Abstract: Complexes formed between (a) an amino di- or poly-phosphonate in which phosphonate groups comprise separate carbon atoms and (b) a paramagnetic metal ion such as Gd.sup.3+, have calcified tissue seeking properties which make them useful as contrast agents for investigating bone metabolism by NMR scanning. Two preferred poly-phosphonates are ethylenediamine tetramethylphosphonate and meta-xylene-diamine tetramethylphosphonate.

Abstract: Dimeric proteins having substantially the same biological activity as PDGF are disclosed. More specifically, the proteins may have two polypeptide chains, one of the chains being a mosaic of amino acid sequences substantially identical to portions of the A- or B-chains of PDGF, the second of the chains being substantially homologous to either the A-chain or the B-chain of PDGF, the proteins being chemotactic or mitogenic for fibroblasts. Alternatively, each of the two polypeptide chains may be a mosaic of amino acid sequences as described above. Therapeutic compositions containing these proteins and methods for enhancing the wound-healing process in warm-blooded animals are also disclosed.

Abstract: Dimeric proteins having substantially the same biological activity as PDGF are disclosed. More specifically, the protein may have two substantially identical polypeptide chains, each of the chains being substantially homologous to the B-chain of PDGF. Alternatively, the protein may have two polypeptide chains that are substantially identical to the B-chain of PDGF. In addition, proteins comprising polypeptides that are variants or derivatives of the B-chain of PDGF are also disclosed. Therapeutic compositions containing these proteins and methods for enhancing the wound-healing process in warm-blooded animals are also disclosed.

Abstract: A composition for use in the preparation of a bone-scanning agent comprises a mixture of a bis-phosphonic acid of formula (I), wherein R.sup.1 and R.sup.3 may be the same or different group selected from H, --SO.sub.3 H and a lower aliphatic group which may optionally contain one or more hetero atoms and which contains at least one --SO.sub.3 H group; R.sup.2 is a group selected from H, --OH, --NH.sub.2, --NHMe, --NMe.sub.2 and lower alkyl optionally substituted by one or more polar groups; R.sup.4 is a group selected from H, --OH, --NH.sub.2 --NHMe, --NMe.sub.2, --SO.sub.3 H and a lower alkyl optionally substituted by one or more polar groups; and n is 0 or 1; with the proviso that when n is 0, R.sup.1 is not H and that when n is 1, R.sup.1 and R.sup.3 cannot both be H; or a non-toxic salt thereof, together with a reducing agent for pertechnetate ions. Technetium-99m, as an aqueous solution of pertechnetate ions, is added to the composition to form a complex of Tc-99m, and the bisphosphonate.

Abstract: Biologically active PDGF analogs expressed in eucaryotic cells are disclosed. The analogs are produced by yeast strains transformed with an extrachromosomal element composed of a strong transcriptional promoter directing the expression of a gene which encodes a protein having substantially the same biological activity as PDGF. Suitable genes include the v-sis gene or a derivative of the v-sis gene of simian sarcoma virus or portions thereof, or the human cDNA gene for PDGF or portions thereof. In particular, DNA sequences encoding polypeptides substantially homologous to the B chain of PDGF are preferred. A secretory signal sequence may be provided upstream of the gene, enabling secretion of the gene product from the host cell. Mitogenic activity is one of the biological activities possessed by these PDGF analogs, making them useful in promoting the growth of mammalian cells.

Abstract: Biologically active PDGF analogs expressed in yeast are disclosed. The analogs are produced by yeast strains transformed with an extrachromosomal element composed of a strong transcriptional promoter directing the expression of a gene which encodes a protein having substantially the same biological activity as PDGF. Suitable genes include the v-sis gene or a derivative of the v-sis gene of simian sarcoma virus or portions thereof, or the human cDNA gene for PDGF or portions thereof. A secretory signal sequence may be provided upstream of the gene, enabling secretion of the gene product from the yeast host cell. Mitogenic activity is one of the biological activities possessed by these PDGF analogs, making them useful in promoting the growth of mammalian cells.

Abstract: Methods for expressing a variety of biologically active PDGF analogs in eucaryotic cells are disclosed. The methods generally comprise introducing into a eucaryotic host cell a DNA construct capable of directing the expression and secretion of biologically active PDGF analogs in eucaryotic cells. The DNA construct contains a transcriptional promoter followed downstream by a suitable DNA sequence. The DNA sequence may encode a protein substantially homologous to the A-chain or the B-chain of PDGF, or a portion thereof, or an A-B heterodimer. In addition, a portion of the DNA sequence may encode at least a portion of the A-chain, while another portion encodes at least a portion of the B-chain of PDGF. Eucaryotic cells transformed with these DNA constructs are also disclosed. Methods of promoting the growth of mammalian cells, comprising incubating the cells with a biologically active PDGF analog expressed by a eucaryotic host cell transformed with such a DNA construct, are also disclosed.

Abstract: A bone-seeking, Technetium-99m-ethylene glycol-1,2-bisphosphonate complex has been found to be useful as a bone-scanning agent. The complex, which is prepared by adding Technetium-99m, as an aqueous solution of pertechnetate, to a composition comprising a mixture of ethylene glycol-1,2-bisphosphonic acid or a non-toxic salt thereof with a reducing agent for pertechnetate, is taken up rapidly in bone to give scans of high definition and compares favorably in this and other respects to other bone-scanning agents.

Abstract: A method of making a radiopharmaceutical composition by mixing an aqueous solution of pertechnetate with a reducing agent comprising tin metal or stannous ion to reduce the pertechnetate and a complexing agent to form a complex with the reduced technetium, is characterized by incorporating nitrate and/or nitrite in an amount to diminish oxidation of Sn.sup.2+ to Sn.sup.4+, and hence to prevent re-oxidation of technetium to pertechnetate, during preparation and storage of the complex. Nitrate and nitrite are superior to organic antioxidants previously proposed.A reagent for the purpose comprises the reducing agent, the complexing agent and the nitrate and/or nitrite usually in a sterile freeze-dried state.

Abstract: An indium-111 preparation comprises a complex of indium-111 with a quinoline compound carrying an 8-hydroxyl group, e.g. oxine, present in an aqueous medium which also contains a surface active agent to prevent the complex from becoming bound to the surface of the vessel on autoclaving, and optionally a buffer to improve blood cell labelling efficiency. The surface active agent is preferably non-ionic, e.g. a polyoxyethylene sorbitan ester of a fatty acid. The buffer is preferably N-2-hydroxyethylpiperazine-N'-2-ethanesulphonic acid.