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Biomedical subjects

D Dichek

Publications and source records attributed to D Dichek.

5 recordsLinked to original sources
PubMed1998

Lipoprotein clearance mechanisms in LDL receptor-deficient "Apo-B48-only" and "Apo-B100-only" mice.

The role of the low density lipoprotein receptor (LDLR) in the clearance of apo-B48-containing lipoproteins and the role of the LDLR-related protein (LRP) in the removal of apo-B100-containing lipoproteins have not been clearly defined. To address these issues, we characterized LDLR-deficient mice homozygous for an "apo-B48-only" allele, an "apo-B100-only" allele, or a wild-type apo-B allele (Ldlr-/- Apob48/48, Ldlr-/-Apob100/100, and Ldlr-/-Apob+/+, respectively). The plasma apo-B48 and LDL cholesterol levels were higher in Ldlr-/-Apob48/48 mice than in Apob48/48 mice, indicating that the LDL receptor plays a significant role in the removal of apo-B48-containing lipoproteins. To examine the role of the LRP in the clearance of apo-B100-containing lipoproteins, we blocked hepatic LRP function in Ldlr-/-Apob100/100 mice by adenoviral-mediated expression of the receptor-associated protein (RAP). RAP expression did not change apo-B100 levels in Ldlr-/-Apob100/100 mice. In contrast, RAP expression caused a striking increase in plasma apo-B48 levels in Apob48/48 and Ldlr-/-Apob48/48 mice. These data imply that LRP is important for the clearance of apo-B48-containing lipoproteins but plays no significant role in the clearance of apo-B100-containing lipoproteins.

Adenoviridae↗
PubMed1989

Variability in messenger RNA levels in human umbilical vein endothelial cells of different lineage and time in culture.

Levels of seven messenger RNA species were compared in human umbilical vein endothelial cells of different lineage and time in culture. Specifically, cells obtained from the American Type Culture Collection (ATCC) and subcultured were compared to early passage cells from cultures produced in our laboratory. Messenger RNA for tissue plasminogen activator, plasminogen activator inhibitor 1, urokinase, and thrombomodulin were expressed at higher levels in the ATCC cells. Thrombospondin, von Willebrand's Factor, and protein S messenger RNA were expressed at higher levels in the cells that we isolated. In addition, in the ATCC cells a shift in the proportion of plasminogen activator inhibitor messenger RNA from the 3.4 to the 2.4 kilobase species was found. We conclude that specific messenger RNA levels can vary considerably between cultured human umbilical vein endothelial cells. The large variation in mRNA levels which we describe has important implications for experiments involving gene expression in cultured endothelium.

Cell Division↗
PubMed1989

Thrombin regulation of mRNA levels of tissue plasminogen activator and plasminogen activator inhibitor-1 in cultured human umbilical vein endothelial cells.

Cultured human umbilical vein endothelial cells release tissue plasminogen activator (t-PA) and type 1 plasminogen activator inhibitor (PAI-1) in response to alpha thrombin stimulation. In order to study the mechanisms of thrombin stimulation, we measured changes in levels of mRNA for t-PA and PAI-1 following exposure of endothelial cells to 3 U/mL alpha thrombin. Alpha thrombin causes a significant and time-dependent increase in the mRNA levels of both t-PA and PAI-1. Catalytically inactivated diisofluorophosphate (DIP) treated thrombin and alpha thrombin pretreated with hirudin do not alter t-PA and PAI-1 mRNA levels. We conclude that the increased secretion of t-PA and PAI-1 by human umbilical vein endothelial cells in response to alpha thrombin is mediated at least partially through an increase in mRNA levels. In addition, an active thrombin catalytic site is required for these increases in mRNA to occur.

Blood Coagulation Factors↗
PubMed1983

IgG1 is the predominant subclass of in vivo- and in vitro- produced anti-tetanus toxoid antibodies and also serves as the membrane IgG molecule for delivering inhibitory signals to anti-tetanus toxoid antibody-producing B cells.

Peripheral blood leukocytes from individuals immunized with tetanus toxoid can be stimulated by pokeweed mitogen to produce IgG anti-tetanus toxoid antibody (IgG-Tet) in vitro. Previous studies have shown that treatment of these cells with tetanus toxoid or anti-human IgG reagents can inhibit this in vitro antibody synthesis. We have examined the four IgG subclasses on the surface of B cells for their relative contributions in the anti-IgG antibody-induced inhibition of IgG-Tet production. With all donors, the inclusion of anti-IgG1, but not anti-IgG2, -IgG3, or -IgG4, antiserum resulted in the in vitro inhibition of IgG-Tet synthesis. The magnitude of this inhibition was similar to that induced by treatment of the B cells with tetanus toxoid antigen. When the supernatants from normal in vitro cultures were assayed for IgG-Tet of the various IgG subclasses, it was observed that the IgG-Tet were almost exclusively IgG1. Similar results were obtained when serum IgG-Tet were measured. Thus, IgG1 appears to be the major subclass for (1) the in vivo-produced IgG-Tet, (2) the in vitro-produced IgG-Tet, and (3) the membrane receptor which can selectively convey an inhibitory signal to the IgG-Tet B cell.

Antibody Formation↗