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Biomedical subjects

A D Bankhurst

Publications and source records attributed to A D Bankhurst.

At least 19 recordsLinked to original sources
PubMed1992

Effects of pertussis toxin treatment on human natural killer cell function.

Membranes from highly purified natural killer (NK) cells were ADP ribosylated by treatment with pertussis toxin (PTX). PTX treatment resulted in a single band of 32P incorporation at M(r) 41,600. PTX treatment of NK cells diminished their ability to lyse K562 tumour cells by about 50%. However PTX treatment had no measurable effect on cAMP levels in NK cells. PTX pretreatment also had no effect on the ability of target cells to induce phosphoinositide turnover or on the ability of the NK cells to conjugate with the K562 tumour cells. Movement toward the chemoattractants interleukin-2 (IL-2) and formylmethionylleucylphenylalanine (FMLP) was significantly inhibited indicating that a PTX substrate in NK cells may be involved in the transduction of signals which are involved in cell motility.

Cell Adhesion↗
PubMed1990

Effects of beta-adrenergic receptor activation, cholera toxin and forskolin on human natural killer cell function.

Membranes from highly purified natural killer (NK) cells were ADP-ribosylated by treatment with cholera toxin (CTX). CTX resulted in a single band of specific 32P incorporation at Mr 43,600. CTX treatment of intact NK cells caused a 9-fold increase in cyclic AMP (cAMP) concentrations. Pretreatment of NK cells with CTX diminished their ability to lyse K562 tumour cells by up to 79%. Forskolin treatment elevated NK cell cAMP levels 8-fold and decreased lysis of K562 cells by up to 45%. Adrenaline and isoprenaline (isoproterenol) both inhibited lysis of K562 cells by approx. 35% and elevated cAMP by at least 2.5-fold, and their inhibition of lysis was reversed by propranolol. These data suggest that the stimulatory guanine-nucleotide-binding protein GS coupled to beta-adrenergic receptors is involved in transducing signals which inhibit NK cell lysis of tumour cells. CTX and forskolin also diminish the ability of NK cells to bind K562 cells (binding is necessary for lysis). This suggests that the NK-cell receptor(s) for the tumour cell may be altered as a consequence of cAMP-mediated events or by activation of GS.

Adenosine Diphosphate Ribose↗
PubMed1990

Human natural killer cells express Na+ channels. A pharmacologic flow cytometric study.

Voltage-gated excitability of purified human NK cells was studied by using flow cytometry and the voltage-sensitive dye, oxonol. Highly purified human NK cells (CD16 = 95 +/- 1%) from normal volunteers were prepared by using a negative panning technique. The Na(+)-channel agonists batrachotoxin (BTX) (1 to 4 microM) and veratridine (Ver) (100 to 400 microM) depolarized a population of highly purified human NK cells as determined by flow cytometry. BTX and Ver responses were concentration-, time-, temperature-, and Na(+)-dependent. The Na+ channel antagonist tetrodotoxin (1 microM) blocked BTX and Ver responses. Ver (100 microM) produced significant inhibition of cytotoxicity when purified NK cells were incubated with K562 tumor target cells in a 4-h 51Cr release cytotoxicity assay. The effect was blocked by tetrodotoxin. These results strongly suggest presence of functional Na+ channels in NK cells. Activation of voltage-dependent Na+ channels depolarizes cells and reduces their in vitro cytotoxic function.

Batrachotoxins↗
PubMed1979

Crossed radioimmunoelectrophoresis for the analysis of lymphocyte surface antigens.

A sensitive crossed radioimmunoelectrophoreses technique is described as a model tool for studying lymphocyte surface antigens, using Triton X-100 solubilized sufface radiolabeled human peripheral blood lymphocytes as the antigen source and experimental antiserum produced by hyperimmunization of rabbits as the antibody source. The technique seems to have potential for qualitative as well as quantitative analyses of lymphocyte surface antigens.

Absorption↗
PubMed1979

Modulation of the adherence of human lymphocytes to measles-infected cells by prostaglandin E1: a differential effect on lymphocyte subpopulations.

Prostaglandins of the E series (PGE) may serve as important regulators of human immune responsiveness. The present study was designed to examine the possibility that PGE may effect human lymphocyte function by the modulation of surface receptors. The presence of surface binding sites on human lymphocytes for measles virus antigens was studied using a rosette adherence assay. We observed that the addition of PGE1 increased the proportion of measles-infected cells (Hela-Kll) with adherent lymphocytes (75% increase at 3 x 10(-6) M PGE1). PGE was observed to enhance the adherence of purified normal peripheral T cells (87%) and T lymphoid cells (Molt 3) (27%). In contrast, no significant change in normal peripheral B cell or B lymphoid cell (Raji) adherence was observed with the addition of PGE. These results are consistent with a selective modulation of surface measles virus binding sites by PGE1 on T and not B lymphoid cells.

Adult↗
PubMed1979

Cell-mediated immunity in Darier's disease.

Darier's disease, often complicated by skin infections, has been linked with a depressed cell-mediated immunity. Four moderate to severely affected patients with a negative history of skin infections were studied. T cell function was evaluated by standard delayed hypersensitivity skin tests, enumeration of peripheral T cell-mediated immunity was found. The significance of the results when compared with prior studies is discussed.

Adolescent↗
PubMed1979

Adherence of human peripheral blood lymphocytes to measles-virus infected cells: modulation by solubilized rhesus erythrocyte membranes and carbohydrates.

The adherence of human peripheral blood lymphocytes to HeLa cells persistently infected with measles virus (HeLa-K11) was studied. The following data were observed. (i) The proportion of HeLa-K11 cells with adherent human peripheral blood lymphocytes of rhesus monkey erythrocytes was similar over a wide range of ratios of HeLa-K11 cells to lymphocytes or erythrocytes. (ii) The great majority of human peripheral blood lymphocytes and erythrocytes reacted with the same HeLa-K11 cell (iii). The adherence of lymphocytes or erythrocytes to HeLa-K11 cells was blocked by rabbit anti-measles virus antibody or solubilized monkey erythrocyte membranes. The pretreatment of erythrocytes or lymphocytes with receptor-destroying enzyme did not alter their adherence properties. (iv) The pattern of inhibition observed with several carbohydrates was similar in both the erythrocyte and the lymphocyte adherence assays. These data are consistent with the possibility that the receptor present on both rhesus monkey erythrocytes and human lymphocytes has similar specificities and biochemical composition.

Animals↗
PubMed1979

Studies of human cord blood and adult lymphocyte interactions with in vitro immunoglobulin production.

Newborns are unable to produce normal amounts of immunoglobulin despite the presence of circulating lymphocytes with surface immunoglobin (Ig). This study was designed to examine the cellular basis of such impaired Ig synthesis in the newborn infant. An in vitro assay for IgG and IgM synthesis was employed which measured the Ig present in the supernates of pokeweed mitogen-stimulated cord blood and/or adult peripheral mononuclear cells (MNC). Results were as follows: (a) the addition of cord blood MNC to adult MNC suppressed both normal IgG and IgM production; (b) addition of a suspension of adult thymus-derived (T) cells to cord bone marrow-derived (B) cells did not enhance the production of Ig; (c) the addition of cord T cells to adult B cells did not enhance normal Ig production but did significantly depress IgM and IgG synthesis; and (d) irradiation of cord T cells with 2,000 rads removed the suppressive effect of cord T cells on adult MNC. A similar reversal of the suppressive effect exerted by cord MNC was also seen in the presence of 10 microM of hydrocortisone. It appears that the inability of newborn infants to make normal amounts of Ig is a result of a combined B-cell defect and the presence of a steroid-sensitive and radiosensitive suppressor cord T cell.

Adult↗
PubMed1978

B-cell leukemia-lymphoma with striking resemblance to Burkitt lymphoma in a 70-year-old woman.

A 70-year-old woman developed acute leukemia and a serum IgM spike. She entered complete remission with an adriamycin, vincristine, cytosine arabinoside, and prednisone combination. Bone marrow remission was maintained with intermittent cytosine arabinoside; however, she developed large skin nodules which partly remitted following adriamycin, vincristine, cyclophosphamide, and prednisone combination. They very rapidly recurred, and she died soon after. Autopsy revealed extensive tumor in the abdomen, pelvis, and thoracic cavity, but no bone marrow involvement. Histology revealed a "starry sky" appearance. Cytology showed undifferentiated cells with vacuolated cytoplasm resembling Burkitt lymphoma cells. Peroxidase and esterase stains were negative. There was strong pyroninophilia and the periodic acid-Schiff reaction showed granular activity in the cytoplasm. Electron microscopic appearances also resembled Burkitt lymphoma. Cytogenetic studies were normal, with no Ph1 chromosome. Immunofluorescence demonstrated surface IgM and a little IgA. 3H-thymidine incorporation was high, indicating rapid growth. Dibutyral cyclic adenosine monophosphate (cAMP) stimulated growth, which was further evidence of the lymphoid origin of the tumor. The close resemblance of this tumor to Burkitt lymphoma emphasizes the difficulties in systematically classifying the lymphomas.

Acute Disease↗
PubMed1978

Clinical immunologic studies in systemic lupus erythematosus.

This review of recent and new directions in clinical immunologic studies of systemic lupus erythematosus (SLE) is restricted to the areas of lymphocyte surface markers, antigen binding lymphocytes, immune complexes, and lymphocyte hyporesponsiveness in lupus patients. First, it is not clear whether the T-lymphopenia observed in SLE is related to viral destruction of T cells, anti-lymphocyte antibodies, or tissue sequestration. Second, the increase in DNA-binding B lymphocytes observed in active lupus patients may be related to minor alterations in the balance of immunoregulatory T cells or to a bypass of DNA-specific helper T cells. Third, it is speculated that the removal of immune complexes which play a role in lupus glomerulitis by various extracorporeal immune absorbents may be important in the future therapy of SLE. Fourth, the mechanisms of T-lymphocyte hypofunction are unexplained. It is postulated from studies done in other diseases that this hypoactivity may be mediated by the secretion of prostaglandin or other humoral agents from one leukocyte subpopulation suppressing another potentially responsive lymphocyte subpopulation. Also an investigation into the lymphocyte subpopulation reactive with virus-infected fibroblasts may be useful in delineating immunoregulatory lymphocytes important in the pathogenesis of SLE.

Antigen-Antibody Complex↗
PubMed1978

Transfer of mouse IgG2 production by IgM-bearing spleen cells separated by a fluorescence-activated cell sorter.

The purpose of the present study was to determine whether at least some splenic B lymphocytes can switch from the synthesis of one isotype of immunoglobulin to another during B cell differentiation. The experimental system invovled the transfer of characterized cell suspensions between allotype congenic strains of mice followed by analysis in the recipient for donor type immunoglobulin production. Donor splenic lymphocytes were incubated with specific fluorescent labelled anti-mu antiserum and passed through the Los Alamos fluorescence-activated cell sorter; mu-depleted cell suspensions were transferred into sublethally irradiated congenic recipients and the amount of donor type immunoglobulin of IgG2 type was measured at weekly intervals. The results demonstrated taht at least some cell bearing membrane bound IgM can differentiate in vivo into IgG2-secreting cells, although not all IgG2-secreting cells have been recently derived from IgM positive precursors.

Animals↗
PubMed1978

Empiric analysis of the interactions involved in the formation of Fc receptor rosettes.

Erythrocytes coated with IgG were used in forming rosettes with lymphocytes and polymorphonuclear leukocytes to investigate Fc receptors. The density of the IgG-Fc coating on erythrocytes predictable influenced the number of rosettes formed with leukocytes. This relationship could be empirically described by application of the Hill equation derived from studies of molecular interactions in other biologic systems. The approximate Hill coefficient for Fc receptors was 2.4. These findings suggest at least two possible models for membrane Fc receptor function.

Binding Sites, Antibody↗
PubMed1978

Studies of cell subpopulations mediating mitogen hyporesponsiveness in patients with Hodgkin's disease.

Hodgkin's disease (HD) is associated with a deficit in T-cell immunity characterized by skin test anergy and decreased lymphocyte responses to phytohemagglutinin (PHA). To investigate this mitogen hyporesponsiveness in HD, we separated peripheral blood mononuclear cells on Ficoll-Hypaque gradients and determined their response to various suboptimal concentrations of PHA. As was expected, patients with HD demonstrated marked mitogen hyporesponsiveness relative to normal controls; however, if the cell suspensions were first passed through glass wool columns to remove adherent cells, the PHA responsiveness of the hyporesponsive HD cells was markedly increased. In contrast, the responsiveness of normal controls was decreased so that the responses of nonadherent normal and HD cells were statistically indistinguishable. Evidently, a glass wool-adherent suppressor cell had been removed from patients with HD, while a glass wool-adherent cell which enhanced mitogenic responses had been removed from normal controls during column passage. Previous to column depletion, patients with HD had decreased proportions of E-rosettes and increased proportions of cells with surface alpha-fetoprotein; however, the proportion of these cells was not changed after column passage. Significant changes with column depletion of glass wool-adherent cells in HD were recorded in the proportions of monocytes (13.2 vs 5.8%) and lymphocytes with C-3 receptors (12.6 vs. 7.8%). The only significant change in normal controls was a decrease in the proportion of monocytes (10 vs. 1.7%). To determine if glass-adherent cells would have a suppressor effect, HD-adherent cells were added in progressively increasing numbers to mononuclear cell suspensions depleted of glass wool-adherent cells. PHA responsiveness returned toward predepletion levels. In summary, patients with HD possess a glass wool-adherent suppressor cell which is responsible at least in part for in vitro mitogen hyporesponsiveness.

Hodgkin Disease↗
PubMed1978

A population of human cord blood mononuclear cells with surface alpha fetoprotein.

Suspensions of mononuclear cells from adult peripheral blood (PBL) and mononuclear cells from cord blood (CBL) were examined for the presence of surface alpha-fetoprotein (AFP) using a fluoresceinated F(ab')2 fragment of rabbit IgG anti-human AFP. The mean proportion of CBL with AFP was increased (10%) when compared with PBL (1%) although some CBL specimens did not demonstrate such an increase (range 0--15%). The presence of AFP on CBL could be either due to cytophilic AFP attached to a unique surface receptor or intrinsic AFP synthesis. The following observations could not distinguish between these two possibilities: (1) After treatment with trypsin, only minor reappearance of surface AFP could be observed in AFP-free medium in contrast to the larger numbers observed in medium containing AFP. Such selective reappearance depending on the media could be related to either cytophilic attachment of heterologous or homologous AFP or preferential stimulation of intrinsic AFP synthesis. (2) The reappearance of AFP positive CBL following trypsin treatment and incubation in media with or without AFP containing sera was inhibited by cyclohexamide. Such inhibition could be due to inhibition of synthesis of an AFP surface receptor or intrinsic AFP. (3) The shedding of surface AFP observed at 2--4 degrees C could be due to release of exogenous cytophilic AFP or the continued "turnover" of intrinsic AFP without concomitant AFP synthesis due to the cold temperature. Finally, the removal of AFP positive cells via selective depletion of B cells using bead columns coated with IgG-anti-IgG and the absence of depletion of AFP positive cells after successive gradient centrifugation of E-rosettes and cells with IgG-Fc receptors are consistent with the identity of AFP positive CBL as cells without IgG-Fc receptors or lymphocytes without conventional T-cell markers as defined by E-rosettes.

Cell Membrane↗
PubMed1978

Human lymphocyte subpopulations defined by double surface markers.

Subpopulations of human peripheral blood lymphocytes were studied with single and double surface marker assays. The markers employed were as follows: (1) Fc receptor, using EA, mean 21.4%; (2) C3 receptor, using Zy-C3, mean 14.6%; (3) Slg, using a fluoresceinated F(ab')2 anti-F(ab')2 mean 8.9%; and (4) T lymphocytes forming E-rosette, mean 69.3%. The proportions of lymphocytes with any given surface marker which also have another surface marker were as follows: (1) EA + Slg/EA = 0.14, (2) EA + Zy-C3/EA = 0.22, (3) Slg + Zy-C3/Slg = 0.83, (4) Zy-C3 + E-rosette/E-rosette = 0.02, (5) EA + E-rosette/E-rosette = 0.06, (6) Slg + E-rosette/E-rosette = 0. The relative percentages of cells which were Slg+EA-, EA+Slg-, and EA+Zy-C3- were confirmed by EA rosette depletion via gradient centrifugation. On the basis of these observations, calculations were made of the theoretical numbers of lymphocytes with triple markers (EA+Slg+Zy-C3+ = 3.0%) and lymphocytes with only a single surface marker (EA+ only = 12.5%, Zy-C3+ only = 1.5%, Slg+ only = 1.5%). Finally a schematic representation of the multiple subpopulations of lymphocytes with various surface markers is presented.

B-Lymphocytes↗