Abstract: The present invention provide purified Flt4 receptor tyrosine kinase polypeptides and fragments thereof, polynucleotides encoding such polypeptides, antibodies that specifically bind such polypeptides, and uses therefor.

Abstract: Methods and compositions comprising antagonists of &agr;v&bgr;6 are provided for the treatment of acute lung injury fibrosis.

Abstract: Methods of modulating macropinocytosis in cells of a target cell population by modulating the binding of Pak1 to DLC1/PIN are disclosed. In addition, the invention provides for methods of screening for modulators of macropinocytosis that involve determining whether a candidate substance inhibits or promotes the binding of Pak1 to DLC1/PIN. Also disclosed are methods of reducing cell proliferation in a target cell population, methods of inhibiting growth and survival of a cancer cell, methods of inhibiting the invasiveness of a cancer cell, and methods of treating viral infection using an agent that modifies the binding of Pak1 to DLC1/PIN.

Abstract: The present invention relates to an isolated target sequence. The target sequence is a splice variant of PDE5 called a PDE5a1, a component of which is presented as SEQ ID No 1. The identified target sequence of the present invention may be used to as a target to identify agents (such as modulators) useful in the prevention and/or treatment of a disease associated with scarring and/or fibrosis or to selectively identify smooth muscle cells and myofibroblasts and myoepithelial cells in samples of normal and diseased tissue from individuals.

Abstract: The invention provides reagents and methods for reducing hyperglycemia and caloric intake in a subject in need thereof. Also provided are screening methods for identifying compounds that reduce hyperglycemia and/or caloric intake. Further provides are screening methods for identifying compounds that enhance glycogen synthesis without substantially impairing responsiveness to glycogenolytic signals.

Abstract: The subject invention concerns a method of inhibiting respiratory syncytial virus (RSV) infection in a patient by decreasing the endogenous protein kinase C (PKC) activity within the patient. Preferably, the preventative and therapeutic methods of the present invention involve administering a PKC inhibitor, to a patient in need thereof. The present inventor has determined that decreasing normal endogenous PKC activity is inhibitory to RSV infection of human cells. The subject invention also pertains to pharmaceutical compositions containing a PKC,inhibitor and a pharmaceutically acceptable carrier.

Abstract: The invention is directed to the treatment of otitis media by administration of protease inhibitors. In some embodiments, the protease inhibitors are alpha one-antitrypsin and/or ilomastat.

Abstract: Isolated human monoclonal antibodies which bind to and inhibit human heparanase, and related antibody-based compositions and molecules, are disclosed. The human antibodies can be produced by a transfectoma or in a nonhuman transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, nonhuman transgenic animals and hybridomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

Abstract: Specific anti-heparanase antibodies which bind specifically to heparanase having sequence homology to human heparanase, which can be used to treat and diagnose conditions associated with heparanase catalytic activity, for purification of heparanase, and for drug development in heparanase associated conditions are disclosed.

Abstract: The present invention provides methods of inhibiting cadherins between Schlemm's canal cells, to a patient suffering from glaucoma as well as screening for substances that inhibit cadherins between the Schlemm's canal cells.

Abstract: A nucleic acid encoding the GPCR protein KOR3L is described, as well as methods for screening for agents capable of modulating KOR3L related activity and treating KOR3L-mediated conditions. More specifically, methods are provided for identifying agents capable of treating KOR3L-mediated loss of balance and sensorimotor integration.

Abstract: The gene for Streptococcus pyogenes DNase B has been cloned and vectors incorporating the cloned DNA have been used to transform Escherichia coli, allowing efficient and rapid production of the DNase in E. coli without the necessity of growing large quantities of S. pyogenes. The enzyme can be produced with a leader peptide at its aminoterminus. An improved method for the purification of naturally occurring S. pyogenes DNase B enzyme is also provided. The DNase B enzyme produced, either by purification of naturally occurring enzyme or by recombinant DNA techniques, can be used to generate antibodies and can also be used in immunochemical assays to detect the presence of anti-DNase B antibodies in serum as a marker of infection by S. pyogenes.

Abstract: Monoclonal antibodies directed against coagulation factors and their use in inhibiting thrombosis in combination with plasminogen activators are disclosed.

Abstract: Monoclonal antibodies directed against amyloid beta peptide and methods of using same for treatment and prevention of Alzheimer's disease and Down's syndrome are described.

Abstract: The invention relates to methods for treatment of asthma and chronic obstructive pulmonary disease (COPD) by administration of antagonists to plasminogen activator inhibitor type-1 (PAI-1). Suitable atagonists include antibodies, peptides, proteins, nucleic acids, small organic molecules and polymers.

Abstract: This application discloses that inositolphosphoglycans (IPGs) can be obtained from basophils, eosinophils and mast cells and that allergen stimulation of these cells results in IPG release. It also shows that IPGs are second messengers for allergic stimulation as the addition of some types of purified IPGs to non-allergen stimulated cells resulted in histamine release or degranulation. Thus, IPG antagonists can be used for the treatment of conditions (especially allergy and asthma) mediated by the release of IPGs from mast cells, basophils or eosinophils. Preferred IPG antagonists include anti-IPG antibodies, inhibitors of the enzyme GPI-PLD and competitive antagonists.

Abstract: The invention provides purified ACT-4 receptor polypeptides, antibodies against these polypeptides and nucleic acids encoding ACT-4 receptor polypeptides. Also provided are methods of diagnosis and treatment using the same. ACT-4 receptors are preferentially expressed on the surface of activated CD4+ T-cells. ACT-4 receptors are usually expressed at low levels on the surface of activated CD8+ cells, and are usually substantially absent on resting T-cells, and on monocytes and B-cells (resting or activated). An exemplary ACT-4 receptor, termed ACT-4-h-1, has a signal sequence, an extracellular domain comprising three disulfide-bonded intrachain loops, a transmembrane domain, and an intracellular domain.

Abstract: A method of inhibiting osteoclast formation including inhibiting eosinophil chemotactic factor-L expression or activity. This may be accomplished by a number of means, including the use of anti-ECF-L antibody, antisense S-oligonucleotide to ECF-L, mECF-L polyclonal antisera, rabbit preimmune antisera, OPG RANK-Fc and combinations thereof, as well as other inhibiting materials. In another embodiment, osteoclast formation is inhibited by inhibiting RANKL formation. In a further embodiment, a method of inhibiting osteoclast formation is accomplished by means of mECF-L in the presence of RANKL.

Abstract: This invention relates to products and methods for treating cancer and for diagnosing tumorigenicity and other diseases associated with alteration in GP88 expression or action. Antagonists to an 88 KDa autocrine growth and tumorigenicity stimulator are provided which inhibit its expression or biological activity. The antagonists include antisense oligonucleotides and antibodies.

Abstract: The present invention provides a novel all-trans-RA inducible all-trans-RA metabolizing cytochrome P450, P450RAI-2, that is predominantly expressed in the brain, cerebellum in particular. It is also expressed in normal and tumour lung tissue and in breast cancer cells and may have a correlation with lung and breast cancer. Human P450RAI-2 show 42% amino acid identity to human P450RAI-1 and when transfected into COS-1 cells causes the rapid conversion of all-trans-RA into more polar metabolites including the inactive products 4-oxo-RA, 4-OH-RA and 18-OH-RA. P450RAI-2, as with P450RAI-1, is also inducible in certain cultured cell lines exposed to all-trans-RA. Methods for and uses of the new polynucleotide, polypeptide, fragments thereof and inhibitors thereof, include the treatment of dermatological disorders, cancer and certain brain disorders.

Abstract: This application describes the cloning of p63, a gene at chromosome 3q27-29, that bears homology to the tumor suppressor p53. The p63 gene encodes at least six different isotypes. p63 was detected in a variety of human and mouse tissue and demonstrates remarkably divergent activities, such as the ability to transactivate p53 reporter genes and induce apoptosis. Isotopes of p63 lacking a transactivation domain act as dominant negatives towards the transactivation by p53 and p63.

Abstract: Human inositol monophosphatase H1 polynucleotide and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptide by recombinant techniques and utilizing such polypeptide for therapeutic purposes, for example, screening and designing compounds capable of inhibiting hIMP-H1 and mapping genetic diseases are disclosed. Further disclosed are antibodies against hIMP-H1 polypeptides and methods for producing such antibodies and utilizing such antibodies for therapeutic or diagnostic purposes. Also disclosed is antagonists against such polypeptide along with procedures for using such antagonists for therapeutic purposes, for example, for treating psychotic and depressive disorders. Diagnostic assays for identifying mutations in nucleic acid sequence encoding a polypeptide of the present invention and for detecting altered levels of the polypeptide of the present invention are also disclosed.

Abstract: The present invention provides methylenetetrahydrofolate reductase (MTHFR) inhibitors for use in selective inhibition of cancer cell growth in a mammal. These inhibitors can be a small molecule, an antisense oligonucleotide, a ribozyme, a triple helix forming oligonucleotide, an anti-MTHFR antibody or fragment thereof, an MTHFR mutant or a fragment of MTHFR. The present invention further provides nucleic acids encoding an inhibitor of MTHFR, and vectors comprising these nucleic acids. Also encompassed by the present invention are methods of using the MTHFR inhibitors for selective inhibition of cancer cell growth, and pharmaceutical compositions comprising the MTHFR inhibitors.

Abstract: The present invention relates to compositions and methods of treating and diagnosing disorders characterized the by the presence of antigens associated with inflammatory diseases and/or cancer.

Abstract: A novel G protein-coupled receptor called MrgC11 has been identified that is expressed in dorsal root ganglia and that is activated by RF amide related peptides.

Abstract: It has been considered that an activation of proMMP-2 induced by MT1-MMP is one of the important steps for invasion of tumor cells such as cancers, but its detailed mechanism for an expression of activation has been unknown. Thus, it has been required that methods for preventing/treating various diseases are developed by elucidating the mechanism of activation expression of proMMP-2 induced by MT1-MMP and elucidating various actions potentially involving MT1-MMP in addition to invasion and metastasis of cancers. A formation of a complex formed of multiple MT1-MMP, particularly a homodimer formation of MT1-MMP is crucial for the activation of proMMP-2 induced by MT1-MMP, and the homodimer formation is based on functions of the PEX domain of MT1-MMP. Utilizing such findings, the homodimer formation of MT1-MMP is inhibited and the activation of proMMP-2 is inhibited leading to developing methods to control invasion/metastasis of cancers.

Abstract: The disclosure provides, among other things, novel angiogenesis-related nucleic acids, polypeptides and methods of use.

Abstract: The present invention relates to at least one novel CNGH0004 polypeptides, antibodies, including isolated nucleic acids that encode at least one CNGH0004 polypeptide or antibody, CNGH0004 vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.

Abstract: Methods of reducing the cholesterol accumulation in a subject, including methods of reducing cholesterol synthesis and methods of increasing cholesterol degradation. Cholesterol synthesis is inhibited by administering a compound capable of increasing 27-hydroxy-7-dehydrocholesterol and/or 27-hydroxy-8-dehydrocholesterol levels, wherein an increase in 27-hydroxy-7-dehydrocholesterol and/or 27-hydroxy-8-dehydrocholesterol levels results in an inhibition of cholesterol synthesis. Cholesterol degradation is increased by increasing the level of 7&agr;-hydroxylase in extrahepatic tissue and cells.

Abstract: The present invention discloses uses for the MKLP1 gene and/or polypeptide and/or modulators thereof in the diagnosis and treatment of apoptosis-related diseases.

Abstract: The invention provides antibodies that specifically bind a membrane protease complex, the complex consisting of two homodimers of seprase and dipeptidyl peptidase IV (DPPIV), obtained from mammalian, preferably human cell membranes. The antibodies specifically bind the DPPIV protease of the seprase-DPPIV complex. This membrane protease complex resides on cell surface invadopodia at the leading edge of angiogenic endothelia, migratory fibroblasts, and invading cancer cells. The antibodies and immunoconjugates of the invention specifically bind the membrane protease complex at the cell surface invadopodia, yet fail to react with resting cells in adjacent human tissues and blood vessels. These antibodies and immunoconjugates block interaction of collagen matrix with the seprase-DPPIV complex in the invasive cells during angiogenesis and cancer spreading but not that with other endothelia or tumor cells.

Abstract: The use and production of immunoglobulins which activate trk receptors and imitate effects of neurotrophins are provided. Immunoglobulins which block trk receptor activation and methods of use are also provided.

Abstract: The present invention is related to use of protein kinase N beta or a fragment or derivative thereof as a downstream target of the PI 3-kinase pathway, preferably as a downstream drug target of the PI 3-kinase pathway.

Abstract: The invention relates to a method to search for male antifertility drugs based on activity determination of phospholipid hydroperoxide glutathione peroxidase (PHGPx) derived from human tissue or human cells or from related mammalian species.

Abstract: Human antibodies that bind to TIMP-1 can be used as reagents to diagnose and treat disorders in which TIMP-1 is elevated, such as liver fibrosis, alcoholic liver disease, cardiac fibrosis, acute coronary syndrome, lupus nephritis, glomerulosclerotic renal disease, benign prostate hypertrophy, colon cancer, lung cancer, and idiopathic pulmonary fibrosis.

Abstract: Reagents which regulate human serine-threonine protein kinase and reagents which bind to human serine-threonine protein kinase gene products can play a role in preventing, ameliorating, or correcting dysfunctions or diseases including, but not limited to, cancer, CNS disorders, diabetes, asthma, and COPD.

Abstract: Disclosed are nucleic acid molecules encoding a protein interacting with the Ser/Thr kinase Akt as well as the encoded protein. Furthermore, the invention describes expression vectors, host cells, antibodies, pharmaceutical compositions and methods for treating disorders associated with impaired endosomal transport.

Abstract: A monoclonal antibody having high affinity for NT-proBNP is described. The monoclonal antibody is prepared against a synthetic peptide having the Sequence ID No. 1 The monoclonal antibody can be used as a reagent in an immunoassay system to identify blood, serum or plasma levels of NT-proBNP. Such an immunoassay system can be used for diagnosing and quantifying congestive heart failure.

Abstract: The invention relates to methods and compositions for the treatment of human or animal disorders associated with pathophysiologically based extracellular Fas ligand titers, as well as methods for determining the prophylactic suitability and quality control of compositions, such as intravenous immunoglobulin mixtures, for use in such methods, and methods of preparing compositions for treating such disorders.

Abstract: Fibrils of two or more different peptides are disclosed; these peptides can be related or unrelated. They have a variety of uses as biomaterials and nanomaterials.

Abstract: The present invention provides methods of treating cancer using inhibitors of protein kinases. The inhibitors of protein kinases are combined with agents that inhibit a cellular ATP synthetic pathway. Inhibitors of ATP synthesis include inhibitors of de novo purine biosynthesis, inhibitors of the salvage pathway of ATP biosynthesis, and inhibitors of the enzyme inosine monophosphate dehydrogenase.

Abstract: The invention provides a grafted antibody, or functional fragment thereof, comprising one or more complementarity determining regions (CDRs) having at least one amino acid substitution in one or more CDRs of a heavy chain CDR, where the grafted antibody or functional fragment thereof has specific binding activity for a cryptic collagen epitope. The invention also provides methods of using an antibody having specific binding activity for a cryptic collagen epitope, including methods of inhibiting angiogenesis, tumor growth, and metastasis.

Abstract: The present invention relates to monoclonal antibody H11 and antigen binding fragments that specifically bind to the antigen recognized by H11, the C-antigen. The C-antigen is found specifically on neoplastic cells and not on normal cells. Also disclosed are polynucleotide and polypeptide derivatives based on H11, including single chain V region molecules and fusion proteins, and various pharmaceutical compositions. When administered to an individual, the H11 antibody is effective in diagnosing, localizing, and/or treating neoplasias. The invention further provides methods for treating a neoplastic disease, particularly melanoma, neuroblastoma, glioma, soft tissue sarcoma, and small cell lung carcinoma. Patients who are in remission as a result of traditional modes of cancer therapy may be treated with a composition of this invention in hopes of reducing the risk of recurrence. Patients may also be treated concurrently with the antibodies and traditional anti-neoplastic agents.

Abstract: Two members of the SNARE membrane fusion machinery, syntaxin 2 and endobrevin/VAMP-8, have been found to be important to cytokinesis in mammalian cells. Inhibition of syntaxin 2 and endobrevin/VAMP-8 function by over-expression of non-membrane anchored mutants of these proteins causes failure of cytokinesis leading to the formation of binucleated cells. Time-lapse microscopy shows that only midbody abscission is prevented by over-expression of these non-membrane anchored mutants, and that other cellular events preceeding midbody abscission, such as furrowing, are unaffected.

Abstract: One approach to treating individuals infected with HIV-1 is to administer to such individuals compounds that directly interfere with and intervene in the machinery by which HIV-1 replicates itself within human cells. Although the specific role of HIV-1 viral protein Vif in the viral life cycle is not known, the vif gene is essential for the pathogenic replication of lentiviruses in vivo. The present invention relates to a method for treating an individual exposed to or infected with HIV-1. Individuals identified as being exposed to or infected by HIV-1 are administered a therapeutically effective amount of one or more compounds that inhibit or prevent replication of said HIV-1 by interfering with the replicative or other essential functions of HIV-1 viral protein Vif by interactively blocking the multimerization domain of Vif, thereby preventing multimerization of Vif protein, which is important for Vif function in the lentivirus life cycle.

Abstract: It is an object of the present invention to provide an IRAP-binding protein. Specifically, the present invention provides the IRAP-binding protein, pharmaceuticals comprising the protein, a method for screening a compound inhibiting binding of the protein to IRAP, and a compound obtained by the screening method.

Abstract: Neuronal cell death, as modeled by removal of serum or NGF from growth medium, is characterized by many changes in gene expression. Gene expression was compared before and after withdrawal of serum or NGF. These results provide clues to underlying molecular processes occurring during neuronal and photoreceptor degeneration, and provide direction for future cell-based studies.

Abstract: The optic nerve axotomy model in mouse exhibits rapid changes in gene expression. Genes identified by microarray analysis as differentially expressed or modulated in this model, can be used diagnostically, therapeutically, and in drug discovery. These results provide clues to underlying molecular processes occurring during optic nerve degeneration, and provide direction for future cell-based studies.

Abstract: Antibodies that specifically bind to VLA-1 integrin and methods of using these antibodies to treat immunological disorders in a subject. Also included are crystal structures of complexes formed by VLA-1 antibodies and their ligands, and VLA-1 antagonists and agonists identified by using the structure coordinates of these structures.

Abstract: ACE-2 modulating compounds for the treatment of body weight disorders are disclosed. Methods of using the compounds and pharmaceutical compositions containing the compounds are also claimed.