Abstract: Induction of neuronal fate in neural stem cells or neural progenitor or precursor cells, or other stem cells, and enhancement of induction of a specific neuronal phenotype, and particularly to induction and enhancement of induction of a midbrain dopaminergic neuronal phenotype. Expressing a nuclear receptor of the Nurr1 subfamily above basal levels within the cell, and regulating GSK-3? inhibition within the cell other than by means of a ligand for a Frizzled receptor.

Abstract: The invention is directed to a method for treating a tissue or organ in a subject by directly administering an effective amount of an exogenous, decellularized extracellular matrix or a mixture of extracellular matrix and mesenchymal stem cells into the intended site of activity, such as bone marrow cavity. In one embodiment, the invention provides methods of treating bone marrow to increase the number of circulating progenitor and stem cells. In some other embodiments of the invention, the decellularized extracellular matrix to be directly administered is configured to be a time released therapeutic.

Abstract: The invention relates to improvements in the field of drug delivery. More particularly, the invention relates to polypeptide derived from aprotinin and from aprotinin analogs as well as conjugates and pharmaceutical compositions comprising these polypeptides. The present invention also relates to the use of these polypeptide for transporting a compound or drug across the blood-brain barrier of an individual and in the treatment and diagnosis of neurological diseases.

Abstract: A novel carboxypeptidase and the encoding gene thereof were successfully identified by screening a human hippocampus extract using brain-APP-cleaving activity as an index. Antibodies against the protein were also prepared. The antibodies are useful in, for example purifying the protein, or examining and diagnosing diseases, such as Alzheimer's disease, which cause accumulation of A? in the brain.

Abstract: Methods are provided for producing a bioscaffold from natural tissues by oxidizing a decellularized tissue to produce a bioscaffold having pores therein. The pore size and porosity is increased to better accommodate intact cells so that live cells can better infiltrate and inhabit the bioscaffold. The bioscaffold may be freeze-dried or lyophilized, sterilized and (optionally) aseptically packaged for subsequent use. A further aspect of the present invention is a bioscaffold produced by the processes described herein. Methods of treatment using the bioscaffold as a graft or as a biomedical implant for implantation are also provided. Also provided are methods of seeding a bioscaffold with mammalian cells, wherein the seeding carried out either in vitro or in vivo, and wherein a bioscaffold produced as described herein is utilized for said seeding.

Abstract: The present invention relates to a method and composition for preventing surgical adhesions during surgery. Tissue surfaces and/or surgical articles involved in the surgery are separated by a biomaterial provided in the form of a non-crosslinked, decellularized and purified mammalian tissue (e.g. bovine pericardium). The biomaterial effectively inhibits fibrosis, scar formation, and surgical adhesions, while also serving as a scaffold for recellularization of the tissue site.

Abstract: The invention concerns a method of conserving biological prostheses, wherein the method includes the following steps: (a) treating biological prostheses with a solution which contains a mixture of epoxide compounds which are at least in part of different lengths; (b) treating the biological prosthesis treated in accordance with step (a) with an antithrombotic-bearing solution; and (c) possibly storing the prosthesis treated in accordance with step (b) in a sterilising solution. The invention further concerns a biological prosthesis produced in accordance with the method of the invention and a conserving agent.

Abstract: Methods and compositions are disclosed that are useful for the prevention and/or treatment of cardiovascular and cardiac diseases and disorders, or damage resulting from surgical or medical procedures that may cause ischemic or ischemic/reperfusion damage in humans; and cardiovascular trauma. The beneficial effects of the compositions and methods are achieved through the use of pharmaceutical compositions that include agents that interfere with the production and/or biological activities of sphingolipids and their metabolites, particularly sphingosine (SPH) and sphingosine-1-phosphate (S-1-P). Also disclosed are methods for identifying and isolating therapeutic agents.

Abstract: A method for inhibiting rejection by a recipient animal of a transplanted tissue, said method comprising modifying, eliminating, or masking an antigen which, when present on the surface of a cell of said tissue, is capable of causing a T-lymphocyte-mediated response in said animal, to inhibit antigen-mediated interaction between said cell and a T-lymphocyte of said animal without causing lysis of said cell.

Abstract: A novel mammalian dihydroouabain-like factor is disclosed which substantially fails to cross-react with mammalian ouabain-like factor (OLF) for binding to anti-OLF antibody, but cross-reacts with plant-related dihydroouabain (dho) for binding to anti-dho antibody, has maximal u.v. absorbance at 196 nm, has a non-peptidic, non-lipidic chemical structure and a fully hydrogenated lactone ring, has a concentration-dependent Na+,K+-ATPase (sodium pump) catalytic inhibitory activity which is 10-fold lower than OLF and 3-fold higher than plant-related dihydroouabain, and a high pressure liquid chromatography elution time about the same as dho. This factor is useful for therapy for congestive heart failure. An antibody and antibody fragments having affinity for mammalian Dh-OLF but not for OLF, and diagnostic and therapeutic methods comprise the antibody and means for quantifying the antibody and are useful for treating a condition caused by high level of OLF or Dh-OLF.

Abstract: The invention describes dendritic cells loaded with toxic substances wherein the toxic substances are selected from the poison of scolopenders of the genera Scolopendra and Hemiscolopendra, snakes of the genera Bitis and Naja, spiders of the genera Loxosceles, Sicarius and Pholcus and Dysdera as well as scorpions of the genus Parabuthus and a combination of one or more of these toxins.

Abstract: A method of producing a sustained localized immunosuppressive effect in localized tissues is achieved by transplanting Sertoli cells proximate to the tissue.

Abstract: The present invention relates to an agent for the expression of long-term potentiation of synaptic transmission, which contains a compound having a brain somatostatin activation property as an active ingredient and to a screening method of an agent for the expression of long-term potentiation of synaptic transmission, which uses a somatostatin releasing property as an index. The present invention is useful for the prophylaxis and/or treatment of cerebral diseases of dementia, amnesia, manic-depressive psychosis, schizophrenia, Parkinson's disease, psychosomatic disease and the like.

Abstract: A method of reconstructing laminae of human epithelium corneae in vitro to be used in grafts from cultures of limbar stem cells as well as a method of selecting and transferring such cells to fibrin substrate.

Abstract: A method for processing and preserving an acellular collagen-based tissue matrix for transplantation is disclosed. The method includes the steps of processing biological tissues with a stabilizing solution to reduce procurement damage, treatment with a processing solution to remove cells, treatment with a cryoprotectant solution followed by freezing, drying, storage and rehydration under conditions that preclude functionally significant damage and reconstitution with viable cells.

Abstract: Neural tissue edema is treated by circulating a hyperoncotic artificial cerebrospinal fluid in the cerebrospinal fluid pathway in the vicinity of edematous tissue to cause the edematous tissue to be dehydrated due to an oncotic gradient between the hypertonic artificial cerebrospinal fluid and intracellular fluid and withdrawing the fluid from the pathway after it has been so circulated.

Abstract: Porcine spinal cord cells and methods for using the cells to treat spinal cord damage due to neurodegeneration resulting from spinal cord injury and neurodegenerative disorders are described. The porcine spinal cord cells are preferably embryonic spinal cord cells obtained from select gestational days. The porcine spinal cord cells can be modified to be suitable for transplantation into a xenogeneic subject, such as a human. For example, the porcine spinal cord cells can be modified such that an antigen (e.g., an MHC class I antigen) on the cell surface which is capable of stimulating an immune response against the cell in a xenogeneic subject is altered (e.g., by contact with an anti-MHC class I antibody, or a fragment or derivative thereof) to inhibit rejection of the cell when introduced into the subject.

Abstract: The present invention provides a method of assaying for and arresting, preventing and/or reversing the impairment of central and peripheral nervous system function comprising reducing &bgr;-amyloid plaque burden by the administration of compounds that reduce apoE expression. The compounds used in the method of the invention may be: 1) inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase; 2) inhibitors of cholesterol biosynthesis; 3) inhibitors of protein isoprenylation, specifically geranylgeranylation; and/or 4) inhibitors of NF-&kgr;B activation or function. Assays for compounds with inhibit apoE expression from microglial cells are also disclosed.

Abstract: This invention provides a composition comprising notochord and extracts thereof in therapeutic amounts. The invention more specifically relates to a method of treating arthritis in mammals, more particularly rheumatoid arthritis in humans through the enteral administration of notochord, notochord extracts or mixtures thereof. In a preferred embodiment, collagen obtained from sturgeon is enterally administered to a human at from 1.0 &mgr;g to 1.05 gms per day.

Abstract: The present invention relates to an agent for the expression of long-term potentiation of synaptic transmission, which contains a compound having a brain somatostatin activation property as an active ingredient and to a screening method of an agent for the expression of long-term potentiation of synaptic transmission, which uses a somatostatin releasing property as an index The present invention is useful for the prophylaxis and/or treatment of cerebral diseases of dementia, amnesia, manic-depressive psychosis, schizophrenia, Parkinson's disease, psychosomatic disease and the like.

Abstract: The present invention is directed to a culture medium for neurons prepared by adding albumin to a culture supernatant obtained from a culture of primary astroglial cells in a trophic medium supplemented with insulin and transferrin. The culture medium of the present invention makes it possible to culture central nerve cells consistently. When nerve cells are cultured at a low cell density, excellent neurite extension is obtained, and synapses are formed rapidly. On the other hand, when nerve cells are cultured at a high cell density, long-term stability of cells that have formed neuronetworks can be obtained.

Abstract: The present invention is directed to compositions and methods for modulating cellular activity. The invention is particularly suited for delivering an agent which modulates cellular activity to a neuronal cell. In a typical embodiment, a composition of the invention includes an agent associated with a neuronal tracer which associates with a neuron to facilitate uptake of the agent by the neuron cell body.

Abstract: The current invention relates to an active factor present in homogenized brain tissue which inhibits antigen-driven proliferation of lymphocytes in culture, but stimulates proliferation in response to most mitogens. The inhibitory activity can be destroyed by treatment with proteases or neuraminadase. The activity is in the insoluble fraction of the homogenate, but becomes soluble in 0.04 M NaOH. After gel filtration chromatography of the NaOH soluble material, the suppressive activity is in the high molecular weight fraction which elutes in the void volume of the column. This fraction contains protein and carbohydrate. The activity is not affected by neutralizing antibodies against regulatory cytokines, does not depend on Fas or FasL, and is not due to the presence of gangliosides. These data suggest that a brain glycoprotein which is either membrane-bound or part of the extracellular matrix has powerful immune regulatory effects in culture.

Abstract: A method for reducing mammalian serum total cholesterol, LDL cholesterol, apolipoprotein B and triglyceride levels, by ingesting a stabilized rice bran derivative selected from the group consisting of an enzyme treated stabilized rice bran, an insolubilized fraction and mixtures thereof, thereby reducing serum total cholesterol, LDL cholesterol, apolipoprotein B and triglyceride levels in said mammal.

Abstract: The present invention relates to a shunt, and a method for treating catheters, more particularly shunts, wherein the catheter is made of a biocompatible material and adapted at least for insertion into the brain of a living organism and enzymes are impregnated, either directly or through a matrix forming system, into the interior of the lumen of the catheter. The enzymes impregnated have at least one of the following characteristics: (1) they require a confirmational form and either completely or substantially lose their activity upon dislocation from the interior of the lumen; (2) they require the presence of co-factors for activation which co-factors are also present in the interior of the lumen but are not otherwise present in the biological system in sufficient quantity to excite activation of the impregnated enzymes.

Abstract: The present invention relates to an agent for the expression of long-term potentiation of synaptic transmission, which contains a compound having a brain somatostatin activation property as an active ingredient and to a screening method of an agent for the expression of long-term potentiation of synaptic transmission, which uses a soniatostatin releasing property as an index. The present invention is useful for the prophylaxis and/or treatment of cerebral diseases of dementia, amnesia, manic-depressive psychosis, schizophrenia, Parkinson's disease, psychosomatic disease and the like.

Abstract: This invention is directed to a novel &bgr;-secretase that produces the A&bgr; peptide found in Alzheimer's Disease. One &bgr;-secretase is a protein having a molecular weight of about 61, 81 or 88 kDa that cleaves an amyloid precursor protein (APP) substrate. Another is a protease complex having a molecular between about 180 and 200 kDa, which, in one embodiment, contains the 61, 81, and 88 kDa proteins and, in another embodiment, contains proteins having a molecular weight of about 66, 60, 33 and 29 kDa. Another &bgr;-secretase has a molecular weight between about 50 and 90 kDA. The invention is also directed to methods of selecting agents that inhibit A&bgr; peptide production and treating Alzheimer's disease in patients.

Abstract: Disclosed is a method for promoting retinal neuronal survival in a mammal, wherein the neuronal cells are at risk of dying. The method comprises administering to the mammal an effective dose of at least one of the following substances: IGF-I; a functional derivative of IGF-I; IGF-II; or a functional derivative of IGF-II.

Abstract: Methods and compositions are disclosed for the use of allogeneic mononuclear phagocytes to promote axonal regeneration in the central nervous system of a mammal. In one embodiment, allogeneic mononuclear phagocytes are cultured together with stimulatory tissue, such as skin, dermis or at least one nerve segment, and are subsequently administered into the central nervous system of a mammal at or near a site of injury or disease. In an alternative embodiment, autologous monocytes, preferably stimulated autologous monocytes, are administered into the central nervous system of a mammal at or near a site of injury or disease. CNS administration of mononuclear phagocytes may optionally be combined with administration of an adjuvant factor (e.g. aFGF) to the CNS, anti-inflammatory therapy of the mammal, or both. Methods for screening stimulatory tissue and cells and methods and compositions for cryopreserved allogeneic mononuclear phagocytes are also disclosed.

Abstract: The present invention discloses the use, in the manufacture of a preventive and therapeutic drug of a brain disease, of a compound represented by formula (1): CH2═CH—CH2—S(O)n—R  (1) [wherein R represents a hydrogen atom, an alkyl group, an alkenyl group, a substituted alkyl group, a substituted alkenyl group, an alkylthio group, an alkenylthio group, a phenyl group, a substituted phenyl group, a heterocyclic group, or a group derived from an amino acid or an oligopeptide by deletion of one hydrogen atom, and which group may have a protective group; and n is 0, 1, or 2], a glycoside thereof, or a salt of the compound or the glycoside. The drug of the present invention for ameliorating brain diseases, inhibiting reduction of brain neurons and promoting branching of neurites, is useful for the prevention and treatment of brain diseases such as dementia in association with degeneration and sloughing of brain neurons.

Abstract: This invention is directed to methods of manufacturing implantable biocompatible cell encapsulation devices, wherein the cell encapsulation devices have a jacket made of a permeable, biocompatible material that is loaded with a core made of a reticulate foam scaffold having interconnected pores, with cells that are dispersed in the interconnected pores.

Abstract: Implantable therapy systems are disclosed for the local and controlled delivery of a biologically active factor to the brain, spinal cord and other target regions of a subject suffering from a dibilatating condition. The method of the invention involves surgically exposing an insertion site, generally located above a predetermined treatment site (12), in a patient. A cannula (20), having an obturator (30) or dilator (104) positioned therein, is inserted at the insertion site, defining a pathway to the treatment site. In some instances, the cannula can be inserted along the path of a guidewire (102) previously positioned at the treatment site. The cannula (20) is preferably a low friction polymeric material such as polytetrafluoroethylene. The cannula (20) generally has an open proximal end for receiving the obturator (30) or dilator (104), and an open distal end, preferably a tapered end, for delivery of neurologically active factors to the treatment site (12).

Abstract: The invention provides means for inducing partial recovery of motor function lost in a mammal as a consequence of an injury to its spinal cord which includes a lesion of the cerebrospinal projections (CST) of the cord. Axonal growth is initiated in the CST, and functional recovery obtained, by delivering neurotrophin-3 to the site of CST injury by expression from a recombinant expression vector.

Abstract: This invention provides a composition comprising notochord and extracts thereof in therapeutic amounts. The invention more specifically relates to a method of treating arthritis in mammals, more particularly rheumatoid arthritis in humans through the enteral administration of notochord, notochord extracts or mixtures thereof. In a preferred embodiment, collagen obtained from sturgeon is enterally administered to a human at from 1.0 .mu.g to 1.05 gms per day.

Abstract: SNAP-25 (synaptosomal associated protein) is purified from cerebrospinal or amniotic fluid for immunoassay and quantitation. Quantitation of these proteins is useful in the diagnosis and monitoring of brain disorders and diseases such as schizophrenia and Alzheimer's.

Abstract: Disclosed are methods for use in transferring nucleic acids into central nervous system cells in vivo and in vitro and/or for stimulating central nervous system cells. Neurotrophic genes are shown to stimulate neurofilament cells and to promote nerve cell growth, repair and regeneration in vivo. Gene transfer protocols are disclosed for use in transferring various nucleic acid materials into central nervous system cells, as may be used in treating various pathologies of the brain and spinal cord.

Abstract: A biocompatible cell device having an internal foam scaffold to provide a growth surface for encapsulated cells which produce a biologically active molecule.

Abstract: The use of Tumor Cytotoxic Factor-II (TCF-II) enables the prevention and/or treatment of radiation-induced disorders.

Abstract: A method for identifying anti-convulsant compounds is presented. The binding of test compounds with a receptor obtained from rat forebrain is determined. The receptor has a Kd of about 40 nM and a molecular weight of about 130 kD. Two pyran compounds that bind to the receptor are also disclosed.

Abstract: The present invention provides a non-human chimeric mammal, comprising a severe-combined immunodeficient mammal engrafted with bovine immune system tissues, wherein said chimeric mammal is functionally reconstituted. Also provided is a method of producing a functionally reconstituted scid-bo mouse with bovine fetal hematopoietic tissues.

Abstract: Topical composition and method for retexturizing skin by peeling the outer layer of dead skin cells, sebum and other impurities, the composition containing unoxidized nerve tissue and a slightly abrasive powdery component in a cosmetically acceptable carrier.

Abstract: Gliotoxic factor in the isolated or purified state, characterized in that it possesses toxic activity with respect to human or animal astrocytic cells, having the effect of a cytomorphological disorganization of their network of intermediate filaments and/or a degradation of the proteins of said intermediate filaments and/or cell death, in particular by apoptosis.

Abstract: A nitric oxide synthase (NOS) protein is obtained from rat brain and purified to a specific activity at least 6,360-fold that of a crude tissue preparation. The NOS protein has a denatured MW of 105 kD determined by SDS-PAGE, a dimeric MW of 230 kD determined by gel filtration and requires FAD, FMN, Ca.sup.2+ and tetrahydropterin for the production of nitric oxide from L-arginine or an arginine-rich peptide, oligopeptide or protein substrate.

Abstract: The therapeutic or dietetic use of a preparation based on phospholipids extracted from pig brains for treating aging disorders consisting of memory disorders, attention disorders, intellectual efficacy disorders, humor and affectivity disorders, and thinking difficulty in a human is disclosed. The purified brain phospholipids are used alone or in combination with carriers and diluents enabling oral delivery.

Abstract: This invention provides a composition comprising notochord and extracts thereof in therapeutic amounts. The invention more specifically relates to a method of treating arthritis in mammals, more particularly rheumatoid arthritis in humans through the enteral administration of notochord, notochord extracts or mixtures thereof. In a preferred embodiment, collagen obtained from sturgeon is enterally administered to a human at from 1.0 .mu.g to 1.05 gms per day.

Abstract: A bioartificial three-dimensional hydrogel extracellular matrix derivatized with a cell adhesive peptide fragment is provided for use in tissue regeneration or replacement. The choice of adhesive peptide fragment depends on the desired target cell type. Cartilage or tendon can be regenerated by implanting a matrix containing adhesive peptide fragments that favor chondrocyte invasion. The matrix can be pre-seeded with cells, and tissue can be reconstituted in vitro and then implanted. A cell-seeded matrix can be encapsulated in a semi-permeable membrane to form a bioartificial organ. An agarose hydrogel matrix having an agarose concentration of 0.5-1.25% (w/v) and an average gel pore radius between 120 nm and 290 nm is preferred. The peptide fragment preferably contains the sequence, ArgGlyAsp or TyrIleGlySerArg or IleLysValAlaVal, and is covalently immobilized to the matrix.

Abstract: Infusions of brain-derived neurotrophic factor, neurotrophin-3 or neurotrophin-4 are used to produce analgesia in mammals. In addition, these neurotrophins are used to treat other diseases or disorders mediated by serotonin.

Abstract: The present invention is directed to plasmalogens and pharmaceutical compositions thereof which are useful for treating neurodegenerative diseases. Carbons 1 and 2 of the phosphoglyceryl backbone of the plasmaolgens have from 10-24 carbon atoms containing from 1 to 6 double bonds. The phosphoryl group is bonded to choline, ethanolamine, serine or inositol.

Abstract: Modulators of neurotransmitter release including substituted guanidines, N"-aminoguanidines, and N,N'N",N"'-tetrasubstituted hydrazinedicarboximidamides, and pharmaceutical compositions thereof are disclosed. Also disclosed are methods involving the use of such neurotransmitter release modulators for the treatment or prevention of pathophysiologic conditions characterized by the release of excessive or inappropriate levels of neurotransmitters. Also disclosed are screening assays for compounds which selectively inhibit glutamate release. Also disclosed are methods of blocking voltage sensitive sodium and calcium channels in mammalian nerve cells.

Abstract: This invention provides a composition capable of stimulating growth and regeneration of epidermal cells. The composition comprises an aqueous, cell-free extract derived from epidermal cells.