specially trained in anthropometric methods, carried out the measurements. The normal range in each resultant database was then established, providing valuable information about major facial characteristics. Comparison of the ethnic groups' databases with the established norms of the North America whites (NAW) offered the most suitable way to select a method for successful treatment. The study group consisted of 1470 healthy subjects (18 to 30 years), 750 males and 720 females. The largest group (780 subjects, 53.1%) came from Europe, all of them Caucasians. Three were drawn from the Middle-East (180 subjects, 12.2%), five from Asia (300 subjects, 20.4%) and four from peoples of African origin (210 subjects, 14.3%). Their morphological characteristics were determined by 14 anthropometric measurements, 10 of them used already by classic facial artists, Leonardo da Vinci and Albrecht Dürer, complemented by four measurements from the nasal, labio-oral and ear regions. In the regions with single measurements, identical values to NAW in forehead height, mouth width, and ear height were found in 99.7% in both sexes, while in those with multiple measurements, vertical measurements revealed a higher frequency of identical values than horizontal ones. The orbital regions exhibited the greatest variations in identical and contrasting measurements in comparison to NAW. Nose heights and widths contrasted sharply: in relation to NAW the nose was very or extremely significantly wide in both sexes of Asian and Black ethnic groups. Among Caucasians, nose height significantly differed from NAW in three ethnic groups, with one shorter and two greater. In the Middle Eastern groups nose width was identical to those of NAW but the height was significantly greater. The present study, conducted by investigators working separately across the world and with small samples of the population, is clearly preliminary in nature and extent. Yet it may fulfill its mission if medical and anthropological investigators continue the work of establishing normative data of the face. These data are urgently needed by medical professionals but have been lacking up till now in western and northern Europe, Asia, and Africa.

Adolescent↗

PubMed2004

Regulation of mast cell activation by complement-derived peptides.

It is known for more than 25 years that the complement-derived anaphylatoxic peptides, C3a, C4a and C5a are potent activators of basophils and certain types of mast cells. Although tissue distribution of receptors for C3a and C5a well exceeds myeloid cells, apparently they are not expressed on mucosal type mast cells, consequently these cells are not activated by C3a and C5a. Our results do however demonstrate that C3a and peptides related to this complement activation product are able to inhibit FcRI-clustering induced activation of mucosal type mast cells-such as RBL-2H3 cells and bone-marrow derived mast cells. Based on the current results we propose the presence of separate "activator" and "inhibitor" sequence motifs in C3a which are in balance under physiologic conditions.

Animals↗

PubMed2004

Unprecedented cyclizations of calix[4]arenes with glycols under the Mitsunobu protocol, part 2.(1) O,O-and O,S-bridged calixarenes.

[reaction: see text] Cycloalkylations of p-tert-butylcalix[4]arene (CA) and p-tert-butylthiacalix[4]arene (TCA) with various aliphatic glycols were performed under the Mitsunobu protocol using the DEAD/TPP system. CA gave 1,3-dialkylated diols, while C(2)-C(10) glycols gave 1,2- and 1,3-bridged calixarenes. The reaction of TCA with C(2) diols afforded sulfonium phenoxide betaines via O,S-cyclization, which is the first example for the alkylation of the sulfide bridge.

Journal Article↗