[Melanoma and cancer emergence in persons of 20-60 years against normal quantity of cambial cells in morphofunctional zones].

In age groups from 20 to 60 years cell proliferation and differentiation happen in the morphofunctional zone in the electric field excited by 12 pairs of mother and daughter cells, which have turned out at cambial cells division. Thus in daughter cells the Src SH2 domain necessary both for cytoskeleton formation and tyrosinase activization is activated. If the conditions for strengthening of tyrosinase activity are created in organism, despite the high maintenance of cambial cells, the portion of Src participating in the cytoskeleton building can decrease to critical level that will lead to development of a malignant tumor. If action of a stimulating factor is quite strong, proliferation of malignant cells begins at a stage of melanocyte, and a melanoma occurs. If action of factors is long and not strong, more remote descendants of daughter cells proliferate, and a cancer appears. For the purpose of normal differentiation of malignant modified daughter cells, it is necessary to block tyrosinase. Thus all SH2 domains will go on cell cytoskeleton formation.

[Participation of morphofunctional zones in aging processes].

There are morphofunctional zones in organism tissues, where proliferation and differentiation processes occur. Daughter cells are differentiated in the electric field excited by 12 mother and daughter cell pairs, turned out at cambial cell division. With aging, the cambial cell number is reduced to 7, close to thresholds level (6 cells), at which the differentiation of daughter cells is absent. The depression of cambial cell number with aging is connected with the work of another morphofunctional zone--the hypothalamus, which is the major center of vegetative regulation and initially has very high RhoA activity, which has been established in embryogenesis. Estrogens, influencing over the hypothalamus and activating Src kinase in its nuclei, reduce the level of RhoA activity, including SCN, responsible for many biorhythms of an organism. As a result, the hyperestrogenemia and therefore a connective tissue at first occur. Then there happens a hypoestrogenemia that leads to sharp falling of proliferative activity of cells, causing the depression of cambial cell number and possibility of a malignant tumor development. Along with this, there are the deep lesions of hormone regulation, leading to some lethal diseases. Thus, the RhoA increasing in hypothalamus and especially in SCN circadian rhythm can counteract the Src kinase intensifying and prevent the processes connected with this.

[Characteristics of proliferation and differentiation of cambial and daughter cells in morphofunctional zones in the normal epithelium and cancer using age aspect].

Work of cambial cells of normal epithelium occurs in morphofunctional zone consisting of two subunits with 12 cells in each. 12 pairs of maternal and daughter cells which have turned out at their division, create the electric field making a differentiation of daughter cells. But it is necessary to relax the cortex of epidermal daughter cells by expression of the SH3 domain of Src-kinase in them with the help of dermal cells that leads to depression of RhoA activity in epidermal cells and the further activation of the SH2 domain of Src in them responsible for a differentiation. With the years, the number of epidermal cambial cells falls from 12 in 20 years to 7 in 75+ in consequence of depression of influence of dermal cells on cambial epidermal cells, which results in dropping of expression of SH2 domain and change of a differentiation of epidermal daughter cells. The reduction of the number of cambial cells to threshold size (6) leads to sharp falling of expression of SH2 domain of Src in daughter cells. This involves augmentation RhoA in relation to Src, falling of formation of stresses-fibrils, microtubules. The stretching of nucleus is sharply decreased, which conducts to formation of incomplete loops of chromosomes, simultaneously nearby a centromere and telomere, thus the cell gets features of an epitheliocyte and a fibroblast, the transcription of proteins is broken, and the daughter epithelial cell becomes malignant.

[The quantitative morphology of the cells in the basal layer of the multilayer epithelium in the mouse cornea and in a human cancerous lung tumor]. / Kolichestvennaia morfologiia kletok bazal'nogo sloia mnogosloinogo épiteliia rogovitsy myshi i rakovoi opukholi legkogo cheloveka.

The following categories of cells are present in the epithelium basal layer: "elongated", "transitional", "narrow", "circular", and "oval", corresponding to peaks 1, 2, A, B, and C. Peak 1 cells with the ellipticity 0.5774 have the highest specific weight. Upon maturation, these cells become "transitional" cells and mitotic, or "elongated", cells. During proliferation, some "elongated" cells mature to become more differentiated "narrow" cells. The "elongated" cells are characterized by synchronization. When 30% of the cells in the population become "elongated", 5% of them enter mitosis. Transition of 5% of the "elongated" cells to mitosis occurs only when the number of peak B cells becomes equal to that of peak A cells. When the "elongated" cells amount to 30% of the population, transition of peak B cells into peak A cells ceases. In the tumor tissue of the human lung, there are the same series and peaks of cell distribution as in the normal epithelium. There is the same functional relationship between the "elongated" cells and peak B and peak A cells as in the normal epithelium, when transition of 4-5% of "elongated" cells to mitosis is possible only upon leveling of peaks B and A. When the relative number of "elongated" cells reaches 30%, transition of peak B cells into peak A cells also ceases.

[Proliferation mechanisms of normal and cancerous cells]. / K voprosu o mekhanizme proliferatsii normal'nykh i opukholevykh kletok.

A morphometric study of the basal layer of the epithelium has established the following cell patterns: round, oval, transitional, elongated and narrow. Also, cell peaks 1, 2, A, B and C have been identified. Some oval (peak 1) cells became elongated during proliferation. After the latter cell fraction accounted for 30% of the total cell population 5% became round thus contributing to the peak C fraction, and entered mitosis. It took place when a full equilibrium between the peak A and B fractions in the oval cell population had been reached. Populations of lung cancer cells revealed identical patterns and peaks while the pattern of cell fraction redistribution during entry into mitosis was similar to that of normal corneal epithelium. The rate of cell pattern redistribution in tumor tissue was found to be much higher than that of normal epithelium.

[The organization and development of the endothelial layer of the cornea in human embryogenesis]. / Organizatsiia i razvitie éndotelial'nogo plasta rogovitsy v émbriogeneze cheloveka.

The main bulk of corneal endothelial cells is formed during early embryonic development. In the course of development, two-layered endothelium becomes single-layered; the cell layer consists of rosette-like structures formed of a central cell (9 to 10% of all endothelial cells) surrounded by peripheral cells. The central cell is not a stem cell, and the peripheral cells are not its descendants. The presence in corneal endothelium of a constant number of peripheral cells surrounding the central cell, as in other epithelia with different proliferative potential, is evidence that the central cells can organize the peripheral cells and exercise control over them.

[Patterns in the organization of the endothelial layer of the human cornea under normal and pathologic conditions]. / Nekotorye zakonomernosti organizatsii éndotelial'nogo plasta rogovitsy cheloveka v norme i pri patologii.

Main proportion of endothelial cells are those of medium size the total surface of which is increasing by 24 microns2 every 20 years. In the population of these cells there exist so-called prevailing cells, i.e. those which are found most frequently. Fluctuations in the total surface of prevailing cells are minimal under pathological conditions and the ratio between the surface of prevailing cells and total surface of all medium-size cells is constant, this showing the existence of genetic regulatory mechanisms.

[Activation of corneal endothelial proliferation in cancers of various sites]. / Aktivatsiia proliferatsii éndoteliia rogovitsy glaza pri rake razlichnoi lokalizatsii.

90 corneas from patients, 40 to 80 years old, who had died from carcinoma of mammary gland, lungs and other organs, and 20 corneas from patients of the same age dying from cardiovascular diseases, were studied. The density of endothelial cells was significantly increased in carcinoma patients (for example, 2939 cells/mm2 versus 2160 in control at the age of 40-60 years) with a simultaneous decrease of the cell surface. There was an increase in the number of cells with a small surface and a decrease in the number of binuclear cells. Mitosis (mainly prophase and telophase) is found in the endothelial cells of cancer patients.

[The reparative potentials of human corneal endothelium from the aspect of age]. / Reparativnye vozmozhnosti éndoteliia rogovitsy cheloveka v vozrastnom aspekte.

Morphometric and cytospectrophotometric studies of the endothelium of human cornea in age aspect, from 20 to 80 years, has revealed the presence of nuclei with double content of DNA (4 c) irrespective of age, as well as binuclear cells. Their number increases with age. At the age of 20-40 years, 4 tetraploid nuclei and 3 binuclear cells were found, and after 80 years of age - 45 tetraploid nuclei and 11 binuclear cells per a cornea. This speaks about the ability of the endothelium cell of the human cornea to incomplete polyploidizing cellular mitosis-variant of a normal proliferation of the cells and is characteristic for long-living and slightly proliferating tissues. The increase of the number of polyploid cells in the corneal endothelium with age speaks about activation of adaptation mechanisms in the course of age involution.