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D Wheaton

Publications and source records attributed to D Wheaton.

7 recordsLinked to original sources

Analysis of the expression and immunostimulatory capacity of class I major histocompatibility antigens on rat trophoblast cell lines.

In rat strains expressing the a and other major histocompatibility complex (MHC) haplotypes, subpopulations of placental trophoblast cells synthesize the nonclassical class I Pa antigen in preference to the classical RT1.Aa antigen. In this study, a rat trophoblast cell line, R8RP.3, which was derived from midgestation placentas of PVG.R8 (RT1.Aa) rats, was shown to express class I antigens similarly to those of trophoblast cells in situ. Both unstimulated and IFN-gamma-exposed metabolically labeled R8RP.3 cells synthesized more Pa than RT1.Aa antigen. The reverse was true for labeled spleen cells from PVG.R8 rats. The R8RP.3 cells failed to stimulate allogeneic lymphocyte proliferation even when high levels of both classical and nonclassical class I MHC antigens were expressed on their membranes after incubation with IFN-gamma. These experiments thus supply the first evidence that the inductive phase of the immune response is not promoted by trophoblast cell class I MHC antigens, which could explain the failure of mothers to mount immune responses to class I MHC positive trophoblast cells.

Animals

Products of lipopolysaccharide-activated macrophages (tumor necrosis factor-alpha, transforming growth factor-beta) but not lipopolysaccharide modify DNA synthesis by rat trophoblast cells exhibiting the 80-kDa lipopolysaccharide-binding protein.

Pregnancy losses from gram negative bacterial infections could be caused by direct effects of LPS on placental cells, or indirectly via LPS activation of macrophages in the uteroplacental unit. To evaluate those alternatives, LPS, LPS-activated peritoneal cells, conditioned medium from LPS-activated peritoneal cells, and some purified and recombinant molecules known to be secreted by activated macrophages were tested for their abilities to modify DNA synthesis by rat trophoblast cells. Three trophoblast cell lines derived from midgestation placentas of outbred and inbred rats were used for the experiments. Although the 80-kDa LPS-binding protein was demonstrated on trophoblast cells, LPS alone had no effect on the ability of trophoblast cells to synthesize DNA. In cocultures, trophoblast cell DNA synthesis was slightly enhanced by low concentrations of both unstimulated and LPS-activated peritoneal cells. At higher concentrations, LPS-activated cells caused significant inhibition of DNA synthesis by trophoblast cells. Conditioned media from LPS-activated peritoneal cells were highly inhibitory to trophoblast cell DNA synthesis. When specific molecules likely to be components of those media were tested, IL-1 was found to have a modest but reproducible stimulatory effect and PGE2 did not change trophoblast cell incorporation of [3H]TdR. In contrast, trophoblast cell DNA synthesis was markedly inhibited in a dose-dependent manner by both TNF-alpha and TGF-beta 1. No differences in the sensitivity of trophoblast cells from outbred and inbred rats were observed. Given the limitations of the experimental model system, the results suggest that in cases of infection by gram-negative bacteria LPS may have an adverse effect on pregnancy by stimulating resident macrophages to generate and release molecules that are inhibitory to trophoblast cell DNA synthesis.

Animals

Isolation of phenotypically distinct trophoblast cell lines from normal rat chorioallantoic placentas.

Growth characteristics and the expression of trophoblast-associated markers by six cell lines generated from midgestation chorioallantoic placentas of outbred (Holtzman) and inbred (Lewis, PVG.RT Ir8) rats were evaluated. The cells comprising all cell lines were epithelioid (contained cytokeratin-type intermediate filaments), had normal (2n, 4n) DNA content, and synthesized the extracellular matrix glycoprotein laminin. Variability was observed among the lines in all other characteristics: median cell size, rate of growth, serum dependency, responses to transferrin and dibutyryl cyclic adenosine-3',5'-monophosphate, synthesis of some major proteins, alkaline phosphatase activity, and the expression of immunoreactive placental lactogen-II. In general, cell lines with smaller mean cell sizes grew rapidly and required little serum for maintenance in vitro; cell lines with larger mean sizes grew more slowly and preferred higher concentrations of serum. Some associations between mean cell size/rate of growth and other characteristics were observed. No major differences were apparent between cell lines generated from outbred and inbred rat placentas. Trophoblast cell lines expressing distinct phenotypes provide a valuable new approach for studying a wide range of trophoblast cell activities.

Allantois

A mimicking red blood cell autoantibody accompanying transfusion and alloimmunization.

A patient with sickle cell disease who concomitantly developed red cell autoimmunity and alloimmunization is reported. The implied but 'wrong' specificity of the autoantibody mimicked one of the alloantibodies in the patient's serum. Although the patient's red blood cells phenotyped at Ro4, anti-rh" was eluted from them on several occasions. Absorption and secondary elution from selected cells proved the cell bound antibody had a unique and independent specificity from the anti-rh" in his serum. Standard antibody identification procedures did not distinguish these differences.

Anemia, Sickle Cell

Professionalism.

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Education, Nursing, Continuing