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V M Mikhel'son

Publications and source records attributed to V M Mikhel'son.

At least 19 recordsLinked to original sources
PubMed2005

[Characteristics of p53 protein stabilization in cells of patients with ataxia-telangiectasia after gamma-irradiation].

Stabilization of P53 protein in cells isolated from patients with a grave hereditary disease ataxia-telangiectasia (AT), characterized by strongly enhanced sensitivity to ionizing radiation and impairment of cell cycle control after DNA damage, was studied. The level of expression of these reactions by patients may vary, and it tends to be linked with the severity of the disease. In all AT strains studied, both acquired by the authors and obtained from foreign colleagues, we observed the alteration of timing and character of stabilization of P53 protein, after the action of ionizing radiation in sublethal dosage, as compared to that in cells from healthy donor.

Ataxia Telangiectasia↗
PubMed2004

[Impact of angiotensin-converting enzyme, angiotensinogen, endothelial NO synthase, and bradykinin receptor B2 gene polymorphisms on myocardium in patients with hypertension and in athletes].

We investigated the role of gene polymorphisms in angiotensin-converting enzyme (ACE), angiotensinogen, endothelial NO (eNO) synthase, and bradykinin receptor B2 in determining the cardiovascular system structure and function in hypertension and "athletic heart" syndrome. Using a PCR-based method, 114 hypertensive patients and 94 athletes were genotyped for I/D polymorphism of ACE, M235T angiotensinogen (ANG), Glu298 Asp endothelial synthase (eNOS), and type 2 receptor for bradykinin (BDKR2). Echocardiography and a 24 hour blood pressure monitoring being performed. The (+)-allel of BDKR2 gene was associated with the left ventricular hypertrophy and greater wall thickness in athletes and hypertensive subjects. The hypertensive patients, that were homozygous for Glu298 allele of eNOS, demonstrated a lower level of diastolic blood pressure than did those with Glu298 Asp and Asp298 Asp genotypes. At the same time, the ACE and AND gene polymorphisms displayed no association with the cardiac structure and function.

Adult↗
PubMed2004

[Age dymamics of stable chromosome aberration frequency in humans with natural and pathological senescence].

The age dynamics of stable chromosome aberration (SCA) frequency was analysed by fluorescent in situ hybridization (FISH) in human blood lymphocytes derived from donors, irradiated by low doses of ionizing radiation (Chernobyl clean-up workers, nuclear weapon testers, etc.) and patients with hereditary premature aging--Werner's syndrome and Hutchinson-Gilford's syndrome. It was found that the level of SCA was age-dependent and increased in irradiated persons. So, the SCA level may be really an index of a so-called "radiation senescence", and may show a real biological age of irradiated persons. The patients with Werner's syndrome demonstrate increased SCA level in blood lymphocytes, corresponding to the premature aging of the organisms. But in the case of another form of premature aging--Hutchinson--Gilford's syndrome-- no rise of SCA level was found. Some possible reasons of such results are discussed.

Adolescent↗
PubMed2003

[Effect of 1,25-dihydroxyvitamin D3 and 17beta-estradiol on hpl-bp74 gene regulation in breast adenocarcinoma cell line].

Data are provided on the upregulation of heterochromatin protein binding protein 74 gene (hpl-bp74) at RNA transcription level under the influence of stimulation of 1,25-dihydroxyvitamin D3. We also showed the absence of action of 17 beta-estradiol on the transcription level of hpl-bp74 breast adencarcinoma cell line (MCF7). The protein encoded by gene hpl-bp74 can be involved in generalized transcriptional regulation and thus take part in inhibition of proliferation by 1,25(OH)2D3. Computer analyses of DNA sequences of hpl-bp74 enabled us to identify some potential hormone responsive elements responsible for the binding of nuclear receptor for vitamin D with the DNA motifs.

Adenocarcinoma↗
PubMed2002

[Cytological and molecular changes in the atypical case of accelerated human aging].

A complex research of cells of a patient with unusual form of premature ageing was made. The clinical picture is not typical for any of known forms of hereditary premature aging--progerias. Skin fibroblasts of the patient AG has limited proliferation capacity in vitro. It was shown by fluorescent-immunochemical hybridization (FISH-method), that the level of stable chromosome aberrations in AG blood lymphocytes was characteristic of aged 55-65 years, though as he was only 26 years old. Some characteristic peculiarities, typical for progerias, were found in the reaction of skin fibroblasts of AG to growth factors addition. Some clinical and biochemical peculiarities are results rather, than reasons of the disease. The conclusion is that the premature ageing in this case is a manifestation of Werner's syndrome--one of hereditary forms of accelerated senescence.

Adult↗
PubMed2002

[Reorganization of DNA replicating system induced by 5-fluorodeoxyuridine and caffeine as the basis for radiosensitivity in human calls].

Treatment of diploid human fibroblasts with 5-fluorodeoryuridine (FUdR) and caffeine results in the increase in cellular radiosensitivity in terms of survival and chromosomal aberrations, on the one hand, and in radioresistant DNA synthesis (RDS), on the other hand, i.e. rather mimics those in mutant cells from patients with AT, XPII, Down syndrome, and others. A study was made of the autoradiographic length of simultaneously active adjacent replicon clusters. After incubation of diploid human cells with FUdR (10(-6) M, 6 h), this parameter was shown to reduce by two-fold, remaining unchanged upon 5 Gy irradiation. In contrast, after incubation of the cells with caffeine (2 mM, 30 min), this parameter was longer, compared to that in intact cells; upon 5 Gy irradiation the values remained almost the same as in the control. A possible relation of the data to the cellular radiosensitivity and RDS in the cells incubated with FUdR and caffeine is discussed.

Caffeine↗
PubMed2002

[Stimulation of DNA repair in human cells damaged by UV and ionizing radiation with soluble growth factors of photomodified blood].

Exposure of a small skin area of volunteers to UV light in 1 minimal erythemal dose is accompanied by rapid appearance in the circulating blood of soluble factors able to restore proliferation of X-ray-damaged autologous lymphocytes, to decrease frequency of chromosome breaks, and to stimulate unscheduled DNA synthesis. The appearance of such an activity in the blood can be also induced without skin irradiation. For this, one volume of a directly UV-irradiated blood is to be mixed in vitro with 10-fold volumes of intact blood, thus modeling the in vivo situation, when a small amount of transcutaneously UV-irradiated blood mixes with intact blood in the circulation. It has been found that the platelet-derived growth factor and epidermal growth factor, added at physiological concentrations to the culture medium, decrease chromosome break frequency in X-damaged cells.

Adult↗
PubMed2001

[Decreased frequency of activation of replicon clusters in Down syndrome lymphocytes].

Human blood lymphocytes from two normal and seven Down syndrome (DS) subjects were examined to determine rates of synthesis of individual replicon and adjacent clusters of replicons, using DNA fiber autoradiography. Lymphocytes in 6 of 7 DS patients were shown to have significantly slower synthesis of simultaneously active adjacent replicon clusters compared to normal controls. Rates of synthesis of individual replicons were the same in lymphocytes from all the subjects investigated. These results demonstrate differences in respect to the structural organization of clusters of replicons between DS and normal lymphocytes. A possible relation of the above phenomenon to the chromosomal radiosensitivity in DS cells is discussed.

Case-Control Studies↗
PubMed2001

[Identification of elements responsible for regulation of keratinocyte growth factor gene by steroid hormones and 1,25-dihydroxyvitamin D3].

Data are provided on the up-regulation of keratinocyte growth factor gene (kgf) at mRNA and protein level in prostate cancer cells (LNCaP) stimulated by 1,25-dihydroxy-vitamin D3 and 17-beta-estradiol (E2). The computer analysis of the 5-flanking region of kgf gene using different software and databases (TESS, TRANSFAC etc.) enabled us to identify some potential elements responsible for binding the nuclear receptors of vitamin D3, E2, and some other steroid hormones.

5' Untranslated Regions↗
PubMed1999

[Defect of preferential repair of gamma-ray-induced single-strand breaks in transcribed DNA in ataxia-telangiectasia cells].

Transcriptionally activity-dependent heterogeneity of gamma-induced DNA single-strand break repair in ataxia-telangiectasia cells has been investigated. It is found that in AT cells no increased induction of damage in the c-myc gene compares with normal human fibroblasts. At the same time an evident defect of preferential accelerated repair of single-strand breaks in the c-myc gene was observed. DNA single-strand breaks repair in human satellite III and total DNA single-strand breaks in c-myc gene in AT cells correlate with increased radiosensitivity of cells.

Ataxia Telangiectasia↗
PubMed1999

[Features of the radiosensitivity of cells from ataxia-telangiectasia patients].

Cell survival, single and double DNA strand breaks formation and removal, spontaneous and induced chromosome aberrations and sister chromatid exchange (SCE) levels in gamma-irradiated cells of patients with ataxia-telangiectasia (AT) were studied. Except SCE all of the above indexes of AT cells sensitivity, were higher, than in normal human cells, but lower, than it is commonly characteristic of AT cells in literature. A conclusion is that the analysed AT cells belong to the AT-variant form. Possible mechanisms of high radiosensitivity of AT cells, accompanied by radioresistance of DNA replication, are discussed. The authors suppose that the DNA repair defect in AT cells is not primary.

Ataxia Telangiectasia↗
PubMed1999

[P53-status of cells from patients with progeria and ataxia-telangiectasia exposed to ionizing irradiation].

P53 protein expression and stabilization in cell strains derived from patients suffering from progeria and ataxia-telangiectasia following gamma-irradiation have been described. A similar pattern of P53-status in healthy donor and progeria patient cells was shown using immunofluorescent cell staining. In ataxia-telangiectasia cells (strain AT2SP) the P53 protein was not detected by the same method. These data well compare with literary evidence on a disturbed P53-status at ataxia-telangiectasia.

Adult↗
PubMed1999

[Morphofunctional characteristics of fibroblasts in basal cell nevus and Cockayne syndrome].

Some morphofunctional characters of fibroblasts in two genetic disorders--Cockayne syndrome (CS) and Basal cell naevus syndrome (BCNS) have been examined. The size of nucleus in BCN1SP line has been shown to be about 1.5 times less as well as the total size of nucleoli per nucleus, while the number of nucleoli was 2 times more compared with other cell lines investigated. Using the method of silver staining numerous nucleoli were shown to contain active loci of the nucleolus organizer regions. With the help of hybridization in situ the number of transcripts of 18S RNA molecules was shown to be 5 times more in BCN1SP cell line, and about 2.8 times more than in the other cell lines tested. The data obtained may be interpreted as a suggestion in favour of a greater activity of the nucleolus organizer regions in BCN1SP cell line followed by the disturbance in protein homeostasis of the cells.

Cell Nucleus↗
PubMed1998

[Defect of preferential repair of gamma-ray-induced single-strand breaks in transcribed and non-transcribed DNA in Cockayne syndrome cells].

The repair of gamma-ray-induced DNA single-strand breaks in transcribed (protooncogene c-myc) and non-transcribed (human satellite III) DNA of normal human fibroblasts and fibroblasts obtained from a patient with Cockayne's syndrome (CS) has been investigated. A method of alkaline sucrose sedimentation was applied besides the Southern hybridization of 32P-DNA, containing sequences analysed with total 3H-DNA distributed through sucrose gradient fractions. No increase in the induction of DNA single-strand breaks was found in gamma-irradiated CS fibroblasts, compared to normal human fibroblasts. At the same time, an evident defect in the preferential repair of single-strand breaks in c-myc gene was observed.

Blotting, Southern↗
PubMed1997

[The mechanism of radioresistant DNA synthesis in ataxia telangiectasia].

Using DNA fiber autoradiography, DNA replication in cells of healthy donors and in those of patients with ataxia telangiectasia (AT) was estimated. A new fact has been demonstrated showing a decreased number of simultaneously operating in tandem groups of replicon clusters in AT cells compared to that in normal cells. The data obtained suggest a reduced frequency of activation in the adjacent replicon clusters in AT cells. It should be noted that the rate of fork movement remained unchanged in AT cells. Besides, the frequency of replication in adjacent replicon clusters remained unaltered after 5 Gy irradiation in AT cells, while the normal cells were radiosensitive to reduction in this replication parameter to the low level seen in both non-irradiated and 5 Gy irradiated AT cells. The relation of the above data to radioresistant DNA synthesis is discussed.

Adult↗
PubMed1997

[Decreased survivability and a DNA repair defect in the cells of patients with xeroderma pigmentosum and Cockayne syndrome under the action of radiation and chemical mutagens].

The action of ionizing radiation and chemical mutagens--epoxides (ethylene oxide, propylene oxide, epichlorohydrin)--upon survival and repair processes in xeroderma pigmentosum (XP2SP) and Cockayne syndrome (CS1SP) patients' cells was studied, compared to healthy donor's cells VH-10 and C5RO. Ionizing radiation was demonstrated to enhance significantly higher survival decrease of XP2SP and CS1SP fibroblasts, compared to healthy donor's cells, according to the cloning efficiency criterion. In contrast to this, no significant difference between XP2SP and healthy donor's cells was found, according to cells' ability to replicative DNA synthesis after gamma irradiation. Differences in survival of mutant cells and healthy donor's cells after treatment by epoxides were found significant only following XP2SP being treated by ethylene oxide. DNA single-string breaks in XP2SP and in CS1SP cells treated by mutagens studied were proved to occur with the same frequency as in the DNA of the control cells; however the DNA repair according to this criterion was significantly suppressed in mutant cells.

Cell Survival↗
PubMed1997

[The isolation and analysis of lymphoblastoid cell lines from patients with xeroderma pigmentosum and progeria].

Lymphoblastoid cell lines from patients with xeroderma pigmentosum (2 forms) and progeria (unusual form) were established using transformation of peripheral blood lymphocytes by Epstein--Barr virus. The influence of different UV doses on cell vitality, proliferation and cell cycle progression was studied by means of flow cytometry. The cell vitality was determined after incubation of cells with etidium bromide and FDA. We used cytograms with two logarithmic signals (log green/log red) to discriminate the cell cycle status. Cell cultures were used with density of 500,000 cells per 1 ml, previously synchronized at G-phase by the incubation in a medium with low serum content. The effect of UV irradiation was followed during 72 h. Among four analysed cell lines only line XP2SP demonstrated enhanced UV sensitivity, expressed by decreasing of the amount of living cells after the UV dose of 2.5 J/m2 and higher. The cell cycle studies showed that cells were blocked in S-phase and simultaneously the amount of apoptotic cells with both reduced DNA content and ability to bind FDA was seen increased. Similar events were observed in the control line only after the dose of 20 J/m2 and higher.

Cell Line↗