Abstract: Methods for modulating immune cell signaling are provided. In general such methods involve modulating an interaction between a PDZ protein and a PDZ ligand protein whose interaction affects the composition and/or distribution of lipid rafts in an immune cell. Modulators that enhance or inhibit such interactions are also disclosed, as well as methods of screening for such modulators.

Abstract: Disclosed is a method of directing a cellular response in a mammal by expressing in a cell of the mammal a chimeric receptor which causes the cells to specifically recognize and destroy an infective agent, a cell infected with an infective agent, a tumor or cancerous cell, or an autoimmune-generated cell. The chimeric receptor includes an extracellular portion which is capable of specifically recognizing and binding the target cell or target infective agent, and (b) an intracellular portion of a protein-tyrosine kinase which is capable of signalling the therapeutic cell to destroy a receptor-bound target cell or a receptor-bound target infective agent. Also disclosed are cells which express the chimeric receptors and DNA encoding the chimeric receptors.

Abstract: Provided are methods of treating psychological diseases and conditions by administration of a preferential muscarinic acetylcholine receptor M1 antagonist, optionally with at least one antidepressant other than a selective muscarinic acetylcholine receptor M1 antagonist. The invention also provides for pharmaceutical compositions and kits for administration of at least one selective muscarinic acetylcholine receptor M1 antagonist in combination with at least one antidepressant other than a selective muscarinic acetylcholine receptor M1 antagonist.

Abstract: Provided are methods of treating obesity and effecting desired weight loss or preventing undesired weight gain by administration of a preferential muscarinic acetylcholine receptor M1 antagonist, optionally with at least one antidepressant other than a selective muscarinic acetylcholine receptor M1 antagonist. The preferential muscarinic acetylcholine receptor M1 antagonist, optionally can be administered with an anti-obesity agent, for example, an anorexiant. The invention also provides for pharmaceutical compositions and kits for administration of at least one selective muscarinic acetylcholine receptor M1 antagonist in combination with at least one antidepressant other than a selective muscarinic acetylcholine receptor M1 antagonist.

Abstract: Provided are compounds having an inhibitory effect on sodium-dependent glucose cotransporter SGLT. The invention also provides pharmaceutical compositions, methods of preparing the compounds, synthetic intermediates, and methods of using the compounds, independently or in combination with other therapeutic agents, for treating diseases and conditions which are affected by SGLT inhibition.

Abstract: Disclosed are replicatable viral DNA vectors encoding a site-specific DNA-altering enzyme and a DNA target recognized by the enzyme, the enzyme selectively converting, in a cell expressing the enzyme, the DNA vector to a rearranged form. The invention further relates to methods for assembling recombinant adenoviral DNAs. These methods include the steps of: (a) providing a first linearized DNA vector including a restriction site and a cos site and a second linearized DNA vector including the restriction site, an adenoviral nucleic acid molecule, and a cos site; and (b) ligating the first and second linearized DNA vectors, the ligation assembling a recombinant adenoviral DNA.

Abstract: The invention relates to genetically engineered soluble fusion proteins composed of human proteins not belonging to the immunoglobulin family, or of parts thereof, and of various portions of the constant region of immunoglobulin molecules. The functional properties of the two fusion partners are surprisingly retained in the fusion protein.

Abstract: Disclosed are replicatable viral DNA vectors encoding a site-specific DNA-altering enzyme and a DNA target recognized by the enzyme, the enzyme selectively converting, in a cell expressing the enzyme, the DNA vector to a rearranged form. The invention further relates to methods for assembling recombinant adenoviral DNAs. These methods include the steps of: (a) providing a first linearized DNA vector including a restriction site and a cos site and a second linearized DNA vector including the restriction site, an adenoviral nucleic acid molecule, and a cos site; and (b) ligating the first and second linearized DNA vectors, the ligation assembling a recombinant adenoviral DNA.

Abstract: A simple and highly efficient method for cloning cDNAs including CD27 (SEQ ID NO:28) from mammalian expression libraries based on transient expression in mammalian host cells has been discovered. Novel expression vectors allowing highly efficient construction of mammalian cDNA libraries are disclosed. The cloning method of the invention which has been used to clone genes for cell surface antigens of human lymphocytes, has general application in gene cloning. Cell surface antigens cloned according to the present invention have been purified, and the nucleotide and amino acid sequences determined. These antigens have diagnostic and therapeutic utility in immune-mediated infections in mammals, including humans.

Abstract: Disclosed are methods and compositions for reducing coronary artery stenosis, restoring blood flow to infarcted myocardium, improving myocardial perfusion, reducing heart attacks or other adverse cardiovascular events, or treating symptoms of inadequate myocardial function in a mammal involving administering to the mammal (a) a compound that includes eicosapentaeneoic acid or docosahexaeneoic acid and (b) a cholesterol-lowering therapeutic, combined with dietary restrictions (resulting in aggressive loading of marine lipids), whereby a serum LDL concentration of less than 75 mg/dl (and preferably less than 55 mg/dl) is achieved. One particular method involves administering to the mammal a combination that includes (a) a compound that includes an eicosapentaeneoic or docosahexaeneoic acid (for example, a marine lipid) and (b) a cholesterol synthesis or transfer inhibitor, and which may also optionally include aspirin and/or niacin.

Abstract: Disclosed is a method of directing a cellular immune response against an HIV-infected cell in a mammal involving administering to the mammal an effective amount of therapeutic cells which express a membrane-bound, proteinaceous chimeric receptor comprising (a) an extracellular portion which includes a fragment of CD4 which is capable of specifically recognizing and binding the HIV-infected cell but which does not mediate HIV infection and (b) an intracellular portion which is capable of signalling the therapeutic cell to destroy the receptor-bound HIV-infected cell. Also disclosed are cells which express the chimeric receptors and DNA and vectors encoding the chimeric receptors.

Abstract: Disclosed is a method of directing a cellular response in a mammal by expressing in a cell of the mammal a chimeric receptor which causes the cells to specifically recognize and destroy an infective agent, a cell infected with an infective agent, a tumor or cancerous cell, or an autoimmune-generated cell. Also disclosed are cells which express the chimeric receptors and DNA encoding the chimeric receptors.

Abstract: The present invention features novel methods for generating cell lines and mammals with site-specific genetic modifications of interest. The methods involve homologous recombination between an artificial chromosome having a modification of interest and an endogenous chromosome of a cell. The resulting modified cells can be used in standard methods to generate genetically modified mammals. These mammals can be used in a variety of screening methods to identify compounds useful for the treatment or prevention of disease. Additionally, cells that have been modified to eliminate a mutation associated with a disease can be transplanted into patients for the treatment of a disease.

Abstract: Isolated native immunoglobulin binding reagents including antibodies are provided, along with articles of manufacture, compositions and kits that include the native immunoglobulin binding reagents. Labeled reagents and substrates that comprise samples or the reagents are provided. Methods of screening for, making and using the reagents are also provided.

Abstract: The present invention relates to an antigen presenting membrane vesicle comprising on its surface a composition of either relevant molecules for antigen-specific activation or deactivation of T lymphocytes and which is present in the form of an artificially induced lipid vesicle budded from a plasma membrane of a eukaryotic, preferably human, cell, and wherein the composition of said relevant molecules for activation or deactivation present on the vesicle surface is adjustable to a recipient's needs or requirements independently of any blood or tissue cells of said recipient. The invention further relates to a method of manufacture of the vesicles and to compositions containing the vesicles as well as to the use of the vesicles for various purposes including medical and diagnostic applications.

Abstract: Disclosed is a method of directing a cellular immune response against an HIV-infected cell in a mammal involving administering to the mammal an effective amount of therapeutic cells which express a membrane-bound, proteinaceous chimeric receptor comprising (a) an extracellular portion which includes a fragment of CD4 which is capable of specifically recognizing and binding the HIV-infected cell but which does not mediate HIV infection and (b) an intracellular portion which is capable of signalling the therapeutic cell to destroy the receptor-bound HIV-infected cell. Also disclosed is a second method of treating HIV in a mammal involving administering to the mammal an effective amount of therapeutic cells expressing a membrane-bound, proteinaceous chimeric receptor comprising an extracellular portion which includes a fragment of CD4 which is capable of specifically recognizing and binding the HIV-infected cell but which does not mediate HIV infection.

Abstract: A simple and highly efficient method for cloning cDNAs from mammalian expression libraries based on transient expression in mammalian host cells has been discovered. Novel expression vectors allowing highly efficient construction of mammalian cDNA libraries are disclosed. The cloning method of the invention which has been used to clone genes for cell surface antigens of human lymphocytes, has general application in gene cloning. Cell surface antigens cloned according to the present invention have been purified, and the nucleotide and amino acid sequences determined. These antigens have diagnostic and therapeutic utility in immune-mediated infections in mammals, including humans.

Abstract: Disclosed are methods for potentiating the anti-cancer properties of an anti-cancer therapy in a mammal by administering with the therapy a compound (such as relaxin or &ggr;-IFN) that has a tissue tensile modulus-reducing property, an ability to reduce the interstitial viscosity of the cancer, an ability to increase the hydraulic conductance of the cancer, or an ability to increase collagen turnover or decrease collagen formation at or near the cancer, where the therapy and the compound are administered at dosages which together are sufficient to destroy, slow, or arrest the cancer. Also disclosed is a method for treating cancer in a mammal involving the administration of relaxin and/or &ggr;-IFN peptides and an anti-cancer therapy to the mammal, where the peptides and the therapy are administered at dosages which together are sufficient to destroy, slow, or arrest the cancer.

Abstract: Disclosed are replicatable viral DNA vectors encoding a site-specific DNA-altering enzyme and a DNA target recognized by the enzyme, the enzyme selectively converting, in a cell expressing the enzyme, the DNA vector to a rearranged form. The invention further relates to methods for assembling recombinant adenoviral DNAs. These methods include the steps of: (a) providing a first linearized DNA vector including a restriction site and a cos site and a second linearized DNA vector including the restriction site, an adenoviral nucleic acid molecule, and a cos site; and (b) ligating the first and second linearized DNA vectors, the ligation assembling a recombinant adenoviral DNA.

Abstract: Disclosed is a method of directing a cellular response in a mammal by expressing in a cell of the mammal a chimeric receptor which causes the cells to specifically recognize and destroy an infective agent, a cell infected with an infective agent, a tumor or cancerous cell, or an autoimmune-generated cell. Also disclosed are cells which express the chimeric receptors and DNA encoding the chimeric receptors.