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Biomedical subjects

P Ponka

Publications and source records attributed to P Ponka.

At least 91 records · Page 5Linked to original sources
PubMed1981

Decreased sensitivity to hydroxyurea and to [3H]thymidine suicide in the middle of the S phase.

Pluripotent haemopoietic stem cells (CFUs) move synchronously through the cell cycle in hydroxyurea-treated mice in a cohort 1--2 hr broad. Ten to fifteen hours after hydroxyurea they pass through S phase. DNA synthesis appears to be depressed 5--10 times when the cells are in the middle part of the S phase but does not seem to be completely interrupted. High concentrations of [3H]thymidine must be used for 'suicide' in order to achieve lethality for the cells with depressed DNA synthesis. At the time when DNA synthesis is depressed, the sensitivity of the cells to hydroxyurea also decreases. This may lead to a significant underestimation of the S phase fraction by the hydroxyurea method, because CFUs with low DNA synthesis rate are resistant to hydroxyurea although being in S phase.

Animals↗
PubMed1980

Iron and transferrin distribution in reticulocytes incubated with heme synthesis inhibitors.

A high level of non-heme iron (either labelled or unlabelled) in mitochondria, ferritin and low-molecular-weight pool of reticulocytes was induced by preincubation with isonicotinic acid hydrazide or penicillamine together with either 59Fe- of 56Fe-labelled transferrin. Addition of apotransferrin during reincubation of 59Fe-labelled reticulocytes was accompanied by the transfer of 59Fe from low-molecular-weight pool to transferrin, which was found in the reticulocyte cytosol both free and bound to a carrier. Similarly, when cells were reincubated with 125I-labelled transferrin, more 125I-labelled radioactivity was found, in both free and carrier-bound transferrin peaks, in reticulocytes with a high level of low-molecular-weight cold iron than in control ones. These results suggest that transferrin enters reticulocytes and takes up iron from low-molecular-weight pool.

Animals↗
PubMed1980

Biliary iron excretion in rats following pyridoxal isonicotinoyl hydrazone.

Biliary excretion of iron after administration of pyridoxal isonicotinoyl hydrazone (PIH), a recently identified effective iron-chelating agent, was investigated in rats. PIH administered both intraperitoneally and orally was shown to increase significantly 59Fe excretion into bile of rats which had previously been injected with 59Fe-transferrin to label hepatic parenchymal cells. 59Fe-PIH appears in bile as early as 15 min after chelator administration and the peak of 59Fe-radioactivity in bile is seen 1--5 h following intraperitoneal PIH injection. PIH, administered intraperitoneally, 125--250 mg/kg, increased 24 h biliary radioiron excretion about 35 times and in addition increased urinary and faecal iron excretion. When PIH was given immediately before 59Fe-transferrin, 24 h cumulative biliary 59Fe excretion was even higher. PIH was also demonstrated to increase biliary excretion of radioiron released from 59Fe-haemoglobin catabolysed in reticuloendothelial cells. The effect of PIH was confirmed by estimation of biliary iron concentration using the method of atomic absorption spectrophotometry. Repeated PIH administration to rats decreased 59Fe radioactivity in liver and kidney and increased urinary and faecal iron excretion.

Animals↗
PubMed1979

Effect of some cytostatics on the haemopoietic stem cells (CFUs) in blood.

The effect of some cell-cycle stage-specific cytostatics on the pluripotent stem cells (CFUs) present in the blood was investigated. The amount of these cells in the blood responds markedly and very quickly to a single administration of any of these drugs. Their effects on the circulating CFUs allowed the drugs tested to be divided into groups: (1) Hydroxyurea and arabinosyl cytosine induced a profound decrease in the number of CFUs in the blood, which was followed by a return to the normal value and an overshoot that lasted several days; (2) Colchicine, vinblastine, vincristine, and methotrexate first induced an increase in the number of CFUs in the blood, which was followed by a decrease to below the normal values, and still later an overshoot that lasted several days. The preliminary data on the effect of hydroxyurea on the CFUs circulating in large quantities in the blood of mice with Friend virus leukaemia indicate that the tumorous stem cells (CFUs) might respond to these cytostatics in a similar way.

Animals↗
PubMed1979

Effective iron chelation following oral administration of an isoniazid-pyridoxal hydrazone.

When isoniazid and pyridoxal are mixed in equimolar quantities a hydrazone is formed which is able to complex with iron. The oral administration of this compound to rats in single doses of 25--100 mg/kg leads to an increase in faecal iron excretion up to 8 times the normal level. In tissue culture the compound is able to remove iron from Chang cells. The results suggest that this compound may be of potential value for the oral therapy of iron overload.

Animals↗
PubMed1978

Changes in stem cell compartments in mice after hydroxyurea.

Hydroxyurea injection kills only approximately 10% of CFUs which are in the S phase of the cell cycle. In mice given a single injection of hydroxyurea CFUs in the femur decreased only about 50% in 2--4 days after hydroxyurea, and then started to return to normal levels with an overshoot evident after the eighth day after hydroxyurea. CFUs in spleens of mice given a single injection of hydroxyurea show an evident overshoot as early as 3 days after the drug, reaching levels which are about 300% of normal. CFUs from blood disappear rapidly, but equally rapidly return to normal values followed by a significant overshoot. The radioresistance of mice increased up to 4 days after hydroxyurea.

Animals↗
PubMed1978

A contribution to the technique of mouse bone marrow cell culture in semisolid agar.

A method of cultivation of mouse bone marrow cells in semisolid agar is described. Colony-stimulating factor was provided either by a "feeder layer" containing kidney cells (from 8-day-old mice) or by the addition of "lung conditioned medium" or post-endotoxin serum. The effect of various factors and media on the formation of colonies was tested. The best growth of colonies was observed in medium RPMI 1640 or in Eagle's minimal essential medium containing 0.2% bactotryptose supplemented with 20% foetal calf serum. Both the morphology of cells found in the colonies and the proliferative state of the cells that give rise to colonies indicate that CFU-C represent the committed progenitor for myelopoiesis.

Agar↗
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↗
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↗