Abstract: Laboratory non-human animals in which the immune system of a donor is induced in and thrives in vivo and expresses the immune response of the donor animal in a recipient non-human animal of a different species than the donor, and wherein malignant immune system cells of the donor can be induced in the recipient non-human animal by injection of non-malignant donor into the recipient are disclosed.

Abstract: A method for the direct treatment towards the specific sites of a disease is disclosed. This method is based on the delivery of proteins by catheterization to discrete blood vessel segments using genetically modified or normal cells or other vector systems. Endothelial cells expressing recombinant therapeutic agent or diagnostic proteins are situated on the walls of the blood vessel or in the tissue perfused by the vessel in a patient. This technique, provides for the transfer of cells or vectors and expression of recombinant genes in vivo and allows the introduction of proteins of therapeutic or diagnostic value for the treatment of diseases.

Abstract: Methods useful for the determination of oligomers which have specific activity for a target molecule from a pool of primarily randomly assembled oligomers are provided. The disclosed methods involve repeated syntheses of increasingly simplified sets of oligomers coupled with selection procedures for determining oligomers having the highest activity. Freedom from the use of enzymes allows the application of these methods to any molecules which can be oligomerized in a controlled fashion.

Abstract: The invention provides a method and materials for sorting polynucleotides with oligonucleotide tags. Oligonucleotide tags of the invention are capable of hybridizing to complementary oligomeric compounds consisting of subunits having enhanced binding strength and specificity as compared to natural oligonucleotides. Such complementary oligomeric compounds are referred to herein as "tag complements." Subunits of tag complements may consist of monomers of non-natural nucleotide analogs, referred to herein as "antisense monomers" or they may comprise oligomers having lengths in the range of 3 to 6 nucleotides or analogs thereof, including antisense monomers, the oligomers being selected from a minimally cross-hybridizing set. In such a set, a duplex made up of an oligomer of the set and the complement of any other oligomer of the set contains at least two mismatches.

Abstract: Disclosed are improved methods for detecting protein-protein interactions. These methods involve either a determination of whether three or more proteins are capable of interacting in a trimeric or higher order complex or whether two or more mammalian proteins interact, the latter method utilizing yeast mating to bring candidate proteins into contact with one another.

Abstract: A vector system comprising a first vector, which is an adeno-associated viral vector, and which includes an adeno-associated virus 5'ITR, an adeno-associated virus 3'ITR, and at least one heterologous DNA sequence. The vector system also includes a second vector which includes an inducible origin of replication, such as an SV40 origin of replication, which is capable of being induced or activated by an agent, such as the SV40 T-antigen. The second vector also includes DNA sequences encoding the adeno-associated virus rep and cap proteins. When induced by an agent, the second vector may replicate to a high copy number, and thereby increased numbers of infectious adeno-associated viral particles may be generated.

Abstract: The present invention provides rapid, reproducible procedures for generating chromosome region-specific probes (CRSPs) for diagnostic and research applications. Region-specific probes are provided by direct in vitro enzymatic amplification (PCR) of microdissected chromosomal or hybridized DNA from the chromosomal region of interest, followed by labelling for in situ hybridization to metaphase chromosomes and interphase nuclei. CRSP specificity can be further enhanced using a linker-based strategy, wherein linkered DNA (LDNA) sequences prepared from DNA libraries are hybridized to chromosomal DNA in situ, microdissected from the chromosomal region of interest and then directly amplified using the linker as primer. These procedures make it possible to generate a vast number of chromosome region-specific probes without microchemical manipulation after dissection and provide means for identifying cryptic chromosomal alterations previously not amenable to routine cytogenetic analysis.

Abstract: The present invention is directed to a method for rapidly analyzing whether known genetic markers which are found in various lengths in the population, e.g., those containing (CA).sub.n repeats, are associated with a disease of interest. The method involves using polymerase chain reactions to amplify the DNA in the marker regions and comparing the amplified DNA lengths seen in the normal population with those seen in an affected population of persons. The method involves a pooling of DNA samples from normal patients to average out the normal marker genotype found in the population and also involves a pooling of DNA from affected individuals to give a summing effect to give a stronger signal. The amplified DNA fragments are labeled with two distinguishable markers such as two different colored fluorescent markers, one used to label the amplified DNA from the normal population and the other to label the amplified DNA from the affected population.

Abstract: A method for producing a mouse having a systemic malignant disease which mimics a human IL-2 expressing. T-cell malignancy, which includes administering to a mouse a mixture of passaged cells comprising cancer causing cells, the mixture having been rendered cancer causing by in vivo passage of tumor inducing cells in athymic mice.

Abstract: New nucleic acid sequences are provided which encode 3' untranslated regions of human protein kinase C.alpha.. Compositions and methods are provided for the treatment and diagnosis of diseases associated with protein kinase C.alpha.. Oligonucleotides are provided which are specifically hybridizable with nucleic acid encoding PKC.alpha.. Methods of treating animals suffering from disease amenable to therapeutic intervention by modulating protein kinase C expression with an oligonucleotide specifically hybridizable with RNA or DNA corresponding to PKC are disclosed. Polynucleotide probes for PKC.alpha. are also disclosed.

Abstract: A novel method of tumor immunotherapy is described comprising the genetic modification of cells resulting in the secretion of cytokine gene products to stimulate a patient's immune response to tumor antigens. In one embodiment, autologous fibroblasts genetically modified to secrete at least one cytokine gene product are utilized to immunize the patient in a formulation with tumor antigens at a site other than an active tumor site. In another embodiment, cells genetically modified to express at least one tumor antigen gene product and to secrete at least one cytokine gene product are utilized in a formulation to immunize the patient at a site other than an active tumor site.

Abstract: The present invention concerns yeasts of the genus Kluyveromyces having one or more genetic modifications of at least one gene coding for a protease, said gene reducing or modifying the proteolytic actively of said yeasts, as well as their use as a cellular host for the secretion of recombinant proteins.

Abstract: A novel method of tumor immunotherapy is described comprising the genetic modification of cells resulting in the secretion of cytokine gene products to stimulate a patient's immune response to tumor antigens. In one embodiment, autologous fibroblasts genetically modified to secrete at least one cytokine gene product are utilized to immunize the patient in a formulation with tumor antigens at a site other than an active tumor site. In another embodiment, cells genetically modified to express at least one tumor antigen gene product and to secrete at least one cytokine gene product are utilized in a formulation to immunize the patient at a site other than an active tumor site.

Abstract: Expression of proteins in filamentous fungal hosts is achieved in the presence of glucose using promoter variants in which creA binding sites are functionally disrupted.

Abstract: Novel methods are provided for producing rabbit fusion partners for the production of specific binding proteins, particularly immunoglobulins. Nuclei of rabbit fertilized ova are microinjected with an oncogene to express specifically in lymphoid cells (i.e., lymphoid specific) and the embryos are then implanted in appropriate hosts. The newborns are maintained to sexual maturity and are either mated with rabbit hosts that developed from embryos that had been microinjected with a different lymphoid-specific oncogene or their fertilized eggs are microinjected with another oncogene specific for lymphoid cells. The immortalized lymphoid cells that develop in these animals may be genetically altered and used as fusion partners to produce rabbit hybridomas for the production of monoclonal antibodies.

Abstract: Novel dividing cells of the yeast Saccharomyces. A first portion of dividing yeast cells is transformed with DNA encoding superoxide dismutase protein and DNA encoding catalase protein, and a second portion of yeast cells is not transformed with DNA grown at the same cell density as the first portion. When both portions of cells are heated in the presence of oxygen containing gas to a temperature of 50 degrees Celsius and are maintained at such temperature for 20 minutes, at least twice as many cells of the first portion of cells survive.

Abstract: The present invention is directed to an assay system, a kit and a process for detecting at least one short tandem repeat sequence from DNA at a specific locus utilizing an allelic ladder containing at least two short tandem repeat sequences of the same lengths as two or more known alleles for the locus.

Abstract: A mouse model for transplant arteriosclerosis useful for identifying compounds which reduce or prevent such arteriosclerosis, consisting of a mouse engrafted with a histoincompatible artery which exhibits detectable arteriosclerosis within 30 days of transplantation. Also disclosed are therapeutic methods for inhibiting the development of transplant arteriosclerosis in mammalian recipients of allografted organs.

Abstract: Methods useful for the determination of oligomers which have specific activity for a target molecule from a pool of primarily randomly assembled subunits are provided. The disclosed methods involve repeated syntheses of increasingly simplified sets of oligomers coupled with selection procedures for determining oligomers having the highest activity. Freedom from the use of enzymes allows the application of these methods to any molecules which can be oligomerized in a controlled fashion.

Abstract: Biological effects of agents for diagnostic or therapeutic use are evaluated by administration of the agents to transgenic animals which are transformed with heterologous DNA and which are immune tolerant to the expression product of the heterologous DNA. In a further embodiment, preparations that are immunogenic in the transgenic animal model are purified by reverse immunoaffinity chromatography on antibody obtained from responding transgenic animals.