[Apoptosis and neutrophils on the regulation of proliferation and differentiation ex vifo of myeloid cells with Ph-chromosome].

Human myeloid cells with Ph chromosome (Ph+ cells) from chronic myeloid leukemia (CML) in the course of proliferation and differentiation ex vivo are regulated under alternation of cell proliferation and neutrophil maturation stages by consecutive blocking and inducing apoptosis with of neutrophils participation as well bcr/abl, bax and bcl2 genes expression. Apoptosis regulation of three main Ph+ cells types from CML patients depends on alternation sequences of proliferation (1) and maturation (2) cell stages and realized by two ways. The first one is performed by consecutive blocking and inducing apoptosis under 2/1/2 stage alternation. The way is not described early. Neutrophils accumulation correlates with apoprosis blocking. Apoptosis level enhances under neutrophils exhausted. Apoptosis blockage allows cells to proliferate and, thus, to form new portion of neutrophils with consecutive regular their death as well a consequent alternation of apoptosis blocking and inducing. This way regulates proliferation efficiency indexes P/D that reflect Ph+ cells proliferating potential and performs cycle completion for proliferation and differentiation. The second way of apoptosis regulation starts from proliferation stage and performs for 1/2/1 alternations under diminished content of neutrophils and a little increase under next maturation. It leads to resistant depressed apoptosis levels that, at maximal points, are 3-8 times lower than those under alternation 2/1/2. Resistant apoptosis blocking is observed in the Ph+ cells with prolong proliferation or maturation stages, when blasts and myelosytes are accumulated under enhanced bcr/abl and bcl2 > box gene expression and remain under next maturation. Stable apoptosis blocking is accompanied by increasing amounts of blasts and myelocytes and enhancing bcr/abl and bcl 2 > bax expression. This is observed under CML progression. Ph+ cells cultivation may be useful for more distinct diagnostics of CML phases of individual CML patients and optimization of the treatment.

[Cytogenetic characteristics of hematopoietic and stromal progenitor cells in myelodysplastic syndrome].

AIM: To study and compare cytogenetic abnormalities in the bone marrow (BM) and peripheral blood (PB) CD34+ hematopoietic progenitor cells and in the BM mesenchymal stromal cells (MSCs) in patients with myelodysplastic syndrome (MDS). Subjects and methods. The results of a cytogenetic analysis of the total population of BM cells (BMC), CD34+ hematopoietic progenitor cells from BM and PB, and BM MSCs were analyzed in 35 patients (29 patients with MDS and 6 with MDS transformed into acute myeloid leukemia (AML)) and 7 healthy BM donors. Cytogenetic examinations were performed by G-banding of chromosomes and fluorescence in situ hybridization (FISH). RESULTS: The BMC karyotype was abnormal in 17 (49%) of the 35 patients (13 with MDS and 4 with AML); the others were found to have a normal BM karyotype. The FISH analysis confirmed the same cytogenetic abnormalities in the BM and PB CD34+ hematopoietic progenitor cells in all the examinees with an abnormal karyotype. The mean abnormal clone sizes in the total population of BMCs and BM and PB CD34+ progenitor cells did not differ and constituted 65.8, 73.1, and 74.8%, respectively. The patients with a normal BM karyotype had no chromosome abnormalities in the CD34+ cells either. The karyotype of MSCs was analyzed in 23 (19 with MDS and 4 with AML) of the 35 patients. No karyotype abnormalities were revealed in the patients with MDS transformed into AML. There were structural chromosome aberrations in 2 (11%) of the 19 patients with MDS (one with constitutional inv(9)(p1 3q21) was found to have non-clonal translocation t(2;22)(p10;q1 1) and the other had a clone with an additional segment of the long arm of chromosome 2 in 35% of the cells. No numerical MSC karyotype abnormalities were detected. A normal MSC karyotype was defined in 7 healthy BM donors. CONCLUSION: The cytogenetic analysis of hematopoietic and mesenchymal progenitor cells showed that the chromosome abnormalities revealed in these cell populations were different in the patients with MDS. The isolated CD34+ cells displayed the same cytogenetic abnormalities as in a total population of BMC. Examination of the latter could reveal no cytogenetic abnormalities in the majority of the patients. A normal BMC karyotype was detectable in the patients with AML. Two (11%) patients with MDS were found to have structural chromosome abnormalities that differed from those detected in the total population of BMC and in isolated CD34+ cells. The differences of chromosome abnormalities in the hematopoietic and mesenchymal progenitor cells point to the fact that the stromal microenvironment is not part of the abnormal clone in MDS, however, it may be of great importance in the pathogenesis of the disease.

VCAM-1 expression on bone marrow stromal cells from patients with myelodysplastic syndromes.

We studied the expression of VCAM-1 adhesion molecules on stromal cells from the bone marrow of patients with myelodysplastic syndromes, healthy donors, and patients with chronic myeloproliferative diseases and acute leukemias. Expression of adhesion molecule on mesenchymal stromal cells from the bone marrow of patients and healthy donors was evaluated after 2-4 passages by the methods of immunoprecipitation and electrophoresis. VCAM-1 expression in the majority of patients with myelodysplastic syndromes was lower than in healthy donors. At the same time, VCAM-1 expression was not identified on mesenchymal cells from acute leukemia patients. VCAM-1 expression on cells from patients with chronic myeloproliferative diseases did not differ from that in healthy donors. We conclude that VCAM-1 synthesis in bone marrow stromal cells is impaired in patients with myelodysplastic syndromes and acute leukemias. These changes can be followed by the loss of relationships between hemopoietic cells and stromal microenvironment in bone marrow niches. Hemopoietic cells gain the ability for uncontrolled growth, which results in progression of the disease.

Liver abscess in human toxocariasis.

BACKGROUND: Toxocariasis is a parasitic infection caused by Toxocara canis or Toxocara cati. It is distributed worldwide. Liver is the main organ affected by Toxocara infection, typically with multiple eosinophilic infiltrates. Liver abscess formation is a very rare condition. METHOD: The authors report on a case of Toxocariasis infection with abscess formation in the right liver lobe. The diagnosis was made upon patient's history, clinical examination, use of ultrasonography, computed tomography and especially upon positive serologic test and hypereosinophilia. After unsuccessful conservative treatment (Mebendazole, antibiotics and corticoids), right hepatectomy was performed. RESULTS: The postoperative course was complicated by biliary fistula in the resection area. The complication was successfully managed by temporary stent implantation to the left hepatic duct. Six months after the operation, the patient is with no complications. CONCLUSION: Liver abscess formation is a rare condition associated with Toxocara infection. It is still a matter of debate whether liver abscess results from severe parasitic infection or whether human toxocariasis is a predisposing cause of pyogenic liver abscess formation. Liver resection is the only treatment option when sepsis fails to respond to conservative treatment (Fig. 5, Ref. 22).

[Persistent diarrhoea, hypotension, polyneuropathy]. / Perzistentní prujmy, hypotenze a polyneuropatie.

We present a case report of a 59-year-old man with a history of arterial hypertension and excision of malignant melanoma. He was admitted to the hospital because of two months history of diarrhoea, weight loss and circulatory collapse. In addition, the patient suffered from marked vegetative instability with symptomatic hypotension, polyneuropathy and progression of renal insufficiency, without proteinuria. Complex examination did not reveal neoplasms, endocrine, autoimmune, infectious or neurodegenerative disorders. A serial biopsy of colon failed to provide a clue to the diagnosis. However, AA amyloidosis was found on the kidney biopsy. Neither chronic inflammation nor malignancy was revealed and, hence, no causal treatment could have been established. The patient died from multiple organ failure. The autopsy confirmed systemic AA amyloidosis. The triad consisting ofdiarrhoea, polyneuropathy and hypotension should rise the suspicion on amyloidosis.

[Kinetics of proliferation, differentiation and transcription of genes regulating apoptosis in cultured human BCR/ABL+ Ph+-cells].

Ph+, bcr/abl+ cells arise due to t(9,22) chromosome translocation and Ph+ chromosome formation in hematopoietic stem cells. The cells show appreciable apoptosis suppression but retain their ability to differentiate and maturate. Ph chromosome, bcr/abl oncogene and Ph+, bcr/abl+ cells themselves are the hallmark of chronic myeloid leukemia. Under leukemia progression differentiating Ph+, bcr/abl+ cells transform into leukemic malignant cells with differentiation block. It is assumed to be a result of subsequent mutations or activation of proliferation of long silent Ph+ cells arisen previously in the stem cells because of the translocation. Real mechanism underlying the cell transformation remains unknown. This work was performed to develop a proper cell model allowing us to study functioning of differentiating Ph+, bcr/abl+ cells and their real transformation into malignant cells with block of differentiation. For this purpose we have investigated kinetics of Ph+, bcr/abl+ cells proliferation, differentiation, cell death and transcription of antiapoptotic genes in cultured 14-day of Ph+ mononuclear cells isolated from peripheral blood of a patient in chronic phase of chronic myeloid leukemia before treatment. The results obtained revealed that Ph+ cell differentiation proceeded in accord with characteristic scheme of chronic myeloid leukemia in vivo. Myeloid cells of hematopoietic cell lineage amounted to 3/4 of live Ph+ mononuclear cells undergoing accumulation and subsequent consumption in the course of differentiation. 95% myeloid cells were differentiating Ph+ granulocytes. The most deal of differentiating Ph+ cells was myelocytes. The rate ratio of myelocyte accumulation to its subsequent consumption showed that the rate of transformation into metamyelocytes was significantly decreased at this differentiation stage. Ph+ cells cultivation curves characterized cell death at different differentiation stages. There were observed the cell death of proliferating Ph+ cells and Ph+ myelocytes, and intensive death of mature cells as well. P/D index, that is ratio of immature Ph+ granulocytes differentiated by cell dividing (blasts, promyelocytes and myelocytes) to the cells differentiated without dividing (metamyelocytes and mature neutrofiles), revealed active of proliferation at the beginning of cultivation and unexpected new proliferative activity at the end of cultivation in the presence of growth factor. The peaks of antiapoptotic bcr/abl gene transcription activity coincided with the observed active proliferation at the beginning and at the end of cultivation. Cell proliferation, differentiation and apoptosis were noticeably accelerated by growth factor treatment. Thus, the study of the Ph+ cells cultivation kinetics is rather informative approach to investigation of continuous regulation of cellular and molecular processes in vitro in the case of chronic myeloid leukemia and allows more complete consideration of Ph+, bcr/abl+ cells hematopoiesis.

[Hyperhomocysteinemia--one of the factors underlying thrombotic complications in patients with chronic myeloproliferative diseases].

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.

[Chronic myeloproliferative diseases and pregnancy].

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.

Lifelong hematopoiesis in both reconstituted and sublethally irradiated mice is provided by multiple sequentially recruited stem cells.

OBJECTIVE: To evaluate the dynamics of stem cell production to hematopoiesis, the number of active stem cell clones and the lifespan of individual clones were studied. MATERIALS AND METHODS: The clonal contribution of primitive hematopoietic stem cells (HSC) responsible for long-term hematopoiesis was determined using two approaches. In one model, irradiated female mice were reconstituted with retrovirally marked male hematopoietic cells. In the second model, mice were irradiated sublethally without hematopoietic cell transplantation. In both models, bone marrow cells were serially sampled from the same mouse throughout a 12- to 20-month period and injected into irradiated recipients for analysis of day 10 colony-forming unit-spleen (CFU-S). The donor origin of CFU-S was determined by the presence of retrovirally marked cells or cells with chromosomal aberrations. RESULTS: The results of the two essentially different models show that 1) hematopoiesis is mainly the product of small clones of hematopoietic cells; 2) the lifespan of the majority of clones is only 1 to 2 months; 3) the clones usually function locally; and 4) the vast majority of the clones replace one another sequentially. Primitive HSCs capable of producing long-lived clones (about 10% among all clones), which exist during the entire life of a mouse, were detected by the radiation-marker technique only. CONCLUSION: Multiple short-living clones (at least on the level of CFU-S production) comprise the vast majority of the active stem cells in transplanted recipients or after endogenous recovery from sublethal irradiation.

[Biological effect of human erythropoietin in transgenic mice]. / Biologicheskii éffekt éritropoétina cheloveka u transgennykh myshei.

Transgenic mice were obtained inheriting the human erythropoietin gene under the control of viral regulatory elements. The reliable difference in haematocrit, the content of haemoglobin and percentage of reticulocytes in peripheral blood were not revealed. The level of serum erythropoietin in transgenic mice is several fold higher than in control mice. The increased pool of erythroid cells was observed in the bone marrow of transgenic mice, especially of normoblasts (3-fold) and reticulocytes (4,5-fold).

[The effect of treatment with human recombinant erythropoietin on the functional status of patients on maintenance hemodialysis]. / Vliianie lecheniia rekombinantnym chelovecheskim éritropoétinom na funktsional'noe sostoianie bol'nykh na podderzhivaiushchem gemodialize.

As many as ten patients with terminal uremia on maintenance hemodialysis (MH) performed from 11 to 52 months (28 +/- 4 on the average) were treated with recombinant human erythropoietin (rhERP) manufactured by Cilag (Switzerland). The preparation was injected i.v. in the initial dose 65 U/kg bw thrice a week after each session of MH. If the effect was lacking for 2 weeks, the doze was augmented by 25 U/kg (maximally up to 218 U/kg). Provided the Hb content increased to 100-120 g/l, the maintenance therapy was initiated (108 +/- 13 U/kg). The treatment lasted 17 +/- 2 weeks. As a result, the Hb content in the patients rose from 63.0 to 102.0 g/l, the hematocrit index from 21.2 to 34.4%, the red blood cell count from 2.09 to 3.18 x 10(12)/l; there was a transitory increase of the reticulocyte and platelet counts (from 2.2 to 3.3% and from 172.0 to 284.0 x 10(9)/l) whereas the leukocyte count remained unchanged. It has been demonstrated by the bicycle ergometry data that in addition to the amelioration of the hematological parameters, the patients showed an increase of oxygen consumption at rest, rise of the economy of energy losses at exercise, and a decline of oxygen "cost" of work. According to echocardiography, the patients manifested a reduction of the size of the left heart, of the minute and stroke volumes. In men, the treatment with rhERP brought about libido elevation in the absence of significant alterations in the blood gonadotrophin and testosterone concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Regulation of Proliferation and Differentiation ex vivo for Cells Containing Ph Chromosome in Chronic Myeloid Leukemia.

Cell regulation of Ph(+)cell proliferation and differentiation has been studied ex vivo in various chronic myeloid leukemia (CML) patients. The regulation is provided by alternation of effective stages of proliferation and maturation with inhibition of Ph(+) cell proliferation by accumulating neutrophils under apoptosis blockage. The alternation of stages consists of switching stage 1 (effective proliferation) to stage 2 (effective maturation) and proceeds according to the 1/2 -1/2/1 or 2/1-2/1/2/1 schemes. The kinetic plots of alternations pass through control points of crossing plots, where the parameters of proliferation and maturation are equal. The indices of P/D efficiency (ratio of proliferation and maturation rates) are 1.06±0.23 and don't depend on time, alternation order, or sources of Ph(+) cells - CML patients. During stages alternation, conversely, the parameters of Ph+ cell proliferation and maturation vary. The proliferation stages are characterized by increased proliferating cells content, a decreased number of neutrophils, and apoptosis induction. At the maturation stages, conversely, apoptosis is inhibited, the number of mature neutrophils increases, while immature Ph(+) cells decrease. High content neutrophils inhibit the proliferation of Ph(+) cells and impair their own maturation by inversion of maturation order, probably through a feedback mechanism. The regulation differences ex vivo reveal three types of Ph(+) cells from various individual CML patients, distinguished by the number and duration of alternating stages of proliferation and maturation. Ph(+) cells types 1 and 2 have one prolonged stage of effective proliferation or effective maturation with efficiency indices P/D(1) = 1-20 or P/D(2) ⇐ 1. At the same time period, the proliferation and differentiation of the Ph(+) cells type 3 proceeds with repeated alternations of stages with P/D(1) = 1-4 or P/D(2) ⇐ 1. Type 1 Ph(+) cells (~20%) were isolated from patients in advanced stages of CML, while Ph(+) cells types 2 and 3 (30 and 50% correspondingly) were isolated from CML chronic phase patients sensitive to chemotherapy.

Application of PRV-1 mRNA expression level and JAK2V617F mutation for the differentiating between polycytemia vera and secondary erythrocytosis and assessment of treatment by interferon or hydroxyurea.

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.

Defective adhesion and homing of hemopoietic precursors from the bone marrow of patients with myelodysplasia to stromal cells of normal bone marrow cultures.

Hemopoietic precursors from the bone marrow of patients with myelodysplastic syndrome were characterized by lower adhesion to normal stromal sublayer compared to bone marrow precursors from healthy donors, while adhesion to fibroblast monolayer and fibronectin was similar in bone marrow cells from patients and donors. In vitro experiments showed that the percentage of adherent hemopoietic precursors from the bone marrow of patients with myelodysplastic syndrome in normal stromal sublayer and fibroblasts was lower compared to healthy donors. The decrease in adhesive activity of hemopoietic precursors from the bone marrow of patients with myelodysplastic syndrome probably contributes to impairment of cell-cell interactions in the bone marrow of these patients.

[Effect of the lining of the thymus gland on hematopoietic stem cell kinetics in a suspension of embryonic mouse liver]. / Vliianie timicheskoi podlozhki na kinetiku stvolovykh krovetvornykh kletok v suspenzii émbrional'noi pecheni myshei

A study was made of the kinetics of hemopoietic stem cells in the organic culture of a suspension of mouse embryonic liver cultivated directly on the filters and on the preliminarily grown embryonic thymic feeder. It was shown that stem hemopoietic cells were retained in the course of one month of cultivation in the embryonic liver suspensions; during the first two weeks hemopoiesis in the suspension practically failed to differ from such in the fragments of the same age and cultivation period, whereas during the subsequent periods hemopoiesis proved to be more active in the suspension cultivated on thymic feeder. A possible participation of the thymus in the hemopoiesis is discussed.

[Determination of serum and plasma erythropoietin in mice with phenylhydrazine-induced anemia]. / Opredelenie aktivnosti éritropoétina v syvorotke i plazme myshei pri anemii, vyzvannoi fenilgidrazinom.

The simple, specific and sensitive erythropoietin bioassay in serum and plasma from phenylhydrazine treated mice is described, based on H3-thymidine incorporation into divided hemopoietic cells. Spleen cells taken from mice on the third day following the second of 2 daily injections of phenylhydrazine were cultured in 24 hours in the presence of test material. Following incubation for 2 hours with H3-thymidine solution radioactivity was measured.

[Plasma erythropoietic activity in children with sepsis]. / Eritropoéticheskaia aktivnost' plazmy u detei pri sepsise.

The low plasma erythropoietic (Epo) activity which is non-adequate to manifestation of anemia, and the lack of correlation between Epo activity and the degree of anemia and hypoxia were found in children with sepsis. The lowest Epo activity was determined in plasma of patients after repeatedly blood transfusion and in emaciated children. The non-specific Epo activity inhibitor was determined in acute period of sepsis in majority of patients. We suppose that the low Epo activity was due to the violation of Epo synthesis regulation mechanism or was connected with the presence of non-specific inhibitors. These results suggest recombinant Epo for the treatment of anemia in children with sepsis.

[Plasma erythropoietic activity in healthy children and in children with iron-deficiency anemia]. / Eritropoéticheskaia aktivnost' plazmy u zdorovykh i bol'nykh zhelezodefitsitnoi anemiei detei.

The level of plasma erythropoietic activity was determined in healthy and iron deficiency anemia children by bioassay in vitro. The erythropoietic activity in healthy children was 13.6 +/- 2.9 (5.0-24.8) mU/ml and the lowest activity was in two month (6.3 +/- 0.7) and three month (6.9 +/- 1.4) mU/ml healthy children. The erythropoietic activity was increased from 40.5 to 715.0 mU/ml in iron deficiency anemia children and its level distinctly depends on anemia stage and iron deficiency. From this study we suggest, that erythropoietin is produced in response of anemia. The results also demonstrate the necessity of erythropoietin treatment in iron deficiency anemia in early infants.

[Properties of eeythropoietin-independent mouse bone marrow precursor cells of the erythroid series]. / Svoistva éritropoétinnezavisimykh kletok-predshestvennikov éritroidnogo riada kostnogo mozga myshei.

The properties of early (BFUen) and late (CFUen) erythropoietin-independent progenitors were studied in bone marrow plasma clot cultures of mice. Syngeneic serum was used as a stimulant of colony formation. It was revealed that serum from polycytemic mice did not alter the efficacy of cloning the erythroid progenitors. Varying effects produced on erythropoiesis in vivo did not significantly change the number of CFUen and BFUen, with the exception of posttransfusion polycytemia where the number of CFUen showed a statistically significant rise. Assessment of radiosensitivity and proliferative activity of the erythroid progenitors showed that for CFUen Do=206 rad and n=1.3; for BFUen Do=118 rad and n=1.4; the proportion of proliferating CFUen was 42% +/- 12.5 and that of BFUen 46% +/- 4.5. The data obtained confirm the hypothesis of the erythropoietin-independent nature of the erythroid progenitors expressed under the culture conditions used.