Abstract: Modified oligonucleotides 3'-NHP(O)(O.sup.-)O-5' phosphoramidates were synthesized on a solid phase support. The phosphoramidate analogs were found to have significantly increased resistance toward phosphodiesterase digestion. Thermal dissociation experiments demonstrated that these compounds form more stable duplexes than phosphodiesters with complementary DNA and particularly RNA strands. Further, the phosphoramidate analogs can also form stable triplexes with double-stranded DNA target, where under similar conditions parent phosphodiester compounds failed to do so.

Abstract: Invertebrate and vertebrate patched genes are provided, including the mouse and human patched genes, as well as methods for isolation of related genes, where the genes may be of different species or in the same family. Having the ability to regulate the expression of the patched gene, allows for the elucidation of embryonic development, cellular regulation associated with signal transduction by the patched gene, the identification of agonist and antagonist to signal transduction, identification of ligands for binding to patched, isolation of the ligands, and assaying for levels of transcription and expression of the patched gene.

Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of cardiovascular disease, including, but not limited to, atherosclerosis, ischemia/reperfusion, hypertension, restenosis, and arterial inflammation. Specifically, the present invention identifies and describes genes which are differentially expressed in cardiovascular disease states, relative to their expression in normal, or non-cardiovascular disease states, and/or in response to manipulations relevant to cardiovascular disease. Further, the present invention identifies and describes genes via the ability of their gene products to interact with gene products involved in cardiovascular disease. Still further, the present invention provides methods for the identification and therapeutic use of compounds as treatments of cardiovascular disease.

Abstract: This invention relates to human galactokinase and the identification of galactokinase mutations, a missense and nonsense, as well as isolated nucleic acids encoding same, recombinant host cell transformed with DNA encoding such proteins and to uses of the expressed proteins and nucleic acid sequences in therapeutic and diagnostic applications.

Abstract: The present invention includes yeast vehicles and their use as delivery vehicles. Yeast vehicles include a yeast portion and a heterologous compound. Such yeast vehicles can be used to protect animals from disease and to otherwise carry compounds to given cell types. Examples of yeast vehicles include gene delivery vehicles, drug delivery vehicles, and immunomodulatory vehicles. Immunomodulatory vehicles are capable of modulating an immune response. When stimulating an immune response, such yeast vehicles effect cell-mediated as well as humoral immunity.

Abstract: The invention is based on the discovery of a pharmaceutical preparation for use in gene therapy which includes a therapeutic nucleic acid associated with Insulin-NHCO--CH.sub.2 --O--N.dbd.CH--C-Lys.sub.18 -Cys(S-Pyridyl)-OH in combination with a pharmaceutically acceptable carrier.

Abstract: A DNA sequence encoding insulin receptor substrate 1 (IRS-1), the DNA sequence containing a mutation of at least one nucleotide, and the protein encoded by said DNA sequence.

Abstract: This invention discloses novel methods of making fermented food products such as yogurt. It also discloses novel Lactobacillus bulgaricus organisms for making fermented food products which are conditionally sensitive, that is, operate to metabolize a desired compound normally under the processing conditions for fermented food products but slow or decrease in activity beyond what is normal under the routine storage temperatures for the fermented food products. Such fermented food products exhibits improved shelf life and long-term taste.

Abstract: Disclosed in this invention is a transgenic mouse containing rcombinant DNA including a promoter and a heat shock protein 70 gene attached to downstream of the promoter. Transgenic mice line inducing non-insulin dependent diabetes having a blood glucose level of 300 mg/dl was obtained.

Abstract: One aspect of the invention relates to a phage-display library that expresses single-chain recombinant binding proteins. Inserts in the library comprise immunoglobulin heavy chain framework regions flanking highly divergent, synthetically produced hypervariable regions. A second aspect of the invention relates to the use of single-chain recombinant binding proteins to inhibit the activity of an intracellular constituent. In the exemplary case presented, the activity of intracellular glucose-6-phosphate dehydrogenase was inhibited by intracellular expression of a cloned single-chain recombinant binding protein.

Abstract: Recombinant transgenic mice expressing leukemia inhibitory factor (LIF) in the pituitary. The transgenic mice of the invention are suitable for use as animal models of pituitary disorders, as well as for identifying compounds which stimulate growth hormone production, for the treatment of physiological disorders associated with growth retardation and pituitary developmental retardation disorders, such as chraneopharyngioma, and pituitary cysts, among others.

Abstract: Medicaments and methods of using the same are disclosed for treating or preventing diseases resulting from undesirable cell adhesion of IL-1 receptor positive cells to biological materials, particular to endothelial cells, or autoimmune related diseases, preferably graft versus host disease, or IL-1 dependent cancers.

Abstract: The present invention relates to novel adenovirus vectors for use in gene therapy which are designed to prevent the generation of replication-competent adenovirus (RCA) during in vitro propagation and clinical use. The invention also provides methods for the production of the novel virus vectors. These vectors maximize safety for clinical applications in which adenovirus vectors are used to transfer genes into recipient cells for gene therapy.

Abstract: The present invention provides a method for diagnosing BS as well as determining whether a subject is a carrier of a mutated BLM gene. The present invention also provides one or more single-stranded nucleic acid probes and antibodies which may be formulated in kits, and used for diagnosing BS or determining whether a subject is a carrier of a mutated BLM gene. In addition, the present invention provides a method for treating or preventing the onset of BS in a subject in need of such treatment or prevention, as well as vectors and stem cells useful for such treatment or prevention. The present invention also provides a purified and isolated nucleic acid encoding an enzymatically active BLM protein, a vector comprising this nucleic acid, a cell stably transformed with this vector, as well as a method for producing recombinant, enzymatically active BLM protein. A purified, enzymatically active BLM protein is also provided by the present invention.

Abstract: A method of obtaining an oligonucleotide capable of carrying out a predetermined biological function. A heterogeneous pool of oligonucleotides, x+y+z nucleotides in length, is first generated. Each oligonucleotide has a 5' randomized sequence, x nucleotides in length, a central preselected sequence, y nucleotides in length, and a 3' randomized sequence, z nucleotides in length. The resulting heterogeneous pool contains nucleic acid sequences representing a random sampling of the 4.sup.x+z possible sequences for oligonucleotides of the stated length. A random sampling of the heterogeneous pool of oligonucleotides is introduced into a population of cells that do not exhibit the predetermined biological function. The population of engineered cells is then screened for a subpopulation of cells exhibiting the predetermined biological function. From that subpopulation of cells is isolated an oligonucleotide containing the preselected sequence and capable of carrying out the predetermined biological function.

Abstract: A vector plasmid containing(a) the OriA region of plasmid pBA1 derived from Anacystis nidulans,(b) the multicloning region and(c) the region of colicin E1 plasmid, which contains the OriE region thereof and wherein the gene defined by the rop region thereof is removed.This plasmid is replicable in the cells of both Escherichia coli and cyanobacteria and thus useful as a shuttle vector.

Abstract: A method is provided for targeting a diagnostic agent for delivery to a folate receptor-bearing cell of an animal. The method comprises the step of administering to an animal a composition comprising a diagnostic agent complexed with a targeting ligand selected from the group consisting of folate, folate receptor-binding analogs of folate, or other folate receptor-binding ligands.

Abstract: The present invention relates to a method for the preparation of a protein by yeasts, according to which:yeast cells which contain the following are cultured:a DNA sequence coding for the protein under the control of elements providing for its expression in yeasts, the elements comprising a transcription control sequence which is inducible by a complex formed by a receptor and a ligand,a DNA sequence which is functional in yeast, coding for the receptor, the receptor comprising two essential portions, one of which recognizes the ligand so as to form a complex with the ligand and the other binds to the said transcription control sequence; the portion of the receptor which recognizes the ligand is of higher eukaryotic origin, and the ligand is not necessary for the culturing of the cells but is capable of entering the cells when added to the culture medium,the ligand is added to the culture medium at an appropriate time point for induction,the synthesized protein is recovered.

Abstract: A transgenic, non-human animal is provided which overexpresses a gene responsible for the accumulation of monocytes and leukocytes. The animal is preferably a mammal and more preferably a mouse, rat or guinea pig. The transgenic animal is created by artificially inserting a transgene into a fertilized egg of the animal which egg is then inserted within a pseudo pregnant female where it is allowed to grow. The transgene preferably expresses human Monocyte Chemoattractant Protein-1 (MCP-1) and more preferably overexpresses MCP-1 in type II pulmonary epithelial cells. The invention includes DNA constructs and vectors containing the constructs with a particularly preferred vector being SPC-MCP-1. The plasmid SPC-MCP-1 includes a promoter operatively linked to a human MCP-1 coding sequence. The transgenic animal provides a useful animal model for testing drugs for their efficacy with respect to the treatment of diseases and conditions which result in an acceptable high accumulation of monocytes and/or lymphocytes.

Abstract: Avian diseases, particularly those which threaten birds early in life, are controlled by embryonal vaccination using water-in-oil-in-water emulsion vaccines. The site of inoculation is the albumin end of the egg via entry through the air cell end of the egg.