Abstract: The present invention relates generally to methods and compositions for targeting the vasculature of solid tumors using immunological- and growth factor-based reagents. In particular aspects, antibodies carrying diagnostic or therapeutic agents are targeted to the vasculature of solid tumor masses through recognition of tumor vasculature-associated antigens, such as, for example, through endoglin binding, or through the specific induction of endothelial cell surface antigens on vascular endothelial cells in solid tumors.

Abstract: The present invention is directed to screening for an agent that inhibits the effect of a neurotoxin from a plaque component activated mononuclear phagocyte on a neuron. In addition, the present invention is directed to methods of screening for agents that inhibit mononuclear phagocyte-plaque component complex formation, plaque component activation of a mononuclear phagocyte, plaque component induced neurotoxicity of a mononuclear phagocyte. An agent obtained by the method of screening for an agent that inhibits mononuclear phagocyte-plaque component complex formation and a pharmaceutical composition comprising the agent are embodied by the present invention.

Abstract: A highly conserved active site helix present within the P-450 superfamily of proteins is found also in monoamine oxidase (MAO) B, a major enzyme that catalyzes deamination of neuro- and vaso-active amines in the nervous system of mammals. Mutation within the conserved region of the MAO B enzyme directly reduces MAO B's activity and alters its pH profile, which allows for indirect regulation of the cellular neurotransmitters and vasoamines.

Abstract: The invention relates to NKAF II polypeptides, polynucleotides encoding the polypeptides, methods for producing the polypeptides, in particular by expressing the polynucleotides, and agonists and antagonists of the polypeptides. The invention further relates to methods for utilizing such polynucleotides, polypeptides, agonists and antagonists for applications, which relate, in part, to research, diagnostic and clinical arts.

Abstract: This invention relates to the method of using neurotrophic cyclophilin inhibitor compounds having an affinity for cyclophilin-type immunophilins as inhibitors of the enzyme activity associated with immunophilin proteins, and particularly inhibitors of peptidyl-prolyl isomerase or rotamase enzyme activity.

Abstract: The role of synapsin II in both the reformation and the maintenance of synaptic connections in cultured hippocampal neurons can be the basis of therapy for neurodegenerative disorder, particularly Alzheimer disease, which involve the disruption of synapses. When synapsin II expression in neurons is blocked by antisense synapsin II oligonucleotides, the ability of hippocampal neurons to reform as well as to maintain synapses is severely disrupted. Antisense suppression of synapsin II after axon formation but immediately before synaptogenesis prevents synapse formation. Suppression of synapsin II after synaptogenesis disrupts the majority of existing synapses. Re-expression of synapsin II in synapsin deficient neurons achieved after removing the antisense oligonucleotides leads to the re-establishment of synaptic connections, providing direct evidence that synapsin II is required for the maintenance and/or restoration of synapses.

Abstract: Modified ciliary neurotrophic factors and methods for their production and therapeutic use. Also described is a method of screening for novel therapeutic proteins by determining altered electrophoretic binding properties.

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. 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: 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: The present invention relates to methods of ex-vivo expansion of hematopoietic cells by culturing hematopoietic cells in a growth medium comprising a chimera protein which comprises 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: The present invention is based on the discovery and isolation of a co-factor for trophic factors. It has been discovered that trophic factors require a co-factor to stimulate and/or potentiate the trophic factor activity and/or specificity. This was clearly identified in low density cells where trophic factors are unable, or at best, at minimal levels, able to proliferate undifferentiated cells without a co-factor. In a particular embodiment of the present invention, there is provided a composition comprising glycosylated cystatin C, (CCg), an FGF co-factor that stimulates proliferation of neural and fibroblast associated undifferentiated cells. The N-glycosylation of cystatin C is required for its activity. Moreover, CCg acts in cooperation with basic fibroblast growth factor (FGF-2) to induce neural progenitor cell proliferation.

Abstract: The present invention relates generally to a nucleic acid molecule which encodes a protein associated with the modulation of obesity, diabetes and metabolic energy levels. More particularly, the present invention is directed to a nucleic acid molecule and a recombinant and purified naturally occurring protein encoded thereby and their use in therapeutic and diagnostic protocols for conditions such as obesity, diabetes and energy imbalance. The subject nucleic acid molecule and protein and their derivatives, homologues, analogues and mimetics are proposed as therapeutic and diagnostic agents for obesity, diabetes and energy imbalance.

Abstract: A novel neuronal cell growth factor, neuronal-activity regulated pentraxin, Narp, is provided, as well as polynucleotides encoding Narp. Narp is useful for induction of dendritic neurite outgrowth as well as promotion of neuronal migration. Methods for treatment of subjects having a neuronal cell disorder, utilizing Narp of the invention, are also provided.

Abstract: The present invention is drawn to a method of treating acute renal failure caused by rhabdomyolysis by administering a therapeutically effective amount of hepatocyte growth factor (HGF). The present invention is further drawn to a method of treating rhabdomyolysis by administering a therapeutically effective amount of hepatocyte growth factor (HGF).

Abstract: Purified BMP-3 proteins and processes for producing them are disclosed. They may be used in the treatment of bone and cartilage defects and in wound healing and related tissue repair.

Abstract: Genes encoding opioid receptors (including opioid-like receptor (ORL) proteins) can be retrieved from vertebrate libraries using the murine probe disclosed herein under low-stringency conditions. The DNA sequence shown in FIG. 5 or its complement can be used to obtain the human delta, kappa and mu genes as well as the murine mu gene and human ORL-1. The probe provided encodes the murine delta opioid receptor.

Abstract: DAN (Differential-screening-selected gene Aberrative in Neuroblastoma) and gremlin proteins and related nucleic acids are provided. Included are natural DAN and gremlin homologs from several species and proteins comprising a DAN or gremlin domain having specific activity, particularly the ability to antagonize a bone morphogenic protein. The proteins may be produced recombinantly from transformed host cells with the subject nucleic acids. Also provided are isolated hybridization probes and primers capable of specifically hybridizing with the disclosed genes, specific binding agents and methods of making and using the subject compositions.

Abstract: The semaphorin family contains a large number of plylogenetically conserved proteins and includes several members that have been shown to function in repulsive axon guidance. Semaplorin III (Sema III) is a secreted protein that in vitro causes neuronal growth cone collapse and chemorepulsion of neurites, and is required in vivo for correct sensory afferent innervation and other aspects of development. The mechanism of Sema III function, however, is unknown. Here, we report that neuropilin, a type I transmembrane protein, is a Sema III receptor. We also describe the identification of neuropiln-2, a related neuropilin family member, and show that neuropilin and neuropilin-2 are expressed in overlapping, yet distinct, populations of neurons in the rat embryonic nervous system.

Abstract: The present invention is directed to nucleic acid sequences encoding a limbic-system associated membrane protein (“LAMP”) and to purified proteins with LAMP activity. LAMP is a self-binding, antibody-like cell surface adhesion protein, the presence of which on one neuron of the limbic system stimulates the formation of connections with adjacent neurons. The invention provides a nucleic acid sequence encoding a polypeptide with at least about 90% homology to a LAMP self-binding domain, and corresponding proteins. The invention also provides nucleic acids that hybridize to LAMP encoding nucleic acids.

Abstract: This invention provides isolated nucleic acid molecules encoding Y2 receptors, an isolated, purified Y2 receptor protein, vectors comprising isolated nucleic acid molecules encoding Y2 receptors, mammalian, insect, bacterial and yeast cells comprising such vectors, antibodies directed to the Y2 receptors, nucleic acid probes useful for detecting nucleic acid encoding Y2 receptors, antisense oligonucleotides complementary to unique sequences of a nucleic acid molecule which encodes a Y2 receptor, pharmaceutical compounds related to the Y2 receptors, and nonhuman transgenic animals which express nucleic acid encoding a normal or mutant Y2 receptor. This invention further provides methods for determining ligand binding, detecting expression, drug screening, and methods of treatment involving Y2 receptors.