Abstract: A potent serine protease inhibitor capable of inhibiting Factor VIIa, Factor XIa, plasma kallikrein, and plasmin is provided. The inhibitor is provided in a pharmaceutical composition for treatment of diseases where inhibition of Factor VIIa, Factor XIa, plasma kallikrein, or plasmin is indicated.

Abstract: Root rots are serious conifer nursery diseases. At present, seedlings are inspected visually to determine whether they show symptoms of disease. Cylindrocarpon destructans and Cylindrocarpon floridanum are two important causal agents of root rots. A substantially more efficient and reliable method of detecting the presence of these fungi directly from infected tissue involves the use of a set of DNA primers which can be used in conjunction with the polymerase chain reaction (PCR) to create species specific probes for detecting species of each fungi.

Abstract: Described is a polypeptide comprising one or more zinc fingers. The polypeptide binds to new polynucleotide subsites with high affinity and consequently has a binding specificity that differs from wild type zinc finger proteins. The binding occurs through contacts between certain amino acid residues of the zinc fingers and the nucleic acids of the subsites. The polypeptide sequence of at least one zinc finger differs from wild type zinc fingers, and the difference involves at least one amino acid residue that contacts the bases of the polynucleotide during binding.

Abstract: Recombinant protein complexes having human Factor VIII:C activity are expressed in a eukaryotic host cell by transforming the host cell with first and second expression cassettes encoding a first polypeptide substantially homologous to human Factor VIII:C A domain and a second polypeptide substantially homologous to human Factor VIII:C C domain, respectively. In the present invention, the first polypeptide may be extended having at its C-terminal a human Factor VIII:C B domain N-terminal peptide, a polypeptide spacer of 3-40 amino acids, and a human Factor VIII:C B domain C-terminal peptide. Expression of the second polypeptide is improved by employing an .alpha..sub.1 -antitrypsin signal sequence.

Abstract: The present invention relates, in general, to a protein prenyltransferase and, in particular, to protein geranylgeranyltransferase (GGTase-I) and to a nucleic acid sequence encoding same. The invention also relates to methods of producing GGTase-I and geranylgeranyl modified polypeptides. The invention further relates to a method of screening compounds for the ability to alter GGTase-I activity.

Abstract: The invention provides two novel members of the cytochrome P450 2C subfamily of enzymes, designated 2C18 and 2C19. DNA segments encoding these enzymes are also provided. The 2C19 polypeptide represents the principal human determinant of human S-mephenytoin 4'-hydroxylase activity. The invention also provides methods of identifying drugs metabolized by S-mephenytoin 4'-hydroxylase activity. Drugs shown to be metabolized by this activity should in general not be administered to individuals having, or belong to an ethnic group at risk of, a polymorphic deficiency in S-mephenytoin 4'-hydroxylase activity.

Abstract: A novel polypeptide derived from the leech Hirudo medicinalis was found to be able to inhibit Factor Xa thereby reducing the extent of blood coagulation. The polypeptide is useful in treating conditions of excessive blood coagulation. A recombinant organism containing cDNA encoding the polypeptide has been deposited in the ATCC under Accession No. 69134. Recombinant microorganisms able to produce the polypeptide have been deposited in the ATCC under Accession Nos. 69135, 69137 and 69269.

Abstract: Complementary DNAs (cDNAs) encoding inducible nitric oxide synthase are isolated and purified from a cDNA library prepared from macrophage-like cells activated with interferon gamma and bacterial lipopolysaccharide. The full length cDNAs of at least two isoforms of the enzyme are identified and sequenced.

Abstract: Tissue plasminogen activator (t-PA) derivatives are produced in useful quantities using recombinant DNA techniques. Specific derivatives include amino acid deletion derivatives and amino acid substitution derivatives. A deletion derivative lacking the N-terminal first 68 amino acids is specifically exemplified having requisite t-PA characteristics. The invention disclosed thus enables the production of t-PA derivatives via recombinant means. Methods, expression vehicles and various host cells useful in the production of said t-PA derivatives are also disclosed.

Abstract: A human tissue plasminogen activator (t-PA) is produced in useful quantities using recombinant DNA techniques. The invention disclosed thus enables the production of t-PA free of contaminants with which it is ordinarily associated in its native cellular environment. Methods, expression vehicles and various host cells useful in its production are also disclosed.

Abstract: The invention provides hisS polypeptides and DNA (RNA) encoding hisS polypetides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing hisS polypeptides to screen for antibacterial compounds.

Abstract: The invention provides aspS polypeptides and DNA (RNA) encoding aspS polypetides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing aspS polypeptides to screen for antibacterial compounds.

Abstract: A tissue factor protein mutant capable of neutralizing the ability of endogenous tissue factor to induce coagulation is provided. A representative tissue factor mutant designated K165A, K166A TF is useful in a method for inhibiting thrombin-induced platelet aggregation in a mammal, either separately or in combination with a thrombolytic agent, an anticoagulant, or a GPII.sub.b III.sub.a inhibitor.

Abstract: A screening method for the selection of mutagenized proteins that are normally secreted by cells is described. The method includes the development of a cloning vector for the expression of secretory proteins as fusion proteins on the cell surface of transfected mammalian cells. The secreted protein is displayed on the cell surface by fusion with the glycophospholipid membrane anchor of decay accelerating factor (DAF). Tissue-type plasminogen activator (t-PA), which is normally secreted, is used as a model protein. PCR mutagenesis is used to generate random mutations within the Kringle 1 (K1) domain of t-PA. Fluorescence activated cell sorting (FACS) is employed to screen for t-PA mutants possessing a loss of an epitope to a specific Mab, whose nonlinear binding domains overlap with the t-PA clearance receptor contact regions novel t-PA mutants designated N115S, N1425S, and K159R were discovered by this method.

Abstract: A novel insecticidal protein isolated from Bacillus thuringiensis var. galleria is described and its DNA sequence is given. This protein, called CryIC(b), is toxic to Lepidoptera, including Spodoptera.

Abstract: A new plasmid vector is described which can replicate in B. subtilis and which can express and secrete, in the culture medium, human beta interleukin-1 (beta IL-1) without amino acid sequences extraneous to the natural molecule, a strain of B. subtilis transformed by the vector and a method for the expression and secretion of mature human beta interleukin-1. The human beta interleukin-1 thus obtained shows a specific acitvity of 1.times.10.sup.9 U/mg of protein and is particularly suitable as a stimulant for the immune system, as an adjuvant in vaccines for the activation of the repair mechanism in cases of tissue damage, and for the treatment of auto-immune diseases in man.

Abstract: Tissue plasminogen activator (t-PA) derivatives are produced in useful quantities using recombinant DNA techniques. Specific derivatives include amino acid deletion derivatives and amino acid substitution derivatives. A deletion derivative lacking the N-terminal first 68 amino acids is specifically exemplified having requisite t-PA characteristics. The invention disclosed thus enables the production of t-PA derivatives via recombinant means. Methods, expression vehicles and various host cells useful in the production of said t-PA derivatives are also disclosed.

Abstract: Tissue plasminogen activator (t-PA) derivatives are produced in useful quantifies using recombinant DNA techniques. Specific derivatives include amino acid deletion derivatives and amino acid substitution derivatives. A deletion derivative lacking the N-terminal first 68 amino acids is specifically exemplified having requisite t-PA characteristics. The invention disclosed thus enables the production of t-PA derivatives via recombinant means. Methods, expression vehicles and various host cells useful in the production of said t-PA derivatives are also disclosed.

Abstract: Full-length and deletion subclones of cDNAs for Factor C of Carcinoscorpius rotundicauda are provided. These cDNAs have been cloned into .lambda.gt 22 and pGEM 11Zf(+). Further manipulations of the 5' and 3' ends of these cDNAs have been carried out, and these cDNAs have been further subcloned into other expression vectors such as pGEMEX-1, pET 3b, and the yeast shuttle vectors YEpsec 1 and pEMBLyex 4, and pPIC 9 and pHIL D2. Also provided are host cells transformed with expression vectors containing DNA molecules encoding proteins having Factor C-like enzymatic activity, methods of producing such proteins, methods for purifying Factor C zymogens, and methods for protecting Factor C zymogens from autoactivation by Gram negative bacterial endotoxin while the proenzyme is being purified and/or processed from amoebocyte lysates or from recombinant clones, or during storage or subsequent handling. This protection is afforded by the addition of 5-30% Me.sub.2 SO, which reversibly inhibits the Factor C zymogen.

Abstract: Biologically active mutant tissue plasminogen activators are disclosed wherein site directed mutagenesis, for example, of a two-chain activation site renders said mutants resistant to conversion to the two-chain form. In addition, mutant tissue plasminogen activators are disclosed which have amino acid substitutions or deletions in the region of positions 274-277, which may or may not be resistant to conversion to the two-chain form, but show enhanced fibrin specificity relative to wild-type tissue plasminogen activator.