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PubMed2006

Hematopoietic stem cell senescence and long-term bone marrow injury.

Radiotherapy and chemotherapy are commonly used or treatment of cancer. Unfortunately, these treatments frequently cause acute and/or long-term bone marrow (BM) injury that can adversely affect the quality of life and the course of treatment. Our recent studies suggest that induction of hematopoietic stem cell (HSC) senescence by ionizing radiation (IR) and certain chemotherapeutic agents may contribute to long-term BM injury by impairing the ability of HSCs to self-renew. This suggestion is in agreement with a growing body of evidence demonstrating that HSCs from Bmi-1(-/-) and ATM(-/-) mice can lose their ability to self-renew by undergoing premature senescence. Interestingly, IR and different chemotherapeutic agents may induce HSC senescence and long-term BM injury in an agent-specific manner by activation of the p53-p21 and/or p16-Rb pathways. It will be of a great interest to determine if inhibition of these pathways can ameliorate radiotherapy and chemotherapy induced long-term BM injury.

Animals↗
PubMed2004

Myelodysplastic syndrome: from morphology to biology.

Myelodysplastic syndrome is characterized by ineffective hematopoiesis manifesting as peripheral cytopenia, despite adequate or increased cellularity in bone marrow. Increased intramedullary apoptosis is thought to be the mechanism underlying this phenomenon. However, the mechanisms leading to this increased apoptosis remain largely unknown. Although less apoptosis is seen in more advanced disease with increased blasts, apoptosis remains the major characteristic feature of this disease and data suggest that all cases are biologically similar, irrespective of the blast count. Myelodysplastic syndrome is a highly aggressive disease that carries a poor prognosis, especially in symptomatic patients. New therapeutic agents that target histone deacetylation, DNA methylation, or angiogenesis show promise, but focused biologic and therapeutic studies are needed to improve the outcome of this disease.

Apoptosis↗
PubMedDate not supplied

[Radiation injuries to mice in relation to the modes of administration of adeturon].

In experiments with mice the influence of adeturon, a preparation obtained in Bulgaria, on the survival rate, leucocytes dynamics, cellularity of bone marrow and spleen, and on nucleic acids in the peripheral blood has been investigated. The comparative analysis of the results obtained indicates that the protective and therapeutic administration of adeturon is more effective than a single injection of the drug immediately after irradiation.

Adenosine Triphosphate↗
PubMedDate not supplied

[The modifying effect of an electric current on the course of radiation injuries in animals].

A simultaneous action of the modified electric current and ionizing radiation (5.5-25 Gy) was shown to decrease the death rate, to increase the life-span of rats, and to induce the intestinal syndrome at higher doses than the action of each factor delivered separately. There was a correlation between the modifying effect and the faster restoration of cellularity of bone marrow and peripheral blood, and the number of nucleate enterocytes of the small intestine mucosa.

Animals↗
PubMedDate not supplied

[Effect of the radioprotector adeturon on radiation injury in mice with Lewis carcinoma of the lung].

A study was made of the radioprotective effect of Adeturon, a protective agent obtained in Bulgaria, on mice with Luis lung tumors exposed to fractionated radiation. The effect of the radioprotector on a radiation-induced injury to normal tissue was estimated by the number of leucocytes in the peripheral blood and its count, cellularity of bone marrow and spleen and the mass of the latter, and by the number of exogenous and endogenous CFUs. A pronounced radioprotective effect of Adeturon was implemented through maintaining or normalizing the indices under study impaired by tumor inoculation or irradiation.

Adenosine Triphosphate↗
PubMed1986

Haematological remission of leukaemic polymorphic immunocytoma following splenectomy. Case report with longitudinal immunological and cytogenetic studies.

A 56-year old man with a Rai stage IV B-cell chronic lymphocytic leukaemia (polymorphic immunocytoma according to the Kiel classification) of mu kappa-phenotype with a clonal chromosomal abnormality in cells from peripheral blood, bone marrow, and spleen is reported on. Following splenectomy (without further therapy) the blood lymphocytosis gradually decreased to normal and the patient entered a remission, assigned 42 months after splenectomy by immunological and cytogenetic studies that revealed no cells of clonal origin in blood or bone marrow. Utilizing cellular markers of clonality, we thus confirm that haematological remissions may follow splenectomy. A subsequently developed orbital lymphoma (without leukaemia) consisted of tumor cells derived from the initial leukaemia cell clone as indicated by their immune and cytogenetic phenotype. The case report is discussed in relation to previous reports on "spontaneous" remissions of lymphoid leukaemias.

Antigens, Neoplasm↗
PubMed1982

Peculiarities of erythropoiesis in patients with chronic renal failure.

In 600 patients suffering from chronic renal insufficiency the cellularity of bone marrow, erythroid cells proliferative activity, erythroid cells destruction and iron incorporation rate, data of ferrokinetics, intracellular iron distribution, porphyrin synthesis rate were examined. On the basis of the obtained data the suggestion is put forward that metabolic disturbances are important in anemia development in uremic patients. One of the aspects of this problem is the role of disorders in the protein turnover causing changes in the synthesis of globin and porphyrin which are the primary components for heme synthesis. Special importance is attached to the changes in iron turnover, i.e. to its redistribution between stromal and heme pools.

Anemia↗
PubMed1982

Shielding of the thymic region during X-irradiation: effect on haemopoiesis in mice.

The course of radiation damage and regeneration of the thymus and haemopoiesis were followed in mice after whole-body X-irradiation and in mice with the shielded thymic region during irradiation with 7 Gy, using several indicators (125IUdR incorporation, thymus weight, cellularity of bone marrow and changes in the peripheral blood leucocyte counts). It was demonstrated that radiation damage, manifested in a significant decrease in the values of the indicators studied immediately after irradiation, followed the same pattern in both groups, shielding, however, accelerated regeneration of the thymus and restoration of haemopoiesis. The favourable effect of thymic shielding was also reflected in a significant increase of LD50/30, and the dose reduction factor was equal to 2.

Animals↗
PubMed1994

Accumulation of 5-hydroxytryptamine by aging platelets: studies in a model of suppressed thrombopoiesis in dogs.

Thrombocytopenia was induced in healthy, male mongrel dogs by intramuscular injection of a single dose of estradiol valerate (1 mg/kg). A steady, almost linear decay of the blood platelet count starting about day 6 post-estradiol and attaining a mean value of 14 x 10(3) platelets/microliters one week later was observed. Thrombocytopenia is explained mainly by suppression of thrombocytopoiesis, as established by two independent ways: 1. Megakaryocytes in the bone marrow were markedly reduced. 2. Kinetic studies with 111In labeled autologous platelets revealed a nearly linear decay of the radioactivity and mean survival times within the expected range. The progressive reduction in the platelet count is associated with an increase in the mean age of the platelets still circulating. Following estradiol injection, platelet 5-hydroxytryptamine (5-HT) increased from a basal value of 130 +/- 30 ng/10(8) platelets (platelet count of 351 +/- 53 x 10(3) platelets/microliters) to 343 +/- 100 ng/10(8) platelets eleven days latter, when the platelet count dropped to 32 +/- 18 x 10(3) platelets/microliters. No significant changes in the number or affinity of the 5-HT uptake receptors could be demonstrated in platelets exposed in vitro and in vivo to estradiol. Our results indicate that aging platelets accumulate 5-HT, probably by a sustained exposure to the monoamine in plasma, confirming previous observations based on models in which thrombopenia was induced by immune and mechanical means.

Animals↗
PubMedDate not supplied

[The link between the prognostic factors in acute leukemia and patient age].

A total of 464 case records of those patients with acute leukosis 15 to 80 years old have been analysed. Age was found to have unfavourable potential for achieving complete remission as well as length of life of the patients. Other parameters of prognostic significance for the course of acute leukosis (cellularity of bone marrow, enlargement of peripheral lymph nodes, percentage of blast cells in haemogramme and myelogramme, thrombocytopenia) were not recognized to be directly age-associated. Age appeared to correlate significantly with infectious complications, pneumonia, as an immediate cause of death of the patients.

Adolescent↗