Abstract: This disclosure relates to TGF-&bgr; family protein fusions that display substantial native TGF-&bgr; family protein function while also having an additional functionality conveyed by the addition of a functionalizing peptide domain. Such functionalizing peptide domain can be a tag peptide (e.g., an epitope tag, a purification tag, a molecular size differentiation tag, etc.) or a passenger or targeting protein. Also provided are methods of making these fusions, as well as methods of using them for diagnosis and diagnosis of various conditions, in measuring and monitoring levels of the fusion molecule in experimental systems and subjects, and in measuring and detecting receptor proteins.

Abstract: The present invention concerns therapeutic agents that modulate the activity of PTH and PTHrP. In accordance with the present invention, modulators of PTH and PTHrP comprise: (a) a PTH/PTHrP modulating domain; and (b) a vehicle, such as a polymer (e.g., PEG or dextran) or an Fc domain, which is preferred; wherein the vehicle is covalently attached to the C-terminus of the PTH/PTHrP modulating domain. The vehicle and the PTH/PTHrP modulating domain may be linked through the N- or C-terminus of the PTH/PTHrP modulating domain, as described further below. The preferred vehicle is an Fc domain, and the preferred Fc domain is an IgG Fc domain. Preferred PTH/PTHrP modulating domains comprise the PTH and PTHrP-derived amino acid sequences described hereinafter. Other PTH/PTHrP modulating domains can be generated by phage display, RNA-peptide screening and the other techniques mentioned herein.

Abstract: The invention provides improved agents and methods for treatment of diseases associated with amyloid deposits of A&bgr; in the brain of a patient Such methods entail administering agents that induce a beneficial immunogenic response against the amyloid deposit The methods are useful for prophylactic and therapeutic treatment of Alzheimer's disease. Preferred agents including N-terminal fragments of A&bgr; and antibodies binding to the same.

Abstract: The present invention provides molecules that home to a selected organ. For example, the invention provides peptides that selectively home to brain or to kidney.

Abstract: The invention provides improved agents and methods for treatment of diseases associated with amyloid deposits of A&bgr; in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the amyloid deposit. The methods are useful for prophylactic and therapeutic treatment of Alzheimer's disease. Preferred agents including N-terminal fragments of A&bgr; and antibodies binding to the same.

Abstract: Novel human chemokine receptors, MCP-1RA and MCP-1RB, and processes for producing them are disclosed. The receptors, which are alternately spliced versions of MCP-1 receptor protein may be used in an assay to identify antagonists of MCP-1 which are therapeutically useful in the treatment of atherosclerosis and other diseases characterized by monocytic infiltrates.

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 relates to a method for producing interleukin-1 receptor antagonists, a prophylatically or therapeutically effective protein. A syringe is filled with a body fluid and incubated. The prophylatically or therapeutically effective protein is then produced in the body fluid.

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: 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: 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: A ligand for a neuropeptide Y receptor which has the formula: Ac-Ala-Arg-Ala-Ala-Leu-Asn-Ala-Ala-Thr-Arg-Gln-Arg-Tyr-NH2 (SEQ ID NO:1), or Ac-Ala-Arg-His-Tyr-Leu-Asn-Leu-Leu-Thr-Arg-Gln-Arg-Tyr-NH2 (SEQ ID NO:2), or Ac-Leu-Ala-His-Tyr-Leu-Asn-Leu-Leu-Thr-Arg-Gln-Arg-Tyr-NH2 (SEQ ID NO:3), or Ac-Leu-Arg-Ala-Tyr-Leu-Asn-Leu-Leu-Thr-Arg-Gln-Arg-Tyr-NH2 (SEQ ID NO:4), or Ac-Leu-Arg-His-Ala-Leu-Asn-Leu-Leu-Thr-Arg-Gln-Arg-Tyr-NH2, (SEQ ID NO:5), or Ac-Leu-Arg-His-Tyr-Ala-Asn-Leu-Leu-Thr-Arg-Gln-Arg-Tyr-NH2(SEQ ID NO:6), or Ac-Leu-Arg-His-Tyr-Leu-Ala-Leu-Leu-Thr-Arg-Gln-Arg-Tyr-NH2, (SEQ ID NO:7), or Ac-Leu-Arg-His-Tyr-Leu-Asn-Ala-Leu-Thr-Arg-Gln-Arg-Tyr-NH2, (SEQ ID NO:8), or Ac-Leu-Arg-His-Tyr-Leu-Asn-Leu-Ala-Thr-Arg-Gln-Arg-Tyr-NH2, (SEQ ID NO:9), or Ac-Ala-Arg-His-Ala-Leu-Asn-Leu-Leu-Thr-Arg-Gln-Arg-Tyr-NH2, (SEQ ID NO:10), or Ac-Leu-Arg-Ala-Ala-Leu-Asn-Leu-Leu-Thr-Arg-Gln-Arg-Tyr-NH2, (SEQ ID NO:11), wherein Ac is acetyl.

Abstract: The present invention provides methods of modulating neurotrophic factor-associated activity, especially CNTF-associated levels and activity, using aldose reductase inhibitors. These methods are especially useful in individuals suffering from, or at risk of developing, neurological disorders, including neurodegenerative disorders. The invention also provides methods of palliating neurological disorders and delaying development of neurological disorders using aldose reductase inhibitors.

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: Methods of modulating long term memory, identifying a substance capable of affecting long term memory and assessing the effect of a drug on long term memory are disclosed.

Abstract: The present invention provides mutant presenilin 1 and presenilin 2 polpeptides and polynucleotides encoding the polypeptides and methods for their production by recombinant and PCR techniques are disclosed. Methods for utilizing the mutant polypeptides in screens for inhibitors of activity are also disclosed.

Abstract: The present invention is directed to compositions comprising 1-(&bgr;-D-ribofuranosyl)-1H-1,2,4-triazole compounds and either endogenous or exogenous neurotrophic factors. Methods of using such compounds and compositions are also provided. In one aspect, the invention provides methods of using invention compositions and compounds to enhance neurite outgrowth, neuronal survival and neuronal proliferation in mammalian cells. In a preferred embodiment, a 1-(&bgr;-D-ribofuranosyl)1H-1,2,4-triazole compound is infused directly to a desired situs. In a more preferred embodiment the 1-(&bgr;-D-ribofuranosyl)-1,2,4-triazole compound is administered orally. In another aspect, the invention provides methods of treating a neurological disease in a mammal subject. In a further aspect, the invention provides methods of treating neuronal trauma in a mammal subject.

Abstract: A hybridoma producing a monoclonal antibody recognizing the C-terminus of human brain natriuretic peptide (hBNP) was cultivated in a medium or the abdominal cavity of a mouse to recover the monoclonal antibody from the medium or ascites accumulated in the abdominal cavity. An immunoassay for hBNP was established using the monoclonal antibody. The immunoassay for hBNP of the invention is so sensitive that the minimum detection limit is 1 pg/ml and can therefore determine the hBNP level in blood plasma directly, without the extraction of hBNP from blood plasma. It is useful for diagnosing diseases such as hypertension and the like, and states of the heart, kidney, and the like by using the increase/decrease of the hBNP level as an index.

Abstract: The present invention provides the use and composition of matter of angiogenic or other growth factors expressed by combining various types and stages of differentiation of allogeneic human cell strains or lines in unencapsulated pastes (mixed with or applied to extracellular matrix material or synthetic biocompatible substances) to be temporarily applied to wounds or defects in the skin or other tissues for the restoration of blood supplying connective tissue to enable organ-specific cells to reestablish organ integrity as well as to inhibit excessive scar formation.