Abstract: The present invention provides the enzyme and enzymatic procedures for cleaving the &bgr; secretase cleavage site of the APP protein and associated nucleic acids, peptides, vectors, cells and cell isolates and assays. The invention further provides a modified APP protein and associated nucleic acids, peptides, vectors, cells, and cell isolates, and assays that are particularly useful for identifying candidate therapeutics for treatment or prevention of Alzheimer's disease.

Abstract: This invention provides compositions and methods for increasing cellular respiration of melanized catecholamine neurons, and methods for alleviating symptoms or stopping appearance and/or progression of symptoms of Parkinson's Disease, and methods for preventing symptoms of on-off syndrome associated with treatment with dopamine or a dopamine agonist of a patient suffering symptoms of a disease selected from the group consisting of idiopathic and atypical Parkinson's disease, conditions characterized by nigrostriatal degeneration and multiple system atrophy, said methods comprising administering to said patient an effective amount of a neuromelanin-binding composition having a quinoline ring in a suitable pharmaceutical carrier. Preferably the composition comprises (−)-chloroquine.

Abstract: The present invention provides mutated proteins of steroid hormone receptors. These mutated proteins are useful as gene medicines. In particular, these mutated proteins are useful for regulating expression of genes in gene therapy. In addition, the present invention provides plasmids encoding for the desired mutated steroid hormone receptor proteins, as well as cells transfected with those plasmids.

Abstract: The present invention provides methods and compositions for enhancing the effect of a neurotrophin on a cell expressing a neurotrophin receptor. The effect is preferably neurotrophin-mediated growth and/or survival, such as neurite growth. The invention employees amphipathic compounds having a hydrophobic membrane-associating face and a hydrophilic face opposed thereto, which preferably mimic the amphipathic domain of the common neurotrophin receptor p75 from amino acid residue 367 to residue 379. Such compounds have charged moieties, polar moieties or combinations that mimic the charged and polar group relationships of p75NTR367-379, and include but are not limited to peptide analogues thereof. The hydrophobic membrane-associating face can interact with a membrane-bound neurotrophin receptor, such as TrkA, and the opposing hydrophillic face can interact with a DNA binding protein, such as nuclear transcription factor NFkB.

Abstract: The present invention is related to novel synthetic and/or recombinant biologically active peptide derivatives of parathyroid hormone (PTH). In particular, the invention relates to PTH derivatives of 28 amino acids or less, with one or more amino acid substitutions, methods of their preparation and use.

Abstract: DNAs encoding the human histamine H3 receptor have been cloned and characterized. The recombinant protein is capable of forming biologically active histamine H3 receptor protein. The cDNA's have been expressed in recombinant host cells which produce active recombinant protein. The recombinant protein is also purified from the recombinant host cells. In addition, the recombinant host cells are utilized to establish a method for identifying modulators of the receptor activity, and receptor modulators are identified.

Abstract: The present invention provides for a gene, designated as musk, that encodes a novel tyrosine kinase receptor expressed in high levels in denervated muscle. The invention also provides for an isolated polypeptide which activates MuSK receptor. The invention further provides for a polypeptide which is functionally equivalent to the MuSK activating polypeptide. The invention also provides assay systems that may be used to detect and/or measure ligands that bind the musk gene product. The present invention also provides for diagnostic and therapeutic methods based on molecules that activate MuSK.

Abstract: Methods of treating and/or prophylaxis Alzheimer's disease by preventing the formation of cerebral amyloid due to the growth and disruption of dense microspheres (DMS) are disclosed utilizing medicaments that are effective in preventing or inhibiting the growth and disruption of DMS.

Abstract: The present invention relates to methods of ex-vivo expansion of hematopoietic cells by culturing hematopoietic cells in a growth medium comprising a variant of human interleukin-3 (hIL-3), which contains multiple amino acid substitutions and which may have portions of the native hIL-3 molecule deleted, and a hematopoietic growth factor. The present invention also relates to the ex-vivo expansion of hematopoietic cells for gene therapy. Additionally, the present invention relates to the use of the expanded hematopoietic cells for treating patients having a hematopoietic disorder.

Abstract: Modified ciliary neurotrophic factors and methods for their production and therapeutic use, especially in the treatment of Huntington's disease.

Abstract: The present invention relates to the field of GABA receptor structure and function. In one aspect, the present invention relates to impairment of the gamma-aminobutyric acid (GABA) receptors in parasitic nematodes, for the purpose of crop protection and/or soil treatment. The invention includes mutated nematode GABA receptor subunits, nematode GABA neuromuscular junction receptor complexes, nucleic acids which encode the mutated and functional receptor complexes, antibodies which selectively bind the GABA receptor complexes and/or subunits, and assays for compounds which adversely affect nematode GABA neuromuscular junction receptor function. The present invention therefore relates broadly to recombinant DNA technology, molecular biology tools, and crop protection and/or soil treatment.

Abstract: A cell division mechanism controlling protein which is not expressed in the interphase but is expressed in the nucleus after entering into a cell cycle, in the cell cycle of mammalian cell, and fragments thereof, as well as DNAs coding for said protein or fragments thereof, as well as antibodies against said protein or fragment thereof.

Abstract: The present invention relates to a novel mammalian opioid receptor protein and ligands that bind to such proteins. The invention is directed toward the isolation, characterization and pharmacological use of an endogenous ligand that specifically binds to a novel mammalian opioid receptor protein heterologously expressed in mammalian cells. The invention specifically provides the isolated peptide ligand and analogues, derivatives and variants thereof. The invention specifically provides tyrosine substitution variants of the peptide ligand that specifically bind to the opioid receptor and can be radioiodinated. Also provided are methods of making such peptide ligands and methods of using the ligands for diagnostic and therapeutic uses and for the identification of other naturally-occurring or synthetic opioid receptor ligands.

Abstract: Methods and compositions for the prevention and treatment of preterm labor and premature rupture of fetal membranes are provided. The methods of the invention inhibit the upregulated production of certain pro-inflammatory cytokines in amniochorionic membranes, including IL-6, IL-8 and TNF-&agr;, and inhibit preterm labor and the premature rupture of fetal membranes. The practice of the method of the invention using the cytokine IL-10 is specifically described. IL-10 demonstrates the capacity to inhibit pro-inflammatory cytokine production in amniochorionic membranes in vitro as well as the capacity to inhibit uterine contractility and preterm labor in rhesus monkeys in vivo. The methods of the invention may be particularly useful in preventing infection-induced preterm labor and premature rupture of fetal membranes as well as preterm labors with a non-infectious etiology.

Abstract: A novel growth factor, persephin, which belongs to the GDNF/neurturin family of growth factors, is disclosed. The mouse and rat amino acid sequences have been identified. Mouse and rat persephin genomic DNA sequences have been cloned and sequenced and the respective cDNA sequences identified. In addition, methods for treating degenerative conditions using persephin, methods for detecting persephin gene alterations and methods for detecting and monitoring patient levels of persephin are provided. Methods for identifying additional members of the persephin-neurturin-GDNF family of growth factors are also provided.

Abstract: The present invention relates to human interleukin-3 (hIL-3) variant or mutant proteins (muteins) functionally co-administered with a other colony stimulating factors (CSF), cytokines, lymphokines, interleukins, hematopoietic growth factors or IL-3 variants.

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

Abstract: A pharmaceutical preparation contains protein C and a thrombolytically active substance that does not activate protein C. This preparation prevents reocclusion usually occurring in the course of thrombolysis therapy.

Abstract: We describe here a new class of protein tyrosine phosphatases (PTP), called “PTP-NP” (for neural and pancreatic) receptors. The sequence of an exemplary PTP-NP gene (SEQ ID No. 1) indicates it encodes a receptor type PTP (SEQ ID No. 2) with a single tyrosine phosphatase domain. Comparison of PTP-NP with the other known PTPs reveals a cysteine-conserved motif in the extracellular domain and, together with their homology in the phosphatase domain, this defines a new subclass of receptor type PTPs.

Abstract: In accordance with the present invention, there are provided novel G-protein-coupled receptor proteins (CRF-R) characterized by having sufficient binding affinity for corticotropin releasing factor (CRF) such that concentrations of ≦10 nM of CRF occupy ≧50% of the binding sites of said receptor protein. Nucleic acid sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed. Invention CRF-Rs can be employed in a variety of ways, such as, for example, in bioassays, for production of antibodies thereto, in therapeutic compositions containing such proteins and/or antibodies.