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Biomedical subjects

A D Bankhurst

Publications and source records attributed to A D Bankhurst.

At least 73 records · Page 4Linked to original sources
PubMed1983

Abrogation of in vitro suppressor cell activity in adult common variable hypogammaglobulinemia after TP5 treatment.

TP5, a pentapeptide containing the active site of thymopoietin, was administered to five adult patients with CVH subcutaneously three times weekly for periods of 3 to 5 months. No significant consistent changes in lymphocyte cell surface markers or serum immunoglobulin levels were recorded; however, three of the five patients showed apparent partial reversal of in vitro suppressor T cell activity. In two of these three patients, initial skin test anergy showed temporary reversal during TP5 treatment. Two patients also showed an increase in ability of their B cells to synthesize lg in vitro when co-cultured with autologous or isologous T cells from normal donors. These changes did not persist after withdrawal of TP5 treatment.

Adult↗
PubMed1983

Natural killer cell function and lymphocyte subpopulation profiles in inflammatory bowel disease.

Peripheral blood natural killer (NK) cell activity and lymphocyte subpopulation profiles were studied in 23 patients with inflammatory bowel disease (IBD) and in 16 healthy control subjects. NK activity was assessed by a 4-hr 51Cr release assay using K-562 erythroleukemia cell line targets. Both monocyte depleted and nondepleted lymphocyte preparations were tested using 50:1 and 25:1 effector to target cell ratios. Lymphocyte subpopulation profiles were determined by incubation of cell suspensions with the monoclonal anti-lymphocyte antibodies (OK-M1, OK-T4, Leu-4 and Leu-2) labeling with goat anti-mouse FITC and sorting by flow cytometry on the fluorescence-activated cell sorter (FACS). NK activity in patients with IBD showed wide variation, but mean activity was not significantly different from normal controls. Analysis of patient subgroups by disease activity, disease type, duration or treatment also failed to reveal significant differences from controls. Parallel measurements of peripheral blood lymphocyte subpopulations using these phenotypic markers revealed no significant differences between patients with IBD and control subjects.

Adolescent↗
PubMed1983

alpha-Interferon increases immunoglobulin production in cultured human mononuclear leukocytes.

Interferons (IFN) are known to modulate immune responses in either an inhibitory or a stimulating manner. The present study was initiated to investigate the mechanisms by which alpha-IFN modulates Ig production of human peripheral blood mononuclear cells (PBMC). IgG and IgM production was measured in pokeweed mitogen- (PWM) stimulated 7-day cultures of PBMC. Significant enhancement of IgM and IgG production was observed when alpha-IFN was added. Overnight preincubation followed by washing also produced significant enhancement. The effect of alpha-IFN was not obtained in the absence of PWM or T cells. The effect of alpha-IFN on cultures of B and T cells was not altered by irradiation of T cells (2000 rad). alpha-IFN was not shown to enhance the production of helper factor but did increase the responsiveness of B cells to helper factor if the B cells were preincubated with alpha-IFN. Finally, alpha-IFN did not increase the Ig production of PBMC induced by Epstein Barr virus (EBV), and the outgrowth of EBV-infected PBMC was not affected. Overall, these results show for the first time that the effect of alpha-IFN on PBMC is due to an enhanced responsiveness of B cells to helper factors produced by radioresistant T cells.

Adult↗
PubMed1983

Enhancement of natural cytotoxicity by beta-endorphin.

The role of enkephalins, beta-endorphin, or other neuropeptides produced by the nervous system in the alteration of immune responsiveness is generally unknown. The present studies were undertaken to investigate the role of these neuropeptides in the modulation of human spontaneous cytotoxicity induced by natural killer (NK) cells. Natural cytotoxicity was measured by using a standard 51Cr release assay with radiolabeled K562 cells. NK activity was significantly enhanced by both beta-endorphin (30.5 +/- 11.5%, M +/- SE, relative enhancement at 50:1, effector:target (E:T) ratio, 10(-14)M beta-endorphin) and methionine-enkephalin (met-enkephalin) (27.4 +/- 9.7% relative enhancement at 10(-9)M). The magnitude of relative enhancement significantly correlated with increasing concentrations of beta-endorphin. Leucine-enkephalin, alpha-endorphin, and morphine did not augment NK activity. The enhancement of NK activity with beta-endorphin increased at all E:T ratios tested. Naloxone inhibited the augmentation of NK activity produced by beta-endorphin and met-enkephalin. By using a combination of a standard 51Cr release and soft agarose single cell analysis assays, beta-endorphin increased both the number of E:T cell conjugates and the number of active killer cells among target-binding cells. The maximal effector cell recycling capacity was increased by 170%. These studies provide new insight into the mechanisms by which neuropeptides produced by the nervous system can alter immune responsiveness.

Binding, Competitive↗
PubMed1983

Natural cytotoxicity in systemic lupus erythematosus: mechanisms of suppression by inhibitory serum factors.

Spontaneous cytotoxicity mediated by natural killer (NK) cells is impaired in several human diseases including systemic lupus erythematosus (SLE). The present study was designed to describe factors in SLE sera which suppress the NK function of unfractionated mononuclear cells and NK enriched suspensions. NK activity was determined in 19 SLE patients and 25 normal controls by a standard chromium release assay. Sera obtained from SLE patients suppressed normal NK activity by an average of 29.4%. The presence of anti-lymphocyte antibodies (ALA) of the IgM class which were reactive with unfractionated mononuclear cells or the NK cell enriched OKM1 positive subset correlated with serum-mediated suppression. NK inhibitory SLE sera did not interfere with normal effector-target conjugate formation. These results demonstrate the modulatory effects of immune aggregates and ALA on lymphocyte function in SLE. These factors suppress NK function without evidence of lymphocyte cell death or inhibition of NK effector cell binding to tumour targets.

Adult↗
PubMed1982

Contrasting patterns of protein kinase activities among normal peripheral blood lymphocyte subpopulations and lymphoid cell lines.

Human peripheral mononuclear cell suspensions were separated into E-rosette-positive (T cell) and E-rosette-negative (non-T cell) fractions and assayed for cAMP binding activity and histone and casein kinase activity, in the presence and absence of cAMP. Each of these activities was higher in E-rosette-positive than E-rosette-negative fractions. Cyclic AMP binding and histone kinase activities were further noted to be higher in T lymphoblastoid cell lines when compared to lines of non-T lymphoid cell origin. In addition. DEAE-cellulose chromatography revealed a qualitative contrast of isoenzymic composition of protein kinase from these cell lines. Cyclic AMP-independent casein kinase activity was high in both types of cell lines. These results suggest that high protein kinase activity is characteristic of T cells and may be related to their higher sensitivity to cAMP agonists in comparison to non-T cells. This study also provides further evidence for an association between increased cAMP-independent protein kinase activity and the transformed state, which has been noted for a variety of other cell types.

Binding Sites↗
PubMed1982

The modulation of human natural killer cell activity by prostaglandins.

Prostaglandins (PGs) have been implicated as a regulator of tumor growth in mice and humans. Since natural killer cell (NK) cytotoxicity may be an important component of immune surveillance against cancer, it is appropriate to study whether the amount of PGs produced by tumors may be sufficient to suppress NK activity. Accordingly, the effect of various PGs on the NK activity of human peripheral mononuclear cells was investigated. The percentage cytotoxicity was measured by the release of Cr51 from labeled K562 and other target cells. At very high concentrations of PG (10(-6) M), suppression was seen with PGE2, PGD2, PGA2, and PGF2 alpha. However, at concentrations of PG in the physiologic range (10(-8) M), significant suppression was seen with PGE2 and PGD2 only. The percentage suppression with PGE2 ranged from 77% to 9.5% over a range of concentrations from 10(-5) to 10(-9) M (45% at 10(-8) M). Significant suppression was observed at 10(-8) M PGE2 with 4 different targets and at effector:target ratios varying from 50:1 to 12.5:1. To assess whether the suppressive effect of PGE2 was directed at the effector and/or target cell, K562 cells or effector cells were pretreated with PGE2. Significant suppression was seen with effector cell pretreatment but not with target cell pretreatment. Finally, the suppressive effects of supernatants obtained from tumor cell lines (polyoma virus-transformed murine fibroblast cell line, PY3T3) was determined. The marked suppressive effect of the supernatant could be attributed to its content of PGE. Thus, it appears that the production of PGE by tumor cells may be an important modulator of human NK activity.

Cytotoxicity, Immunologic↗
PubMed1981

Flow cytometry and cytoadherence studies of sera from children with juvenile rheumatoid arthritis and normal controls.

Recently, antibodies reactive with T cell subpopulations have been reported to exist in children with active juvenile arthritis (JRA). In an attempt to verify and extend these observations, we have studied children with JRA for the presence of anti-T cell antibodies by flow cytometry and cytoadherence rosette techniques. T cells were isolated from peripheral blood mononuclear cells (PBL) by two methods: 1) Differential sedimentation of PBL rosetted with neuraminidase-treated sheep erythrocytes, and 2) removal of immunoglobulin positive PBL by rosetting with rabbit anti-human F(ab')2 coated bovine erythrocytes and differential sedimentation. Utilizing these methods to detect lymphoreactivity of JRA sera to either population of T cell isolates, we observed the binding of ultracentrifuged normal human sera (NHS) to be comparable to JRA sera (active and quiescent). NHS reacted with 15-25% of T cells. Further studies demonstrate that monomeric IgG was chiefly responsible for lymphoreactivity. The results of these studies are discussed in the context of previous observations.

Adolescent↗
PubMed1981

Characterization of the suppressor cell activity in human cord blood lymphocytes.

Newborn mononuclear cells are known to have increased suppressor activity when compared with adult cells. However, the precise phenotypic description of the suppressor cell subpopulation has not yet been reported. This study was designed to examine the surface markers on human cord blood cells as defined by monoclonal antibodies and to characterize cord blood mononuclear cells that suppress in vitro pokeweed mitogen-driven immunoglobulin production. The pattern of fluorescence with the 9,6-monoclonal antibody suggested either a decreased density or a partial blocking of E-receptors on cord blood lymphocytes. Otherwise, human cord and adult cells had similar proportions of T cell subpopulations. Different subsets of newborn cells isolated by a monoclonal antibody rosetting technique were tested for suppressor activity. Cord blood lymphocytes recognized by the OKT8 monoclonal antibody constituted the major functional suppressor cell subpopulation. These cells were present in both E-rosetting and non-E-rosetting populations. Removal of OKT8+ mononuclear cord blood cells abrogated most of the suppressor activity. Thus the major suppressor cell present in cord blood is an OKT8 positive lymphocyte.

Adult↗
PubMed1981

A human suppressor lymphocyte subpopulation identified by a heteroantiserum.

A rabbit antiserum has been prepared using peripheral mononuclear cells from a patient with common variable hypogammaglobulinaemia (CVH) who had demonstrable suppressor cells in vitro. This antiserum (anti-Ck), after absorption with pooled normal glass-non-adherent cells and platelets, showed selective reactivity with subpopulations of normal human peripheral lymphocytes. Using indirect immunofluorescence, anti-Ck labelled 36 +/- 8% (mean +/- 1 s.d.) of normal human peripheral lymphocytes. Anti-Ck has the following pattern of reactivity with enriched cell populations: 18% of normal E-rosette-positive cells, 70% of normal E-rosette-negative cells, 60% of lymphocytes from CVH patients, 82% of T gamma lymphocytes, 82% of Con A-activated lymphocytes and 81% of Fc receptor-positive lymphocytes. Anti-Ck reacted neither with glass non-adherent cells (which had been used for absorption), nor with thymocytes, monocytes, granulocytes, membrane immunoglobulin-positive lymphocytes, lymphocytes from patients with chronic lymphocytic leukaemia, or Bristol 7 (B-cell line) cells. The in vitro proliferative response to concanavalin A, phytohaemagglutinin and pokeweed mitogen was significantly enhanced after complement-mediated lysis of normal peripheral lymphocytes using anti-Ck. Immunoglobulin production as measured by a reverse haemolytic plaque assay was also significantly increased by lysis of cell subpopulations with anti-Ck. These studies show that a heteroantiserum can be prepared which identifies antigens common to subsets of human lymphocytes which contain functional suppressor cells.

Absorption↗
PubMed1981

Effect of Mylanta on naproxen bioavailability.

The effect of Mylanta on naproxen bioavailability was studied in 11 healthy volunteers. In separate experiments, single oral doses of naproxen (250 mg) and multiple oral doses (250 mg twice daily for 7 days) were administered with and without Mylanta. Coadministration of naproxen with Mylanta in the single-dose experiment did not significantly affect the area under the curve (579 vs. 580 microgram/ml X hr with and without Mylanta, respectively), time to peak serum concentration (2.5 vs. 2.6 hr), peak serum concentration (37.2 vs. 34.8 microgram/ml) or plasma half-life (16.1 vs. 16.4 hr). There was no significant difference between trough level naproxen concentrations at steady state (29.6 microgram/ml with Mylanta vs. 30.7 microgram/ml without Mylanta). The data were also used to investigate naproxen pharmacokinetics predicted by two different pharmacokinetic models, one of which allowed for protein binding. The nonlinear protein-binding model accurately predicted steady-state concentration, while the values predicted by the linear model exceeded actual values by 33-54%.

Adult↗
PubMed1981

The nature of the prostaglandin-producing mononuclear cell in human peripheral blood.

The purpose of this investigation was to identify the human peripheral mononuclear cell responsible for PGE production. The prostaglandin-producing cell had the following characteristics: (1) was glass adherent; (2) was removed by techniques that effectively removed phagocytic cells (carbonyl iron); and (3) was not an E-rosette cell. Furthermore, the peripheral mononuclear cells that contain cytoplasmic PGE by indirect immunofluorescence also ingest latex particles. B and T lymphoid cell lines did not produce large quantities of PGE. Mononuclear cells separated on discontinuous BSA gradients varied greatly in their ability to produce prostaglandin (low density > high density). These data constitute strong evidence that the majority of PGE produced in peripheral mononuclear cell suspensions emanates from a population of low-density monocytes.

Cell Adhesion↗