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N G Testa

Publications and source records attributed to N G Testa.

161 records · Page 9Linked to original sources

Radiation induced hemopoiesis in adult mouse liver.

Repeated whole-body irradiation of adult mice induced hemopoiesis in liver, as shown by the presence of stem cells (CFUS), progenitor cells of granulocytes and macrophages (CFUC) and foci of granulocytic cells. The largest numbers of CFUS (up to 700) were found 24 to 47 days after four doses of 450 rad x-rays given at 24 day intervals and 15-17 days after 2310 rad gamma radiation given at a low dose-rate (70 rad per day). CFUS were still present (although in smaller numbers) up to 210 days after four doses of 375 rad x-rays or 225 rad neutrons. CFUC were also present in liver after four doses of 450 rad x-rays, but their numbers could not be calculated accurately because of the marked inhibitory effect of liver cells on in vitro colony growth. Irradiation with one dose of 450 rad x-rays did not result in the appearance of CFUS in liver, suggesting that hepatic hemopoiesis can be induced by radiation only after repeated or prolonged bone marrow injury.

Animals↗

Lack of effect of a granulocyte proliferation inhibitor or their committed precursor cells.

Using the agar culture technique, we have measured the effect of granulocyte extracts GCE (and of erythrocyte-RCE and lymph node extracts-LNE) on the growth and proliferation of the committed granulocytic precursor cells, CFU-C. In addition we have determined their effects on the proliferation of the developing colony cells and on the ultimate cell production in the colonies. The results show that GCE has no effect on the growth or proliferative activity on the CFU-C. It does, however, reduce both the autoradiographic labelling indices of the developing colony cells and the net colony cellularities, acting as a cell cycle modulator. These are effects specific to the GCE since at the dose levels used, neither RCE nor LNE affected these measurements.

Animals↗

The relative spatial distributions of CFUs and CFUc in the normal mouse femur.

Femoral bone marrow was divided longitudinally into two groups of cells of varying size. By assaying CFU and CFU in the two zones of the marrow, their distributions across the diameter of the femur was determined. It is shown that the concentration of CFU increases from the femoral axis (15 CFU/105 bone marrow cells) to the bone surface (44 CFU/105 cells), obeying approximately a square-law relationship. The CFU concentration, on the other hand, increases from the femoral axis (32CFU/105 cells) to a peak value (260 CFU/105 cells) at about 330 um from the axis and thence falls off against to the bone surface (77 CFU/105 cells). Selective kinning cells in DNA synthesis using the tritiated thymidine suicide technique, in vivo, showed that CFU, near the bone surface are proliferating at a faster rate than those more distant from bone, but that CFU have a fast proliferation rate irrespective of their position in the distribution. Thus, bone marrow cell populations are shown to conform to a well-defined spatial organization corresponding to the chronologic relationships between marrow cells.

Animals↗

Properties of peripheral blood and cord blood stem cells.

Mobilized peripheral blood and cord blood are used for transplantation in adults and children. Currently methods which assess the engraftment potential of these cells rely on nucleated cell count, clonogenic colony assays (GM-CFC) and CD34+ cell enumeration. However, data have accumulated which indicate that the cells responsible for short-term and long-term engraftment are different and may be identified by a variety of techniques, including immunophenotyping, in vitro and in vivo assays. There is also evidence that primitive cells in peripheral blood progenitor cell grafts and cord blood are heterogeneous, as cells with similar functional behaviour express different phenotypes. Despite intensive research, the isolation and identification of a homogeneous population of human stem cells is still elusive. Nevertheless, it is possible to obtain CD34+ subpopulations enriched in primitive cells with many of the properties expected of stem cells. Using these cell fractions, the cytokines that induce proliferation, amplification, differentiation and self-renewal are being defined in order to develop improved protocols for expansion of specific populations. From these studies a number of interesting facts have emerged. Certain growth factors frequently used for progenitor cell expansion and gene transduction studies also induce differentiation and impair long-term engraftment. Further, the cytokines required for progenitor cell expansion are probably different to those which favour expansion of the primitive cells, with both the cell cycle status of CD34+ cells as well as the implication of telomere shortening probably needing to be considered where ex vivo manipulation is contemplated.

Antigens, CD34↗

In vitro effects of recombinant human megakaryocyte growth and development factor on primary human tumour colony growth.

A study was made of the in vitro effects of recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on breast, prostate, cervix and colon cancers. Tumour growth was assessed using a soft agar clonogenic assay. Stimulation of megakaryocyte numbers was seen in liquid culture following 10 ng/ml PEG-rHuMGDF. The same concentration led to no significant difference in colony-forming efficiencies for 22 of 25 tumour samples. A significant reduction in colony-forming efficiencies was seen for the remaining 3 specimens. These results suggest that PEG-rHuMGDF will not stimulate tumour growth in vivo.

Breast Neoplasms↗

Long-term bone marrow damage in experimental systems and in patients after radiation or chemotherapy.

Long-term bone marrow damage, characterised by stem, progenitor and stromal cell abnormalities is a frequent occurrence after cytotoxic treatments. The relative contributions of each of these components are difficult to analyse, especially in the case of patients who have received combined chemotherapy. The damage may be latent, and not manifested in low numbers of mature functional cells in the blood, but may become apparent as an hypoplastic syndrome at later times. Little tendency of recovery to normal parameters is seen in experimental animals and in patients.

Animals↗