[Time course of changes in iron metabolic and oxidative-antioxidative system parameters in patients with acute myeloid leukemia].

AIM: To study an association between iron metabolism, free radical oxidation (FRO), and antioxidative system (AOS) in patients with acute myeloid leukemia (AML) during intensive chemotherapy. SUBJECTS AND METHODS: AML patients (n = 14) with a median age of 46 years received 7+3 courses (n = 3) containing cytarabine > or = 1 g/m2/introduction (n = 8) and myeloablative conditioning regimen before hematopoietic stem cell transplantation (n = 3). The concentrations of iron, ferritin, transferrin saturation (TFS), and malonic dialdehyde and the activity of superoxide dismutase (SOD), ceruloplasmin (CP), and catalase were investigated in their sera. The investigations were performed before and after chemotherapy and during hemopoietic recovery and rehospitalization. RESULTS; After therapy termination, there was a significant increase in TFS (6.8% vs 41.9%; p < 0.0001), which gave way to its reduction during hemopoietic recovery (89.5% vs 96.8%; p = 0.003). The activity of antioxidant enzymes was found to be altered at a time. That of catalase was enhanced throughout cytopenia (3.8 and 3.3 vs 5.7 conventional units (CU)/ml; p = 0.028 and p = 0.011). The lower activity of SOD (21.0 vs 41.0 CU/ml; p = 0.018) and the higher activity of CP (1.1 vs 0.8 g/l) were ascertained when leukocyte count increased up to > or = 1 x 10(9)/l. CONCLUSION: After intensive cytostatic therapy, there was a phasic TFS increase accompanied by the compensatory change in AOS activity, which is aimed at neutralizing FRO products.

[Non-specific changes in the complement system in neoplastic processes]. / Nespetsificheskie izmeneniia sistemy komplementa pri neoplasticheskikh protsessakh.

The study using immunochemical and biological methods was concerned with assaying complement components C1q, C3, C4, and C5, C3 derivatives--C3a and, C3(H2O), C1ing control protein, hemolytic activity (CH50), total proteolytic activity and regulatory immune complexes in sera from patients with cancer of the stomach, breast and ovary, subjects at risk of cancer and healthy donors. Neoplasia was associated with lowered levels of intact C3 and C1ing matched by high concentrations of C3a, C1q and C4. Hemolytic activity (CH50) was increased against the background of relatively higher total proteolytic activity both in healthy subjects and cancer patients. Significant decrease in C1ing concentration may be used as an additional biochemical prognosticator in breast cancer.

[Diagnostic and prognostic significance of blood-serum ceruloplasmin, acetylcholinesterase and total proteolytic activity in patients with multiple myeloma]. / Diagnosticheskoe i prognosticheskoe znachenie opredeleniia tseruloplazmina, atsetilkholinesterazy i obshchei proteoliticheskoi aktivnosti v syvorotke krovi bol'nykh mnozhestvennoi mielomoi.

The study included 82 patients with multiple myeloma (MM) to evaluate the diagnostic and prognostic significance of correlation between of levels of ceruloplasmin (CP), acetylcholinesterase (ACE) and total proteolytic activity (TPA) in blood serum and immunochemical pattern, tumor mass and response to chemotherapy. It was shown that CP, ACE and TPA determination may be used as additional markers to confirm therapeutic benefits, to timely detect relapse and to verify resistance to chemotherapy. It was also demonstrated that resultant decrease in CP and TPA and increase in ACE levels are reliable indicators of changes developing in MM course and remission fulfillment. High values for CP and low ones for ACE point to pathological activity. Both diagnostic and prognostic significance of the indices has been shown. The highest levels of CP and TPA in blood serum were identified in cases of A-myeloma and myeloma of Bence Jones while ACE concentrations in those patients were lower than in G-myeloma which correlated with median survival. Application of said assays might improve diagnosis, management and prognosis of MM.

[Certain biochemical features of leukocytes in blast crisis of chronic myelogenous leukemia]. / Nekotorye biokhimicheskie osobennosti leikotsitov pri blastnom krize khronicheskogo mieloleikoza.

The content of nuclear high mobility group (HMG) proteins, activities of ornithine decarboxylase (ODC), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) and also glycosaminoglycan (GAG) content and composition were studied in leukocytes of patients with chronic myelogenous leukemia in the phase of blast crisis (BC CML). Myeloid and lymphoid cytochemical variants of BC CML differ by biochemical parameters. It is suggested, that the content of HMG-proteins, activities of ODC and PNP, and electrophoretic patterns of GAGs could be used in diagnostics of two main variants of BC CML.

[Experimental study of the biopreparation Lymphotilin as an antiproliferative and antitumor agent]. / Eksperimental'noe izucheniie biopreparata Limfotilin kak antiproliferativnogo i protivoopukholevogo sredstva.

We found in experiments involving the use of a biopreparation lymphotilin that its administration was followed by a decrease in proliferative activity of cultured tumor cells and a longer survival of mice bearing transplantable leukemia. An intensified intercalation of ethidium bromide in nucleic acids of tumor cells in lymphotilin culture points to the drug activity on nuclear level. Tumor cell inhibition by lymphotilin holds much promise for the practice of hematology.

[The role of glycosaminoglycans and proteoglycans in hemopoiesis and the physiological functions of the blood cells]. / Rol' glikozaminoglikanov i proteoglikanov v gemopoéze i fiziologicheskikh funktsiiakh kletok krovi.

Literature review as well as own data on the role of glycosaminoglycans and proteoglycans of leukocytes, platelets and hemopoietic microenvironment are presented. These compounds are involved in the storage of lysosomal enzymes, cationic antibacterial polypeptides and other granular constituents of blood cells, take part in mediating of cellular interactions, occurring in hematopoiesis, phagocytosis, immunity and other processes. Due to the capacity to react with many substances, including enzymes, cell growth factors, cytokines, receptors, changing their conformation and biological activity glycosaminoglycans and proteoglycans can take part in regulation of cell adhesion, migration, proliferation differentiation and special functions of various types of hematopoietic and lymphoid cells.

[Levels of complement components in plasma of onco-hematologic patients with defective hemopoiesis]. / Soderzhanie komponentov komplementa v plazme onkogematologicheskikh bol'nykh pri nedostatochnosti gemopoéza.

Immunochemical assay using monoclonal antibodies was carried out to determine levels of a number of complement components (C3 and its derivatives-C4 and C5) and immunoglobulins (lg) in plasma of patients with onco-hematological diseases involving defective hemopoiesis: leukemia, myelodysplastic syndrome (clonal diseases) or aplastic anemia (delayed clonal disease). The most significant disorders were registered in the concentrations of component C3 and its derivatives. In acute leukemia, the nature and extent of C3 splitting was found to depend on disease while Ig level-on stage. Myelodisplasia usually involved a 2-3-fold decrease in C3 level matched by a rise in the concentrations of its derivatives-C3-like form and C3a fragment. Reduced C3 levels matched by increased ones of Ig were observed in some cases of aplastic anemia. It is suggested that disturbances in complement component level may cause changes in cascade reactions of the complement in onco-hematological patients and thus indirectly influence immune response regulation processes.

[Lysosomal enzyme activity in white blood cells in leukemias]. / Aktivnost' nekotorykh lizosomal'nykh fermentov v belykh kletkakh krovi pri leikozakh.

Total enzyme activity of acidic hydrolases and total neutral proteinase were compared in the post-nuclear fraction of leukocytes from healthy subjects and leukemia patients. The levels of acidic phosphotase and neutral proteinase in lymphoid cells of healthy donors were 11 and 7 times lower than those in myeloid cells, respectively. Patients suffering chronic myeloid leukemia revealed enhanced levels of beta-glucuronidase and neutral proteinases whereas B-chronic lymphoid leukemia involved acidic hydrolase concentrations lower than normal. As chronic myeloid leukemia advanced, neutral proteinase activity dropped dramatically (2.5 times); an aggressive course of B-chronic lymphoid leukemia was accompanied by a 3-fold decrease in acidic hydrolase level. The results may be used as indirect evidence of differences in the role of lysosomal enzymes in the mechanism of protein processing involved in myeloid and lymphoid proliferative pathologies.

[Modification of complement components under the effect of cationic proteins from leukocytes from donors and leukemia patients]. / Modifikatsiia komponentov komplementa pod deistviem kationnykh belkov leikotsitov donorov i bol'nykh leikozami.

Cation proteins (CP) were isolated from leukocytes by means of ion exchange chromatography. Enzyme immunoassay showed that these cation proteins modified C3 component of complement in vitro. CP obtained from healthy volunteers decreased the content of C3 purified by affinity chromatography and C3 of blood serum; however, content of C3.H2O op C3b-like form and C3a-fragment were not altered. Effect of CP isolated from leukocytes of patients with chronic myeloleukemia and chronic lympholeukemia on C3 component was less distinct as compared with that of healthy volunteers. At the same time, content of C3b-like form was increased the presence of CP from patients with myeloleukemia and of C3a-fragment--in the presence of the proteins from patients with lympholeukemia. Excess of physiologically active C3 fragments, developed under conditions of these diseases, may contribute to a decrease in unspecific body resistance.

[Nuclear proteins of human leukocytes in health and in chronic leukemias]. / Iadernye belki leikotsitov cheloveka v norme i pri khronicheskikh leikozakh.

The levels and fractional composition of nuclear proteins of human leukocytes (histones, total non-histone proteins and HMG-proteins) have been studied in healthy subjects and cases of leukemia. It has been shown that the levels of histones and total non-histone proteins in normal myeloid cells are, on the average, 1.5 times those in lymphoid cells. Leukemia has been shown to involve elevated concentrations of high-molecular components in the histone and HMG-protein fraction of white blood cells as well as a slight decrease in both high- and low-molecular components in the fraction of total non-histone proteins. This points to disturbances in the epigenomic regulation of the genome involved in leukemia.

[Escherichia coli reactions to the action of the cationic proteins of blood leukocytes]. / O reaktsiiakh Escherichia coli na deistvie kationnykh belkov leikotsitov krovi.

The antibacterial effect of cation proteins (CP) of swine leukocytes with respect to Escherichia coli strain 17 has been demonstrated in vitro. The composition and properties of these CP have been studied; as a result, a comparatively high content of basic and dicarbonic amino acids and the presence of protease activity have been established. The release of the components of the metabolic fund by E. coli under the influence of CP of swine leukocytes is indicative of changes in the permeability of microbial membranes and, probably, of the deficiency of energy resources. The addition of heparin to CP of swine leukocytes levels their antibacterial effect with respect to E. coli.

[Nuclear nonhistone proteins in normal and leukemic leukocytes]. / Iadernye negistonovye belki leikotsitov v norme i pri leikozakh.

Leukemic transformation was shown to be associated with alteration in the level, profile, amino acid composition and metabolic activity of nuclear nonhistone proteins (NHP) of human leukocytes. The level of HMG-protein in patients with blast crisis of chronic myeloid leukemia of the lymphoid type was 5 times that in patients with the myeloid type of blast crisis. The NHP of both transformed and non-transformed leukocytes were shown to undergo glycosylation. A correlation was established between carbohydrate precursor uptake level, on the one hand, and cell specificity, degree of cell differentiation, and cell proliferation rate, on the other. Successful treatment was followed by a rise in NHP level and metabolic activity, improvement in their profile (it became similar to that in donors) and an increase in the share of high-molecular components.

[The effect of the cationic proteins of human blood cells on the growth of Escherichia coli]. / Vliianie kationnykh belkov kletok krovi cheloveka na rost Escherichia coli.

The antibacterial effect of cationic proteins (CP) on donor leukocytes and thrombocytes with respect to the growth of E. coli has been demonstrated in vitro, the maximum recorded inhibition being caused by the action of leukocytic CP. Differences in the inhibitory action may be linked with the presence of anomalies in the amino acid composition of leukocytic CP and thrombocytic CP, manifested by the deterioration of the basic properties of the latter, as well as by the fractional composition whose characteristic features for thrombocytic CP are the appearance of high-molecular components and a decrease in the proportion of low-molecular fractions. In patients with different forms of leukosis (chronic myeloleukemia, chronic lympholeukemia, acute myelomonoblastic leukosis) leukocytic CP retain their antibacterial activity. Under the action of blood cell CP changes in the outer and cytoplasmic membranes have been noted.

[Effects of a lymph node extract on hemopoietic and lymphoid cells in normal state and in different forms of leukemia]. / Vliianie ékstrakta limfaticheskikh uzlov na gemopoéticheskie i limfoidnye kletki v norme i pri razlichnykh formakh leikoza.

The chemical composition and properties of the lymphatic node extract (LNE) obtained from the porcine submandibular lymphatic nodes have been studied. It has been established that the LNE is the mixture of low-molecular weight peptides and the components of nucleic acids with the molecular mass below 2 kD. It possesses antiproliferative, immunosuppressive and antileukemic activities in vitro and in vivo. The inhibitory effect was the most pronounced in respect to lymphoid cells rather than myeloid cells of the patients with leukemia.

[Glycosaminoglycans in leukocytes in myeloproliferative disorders]. / Glikozaminoglikany leikotsitov pri mieloproliferativnykh zabolevaniiakh.

Content and composition of glycosaminoglycans (GAG) was studied in leukocytes of 30 healthy persons and of patients with different types of myeloproliferative disorders: 32 patients with chronic myeloid leukemia (CML), 10 patients with polycythemia vera (PV), 5 patients with idiopathic myeloid fibrosis (IMF) and 10 patients with acute myelo blast leukemia (AML). The total content of GAG in healthy persons was 97.7 +/- 3.9 micrograms of uronic acid per 100 mg of dry cells, in CML and IMF it was 2-4-fold increased, in PV it was elevated by 20%, in AML it was diminished 3-5-fold. The elevated level of GAG in CML and IMF was due to presence of basophils and considerable quantity of immature cell forms: promyelocytes and myelocytes. In these cells changes in GAGs composition and their properties were shown: an increase of chondroitins deficient in sulfate groups and of heparan sulfate content, especially in basophils. The observed changes in GAG content and composition may be important for biological activity of the leukemic cells.

[Nuclear and lysosomal protein distribution in granulocytes of varying degrees of maturity]. / Raspredelenie iadernykh i lizosomnykh belkov v granulotsitakh raznoi stepeni zrelosti.

An experimental quantitation of nuclear and lysosomal proteins of granulocytes was made in healthy individuals and in patients with chronic and acute myelogenous leukaemia. The patients were divided into three (II-IV) groups according to the cell maturity coefficient (K) calculated as the ratio of the total amount of myeloblasts + myelocytes and metamyelocytes towards the number of mature granulocytes of the neutrophil series. The group of donors designated as group I had K = 0. The content of nuclear (histones and non-histones) and lysosomal proteins in granulocytes at different stages of maturity was determined by means of the equations in whose left sides the unknown quantities were X1 (mature granulocytes), X2-3 (metamyelocytes and myelocytes), X4-5 (promyelocytes and myeloblasts), and in the right sides the experimental M1, M2, M3 and M4 corresponded to the quantities of proteins found for the group of patients with the determined K. The role of changes in ratios of the proteins studied in the malignant transformation of leucocytes has been discussed.

[Effect of lysosomal acid-soluble proteins on the respiratory activity of the granulocytes of healthy subjects and chronic myeloid leukemia patients]. / Vliianie lizosomal'nykh kislotorastvorimykh belkov na dykhatel'nuiu aktivnost' granulotsitov zdorovykh liudei i bol'nykh khronicheskim mieloleikozom.

A rate of oxygen consumption by granulocytes was measured before cell stimulation and following their stimulation by zymosan in healthy persons and in patients with chronic myelocytic leukemia (CML). The rate of oxygen consumption by granulocytes of donors was higher than that of patients with CML. Addition of lysosomal acid soluble proteins, extracted from normal granulocytes, affected the respiratory activity of stimulated and non-stimulated both normal and leukemic cells, depending upon the protein concentration. The alterations were more marked in granulocytes of donors. Lysosomal acid soluble proteins, extracted from granulocytes of patients with CML did not change the cell respiratory activity.