[Features of allele polymorphism of genes involved in homocysteine and folate metabolism in patients with atherosclerosis of the lower extremity arteries].

Under study were features of allele polymorphism of genes of methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), methionine synthase (MS A 2756G), methionine synthase reductase (MTRR A66G) and methylenetetrahydrofolate dehydrogenase (MTHFD G1958A) in patients with atherosclerosis of the lower extremity arteries (ALEA). Patients with hyperhomocysteinemia (HHcy) had statistically significant increase of allele MTHFR 677T and MTRR 66GG as compared both with the control group and with the group of patients without HHcy. It suggests that polymorphism of genes involved in homocystein and folate metabolism might affect the risk of HHcy in patients with ALEA.

[Study of lactate dehydrogenase isoenzyme in the cerebrospinal fluid of patients with acute lymphoblastic leukemia].

Lactate dehydrogenase isoenzymes were profiled in cerebrospinal fluid in patients with acute lymphoblastic leukemia. Cytological examination of patients with central nervous involvement identified isoenzyme 5 which failed to show after selective treatment. The isoenzyme's detection in cerebrospinal fluid without typical cytological characteristics may be regarded as a precursor of such complication. Hence, this may be used as an additional criterion for refinement of cytological evidence employed in diagnosis and prognosis of central nervous involvement in patients with acute lymphoblastic leukemia.

[The role of proto-oncogenes in normal hemopoiesis and the genesis of leukosis]. / Rol' protoonkogenov v normal'nom gemopoéze i leikozogeneze.

Results of investigations on the role of protooncogenes in the regulation of proliferation and differentiation of normal hemopoietic cells and in the pathogenesis of tumoral hemopoietic diseases are reviewed. The ways of the protooncogene activation in leukemias are discussed.

[Polyamine levels and biosynthesis in leukocytes during leukemic transformation]. / Soderzhanie i biosintez poliaminov v leikotsitakh pri leikoznoi transformatsii.

The content of polyamines, rate of their biosynthesis, and activity of ornithine decarboxylase (ODK), the key regulatory enzyme in the polyamine biosynthetic pathway, have been studied in the leukocytes of healthy persons and of patients with various forms of leukemia. The polyamine levels and the rate of their biosynthesis were considerably higher in lymphocytes than in granulocytes. In leukemias, as the cell population rejuvenated, both the polyamine content and the spermidine/spermine ratio were found to be markedly elevated approaching the maximal values in human blast cells of K-562 line. The leukemic transformation of myeloid cells was associated with the increase in the ornithine decarboxylase activity and in the rate of polyamine synthesis, whereas these items were significantly lowered in lymphoid leukemic cells. The changes observed in polyamine metabolism in leukemias are considered to be related to the proliferative and biosynthetic activity of the cells.

[Interrelation between the ribosome content of lymphocytes and hypogammaglobulinemia in chronic B-cell lymphatic leukemia]. / O vzaimosviazi mezhdu kolichestvom ribosom v limfotsitakh i gipogammaglobulinemiei pri B-kletochnom khronicheskom limfoleikoze.

The serum immunoglobulin levels, ribosome contents and protein synthesis rate in peripheral blood lymphocytes have been studied in 35 patients with chronic lymphatic leukemia. It is shown that in patients whose lymphocyte ribosome content corresponds to that of the donors IgG, IgA, IgM levels were on the average normal whereas in the patients with the decreased ribosome content IgG and IgA were 2-2.7 times lower, while the IgM concentration was normal. Hypogammaglobulinemia of IgG, IgA and IgM types in 47% of patients with the normal ribosome contents was 23%, 29% and 23%, respectively, and in 100% of patients with the low ribosome content it was 72%, 83% and 68%, respectively. There was no distinct correlation between the immunoglobulin levels and the protein synthesis rate. The ribosome pattern in the lymphocyte maturation in chronic lymphatic leukemia is discussed.

[Cytostatic activity of granulocytes in patients with acute leukemia]. / Izuchenie tsitostaticheskoi aktivnosti granulotsitov u bol'nykh ostrym leikozom.

The in vitro spontaneous cytostatic activity of peripheral blood granulocytes against human tumour cell of erythromyeloid line K-562 has been studied in healthy persons and in patients with acute leukemia. It has been found that with the target cell K-562: granulocyte ratio of 1:20, the normal granulocytes inhibit the K-562 cell growth by 44.3 +/- 3.1% at 37 degrees C within 42 h; in patients with acute leukemia in the acute phase of the disease the cytostatic activity is greatly lowered, while in remission up to two years it increases, however, without reaching the normal values. In remissions of more than three years, this physiological function of granulocytes is normalized.

[Ribosome content, spontaneous damage and repairing DNA synthesis in patients with chronic B-lymphocytic leukemia depending on stage and form of disease]. / Soderzhanie ribosom, spontannye povrezhdeniia i reparatsionnyi sintez DNK u bolnykh B-khronicheskim limfoleikozom v zavisimosti ot stadii i formy zabolevaniia.

The ribosome content (84 patients), DNA alkaline-labile sites or strand breaks (21 patients) and unscheduled DNA synthesis in lymphocytes under normal and B-cell chronic lymphocytic leukemia (B-CLL) were studied. It has been shown that the alkaline-labile DNA damages increased about 3-5 fold while the ribosome content was normal at an early (corresponding to Rai's O-I stages) and an advanced (II-III stages by Rai) stages of B-CLL. In the course of B-CLL, the DNA strand breaks and number of ribosomes per cell decreased with the correlation coefficient r = 0.72. The slowing down of the unscheduled DNA synthesis at the advanced and terminal (IV stage by Rai) B-CLL stages does not correlate with the DNA strand breaks. In the advanced stage with its established clinical variability of forms, when an adequate treatment was necessary, the lymphocyte ribosome levels drop following the expansion of main compartments involved by the leukemic spread.

[Functional changes in the natural killer cells of patients with acute leukemia]. / Funktsional'nye izmeneniia estestvennykh killernykh kletok u bol'nykh ostrym leikozom.

The results of study of NKC activity (51Cr release assay, conjugate-forming and lytic activity) in healthy persons and patients with acute leukemia (AL) in active phase and in remission are presented. It has been shown that the depression of the NKC activity in acute phase of AL (6 times as low as in norm) and in remission (3 times as low as in norm) depended upon disturbances of the processes of conjugate formation, lytic and recycling activity. Correlation has been found between percentage of lytic conjugates and that of cytotoxicity. The increase of NKC activity in remission seemed to be due to tendency to normalization of functional state of NK-cells (conjugate-forming and recycling activity).

[Effect of purine nucleosides on human leukocytes in normal conditions and in leukemias]. / Vliianie purinovykh nukleozidov na leikotsity cheloveka v norme i pri leikozakh.

The degree of action of purine nucleosides (adenosine, deoxyadenosine (d-ado) and deoxyguanosine (d-gua] on peripheral blood leukocytes in leukemias has been shown to change, as estimated by their inhibition of the protein biosynthesis. The inhibitory effect of purines on lymphocytes of the CLL patients and on myeloid cells of patients is decreased as compared to the normal cells. On the contrary, blast cells in T-ALL and AML exhibit the increased sensitivity to d-gua and d-ado. The cytotoxicity of d-ado, as compared to that of other nucleosides, is markedly higher against both the normal and leukemic lymphoid and myeloid cells. The relationship between the differences in purine nucleoside action on the normal and leukemic cells and the peculiar features of the nucleotide metabolism in these cells is discussed.

[Interrelation of degradation processes of purine nucleotides and their biosynthetic transformation in the blood cells of patients with acute leukemia]. / Vzaimosviaz' protsessov degradatsii purinovykh nukleotidov i ikh biosinteticheskikh prevrashchenii v kletkakh krovi bol'nykh ostrym leikozom.

It has been shown that the leukemic process shifts the balance of individual enzymatic steps of the purine nucleotide degradation and biosynthesis. In acute lymphoblastic leukosis (ALL) and acute myeloblastic leukosis (AML) the rate of purine degradation, as estimated by the ADA enzyme activity (ES 3.5.4.4.) and PNP (EC 2.4.2.1), exceeds considerably that of their enzymes AMP-DA (EC 3.5.4.6.) and IMP-DH (EC 1.2.1.14.) biosynthesis. The data obtained suggest the existence of differences in the enzymatic program of purine metabolism in the malignant transformation of hematopoietic tissue and in other tumours.

[Ultrastructural organization of nucleoli and ribosome level in lymphocytes at different stages of maturation in patients with chronic B-cell lymphocytic leukemia]. / Ul'trastrukturnaia organizatsiia iadryshek i uroven' ribosom v razlichnykh po stepeni zrelosti limfotsitakh krovi bol'nykh B-kletochnym khronicheskim limfoleikozom.

To clarify the role of the ribosome apparatus in the differentiation and maturation, the nucleolar ultrastructure, ribosome level and maturation stages of lymphocytes and their phorbol ester-induced differentiation capacity were studied immunologically, cytochemically and electron-microscopically in 16 patients with B-chronic lymphoid leukemia (B-CLL) and in one with small lymphocyte lymphoma. Most B-CLL cases had the clones mainly consisting of cells at an intermediate maturation stage. The cases with immature and mature lymphocyte clones were observed more rarely. The acid phosphatase activity did not correlate with the maturation stages of the lymphoid cells. The nucleolus activity ranged from virtually zero to high one. In general, there was a relationship between the ribosome content and nucleolus activity, although there were exceptions suggesting the impaired ribosome biogenesis. There was no correlation between the ribosome content and maturation degree of B-CLL lymphocytes and their phorbol-ester-induced differentiation capacity.

[Relative polyribosome content in peripheral blood lymphocytes and lymphoid organs in the human]. / Otnositel'noe soderzhanie poliribosom v limfotsitakh perifericheskoi krovi i limfoidnykh organov cheloveka.

Using ultracentrifugation, relative contents of polysomes and free ribosomes were calculated in human PHA activated or non-activated peripheral lymphocytes, peripheral chronic lymphocytic leukemia lymphocytes, and in spleen and adenoid lymphocytes in the total fraction as well as in that separated into T and B lymphocytes. The polysome amount in B cells was higher (47%) that in T cells (30%). The polysome and free ribosome correlation in lymphocytes of lymphoid organs and in peripheral blood was different to be presumably dependent on population composition of lymphocytes and on their maturation and proliferation. 20-25% of ribosomes in peripheral lymphocytes are found in polysomes; in PHA stimulated leukemic and spleen lymphocytes they reach 50-70%, and in adenoid lymphocytes, -40%. The participation of polysomes, rather than monosomes, in protein synthesis in lymphocytes has been shown irrespective of the polysome--free ribosome correlation in these.

[Poly(A) RNA distribution and the polysome-monosome ratio in the lymphocytes of healthy persons and chronic lympholeukemia patients]. / Raspredelenie poli(A) RNK i sootnoshenie polisom i monosom v limfotsitakh zdorovykh i bol'nykh khronicheskim limfoleikozom liudei.

Intact polysomes from lymphocytes of donors and patients with chronic lymphocytic leukemia (CLL) were isolated using diethyl pyrocarbonate. It has been shown that only 3/4 of ribisomes are bound to polysomes of a comparatively small size. Poly(A) RNA of the postmitochondrial fraction is largely associated with polysomes. Cyclohexamide treatment results in recruitment of monosomes into polysomes and in a shift of ribosomes in larger polysomes. There are no differences in the polysome content and size, the effect of cyclohexamide treatment and the distribution of the polysomal and non-polysomal poly(A) RNA in normal and CLL lymphocytes. It is suggested that during the transition of resting lymphocytes into the growth state, when protein synthesis increases, the mobilization of mRNP and ribosomes into polysomes is not essential.

[Characteristics of ribosomal RNA synthesis in the blood lymphocytes of chronic lympholeukemia patients]. / Osobennosti sinteza ribosomnoi RNK v limfotsitakh krovi bol'nykh khronicheskim limfoleikozom.

A study was made of the number of silver grains over the nucleoli and of the content of ribosomes in the lymphocyte cytoplasm for six healthy persons and for 20 patients with chronic lymphatic leukemia. Besides ratios of compact, nucleolonemic and ring types of nucleoli were evaluated in addition to counts of the specific radioactivity of mature 28S rRNA in lymphocytes. In the majority of cases examined, cells with 1 or 2 nucleoli of compact and nucleolonemic types were seen dominating. The number of silver grains over the nucleoli in the control healthy persons did not differ from that in patients who did not receive any treatment, which contrasted with high value grain counts in the treated patients. The lymphocyte ribosome contents varied within the normal and decreased values in both the patient groups. The specific radioactivity in 28S rRNA leukemic lymphocytes was significantly lower in groups of patients with low ribosome contents than in those with the normal ones. The data suggest that in the leukemic cells with a high or unaltered activity of ribosome cistrons and low ribosome levels rRNA processing is broken.

[The prognostic role of determining spontaneous leukocyte DNA damage and that occurring during chemotherapy in leukemia patients]. / Prognosticheskaia rol' opredeleniia spontannykh i voznikaiushchikh v protsesse khimioterapii povrezhdenii DNK leikotsitov bol'nykh leikozami.

The authors studied spontaneous DNA damages and the extra plan synthesis of DNA in various leukemias (chronic lympholeukemia, chronic myeloleukemia, acute leukemia) to predict the natural course of leukemias and the efficiency of chemotherapy. The level of genuine DNA breaks, which had been determined by the nic-translation test, was lower in peripheral blood cell DNA in all leukemias than that in the lymphocytes and granulocytes from donors. On the contrary, the levels of alkaline-labile DNA sites and nuclear matrix protein-bound DNA in the mature and maturing leukemia cells are high and decrease with progression of chronic lympholeukemia and chronic myeloleukemia. The extra plan DNA synthesis largely reflects the cellular levels of genuine DNA breaks, and the ultraviolet-induced DNA repair capacity is the highest in the lymphocytes in chronic lympholeukemia and particularly in the blasts in acute leukemia. The efficiency of chemotherapy was predicted during chemotherapy from the intensity of formation of genuine blast cell DNA breaks.

[DNA-binding blood proteins in hemoblastoses]. / DNK-sviazyvaiushchie belki syvorotki krovi pri gemoblastozakh.

Some differences were detected in the spectrum of DNA-binding proteins in blood serum of healthy volunteers and of patients with various forms of hemoblastoses. Two fractions of high molecular mass proteins were found to be main components of DNA-binding proteins in blood serum of both healthy persons and these patients. The DNA-binding proteins with a molecular mass less than 150 kDa were not detected under conditions of normal state, in myeloblast and lymphoblast forms of acute leukemia and in chronic phase of chronic myeloleukemia. However, additional fraction of DNA-binding proteins about 30-40 kDa was found in blast crisis of chronic myeloleukemia and in refractory anemia with increase of blast forms.

[Comparative study of nuclear RNA in leukocytes of normal individuals and patients with leukemia by the method of molecular DNA-RNA hybridization]. / Sravnitel'noe izuchenie iadernykh RNK leikotsitov cheloveka v norme i pri leikozakh metodom molekuliarnoi DNK-RNK-gibridizatsii.

Spectra of nuclear RNA were studied in leukocytes in healthy donors and in patients with leukoses by DNA-RNA hybridization. Cross competitive hybridization showed that in chronic lymphoid leukosis and acute myeloblastosis new forms of nuclear RNA were observed, which were not found in normal state; in myeloleukosis the nuclear RNA spectra were similar to those of normal granulocytes. The results obtained suggest that universal type of impairments appears to be absent in regulation of transcription in leukoses; it may be related not only to leukosis transformation but depends on variations in cell content of leukocyte populations studied.

[Comparative study of the lymphocyte protein-synthesizing activity of donors and chronic lympholeukemia patients]. / Sravnitel'noe izuchenie beloksinteziruiushchei aktivnosti limfotsitov donorov i bol'nykh khronicheskim limfoleikozom.

An assay of lymphocyte ribosomes in blood of donors and patients with chronic lymphocytic leukemia established the normal level of ribosomes in 11 cases and half that value in 6 cases of leukemia. The decreased level of ribosomes in cells was largely, registered at the terminal stage of the disease. The 14C-leucine uptake by leukemic lymphocytes was reduced 2-3-fold while the relative level of 14C-leucyl-tRNA in diseased and normal cells was identical. The rate of lymphocyte protein synthesis was lowered in a wide range (2-8-fold), in most of patients (7 out of 8). The rate of protein synthesis (radioactivity of acid insoluble fraction per mg of ribosomes) was half the normal value and constant in leukemic lymphocytes. An important role of ribosome level in protein biosynthesis regulation in the course of disease progression is suggested.

[Selection of appropriate ribonuclease inhibitors in the study of polysomes in human lymphocytes]. / K voprosu o podbore adekvatnykh ingibitorov ribonukleaz pri izuchenii polisom v limfotsitakh cheloveka.

Polysome profiles are described for lymphocytes of donor peripheral blood treated with various inhibitors of RNAases. The most effective inhibitor was diethyl pyrocarbonate, which enabled to maintain high content of polysomes (up to 70%) in these cells. Ribosomes, treated with diethyl pyrocarbonate, exhibited functional activity in the puromycin test. A natural inhibitor of RNAases from liver tissue inhibited incompletely the enzymatic activity in lymphocytes. Heparin proved to be an inadequate inhibitor of RNAases in all the cells of lymphoid origin (lymphocytes from peripheral blood of donors and of the patients with chronic lympholeukosis, lymphocytes isolated from adenoids and spleen tissue); it induced disaggregation of polysomes and dissociation of ribosomes.

[Biochemical heterogeneity of lymphocytes in chronic lympholeukemia based on the analysis of the protein-synthesizing apparatus]. / Biokhimicheskaia neodnorodnost' limfotsitov pri khronicheskom limfoleikoze po dannym analiza beloksinteziruiushchego apparata.

Duration of middle polypeptide synthesis, the rate of protein synthesis, content of ribosomes in lymphocytes were studied in the cells from 9 healthy persons and 28 patients with lympholeukosis. In 14 of the patients examined the content of ribosomes was decreased 2-fold; in the other patients it approached the control values. The rate protein synthesis was distinctly decreased in the patients with low content of ribosomes; in patients with normal content of the ribosomes this rate was either increased or decreased. Acceleration of the middle peptide synthesis was detected in leukemic lymphocytes as compared with controls. The data obtained suggest that lymphocytes exhibited biochemical heterogeneity in chronic lympholeukosis as well as that not only the content of ribosomes but other factors, importance of which in regulation of protein synthesis is discussed, influenced the rate of protein synthesis in lymphocytes of the patients.