Abstract: The disclosure describes the purification and isolation of a novel human protein Z-dependent protease inhibitor (ZPI) from plasma characterized as having a molecular weight of about 72 kDa, being a single chain protein with an N-terminal amino acid sequence of LAPSPQSPETPA, and which produces a rapid inhibition of factor Xa in the presence of human protein Z (PZ), calcium ions and cephalin. The disclosure further describes the isolation and cloning of the ZPI cDNA from a human cDNA library. The ZPI cDNA is 2.44 kb in length and has an open reading frame that encodes the 423 residue mature ZPI protein and a 21 residue signal peptide. PZ, ZPI and the combination of PZ and ZPI are used to inhibit blood coagulation.

Abstract: Provided are methods and compositions for treating hepatitis virus infections in mammals, especially humans. The methods comprise (1) administering N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds alone or in combination with nucleoside antiviral agents, nucleotide antiviral agents, mixtures thereof, or immunomodulating/immunostimulating agents, or (2) administering N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds alone or in combination with nucleoside antiviral agents, nucleotide antiviral agents, or mixtures thereof, and immunomodulating/immuno-stimulating agents.

Abstract: N-Substituted glucamine compounds of formula I are effective in treatment of hepatitis infections, including hepatitis B and hepatitis C. In treating hepatitis infections the compounds of formular I may be used alone, or in combinatioin with another antiviral agent selected from among nucleosides, nucleotides, immunomodulators, immunostimulants or various combination of such other agents.

Abstract: A combination drug therapy is disclosed for the treatment of a patient affected with Gaucher's disease or other such glycolipid storage diseases. The method comprises administering to said patient a therapeutically effective amount of both a N-alkyl derivative of deoxynojirimycin (DNJ) and a glucocerebrosidase enzyme to alleviate or inhibit the glycolipid storage disease. The alkyl group has from about two to about 20 carbon atoms and preferably is butyl, nonyl or decyl.

Abstract: Provided are methods and compositions for treating hepatitis virus infections in mammals, especially humans. The methods comprise (1) administering N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds in combination with nucleoside antiviral agents, nucleotide antiviral agents, mixtures thereof, or immunomodulating/immunostimulating agents, or (2) administering N-substituted-1,5-dideoxy-1,5-imino-D-glucitol compounds in combination with nucleoside antivirals agents, nucleotide antiviral agents, or mixtures thereof, and immunomodulating/immunostimulating agents.

Abstract: A novel method is disclosed for the treatment of a patient affected with Gaucher's disease or other such glycolipid storage diseases. The method comprises administering to said patient a therapeutically effective amount of a long-chain N-alkyl derivative of deoxynojirimycin to alleviate or inhibit the glycolipid storage disease. The long-chain alkyl group has from nine to about 20 carbon atoms and preferably is nonyl or decyl.

Abstract: An improved method of gene targeting, referred to as PCR-based gene targeting is disclosed, which generates cell lines or mice in which at least one allele of a specific gene is disrupted by double homologous recombination of a PCR-derived targeting vector with chromosomal DNA. The method is especially applied to murine macrophage cytokine-inducible nitric oxide synthase (MøiNOS).

Abstract: Disclosed is a 178 kDa glucose-inducible human fatty acid synthase (FAS) mRNA binding protein which has been purified to homogeneity and its binding element characterized. This large phosphoprotein binds to a novel repetitive element in the 3′ untranslated region (UTR) of the FAS mRNA. In particular, the binding has been mapped to a 37 nucleotide stretch within the first 65 bases of the 3′ UTR of mRNA. The binding protein is useful for mediating FAS expression, for regulating lipoprotein secretion and cell growth and for screening of test compounds for activity as inhibitors of FAS.

Abstract: A novel combination drug therapy is disclosed for the treatment of a patient affected with Gaucher's disease or other such glycolipid storage diseases. The method comprises administering to said patient a therapeutically effective amount of both a N-alkyl derivative of deoxynojirimycin (DNJ) and a glucocerebrosidase enzyme to alleviate or inhibit the glycolipid storage disease. The alkyl group has from about two to about 20 carbon atoms and preferably is butyl, nonyl or decyl.

Abstract: Novel short peptides are described that bind to the thrombospondin 1 receptor, which preferably have five amino acid residues which share the tetrapeptide Arg-Val-Ala-Val and have the following sequences: Ile-Arg-Val-Ala-Val [SEQ ID NO:13] and Val-Arg-Val-Ala-Val [SEQ ID NO:14].

Abstract: Disclosed is a 178 kDa glucose-inducible human fatty acid synthase (FAS) mRNA binding protein which has been purified to homogeneity and its binding element characterized. This large phosphoprotein binds to a novel repetitive element in the 3′ untranslated region (UTR) of the FAS mRNA. In particular, the binding has been mapped to a 37 nucleotide stretch within the first 65 bases of the 3′ UTR of mRNA. The binding protein is useful for mediating FAS expression, for regulating lipoprotein secretion and cell growth and for screening of test compounds for activity as inhibitors of FAS.

Abstract: The disclosure describes the purification and isolation of a novel human protein Z-dependent protease inhibitor (ZPI) from plasma characterized as having a molecular weight of about 72 kDa, being a single chain protein with an N-terminal amino acid sequence of LAPSPQSPETPA, and which produces a rapid inhibition of factor Xa in the presence of human protein Z (PZ), calcium ions and cephalin. The disclosure further describes the isolation and cloning of the ZPI cDNA from a human cDNA library. The ZPI cDNA is 2.44 kb in length and has an open reading frame that encodes the 423 residue mature ZPI protein and a 21 residue signal peptide. PZ, ZPI and the combination of PZ and ZPI are used to inhibit blood coagulation.

Abstract: There is disclosed herein a combination of lipoprotein-associated coagulation inhibition (LACI) and sulfated polysaccharides, e.g. heparin, which exerts a synergistic anticoagulant action in whole plasma.

Abstract: Novel N-alkyl derivatives of deoxygalactonojirimycin are provided in which said alkyl contains from 3-6 carbon atoms. These novel compounds are useful for selectively inhibiting glycolipid synthesis.

Abstract: Disclosed are a peptide and its use in a method of screening test compounds as potential inhibitors of matrix metalloproteinases. The peptide consists of residues Trp 574 to Asp 656 in the TIMP-2 binding site of the C-terminal domain of gelatinase-A as shown by SEQ ID NO:19. The method comprises determining the inhibitory effect of a test compound in a competitive inhibition assay with said peptide in which a Ki/Kd=>1 is deemed an inhibitory effect of said test compound, and in which Ki is the inhibitor constant of said test compound and Kd is the dissociation constant of said peptide.

Abstract: The disclosure describes the purification and isolation of a novel human protein Z-dependent protease inhibitor (ZPI) from plasma characterized as having a molecular weight of about 72 kDa, being a single chain protein with an N-terminal amino acid sequence of LAPSPQSPETPA, and which produces a rapid inhibition of factor Xa in the presence of human protein Z (PZ), calcium ions and cephalin. The disclosure further describes the isolation and cloning of the ZPI cDNA from a human cDNA library. The ZPI cDNA is 2.44 kb in length and has an open reading frame that encodes the 423 residue mature ZPI protein and a 21 residue signal peptide. PZ, ZPI and the combination of PZ and ZPI are used to inhibit blood coagulation.

Abstract: A diagnostic method and screening test for atherosclerosis and analogous diseases involving activated phagocytes and/or inflammation is provided which comprises determining the presence of 3-chlorotyrosine in a test sample of a body fluid or tissue at a level which is elevated relative to the level in a normal patient.

Abstract: The disclosure describes the purification and isolation of a novel human protein Z-dependent protease inhibitor (ZPI) from plasma characterized as having a molecular weight of about 72 kDa, being a single chain protein with an N-terminal amino acid sequence of LAPSPQSPETPA, and which produces a rapid inhibition of factor Xa in the presence of human protein Z (PZ), calcium ions and cephalin. The disclosure further describes the isolation and cloning of the ZPI cDNA from a human cDNA library. The ZPI cDNA is 2.44 kb in length and has an open reading frame that encodes the 423 residue mature ZPI protein and a 21 residue signal peptide. PZ, ZPI and the combination of PZ and ZPI are used to inhibit blood coagulation.

Abstract: The disclosure describes the purification and isolation of a novel human protein Z-dependent protease inhibitor (ZPI) from plasma characterized as having a molecular weight of about 72 kDa, being a single chain protein with an N-terminal amino acid sequence of LAPSPQSPETPA, and which produces a rapid inhibition of factor Xa in the presence of human protein Z (PZ), calcium ions and cephalin. The disclosure further describes the isolation and cloning of the ZPI cDNA from a human cDNA library. The ZPI cDNA is 2.44 kb in length and has an open reading frame that encodes the 423 residue mature ZPI protein and a 21 residue signal peptide. PZ, ZPI and the combination of PZ and ZPI are used to inhibit blood coagulation.

Abstract: A novel 54 kDa human macrophage metalloelastase (HME) having elastolytic activity and the cDNA which encodes for this enzyme are disclosed.