Abstract: The present invention relates to newly identified human polynucleotides and the polypeptides encoded by these polynucleotides. Also provided are vectors, host cells, antibodies, and recombinant methods for producing human antigens. The invention further relates to diagnostic and therapeutic methods useful for diagnosing and treating disorders related to these novel human antigens.

Abstract: Provided herein are combinatorial libraries containing chimeric Major Histocompatibility Comples (MHC) Class I proteins displayed on the surfaces of recombinant yeast cells. Members of the libraries, especially where those libraries have been mutagenized either with error-prone Polymerase Chain Reaction or with site-directed oligonucleotide mutagenesis, are improved in conformation stability or in binding to a target, e.g., a peptide or other ligand as compared with the stability or binding affinity of a wild type MHC Class I chimeric protein. The improved mutant chimeric proteins can be selected by various means, including fluorescence activated cell sorting with a fluorescent ligand bound to the surfaces of the yeast cells displaying the improved mutant chimeric protein.

Abstract: A search of the public human genome database identified a human EST, GenBank accession number AW293249, which has high homology to known pufferfish urocortin sequences. The full length sequence was amplified from human genomic DNA and sequenced. Sequence homology comparisons of the novel sequence with human urocortin I and urocortin II revealed that the sequence encoded a novel human urocortin, which was designated urocortin III (UcnIII). While urocortin III does not have high affinity for either CRF-R1 or CRF-R2, the affinity for CRF-R2 is greater than the affinity for CRF-R1. Urocortin III is capable stimulating cyclic AMP production in cells expressing CRF-R2&agr; or &bgr;. Thus, the affinity is high enough that urocortin III could act as a native agonist of CRF-R2. However, it is also likely that urocortin III is a stronger agonist of a yet to be identified receptor.

Abstract: The present invention provides novel polynucleotides and proteins encoded by such polynucleotides, along with therapeutic, diagnostic and research utilities for these polynucleotides and proteins. In particular, the polypeptides of the invention is useful for detecting cancers, treating cancer and treating degenerative disorders by stimulating cell growth.

Abstract: Disclosed are TGF-60 mimetics that PEGylated TGF-&agr; polypeptides and PEGylated TGF-60 related polypetides or fragments thereof.

Abstract: The present invention provides novel human cell division cycle proteins (collectively called HCDC) and polynucleotides which identify and encode HCDC. The invention also provides genetically engineered expression vectors and host cells comprising the nucleic acid sequences encoding HCDC. The invention also provides pharmaceutical compositions containing HCDC or antagonists to HCDC, and in the use of these compositions for the treatment of diseases associated with the expression of HCDC. Additionally, the invention provides for the use of antisense molecules to polynucleotides encoding HCDC for the treatment of diseases associated with the expression of HCDC. The invention also provides diagnostic assays which utilize the polynucleotide, or fragments or the complement thereof, to hybridize to the genomic sequence or transcripts of polynucleotides encoding HCDC or anti-HCDC antibodies which specifically bind to HCDC.

Abstract: Methods for improving purification and quantification of platelet derived growth factor (PDGF) proteins having structural heterogeneity are provided. Preparation of substantially pure isoforms of these proteins is achieved using TSK sulfopropyl cation exchange chromatography and reverse phase high performance liquid chromatography. A reverse charged capillary zone electrophoresis method enables quantification of substantially pure isoforms of these proteins resulting from endoproteolytic post-translational modifications. Compositions of the invention are substantially purified isoforms of secreted PDGF proteins having structural heterogeneity, more particularly purified intact, single-clipped, and double-clipped isoforms of recombinant PDGF-BB. Pharmaceutical compositions comprising at least one of these substantially purified recombinant PDGF isoforms and methods for their use in promoting wound healing are also provided.

Abstract: Leptin resistance ameliorating agents comprising as the active ingredient a neurotrophic factor such as BDNF or a trk receptor ligand, namely, agents for ameliorating, treating or preventing hypertension, sterility, obesity, glucose metabolic disorders, ischemic diseases, growth hormone secretion insufficiency, growth hormone hyposecretion, immune function disorder, etc. caused by leptin resistance.

Abstract: A method of treating lymphoma, ovarian cancer, colorectal cancer, or gastric cancer by administering an effective amount of Mesna to a patient is provided. A method for treating and reducing the effective dose of an anti-cancer agent by administering Mesna in conjunction with an anti-cancer agent is also provided.

Abstract: The present invention is directed to a group of linear and cyclic peptides having the structures:

Abstract: Multiple myeloma and other hematologic tumors and/or malignancies can be treated by administration of a G1 and/or S phase drug, which is preferably &bgr;-lapachone, or a derivative or analog thereof, combined with a G2/M phase drug such as a taxane derivative, which is advantageously paclitaxel. This combination of the G1 and/or S phase drug with the G2/M phase drug results in an unexpectedly greater than additive (i.e., synergistic) apoptosis in multiple myeloma cells. The invention includes methods of treating multiple myeloma by administering the combination of the G1 and/or S phase drug and the G2/M phase drug, pharmaceutical compositions comprising the combination of drugs used in these methods, as well as pharmaceutical kits.

Abstract: The invention relates to modified oligonucleotides that are useful for studies of gene expression and for the antisense therapeutic approach. The invention provides modified oligonucleotides that inhibit gene expression and that produce fewer side effects than conventional phosphorothioate oligonucleotides. In particular, the invention provides modified CpG-containing oligonucleotides that result in reduced splenomegaly and platelet depletion when administered to a mammal, relative to conventional CpG-containing phosphorothioate oligonucleotides. The invention further provides methods for using such oligonucleotides to modulate gene expression in vivo, including such use for therapeutic treatment of diseases caused by aberrant gene expression.

Abstract: A method of identifying accessible regions in a target RNA molecule using trans-splicing nucleic acid molecules is disclosed. Also disclosed is a method of revising mutant globin gene sequences using trans-splicing nucleic acid molecules and a method of tagging nucleic acid molecules with Tag moieties using trans-splicing nucleic acid molecules.

Abstract: The invention concerns an artificial membranous structure analogous to fixed plasmic membranes which comprise a solid substrate (61); a functional membrane (63) which does not circumscribe the external medium; and at least one bifunctional fixing compound (62) inserted between the membrane (63) and the substrate (61), cooperating by polyelectrolytic complexing with the substrate (61) and by lyotropic bonds with the membrane (63). The invention also concerns the use of this structure for obtaining a medicament, a particle, a film, its method of preparation, as well as a lipidic polycationic polymer, and a method for its preparation, acting as a bifunctional compound (62).

Abstract: The present invention provides a method of upregulating expression of a protein of interest (e.g., a native protein) in a cell, the cell containing a DNA encoding the protein, which DNA contains a mutation that causes downregulation of the protein by aberrant splicing in a pre-mRNA, wherein the DNA encodes the pre-mRNA; wherein the pre-mRNA contains a native intron having a first set of splice elements, which native intron is removed by splicing when the mutation is absent to produce a first mRNA encoding the protein; and wherein the pre-mRNA further contains an aberrant intron different from the native intron having a second set of splice elements, which aberrant intron is removed by splicing when the mutation is present to produce an aberrant second mRNA different from the first mRNA.

Abstract: In the present invention, a procedure is described which allows for the efficient delivery of gene and cell based vaccines to the rectal mucosal tissue, and which results in efficient and prolonged transferred gene expression in the mucosal tissue resulting in a potent local mucosal immune response directed against the antigen encoded by the administered nucleic acid. This invention provides a unique and potent approach for the development of vaccines and vaccination strategies to develop mucosal immune protective responses in the lower GI and GU tract in the prevention and/or treatment of sexually transmitted diseases and other conditions. This approach also provides a means for the successful transfer of genetic material in gene therapy approaches in the treatment or prevention of colonic diseases.

Abstract: The present invention provides methods of using antisense ADNF III oligonucleotides to inhibit the growth of pathologically proliferating cells. The invention also provides methods and kits for using ADNF III nucleic acid probes to detect the presence of pathologically proliferating cells in human tissues.

Abstract: Pluripotent cells that are suitable for transplantation therapy, to repair neural damage, are identified, e.g. by differential display, from a gene expression profile for a selected cell, which can be compared with that obtained from a control cell.

Abstract: The invention relates to a recombinant human cell of undifferentiated mesenchyma for bone and cartilage cell formation, the human cell having the ability to express Tbr-1, Brachyury or another member of the T-box family.

Abstract: This invention relates to anti-cancer therapy. More specifically the invention relates to methods of sensitising endothelial cells to prodrugs, to recombinant viral vectors, and to methods of inhibiting angiogenesis of tumors.

Abstract: A method of treating a human suffering a disease or condition caused by a gene, cDNA or RNA-DNA oligonucleotide or RNA-DNA oligonucleotide hybrids or messenger RNA implicated in a disease or condition involving cells that express hyaluronic acid receptors is provided, the method comprising administering to such human, an effective dosage amount of a pharmaceutical composition comprising an effective amount of a form of hyaluronic acid selected from hyaluronic acid and/or a pharmaceutically acceptable salt thereof associated with/bound with an effective amount of anti-sense to the gene, cDNA or RNA-DNA oligonucleotide or RNA-DNA oligonucleotide hybrids or messenger RNA implicated in the disease or condition in a suitable pharmaceutically acceptable diluent.

Abstract: Methods of activating a signaling cascade comprising, introducing leptin and/or a cytokine to a receptor complex comprising gp 130, optionally in combination with a compound acting on adenylate cyclase or acting on one or more downstream targets of adenylate cyclase, thereby inducing genes in neuro-endocrine cells or cells of neuro-endocrine origin. Two distinct gene-sets are induced, immediate early response genes (STAT-3, SOCS-3, Metallothionein-II, the serine/threonine kinase Fnk and the rat homologue of MRF-1), and late induced target genes (Pancreatitis Associated Protein I, Squalene Epoxidase, Uridinediphosphate Glucuronyl Transferase and Annexin VIII). Strong co-stimulation with the adenylate cyclase activator forskolin was shown with respect to late induced target genes. Transcripts encoding Leptin Induced Protein I (LIP-I) and Leptin Induced Protein II (LIP-II) were identified; however, no forskolin co-stimulatory effect was observed.

Abstract: The present invention is directed to a method of stimulating ciliary beat frequency to promote mucociliary or cough clearance of retained mucus secretions from the lungs, sinuses, upper airways, ears, eyes, genito-urinary tract, spermatozoa, ovaries, fallopian tubes, neutrophils, and macrophages of a patient. The method comprises administering uridine triphosphates, adenosine triphosphates, cytidine triphosphates, or dinucleoside tetraphosphates and the derivatives thereof to an affected body of a patient, to treat dysfunction of the mucociliary clearance system as a result of impaired ciliary movement in the patient.

Abstract: Compounds and pharmaceutical compositions active against HIV are provided, as is a method for the treatment of HIV infection in humans and other host animals is provided comprising administering an effective amount of a &bgr;-L-(2′ or 3′-azido)-2′,3′-dideoxy-5-fluorocytosine of the formula 1

Abstract: Compositions and methods for inhibiting arginase activity, including arginase activity in a mammal, are provided. Methods of making the compositions of the invention are also provided as are methods of using the compositions therapeutically. The compositions described herein are useful for alleviating or inhibiting a variety of arinase- and NO synthase-related disorders, including heart diseae, gastrointestinal motility disorders, and penile erectile dysfunction in humans.

Abstract: Pesticidal compositions for the control of human body louse containing one or more plant essential oils. In addition, the present invention is directed to a method for controlling human body louse by applying a pesticidally-effective amount of the above pesticidal compositions to a locus where pest control is desired.

Abstract: The present invention relates to the use of certain lysophospholipids to inhibit phospholipase D activity and the growth of tumor cells in a mammal.

Abstract: The invention relates to the use of compounds of formula (I), wherein n=0-3; R1, R2=H, alkyl, aryl, heteroaryl, acyl; R3=H, halogen, alkyl, aryl, heteroaryl, arylalkyl, acyl, CN, NO2, R4—X—; R4=H, alkyl, aryl, heteroaryl, aralkyl, acyl; X=NH, O, S, SO2, NHSO2, OSO2, and A, B, C=organic groups. The inventive compounds are used for the prophylaxis and the therapeutic treatment of infectious processes, especially of infectious processes caused by parasites. The invention further relates to medicaments that contain the inventive compounds.

Abstract: Use of phosphorous organic compounds of general formula (I) 1

Abstract: The present invention relates to pharmaceutical compositions and methods for treating a retinal disorder or glaucoma using NAALADase inhibitors.

Abstract: The present invention is directed to a physiological method for improving vision in a human patient. This method involves topical application to the eye, an amount of acetylcholine esterase inhibitor containing composition so that it is sufficient to provide a therapeutic benefit to improve the visual acuity in the human patient. The composition is administered topically and at bedtime after an eye straining work for about 20 minutes. The method disclosed herein is used for treatment and prevention of congenital and acquired color vision blindness, treatment of ocular hypertension and glaucoma, prevention of the progression of myopia, treatment of strabismus or squint, potentiation of best visual acuity, neuro-protection, treatment of aberrations secondary to pupil dilation.

Abstract: Styryl benzylsulfones of formula I are useful as antiproliferative agents, including, for example, anticancer agents: 1

Abstract: The present invention relates to derivatives of 1-hydroxymethylene-1,1-bisphosphonic acid, the pharmaceutical compositions comprising them, and their application in therapeutics, particularly for the treatment of cancerous tumors. It is also directed to a methods of preparation of such derivatives.

Abstract: The present invention discloses dye-sulfenate derivatives and their bioconjugates for dual phototherapy of tumors and other lesions. The compounds of the present invention may contain either a mixture of Type 1 and Type 2 agents or a single entity that integrates both units in the same molecules. The compounds are designed to produce both Type 1 and Type 2 phototherapeutic effect at once using dual wavelength light source that will produce singlet oxygen and free radicals at the lesion of interest.

Abstract: The use of 2-methoxyestradiol in the prevention of initial onset cancers and the recurrence of previously existing cancers, through use of such compound in a manner to promoteo pro-apoptotic activities in target cells and tissues.

Abstract: The present invention is directed to betulinol derivatives and betulinol-antibody conjugates having the formulae: 1

Abstract: The invention provides compounds of formula I and IV: 1

Abstract: The invention provides compounds or salts thereof of the general formula (I): 1

Abstract: This invention describes novel pyrazole compounds of formula IIIa: 1

Abstract: A compound of formula 1

Abstract: This invention pertains to compounds which specifically inhibit the adenosine A2a receptor and the use of these compounds to treat a disease associated with A2a adenosine receptor in a subject, comprising administering to the subject a therapeutically effective amount of the compounds.

Abstract: Methods of treating a human suffering from the Syndrome of Lipodystrophy or one or more HIV-related abnormalities included therein are provided. One method may include administering, by a pharmaceutically effective mode, a drug composition comprising an opioidergic agent, or alternatively, an opioidergic agent and an insulin secretagogue. The method may also include administering, by a pharmaceutically effective mode, a drug composition comprising an opiate agonist and opiate antagonist, or alternatively, an opiate agonist, opiate antagonist and an insulin secretagogue.

Abstract: The present invention relates to yohimbine dimer compounds, pharmaceutical compositions containing such dimer compounds, methods of making such dimer compounds, and uses thereof.

Abstract: A method of treating anhedonia in a patient in need thereof, comprising administering to the patient an effective amount of a dopamine agonist

Abstract: This invention relates to the use of 5-HT3 receptor antagonists in the treatment of nonconstipated female IBS patients.

Abstract: Compounds which are highly potent and highly specific &bgr;3-Adrenoreceptor agonists are provided. The compounds are formulated into pharmaceutical preparations and administered for stimulating, regulating and modulating metabolism of fats in adipose tissues in animals, particularly humans and other mammals. The compounds of the invention have the structure (A). R1 and R2 arc each independently members selected from the group consisting of H, OH, Cl, NO2, CH3SO2NH, NH2, CH3O and weak e4 acids of the structure R7—NH, where R7 is an acyl group, wherein at least one of R1 and R2 is OH. It is generally preferred that R2 be OH; R3, R4, and R5 are variously and independently members selected from I, Br, Cl, F, OCH3, CH3, alkyl, alkylaryl, aminoalkyl, thioalkyl, and O-alkyl. Preferably, R4 and R5 are each a halogen, the same or different; R6 is an acid moiety which forms an acid salt with the NH group. R6 is desirably HCl or (COOH)2.

Abstract: 1 Compounds of formula (I) wherein Q is a monocyclic or bicyclic aryl or heteroaryl ring; R1 is hydrogen; R2 is hydrogen or up to three substituents selected from halogen, NO2, CN, N3, CF3O—, CF3S—, CF3SO2—, CF3CO—, C1-6alkyl, C1-6alkenyl, C1-6alkynyl, C1-6perfluoroalkyl, C3-6cycloalkyl, C3-6cycloalkyl-C1-4alkyl-, C1-6alkylO—C1-6alkylCO—, C3-6cycloalkylO—, C3-6cycloalkylCO—, C3-6cycloalkyl-C1-4alkylO—, C3-6cycloalkyl-C1-4alkylCO—, phenyl, phenoxy, benzyloxy, benzoyl, phenyl-C1-4alkyl-, C1-6alkylS—, C1-6alkylSO2—, (C1-4alkyl)2NSO2—,(C1-4alkyl)NHSO2—, (C1-4alkyl)2NCO—, (C1-4alkyl)NCHO—, or CONH2, or —NR3R4 where R3 is hydrogen or C1-4alkyl, and R4 is hydrogen, C1-4alkyl, formyl, —CO2C1-4alkyl, or —COC1-4alkyl, or two R2 groups together form a carbocyclic ring that is saturated or unsaturated and unsubstituted or substituted by —OH or ═O; X is halogen, C1-6alkoxy, C1-6 alkyl, or C1-6

Abstract: Compounds of general formula (I), R1 is selected from any one of phenyl, pyridinyl, thiophenyl, furanyl, imidazolyl, and triazolyl; where each R1 phenyl ring and R1 heteroaromatic ring may optionally and independently be further substituted by 1, 2 or 3 substituents selected from straight and branched C1-C6 alkyl, NO2, CF3, C1-C6 alkoxy, chloro, fluoro, bromo, and iodo. The substitutions on the phenyl ring and on the heteroaromatic ring may take place in any position on said ring systems; Ra and Rb is each and individually selected from any one of hydrogen, a straight and branched C1-C6 alkyl, NO2, CF3, C1-C6 alkoxy, chloro, fluoro, bromo, and iodo; are disclosed and claimed in the present application, as well as their pharmaceutically acceptable salts and pharmaceutical compositions comprising the novel compounds and their use in therapy, in particular in the management of pain.

Abstract: The present invention is directed to use of (+)-&agr;-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol or its prodrug (Formula II) in treating patients for symptoms of dementia and dopamine induced psychosis.

Abstract: Improved processes for preparing substituted 2-(2-pyridylmethyl)sulfinyl-1H-benzimidazoles are disclosed.