Abstract: Parkinson's disease (PD) is a neurodegenerative disorder which is pathologically characterized by the presence of intracytoplasmic Lewy bodies, the major component of which are filaments consisting of &agr;-synuclein. The present invention provides &agr;-synuclein mutations which accelerate &agr;-synuclein aggregation and can thus be utilized for transgenic animal production and generation of the first progressive PD model. Also provided is an in vitro aggregation assay which can be utilized to identify &agr;-synuclein nucleation inhibitors for the treatment of PD.

Abstract: Selected novel substituted pyridine compounds are effective for prophylaxis and treatment of diseases, such as TNF-&agr;, IL-1&bgr;, IL-6 and/or IL-8 mediated diseases, and other maladies, suchas pain and diabetes. The inventin encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving inflammation, pain, diabetes, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermedates useful in such processes.

Abstract: A method of inhibiting the production of cytokines, particularly inhibiting the production of tumor necrosis factor&agr;, interleukin-10, and macrophage inflammatory protein-1&agr; and the like, in a mammal, including a human, in need thereof which involves administering to such mammal an effective amount, preferably cytokine production inhibiting amount, of a polymethoxylated flavone.

Abstract: The invention relates generally to recombinant methods and materials for effecting the microbial production of useful polypeptides. More particularly, the invention relates to expression vector systems which utilize a translational repressor system, and transcriptional control proteins to provide a highly efficient, tightly regulated, staged inducible promoter system capable of expressing exogenous genes, including toxic genes, in E. coli.

Abstract: The present invention comprises a new class of novel aryl and heteroaryl substituted fused pyrrole compounds useful for the prophylaxis and treatment of diseases or conditions, such as TNF-&agr;, IL-1&bgr;, IL-6 and/or IL-8 mediated diseases, and other maladies, such as pain and diabetes. In particular, the compounds of the invention are useful for the prophylaxis and treatment of diseases or conditions involving inflammation. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of inflammation and other maladies, such as pain and diabetes, using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract: Selected novel substituted pyridine and pyridazine compounds are effective for prophylaxis and treatment of diseases, such as TNF-&agr;, IL-1&bgr;, IL-6 and/or IL-8 mediated diseases, and other maladies, such as cancer, pain and diabetes. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving inflammation, cancer, pain, diabetes and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract: Disclosed are nucleic acid molecules encoding polypeptides that specifically bind telomerase RNA. Also disclosed are methods of preparing the nucleic acid molecules and polypeptides, and methods of using these molecules.

Abstract: Polypeptides which bind to one or more EPH-like receptors, particularly the HEK4 receptor, are described. The polypeptides are designated HEK4 binding proteins. Nucleic acids encoding HEK4 binding proteins, and expression vectors, host cells and processes for the production of the polypeptides are also described. The polypeptides are useful for modulating the growth and/or differentiation of a variety of tissues, including those from liver, kidney, lung, skin, digestive tract and nervous system and may be used to regenerate damaged or depleted tissue and to treat cancer or nervous system disorders.

Abstract: The present invention provides a chemically-modified protein prepared by binding polyethylene glycol to a polypeptide characterized by being the product of expression by a host cell of an exogenous DNA sequence and substantially having the following amino acid sequence: (Het)n - Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln - Ser Phe Leu Leu Lys Cys Leu Glu Gln Val Arg - Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu - Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro - Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly - Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser - Gln Ala Leu Gln Leu Ala Cly Cys Leu Ser Gln - Leu His Ser Gly Leu Phe Leu Tyr Gln GIY Leu - Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu - Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val - Ala Asp Phe Ala Thr Tbr Ile Trp Gln Gln Het - Glu Glu Leu Gly Het Ala Pro Ala Leu Gln Pro - Thr Gln Gly Ala Het Pro Ala Phe Ala Ser Ala - Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala - Ser His Leu Gln Ser Phe Leu Glu Val Scr Tyr - Arg Val Leu Arg His Leu Ala Gln Pro (n = 0 or 1)The ch

Abstract: Disclosed are nucleic acid molecules encoding novel cyclin E2 polypeptides. Also disclosed are methods of preparing the nucleic acid molecules and polypeptides, and methods of using these molecules.

Abstract: The present invention provides methods for treating interleukin-1 mediated diseases including arthritis, inflammatory bowel disease, sepsis and septic shock, ischemia injury, reperfusion injury, multiple sclerosis and cerebral infarctions such as cerebral palsy. The methods are accomplished by administering to a patient in need thereof a therapeutically effective amount of an interleukin-1 inhibitor.

Abstract: Methods for identifying novel secreted mammalian proteins in mammalian host cells are described. Reporter polypeptides which allow detection of signal sequences by growth selection or by enzymatic activity are also described.

Abstract: At least two substantially purified tumor necrosis factor (TNF) inhibitors are disclosed which are glycoproteins that are active against TNF. The isolation of 3O kDa and 40 KDa TNF inhibitor from urine is disclosed. The deglycosylated form of the 3O kDa TNF inhibitor and 40 kDa TNF inhibitor are described as being active against TNF. The 40 kDa TNF inhibitor is active against both TNF alpha a TNF beta. The amino acid sequence of the 30 kDa TNF inhibitor and the 40 kDa TNF inhibitor are disclosed. Methods for isolating the TNF inhibitors from human U937 cell medium and producing the proteins by recombinant-DNA methods are also described.

Abstract: Disclosed are nucleic acids encoding novel neurotrophic factors, designated NNT-1. Also disclosed are amino acid sequences for NNT-1 polypeptides, methods for preparing NNT-1 polypeptides, and other related aspects. Such polypeptides are active in stimulating B-cell and/or T cell production, as well as reducing inflammatory responses.

Abstract: A synthetic DNA sequence and its genetic equivalents are disclosed which sequences are capable, when used in a recombinant DNA method, of directing production of a serine protease inibitor protein. Recombinant DNA methods for the production of serine protease inhibitor proteins are also disclosed. These methods incorporate either the synthetic DNA sequence of the present invention or natural DNA sequences isolated from human cDNA or genomic libraries.In addition, a single polypeptide chain protein is disclosed which is capable of inhibiting chymotrypsin and elastase but not trypsin. In one embodiment, this protein is a shortened from (single domain) of the protein produced by the method described herein.

Abstract: Selected novel azepine and larger medium ring compounds are effective for prophylaxis and treatment of inflammation, tissue degradation and related diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of inflamation, tissue degradation and related diseases. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract: Method for identifying novel secreted mammalian proteins in yeast are described. Reporter polypeptides which allow detection of signal sequences by growth selection are also described.

Abstract: A pharmaceutical composition comprising (a) an effective amount of controlled release polymer and (b) an effective amount of a proteinaceous IL-1 inhibitor. The composition exhibits a therapeutic effect on inflammation and is useful for treating IL-1 mediated inflammatory diseases, particularly diseases of the joint.

Abstract: Selected novel substituted pyrimidinone and pyridone compounds are effective for prophylaxis and treatment of diseases, such as TNF-.alpha., IL-1.beta., IL-6 and/or IL-8 mediated diseases, and other maladies, such as pain and diabetes. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving inflammation, pain, diabetes and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract: The present invention relates to mutants of the green fluorescent protein having improved fluorescent properties at 37.degree. C. The mutants provide for improved methods of monitoring gene expression, e.g., for use as cell markers or protein expression indicators in prokaryotic and, especially, eucaryotic systems where the standard physiological temperature is 37.degree. C.