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Biomedical subjects

A D Bankhurst

Publications and source records attributed to A D Bankhurst.

At least 91 records · Page 5Linked to original sources

Studies on the modulation of immunoglobulin production by prostaglandins.

The present study investigated the effect of prostaglandins (PG) on the in vitro production of polyclonal IgG and IgM by pokeweed mitogen- stimulated normal human peripheral mononuclear cells. Concentrations of PGE1 and PGA1 in excess of 10(-6)M were suppressive. PGE2 and PGs of the F series were less effective and significant suppression was seen in concentrations greater than 10(05)M. Indomethacin added to cell cultures did not enhance Ig production. This discrepancy between physiologic PG concentrations and the very large pharmacologic concentration necessary to suppress Ig synthesis in vitro makes the physiologic role of PG in the modulation of Ig synthesis questionable.

Adolescent↗

Studies of T- and B-cell interactions in adult patients with combined immunodeficiency.

Cellular interactions involved in the pathogenesis of hypogammaglobulinemia were studied in six patients with common variable immunodeficiency. Amounts of immunoglobulin (Ig)G and IgM in the supernate of pokeweed mitogen-stimulated cocultures of normal and immunodeficient mononuclear cells were measured by radioimmunoassays. Mononuclear cells from three of six patients inhibited Ig production of normal B cells (P < 0.005). When purified patient and normal T cells were added to B cells in various autologous or allogeneic combinations, it was observed that immunodeficient T cells (AT) from four patients suppressed normal IgM synthesis. Allogeneic normal T cells did not provide help for B cells from these same immunodeficient patients. In two patients, autologous T cells were able to help autologous B-cell IgM synthesis in vitro. In five patients, AT cells inhibited normal B-cell IgG synthesis. Removal of T cells bearing Ia determinants or T cells with Fc-IgG receptors did not diminish the suppressive effect of AT cells on normal B-cell Ig synthesis. Addition of indomethacin, a prostaglandin synthetase inhibitor, did not abrogate the suppressive effect of immunodeficient mononuclear cells. Addition of hydrocortisone succinate (10 muM) did reverse the suppressive effect of AT cells on IgM production in one patient; however, no in vitro reversal of suppressor cell effect was recorded in five. Suppression by immune-deficient T cells was eliminated by 2,000 rad of x-ray irradiation in three patients. After x-ray irradiation immunedeficient T cells could function as helpers of normal B cells.

Adult↗

Studies on the pharmacologic manipulation of suppressor cells associated with impaired immunoglobulin production.

Several agents were tested for their potential to reverse the suppression of normal IgG and IgM production mediatd by human cord T cells and cells from patients with agammaglobulinemia. No reversal of suppression was observed with in vitro incubation of co-cultured normal and immune-deficiency suppressor cells with cimetidine, lithium, or levamisole. Allogeneic helper factor prepared from normal mononuclear cells was able to overcome the suppression of normal IgG production mediated by cord T cells but did not overcome suppression of IgG or IgM production mediated by suppressor cells from agammaglobulinemic patients.

Agammaglobulinemia↗

Suppressor leukocytes in anergic patients with solid tumors.

Anergic patients with solid tumors were studied for the presence of suppressor cells which could be responsible for their significantly impaired phytohemagglutinin induced lymphocyte proliferation. Three types of suppressor cell assays were measured. First, no increased activity of prostaglandin producing suppressor cells was found in 10 cancer patients. Second, 5 cancer patients did not have significantly increased activity of short-lived suppressor cells in comparison with normal subjects. Third, no enhanced activity of concanavalin A induced suppressor cells was seen in 6 patients. This study emphasizes that the in vitro T cell immunodeficiency in this group of cancer patients was not due to suppressor cells as measured by conventional in vitro assays and emphasizes the potential importance of a loss of responder cells or other suppressor mechanisms in immune deficient patients with solid tumors.

Adult↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗