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Biomedical subjects

A V Blokhin

Publications and source records attributed to A V Blokhin.

18 recordsLinked to original sources

Cell proliferation in normal and malignant transformed cells: thermodynamic model of signal transduction.

We present a new thermodynamic model for the mechanism of activation and regulation of cell proliferation in the G1 stage. In this model, the interactions between growth factors and transmembrane proteins play a crucial role in cell growth control for a normal tissue-culture system. We calculate a phase diagram of normal and malignant transformed states of a cell signal transduction system. We propose thermodynamic reasons why cancer cells can continually grow without activation by the growth factors.

Biophysical Phenomena↗

Inhibition of topoisomerase II by ICRF-193, the meso isomer of 2,3-bis(2,6-dioxopiperazin-4-yl)butane. Critical dependence on 2,3-butanediyl linker absolute configuration.

The bis(2,6-dioxopiperazine)s are a structurally and mechanistically unique class of topoisomerase II inhibitors that do not bind DNA and that do not stabilize topoisomerase II-DNA strand passing intermediates ("cleavable complexes"). The most effective topoisomerase II inhibitor in the bis(2,6-dioxopiperazine) series is ICRF-193 (meso or S*, R* isomer), with a meso 2,3-butanediyl linker connecting the dioxopiperazine rings. The two enantiomeric diastereomers, (R,R) and (S,S), of ICRF-193 possessing the two optically active 2,3-butanediyl linkers have been prepared from their respective optically pure 2,4-diaminobutanes via 2,3-diaminobutane-N,N,N',N'-tetraacetic acid, esterification, and imide formation. Both in vivo and in vitro assays for catalytic inhibition of topoisomerase II were employed to show that the (S,S)- and (R,R)-isomers are almost inactive as topoisomerase II inhibitors. The data indicate that the meso stereochemistry of the alkanediyl linker is crucial for activity and provides additional evidence that the cytotoxicity of the bis(2,6-dioxopiperazine)s is due to their ability to inhibit topoisomerase II.

Animals↗

Influence of long-term limitation of cell proliferation on the cell cycle duration.

The hypothesis was tested that constant, long-term inhibition of cell proliferation is the primary cause of cellular senescence. Mouse L-929 fibroblasts were maintained in confluent cultures for periods of 6 and 12 months with cell viability maintained by regular replacement of medium and serum. The mitotic activity of the cell population under these conditions was one mitosis per 10(4) cells. No changes in the duration of the cell cycle were observed when, following long-term quiescence, the cell were replated and grown at low cell density. The results do not support the hypothesis that prolonged suppression of cell proliferation induces cell senescence.

Animals↗

Characterization of the interaction of the marine cyanobacterial natural product curacin A with the colchicine site of tubulin and initial structure-activity studies with analogues.

Curacin A, the major lipid constituent of a strain of the marine cyanobacterium Lyngbya majuscula obtained off the coast of Curaçao, is a potent antimitotic agent that we have previously shown to inhibit microtubule assembly and colchicine binding to tubulin. In the present study, we report that curacin A probably binds in the colchicine site because it competitively inhibits the binding of [3H]colchicine to tubulin with an apparent Ki value of 0.6 microM and stimulates tubulin-dependent GTP hydrolysis, as do most other colchicine-site agents. The binding of curacin A to tubulin resembled the binding reactions of combretastatin A-4 and podophyllotoxin in contrast to that of colchicine in that it occurred as extensively on ice as at higher temperatures. However, once bound, the dissociation rate of curacin A from tubulin is very slow, more closely resembling that observed with colchicinoids (thiocolchicine was the drug examined) than the faster dissociation that occurs with combretastatin A-4 and podophyllotoxin. Because the molecular structure of curacin A is so different from that of previously described colchicine-site drugs (e.g., there is no aromatic moiety, and there are only two conjugated double bonds in its linear hydrocarbon chain), we have been examining the activities of natural isomers and synthetic derivatives. So far, only modest enhancement or reduction of activity has been observed with a variety of structural changes.

Animals↗

[The long-term limitation of the proliferation of cells in culture does not lead to their proliferative aging].

A hypothesis was tested about a long-term limitation of cell proliferation as the primary cause of their senescence and, consequently, the senescence of the whole organism. Both half-yearly and yearly maintenance of mouse fibroblast-like cells L-929 in a high density permanent culture with low level of mitotic activity (less than 1 mitosis per 10,000 cells) has not revealed any irreversible changes in their proliferative features and has not confirmed the hypothesis under examination.

Animals↗

[Chronic berylliosis of the lungs].

An autopsy case of the chronic lung berylliosis in a patient having an occupational contact with a beryllium bronze is described. Clinically the disease had no specific features and was diagnosed as chronic obstructive bronchitis and pneumosclerosis. Sclerotic granulomas with giant cells, conchoidal bodies, iron deposition in the pulmonary stroma--all these lung alterations allowed one to establish a diagnosis of lung berylliosis.

Aged↗

[The morphology of amebiasis].

Amebiasis--a protozoan human disease caused by Entamoeba histolytica--occurs in the USSR sporadically in particular geographic regions and in particular populations. The paper reports morphologic findings made in patients with amebiasis involving the intestine or other organs. In typical cases, amebiasis affects the large intestine, particularly the cecum and ascending colon, and has the development of distinctive ulcers as its characteristic feature. As the disease progresses, these appear in all parts of the large intestine; less commonly, the terminal portion of the small intestine is also involved. The most frequent complications of amebic colitis are perforation and phlegmon, which result in peritonitis. Not infrequently, amebic abscesses arise in the liver or other organs through hematogenous dissemination of amebas. Histologic diagnosis of amebiasis may be difficult. Recommendations on how to detect amebas and the tissue changes peculiar to amebiasis are given.

Adult↗

[Interdependence of the cell cycles of mammalian sister cells in monolayer cultures detected through their desynchronization by UV microirradiation].

The duration and variability of cell cycles in epithelial and fibroblast-like mammalian sister cells with different types of intercellular contacts were estimated using time-lapse cinemicrographic technique. To study a possible interrelation between cell cycles of the sister cells, one cell in each pair of sister cells was inactivated by selective UV microbeam irradiation at the beginning of its cell cycle. It is shown that this action may delay the cycle of the intact cell as well. Such an interrelation of sister cells was found only at the G1 phase of the cell cycle and only in epithelial cells.

Animals↗

[Variability of the duration of the cell cycle in pig embryo kidney cells in monolayer culture and correlation of the cycle duration in sister cells].

The distribution of generation time of sister cells for the exponentially proliferating monolayer SPEV culture was obtained with time lapse cinemicrographic technique. The distribution is characterized by the average generation time equal to 24.3 hour, with the variation coefficient, asymmetry coefficient and correlation coefficient for sister pair cell being, respectively, 17%, 0.2 and 0.78. The results obtained are compared with the prediction of "a random transition" in the cell cycle.

Animals↗

[Thickness of mammalian cells in culture, the absorption of UV radiation in the cells and the related shift in action spectra].

The thickness of SPEV cells in monolayer with different cell densities was measured by means of 3-dimensional reconstruction from serial vertical sections. No significant changes in the mean cell thickness were detected despite the wide range of volume and cell density variations. UV absorption at different wave-lengths was measured in various sites of single cells. It is shown that the well known shift between peaks of the UV action spectrum for mammalian and bacteria cells may result from the cell self-shielding at short wavelengths.

Absorption↗

[Effect of shielding as a cause of UV-action spectra shift in mammalian cells].

UV absorption at different wavelengths from 250 to 313 nm was measured in various sites of single SPEV cells in monolayer during the stage of the best cell flattening. At the 260 nm, transmittancy of nuclear regions was less than 50%. The absorption by nucleolar regions was twice as much as by cytoplasmic ones. The influence of self-shielding on the action spectra shape was estimated. It has been shown that the well-known difference between the peaks of the action spectra for mammalian and bacteria cells killing may be the result of the cell self-shielding at short wavelengths but not the sequence of the difference in the active chromophore of these cells.

Animals↗

[Tuberous sclerosis].

Tuberous sclerosis is a rare congenital disease characterized by developmental defects of the central nervous system, skin and inner organs with the development of tumours. One case of tuberous sclerosis is described in a 45-year-old female with the involvement of the brain, eyes, skin, kidneys and lungs. The cause of death was uremia as a consequence of large kidney angiomyolipomas.

Brain↗

[The use of a local computer network in a pathology bureau].

The activities of a large bureau of pathology using local computer network are analyzed. Every pathologist has at his working place a personal computer switched in the local computer network. The latter and relevant program is employed for all cases of surgical and biopsy material. The advantages of such work are described.

Computer Communication Networks↗