Biomedical subjects

I A Ivanova

Publications and source records attributed to I A Ivanova.

At least 19 recordsLinked to original sources

PubMed2006

Activation of p38- and CRM1-dependent nuclear export promotes E2F1 degradation during keratinocyte differentiation.

E2F factors modulate a plethora of cell functions, including proliferation, differentiation, DNA repair and apoptosis. We have shown that differentiation in primary epidermal keratinocytes leads to E2F1 downregulation via activation of protein kinase C and p38 mitogen-activated protein kinase. We now demonstrate that E2F1 downregulation in differentiating keratinocytes involves its ubiquitination, as well as proteasomal degradation subsequent to CRM1-dependent nuclear export. E2F1 nuclear export specifically in response to differentiation requires regions adjacent to the cyclin A-binding domain in the N-terminus of this protein. Significantly, inhibition of p38 interferes with nuclear export and degradation of E2F1 during differentiation, but has no effect on E2F1 in undifferentiated cells. Thus, induction of differentiation in epidermal keratinocytes activates a specific program for post-transcriptional downregulation of E2F1, which involves signaling through p38 and activation of nuclear export pathways.

Active Transport, Cell Nucleus↗

PubMed2006

E2F1 stability is regulated by a novel-PKC/p38beta MAP kinase signaling pathway during keratinocyte differentiation.

E2F transcription factors regulate proliferation, differentiation, DNA repair and apoptosis. Tight E2F regulation is crucial for epidermal formation and regeneration. However, virtually nothing is known about the molecular events modulating E2F during epidermal keratinocyte differentiation. Elucidation of these events is essential to understand epidermal morphogenesis, transformation and repair. Here we show that, in differentiating keratinocytes, Ca(2+)-induced protein kinase C (PKC) activation downregulates E2F1 protein levels. Further, we have identified PKC delta and eta as those isoforms specifically involved in induction of E2F1 proteasomal degradation. We also demonstrate that E2F1 downregulation by novel PKC isozymes requires activation of p38beta mitogen-activated protein kinase (MAPK). This is the first example of regulation in the E2F transcription factor family by activation of PKC and MAPK in the context of biologically significant differentiation stimuli in epithelia.

Animals↗

PubMed2004

[Use of detergents for elimination of non-specific reactions of monoclonal antibodies].

The purpose of the case study was elaboration of methods for removing the false-positive results in the detection of virus antigens that cause acute respiratory lesions both in the plane and dot-membrane variations of immune-enzyme assays of monoclonal antibodies. Modeled experiments showed that the non-specific staining of biological samples, in which the above viral antigen are looked for, is preconditioned by a direct reaction of the substrate with its own oxidizing enzymes and by the binding of monoclonal antibodies with biological macromolecules free of any viral adherence and sorbated in the solid phase. Approaches to solving such issues are described in the paper. They comprise the inhibition of the own oxidizing activity of wash-outs by the substrate and the application of detergents. Different detergents were comparatively analyzed and the optimal compounds were chosen for each variation of immune-enzyme test-systems. The described techniques ensure more reliable results in the viral antigen detection by immune-enzyme assay.

Animals↗

PubMed2004

[Anticholinergic Effect of a New Antiarrhythmic Class III Drug RG-2].

In experiments on isolated rat and rabbit right atrium, a new class III antiarrhythmic drug RG-2 (0,01-1 microM) was shown to have anticholinergic action competing with 0.2-1 mM carbachol. RG-2 (0.1-1 microM) produced dose-dependent increase of APD90% in rat and rabbit atrial cells and had no effects on other action potential parameters. In presence of carbachol RG-2 produced significantly greater increase of APD90% and caused significant increase of APD50%. Thus RG-2 exerts anticholinergic action, which can take important part in RG-2 antiarrhythmic activity.

Action Potentials↗

PubMed2002

[Effect of monokines induced by Yersinia pestis EV on the functional activity of neutrophils during development of antiplague immunity].

A study was made of the Yersinia pestis EV induced monokine complex influence on neutrophil (Nph) functional activity in the course of antiplague immunity formation. The obtained monokines essentially enhance Nph killing, chemotactic activities and Fc-receptor expression, and stimulate lysosome membrane labilization of these cells. The helper effect of the Y. pestis EV induced monokines on Nph functional activity is more pronounced during the secondary immune response, than in the course of the primary one.

Animals↗

PubMed2002

[Microvzor-2: a system for automated dry blood smear analysis].

Upgraded system Microvzor-2 for investigation of blood morphology in space flight is composed of soft- and hardware for dry smear image analysis. Ground-based testing showed that it could be utilized to investigate a broad spectrum of blood parameters in space flight, including erythrocytes, hemoglobin content in erythrocytes, volumetric erythrocyte distribution, diagnostics of anisocytosis, and poikilocytosis, leukocytes and leukocyte count. Analyzed are smears prepared from a fixed volume of finger blood. The process consists of smear scanning, input of the vision field images in the spacecraft computer and ensuing automated identification and counting. Information is stored in a dedicated database. Results of analysis are displayed as forms and cell galleries.

Adaptation, Physiological↗

PubMed2001

[Alirinomycin C--a novel macrolide antibiotic from Streptomyces felleus VIZR 8].

The culture of Streptomyces felleus VIZP 8 producing new macrolide antibiotic alirinomycin C was isolated in the screening of new insecticide substances. Antibiotic was related to the carbomycin-cirramycin group. Physico-chemical and biological properties investigation and identification were performed in comparison with other antibiotics of the same group, described in literature.

Anti-Bacterial Agents↗

PubMed2001

[Cytokines--a general system of homeostatic regulation of cell functions].

The paper reviews biological characteristics of cytokines, which are short living molecules exerting pleiotropic and redundant effects on a variety of target cell types, influencing cell activation and differentiation. Significance of cytokines for patho- and immunogenesis of infections and other diseases is analysed, in addition to further perspectives of cytokine employment for prophylaxis and treatment of various diseases.

Animals↗

PubMed2001

[Monokine-producing activity of human monocyte-like cell line U937 induced by Yersinia pestis EV antigens].

The data on a study of the monokine-producing ability of human monocyte-like cell line U937 are presented. Antigens of Yersinia pestis EV (lipopolysaccharide and fraction 1A) induce monokine production by cell line U937. The obtained monokines essentially enhance neutrophil killer and chemotactic activities, stimulate FcR expression, increase the number of lysosomes, and the lability of lysosomal membranes in neutrophils. F1A significantly suppresses LPS in respect to the ability to induce monokine production, which stimulate neutrophil functional activity.

Animals↗

PubMed2000

Characterization of the elongating alpha-D-mannosyl phosphate transferase from three species of Leishmania using synthetic acceptor substrate analogues.

Leishmania express lipophosphoglycans and proteophosphoglycans that contain Galbeta1-4Manalpha1-P phosphosaccharide repeat structures assembled by the sequential addition of Manalpha1-P and betaGal. The synthetic acceptor substrate Galbeta1-4Manalpha1-P-decenyl and a series of analogues were used to probe Leishmania alpha-D-mannosyl phosphate transferase activity. We show that the activity detected with Galbeta1-4Manalpha1-P-decenyl is the elongating alpha-D-mannosyl phosphate transferase associated with lipophosphoglycan biosynthesis (eMPT(LPG)). Differences in the apparent K(m) values for the donor and acceptor substrates were found using L. major, L. mexicana, and L. donovani promastigote membranes, but total activity correlated with the number of lipophosphoglycan repeats. Further comparisons showed that lesion-derived L. mexicana amastigotes, that do not express lipophosphoglycan, lack eMPT(LPG) and that nondividing L. major metacyclic promastigotes contain 5-fold less eMPT(LPG) activity than dividing procyclic promastigotes. The fine specificity of promastigote eMPT(LPG) activity was determined using 24 synthetic analogues of Galbeta1-4Manalpha1-P-decenyl. The three species gave similar results: the negative charge of the phosphodiester and the C-6 hydroxyl of the alphaMan residue are essential for substrate recognition, the latter most likely acting as a hydrogen bond acceptor. The C-6' hydroxyl of the betaGal residue is required for substrate recognition as well as for catalysis. The rate of Manalpha1-P transfer declines with increasing acceptor substrate chain length. The presence of a monosaccharide substituent at the C-3 position of the terminal betaGal residue abrogates Man-P transfer, showing that chain elongation must precede side chain modification during lipophosphoglycan biosynthesis. In contrast, substitution of the penultimate phosphosaccharide repeat does not abrogate transfer but is slightly stimulatory in L. mexicana and inhibitory in L. major.

Amino Acid Sequence↗

PubMed2000

A survey of 16S rRNA and amoA genes related to autotrophic ammonia-oxidizing bacteria of the beta-subdivision of the class proteobacteria in contaminated groundwater.

In this study, we investigated the size and structure of autotrophic ammonia oxidizer (AAO) communities in the groundwater of a contamination plume originating from a mill-tailings disposal site. The site has high levels of dissolved N from anthropogenic sources, and exhibited wide variations in the concentrations of NO3- and NH3 + NH4+. Community structures were examined by PCR-DGGE targeting 16S rDNA with band excision and sequence analysis, and by analysis of amoA fragment clone libraries. AAO population sizes were estimated by competitive PCR targeting the gene amoA, and correlated significantly with nitrate concentration. Most samples revealed novel diversity in AAO 16S rDNA and amoA gene sequences. Both 16S rDNA and amoA analyses suggested that all samples were dominated by Nitrosomonas sp., Nitrosospira sp. being detected in only 3 of 15 samples. This study indicated numerical dominance of Nitrosomonas over Nitrosospira in groundwater, and suggests that groundwater ammonia oxidizers are more similar to those dominating freshwater sediments than bulk soil.

Ammonia↗

PubMed2000

Signal transduction pathways, and nuclear translocation of zinc and metallothionein during differentiation of myoblasts.

The changes in subcellular localization of metallothionein during differentiation were studied in two myoblast cell lines, L6 and H9C2. Addition of insulin like growth factor-I or lowering foetal bovine serum to 1% can induce differentiation of myoblasts to myotubes. Metallothionein and zinc were localized mainly in the cytoplasm in myoblasts but were translocated into the nucleus of newly formed myotubes during early differentiation. In fully differentiated myotubes, metallothionein content was decreased with a cytoplasmic localization. Addition of an inhibitor of mitogen-activated protein kinase, PD 98059, did not affect differentiation but blocked nuclear translocation of metallothionein. LY 294092, an inhibitor of PI3 kinase, and rapamycin, an inhibitor of p70S6 serine/threonine kinase, abolished insulin-like growth factor-I induced differentiation of myoblasts, retained metallothionein in the cytoplasm, and decreased metallothionein content. These results demonstrate that the cytoplasmic-nuclear translocation of metallothionein occurs during the early stage of differentiation of myoblasts to myotubes and can be blocked by inhibition of certain signal transduction pathways. The transient nuclear localization of metallothionein and zinc may be related to a high requirement for zinc for metabolic activities during the early stage of differentiation.

Animals↗

PubMed1999

Metallothionein and apoptosis during differentiation of myoblasts to myotubes: protection against free radical toxicity.

The changes in subcellular localization of metallothionein (MT) during differentiation were studied in two muscle cell lines, L6 and H9C2, myoblasts in order to understand the nuclear presence of MT and its antiapoptotic property. In myoblasts, MT and zinc were localized mainly in the cytoplasm but were translocated into the nucleus of newly formed myotubes during early stage of differentiation, which was initiated by lowering FBS from 10% to 1%. In fully differentiated myotubes, metallothionein content was decreased with a cytoplasmic localization. These changes in subcellular localization of MT and Zn were accompanied by increased apoptosis in myotubes. The changes in the apoptosis at different stages of differentiation were measured by both DNA ladder formation and TUNEL technique. The results also show that the apoptosis may be initiated by free radical generation and may be accompanied by p53 expression. The H9C2 cells contained high levels of MT, differentiated slowly, and had low incidence of apoptotic bodies compared to L6 cell line.

Animals↗

PubMed1999

[Adamantane derivatives enhancing body's resistance to emergencies].

A total of 329 novel adamantane derivatives have been synthesized and pharmacologically studied. Among them, the compounds containing halogen-containing aromatic radicals in the second position show the most pronounced effect on animal resistance to the emergencies induced by its habitat and performance. N-(2-adamantyl)-N-(para-bromphenyl)amine (bromantane) possesses a low toxicity, a high ability to enhance the physical and operant working maintenance of animals, to accelerate its recovery in developed fatigue, in hyperthermia and hypoxia in particular. 2-(para-chlorobenzoylamine)adamantane (chlodantane) has the processes of a rapid-action adaptogenic agent by enhancing the resistance of animals to various physical and toxically chemical noxious agents. The two compounds have immunostimulating effects in secondary stress-induced immunodeficiencies whose mechanism of action is a membranous protective activity.

Adamantane↗

PubMed1997

[Automated cytophotomorphometric tests of blood smears in general clinical studies and population screening].

Automation of routine operations of photomorphometry of blood smears realized in the MEKOS-C cytoanalyzer helped create a new level of using a set of cytological tests, such as assessment of the leukocyte and erythrocyte formulae and of the histogram of hemoglobin distribution in red cells, estimation of leukocyte subtypes, assessment of the characteristics of the nucleolar system and the nucleoli-forming sites. Automated complex analysis of an increase in the measured characteristics of red and white blood cells impossible in common microscopy and flow cytoanalyzers appreciably improves the sensitivity and accuracy of tests and extends the range of their application. Low cost of analysis of a blood smear permits the use of MEKOS-C not only in clinical studies, but even in overall prophylactic screenings of the population.

Automation↗

PubMed1993

The stepwise synthesis of oligo(glycosyl phosphates) via glycosyl hydrogenphosphonates. The chemical synthesis of oligomeric fragments from Hansenula capsulata Y-1842 exophosphomannan and from Escherichia coli K51 capsular antigen.

A stepwise approach has been used in the syntheses of pentamannosyl tetraphosphate HO-[-6Man(alpha)-PO4-]4-6Man(alpha)-OMe and tetra(N-acetylglucosaminyl) triphosphate HO-[-3GlcNAc(alpha)-PO4]3- 3GlcNAc(beta)-OC6H4NO2, which are fragments of the yeast and bacteria extracellular phosphoglycans. Elongation of the chain was performed with the use of suitably protected glycosyl hydrogenphosphonate derivatives for successive introduction of glycosyl phosphate residues. Partially protected monosaccharide derivatives and oligomeric blocks served as hydroxylic components.

Antigens, Bacterial↗

PubMed1992

Significance of long lasting persistence of influenza virus antigens at the portal of infection and in the spleen of mice.

Distribution of virus, its antigens and development of cellular factors of immunity were followed in the course of different forms of acute influenza virus infection in mice. Long term persistence of influenza virus antigens in the portal of entry and spleen were typical for of acute influenza. Lethal effect of influenza infection was caused by massive lesions induced by the virus and due to cell mediated immune response. The fate of infected individual seems to be decided during the first days of post-inoculation and depends on the ability of the virus to modify the cell membranes of the infected individual.

Acute Disease↗

PubMed1992

[Fragments of biopolymers containing glycosylphosphates residues. 9. Synthesis of tetra(2-acetamido-2-deoxy-D-glucopyranosyl)triphosphate-- a tetrameric fragment of the capsule antigen from Escherichia coli K51].

Linear tetra(N-acetylglucosaminyl)triphosphate GlcNAc(alpha)-P-3GlcNAc (alpha)-P-3GlcNAc(alpha)-P-3GlcNAc(beta)-ONp, a fragment of the capsular antigen of E. coli K51, was synthesized by the step-by-step approach with the use of the H-phosphonate method, starting the chain from p-nitrophenyl 2-acetamido-4,6-di-O-benzoyl-2-deoxy-beta-D-glucopyranoside. The elongation cycle included the coupling of 2-acetamido-4,6-di-O-benzoyl-2-deoxy-3-O-p-methoxybenzyl-alpha-D-gluc opy ranosyl H-phosphonate with a hydroxyl component in the presence of Me3CCOCl followed by oxidation (I2) and de (methoxybenzylation) (Ce(NH4)2(NO3)6). 2-Acetamido-3,4,6-tri-O-benzoyl-2-deoxy-alpha-D-glucopyranosyl H-phosphonate was employed in the final step. After mild debenzoylation the title tetramer was isolated by anion-exchange chromatography. The data of 1H, 13C and 31P NMR spectra of the synthesized oligomers are discussed.

Acetylglucosamine↗