Abstract: This invention provides improved devices and methods for long-term, stable expression of a biologically active molecule using a biocompatible capsule containing genetically engineered cells for the effective delivery of biologically active molecules to effect or enhance a biological function within a mammalian host. The novel capsules of this invention are biocompatible and are easily retrievable. This invention specifically provides improved methods and compositions which utilize cells transfected with recombinant DNA molecules comprising DNA sequences coding for biologically active molecules operatively linked to promoters that are not subject to down regulation in vivo upon implantation into a mammalian host. Furthermore, the methods of this invention allow for the long-term, stable and efficacious delivery of biologically active molecules from living cells to specific sites within a given mammal.

Abstract: Methods, including culture media conditions, which provide for in vitro human stem cell division and/or the optimization of human hematopoietic progenitor cell cultures and/or increasing the metabolism or GM-CSF secretion or IL-6 secretion of human stromal cells and/or a method for assaying the effect of a substance or condition on a human hematopoietic cell population, and/or depleting the malignant cell or T-cell and B-cell content of a human hematopoietic cell population are disclosed. The methods rely on culturing human stem cells and/or human hematopoietic progenitor cells and/or human stromal cells in a liquid culture medium which is replaced, preferably perfused, either continuously or periodically, at a rate of 1 ml of medium per ml of culture per about 24 to about 48 hour period, and removing metabolic products and replenishing depleted nutrients while maintaining the culture under physiologically acceptable conditions. Optionally, growth factors are added to the culture medium.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies, i.e., antibodies encoded by immunoglobulin heavy and light chain genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, transgenes encoding unrearranged heterologous human immunoglobulin heavy and light chains are introduced into a non-human animal thereby forming a transgenic animal capable of producing antibodies encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g., by fusing with an immortalizing cell line such as a myeloma or by manipulating such B-cells by other techniques to perpetuate a cell line capable of producing a monoclonal heterologous antibody.

Abstract: A human HL-60 lectin having an amino acid sequence different from other known animal lectins is disclosed. This is one member of a class of mammalian lectins extractable in lactose or detergent and specific for beta-D-galactosides (14-beta-gal lectin which contains at least one glycosylation site). Recombinant methods and materials for production of the mammalian 14-beta-gal lectins, especially HL-60 lectin, in a variety of hosts, and methods to utilize the resulting lectins are also described.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies and methods for producing human sequence antibodies which bind to human antigens with substantial affinity.

Abstract: A population of T lymphocyte precursor cells is disclosed. In bone marrow, the earliest identifiable T lymphocyte precursor is CD34.sup.+, CD7.sup.+ and Leu 8.sup.+++. Methods of isolation and methods of therapeutic use of such cells also are disclosed.

Abstract: Recombinant DNA vectors which express chimeric T cell receptors are disclosed. These chimeric T cell receptors contain one human element, and the rest of the elements are all of the same, non-human animal species, such as a mouse. Of particular interest are chimeras where the human element is V.alpha. or V.beta.. The vectors are used to transfect cells which derive from the same non-human animal species as the non-human animal species of the chimera, and the resulting transfectants are used to produce monoclonal antibodies against the human element of the chimera.

Abstract: In general, the invention features, a method of inducing tolerance in a recipient mammal, e.g., a human, of a first species to a tissue obtained from a mammal, e.g., a swine, e.g., a miniature swine, of a second species, which tissue expresses an MHC antigen, including inserting DNA encoding an MHC antigen of the second species into a bone marrow hematopoietic stem cell from the recipient mammal, and allowing the MHC antigen encoding DNA to be expressed in the recipient.

Abstract: In the production of proteins of biological interest by means of a stress inducible gene expression unit/eukaryotic host cell system, the transformed cell lines are multiplicated by tumour growing in immunodefficient warm-blooded animals, after which the multiplicated cells are cultured in vitro and subjected to stress, whereby expression occurs in high yield. In vivo multiplication rates of 10.sup.5 -10.sup.6 the innoculated quantity/2 weeks are reported without any loss of the latent inducible expression capacity.

Abstract: Described is a antigen and antigenic amino acid sequence consisting of repeating units of the immunodominant epitope region of the circumsporozoite surface protein of a parasite of the genus Plasmodium. Also described is a related fusion protein produced by a recombinant microorganism and a vaccine for immunizing mammals against malaria.

Abstract: The invention relates to methods for intracellularly producing DNA segments by homologous recombination of smaller overlapping DNA fragments and transgenic mammalian cells and transgenic non-human mammals produced by such methods.

Abstract: The invention provides transgenic non-human animals and transgenic non-human mammalian cells harboring a transgene encoding an APP polypeptide comprising the Swedish mutation.

Abstract: In a process for producing proteins with FVIII activity and FVIII derivatives by in vitro culturing of mammalian cells, the culturing is carried out at temperatures below 32.degree. C. and the culturing times used are below 24 hours.

Abstract: A cDNA sequence encoding human T11 or a fragment thereof which is capable of inhibiting T-lymphocyte activation.

Abstract: Methods, compositions and devices are provided for the growth of hematopoietic cells in culture. Bioreactors are provided in which diverse cell types are simultaneously cultured in the presence of appropriate levels of nutrients and growth factors substantially continuously maintained in the bioreactor while removing undesirable metabolic products. This simultaneous culture of multiple cell types is required for the successful reconstruction of hematopoietic tissue ex vivo. At least one growth factor is provided through excretion by transfected stromal cells, particularly heterologous cells. Means are provided for maintaining the stromal cells and hematopoietic cells separately, to allow for early removal of the hematopoietic cells.

Abstract: Processing of .beta.-amyloid precursor protein (.beta.APP) is monitored by detecting the secretion of a soluble amino-terminal fragment or .beta.APP (ATF-.beta.APP) resulting from cleavage of .beta.APP at the amino-terminus of .beta.-amyloid peptide. Secretion of ATF-.beta.APP in animal models may be monitored to identify inhibitors of .beta.-amyloid production. The ATF-.beta.APP may be detected using antibodies and other specific binding substances which recognize a carboxy terminal residue on the fragment. Animals expressing the Swedish mutation of .beta.APP are described which produce abundant amounts of ATF-.beta.APP.

Abstract: The present invention describes a novel immunodeficient rodent model comprising an organ graft, such as a human skin graft, said graft containing microvessels lined by endothelial cells, human T lymphocytes and, optionally, at least one agent capable of substantially depleting the rodent's Natural Killer cells. The human T lymphocytes are engrafted and circulating in the animal's blood, enabling interaction with the endothelial cells which can be allogenic to the donor for the skin graft. The immunodeficient rodent used can be a SCID mouse. Preferably, the endothelial cells are provided by grafting said human skin with an intact dermal superficial vascular plexus. This immunodeficient rodent can be used as a model for studying inflammatory human immune responses of the engrafted T lymphocytes to foreign antigen as well as for studying human allograft rejection, e.g. human microvessel destruction and the T cell-endothelial cell in vivo interactions associated with a human allograft rejection.

Abstract: The invention relates to cDNA genetic sequences, vehicles containing same as well as hosts transformed therewith, for the production of chimeric immunoglobulin molecules, functional fragments thereof and immunoglobulin derivatives exhibiting novel functional properties comprising human constant region modules and non-human variable region modules, or for class switching antibody molecules and/or chains.The invention also relates to DNA coding for pectate lyase signal peptide has been cloned on a plasmid to create a secretion vector which is capable of producing a chosen protein which is transported across the bacterial membrane. The secretion vector has been used to secrete extracellular thaumatin and extracellular chimeric antibody fragments. The proteins produced by this vector have biological activity. The thaumatin is properly folded and the antibody fragments are capable-of binding antigens on target cancer cells.

Abstract: A gene fragment which comprises a DNA sequence coding for an amino acid sequence of a constant region of canine immunoglobulin lambda chain; a gene fragment which comprises a DNA sequence coding for an amino acid sequence of a constant region of canine immunoglobulin kappa chain; a gene fragment which comprises a DNA sequence coding for the constant region of canine immunoglobulin gamma chain; a recombinant DNA molecule coding for an amino acid sequence of a mouse-dog chimeric antibody which comprises a gene fragment coding for an amino acid sequence of a variable region of a mouse immunoglobulin and a gene fragment coding for an amino acid sequence of a constant region of a canine immunoglobulin; a polypeptide of a mouse-dog chimeric antibody which is expressed from a cell transformed with an expression vector for cells wherein said recombinant DNA molecule cording for an amino acid sequence of the mouse-dog chimeric antibody is incorporated; a dog-mouse heterohybridoma which produces canine immunoglobulin;

Abstract: The invention provides expression vectors containing the promoter, enhancer and substantially complete 5'-untranslated region including the first intron of the major immediate early gene of human cytomegalovirus. Further vectors including the hCMV-MIE DNA linked directly to the coding sequence of a heterologous gene are described, Host cells transfected with the vectors and a process for producing heterologous polypeptides using the vectors and the use of the hCMV-MIE DNA for expression of a heterologous gene are also included within the invention.