Abstract: Recombinant Factor IX characterized by a high percentage of active protein can be obtained in the milk of transgenic animals that incorporate chimeric DNA molecules according to the present invention. Transgenic animals of the present invention are produced by introducing into developing embryos DNA that encodes Factor IX, such that the foreign DNA is stably incorporated in the DNA of germ line cells of the mature animal. Particularly efficient expression was accomplished using a chimeric construct comprising a mammary gland specific promoter, Factor IX cDNA that lacked the complete or any portion of the 5?-untranslated and 3?-untranslated region, which is substituted with a 5-? and 3?-end of the mouse whey acidic protein gene. In vitro cell cultures of cells explanted from the transgenic mammal of the invention and methods of producing Factor IX from such said culture and methods of treating hemophilia B are also described.

Abstract: The present invention relates to full-length WF-HABP, WF-HABP, OE-HABP, and BM-HABP, members of the hyaluronan receptor family. The invention provides isolated nucleic acid molecules encoding human to full-length WF-HABP, WF-HABP, OE-HABP, and BM-HABP receptors. Full-length WF-HABP, WF-HABP, OE-HABP, and BM-HABP polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of full-length WF-HABP, WF-HABP, OE-HABP, and BM-HABP receptor activity. Also provided are diagnostic methods for detecting disease states related to the aberrant expression of full-length WF-HABP, WF-HABP, OE-HABP, and BM-HABP receptors.

Abstract: The present invention relates to a novel BAIT protein which is a member of serpin superfamily which is expressed primarily in brain tissue. In particular, isolated nucleic acid molecules are provided encoding the human and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of BAIT activity. Also provided are diagnostic methods for detecting nervous system-related disorders and therapeutic methods for treating nervous system-related disorders. Additionally, the present invention is related to methods of treating patients with BAIT polynucleotides or polypeptides, wherein said patients have had a stroke.

Abstract: A transgenic, non-human mammalian animal is capable of expressing a heterologous gene for human or other recombinant physiologically functional fibrinogen holoprotein or individual subunit chain polypeptides thereof or a modified or fusion fibrinogen in mammary glands of the animals and secreting the expressed product into a body fluid. Methodology employing such a mammal yields recombinant physiologically functional fibrinogens, subunit chain polypeptides thereof, and modified or fusion fibrinogens.

Abstract: The present invention relates to full-length WF-HABP, WF-HABP, OE-HABP, and BM-HABP, novel members of the hyaluronan receptor family. The invention provides isolated nucleic acid molecules encoding human to full-length WF-HABP, WF-HABP, OE-HABP, and BM-HABP receptors. Full-length WF-HABP, WF-HABP, OE-HABP, and BM-HABP polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of full-length WF-HABP, WF-HABP, OE-HABP, and BM-HABP receptor activity. Also provided are diagnostic methods for detecting disease states related to the aberrant expression of full-length WF-HABP, WF-HABP, OE-HABP, and BM-HABP receptors.

Abstract: The present invention relates to full-length WF-HABP, WF-HABP, OE-HABP, and BM-HABP, novel members of the hyaluronan receptor family. The invention provides isolated nucleic acid molecules encoding human to full-length WF-HABP, WF-HABP, OE-HABP, and BM-HABP receptors. Full-length WF-HABP, WF-HABP, OE-HABP, and BM-HABP polypeptides are also provided, as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of full-length WF-HABP, WF-HABP, OE-HABP, and BM-HABP receptor activity. Also provided are diagnostic methods for detecting disease states related to the aberrant expression of full-length WF-HABP, WF-HABP, OE-HABP, and BM-HABP receptors.

Abstract: The invention provides methods and compositions for inducing and maintaining tolerance to epitopes or antigens containing the epitopes. The compositions include expression cassettes and vectors including DNA sequences coding for a fusion immunoglobulin operably linked to transcriptional and translational control regions functional in a hemopoietic or lymphoid cell. The fusion immunoglobulin includes at least one heterologous tolerogenic epitope at the N-terminus variable region of the immunoglobulin. Cells stably transformed with the expression vector are formed and used to produce fusion immunoglobulin. The invention also provides methods for screening for novel tolerogenic epitopes and for inducing and maintaining tolerance. The methods of the invention are useful in the diagnosis and treatment of autoimmune or allergic immune responses.

Abstract: The present invention relates to a novel BAIT protein which is a member of serpin superfamily which is expressed primarily in brain tissue. In particular, isolated nucleic acid molecules are provided encoding the human and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of BAIT activity. Also provided are diagnostic methods for detecting nervous system-related disorders and therapeutic methods for treating nervous system-related disorders. Additionally, the present invention is related to methods of treating patients with BAIT polynucleotides or polypeptides, wherein said patients have had seizures or epilepsy.

Abstract: The present invention relates to a novel BAIT protein which is a member of serpin superfamily which is expressed primarily in brain tissue. In particular, isolated nucleic acid molecules are provided encoding the human and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of BAIT activity. Also provided are diagnostic methods for detecting nervous system-related disorders and therapeutic methods for treating nervous system-related disorders. Additionally, the present invention is related to methods of treating patients with BAIT polynucleotides or polypeptides, wherein said patients have had a stroke.

Abstract: A library of mutants of metastable proteins, such as proteinase inhibitors, can be screened for the specific loss of a wild-type capability to bind an antibody, yielding valuable drug-design information which otherwise is unavailable. By this approach, for example, a mutant proteinase inhibitor can be obtained that has the amino acid sequence of a wild-type protein, or an active fragment thereof, save for the presence of one or more mutations in at least one epitope, thereby altering interaction of the mutant with an anti-proteinase inhibitor antibody.

Abstract: Mutants of the human PAI-1 protein are described which are inhibitors of neutrophil elastase or are inhibitors of vitronectin (Vn)-dependent cell migration. These mutants preferably comprise one or two amino acid substitutions in the reactive center loop of PAI-1, particularly at positions 331 and 346 of the mature protein. These mutants are notable in being resistant to inactivation by elastase, having high affinity for Vn, or both properties. These mutant proteins as pharmaceutical compositions are used to inhibit elastase in a subject, thereby treating a number of disorders associated with elastase activity, most notatably emphysema, ARDS, inflammatory lung injury and cystic fibrosis. The mutants which interact with Vn are used to inhibit cell migration in a subject, thereby treating diseases or conditions associated with undesired cell migration and proliferation, particularly of smooth muscle cells.

Abstract: A new and improved trainer mannequin comprising a body having a head and a torso made of common household items. The head and the torso are hollow. The head has openings for a mouth and two nostrils, and additionally has a neck and a neck opening. All the openings provide access to the interior of the head. The torso also has a neck and neck opening, and is secured to the head by connecting the necks in a way that provides a seal between the interior of the head and the torso. The torso additionally can be interchanged to provide training in three basic aid training techniques. For mouth-to-mouth breathing, the torso is an attached bag collapsible and expandable to simulate a lung. For aid in choking, also known as the Heimlich maneuver, the torso is self-supporting in order to provide a more constant volume and greater resistance to collapsing. This torso also simulates a full human torso including stomach and chest.

Abstract: Recombinant Factor IX characterized by a high percentage of active protein can be obtained in the milk of transgenic animals that incorporate chimeric DNA molecules according to the present invention. Transgenic animals of the present invention are produced by introducing into developing embryos DNA that encodes Factor IX, such that the foreign DNA is stably incorporated in the DNA of germ line cells of the mature animal. Particularly efficient expression was accomplished using a chimeric construct comprising a mammary gland specific promoter, Factor IX cDNA that lacked the complete or any portion of the 5′-untranslated and 3′-untranslated region, which is substituted with a 5′- and 3′-end of the mouse whey acidic protein gene. In vitro cell cultures of cells explanted from the transgenic mammal of the invention and methods of producing Factor IX from such said culture and methods of treating hemophilia B are also described.

Abstract: An isolated DNA sequence which regulates the expression of a heterologous gene composed of a mouse whey acidic protein promoter having a length of greater than about 2.4 kb extending upstream from the unique KpnI site in the mouse whey acidic protein gene is disclosed. Specifically a mouse whey acidic protein promoter of about 4.1-4.2 kb in length extending upstream from the unique KpnI site is preferred. This mouse whey acid protein promoter is operably linked to a DNA sequence encoding a heterologous polypeptide and used to prepare transgenic non-human mammals expressing the heterologous polypeptide in their milk. Particularly efficient expression of both cDNAs and genomic DNAs encoding heterologous polypeptides was obtained in transgenic non-human mammals using this promoter, known as the long whey acidic protein promoter.

Abstract: The present invention relates to a novel BAIT protein which is a member of serpin superfamily which is expressed primarily in brain tissue. In particular, isolated nucleic acid molecules are provided encoding the human BAIT protein. BAIT polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of BAIT activity. Also provided are diagnostic methods for detecting nervous system-related disorders and therapeutic methods for treating nervous system-related disorders.

Abstract: The present invention relates to a novel BAIT protein which is a member of serpin superfamily which is expressed primarily in brain tissue. In particular, isolated nucleic acid molecules are provided encoding the human BAIT protein. BAIT polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of BAIT activity. Also provided are diagnostic methods for detecting nervous system-related disorders and therapeutic methods for treating nervous system-related disorders.

Abstract: The invention relates to transgenic non-human multicellular organisms that contain polynucleotides for expressing proteins that alter posttranslational modification. In particular, the invention provides multiply-transgenic animals in which a first transgene encodes a first protein, a second transgene encodes a second protein, and expression of the second protein affects the posttranlational modification of the first protein in cells of said organism. Expression in preferred embodiments is in specific cells and the modified protein is secreted into a bodily fluid. The invention provides related methods, proteins and products. An example provides transgenic animals that express human Protein C and the processing protease PACE/furin in mammary glands and secrete both proteins into milk.

Abstract: Heterologous polypeptides are produced in the milk of transgenic non-human mammals by the expression of a stably integrated DNA sequence containing the long whey acidic protein promoter operably linked to a DNA sequence encoding a heterologous polypeptide and a signal sequence. The transgenic non-human mammals of the present invention are produced by introducing this DNA sequence such that the DNA sequence is stably integrated into the DNA of germ line cells of the mature mammal and inherited in normal Mendelian fashion. A representative heterologous polypeptide is protein C.

Abstract: Recombinant protein C characterized by a high percentage of active protein can be obtained in the milk of transgenic mammals that incorporate DNAs according to the present invention. Transgenic mammals of the present invention are produced by introducing into developing embryos DNA that encodes protein C, such that the DNA is stably incorporated in the DNA of germ line cells of the mature mammals and inherited in normal, mendelian fashion.

Abstract: The invention is a sterile, plasma-free storage medium for blood components including red blood cells and for platelets processed separately or together. The red cell storage medium includes a physiologically compatible, aqueous electrolyte solution. In one liter of this electrolyte solution there is between about 3.0 grams and about 25.0 grams of dextrose, between about 3.0 grams and about 6.0 grams of sodium citrate, and between about 2.0 grams and about 4.2 grams of sodium bicarbonate. The red cell storage medium is isotonic and has a pH in a range of between about 6.8 and about 7.4. The red cell storage medium is capable of storing and preserving red cells for at least 49 days. The medium can also contain adenine.