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Biomedical subjects

A J Edwards

Publications and source records attributed to A J Edwards.

At least 73 records · Page 4Linked to original sources

Characterisation of Epstein-Barr virus-specific memory T cells from the peripheral blood of seropositive individuals.

We have investigated the regression phenomenon which occurs when EBV-infected peripheral blood mononuclear cells from seropositive individuals are cultured for one month at high cell concentration and have confirmed that regression is mediated by E+ lymphocytes. When helper/inducer (Leu 3a+) and suppressor/cytotoxic (Leu 2a+) cells are separated by fluorescence-activated cell sorting from fresh peripheral blood and co-cultured with EBV-infected autologous E- mononuclear cells, regression only regularly occurs in cultures receiving suppressor/cytotoxic lymphocytes. Titration experiments show that suppressor/cytotoxic lymphocytes are more active in the regression assay that unfractionated E+ cells. When Ia+ E+ and Ia- E+ cells are separated one week after initiation of co-cultures of E+ cells and EBV-infected E- cells, both Ia+ E+ and Ia- E+ cells are active in the regression assay although regression occurs earlier in cultures receiving Ia+ E+ cells. Experiments in which NK cells are isolated using the monoclonal antibodies H25 and H366 show that NK cells do not influence the regression phenomenon in normal individuals.

Adult↗

Hydroxyurea increases in vitro, antigen-independent B cell development in bone marrow.

The fluorescence-activated cell sorter and Coulter counter were used to study the effect of hydroxyurea in vitro in B cell development in 24 hr cultures of adult mouse bone marrow. This agent, which kills cells in the S phase of the cell cycle, caused a 40-70% increase in the absolute number of B cells in bone marrow cultures as compared with untreated cultures. There was also an increased response to the B cell mitogen, bacterial lipopolysaccharide, as measured by the stimulation index for 3H-thymidine incorporation. Hydroxyurea in vitro increased B cells numbers in fetal liver which contains pre-B cells, but not in lymph nodes or spleen which lack these cells.

Animals↗

Hepatic encephalopathy in feedlot calves.

A case of bovine hepatic encephalopathy occurred in southwest Kansas. Of 548 calves involved, 150 died over 30 days. The suspected cause of the condition was an unidentified hepatotoxin from moldy silage. The syndrome was experimentally reproduced in silage fed laboratory mice.

Animals↗

Generation of effector cells from T cell subsets. III. Synergy between Lyt-1 and Lyt-123/23 lymphocytes in the generation of H-2-restricted and alloreactive cytotoxic T cell.

Lyt-123/23 and Lyt-1 T cell subsets, positively selected by separation on the fluorescence-activated cell sorter, were tested in vitro for their role in the generation of H-2-restricted and alloreactive cytotoxic T cells. It is shown that in the proliferation assay, both T cell subsets responded equally well to H-2 and non-H-2 antigens (H-Y), respectively. In contrast, none of the selected Lyt subsets, but only the mixed population containing Lyt-1 and Lyt-123/23 lymphocytes gave rise to both H-2-restricted (anti H-Y, anti-trinitrophenyl) and alloreactive (anti-H-2) cytotoxic lymphocytes. The data imply an essential role of Lyt-1 cells as inducers or helpers in the generation of all cytotoxic lymphocytes from their precursors in the Lyt-123/23 pool.

Animals↗

Immunological characterization of hemopoietic cells in the common marmoset, rhesus monkey, and man. In search of a model for human marrow transplantation.

Bone marrow, lymphoid, and peripheral blood cells from the common marmoset and rhesus monkey have been tested with a panel of heterologous and monoclonal antibodies, and their reactivity pattern has been compared with that of blood and bone marrow cells from human donors. Conventional antibodies reveal extensive cross-reactivity within the B cell, T cell, and granulocytic systems in all three species, however, some important differences have been exposed. Only the monoclonal antibodies to HLA-A,B,C and Ia-like antigens react with marmoset cells, and we have exploited this finding to show that the vast majority of colony-forming units (CFU-c) in the marmoset bone marrow (as in man) are Ia positive. The use of the common marmoset as a suitable model for human bone marrow transplantation is discussed in the light of these findings.

Animals↗

Reactivity of monoclonal antibodies with human myeloid precursor cells.

Five monoclonal antibodies have been tested for their ability to bind to myeloid precursor cells in normal human bone marrow. Indirect immunofluorescence and the fluorescence activated cell sorter was used to separate cells according to their reactivity for trial culture in vitro in order to grow granulocyte-macrophage colony forming cells (CFUc). Two antibodies (OKT3 and OKT11) which react strongly with bone marrow T lymphocytes were found to be unreactive with CFUc. YD1/23 reacts very strongly with both T and B lymphocytes but is only weakly reactive with CFUc. In contrast, OKT10 and YE2/36 did react with CFUc. The consequences of these findings and the potential clinical use of these antibodies in bone marrow transplantation are discussed.

Adult↗

Control of B-cell maturation in mice. I. Increased B-cell maturation in vitro by bone marrow protected during whole body irradiation.

The possibility of a homeostatic control on the production of B cells was studied in CBA mice following whole body irradiation (750 rads). Bone marrow cells from femurs shielded from irradiation were taken at 24 h and the number of surface immunoglobulin positive cells assessed with a fluorescence-activated cell sorter after 24 h in vitro. The cells from the irradiated shielded mice showed greater absolute number of 'bright' B cells with a high density of surface immunoglobulin (mean increase 60%--100%) than cells from control unirradiated mice. These bright B cells did not incorporate (3H) thymidine in vitro and treatment with hydroxyurea (an inhibitor of DNA synthesis) did not prevent their increase. It was concluded that the increased number of bright B cells in vitro arose from augmented maturation or differentiation and not from a proliferative process.

Animals↗

Distribution of immunogenic cells after painting with the contact sensitizers fluorescein isothiocyanate and oxazolone. Different sensitizers form immunogenic complexes with different cell populations.

The distribution of fluorescent cells in the draining lymph nodes of mice painted with the contact sensitizing agent fluorescein isothiocyanate (FITC) was investigated using a fluorescence-activated cell sorter. Up to 30% of the cells were fluorescent after 18 h and this decreased thereafter becoming undetectable after 4-5 days. Most of the fluorescent cells were morphologically lymphocytes, theta - ve and adherent to nylon wool. Immunogenicity of these cells was tested by injecting them into the footpads of normal mice and measuring contact sensitivity after 6 days. This was restricted to large cells which represented less than 5% of the white cell population and nearly all of which became fluorescent after skin painting. The large fluorescent cells were a mixture of monocytes and lymphocytes. Most of the lymphocytes had surface immunoglobulin. The immunogenicity was reduced by nylon filtration but was not affected by silica and anti-theta. These results showed that the immunogenicity is not associated with T cells. In contrast, similar immunogenic activity in the draining lymph nodes of mice painted with oxazolone is associated with T cells. The results therefore showed that different sensitizers form immunogenic complexes with different cell populations, perhaps in this case becuase of the different water solubilities of FITC and oxazolone. They also suggested that this may cause important differences in antigen presentation, for example in their association with different MHC products.

Animals↗

Antilymphocyte serum produced by immunization with purified mouse thymocyte plasma membrane.

A predominantly plasma membrane fraction was isolated from mouse thymocytes and characterised. Immunization of rabbits with this material yielded highly potent antilymphocyte sera as measured by prolongation of skin allograft survival. Potency was maintained after repeated boosting of the rabbits, yet the generation of irrelevant antibodies was contained. Binding of antilymphocyte sera to lymphocytes was studied by immunofluorescence using the analytical facility of a fluorescence activated cell sorter (FACS-1). The results demonstrated that these anti-membrane sera recognise antigens common to thymocytes and spleen lymphocytes, bind more to T-cells and thymocytes than to B-cells and bind more avidly than antisera raised with intact cells. It was concluded that this thymocyte plasma membrane preparation is highly effective in raising powerful antilymphocyte serum.

Animals↗

Actin may be present on the lymphocyte surface.

Lymphocytes were assessed for the presence of surface actin and myosin by lactoperoxidase-catalyzed iodination and indirect immunofluorescence using antisera against purified pig skeletal muscle actin and pig smooth muscle myosin. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of 125I-labeled pig, mouse, and human B lymphocytes revealed an intense radioactive band of 43,000 molecular weight, whereas pig and mouse T lymphocytes gave a much less intense band. This band comigrated with actin, was nonglycosylated as judged by lack of binding to lentil lectin-Sepharose, was bound specifically by myosin fibers, and could be distinguished from a polypeptide of similar mobility derived from the major histocompatibility antigens. These results suggest that actin is present on the surface of B lymphocytes and, to a lesser extent, on T lymphocytes. Pig, mouse, and human Ig-bearing cells were stained by antiactin and antimyosin antisera, as judged by indirect immunofluorescence, whereas non-Ig-bearing cells were not stained. Antibody binding, however, was depleted by adsorbing the antisera with Ig-Sepharose. It was concluded that the immunofluorescence results are misleading and reflect the presence of antibodies that crossreact with Ig.

Actins↗

Lymphocyte depression by cancer.

We believe we have shown in the animal model that in cancer the host's lymphoreticular tissues are engaged by a systemically disseminated antilymphocytic humoral factor that destroys the T-cell-dependent pathway, allowing the dissemination of the disease that results in the death of the animal. From studies on patients with cancer there appears to be a real possibility of the presence of a similar substance in man. Such a factor may form the basis for the definiation of cancer and an explanation of cancer illness on the runt hypothesis. Moreover, if the factor could be identified and antagonized a major therapeutic advantage would be achieved.

Adenocarcinoma↗

Neoplastic change in duplications of the alimentary tract.

Two cases of adenocarcinoma arising in sequestrated duplications of the bowel in adults are reported. The literature is reviewed and a tendency for duplications to present in early childhood is noted. Although relatively few of these anomalies persist into adult life 8 cases of neoplastic change have now been reported. The histological features of many of the duplications undergoing malignant degeneration suggest the presence of underlying epithelial instability in this condition. It is postulated that duplications of the large bowel have malignant potential.

Adenocarcinoma↗