Abstract: Disclosed is a composition that synergistically prevents proteolysis or modification of peptides in sampled biological fluids using sulfonyl fluoride family protease inhibitors at high concentrations combined with at least one additional protease inhibitor of a different type, preferably a broad spectrum protease inhibitor, and a chelator. A preferred embodiment uses AEBSF at 10 mM, Benzamidine at 20 mM and EDTA as the chelator. The disclosed composition may be combined with other protease inhibitors to further modulate its specificity, for instance to additionally target acidic proteases. Additional protease inhibitors, reducing agents, stabilizers and buffering agents may be combined with the disclosed compositions in devices for sampling or testing biological fluids for levels of peptides of interest, or methods therefore. The disclosed devices, compositions and methods are of particular use in sampling and testing for the level of natriuretic peptides.

Abstract: The invention concerns new secreted factors encoded by clones P00184_D11 (SEQ ID NO: 1), P00185_D11 (SEQ ID NO: 3), P00188_D12 (SEQ ID NO: 5), P00188_E01 (SEQ ID NO: 7), P00194_G01 (SEQ ID NO: 9), P00194_G05 (SEQ ID NO: 11), P00194_H10 (SEQ ID NO: 13), P00199_D08 (SEQ ID NO: 15), P00203_D04 (SEQ ID NO: 17), P00203_E06 (SEQ ID NO: 19), P00209_F06 (SEQ ID NO: 21), P00219_D02 (SEQ ID NO: 23), P00219_F06 (SEQ ID NO: 25), P00220_H05 (SEQ ID NO: 27), P00222_G03 (SEQ ID NO: 29), P00225_C01 (SEQ ID NO: 32), P00227_D11 (SEQ ID NO: 34), P00228_F03 (SEQ ID NO: 36), P00233_H08 (SEQ ID NO: 38), P00235_G08 (SEQ ID NO: 40), P00239_C11 (SEQ ID NO: 42), P00240_E05 (SEQ ID NO: 45), P00247_A04 (SEQ ID NO: 50), P00248_B04 (SEQ ID NO: 52), P00249_F09 (SEQ ID NO: 54), P00258_A10 (SEQ ID NO: 56), P00262_C10 (SEQ ID NO: 58), P00269_H08 (SEQ ID NO: 62), P00628_H02 (SEQ ID NO: 66), P00629_C08 (SEQ ID NO: 68), P00641_G11 (SEQ ID NO: 71), P00648_E12 (SEQ ID NO: 73), P00697_C03 (SEQ ID NO: 75), and other mammalian homologues and variants

Abstract: The present invention is based on the findings that BACE2, a homolog of ?-secretase BACE, is able to stimulate processing of APP in a non-amyloidogenic pathway, thereby suppressing the level of A?. Accordingly, the present invention provides methods and means for the identification and use of modulators of this unique activity of BACE2 to suppress A? production. The compounds identified using the methods and means provided herein may be used as potential candidates for the treatment of Alzheimer's disease and other neurological diseases by reducing ?-amyloid deposit formation.

Abstract: The invention concerns a novel ?-secretase, a method of partially purifying this novel ?-secretase, and its use in assays to screen for potential drug candidates against Alzheimer's disease and other neurological diseases. The novel ?-secretase has an estimated molecular weight of about 32–39 kDa or 22–26 kDa in HEK293 cell membrane extracts and human brain samples, respectively, as calculated from radiation inactivation analysis, and has a pH optimum at about pH 6.5–7.0.

Abstract: The invention concerns new secreted factors encoded by clones P00184_D11 (SEQ ID NO:1), P00185_D11 (SEQ ID NO:3), P00188_D12 (SEQ ID NO:5), P00188_E01 (SEQ ID NO:7), P00194_G01 (SEQ ID NO:9), P00194_G05 (SEQ ID NO:11), P00194_H10 (SEQ ID NO:13), P00199_D08 (SEQ ID NO:15), P00203_D04 (SEQ ID NO:17), P00203_E06 (SEQ ID NO:19), P00209_F06 (SEQ ID NO:21), P00219_D02 (SEQ ID NO:23), P00219_F06 (SEQ ID NO:25), P00220_H05 (SEQ ID NO:27), P00222_G03 (SEQ ID NO:29), P00225_C01 (SEQ ID NO:32), P00227_D11 (SEQ ID NO:34), P00228_F03 (SEQ ID NO:36), P00233_H08 (SEQ ID NO:38), P00235_G08 (SEQ ID NO:40), P00239_C11 (SEQ ID NO:42), P00240_E05 (SEQ ID NO:45), P00247_A04 (SEQ ID NO:50), P00248_B04 (SEQ ID NO:52), P00249_F09 (SEQ ID NO:54), P00258_A10 (SEQ ID NO:56), P00262_C10 (SEQ ID NO:58), P00269_H08 (SEQ ID NO:62), P00628_H02 (SEQ ID NO:66), P00629_C08 (SEQ ID NO:68), P00641_G11 (SEQ ID NO:71), P00648_E12 (SEQ ID NO:73), P00697_C03 (SEQ ID NO:75), and other mammalian homologues and variants of such factor, as well as polyn

Abstract: The substitution of the L-Pro at the 7-position of the peptide hormone bradykinin or other substituted analogs of bradykinin with a D-configuration hydroxyproline ether or thioether converts bradykinin agonists into bradykinin antagonists. The invention further includes the intermediate compounds and additional modifications at other positions within the novel 7-position modified bradykinin antagonists which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected such as by insect bites.

Abstract: The present invention provides cell-free &ggr;-secretase activity. The method of the invention utilizes a membrane source of APP/&ggr;-secretase mixture in the assay to determine factors that may enhance or decrease enzymatic activity affecting &bgr;-amyloid peptide production. The cell membranes used in the assay may be from cells expressing an endogenous APP or, preferably, cells expressing a recombinant APP. The APP may be full-length or a fragment capable of being proteolytically cleaved by &ggr;-secretase. In addition, the APP expressed in the cells may have one or more mutation, such as a point mutation, small deletion, etc.

Abstract: The present invention provides assays to identify compounds that affect microglial cell activation, and specifically assays to identify compounds that affect secretion of cytokines from these microglial cells by modulating PGE2-mediated activity. The assays of the invention include assays for testing microglial cell activation by contacting microglia with compounds that modulate &bgr;-amyloid PGE2-mediated activation, which can be identified by cellular activity such as secretion of cytokines, e.g., TNF-&agr; and IL-1&agr;. The effect of the candidate compound can be determined by comparing the effect with a control culture which is not contacted with the compound, or by comparing the effect with a standardized profile.

Abstract: The present invention provides cell-free &ggr;-secretase activity. The method of the invention utilizes a membrane source of APP/&ggr;-secretase mixture in the assay to determine factors that may enhance or decrease enzymatic activity affecting &bgr;-amyloid peptide production. The cell membranes used in the assay may be from cells expressing an endogenous APP or, preferably, cells expressing a recombinant APP. The APP may be full-length or a fragment capable of being proteolytically cleaved by &ggr;-secretase. In addition, the APP expressed in the cells may have one or more mutation, such as a point mutation, small deletion, etc.

Abstract: There are disclosed methods for the treatment of non-insulin dependent diabetes mellitus in a mammal comprising the prolonged administration of GLP-1 (7-37), and related peptides. Also disclosed are compositions to prolong the administration of the peptides.

Abstract: The substitution of the L-Pro at the 7-position of the peptide hormone bradykinin or other substituted analogs of bradykinin with an isoquinoline derivative which converts bradykinin agonists into bradykinin antagonists. The invention further includes the novel 7-position modified bradykinin antagonists which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected as by insect bites.

Abstract: The present invention provides a method of assaying for and arresting, preventing and/or reversing the impairment of central and peripheral nervous system function comprising reducing &bgr;-amyloid plaque burden by the administration of compounds that reduce apoE expression. The compounds used in the method of the invention may be: 1) inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase; 2) inhibitors of cholesterol biosynthesis; 3) inhibitors of protein isoprenylation, specifically geranylgeranylation; and/or 4) inhibitors of NF-&kgr;B activation or function. Assays for compounds with inhibit apoE expression from microglial cells are also disclosed.

Abstract: The present invention concerns methods for the treatment of salt-sensitive hypertension. The methods generally involve administering a vascular endothelial growth factor (VEGF) in an amount effective to reduce the blood pressure of a patient suffering from salt-sensitive hypertension to a normal range.

Abstract: Compositions and methods are disclosed for the controlled release delivery of polypeptide growth factors. The compositions of the invention are hydrogels which comprise: a polypeptide growth factor having at least one region of positive charge; a physiologically acceptable water-miscible anionic polymer; a physiologically acceptable non-ionic polymeric viscosity controlling agent; and water.

Abstract: A method is described for producing a peptide having a pI above 8 or below 5 wherein the peptide is expressed as a fusion protein in which it is linked to a fusion partner through an acid cleavage site. The peptide is released from the fusion partner by acid cleavage in the absence of chaotrope. The fusion partner and its acid cleavage products, if any, have a net charge sufficiently different from that of the desired peptide to allow isolation of the peptide by ion-exchange chromatography.

Abstract: The DNA sequences encoding analogs of human acidic and basic fibroblast growth factors (FGF) can be recombinantly expressed to obtain practical amounts of proteins useful in effecting both pathologies related to persistent angiogenesis and wound healing and related tissue repair.

Abstract: The substitution of the L-Pro at the 7-position with D-Phe or D-Tic and substitution of the L-Phe at the 8-position with hydroxyproline ethers and thioethers of the peptide hormone bradykinin and other additional substituted analogs of bradykinin converts bradykinin agonists into bradykinin antagonists. The invention further includes additional modifications at other positions within the novel 7- and 8-position modified bradykinin antagonists, which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected as by insect bites.

Abstract: The present invention relates to systems, integrated computer software programs, and related methods for manipulation and analysis of gene expression data. The methods of the invention are particularly suited for use with gene expression data generated with microarray and genechip technologies. A particular embodiment of the invention relates to systems utilizing clustering algorithms, which may be used to correlate temporal patterns of gene expression. The invention also relates to graphical tools, search and sort functions for viewing both the original and processed gene expression data. The present invention also relates to a graphical user interface for data clustering, graphical viewing, and browsing.

Abstract: The present invention provides methods that can be used to identify &bgr;-amyloid reducing compounds. The present invention is based on the use of organotypic brain slice culturing methods to simultaneously assess the toxicity and &bgr;-amyloid reducing activity of a test compound.

Abstract: Compositions and devices for the controlled release delivery of a peptide or protein drug are produced by dispersing a glassy matrix phase comprising the peptide or protein drug and a thermoprotectant in a bioerodable, biocompatible polymer at a temperature that is below the glass transition temperature of the glassy matrix phase and above the melting point of the polymer. The method and composition of the invention may be employed for the local delivery of angiogenic amounts of basic fibroblast growth factor or vascular endothelial growth factor.