Abstract: A novel nucleic acid construct for delivery of antisense targeting sequences is provided. The construct includes intact stem loop structures and an antisense nucleic acid. Optionally, a ribozyme nucleic acid is included in the construct. The construct is useful for inhibition of selected genes in a cell. This allele-specific targeting is also useful in combination with replacement gene therapy.

Abstract: Monoclonal antibodies and method for ameliorating an immune response disorder. The monoclonal antibodies are specific for an epitope present on the leukocyte adhesion receptor ?-chain.

Abstract: This invention provides methods and compositions for inducing weight loss and maintaining optimum weight comprising administering an agent that stimulates carnitine palmitoyl transferase-1 (CPT-1) activity to the patient in need, including human patients. These methods do not require inhibition of fatty acid synthesis. In particular, this invention provides methods for development of therapeutics that selectively enhance fatty acid oxidation, increase energy production, and reduce adiposity while preserving lean mass, through the pharmacological stimulation of CPT-1 activity. In a preferred mode, the agent is administered in an amount sufficient to increase fatty acid oxidation. In another preferred mode, the agent is administered in an amount sufficient to antagonize malonyl CoA inhibition of CPT-1. In yet another preferred mode, the agent is administered in an amount sufficient to increase malonyl CoA level.

Abstract: The present invention provides two novel polypeptides, referred to as the “N” and “C” fragments of hedgehog, or N-terminal and C-terminal fragments, respectively, which are derived after specific cleavage at a G?CF site recognized by the autoproteolytic domain in the native protein. Also included are sterol-modified hedgehog polypeptides and functional fragments thereof. Methods of identifying compositions which affect hedgehog activity based on inhibition of cholesterol modification of hedgehog protein are described.

Abstract: The present invention provides a substantially purified growth differentiation factor (GDF) receptor, including a GDF-8 (myostatin) receptor, as well as functional peptide portions thereof. In addition, the invention provides a virtual representation of a GDF receptor or a functional peptide portion thereof. The present invention also provides a method of modulating an effect of myostatin on a cell by contacting the cell with an agent that affects myostatin signal transduction in the cell. In addition, the invention provides a method of ameliorating the severity of a pathologic condition, which is characterized, at least in part, by an abnormal amount, development or metabolic activity of muscle or adipose tissue in a subject, by modulating myostatin signal transduction in a muscle cell or an adipose tissue cell in the subject.

Abstract: Methods for diagnosing pancreatic endocrine neoplasms are provided. Methods include obtaining a nucleic acid sample from the subject; contacting nucleic acids of the sample with an array comprising a plurality of DNAs under conditions to form one or more hybridization complexes; detecting the hybridization complexes; and comparing the levels of the hybridization complexes detected with the level of hybridization complexes detected in a non-diseased sample, wherein an altered level of hybridization complexes detected compared with the level of hybridization complexes of a non-diseased sample correlates with the presence of PEN in the subject. Nearly 200 differentially expressed genes identified in well-differentiated PENs versus enriched normal islet cells are provided, and a subset of these genes was validated at the protein level using PEN tissue microarrays.

Abstract: The present invention makes availables assays and reagents inhibiting paracrine and/or autocrine signals produced by a hedgehog protein or aberrant activation of a hedgehog signal transduction pathway, e.g., which involve the use of a steroidal alkaloid or other small molecule.

Abstract: Among the genes identified, in a comparison of the global gene expression profile of metastatic colorectal cancer to that of primary cancers, benign colorectal tumors, and normal colorectal epithelium, the PRL-3 protein tyrosine phosphatase gene was of particular interest. It was expressed at high levels in each of 18 cancer metastases studied but at lower levels in non-metastatic tumors and normal colorectal epithelium. In three of twelve metastases examined, multiple copies of the PRL-3 gene were found within a small amplicon located at chromosome 8q24.3. These data suggest that the PRL-3 gene is important for colorectal cancer metastasis and provides a new therapeutic target for these intractable lesions.

Abstract: A transgenic non-human animal of the species selected from the group consisting of avian, bovine, ovine and porcine having a transgene which results in disrupting the production of and/or activity of growth differentiation factor-8 (GDF-8) chromosomally integrated into the germ cells of the animal is disclosed. Also disclosed are methods for making such animals, and methods of treating animals with antibodies or antisense directed to GDF-8. The animals so treated are characterized by increased muscle tissue.

Abstract: The present invention provides methods relating to chemotherapeutic treatment of a cell proliferative disorder. In particular, a method is provided for predicting the clinical response to certain types of chemotherapeutic agents. Alkylating agents, used for the treatment of certain types of tumors including tumors of the nervous system and lymph system, are efficacious agents when the damage they do to tumor cell DNA is not repaired by cellular DNA repair mechanisms. The present invention provides a method for determining the activity of a gene encoding a DNA repair enzyme, thus providing a prediction of the clinical response to alkylating agents.

Abstract: The invention is directed to a method of diagnosing a cell proliferative disorder of breast tissue by determining the methylation status of nucleic acids obtained from a subject. Aberrant methylation of several genes including TWIST, HOXA5, NES-1, retinoic acid receptor beta (RAR&bgr;), estrogen receptor (ER), cyclin D2, WT-1, 14.3.3 sigma, HIN-1, RASSF1A, and combinations of such genes serve as markers of breast malignancy.

Abstract: Methods of reducing the risk of transmission of a sexually transmitted pathogen by contacting the pathogen or cells susceptible to infection by the pathogen with a &bgr;-cyclodextrin are provided. Methods for reducing the risk of transmission of a sexually transmitted pathogen to or from a subject by contacting the pathogen or cells susceptible to the pathogen in the subject with a pharmaceutical composition containing a &bgr;-cyclodextrin also are provided. Accordingly, pharmaceutical compositions, which include 1) a &bgr;-cyclodextrin, which is in an amount that blocks passage of the pathogen through lipid rafts in the membrane of a cell susceptible to the pathogen, and 2) a contraceptive, an agent for treating a sexually transmitted disease, a lubricant, or a combination thereof, are provided, as are composition formulated from a solid substrate that contains an amount of &bgr;-cyclodextrin useful for reducing the risk of transmission of a sexually transmitted pathogen.

Abstract: Disclosed are nucleotide coding sequences and polypeptide sequences for synaptic activation binding proteins that are characterized by induction in the central nervous system following neuronal activity in rat hippocampus. Such proteins are identified by (i) substantial homology at the nucleotide or protein sequence level to specifically defined rat, human or mouse coding sequences or proteins, (ii) ability to bind to and affect the activity of effector proteins in the CNS, such as metabotropic glutamate receptors, (iii) binding specificity for a particular binding sequence, and (iv) presence in the sequence of a PDZ-like domain. Nucleotides and polypeptides of the invention are useful in screening and diagnostic assays.

Abstract: The present invention generally relates to the field of treating degenerative disease by administering a pharmaceutically effective amount of a compound that elevates glutathione or at least one Phase II detoxification enzyme in diseased tissue. The present invention also relates to a pharmaceutical composition useful for the treatment of degenerative diseases, as well as a method of identifying agents that modulate intracellular levels of glutathione or intracellular levels of at least one Phase II enzyme in neuronal cells.

Abstract: Glutamate Transporter Associated Proteins and nucleotide encoding Glutamate Transporter Associated Proteins are provided. Also provided is a method for identifying a compound that modulates a cellular response mediated by a Glutamate Transporter Associated Protein. A method is further provided for identifying a compound that inhibits an interaction between a Glutamate Transporter Associated Protein and a glutamate transporter protein. A method is provided for treating a disorder associated with glutamate transport.

Abstract: Biodegradable, flowable or flexible polymer compositions are described comprising a polymer having the recurring monomeric units shown in formula I: wherein: each of R and R′ is independently straight or branched alkylene, either unsubstituted or substituted with one or more non-interfering substituents; L is a divalent cycloaliphatic group; R″ is selected from the group consisting of H, alkyl, alkoxy, aryl, aryloxy, heterocyclic or heterocycloxy; and n is 5 to 1,000, wherein said biodegradable polymer is biocompatible before and upon biodegradation. In one embodiment, one or more of R, R′ or R″ is a biologically active substance. Amorphous compositions containing a biologically active substance, in addition to the polymer, and methods for controllably releasing biologically active substances using the compositions, are also described.

Abstract: A novel T-type calcium channel (CACNA1G) is provided, as are polynucleotides encoding the same. CACNA1G has been implicated in cellular proliferative disorders. More specifically, it has been observed that the methylation state of specific regions within CpG island associated with the CACNA1G gene correlates with a number of cancerous phenotypes involving a variety of tissue and cell types. Also provided are methods for detecting cellular proliferative disorders by determining the methylation state of genes or regulatory regions associated therewith, including CACNA1G, as well as kits containing reagents for performing invention methods.

Abstract: The present invention relates to the detection of a cell proliferative disorder associated with alterations of microsatellite DNA in a sample. The microsatellite DNA can be contained within any of a variety of samples, such as urine, sputum, bile, stool, cervical tissue, saliva, tears, or cerebral spinal fluid. The invention is a method to detect an allelic imbalance by assaying microsatellite DNA. Allelic imbalance is detected by observing an abnormality in an allele, such as an increase or decrease in microsatellite DNA which is at or corresponds to an allele. An increase can be detected as the appearance of a new allele. In practicing the invention, DNA amplification methods, particularly polymerase chain reactions, are useful for amplifying the DNA. DNA analysis methods can be used to detect such a decrease or increase. The invention is also a method to detect genetic instability of microsatellite DNA.

Abstract: Disclosed are nucleotide coding sequences and polypeptide sequences for synaptic activation binding proteins that are characterized by induction in the central nervous system following neuronal activity in rat hippocampus. Such proteins are identified by (i) substantial homology at the nucleotide or protein sequence level to specifically defined rat, human or mouse coding sequences or proteins, (ii) ability to bind to and affect the activity of effector proteins in the CNS, such as metabotropic glutamate receptors, (iii) binding specificity for a particular binding sequence, and (iv) presence in the sequence of a PDZ-like domain. Nucleotides and polypeptides of the invention are useful in screening and diagnostic assays.

Abstract: The present invention provides methods relating to chemotherapeutic treatment of a cell proliferative disorder. In particular, a method is provided for predicting the clinical response to certain types of chemotherapeutic agents. Alkylating agents, used for the treatment of certain types of tumors including tumors of the nervous system and lymph system, are efficacious agents when the damage they do to tumor cell DNA is not repaired by cellular DNA repair mechanisms. The present invention provides a method for determining the activity of a gene encoding a DNA repair enzyme, thus providing a prediction of the clinical response to alkylating agents.