Abstract: The present invention provides methods for inducing insulin gene expression in cultured pancreas cells, the method comprising contacting a culture of endocrine pancreas cells expressing a PDX-1 gene with a GLP-1 receptor agonist, wherein the cells have been cultured under conditions such that the cells are in contact with other cells in the culture, thereby inducing insulin gene expression in the ceils. The invention also provides methods of treating a diabetic human subject using the methods of the invention.

Abstract: The present invention relates to improved continuous (immortalized) cell lines, in particular keratinocytes and melanocytes derived from normal human skin tissue. The present invention also relates to novel serum-free media for isolating, producing and maintaining said improved continuous keratinocyte and melanocyte cell lines. The present invention also relates to methods for producing primary melanocytes and keratinocytes under serum-free conditions without any feeder cells.

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 sit-directed mutagenesis of this promoter reveal two negative and one positive element. The positively acting sequence includes one functional E-box.

Abstract: The invention features apoptosis-resistant, non-transformant immortalised avian cells, in particular, avian tissues, i.e., other than blood or haematopoietic cells, particularly fibroblasts and epithelial cells, for instance embryos.

Abstract: A human keratinocyte cell line immortalized by at least one functional tumor gene of DNA viral origin characterized in that it is: (1) non-tumorigenic, (2) conserves the capacity for differentiation and for the expression of proteins and of enzymes expressed by normal differentiated keratinocytes even after an elevated number of passages in culture; and (3) forms a stratified and polarized epithelium having a stratum corneum ortho-keratinocyte, if cultivated in an organo-typical culture in a medium without serum and without a layer of nourishing cells. An improved process to immortalize human skin cells to obtain immortalized keratinocytes. Also, the use of keratinocytes for immunological, pharmacological, photo- and chemical-toxicological analyzes of skin reaction and for expression of heterologous genes and for the construction of artificial skin.

Abstract: Described is a process for generating a mammalian cell line from primary mammalian cells, comprising the step of: a) pre-treating a culture of said primary mammalian cells or a suspension thereof with at least one glucocorticoid, b) optional step comprising obtaining a suspension of said pre-treated culture of step a), c) transferring into the pre-treated cells of the suspension of step a) or b) at least one nucleic acid vector which is not of retroviral origin and which is competent to immortalize said pre-treated cells and d) culturing the transferred cells of step c). Furthermore, mammalian cell lines and cells obtainable by the described process are provided as well as pharmaceutical and diagnostic compositions containing such cells.

Abstract: Methods, transformation constructs, and transgenic animals for identifying anti-tumor agents and anti-tumor drug targets are described. The transformation constructs are used to generate transgenic animals that have altered expression of an oncogene or tumor suppressor gene in a target tissue that is dispensable for viability and reproduction. In some embodiments, the altered expression results in abnormal proliferation of the target tissue and normal proliferation in all other tissues. Anti-tumor drug targets can be identified by generating progeny of the transgenic animals that have mutations in various genes. Gene mutations that result in a specific reduction or killing of the target tissue are identified as possible anti-tumor drug targets and are further evaluated. Anti-tumor agents are identified that mimic the effect of the gene mutations that result in specific reduction of the target tissue.

Abstract: The present invention relates to methods of immortalizing various primary cell cultures, including pituitary cells, neurons, beta islet cells, glial cells, corneal epithelial cells and follicular stellate cells. The primary cells are transfected with a vector containing an establishment oncogene, resulting in non-transformed immortalized cells. The primary cells and/or the subsequent immortalized cells are cultured in a defined media containing one or more environmental factor(s) that control the proliferation and/or differentiation of the cells.

Abstract: Methods and compositions for introducing a nucleic acid into the genome of at least one cell of a multicellular organism are provided. In the subject methods, a Sleeping Beauty transposon that includes the nucleic acid is administered to the multicellular organism along with a source of a Sleeping Beauty transposase activity. Administration of the transposon and transposase results in integration of the transposon, as well as the nucleic acid present therein, into the genome of at least one cell of the multicellular organism The subject methods find use in a variety of different applications, including the in vivo transfer of genes for use in, among other applications, gene therapy applications.

Abstract: The present invention relates to improved continuous (immortalized) cell lines, in particular keratinocytes and melanocytes derived from normal human skin tissue. The present invention also relates to novel serum-free media for isolating, producing and maintaining said improved continuous keratinocyte and melanocyte cell lines. The present invention also relates to methods for producing primary melanocytes and keratinocytes under serum-free conditions without any feeder cells.

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: Human middle ear epithelial cell lines permanently transformed by human papilloma viruses have been obtained. These cell lines are useful for the study of gene and protein expression in otitis media and the identification of chemical and biological agents that may be useful in the therapy of human otitis media and other diseases of the ear.

Abstract: The invention relates to a method for producing human cell lines and cell and cell-lines produced by such a method. The method comprising the use of precursor or undifferentiated cells treated with an immortalising agent which is susceptible to environmental conditions so as to provide for selective activation/deactivation of said immortalising agent and so selective activation of differentiation.

Abstract: The invention relates generally to compositions of and methods for obtaining and using a polypeptide other than BCL-2 that affects programmed vertebrate cell death. The invention relates as well to polynucleotides encoding those polypeptides, recombinant vectors carrying those sequences, the recombinant host cells including either the sequences or vectors, and recombinant polypeptides. The invention further provides methods for using the isolated, recombinant polypeptides in assays designed to select and improve substances capable of altering programmed cell death for use in diagnostic, drug design and therapeutic applications.

Abstract: The invention features apoptosis-resistant, non-transformant immortalised avian cells, in particular, avian tissues, i.e., other than blood or haematopoietic cells, particularly fibroblasts and epithelial cells, for instance embryos.

Abstract: Conditionally-immortalized human spinal cord cell lines are provided. Such cell lines, which may be clonal, may be used to generate neurons, including motoneurons. The cell lines and/or differentiated cells may be used for the development of therapeutic agents to prevent and treat a variety of spinal cord-related diseases and injuries. The cell lines and/or differentiated cells may also be used in assays and for the general study of spinal cord cell development and differentiation.

Abstract: The invention relates to a method for producing human cell lines and cell and cell-lines produced by such a method. The method comprising the use of precursor or undifferentiated cells treated with an immortalising agent which is susceptible to environmental conditions so as to provide for selective activation/deactivation of said immortalising agent and so selective activation of differentiation.

Abstract: T cells having a desired antigen specificity are stimulated by (a) introducing immortalizing genes into antigen-presenting cells in a manner permitting regulation of the expression and/or function of at least one of these genes to achieve conditionally immortalized antigen-presenting cells; (b) introducing a gene encoding the desired antigen into the immortalized cells in a manner permitting the antigen to be expressed after the expression and/or abolishment of the function of at least one of the immortalizing genes stops; (c) expanding the immortalized antigen-presenting cells by expression and/or functional activation of the immortalizing genes; (d) completing the proliferation of the immortalized antigen-presenting cells by stopping the expression and/or abolishing the function of at least one of the controllable immortalizing genes; (e) continuing the expression of the antigen; (f) adding leucocytic cells including T cells and cultivating the cell mixture to stimulate the T cells directed against the desi

Abstract: Immortalized cell lines from human adipose tissue, process for preparing same and applications thereof as a study model for the physiopathology of the metabolism and particularly for obesity and diabetes, as tools for developing drugs for the treatment of disease states linked to metabolic disorders such as obesity and diabetes, and as drugs. The cell lines are formed of pre-adipocytes containing a nucleic acid fragment including at least one fragment immortalizing a viral oncogene, and at least one promoter selected from the group containing a promoter of said viral oncogene and a human vimentine gene regulatory region fragment. They express at least one of the following proteins: the .beta.1 and .beta.2-adrenergic receptors, the uncoupling protein (UCP), the glucose transporters, Glut1 and Glut 4 and lipoprotein lipase (LPL). They are capable of being converted into mature adipocytes which product fat and further express the .alpha.2.sub.A and .beta.

Abstract: The invention refers to a new human liver cell line which may be used for toxicological, physiological and, in particular, gene therapeutic examinations. Fields of application are molecular biology, medicine and pharmaceutical industry. The new human liver cell line is marked positive owing to the parameters albumin and alpha-1-antitrypsin (ATT) and negative owing to alpha-fetoprotein (AFP). It has been deposited in the Deutsche Sammlung von Mikroorganismen (DSM ACC2302).

Abstract: The present invention provides two human conjunctival epithelial cell lines with an extended life span, designated HC0597 and HC0708, and methods for producing such cell lines. These conjunctival cell lines can be cultured as stratified 3-dimensional (3-D) cultures. In turn, the 3-D cultures can be used as tissue- and species-specific cellular models of the human conjunctival ocular surface. These human conjunctival cultures are particularly useful, for example, in product safety evaluations to test products for their eye irritation potential.

Abstract: An objective of the present invention is to provide a packaging cell for preparing a retrovirus having a high viral titer. The cell producing a recombinant retrovirus is constructed by introducing, the Polyoma virus early region gene together with a recombinant plasmid or a recombinant retrovirus free from any replication origin derived from Polyoma virus into a packaging cell for preparing a recombinant retrovirus.

Abstract: A method is described for producing recombinant eukaryotic cell lines expressing multiple proteins of interest. Eukaryotic host cells are transfected with (a) a first episome which contains an EBV origin of replication and a first gene encoding a protein of interest; and (b) a second episome containing an EBV origin of replication and a second gene encoding a protein of interest. Transfected cells are obtained expressing an EBNA 1 protein. The cells are grown under conditions wherein the episomes express the first and second genes.

Abstract: Isolation, characterization, proliferation, differentiation and transplantation of mammalian neural stem cells is disclosed.

Abstract: The present invention relates to transgenic mice in which the biological function of at least one cell cycle regulatory proteins of the INK4 family is altered.

Abstract: Transformed cell lines containing a reporter gene operatively linked to a genetic control element that is responsive to growth factor-stimulated cell proliferation and/or oncogene-mediated neoplastic transformation are provided. Also provided are methods for using such transformed cell lines to screen for growth factor antagonists and/or antineoplastic agents.

Abstract: A methodology that allows for highly efficient transfer and stable integration of DNA into both established eukaryotic cell lines and primary cells, including non-dividing cells such as human peripheral blood monocytes and macrophages, entails the use of a synthetic polypeptide comprised of a peptide domain which corresponds to a nuclear localization signal sequence and a DNA binding domain which is rich in basic amino acids, separated by a hinge region of neutral acid which prevents stearic interference between the two domains. A synthetic polypeptide that allows for highly efficient transfer of DNA into eukaryotic cells, including, for example, non-dividing cells such as human peripheral blood monocytes and macrophages.

Abstract: The invention relates to methods for the identification of metastatic sequences. Cells from a cell line or an animal tissue are treated to form a cell line predisposed to metastasis. Treated cells are implanted in an animal of at a primary site and incubated for a period of time sufficient for the cells to proliferate and develop metastases at secondary sites. Expressed sequences from cells at the primary and secondary sites are amplified by differential display polymerase chain reaction and compared. Differentially expressed sequences are identical identified and can be cloned and sequenced. These sequences can be used as probes in the diagnosis of metastatic disorders, as probes to isolate metastatic sequences and as a therapeutic agent.