Abstract: The present invention relates to isolated polypeptides which comprise an amino acid sequence consisting of a mutated functional Abl kinase domain, said mutated functional kinase domain being resistant to inhibition of its tyrosine kinase activity by N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(4-methyl-piperazin-1-ylmethyl)-benzamide or a salt thereof, to the use of such polypeptides to screen for compounds which inhibit the tyrosine kinase activity of such polypeptides, to nucleic acid molecules encoding such polypeptides, to recombinant vectors and host cells comprising such nucleic acid molecules and to the use of such nucleic acid molecules in the production of such polypeptides for use in screening for compounds which inhibit the tyrosine kinase activity of such polypeptides.

Abstract: The invention provides a method of ameliorating a Th1-mediated immune pathology in a mammal. The method is practiced by administering a low dose of estrogen to the mammal. Optionally, an immunotherapeutic agent can also be administered to the mammal. Also provided are kits containing a low dose of estrogen and an immunotherapeutic agent.

Abstract: Methods are disclosed for decreasing calorie intake, food intake, and appetite in a subject. The methods include peripherally administering a therapeutically effective amount of PYY or an agonist thereof to the subject, thereby decreasing the calorie intake of the subject.

Abstract: A device for occluding septal defects or other bodily passageways including PFOs, includes an occluding body formed from a plurality of flexible outwardly radiating occluding wires connected to one or more biocompatible sheet materials. The occluding wires are joined together at proximal wire ends. Linking members connectively link the occluding body to a flexible, substantially linear anchor formed from at least one tube, coil, or bar. The anchor is configured for placement on one side of bodily passageway, whereby the longitudinal axis of at least one anchor extends across a transverse cross-section of the bodily passageway, anchoring the occluding body in place against the other side of a bodily passageway to close, occlude, or fill at least a lumenal portion of a bodily passageway. The anchor may include one or more grasping member(s) integrally formed or connected to the tube, coil, or bar for releasable attachment to an anchor engaging member, such as a biopsy forceps.

Abstract: Methods are disclosed for identifying agents for the treatment of cancer and/or Fanconi anemia using Xenopus egg cell free extracts from which the endogenous DNA has been removed. The assays and method described herein are easily adaptable to high throughput techniques for example to screen large numbers of agents as possible agents for the treatment of cancer and/or Fanconi anemia. Kits for carrying out the disclosed assays and methods also are disclosed. Agents identified by these methods are also disclosed as are methods for treating a subject with cancer and/or Fanconi anemia with these agents.

Abstract: Methods are disclosed for decreasing calorie intake, food intake, and appetite in a subject. The methods include peripherally administering a therapeutically effective amount of PYY or an agonist thereof to the subject, thereby decreasing the calorie intake of the subject.

Abstract: This invention provides methods of treating a disease in a mammal where the disease is characterized by a symptom ameliorated by inhibition of cellular calcium influx. The methods involve administering to the mammal an effective amount of a retinoid and a pharmacologically acceptable excipient.

Abstract: There is disclosed a pharmaceutical composition for treating solid tumors that overexpress HER-2, comprising an agent selected from the group consisting of (a) an isolated polypeptide having from about 50 to 79 amino acids taken from the sequence of SEQ ID NO. 1, wherein the polypeptide binds to the extracellular domain ECD of HER-2 with an affinity binding constant of at least 108 M?1, (b) an isolated and glycosylated polypeptide having from about 300 to 419 amino acids taken from the sequence of SEQ ID NO. 2, wherein the C terminal 79 amino acids are present, and wherein at least three N-linked glycosylation sites are present, (c) a monoclonal antibody that binds to the ECD of HER-2, and (d) combinations thereof, with the proviso that the agent cannot be the monoclonal antibody alone, and a pharmaceutically acceptable carrier.

Abstract: The present invention relates to isolated polypeptides which comprise an amino acid sequence consisting of a mutated functional Abl kinase domain, said mutated functional kinase domain being resistant to inhibition of its tyrosine kinase activity by N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(4-methyl-piperazin-1-ylmethyl)-benzamide or a salt thereof, to the use of such polypeptides to screen for compounds which inhibit the tyrosine kinase activity of such polypeptides, to nucleic acid molecules encoding such polypeptides, to recombinant vectors and host cells comprising such nucleic acid molecules and to the use of such nucleic acid molecules in the production of such polypeptides for use in screening for compounds which inhibit the tyrosine kinase activity of such polypeptides.

Abstract: Vif binds to APOBEC3G and induces its rapid degradation, thus eliminating it from cells and preventing its incorporation into HIV-1 virions. Vif contains two domains, one that binds APOBEC3G and another with a conserved SLQ(Y/F)LA motif that mediates APOBEC3G degradation by a proteasome-dependent pathway. Provided herein are methods of exploiting these discoveries to develop compounds useful to inhibit Vif degradation of APOBEC3G, and thereby inhibit viral infection and/or replication.

Abstract: The present invention relates to novel bacterial hemoglobin receptor proteins and genes that encode such proteins. The invention is directed toward the isolation, characterization, diagnostic and therapeutic use of bacterial hemoglobin receptor proteins, nucleic acid encoding such proteins, recombinant expression constructs comprising such nucleic acids and cells transformed therewith, and antibodies and epitopes of such hemoglobin receptor proteins. The invention relates particularly to hemoglobin receptor proteins and genes encoding such proteins from Neisseria species, especially N. meningitidis and serotypes thereof, and N. gonorrhoeae. Methods for the diagnostic and therapeutic use of the proteins, epitopes, antibodies and nucleic acids of the invention are also provided, including the use of the proteins, epitopes, antibodies and nucleic acids of the invention for the production of vaccines effectinve in providing immunization of a human against infection by pathogenic bacteria of Neisseria species.

Abstract: A mammalian D2 dopamine receptor gene has been cloned. Thus, DNA sequences encoding all or a part of the dopamine receptor are provided, as well as the corresponding polypeptide sequences and methods for producing the same both synthetically and via expression of a corresponding sequence from a host transformed with a suitable vector carrying the corresponding DNA sequence. The various structural information provided by this invention enables the preparation of labeled or unlabeled immunospecific species, particularly antibodies, as well as nucleic acid probes labeled in conventional fashion. Pharmaceutical compositions and methods of using various products of this invention are also provided.

Abstract: FK506 and geldanamycin promote nerve regeneration by a common mechanism that involves the binding of these compounds to polypeptide components of steroid receptor-complexes other than the steroid hormone binding portion of the complex (FKBP52 and hsp90, respectively). These and other agents cause hsp90 dissociation from steroid receptor complexes or block association of hsp90 with steroid receptor complexes.

Abstract: Methods and reagents are provided for specifically targeting biologically active compounds such as antiviral and antimicrobial drugs, or prodrugs containing the biologically active compound to specific sites such as specific organelles in phagocytic mammalian cells. The biologically active compound or prodrug is linked to a microparticle with a linker that is non-specifically or specifically cleaved inside a phagocytic mammalian cell. Alternatively, the biologically active compound or prodrug is impregnated into a porous microparticle or coated on a nonporous microparticle, and then coated with a coating material that is non-specifically or specifically degraded inside a phagocytic mammalian cell. The prodrug contains the biologically active compound linked to a polar lipid such as ceramide with a specific linker such as a peptide that is specifically cleaved to activate the prodrug in a phagocytic mammalian cell infected with a microorganism.

Abstract: Analogs of FK506 that do not bind FKBP-12 have been found to effectively promote nerve cell growth and regeneration, thereby speeding functional recovery of damaged nervous tissue and axonal regeneration without causing immunosuppression.

Abstract: A method for treating circadian rhythm phase disorders is described. The invention provides methods to specifically advance or delay the phase of certain circadian rhythms in humans. The disclosed methods relate to the administration of melatonin at times determined with relation to the time of dim light endogenous melatonin onset. Embodiments capable of alleviating the effects of jet lag, winter depression and shift-work sleep disturbance are provided.

Abstract: A stent tissue graft prosthesis (20) for repairing, excluding and/or reinforcing a vessel, duct and the like in a patient. The prosthesis includes an inner expandable stent (21) of which a tissue graft (24) and preferably a multilayered tissue construct (33) is disposed thereon for application to the host tissue of a vessel, duct and the like. The tissue construct includes an extracellular matrix material (36) such as small intestine submucosa (37) for remodeling the host tissue into the prosthesis. The prosthesis further includes an outer tubular member (25) such as an outer expandable stent (44) for retaining the tissue graft on the inner stent. The ends of the inner and outer stents are coincident with or extend beyond the ends of the tissue graft to prevent eversion or fold back of the tissue graft during withdrawal of a delivery catheter in a placement procedure.

Abstract: This invention provides methods and reagents for specifically delivering biologically active compounds to phagocytic mammalian cells. The invention also relates to specific uptake of such biologically active compounds by phagocytic cells and delivery of such compounds to specific sites intracellularly. The invention specifically relates to methods of facilitating the entry of antimicrobial drugs and other agents into phagocytic cells and for targeting such compounds to specific organelles within the cell. The invention specifically provides compositions of matter and pharmaceutical embodiments of such compositions comprising conjugates of such antimicrobial drugs and agents covalently linked to particulate carriers generally termed microparticles. Alternative embodiments of such specific drug delivery compositions also contain polar lipid carrier molecules effective in achieving intracellular organelle targeting in infected phagocytic mammalian cells.

Abstract: This invention provides reagents and methods for specifically delivering antibiotic, antimicrobial and antiviral compounds, drugs and agents to phagocytic mammalian cells. The invention also relates to specific delivery to and uptake of such compounds by phagocytic cells. The invention specifically relates to reagents and methods for facilitating the entry of antibiotic, antimicrobial and antiviral compounds, drugs and agents into phagocytic cells. The invention specifically provides compositions of matter and pharmaceutical embodiments of such compositions comprising such antibiotic, antimicrobial or antiviral compounds, drugs and agents conjugated to, impregnated with or coated onto particulate carriers generally termed microparticles. In particular embodiments, the antibiotic, antimicrobial and antiviral compounds, drugs and agents are covalently linked to a microparticle via a specifically-degradable linker molecule which is the target of a microorganism-specific protein having enzymatic activity.

Abstract: A method for treating circadian rhythm disorders is described. The method involves the administration of melatonin, melatonin agonists or compounds that stimulate endogenous melatonin production so that the durations of the effective plasma concentrations of melatonin, melatonin agonists or compounds that stimulate endogenous melatonin production overlap with onset or offset of pre-treatment endogenous melatonin production, to provide a circadian-rhythm phase advance or phase delay, respectively. The methods of the invention also provide for concentration and/or duration of the effective plasma concentrations of melatonin, melatonin agonists or compounds that stimulate endogenous melatonin production to be greater in the time interval between about 8 hours before the dim light endogenous melatonin onset (DLMO) to about 4 hours after DLMO than in the time interval from about 4 hours after DLMO to about 8 hours before DLMO to achieve a circadian-rhythm phase advance.