Abstract: Human chemokine Alpha-2 polypeptides and DNA (RNA) encoding such chemotactic cytokines and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such chemotactic cytokines for the treatment of leukemia, tumors, chronic infections, auto-immune disease, fibrotic disorders, wound healing and psoriasis. Antagonists against such chemotactic cytokines and their use as a therapeutic to treat rheumatoid arthritis, autoimmune and chronic and acute inflammatory and infective diseases, allergic reactions, prostaglandin-independent fever and bone marrow failure are also disclosed. Also disclosed are diagnostic assays for detecting diseases related to mutations in the nucleic acid sequences and altered concentrations of the polypeptides. Also disclosed are diagnostic assays for detecting mutations in the polynucleotides encoding the chemotactic cytokines and for detecting altered levels of the polypeptides in a host.

Abstract: There is disclosed a pharmaceutical composition and method for treating sepsis, including septic shock and ARDS (acute respiratory distress syndrome), comprising administering an effective amount of a HMG1 antagonist. There is further disclosed a diagnostic method for monitoring the severity or potential lethality of sepsis or septic shock, comprising measuring the serum concentration of HMG1 in a patient exhibiting or at risk or exhibit sepsis or septic shock symptoms. Lastly, there is disclosed a pharmaceutical composition and method for effecting weight loss or treating obesity, comprising administering an effective amount of HMG1 or a therapeutically active HMG1 fragment.

Abstract: Recombinant materials for preparation of a new form of human 5-HT3 receptor are provided. These materials permit the production of said receptor, display of said receptor on host cells, and compositions of diagnostic and therapeutic utility.

Abstract: There is disclosed a pharmaceutical composition and method for treating sepsis, including septic shock and ARDS (acute respiratory distress syndrome), comprising administering an effective amount of a HMG1 antagonist. There is further disclosed a diagnostic method for monitoring the severity or potential lethality of sepsis or septic shock, comprising measuring the serum concentration of HMG1 in a patient exhibiting or at risk or exhibit sepsis or septic shock symptoms. Lastly, there is disclosed a pharmaceutical composition and method for effecting weight loss or treating obesity, comprising administering an effective amount of HMG1 or a therapeutically active HMG1 fragment.

Abstract: The present invention relates to a newly identified receptor belonging to the superfamily of G-protein-coupled receptors. The invention also relates to polynucleotides encoding the receptor. The invention further relates to methods using the receptor polypeptides and polynucleotides as a target for diagnosis and treatment in receptor-mediated disorders, specifically, cardiovascular diseases, including congestive heart failure. The invention further relates to drug-screening methods using the receptor polypeptides and polynucleotides to identify agonists and antagonists for diagnosis and treatment. The invention further encompasses agonists and antagonists based on the receptor polypeptides and polynucleotides. The invention further relates to procedures for producing the receptor polypeptides and polynucleotides.

Abstract: The present invention relates to vanilloid receptor-2, a novel member of the vanilloid receptor family. The invention provides isolated nucleic acid molecules encoding human VR2 receptors. VR2 polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of VR2 receptor activity. Also provided are diagnostic methods for detecting disease states related to the aberrant expression of VR2 receptors. Further provided are therapeutic methods for treating disease states including, but not limited to, chronic pain syndromes, congenital pain insensitivity, inflammation, ischemia, host defense dysfunction, immune surveillance dysfunction, arthritis, multiple sclerosis, autoimmunity, immune dysfunction, and allergy.

Abstract: Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of deleting at least one amino acid residue on the protein, replacing the at least one amino acid residue with an amino acid residue that does not react with, polyethylene glycol, and contacting the protein with polyethylene glycol under conditions sufficient to conjugate the polyethylene glycol to the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains free to interact with a binding partner ligand or cognate subsequent to the conjugation process.

Abstract: Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of deleting at least one amino acid residue on the protein, replacing the at least one amino acid residue with an amino acid residue that does not react with, polyethylene glycol, and contacting the protein with polyethylene glycol under conditions sufficient to conjugate the polyethylene glycol to the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains free to interact with a binding partner ligand or cognate subsequent to the conjugation process.

Abstract: A gene for type C Niemann-Pick disease (NP-C) is disclosed, along with the amino acid sequence of the encoded peptide. Applications which are made possible by the present invention include detection of NP-C carriers and diagnosis of NP-C sufferers. The murine ortholog of the human gene is also disclosed.

Abstract: The invention provides methods and compositions relating to odorant receptors, including a general expression cloning methodology which is useful for identifying novel G protein-coupled receptors and a novel family of odorant receptors and related nucleic acids, ligands, agonists and antagonists. These compositions provide a wide variety of applications such as screening for related receptors, and by modulating the function of the disclosed receptors by modulating their expression or contacting them with agonists, antagonist or ligands modulating reproductive/sexual and non-sexual social behaviors mediated via the olfactory system, reproductive physiologies and olfactory system regulated feeding behaviors, migratory behaviors and events such as conception, implantation, estrous and menstruation.

Abstract: The present invention relates to a newly identified receptor belonging to the superfamily of G-protein-coupled receptors. The invention also relates to polynucleotides encoding the receptor. The invention further relates to methods using the receptor polypeptides and polynucleotides as a target for diagnosis and treatment in receptor-mediated disorders, specifically, cardiovascular diseases, including congestive heart failure. The invention further relates to drug-screening methods using the receptor polypeptides and polynucleotides to identify agonists and antagonists for diagnosis and treatment. The invention further encompasses agonists and antagonists based on the receptor polypeptides and polynucleotides. The invention further relates to procedures for producing the receptor polypeptides and polynucleotides.

Abstract: The present invention provides heregulin variants that are capable of binding an ErbB receptor. Included in the invention are variants of human heregulins, and, in particular, variants of human heregulin-&bgr;1 having enhanced affinity for the ErbB-3 and ErbB-4 receptors. These variants include at least one amino acid substitution and can include further modifications. The invention also provides nucleic acid molecules encoding heregulin variants and related vectors, host cells, pharmaceutical compositions, and methods.

Abstract: The present invention provides an isolated nucleic acid comprising a first nucleotide sequence encoding an amino acid sequence comprising at least three positively charged amino acid residues, positioned upstream and in frame with a second nucleotide sequence encoding a protein. In addition, the present invention provides an isolated nucleic acid comprising a first nucleotide sequence encoding a DNA binding protein, positioned upstream and in frame with a second nucleotide sequence encoding a protein. An isolated nucleic acid is also provided, which comprises a first nucleotide sequence encoding a bacteriophage lambda repressor protein, positioned upstream and in frame with a second nucleotide sequence encoding a protein.

Abstract: The invention provides isolated nucleic acid and amino acid sequences of sensory cell specific G-protein coupled receptors, antibodies to such receptors, methods of detecting such nucleic acids and receptors, and methods of screening for modulators of sensory cell specific G-protein coupled receptors.

Abstract: The present invention provides a method of obtaining a composition which comprises determining whether a chemical compound binds to a human 5-HT2 receptor expressed on the surface of a mammalian cell transfected with a vector adapted for expressing the receptor in the cell, and if the compound binds to the receptor, admixing the compound with a carrier. The present invention further provides a method of obtaining a composition which comprises determining whether a chemical compound binds to and activates or binds to and inhibits activation of a human 5-HT2 receptor expressed on the surface of a mammalian cell, wherein the human 5-HT2 receptor is expressed on the surface of a mammalian cell transfected with a vector adapted for expressing the receptor in the cell, and if the compound binds to and activates or binds to and inhibits activation of the receptor, admixing the compound with a carrier.

Abstract: The present invention includes the receptor protein 4-1BB and the cDNA gene encoding for receptor protein 4-1BB. The nucleotide sequence of the isolated cDNA is disclosed herein along with the deduced amino acid sequence. The 4-1BB protein and fragments and derivatives can be used: 1) as a probe to isolate ligands to receptor protein 4-1BB, 2) to stimulate proliferation of B-cell's expressing 4-1BB, or 3) to block 4-1BB ligand binding. A monoclonal antibody against 4-1BB was developed which specifically recognizes an epitope on the extracellular domain of receptor protein 4-1BB. The monoclonal antibody can be used enhance T-cell proliferation and activation by treating T-cells that have expressed receptor protein 4-1BB with the monoclonal antibody. The effectiveness of the treatment was enhanced when conducted in the presence of protein tyrosinase kinase. A fusion protein for detecting cell membrane ligands to receptor protein 4-1BB was developed.

Abstract: The invention relates to methods for determining degree of integrin-mediated maintenance of cell invasive capacity of tumors, and to methods and compositions for inhibiting or preventing metastasis of cancers. In one aspect, the invention provides a method to determine degree of integrin-mediated maintenance of cell invasive capacity of epithelial derived tumors, particularly prostatic, breast, and lung cancers. In these regards, the invention relates to determining protein or mRNA of effectors of integrin-mediated maintenance of cell invasive capacity, particularly uteroglobin protein or mRNA, or to gauge degree of integrin-mediated maintenance of cell invasive capacity of prostatic, breast, or lung tumors. The invention also relates to methods and compositions, such as uteroglobin, which specifically bind to integrin and are effectors of integrin-mediated maintenance of tumor cell invasive capacity and thus inhibit metastasis.

Abstract: Novel 4-1BB ligand (4-1BB-L) polypeptides and a human cell surface receptor designated 4-1BB that binds 4-1BB-L are provided. Isolated 4-1BB-L-encoding and human 4-1BB-encoding DNA sequences, recombinant expression vectors comprising the isolated DNA sequences, and host cells transformed with the recombinant expression vectors are disclosed, along with methods for producing the novel polypeptides by cultivating such transformed host cells. Soluble forms of the 4-1BB-L or 4-1BB polypeptides are derived from the extracellular domains thereof.

Abstract: The invention provides yeast cells which comprise a mutation in an endogenous yeast stp22 gene and which express a heterologous G protein coupled receptor. The instant yeast cells display enhanced sensitivity to ligand induced stimulation of heterologous G protein coupled receptors and, therefore, show improved properties in drug screening assays.

Abstract: The present invention relates to nucleotide sequences, including expressed sequence tags (ESTs), oligonucleotide probes, polypeptides, antibodies, vectors and host cells expressing, immunoadhesins, agonists and antagonists to patched-2.