Risk of lymphoma in patients with RA treated with anti-TNFalpha agents.
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Biomedical subjects
Publications and source records attributed to J P Franklin.
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When human peripheral blood lymphocytes (PBL) are cultured with either concanavalin A (Con A)-treated or control autologous T lymphocytes, the mitogenic responses of the PBL co-cultured with Con A-treated cells are much lower. We have investigated the cell surface receptor changes during culture of T cells with and without mitogen in an attempt to explain this differential regulatory phenomenon. We present data here which show that human T cells cultured in complete medium alone gain helper cells with time. Con A-treated T cells are known to lose helper cells during culture. Erythrocyte rosette-purified T cells were cultured with or without Con A for 84 h and the numbers of cells with receptors for the Fc regions of either IgM (T mu) or IgG (T gamma) were enumerated daily. T mu cells have been associated with helper activity while T gamma cells have predominantly suppressor activity. Treatment with 10 micrograms/ml of Con A decreased T mu by approximately 50%. Untreated cells, however, showed significant increases in T mu (44 +/- 30.5% in twelve individuals). The great variance in T mu increases is due to the fact that individuals having higher initial T mu values showed smaller increases. These changes probably represent the gain or loss of receptors because total cell numbers did not change. There was no significant change in the number of T gamma cells in either control or Con A-treated cultures during the same 84 h period. In co-culture experiments in which the responses of fresh autologous PBL were determined, 60-h control T-cell cultures enhanced the mitogen responses of the fresh cells.(ABSTRACT TRUNCATED AT 250 WORDS)
The integration site of reticuloendotheliosis virus proviral DNA in the DNA from a cloned reticuloendotheliosis virus-transformed bone marrow cell line was studied. These reticuloendotheliosis virus-transformed bone marrow cells produce a replication-defective transforming virus (REV-T) and a nontransforming helper virus, designated reticuloendotheliosis-associated virus (REV-At). The DNA from this REV-T transformed bone marrow cell line was hybridized with 3H-labeled in vitro synthesized DNA complementary to the reticuloendotheliosis virus (RE) genome to show that these cells contain approximately five genome equivalents per haploid genome. These hybridization experiments did not distinguish between the transforming and nontransforming virus sequences in these cells. Metaphase chromosomes have been isolated from colcemid-treated bone marrow cells and separated into four different size classes on zonal gradients. Hybridization experiment with RE-specific cDNA indicated that all four size classes of chromosomes contain RE-specific sequences. To locate the infectious provirus DNA of the helper virus REV-At, transfection experiments were performed with DNA extracted from the chromosomes of each size class. Infectious REV-At provirus DNA was found principally in one size class. This size class contained the intermediate size macrochromosomes 5 through 11. These results suggest that REV-At proviral DNA must be integrated into a specific chromosome to produce infectious virus.
The attachment kinetics of monocytes to polystyrene surfaces from cultures of human peripheral blood mononuclear leukocytes has been determined. Initial experiments showed that the relative monocyte depletion efficiency was much higher after one hour than after twenty hours of incubation. The supernatants from samples incubated for one hour also contained fewer monocytes than did supernatants from samples incubated for twenty hours. Further studies showed that a large percentage of monocytes which initially attach during the first hour later detach. These cells retain their ability to attach to a new culture substrate and to mature into macrophages.