Abstract: This invention relates to Kunitz domain proteins that bind to, and preferably inhibit, one or more kallikreins, and to therapeutic, diagnostic, and purification use of these proteins.

Abstract: This invention relates to novel mutants of the first Kunitz domain (K.sub.1) of the human lipoprotein-associated coagulation inhibitor (LACI) which inhibit plasmin. The invention also relates to other modified Kunitz domains that inhibit plasmin and to other plasmin inhibitors.

Abstract: Transgenic cell and animal models for Alzheimer's disease are described. Cells of the animals and the cell models themselves comprise a recombinant DNA construct comprising a control sequence and, under the control of the control sequence, a DNA sequence encoding a kinase that is capable, directly or indirectly, of modulating the phosphorylation of the microtubule-forming protein tau. The transgenic cells and animals may be used for testing potential therapeutic agents for Alzheimer's disease.

Abstract: Proteins are disclosed that are homologous to bovine pancreatic trypsin inhibitor (BPTI) Kunitz domains, and especially proteins that are homologous to lipoprotein-associated coagulation inhibitor (LACI) Kunitz domains, which inhibit one or more plasma and/or tissue kallikreins, and uses of such proteins in therapeutic and diagnostic methods also are disclosed. In particular, Kunitz domains derived from Kunitz domains of human origin and especially to the first Kunitz domain of LACI are disclosed.

Abstract: The present invention relates to the C3b/C4b receptor (CR1) gene and its encoded protein. The invention further provides for the expression of the CR1 protein and fragments thereof. The genes and proteins of the invention have uses in diagnosis and therapy of disorders involving complement activity, and various immune system or inflammatory disorders. In specific embodiments of the present invention detailed in the examples sections infra, the cloning, nucleotide sequence, and deduced amino acid sequence of a full-length CR1 cDNA and fragments thereof are described. The expression of the CR1 protein and fragments thereof is also described. Also described is the expression of a secreted CR1 molecule lacking a transmembrane region. The secreted CR1 molecule is shown to be useful in reducing damage caused by inflammation and in reducing myocardial infarct size and preventing reperfusion injury.

Abstract: The present invention provides compositions comprising at least one complement moiety and at least one carbohydrate moiety, and methods of producing such compositions. In particular, the compositions of the invention comprise complement proteins related to the complement receptor type 1, and further comprise ligands for intracellular molecules, such as selectins. In a preferred embodiment, the compositions comprise a complement-related protein in combination with the Lewis X antigen or the sialyl Lewis X antigen. The compositions of the invention have use in the diagnosis or therapy of disorders involving complement activity and inflammation. Pharmaceutical compositions are also provided for treating or reducing inflammation mediated by inappropriate complement activity and intercellular adhesion.

Abstract: Microporous macrocapsules are disclosed which are useful as implantation devices for cell therapy. The macrocapsule comprises living cells that secrete biological substance that are therapeutically useful and that are released from the macrocapsule to the site of implantation. The capsules can have selected permeability characteristics based upon their particular usage and desired viral retentivity characteristics.

Abstract: A sealed, implantable, encapsulation device (20) for diffusing a biologically active product or function to an individual which includes a substantially non-porous fitting (32) including an inner surface (33) defining an access port (34). A permselective, porous, membrane (21), having an interior surface (22), cooperates with the fitting inner surface (33) to form a storage cavity (23) therebetween. The membrane interior surface (22) is in substantially cell-tight dry sealing engagement with fitting (32) to seal cavity (23). Living cells (24) are disposed in the cavity (23) which are capable of secreting the biologically active product to an individual. The membrane (21) is of a material capable of permitting the passage of substances between the individual and cells required to provide the biological product or function. A plug member (35) is positioned in the access port (34) and seated in cell-tight sealing engagement with the fitting inner surface (33).

Abstract: Methods are disclosed for the alleviation of movement disorders via the implantation of static devices which focally release neuroinhibitory compounds to preselected brain areas. Pathological conditions to be treated by these methods include parkinsonian movement disorders, Huntington's chorea, and epileptiform seizure activity. In the treatment of parkinsonism, target areas implantation include the subthalamic nucleus, the globus pallidus internus, and the substantia nigra pars reticulata. In the treatment of epilepsy, implants may be placed in an epileptogenic focus area of neural over-activity. The devices may be polymeric implants that release neuroinhibitory compounds such as GABA, GABA agonists, GABA potentiators, action potential blockers and voltage dependent calcium channel blockers, and glutamate antagonists. Alternatively, the devices may contain living cells which secrete neuroinhibitory compounds.

Abstract: Vehicles containing cells for implanting in the tissue of an individual are prepared having cells dispersed in a particulate, essentially non cross-linked chitosan core matrix that is enclosed within a semipermeable membrane. The cells are entrapped between chitosan particles of the core matrix and there is essentially no interfacial cross-linking between the core matrix and the membrane. The core matrix provides a physical support for viable cells within the vehicle such that the cells are evenly dispersed throughout the core matrix so as to allow their maintenance, growth, proliferation and differentiation. The vehicle can be prepared by mixing viable cells with a solution of chitosan, encapsulating the resultant mixture in a semipermeable membrane and causing the chitosan to precipitate such as by changing the pH to form the core matrix. Alternatively, the chitosan is precipitated to form the core matrix containing cells and then the core matrix is encapsulated in a semipermeable membrane.

Abstract: A storage compartment for mounting to a snowboard having a plurality of pre-existing threaded mounting holes includes a base member, a lid member hinged to the base member, and an insert fitted within the base member for receiving loose objects such as a wrench, wax, a locking cable and/or personal items. An anchoring post is secured to the base member. A closed loop end of a locking cable is passed around the anchoring post and the other end of the locking cable extends through an aperture formed in an end wall of the lid or base member where it is secured to a fixed object. A lock is provided to lock the lid member to the base member to prevent removal of the locking cable and theft of the snowboard when the snowboard is secured to the fixed object.

Abstract: Provided are therapeutic methods employing preparations of recombinant soluble Complement Receptor type 1 (sCR1) defined with respect to the distribution of sCR1 glycoforms. The methods are suitable for treatment of disease involving inflammation, inappropriate complement activation, and in thrombotic or shock state conditions. Preferred methods employ sCR1 glycoforms that are sialylated, have a pI of .ltoreq.5.1, or have a sialic acid:mannose molar ratio of .gtoreq.0.25.

Abstract: Human complement receptor type 1 (CR1). Nucleic acid molecules encoding full-length CR1 protein and fragments thereof having complement regulatory activity are described, as well as recombinant CR1 protein and polypeptides, vectors for their expression, and cell lines expressing or bearing DNA molecules encoding such proteins and polypeptides, including a soluble CR1 polypeptide consisting of the extracellular 30 short consensus repeat domains of the mature CR1 protein. The nucleic acids and polypeptides described are useful in diagnosis and treatment of disorders involving complement activity and inflammation. Compositions useful in therapeutic applications are also disclosed.

Abstract: The present invention provides compositions comprising at least one complement moiety and at least one carbohydrate moiety, and methods of producing such compositions. In particular, the compositions of the invention comprise complement proteins related to the complement receptor type I, and further comprise ligands for intracellular molecules, such as selectins. In a preferred embodiment, the compositions comprise a complement-related protein in combination with the Louis X antigen or the sialyl Lewis X antigen. The compositions of the invention have use in the diagnosis or therapy of disorders involving complement activity and inflammation. Pharmaceutical compositions are also provided for treating or reducing inflammation mediated by inappropriate complement activity and intercellular adhesion.

Abstract: Several innovative systems for an aircraft, and aircraft incorporating them, are disclosed. Features include inboard-mounted engine(s) with a belt drive system for turning wing-situated propellers; compound landing gear integrating ski, pontoon and wheel subcomponents; pivotal mounting armatures for landing gear and/or propellers which provide a plurality of possible landing gear and/or propeller configurations; and a compound wing structure featuring extendable wing panels that permit the wing span of the aircraft to be nearly doubled while in flight. Aircraft incorporating such features will enjoy several safety advantages over conventional multi-engine aircraft and will be capable of modifications during flight which permit landings on any of snow, hard surfaces (runways) and water.

Abstract: This invention relates to the application of immobilized metal affinity chromatography to the purification of complement receptor proteins.

Abstract: Proteins are disclosed that are homologous to bovine pancreatic trypsin inhibitor (BPTI) Kunitz domains, and especially proteins that are homologous to lipoprotein-associated coagulation inhibitor (LACI) Kunitz domains, which inhibit one or more plasma and/or tissue kallikreins, and uses of such proteins in therapeutic and diagnostic methods also are disclosed. In particular, Kunitz domains derived from Kunitz domains of human origin and especially to the first Kunitz domain of LACI are disclosed.

Abstract: A line of .beta. cells is described which is capable of maintaining high levels of insulin secretion in culture. Such cells are useful in the treatment of diabetes, for example, by encapsulation of the cells in an insulin-permeable membrane device, followed by implantation into a diabetes patient.

Abstract: The invention is directed to monoclonal antibodies reactive with a member of the V.beta.3 family variable region of the beta chain of the TCR. More particularly, the invention provides for detection of the V.beta.3.1 subfamily. In a specific embodiment the invention provides for detection of V.beta.3.1, without cross-reacting with other V.beta.3 family variable regions. In a specific embodiment, the monoclonal antibodies of the invention do not react with V.beta.3.2. In particular, the invention provides monoclonal antibodies, termed 5E4 and 8F10, which react with the variable region of a member of the V.beta.3 family. In various embodiments of the invention, these antibodies, or fragments or derivatives thereof, can be used to bind with a member of the V.beta.3 family TCR variable region amino acid sequences, either as part of an intact TCR or peptide, or T cell-surface molecule, or a fragment thereof.

Abstract: A sealed, implantable, encapsulation device (20) for diffusing a biologically active product or function to an individual which includes a substantially non-porous fitting (32) including an inner surface (33) defining an access port (34). A permselective, porous, membrane (21), having an interior surface (22), cooperates with the fitting inner surface (33) to form a storage cavity (23) therebetween. The membrane interior surface (22) is in substantially cell-tight dry sealing engagement with fitting (32) to seal cavity (23). Living cells (24) are disposed in the cavity (23) which are capable of secreting the biologically active product to an individual. The membrane (21) is of a material capable of permitting the passage of substances between the individual and cells required to provide the biological product or function. A plug member (35) is positioned in the access port (34) and seated in cell-tight sealing engagement with the fitting inner surface (33).