Biomedical subjects

D R Senger

Publications and source records attributed to D R Senger.

58 records · Page 4Linked to original sources

PubMed1976

The programmed switch in lysine-rich histone synthesis at gastrulation.

The pattern of histone synthesis changes during development in sea urchins. One change involves two different lysine-rich histones. In Lytechinus, the late appearing histone, H1g, begins to be synthesized at gastrulation. Preformed ("maternal") mRNA of unfertilized eggs contains sequences that direct the synthesis of a part of the histone made during the period of cleavage. During that interval a different lysine-rich hsitone, H1m, is produced. Maternal mRNA is not, however, the sole source of templates for histone synthesis. Transcription of embryonic genomes provides the major translate both maternal and embryonic messages. A cell-free system derived from wheat germ was used to test RNAs from unfertilized eggs and from post-gastrula embryos for their capacity to direct the synthesis of histones, including the H1 types in vitro. Maternal mRNA includes templates for the synthesis of H1m, but it appears to lack those for H1g, since the cell-free system yields only H1m when challenged wigh egg RNA. Since the cell-free system is capable of translating H1g mRNA when presented with it, the synthesis of H1g is probably a very early developmental event controlled at the level of transcription.

Cell-Free System↗

PubMedDate not supplied

Vascular permeability factor/vascular endothelial growth factor: an important mediator of angiogenesis in malignancy and inflammation.

Vascular permeability factor (VPF), also known as vascular endothelial growth factor (VEGF), is a multifunctional cytokine that is overexpressed in many transplantable animal and autochtonous human cancers, in healing wounds, and in chronic inflammatory disorders such as psoriasis and rheumatoid arthritis. All of these entities are characterized by angiogenesis, altered extracellular matrix, and variable degrees of hypoxia. In addition, two VPF/VEGF receptors, flt-1 and kdr, are overexpressed by endothelial cells that line the microvessels that supply these tumors/inflammatory reactions. On the basis of these and other data, we have proposed a model of angiogenesis in which VPF/VEGF plays a central role: this model is applicable to tumors and also to the angiogenesis that occurs in non-neoplastic processes.

Animals↗

PubMedDate not supplied

Elevated expression of secreted phosphoprotein I (osteopontin, 2ar) as a consequence of neoplastic transformation.

Several lines of evidence have recently been presented indicating that proteins previously referred to as Mr 62,000-67,000 transformation-associated secreted phosphoprotein, 2ar, osteopontin, bone sialoprotein I, and 44K Dal bone phosphoprotein are all very likely encoded by the same gene. We have found that markedly elevated expression of this protein, which henceforth is referred to as secreted phosphoprotein I (Sppl) closely correlates with neoplastic transformation of a variety of cell types and that patients with advanced stage metastatic cancers have elevated levels of Sppl in their blood. Moreover, Sppl expression is induced in mouse epidermal cells in vitro and mouse epidermis in vivo with the tumor promoter TPA (Craig et al, J. Biol. Chem. 264: 9682-9689, 1989). Sppl amino acid sequence deduced from cDNA nucleotide sequence (Oldberg et al, Proc. Natl. Acad Sci. U.S.A. 83: 8819-8823, 1986) contains the GRGDS cell-binding sequence which is known to be important for cell attachment to several adhesive proteins found in extracellular matrices. Because of the presence of the GRGDS cell-binding sequence in Sppl, it is probable that abnormally high expression of this soluble protein by tumor cells has important consequences for interactions between tumor cells and the host tissue matrix.

Amino Acid Sequence↗

PubMedDate not supplied

Vascular permeability factor, tumor angiogenesis and stroma generation.

Vascular permeability factor (VPF/VEGF) is a highly conserved multifunctional cytokine that acts directly on endothelial cells (ECs) to activate phospholipase C and induce [CA2+]i transients. Two high-affinity receptors, both tyrosine kinases, have been described. VPF/VEGF has at least two important roles in tumor biology: (1) it potently increases microvascular permeability to plasma proteins, thereby modifying the tumor extracellular matrix to promote the ingrowth of fibroblasts and new blood vessels, and (2) it is a selective EC mitogen. VPF/VEGF is also involved in several other nonmalignant processes with a pathogenesis analogous to that of tumor stroma generation, including wound healing and rheumatoid arthritis.

Endothelial Growth Factors↗