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Biomedical subjects

G Prindull

Publications and source records attributed to G Prindull.

At least 55 records · Page 3Linked to original sources

Differential characterization of colony-forming units in diffusion chambers from pluripotent stem cells and progenitors of granulocytes/macrophages.

Colony-forming units in diffusion chambers (CFU-D), pluripotent stem cells (CFU-S) and colony-forming units in agar cultures (CFU-C) were studied in the bone marrow of weanling mice injected twice with hydroxyurea (HU). CFU-D, CFU-S and CFU-C were assayed 2 h, 2 days and 4 days after HU administration. After 2 h the total number of CFU-D/femur marrow cells did not change, while CFU-S and CFU-C decreased to 16.6 and 13.5% of control levels, respectively. On Day 2, CFU-D and CFU-S increased to 25 and 16.6%, respectively, above control levels and CFU-C was only 52% of the normal level. Four days after HU administration, CFU-S decreased steeply to 7.6%, CFU-D 80% and CFU-C to 32% of their pretreatment levels. Bone marrow of HU-treated weanling mice was also incubated in liquid medium where CFU-S decreased more rapidly than did CFU-D. It is concluded that CFU-D in weanling mice represent a noncycling and more primitive stem cell pool than CFU-S and probably constitute a reserve pool, the mobilization of which is secondary to that of CFU-S.

Animals↗

Changes of bone marrow stromal cells (MSC) in mice after drug induced eradication of hematopoietic cells: in vitro effects on normal bone marrow.

This study deals with murine marrow stromal cells (MSC) during hematopoietic regeneration. Regenerative marrow was induced in infant mice by two consecutive i. p. injections of hydroxyurea (HU) (2 X 1,000 mg/kg) which kill most cells in DNA synthesis. Two days later the marrow becomes enriched in pluripotent stem cells (CFU-S) and committed progenitors. It was found that fibroblastoid colony-forming-units (CFU-F) become concentrated approximately four fold above controls and give rise to significantly larger fibroblastoid colonies than CFU-F in control marrow. In split-phase semisolid agar cultures, i. e. adherent cells of HU-treated marrow (in under layers) and normal bone marrow cells (in upper layers), inhibition of G/M colonies in the upper layer in observed. In control split-phase cultures of both under layers and upper layers of normal bone marrow, CFU-C inhibition is by far less pronounced. In liquid cultures, pre-established adherent layers of HU-treated marrow have a stimulatory effect on normal marrow CFU-C. It is concluded that during increased demand for pluripotent stem cells and progenitors, such as after HU administration, marrow stromal cells and possibly other adherent cells produce inhibitory factor(s) of CFU-C differentiation. The inhibitory activity possibly is an effective mechanism for stem cell pool preservation. The differing effect of adherent cells of HU-treated marrow on CFU-C in liquid and in semi-solid medium suggests production of two different factors with opposing influences on CFU-C, depending upon the culture conditions.

Animals↗

Circulating myelopoietic stem cells (CFUc): high levels in healthy pre-term infants and reduced levels in sick pre-term infants.

In healthy and diseased pre-term infants at birth, levels of circulating CFUc are 2,586 +/- 3,063 (s. d.) and 269 +/- 292 (s.d.) per 5 X 10(5) lymphoid cells, as compared to data from the literature of 5 CFUc per 5 X 10(5) mononuclear cells from the blood of adults [8]. Hypotrophic infants have the lowest concentration of CFUc in the blood, namely 78 +/- 105 (s.d.). In formerly sick infants recovering from their perinatal illness, blood CFUc levels increase to approach those from healthy infants of the same age. Our results provide evidence that blood CFUc levels in pre-term infants reflect the strong myelopoietic activity of fetal bone marrow and suggest a correlation to the clinical status of the infant.

Female↗

Effect of hydroxyurea on two different types of hematopoietic stem cells (CFU-S and DCPC) of newborn mice.

Pluripotent hematopoietic stem cells from the bone marrow of newborn mice (9--13 days of age) have been studied following the administration of hydroxyurea (HU, 1,000 mg/kg). Following a single injection as well as a regimen of eight injections complete bone marrow reconstitution was achieved after 7 days. During the recovery phase diffusion chamber progenitor cells (DCPC) from pretreated newborn mouse bone marrow proliferated strongly to give significantly higher cell yields than DCPC from control animals. By contrast (colony-forming units-spleen [CFU-S]) levels were reduced at the same time to between 15 and 40% of controls suggesting a small-sized reserve pool of resting CFU-S in newborn mice. Assuming that DCPC are less differentiated than CFU-S and are non-cycling stem cells they may possibly pass through the CFU-S stage rapidly in newborn mice under the stress of hematopoietic reconstitution and proceed directly to myelopoiesis.

Animals↗

Dexamethasone binding to chromatin, inhibition of in vitro RNA synthesis, and therapeutic effect on human lymphosarcoma.

A very high degree of specific dexamethasone binding to chromatin and a marked in vitro inhibition of RNA-synthesizing capacity of purified lymphoma cell nuclei was found to correlate closely with the very strong cytolethal effect of glucocorticoids on lymphoma cells (in this case neither B- nor T-cells) of a young patient, whose condition rapidly and unexpectedly deteriorated after a total dose fo 90 mg of Prednisone given during a two day period; and in spite of prophylactic antihyperuricaemia treatment, the patient subsequently died. In this case the amount of glucocorticoid bound specifically by lymphoma chromatin was about 400% larger than is normally found in chromatin isolated from normal human thymus cells in persons on this age. The in vitro inhibition of RNA-Synthesizing activity measured with the aggregate enzyme and with isolated nuclei from lymphoma cell-nuclei by dexamethasone correlates closely to the specific dexamethasone binding capacity of chromatin. Thus a better prediction of the therapeutic effect of such lymphosarcoma cells to glucocorticoid may be possible.

Child↗

Rheological properties of young and aged human erythrocytes.

Rheological properties were studied of young and old human erythrocytes from healthy adults. Viscosity measurements of packed erythrocyte suspensions as well as filtration of cells through polycarbonate sieves show that young cells are more flexible than aged ones. Since deformability of erythrocytes is the product of cell shape, flexibility of the membrane and fluidity of the intracellular hemoglobin, we studied the manner in which these factors are relevant to the diminished flexibility of aged erythrocytes. The biconcave cell shape is maintained during the process of aging. The viscosity of packed ghost suspensions from aged erythrocytes is increased versus that of young ones. The diminished flexibility of old ghosts correlates well with their smaller cell volume. The fluidity of the hemoglobin in the interior of the cells is decreased as indicated by an increased hemoglobin content of the isolated ghosts. We conclude that aged erythrocytes loose their deformability as a result of both a decreased fluidity of the intracellular hemoglobin and a diminished flexibility of the membrane.

Blood Viscosity↗

Myelopoietic stem cells (CFUc) in the blood and bone marrow of children with acute lymphoblastic leukaemia and lymphosarcoma, cultivated without an exogenous supply of colony stimulating factor (CSF).

26 children with acute lymphoblastic leukemia (ALL) and 7 additional patients with lymphosarcoma in leukaemic transformation (LSA) have been studied with respect to the content of myelopoietic stem cell (CFUc) in blood and bone marrow. The methylcellulose culture technique (Iscove et al 1974) was employed in the absence of an exogenous source of colony stimulating factor (CSF). During active disease, CFUc colony formation was absent from patients with ALL, but was present in 2 patients with LSA. 2 therapeutic regimens were employed. Colony formation from bone marrow CFUc was highly variable during remission maintained by either regimen, with no clear relation to clinical stage, number of monocytes or circulating neutrophils. Patients with LSA consistently had high numbers of bone marrow CFUc. CFUc were low or absent from the blood. In conclusion, CFUc are absent from the bone marrow in active ALL, but may be present in active LSA. For the purpose of monitoring children with ALL during therapy, determination of blood or bone marrow CFUc was not found in this study to be helpful.

Antineoplastic Agents↗

Circulating haematopoietic stem cells (CFUc) in healthy and diseased pre-term infants.

During fetal life, haematopoiesis is in a physiologic state of rapid expansion. The activity of the pluripotent haematopoietic stem cell compartment of the bone marrow probably is reflected by the number and proliferative potentiality of CFUc in the blood circulation. We have studied, by the methylcellulose culture technique and without addition of exogenous colony stimulating factor (CSF), blood CFUc in pre-term and full-term newborn infants, in full-term infants 10 to 17 d of age, and in adults. Two groups of pre-term infants were studied: otherwise healthy infants and sick infants, including infants small-for-date and in perinatal distress. In healthy pre-term infants and in full-term infants 147 +/- 25 (SD) and 105 +/- 41 (SD) colonies per 100 000 lymphoid cells were formed, respectively. This is clear evidence for the presence in the blood of both. CFUc and CSF producing cells. By contrast, there was no or only slight spontaneous colony formation by sick pre-term infants, by older infants, and by adult.

Adult↗

[Multidrug chemotherapy of osteogenic sarcoma (author's transl)].

Osteogenic sarcoma may be treated effectively by radical surgical removal of the primary tumor and combined chemotherapy, including Adriamycin and high dose Methotrexate. In order to render any protocol a safe procedure, strict precautions are required to avoid drug toxicity. We present a protocol, "COSS 77", presently employed in several university hospitals of West Germany and Austria. Final results concerning long term prognosis and long term side effects are not yet available.

Doxorubicin↗

Fanconi's anaemia developing erythroleukaemia.

A 15-year-old boy with Fanconi's anaemia (FA) for 10 years developed acute erythroleukaemia. During the leukaemic phase, granulopoietic stem cells (CFUc) were absent from his bone marrow and blood, but proliferation and differentiation of bone marrow cells could be seen in semipermeable diffusion chambers in vivo, and globin synthesis of erythroblasts had become imbalanced. Chromosomal lesions of peripheral blood lymphocytes differed in the leukaemic phase from those in the pancytopenic phase. These data indicate that erythro-, myelo-, thrombo-, and lymphocytic cell lines all were involved in both the leukaemic and the pancytopenic process. It is suggested that terminal myeloproliferative disease developed as part of the natural history of FA.

Adolescent↗

Fetal blood-borne myelo- and thrombopoietic stem cells in diffusion chambers.

The potential of hematopoietic stem cells from cord blood for proliferation and differentiation have been studied by the diffusion chamber technique. In a pilot study, it was shown that blast cell production and myelopoiesis from the original lymphoid cell suspension starts 6 days after implantation. Mature granulocytes and megakaryocytes respectively appear in the chambers from the 16th and 10th days onwards. Myelopoiesis is ten times more active in fetal than in adult blood. There were thrombopoietic stem cells in 7 of 10 cord blood samples but in only one of 10 adult blood specimens. It is concluded that the high hematopoietic activity of the bone marrow at term is reflected by an increase in the number of stem cells circulating in the blood. Myelo- and thrombopoietic stem cells must be sought among the lymphoid cells of the original cord blood cell suspension.

Animals↗

Haematopoietic stem cells (CFUc) in human cord blood.

Colony forming units (CFUc) giving rise to myelocytic colonies in methylcellulose cultures were found among non-adherent mononuclear cells of human cord blood with a frequency of one in 1678. The number decreased makredly during the first 8 to 10 days of life. They were rarely detected in adult blood by this technique.

Adult↗