Abstract: Disclosed are novel polypeptides possessing part or all of the primary structural conformation and one or more of the biological properties of a mammalian (e.g., human) pluripotent granulocyte colony-stimulating factor (“hpG-CSF”) which are characterized in preferred forms by being the product of procaryotic or eucaryotic host expression of an exogenous DNA sequence. Sequences coding for part or all of the sequence of amino acid residues of hpG-CSF or for analogs thereof may be incorporated into autonomously replicating plasmid or viral vectors employed to transform or transfect suitable procaryotic or eucaryotic host cells such as bacteria, yeast or vertebrate cells in culture. Products of expression of the DNA sequences display, e.g., the physical and immunological properties and in vitro biological activities of isolates of hpG-CSF derived from natural sources. Disclosed also are chemically synthesized polypeptides sharing the biochemical and immunological properties of hpG-CSF.

Abstract: The present invention relates to a novel Neutrokine-a, and a splice variant thereof designated Neutrokine-aSV, polynucleotides and polypeptides which are members of the TNF family. In particular, isolated nucleic acid molecules are provided encoding the human Neutrokine-a and/or Neutrokine-aSV polypeptides, including soluble forms of the extracellular domain. Neutrokine-a and/or Neutrokine-aSV 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 Neutrokine-a and/or Neutrokine-aSV activity. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders.

Abstract: The invention is based on the discovery that the presence of a discordant helix in a protein or peptide is predictive of that protein or peptide's ability to form amyloid. The invention includes methods for detecting discordant helices and methods of screening for compounds that stabilize the &agr;-helix of a discordant helix-containing polypeptide. Compounds discovered using these methods are useful for treating or preventing disorders in which amyloid is produced. Such disorders include Alzheimer's disease and prion-associated disorders.

Abstract: The HIV-1 envelope protein gp120 is toxic to rodent and human neurons by indirect mechanisms requiring accessory glial cells. Chemokines are known to block gp120 interactions with chemokine receptors on T cells, macrophanges, and microglia, thereby preventing viral infection. Gp120-induced neuronal killing in rat hippocampal cultures was partially or completely prevented by a specific short peptides related to chemokines, specially IKEYFTS (SEQ. ID NO: 2) and LESYT (SEQ. ID NO: 1). These peptides thus have use in the treatment of neurological degenerative diseases having symptoms associated with neuronal cell death.

Abstract: The present invention provides an isolated, functionally-active protein that catalyzes cleavage of a gamma-secretase substrate. The functional activity of the isolated protein suggests that the isolated protein includes gamma-secretase. In one embodiment, the isolated gamma-secretase protein is associated with PS1. The present invention also relates to homogeneous methods for monitoring cleavage of &bgr;-amyloid precursor protein (&bgr;APP) by gamma-secretase, wherein the steps of of isolating and retrieving cleavage products have been eliminated. Cleavage can be detected by binding a pair of fluorescent adducts to the gamma-cleaved &bgr;APP fragment. Preferably, a first fluorescent adduct binds to the carboxy-terminal end of the gamma-cleaved &bgr;APP fragment, with substantially no cross-reactivity to uncleaved &bgr;APP or to other types of gamma-cleaved &bgr;APP fragments, while a second fluorescent adduct binds to a portion within the amino-terminal region on the gamma-cleaved &bgr;APP fragment.

Abstract: Compounds having the following peptide sequence: X Leu Y, wherein X is H or Ala or Leu-Ser-Ala, Y is OH or peptide sequence having from 1 to 10 amino acids, with the terminal carboxy end being amidified by a NH2 group, or esterified by a substituted or non-substituted hydrocarbyloxy, with the proviso that X and Y are not simultaneously H and OH, respectively, The invention also concerns the corresponding compounds wherein the peptide binding group —CO—NH— is replaced by a binding group resisting protease enzymatic degradation, or wherein the peptide backbone comprises one or more intercalated groups making the peptide binding resistant to enzymatic degradation. Also described are compounds comprising a grouping whose spatial structure is substantially identical to that of a peptide of the sequence X-Leu-Y wherein X and Y have the above-mentioned definition.

Abstract: A pharmaceutical composition comprising 250-20,000 U of an EPO preparation and 5-20 mg of a Fe(III) complex is disclosed. This pharmaceutical composition is useful in treating anaemias as well or as haemodialysis patients.

Abstract: An unconventional approach to purifying CCK receptor protein to sequenceable-grade homogeneity has been discovered. By this approach, CCK receptor protein can be obtained and sequenced, routinely from a variety sources, and from the sequence information thus obtained it is possible to prepare oligonucleotides suitable for cloning CCK receptor genes. “CCK receptor” in this context denotes any from a group of proteins that displays a characteristic CCK binding affinity and that is encoded by a nucleotide sequence which hybridizes a oligonucleotide probe designed in accordance with the criteria elaborated herein.

Abstract: Chimeric, humanized and other IL-18 mAbs, derived from high affinity neutralizing mAbs, pharmaceutical compositions containing same, methods of treatment and diagnostics are provided.

Abstract: There are disclosed novel polypeptides referred to as Pellino polypeptides, as well as fragments thereof, including immunogenic peptides. DNAs encoding such polypeptides as well as methods of using such DNAs and polypeptides are also disclosed.

Abstract: The invention features a polypeptide complex synthesized by bacteria of the genus Clostridia that contains the serotype E botulinum neurotoxin and five neurotoxin associated polypeptides having molecular weights of about 118, 80, 65, 40, and 18 kDa, respectively. The complex is useful in the treatment of diseases or conditions that are caused by excessive release of acetylcholine from presynaptic nerve terminals.

Abstract: The present invention has found that a series of peptides having sequences that substantially correspond to specific regions of the C-terminus of IL-16 can inhibit the activity of IL-16. The present invention has demonstrated that such IL-16-inhibiting peptides can be as short as 4 amino acids in length. Based on these discoveries, the present invention provides IL-16 antagonist peptides and the use thereof for the treatment of IL-16-mediated disorders such as certain inflammatory diseases.

Abstract: The present invention relates to methods of treating obesity, diabetes, sexual dysfunction, atherosclerosis, insulin resistance, impaired glucose tolerance, hypercholesterolemia or hypertrigylceridemia using a neurotensin receptor ligand. The present invention also relates to pharmaceutical compositions and kits that comprise a neurotensin receptor ligand.

Abstract: G Protein-coupled receptor proteins originating in the vicinity of rat brain stem and human brain or salts thereof, or peptide fragments thereof or amides, esters or salts of the same; ligands thereto; a method/kit for screening compounds capable of altering the binding properties of the ligands to the G protein-coupled receptor proteins; the compounds or salts thereof obtained by the above screening; antibodies against the G protein-coupled receptor proteins, etc.

Abstract: This invention relates to a DNA sequence comprising a nucleotide sequence encoding a variant &agr;2B-adrenoceptor protein and to the variant &agr;2B-adrenoceptor protein as well as a method for screening a subject to determine if the subject is a carrier of a variant gene that encodes the variant &agr;2B-adrenoceptor protein. Further this invention relates to a method for treating a mammal suffering from vascular contraction of coronary arteries, the method comprising the step of administering a selective &agr;2B-adrenoceptor antagonist to the mammal and to transgenic animals comprising a human DNA molecule encoding human &agr;2B-adrenoceptor protein or the variant &agr;2B-adrenoceptor protein.

Abstract: The present invention relates to novel compounds and their pharmaceutical or diagnostic use, or use as a pharmacological target. More particularly, the present invention describes the identification of partners of the FE65 protein and the use of these partners, or of any compound which is capable of modulating, at least partially, their interaction with FE65, for regulating the activity of FE65, and in particular the phenomenon of intracellular transport or of endocytosis of the APP.

Abstract: One aspect of the present invention is an isolated nucleic acid molecule encoding canine erythropoietin. The present invention also relates to an isolated canine erythropoietin protein or polypeptide. Another aspect of the present invention is a method for providing erythropoietin therapy to a dog or a cat including administering recombinant canine erythropoietin to a dog or a cat in need of erythropoietin therapy in an amount sufficient to increase production or reticulocytes and red blood cells in the dog or cat.

Abstract: Agents for protecting or ameliorating pancreatic cells and tissues which contains as the active ingredient a neurotrophic factor such as BDNF. By using these drugs, degenerative dropout of pancreatic cells and pancreatic hypofunction caused by diabetes, acute/chronic pancreatitis, etc. can be efficaciously prevented and treated.

Abstract: A method utilizing GM-CSF to promote accelerated wound healing in mammals is described. This method comprises administering topically to the mammal a therapeutically effective amount of this polypeptide. In addition, such methods comprising admixtures containing GM-CSF and at least one other protein are also disclosed.

Abstract: The present invention relates to a novel Neutrokine-&agr; protein which is a member of the TNF protein family. In particular, isolated nucleic acid molecules are provided encoding the human Neutrokine-&agr; protein including soluble forms of the extracellular domain. Neutrokine-&agr; 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 Neutrokine-&agr; activity. Also provided are diagnostic methods for detecting immune system-related disorders and therapeutic methods for treating immune system-related disorders.