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Biomedical subjects

V N Ivanov

Publications and source records attributed to V N Ivanov.

At least 37 records · Page 2Linked to original sources
PubMed1999

Down-regulation of tumor necrosis factor alpha expression by activating transcription factor 2 increases UVC-induced apoptosis of late-stage melanoma cells.

To identify mechanisms whereby activating transcription factor 2 (ATF2) alters the radiation resistance of human melanoma cells, we examined the possible role of ATF2 in UVC-induced apoptosis. Forced expression of full-length or truncated (Delta1-195 amino acids) forms of ATF2 in LU1205, a late-stage human melanoma cell line, elevated the levels of UVC-induced apoptosis. At the same time, either truncated or full-length forms of ATF2 reduced UVC-induced activation of the tumor necrosis factor-alpha (TNFalpha) promoter and decreased expression of TNFalpha. Forced expression of c-Jun in ATF2-expressing melanoma cells restored TNFalpha expression, suggesting that both forms of ATF2 sequestered transcription factors that positively regulate TNFalpha expression in response to UV irradiation. Antagonistic antibodies to Fas, but not to TNFR1, efficiently suppressed UVC-induced apoptosis, suggesting that the Fas pathway mediates the primary apoptotic signal in melanoma cells whereas the TNFR1 pathway elicits a survival signal. Indeed, treatment of melanoma cells with TNFalpha before UVC irradiation partially suppressed UVC-induced apoptosis, further supporting the protective role of TNFalpha in UVC-treated melanoma cells. Taken together, our findings suggest that ATF2 contributes to UVC-induced apoptosis through transcriptional silencing of TNFalpha, which balances Fas-mediated cell death in melanoma.

Activating Transcription Factor 2↗
PubMed1999

Taxon-specific content of oligonucleotide triplets in 16S rRNAs of anoxygenic phototrophic and nitrifying bacteria.

Theoretical evaluation of the content of oligonucleotide triplets AAA, CCC, and UAU in 16S rRNAs of anoxygenic phototrophic bacteria (genera Chlorobium; Chloroflexus; Chromatium: Rhodopseudomonas) and nitrifying bacteria (genera Nitrosococcus, Nitrosomonas, Nitrosolobus, Nitrosovibrio, Nitrospira, Nitrospina, Nitrobacter) showed that the number of the AAA, CCC or UAU triplets in 16S rRNAs specifically corresponds to the genus and species of bacteria. The ratio of AAA and CCC triplet numbers in the sequences of 16S rRNA (AAA/CCC) of anoxygenic phototrophic bacteria was within the range of 0.61 to 2.03, and the ratio of AAA and UAU (AAA/UAU) triplet numbers in the sequence of 16S rRNA was within the range of 2.88 to 12.00. The regions of any genus within the AAA/CCC and AAA/UAU axes did not overlap. The combination of the numbers of nucleotide triplets in 16S rRNA is genus-specific character. The similar data were obtained in the study of a physiological group of nitrifying bacteria. The range of AAA/UAU ratio was from 1.8 to 9.0, and range of AAA/CCC was from 0.9 to 2.6 for this taxon. The number of triplets in 16S rRNAs of the studied taxa was genus- and species-specific character. The biological significance of these data is the evidence that not only the sequence but the number of nucleotide triplets in 16S rRNAs reflects the phylogeny of corresponding taxa.

Bacteria↗
PubMed1998

Biochemical and kinetic characterization of the glucocorticoid-induced apoptosis of immature CD4+CD8+ thymocytes.

We characterized kinetic and biochemical changes during glucocorticoid (GC)-induced apoptosis of immature CD8+CD4+ double-positive (DP) thymocytes. A GC analog dexamethasone (Dex) induced rapid apoptotic commitment and a transient up-regulation of the NF-kappaB/RelA-p50-binding activity in DP cells. This required an early activation of proteasome, as judged by the ability of a specific proteasomal inhibitor, lactacystine, to delay apoptosis and to suppress Dex-dependent NF-kappaB activation. Dex-induced apoptotic commitment was preceded by the rapid (3 h) cleavage of both a typical caspase substrate, poly(ADP-ribose) polymerase (PARP), and of nuclear transcription factors AP-1, NF-kappaB p50-p50 and NUR-77. By contrast, phorbol myristate acetate (PMA) and/or ionomycin-induced apoptosis had much slower kinetics, were preceded by an early increase of NF-kappaB/RelA-p50, AP-1 and NUR-77 activities, and were insensitive to proteasome inhibition. Both the transgenic Bcl-2 and zVAD-fmk, an inhibitor of caspases, affected all features of Dex-induced apoptosis in a similar fashion, by inhibiting cell death and PARP cleavage, and by stabilizing AP-1, NF-kappaB p50-p50 and NUR-77 levels. Furthermore, Bcl-2 prevented Dex-induced RelA-p50 activation. However, a higher gene dosage of the transgenic Bcl-2 was required for protection against Dex, compared to the PMA and/or ionomycin-induced apoptosis. These findings highlight the unique mechanistic features of GC-induced apoptosis.

Acetylcysteine↗
PubMed1997

Regulation of Fas-dependent activation-induced T cell apoptosis by cAMP signaling: a potential role for transcription factor NF-kappa B.

TCR-mediated activation of T cell hybridomas induces programmed cell death by a Fas-dependent pathway. We now show that costimulation of 2B4 cells, in the absence or presence of transgenic Bcl-2, with anti-CD3 epsilon and forskolin, an activator of cAMP signaling, resulted in antagonism of Fas-dependent activation-induced cell death that was always accompanied by selective downregulation of the nuclear levels of NF-kappa B p65-p50 (RelA-p50) transcription factor. Forskolin not only inhibited activation-induced cell death and NF-kappa B activation, but also suppressed expression of Fas and Fas ligand (Fas-L). Furthermore, NF-kappa B p65 antisense oligonucleotide down-regulated nuclear levels of NF-kappa B, inhibited cell surface expression of Fas-L and apoptosis of 2B4. Collectively, these finding demonstrate a potential role of NF-kappa B in the regulation of activation-induced apoptosis in T lymphocytes.

Antibodies↗
PubMed1997

Transcription factor activation during signal-induced apoptosis of immature CD4(+)CD8(+) thymocytes. A protective role of c-Fos.

Many signals that cause apoptotic cell death operate by inducing transcription and translation of other (presumably death effector) mediators, and it is well established that stimulus-induced apoptosis can often be blocked by inhibiting transcription and translation. Transcriptional regulation of apoptosis, however, is incompletely understood. To gain insight into nuclear events associated with signal-induced apoptosis during T cell development, we studied signal-induced apoptosis of ex vivo isolated immature CD8(+)4(+) double-positive (DP) thymocytes. Stimuli utilizing the T cell receptor (TCR) signaling pathway or its parts (an alphaCD3/TCR monoclonal antibody, a Ca2+ ionophore, or a protein kinase C-activating phorbol ester) or a stimulus that antagonizes TCR signaling and apoptosis in T cell hybridoma (forskolin, a cyclic AMP-signaling activator) resulted in massive apoptosis of DP thymocytes. At the same time, these stimuli induced qualitatively similar but quantitatively unique patterns of inducible transcription factors (TFs) NF-kappaB/RelA-p50, AP-1 (Fos-Jun), and NUR-77. We focused our attention on the role of AP-1 (Fos-Jun) complex, which was strongly induced by all of the above stimuli and thus was a candidate for a proapoptotic TF. However, we found that AP-1/c-Fos induction was vital in prolonging DP thymocyte life, as judged by increased spontaneous and induced death of DP cells in Fos-/- mice. In direct support of this hypothesis, experiments with antisense oligonucleotides demonstrated that c-Fos plays an essential role in protecting normal DP thymocytes from Ca2+- and cAMP-induced apoptosis but not from TCR-mediated death. Together, these results demonstrate a physiological role for c-Fos in maintaining longevity of DP thymocytes.

Adaptor Protein Complex alpha Subunits↗
PubMed1995

Pleiotropic effects of Bcl-2 on transcription factors in T cells: potential role of NF-kappa B p50-p50 for the anti-apoptotic function of Bcl-2.

Bcl-2 functions to repress apoptosis by regulation of genes which encode proteins required for programmed cell death and by interference with peroxidative damage. We investigated the interrelationship between expression of bcl-2 and regulation of transcription factor DNA binding activities in the 2B4 T cell hybridoma and IL-2-dependent CTLL T cell line. Over-expression of bcl-2 in 2B4 resulted in enhanced basal levels of activator protein (AP)-1, octamer binding factor (Oct)-1, lymphoid enhancer binding factor (LEF)-1, RelA-p50 and NF-kappa B p50-p50 DNA binding activities. After apoptotic signaling, down-regulation of AP-1, NF-AT and Oct-1 binding activities was observed in control 2B4 and CTLL, whereas suboptimal, but higher, levels of these transcription factors were found in bcl-2-transfected cells, potentially promoting cell survival. Furthermore, after apoptotic signaling, expression of bcl-2 led to differential changes of NF-kappa B levels, resulting in a decrease in RelA-p50 and an increase in NF-kappa B p50-p50, altering the ratio of these DNA binding activities such that now p50-p50 markedly predominated in both 2B4-Bcl-2 and CTLL-Bcl-2. Apoptotic signaling in the presence or absence of Bcl-2 resulted in induction of the RelB-p50 heterodimer in 2B4. The changes in NF-kappa B/Rel levels raise the possibility that this family of transcription factors may play an important role in the regulation of apoptosis.

Animals↗
PubMed1994

Neutron brachytherapy in the treatment of melanoma.

PURPOSE: The use of Cf-252 for treatment of cutaneous malignant melanoma is presented. METHODS AND MATERIALS: From 1975 to 1992, plaque Cf-252 applicator neutron brachytherapy was performed in nine patients with skin malignant melanoma of head and neck or chest wall. Neutron brachytherapy alone was applied in six patients; two patients received neutron brachytherapy before and one after photon teletherapy. Tumor neutron brachytherapy doses ranged from 3.9-11.5 Gy. Four patients underwent surgical resection of the primary tumor and in six cases, regional lymph node dissection was done. RESULTS: The patients survival times ranged from 3 months to 12 years; 2-year survival was 50% and 30% of the patients lived 3 years. The mean survival time was 39 months. All but 1 patients died because of distant metastases. Local tumor control was achieved in all cases. CONCLUSION: The clinical study shows the relative sensitivity of melanoma to the neutron irradiation and offer new possibilities in Cf-252 brachytherapy.

Adult↗
PubMed1994

Factors affecting the selenium intake of people in Transbaikalian Russia.

The selenium concentration in foods grown and consumed and in plasma, red blood cells, and toenails of people living in the district of Chita in the transbaikalian part of Russia were studied in August 1991. Preliminary results from the area have suggested low selenium intakes and the possible occurrence of cardiomyopathy (Keshan disease) in the population. A low selenium concentration in foods grown locally was found: mean selenium concentration in wheat grains was 1, 5, and 28 micrograms/kg, respectively, in three villages studied, that of oats was between 3-6 micrograms/kg, and of cow's milk 10-27 micrograms/kg dry matter. The selenium concentration of bread was considerably higher, between 87-337 micrograms/kg dry wt, presumably because wheat imported from the US had been used for baking. Occasional samples of pork, beef, and mutton contained between 32-218 micrograms selenium/kg dry wt. Low selenium concentrations were observed in samples of soil and river water. The mean plasma selenium concentration of 52 persons was 1.02 mumol/L, including 33 children and 19 adult subjects. The selenium concentrations in red blood cells and toenails were 1.95 mumol/L and 0.61 mg/kg, respectively. No symptoms of heart disease caused by selenium deficiency were observed. It is concluded that the selenium status of people was fairly good thanks to the contribution to dietary intake of imported wheat with a high selenium content. As the selenium concentration was very low in foods grown in the area, the selenium intake of the population will be reduced to a very low level if only locally produced foods are consumed.

Adolescent↗
PubMed1994

[Diagnostic value of investigating exhaled air condensate in lung cancer].

Parameters of lipid peroxidation and the levels of calcium ions in blood plasma and exhaled air condensate (EAC) were studied in 47 patients with lung cancer. The changes in EAC turned out to be more specific than those of blood plasma. The level of lipoperoxidation in condensate in cancer patients was lower than in healthy subjects. However, calcium cations concentrations in both blood and EAC were relatively higher, the latter difference being significant. The investigation pointed to a greater diagnostic value of EAC measurements, as compared with blood plasma, in lung cancer patients.

Adult↗
PubMed1993

[Changes in lipid peroxidation and phospholipid spectrum of blood in patients with lung cancer].

The parameters of the lipid peroxidation - antioxidants system, phospholipid profile, erythrocytes and blood plasma of 47 patients with lung cancer were studied. Serious disturbances in phospholipids profile in cases of central and peripheral lung cancer were identified. They included a decreased phosphatidycholine level, accumulation of lysophospholipids and appearance of phosphatidyglyceral fraction in blood plasma. Those shifts occurred alongside with enhanced lipid peroxidation and a deficit of antioxidation protection factors.

Adult↗