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: A chimeric non-human mammal M3 having its hematopoietic cells substantially destroyed and replaced by hematopoietic cells from a hematopoietic deficient mammal, wherein M3 is susceptible to bacterial toxin-related pathologies found in humans, and to methods of making and using thereof.

Abstract: Provided is a non-human animal in which an exogeneous gene, a mutant gene thereof of a monocyte chemoattractant protein and/or a receptor thereof is introduced. The present transgenic animals can be utilized as a pathologic model animal for heart diseases, respiratory diseases, joint diseases, kidney diseases, arteriosclerosis, psoriasis, hyperlipidemia, allergic diseases, bone diseases, blood diseases, cerebrovascular disorders, traumatic cerebral disorders, infections diseases, demantia or chroric inflammatory diseases etc. Thus, it is possible to elucidate the mechanism of pathogenesis of these diseases, to determine therapies, and to screen for candidate compounds for the purpose of research and development of therapeutic drugs.

Abstract: The subject invention provides non-human mammalian hosts characterized by inactivated endogenous Ig loci and functional human Ig loci for response to an immunogen to produce human antibodies or analogs thereof. The hosts are produced by multiple genetic modifications of embryonic cells in conjunction with breeding. Different strategies are employed for recombination of the human loci randomly or at analogous host loci. Chimeric and transgenic mammals, particularly mice, are provided, having stably integrated large, xenogeneic DNA segments. The segments are introduced by fusion with yeast spheroplasts comprising yeast artificial chromosomes (YACs) which include the xenogeneic DNA segments and a selective marker such as HPRT, and embryonic stem cells.

Abstract: The present invention discloses nucleic acid molecules encoding WRN gene products, expresion vectors, viral vectors, and host cells suitable for expressing such products.

Abstract: The present invention relates to the use of tumor suppressor genes in combination with a DNA damaging agent or factor for use in killing cells, and in particular cancerous cells. A tumor suppressor gene, p53, was delivered via a recombinant adenovirus-mediated gene transfer both in vitro and in vivo, in combination with a chemotherapeutic agent. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into tumors subcutaneously, followed by intraperitoneal administration of a DNA damaging agent, cisplatin, induced massive apoptotic destruction of the tumors. The invention also provides for the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.

Abstract: Isolated DNA encoding a protein or polypeptide having at least one biological activity of a vertebrate fringe protein, as well as the protein or polypeptide encoded thereby, are described. Assays for identifying agents which alter the expression of the described fringe genes and assays for agents which alter the production of angiogenic precursors, the formation of the apical ectodermal ridge and the subdivisions of the neural tube are also described.

Abstract: A method of regulating long term memory is disclosed. Also disclosed is isolated DNA encoding a cyclic 3',5'-adenosine monophosphate responsive transcriptional activator, isolated DNA encoding an antagonist of cyclic 3',5'-adenosine monophosphate-inducible transcription, isolated DNA encoding an enhancer-specific activator, and isolated DNA encoding a nitric oxide synthase. A method for assessing the effect of a drug on long term memory formation is also disclosed.

Abstract: A DNA comprises an oligonucleotide antisense to mRNA encoding an adenosine A.sub.1 or A.sub.3 receptor. The oligo is provided as a composition, various formulations, a capsule, and cartridge and in the form of a kit. The oligonucleotide of the invention is effective for reducing bronchoconstriction and/or allergy, and may be administered to a subject to treat respiratory ailments such as asthma and other conditions associated with the expression of adenosine receptors.

Abstract: The present invention is directed to a method of detecting persistent hyperinsulinemic hypoglycemia of infancy comprising obtaining a sample comprising patient nucleic acids from a patient tissue sample; amplifying sulfonylurea receptor specific nucleic acids from said patient nucleic acids to produce a test fragment; obtaining a sample comprising control nucleic acids from a control tissue sample; amplifying control nucleic acids encoding wild type sulfonylurea receptor to produce a control fragment; comparing the test fragment with the control fragment to detect the presence of a sequence difference in the test fragment, wherein a difference in said test fragment indicates persistent hyperinsulinemic hypoglycemia of infancy. A diagnostic kit and primers for the detection of persistent hyperinsulinemic hypoglycemia of infancy are also within the scope of the present invention.

Abstract: The novel gene, Rasp-1, which is up-regulated in regenerating liver, is disclosed. The novel RASP-1 protein, which is encoded by the Rasp-1 gene, is also disclosed. In addition, antibodies against the Rasp-1 gene products are also disclosed. Furthermore, the use of Rasp-1 nucleic acid sequences, Rasp-1 gene products, and antibodies against Rasp-1 gene products in the treatment and diagnosis of liver disorders is also disclosed.

Abstract: A target-specific gene delivery system is made of enzymatically degradable gelatin and nucleic acids (DNA or RNA) microparticles with a linking moiety or a targeting ligand attached to the surface. The delivery system can be made by a simple method. Targeting ligands can be attached to the microparticle directly or via a linking moiety. The linkage design allows the attachment of any molecule onto the microparticle surface including antibodies, cell adhesion molecules, hormones and other cell-specific ligands.

Abstract: A method of reducing bronchoconstriction in a subject in need of such treatment is disclosed. The method comprises administering to the subject an antisense oligonucleotide molecule directed against the A.sub.1 or A.sub.3 adenosine receptor in an amount effective to reduce bronchoconstriction. The method is useful for treating patients afflicted with asthma. Pharmaceutical formulations are also disclosed.

Abstract: A composition for the transfection of higher eucaryotic cells, comprising complexes of nucleic acid, a substance having an affinity for nucleic acid and optionally an internalizing factor, contains an endosomolytic agent, e.g. a virus or virus component, which may be conjugated. The endosomolytic agent, which is optionally part of the nucleic acid complex, is internalized into the cells together with the complex and releases the contents of the endosomes into the cytoplasm, thereby increasing the gene transfer capacity. Pharmaceutical preparations, transfection kits and methods for introducing nucleic acid into higher eucaryotic cells by treating the cells with the composition are also disclosed.

Abstract: The present invention provides novel recombinant nucleic acid vectors which may be used to produce .alpha.-globin as well as other proteins of interest in quantity in the red blood cells of transgenic animals or cell cultures of erythroid lineage. The present invention also provides for the transgenic animals which contain these recombinant nucleic acid vectors. The vectors of the invention comprise at least one of the major DNase I hypersensitivity sites associated with the .beta.-globin locus together with a gene of interest. According to various embodiments of the invention, the vectors may be used to create transgenic animals or to transfect cells in culture. In a specific embodiment of the invention, a vector which comprises two DNase I hypersensitivity sites together with the human .alpha.-globin gene is used to create transgenic animals which produce human .alpha.-globin protein in erythroid tissues, including red blood cells.

Abstract: A protein having polysialyl transferase activity, which a) is a product of a prokaryotic or eukaryotic expression of an exogenous DNA, b) is coded by the DNA sequence shown in SEQ ID No. 1, c) is coded by the DNA sequences which hybridize with the sequences SEQ ID No. 1 and/or SEQ ID No. 3, d) is coded by DNA sequences which if there was no degeneracy of the genetic code, would hybridize with the sequences defined in b) to c), and e) catalyzes the polycondensation of .alpha.-2,8-linked sialic acids, and its related nucleic acid molecules and fragments are useful for the production of therapeutic agents for tumor therapy.

Abstract: A chimeric, non-human, genetically-immunocompetent mammal is disclosed. The hematopoietic system of the mammal has human passaged bone marrow stromal cells and human hematopoietic stem cells obtained from a CD34.sup.+ -enriched bone marrow fraction, and also contains transplanted syngeneic non-lymphoid spleen colony cells. The mammal may be a mouse, a rat, a rabbit, a cat, a dog, a pig, a sheep or a non-human primate. The mammal can be produced by providing a non-human, genetically-immunocompetent mammal in which its immunologic genotype comports with the norm for the species of the mammal, exposing the mammal to a level of x- or gamma-radiation that is sufficient to destroy substantially all bone marrow in the mammal to render the mammal phenotypically immunodeficient, then transplanting into the mammal syngeneic non-lymphoid spleen colony cells and human passaged bone marrow stromal cells, and transplanting into the mammal human hematopoietic stem cells obtained from a CD34.sup.

Abstract: The present invention provides a novel family of apoptosis-modulating proteins. Nucleotide and amino acid residue sequences and methods of use thereof are also provided.

Abstract: Human fibroblast cells that comprise a gene construct that comprises a duplication mutated fibrillin 1 gene operably linked to functional regulatory elements and compositions comprising such cells are disclosed. Methods of treating wounds and kits for practicing such methods are disclosed. Transgenic animals comprising a duplication mutated fibrillin 1 gene operably linked to a tissue specific and/or inducible promoter are disclosed. Methods of identifying individuals with a duplication mutated fibrillin 1 gene are disclosed. The methods comprises detecting a duplication of exons 17-40 of a fibrillin 1 gene or a gene product produced by expression of a duplication mutated fibrillin 1 gene. Methods of preventing expression of a duplication mutated fibrillin 1 gene are disclosed.

Abstract: A novel protein associated with multidrug resistance in living cells and capable of conferring multidrug resistance on a cell is disclosed. Nucleic acids encoding the novel multidrug resistance protein are also disclosed. Transformant cell lines which express the nucleic acid encoding the novel protein are also disclosed. Antibodies which bind the novel multidrug resistance protein are also disclosed. Diagnostic and treatment methods using the novel proteins, nucleic acids, antibodies and cell lines of the invention are also encompassed by the invention.