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Biomedical subjects

N Williams

Publications and source records attributed to N Williams.

At least 379 records · Page 21Linked to original sources
PubMed1979

Maturation and regulation of megakaryocytopoiesis.

The in vitro cloning technique for detecting megakaryocyte precursor cells was employed to compare stimuli known to influence megakaryocytopoiesis. Preparations of thrombopoietic stimulating factor (TSF) did not directly stimulate the growth of megakaryocyte colonies (CFU-m) but increased the frequency of CFU-m when TSF was added to the cultures with a constant amount of megakaryocyte colony stimulating factor. Platelets or platelet homogenates did not influence the frequency of CFU-m or the size of individual colonies. Analysis of cell surface properties of megakaryocytes obtained either by isolation from bone marrow or from in vitro colonies revealed species differences. The possibility that megakaryocytopoiesis and platelet release are regulated both within the marrow as well as by humoral factors is discussed.

Animals↗
PubMed1979

Abnormalities in clonable B lymphocytes and myeloid progenitors in autoimmune NZB mice.

Cloning procedures were used to study B lymphocytes and progenitors of granulocytes and macrophages in NZB mice. Numbers of B cells that were detected in sheep erythrocyte-containing semisolid cultures were only slightly elevated in NZB tissues, and these were normally sensitive to inhibition by anti-mu or anti-delta antibodies or prostaglandin E. However, NZB mice rapidly developed large numbers of B cells that could be cloned in the presence of lipopolysaccharide, and these included unusual anti-mu resistant cells. Numbers of myeloid precursors in NZB bone marrow that were responsive to colony-stimulating activity in L-cell conditioned medium or endotoxin serum were at least normal, but at all ages granulocyte-macrophage precursors were poor responders in cultures stimulated by WEHI-3 cell conditioned medium. Almost no colonies were elicited in NZB cultures with a colony-stimulating activity moiety from WEHI-3 cells. Prostaglandin sensitivity of myeloid precursors from NZB and CBA mice was also different. Codominant genetic control of these abnormalities was suggested by their partial expression in F1 hybrid NZB X CBA and NZB X NZW mice. NZB mice expressed an unexpected IgD allotype allele.

Animals↗
PubMed1979

Immune adherence of platelets to sensitized leukocytes: a model of hyperacute rejection.

Specifically hypersensitized recipients of canine renal allotransplants demonstrate an accumulation of host platelets in the transplanted kidney within minutes following implantation. Transplant function is ra,idly lost. The present work describes an in vitro model of this hyperacute rejection mechanism. Renal donor leukocytes sensitized with host serum are incubated with donor platelets. Within a few minutes the platelets adhere to the sensitized leukocytes to form rosettes. Serum complement is required for platelet rosette formation. Platelets act as indicators in this reaction and they may be obtained from any dog. Donor platelets were used to avoid the transfer of specific antibody to the test mixture. The in vitro model supports the view that hyperacute rejection in the dog is a specific example of the immune adherence reaction in which platelets bind to antigen-antibody-complement complexes.

Animals↗
PubMed1979

Matching of chemotherapy to mouse strain and lymphoid tumor type to prevent tumor-induced suppression of specific T- and B-cell functions.

Specific immunological and hematopoietic functions were studied during treatment with antineoplastic agents in mice bearing syngeneic lymphoid tumors: 70Z/2, a B-cell lymphoma of C57BL X DBA/2 F1 (hereafter called (BD2F1) mice; EL4, a T-cell lymphoma of C57BL/6 mice; or J774, a macrophage tumor of BALB/c mice. Both B- and T-lymphocyte function (antibody-forming cells and cell-mediated lymphocyte lympholysis toward alloantigens) were suppressed in spleen cells of mice bearing these tumors. Other hematopoietic functions (granulocyte, macrophage, and megakaryocyte progenitor cells) were variably influenced by growth of these lymphoid tumors. J774 enhanced, but 70Z/2 suppressed, megakaryocyte progenitor cells. J774 and 70Z/2 increased levels of granulocyte-macrophage progenitor cells. EL4, the T-cell lymphoma, did not influence either cell type. Significant variation in strain sensitivity to drug toxicity and drug effectiveness in different tumor-host systems was observed. Increased median survival time with reversal of tumor-induced immune dysfunction, without toxicity to hematopoietic progenitor cells, was realized in two tumor-host-drug combinations. Polyinosinic-polycytidylic acid was effective against J774, while actinomycin D was active against 70Z/2. Mitomycin C effectively reduced tumor load, as evidenced by loss of splenic tumor colony-forming cells for all three tumors. This agent prolonged survival and concomitantly restored immunological responsiveness in hosts immunosuppressed by growth of 70Z/2 or J774. Paralleling tumor reduction with mitomycin C therapy, the splenic hematopoietic progenitor and colony-forming B-cells were reduced in tumor-bearing and tumor-free mice, thus compromising its therapeutic effectiveness. 1-beta-D-Arabinofuranosylcytosine reduced tumor load with marginal toxicity toward hematopoietic progenitor and colony-forming B-cells. However, immune responsiveness was only partially restored, and median survival was not increased. The results presented show the diversity of therapeutic drug effectiveness in increasing mean survival time and influencing other life-sustaining parameters (immunological and hematopoietic functions).

Animals↗
PubMed1979

Isolation of pluripotent hemopoietic stem cells and clonable precursor cells of erythrocytes, granulocytes, macrophages and megakaryocytes from mouse bone marrow.

Murine pluripotent hematopoietic stem cells and precursor cells with restricted commitment to erythrocytes, granulocytes and macrophages as well as megakaryocytes have been purified 30- to 50-fold from mouse bone marrow cells. Purification was achieved by a three-step procedure. Bone marrow cell populations free of erythroid cells and lymphocytes were obtained by culturing the cells for several weeks. Macrophages and adherent polymorphic neutrophils (PMN) were removed by adherence to plastic. The remainder of the PMN along with more primitive granulocytes (but not promyelocytes and some monocytoid cells) were removed either by neutral density centrifugation or by differential centrifugation after rosette formation with sheep erythrocytes coated with immunoglobulin (EA rosettes). The remaining population of marrow-derived cells contained 40-66% blast cells, 20-35% promyelocytes and 5-10% other cells (usually PMNs and monocytes). Using cloning techniques to detect immature hemopoietic cells, this population contained 15-35% granulocyte-macrophage progenitor cells, approximately 0.2% erythroid burst-forming cells, approximately 0.1% megakaryocyte progenitor cells and 1-3% pluripotent stem cells (based on seeding efficiency 0.06).

Animals↗
PubMed1979

Preferential inhibition of murine macrophage colony formation by prostaglandin E.

Murine bone marrow progenitor cells that gave rise to macrophage colonies in semisolid agar were found to be more sensitive to prostaglandins of the E series (PGE) than were precursor cells of granulocytes and megakaryocytes. Macrophage colonies themselves had different sensitivities to the molecule. Precursor cells of macrophages that formed colonies in the presence of a stimulating activity from L cells (L-cell CSA) were inhibited to 50% levels by 3 x 10(-9)-M PGE. Macrophage progenitor cells, which require both L-cell CSA and rat hemolysate for colony growth, were inhibited to the same level by 3 x 10(-7)-M PGE. Other colony types (granulocytes and megakaryocytes) were sensitive to PGE only at concentrations greater than 10(-6) M. Accordingly, addition of different PGE concentrations to the culture assay should allow easy detection of precursor cells with morphologically distinct end cells. The different sensitivities to PGE of two macrophage colony types of different maturation stages indicate that PGE may provide feedback to control macrophage formation by inhibiting proliferation and differentiation of immature monocytoid cells.

Animals↗
PubMed1979

The effect of morphine on the endogenous phosphorylation of synaptic plasma membrane proteins of rat striatum.

The synaptic plasma membrane (SPM) fraction was prepared from rat striata and assayed for endogenous phosphorylation in vitro. After the separation of membrane proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the incorporation of phosphate into specific membrane proteins was analyzed by gel slicing and autoradiographic techniques. Phosphate was incorporated into several SPM protein bands, two of which were regulated by cyclic adenosine 3':5' monophosphate. As a consequence of the chronic (in vivo) administration of morphine, the phosphorylation of two protein bands, designated protein II (MW 48,000-52,000) and protein III (MW 11,000-18,000), was reduced by approximately 20 and 50%, respectively; the phosphorylation of the former proteins was regulated by cyclic adenosine monophosphate whereas the phosphorylation of the latter proteins was not. The incorporation of phosphate into these same two protein bands was similar to control values when the membranes were obtained from rats undergoing naloxone-precipitated withdrawal. Morphine, in vitro, did not alter the phosphorylation of any SPM proteins in the assay, although at a high concentration morphine did antagonize the calcium-stimulated phosphorylation of one or more proteins in band II. The development of tolerance to and dependence on opiates may include changes in the phosphorylation of specific SPM proteins.

Animals↗
PubMed1978

Membrane receptors of mouse leukocytes. II. Sequential expression of membrane receptors and phagocytic capacity during leukocyte differentiation.

Analysis of four mature cell markers on mouse bone marrow leukocytes grown in vitro, demonstrated a distinct sequence of marker appearance during the terminal phases of granulocytic cell differentiation. A similar pattern of marker expression was also suggested by analysis of mature neutrophils and macrophages isolated from normal tissues. Among cultured neutrophils, receptors for the Fc portion of IgG (FcR) were first expressed on myelocytes and metamyelocytes, and then subsequently on more mature cells. Morphologically mature colony neutrophils (polymorphs) from agar cultures contained only FcR and complement receptor type two (CR(2)) (C3d receptor), and lacked both complement receptor type one (CR(1)) (C3b receptor) and the capacity to ingest latex, bacteria, or iron particles. Neutrophils from 2 and 3 wk liquid media cultures of marrow cells differed from agar grown neutrophils in that they had phagocytic capacity (particle ingestion) [Pi] in addition to FcR and CR(2). Furthermore, in the 4th and 5th wk of these continuous liquid cultures, CR(1) was also expressed, completing the surface marker profile of normal blood neutrophils. Based on these studies, the following order of appearance of these four markers on cells from the myelocytic series was proposed: FcR {arrow} FcR CR(2) {arrow} FcR CR(2) Pi {arrow} FcR CR(2) Pi CR(1). Differential studies of tissue leukocytes containing these same markers revealed that a heterogeneity existed among morphologically mature neutrophils. Even though 95 percent of blood polymorphs contained all four markers, the same was true of only half of spleen polymorphs and only 20 percent of bone marrow polymorphs. Cells of the monocyte-macrophage series were studies in parallel with neutrophils. Cultured marrow monocytes acquired the four mature cell markers so rapidly that the order of receptor appearance could not be determined. However, it was found that CR2 was lost during the terminal phase of monocyte maturation into activated macrophages.

Animals↗
PubMed1978

Effect of smoking during pregnancy upon the haematological values of cord blood.

Haematological indices in cord blood, measured by a Coulter Counter, in 50 mothers who smoked 10 or more cigarettes a day were compared with those in 75 control mothers who were non-smokers, but of similar age and parity. Smoking during pregnancy was associated with higher levels, of haemoglobin, and the haematocrit, as well as with higher red cell counts and a higher mean corpuscular haemoglobin. The percentage of fetal haemoglobin in cord blood was not affected by smoking. There was no correlation between social class and cord blood haemoglobin; but within social class groups, higher cord blood haemoglobin levels were associated with smoking. It is suggested that smoking during pregnancy stimulates fetal erythropoeisis.

Bilirubin↗
PubMed1978

Leucocyte ascorbic acid in Crohn's disease.

Leucocyte ascorbic acid levels have been found to be lower in patients with Crohn's disease than in normal controls. This appears to be due to the disease rather than the effect of drug or operative treatment. Prescribing supplementary ascorbic acid is an appropriate step in correcting this deficiency.

Adult↗
PubMed1978

Differences in the buoyant density characteristics of murine granulocyte-macrophage progenitor cells cloned in the presence of serum and/or hemolysate.

Bone marrow-derived progenitor cells of granulocytes and macrophages undergo proliferation and maturation in vitro in the presence of colony-stimulating factors and suitable sera. It has recently been found that rat hemolysate can replace serum as a source of growth-supporting activities for cloning these progenitor cells. It is unclear, however, whether serum or hemolysate allows the growth of separate or identical precursor cell subpopulations. Granulocyte-macrophage progenitor cell populations cloned in either serum or hemolysate were identical in their buoyant density characteristics. However, an additional population of granulocyte-macrophage progenitors was preferentially detected when both substances were added to the cell cultures. Different responding cells may, therefore, differ in their nutritional requirements for in vitro cloning. Variability in the respective amounts of these growth factors in the stimulator source would influence the number of CFU-C cloned. The actual amount of stimulator in unpurified sources may, therefore, be grossly overestimated.

Animals↗
PubMed1978

Regulation of megakaryopoiesis in long-term murine bone marrow cultures.

Megakaryocytes and their precursor cells were sustained in mouse bone marrow suspension cultures for over 4-6 wk. Megakaryocyte precursor cells were detected by their capacity to form colonies of megakaryocytes in semisolid agar cultures. Colony formation was dependent on the presence of medium conditioned by a myelomonocytic leukemic cell line (WEHI-3CM). Megakaryocytes from the liquid and semisolid cultures were identified by cytoplasmic acetylcholine esterase and by ultrastructural analysis. The suspension medium from the bone marrow liquid cultures which sustained megakaryopoiesis was not directly acitive in stimulating megakaryocyte colony formation in the semisolid agar cultures, but potentiated the number of colonies detected when WEHI-3CM was present. Bone marrow-conditioned medium increased the sensitivity of megakaryocyte progenitor cells to the stimulus in WEHI-3CM. Addition of the activities present in the two sources produced a quantitative assay for the detection of mouse megakaryocyte progenitor cells. These studies showed: (1) that no inductive regulator of in vitro clones of megakaryocytes was present in the supernatants from the long-term marrow cultures and, (2) that at least two factors were necessary for the induction of megakaryocyte progenitors to proliferate and differentiate in semisolid cultures in vitro.

Animals↗
PubMed1978

Regulation of proliferation of murine megakaryocyte progenitor cells by cell cycle.

The extent to which mouse megakaryocyte progenitor cells (colony-forming unit-megakaryocyte, CFU-M) can proliferate in semisolid cultures prior to endomitosis, and conditions that may regulate that differentiation step, were investigated. The proliferative capacity of CFU-M was determined by estimating the number of megakaryocytes per colony. A bimodal distribution was observed (modal values, 10-15 and 25-30 cells/colony), indicating that separate megakaryocyte progenitor cells may be biased in their capacity for proliferation versus endomitosis. Differences were observed in the cell cycle characteristics of CFU-M as determined in vivo and in vitro that suggest that maturation of CFU-M into megakaryocytes may be regulated within the marrow by control of the cell cycle of the megakaryocyte precursor cell.

Animals↗
PubMed1978

Effect of myleran on murine hemopoiesis. III. Changes in the density distribution of spleen colony forming (CFU-S) and agar gel colony forming cells (CFU-C).

Spleen colony forming cells (CFU-S) and agar-gel colony forming cells (CFU-C) are separate but heterogeneous cell populations, as measured by buoyant density. Myleran (MY) abrogated the major (lighter density) components of the CFU-S and CFU-C compartments, thus shifting the surviving CFU-S and CFU-C density profiles into the higher density region. The normal spleen colony erythrocytic : granulocytic (E:G) ratio profile showed three density regions with different distributions of erythroid and granulocytic colonies. The preponderantly erythrocytic colony-generating CFU-S of the intermediate density regions were eradicated by MY. Comparison of the density distribution of erythrocytic and granulocytic colony-generating CFU-S of normal bone marrow showed that the erythrocytic CFU-S profile paralleled that of total CFU-S, while most of the granulocytic CFU-S were contained in the major (and lowest density) peak. MY eradicated the two main (and lowest density) peaks of CFU-S; surviving CFU-S occurred preponderantly in a minor (higher density) peak which has a high potential for generating erythrocytic colonies.

Animals↗
PubMed1977

Proliferation and differentiation of normal granulopoietic cells in continuous bone marrow cultures.

Modified conditions are reported for successful continuous bone marrow cultures with stem cell self-renewal and granulocyte-macrophage differentiation. Cells cultured over several weeks were found to be identical to freshly isolated bone marrow cells. Polymorphic neutrophils derived from cultures and primary bone marrow neutrophils both showed C3 AND IgG receptors and both actively phagocytosed foreign particles. Cultured and normal CFU-c were identical, both in their dose responsiveness to CFS and in their sedimentation rate characteristics.

Bone Marrow Cells↗