Vasodilators and regional blood flow

Nowadays many different antihypertensive drugs are available which lower the blood pressure through various mechanisms of action. Accordingly, the haemodynamics changes that accompany the fall in blood pressure vary considerably depending upon the respective site of action of the drug and the more or less pronounced contribution of cardiovascular reflex mechaniSmS in the overall haemodynamics response. The aim of the studies described in the present thesis is to characterize and compare the haemodynam.ic profiles of various types of antihypertensive drugs with special emphasis on the drug i.nduced changes in regional blood flows. For this purpose we have used the radioactive microsphere technique to study the systermic and regional haemodynamic effects of a series of "direct" and "indirect" vasodilators in conscious hypertensive rabbits

The human prostatic cancer cell line LNCaP and its derived sublines: An in vitro model for the study of androgen sensitivity

__Abstract_ The LNCaP-FGC (fast growing colony) cell line, a subline derived from the LNCaP cell line, shares all the main characteristics, including its androgen sensitivity, described for the parental line. A number of sublines originating from the FGC line were characterized with respect to their response to steroid-depleted medium and to the synthetic androgen R1881. The growth of FGC cells in DCC medium with 0.1 nM R1881 was stimulated 2–3-fold compared to growth in DCC medium only. FGC cells that were continuously grown in DCC medium did not die, but their growth rate was clearly slowed down, and the cells remained responsive to androgen. These cells, therefore, have the androgen-sensitive, rather than the androgen-dependent phenotype. As cells of the subline FGC-JB could not be maintained in DCC medium, these cells better represent the androgen-dependent cell type. In contrast to the FGC line, cells of the R line, grew equally well in medium with complete or DCC serum. Under none of these culture conditions, R cells could significantly be stimulated further with R1881. Further analysis of the LNCaP-FGC sublines should provide valuable information concerning the development of androgen resistance in human prostate cancer

The role of subtilisin-like proprotein convertases for cleavage of the measles virus fusion glycoprotein in different cell types

AbstractThe fusion (F) glycoprotein gene of measles virus (MV) encodes a nonfusogenic precursor protein (F0) that is activated by cleavage into the F1and F2subunits during transport to the cell surface. The F protein of both the Edmonston strain and a wild-type MV was found to be cleaved in thetrans-Golgi cisternae and/or thetrans-Golgi network (TGN). In HEp-2 cells, B lymphoblastoid cells, and PBMC, the cleavage process required calcium, and calcium deprivation prevented syncytium formation. The calcium dependence indicated the involvement of the pro-protein convertase (PC) endoprotease family. The expression of the presently recognized members of the PC family in human cell types known to be infected during measles was examined by RT–PCR. Among the PCs residing in the TGN, only furin was expressed in all cells. Soluble secreted human furin produced by a recombinant baculovirus cleaved MV F0into proteins the exact size of F1and F2and increased the titer of MV particles released from calcium-deprived or endoprotease defective infected cells. These results strongly indicate that furin is the most important and maybe the only endoprotease involved in activation of the MV F protein

Measles virusinduced modulation of host-cell gene expression

The influence of measles virus (MV) infection on gene expression by human peripheral blood mononuclear cells (PBMCs) was examined with cDNA microarrays. The mRNA levels of more than 3000 cellular genes were compared between uninfected PBMCs and cells infected with either the Edmonston MV strain or a wild-type MV isolate. The MV-induced upregulation of individual genes identified by microarray analyses was confirmed by RT–PCR. In the present study, a total of 17 genes was found to be upregulated by MV infection. The Edmonston strain grew better in the PBMC cultures than the wild-type MV, and the Edmonston strain was a stronger inducer of the upregulated host cell genes than the wild-type virus. The anti-apoptotic B cell lymphoma 3 (Bcl-3) protein and the transcription factor NF-κB p52 subunit were upregulated in infected PBMCs both at the mRNA and at the protein level. Several genes of the interferon system including that for interferon regulatory factor 7 were upregulated by MV. The genes for a number of chaperones, transcription factors and other proteins of the endoplasmic reticulum stress response were also upregulated. These included the gene for the pro-apoptotic and growth arrest-inducing CHOP/GADD153 protein. Thus, the present study demonstrated the activation by MV of cellular mechanisms and pathways that may play a role in the pathogenesis of measles