Abstract: Fusion proteins and a process for their purification by means of metal chelate affinity chromatography on NTA resins are provided by this invention.

Abstract: Methods and compositions for blocking Ca.sup.2+ channels within an organism are provided. For example, a toxin was isolated from the Agelenopsis aperta spider. The toxin comprised a 48 amino acid toxin having a molecular weight of approximately 5,274. This toxin was found to block calcium channels within the central nervous system. The Agelenopsis gene responsible for producing this toxin has been identified and cloned. This gene and/or its derivatives provide a mechanism by which the toxin can be produced using recombinant DNA expression technologies.The present invention further relates to methods of treating neurological diseases by applying the toxins isolated and identified. The toxin may provide beneficial effects on certain neurological conditions including seizures, ischemic-hypoxic CNS damage, and neurodegenerative disorders. It is also found that the toxins are effective as tags in probing calcium channels.

Abstract: This invention provides an imaging agent which comprises a polypeptide labeled with an imageable marker, such polypeptide having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin. The invention further provides a method wherein the imaging agent is used for imaging a fibrin-containing substance, i.e., a thrombus or atherosclerotic plaque. Further provided are plasmids for expression of polypeptides having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin, hosts containing these plasmids, methods of producing the polypeptides, methods of treatment using the polypeptides, and methods of recovering, refolding and reoxidizing the polypeptides.

Abstract: Cloning and expression of the gene encoding human phosphlipase inhibitory protein (hPIP) permits production of an anti-inflammatory protein in practical quantities using recombinant techniques.

Abstract: Novel fusions of a phospholipid anchor domain and a polypeptide heterologous to the anchor domain donor polypeptide are provided for industrial use. Therapeutic administration of the fusions enables the targeting of biological activity to cell membrane surfaces.

Abstract: Polypeptides derived from the ligand-binding portion of an Integrin alpha subunit are disclosed as are their use for modulation of Integrin ligand binding. Anti-peptide antibodies, hybridomas secreting the antibodies, as well as methods of making and using such antibodies and recombinant DNA molecules coding for the polypeptides are also described. The polypeptides and antibodies to the polypeptides are effective inhibitors of fibrinogen binding to platelets.

Abstract: Novel soluble oxidation resistant thrombomodulin analogs are produced for various therapeutic and other uses, such as in thrombotic and vascular disease therapies. These analogs exhibit the characteristic therapeutic properties of native thrombomodulin, yet they are soluble and are not inactivated after they have been exposed to oxidants. Some of the analogs disclosed are multifunctional fusion proteins having both antithrombotic activity and some additional bioactivity.

Abstract: Novel polypeptide compositions are provided which inhibit human tumor cell growth, which may or may not stimulate autophosphorylation of pp6src and induce the release of a 52 kD polypeptide from neoplastic cells. Individual polypeptides may be isolated from mammalian blood platelets by selected extraction and purification procedures, may be synthesized or produced by hybrid DNA technology.

Abstract: A new method is described for the preparation of a safe, immunogenic and efficacious vaccine for protection against the disease pertussis. In development of this vaccine, specific functional sites of pertussis toxin have been identified, and using this information, defined mutant holotoxins have been produced by site directed mutagenesis of the toxin gene. A number of these holotoxin analogs are detoxified, retain an immunodominant S1 epitope, are immunogenic and are protective in the standard pertussis vaccine potency test in mice.

Abstract: The present invention relates to genes and their encoded proteins which induce immunological effector cell activation and chemattraction. The proteins of the invention attract subsets of immunological effector cells and stimulate them to express their specialized effector cell functions. Such proteins, termed Ap-1 proteins, are expressed by lymphoid cells, and bind to effector cells such as macrophages and mast cells. In particular, the ApPursuant to the provisions of 35 U.S.C. .sctn.202(c), it is hereby acknoledged that the Governament has certain rights in this invention, which was made in part with funds from the National Institutes of Health.

Abstract: Described herein is the cloning and characterization of DNA encoding a protein which appears at an early stage in spinal cord development, is concentrated in motor neurons, and appears to have a role in neuromuscular junction formation. This protein copurifies with an activity which induces acetylocholine receptor synthesis in muscle fibers. A method for enhancing neurotransmitter receptor synthesis or accumulation in cells, especially that of the acetylcholine receptor, is also described.

Abstract: The following new polypeptides are described: (a) H-X.sup.1 -Asp-Asp-Pro-Pro-Ala-Thr-Val-Tyr-Arg-Tyr-Asp-Ser-Arg-Pro-Pro-Glu-Asp-X.sup .2 -Y, (b) H-X.sup.1 -Ser-Glu-Tyr-Leu-Ala-His-Arg-Arg-Ile-Pro-Pro-Glu-Asn-Ile-Arg-Arg-Val-Thr-A rg-Val-X.sup.2 -Y, (c) H-X.sup.1 -Ala-Phe-Val-Ser-Thr-Ser-Ser-Ser-Arg-Arg-Tyr-Thr-Glu-Val-Tyr-X.sup.2 -Y, (d) H-X.sup.1 -Gly-Ile-Thr-Gly-Glu-Thr-Thr-Thr-Thr-Glu-Tyr-Ser-Asn-Ala-Arg-Tyr-Val-X.sup .2 -Y, and (e) H-X.sup.1 -Leu-Glu-His-Arg-Met-Gln-Glu-Ala-Val-Glu-Ala-Glu-Arg-Ala-Gly-Arg-Gly-Thr-G ly-His-Phe-Ile-X.sup.2 -Y, in which X.sup.1 and X.sup.2 each represents an optional coupling-facilitating amino acid residue, and Y represents --OH or --NH.sub.2. Additionally, there is described an artificial pertussis toxin antigen, which mainly consists of at least one peptide sequence reacting with antibodies induced by the native pertussis toxin selected from the above polypeptides (a) to (e) and parts thereof.

Abstract: A previously isolated hepatitis B virus (HBV) integration in a 147 bp cellular DNA fragment linked to hepatocellular carcinoma (HCC) was used as a probe to clone the corresponding complementary DNA from a human liver cDNA library. Nucleotide sequence analysis revealed that the overall structure of the cellular gene, which has been named hap, is similar to that of the DNA-binding hormone receptors. Six out of seven hepatoma and hepatoma-derived cell-lines express a 2.5 kb hap mRNA species which is undetectable in normal adult and fetal livers, but present in all non-hepatic tissues analyzed. Low stringency hybridization experiments revealed the existence of hap related genes in the human genome. The cloned DNA sequence is useful in the preparation of pure hap protein and as a probe in the detection and isolation of complementary DNA and RNA sequences.

Abstract: DNA sequences encoding .beta.-amyloid-related proteins associated with Alzheimer's disease are disclosed. Also provided herein is a DNA sequence encoding a novel protease inhibitor. These sequences are used in producing or constructing recombinant .beta.-amyloid core protein, .beta.-amyloid-related proteins and recombinant or synthetic immunogenic peptides. Antibodies generated against the recombinant proteins or immunogenic peptides derived therefrom can be used for cerebral fluid or serum protein diagnosis of Alzheimer's disease.

Abstract: Disclosed are (1) a hybridoma carrying a vector for expressing a fibroblast growth factor (FGF) protein gene; (2) a method for producing the hybridoma of (1) which comprises transforming a hybridoma with the vector for expressing the FGF protein gene; and (3) a method for producing a biologically active substance which comprises cultivating in a culture medium the hybridoma obtained by the method of (2) using a hybridoma producing a biologically active substance other than the FGF protein, producing the FGF protein and producing and accumulating the biologically active substance in a culture, and recovering the biologically active substance, whereby the biologically active substance can be efficiently produced and recovered using the serum-free medium, which is advantageous for industrial production and very useful for an improvement in the breeding of the hybridoma.

Abstract: This invention provides a purified polypeptide useful as an antimicrobial agent. This purified polypeptide has been derived from human granulocytes, and has a molecular weight of about 3,700 daltons and the N-terminal amino acid sequence val-cys-ser-cys-arg-leu-val-phe-cys-arg-arg-thr-glu-leu-arg-val-gly-asn-cy s-leu-ilu-gly-gly-val-ser-phe-thr-tyr-cys-cys-thr-arg-val. This invention also provides methods for producing this polypeptide, pharmaceutical compositions containing the polypeptide, and uses thereof.

Abstract: An Entamoeba histolytica specific cDNA clone which encodes an antigenic surface membrane protein possessing multiple tandem repeats and expression in E. coli is disclosed. This surface membrane protein is useful in a diagnostic assay for amebiosis.

Abstract: The protein PP4-X, whose amino acid sequence and the DNA sequence coding for this have been determined, has anticoagulative properties and can be prepared by genetic manipulation. PP4-X is used for therapeutic and diagnostic purposes.

Abstract: Polypeptides which are derived from the ligand-binding portion of an Integrin alpha subunit are disclosed as are their use for modulation of Integrin ligand binding. Anti-peptide antibodies, hybridomas secreting these antibodies, as well as methods of making and using such antibodies, and recombinant DNA molecules that define the structural gene coding for the polypeptides are also contemplated as within the scope of the present invention.

Abstract: The present invention relates to polypeptide inhibitors of platelet activation and derivatives thereof, purified from the venom of the North American Water Moccasin and to methods for their purification. This invention also relates to DNA sequences and recombinant DNA molecules which code for these polypeptide inhibitors of platelet activation. And this invention relates to recombinant DNA molecules which code for fusion proteins comprising both a polypeptide inhibitor of platelet activation and a conventional anti-thrombin polypeptide. This invention also relates to pharmaceutically acceptable compositions and methods characterized by at least one of these natural or recombinant inhibitors of platelet activation, alone or in combination with conventional anti-thrombin compounds. The compositions, combinations and methods of this invention are particularly useful in the treatment of thrombotic diseases.