Abstract: Compositions and methods are provided for adhering and binding biologically active proteins and protein-containing composites to substrates. Adhesive formulations comprising a nonproteinaceous polymer of monomeric units comprising an aromatic moiety substituted with at least one hydroxyl group such as poly(p-hydroxy-styrene) are applied to substrates and subsequently contacted with proteins. Beads comprising a nonproteinaceous polymer of monomeric units comprising an aromatic moiety substituted with at least one hydroxyl group are also provided, and the beads are coated with a protein. Substrates to which the adhesive formulations have been applied, as well as the beads, can be used to adhere cells and tissues, to sort cell types, to perform immunoassays, to perform chromatography and to remove protein from samples.

Abstract: The invention relates to a fusion protein which comprises an immunoglobulin of the IgM, IgG1 or IgG3 immunoglobulin class, wherein the variable region of the light or heavy chain has been replaced with CD4 or fragment thereof which is capable of binding to gp120. The invention also relates to an immunoglobulin-like molecule comprising the fusion protein of the invention together with an immunoglobulin light or heavy chain. The invention also relates to a method of treating HIV or SIV infection comprising administering the fusion proteins or immunoglobulin-like molecules of the invention to an animal. The invention also relates to assays for HIV or SIV comprising contacting a sample suspected of containing HIV or SIV gp120 with the immunoglobulin-like molecule or fusion protein of the invention, and detecting whether a complex is formed.

Abstract: Disclosed is a method of directing a cellular response in a mammal by expressing in a cell of the mammal a chimeric receptor which causes the cells to specifically recognize and destroy an infective agent, a cell infected with an infective agent, a tumor or cancerous cell, or an autoimmune-generated cell. The chimeric receptor includes an extracellular portion which is capable of specifically recognizing and binding the target cell or target infective agent, and (b) an intracellular portion of a protein-tyrosine kinase which is capable of signalling the therapeutic cell to destroy a receptor-bound target cell or a receptor-bound target infective agent. Also disclosed are calls which express the chimeric receptors and DNA encoding the chimeric receptors.

Abstract: A rapid mutational analysis method for mapping protein epitopes is disclosed. This method has been used to identify the binding sites for 16 anti-CD2 and anti-CD4 monoclonal antibodies. The powerful, rapid, and simple method of the present invention allows isolation of a very large number of mutants, and is applicable to any intracellular or surface protein for which a cDNA and monoclonal antibodies are available. The present method is especially useful in ligand binding site studies for the design of new ligands and drugs.

Abstract: Disclosed herein are methods for reducing or preventing cytokine production associated with an inflammatory response, involving administering to a mammal a therapeutically-effective amount of a thiazolidinedione PPAR.gamma. agonist.

Abstract: Disclosed is a method of directing a cellular response in a mammal by expressing in a cell of the mammal a chimeric receptor which causes the cells to specifically recognize and destroy an infective agent, a cell infected with an infective agent, a tumor or cancerous cell, or an autoimmune-generated cell. The chimeric receptor includes an extracellular portion which is capable of specifically recognizing and binding the target cell or target infective agent, and (b) an intracellular portion of a protein-tyrosine kinase which is capable of signalling the therapeutic cell to destroy a receptor-bound target cell or a receptor-bound target infective agent. Also disclosed are cells which express the chimeric receptors and DNA encoding the chimeric receptors.

Abstract: Disclosed are methods and compositions for reducing coronary artery stenosis, restoring blood flow to infarcted myocardium, improving myocardial perfusion, reducing heart attacks or other adverse cardiovascular events, or treating symptoms of inadequate myocardial function in a mammal involving administering to the mammal (a) a compound that includes eicosapentaeneoic acid or docosahexaeneoic acid and (b) a cholesterol-lowering therapeutic, combined with dietary restrictions (resulting in aggressive loading of marine lipids), whereby a serum LDL concentration of less than 75 mg/dl (and preferably less than 55 mg/dl) is achieved. One particular method involves administering to the mammal a combination that includes (a) a compound that includes an eicosapentaeneoic or docosahexaeneoic acid (for example, a marine lipid) and (b) a cholesterol synthesis or transfer inhibitor, and which may also optionally include aspirin and/or niacin.

Abstract: Purified DNA encoding .alpha.(1,3)fucosyltransferase and the recombinant proteins expressed from such DNA are disclosed. The recombinant fucosyltransferase polypeptides are used to fucosylate proteins to produce therapeutics useful for the treatment of disease, e.g., an adverse immune reaction such as septiciemia or septic shock.

Abstract: Disclosed is a method of inhibiting the binding of a cell bearing a cell adhesion protein to a molecule or cell bearing a carbohydrate determinant specific for the cell adhesion molecule. The method involves contacting the cell adhesion protein-bearing cell with an inhibitor molecule bearing the carbohydrate determinant. Also disclosed is a method of inhibiting the binding of the first member of a specific binding pair to the second member of the specific binding pair, involving contacting the first member with an antibody which is specific for the first member and which is covalently bonded to a carbohydrate moiety which interferes with the antibody's ability to fix complement and bind an F.sub.c receptor. The methods of the invention may be used, for example, to reduce inflammation.

Abstract: Disclosed is a method of directing a cellular immune response against an HIV-infected cell in a mammal involving administering to the mammal an effective amount of therapeutic cells which express a membrane-bound, proteinaceous chimeric receptor comprising (a) an extracellular portion which includes a fragment of CD4 which is capable of specifically recognizing and binding the HIV-infected cell but which does not mediate HIV infection and (b) an intracellular portion which is capable of signalling the therapeutic cell to destroy the receptor-bound HIV-infected cell. Also disclosed are cells which express the chimeric receptors and DNA and vectors encoding the chimeric receptors.

Abstract: A simple and highly efficient method for cloning cDNAs from mammalian expression libraries based on transient expression in mammalian host cells has been discovered. The present invention specifically provides the CD40 cDNA sequence.

Abstract: Disclosed is a method of directing a cellular response in a mammal by expressing in a cell of the mammal a chimeric receptor which causes the cells to specifically recognize and destroy an infective agent, a cell infected with an infective agent, a tumor or cancerous cell, or an autoimmune-generated cell. Also disclosed are cells which express the chimeric receptors and DNA encoding the chimeric receptors.

Abstract: A simple and highly efficient method for cloning cDNAs from mammalian expression libraries based on transient expression in mammalian host cells has been discovered. Novel expression vectors allowing highly efficient construction of mammalian cDNA libraries are disclosed. The cloning method of the invention which has been used to clone genes for cell surface antigens of human lymphocytes, has general application in gene cloning. Cell surface antigens cloned according to the present invention have been purified, and the nucleotide and amino acid sequences determined. These antigens have diagnostic and therapeutic utility in immune-mediated infections in mammals, including humans.

Abstract: Disclosed is a method of inhibiting the binding of a cell bearing a cell adhesion protein to a molecule or cell bearing a carbohydrate determinant specific for the cell adhesion molecule. The method involves contacting the cell adhesion protein-bearing cell with an inhibitor molecule bearing the carbohydrate determinant. Also disclosed is a method of inhibiting the binding of the first member of a specific binding pair to the second member of the specific binding pair, involving contacting the first member with an antibody which is specific for the first member and which is covalently bonded to a carbohydrate moiety which interferes with the antibody's ability to fix complement and bind an F.sub.c receptor. The methods of the invention may be used, for example, to reduce inflammation.

Abstract: The invention features a synthetic gene encoding a protein normally expressed in a mammalian cell or eukaryotic cell wherein at least one non-preferred or less preferred codon in the natural gene encoding the mammalian protein has been replaced by a preferred codon encoding the same amino acid.

Abstract: The invention features a synthetic gene encoding a protein normally expressed in mammalian cells wherein at least one non-preferred or less preferred codon in the natural gene encoding the mammalian protein has been replaced by a preferred codon encoding the same amino acid.

Abstract: Disclosed is a method of isolating a protein from a sample, involving (i) providing a first molecule which is capable of forming an affinity complex with the protein; (ii) contacting the sample with the first molecule under conditions which allow affinity complex formation; (iii) isolating the complex; (iv) treating the complex with imidazole to disrupt the complex, causing the release of the protein from the complex; and (v) isolating the protein. According to one embodiment, imidazole is used as a very gentle elution reagent to disrupt a protein A-antibody fusion protein complex, a technique which has general application for the isolation of antibodies or recombinant antibody fusion proteins.

Abstract: Disclosed is a method of inhibiting the binding of a cell bearing a cell adhesion protein to a molecule or cell bearing a carbohydrate determinant specific for the cell adhesion molecule. The method involves contacting the cell adhesion protein-bearing cell with an inhibitor molecule bearing the carbohydrate determinant. Also disclosed is a method of inhibiting the binding of the first member of a specific binding pair to the second member of the specific binding pair, involving contacting the first member with an antibody which is specific for the first member and which is covalently bonded to a carbohydrate moiety which interferes with the antibody's ability to fix complement and bind an F.sub.c receptor. The methods of the invention may be used, for example, to reduce inflammation.

Abstract: Disclosed is a protein, designated RIP, which contains a death domain at its carboxy terminus and a kinase domain at its amino terminus. RIP interacts with the Fas/APO-1 intracellular domain and the TNFR1 intracellular domain. When expressed in transformed host cells, recombinant RIP promotes apoptosis. Also disclosed are DNA molecules encoding RIP, anti-RIP antibodies, and screening methods for discovering inhibitors of RIP-dependent apoptosis.

Abstract: Disclosed is a method of reducing pain in a mammal involving administration of relaxin to the mammal.