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1.
Ter Arkh ; 92(8): 118-127, 2020 Sep 03.
Article in Russian | MEDLINE | ID: mdl-33346471

ABSTRACT

The review provides present information on the pathogenesis of irritable bowel syndrome (IBS), the relationship of endogenous and exogenous factors with the development of IBS-symptoms, questions of diet therapy are discussed, diets traditionally prescribed in IBS treatment and diets, such as FODMAP and gluten-free diet, which are the most promising and have a positive effect on the symptoms of IBS.


Subject(s)
Irritable Bowel Syndrome , Diet, Gluten-Free , Humans , Irritable Bowel Syndrome/diet therapy
2.
Sci Rep ; 10(1): 15360, 2020 09 21.
Article in English | MEDLINE | ID: mdl-32958812

ABSTRACT

Skeletal muscle tissue demonstrates global hypermethylation with age. However, methylome changes across the time-course of differentiation in aged human muscle derived cells, and larger coverage arrays in aged muscle tissue have not been undertaken. Using 850K DNA methylation arrays we compared the methylomes of young (27 ± 4.4 years) and aged (83 ± 4 years) human skeletal muscle and that of young/aged heterogenous muscle-derived human primary cells (HDMCs) over several time points of differentiation (0, 72 h, 7, 10 days). Aged muscle tissue was hypermethylated compared with young tissue, enriched for; pathways-in-cancer (including; focal adhesion, MAPK signaling, PI3K-Akt-mTOR signaling, p53 signaling, Jak-STAT signaling, TGF-beta and notch signaling), rap1-signaling, axon-guidance and hippo-signalling. Aged cells also demonstrated a hypermethylated profile in pathways; axon-guidance, adherens-junction and calcium-signaling, particularly at later timepoints of myotube formation, corresponding with reduced morphological differentiation and reductions in MyoD/Myogenin gene expression compared with young cells. While young cells showed little alterations in DNA methylation during differentiation, aged cells demonstrated extensive and significantly altered DNA methylation, particularly at 7 days of differentiation and most notably in focal adhesion and PI3K-AKT signalling pathways. While the methylomes were vastly different between muscle tissue and HDMCs, we identified a small number of CpG sites showing a hypermethylated state with age, in both muscle tissue and cells on genes KIF15, DYRK2, FHL2, MRPS33, ABCA17P. Most notably, differential methylation analysis of chromosomal regions identified three locations containing enrichment of 6-8 CpGs in the HOX family of genes altered with age. With HOXD10, HOXD9, HOXD8, HOXA3, HOXC9, HOXB1, HOXB3, HOXC-AS2 and HOXC10 all hypermethylated in aged tissue. In aged cells the same HOX genes (and additionally HOXC-AS3) displayed the most variable methylation at 7 days of differentiation versus young cells, with HOXD8, HOXC9, HOXB1 and HOXC-AS3 hypermethylated and HOXC10 and HOXC-AS2 hypomethylated. We also determined that there was an inverse relationship between DNA methylation and gene expression for HOXB1, HOXA3 and HOXC-AS3. Finally, increased physical activity in young adults was associated with oppositely regulating HOXB1 and HOXA3 methylation compared with age. Overall, we demonstrate that a considerable number of HOX genes are differentially epigenetically regulated in aged human skeletal muscle and HDMCs and increased physical activity may help prevent age-related epigenetic changes in these HOX genes.


Subject(s)
DNA Methylation/genetics , Exercise/physiology , Genes, Homeobox/genetics , Genome, Human/genetics , Muscle Cells/physiology , Muscle, Skeletal/physiology , Adult , Aged, 80 and over , CpG Islands/genetics , Epigenesis, Genetic/genetics , Epigenomics/methods , Female , Gene Expression/genetics , Humans , Male , Signal Transduction/genetics
3.
Adv Virol ; 2016: 8059607, 2016.
Article in English | MEDLINE | ID: mdl-26989413

ABSTRACT

Establishment of small animal models of Ebola virus (EBOV) infection is important both for the study of genetic determinants involved in the complex pathology of EBOV disease and for the preliminary screening of antivirals, production of therapeutic heterologic immunoglobulins, and experimental vaccine development. Since the wild-type EBOV is avirulent in rodents, the adaptation series of passages in these animals are required for the virulence/lethality to emerge in these models. Here, we provide an overview of our several adaptation series in guinea pigs, which resulted in the establishment of guinea pig-adapted EBOV (GPA-EBOV) variants different in their characteristics, while uniformly lethal for the infected animals, and compare the virologic, genetic, pathomorphologic, and immunologic findings with those obtained in the adaptation experiments of the other research groups.

4.
Med Tr Prom Ekol ; (5): 6-11, 2016 Aug.
Article in English, Russian | MEDLINE | ID: mdl-30351696

ABSTRACT

Complex medical examination covered 87 metallurgists of aluminium production with chronic fluorine intoxication and 43 metallurgists witout occupational diseases, aged 40 to 60, to evaluate factors associated with multi-focal atherosclerosis risk in aluminium production workers with chronic fluorine intoxication. Findings are increased incidence of ischemic heart disease and combined atherosclerosis of extracranial and peripheral arteries in workers with long exposure to fluorine compounds. Metallurgists with chronic fluorine intoxication appeared to have more frequent hyperfibrinogenemia and coronary personality type A, if compared to those without occupational diseases.


Subject(s)
Atherosclerosis/etiology , Fluorides/toxicity , Metallurgy , Occupational Diseases/etiology , Occupational Exposure/adverse effects , Adult , Atherosclerosis/diagnostic imaging , Atherosclerosis/epidemiology , Chronic Disease , Echocardiography , Humans , Male , Middle Aged , Occupational Diseases/drug therapy , Occupational Diseases/epidemiology , Risk Factors , Russia
5.
Gig Sanit ; 94(5): 91-4, 2015.
Article in Russian | MEDLINE | ID: mdl-26625626

ABSTRACT

In workers employed in the aluminum industry, the main harmful production factor is exposure to fluoride salts, which can cause chronic fluoride intoxication. For the assessment of the impact of chronic fluoride intoxication on the development of atherosclerosis, we conducted a comprehensive survey of 87 aluminum-metal makers with chronic fluoride intoxication and 43 aluminum-metal makers without occupational diseases, mean age--52.1 ± 0.4 years. There were considered the presence and severity of atherosclerosis of brachiocephalic arteries, and the arteries of the lower extremities in the studied group, there was evaluated the effect of other risk factors for atherosclerosis (smoking, presence of hypertension, diabetes, dyslipidemia). With the use of Doppler ultrasound of the arteries it was revealed that in metallurgists with chronic fluoride intoxication atherosclerosis was detected in 73.6% versus 55.8% in persons of the comparison group. The performed analysis of the prevalence of main risk factors for atherosclerosis showed that in metal makers with chronic fluoride intoxication in combination with atherosclerosis hypertension is more common (in 54.7%) than in metallurgists with chronic fluoride intoxication without atherosclerosis--only 26.1%. According to the frequency of occurrence of smoking, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia, there were no significant differences between the metallurgists with chronic fluoride intoxication, with and without atherosclerosis, and the control group, the increase in LDL cholesterol occurs significantly more often in metal-makers with chronic fluoride intoxication in combination with atherosclerosis if compared to workers without occupational diseases. Thus, chronic fluoride intoxication acts as a risk factor in the development of atherosclerosis: atherosclerosis in metal-makers with chronic fluoride intoxication occurs more frequently than in workers who do not have professional pathology. Hypertension and elevated levels of LDL cholesterol were established to increase the relative risk of developing atherosclerosis in metallurgists with chronic fluoride intoxication. At that there are no significant differences in the prevalence of common risk factors for atherosclerosis (smoking, diabetes, hypercholesterolemia, hypertriglyceridemia).


Subject(s)
Atherosclerosis/etiology , Fluoride Poisoning/complications , Metallurgy , Occupational Diseases/etiology , Occupational Exposure/adverse effects , Atherosclerosis/blood , Atherosclerosis/diagnostic imaging , Atherosclerosis/epidemiology , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Chronic Disease , Endothelium, Vascular/diagnostic imaging , Fluoride Poisoning/blood , Fluoride Poisoning/diagnostic imaging , Fluoride Poisoning/epidemiology , Humans , Middle Aged , Occupational Diseases/blood , Occupational Diseases/diagnostic imaging , Occupational Diseases/epidemiology , Occupational Exposure/analysis , Risk Factors , Russia , Tunica Media/diagnostic imaging , Ultrasonography, Doppler
7.
Ter Arkh ; 84(7): 72-4, 2012.
Article in Russian | MEDLINE | ID: mdl-23038976

ABSTRACT

The paper describes a rare case of verified foreign body (silicone) migration into the spleen. The specific feature of this clinical case is a rare clinical finding through histological study and the use of inductively coupled plasma-mass spectrometry for the determination of silicone in splenic tissues.


Subject(s)
Foreign-Body Migration , Silicones , Spleen/pathology , Adult , Female , Humans , Mass Spectrometry/methods
8.
Klin Med (Mosk) ; 90(5): 4-6, 2012.
Article in Russian | MEDLINE | ID: mdl-22993941

ABSTRACT

This review concerns the role of acquired androgen deficiency in pathogenesis of chronic cardiac failure (CCF) in men. It shows that patients with CCF and CHD suffer reduced testosterone production that correlates with impaired contractile activity of myocardium. It means that androgen deficiency due to combined bronchopulmonary and cardiovascular pathology promotes the early development of CCF.


Subject(s)
Heart Failure/complications , Testosterone/deficiency , Chronic Disease , Heart Failure/physiopathology , Humans , Male , Testosterone/metabolism
10.
Ter Arkh ; 82(12): 47-51, 2010.
Article in Russian | MEDLINE | ID: mdl-21516739

ABSTRACT

AIM: To define an association of bone marrow microvessel density (MVD) with histological properties (the magnitude of fibrosis and quantification of megakaryocytes (MGKC)) in patients with Ph-negative chronic myeloproliferative diseases (CMPD). SUBJECTS AND METHODS: MVD was analyzed in 93 patients with different forms of CMPD, by estimating histological parameters. True polycythemia (TP) was present in 28 patients; 20 patients had essential thrombocythemia (ET), 36 had subleukemic myelosis, out them 6 were in a prefibrotic stage, and 9 with diagnosed post-TP (ET) myelofibrosis. The grade of myelofibrosis was estimated from the degree of bone marrow fibrosis as 0, 1, 2, and 3 and the clusters of MGKC were in accordance with degrees: 0, 1, and 2. MVD was studied from the absolute number of CD34-positive vascular structures. RESULTS: In patients with TP, fibrosis was defined as grade 0 and 1 in 23 (82%) and 5 (18%) cases, respectively. The content of reticulin fiber was in the normal range in 19 (95%) of the 20 patients with ET. The clusters of MGKC of grades 1 and 2 showed an even distribution among patients with ET and those with TP. Fibrosis was absent in all the patients (n = 6) with prefibrotic-stage primary myelofibrosis (PMF). The patients with PMF had high MVD values [6.5 (range 2.8-22)] than those with TP [4.0 (range 1.76-10.2)] or ET [3.7 (range 2-8.5)] and the controls [3.2 (range 2-4.1)] (p < 0.001) confirming that angiogenesis is uninvolved at the onset of disease in patients with ET and those with TP. The patients with prefibrotic-stage PMF had higher values [6.0 (range 4.8-10.6)] than those with ET [3. 7 (range 2-8.5)] (p < 0.001). This suggests that angiogenesis is an early sign preceding the development of fibrosis. CONCLUSION: Bone marrow angiogenesis assessment (from MVD measurements) may be an additional criterion for the diagnosis of disease evolution and an additional criterion between ET and PMF in a prefibrotic stage.


Subject(s)
Bone Marrow/blood supply , Microvessels/pathology , Myeloproliferative Disorders/diagnosis , Adolescent , Adult , Aged , Chronic Disease , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neovascularization, Pathologic/pathology , Reproducibility of Results , Young Adult
11.
Ter Arkh ; 81(7): 29-36, 2009.
Article in Russian | MEDLINE | ID: mdl-19708570

ABSTRACT

AIM: To analyse clinical implications of chromosome 8 trisomy in Ph-negative cells of the bone marrow in patients with chronic myeloid leukemia (CML) treated with inhibitors of tyrosinkinases (ITK). MATERIAL AND METHODS: A total of 386 patients with CML (chronic phase--288, acceleration phase--77) received imatinib (400-800 mg/day). Because of resistance and/or intolerance some patients were switched to ITK II (nilotinib, dasatinib, bozutinib). This study included 8 CML patients (7 in a chronic phase, 1 in acceleration phase) treated with BCR-ABL ITK inhibitors of the first (imatinib) and the second line (ITK-II). The standard cytogenetic examination, on demand--investigation of the interphase nuclei with FISH, in some cases morphological, cytochemical and histological examinations of the bone marrow were made. RESULTS: The existence of a Ph-negative clone with trisomy of chromosome 8 had no negative effect on the course of the disease. The patients showed a stable hematological and cytogenetic response and no need in changing treatment policy. In long-term follow-up Ph-negative clone with trisomy of the chromosome 8 persisted without a clear trend to rise in most patients. CONCLUSION: Detection of a Ph-negative clone with chromosome 8 trisomy at early stages suggests parallel existence of Ph-positive and Ph-negative clones. None of the patients had myelodisplasia.


Subject(s)
Bone Marrow Cells/drug effects , Chromosomes, Human, Pair 8/genetics , Fusion Proteins, bcr-abl/antagonists & inhibitors , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Philadelphia Chromosome/drug effects , Protein Kinase Inhibitors/therapeutic use , Trisomy , Adult , Benzamides , Bone Marrow Cells/enzymology , Bone Marrow Cells/pathology , Drug Administration Schedule , Female , Humans , Imatinib Mesylate , Karyotyping , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/enzymology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Male , Middle Aged , Piperazines/administration & dosage , Piperazines/therapeutic use , Protein Kinase Inhibitors/administration & dosage , Pyrimidines/administration & dosage , Pyrimidines/therapeutic use , Time Factors
12.
Ter Arkh ; 81(7): 82-4, 2009.
Article in Russian | MEDLINE | ID: mdl-19708581
13.
Biochemistry (Mosc) ; 74(2): 175-85, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19267673

ABSTRACT

The interaction of human cytoplasmic phenylalanyl-tRNA synthetase (an enzyme with yet unknown 3D-structure) with homologous tRNA(Phe) under functional conditions was studied by footprinting based on iodine cleavage of thiophosphate-substituted tRNA transcripts. Most tRNA(Phe) nucleotides recognized by the enzyme in the anticodon (G34), anticodon stem (G30-C40, A31-U39), and D-loop (G20) have effectively or moderately protected phosphates. Other important specificity elements (A35 and A36) were found to form weak nonspecific contacts. The D-stem, T-arm, and acceptor stem are also among continuous contacts of the tRNA(Phe) backbone with the enzyme, thus suggesting the presence of additional recognition elements in these regions. The data indicate that mechanisms of interaction between phenylalanyl-tRNA synthetases and specific tRNAs are different in prokaryotes and eukaryotes.


Subject(s)
Phenylalanine-tRNA Ligase/chemistry , Phosphates/chemistry , RNA, Transfer, Amino Acyl/chemistry , Amino Acid Sequence , Aminoacylation , Base Sequence , Humans , Hydrolysis , Molecular Sequence Data , Nucleic Acid Conformation , Protein Conformation
14.
Vestn Oftalmol ; 125(6): 11-5, 2009.
Article in Russian | MEDLINE | ID: mdl-20143533

ABSTRACT

Thirty-eight patients (16 males and 22 females) with recurrent and residual choroidal melanomas who had undergone brachytherapy were followed up. The indication for transpupillary thermotherapy (TTT) was an active residual tumor (36 patients) and recurrent melanoma (2 patients). The follow-up interval between brachytherapy and TTT was 10 to 127 months. TTT using a diode laser was performed on a Nidek DC 3300 device at a wavelength of 810 nm. The mean tumor prominence prior to TTT was 1.9 mm (range 1 to 3.5 mm), its mean diameter was 8.6 mm (range 4-14.5 mm). Twenty patients were observed over time. The follow-up time after TTT was 3 to 15 months. After the first session of TTT, a positive effect was observed in 15 patients. In 9 patients, the effect was inadequate, which required additional sessions of TTT. Among the early TTT complications, there were superficial petechial hemorrhages, macular edema, exudative retinal detachment above the tumor. Treatment resulted in no complications in 18 patients. Late metastases were seen in none patients. Our investigations have indicated that TTT is a highly effective treatment for recurrent and residual uveal melanomas, which provides complete tumor resorption in 29% of the patients.


Subject(s)
Choroid Neoplasms/therapy , Hyperthermia, Induced/methods , Melanoma/therapy , Choroid Neoplasms/diagnosis , Female , Fluorescein Angiography , Follow-Up Studies , Fundus Oculi , Humans , Male , Melanoma/diagnosis , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/therapy , Pupil , Treatment Outcome , Ultrasonography, Doppler, Duplex
15.
Hematology ; 12(6): 473-9, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17852451

ABSTRACT

Increased PRV-1 mRNA expression and the presence of Jak2(V617F) mutation in peripheral blood granulocytes are specific markers for chronic myeloproliferative disorders (MPD), which facilitate the differential diagnosis between polycythemia vera (PV) and secondary erythrocytosis (SE) and may be helpful for monitoring treatment efficacy in MPD patients. We evaluated the presence of the Jak2V617F mutation and increased PRV-1 mRNA expression along with previously established markers - erythropoietin (EPO) independent colony formation (EEC) and erythropoietin level for diagnosis of PV and assessment of treatment efficiency. Increased PRV-1 expression was found in 37 out of 46 patients diagnosed with PV (80%), in 4 out of 15 patients diagnosed with essential thrombocythemia (ET) (27%) and in 4 out of 8 patients with chronic idiopathic myelofibrosis (CIMF) (50%), and increased PRV-1 expression plus EEC formation was observed in 19 of 36 examined MPD patients indicating the superiority of PVSG and WHO bone marrow criteria for the diagnosis of ET, PV and CIMF. We could confirm a very high sensitivity, specificity and utility of the Jak2(V617F) mutation for differential diagnosis between PV and SE. Spontaneous EEC, serum EPO levels, PRV-1 expression was evaluated in 22 PV patients who carried the Jak2(V617F) mutation. A concordance of increased PRV-1 expression and presence of Jak2(V617F) mutation in 19/22 (85%); of increased PRV-1/Jak2/EEC in 14/22 (63%); and of Jak2/PRV-1/EEC/low Epo level in 10/22 (45%) patients was found indicating the superiority of the presence of Jak2(V617F) mutation for the diagnosis of PV. IFN-alpha therapy in patients with PV was more effective then hydroxyurea treatment and significantly reduced increased PRV-1 expression together with higher levels of Jak2(V617F) mutation (50-100%) in PV patients treated with hydroxy urea (HU) and lower levels of Jak2(V617F) mutation (35-90%) in PV patients treated with IFN-alpha. Normal PRV-1 expression level was observed in 44% of PV patients who achieved clinical remission and only in 3% of patient who did not. These preliminary observations indicate that the Jak2(V617F) mutation in particular and PRV-1 overexpression appear to be suitable markers for monitoring treatment efficiency in prospective randomised clinical studies comparing pegylated interferon and hydroxyurea in well defined PV patients with a clear indication for cytoreductive therapy.


Subject(s)
Isoantigens/genetics , Janus Kinase 2/genetics , Membrane Glycoproteins/genetics , Polycythemia Vera/diagnosis , Polycythemia/diagnosis , Receptors, Cell Surface/genetics , Diagnosis, Differential , GPI-Linked Proteins , Humans , Hydroxyurea/therapeutic use , Interferon-alpha/therapeutic use , Mutation, Missense , Polycythemia/drug therapy , Polycythemia Vera/drug therapy , Primary Myelofibrosis/diagnosis , RNA, Messenger/analysis , Sensitivity and Specificity
16.
Ter Arkh ; 79(12): 57-62, 2007.
Article in Russian | MEDLINE | ID: mdl-18220034

ABSTRACT

AIM: To assess incidence of hyperhomocysteinemia (HHC) in patients with chronic myeloproliferative diseases (CMPD) and to analyse possible correlation between an elevated concentration of plasma homocystein (HC) and thrombotic complications. MATERIAL AND METHODS: The trial enrolled 61 patients: 39 CMPD patients with thrombotic complications and free of them, 22 nonhematological patients with thrombosis. The control group consisted of 40 healthy donors. The examination protocol included determination with standard methods of HC plasma concentration, platelet and plasma components of hemostasis, mutation of factor V Leiden gene, prothrombin and methylenetetrahydrofolate reductase (MTHFR). RESULTS: Mean HC concentration in the serum in CMPD patients was 19 +/- 1.7 mcmol/l which appeared higher than in healthy donors (12 +/- 1.3 mcmol/l). The highest HC was in patients with subleukemic myelosis (SLM)--23 +/- 2.3 mcmol). No difference in HC concentration in plasma was observed in CMPD carriers of homo- or heteroxygous mutation of C667T gene or CMPD patients without the mutation. In CMPD content of factor VIII was higher in HHC than in normal HC (222 +/- 26.5 and 116 +/- 20%, respectively, p = 0.002). For von Willebrand factor 202 +/- 15.6 and 120 +/- 14.6%, respectively (p < 0.003). HC reduction in response to vitamin therapy was the greater the higher its initial level was. CONCLUSION: There is correlation between HHC and thrombosis in CMPD patients. HC concentration may depend on the proliferative stage of CMPD. As HC is a significant independent factor of thrombotic complications risk, it is necessary to detect and treat HHC.


Subject(s)
Factor V/metabolism , Homocysteine/blood , Hyperhomocysteinemia/complications , Myeloproliferative Disorders/complications , Thrombosis/etiology , Adolescent , Adult , Biomarkers/blood , Chronic Disease , DNA/genetics , Factor V/genetics , Female , Follow-Up Studies , Humans , Hyperhomocysteinemia/epidemiology , Hyperhomocysteinemia/genetics , Incidence , Male , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Middle Aged , Myeloproliferative Disorders/blood , Myeloproliferative Disorders/genetics , Platelet Count , Point Mutation , Polymerase Chain Reaction , Prognosis , Prothrombin/genetics , Thrombosis/blood , Thrombosis/epidemiology
17.
Ter Arkh ; 78(10): 68-72, 2006.
Article in Russian | MEDLINE | ID: mdl-17180943

ABSTRACT

AIM: To analyse the course of pregnancy in chronic myeloproliferative diseases (CMPD) with hyperthrombocytosis, primarily, essential thrombocytemia. MATERIAL AND METHODS: The analysis of thrombogenic risk factors covered literature data and 8 cases observed by the authors. RESULTS: Six pregnant women received long-term treatment with preparations of interferon-alpha in a dose 9-20 million IU a week (both before and during pregnancy). Rapid reduction of hyperthrombocytosis (1100-4000 x 10(9) l) and the absence of a negative effect on development of the fetus were seen in all the cases. Normal delivery on week 37-39 was in 4 patients, spontaneous abortion on week 24 was provoked by a car accident. Three gravidas (gestational week 28, 33 and 34) are still under observation. Lupus anticoagulant or elevation of anticardiolipin antibodies level was detected in 4 of 8 patients, 2 patients had heterozygous mutation of methylentetrahydrofolatereductase genes and factor V (Leiden). These patients were given lannacher, faxiparine, folic acid and discrete plasmapheresis (in 2 cases). CONCLUSION: Gravidas with hyperthrombocytosis, if not contraindicated, must be treated with aspirin and interferon-alpha preparations at any gestational term. Moreover, it is necessary to exclude additional most prevalent causes of thrombophilia for adequate prevention of thromboses.


Subject(s)
Myeloproliferative Disorders/epidemiology , Pregnancy Complications, Hematologic/epidemiology , Adult , Chronic Disease , Female , Humans , Myeloproliferative Disorders/immunology , Pregnancy , Thrombocytosis/epidemiology , Thrombophilia/epidemiology , von Willebrand Factor/immunology
20.
Ter Arkh ; 76(7): 44-50, 2004.
Article in Russian | MEDLINE | ID: mdl-15379127

ABSTRACT

AIM: To investigate factors determining prognosis and efficacy of induction therapy including interferon-alpha-2b (intron-A, Schering Plough) in patients at an early chronic stage of Ph-positive chronic myeloid leukemia (CML) as shown by histomorphological examination. MATERIAL AND METHODS: The analysis covered 52 CML patients treated at an early chronic phase with intron-A in a standard daily dose 5 IU/m2 in combination with low-dose cytosinearabinoside (10 mg/m2, s.c. , daily for 10 days of each month). The treatment efficacy was assessed by the international criteria of complete and partial hematological remission and cytogenetic response. The cytogenetic study employed the direct method, even and G-differential staining, fluorescent hybridization in situ (FISH). The sections were stained with hematoxilin-eosine by Gomori, van Gieson. Histological samples were examined with histomorphometry. Immunohistochemical examination was made on paraffin sections using a panel of monoclonal antibodies CD3, CD4, CD8, CD20, NK, PCNA, Ki-67 (Dako, Denmark). RESULTS: Repeated assessment of histomorphological parameters such as erythroid lineage, degree of myelofibrosis and reduction of leukemic population indicate the treatment efficacy. Estimation of the level of leukemic population proliferation in trephine biopsies from CML patients with monoclonal antibodies PCNA and Ki-67 before the treatment is prognostically significant as it further correlates with the cytogenetic response (r = 0.821, p = 0.000000). CONCLUSION: It is valid to study histomorphological picture of CML to prognosticate and assess treatment efficacy with standard doses of interferon-alpha with high probability.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow Cells/drug effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bone Marrow Cells/pathology , Cohort Studies , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Interferon-alpha/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Male , Middle Aged , Prognosis
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