Abstract: A transgenic non-human animal with alterations in a bradykinin B2 receptor gene is prepared by introduction of a gene encoding an altered bradykinin B2 receptor into a host non-human animal.

Abstract: The present invention relates to anti-tumor vaccines comprising at least one type of tumor cell into each of which at least two genes encoding MHC proteins of different haplotypes have been inserted, or naturally expressed, said genes being expressed in said tumor cells and wherein at least one of said MHC proteins has the same haplotype as a haplotype of the individual to be vaccinated. The invention furthermore relates to a method of treating a patient suffering from a tumorous disease comprising administering a vaccine of the invention and to the use of a vaccine of the invention for the preparation of an anti-tumor vaccine.

Abstract: This invention provides recombinant adenoviral vectors having an expression control sequence operatively linked to a gene that encodes an anti-inflammatory polypeptide or that produces on transcription an anti-inflammatory ribozyme or antisense RNA molecule. This invention also provides methods of transferring a gene to a synovial cell by transducing the synovial cell in vivo, with a recombinant adenoviral vector. This invention also provides methods of treating an inflammatory condition in the joint of a subject comprising administering to the joint a therapeutically effective amount of a recombinant adenoviral vector having an expression control sequence operatively linked to a gene that encodes an anti-inflammatory polypeptide or that produces on transcription an anti-inflammatory ribozyme or antisense RNA molecule.

Abstract: Transgenic mice whose germ cells and somatic cells contain a simian SV40 T-oncogene operably linked to the promoter of the retinoblastoma susceptibility (RB) gene effective for expression of the T-oncogene in somatic cells of the mouse under control of the promoter spontaneously develop tumors of the ocular tissues as well as osteosarcomas and soft-tissue sarcomas. Such transgenic mice are useful as sources of tissue cultures of tumor cells and as animal models for the occurrence of osteosarcomas and soft-tissue sarcomas in humans and other animals.

Abstract: The present invention relates to a DNA molecule containing intron sequences and encoding a human protein which is, depending on the site of action, called Bile Salt-Stimulated Lipase (BSSL) or Carboxyl Ester Lipase (CEL). The DNA molecule is advantageously used in the production of recombinant human BSSL/CEL, preferably by means of production in transgenic non-human mammals. The recombinant human BSSL/CEL can be used as a constituent of infant formulas used for feeding infants as a substitute for human milk, or in the manufacture of medicaments against e.g. fat malabsorption, cystic fibrosis and chronic pancreatitis.

Abstract: Disclosed is the in vitro development of mammalian embryos to the implantation stage by culturing the embryos in a medium containing leukemia inhibitory factor (LIF). Inclusion of LIF in the medium containing embryos also enhances the ability of the embryos to develop normally.

Abstract: Non-human chimeric mammals are created from a mammal having hematopoietic cells replaced with hematopoietic cells from a hematopoietic deficient mammal donor, and optionally in which xenogeneic cells and/or tissue are engrafted. The xenogeneic, preferably human, cells or tissue may be hematopoietic cells, in which case the chimeric mammal can produce xenogeneic B and/or T cells, and can be used as a source of mammalian, preferably human, monoclonal antibodies and/or T cells. Alternatively, the xenogeneic cells or tissue may be non-hematopoietic, such as normal or pathological cells or tissue, which can form a stable transplant in the chimeric mammal and thus can be used as an animal model of various pathologies or to test therapeutic or diagnostic agents or modalities.

Abstract: A composition of human neutrophil precursor cells is disclosed wherein at least 16% of the cells are human myeloblasts and promyelocytes. The myeloblasts and promyelocytes are derived from human neutrophil progenitor cells that were obtained from peripheral blood, bone marrow or cord blood. The neutrophil precursor cells contain less than 5% colony forming units. Also disclosed are human neutrophil precursor cells made up of about 16% CD15+CD11b- cells and less than 5% colony forming units and methods of preparing these compositions.

Abstract: A transgenic, non-human animal model is disclosed which lacks receptors which mediate some of the central nervous system (CNS) actions of serotonin. The animal is preferably from a genus selected from the group consisting of Mus (e.g., mice), Rattus (e.g., rats), Oryctologus (e.g., rabbits) and Mesocricetus (e.g., hamsters). More preferably the animal is a mouse which lacks 5HT.sub.2c receptors. Animals lacking such receptors are overweight due to abnormal control of feeding behavior and are prone to spontaneous death from seizures. Thus, such animals provide an animal model for the testing of drugs which are potentially useful in the treatment of eating disorders and diseases such as epilepsy which result in seizures.

Abstract: The claimed invention is directed towards non-murine pluripotential cells that have the ability to be passaged in vitro for at least 20 passages and which differentiate in culture into a variety of tissues. The scope of the claimed cells includes any non-murine ES cells and particular claims are drawn to human pluripotential cells.

Abstract: Antigens are produced by self-assembly of polypeptide components. The production of bluetongue virus antigens (BTV) in the form of assembled particles comprising separate polypeptide components, particularly proteins VP2, VP3, VP5 and VP7 is described.

Abstract: The multiple biological activities of tumor necrosis factor (TNF) are mediated by two distinct cell surface receptors of 55 and 75 kDa. Mutant mice of the invention lacking tumor necrosis factor receptor (TNFR) p55 still express functional TNFRp75 molecules at the cell surface. Normal weight and size of the mutant mice are not altered. Thymocyte development and lymphocyte populations are normal, and clonal deletion of potentially self-reactive T cells is not impaired. Activation of the nuclear transcription factor .kappa.B (NF-.kappa.B), however, is completely abrogated after stimulation with TNF. Moreover, TNFRp55 mutant mice are protected from septic shock induced by bacterial endotoxin or superantigen, but Listeria clearance is severely impaired and mutant mice easily succumb to Listeria infection. Thus, the two TNF receptors are not redundant, are independently controlled, and play different roles in normal and pathological physiology.

Abstract: Cell lines have been prepared from growth suppressor gene deficient animals. The cells include immortalized precursor cells and differentiated cells such as osteoclast precursors, osteoblast precursors, megakaryocytes, osteoclasts, osteoblasts, pancreatic .alpha.-cells, pancreatic .beta.-cells, pancreatic .delta.-cells, adipocytes, macrophages, chondrocytes and hepatocytes. The cells are useful for constructing cDNA and protein libraries, screening agonists and antagonists of compounds and factors that affect metabolic pathways of specific cells and generating cell-specific antibodies.

Abstract: The present application discloses retrovirus-derived vectors in which the retroviral envelope glycoprotein has been replaced by the G glycoprotein of vesicular stomatitis virus, and the use of these vectors in the transfer of exogenous genes into the cells of a wide variety of non-mammalian organisms. Also disclosed is a method for the generation of retroviral vectors in high titers, wherein a recombinant, stable host cell line is provided which harbors the retroviral vector of interest without envelope protein. High-titer retroviral vector production is initiated by introducing nucleic acid encoding a functional membrane-associated protein into the cell line. The vectors disclosed in the present application can be concentrated by ultracentrifugation to titers greater than 10.sup.9 cfu/ml which are especially useful in human gene therapy trials, and can also infect cells, such as hamster and fish cells, that are ordinarily resistant to infection with vectors containing the retroviral envelope protein.

Abstract: Disclosed are methods that achieve i) site-directed delivery, ii) in situ amplification, and iii) sustained expression of an exogenous gene product within renal glomeruli. An exogenous gene, E. coli .beta.-galactosidase, was introduced into cultured rat mesangial cells using a replication-defective retrovirus, and stable infectants were administered to a rat kidney via the renal artery. In the injected kidney, the engineered, cultured mesangial cells populated 40% of glomeruli site-specifically. The gene product was detected throughout a 14-week period of observation. In an alternative method, engineered, cultured mesangial cells were injected into a kidney subjected to an antibody that induces mesangiolysis followed by mesangial regeneration. Under these conditions, expression of .beta.-galactosidase was dramatically amplified in situ, and high level expression continued for at least 8 weeks.

Abstract: Production of human procollagen or collagen in cells which ordinarily do not produce these molecules is effected by constructing expression systems compatible with mammary glands of non-human mammals. For example, expression systems can be microinjected into fertilized oocytes and reimplanted in foster mothers and carried to term in order to obtain transgenic non-human mammals capable of producing milk containing recombinant human procollagen or collagen. Human procollagen or collagen produced in this manner can be made of a single collagen type uncontaminated by other human or non-human collagens.

Abstract: Immortalized cell lines derived from normal adult human liver are described which express phenotypic characteristics of normal adult liver epithelial cells.

Abstract: The expression of polynucleotide introduced into a cell by means of a targeted complex of the polynucleotide linked to a cell-specific binding agent can be enhanced and prolonged by inhibiting translocation or fusion of endosomes to lysosomes using colchicine.

Abstract: Non-human chimeric mammals are created from a mammal having hematopoietic cells replaced with hematopoietic cells from a hematopoietic deficient mammal donor, and optionally in which xenogeneic cells and/or tissue are engrafted. The xenogeneic, preferably human, cells or tissue may be hematopoietic cells, in which case the chimeric mammal can produce xenogeneic B and/or T cells, and can be used as a source of mammalian, preferably human, monoclonal antibodies and/or T cells. Alternatively, the xenogeneic cells or tissue may be non-hematopoietic, such as normal or pathological cells or tissue, which can form a stable transplant in the chimeric mammal and thus can be used as an animal model of various pathologies or to test therapeutic or diagnostic agents or modalities.

Abstract: A method for initiating metastasis of human tumor cells under experimental conditions is provided. Immunocompromised non-human mammals having a viable, xenogeneic organ or tissue are used as a host for human tumor cells. The cells are introduced into the chimeric animal after the solid tissue is implanted and are then able to grow and metastasize as they would in situ. Therapeutic regimens may be evaluated in this system to determine efficacy against metastatic processes.