Abstract: The specification describes a process for producing human proinsulin in Escherichia coli (E. coli) using gene manipulation technology. The process can provide for human proinsulin in high yields by a novel expression vector having strong regulatory elements of an insulin gene and a stable recombinant gene product. The expression vector of the present invention is characterized in that: 1) it has an 11 amino acid leader peptide containing six threonines in order to ensure an intracellular stability of proinsulin fusion protein, 2) it contains two copies of a DNA expression cassette each comprising a strong lambda P.sub.R promoter, a lac ribosome binding site, a proinsulin gene with a 17 amino acid leader peptide sequence containing a DNA sequence encoding (Thr).sub.6, and a strong fd phage transcription terminator (combination of phage fd terminator and translation stop codon), etc.

Abstract: A granulocyte stimulating factor (G-CSF) or a G-CSF variant differs from natural G-CSF in that one or several amino acids of the sequence ##STR1## at position 50 to 56 of the mature G-CSF with 174 amino acids or at position 53 to 59 of the mature G-CSF with 117 amino acids or/and at least one of the 4 His residues at position 43, 79, 156 or 170 of the mature G-CSF with 174 amino acids position 46, 82, 159 or 173 of the mature G-CSF with 177 amino acids are mutagenized. It is suitable for immunotherapy.

Abstract: The present invention relates to a purified monocyte-derived insulin receptor regulatory factor, which has the biological activity of reducing insulin receptor binding on T-lymphocytes. Additionally, the invention relates to a nucleic acid that codes for the monocyte-derived insulin receptor regulatory factor, a recombinant protein produced therefrom, and an antibody to the factor. The present invention also relates to a method of reducing insulin receptor binding on activated T-lymphocytes, including administration of the protein to a subject.

Abstract: A new cellular protein produced by activated monocytes/neutrophils and mononuclear cells, and involved in the binding of lipocortin-1 has been discovered. Methods for isolating and purifying this substantially pure lipocortin-1 receptor protein are disclosed herein as well as techniques for cloning and expressing the protein and related materials. Techniques for raising monoclonal antibodies to this protein, and diagnostic and therapeutic uses for this protein are also disclosed.

Abstract: The present invention relates to a novel cell line isolated from a rat osteosarcoma wherein the cell line has the following characteristics: a) a mutated p53 system, b) a normal RB-1 gene as compared to a non-tumorigenic Sprague-Dawley rat cell control, c) a normal c-myc gene as compared to a non-tumorigenic Sprague-Dawley rat cell control, d) a normal c-fos gene as compared to a non-tumorigenic Sprague-Dawley rat cell control, e) a deregulated immediate early gene response, f) a canalicular network MATRIGEL.TM.

Abstract: The present invention relates to a novel cell line isolated from a rat osteosarcoma having the following characteristics: A) a non-expressed p53 protein; B) a normal RB-1 gene as compared to a non-tumorigenic Sprague-Dawley rat cell control; C) a normal c-fos gene as compared to a non-tumorigenic Sprague-Dawley rat cell control; D) a 50-fold amplified c-myc gene as compared to a non-tumorigenic Sprague-Dawley rat cell control; E) a monolayer MATRIGEL.TM. growth pattern; F) tumorigenic in nude mice; G) normal alkaline phosphatase activity; H) an ability to be serially propagated greater than fifty population doublings; I) an ability to produce a growth factor selected from the group consisting of: 1) a mesenchymal inhibitory growth factor; 2) a non-heparin binding mitogenic growth factor; 3) a first heparin binding mitogenic growth factor; 4) a second heparin binding mitogenic growth factor; 5) a third heparin binding mitogenic growth factor; and 6) a fourth heparin binding mitogenic growth factor.

Abstract: Targeted drug conjugates which enable a large number of molecules of drug to be directed to a cell by a single molecule of antibody are provided. The invention also provides intermediates for the synthesis of such conjugates and cytotoxic drugs modified in accordance with the cluster concept of the invention.