Abstract: The present invention provides methods for the production of N-deacetylate N-sulfate derivatives of non-sulfated N-acetyl heparosan (HS) polysaccharides, compounds thus obtained and compositions comprising same. This invention also provides applications of N-deacetylate N-sulfate derivatives of non-sulfated N-acetyl heparosan (HS) polysaccharides, and compositions comprising same, for use in controlling coagulation and treating thrombosis.

Abstract: The invention relates to methods for detecting and characterizing enzymatic modifications of oligosaccharides, such as heparan sulfate, and their interaction with binding partners, such as proteins, using an oligosaccharide-binding partner binding assay, such as a gel mobility shift assay. The instant invention relates to a rapid, convenient, sensitive and inexpensive method for identifying or studying oligosaccharide-binding partner interactions, identifying and characterizing structural features on oligosaccharides, identifying and characterizing binding partners, identifying agents capable of interfering with, enhancing, or facilitating the binding of an oligosaccharide to its binding partner, diagnosing conditions associated with altered oligosaccharide-binding partner binding, and generating oligosaccharide libraries and kits therefor.

Abstract: The present invention provides methods for the production of N-deacetylate N-sulfate derivatives of non-sulfated N-acetyl heparosan (HS) polysaccharides, compounds thus obtained and compositions comprising same. This invention also provides applications of N-deacetylate N-sulfate derivatives of non-sulfated N-acetyl heparosan (HS) polysaccharides, and compositions comprising same, for use in controlling coagulation and treating thrombosis.

Abstract: Disclosed are methods of 6-O sulfating glucosaminyl N-acetylglucosamine residues (GlcNAc) in a polysaccharide preparation and methods of converting anticoagulant-inactive heparan sulfate to anticoagulant-active heparan sulfate and substantially pure polysaccharide preparations made by such methods. Also disclosed is a mutant CHO cell which hyper-produces anticoagulant-active heparan sulfate. Methods for elucidating the sequence of activity of enzymes in a biosynthetic pathway are provided.

Abstract: Disclosed are methods of 6-O-sulfating glucosaminyl N-acetylglucosamine residues (GlcNAc) in a polysaccharide preparation and methods of converting anticoagulant-inactive heparan sulfate to anticoagulant-active heparan sulfate and substantially pure polysaccharide preparations may by such methods. Also disclosed is a mutant CHO cell which hyper-produces anticoagulant-active heparan sulfate. Methods for elucidating the sequence of activity of enzymes in a biosynthetic pathway are provided.

Abstract: The invention relates to methods for detecting and characterizing enzymatic modifications of oligosaccharides, such as heparan sulfate, and their interaction with binding partners, such as proteins, using an oligosaccharide-binding partner binding assay, such as a gel mobility shift assay. The instant invention relates to a rapid, convenient, sensitive and inexpensive method for identifying or studying oligosaccharide-binding partner interactions, identifying and characterizing structural features on oligosaccharides, identifying and characterizing binding partners, identifying agents capable of interfering with, enhancing, or facilitating the binding of an oligosaccharide to its binding partner, diagnosing conditions associated with altered oligosaccharide-binding partner binding, and generating oligosaccharide libraries and kits therefor.

Abstract: The invention relates to methods for detecting and characterizing enzymatic modifications of oligosaccharides, such as heparan sulfate, and their interaction with binding partners, such as proteins, using an oligosaccharide-binding partner binding assay, such as a gel mobility shift assay. The instant invention relates to a rapid, convenient, sensitive and inexpensive method for identifying or studying oligosaccharide-binding partner interactions, identifying and characterizing structural features on oligosaccharides, identifying and characterizing binding partners, identifying agents capable of interfering with, enhancing, or facilitating the binding of an oligosaccharide to its binding partner, diagnosing conditions associated with altered oligosaccharide-binding partner binding, and generating oligosaccharide libraries and kits therefor.

Abstract: The present invention provides methods, processes and reaction mixtures, which produce sulfated heparosan polysaccharides. This invention also provides methods and reaction mixtures for the synthesis of N-deacetylate N-sulfate derivatives of non-sulfated N-acetyl heparosan (HS) polysaccharides.

Abstract: This invention provides methods for the synthesis of HS polysaccharides or oligosaccharides. This invention provides HS polysaccharides and oligosaccharides thus obtained, and polysaccharides and oligosaccharides with anticoagulant activity.

Abstract: An animal selected for lacking heparan sulfate 3-O-sulfotransferase-1 activity is provided. This animal exhibits characteristics associated with myxomatous valvular disease and is useful for identifying agents which prevent, delay or treat myxomatous valvular disease. Methods of diagnosing myxomatous valvular disease are also provided.

Abstract: Disclosed herein are polysaccharide preparations enriched in 3-OST-3 modified heparan sulfate. Also disclosed are methods of treating herpes simplex viral type-1 infection using the pharmaceutical preparations of the invention.

Abstract: Disclosed are novel isolated nucleic acids and substantially pure protein preparations for naturally occurring and synthetic or chimeric heparan sulfate D-glicosaminyl 3-O-sulfo-transferases (3-OSTs). Also disclosed are uses for these genes and proteins, including uses for the modification and sequencing of glycosaminoglycans.

Abstract: Molecularly-mediated and cellular-based &bgr;-adrenergic receptor-dependent biological pacemakers are disclosed. Methods of using these compositions to improve cardiac chrontropic responsiveness by upregulating heart rate and altering cardiac rhythm are also disclosed.

Abstract: An animal selected for lacking heparan sulfate 3-O-sulfotransferase-1 activity is provided. This animal exhibits characteristics associated with myxomatous valvular disease and is useful for identifying agents which prevent, delay or treat myxomatous valvular disease. Methods of diagnosing myxomatous valvular disease are also provided.

Abstract: The invention relates to methods for detecting and characterizing enzymatic modifications of oligosaccharides, such as heparan sulfate, and their interaction with binding partners, such as proteins, using an oligosaccharide-binding partner binding assay, such as a gel mobility shift assay. The instant invention relates to a rapid, convenient, sensitive and inexpensive method for identifying or studying oligosaccharide-binding partner interactions, identifying and characterizing structural features on oligosaccharides, identifying and characterizing binding partners, identifying agents capable of interfering with, enhancing, or facilitating the binding of an oligosaccharide to its binding partner, diagnosing conditions associated with altered oligosaccharide-binding partner binding, and generating oligosaccharide libraries and kits therefor.

Abstract: Antisense oligonucleotide gene therapy selective for the 5′ region of PDGFR-&bgr; subunit mRNA was used in attempt to prevent intimal thickening following rat carotid arterial injury. Sustained perivascular application of the antisense oligomers for 14 days reduced PDGFR-&bgr; protein overexpression and prevented neointima formation by 80%. Alternatively, a bolus of antisense oligomers reduced the PDGFR-&bgr; protein expression by at least 90% for at least 28 days. Specificity was verified by the absence of effects on the expression of a non-targeted gene PDGFR-&agr;. These data demonstrated that antisense oligonucleotide sequences can effectively suppress a growth factor receptor, and the reduction of intimal hyperplasia after injury correlates with the extent to which these oligomers inhibited PDGFR-&bgr; protein expression. Advantageously, reduction of intimal hyperplasia was also accomplished with an almost completely restored endothelial function.

Abstract: Disclosed is a method for localized application of antisense oligonucleotides, which has been found to be effective in inhibiting expression and translation of a variety of genes. The method utilizes antisense oligonucleotides which are specific for the mRNA transcribed from the gene of interest. The antisense oligonucleotides are applied directly to the desired locus of the cells to be treated, where they hybridize with the mRNA and inhibit expression of the gene. Devices for localized antisense application and methods for making them also are described.

Abstract: New therapies for treating blood platelet disorders based on the megapoietin gene and protein are described. Additional utilities for megapoietin such as increasing the storage life of platelet and whole blood preparations, a means for selectively targeting therapeutic or imaging agents to arterial clots, and a means for selectively stimulating platelet production from megakaryocytes in vivo and in vitro (e.g., as a source of platelets for transplantation) and to stimulate stem cell growth are also described.

Abstract: The present invention relates to the isolation of genes encoding novel protein tyrosine phosphatases (PTPs) having SH2 domains, the nucleic acid sequences isolated, and the encoded phosphatases. The invention further relates to methods of altering tyrosine phosphatase activities encoded by the novel phosphatases. By altering (i.e., increasing or decreasing) tyrosine phosphatase activity, one can alter megakaryocyte cell function, and thereby alter platelet production. Alteration of the genes is associated with neoplastic disease.

Abstract: A megakaryocyte stimulatory factor (MSF), purified to homogeneity, is an acidic protein (pI=5.1) with an Mr=15,000 which stimulates PF4-like protein synthesis in rat promegakaryoblast cells by as much as 7-fold, and exhibits half-maximal activity at a concentration of 0.8 pM. MSF exhibits no biologic activity corresponding to other known hemopoietic growth factors, and appears to be specific for the megakaryocyte lineage.In the given examples, MSF was purified to homogeneity (as judged by SDS-PAGE and isoelectric focusing in the presence of 9.2 M urea) from serum-free conditioned medium obtained from cultured human embryonic kidney (HEK) cells, and to near homogeneity from thrombocytopenic plasma.