NEUROPSYCHOBIOLOGICAL MECHANISMS OF AFFECTIVE AND COGNITIVE DISORDERS IN THE CHORNOBYL CLEAN-UP WORKERS TAKING INTO ACCOUNT THE SPECIFIC GENE POLYMORPHISMS. / NEIROPSYKhOBIOLOGIChNI MEKhANIZMY AFEKTYVNYKh I KOGNITYVNYKh ROZLADIV V UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChORNOBYL'S'KII AES Z URAKhUVANNIaM POLIMORFIZMU GENIV.

Relevance of the present work is determined by the considerable prevalence of both affective and cognitive disor-ders in the victims due to the Chornobyl accident, the pathogenesis of which is insufficiently studied.Objective is to identify the neuropsychiobiological mechanisms of the formation of the remote affective and cog-nitive disorders following exposure to ionizing radiation taking into account the specific gene polymorphisms.Design, object and methods of research. The retrospective and prospective cohort study with the external andinternal control groups. The randomized sample of the male participants in liquidation of the consequences of theaccident (Chornobyl clean-up workers, liquidators) at the Chornobyl nuclear power plant (ChNPP) in 1986-1987(n = 198) recruited from the Clinico-epidemiological registry (CER) of NRCRM aged 39-87 (M ± SD: 60.0-8.5 years)with the external irradiation dose ranged 0.6-5900.0 mSv (M ± SD: 456.0 ± 760.0 mSv) was examined. The compar-ison group (n = 110) consisted of the unexposed patients of the Radiation Psychoneurology Department with thecorresponding age and sex (the external control group). The internal control group included the liquidators irradi-ated at doses < 50.0 mSv (n = 42). The standard diagnostic neuropsychiatric scales, psychodiagnostic questionnairesand tests, neuropsychological methods (including the Wechsler Adult Intelligence Scale (WAIS) with premorbid IQ(pre-IQ) assessment), neuropsychiatric and psychophysiological methods (quantitative EEG (qEEG) and the audito-ry cognitive evoked potentials (Event-Related Potentials, ERP) were applied. The genotypes of the serotonin trans-porter gene SLC6A4 were determined by the 5_HTTLPR and rs25531 polymorphisms. The methods of descriptive and vari-ation statistics, non-parametric criteria, regression-correlation analysis, survival analysis by Kaplan - Meier and riskanalysis were used.Results. Cerebrovascular diseases, organic mental and depressive disorders, mainly of radiation-stress-relatednature, prevail among the liquidators. The overall risk of neuropsychiatric pathology increases (Pv < 0.001) with theirradiation dose. The verbal memory and learning are impaired, as well as the full IQ is reduced at the expense of theverbal one. The frequency of both mild cognitive impairment and dementia is risen. The cognitive impairment atdoses > 0.3 Sv is dose-dependent (r = 0.4-0.7; p = 0.03-0.003). Affective disorders (depression) and neurocogni-tive deficit are more severe at higher doses of irradiation (> 50 mSv). In the left posterior temporal region(Wernicke's area) the qEEG indices changes become dose-dependent at doses greater than 0.25-0.3 Sv. The dis-turbed brain information processes lateralized to the Wernicke's area are observed even at doses > 50 mSv. The car-riers of intermediate and low-level genotypes (LА/S, LА/LG, LG/LG, LG/S, S/S) of the serotonin transporter gene SLC6A4have more depressive disorders, especially severe ones, and tend to have more frequent and severe cognitive andstress-related disorders.The debut of depressive disorders in the carriers of the intermediate and low-activity genotypes occurs much earli-er (Log-Rank Test = 4.43, p = 0.035) in comparison with the carriers of the high-performance genotype LА/ LА.Conclusions. The radiation-induced dysfunction of the cortico-limbic system in the left dominant hemisphere ofthe human brain with a specific involvement of the hippocampus is considered to be the key cerebral basis of post-radiation organic brain damage. The association of genotypes by 5_HTTLPR and rs25531 polymorphisms of the SLC6A4gene with affective and cognitive disorders suggests the presence of neuropsychobiological features of these dis-orders associated with ionizing radiation depending on the certain gene polymorphisms.

[Expression of PRAME gene in multiple myeloma]. / Ekspressiia gena PRAME pri mnozhestvennoi mielome.

AIM: To determine clinical significance of PRAME gene expression in multiple myeloma (MM) and feasibility of its use as a marker of residual tumor clone. MATERIAL AND METHODS: 35 MM patients, of them 15 were newly diagnosed and 20 had resistance to previous therapy. PRAME was made if the patients received programmed therapy with high-dose chemotherapy (VD) and autologous transplantation of peripheral cell stem cells. 12 PRAME-positive patients were examined on the day +100, 5 patients--a year later. Monoclonal paraprotein was detected by electrophoresis and radial immunodiffusion of blood serum. Bone marrow affection was assessed at roentgenography and/or MRI. PRAME gene expression in bone marrow biopsy was measured by reverse transcription and PCR amplification. RESULTS: Activation of expression of PRAME gene in MM was found in 68.57% patients. It was higher in patients with MM duration more than 1 year and if they were treated before (85%) than in new cases (46.67%). Expression of PRAME tended to associate with activity of LDP of blood serum. After the above chemotherapy and autotransplantation transcript PRAME did not disappear in 8 of 12 cases. One year after the treatment, of 5 PRAME-positive patients 2 died, 1 had recurrence, 2 are in a compete clinicohematological remission. CONCLUSION: Frequent activation of transcription of the gene PRAME in MM, its assay can be used for monitoring of the disease course, assessment of remission completeness, detection of tumor cell contamination of preparations of autologous stem cells of peripheral blood.

[Immunophenotypic heterogeneity of CD7+CD4-CD8--acute leukemia]. / Immunofenotipicheskaia geterogennost' CD7+CD4-CD8--ostrykh lekozov.

Fourteen cases of lymphoid and myeloid acute leukemia (AL) were studied for expression on blast cells of CD7 antigen, a cell surface marker found early during T lineage differentiation. This heterogenic group of CD7+ CD4-CD8- AL includes distinct cytological subvariants with: myeloid (AML MO, M1, M4, M5) and lymphoid (pre-T-cell) commitment, biphenotypic or mixed lineage AL and AL with minimal signs of blast cell differentiation, which appear not to follow lineage restriction. The latter subset of AL may represent the transformed counterpart of an early stem cell prior to lineage commitment.