[The laryngeal condition in the patients presenting with euthyroid multinodular goiter as evaluated by direct laryngoscopy]. / Sostoianie gortani u bol'nykh éutireoidnym mnogouzlovym zobom po dannym priamoi laringoskopii.

The objective of the present study was to improve diagnostics of disturbances in the laryngeal condition of the patients presenting with euthyroid multinodular goiter with special reference to the condition of the upper respiratory passages. The preoperative characteristic of 398 patients included the description of the predominant clinical syndrome (the neoplastic and compressive variants) and specification of the morphological type of the disease to promote the decrease of operative activity with respect to colloidal proliferative goiter. Direct laryngoscopy was employed in addition to the traditional diagnostic techniques during both the surgical operation and the follow-up observation. Hoarseness developed in the postoperative period in 13.4% to 16.9% of the patients. Postoperative transient and persistent laryngeal paresis was documented in 1.5% and from 1.5% to 4.2% of the cases respectively. Direct laryngoscopy revealed the symptoms of laryngitis and laryngotracheitis as well as foci of leukoplakia, laryngeal cysts and nodules, besides disturbances in the mobility of the vocal chordae. It is concluded that the above pathological changes in the laryngeal structures should be identified during the preoperative examination of the patients presenting with euthyroid multinodular goiter while direct laryngoscopy must be included in the program of postoperative supervision.

[Drosophila melanogaster imaginal discs mitotic anomalies induced by tumor-supressor dlg silencing construction].

Mitosis, cytokinesis and nuclear texture of wing imaginal discs cells silenced by UAS-RNAi-dlg construct induced by 1096-Ga 14 driver were studied. The silencing construct contains coding region of dlg gene and the complementary region. Further, this RNA hairpin (Dietzl et al., 2007) is processed by endogenous protein Dicer and the resulting RNA fragments silence mRNA dlg. Tumor suppressor gene dlg is encoding for 21 transcripts. The construct UAS-RNAi-dlg inactivates 14 transcripts--RE, RH, RQ, RS, RG, RD, RL, RB, RK, RR, RT, RN, RA, RP--and does not silenced the other 7 (RO, RF, RI, RU, RJ, RC, RM). This permits to study functions of proteins containg guanilate-kinase domain IPR008145 at C-end of the protein. The most important consequences of the silencing are abnormal mitotic exit and the formation of binuclear cells. Quantitative fluorescence measurements of anti-H3-p histone and DAPI signals showed phase-specific changes in nuclear texture. The inactivation of cellular cortex polarization is the most likely target of dlg inactivation in mitosis.

[Fluorometric identification of chromatin packing level laying out of the light microscopy resolution].

Confocal microscopy permits to perform quantitative analysis of the fluorescent signals of the nuclei. We determined the level of DAPI and phosphorylated histone-H3 fluorescence, the volume of DAPI and phosphorylated histone-H3 fluorescence in normal (Hikone AW) and colchicine treated third instar Drosophila melanogaster wing imaginal disc mitotic cells. Our analysis permitted to indentify two unknown levels of chromatin package; one in the prometaphase and another at the end of metaphase. These levels disappeared in colchicine treated mitoses. We conclude that quantitative analysis of confocal images is able to detect the differences in chromatin package laying over the resolution of light microscopy.

[Nuclear texture in mitotic cells].

Changes of nuclear texture in mitotic cells of Drosophila melanogaster imaginal discs were studied. The distribution of voxels DAPI fluorescence intensities was used as the quantitative measure of the nuclear texture. The integral characteristics such as the portion of voxels with a given fluorescent signal level and autocorrelation of pixel intensities were used. We showed the nuclear texture has specific changes at different mitotic stages and this can be used for more precise staging of mitosis. Colchicines treatment pathologies, connected to abnormal mitoses, by nuclear-texture approach.

[Dynamics of the spatial organization of the chromosome set in cells of Drosophila melanogaster imaginal disks normally and under the action of the tumor-inducing mutation Merlin].

Fluorescence of H3-p histone and DAPI was studied at different stages of interphase and mitosis in cells of imaginal disks of third-instar Drosophila melanogaster larvae. Three stages differing in the spatial organization of the chromosome set in mitosis were revealed. At the first stage (prophase, prometaphase), the histone 3 phosphorylation level rises, and the volume occupied by the chromosome set in the nucleus increases. The distinctive features of the second stage (metaphase) are a gradual decrease in the histone 3 phosphorylation (the density ofphosphorylation remaining constant) and a reduction of the volume occupied by the chromosome set. At the third stage (anaphase, telophase), the intensity and density of the signal from H3-p histone decrease, and the volume occupied by the chromosome set reduces. At this stage, in Mer4 larvae, in contrast to the control strain, the cells prematurely pass from anaphase into telophase. In addition, a subpopulation of cells with an abnormally large volume of nuclear DNA during the G1 period was revealed in Mer4 larvae. The cells of this subpopulation do not enter into the DNA synthesis and quit the cycle.

[Specifics of anaphase chromatid disjunction in Drosophila melanogaster mitotic mutants].

Anaphase chromatid behavior defects (CBDs) were quantitatively and qualitatively studied in nerve ganglion cells of third-instar larvae of several control wild-type Drosophila melanogaster strains and four strains with mutations of the aar(v158), ff3, mast(v40), and CycB(2g) cell-cycle genes. A linear specificity was observed for the CBD frequency, type, determination, and correction probability. The probability of anaphase CBD correction was close to unity in the control strains and lower in the mutant strains. The lower correction probability in the mutant strains was explained in the context of two findings, that the mutations induced the CBDs that were atypical of the wild-type strains and were potentially uncorrectable in anaphase and that the mutations negatively affected the relative anaphase time in mitosis.

[The distribution of mitoses in the imaginal disks of third-instar Drosophila melanogaster larvae].

Development of Drosophila imaginal discs is accompanied by a high-ordered cell proliferation. However, the distinctions in the topographic distribution of mitoses at different developmental stages are insufficiently studied. In this work, we have analyzed the distribution of mitoses in the wing disc of third-instar larvae and determined the regions where mitotic clustering. The results obtained demonstrate that the proliferation rate is region-specific, which is determined by the location of cell cycle regulators and/or the location of growth factors. A comparison of the topography of mitoses with the activity patterns of the regulatory regions of gene string (stg), a known regulator of the mitotic M phase, has demonstrated a similarity between the topography and the activity pattern of one of these regions. The similarity between mitotic distributions in the left and right discs of the same larva (compared with the similarity of gene neuralized expression patterns is considered, and the degree of histone H3 phosphorylation at various mitotic stages is analyzed.

[Genetics of the cell cycle: adaptive modification of the cycB2g mutation expression in dividing cells of Drosophila melanogaster].

The effect of mutation CycB2g on mitosis in neural ganglia and imaginal disks was studied in third-instar larvae of Drosophila melanogaster. Chromosome condensation and segregation were shown to be impaired in dividing cells of mutant larvae. During the three-year period of maintenance of the mutation in heterozygote, frequencies of some defects decreased via cellular adaptive modification.

[Genetic control of mitosis. Mast(v40) protein--an element of checkpoints system?]. / Geneticheskii kontrol' mitoza. Belok MASTv40--élement sistemy checkpoints?

The effect of the mastv40 mutation was studied using neural ganglion cells of third-instar larvae of Drosophila melanogaster. The distributions of the cells by the interphase nucleus diameter and by the distance between the sister chromosome sets in anaphase were analyzed. Three following types of defects induced by the mutation were described: (1) Monopolar mitosis or, in the case of bipolar mitosis, an abnormally short distance between the sister chromosome sets in anaphase and early telophase. We believe that these abnormalities are caused by damage of the start and (or) motor mechanisms of centrosome separation at the beginning and in the end of mitosis. (2) Lagging and bridging of chromosomes in anaphase and early telophase. These defects seem to be related to the disruption of functioning of mitotic spindle microtubules and (or) their defective attachment to the appropriate kinetochores. (3) Unlimited division of aneuploid and polyploid cells, which may be explained either by inactivation of the checkpoint system controlling the genome ploidy or by checkpoint adaptation. Taken collectively, our results and literature data suggest that the MAST protein is an element of the checkpoint system and that division of aneuploid and polyploid cells results from inactivation of the checkpoints.

[Key events in the cell cycle, their regulation and organization]. / Osnobnye sobytiia kletochnogo tsikla, ikh reguliatsiia i organizatsiia.

The review surveys the studies of molecular genetic mechanisms of the cell cycle control on various eukaryotic models. The major cell cycle phenomena are considered: (1) checkpoints and their role in preserving DNA integrity and fidelity of mitosis, (2) the cell oscillator model, and (3) the role of cyclins in timing of cell division and coordination of mitotic events. The main classes of regulatory proteins involved in the cell cycle are discussed in detail.

[Mitosis: regulation and organization of cell division]. / Mitoz. Reguliatsiia i organizatsiia deleniia kletochnogo iadra.

Modern views on genetic, cytological and molecular bases of the structure and regulation of preparing and implementing mitotic chromosome segregation are discussed.

[Genetic control of mitosis: features of origin of sister chromatid sets in anaphase in Drosophila melanogaster mutant line aar(V158)]. / Geneticheskii kontrol' mitoza osobennosti rakhozhdeniia sestrinskikh naborov khromatid v anafaze u mutantnoi linii aar(V158) Drosophila melanogaster.

The effect of mutation aarV158 on anaphase separation of chromatids was studied on fixed cells of neural ganglia of Drosophila melanogaster larvae. It was shown that mutation aarV158 causes three types of defective chromosome segregation manifested as (1) monopolar anaphase, (2) separation of chromatids to an abnormally short distance in anaphase, and (3) bridging and lagging of some chromatids or prolonged asynchronous separation of sister chromatid sets to the poles in anaphase. We believe that the former two types of defective segregation are caused by disturbed centrosome separation at the beginning of mitosis and the third type, by defects in chromatid separation during anaphase. During the two-year maintenance of the mutation in a heterozygous state, partial correction (adaptive modification) of the defects of type 1 and type 2 (but not type 3) occurred. The correction of type 1 and type 2 defects during adaptogenesis depended on the genotype: in heterozygotes and homozygotes, respectively type 1 and type 2 were preferentially corrected. The frequency of type 3 defects remained constant during the two-year period of maintenance of the mutation in a heterozygous state. However, in all variants of the experiment, their frequency decreased with increasing distance between the sister chromatid sets. In the cells that completed the previous division with abnormalities, the checkpoint system is supposed to effectively arrest the cell cycle in the subsequent division.

[Genetic control of mitosis. Premature beginning of telophase chromatin reorganization in cells of the Drosophila melanogaster strain with ff3 mutation]. / Geneticheskii kontrol' mitoza. Prezhdevremennoe nachalo telofaznoi reorganizatsii khromatina v kletkakh mutantnoi linii ff3 Drosophila melanogaster.

The effect of cell cycle mutation ff3 on chromosome segregation was studied on fixed cells of neural ganglia. The cell distributions by diameter of interphase nuclei and by distance between sister chromatid sets were compared at anaphase and telophase. In the control wild-type strain Lausenne, the cell distribution by distance between sister chromatids in anaphase was similar to their distribution by nuclear size. The mean distance between segregating chromatids at anaphase (lcp) coincided with the mean diameter of interphase nuclei (dcp) and was 8.3 microns. Cells passed to telophase when chromatids were at least 10 microns apart. The mutant ff3 strain differed from the control strain Lausenne in cell distribution by interphase nuclear diameter and distance between sister chromatids in anaphase; the mean nuclear diameter and mean distance between segregating chromatids similarly increased to 9.3 microns. A specific feature of mitosis in mutant strain ff3 was a premature beginning of telophase chromatin reorganization. This caused the occurrence of cells with abnormally short (less then the interphase nuclear diameter) distance between sister chromatid sets in telophase but not in anaphase, as if these cells had passed from anaphase to telophase prematurely, during the chromatid movement toward poles in anaphase A.

[The effect of some mutations in the Trl gene on mitosis in embryonal and larval tissues and egg chamber morphology in Drosophila melanogaster]. / Vliianie nekotorykh mutatsii po genu Trl na mitoz v émbrional'noi i lichinochnykh tkaniakh i morfologiiu iaitsevykh kamer u Drosophila melanogaster.

A study was made of three insertional mutations (Trl13C, Trls2325, and TrlEP(3)3184) located in the second intron of the Trithorax-like (Trl) gene for the GAGA transcription factor (GAF). Their cytological effects were analyzed in oogenesis, early embryonic development, and in larval development (96-108 h) in cells of nervous ganglia and imaginal disks. Notwithstanding an interallelic difference in expression, all three P-element insertions proved to be dominant as far as the examined parameters were concerned. The most substantial defects were the formation of "granular" chromatin during the interphase and mitosis and high proportions of cells with hypercondensed chromatin (which were arrested at the G2/M boundary) and cells with abnormal chromosome segregation. A higher frequency of egg chambers with trophocytes defective in number and in chromatin condensation was observed in females carrying the mutant Trl gene. The defects were assumed to result from poor coordination of the chromosome and cell cycles and, including, the nuclear and centrosomal cycles in embryonic development and the cycles of chromosome condensation and spindle formation in cells of larval imaginal disks and nervous ganglia.

[Genetic control of mitosis. Adaptive modifications of v158 mutation expression]. / Geneticheskii kontrol' mitoza. Adaptivnye modifikatsii proiavleniia mutatsii v158.

Cytogenetic parameters of mitosis were studied in the neural ganglions and imaginal disks of the third-instar Drosophila larvae of the marker lines ry506 and w; Cy/L; D/Sb; two wild-type lines Lausenne and Hikone-AW; and the v158 line mutant for the cell-cycle gene in the 85F locus. The control lines and their various tissues differ in a number of mitotic traits, which are believed to be the natural modifications of chromosome condensation and segregation and do not disturb homeostasis of the developing ry506, Lausenne, and Hikone-AW flies. Mutation v158 affects centromere disjunction. In imaginal disks, this results in arrest of either mitosis or anaphase initiation, whereas, in the neural ganglions, chromosomes integrate into a monopolar spindle at prophase and unipolar cells appear in anaphase. Different effects of the mutation in various tissues are assumed to be caused by different activity of the checkpoint system. When the mutation was maintained heterozygous for a long time, adaptive modification of its expression was observed. A comparison of the rates of two major and parallel mitotic processes, spindle formation and chromosome condensation, showed that adaptive modification can proceed via the adjustment of these rates.

[Insertion mutation 22w of Drosophila melanogaster blocks the cell cycle in metaphase]. / Insertsionnaia mutatsiia 22w Drosophila melanogaster blokiruet kletochnyi tsikl v metafaze.

We studied the cytogenetic effect of P[lArB] transposon insertion into the 42A region of the second D. melanogaster chromosome (mutation 22w). This mutation was shown to induce metaphase (rarer anaphase) block of the cell cycle. The chromosomes have an abnormal "lump" morphology. Possible involvement of the corresponding gene product in functioning of the cell oscillator is discussed.

[Comparative dynamics of elimination of potential chromosome damage in mouse bone marrow cells after low and moderate doses of radiation]. / Sravnitel'naia dinamika osvobozhdeniia kletok kostnogo mozga myshi ot potentsial'nykh povrezhdenii khromosom pri malykh i umerennykh dozakh radiatsii.

Possible dynamics of the incidence, repair, and realization of potential chromosome aberrations (PAs) was examined by indirect methods based on cytogenetic analysis of radiation effects. PAs were characterized as chemical modifications of DNA responsible for the incidence of structural aberrations of chromosomes. We interpreted our data as providing evidence that two types of radiation-induced PAs, differing in repair rates, could occur in the exposed cells: quick- (short-term) and slow (long-term) repairing PAs. We showed that the PA spectrum gradually changed with an increase in radiation dose within the interval from 24 to 150 cGy. This process was paralleled by changes in the cell response and chromosome resistance to radiation. Short-term PAs were induced mainly by low radiation doses ranging from 24 to 75 cGy. Their incidence was associated with activation of the corresponding repair process. Further increase in radiation dose resulted in changes in the PA spectrum, and doses of 150 cGy induced predominantly long-term PAs with concomitant activation of the appropriate repair process. Induction of repair occurred in the dose intervals limited by lower and upper threshold doses, Dl and Du. In our experiments, short-term PAs were repaired when Dl < 24 cGy and 126 cGy < Du < < 150 cGy. Long-term PAs were repaired when 75 cGy < Dl < 99 cGy and Du > 150 cGy.

[Possible mechanisms of the emergence of chromosome aberrations. VIII. Cytogenetic analysis of the dynamics of repair and occurrence of potential chromosome damage in bone marrow cells of gamma-irradiated mice]. / Vozmozhnye mekhanizmy vozniknoveniia perestroek khromosom. VIII. Tsitogeneticheskii analiz dinamiki reparatsii i realizatsii v kletakh kostnogo mozga gamma-obluchennykh myshei.

The dynamics of mitosis delay and appearance of structural chromosomal aberrations (SCA) in relation to radiation dose and time after postradiation are studied. The results obtained suggest that potential DNA damage (PD)--chemical modifications responsible for SCA formation--induce a G2-block. According to this result, it was concluded that PD arose in 30, 80, 90, and 95% of cells at radiation doses of 9, 24, 51, and 75 cGy, respectively. In cycling cells, PD are either repaired or become SCA. If within the first hour after radiation, it was more probable that they would be repaired. The rate of PD repair decreased and the probability of SCA increased as the length of time after radiation increased. The probability of PD also depended on the separation rate of sister chromatids in mitosis. Radiation affects the rate of chromatid separation and, consequently, the occurrence of PD.

[Possible mechanisms of the emergence of chromosome rearrangements. VI. Mitotic delay as a protective mechanism. Origin of spontaneous chromosome breaks]. / Vozmozhnye mekhanizmy vozniknoveniia perestroek khromosom. VI. Zaderzhka mitoza kak protektornyi mekhanizm. Proiskhozhdenie spontannykh razryvov khromosom.

It was proved by the investigation of the bone marrow cells and the culture of embryonic fibroblasts of mice, that experimental induction of chromosome breaks having such a distinctive feature as disposition of acentrics outside the equatorial plate at metaphase, results in reduction of the mitotic index and the radiation induced structural mutations frequency. Such disposition of acentrics--outside the equatorial plate--is typical for spontaneous chromosome breaks. It was suggested, that the process resulting in spontaneous chromosome breaks is a component of the protective mechanism, which is put into effect through the mitotic delay.