Abstract: Intestinal epithelial cells of a mammalian subject are genetically altered to operatively incorporate a gene which expresses a protein which has a desired therapeutic effect. Intestinal cell transformation is accomplished by administration of a formulation composed primarily of naked DNA, and is preferably administered orally. Oral or other intragastrointestinal routes of administration provide a simple method of administration, while the use of naked nucleic acid avoids the complications associated with use of viral vectors to accomplish gene therapy. The expressed protein is secreted directly into the gastrointestinal tract and/or blood stream to obtain therapeutic blood levels of the protein thereby treating the patient in need of the protein. The transformed intestinal epithelial cells provide short or long term therapeutic cures for diseases associated with a deficiency in a particular protein or which are amenable to treatment by overexpression of a protein.

Abstract: The invention features methods of identifying a compound which suppresses ventricular muscle cell hypertrophy. In one embodiment, ventricular muscle cells are contacted with a test compound, which acts through an RAR or RXR receptor, in the presence of an inducer of hypertrophy. Development of ventricular muscle cell hypertrophy is then measured to identify compounds having the desired activity.

Abstract: Methods and compositions relating to chimeric genes containing (i) a tissue-specific promoter and (ii) a hypoxia response enhancer element, both of which are operably linked to a selected gene, such as a reporter gene, therapeutic gene (e.g., bcl-2, NOS, catalase and SOD), or deleterious gene are disclosed. Expression of the selected gene is enhanced in the target tissue under hypoxia conditions, such as conditions encountered during episodes of ischemia and reperfusion. The methods and compositions may be used as therapeutics and/or diagnostics.

Abstract: The present invention features a method of producing a multimeric protein from a hybrid cell formed from the fusion of two or more cells, each of which cell is engineered to express one component of the multimeric protein, as well as a method for screening for successful fusion of the cells to produce a desired hybrid cell. The methods of the invention are widely applicable to the production of proteins having two or more components.

Abstract: This invention comprises cellular vaccines and methods of using them in cancer immunotherapy, particularly in humans. The vaccines comprise stimulated lymphocytes allogeneic to the subject being treated, along with a source of tumor-associated antigen. The allogeneic lymphocytes can be stimulated by combining or coculturing them with leukocytes obtained from the subject to be treated or from another third-party donor. Tumor antigen may be provided in the form of primary tumor cells, tumor cell lines or tumor extracts prepared from the subject. Stimulated allogeneic lymphocytes and tumor antigen are combined and administered at a site distant from the primary tumor, in order to prime or boost a systemic cellular anti-tumor immune response. This approach overcomes the natural refractory nature of the immune system to stimulation by tumor antigens, generating a host response and potentially improving the clinical outcome.

Abstract: This invention provides methods and compositions for treating tumors by implanting near the tumor an alloactivated cell population. The cell population is made up of a plurality of third-party donor cells that have been cultured together ex vivo, and harvested near the time of peak cytokine secretion. Once placed in the tumor bed, the alloactivated cells recruit active participation of the host, which then reacts against the tumor and provides a level of ongoing protection. Employing multiple third party donor cells confers particular advantages in terms of effectiveness, timing, and ease of use.

Abstract: Fibroblast cells are treated with a chemical inhibitor of protein kinase C such as staurosporine, in conjunction with functionally hypoxic micromass culture so as to be induced into chondrogenic differentiation. Such fibroblast-derived, chondrocyte-like cells may be seeded onto three-dimensional polymer scaffolds for use in the repair of articular cartilage lesions, and thus can obviate the need for invasive techniques to harvest autologous chondrocytes from a limited supply of existing articular cartilage, or to avoid the need for obtaining allogeneic chondrocytes from non-biocompatible donor tissues.

Abstract: The invention is based on the discovery of methods for purification of an acid active hyaluronidase found in human plasma (hpHAse), including both biochemical and immunoaffinity purification methods. The method of immunoaffinity purification of the invention is based on the discovery of a method for identifying antibodies that specifically bind native hpHAse (anti-native hpHAse antibodies), and anti-native hpHAse antibodies identified by this screening method. The invention also features an assay for sensitive detection of HAse activity using biotinylated hyaluronic acid (bHA). Purification and characterization of hpHAse lead to the inventors' additional discovery that hpHAse is encoded by the LuCa-1 gene, which gene is present in the human chromosome at 3p21.3, a region associated with tumor suppression. The invention additionally features methods of treating tumor-bearing patients by administration of hpHAse and/or transformation of cells with hpHAse-encoding DNA.

Abstract: The present invention is directed to compositions and methods for selective induction of apoptosis in cancer cells, particularly malignant cancer cells, by delivery of a IL-1&agr; propiece polypeptide (e.g., a native IL-1&agr; propiece polypeptide, including IL-1&agr; propiece polypeptide variant) to a cancer cell.

Abstract: The present invention features non-human transgenic animal models for Alzheimer's disease (AD) and CAA, wherein the transgenic animal is characterized by 1) overexpression of bioactive transforming growth factor-&bgr;1 (TGF-&bgr;1) or 2) both overexpression of bioactive TGF-&bgr;1 and expression of a human amyloid &bgr; precursor protein (APP) gene product. The transgenic animals may be either homozygous or heterozygous for these alterations. Bigenic animals are further characterized by development of AD-associated and/or CAA-associated pathology within about two to three months of age.

Abstract: The invention features compositions and methods for the detection of and differentiation between Taenia solium and/or Taenia saginata. Specifically, the invention features nucleic acid probes comprising specific repetitive sequences of T. solium and T. saginata. These sequences make it possible to distinguish, with a high level of sensitivity and specificity, the eggs of these species of Taenia, thus enabling the diagnosis of taeniasis and the identification of carriers of Taenia solium. The invention is of great importance in controlling spread of T. solium due to ingestion of infected pork and/or exposure to human carriers of T. solium, thus facilitating the eradication of human and swine cysticercosis. The invention is thus of great importance in supporting eradication of human and swine cysticercosis.

Abstract: The present invention is directed to methods of detecting the presence of a bipolar mood disorder susceptibility locus in an individual, comprising analyzing a sample of DNA for the presence of a DNA polymorphism on the long arm of chromosome 18 between markers D18S469 and D18S554, wherein the DNA polymorphism is associated with a form of bipolar mood disorder. The invention for the first time provides strong evidence of a susceptibility gene for bipolar mood disorder that is located in the 18q22-q23 region of the long arm of chromosome 18. The disclosure describes the use of linkage analysis and genetic markers in this 18q22-q23 region to fine map the region and the use of genetic markers to genetically diagnose (genotype) bipolar mood disorder in individuals, to confirm phenotypic diagnoses of bipolar mood disorder, to determine appropriate treatments for patients with particular genotypic subtypes.

Abstract: A method to produce a cell expressing an antibody from a genomic sequence of the cell comprising a modified immunoglobulin locus using Cre-mediated site-specific recombination is disclosed. The method involves first transfecting an antibody-producing cell with a homology-targeting vector comprising a lox site and a targeting sequence homologous to a first DNA sequence adjacent to the region of the immunoglobulin loci of the genomic sequence which is to be converted to a modified region, so the first lox site is inserted into the genomic sequence via site-specific homologous recombination. Then the cell is transfected with a lox-targeting vector comprising a second lox site suitable for Cre-mediated recombination with the integrated lox site and a modifying sequence to convert the region of the immunoglobulin loci to the modified region.

Abstract: A method to produce a cell expressing an antibody from a genomic sequence of the cell comprising a modified immunoglobulin locus using Cre-mediated site-specific recombination is disclosed. The method involves first transfecting an antibody-producing cell with a homology-targeting vector comprising a lox site and a targeting sequence homologous to a first DNA sequence adjacent to the region of the immunoglobulin loci of the genomic sequence which is to be converted to a modified region, so the first lox site is inserted into the genomic sequence via site-specific homologous recombination. Then the cell is transfected with a lox-targeting vector comprising a second lox site suitable for Cre-mediated recombination with the integrated lox site and a modifying sequence to convert the region of the immunoglobulin loci to the modified region.

Abstract: The invention provides a method of suppressing ventricular muscle cell hypertrophy induced by an .alpha..sub.1 -adrenergic agonist or endothelin, by providing an effective amount of a retinoic acid compound.

Abstract: DNA segments encoding two slightly different protease nexin I forms (PN-I.alpha. and PN-I.beta.) are cloned and expressed to provide practical quantities of PN-I for diagnostic and therapeutic use. PN-I is a serine protease inhibitor useful in controlling conditions mediated by proteolytic activity.

Abstract: Several natural polypeptides (basophil granule proteins, "BGP") derived from the cytoplasmic granules of human basophils, and modified forms thereof, are described. These polypeptides, the DNA which encodes them and antibodies which recognize them, are useful as diagnostics for, and treatments for, pathologies involving inflammatory and IgE-mediated responses, parasitic and helminthic infections, hypersensitivity reactions and certain types of leukocytic leukemias.

Abstract: One or more amino acid residues within the reactive site region of protease nexin-I are altered in order to create analogs or variants of protease nexin-I. These analogs have substantially different protease specificities as well as different effects on regulating the activity of proteolytic enzymes which enzymes have substantial effects on a number of different physiological functions. Formulations containing the protease nexin-I variants and methods for administering these formulations to obtain desirable therapeutic results are disclosed.

Abstract: A method for correcting the drift offset of a transducer is disclosed which method is used in connection with a portable, battery-powered, hand-held system for releasing a controlled dose of aerosol medication for inhalation by a patient. The device includes a durable body and a medication cassette inserted in the durable body. The body includes a flow sensor having an asymmetrical orifice that is calibrated, independent of the cassette, to convert the sensed pressure due to flow into a flow rate. The orifice is separately calibrated for an inhalation flow rate range and an exhalation flow rate range over a selected number of known flow rates. The sensed pressure value is corrected for transducer offset drift and converted to a flow rate using the calibration data and piecewise linear interpolation.