Acetylcholinesterase in red blood cells.
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Acetylcholinesterase↗
Biomedical subjects
R D Barr
Publications and source records attributed to R D Barr.
Terminal deoxynucleotidyl transferase (TdT)-containing peripheral blood mononuclear cells during remission of acute lymphoblastic leukemia.
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Child↗
Primary thrombocythaemia in childhood: symptomatic episodes and their relationship to thromboxane A2, 6-keto-PGE1 and 12-hydroxy-eicosatetraenoic acid production: a case report.
In a child with primary thrombocythaemia, observations have been made over a period of five years, during which, transient apparently thrombotic events occurred in the central nervous system on several occasions. Spontaneous platelet aggregation was noted and deaggregation took place even after exposure to ADP in vitro. Associated findings included pronounced elevation in plasma levels of 6-keto-PGF1 alpha and 6-keto-PGE1, the latter described for the first time. Production of 12-HETE by platelets was markedly reduced, probably reflecting lipoxygenase deficiency which has been reported in other myeloproliferative disorders. It has been suggested that 12-HETE is a natural inhibitor of thromboxane synthetase, so the further finding of enormous generation of TxA2, measured as TxB2, by this patient's platelets may be explicable. It is suggested that the increase in TxA2 is responsible for spontaneous platelet aggregation. In response to these massive events, there is a production of 6-keto-PGE1 which in turn, promotes platelet deaggregation. Administration of aspirin resulted in symptomatic relief and complete inhibition of TxB2 production.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
Analysis of ultratrace lithium and boron by neutron activation and mass-spectrometric measurement of 3He and 4He.
A new technique for analysis of lithium and boron at ultratrace concentrations (less than 10(-8)g g-1) is described. The method consists of mass-spectrometric assay of 3He from decay of tritium produced by thermal-neutron reaction on 6Li, and 4He produced by thermal-neutron reaction on 10B. Two neutron-irradiation facilities were used: the McMaster reactor, which is 235U-enriched and light-water moderated; and a graphite-moderated thermal column attached to the 235U-enriched, heavy-water-moderated core at the National Bureau of Standards (NBS) reactor. In the McMaster irradiations, fast neutrons (greater than 0.2 MeV) induce the reactions 14N(n, 3H)12C, 12C(n, alpha)9Be, 16O(n, alpha)13C, and 14N(n, alpha)11B. These reactions become serious sources of error in samples such as human blood which have very low concentrations of lithium and boron, and high concentrations of nitrogen, carbon and oxygen. In the NBS thermal column, fast-neutron reactions are virtually absent, and only corrections for thermal-neutron capture by deuterium, and thermal-neutron (n, alpha) reactions on oxygen, sulfur, chlorine, potassium, and calcium need to be taken into account. Results are presented for various actual samples including human blood and its components, and some standard biological reference materials, to provide a realistic base for other workers to judge the reliability of the method.
Boron↗
Relationship between platelet aggregating factor and von Willebrand factor in thrombotic thrombocytopenic purpura.
The pathophysiology of the platelet thrombotic disorder, thrombotic thrombocytopenic purpura (TTP), is not well understood. Two apparently unrelated laboratory abnormalities have recently been described in patients with TTP: a platelet aggregating factor and abnormalities in von Willebrand factor (vWF). Although an interaction between these two abnormalities has been postulated to participate in the disease, this has not been proved. In this report we describe studies on a patient with relapsing TTP. These studies demonstrate that a consistent relationship exists between the platelet aggregating factor present in the patient's serum and vWF. The patient had chronic low-grade thrombocytopenic and schistocytic haemolytic anaemia that could be temporarily cured by infusions of plasma and certain other blood products. During acute exacerbations of the illness, a platelet aggregating factor was detectable in the patient's serum and this was associated with the loss of the larger multimers of vWF. During remissions of the illness, abnormally large multimers of vWF were present. The results of this study support the concept that a platelet aggregating factor plus large multimers of vWF participate in the acute platelet thrombi that characterize TTP.
Anemia, Hemolytic↗
Modulation of human erythropoiesis by hydrocortisone in vitro.
The effect of hydrocortisone on the formation of erythroid colonies was studied in vitro in cultures of normal human bone marrow in an agar system. A range of concentrations of hydrocortisone (10(-10) to 10(-3) mol/l) showed significant effects on erythroid burst formation, in terms of the number of colonies, on d 10 and 14 of culture. At subphysiological concentrations (10(-10) to 10(-8) mol/l), no effect was seen, but at both physiological (10(-7) mol/l) and pharmacological (10(-6) and 10(-5) mol/l) concentrations stimulation of erythroid burst formation was noted. At 10(-4) mol/l hydrocortisone inhibited erythroid colony formation and 10(-3) mol/l was uniformly lethal. In the concentration range of 10(-7) to 10(-5) mol/l hydrocortisone also appeared to increase erythroid colony size. Thus hydrocortisone (10(-7) to 10(-5) mol/l) stimulates erythroid colony growth and it is suggested that the hormone may play a role in the physiological regulation of human erythropoiesis.
Bone Marrow↗
Stimulation of human eosinophilopoiesis by hydrocortisone in vitro.
Excess hydrocortisone (HC) evokes neutrophilia and eosinopenia in man. In addition, the hormone enhances human granulopoiesis in vitro at physiological as well as pharmacological concentrations. This study addressed the prospect that HC exerts opposite effects on the precursors of neutrophils and eosinophils, stimulating the former and inhibiting the latter. Experiments conducted on unseparated bone marrow (BM) cells demonstrated an increase in eosinophil clonogenesis in vitro with the addition of HC to the culture system. Secondary cultures, established from such primary harvests, revealed that HC had a direct impact on the clonogenic cells. Furthermore, administration of HC to normal subjects, at a dose which resulted in consistent eosinopenia, prompted an increase in the generation of eosinophil clones from peripheral blood cells ex vivo. Thus the hormone stimulates production of both neutrophils and eosinophils. Previous reports of opposite effects appear to have resulted from deficiencies of growth factors in the cell cultures. The contrasting effects of HC on neutrophil and eosinophil concentrations in the peripheral blood are more likely due to opposite effects on the distribution of these terminally differentiated cells in the circulation and extravascular tissues.
Adult↗
Indices of growth and death of liver cells in human chronic liver disease.
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Aspartate Aminotransferases↗
Lithium and boron in human blood.
A new method for determination of lithium and boron in biologic material has been developed. It uses neutron irradiation and subsequent measurements of helium 3 and helium 4 in a static mass spectrometer. Concentrations of lithium and boron in blood from seven apparently healthy donors were in rather narrow ranges (Li = 2.64 +/- 0.94 ng/gm dry weight, B = 97 +/- 22 ng/gm dry weight), and these concentrations also appeared to be correlated at the 0.05 level of significance.
Boron↗
Putative role for lithium in human hematopoiesis.
Ingestion of lithium salts increases production of neutrophil granulocytes from the bone marrow in human subjects when the concentration of the ion in blood is within the range 5 to 10 X 10(-4) mol/L. Results of preliminary dose-response experiments appeared to indicate that nanomolar levels of lithium stimulated clonal proliferation of granulocyte precursors from normal bone marrow in vitro, suggesting the possibility that this element may contribute to the physiologic regulation of blood cell formation in humans. The present studies confirm that the influence of lithium on hematopoiesis is evident in vitro at concentrations equivalent to that demonstrable in normal blood (2 to 4 X 10(-7) mol/L). Furthermore, such effects are not cell lineage specific, being observed also in clonogenic cultures of erythroid and eosinophil granulocyte progenitor cells, and the phenomenon attributed to lithium is a property shared with rubidium and cesium salts. These findings point to a role for lithium and its elemental relatives in the biophysical mechanisms involved with the control of human blood cell production.
Cells, Cultured↗
Hydrocortisone promotes clonal granulopoiesis in cultures of normal human bone marrow--a "nutritional" advantage or true stimulation of growth?
The generation of normal human hemopoietic clones is promoted, in tissue culture, by physiological as well as pharmacological concentrations of hydrocortisone. In part this may reflect a facilitative, nutritional effect of the hormone which may be more evident in particular culture media. However, the findings, in liquid suspension cultures, of an increase in the absolute number of cells and a rise in the mitotic index in the presence of hydrocortisone, point to a real stimulation of cellular proliferation. Measurements of the number of clones early in culture, and the size of clones after longer intervals, indicate respectively that the hormone influences both recruitment of clonogenic cells into cytokinesis and amplification of established clones. The target cell in both processes may be the same, namely a morphologically recognizable entity, in the granulocyte lineage, having limited proliferative potential. Evidence in support of this interpretation includes the high cloning efficiency, small mean clonal size and brief clonal lifespan. These features suggest that members of the myeloblast-promyelocyte-myelocyte hierarchy are likely candidates, but whether the action of hydrocortisone is exerted directly on these cells, or on a more mature accessory population, remains to be determined.
Bone Marrow↗
Interactions of stem cells and T lymphocytes contribute to the physiological control of cell proliferation in rapidly renewing tissues.
Control of cell proliferation, in tissues which replicate rapidly, may be exercised, at least in part, by common populations of circulating cells. Thymus-derived (T) lymphocytes possess properties which would fit them for this purpose. Among these are the functional manifestations of 'help' and 'suppression' with respect to defined physiological processes, such as immunoglobulin production; and unique traffic patterns in blood and extra-vascular tissues, including those in non-lymphoid organs such as bone marrow, skin and gut epithelium. This tropism may involve specific chemotactic agents and result in a predominance of 'suppressor' cells in target tissues. A 'steady-state' of cell proliferation could be maintained by this mechanism which is subject to humoral modulation, for instance by corticosteroids. Influx of 'helper' T lymphocytes would stimulate cell production while an excess of 'suppressors' would diminish cell renewal, as has been observed in some forms of bone marrow aplasia. Fulfillment of these roles by T cells may depend on the expression of antigens in the HLA-DR complex and it has implications for further insight into the pathogenesis of auto-immunity and neoplasia.
Animals↗
Spurious detection of terminal deoxynucleotidyl transferase in phytohemagglutinin-stimulated lymphocytes.
Expression of terminal transferase (TdT) is believed to be restricted to primitive lymphoid cells; recently, however, indirect immunofluorescent (IF) assays have been used to demonstrate the apparent presence of TdT in phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes and in various nonlymphoid malignancies. Using an IF assay, we found that a heteroantiserum to TdT reacted with cultured and PHA-stimulated human peripheral blood mononuclear cells, but we were unable to confirm the presence of TdT in these cells using immunoblotting and biochemical assays. We conclude that the IF results are spurious and most likely represent recognition by the heteroantiserum of inducible protein(s) other than TdT.
Clinical Enzyme Tests↗
Growth of erythroid colonies in agar cultures of normal human bone marrow.
The use of methylcellulose (MC) gels or plasma clots, for the support of human erythropoiesis in vitro, is associated with several technical disadvantages. Substitution of soft agar offers the prospect of overcoming these difficulties. In comparative studies, normal human bone marrow cells were cultured with erythropoietin (Epo) in agar (0.1%-0.3%) and MC. Concentrations of 0.175% and 0.2% agar proved to be optimal with respect to the combination of cloning efficiency and colony density. Further morphological examination revealed that subcolony formation in erythroid 'bursts' was influenced by gel viscosity. In additional experiments, miniaturising the assay system, to 0.25 ml culture volumes, increased cloning efficiency and reduced Epo utilization. These results confirm and expand earlier observations, and support a preference for the general use of agar in human erythroid cell cultures.
Agar↗
A fatal lymphoproliferative disorder with a suppressor T-cell phenotype. Neoplastic, reactive, or both?
We describe the case of a boy who presented with clinical features of lymphadenitis accompanied by a lymphocytic leukemoid reaction of suppressor/cytotoxic T-cell phenotype. Progressive involvement of the bone marrow, liver, and spleen, and subsequently parotid and lacrimal glands, in the disease process, suggested the alternative diagnosis of malignant lymphoma. An initial dramatic response to Prednisolone was not sustained and he died within 8 weeks of the original onset of symptoms. Postmortem examination revealed extensive lymphocytic infiltration in many organs, and a differential diagnosis of lymphoproliferation is considered. The pathogenesis of this disorder is not established; whether it was essentially neoplastic or reactive is unresolved.
Child↗
Detection of terminal deoxynucleotidyl transferase.
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Acquired Immunodeficiency Syndrome↗
Simultaneous or sequential expression of lymphoid and myeloid phenotypes in acute leukemia.
Acute mixed myeloid-lymphoid leukemia is uncommon. We report four cases in which myeloid and lymphoid cell markers were observed simultaneously or sequentially when 94 patients with acute leukemia were phenotyped according to the French-American-British (FAB) classification system, with cytochemical stains, and with immunologically defined differentiation markers (identified by monoclonal antibodies and antiterminal deoxynucleotidyl transferase [TdT]). In one case, conversion from acute lymphoblastic leukemia to acute myeloid leukemia was noted (FAB L1, TdT+ to FAB M4, Auer rods, TdT-). In another patient, two distinct populations of myeloid and lymphoid blast cells were observed simultaneously (TdT-, LeuM1+/TdT+, LeuM1-). In two additional patients, acute leukemia was characterized by the expression of both lymphoid and myeloid markers on the same cell (TdT+/Leu M1+, B4+/Leu M1+ and greater than or equal to 70% TdT+, T11+, My9+). The Philadelphia (Ph1) chromosome was negative in all cases, though other chromosomal abnormalities were noted in three out of four cases. Malignant transformation of a pluripotential stem cell for both lymphoid and myeloid lineages, with or without the Ph1 chromosome marker, could explain the coexistence of distinct populations of lymphoblasts and myeloblasts in acute leukemia. Acute leukemia with a biphenotypic profile may reflect genome depression accompanying neoplasia.
Adult↗
Human granulopoiesis in vitro: an advantage in the use of Iscove's modified Dulbecco's medium.
With the aim of determining whether Iscove's Dulbecco's medium (IMDM) provides a growth advantage in the support of granulopoiesis from cultures of human bone marrow in agar, samples from 20 normal subjects were examined in triplicate after 7, 10 and 14 days in parallel cultures containing IMDM or Dulbecco's medium. From every sample, more granulocyte-macrophage colonies were obtained at each culture interval with IMDM. In particular, the number of colonies with IMDM at 14 days (96 +/- 13 per 2x10(5) bone marrow cells) was almost double that with Dulbecco's medium (50 +/- 10). This increment consisted almost entirely of pure granulocyte colonies (P less than 0.001). No significant change in the proportion of eosinophil colonies was observed. These data indicate that IMDM does provide a growth advantage over Dulbecco's medium in the generation of granulocyte (neutrophil and eosinophil) colonies from agar cultures of normal human bone marrow.
Bone Marrow Cells↗