Abstract: A homogeneous interleukin 1.beta. (IL-1.beta.), its derivative having a modified amino acid sequence of IL-1.beta., a gene coding for said derivative, medical composition comprising said derivative as a pharmaceutically effective component and a medicinal use of homogeneous IL-1.beta. and the derivative.

Abstract: Treatment of solid tumors, including their metastases, without radiation, surgery or standard chemotherapeutic agents is described. Ex vivo stimulation of cells, selection of specific V.beta. subsets of stimulated cells and reinfusion of the V.beta. subsets of stimulated cells is employed for cancer therapy.

Abstract: A highly efficient genetic cloning system is disclosed which is particularly useful for cloning cDNA copies of eukaryotic mRNAs and can direct the orientation of inserts in .lambda.-plasmid composite vectors with large cloning capacities. Cleavage of such vector DNA, by the restriction enzyme SfiI, for example, creates two different non-symmetrical 3' extensions at the ends of vector DNA. Using a linker-primer and an adaptor, cDNA is prepared to have two different sticky ends which can be ligated to those of the vector. When the cDNA fragments and the vector DNAs are mixed, both the molecules can assemble without self-circularization due to base-pairing specificity. This system provides (1) high cloning efficiency (10.sup.7 -10.sup.8 clones/.mu.g poly(A).sup.

Abstract: A method of determining collagen degradation in vivo, comprising quantitating the concentration of a peptide in a body fluid, the peptide being a C-terminal type II collagen telopeptide containing a hydroxylysyl pyridinoline cross-link or a type III collagen telopeptide containing a hydroxylysyl pyridinoline cross-link. The method includes immunometric assays, fluorometric assays, and electrochemical titrations for quantitation. The structures of specific peptides having cross-links and kits for quantitating these peptides in a body fluid are described.

Abstract: A method of testing the cytotoxicity and mutagenicity of a chemical includes the steps of exposing test cells to the chemical in vitro, intracellularly metabolizing the chemical into a mutagenic or cytotoxic metabolite and then detecting gene/protein/cell damage in the test cells as an indication of the mutagenicity/cytotoxicity of the chemical.A cell line is provided for testing cytotoxicity and mutagenicity of the chemicals, the cell line consisting essentially of fibroblasts normally having no detectable cytochrome P450 mixed function oxidase enzyme activity. The fibroblasts are transformed with chimeric gene constructs containing cytochrome P450 coding sequences and have intracellular cytochrome P450 oxidative metabolizing activity.

Abstract: A method for directionally cloning an insert DNA fragment into a target sequence using differential phosphorylation is disclosed, Monophosphorylated PCR fragments are directionally cloned into a monophosphorylated plasmid, Methods for directionally cloning non-PCR fragments into target DNA sequences are also discussed.

Abstract: A DNA signal sequence initially isolated from Streptomyces griseus encodes a signal peptide which directs the secretion, via a fused intermediate, of a protein from the cell within which the DNA signal sequence is expressed. The signal sequence is derived from genes encoding protease A and protease B of S. griseus. The DNA signal sequence encodes a thirty-eight amino acid signal peptide. A DNA construct, including the DNA signal sequence and a gene sequence encoding a protein, when transformed into a living cell by a suitable vector, results in the signal peptide correctly directing the secretion of a mature protein of desired structure, particularly from prokaryotic genera selected for their ability to display enzymatic activity of a type typified by, but not exclusive to, that of protein disulphide oxidoreductase, EC 5.3.4.1, more particularly in the genera Streptomyces, and most particularly in Streptomyces lividans 66.

Abstract: A method for the isolation and sorting of biological materials has been developed. Biological material includes chromosomes, segments of chromosomes, cell organelles, or other minute cellular components. The biological material is separated from the cellular milieu, if necessary, and anchored to a support. Example of a support are glass coverslips, glass or polymer beads. The anchoring is by means of a reversible cross-linking system. The supported biological material is then labelled with compositions capable of binding to said material, and with magnetic particles. Examples of the binding material include nucleic acid probes and antibodies. An example of the antibodies would be those directed to histones. Other labels, for example, fluoresceinbiotin-avidin may be used. The material may be released from the support and sorted by a magnetic force.

Abstract: The present invention provides a recombinant infectious bovine rhinotracheitis virus which is characterized by an insertion of an expressible foreign DNA sequence encoding a polypeptide into the BamHI C fragment of the infectious bovine rhinotracheitis virus genome.

Abstract: Hybrid proteins comprising a cross-linking domain derived from a protein that acts as an acyl-donor substrate for factor XIIIa, a fibrin-binding domain, and a serine protease domain are disclosed. Host cells transfected or transformed with an expression vector comprising a transcriptional promoter operably linked to a DNA sequence encoding such hybrid proteins are also disclosed, as well as methods for producing the proteins. The proteins may be utilized in combination with a suitable carrier or diluent as pharmaceutical compositions.

Abstract: Two novel genomic clones, ZZA1 and ZZA2, were isolated which encode for Pichia pastoris alcohol oxidase isozymes. The 5' non-coding region of ZZA1 contains common structural features involved in the transcription and translation of eukaryotic genes. Comparison of the nucleotide sequences of the ZZA1 and AOX15' noncoding regions showed that they are 66% similar to each other.The rice .alpha.-amylase gene OS103 was placed under the transcriptional control of the ZZA1 promoter. The nucleotide sequences of ZZA1 and other methanol-regulated promoters were analyzed. A highly conserved sequence (TTGNNNGCTTCCAANNNNNTGGT) (SEQ ID NO: 2) was found in the 5' flanking region. A yeast strain containing the ZZA1-OS103 fusion and secreting biologically active .alpha.-amylase into the culture media while converting starch to ethanol was produced. The ZZA1 and ZZA2 regulatory sequences may be used to contol the expression of other heterologous proteins in multiple yeast species.

Abstract: An assay for screening snake venom for the presence or absence of platelet aggregation inhibitors (PAIs) based on specific receptor binding is described. Using this assay, the identification and characterization of PAIs in a wide range of snake venom samples was accomplished. The isolated and purified PAI from several of these active snake venoms is described and characterized. In addition, PAIs lacking the Arg-Gly-Asp (RGD) adhesion sequence but containing K*-(G/Sar)-D wherein K* is a modified lysyl residue of the formulaR.sup.1.sub.2 N(CH.sub.2).sub.4 CHNHCO--wherein each R.sup.1 is independently H, alkyl(1-6C) or at most one R.sup.1 is R.sup.2 --C.dbd.NR.sup.3 wherein R.sup.2 is H, alkyl(1-6C) or is NR.sup.4.sub.2 in which each R.sup.4 is independently H or alkyl(1-6C) and R.sup.3 is H, alkyl(1-6C), phenyl or benzyl, or R.sup.2 --C.dbd.NR.sup.3 is a radical selected from the group consisting of: ##STR1## where m is an integer of 2-3, and each R.sup.

Abstract: The present invention relates to a broad-spectrum tumor suppressor gene and the protein expressed by that gene in appropriate host cells. The protein is a second in-frame AUG codon-initiated retinoblasoma protein of about 94 kD relative molecular mass. The present invention also relates to methods of treating a mammal having a disease or disorder characterized by abnormal cellular proliferation, such as a tumor or cancer and methods of treating abnormally proliferating cells, such as tumor or cancer cells. Treatment is accomplished by inserting a host cell compatible p94.sup.RB expression vector or an effective amount of p94.sup.RB protein into a cell or cells in need of treatment.

Abstract: The present invention provides regulatory elements that are linked to genes involved in cell death and are regulated by p53 tumor suppressor protein. Examples of such p53 responsive elements (p53-RE) include p53-RE.sup.D, which is involved in p53-mediated down-regulation of the Bcl-2 gene, and p53-RE.sup.U, which is involved in p53-mediated up-regulation of the Bax gene. The invention also provides screening assays for identifying agents such as drugs that effectively modulate expression of a gene that is involved in cell death and contains a p53-RE.

Abstract: The invention relates to glycoprotein ligands of selectins. The invention further relates to methods and means for preparing and to nucleic acids encoding these ligands. The invention further concerns a method of treating a symptom or condition associated with excessive binding of circulating leukocytes to endothelial cells by administering to a patient in need of such treatment a glycoprotein ligand of a selectin.

Abstract: Circulating heparin in a mammal may be neutralized without substantial depletion of platelets or leukocytes by administering to the mammal a heparin neutralizing amount of a purified heparin binding fragment of PF4 or of recombinant PF4.

Abstract: The present invention provides vectors for the efficient and position-specific integration of expressible, exogenous nucleotide sequences into cellular genomes. This invention takes advantage of the discovery of a position-specific endonuclease and position-specific insertion markers for the design of said vectors. In addition, a gene comprising a recombinant nucleic acid molecule encoding a polypeptide possessing the biological activity of a position-specific endonuclease, wherein the biological activity of said endonuclease is the catalysis of position-specific insertion of genetic material carried between the position-specific integration markers, is disclosed.

Abstract: The present invention relates to a system for replication and encapsidation of recombinant DNA fragments into virus particles comprised of adenovirus associated viral (AAV) capsid proteins. The invention provides a means of obtaining recombinant viral stocks that may be used to treat patients suffering from genetic diseases.

Abstract: Methods and compositions are described for making ribozymes which can release or activate molecules including autocatalytically replicatable RNA such as MDV-1.

Abstract: Methods of determining collagen degradation in vivo, by quantitating the concentration of a peptide in a body fluid, the peptide being a C-terminal type II collagen telopeptide containing a hydroxylysyl pyridinoline cross-link or a type III collagen telopeptide containing a hydroxylysyl pyridinoline cross-link. Suitable methods include immunometric assays, fluorometric assays, and electrochemical titrations for quantitation. The structures of specific peptides having cross-links and kits for quantitating these peptides in a body fluid are described.