Kirov Research Institute of Hematology and Blood Transfusion

Arkhangel’sk, Russia

Kirov Research Institute of Hematology and Blood Transfusion

Arkhangel’sk, Russia
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Ikonnikova A.Y.,RAS Engelhardt Institute of Molecular Biology | Yatsenko Y.E.,RAS Engelhardt Institute of Molecular Biology | Kremenetskaya O.S.,Russian Academy of Sciences | Fesenko D.O.,RAS Engelhardt Institute of Molecular Biology | And 3 more authors.
Molecular Biology | Year: 2016

A biochip-based method was developed to identify the BCR-ABL mutations that affect the thyrosine kinase domain and determine resistance to targeted therapy with thyrosine kinase inhibitors. The method is based on RT–PCR followed by allele-specific hybridization on a biochip with immobilized oligonucleotide probes. The biochip addresses 11 mutations, which are responsible for up to 85% of imatinib resistance cases. A method to decect the clinically significant mutation T315I was designed on the basis of LNA-clamped PCR and proved highly sensitive, detecting the mutation in clinical samples with a leukemic cell content of 5% or higher. The method was validated using clinical samples from chronic myeloid leukemia (CML) patients with acquired resistance to imatinib. The results of hybridization on biochip were verified by Sanger sequencing. © 2016, Pleiades Publishing, Inc.


PubMed | Russian Academy of Sciences, RAS Engelhardt Institute of Molecular Biology and Kirov Research Institute of Hematology and Blood Transfusion
Type: Journal Article | Journal: Molekuliarnaia biologiia | Year: 2016

A biochip-based method was developed to identify the BCR-ABL mutations that affect the thyrosine kinase domain and determine resistance to targeted therapy with thyrosine kinase inhibitors. The method is based on RT-PCR followed by allele-specific hybridization on a biochip with immobilized oligonucleotide probes. The biochip addresses 11 mutations, which are responsible for up to 85% of imatinib resistance cases. A method to decect the clinically significant mutation T315I was designed on the basis of LNA-clamped PCR and proved highly sensitive, detecting the mutation in clinical samples with a leukemic cell content of 5% or higher. The method was validated using clinical samples from chronic myeloid leukemia (CML) patients with acquired resistance to imatinib. The results of hybridization on biochip were verified by Sanger sequencing.


Kenet G.,Tel Aviv University | Chambost H.,Aix - Marseille University | Male C.,Medical University of Vienna | Halimeh S.,Coagulation Research Center GmbH | And 16 more authors.
Thrombosis and Haemostasis | Year: 2016

A global phase 3 study evaluated the pharmacokinetics, efficacy and safety of a recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) in 27 previously treated male children (1–11 years) with severe and moderately severe haemophilia B (factor IX [FIX] activity ≤2 IU/dl). All patients received routine prophylaxis once every seven days for up to 77 weeks, and treated any bleeding episodes on-demand. The mean terminal half-life of rIX-FP was 91.4 hours (h), 4.3-fold longer than previous FIX treatment and clearance was 1.11 ml/h/kg, 6.4-fold slower than previous FIX treatment. The median (Q1, Q3) annualised spontaneous bleeding rate was 0.00 (0.00, 0.91) and was similar between the <6 years and ≥6 years age groups, with a weekly median prophylactic dose of 46 IU/kg. In addition, patients maintained a median trough level of 13.4 IU/dl FIX activity on weekly prophylaxis. Overall, 97.2 % of bleeding episodes were successfully treated with one or two injections of rIX-FP (95 % CI: 92 % to 99 %), 88.7 % with one injection, and 96 % of the treatments were rated effective (excellent or good) by the Investigator. No patient developed FIX inhibitors and no safety concerns were identified. These results indicate that rIX-FP is safe and effective for preventing and treating bleeding episodes in children with haemophilia B with weekly prophylaxis. Routine prophylaxis with rIX-FP at treatment intervals of up to 14 days are currently being investigated in children with severe and moderately severe haemophilia B. Clinicaltrials.gov (NCT01662531). © Schattauer 2016.


Kulikov S.M.,Hematology Research Center | Vinogradova O.Yu.,Russian National Research Medical University | Chelysheva E.Yu.,Hematology Research Center | Tishchenko I.A.,Hematology Research Center | And 12 more authors.
Terapevticheskii Arkhiv | Year: 2014

Aim: To assess the main epidemiological characteristics of chronic myeloid leukemia (CML) in the Russian Federation. Subjects and methods: A planned epidemiological prospective study was conducted in 2009-2012 in 6 Russian regions with the total number of 10.1 million inhabitants, which notified all new CML cases. Results: The unstandardized (unnormalized, baseline) recorded incidence of CML in the examined regions was 0.58 per 100,000 annually. Its standardized (normalized) incidence was 0.70 for the WHO standard population and 0.72 for the European standard population. The regional variations in the incidence were 0.44 to 0.69. The structural analysis of the incidence in the age strata indicated that the overall morbidity was less due to the decreased rate of registration in old age groups. The morbidity rates in patients aged less than 60 years were nearly similar to the European rates; those in patients aged over 70 years were almost 10 times lower. The lower rate of detection and screening diagnosis of CML in pensioners in primary health care is discussed. Conclusion: The data obtained in this study may serve as the starting point for monitoring the CML epidemiological situation.


Zotina E.N.,Kirov Research Institute of Hematology and Blood Transfusion | Zagoskina T.P.,Kirov State Medical Academy | Shardakov V.I.,Kirov Research Institute of Hematology and Blood Transfusion | Yovdy A.V.,Kirov Research Institute of Hematology and Blood Transfusion | Zaitseva G.A.,Kirov Research Institute of Hematology and Blood Transfusion
Medical Immunology (Russia) | Year: 2016

The prognostic value of tumor necrosis factor-Alfa (TNFα), a pro-inflammatory cytokine was studied in 140 patients with a newly diagnosed chronic lymphocytic leukemia (CLL). TNFα contents in blood serum was determined using ELISA method. A significant increase of serum TNFα was shown in patients with newly diagnosed CLL, as compared to healthy individuals. Dependence of the cytokine concentration on clnical stage and course of disease was revealed: The highest levels of serum TNFα were registered in patients with advanced disease and/or CLL progression. Distinct correlations were revealed between the studied cytokine amounts and clinical laboratory parameters reflecting the cell proliferative activity and tumor clone size. Immunochemotherapy was accompanied by a significant reduction of TNFα levels. According to the data from multivariate regression analysis. TNFα level of at the time of the diagnosis was an independent predictor of overall survival. Hence, TNFα plays an important role in CLL pathogenesis and may be used as an additional predictive factor for CLL outcomes. © 2016, SPb RAACI.


Korotayeva K.N.,Vyatka State Humanities University | Vyaznikov V.A.,Kirov Regional Clinical Hospital | Tsirkin V.I.,Kirov State Medical Academy | Kostjaev A.A.,Kirov Research Institute of Hematology and Blood Transfusion
Human Physiology | Year: 2011

Influence of adrenaline (10-9 to 10-4 g/ml) on the contraction amplitude caused by electrostimuli (1Hz, 5 ms, 25-30 V) and inotropic and adrenomodulation activities of blood serum of nonpregnant women (at dilutions of 1: 10 000, 1 : 1000, 1 : 500, 1 : 100, 1 : 50, 1 : 10, and 1 : 5) have been studied. The study has been carried out on isolated myocardium strips of the right atrial auricle that were taken from 43 patients with ischemic illness of the heart and 9 patients with valvular heart diseases of various etiologies upon venous cannula insertion during an aortocoronary bypass. Direct dependence of the contraction amplitude on the cardiac output according to Teicholz has been found. This meant that strips of the right atrial auricle reflected the contractility of the left ventricle myocardium. Adrenaline has been shown to dose-dependently increase the amplitude of evoked contractions in the concentration interval from 10-7 to 10-6 g/ml and had no influence from 10-9 to 10-8 g/ml (dissociation constant, 2 × 10-7 g/ml), which proved a decrease in the β-adrenoreceptor's (β-AR) activation. Blood serum in a dilution range from 1 : 10 000 to 1 : 50 had no effect on the contraction amplitude, but an enhanced effect has been found in a dilution range from 1 : 10 and 1 : 5. The presence of the endogenous activator of myocytes contractility (EAMC) has explained this enhanced effect. The β-adrenomodulation activity of blood serum has been explained by the presence of the endogenous sensitizer of β-AR (ESBAR) and the endogenous blocker of β-AR (EBBAR). The ESBAR activity of blood serum (dilutions: 1 : 1000, 1 : 500, 1 : 100, and 1 : 50) has been found in experiments with a subthreshold adrenaline concentration (10-8 g/ml). ESBAR (dilutions: 1 : 50 and 1 : 10) and EBBAR (dilution 1 : 500) activities of blood serum have been found in experiments with the maximum effective concentration of adrenaline (10-6 g/ml). Therefore, blood serum endogenous modulators of β-adrenergic reactivity, ESBAR and EBBAR, can modulate the activation of β-AR of human cardiomyocytes. These prove the prospects of the ESBAR analogue application in cardiology. © 2011 Pleiades Publishing, Ltd.


Illek Y.Y.,Kirov State Medical Academy | Zaytseva G.A.,Kirov Research Institute of Hematology and Blood Transfusion | Galanina A.V.,Kirov State Medical Academy | Vasilieva Y.A.,Kirov Children Clinical Hospital | And 2 more authors.
Sovremennye Tehnologii v Medicine | Year: 2013

The aim of the investigation was to study the state of immunologic responsiveness, immunomodulating and anti-relapse effects of ozone therapy in children with severe extended atopic dermatitis. Materials and Methods. We examined 64 children (38 boys and 26 girls) aged 5-10 years with severe extended atopic dermatitis. Group 1 patients (n=33) received complex standard treatment, group 2 (n=31) - complex therapy in combination with ozone therapy. Results. Complex standard therapy resulted in complete, though short, clinical remission; and in remission the patients preserved the changed parameters of cellular and humoral components of immune system, nonspecific resistance and the levels of pro-inflammatory cytokines in blood serum; while the patients receiving complex therapy combined with ozone therapy were found to have more rapid improvement of clinical indices, normalization of the most parameters of immunologic responsiveness and a long clinical remission.


Razin M.P.,Kirov State Medical Academy | Zaitseva G.A.,Kirov Research Institute of Hematology and Blood Transfusion | Sukhikh N.K.,Kirov State Medical Academy
Medical News of North Caucasus | Year: 2015

143 children of Russian ethnic group aged 5 - 15 years with various forms of congenital obstructive uropathy were observed. All patients underwent standard urological and immunogenetic examination to determine the factors of resistance to the development of pathology. In the study it was found that resistance to the development of congenital obstructive uropathies presents in individuals with HLA-alleles DRB1∗07, DRB1∗15 (2), DQB1∗0302; phenotypes A1, A9; A9, A11 and haplotype combinations A3, B7; A11, B35; A19, B27. Congenital resistance to the development of secondary pyelonephritis was in individuals with HLAantigens DRB1∗07, DRB1∗09, DRB1∗15 (2); phenotype A9, A11 and haplotype combinations A2, B12; A3, B7; A11, B35. Protective role in the development of congenital hydronephrosis in individuals was played by a specificities of HLA-system A11 and DQB1∗0302; phenotypic combinations A2, A9; A9, A11 and haplotypes A2, B7; A2, B12. Resistance to the presence of pyeloectasia (minor anomalies of the urinary tract) was in individuals with alleles HLA DRB1∗01, DRB1∗11 (5) and haplotype combination of antigens A3, B7.


Khudyakov A.N.,Russian Academy of Sciences | Polezhaeva T.V.,Russian Academy of Sciences | Zaitseva O.O.,Russian Academy of Sciences | Laptev D.S.,Russian Academy of Sciences | And 2 more authors.
Problems of Cryobiology and Cryomedicine | Year: 2013

Using chemiluminescence method it was shown that after addition of several cryoprotectants 1,2-propane diol (21% initial concentration hereinafter and added 1:1) and dimethyl sulfoxide (8%) to leukocyte suspension the level of LPO and antioxidant activity decreased. Presence of glycerol (7%) and hexa-methylene bis-tetra hydroxyethyl urea (30%) resulted in simultaneous stimulation of LPO and antioxidant systems. Hydroxyethylated starch (5.7%) and gelatine (molecular weight of 16,000; 7.5%) increase LPO. After storage in combined cryoprotective media at -10, -20 and -40°C the leukocytes revealed the activation of antioxidant systems on the background of stable LPO indices, that, probably, contributed to morphofunctional preservation of 75% of cells. © 2013 Institute for Problems of Cryobiology and Cryomedicine.


Ovsepyan V.A.,Kirov Research Institute of Hematology and Blood Transfusion | Luchinin A.S.,Kirov Research Institute of Hematology and Blood Transfusion | Zagoskina T.P.,Kirov Research Institute of Hematology and Blood Transfusion
Bulletin of Experimental Biology and Medicine | Year: 2014

The effects of GSTM1 and GSTT1 gene deletion (“zero”) polymorphisms on the risk of chronic myeloid leukemia development and progress and on response to imatinib monotherapy were studied in the representatives of the Russian nationality in the Vyatka region of Russia. Homozygotic carriership of GSTT1 “zero” allele was associated with a 3.66 times higher risk of chronic myeloid leukemia development in residents of the Vyatka region (OR=3.66, 95% CI=2.12-6.30; p<0.0001). Combinations of the “zero” GSTM1 and GSTT1 genotypes were risk factors indicating the probable disease progress and failure of high cytogenetic response after 12 months of imatinib therapy (400 mg daily). © 2014, Springer Science+Business Media New York.

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