[The role of assessing UGT1A1 gene polymorphism in the prediction of irinotecan-induced toxicity in the course of chemotherapy for colorectal cancer].

There was performed a molecular genetic study of UGTlAl gene allelic variants polymorphism in patients with colorectal cancer who had had chemotherapy irinotecan-containing regimens FOLFIRI. Comparison of toxicity and the results of polymorphism of UGTlAl showed that dose-limiting hematologic and non-hematologic toxicities in patients with moderate and high risk of toxicity were higher (p = 0.050- 0.061) and the frequency of thrombocytopenia (p = 0.0257) and hyperbilirubinemia (p = 0.0439) were significantly higher compared to the low-risk group. Molecular genetic study of a complex examination of patients, which was planned to irinotecan should be performed to select the optimal dose and reduce the risk of toxicity of chemotherapy.

[Medical treatment for Graves' disease: principles, markers of a relapse and remission].

Graves' disease (diffuse toxic goiter) is a systemic autoimmune disease that develops as a result of the production of antibodies to the thyroid stimulating hormone receptor (AT-rTSH), which is clinically manifested by thyroid damage with the development of thyrotoxicosis syndrome in combination with extrathyroid pathology (pretibial endocrine) myxedema, acropathy). The disease was first described by S. Ives in 1722, then Peri in 1786 and Flayani in 1802. In 1835, R. Graves associated the occurrence of the described symptom complex, now known as thyrotoxicosis syndrome, with thyroid pathology. In 1840, K. Bazedov singled out a triad in the clinical picture: goiter, buccalis, tachycardia.

[Thyroid-stimulating hormone receptor antibodies in the differential diagnosis of toxic goiter].

The production of stimulating thyroid-stimulating hormone (TSH) receptor antibodies (TSHR-Ab) whose level measurement has come into clinical use underlies the pathogenesis of Graves'disease (GD). This paper deals with the diagnostic and differentially diagnostic value of measurement of TSHR-Ab levels using two first-generation techniques (with heterological TSH): radioreceptor assay ("CIS bio international", France) and enzyme immunoassay ("Medizym" T.R.A."). The levels of TSHT-Ab, as well as thyroid peroxidase antibodies (TH-Ab) and thyroglobulin antibodies (TG-Ab) were studied in 206 patients among whom 176 patients were diagnosed as having GD and 30 had clinical thyroid functional autonomy (FA) generally appeared as multinodal toxic goiter. A comparative analysis of these two assays did not reveal some advantages of them and their results showed a significantly positive correlation (r = 0.91; p < 0.001). The diagnostic sensitivity of the assays was about 80-88% and their specificity was 60-70%. The findings led to the conclusion that in the absence of significant endocrine ophthalmopathy (EOF), clinical and routine instrumental and laboratory studies fail to differentiate GD and throid FA to sufficient accuracy whereas the measurement of the levels of TSHR-Ab substantially makes diagnosis easier. Moreover, it has been shown that the determination of the level of TBII using the test systems containing heterological TSH may not be used for the evaluation of the course of EOF.

[Higher cortical functions in children with spastic forms of cerebral palsy]. / Vysshie psikhicheskie funktsii u detei so spasticheskimi formami tserebral'nykh paralichei.

Kinestatic praxis was studied in 75 children, aged 7-11 years, with spastic forms of cerebral palsy (CP) and in 30 of them other higher cortical functions were examined. The disturbances of kinestatic praxis were more expressed in hemiparetic forms of CP, being observed in all the cases, and frequently occurred in spastic diplegias (75-94.3%) as well. Dynamic praxis was disturbed in 90% cases, spatial praxis--in 53.3%, visual-acoustic gnosis--in 36.6%, visual-object gnosis--in 50%, visual-spatial--in 80%, visual memory--in 40%, visual imaging reasoning--in 30%, verbal logic reasoning--in 43.3%.

[The hierarchical relationships between the organs of the hypothalamo-hypophyseal-adrenal system (HHAS) in inflammation]. / Ierarkhicheskie vzaimootnosheniia mezhdu organami gipotalamo-gipofizarno-adrenalovoi sistemy (GGAS) pri vospalenii.

The HPA axis is the major system of adaptation to the action of different stressors, including inflammatory agents. The glucocorticoids, the end product of HPA axis prevent the extension of inflammation. In this article we discuss the classic direct and feedback loops in the HPA axis during acute bacterial inflammation. On the basis of literary and own findings we put forward a speculation that different systemic cytokines released one by one during inflammation induce the appearance of new functional relations between the organs of HPA axis. Because of cytokines are involved in the modulation of hormonal sensitivity in the HPA axis the serious modification of direct as well as feedback relations is postulated. On the other hand cytokines and immune cells induce autocrine and paracrine production of cytokines in the HPA axis, that result in autonomization of pituitary and adrenals functions. So, the acute inflammation factors could be seen as "short-time" functional dominants of HPA axis functioning.

Interaction between replication protein A and p53 is disrupted after UV damage in a DNA repair-dependent manner.

Replication protein A (RPA) is required for both DNA replication and nucleotide excision repair. Previous studies have shown that RPA interacts with the tumor suppressor p53. Herein, we have mapped a 20-amino acid region in the N-terminal part of p53 that is essential for its binding to RPA. This region is distinct from the minimal activation domain of p53 previously identified. We also demonstrate that UV radiation of cells greatly reduces the ability of RPA to bind to p53. Interestingly, damage-induced hyperphosphorylated RPA does not associate with p53. Furthermore, down-regulation of the RPA/p53 interaction is dependent upon the capability of cells to perform global genome repair. On the basis of these data, we propose that RPA may participate in the coordination of DNA repair with the p53-dependent checkpoint control by sensing UV damage and releasing p53 to activate its downstream targets.

The conserved HR domain of the Drosophila suppressor 2 of zeste [Su(z)2] and murine bmi-1 proteins constitutes a locus-specific chromosome binding domain.

The related Drosophila Suppressor 2 of zeste [Su(z)2] and Posterior sex combs (Psc) proteins are both locus-specific chromosome binding proteins. They are found at many of the same polytene chromosome loci as other Polycomb-group proteins. The 1,365 amino acid Su(z)2 protein and the 1,603 amino acid Psc protein share a conserved 200 amino acid domain, the homology region (HR). To identify the protein domain responsible for locus-specific chromosome binding, we made a series of Hsp70:cDNA deletion constructs of the Sz(z)2 gene and transformed these into flies. We found that the HR is necessary and sufficient for Su(z)2 locus-specific polytene chromosome binding. The murine Bmi-1 protein also shares the conserved HR domain. When expressed in flies, the Bmi-1 protein showed a locus-specific chromosome binding pattern similar to that of the Su(z)2 and Psc proteins. These results argue that a locus-specific chromosome binding function resides in the HR domain. Other results show that a second, low affinity, non-specific chromosome binding function is localized outside the HR in the Su(z)2 protein, and that the Su(z)2 protein contains at least two nuclear localization signals.

[Properties of inbred Drosophila melanogaster lines obtained from a population selected for an increased rate of embryonic development]. / Svoistva inbrednykh linii Drosophila melanogaster, poluchennykh iz populiatsii, selektirovannoi na povyshennuiu skorost' émbrional'nogo razvitiia.

Two heterogeneous Drosophila melanogaster populations were subjected to selection for an increased rate of embryonic development by picking out the first 10% of hatching larvae. After repeating this procedure in 15 generations, "fast" populations were obtained, in which the duration of embryonic development at high temperature (31-32 degrees C) was 30-40 min less than in nonselected control populations. The results of preliminary experiments on substituting the second and third chromosomes in the selected and control populations provide evidence that selected genes responsible for accelerated development are located on the second chromosome. Inbreeding in 12 generations of selected populations was used to obtain about 40 lines homozygous, in particular, at the alcohol dehydrogenase gene. In four lines, the developmental rate was higher than in a homozygous control line, but others did not differ from control or developed more slowly. The duration of embryonic development at 32 degrees C in fast lines was 50-70 min shorter than in control, but this difference was significantly less at lower temperatures (25 and 17 degrees C). Hence, high temperature is primarily a factor in providing conditions for the expression of genes determining the developmental rate, rather than a factor of selection for these genes. It is suggested that selected genes modify developmental rate dependence on temperature.

[Interaction between the enhancers of yellow and the yellow gene in Drosophila melanogaster]. / Vzaimodeistvie genov--énkhanserov yellow s genom yellow u Drosophila melanogaster.

Earlier, mutations at six loci designated enhancers of yellow (e(y)1-6) were obtained in the system of prolonged instability, where transpositions of Stalker mobile element occur. These mutations decrease pigmentation of the cuticle in a number of alleles. In the present work, genetic analysis of the mechanism of action of e(y)1u1, e(y)3u1 and newly described e(y)7u1 mutations on the yellow locus expression was conducted. The data are obtained proving that the enhancers of yellow 1 and 3 control transcription of the yellow locus. At the same time, the interaction of here described gene e(y)7 with the yellow gene is likely to occur at the level of protein products.

[New genes interacting with the zeste gene in Drosophila melanogaster]. / Novye geny, vzaimodeistvuiushchie s genom zeste u Drosophila melanogaster.

We have found that mutations in the enhancer of yellow, 1,2 and 3 loci strongly enhance the effect of zv77h-mutation (full inactivation of the zeste locus) on the white locus expression. Their effect is realized through the distal white enhancer which is located 1,1 kb upstream to the promoter. It is suggested that the protein products of enhancers of yellow 1,2 and 3 represent a family of proteins which, like zeste protein, are responsible for formation of contacts between elements located at a large distance in the genome.

[Radiation and combination treatment of breast cancer metastases to the lungs]. / Luchevoe i kompleksnoe lechenie metastazov raka molochnoi zhelezy v legkie.

The authors describe methodological and clinical results of the so-called large field irradiation of 56 patients with breast cancer metastases to the lungs. Of these, 46 received radiotherapy alone, 10 radiotherapy in combination with polychemotherapy using the CMF scheme (cyclophosphamide, methotrexate and 5-fluorouracil). As a result of radiotherapy (46 women), a noticeable objective response was achieved in 44% of the cases; among 10 patients on multimodality therapy it was achieved in 4. Average remission was 9 mos. in the 1st group and 8 mos. in the 2nd group. The patients were treated in the outpatient department. Proceeding from our experience radio- and multimodality therapy can be used as conservative therapy for patients with breast cancer metastases to the lungs.

[Conservative methods of treating breast cancer metastases to the lungs]. / K voprosu o konservativnykh metodakh lecheniia metastazov raka molochnoi zhelezy v legkie.

An analysis is presented of different routine methods of treatment (radiotherapy, mono- and polychemotherapy; chemo-radiation treatment) used in 77 patients with breast cancer metastases in the lung. According to the data obtained positive results were gained in 53% of cases, a considerable effect being noted in 46% of patients.