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Biomedical subjects

A D Bankhurst

Publications and source records attributed to A D Bankhurst.

At least 109 records · Page 6Linked to original sources

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↗

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↗

Human eosinophils: surface receptors and antibody-dependent cytotoxicity.

Neutrophils and eosinophils from normal donors were tested for the presence of complement and Fc receptors with the use of EAC and EA. When cytocentrifuged, stained rosette preparations were used, the mean +/- 1 standard deviation for the percentage of neutrophils and eosinophils forming EAC rosettes was 71.1% +/- 19.1 and 22.2% +/- 16.1, respectively. The percentage of neutrophils and eosinophils forming EA rosettes was 78.0% +/- 10.0 and 23.5% +/- 5.6, respectively. In parallel with these observations, these cell types were tested for their ability to mediate ADC. Neutrophils were much more efficient than eosinophils in ADC, which may reflect differences in surface receptor binding and/or the absence of eosinophil cellular constituents essential for target cell lysis.

Animals↗

Partial reversal of the cellular immune defect in common variable immunodeficiency with indomethacin.

We administered indomethacin (25 mg q.i.d.) to two patients with common variable immunodeficiency and measured the effect on their depressed cellular immune responses. The in vitro response of both patients' lymphocytes to phytohemagglutinin increased during indomethacin administration. Both patients were anergic to skin testing before treatment and responded to two of four skin tests during treatment with indomethacin. Thus indomethacin administration in vivo appears to enhance the cellular immune respone, paralleling its previously described effects in vitro.

Adolescent↗

Suppression of human T-cell mitogenesis by prostaglandin. Existence of a prostaglandin-producing suppressor cell.

Small amounts of PGE inhibit mitogen-induced [3H]thymidine incorporation in human peripheral lymphocytes. The 50% inhibitory concentration is approximately 10(-7) M, and this is reduced to approximately 10(-8) M when endogenous PGE production is blocked. PGE inhibits PHA- and Con A-stimulated cultures much better than PWM cultures, suggesting a differential effect of PGE on T-cell vs. B-cell function. In vitro blockade of PG synthesis results in approximately 50% increase in [3H]thymidine incorporation in PHA cultures. PGE is produced endogenously in PHA cultures by glass adherent suppressor cells.

Cyclooxygenase Inhibitors↗

Prostaglandin-producing suppressor cells in Hodgkin's disease.

We examined the role of a prostaglandin-producing suppressor cell in the hyporesponsiveness to phytohemagglutinin seen in Hodgkin's disease. Addition of indomethacin to phytohemagglutinin cultures of lymphocytes from six patients with Hodgkin's disease resulted in an increase of 182 +/- 60 per cent in 3H-thymidine incorporation versus a 44 +/- 18% increase in 29 controls (mean +/- S.D., P less than 0.001). Without indomethacin the mean response of the lymphocytes in Hodgkin's disease was 48% of that of control. With indomethacin it was 94% of the control value. Phytohemagglutinin cultures of Hodgkin-disease lymphocytes produced approximately fourfold more prostaglandin E2 after 48 hours than did normal lymphocytes (P less than 0.02). Removal of glass-adherent cells markedly decreased the enhancement seen with indomethacin; it reduced prostaglandin E2 production by more than 80% and eliminated the differences in response to phytohemagglutinin between Hodgkin-disease and normal lymphocytes. Thus, a glass-adherent, prostaglandin-producing suppressor cell is responsible for the hyporesponsiveness to phytohemagglutinin seen with Hodgkin-disease lymphocytes.

Adult↗

Immunohistochemical localization of prostaglandin E in rheumatoid synovial tissues.

Synovial tissues removed at synovectomy from patients with active rheumatoid arthritis (RA) or osteoarthritis (OA) were examined for prostaglandin E (PGE) by immunohistochemical techniques using rabbit antisera specific for PGE. Marked increments of PGE were noted in RA synovia in comparison to OA, with staining concentrated in synovial lining cells, interstitial inflammatory cells, and endothelial cells of blood vessels. A correlation was noted between the degree of synovial lymphocytic infiltrate and the intensity of PGE staining. These studies provide initial cellular localization of PGE in such tissues.

Arthritis, Rheumatoid↗

Casein-mediated neutrophil chemotaxis: a parallel between surface binding and chemotaxis.

This study was directed toward demonstrating an interaction between human polymorphonuclear leukocytes (PMNs) and the chemotactic factor,casein. Experiments conducted using fluorescein-labeled casein indicated that PMNs have a membrane receptor for this chemotactic factor. This receptor was specific for casein and was not found on lymphocytes. A direct parallel was shown between the binding of FITC--casein and the PMN chemotactic response to this protein. Binding to the receptor was optimal at 25 degrees C, unaffected by sodium azide, and partially reduced by iodoacetate. Enzymatic treatment of PMNs with pronase and trypsin resulted in a loss of both FITC--casein-mediated PMN fluorescence and chemotaxis. Our data indicate that human PMNs have a membrane receptor for casein and that interaction with this receptor results in a chemotactic response.

Binding, Competitive↗

Antacid-induced hypophosphatemia: an unusual cause of "pseudo-myopathy".

A 69 year old man presented with painful proximal muscle weakness which clinically simulated polymyositis. Further evaluation revealed normal muscle enzymes and hypophosphatemia which resulted from unsuspected antacid abuse. "Pseudo-myopathy" is one example of the myriad of rheumatic diseases which may be mimicked by hypophosphatemia.

Aged↗

Features of the immune response to DNA in mice II. Participation of B and T cells.

The respective roles of thymus-derived and bone marrow-derived lymphocytes in the immune response to DNA was investigated in mice reconstituted with various cell populations using cell transfers. A helper effect of thymus-derived cells in the immune response to DNA was suggested by experiments performed in athymic nude BALB/c mice. Reconstitution experiments performed in low responder DBA/mice indicated that the immune response to DNA can be increased after transfer of bone marrow cells from high responder NZB mice, even in the presence of thymocytes from DBA/2 mice. In NZB X NZW mice, a major role of bone marrow cells, with a possible modulation by thymus-derived cells during aging, was observed in the spontaneous development of anti-DNA antibodies.

Animals↗

Identification of DNA-binding lymphocytes in patients with systemic lupus erythematosus.

Antigen-ginding lymphocytes capable of binding native DNA (DNA-ABC) were identified in the peripheral blood of normal controls and patients with systemic lupus erythematosus (SLE) by autoradiography with 125I-nDNA. 12 patients with active SLE had 404 +/- 273 (mean +/- SD) DNA-ABC/105 lymphocytes, while 7 inactive SLE patients and 13 normals had 120 +/- 48 and 48 +/- 36, respectively. All three groups were significantly different from one another (p less than 0.01). No significant correlation was detected between the quantity of anti-native DNA (nDNA) antibody and number of DNA-ABC; however, most patients with large amounts of anti-nDNA antibody had both active disease and large numbers of DNA-ABC. Numbers of DNA-ABC and lymphocytes with surface immunoglobulin (Ig) did not change significantly after an 18-h incubation at 37degreeC. After depletion of B-lymphocytes by passage over bead columns coated with a complex of IgG and anti-IgG, the great majority of DNA-ABC were removed in both normal subjects and SLE patients. Labeling lymphocytes sequentially with 125I-nDNA, followed by an indirect fluorescence technique for identification of surface Ig, indicated that the great mahority of radiolabeled cells had surface Ig by fluorescence microscopy in four normals (average 93%) and five patients with active SLF (average 82%). The predominance of nDNA-sensitive B-lymphocytes in the peripheral blood of both normals and SLE patients is consistent with the concept that the induction of the anti-nDNA antibody response is due to the stimulation of preexisting nDNA-specific B lymphocytes by mechanisms other than those necessarily involving participation of nDNA-specific T lymphocytes.

Antibodies, Antinuclear↗

Studies on the thymic dependence of the immunoglobulin classes of the mouse (38570).

The influence of the thymus on serum immunoglobin (Ig) concentration was studied by a comparison of serum Ig levels in congenitally athymic (nu/nu) mice versus control littermate heterozygotes and adult thymectomized, irradiated, bone marrow reconsituted mice (ATx plus B) versus adult thymectomized, irradiated mice reconstituted with bone marrow and thymus (ATx plus BT). IN THE FORMER GROUP IgGl. IgA, and IgG2a were 8%, 17% and 31% of controls. IgM levels were increased (340%) compared to controls. When ATx plus B mice were compared to controls. When ATx plus B mice were compared with nonirradiated controls sigificant depressions were noted in serum IbGl and IgM. The only significant decrease in serum Ig levels between ATx plus B and ATx plus BT was in IgGl. These results are discussed in terms of the effects of thymic influence, residual T lymphocyte population differences between the two groups, and the effect of irradiation.

Animals↗