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Biomedical subjects

F Carbonell

Publications and source records attributed to F Carbonell.

At least 91 records · Page 5Linked to original sources

Ontogeny of the granulocyte/macrophage progenitor cell (GM-CFC) pools in the beagle.

The pattern of development of the granulocyte/macrophage progenitor cell (GM-CFC) pools in the course of canine ontogeny was studied by means of the agar culture technique. Colony formation was stimulated by colony stimulating activity (CSA) in serum from lethally irradiated dogs in combination with erythrocyte-depleted peripheral blood leukocytes from normal adult dogs. The colonies thus obtained in cultures from the different organs were in general large (estimated maximum 50 000 cells) and consisted predominantly of mononucleated macrophages, suggesting that, in these studies, a progenitor cell with high proliferative potential (HPP-CFC) has been monitored. In the yolk sac, a transitory GM-CFC pool became established between day 23 and day 48 of gestation, reaching maximum numbers of approximately 41 X 10(3) per organ on days 36/37. At the same time the GM-CFC concentration in blood collected from the heart also reached a maximum of about 31 X 10(3)/ml, indicating its carrier function for the migration of GM-CFC. In the liver a quasi-exponential increase in the GM-CFC numbers took place between days 36/37 and days 57 to 59 when a total of about 15.2 X 10(6) was found but thereafter and up to day 4 post partum the GM-CFC numbers decreased by almost two orders of magnitude. A continuous increase in the GM-CFC numbers was found in the spleen between day 42 of gestation and day 4 post partum when a maximum of 5.1 X 10(6) to 8.7 X 10(6) was reached. In contrast to the GM-CFC numbers in the liver, the splenic GM-CFC dropped only by 50% of peak values when the dogs reached adulthood. The bone marrow always had the highest incidence of GM-CFC, the concentration per 10(6) cells being 18.7 X 10(3)/10(6) cells on days 45/46, the earliest time point at which cultures could be set up. The absolute GM-CFC numbers in the two femora increased continuously between days 45/46 and day 4 post partum in parallel with the growth of the bones. In the thymus a relatively small population of GM-CFC developed between days 42 and 48 of gestation that was kept quite constant at average numbers between 13 X 10(3) and 30 X 10(3) up to day 4 post partum.

Animals↗

The seeding of a transplanted murine leukemia and its influence on hemopoietic stem cells and immune function of the host.

A butylnitrosourea-induced murine T-cell leukemia, L40, was transplanted in BDF1 mice; 1 X 10(3) cells killed all recipients after conditioning with 400 rad, whereas 1 X 10(5) were needed with normal recipients. No leukemic cells could be detected by transplantation or cytogenetic analysis in the femur or the spleen at day 6 after L40 inoculation and, at day 11, leukemic cells were found in one out of two experiments, more if the host had been irradiated. Up to day 17, when leukemic cells were present, the CFU-S and CFU-C content of the femur was normal, but later a loss was observed with an increase in the enlarging spleen. Lymphocyte-stimulation assays with spleen cells gave normal results up to day 17, but later the 3H-thymidine uptake of stimulated T and B cells was reduced. The NK-cell activity with and without stimulation by Corynebacterium parvum in the spleen began to fall at day 17 and was absent later; this loss was also observed with peritoneal exudate cells. In vitro mixing experiments of L40 cells with normal spleen cells showed "cold target inhibition" by L40 cells in the NK-cell assay as well as interference with the lymphocyte stimulation.

Animals↗

Chronic myelocytic leukaemia: cytogenetical studies on haemopoietic colonies and diffusion chamber cultures.

In 20 patients with chronic myelocytic leukaemia in the chronic phase or in blast crisis, several in vitro (CFU-C, BFU-E) and in vivo (diffusion chamber) culture techniques were used to demonstrate the existence of a still diploid cell clone. In 4 out of 12 patients in the chronic phase, Ph1-negative metaphases were found in the various cultures for haemopoietic progenitor cells but not in the standard suspension cultures used for cytogenetics. However, all the 8 patients investigated during blast crisis had only Ph1-positive and other abnormal clones, indicating the loss of the diploid clone during progression of the disease.

Acute Disease↗

Cytogenetic studies in chronic myeloproliferative disorders.

Cytogenetic studies were performed on 113 patients with the clinical diagnosis of a chronic myeloproliferative disorder: 70 were classified as chronic myelocytic leukemia (CML), 8 as polycythemia vera (PV), 10 as osteomyelofibrosis/sclerosis (OMS), and 15 as unclassified myeloproliferative disorder (UMPD). 2 patients, 1 with UMPD and 1 with subacute leukemia, were reclassified as CML after the cytogenetic study. In the group comprising PV, OMS, and UMPD, 28% (9/32) had a chromosomally abnormal clone. The chromosomes affected involved those reported to show nonrandom alterations in myeloproliferative disorders, namely the chromosomes, 1, 7, 8, and 9.4 patients exhibited a loss of the Y-chromosome.

Adult↗

The fate of cells with chromosome aberrations after total-body irradiation and bone marrow transplantation.

Cytogenetic studies were done on bone marrow cells and peripheral lymphocytes of four patients (three with acute nonlymphocytic leukemia, one with aplastic anemia) at various intervals up to 861 days after total-body X irradiation (TBI) at doses between 4.5 and 10 Gy (450-1000 rad) followed by syngeneic or allogeneic bone marrow transplantation. Whereas no radiation-induced aberrations could be found in the bone marrow, apart from a transient finding in the patient with the lowest radiation dose, aberrant metaphases were seen in the peripheral lymphocytes of three patients in the range from 2.5 to 46% even at 861 days after the exposure. There were no demonstrable aberrations related to TBI in the only patient developing graft-versus-host disease. The dicentric yield as determined in the aberrant metaphases with 46 centromeres ranged between 3.4 +/- 1.3 and 4.9 +/- 0.4. In one patient it was demonstrated by BUdR-labeling that after 10 Gy (1000 rad) TBI the surviving and heavily damaged lymphocytes can go into cell cycle and reach at least the third mitosis. The percentage of aberrant cells diminished by about 25% at each mitotic division.

Acute Disease↗

Chromosome changes in butylnitrosourea (BNU)-induced mouse leukemia.

G-banding analysis was carried out in 45 mice after exposure to the leukemogen butylnitrosourea (BNU). Of 27 animals without clinical signs of leukemia, 2 had chromosomal rearrangements (7%) while, of 18 leukemic mice, 5 showed abnormal karyotypes (28%). The chromosomal abnormalities were not random and showed preferential changes of chromosomes Nos. 14 and 15. The organ distribution of the chromosomal abnormalities showed a preferential involvement of the thymus with a secondary presence of chromosome anomalies in peripheral lymphoid organs and the bone marrow. The findings are discussed in relation to the recent reports on the specificity of trisomy 15 in murine leukemia and lymphoma.

Animals↗

Promotion of erythropoietic bursts in culture of human bone marrow by blood-derived Mononuclear cells.

In this report we give evidence that the addition of different amounts of irradiated mononuclear cells (MNC) from normal blood to bone marrow cell cultures containing erythropoietin produces an increase in number and size of erythropoietic bursts proportional to the number of irradiated MNC added. There was no consistent difference in the use either of autologous or of allogeneic MNC as burst-promoting activity source in normal individuals. Plating efficacy studies demonstrated that the number of BFU-E detected had a linear relationship to the number of bone marrow cells plated when 5 X 10(5) blood MNC were present as BPA source. A comparison between different preparations of human leukocyte conditioned media and 5 X 10(5) irradiated MNC, demonstrated that in all experiments irradiated cells stimulated the growth of a higher number of marrow-derived BFU-E. Therefore the use of 5 X 10(5) irradiated MNC from normal blood is proposed as standard BPA source in human bone marrow erythropoietic cultures.

Bone Marrow↗

Cytogenetic studies using HPCM-stimulated short-term liquid cultures of circulating hemopoietic precursor cells in patients with myelofibrosis.

Cytogenetic studies were performed on nine patients with myelofibrosis. Mononuclear cells from the peripheral blood were cultured for two days in the presence of human placenta-conditioned medium (HPCM) prior to the preparation of metaphases. Two patients showed abnormal clones. In one of them the Y chromosome was missing. In the other patient the abnormal clone was characterized by the involvement of the chromosomes 7 and 9 (46,XX,7q-,-9,+mar). The significance of cytogenetically abnormal circulating hemopoietic precursor cells in patients with myelofibrosis is discussed.

Adult↗

Chromosome banding patterns in patients with chronic myelocytic leukemia.

One hundred and nine patients with Ph1-positive chronic myelocytic leukemia were cytogenetically studied with banding methods. Seventy-eight patients were studied in the chronic phase and 39 patients in the blastic phase. The standard translocation was present in 107 cases. Two patients showed complex translocations involving chromosomes No. 6, 9, 22, 11 and No. 9, 22, 11, respectively. Ph1-negative cells were detected in 8 cases (7%). Chromosome aberrations in addition to the Ph1 chromosome were observed in 6 cases (8%) during the chronic phase. The karyotypic findings during the blastic phase were similar to those reported in the past [trisomy 8, iso(17q), and a second Ph1]. The significance of Ph1-negative cells, the geographic heterogeneity of the chromosomal aberrations, the effect of chemotherapy on the appearance of new clones, and the importance of the materials and methods used for the comparison of cytogenetic patterns at different laboratories are discussed.

Chromosome Aberrations↗

Ph1 -positive CML associated with megakaryocytic hyperplasia and thrombocythemia and an abnormality of chromosome no. 3.

A patient with Philadelphia (Ph1) chromosome positive chronic myelocytic leukemia is described, who had in blast crisis in addition an abnormality of chromosome No. 3; ins(3; 3)(q26; q21q26). This abnormality might be connected with hyperplasia of megakaryocytes and thrombocythemia, as recently reported in patients with acute leukemia. In the initial phase of the disease our patient had also thrombocythemia, hyperplasia of megakaryocytes with morphological abnormalities. Furthermore, when blast cells were culture in diffusion chambers, differentiation into several cell lines occurred but not into megakaryopoiesis. It is, therefore, concluded that the involved band on chromosome No. 3 might contain the locus which controls megakaryocytic proliferation and platelet production but additional factors seem to be required for their expression.

Bone Marrow↗

Effect of blood derived monocytes on the promotion of in vitro erythropoietic colony growth in human bone marrow cultures.

The effect of monocytes on the promotion of erythropoietic burst formation in human bone marrow methylcellulose cultures was studied in a burst-promoting activity (BPA)-poor system. Irradiated Ficoll-Isopaque separated blood mononuclear cells stimulated BFU-E growth proportionally to the number of irradiated cells added. Monocyte-depleted mononuclear cells stimulated as well as total mononuclear cells. Monocyte-concentrates stimulated when added at low concentrations. Monocyte-depleted mononuclear cells, although stimulatory at higher concentrations, did not stimulate at the concentrations used for monocyte-concentrates.

Bone Marrow Cells↗

Cellular composition of human fetal bone marrow. Histologic study in methacrylate sections.

The cellular composition of the human marrow was studied in thin sections of undecalcified bone 24 fetuses aged from 11 to 22 weeks of gestation, embedded in methacrylate and stained by the Giemsa method. This procedure provides much better cellular detail than the decalcified bone sections embedded in paraffin used in previous studies. Hemopoiesis is already present at the 11th week of gestation in the long bones of the extremities. The cellularity of their marrow increases during the 4th month and is abundant in the months thereafter. Its composition is similar to that of adults but differs by the presence of a large number of stromal cells and by the absence of plasma cells and lymph follicles in the fetal marrow. Differential counts for blood-forming cells and stromal elements are given for the initial period of marrow development.

Bone Marrow Cells↗