[Assembly and Disassembly of the Nuclear Pore Complex: A View from the Structural Side].

Nucleocytoplasmic exchange in the cell occurs through the nuclear pore complexes (NPCs). NPCs are large multiprotein complexes with octagonal symmetry about their axis and imperfect mirror symmetry about a plane parallel with the nuclear envelop (NE). NPC fuses the inner and outer nuclear membranes and opens up a channel between nucleus and cytoplasm. NPC is built of nucleoporins. Each nucleoporin occurs in at least eight copies per NPC. Inside the NPC a permeability barrier forms by which NPCs can provide fast and selectable transport of molecules from one side of the nuclear membrane to the other. NPC architecture is based on hierarchical principle of organization. Nucleoporins are integrated into complexes that oligomerizes into bigger octomeric high-order structures. These structures are the main components of NPCs. In the first part of this work, the main attention is paid to NPC structure and nucleoporin properties. The second part is dedicated to mechanisms of NPC assembly and disassembly at different stages of the cell cycle.

[Medical rehabilitation of patients with alcohol dependency at risk of parental rights deprivation]. / Meditsinskaia reabilitatsiia bol'nykh s alkogol'noi zavisimost'iu s riskom lisheniia roditel'skikh prav.

AIM: To study the efficacy of medical rehabilitation outpatient program 'Point of Soberness' with the use of prolonged injectable naltrexone for alcohol dependent parents of minor children. MATERIAL AND METHODS: One hundred and seventeen patients with severe disease form without remissions were enrolled in the study. All patients were parents at risk of deprivation of parental rights. RESULTS AND CONCLUSION: A complex approach, used during the rehabilitation, helped 87% of patients to maintain social and professional status and finish treatment program. More than 95% of patients retained their parental rights. The 'Point of Soberness' program allows achievement of remission of alcohol dependence and retaining parental rights.

The role of SAGA coactivator complex in snRNA transcription.

The general snRNA gene transcription apparatus has been extensively studied. However, the role of coactivators in this process is far from being clearly understood. Here, we have demonstrated that the Drosophila SAGA complex interacts with the PBP complex, the key component of the snRNA gene transcription apparatus, and is present at the promoter regions of the snRNA genes transcribed by both the RNA polymerase II and RNA polymerase III (U6 snRNA). We show that SAGA interacts with the Brf1 transcription factor, which is a part of the RNA polymerase III transcription apparatus and is present at promoters of a number of Pol III-transcribed genes. Mutations inactivating several SAGA subunit genes resulted in reduced snRNA levels in adult flies, indicating that SAGA is indeed the transcriptional coactivator for the snRNA genes. The transcription of the Pol II and Pol III-transcribed U genes was reduced by mutations in all tested SAGA complex subunits. Therefore, the transcription of the Pol II and Pol III-transcribed U genes was reduced by the mutations in the deubiquitinase module, as well as in the acetyltransferase module of the SAGA, indicating that the whole complex is essential for their transcription. Therefore, the SAGA complex activates snRNA genes suggesting its wide involvement in the regulation of gene transcription, and consequently, in the maintenance of cellular homeostasis.

[The efficiency of the medical rehabilitation program with the use of injectable naltrexone for alcohol addicted patients who are at risk of parental rights deprivation]. / Éffektivnost' programmy meditsinskoi reabilitatsii s ispol'zovaniem in''ektsionnogo naltreksona u bol'nykh s alkogol'noi zavisimost'iu, nakhodiashchikhsia v gruppe riska po lisheniiu roditel'skikh prav.

AIM: To evaluate the efficacy of treatment of patients at risk of deprivation of parental rights due to alcohol dependence under the 'Point of Soberness' program including psychotherapy and intramuscular injections of extended-release naltrexone (vivitrol). MATERIAL AND METHODS: Results of therapy of 45 patients, 39 women and 6 men, are presented. Out of 45 patients, 42 (93.3%) received a full course of injections of prolonged naltrexone (6 or more) as part of a comprehensive outpatient rehabilitation program. RESULTS AND CONCLUSION: Thirty-six (80.0%) patients maintained a remission. In 9 patients (20.0%), single breakdowns and breakdowns, resulting in a relapse of the disease were recorded. Forty-two patients (93.3%) retained their parental rights. The return of children was made in one case. The 'Point of Soberness' program makes it possible to achieve long remission of alcohol dependence, and to keep parental rights for these patients.

Comparative results of preoperative chemoradiotherapy and thermochemoradiotherapy for locally advanced laryngeal cancer.

The study is based on the results of treatment of 60 patients with locally advanced laryngeal cancer (T3-4N0-3M0) exposed to combined treatment: 31 with preoperative chemoradiothera-py, 29 thermochemoradiotherapy. Radiotherapy was performed in the hyperfractionated mode: "1 Gy +1 Gy" (every 4-5 hours) 5 times a week to 30-40 Gy in total. Local hyperthermia was performed 2 times a week before the second fraction of radiotherapy in 3-4 sessions. Eight-day courses of chemotherapy were administered in the beginning of radiotherapy by scheme: vincristine (1. 4 mg/m2 per 1day), cisplatin (20 mg/m2 2, 3, 4 days), bleomycetin (10 mg/m2 5, 6 days), cyclophosphamide (200 mg/m2 7, 8 days). Surgical treatment was performed through 2,5 3 weeks after completion of radiotherapy. Local hyperthermia intensified the course of radiation reaction on the mucous of the larynx but not significant influenced on healing of surgical wounds. Thermochemoradiotherapy compared with chemoradiotherapy raised local relapse-free survival from 75 to 93% (p = 0. 07), regional, for a group of patients with stage N1-3 from 33 to 70%, N1-2 from 40 to 78% (p = 0. 1), loco -regional from 67 to 87% (p = 0. 04). Our findings suggest the necessity for further research on the use of thermochemoradiotherapy in combined treatment of patients with locally advanced laryngeal cancer.

[Possibilities of local hyperthermia in treatment for edematous breast cancer patients].

The paper presents an analysis of literature on the results of treatment of edematous breast cancer as well as own data on the use of local hyperthermia for this pathology. Local hy- perthermia in combination with chemotherapy (thermochemo- therapy) was applied in 14 patients with secondary edematous breast cancer. Age of patients ranged from 37 to 72 years (mean 53 years). The study results indicate promising applica- tions of thermochemotherapy in edematous breast cancer: for operable patients as neoadjuvant, for inoperable patients as palliative method of treatment.

[The results of combined treatment of patients with locally advanced laryngeal cancer using preoperative chemoradiotherapy].

The combined treatment with preoperative chemoradiotherapy (CRT) was performed in 28 patients with locally advanced laryngeal cancer (T3-4N0-3M0). Radiation therapy (RT) was carried out according to the scheme "1 + 1 Gy" (interval 4-5 hours) 5 times a week till 30-40 Gy. RT was accompanied by simultaneous polychemotherapy: vincristine (1.4 mg/m² per day), cisplatin (20 mg/m²--2-4 days) bleomicetin (10 mg/ m²--5, 6 days), cyclophosphamide (200 mg/m²--7, 8 days). Surgical treatment was carried out in 2.5-3 weeks after CRT. CRT allowed conducting organ-saving surgery on the larynx in 11 (52%) of 21 patients with T3 of primary tumor. All other patients underwent laryngectomy at a different volume. Five-year disease-free survival for the whole group in total (T3-4) was 88%. Relapses of regional metastases (MTS) occurred in 7 of 9 patients including in 4 of 5 patients after lymphadenectomy. The overall survival of patients with T3N02 was 71%, with T4N0-3--20%. Thus we have developed a method of treatment allowing to achieve high local relapse-free survival in patients with locally advanced laryngeal cancer. However organ-saving effectiveness of preoperative CRT and its effect on regional MTS remain low, which requires further research in this direction.

[The results of chemoradiotherapy for locally advanced laryngeal cancer with hyperfractionated radiotherapy].

Single chemoradiotherapy (CRT) was performed in 27 patients with laryngeal cancer (T3-4N0-3M0). Radiotherapy (RT) was carried out in hyperfractionated mode 1+1 Gy (every 4-5 hours), 5 times a week to CFD 60 Gy with a 2-week break after CFD 30-40 Gy. Courses of polychemotherapy (PCT) were performed simultaneously with RT at each stage of treatment. Overall 5-year survival of patients in the whole by the group (T3-4N0-3) was 44.6%, for patients with T3N0--72.7%, T3N1-20--42.9%, T4N1-2--40.0% with an average life expectancy 38.1; 50.8; 39.0 and 39.8 months respectively. During a 5-year follow-up the local control of the primary tumor at T3 was equal to 61%, T4--25% with a median remission of 40.6 and 13.5 months respectively. During this period the regional control at metastases N1 was 50%, with a median remission of 32.7 months. In 4 patients of 5 with N2 and in all 3 patients with N3 during the first year after CRT continued growth or tumor recurrence was diagnosed. Thus, conservative CRT provides relatively satisfactory 5-year outcomes in patients with tumors T3N0-1.

[Comparative results of conservative chemoradiotherapy and thermochemoradiotherapy for locally advanced laryngeal cancer].

There were analyzed results of treatment of 58 patients with laryngeal cancer T3-4N0-3M0. Chemoradiotherapy (CRT) was carried out in 27 patients, thermochemoradiotherapy (TCRT)-in 31 patients. Radiotherapy (RT) was performed in hyperfractionated mode (1 Gy + 1 Gy with an interval of 4-5 hours) 5 times a week to CTD 52-60 Gy with a 2-week break after CTD 30-40 Gy. Local hyperthermia (LHT) was carried out 2 times a week before the second fraction of RT in an amount of 3-6 sessions. The first cycle of polychemotherapy was administered at the beginning of RT and the second one-after the break. The local control under the primary tumor category T3 after CRT was equal to 58% and after TCRT--88%, at T4--72% and 25%, respectively. Late radiation damage of the larynx in the form of mucosal edema and perichondritis after CRT was in 2 patients (7%) and after TCRT--in 3 patients (10%). Thus, TCRT for locally advanced laryngeal cancer allows obtaining a higher overall survival and a local control as compared to CRT and does not lead to a significant increase of frequency of perichondritis.

[The quality management in clinical diagnostic laboratory in conditions of the Federal Center of traumatology, orthopedics and endoprosthesis replacement of Minzdrav of Russia (Cheboksary)].

The article presents experience of clinical diagnostic laboratory of the Federal Center of traumatology, orthopedics and endoprosthesis replacement of Minzdrav of Russia (Cheboksary) in the area of quality management of medical laboratory services on the basis of evaluation of efficacy and effectiveness of processes. The factors effecting quality of functioning of clinical diagnostic laboratory are indicated. The criteria and indicators of efficacy of work of employees of clinical diagnostic laboratory are presented.

[Conservative thermochemoradiation therapy of locally advanced laryngeal cancer].

Thermochemoradiation therapy was performed in 31 patients with laryngeal cancer (T3-4N0-3M0). Radiotherapy was performed in 2 stages 1+1 Gy (every 4-5 hours), 5 times a week to SOD 52-60 Gy with a 2-week break after SOD 30-32 Gy. Local hyperthermia was carried out two times a week before the second fraction in an amount of radiation therapy sessions 3-6. In the days of local hyperthermia second fraction of radiotherapy increased to 3 Gy. Courses of chemotherapy were combined with radiation therapy and local hyperthermia at the beginning of each stage of treatment. For the whole group a complete response of the primary tumor was diagnosed in 25 (80.6%) patients, partial - in 6 (19.3%). Of the 12 patients with N1-3 complete regression of metastases occurred in 5 (41.7%), partial - also in 5 (41.7%). Five-year overall survival was 88.2% T3N0, T4N1 in 3 - 62.1%. Local control of the primary tumor in these terms in the group T3 was detected in 88.2%, in the group T4 - 77.8%, regional control of metastases with N1-3 - 33.3%. Late swelling of the mucous membrane of the larynx developed in 4 (12.9%) patients, perichondritis - in 3 (9.7%). Thermochemoradiation therapy of locally advanced cancer of the larynx provides a fairly good results comparable with those of the combined treatment.

[Results of combined treatment in locally advanced cancer of the larynx using preoperative thermochemoradiotherapy].

This paper analyzes the results of combined treatment with preoperative thermochemoradiotherapy in 28 patients with locally advanced laryngeal cancer (T3-4N0-3M0). Radiation therapy (RT) 32 Gy was carried out 5 times a week with splitting the daily dose of radiation on the 2 factions (interval 4 hours) on a "1 Gy + 1 Gy," in the days of the local hyperthermia (LGT)--on a "1 Gy + 3 Gy". LGT in an amount of 3-4 sessions was performed two times a week before the 2nd fraction of RT. The course of polychemotherapy was administered concurrently with RT and LGT. In 2-3 weeks after completion of the course thermochemoradiotherapy patients were operated. Organ-saving operations were performed 10 (56%) of 18 patients with primary tumors categories T3 and 2 (20%) of 10 with T4. Postoperative wounds healed by first intention in 21 (75%) patients. The cumulative 5-year overall survival in the whole group (T3-4N0-3) was 89%, for patients without regional metastases (T3-4N0)--100%. Relapse-free survival time for those patients with a primary tumor T3 equaled 94%, T4--90%. Relapse metastases occurred in 20% of patients. Thus, preoperative thermochemoradiotherapy is a highly effective method of treatment for locally advanced cancer of the larynx and does not lead to the development of severe postoperative complications.

[Multifunctional factor ENY2 integrates the various stages of gene expression].

The ENY2/Sus1 is a multifunctional transcription factor which couples transcription with mRNA export. It is the component of the SAGA/TFTC and TREX-2/AMEX protein complexes. Recently, we described the interaction of ENY2 with one more protein complex, THO. Moreover, our data indicate that ENY2 associates with other nuclear and cytoplasmic factors. Thus, being the component of a number of protein complexes, ENY2 plays the role of an adaptor molecule, involved into the integration of different cellular processes, specifically, subsequent stages of gene expression.

[Autoantibodies to steroid-producing ovarian cells in cancer patients].

Our investigation included 158 women, aged 23-73: patients with tumors of the ovary, breast and endometrium--117 and subjects without oncological pathology--41. Autoantibodies to microsomal fraction of follicular ovarian cells (> 500 Unit/ml) in healthy subjects were revealed 8.3% while in patients with ovarian, breast and endometrial malignancies (without significant differences between benign and malignant tumors) in 33.30%, 45.60% and 25.0%, respectively. Higher level of anti-ovarian autoantibodies involved an inverse correlation between blood levels of FSH and estradiol in ovarian and endometrial carcinoma patients. It also co-occurred with a tendency of increasing levels of autoantibodies to thyroglobulin. Whatever apparent predictive accuracy in oncological clinic, high concentrations of anti-ovarian autoantibodies point to certain shifts taking place in the formation of reproductive system pathology. Besides, they may have considerable prognostic significance.

[A uniform approach to the synthesis of carbohydrate conjugates of polyhedral boron compounds as potential agents for boron neutron capture therapy].

A uniform approach to the synthesis of carbohydrate conjugates with polyhedral boron compounds (PBCs) was developed. Oligosaccharide derivatives with an aglycone moiety amino group can be coupled with PBC carboxyl derivatives using N-methyl-N-(4,6-dimethoxy-1,3,5-triazin-2-yl)morpholinium chloride as a coupling agent. Both N- and O-glycosides differing in the conformational mobility around the glycoside bond were shown to be useful as oligosaccharides with a functional group in the aglycone moiety. This allows the application of this approach to the synthesis of PBC conjugates with a wide range of oligosaccharides. For example, not only oligosaccharides obtained by chemical synthesis but also reducing oligosaccharides isolated from natural sources can be transformed into N-glycosides. The approach was tested by the example of conjugation of the carboxyl derivatives of ortho-carborane and dodecaborate anion with lactose as a model oligosaccharide. Lactose, an easily available disaccharide, is a ligand for lectins expressed on the surface of melanoma cells. The approach suggested is the first example of the synthesis of such conjugates that does not require protective groups for the carbohydrate residue. It is especially important for obtaining dodecaborate-carbohydrate conjugates for which the removal of protective groups is often a non-trivial task.

[Effect of humoral factors of the spleen after irradiation]. / Osobennosti deistviia gumoral'nykh faktorov selezenki pri obluchenii.

It is stated that therapeutic effect of humoral factors isolated from the cattle spleen is associated with its influence on alpha 2-macroglobulin (alpha 2-MG) performing a protective function. The results obtained permit recommending the isolated preparations to increase total resistivity of the organism under irradiation.

[Interrelations of trypsin-type serine proteases with the hemostatic system in diabetics]. / Vzaimosviaz' serinovykh proteaz tripsinovogo tipa s sistemoi gemostaza u bol'nykh sakharnym diabetom.

Patients with diabetes showed disorders of the dynamic balance of the system of protease inhibitors of the blood serum and lymphocytes which depend on the type of diabetes, severity and compensation of diabetes. Disorders of the proteolytic systems were accompanied by changes of hemostasis. It is of importance to control the above disorders in the complex treatment of diabetes mellitus and its complications.

[Activity of serum and lymphocyte serine proteases of patients with diabetes mellitus and the possibility of using protease blockers in combined therapy]. / Aktivnost' serinovykh proteaz syvorotki krovi i limfotsitov bol'nykh sakharnym diabetom i vozmozhnosti primeneniia blokatorov proteaz v kompleksnoi terapii.

The role of serine proteases of trypsin type was shown in the pathogenesis of autoimmune processes and nonspecific reactivity in diabetes mellitus. The use of protease blockers and thymic hormonal factors was proposed for patients suffering from diabetes mellitus with changed immunological reactivity.