Abstract: The present invention provides a method for diagnosing breast cancer in a subject. The present invention also provides a method for treating breast cancer in a subject. Finally, the present invention provides a method for assessing the efficacy of breast cancer therapy in a subject who has undergone or is undergoing treatment for breast cancer.

Abstract: This invention relates to the identification, cloning, sequencing and characterization of the iniB, iniA and iniC genes of mycobacteria which are induced by a broad class of antibiotics that act by inhibiting cell wall biosynthesis, including the first line antituberculosis agents, isoniazid and ethambutol. The present invention provides purified and isolated iniB, iniA, iniC and iniB promoter nucleic acids which may comprise the iniBAC operon, as well as mutated forms of these nucleic acids. The present invention also provides one or more single-stranded nucleic acid probes which specifically hybridize to the iniB, iniA, iniC and iniB promoter nucleic acids, and mixtures thereof, which may be formulated in kits, and used in the diagnosis of drug-resistant mycobacterial strain. The present invention also provides methods for the screening and identification of drugs effective against Mycobacterium tuberculosis using induction of the iniB promoter.

Abstract: A new protein capable of modulating or mediating the intracellular activity of RIP in inflammation, cell survival and cell death pathways is provided. DNA encoding it, a method for its production and its uses are also provided.

Abstract: The present invention provides a method of identifying novel agents that increase glucose dependent insulin secretion in pancreatic islet cells as well as methods of treating diabetes using the agents which have an inhibitory effect on the activity of pancreatic islet cell phosphodiesterases (“PDE”) enzyme, namely PDE1C. The methods described herein are based upon the inventor's surprising discovery that inhibition of PDE1C increases glucose dependent insulin secretion. Specifically, the present invention provides for a method of identifying therapeutic agents that act to increase the release of insulin from pancreatic islet cells. The method of identification provided herein is used to determine the effects of isozyme specific phosphodiesterase inhibitors on insulin secretion from cultured pancreatic &bgr;-cells. Also provided are agents that have an inhibitory effect on the activity of PDE1C in pancreatic cells.

Abstract: The present invention provides a purified and isolated nucleic acid encoding a sodium/iodide symporter. The present invention also provides purified sodium/iodide symporter, a vector comprising nucleic acid encoding sodium/iodide symporter, a host cell transformed with the vector, and a method for producing recombinant sodium/iodide symporter. In addition, the present invention provides nucleic acid probes and mixtures thereof specific for sodium/iodide symporter nucleic acid and antibodies immunoreactive with sodium/iodide symporter. The present invention also provides a method for diagnosing and treating thyroid disorders associated with non-functional sodium/iodide symporter. Furthermore, the present invention provides a method for the selective ablation of tissue. The present invention also provides a method for identifying an iodide transport protein in non-thyroid tissue. Finally, the present invention provides a non-human, transgenic model for a thyroid disorder.

Abstract: The present invention provides compounds having the formula: wherein A is CH or N; B is chosen from OH, NH2, NHR, H or halogen; D is chosen from OH, NH2, NHR, H, halogen or SCH3; R is an optionally substituted alkyl, aralkyl or aryl group; and X and Y are independently selected from H, OH or halogen except that when one of X and Y is hydroxy or halogen, the other is hydrogen; and Z is OH or, when X is hydroxy, Z is selected from hydrogen, halogen, hydroxy, SQ or OQ, Q is an optionally substituted alkyl, aralkyl or aryl group; or a tautomer thereof; or a pharmaceutically acceptable salt thereof; or an ester thereof; or a prodrug thereof; and compounds having the formula: wherein A, X, Y, Z and R are defined for compounds of formula (I) where first shown above; E is chosen from CO2H or a corresponding salt form, CO2R, CN, CONH2, CONHR or CONR2; and G is chosen from NH2, NHCOR, NHCONHR or NHCSNHR; or a tautomer thereof, or a pharmaceutically acceptable salt thereof, or an este

Abstract: An animal, e.g., transgenic mouse, in which the MSH4 gene is misexpressed. The animal is useful for screening treatments for a number of conditions. Methods for identifying contraceptive agents are also described.

Abstract: A method is provided for repopulating degenerated of immunetolerant mice which lack mature B and T lymphocytes with xenogenic mammalian hepatocytes, particularly primate hepatocytes to generate chimeric mice. In addition, a method of generating a human hepatitis virus-infected chimeric mouse is provided. A preferred xenogenic primate hepatocyte is derived from human, chimpanzee or baboon. These chimeric mice are useful in the investigation of host and viral mechanisms determining hepadnaviral persistence and hepatocarcinogenesis. Methods for monitoring the development of hepatitis and hepatocellular carcinoma as well as methods for testing and screening anti-viral and anti-cancer compounds with this model system are also provided.

Abstract: This invention provides for murine telomerase reverse transcriptase (mTERT) enzyme proteins and nucleic acids, including methods for isolating and expressing these nucleic acids and proteins, which have application to the control of cell proliferation and aging, including the control of age-related diseases, such as cancer.

Abstract: The invention relates to a method of detecting and/or assaying nucleoside hydrolases or nucleoside phosphorylases using a chromogenic substrate. Preferred chromogenic substrates have formula (I) where X is OH, or H, and Y is the residue of Y—OH where Y—OH is a chromophore or a compound readily converted to a chromophore and the substrates are hydrolyzed by the nucleoside hydrolase to yield ribose or 2-deoxyribose plus Y—OH. Alternatively, those substrates may be phosphorylysed by nucleoside phosphorylase to yield ribose-1-phosphate plus Y—OH. The methods may be used to detect and/or assay parasites in biological samples.

Abstract: The invention generally relates to compositions and methods with tramadol and an opioid antagonist to enhance analgesic potency and/or attenuate one or more adverse effects of tramadol, including adverse side effect(s) in humans such as nausea, vomiting, dizziness, headache, sedation (somnolence) or pruritis. This invention relates to compositions and methods for selectively enhancing the analgesic potency of tramadol and simultaneously attenuating anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects associated with the administration of tramadol. The methods of the present invention comprise administering to a subject an analgesic or subanalgesic amount of tramadol and an amount of excitatory opioid receptor antagonist such as naltrexone or nalmefene effective to enhance the analgesic potency of tramadol and attenuate the anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects of tramadol.

Abstract: A mutated mycobacterium selected from the class consisting of mutated M. bovis-BCG, mutated M. tuberculosis, and mutated M. leprae. The mutation of M. bovis-BCG, M. tuberculosis, or M. leprae is preferably effected through an insertional mutation of a mycobacterial gene. The insertional mutagenesis may be effected, for example, through illegitimate recombination or by a mycobacterial transposon. Such mutated mycobacteria may then be transformed with an expression vector(s) containing a complement gene to the gene which is mutated, and preferably also including a heterologous gene.

Abstract: The present invention provides a transgenic non-human animal whose genome comprises a disruption in its endogenous PDE7A gene, wherein the transgenic animal exhibits decreased expression of functional PDE7A protein relative to wild-type. The present invention further provides a method for creating a transgenic non-human animal exhibiting decreased expression of functional PDE7A protein relative to wild-type. Finally, the present invention provides a method for screening a PDE7A inhibitor for at least one side-effect.

Abstract: This invention relates to a method for treating a subject with irritable bowel syndrome (“IBS”) which comprises long-term administration of an opioid receptor antagonist at an appropriately low dose which will selectively antagonize excitatory opioid receptor functions, but not inhibitory opioid receptor functions, in myenteric neurons in the intestinal tract as well as in neurons of the central nervous system (“CNS”). The administration of the opioid receptor antagonist at a low dose enhances the potency of the inhibitory effects of endogenous opioid peptides present in the intestinal tract and the CNS, thereby reducing abdominal pain and stool frequency resulting from abnormally supersensitized excitatory opioid receptor functions. The invention also relates to a composition for treating a subject with IBS, which comprises an effective dose of an opioid receptor antagonist, and a pharmaceutically acceptable carrier.

Abstract: The present invention provides a purified and isolated nucleic acid encoding mycobacterial isocitrate lyase, as well as mutated forms of the nucleic acid. Further provided are purified and isolated isocitrate lyase proteins and mutated isocitrate lyase proteins. Additionally, the present invention provides vectors which comprises nucleic acid sequences encoding mycobacterial isocitrate lyase and mutated forms of this nucleic acid, as well as host cells containing these vectors. Also provided is a mycobacterium containing one or more mutations in its isocitrate lyase gene. Further provided by the present invention are agents that inhibit the activity or expression of a mycobacterial lyase protein, a method of identifying these, and a method of producing them. Finally, the present invention also provides a method of identifying genes required for persistence of mycobacteria.

Abstract: A protein capable of modulating or mediating the intracellular activity of RIP in inflammation, cell survival and cell death pathways is provided. DNA encoding it, a method for its production and its uses are also provided.

Abstract: This invention relates to a method for increasing the usefulness, sensitivity and specificity of tests that measure memory and facets of memory, including learning, retention, recall and/or recognition. Specifically, the sensitivity and specificity of such tests are enhanced by selectively weighting the value of specific items recalled by the test subject, either by weighting such items within any specific testing trial or across numerous testing trials. Also disclosed are various methods of reducing ceiling effects in memory tests. The invention also provides improved tests which employ item-specific weighting for the diagnosis of Alzheimer's Disease and other dementia characterized by memory impairment, as well as a method of screening for and evaluating the efficacy of potential therapeutics directed to the treatment of such dementia.

Abstract: The present invention provides a novel MHRII-associated protein designated MHRII-AP62 and antibodies immunoreactive with the MHRII-AP62 protein. Also provided are kits containing these antibodies and methods of using the antibodies for the detection of the MHRII-AP62 protein. The present invention also provides for a nucleic acid encoding the MHRII-AP62 protein and nucleic acid probes for use in the detection of the MHRII-AP62 protein. Further provided by the present invention are agents that mimic the activity of the MHRII-AP62 protein by binding to the MHRII, agents that inhibit the activity of the MHRII-AP62 protein by binding to the MHRII-AP62 protein, or by binding to the nucleic acid encoding the MHRII-AP62 protein, and methods of using these agents to treat cancer and cancer causing diseases.

Abstract: A new method to analyze and predict the binding energy for enzyme-transition state inhibitor interactions is presented. Computational neural networks are employed to discovery quantum mechanical features of transition states and putative inhibitors necessary for binding. The method is able to generate its own relationship between the quantum mechanical structure of the inhibitor and the strength of binding. Feed-forward neural networks with back propagation of error can be trained to recognize the quantum mechanical electrostatic potential at the entire van der Waals surface, rather than a collapsed representation, of a group of training inhibitors and to predict the strength of interactions between the enzyme and a group of novel inhibitors. The experimental results show that the neural networks can predict with quantitative accuracy the binding strength of new inhibitors.

Abstract: The present invention provides a novel method of inhibiting the growth of tumor cells based upon the discovery that p19ARF acts as a suppressor of oncogenic transformation by binding to the MDM2 oncoprotein and blocking MDM2's ability to target associated proteins, such as p53 and Rb, for proteosomal degradation. The method provided by the present invention inhibits the growth of a tumor cell by administering to the cell an effective amount of p19ARF or a mimetic thereof, and p53 to inhibit the growth of the tumor cell. Also provided by the present invention are pharmaceutical composition comprising p19ARF or a mimetic thereof, and/or p53.