Abstract: This invention provides a system for modeling neurodegenerative and other diseases through somatic gene transfer. In addition, methods of multiple gene transfer, disease analysis and drug testing are provided for.

Abstract: Pharmaceutical compositions and methods of use in regulation of mammalian bone forming activities of SFRPs (secreted frizzled-related proteins) are disclosed. SFRPs are secreted receptors for Wnts that are important polypeptide growth factors that are known to regulate fundamental biological processes like tissue polarity, embryonic development and tumorigenesis. A SFRP was isolated in human osteoblast cells and identified as SFRP-1 (also known as SARP-2) and shown to be regulated by osteogenic agents in the HOB cells in a differentiation selective manner modulating the life of osteoblasts/preosteocytes.

Abstract: The present invention makes available powerful tools for the study of cancer, based on a novel expression construct for a constitutively active hydrocarbon receptor CA-AhR. The invention further comprises transgenic non-human animals, preferably mammals, expressing CA-AhR in one or more tissues thereof. An animal model based on the transgenic non-human animals forms the basis for novel methods e.g. for the study of cancer; for the screening of compounds, such as drug candidates; for the investigation of the molecular mechanisms of cancer, in particular stomach cancer; for the investigation of the mechanisms of highly differentiated adenocarcinoma etc. Likewise, in vitro models based on transformed cells or cell lines, functionally incorporating the inventive construct are disclosed.

Abstract: The invention relates to a DNA sequence comprising a nucleotide sequence encoding a prepro-neuropeptide Y (preproNPY) where the leucine amino acid in position 7 of the signal peptide part of said preproNPY has been replaced by proline. The invention concerns further the mutant signal peptide or the mutant signal peptide associated with any other cleavage product of preproNPY, methods for the determination, in a biological sample, of the DNA sequence or the peptide. Furthermore, this invention relates to a method for diagnosing a predisposition for increased serum cholesterol or LDL cholesterol level in a human subject, and to methods for treating a human subject diagnosed for predisposition for increased serum cholesterol or LDL cholesterol. The present invention also relates to transgenic animals carrying either the mutant sequence or the normal sequence.

Abstract: The present invention provides a model animal with favorite onset of rheumatoid arthritis wherein the severity of arthritis reaches the maximum level and its onset ratio is a hundred percent, and a screening method of a remedy for rheumatoid arthritis by using the model animal. A mouse whose function of immunoglobulin Fc? receptor IIB gene is deficient on its chromosome and a wild-type collagen-induced arthritis-susceptible DBA/1J mouse are backcrossed six times or more, and a model mouse with favorite onset of rheumatoid arthritis is constructed. This model mouse with favorite onset of rheumatoid arthritis is immunized with bovine joint-origin type II collagen to develop collagen-induced arthritis.

Abstract: The invention provides gene-targeted non-human animals comprising a genetically modified apoE gene encodes a recombinant apoE polypeptide displaying domain interaction. The invention further provides cells isolated from the gene-targeted animals, which cells produce a recombinant apoE polypeptide displaying domain interaction. The invention further provides methods of identifying agents that reduce apoE4 domain interaction, and which are useful to treat apoE4-related neurological and cardiovascular disorders.

Abstract: DNA vaccine against a pathogen affecting farm animals, in particular bovines or porcines, comprising a plasmid containing a nucleotide sequence encoding an immunogen of a pathogen of the animal species considered, under conditions allowing the in vivo expression of this sequence, and a cationic lipid containing a quaternary ammonium salt, of formula in which R1 is a saturated or unsaturated linear aliphatic radical having 12 to 18 carbon atoms, R2 is another aliphatic radical containing 2 or 3 carbon atoms, and X a hydroxyl or amine group, this lipid being preferably DMRIE.

Abstract: Transgenic ungulates and compositions and methods for making and using same, are provided. Central to the invention are porcine, bovine, ovine and caprine embryonic stem cell lines and methods for establishing them. Cells of such lines are transformed with exogenous genetic material of interest and then used to provide chimeric ungulates confirmed by genetic markers which have germ cells comprising the exogenous genetic material. The chimeric ungulates are bred to provide transgenic ungulates. The transgenic animals of the invention may show improved qualities and can be used to provide human proteins or peptide hormones or can be used as xenograft donors.

Abstract: Marrow stromal cells (MSCS) are adult stem cells from bone marrow that can differentiate into multiple non-hematopoietic cell lineages. Colonies of human MSCs were shown to contain both small, rapidly self-renewing stem cells (RS cells) and large, more mature cells (mMSCs). Samples enriched for RS cells had a greater potential for multipotential differentiation than samples enriched for mMSCs. Also, RS cells have a series of surface epitopes and expressed proteins that can be used to differentiate RS cells from mMSCs. The results suggest that it will be important to distinguish the two major sub-populations of MSCs in defining their biology and their potentials for cell and gene therapy.

Abstract: The invention includes methods of enucleating avian eggs comprising visualizing internal structure of an avian egg utilizing TPLSM and ablating the nucleus of the egg by near-infrared light.

Abstract: The present invention provides a procaryotic host cell stably transformed or transfected by a vector including a DNA sequence encoding for mutant purine nucleoside phosphorylase or hydrolase. The transformed or transfected procaryotic host cell can be used in combination with a purine substrate to treat tumor cells and/or virally infected cells. The present invention provides nucleotide sequences encoding mutant E. coli derived purine nucleoside phosphorylase proteins which can be used in conjunction with an appropriate substrate to produce toxins which impair abnormal cell growth. The invention provides for delivery of the toxin by generation within target cells or by administration and delivery to the cells from without.

Abstract: The invention is directed to immunologically privileged cells, e.g., autologous, allogeneic, and xenogeneic intermediate lobe pituitary cells, for delivering polypeptides, e.g., insulin, to a subject, and to methods of using the same.

Abstract: Methods and compositions for diagnosing and treating glaucoma are disclosed.

Abstract: A method for producing viral gene delivery vehicles which can be transferred to pre-selected cell types by using targeting conjugates. The gene delivery vehicles comprise: 1) the gene of interest; and 2) a viral capsid or envelope carrying a member of a specific binding pair, the counterpart of which is not directly associated with the surface of the target cell. These vehicles can be rendered unable to bind to their natural cell receptor. The targeting conjugates include the counterpart member of the specific binding pair, linked to a targeting moiety which is a cell-type specific ligand (or fragments thereof). The number of the specific binding pair present on the viral vehicles can be, for example, an immunoglobulin binding moiety (e.g., capable of binding to a Fc fragment, protein A, protein G, FcR or an anti-Ig antibody), or biotin, avidin or streptavidin. The virus' outer membrane or capsid may contain a substance which mediates entrance of the gene delivery vehicle into the target cell.

Abstract: The present invention relates to the stabilization of milk from transgenic animals. In particular, the invention relates to the protection of proteins (e.g. fibrinogen) expressed in milk from transgenic animals by co-expression of a serine proteinase inhibitor (e.g., ?1-antitrypsin) in the milk of the transgenic animals.

Abstract: The present disclosure relates to a method for introducing a hematopoietic cell into the brain of a mammal, by administering bone marrow-derived progenitor cells into the body of the mammal by intravenous injection. The bone marrow-derived cell is preferably a cell that differentiates into a glial cell. The disclosure also relates to a method for delivery of therapeutic protein molecules into the brain of a mammal, by administering to a mammal an effective amount of bone marrow-derived progenitor cells which contain a gene having a nucleic acid sequence that encodes a functional therapeutic protein. Isolated recombinant cells and a pharmaceutical composition are also provided.

Abstract: Disclosed are methods of selectively delivering a medicant to an abnormal brain region and/or to a malignant tumor in a mammalian subject, including a human. A medicant is administered simultaneously or substantially simultaneously with a potassium channel agonist (other than bradykinin or a bradykinin analog), such as NS-1619,1-EBIO, a guanylyl cyclase activator, a guanylyl cyclase activating protein, minoxidil, pinacidil, cromakalim, or levcromakalim, whereby the medicant is delivered selectively to the cells of the abnormal brain region and/or to the tumor, compared to normal tissues. Thus, among the disclosures is a method of treating a malignant tumor in a human subject. Also disclosed are pharmaceutical compositions that combine a potassium channel agonist together with a medicant and a kit for enhancing the delivery of a medicant to an abnormal brain region and/or to a malignant tumor.

Abstract: A gene trap vector comprises a DNA construct containing an expression unit of an internal ribosome binding site (IRES) coupled to a heterologous gene sequence; this expression unit is used in gene trap protocols to obtain expression of the heterologous gene in the host.

Abstract: The present invention provides a method to enhance apoptosis in a cell by the administration of p53 in combination with a calpain inhibitor. The present invention provides a method of increasing the infectivity of a cell to a viral vector by treatment of the cell with a calpain inhibitor. the present invention further provides a method of enhancing transciption of a therapeutic transgene from the CMV promoter. The present invention also provides a method of suppress the in vivo CTL response to viral vectors by the use of calpain inhibitors. The present invention further provides a pharmaceutical formulations of p53 and a calpain inhibitor in a pharmaceutically acceptable carrier. The present invention provides a method of ablating neoplastic cells in a mammalian organism in vivo by the co-administration of a calpain inhibitor and p53.

Abstract: The present invention provides human transplantable inflammatory breast carcinoma xenografts. Such xenografts exhibit a number of unique characteristics which allows their use in experimental models of inflammatory carcinoma in order to dissect out the molecular basis of this phenotype. This experimental model of inflammatory carcinoma can be used to identify molecular targets for therapeutic intervention and to assess the efficacy of a broad spectrum of diagnostic and therapeutic agents. Specific animal models of inflammatory breast cancer are described as well as methods for evaluating diagnostic and therapeutic agents for treating inflammatory breast cancer. Methods for identifying molecules whose expression is modulated in inflammatory breast cancer are provided. In addition, methods for diagnosing and inhibiting the growth of inflammatory breast cancer metastases in vivo are provided.