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Biomedical subjects

M Y Gordon

Publications and source records attributed to M Y Gordon.

At least 145 records · Page 8Linked to original sources
PubMed1978

Simultaneous assay by six methods of the effect on haemopoietic precursor cells of adriamycin, methyl CCNU, 60Co gamma-rays, vinblastine, and cytosine arabinoside.

The spleen colony assay, three agar colony assays and two repopulating assays have been employed to measure the effect of single doses of adriamycin, methyl CCNU, 60CO gamma-rays, vinblastine and repeated injection of cytosine arabinoside on early haemopoietic precursors. The results show that there is no consistent correlation between the effect of these agents on the six assays, and the differences in proliferation rate of the cells contributing to the various assays could not be demonstrated by the phase specific agents vinblastine and cytosine arabinoside. The relatively high survival of granulocyte repopulating ability after adriamycin and methyl CCNU indicates that the capacity for differentiation and maturation can be influenced by cytotoxic agents so that colony assays while estimating the number of progenitor cells surviving do not necessarily provide a reliable guide to the capacity of the cells for restoring haemopoiesis. Comparison of colony formation by normal bone marrow cells with the three agar colony assays showed that the agar diffusion chamber method gave three times as many colonies and a much smaller variation between experiments compared to the in vitro agar assay with endotoxin mouse serum as colony stimulating factor. The thin layer feeder cell method gave an intermediate number of colonies.

Animals↗
PubMed1977

Responsiveness to humoral factors of mouse marrow colony forming cells after treatment with cyclophosphamide.

Humoral factors affecting granulopoiesis have been detected by culturing bone marrow cells in intraperitoneal diffusion chambers. This study investigated the possibility that treatment with drugs alters the ability of cells to respond to these factors. Three days after treatment with 200 mg kg-1 cyclophosphamide, donor marrow cells were more responsive than normal cells to the factors produced in cyclophosphamide pretreated hosts. The optimum timing of host pretreatment for maximum colony stimulation also differed for cells from cyclophosphamide treated and untreated donors and these effects were found to depend on the dose of drug given to the animals.

Animals↗
PubMed1977

Colony-forming ability of marrow from patients receiving immunotherapy during chemotherapy-induced remission in acute myeloid leukaemia.

An in vivo culture system, the agar diffusion chamber technique, has been used to measure the population of colony-forming precursor cells in the bone marrow of patients receiving immunotherapy during acute myeloid leukaemia in remission. The results of these assays indicate that (1) the level of committed granulocytic stem cells usually remains below the range found in normal marrow throughout remission, and (2) the maintenance of adequate cell counts in the blood may be due to increased cell production by these early granulocytic precursor cells. The relevance of these findings to the possible protective effect of immunotherapy against cytotoxic chemotherapy is discussed.

Adolescent↗
PubMed1977

Comparative studies of humoral factors stimulating granulopoiesis in agar in vitro and in diffusion chambers.

The factor stimulating granulopoiesis in diffusion chambers (DCF) was compared with the CSA in post-EMS in two ways: (1) Mouse bone marrow cells were maintained in suspension cultures, containing DCF or EMS, which were assayed at intervals for colony-forming cells, both in agar in vitro and in diffusion chambers. (2) The enhanced growth seen in chambers incubated in pretreated mice was compared with the CSA of serum and DCF recovered from these animals. The results show that the cells forming granulocytic colonies in agar in vitro and in diffusion chambers are closely related, if not identical, and that different sources of CSA may differ in their ability to maintain precursor cell numbers in suspension culture. The CSA of DCF did not correlate with growth enhancement in diffusion chambers or with the levels of CSA in the serum.

Animals↗
PubMed1977

The effect of peripheral blood contamination on colony yield from human bone marrow aspirates.

Serial bone marrow aspirates were taken from a single site in each of nine individuals. The colony forming capacity of these samples, measured by culturing the cells in semi-solid agar in diffusion chambers, fell as the aspirate volume increased. Comparison of the results from different individuals showed that this effect was consistent within the group and may be useful as a simple method for standardizing results from human bone marrow cultures.

Bone Marrow↗
PubMed1976

A colony-forming assay for human tumour xenografts using agar in diffusion chambers.

A technique for growing colonies from single-cell suspensions of human tumour xenografts using agar in diffusion chambers is described. Modified Millipore diffusion chambers containing tumour cells in semi-solid agar-medium were implanted into the peritoneal cavity of pre-irradiated mice and provided standard culture conditions for the study of colony-forming cells. All 11 xenograft tumours so far studied produced colonies. The incubation period for colony growth ranged from 12 to 28 days and the plating efficiency ranged from 0-3% to 16% for different tumours, but both parameters were constant for each individual tumour. The reproducibility of the system provides a colony-forming assay which can be used to study the effects of irradiation and cytotoxic drugs on human tumour clonogenic cells and may therefore have some advantages over similar assays based on experimental animal tumours.

Agar↗
PubMed1976

Distribution of granulopoietic activity in the human skeleton, studied by colony growth in agar diffusion chambers.

The colony forming ability of bone marrow cells from 110 haematologically normal patients was investigated by their growth in semi-solid agar in intraperitoneal diffusion chambers. Marrow aspirated from the sternum showed a consistently higher colony yield than that from the iliac crest. Study of site variation in the individual was possible in donors for bone marrow transplantation. In each of four cases, sternal marrow produced more colonies than any other site. Examination of smears made from the aspirated samples suggested that the difference in yield was not due to varying dilution by peripheral blood on aspiration from different sites. It is concluded, therefore, that the incidence of colony precursor cells is not uniform throughout the active marrow.

Agar↗
PubMed1976

Some in vivo effects of pi mesons in mice.

The effect of 70 MeV pi mesons was studied to determine the effectivness of such beams aginst normal tissues in vivo. The end points included thymic weight loss, oocyte and bone marrow CFU-S survival and the induction of macroscopid lens opacities. The results indicate that pi mesons are not signifacantly more effective for these end-points than more conventional radiation sources such as 60Co gama rays, 220 kVp X rays, and 14 MeV X rays and electrons. Nor was there any detectable difference in RBE between the peak and plateau regions of the pi meson beam. The significance of these findings is discussed in relation of the the published pi meson RBE values of between 1 therefore 4 and 5 therefore 0.

Animals↗
PubMed1976

Anaemia and the induction of myeloid leukaemia in RFM mice.

The results from short term experiments provide little support for the idea that the anaemic stress produced by phlebotomy acts as a trigger for myeloid leukaemia in mice genetically prone to the development of the disease. Longer term investigation has also failed to reveal any difference between bled and control mice and at this time (16 months after bleeding) no animals have died from myeloid leukaemia. These observations are in contrast to the recently reported effect of phlebotomy as a trigger for myeloid leukaemia in unirradiated RFM mice and in irradiated rats. The results given in this paper are discussed in relation to the haemopoietic stem cell compartment in leukaemogenesis and the relationship between these cells and the mature cells in the peripheral blood.

Anemia↗
PubMed1976

The sensitivities of human and murine hemopoietic cells exposed to cytotoxic drugs in an in vivo culture system.

An agar diffusion chamber technique has been used to measure the sensitivities of human and murine hemopoietic colony-forming cells to cytotoxic drugs. The cells were held in i.p. diffusion chambers and exposed to the cytotoxic drugs by i.v. injection of the host mice. This method allows some account to be taken of the continuous changes in activity during the metabolic degradation of the drug. To determine how far this system provides a valid measure of the sensitivity of the cells in hemopoietic tissue, the responses of mouse bone marrow exposed to the drugs in situ in the donor mouse were compared with those of mouse cells exposed in diffusion chambers. The dose-response curves for cyclophosphamide and 5-fluorouracil were exponential in all cases. Exponential survival curves were also seen when human and mouse colony-forming cells were exposed to vinblastine or methotrexate in diffusion chambers. The plateaus seen when mouse cells were exposed to these drugs in situ could, however, be regained by omitting agar from the chambers during the exposure period. The results indicate that there are differences between the sensitivities of human and mouse marrow cells to cytotoxic drugs and that any extrapolation from mouse to humans must be viewed with caution.

Agar↗
PubMed1975

Stimulation of granulocytic colony formation in agar diffusion chambers implanted in cyclophosphamide pretreated mice.

The growth of mouse bone marrow colonies in agar diffusion chambers (ADCs) was evaluated using host mice injected with saline or with cyclophosphamide (CY) before chamber insertion. The mice pretreated with cyclophosphamide proved more effective hosts than control (saline pretreated) mice, indicating that cyclophosphamide causes the elaboration of a stimulating factor acting on colony precursor cells. Assays of the factor for colony stimulating activity against mouse bone marrow cells in agar culture in vitro suggest that potentiation may be due to a slight temporary increase in the level of colony stimulating factor (CSF) in the chamber environment, although a parallel increase was not detected in the serum. Stem cell recovery from the ADCs, measured by spleen colony formation, suggests that the stimulus may act by increasing differentiation at the level of the pluripotential stem cell.

Animals↗
PubMed1975

Studies on the humoral regulation of granulopoiesis in leukaemic RFM mice.

Intraperitoneal diffusion chambers have been used to investigate changes in humoral factors during the development of myeloid leukaemia in mice. Normal mouse bone marrow cells form colonies of granulocytes and macrophages when cultured in semi-solid agar medium within intraperitoneal diffusion chambers. The use of mice bearing transplanted myeloid leukaemia as Agar Diffusion Chamber (ADC) hosts enhances colony formation from normal marrow. The humoral basis for this stimulation has been shown by the colony stimulating activity of the fluid entering the diffusion chambers when assayed against normal mouse bone marrow cells in agar culture in vitro. The stimulus to colony growth in ADCs and the in vitro colony stimulating activity depend on the phase in the development of the leukaemia investigated, and the stimulation was abolished by splenectomy. There was no apparent relationship between the growth of the leukaemic cell population in vivo and the level of the stimulating factor detected in leukaemic mice.

Animals↗
PubMed1975

Colony formation by human haemopoietic precursor cells cultured in semi-solid agar in diffusion chambers.

A technique which allows colony growth of haematologically normal human bone marrow cells is described. The cells are supported by semi-solid-agar-medium inside modified Millipore diffusion chambers implanted in the peritoneal cavity of irradiated mice. After 9 days incubation colonies containing up to 1000 cells are found in these Agar Diffusion Chambers. All haematologically normal patients studied so far produced colonies, the majority with between 10 and 40 colonies per 2 X 10(5) bone marrow cells inoculated. This culture system therefore provides a convenient and reliable clonal assay for human bone marrow cells which, in contrast to the agar colony assay in vitro, does not require a source of Colony Stimulating Factor (CSF).

Agar↗
PubMed1975

Age-related changes in the bone marrow and spleen of SAS/4 mice.

The total number of nucleated cells in the bone marrow of SAS/4 mice increase some twofold between 1 and 24 months of age but when related to body weight remains essentially constant over a wide range of ages. The concentration of CFU-S in femoral marrow is also constant with age and since other bones containing marrow appear, at least in young mice, to have the same CFU-S concentration as the femur it is concluded that the CFU-S compartment size of the whole bone marrow is independent of age when expressed on a body weight basis, In contrast, both the absolute number and the concentration of exogenous CFU-S in the spleen decline markedly in old mice. Smilary there is a decline in the number of endogenous colony-forming cells and the spleens of 24-month-old mice seem virtually devoid of such colonies. Not only were older mice less capable of supporting the growth of endogenous colonies, but their spleens also appear to provide a poorer environment for exogenous colony growth when compared with growth in younger recipient spleens.

Aging↗