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J W Adamson

Publications and source records attributed to J W Adamson.

At least 163 records · Page 9Linked to original sources
PubMed1979

Patterns of globin chain synthesis in erythroid colonies grown from sheep marrow of different developmental stages.

Erythroid colonies were grown from fetal sheep bone marrow at different stages of development and from adult marrow. Colony numbers increased with erythropoietin concentration, but fetal erythroid cells were more sensitive to the hormone than adult cells. Haemoglobin synthesis was characterized in the colonies and compared to that in control marrow incubations. No beta chain synthesis was detectable in marrow incubations or erythroid colonies from fetal marrow at 87-96 d gestation. Incubations of 115-120 d marrow shoed 5% beta chain synthesis while erythroid colonies synthesised up to 20% beta chains. Incubations and erythroid colonies from 125 d marrows showed about 27% beta chain synthesis, despite a similar increase in colony numbers with erythropoietin as the other marrows. Later in gestation, beta chain synthesis was lower in erythroid colonies than in marrow incubations and declined further in erythroid colonies as erythropoietin concentration increased. Adult marrow showed no detectable gamma chain synthesis but erythroid colonies produced up to 12% gamma chains, the identity of which was confirmed by peptide mapping. All changes in globin synthesis in vitro were correlated with colony numbers. In adult marrow, the maximal level of gamma chain production was inversely related to the cloning efficiency of the marrow samples studied. Potential uses of this model for studying globin gene expression are discussed.

Animals↗
PubMed1979

Modulation of in vitro erythropoiesis. Studies with euthyroid and hypothyroid dogs.

The interactions of adrenergic agonists and thyroid hormones on the growth of erythroid colony-forming units were studied in cultures of dog marrow before and after the establishment of hypothyroidism. Erythroid colony growth in cultures form euthyroid dogs was enhanced by isoproterenol and other adrenergic agonists having beta 2-receptor specificity. With hypothyroidism, however, this responsiveness was lost, and sensitivity to alpha-agonists, such as phenylephrine and norepinephrine, was acquired. This alteration in receptor specificity appeared to be dependent upon thyroid hormone and was rapidly reversible. Preincubation of marrow cells from hypothyroid animals with thyroid hormone resulted in the reappearance of responsiveness to beta-adrenergic agonists and the loss of sensitivity to alpha-agonists. These findings are in agreement with previous suggestions that beta-adrenergic receptor activity is modulated by thyroid hormone levels and demonstrate that the specificity of adrenergic modulations of erythropoiesis in culture may accurately reflect the thyroid status of the intact animal.

Adenylyl Cyclases↗
PubMed1979

Polycythemia vera. Increased expression of normal committed granulocytic stem cells in vitro after exposure of marrow to tritiated thymidine.

In previous studies of two patients with polycythemia vera (PV) and heterozygous at the X-linked locus for glucose-6-phosphate dehydrogenase (G-6-PD), only type A isoenzyme was found in non-lymphoid hematopoietic cells. However, some granulocytic and erythrocytic colonies grown in vitro had type B G-6-PD and therefore arose from presumably normal progenitors. In this study we exposed marrow cells from these same two patients to high-specific activity tritiated thymidine (3HTdR) before culture to kill cells actively synthesizing DNA. Individual granulocytic colonies were plucked and tested for G-6-PD after 14 d of culture. The frequency of type B colonies rose after exposure to 3HTdR from 8/101 to 11/36 in patient 1 and from 0/32 to 6/31 in patient 2 (P less than 0.003). No increase in the frequency of normal erythroid bursts after 3HTdR exposure was seen, implying that in PV, early granulopoiesis, and erythropoiesis are regulated differently. The results demonstrated that only type A granulocytic colonies, arising from the abnormal clone, were removed by the 3HTdR. In addition, for patient 2, statistical analysis indicated there was an absolute increase in normal granulocytic colonies detected in culture. Thus, PV clonal colony-forming units in culture (CFU-C) cycle more rapidly than do normal CFU-C and may suppress proliferation of normal CFU-C in vitro.

Cell Division↗
PubMed1979

Characteristics of murine megakaryocytic colonies in vitro.

Characteristics of murine megakaryocytic colonies and their progenitor cells (CFU-m) were studied in vitro in agar gel. Colony growth required the presence of poke-weed-mitogen-stimulated spleen-conditioned medium. The number of colonies formed was linearly related to both the number of marrow cells plated and the amount of conditioned medium added. In addition, CFU-m were found in both the spleen and peripheral blood. Conditioned medium was also made without plasma, and this resulted in a cloning efficiency greater than that of conditioned medium prepared with plasma. The percentage of CFU-m in DNA synthesis was low (10%), as determined both in vivo and in vitro. Velocity sedimentation revealed that the majority of CFU-m sedimented at 4.3 mm/hr and had a tritiated thymidine (3H-TdR) suicide rate of 1.5 +/- 1.5%. A shoulder on the profile of CFU-m sedimented at approximately 6 mm/hr, with a suicide rate of 79 +/- 2%. Analysis of these data indicated that the majority of CFU-m were not in cycle or were in a long G1 period. The results suggest that CFU-m is a primitive progenitor, possibly closely related to murine splenic colony-forming units (CFU-s), analogous to erythroid bursts and granulocytic colony-forming units.

Animals↗
PubMed1979

Erythroid colony stimulating and inhibiting cells in peripheral blood of transfused dogs: separation of function by velocity sedimentation.

We have previously shown that the addition of normal dog peripheral blood lymphocytes (PBL) to cultures of allogeneic marrow increases the number of marrow-derived erythroid colonies (EC), but that PBL from transfused dogs usually inhibit EC growth from marrow of the transfusion donor. In this study, the cells in normal dog PBL responsible for stimulating EC growth were shown to sediment in a narrow peak at 4.30 mm/hr. A similar population of stimulating cells exists in transfused dogs and can be separated, on the basis of size, from cells that inhibit EC growth. EC-stimulating cells from transfused dog PBL sediment at 3.3--5.0 mm/hr, while cells responsible for inhibition are larger and sediment more rapidly at 5.4--8.1 mm/hr. These data demonstrate that cells capable of stimulating allogeneic EC are present in transfused dogs, but their stimulating ability is masked by the presence of EC-inhibiting cells. Thus, coculture experiments designed to test lymphocyte/marrow cell interactions may miss significant but opposing effects if unfractionated cells are used.

Animals↗
PubMed1978

Myelofibrosis with complex chromosome abnormality in a patient with erythrocytosis due to hemoglobin Rainier and treated with 32P.

A patient with familial erythrocytosis associated with Hemoglobin Rainier, and previously treated with 32P, developed myelofibrosis with a hyperdiploid chromosome clone in the myeloid cells (51,XX,+1,2q-(q33),+6,+9,+11,-19,+20q+,+mar 1.) This transformation from a benign disorder of differentiated erythrocytes to a malignant disorder may have been secondary to radiophosphorus therapy.

Chromosome Aberrations↗
PubMed1978

Polycythemia vera. The in vitro response of normal and abnormal stem cell lines to erythropoietin.

Bone marrow cells from two glucose-6-phosphate dehydrogenase (G-6-PD) heterozygotes with polycythemia vera were cultured to determine whether progenitors which wre not of the polycythemia vera clone were present, and, if present, which cell lines contributed to the increase in erythroid colonies observed in response to added erythropoietin (ESF). To accomplish this, the G-6-PD isoenzyme activity of individual erythroid colonies was determined. All of the erythroid colonies analyzed in cultures without added ESF, contained the G-6-PD isoenzyme type characteristic of the abnormal clone. With higher ESF concentrations in the culture, however, there was an increase in the colonies that were not of the polycythemia vera clone. Analysis of the ratio of the various types of colonies indicated that normal and polycythemia vera cells are capable of responding to ESF in vitro. In selected patients, this technique permits analysis of the ratios of normal to abnormal cells during the course of the disease, in response to therapy and during late complications, such as myelofibrosis or leukemic transformation.

Clone Cells↗
PubMed1978

Erythropoietin assay: present status of methods, pitfalls, and results in polycythemic disorders.

Mammalian erythropoiesis is regulated primarily by the hormone erythropoietin (ESP). Studies of ESF have provided information about its biochemistry and its role in regulating hemoglobin synthesis. Such studies rely on assays for erythropoietic activity in biological fluid. The assay which has proven most valuable and is used most widely is based upon the incorporation of radioactive iron into newly-formed red cells of polycythemic mice. While this assay has gained wide acceptance, it is expensive, cumbersome, imprecise, and insensitive, capable of reliably detecting no less than 50 milliunits of erythropoietin. Improvements in assay techniques will require new methodology relying primarily on immunologic recognition for the determination of hormone activity. Currently under development and in experimental use are radioimmunoassays and a hemagglutination inhibition assay. While work has progressed in these areas, these assays are not of proven value at present and meaningful physiological correlations have not emerged from their use. Alternatively, assays for hormone activity using suspensions of hematopoietic cells and the measurement of incorporation of radioactive isotopes into hemoglobin have provided both improvement in sensitivity and precision. The disadvantage of these types of assays is that they are sensitive to factors other than ESF and may give misleading information, depending on whether the factors present stimulate or inhibit cellular proliferation and hemoglobin synthesis. While such techniques may provide a temporary solution to some problems associated with assaying ESF for purification or physiological studies, they are not the best answer to the overall problem of hormone detection and characterization. The most important contribution to this field will be the availability of large amounts of highly purified and well-characterized ESF.

DNA↗
PubMed1978

Propranolol effects in long-term hemodialysis patients with renin-dependent hypertension.

We evaluated propranolol effects on blood pressure, plasma renin activity, and erythrocyte production in nine chronically hemodialyzed and four nondialyzed patients with hypertension and high plasma renin concentrations. Propranolol, at a maximum daily dose of 240 mg, controlled blood pressure in 12 of the 13 patients. During propranolol treatment of dialyzed patients, mean blood pressure fell from 133 +/- 1 to 113 +/- 4 mm Hg (P less than 0.005) and plasma renin activity from 3093 +/- 423 to 689 +/- 218 ng/dl 3h (P less than 0.001). Similar results were obtained in nondialyzed patients. In both groups hematocrit and red cell mass were unchanged, although ferrokinetic measurements suggested a decrease in erythropoiesis. Thus propranolol alone reduces blood pressure and renin activity in chronically dialyzed patients with hypertension and high renin concentrations. No hematologic complications or other side effects were observed. These findings suggest that propranolol may be an effective alternative to bilateral nephrectomy in the control of renin-dependent hypertension in selected patients.

Adult↗
PubMed1978

Pharmacological stimulation of marrow function.

Studies of the pharmacological stimulation of marrow function have provided insight into mechanisms which might possibly affect cell proliferation in vivo. However, the most dramatic and clear-cut effects have come with studies employing normal marrow or populations of cells recovering in a predictable manner from suppression. Even with this, a wide number of agents appear to be active and capable of influencing the growth or cycle activity of more than one class of progenitor, including both committed and pluripotent stem cells. Perhaps the most useful clinical insight from these studies is that they provide a rationale for 'rescuing' deliberately damaged marrow (as with high dose chemotherapy) and suggest that it may be possible to reduce the period of severe hypoplasia under controlled circumstances. In cases of idiopathic marrow failure, the situation is less hopeful. The studies do not indicate that we are at a stage where we may hope to enhance marrow function significantly in the severely aplastic patient. Initial suggestions that in vitro culturing of marrow cells with various agents might lead to a programme of specifically designed therapy have resulted in limited, but negative, experiments. It is not likely that this is going to be fruitful. It seems clear, however, that the phenotypic expression of marrow failure in man masks a number of pathogenetic mechanisms, and that further attempts to characterize marrow growth in such patients are warranted. Perhaps by identifying patients with normal growth patterns it will be possible to select individuals for rational pharmacological therapy with some expectation of success.

Androgens↗
PubMed1978

Analysis of erythropoiesis by erythroid colony formation in culture.

The development of clonal assays for hemopoietic progenitors has provided new tools for the analysis of normal and abnormal cell regulation. Such assays have been applied to erythropoiesis and have demonstrated classes of precursors which differ significantly in their growth potential, physical characteristics, and sensitivity to the hormone, erythropoietin. A formal geneology of these classes has been established and insight into the factors that regulate the numbers of the classes provided by studies in anemic and polycythemic animals. The results suggest that commitment to the earliest erythroid progenitors recognizable in culture is not controlled by erythropoietin, whereas the most differentiated elements demonstrate a requirement for the hormone for their maintenance. Recognition of differences in the factors that control erythroid differentiation predict that a variety of mechanisms will be found to account for different forms of erythroid failure in man.

Anemia↗
PubMed1977

Differential in vitro sensitivity of marrow erythroid and granulocytic colony forming cells to chloramphenicol.

The effects of chloramphenicol (CAP) and thiamphenicol (TAP) on mouse and human in vitro erythroid (CFU-E) and granulocytic (CFU-C) colony forming units have been studied. Both drugs inhibited CFU-E growth in a concentration-dependent, stereospecific, manner. Complete inhibition of human CFU-E growth was observed at a CAP concentration of 10 microgram/ml while a concentration ofer 50 microgram/ml was required to inhibit CFU-C growth. Furthermore, whereas the inhibition of CFU-C growth could be blocked in vitro by high colony stimulating factor concentrations, inhibition of CFU-E growth was not affected by increased erythropoietin (ESF) levels. The lack of protection by ESF may account for the apparent vulnerability of erythroid cells to CAP in vivo.

Animals↗
PubMed1977

Cooperative erythropoietic assay of several steroid metabolites in polycythemic mice.

A blinded cooperative assay of several androstane and pregnane steroid metabolites has been carried out in order to determine whether 5beta-H derivatives are as active as testosterone in stimulating in vivo erythropoiesis. The steroids tested were: testosterone, 5alpha-dihydrotestosterone, 5beta-dihydrotestosterone, 5beta-pregnane-3,20-dione, 3alpha-dihydroxy-5beta-pregnane-11,20-dione and 3beta-hydroxy-5beta-pregnan-20-one. The incorporation of radioactive iron into newly formed red cells in exhypoxic polycythemic mice was used to compare the effects of the steroids. Testosterone and 5alpha-dihydrotestosterone both produced significant increases in 59Fe incorporation. 5beta-dihydrotestosterone, 5beta-pregnane-3,20-dione, 3alpha-hydroxy-5beta-pregnane-11,20-dione and 3beta-hydroxy-5beta-pregnan-20-one were all devoid of significant erythropoietic activity in polycythemic mice in almost all instances. Thus, under the conditions chosen, this study failed to demonstrate that 5beta-steroids increase radioactive iron incorporation in red cells of exhypoxic polycythemic mice.

Androstanes↗