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Showing papers on "Haematopoiesis published in 1972"


Journal ArticleDOI
TL;DR: Changes in sex hormone levels exerted a marked influence on immune responsiveness and stem cell differentiation, by increasing numbers of functioning cells, by promoting cellular differentiation, as well as by promotes cellular function via hormonal effects.
Abstract: The primary and secondary immune responses to thymus-dependent and -independent antigens were evaluated in normal male and female mice and in castrated male mice. Both IgM antibody production in the primary response and IgG antibody production in the secondary response were enhanced in females vs. males of equivalent age. Castration of the male converted this animal to a female in terms of responsiveness to the thymus-dependent group of antigens, while inducing equivalent or even greater enhanced responsiveness over the female to the thymus-independent antigen, polyvinylpyrrolidone. Further characteristics of the changes in lymphoid organs were determined in the castrated animal vs. normal males and females. It was shown that the spleen and thymus became markedly hyperplastic, the organ weights exceeding the female, which in turn were greater than in the male. The enhanced weight of the thymus was shown to be due to increased numbers of cortisone-sensitive cells, the absolute number of cortisone-resistant cells remaining equivalent to normal males and females. Thus, the increased thymic weight of the female also resided in the cortisone-sensitive population. Peripheral lymphocyte counts in castrated animals exceeded both normal males and females. Further experiments in gonadectomized males provided evidence that increased thymic cell activity per se played a role in enhanced response to thymus-dependent antigens, but that a thymic-derived hormone mediated the enhanced effect to the thymus-independent antigen in the castrated animal. The capacity for loss of androgenic hormone-producing tissue to generate enhanced differentiation of stem cells was denoted by experiments in which numbers of spleen colonies and uptake of 59Fe, employed as an index of hematopoiesis 1 wk after reconstitution of lethally irradiated castrated and normal recipients, were enhanced in gonadectomized male animals. Thus, in summary, changes in sex hormone levels exerted a marked influence on immune responsiveness and stem cell differentiation, by increasing numbers of functioning cells, by promoting cellular differentiation, as well as by promoting cellular function via hormonal effects.

309 citations


Journal ArticleDOI
28 Jun 1972-Nature
TL;DR: It is shown that non-purified conditioned medium produced by human cells can induce undifferentiated cells from patients with acute myeloid leukaemia to differentiate into mature granulocytes11.
Abstract: VARIOUS types of cells release an inducer for the formation of colonies in vitro with mature differentiated macrophages and granulocytes from single normal undifferentiated haematopoietic cells1–8. Using purified inducer from a cloned line of mouse fibroblasts, we have shown that this induction requires a protein (MGI) with a molecular weight of 65–70,000 and a low molecular weight co-factor, both secreted by the fibroblasts9. Adenine or adenine-containing nucleotides can substitute for the co-factor9,10. We have also shown that non-purified conditioned medium produced by human cells can induce undifferentiated cells from patients with acute myeloid leukaemia to differentiate into mature granulocytes11.

142 citations


Journal ArticleDOI
TL;DR: Analysis of spontaneous colony formation in Rhesus monkey marrow cultures revealed the presence of a cell type in hemopoietic tissue, capable of elaborating colony stimulating factor when used to condition media or as feeder layers.
Abstract: Hemopoietic colony formation in agar occurred spontaneously in mass cultures of marrow cells obtained from a number of species (guinea pig, rat, lamb, rabbit, pig, calf, human and Rhesus monkey). This contrasted with the observation that colony formation by mouse bone marrow exhibited an absolute requirement for an exogenous source of a colony stimulating factor. Analysis of spontaneous colony formation in Rhesus monkey marrow cultures revealed the presence of a cell type in hemopoietic tissue, capable of elaborating colony stimulating factor when used to condition media or as feeder layers. Equilibrium density gradient centrifugation separated colony stimulating cells from in vitro colony forming cells in monkey bone marrow. Separation studies on spleen, blood and marrow characterized the stimulating cells as of intermediate density, depleted or absent in fractions enriched for cells of the granulocytic series and localized in regions containing lymphocytes and monocytes. Adherence column separation of peripheral blood leukocytes showed the stimulating cells to be actively adherent, unlike the majority of lymphocytes, and combined adherence column and density separation indicated that stimulating cells were present in hemopoietic tissue within the population of adherent lymphocytes or monocytes.

119 citations


Journal ArticleDOI
01 Jun 1972-Blood
TL;DR: It is concluded that the early fetal yolk sac is the embryonic site of origin of the macrophage precursor and that this precursor is “proximal” to the promonocyte on the pathway of sequential macrophages maturation.

115 citations


Journal ArticleDOI
TL;DR: There is an antigen on mouse brain tissue which is shared by the hemopoietic colony-forming unit or stem cell of the mouse and the anti-stem cell antibody is not absorbed by thymus cells and thus can be distinguished from theAnti-thymocyte antibody which these antisera also contain.
Abstract: There is an antigen on mouse brain tissue which is shared by the hemopoietic colony-forming unit or stem cell of the mouse. Treatment of bone marrow or fetal liver cells with anti-brain antisera inhibits expression of colony-forming units. The anti-stem cell antibody is not absorbed by thymus cells and thus can be distinguished from the anti-thymocyte antibody which these antisera also contain.

108 citations


Journal ArticleDOI
TL;DR: It is suggested that stem cells in foetal liver have, on average, a higher intrinsic capacity for self‐renewal than do those in bone marrow, and that this capacity falls to the adult level within about ten weeks of transfer.
Abstract: The relative proliferative capacity of haematopoietic cell populations derived from 22-week-old adult bone marrow and 14–18 day foetal liver has been studied in lethally irradiated syngeneic recipients by means of chromosome markers. Although starting at a disadvantage in terms of the number of colony-forming units (stem cells) injected, the foetal liver-derived populations steadily increased their relative numbers in the myeloid and lymphoid tissues over a period of several weeks until a plateau was reached. It is suggested that stem cells in foetal liver have, on average, a higher intrinsic capacity for self-renewal than do those in bone marrow, and that this capacity falls to the adult level within about ten weeks of transfer.

108 citations


Journal ArticleDOI
TL;DR: It is concluded that B-lymphocyte development begins at about the same time as T-ly MPH development, and the order of appearance of cells bearing different immunoglobulin classes is probably IgM, IgG, and IgA, which suggests that their development is an event of normal differentiation rather than one dependent upon random antigenic stimulation.

94 citations


Journal ArticleDOI
01 Nov 1972-Blood
TL;DR: Local production of CSF by nonhematopoietic cells in the marrow appears to be a significant factor in regulating granulopoiesis and monocyte formation.

85 citations


Journal ArticleDOI
TL;DR: Reduced colony formation by human bone marrow does not appear to be solely related to infiltration by recognizable leukaemic cells, but may reflect a disturbance in granulopoiesis occurring prior to the development of overt leukaemia.
Abstract: Summary. Disordered haemopoiesis may precede acute leukaemia for prolonged periods. Three patients are presented in whom splenomegaly, peripheral cytopenia, hypercellular bone marrow, and reduced colony formation in marrow cell culture were present for intervals of 27, 15 and 5 mth prior to definite diagnosis of acute leukaemia. Reduced colony formation by human bone marrow does not appear to be solely related to infiltration by recognizable leukaemic cells, but may reflect a disturbance in granulopoiesis occurring prior to the development of overt leukaemia.

73 citations


Journal ArticleDOI
01 May 1972-Blood
TL;DR: Specific alterations in the microvascular and connective tissue compartments of the hemopoietic microenvironment have been examined during erythropoietics regeneration and suppression in the murine spleen and bone marrow using in vivo microscopic and histochemical methods.

72 citations


Journal ArticleDOI
TL;DR: The ability of a single injection of killed, intact bacteria to effect an increase in the proliferative rate of hemopoietic stem cells was studied and Splenic CFU were observed to rise exponentially due initially to in situ proliferation and later to proliferation in bone marrow with migration via the blood to the spleen.
Abstract: The ability of a single injection of killed, intact bacteria to effect an increase in the proliferative rate of hemopoietic stem cells was studied. The total numbers of colony forming units in bone marrow, spleen and peripheral blood as well as the proportion of CFU in cycle was assessed. Splenic CFU were observed to rise exponentially due initially to in situ proliferation and later to proliferation in bone marrow with migration via the blood to the spleen. The results are discussed in the light of current concepts of stem cell regulation.

01 Jan 1972
TL;DR: It is suggested that CFU-S from normal bone marrow contain precursors for DNA synthesis, e.g., deoxyribonucleotides, because of the increase in sensitivity of spleen colony-forming cells to the cytocidal action of high specific activity 3H-TdR.
Abstract: The treatment of mice with a single, subcutaneous injection of either testosterone propionate or of 5β-dihydrotestosterone results in an increase in the sensitivity of spleen colony-forming cells (CFU-S) to the cytocidal action of high specific activity 3H-TdR. The effect is still present 24 hr after treatment. By 1 hr after exposure in vitro to 2.4 x 10-8 M testosterone hydrogen succinate (THS), CFU-S from mouse bone marrow similarly become more sensitive to 3H-TdR. Sensitivity to the cytotoxic action of 10-3 M hydroxyurea (HU) also increases. Compared with 3H-TdR sensitivity, however, there is a delay in the onset of sensitivity to HU. The lag is shortened if HU is added 1 hr after the addition of THS. The increased sensitivity of CFU-S to HU is prevented by deoxyribonucleoside, i.e., unlabeled thymidine, and the change during the first hour in 3H-TdR sensitivity is unaltered by the presence of HU. From these data, it is suggested that CFU-S from normal bone marrow contain precursors for DNA synthesis, e.g., deoxyribonucleotides. On the assumption that the action of HU is to inhibit the formation of deoxyribonucleotides from ribonucleotides, the delay in the onset of action of HU may depend on the exhaustion of such pools. It is postulated that CFU-S responding to THS are held up in a stage of the cell cycle close to the G1-S boundary.

Journal ArticleDOI
TL;DR: The histopathogenesis of infectious haematopoietic necrosis (IHN) virus infection was studied by exposing juvenile sockeye salmon to the IHN virus, and extensive pathological changes in the kidney were shown, together with variable changes in spleen, liver, pancreas, and gut.
Abstract: The histopathogenesis of infectious haematopoietic necrosis (IHN) virus infection was studied by exposing juvenile sockeye salmon (Oncorhynchus nerka) to the IHN virus. Fish samples were taken every 24 h for histological examination and for determination of virus concentration. A close correlation was found between histopathological changes and virus concentration. The most significant changes occurred 4 days after exposure. The haematopocitic tissue of the kidney was the most extensively involved but minor degenerative changes were seen in the liver, pancreas, and in the granular cells of the digestive tract. On the 4th day, maximum tissue concentration of virus was reached and the mortality increased. By the 5th day, 90% of the samples showed extensive pathological changes in the kidney, together with variable changes in spleen, liver, pancreas, and gut. Similarities in the histopathogenesis of IHN, Oregon sockeye disease (OSD), Sacramento River chinook disease (SRCD) and viral haemorrhagic septicaemia (VHS), are discussed.

Journal ArticleDOI
TL;DR: In vitro suiciding of mouse in vitro granulocytic and macrophage colony-forming cells (CFC) using tritiated thymidine caused an average reduction of bone marrow colonies by 45% in 5 different mouse strains but only a 24% reduction in colony- forming cells from the spleen.
Abstract: SummaryIn vitro suiciding of mouse in vitro granulocytic and macrophage colony-forming cells (CFC) using tritiated thymidine caused an average reduction of bone marrow colonies by 45% in 5 different mouse strains but only a 24% reduction in colony-forming cells from the spleen Most bone marrow CFC appear to be in active cell cycle but many spleen CFC appear to have longer cell cycles or to be in a G0 state

Journal ArticleDOI
TL;DR: Guinea pig and rabbit thymus cells showed a marked capacity for bone formation under the influence of transitional epithelium and decalcified bone matrix and were much superior in that respect to all the other populations of lymphoid and hemopoietic cells studied.
Abstract: Guinea pig and rabbit thymus cells showed a marked capacity for bone formation under the influence of transitional epithelium and decalcified bone matrix and were much superior in that respect to all the other populations of lymphoid and hemopoietic cells studied. Diffusion chambers containing the reacting cells together with inductors of osteogenesis were used.

Journal ArticleDOI
01 Feb 1972-Blood
TL;DR: Leukocyte exchange between the hemopoietic tissues of parabiotic rats was studied subsequent to giving multiple injections of 3 H-thymidine to one member of each pair while arresting the cross-circulation, suggesting that this is a single pool of cells with respect to kinetic behavior and recirculation.

Journal ArticleDOI
TL;DR: Sensitivity of lymphocytes by allowing them to proliferate in the spleens of lethally irradiated allogeneic hosts for five days resulted in an increased reactivity, which was immunologically specific since lymphocytes sensitized against another mouse strain, not cross-reacting with the test bone marrow, exerted no reactivity.

Journal ArticleDOI
TL;DR: Property of the progenitor cells as well as humoral factors from the hosts did influence chamber granulopoiesis in bone marrow cultures, and the formation of macrophages showed a relative decrease when the cell inocula were increased.

Journal ArticleDOI
TL;DR: The number of colony‐forming units (CFU) in the spleen, femoral bone marrow and blood of Friend‐virus (FV)‐infected mice was determined at different times after virus infection, by the exogenous spleen colony assay.
Abstract: The number of colony-forming units (CFU) in the spleen, femoral bone marrow and blood of Friend-virus (FV)-infected mice was determined at different times after virus infection, by the exogenous spleen colony assay. An increase in number occurred in the spleen, following the rise in the number of cells, and also in the blood, but not in the bone marrow. The fraction “f” of CFU which settle in the spleen of irradiated recipients was the same for bone marrow cells from normal or FV-infected donors and slightly decreased in the case of spleen cells from infected mice. The total increase in the CFU compartment was estimated as being six-fold, 30 days after virus infection. Cytological and histological investigations of the colonies developing in the spleen of irradiated recipients grafted with hematopoietic cells from FV-infected donors indicated that the pattern of differentiation along erythrocytic, myelocytic and megakaryocytic lines appeared comparable to the pattern of differentiation observed in spleen colonies derived from the graft of normal hematopoietic cells. From these observations, it can be speculated that the CFU of FV-infected mice behave as normal hematopoietic CFU, in terms of differentiation ability, in the spleens of isogeneic irradiated mice.

Journal ArticleDOI
TL;DR: Bone marrow, spleen and blood from mice bearing transplantable fibrosarcoma contained more CFUs than the same tissues from normal mice, and in all the tissues assayed the pool of CFUs that form myeloid colonies in the spleen of recipient mice was particularly enlarged.

Journal ArticleDOI
28 Jul 1972-Nature
TL;DR: Experiments on the determinants of the host range of FeLV, a leukaemia virus from cats with naturally occurring haematopoietic tumours, report on the growth of feline cells in culture and the isolation of viral isolates.
Abstract: FELINE leukaemia viruses (FeLV) from cats with naturally occurring haematopoietic tumours grow in feline cells in culture1. In addition, of five viral isolates studied by us, four grew in human cells and one did not2,3. This paper reports experiments on the determinants of the host range of FeLV.

Journal ArticleDOI
TL;DR: The data interpreted in a semiquantitative way suggest that the assumption that the thymus is seeded from bone marrow, is not needed to explain a biphasic pattern ofThymus regeneration, rather it appears likely that cells present in thymu or deposited there immediately after injection of injection of bone marrow are likely to be found.
Abstract: Regeneration of thymus, spleen and bone marrow of AKR/T1 Ald mice after whole body irradiation with 605 rad (650R) with or without treatment with 107 syngeneic bone marrow cells from AKR mice was followed. In the non-transplanted irradiated animals, cell division recommences first in the thymus (on day 6) following the biphasic pattern observed by others. Cell division in spleen (day 8) and bone marrow (day 8-12) resume later. After bone marrow treatment, all these organs begin to regenerate at about day 6 and also display a biphasic pattern of cell divisions. The proportion of donor cells remains high in bone marrow and spleen, but drops temporarily in thymus, perhaps as the result of division of damaged thymus cells. The data interpreted in a semiquantitative way suggest that the assumption that the thymus is seeded from bone marrow, is not needed to explain a biphasic pattern of thymus regeneration, rather it appears likely that cells present in thymus or deposited there immediately after injection of ...

Journal ArticleDOI
01 Mar 1972-Blood
TL;DR: Granulopoiesis was studied in mice whose colony-forming units had been suppressed to undetectable levels by Myleran, confirming the existence of such cells in an in vivo system and indicating that intermediate stem cells are not interchangeable.

Journal ArticleDOI
TL;DR: The data are consistent with the view that foetal haematopoietic stem cells are capable, on average, of producing larger descendant populations than are stem cells from young adults.
Abstract: Cell proliferation in mouse spleen colonies, derived from injected foetal liver and young adult bone marrow, was studied by measuring incorporation of radio-iodine-labelled 5-iodo-2′-deoxyuridine (IUdR). Foetal liver-derived colonies incorporated significantly more IUdR than marrow-derived colonies on the 8th and 12th days after cell injection. The data are consistent with the view that foetal haematopoietic stem cells are capable, on average, of producing larger descendant populations than are stem cells from young adults.


Journal ArticleDOI
TL;DR: Progenitor cells were quantified ly limiting dilution analysis of diffusion chamber cultures of haematopoietic cells and by the spleen colony technique to assay granulocyte progenitor cells and those multipotent progenitors cells that become committed to granulopoiesis during chamber culture.
Abstract: Regulation of haematopoiesis was investigated by studying the response of haematopoietic tissues of mice to a perturbation of the steady state by vinblastine (VLB). Progenitor cells were quantified ly limiting dilution analysis of diffusion chamber cultures of haematopoietic cells and by the spleen colony technique. The diffusion chamber technique appears to assay granulocyte progenitor cells and those multipotent progenitor cells that become committed to granulopoiesis during chamber culture. The spleen colony technique probably assays multipotent progenitor cells. Decaying oscillatory responses to VLB were observed for progenitor cells as well as for differentiating cells in bone marrow. The period lengths of the diffusion chamber progenitor cell oscillations might indicate that these were induced by humoral feedback signal(s) from nonproliferative granulocytes. The oscillations of the multipotent progenitor cells of bone marrow were less pronounced and were earlier damped than those of the granulocyte progenitor cells. This may support the hypotesis that multipotent progenitor cells are regulated by more efficient mechanisms, which may depend on short range cell-cell interactions rather than long range humoral regulators.


Journal ArticleDOI
01 Jun 1972-Blood
TL;DR: The results suggest that the splenic microvascular response to erythropoietin may be indirect and may be mediated by the release of a vasoactive metabolite from the erythrogenic tissues surrounding the sinusoids.


Journal ArticleDOI
01 Dec 1972-Blood
TL;DR: The presence of an early proliferative phase in endogenous splenic hemopoietic colonies is confirmed and it is strongly suggested that mononuclear cells, replicating during this period of self-renewal of the stem cell compartment, transform to erythroblasts and other cells.