John C. Fiddes

Vascular endothelial growth factor: A new member of the platelet-derived growth factor gene family

Using applications of the polymerase chain reaction (PCR) technique, cDNA clones have been isolated encoding bovine vascular endothelial growth factor (VEGF), a mitogen with specificity for vascular endothelial cells. Analysis of the clones indicates that VEGF can exist in two forms, probably due to alternative RNA splicing. The amino acid sequences predicted from the clones also show that VEGF shares homologies of about 21% and 24% respectively with the A and B chains of human platelet-derived growth factor (PDGF), and has complete conservation of the eight cysteine residues found in both mature PDGF chains. The homology is not reflected in function, however, since the cell types responsive to VEGF are distinct from those responsive to homo- and heterodimers of the PDGF chains.

Structure, Expression, and Evolution of the Genes for the Human Glycoprotein Hormones

Publisher Summary The recombinant DNA technology is used to understand the tissue-specific, developmentally regulated expression of the four different glycoprotein hormones: chorionic gonadotropin (CG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH). The isolation of a full-length cDNA encoding the common α subunit demonstrates that there is a single human gene for this protein, expressed in the placenta for production of hCG and in the pituitary for the production of hLH, hFSH, and hTSH. From this, it is concluded that the control for the expression of glycoprotein hormones probably resides in the β subunit genes. The isolation of a full-length cDNA encoding the β subunit of hCG allows to isolate the full human complement of seven hCG β subunit genes or pseudogenes and, by cross-hybridization, the single β hLH gene. The β hLH gene is linked to at least three of the β hCG genes, and together, they show a complex organization of inverted and tandem pairs. In the analysis of independently isolated β hCG cDNA clones and from transfection of six of the seven β hCG genes into mammalian tissue culture cells, it was found that only three of the seven hCG genes are expressed. From a comparison of the nucleotide sequence of two of the β hCG genes and of the single β hLH gene, β hCG is shown to arise from β hLH by a series of selected changes with very little neutral drift.

Fibroblast growth factor reverses the bacterial retardation of wound contraction

Chronic granulating wounds were established in rats by excising burns inoculated with Escherichia coli. Recombinant human basic fibroblast growth factor was applied at dosages of 1, 10, and 100 micrograms/cm2 to the wounds of three groups of 20 animals on days 5, 9, 12, 15, and 18 after injury. The rate of wound closure was compared with that of similarly wounded animals treated with saline vehicle alone. High levels of bacteria caused significant retardation of wound contraction. The addition of basic fibroblast growth factor at the 100 micrograms/cm2 dosage level markedly improved the rate of wound closure whereas inert vehicles applied alone were ineffective. Since bacterial counts did not decrease in the basic fibroblast growth factor treated wounds, basic fibroblast growth factor was not inherently bactericidal. Histologic examination of the wounds treated with basic fibroblast growth factor showed increased cellularity with increased numbers of fibroblasts and round cells. These results suggest basic fibroblast growth factor can overcome the defect in healing created by bacterial infection, and this peptide may have efficacy in the management of the contaminated wound.