Abstract: TSG101 is a tumor susceptibility gene whose homozygous functional knock out in fibroblasts leads to transformation and the ability of these cells to form metastatic tumors in nude mice. The cellular transformation that results from inactivation of TSG101 is reversible by restoration of TSG101 function. Decreased expression of TSG101 is associated with the occurrence of certain human cancers, including breast carcinomas. The TSG101 nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as treatment of cancer, identification of cell type based on expression, and the like.

Abstract: Disclosed are synthetic and "humanized" versions of green fluorescent protein (GFP) genes adapted for high level expression in mammalian cells, especially those of human origin. Base substitutions are made in various codons in order to change the codon usage to one more appropriate for expression in mammalian cells. Recombinant vectors carrying such humanized genes are also disclosed. In addition, various methods for using the efficient expression of humanized GFP in mammalian cells and in animals are described.

Abstract: Continuous cultures of pluripotent parenchymal hepatocytes were derived from the epiblasts of pig blastocysts. The cultures are feeder-dependent and grow slowly with doubling times of 3 to 4 days. They differentiate into large secretory duct-like structures or form small canaliculi. In combination with feeder cells and, optionally, adult pig hepatocytes and macrophages, the cells are useful in an artificial liver device which may be utilized as temporary liver support for the mitigation of the pathological effects of liver failure.

Abstract: Recombinant retroviruses carrying a vector construct capable of preventing, inhibiting, stabilizing or reversing infectious, cancerous or auto-immune diseases are disclosed. More specifically, the recombinant retroviruses of the present invention are useful for (a) stimulating a specific immune response to an antigen or a pathogenic antigen; (b) inhibiting a function of a pathogenic agent, such as a virus; and (c) inhibiting the interaction of an agent with a host cell receptor. In addition, eucaryotic cells infected with, and pharmaceutical compositions containing such a recombinant retrovirus are disclosed. Various methods for producing recombinant retroviruses having unique characteristics, and methods for producing transgenic packaging animals or insects are also disclosed.

Abstract: The present invention relates to chimeric viruses, the replication of which is regulated by a transactivation signal produced by diseased host cells. The chimeric viruses of the invention can infect both normal and diseased host cells. However, the chimeric virus replicates efficiently in and kills diseased host cells that produce the transactivation signal. The use of such chimeric viruses to treat infectious diseases and cancers are described. A particularly useful embodiment involves the modification of a murine parvovirus that infects human T cells to generate a chimeric parvovirus that is cytocidal to human T cells that express HIV-tat. The chimeric parvovirus can be used to treat HIV-infection.

Abstract: Methods of controlling the in vivo and in vitro expression of a heterologous protein by transfecting a cell with a first nucleic acid encoding the heterologous polypeptide, wherein at least one codon of mRNA transcribed from the first nucleic acid is replaced by the codon UGA, and a second nucleic acid operably linked to the first nucleic acid, the second nucleic acid directing the translation of the UGA codon as selenocysteine only when the cell can obtain selenium from the medium in which it is grown; and growing the cell under conditions in which the production of the polypeptide is controlled by the level of selenium available to the cell.

Abstract: The present invention is an isolated and purified DNA sequence which encodes a vertebrate mRNA for a neuron specific protein, neuronatin. The mRNA is selectively expressed in brain tissue during rapid brain growth when there is a surge in neuronal proliferation and migration and is repressed in adult tissue. In the human, the genomic DNA is as set forth in SEQ ID No:6 and the cDNA has a nucleotide sequence as set forth in SEQ ID No:5, with the gene mapped to human chromosome 20q11.2-12. The deduced protein is a proteolipid that appears to have a role in ion channel regulation during brain development.

Abstract: The invention describes a novel method for determining the mass of vital tumor cells of xenotransplants in animal models. Cells altered by genetic engineering which form a tumor after transplantation synthesize an excreted reporter gene. This is shown by way of example for a secreted form of human placenta-specific, alkaline phosphate (SEAP). The latter can be demonstrated in the serum of test animals or in culture supernatants. The activity of SEAP in the serum correlates with the number of vital tumor cells in the animal and can be measured prior to the formation of a palpable tumor. The invention shows the use of cell lines altered by genetic engineering in such a manner in subcutaneous and orthotopic tumor models. Dicistronic, eukaryotic expression vectors are used for the stable transfection of the mammalian cell lines or tumor cells used. These vectors contain, under the control of a constitutive or inducible promotor element, the gene coding for SEAP, coupled with a second gene.

Abstract: A process for production of a desired protein comprising the steps of:a culturing animal cells capable of producing the desired protein in a medium containing trichostatin compounds; andrecovering the desired protein from the culture.

Abstract: The invention relates to virally-encoded nucleic acid sequences derived from a region 5' to the transcriptional start site of the virus which contain at least one direct repeat of a fragment of a hormone-responsive element. In a preferred embodiment, the virus is murine mammary tumor virus, and the hormone-responsive element is a glucocorticoid responsive element.

Abstract: The present invention relates to a method and composition for topically administering a Smelophyllum capense extract as a cosmetic, dermatologic, or pharmaceutical composition to promote collagen synthesis. Administration of the composition results in the firming of the skin, improves healing and is suitable for treating various pathologies accompanied with a deficiency in collagen. The extract can also be added to cell culture medium used in the culture of skin cells, particularly skin fibroblasts. The composition can contain between 0.0001% and 1% by weight of the Smelophyllum capense extract, and the extract can be obtained by extraction with a polar solvent. The composition can contain other ingredients including ascorbic acid, madecassic acid, asiatic acid, madecassoside, asiaticoside, alpha-1-protease inhibitor, collagenase inhibitors, elastase inhibitors, lysine, proline, 2-oxoglutarate and ginsenoside Ro.

Abstract: A method for producing high level expression of neuropeptide receptors and stable cell lines useful therein. This method involves culturing a cell line containing amplified copies of a cDNA sequence encoding a neuropeptide receptor containing an expression control sequence taken from the .beta.-actin transcriptional control element.

Abstract: This invention provides methods, compositions and apparatus for increasing the transfection efficiency of target cells by particles, especially retroviral particles, compared with that achieved by current methods. The transfection method comprises depositing the particles on a cell growth support and contacting target cells with the particle-loaded cell growth support.

Abstract: The present invention provides isolated nucleic acids encoding human EHOC-1 protein and isolated receptor proteins encoded thereby. Further provided are vectors containing invention nucleic acids, probes that hybridize thereto, host cells transformed therewith, antisense oligonucleotides thereto and compositions containing, antibodies that specifically bind to invention polypeptides and compositions containing, as well as transgenic non-human mammals that express the invention protein.

Abstract: This invention provides a non-melanocytic eucaryotic cell constitutively expressing biologically active human tyrosinase. The present invention also provides methods of producing biologically active human tyrosinase. Additionally, the invention provides a non-melanocytic eucaryotic cell which constitutively expresses biologically active human tyrosinase which in turn catalyzes the production of melanin. The melanin so produced may then be recovered.

Abstract: A novel regulatable retroviral vector in which the v-myc oncogene is driven by a tetracycline-controlled transactivator and a human cytomegalovirus minimal promoter fused to tet operator sequence useful for immortalization of adult neuronal progenitor cells is provided. Regulation of a heterologous Producer cell lines which produce high titers of the recombinant retrovirus are also provided.

Abstract: A method of genetically engineering a cell line capable of detecting bioactive cytokines or growth factors is provided. Cells lines produced by this method and methods of using these cell lines to detect bioactive cytokines or growth factors in a biological fluid are also provided.

Abstract: The field of the invention is recombinant packaging and producer cell lines for producing infectious retroviral vectors. The invention more specifically relates to the generation of pseudotyped retroviral vectors with a broad host range which can be produced at high titers in specially constructed packaging cell lines. Most specifically, the invention relates to the generation of pseudotyped retroviral vectors having vesicular stomatitis virus-G protein (VSV-G) as the membrane-associated viral envelope protein.

Abstract: The invention proposes a packaging signal (psi) region of at most 400 nucleotides, capable of promoting encapsidation of a retroviral vector, which is substantially homologous to the 5' end of a murine viral-like cellular sequence of type VL30, as well as a retroviral vector comprising said psi region.

Abstract: This invention provides a novel murine cultured cell line which is derived from primary mouse embryo fibroblasts and which exhibits inducer-regulated growth kinetics. The cell line has the potential to grow either linearly or exponentially depending on exposure to an appropriate inducing agent. A corresponding cell line that does not respond to the inducing agent is also provided. The paired cell line system provides a valuable research tool for the development of therapeutic agents that target cells exhibiting deregulated growth kinetics, and also enables the identification of potential carcinogenic agents that alter stem cell renewal kinetics.

Abstract: Materials and methods are described for identifying signal transducing molecules which activate promoters, such as the human c-fos proto-oncogene promoter, as well as antagonists of such molecules. Also described are human c-fos promoter activating proteins, and in particular novel proteins, designated CROC-1 protein and CROC-4 protein, nucleic acids encoding said proteins, and mammalian cells transfected with vectors containing such nucleic acids.

Abstract: The present invention relates to a stably co-transfected eukaryotic cell line capable of expressing a GABA-A receptor, particularly a human GABA-A receptor, which receptor comprises at least one alpha, one beta and one gamma subunit; to the cloning of novel cDNA sequences encoding the .alpha.-2, .alpha.-3, .alpha.-5, .alpha.-6 and .beta.-2 subunits of the human GABA-A receptor; and to the use of the cell line in designing and developing GABA-A receptor subtype-selective medicaments.

Abstract: DNA segments have been discovered, and characterized by sequence, which are response elements operative to confer responsiveness to retinoic acid, or derivatives thereof, for the transcriptional activation of promoters in cells. By using transcriptional control regions comprising response elements of the present invention in combination with a functional promoter, it is now possible to provide recombinant DNA vectors containing a gene, the transcription (and, thereby, also expression) of which is under the control of a promoter, the transcriptional activity of which is responsive to (and increased by) retinoic acid or derivatives thereof.

Abstract: Neurogenic differentiation genes and proteins are identified, isolated, and sequenced. Expression of neuroD has been demonstrated in neural, pancreatic, and gastrointestinal cells. Ectopic expression of neuroD in non-neuronal cells of Xenopus embryos induced formation of neurons.

Abstract: A retroviral vector including a multiple cloning site having no greater than about 70 base pairs, and which includes at least four different enzyme restriction sites, wherein at least two of the sites have an average frequency of appearance in eukaryotic genes of less than one in 10,000 base pairs. Such vector may be employed in conjunction with a shuttle cloning vector having complementary cloning sites to accomplish transfers of genes and/or promoters between the shuttle cloning vector and the retroviral vector. Such a system provides for efficient transfer of genes and/or promoters to a retroviral vector without necessitating reconstruction of the entire retroviral vector. Also contemplated within the scope of the present invention is a retroviral vector having a 3' LTR wherein at least the promoter sequence of the 3' LTR is mutated such that the promoter sequence becomes nonfunctional.

Abstract: The invention provides genetic suppressor elements that confer upon a cell resistance to one or more chemotherapeutic drug, methods for identifying and obtaining such elements, and methods of using such elements. The invention also provides cloned genes associated with sensitivity to chemotherapeutic drugs.

Abstract: The invention features a method for diagnosis of pancreatitis by detecting an elevation in the amount of GP2 pancreatic glycoprotein in a sample of bodily fluid such as human blood, serum, or urine. The invention also features isolated DNA encoding human GP2, a method for producing recombinant human GP2, antibodies which specifically bind to human GP2, a method for producing anti-human GP2 antibodies, and a kit for use in the diagnosis of pancreatitis.

Abstract: The present invention provides an isolated nucleic acid molecule encoding an 5-HT.sub.2 receptor, and an isolated protein which is a human 5-HT.sub.2 receptor.The invention also provides vectors comprising DNA molecules encoding a human 5-HT.sub.2 receptor, and vectors adapted for expression of the 5-HT.sub.2 receptor in bacterial, yeast, or mammalian cells.In addition, the invention provides a DNA probe useful for detecting nucleic acid encoding the 5-HT.sub.2 receptor, a method for determining whether a ligand which is not known to be capable of binding to the 5-HT.sub.2 receptor can bind to the 5-HT.sub.2 receptor, a method for detecting the presence of 5-HT.sub.2 receptor on the surface of a cell, and a method of screening drugs to identify drugs which specifically interact with, and bind to, the 5-HT.sub.2 receptor.The invention herein also concerns an antibody directed to the human 5-HT.sub.2 receptor, such as a monoclonal antibody directed to an epitope of the 5-HT.sub.

Abstract: A novel human protein tyrosine phosphatase (PTP) has been identified and its cDNA has been isolated. This novel PTP, denoted PTP-OB, has a receptor-like three dimensional structure and is present in osteoblasts. PTP-OB is involved in osteoblast differentiation, and modulators of PTP-OB activity in turn modulate osteoblast differentiation, osteoclast differentiation and osteoclast activity.

Abstract: Existing plasmids, such as pHaMDR/A (available from NIH) are large and cumbersome. The size may limit the known utility of MDR1 as an effective selectable marker in gene transfer experiments. The invention provides novel plasmids including heterologous promoters and cDNA sequences positioned between the retroviral LTRs.

Abstract: This invention provides for the cloning and expression of the human Macrophage Inflammatory Protein-1.alpha. (MIP-1.alpha.)/RANTES Receptor. This receptor binds two cytokines MIP-1.alpha. and RANTES which are pro-inflammatory cytokines. The receptor is useful for assaying the levels of these cytokines in biological specimens. These cytokines play key roles in the inflammatory processes afflicting man.

Abstract: The present invention relates to stably co-transfected eukaryotic cell lines capable of expressing a recombinant GABA.sub.A receptor, particularly a recombinant human GABA.sub.A receptor, which comprises at least one alpha, one beta and one gamma subunit; and to the use of the cell line and/or membrane preparation in selecting compounds and designing medicaments which interact with the respective human recombinant GABA.sub.A receptor.

Abstract: Disclosed herein are fully impaired consensus Kozak sequences which are most typically used with dominant selectable markers of transcriptional cassettes which are a part of an expression vector. These vectors are most typically utilized in the expression of proteins in mammalian expression systems. As defined, disclosed and claimed herein, a "fully impaired consensus Kozak" comprises the following sequence: ##STR1## where: Nat nucleotides 2,3,8 and 9 is a nucleotide selected from the group consisting of adenme (A), quanine (G), cytosine (C) or thymine (T)/uracil (U); Nat nucleotides 1 and 7 is a pyrimidine nucleotide, ie C or T/U; "ATG" is a codon encoding for the amino acid methionine, the so-called "start" codon; and -3 and +1 are directional reference points vis-a-vis ATG, ie -3 is meant to indicate three nucleotides upstream of ATG and +1 is meant to indicate one nucleotide downstream of ATG. Dominant selectable markers further comprising artificial intronic insertion regions are further disclosed.

Abstract: The present invention relates to the identification of novel nucleic acid molecules and proteins encoded by such nucleic acid molecules or degenerate variants thereof, that participate in the control of mammalian body weight. The nucleic acid molecules of the present invention represent the genes corresponding to the mammalian tub gene, a gene that is involved in the regulation of body weight.

Abstract: The present invention relates to the preparation of novel vector systems which are generated by in-vitro recombination, using gene technology, of nucleic acids from foamy virus species and of exogenous nucleic acid, and are produced by suitable host cells or by recombinantly altered packaging cell lines. The recombinant preparation of particularly suitable packaging cell lines is likewise a constituent of this invention. The invention is distinguished by the safe and efficient transfer by foamy virus vectors of therapeutic and other genes into eukaryotic cells.

Abstract: Serine proteases of the chymotrypsin superfamily are modified so that they exhibit resistance to serine protease inhibitors. If such modified serine proteases have fibrinolytic, thrombolytic, antithrombotic or prothrombotic properties, they are useful in the treatment of blood clotting diseases or conditions.

Abstract: Novel expression vectors are provided for expressing a fusion glycoprotein. The fusion glycoprotein contains the N-terminal globular domain of a retroviral env surface protein linked to a selected glycopeptide. Truncation glycoproteins as well as insertion glycoproteins are expressed using the vectors.

Abstract: The present invention provides novel human polynucleotide sequences and the recombinant human double-stranded RNA adenosine deaminase enzyme (DRADA) proteins encoded thereby and methods of use thereof.

Abstract: A transformant, which harbors a recombinant vector containing a DNA which codes for human nerve growth factor 2 and a DNA which codes for the pro-region of a nerve growth factor at 5'-terminal of said DNA, produces human nerve factor 2 in stable and large amount in a culture medium.

Abstract: A human oxalyl-CoA decarboxylase polypeptide and DNA(RNA) encoding such polypeptide and a procedure for producing such polypeptide by recombinant techniques and for producing an antibody against such polypeptide are disclosed. Also disclosed is a combination of the polypeptide of the present invention and a suitable pharmaceutical carrier for providing a therapeutically effective amount of the polypeptide for the treatment of urolithiasis and hyperoxaluria. Also disclosed are assays for identifying mutations in nucleic acid sequence encoding a polypeptide of the present invention and for detecting altered levels of the polypeptide of the present invention.

Abstract: The present invention relates to compositions for the diagnosis, prevention and treatment of tumor progression. Novel nucleic acid molecules are identified that are expressed at higher levels in benign (e.g., non-malignant) tumor cells compared to malignant tumor cells exhibiting a high metastatic potential. The nucleic acids and cells including these nucleic acids can be used diagnostically or for therapeutic intervention.

Abstract: Methods and compositions for the conditional immortalization of cells are provided.

Abstract: Retroviruses are used as genetic tools to isolate transcriptionally active chromosomal regions. The retroviruses have a promoterless protein coding sequence located in U3 or U5. The retroviruses may be used to infect cells under conditions which permit selection for instances when the retrovirus integrates in close proximity to and under the control of a cellular promoter. The promoter and its associated gene then may be identified and isolated. In this manner, the retroviruses function as promoter-traps. Related methods and products including vectors, kits and assays are provided.

Abstract: Chimeric complement inhibitor proteins are provided which include a first functional domain (first amino acid sequence) having C3 inhibitory activity and a second functional domain (second amino acid sequence) having C5b-9 inhibitory activity. The first functional domain is amino terminal to the second functional domain. In this way, the chimeric protein exhibits both C3 and C5b-9 inhibitory activity. The other orientation, i.e., the orientation in which the second amino acid sequence is amino terminal to the first amino acid sequence, only produces C3 inhibitory activity. Nucleic acid molecules encoding such proteins are also provided.

Abstract: Disclosed are (1) a DNA sequence encoding a mutant L3T4 protein which, when expressed on the surface of a cell, is capable of facilitating infection of the cell by human immunodeficiency virus; the mutant protein includes at least one amino acid residue substitution or deletion in a segment corresponding to the gp120 binding epitope of a native L3T4 protein so as to increase homology between that segment and its counterpart in a CD4 protein; (2) a murine cell line or strain transfected with such a DNA sequence; and (3) a transgenic rodent susceptible to infection by human immunodeficiency virus.

Abstract: An oligonucleotide comprising the DNA sequence TTTCCNGGAAA (SEQ ID NO:1) in single stranded or double stranded form, or a derivative thereof, binds to transcriptional regulatory proteins induced by cytokines, growth factors or hormones. Such oligonucleotides are useful in detecting, identifying or purifying transcriptional regulatory proteins. Recombinant DNA constructs comprising the oligonucleotide sequence operably linked to a promoter and a reporter DNA sequence and cells transfected therewith are also disclosed. Also disclosed are DNA-binding proteins other than p91 which are inducible in a cell by a cytokine, growth factor or hormone, and which, when tyrosine phosphorylated, bind to the above oligonucleotide DNA sequence.

Abstract: Neurotransmission by excitatory amino acids (EAAs) such as glutamate is mediated via membrane-bound surface receptors. DNA coding for one family of these receptors, of the kainate binding type of EAA receptors, has now been isolated and the receptor protein characterized. Herein described are recombinant cell lines which produce the EAA receptor as a heterologous membrane-bound product. Also described are related aspects of the invention, which are of commercial significance. Included is use of the cell lines as a tool for discovery of compounds which modulate EAA receptor stimulation.

Abstract: A partial murine cDNA clone and a human cDNA clone, each encoding a c-Myc interacting polypeptide termed MIP-99, are provided. Also provided are methods of using the nucleic acid sequences, polypeptides, and antibodies directed against same in the diagnosis and treatment of cancers and hyperplastic disease states.

Abstract: A novel receptor-type protein tyrosine phosphatase-.beta. (RPTP.beta.) protein or glycoprotein, and the DNA coding therefor is disclosed. This protein is naturally expressed in the brain and in neural cell lines. The RPTP.beta. protein or glycoprotein may be produced by recombinant means. Antibodies to the protein, methods for measuring the quantity of the protein, methods for screening compounds, such as drugs, which can bind to the protein and inhibit or stimulate it phosphatase enzymatic activity, are provided.