Abstract: The present invention provides for a novel method of detecting the prion protein and variants thereof which utilizes specific amino acid binding sequences. Specifically, the present invention provides a method of detecting prion proteins, as well as isolating prion proteins, using an agent that binds to the amino acid sequence Gln-Pro-His of prion proteins. Further provided by the present invention is a method of diagnosing prion diseases in a subject using an agent that binds to the amino acid sequence Gln-Pro-His of prion proteins. Also provided are methods of treating and preventing prion diseases in a subject by administering an agent that binds to the amino acid sequence Gln-Pro-His of prion proteins. Finally, a method of inhibiting the dissemination of prion diseases through ingestion or exposure to liquid or solid substances by treating of the liquid or solid substance with biotin is provided herein.

Abstract: Transgene constructs for generating transgenic animals, wherein the transgene encodes a gene product which modulates transcription of a hypertrophy-sensitive gene, are provided. Further provided are recombinant vectors comprising the transgenes of the invention. Further provided are transgenic animals generated using the transgene constructs. Further provided are enzyme-based, cell-based, and whole-animal-based assays for detecting substances having therapeutic activity toward cardiac hypertrophy. Further provided are compositions comprising substances which modulate levels of active product of a hypertrophy-sensitive gene. Further provided are methods of treating cardiac hypertrophy.

Abstract: Tumor Suppressor Activated Pathway (TSAP) genes and nucleotide sequences therefore as well as vectors and cells containing such nucleotide sequences and various uses therefore are described. The mechanism by which TSAP 3 activates apoptosis also is described. Pharmaceutical compositions and methods for preventing tumorigenesis also is described.

Abstract: A method of releasing an agent for example, a chemotherapeutic, under predetermined conditions by protecting the agent within a lipid structure such as a liposome, causing lipase activity to be constituted by combining two or more components, e.g., recombinant N- or C-terminal Clostridium perfringens alpha-toxin fragments, one of these components being conjugated to a targeting molecule e.g., an antibody which binds to a target such as a tumor antigen. The lipid structure is then exposed to the constituted lipase activity such as to release the agent. Also disclose are materials and kits for use in the method.

Abstract: The present invention provides isolated nucleic acid molecules encoding a Herpesviridae thymidine kinase enzyme comprising one or more mutations, at least one of the mutations encoding an amino acid substitution upstream from a DRH nucleoside binding site which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase. Within another aspect, one of the mutations is an amino acid substitution within a DRH nucleoside binding site which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase. Also provided are vectors suitable for expressing such DNA molecules, as well as methods for utilizing such vectors.

Abstract: Several genes encoding subunits of the neuronal nicotinic acetylcholine receptors have been cloned and regulatory elements involved in the transcription of the &agr;:2 and &agr;:7- subunit genes have been described. Yet, the detailed mechanisms governing the neuron-specific transcription and the spatio-temporal expression-pattern of these genes remain largely uninvestigated. The &bgr;2-subunit is the most widely expressed neuronal nicotinic receptors subunit in the nervous system. We have studied the structural and regulatory properties of the 5′ sequence of this gene. A fragment of 1163 bp of upstream sequence is sufficient to drive the cell-specific transcription of a reporter gene in both transient transfection assays and in transgenic mice. Deletion analysis and site-directed mutagenesis of this promoter reveal two negative and one positive element. The positively acting sequence includes one functional E-box.

Abstract: The present invention relates to calcium channel compositions and methods of making and using same. In particular, the invention relates to calcium channel alpha2delta (&agr;2&dgr;) subunits and nucleic acid sequences encoding them. These compositions are useful in methods for identifying compounds that modulate the activity of calcium channels and for identifying compounds as therapeutic for disease.

Abstract: The present invention relates to the use of adenovirus-mediated gene transfer to regulate function in cardiac and vascular smooth muscle cells. A recombinant adenovirus comprising a DNA sequence that codes for a gene product is delivered to a cardiac or vascular smooth muscle cell and the cell is maintained until that gene product is expressed. Delivery is direct injection into a muscle cell or infusing a pharmaceutical composition containing an adenovirus virus vector construct intravascularly.

Abstract: The present invention provides a novel Semaphorin having neurite-outgrowth inhibition activity or proteins analogous thereto, peptide fragments of, or antibodies against, such proteins, genes encoding such proteins, expression vectors for said genes, transformed cells into which said expression vectors have been introduced, methods for producing a recombinant protein which employ said transformed cells, antisense nucleotides against the above genes, transgenic animals involving insertion or deletion of the above genes, and screening methods for antagonists of the above proteins, all of which are useful mainly in diagnoses, treatments, or studies relating to neurological diseases. The present invention further provides use of such proteins, peptides, antibodies, genes, or antisense nucleotides as pharmaceutical or diagnostic agents or laboratory reagents.

Abstract: This invention is concerned with human organic anion transporter (“hOAT”). Isolated nucleic acid encoding hOAT is provided, along with isolated hOAT polypeptide. hOAT nucleic acid and/or hOAT polypeptide are employed in transgenic animals, recombinant cells, replicable vectors and analytical procedures for identifying hOAT agonists or antagonists, assays for identifying hOAT alleles and/or isotypes, screening tests for nephrotoxic or neurologically active compounds, and determination of drug-drug interactions within the kidney or brain.

Abstract: The invention relates to the inhibition of blood coagulation, especially during organ rejection, and in particular the inhibition of delayed vascular rejection. The invention provides anticoagulant proteins which are anchored to cell membranes. The anticoagulant function preferably provided by heparin, antithrombin, hirudin, TFPI, tick anticoagulant peptide, or a snake venom factor. These anticoagulant proteins are preferably prevented from being constitutively expressed at the cell surface. In particular, expression at the cell surface is regulated according to cell activation, for instance by targeting the protein to a suitable secretory granule. Expression of these proteins renders cells, tissues and organs less vulnerable to rejection after transplantation (e.g. after xenotransplantation).

Abstract: The subject of the present invention is the use of a polypeptide comprising at least 6 continuous amino acids of the sequence as shown in the sequence identifiers 1 to 5 as cellular receptor and/or coreceptor for adenoviruses. It also relates to the use of a cell capable of expressing such a polypeptide as well as that of a ligand capable of influencing the attachment of an adenovirus to a host cell and/or its entry into the said host cell. Finally, it also relates to a method for selecting or identifying a cellular receptor for a virus or the part of a viral protein which determines the attachment of the virus to its cellular receptor as well as to the use of a bifunctional ligand to target an adenovirus to a host cell carrying, at its surface, a surface protein other than the natural cellular receptor for the said adenovirus.

Abstract: A DNA construct is disclosed which encodes a fusion protein comprising an amino acid sequence of a blood clotting factor like Factor IX and an amino acid sequence of the cytoplasmic domain of P-Selectin. Such construct may be used for the somatic gene therapy of patients suffering from a defiency of a blood coagulation factor.

Abstract: The present invention relates to the use of virus-like particles (VLP's) of papillomavirus for preparing vector pseudoviruses useful for transferring genetic material into target cells of an organism

Abstract: An immunogenic tumor cell, and method for its formation, which includes a tumor cell treated to have an altered intracellular level of a molecular factor compared to an untreated tumor cell.

Abstract: A method for obtaining a eukaryotic cell transfected with an episome involves transfecting the cell with the episome under conditions wherein cells survive that are successfully transfected with the episome. The resulting cells express both a first protein whose expression causes cell death and a second protein whose expression prevents cell death resulting from expression of the first protein.

Abstract: Nonobese Diabetic Mice (NOD mice) that do not develop diabetes may be bred to produce F1 offspring that develop a condition that closely mimics rheumatoid arthritis (RA) in humans. The RA-like disease in the F1 mice, designated NOD-RA mice, is similar to human RA in clinical, radiological, histological and serological characteristics. The parents (F0) and their progeny (F1) are not diabetic and never develop hyperglycemia, and the parental mice (F0) do not themselves exhibit any symptoms of the RA-like condition that afflicts some of their progeny. The incidence, penetrance, gender domination, progression, and lifelong exacerbation of symptoms after pregnancy shown in the RA-like condition afflicting NOD-RA mice are all comparable to phenomena observed in the human disease. The NOD-RA mice provide a new spontaneous model of human RA that will be useful for studying rheumatoid arthritis and testing new drugs and reagents for treating or diagnosing the disease.

Abstract: A transgenic non-human animal with alterations in the osteopontin gene is prepared by introduction of a gene encoding an altered osteopontin protein into a host non-human animal. Methods for using transgenic mice so generated to screen for agents that effect osteopontin's cellular modulating activity are also provided.

Abstract: A transgenic mammal whose somatic and germ cells having a nucleic acid construct wherein the construct includes a mammalian promoter operably linked to a cDNA genomic sequence is provided for the overexpression of galanin. Also provided is a construct having cDNA for the overexpression of galanin. A method of making a transgenic mammal by producing a mammal having a construct for the overexpression of galanin is provided.

Abstract: The invention discloses the preparation of DNA, in particular plasmid DNA. More particularly it concerns the production of bacterial plasmid DNA to be used in gene therapy, in the form of plasmid, minicircle supercoiled, loose or linear.