Microtubules regulate activity of cell wall lectins in cells of Triticum aestivum L plants during cold hardening.
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Acclimatization↗
Biomedical subjects
O A Timofeeva
Publications and source records attributed to O A Timofeeva.
Species specific hepatocarcinogen inhibition of the glucocorticoid induction of tyrosine aminotransferase gene in mouse and rat liver.
3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB) is a potent hepatocarcinogen in rats and a weak carcinogen in mice, whereas o-aminoazotoluene (OAT) is a potent hepatocarcinogen in mice but weak hepatocarcinogen in rats. They significantly suppress glucocorticoid induction of tyrosine aminotransferase (TAT) in the liver of sensitive animals and have minor effect on the induction of this enzyme in the liver of resistant animals (3'-MeDAB-treated mice and OAT-treated rats). The inhibitory effect of these carcinogens is realized at the level of gene transcription (decreased accumulation of TAT mRNA). This effect is mediated via reduction of DNA-binding activity of transcription factor HNF3 (without decrease of its content) without any involvement of the glucocorticoid receptor. It was shown that carcinogens influence DNA-binding activity of HNF3 via an unknown nuclear factor.
Animals↗
Changes in EEG power spectra and behavioral states in rats exposed to the acetylcholinesterase inhibitor chlorpyrifos and muscarinic agonist oxotremorine.
Organophosphates (OPs) inhibit acetylcholinesterase (AChE) activity causing cholinergic stimulation in the central nervous system (CNS). Cholinergic systems are crucial in electroencephalogram (EEG) generation and regulation of behavior; however, little is known about how OP exposure affects the EEG and behavioral states. We recorded EEG, core temperature and motor activity before and after exposure to the OP pesticide chlorpyrifos (CHP) in adult female rats implanted with telemetric transmitters. The recording and reference electrodes were placed in the occipital and frontal bones, respectively. The animals received CHP, 25 mg/kg, p.o., or oxotremorine (OX), 0.2 mg/kg, s.c. CHP led to a significant increase in delta (0.1-3.5 Hz), slow theta (4-6.5 Hz), gamma 2 (35.5-50 Hz), reduction in fast theta (7-8.5 Hz), alpha/sigma (9-14 Hz), beta 1 (14.5-24 Hz), beta 2 (24.5-30 Hz) and gamma 1 (30.5-35 Hz) powers, slowing of peak frequencies in 1-9 Hz range, hypothermia and decrease in motor activity. The drop in 7-14 Hz was associated with cholinergic suppression of sleep spindles. Changes in behavioral state were characterized by dramatic diminution of sleep postures and exploring activity and prolongation of quiet waking. There was recovery in all bands in spite of continued inhibition of AChE activity [44,45] in rats exposed to CHP. OX-induced EEG and behavioral alterations were similar to CHP except there was no increase in delta and the onset and recovery were more rapid. We did not find a correlation between the EEG and core temperature alterations. Overall, changes in EEG (except in delta band) and behavior following CHP were attributable to muscarinic stimulation. Cortical arousal together with increased quiet waking and decreased sleep after CHP occurred independently from inhibition of motor activity and lowering of core temperature.
Administration, Oral↗
Synthesis and evaluation of oligo-1,3-thiazolecarboxamide derivatives as HIV-1 reverse transcriptase inhibitors.
A set of oligo-1,3-thiazolecarboxamide derivatives able to interact with the minor groove of nucleic acids was synthesized. These oligopeptides contained different numbers of thiazole units presenting dimethylaminopropyl or EDTA moieties on the C-terminus, and aminohexanoyl or EDTA moieties on the N-terminus. The inhibition of such compounds on HIV-1 reverse transcriptase activity was evaluated using different model template primer duplexes: DNA x DNA, RNA x DNA, DNA x RNA and RNA x RNA. The biological properties of the thiazolecarboxamide derivatives were compared to those of distamycin, another minor groove binder which contains three pyrrole rings. Similar to distamycin, the thiazole containing oligopeptides were good inhibitors of the reverse transcription reaction in the presence of DNA x DNA. But in contrast to distamycin, the oligothiazolide derivatives were able to inhibit reverse transcription in the presence of RNA x DNA or DNA x RNA template primers. Both distamycin and oligothiazolecarboxamides had low affinity for RNA x RNA duplexes. The inhibition obtained with the newly synthesized thiazolecarboxamides showed that these compounds were more powerful and versatile inhibitors of the RT-dependent polymerization than the natural minor groove binder distamycin.
Anti-HIV Agents↗
[Mutations in codon 61 in H-ras gene in liver tumors induced by strong and week carcinogens in mice].
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Animals↗
Expression of CYP1A in liver of A/Sn and CC57BR mice differing in sensitivity to hepatocarcinogenesis induced by o-aminoazotoluene.
The induction of P450 cytochromes Cyp1a1 and Cyp1a2 in the liver of male mice differing in sensitivity to the carcinogenic effect of o-aminoazotoluene (OAT) has been studied. The level of Cyp1a1 and Cyp1a2 mRNA was assayed by quantitative competitive polymerase chain reaction (PCR). In both OAT-treated strains, the level of Cyp1a1 mRNA increased more than 1000-fold, while the amount of Cyp1a2 mRNA increased only two- or threefold. Interstrain differences in the Cyp1a mRNA level were revealed. The level of Cyp1a1 mRNA in liver of OAT-induced A/Sn mice was three times higher than in CC57BR mice. The amount of Cyp1a2 mRNA in control and OAT-treated mice was 7 and 13 times higher, respectively, than in CC57BR mice. The enzyme activities of cytochromes P450 1a were assayed. An increase in Cyp1a1 mRNA level in OAT-treated mice correlated with an enhancement of the benzo[a]pyrene hydrolase and 7-ethoxyresofurin o-deethylase activities; the correlation between the level of Cyp1a2 mRNA and 7-ethoxyresofurin o-demethylase activity was much less pronounced. Interstrain variation in Cyp1a1 and Cyp1a2 activities was also shown at the enzyme activity level. We suppose that quantitative differences in the Cyp1a2 mRNA level play a key role in OAT-induced hepatocarcinogenesis.
Animals↗
[Reconstruction of phylogeny of locusts from the family Acrididae (Orthoptera) based on analysis of nucleotide sequences of 16S ribosome RNA gene in mitochondria].
The sequences of two mitochondrial 16S RNA gene fragments (137- and 174-bp in size) were determined in nine grasshopper species belonging to three Acrididae subfamilies. Phylogenetic reconstruction was performed using the sequences of twelve grasshopper species and the cricket Acheta domesticus sequence as an outgroup (some data were purchased from the GeneBank Data Library (NCBI). In the phylogenetic tree, the Acridinae and Locustinae formed compact groups. Annexpected position of Celes scalozubovi (Locustinae) within the subfamily Acridinae indicated its vague phylogeny. The Catantopinae species lied close to the base of the Acridinae. Almost all branches of phylogenetic trees were strongly (55-100%) supported by bootstrap analysis.
Animals↗
[Cyclophosphamide-induced apoptosis of murine lymphosarcoma cells in vivo].
The antitumor action of combination chemotherapy (cyclophosphamide + adriamycin + vincristin + prednisolone) for transplantable nitrosomethylurea-induced lymphosarcoma was studied in male CBA mice. Single injections of the mixture were followed by complete regression of tumors of up to 2 cm in diameter. The effect was shown to be caused by cyclophosphamide (CP) alone, by inducing apoptosis. The other components failed to potentiate the CD effect. Being useless, they are likely to cause harm by contributing to the overall toxic effect of therapy. The nature and duration of CP-induced remission appeared dose-dependent: on day 50 of the administration of 50, 100 and 150 mg/kg body, tumors were detected in 100, 55 and 0% of the animals, respectively. Such means of apoptosis induction as glycocorticoid treatment and ionizing radiation did not cause complete regression.
Animals↗
Dissociation of mossy fiber sprouting and electrically-induced seizure sensitivity: rapid kindling versus adaptation.
It has been shown that massed stimulation (MS) of the amygdala or hippocampus does not result in seizure progression but in the 'phenomenon of adaptation', whereas alternate day rapid kindling (ADRK) produces reliable kindling (Lothman, E.W., Williamson, J.M., 1994. Brain Res. 649, 71-84). The goal of the present experiment was to determine if the two different effects are due to differences in mossy fiber sprouting and/or different seizure and postictal spike propagation patterns. Nine rats underwent MS (66-70 stimulations separated by 5-min interstimulus interval), six were exposed to ADRK (12 stimulations/day, every 30 min, with 4 stimulus days, each separated by 1 stimulus-free day), five rats served as control. All rats had electrodes implanted bilaterally in dorsal and ventral hippocampi (VH) and 14 of them had additional electrodes in the piriform cortex. Animals were stimulated in the left VH at afterdischarge threshold. There was no potentiation in seizure response 4-7 weeks after MS. In contrast, ADRK produced not only kindling but also ongoing epileptogenesis resulting 4-7 weeks later in spontaneous seizures and development of a prolonged convulsive state in response to the initially subconvulsive stimulus. Epileptiform activity during MS was mostly restricted to VH, whereas during ADRK it spread widely among studied structures including piriform cortex. Afterdischarges during MS were elicited frequently but seizures did not progress beyond stage 2-3. During ADRK, afterdischarges were evoked less frequently but seizures reached stage 4-7 by the end of the 3rd and 4th stimulus days. The fully kindled state was not reached at this time, but epileptogenic changes continued to progress. Seven weeks after the initial stimulation, both groups demonstrated mossy fiber sprouting of similar intensity in VH. We suggest, (1) frequent but predominantly local hippocampal afterdischarges induce mossy fiber sprouting, but this is not sufficient to produce significant enhancement in seizure susceptibility, and (2) the involvement of extra-hippocampal structures, possibly piriform cortex, and formation of an aberrant hippocampal-para-hippocampal circuit is required to result in a condition of progressive epileptogenesis.
Adaptation, Physiological↗
[Analysis of the distribution of alleles of a tetranucleotide repeat in intron 6 of the lipoprotein lipase gene among residents of Novosibirsk].
The allele frequencies of a tetranucleotide repeat in intron 6 of the lipoprotein lipase gene (humLPL) were analyzed in 95 people from Novosibirsk. Genotype frequencies were shown to conform to the Hardy-Weinberg equilibrium. The allele frequency distribution of the tested hypervariable loci in the Novosibirsk population did not differ significantly from that in the Austrian population.
Alleles↗
[The study of correlation between the K-ras genotype and murine susceptibility to chemically induced lung neoplasms].
The susceptibility of the ICR, DD/He and CC57/BR mice to urethane-induced lung tumors was analyzed in comparison with the A/He (highly susceptible) and AKR (resistant) lines of mice. Allelic variants of the K-Ras gene intron 2 in these lines have been determined. Susceptibility of the ICR mice was similar to that of the A mice, and intron 2 of the K-Ras ICR gene carried the 37-bp deletion analogous to that described in the A/He line. The DD mice intron 2 also contained the deletion, but despite the presence of the "susceptible" K-Ras allele, the DD/He mice were resistant to urethane induction of lung tumors. The CC57BR line carried the deletion and demonstrated relatively high susceptibility. Our findings indicate that the K-Ras gene may be important in the chemical induction of lung tumors.
Animals↗
Structural constraints in the HIV-1 reverse transcriptase-primer/template complex for the initiation of DNA synthesis from primer tRNALys3.
The topography and functional implications of the complex formed in vitro between human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and its primer tRNALys3 were studied in this work. On the basis of previous results showing the high affinity both of the native primer, tRNALys3, as well as that of mismatched short oligonucleotide primers for HIV-1 RT, we synthesized chimeric primers containing tRNALys3 linked to U and T residues of different lengths. We found that the affinity of the oligonucleotide primers for HIV-1 RT is dramatically increased when linked to primer tRNA. Our results also show that in the tRNA.RT complex, before annealing tRNALys3 to the retroviral RNA genome, the 3'-terminal nucleotide of tRNALys3 is positioned at a distance of one nucleotide unit away from the template in the active polymerization site of the enzyme.
Binding Sites↗
Interaction of tRNA-derivatives and oligonucleotide primers with AZT-resistant mutants of HIV-1 reverse transcriptase.
While the molecular basis of HIV-1 AZT resistance has been widely studied, a biochemical explanation of this process is not well known. No significant changes in the binding affinity of reverse transcriptase (RT) mutants for AZT-triphosphate has been found. Here we analyzed the interaction of wild type and AZT-resistant mutant forms of HIV-1 RT with different primers. Site-directed mutagenesis was used to introduce point mutations on the retroviral enzyme. Primers were either synthetic oligonucleotides or tRNA(Lys3) derivatives containing d(pT)n or r(pU)n at the 3' end. In all cases, determination of kinetic parameters was done in the presence or absence of compounds known to modify protein conformation, such as dimethyl sulfoxide (DMSO), urea, and Triton X-100. Although we found similar K(m) values for all RTs, there was generally an increase in the affinity when enzymes were tested in the presence of DMSO, urea, and Triton X-100. Then, we analyzed the nucleation and elongation steps of the polymerization process. The efficiency of formation of the first base pair was determined by measuring K(m1), the affinity between RT and the 3' terminal nucleotide of the primer. An important difference was found: in the presence of DMSO, urea, and Triton X-100, the K(m1) values for mutated enzymes were higher than those of wild type RTs. Thus, the presence of compounds able to change protein conformation led to a marked destabilization of the interaction of mutated RTs with the 3' terminal nucleotide of the primer. From these results, it can be hypothesized that resistance to AZT is not due to the direct influence of mutations on RT, but rather to conformational changes of the mutated RT in complex with the template-primer altering the ability of the enzyme to select or reject an incoming dNTP.
DNA Primers↗
[Nucleotide level evaluation of the genetic variability of the human population in ecologically unfavorable regions of the Techa river].
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Adolescent↗
Delayed development of spontaneous seizures and prolonged convulsive state in rats after massed stimulation of the anterior piriform cortex.
We studied the short- and long-term epileptogenic effects of massed stimulation (MS) of the piriform cortex. Sprague-Dawley rats with electrodes implanted bilaterally in the anterior piriform cortex and the dorsal and ventral hippocampi underwent MS: electrical stimulation of the left piriform cortex every 5 min for 6 h (afterdischarge threshold, 60 Hz, 1 ms, 1 s). Animals were retested (5 stimulations) 3-4 times later at different time points to check for the kindled state. Our data showed that MS resulted in delayed development of severe epilepsy. The interval between MS and the first appearance of convulsive response (2 weeks) was characterized by deep refractoriness to seizure (silent period). Unexpectedly, dramatic seizure activity occurred 4-7 weeks after MS. This was manifested by (1) generalized tonic-clonic convulsions with multiple failings, which were elicited repeatedly during retest; (2) frequent progression of elicited generalized convulsions into a prolonged (> 8 min) postictal convulsive state expressed mainly by continuous partial seizures and even new bouts of generalized seizures, and (3) development of mild spontaneous seizures. We found that epileptiform activity predominated in the ventral hippocampus. Mossy fiber sprouting was also most pronounced in this area. We propose that the MS resulted in formation of pathological circuits which involve both piriform cortex and ventral hippocampus and lead to severe epilepsy.
Aging↗
Bilateral hippocampal interictal spiking and kindling expression in rabbits.
The temporal/spatial dissemination of interictal spikes among different brain structures was studied during the course of kindling to determine if the long-term dissemination pattern reflects the rate and expression of kindling. The experiments were conducted on adult rabbits with chronically implanted electrodes (dorsal hippocampus, amygdala, caudate, all bilateral, sensory motor and occipital cortices). Rabbits (n = 13) were subjected to once daily electrical stimulation in the left hippocampus. Kindling resulted in the development of two different epileptic phenomena: 7 animals quickly (in 2-3 weeks) achieved a fully kindled state, characterized by generalized seizures, whereas the remaining 6 rabbits did not reliably progress beyond partial seizures even after more prolonged stimulation. Animals were accordingly divided into two groups referred to as generalized seizure and partial seizure. The temporal/spatial dissemination pattern, particularly in the two hippocampi, was very different between the groups. In both groups interictal spiking originated in one of the hippocampi independent of site stimulated and represented formation of the primary hippocampal epileptic focus. The generalized seizure group demonstrated stability of the primary hippocampal epileptic focus with permanent predominance of spiking in it over the course of kindling, and a high level of bilateral synchronous hippocampal interictal spiking. In the partial seizure group the primary hippocampal epileptic focus was established during the first 2-3 weeks of stimulation. This was later suppressed upon the development of an independent secondary focus in the opposite hippocampus. These animals also displayed very low levels of synchronous bilateral hippocampal interictal spiking. We suggest that an antagonistic relationship can develop between mirror hippocampal epileptic foci. This can be associated with a low level of bilateral hippocampal synchronous spiking, kindling retardation, and manifestation of partial seizures.
Analysis of Variance↗
Apparent disappearance of postseizure inhibitions and intensity of seizures during the development of rapid kindling in rabbits.
The evolution of seizures and postseizure inhibitions in the course of 'rapid kindling' and after the termination of stimulation were studied in rabbits with chronically implanted electrodes (neocortex, dorsal hippocampus, amygdala, caudate nucleus). The amygdala (n = 4) or hippocampus (n = 7) was electrically stimulated every 5 min. Generalized convulsions and wide-spread electrographic epileptic changes together with a striking shortening of postictal refractory periods were produced by this procedure within 2-6 h. In most cases, these epileptogenic effects continued their progression after the termination of stimulation for more than 2-4 weeks. The degree of reduction of postseizure inhibition durations was significantly greater than the degree of increase of generalized motor seizure durations. These may be mediated by mechanisms which facilitate the onset of seizure but do not significantly influence seizure expression.
Animals↗
[The central structural interrelations during kindling electrostimulations of the hippocampus].
The rate of kindling development was studied in rabbits with chronic electrodes (neocortex, hippocampus, amygdala, caudate nucleus) in respect to distribution of epileptic activity over the brain structures. The differences of individual kindling development depended on the distribution of interictal spikes over the brain structures and the degree of their subordination to the primary hippocampal focus. The kindling effects seem to develop rapidly in those cases when primary hippocampal epileptic focus plays a role of pathological determiner which subordinates and synchronizes the activity in other structures. When competitive inhibitory influences prevail in the interrelationships between primary and secondary hippocampal foci, neither pathological hippocampal determiner nor kindling effects occur.
Action Potentials↗