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Biomedical subjects

J Neuwirt

Publications and source records attributed to J Neuwirt.

At least 73 records · Page 4Linked to original sources
PubMed1978

Disappearance of haemopoietic stem cells from blood after hydroxyurea.

Haemopoietic stem cells were examined in the blood of mice which had been injected with hydroxyurea. It was observed that the amount of CFU in the blood quickly decreased and after higher doses of hydroxyurea CFU completely disappeared from blood. Since CFU are rather resistant to the killing effect of hydroxyurea, it is assumed that the observed effect is caused either by an interference of hydroxyurea (due to its effect on the blood-forming tissues) with the migration of CFU into blood or by stimulating the removal og CFU from blood.

Animals↗
PubMed1977

The onset of hemoglobin synthesis in spleens of irradiated mice after bone marrow transplantation.

Messenger RNA (mRNA) for globin was isolated from spleens of irradiated mice in which erythroid differentiation was induced by a bone marrow graft. The globin mRNA was isolated either by means of sucrose gradients of reticulocyte polysomal RNA or by affinity chromatography of total spleen RNA on poly (U)-sepharose. The globin mRNA was tested in a wheat embryo cell-free system. The appearance of mRNA in the spleen erythroid colonies was correlated with other parameters of erythroid differentiation such as globin synthesis, activity of delta-aminolevulinic acid synthetase and iron uptake. Poly(A) containing mRNA did appear already on the 3rd day after grafting. However, significant translational activity of globin mRNA could be demonstrated only one day later together with the increase in globin synthesis and delta-aminolevulinic acid synthetase and enhanced iron uptake. In the second part of this study mouse spleen cells rich in erythroid elements were incubated with a specific heme synthesis inhibitor (isonicotinic acid hydrazide, INH) and the synthesis of 9 S RNA was estimated. It was found that a 40-minute incubation with INH reduced uridine incorporation into 9 S RNA fraction by about 40%.

5-Aminolevulinate Synthetase↗
PubMed1977

Bone marrow cell separation on Ficoll gradient.

Cell fraction from rat and murine bone marrow were obtained by sedimentation at unit gravity. A linear gradient of polymerized sucrose (Ficoll) was used and some properties of individual cell fractions were studied. The 3rd cell fraction containing the lymphoblasts and lymphocytes contained also stem cells.

Animals↗
PubMed1977

Effect of hydroxyurea and vinblastine on the proliferation of the pluripotential stem cells.

The population of the pluripotential hemopoietic stem cells in mice, i. e. those cells forming colonies in the spleens of lethally irradiated mice (colony forming cells CFc) is proliferating relatively slowly. After a partial damage the population regenerates which is achieved by means of the increased proliferation rate. The effect of damage caused by different doses of hydroxyurea or vinblastine on the proliferation of the CFc has been investigated. CFc population was measured in femur bone marrow after grafting the sample of the bone marrow into the lethally irradiated mice recipients (spleen colony method). The proliferation rate was estimated either according to the magnitude of the fraction of cells synthesizing DNA in the S phase of the cell cycle, or according to the sensitivity of the population to the repeated injections of vinblastine. Data showed that even after very minute damage caused by hydroxyurea the stem cells started to proliferate intensively. The effect was dose dependent. The comparable damage caused by vinblastine had a significantly weaker effect on the proliferation of the stem cells. From the results it is concluded that the proliferation response of the pluripotential stem cells depends on two factors: one being the extent of the damage caused to the hemopoietic tissue and the second the position of the killed cells in the cell cycle.

Animals↗
PubMed1977

[Changes of erythrocyte criteria of the guinea pig under hypoxia].

In the present study the adequacy of erythrocytic criteria for the diagnosis of hypoxia has been investigated in animal experiments. Guinea pigs were exposed to a defined hypoxia (pO2 equals 48 mm Hg approximately equal to 9000 m height) for 24 and 72 hrs. With increasing duration of hypoxia there is observable a distinct rise in reticulocyte count, 59Fe incorporation and the proportion of erythroblasts in the bone marrow. Hematocrit and hemoglobin concentration have increased significantly after hypoxia compared with the control animals. The mean cellular hemoglobin content shows a marked fall with the duration of hypoxia. The density distribution curves show under hypoxia a shift to lower densities and, therefore, appear to be well suited for the diagnosis of hypoxic states. The activities of the erythrocytic enzymes, G-6-PD and GOT, are increased after 24 and 72 hrs of hypoxia. The GOT isoenzyme pattern is shifted with continued hypoxia in favour of the mitochondrial GOT. The changes of enzyme activities are not pronounced enough under hypoxic conditions to be used for diagnositc purposes.

Animals↗
PubMed1976

Control of haemopoietic stem cell proliferation by cells in DNA synthesis.

It has been demonstrated that for the slowly proliferating population of the haemopoietic pluripotent stem cells (CFUs) the response after damage by hydroxyurea to cells synthesizing DNA differs from that after damage by colchicine to cells entering mitosis. The killing of DNA synthesizing cells elicits increased proliferation in the CFUs population. From this it has been inferred that cells in the S phase may inhibit the entry of nonproliferating GO cells into the cell cycle and in this way control cellular proliferation.

Animals↗
PubMed1976

Study on the proliferative state of haemopoietic stem cells (CFU).

Hydroxyurea was used to study the proliferation rate of haemopoietic stem cells (CFUs) in normal mice, after irradiation or transplantation into irradiated recipients. It was demonstrated that the proliferation rated of endogenous CFUs (endo-CFUs) and exogenous CFUs (exo-CFUs) are identical. After irradiation (650 R) the surviving endo-CFUs begin to proliferate immediately. By contrast exo-CFUs transplanted into the irradiated recipient mouse (850 R), begin to proliferate only after about 30 hr. However, injection of isoproterenol (which stimulates adenyl cyclase) or dibutyryl cyclic adenosin 3',5'-monophosphate shortly after marrow cell graft, triggers the transplanted CFUs into cell cycle as shown by an almost immediately increased sensitivity to hydroxyurea. Isoproterenol is capable of inducing DNA synthesis also in stem cells of normal mice but it takes about 20 hr before CFUs become to be increasingly sensitive to hydroxyurea.

Animals↗
PubMed1976

Study of the effect of hydroxyurea on the erythropoietin-sensitive cells.

The response of polycythaemic mice to a standard dose of erythropoietin has been measured at various time intervals after single or repeated injections of hydroxyurea. The results exclude S phase of the cell cycle as the period responsive to erythropoietin. They suggest the existence of feedback mechanisms within the cell cycle, operating at the G1--S boundary and within the G1 phase. Hydroxyurea given to polycythaemic mice at various time intervals after erythropoietin induced characteristic changes in the response. These changes can be explained if both gradual transit of differentiated cells into the DNA synthesis (S phase) and changes in amount of the erythropoietin sensitive cells caused by the feedback mechanisms operating in the cell cycle are considered.

Animals↗
PubMed1976

Proliferation rate of haemopoietic stem cells after damage by several cytostatic agents.

The haemopoietic tissue of mice was damaged by different cell-cycle-stage specific and cell-cycle-stage non-specific cytostatic agents. The proliferation rate among the surviving pluripotential stem cells, i.e. those cells forming colonies in spleens of lethally irradiated mice (CFUs), was then investigated. The results suggest that, at least in the CFUs population, the cells which synthesize DNA in the S phase of the cell cycle inhibit the entry of the non-proliferating GO cells into cell cycle. This evidence was based on the ability of three cytostatic agents, hydroxyurea, cytosine arabinoside and methotrexate, which are toxic specifically to the S phase cells to increase the proliferation in the CFUs population. This increase was quite out of proportion to the small amount of damage they caused to the population. Colchicine, which kills cells in mitosis, and ionizing irradiation, damaging cells in all stages, proved to be much weaker stimulators of proliferation. It has been suggested that a mechanism for the control of cellular proliferation might be based on the negative feedback in the cell cycle. In this feedback control loop the cells which are preparing for cell division in the S phase of the cell cycle inhibit the entry of the non-proliferating GO cells into cell cycle.

Animals↗
PubMed1976

Species specificity of guinea pig erythropoietin.

Various stimuli (hypoxic hypoxia, bleeding, carbon monoxide hypoxia and cobalt administration), well known to increase erythropoietin plasma level in many species including man, failed to increase the erythropoietin activity in plasma of guinea pigs when measured in the polycythaemic mice assay. Nevertheless, the plasma of these guinea pigs stimulated the erythropoiesis in polycythaemic guinea pigs which, however, failed to respond to rat erythropoietin. From this it was concluded that not only the erythropoietin, but also the erythropoietin responsive cells in the bone marrow of guinea pigs are species specific. Bilateral nephrectomy in guinea pigs exposed to hypoxia prevented the increase in the erythropoietin plasma level, thus suggesting that, similarly as in other species, also in guinea pigs the kidney is the main organ of erythropoietin elaboration. The species specificity of guinea pig erythropoietin - erythropoiesis system is an interesting exception among mammals, since the erythropoietin of a large number of species belonging to this class was demonstrated to lack species specificity.

Animals↗
PubMed1976

Haemoglobin types in peripheral blood and bone marrow cells in rats after a single blood loss.

The authors studied quantitative changes in the synthesis of haemoglobin types in rat peripheral erythrocytes and in the cells of the bone marrow erythrocytic series after a single blood loss. They demonstrated that raised synthesis of given haemoglobin types could be found in the peripheral cells 5-7 days after blood loss. These changes could already be detected in the bone marrow cells 24 hours after blood loss. The question of the probable site and level of the origin of altered haemoglobin synthesis is discussed.

Animals↗
PubMed1975

Erythropoietin formation in rats with experimental hypersplenism.

Splenomegaly accompanied by anaemia, increased reticulocyte and decreased thrombocyte counts, was induced in Wistar rats by a long-term intraperitoneal administration of methylcellulose. Compared to controls, hypersplenic rats showed significantly enhanced utilization of 59-Fe by red cells and increased titre of erythropoietin. After the exposure of rats to hypoxic hypoxia corresponding to an altitude of 7,000 m for 6 h, no difference in the erythropoietin titre was found in either group. The results suggest that experimental hypersplenism alone does not affect the production of erythropoietin and does not stimulate the formation of an inhibitor of erythropoietin or erythropoiesis. The increased titre of erythropoietin and enhanced utilization of radioiron by red cells in rats with hypersplenism were found to be due to haemolytic anaemia leading to the stimulation of erythropoiesis.

Anemia, Hemolytic↗