Abstract: An antiviral agent of an antiviral ability against various viruses and a method of producing the same are provided. A heat treatment is applied to a calcium-containing substance represented by calcium carbonate-containing substances originating from the animal such as clamshell, eggshell, crustacean shell, bone, coral, and pearl, and calcium carbonate-containing minerals such as limestone. When a temperature of the heat treatment is not less than 650° C. and less than a melting point of the calcium component-containing substance, a sufficient time of the heat treatment is 2 to 13 hours.

Abstract: A method for making a composition for administration to a patient, where the method includes: harvesting tissue including cells from a patient, lysing the cells to form a lysate, filtering the lysate to yield a filtrate, and collecting the filtrate as a composition comprising the filtrate for administration to said patient.

Abstract: Cultures of keratinocyte cells are provided which are free from nonautologous fibroblasts and organ extracts, and which have a high speed of cell amplification for a minimum seeding density. The cultures can be cryopreserved in a buffered isotonic medium containing serum and a cryoprotectant. The cultures are produced by a process that does not involve the use of a feeder layer and organ extracts. A culture medium which can be used contains Medium 199, serum, epidermal growth factor, cholera toxin and/or hydrocortisone, and optionally insulin. A substance for wound healing and for cosmetic applications is derived from cultured human keratinocytes. A non-viable total keratinocyte lysate for use in promoting wound healing is produced by growing keratinocyte cells on a support, detaching the cells from the support, and lysing the detached cells to obtain the lysate which may be frozen and lyophilized.

Abstract: A matrix, including epithelial basement membrane, for inducing repair of mammalian tissue defects and in vitro cell propagation derived from epithelial tissues of a warm-blooded vertebrate.

Abstract: This invention relates to media for culturing human cells that the proliferation speed of human cells is increased and the cell expression type is stably manifested, and to a method for culturing human cells using the same. This invention is characterized in that the media used for culturing human cells comprises human serum.

Abstract: A method of inducing resistance to or regression of tumor growth comprising placing tumor cells in culture in vitro or ex vivo supplemented with a pro-apoptotic agent for a period of time, transferring the tumor cells into a diffusion chamber, thereby producing a cell-containing chamber, inserting the chamber into a human for a therapeutically effective time, thereby inducing resistance to or regression of tumor growth.

Abstract: Methods and compositions are disclosed for prevention and/or treatment of diseases in which 5- and 12-lipoxygenase activity contributes to the pathological condition, by administration of 12-methyletradecanoic acids alone and in conjunction with other therapeutic compounds. Methods to inhibit lipoxygenase-mediated inflammations are disclosed.

Abstract: Improved methods for the production of tissue-engineered constructs, including muscular tissue constructs such as vascular constructs, are disclosed. The methods include the use of improved substrates for cell growth, improved cell culture media for cell growth, and the use of distensible bodies to impart pulsatile stretching force to lumens of constructs during growth. Also disclosed are improved products and methods for making those products, including substrates and cell culture media, for tissue engineering and tissue culture generally. Improved muscular tissue constructs, including vascular constructs, are also disclosed, which may be used in medicine for the repair or replacement of damaged natural structures. In an embodiment, a muscular, tubular tissue-engineered construct is prepared having a wall of mammalian smooth muscle cells oriented circumferentially about a lumen of the construct at a cell density of at least 107 cells/cc.

Abstract: Disclosed are a composition of chemically defined components having elevated levels of simple sugars which support the enhanced in vitro chondrogenesis of mesenchymal progenitor cells, a method for in vitro chondrogenic induction of such progenitor cells and a method of forming human chondrocytes in vitro from such progenitor cells.

Abstract: Disclosed is a cartilage repair product that induces both cell ingrowth into a bioresorbable material and cell differentiation into cartilage tissue. Such a product is useful for regenerating and/or repairing both vascular and avascular cartilage lesions, particularly articular cartilage lesions, and even more particularly mensical tissue lesions, including tears as well as segmental defects. Also disclosed is a method of regenerating and repairing cartilage lesions using such a product.

Abstract: This invention relates to a process by which organic solvent-containing solutions are used in lieu of pure water for the preparation of cartilage extracts and fractions thereof. Different organic solvents have been tested for the preparation of extracts containing biologically active components possessing at least an activity against a matrix metalloprotease (anti-MMP). This invention also relates to a process by which a total liquid extract of shark cartilage composed of molecules having molecular weights less than about 500kDa (0-500 fraction) is purified into two well separated fractions composed of molecules having molecular weights less than about 1 kDa (0-1 fraction) and between about 1 to 500 kDa (1-500 fraction). In order to prevent the formation of aggregates, to improve the dissolution and the stability of active components, sucrose or other stabilizing agents can be added.

Abstract: A method of inducing resistance to tumor growth comprising placing tumor cells in culture in vitro supplemented with a pro-apoptotic agent for a period of time, transferring the tumor cells into a diffusion chamber, thereby producing a cell-containing chamber, inserting the chamber into a mammal for a therapeutically effective time, thereby inducing resistance to tumor growth. The pro-apoptotic agents include nucleic acid molecules, proteins or peptides, non-proteins or non-polynucleotide compounds, and a physical conditions.

Abstract: Conditioned media compositions having valuable biological activity are obtained from cultures of immune cells from elasmobranch fishes. Methods are provided for producing the conditioned media compositions. Conditioned media obtained using epigonal cells from bonnethead sharks (Sphyrna tiburo) and lemon sharks (Negaprion brevirostris) demonstrate strong anti-tumor activities. The conditioned media compositions can be used for treating tumor proliferation and in immunosuppressive therapy.

Abstract: Described herein are methods for processing and dispersing animal tissues that involve exposing processed (e.g., decellularized) tissue to an acylating agent, wherein the ratio of acylating agent to wet tissue weight is about 0.003:1 or less. The disclosed methods result in a dispersed tissue matrix that has a high degree of resistance to digestion by non-collagenase proteases, such as trypsin. In order to produce sufficiently high yields of these trypsin-resistant compositions, the processed tissue is preferably cryomilled to increase its surface area prior to acylation.

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: A precementum- and/or cementum-derived chemotactic factor (CCTF) of a tooth of a Mammalian is characterized by a molecular weight measured by SDS-PAGE of 67000±1000. A process for purifying a precementum- and/or cementum-derived gingival fibroblast chemotactic factor (CCTF) of a Mammalian tooth includes eluting a protein mixture from precementum and/or cementum of a Mammalian tooth and purifying the precementum- and/or cementum-derived chemotactic factor (CCTF) from the eluted protein mixture by molecular weight fractionation, ion-exchange adsorption chromatography and hydroxyapatite adsorption chromatography. In the process for purifying the gingival fibroblast chemotactic factor (CCTF) the Mammalian is preferably a bovine.

Abstract: A method of reducing an immune response to a transplant in a recipient by treating said recipient with an amount of mesenchymal stem cells effective to reduce or inhibit host rejection of the transplant. The mesenchymal stem cells can be administered before, at the same time as, or after the transplant. Also disclosed is a method of inducing a reduced immune response against a host by foreign tissue, i.e., graft versus host disease, by treatment with mesenchymal stem cells.

Abstract: A leather hydrolysate metal proteinate to be used as a metal nutrient for an animal feed. Chrome tanned leather scrap and shavings are heated in an aqueous solution with an alkali material to produce a water soluble, low molecular weight protein hydrolysate and insoluble chromium compounds which are subsequently separated from the hydrolysate. The hydrolysate is then oxidized to remove any objectionable trace organic residuals from the tanning process, and a di- or tri-valent water soluble metal salt is mixed with the hydrolysate to provide a metal proteinate. The metal proteinate, either as a liquid or a dried powder, can be used as animal or aquaculture diets.

Abstract: The invention relates to an injectable soft tissue filler composition and methods of preparing the composition.

Abstract: A new chemical compound for treating human inflammatory diseases, tissue damage, stroke, septic shock and cancer. This chemical compound is produced from a process including the following steps: (a) washing human foreskin fibroblasts with a fresh DMEM medium then incubated in a fresh medium containing 2.5%-10% fetal bovine serum for at least 8 hours to form a proliferating phase medium (PPM); (b) subjecting the proliferating phase medium to a 10-kDa ultrafiltration membrane to separate the proliferating phase medium into a <10 kDa fraction, which passes through the 10-kDa ultrafiltration membrane, and a >10 kDa fraction, which is retained by the 10-kDa ultrafiltration membrane; (c) Chromatographing the <10 kDa fraction on a Superdex 30 column by FPLC to separate the <10 kDa fraction into five post-FPLC fractions; (d) Injecting the second post-FPLC fraction into a C18 column in a HPLC system with a gradient elute from 10% to 50% acetonitrile and water containing 0.

Abstract: Methods and materials for tissue reconstruction, repair, and/or augmentation are disclosed. The invention provides isolated bladder submucosa for use in tissue reconstruction. The methods of the invention include the use of isolated bladder submucosa for repair, reconstruction, and/or augmentation of bladder and other organs and tissues.

Abstract: The present invention discloses compositions containing natural human extracellular matrices and methods for the use thereof. More particularly, the present invention provides compositions and methods for the repair of skin defects using natural human extracellular matrix by injection.

Abstract: A method of inhibiting the proliferation and causing the differentiation of undifferentiated cells comprising contacting the undifferentiated cells with an effective amount of an antisense oligonucleotide having a sequence which is complementary to a region of the IGF-1 receptor RNA. The sequence of the antisense oligonucleotide is selected from an oligodeoxynucleotide sequence complementary to codons −29 to −24 of the signal sequence of the IGF-1 receptor and an oligoribodeoxynucleotide sequence complementary to codons 1 to 309 of the sequence of the IGF-1 receptor. The oligoribodeoxynucleotide sequence may be provided by an expression vector.

Abstract: A method and apparatus are disclosed for constructing a virtual microscope slide comprised of digitally scanned images from a microscope specimen. The digitally scanned images are arranged in a tiled format convenient for viewing without a microscope, and for transferring the tiled images for viewing by another at a remote location. Several original microscope views at a low magnification are digitized and stored as digitized images coherently seamed together to provide an overall virtual, macro image of the specimen at a lower resolution. Several original microscope views at higher magnifications are digitized and stored as digitized images coherently seamed together to provide virtual micro images at higher resolution. A data structure is formed with these virtual macro and micro digitized images along with their mapping coordinates. Preferably, a generic viewing program is also provided in the data structure that allows remote users to manipulate and interpret the tiled images on the user's monitor.

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: Methods for detecting the status of an insulin-dependent diabetes mellitus (IDDM)-associated autoimmune response in a mammal are provided. Specifically, the ratio of the frequency of T helper 1 cells to T helper 2 cells specific for a pancreatic &bgr;-cell associated antigen is indicative of the status of the autoimmune response. The methods may be employed prior to the onset of the clinical symptoms of the disease, thereby allowing identification of those at risk for developing clinical symptoms of IDDM, or subsequent to pancreatic tissue transplantation, for example, to measure the efficacy of treatment directed to enhancing the lifetime of the tissue transplant. Methods for prolonging the survival of tissue transplants are also provided. Specifically, a tissue-associated antigen is administered to the mammal which serves to shift the pathogenic Th1 response associated with pathological immunity toward a protective Th2 response.

Abstract: A therapeutic agent for osteoporosis brought about by a decrease in estrogen comprises an extract from inflammatory rabbit skin inoculated with vaccinia virus as an effective component. In ovariectomized rats, a model animal for osteoporosis brought about by a decrease in estrogen, the extract from inflammatory rabbit skin inoculated with vaccinia virus has an excellent action for maintaining bone volume and bone strength. The therapeutic agent containing the extract as an active component is very useful for treatment and prevention of osteoporosis brought about by a decrease in estrogen which is frequently caused by menopause or ovariectomy in women. The extract from inflammatory rabbit skin inoculated with vaccinia virus has a high safety profile even when administered for a long term.

Abstract: Disclosed is an efficient and economical method for the preparation of N-glycolyl neuraminic acid in a high purity from an inexpensive abundant source material. The method comprises dispersing body tissues of an echinodermatous marine animal Cucumaria echinata in an aqueous medium, preferably, using a dry powder of the tissues prepared in advance, in which the tissues are proteolytically decomposed to isolate N-glycolyl neuraminic acid in the form of an aqueous solution containing polypeptides as a by-product, followed by separation of N-glycolyl neuraminic acid from the aqueous solution by removing the polypeptides and purification of the compound in a process utilizing an ion-exchange treatments.

Abstract: The present invention provides a process of prolonging organ allograft survival in an organism comprising down-regulating Th1 activity in the organism. The down-regulation of Th1 activity is accomplished either by infecting the organism with an effective Th2 up-regulating amount of a nematode or by administering to the organism an effective Th2 up-regulating amount of a soluble extract of a nematode. Exemplary and preferred nematodes for use in a process of the present invention are of the genus Nipostrongylus , Trichuris, Ascaris or Caenorhabditis. Most preferred is the nematode Nipostrongylus brasiliensis. A process of the present invention is particularly useful in prolonging kidney allograft survival.

Abstract: Methods and pharmaceutical compositions for modifying the mesothelial cells of a mammalian recipient in situ are provided. The methods include forming a mesothelial cell expression system in vivo or ex vivo and administering the expression system to the mammalian recipient (by way of the body cavities normally lined by mesothelial cells). The mesothelial cell expression system is useful for the localized and systemic delivery of therapeutic agents in situ.

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: Oral drugs and functional foods of the present invention contain type-II collagen denatured (fragmented) under specific conditions. Rheumatoid arthritis (RA) has been considered to be an autoimmune disease against type-II collagen as an antigen. Since denatured type-II collagen of the invention induces high oral immune tolerance and inhibits immune responses against type-II collagen, it can prevent and treat RA. Particularly, RA can effectively be prevented and treated by simple oral administration of type-II collagen.

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

Abstract: The present invention provides the methods to isolate the proteins specifically induced apoptosis (programmed cell death) in prostate cancer cells (LNCAP), leukemia cells (HL-60), and breast cancer cells (MCF-70), but without effect in normal human lung fibroblast cells (CCD 39 Lu). P-1 has no effect on breast cancer cells. Five proteins have been isolated from the conditioned media of culture cells: (1) Apogen P-1: the proteins (Apogen P-1a, Apogen P-1b and Apogen P-1c) isolated from the conditioned medium of XC cells are able to induce apoptosis in prostate cancer cells (LNCAP) without effect in normal human lung fibroblast (CCD 39 Lu), colon cancer (T84), breast cancer (MCF-7) and leukemia (HL-60) cells. (2) Apogen P-2: the protein isolated from the conditioned medium of C3H10T1/2 cells is able to induce apoptosis in prostate cancer cells (LNCAP) and breast cancer (MCF-7) without effect in normal human lung fibroblast (CCD 39 Lu) and colon cancer (T84) cells.

Abstract: The present invention relates to methods for inhibiting the complement pathway in a mammal comprising administering an effective dose of a composition comprising an active ingredient selected from the group consisting of isolated sea cucumber (Phylum Echinodermata, Class Holothuroidea) body wall, isolated sea cucumber epithelial layer, isolated sea cucumber flower, sea cucumber fucosylated chondroitin sulfate, combinations thereof, active derivatives thereof or combinations of active derivatives thereof.

Abstract: The present invention provides inhibition of angiogenesis in a warm-blooded animal by the administration of preparations isolated from the echinoderm sea cucumber (Class Holothuroidea). This preparation is useful as a therapeutic agent against malignant tumors and as a preventive or therapeutic drug against various diseases, such as rheumatoid arthritis, caused by vascular hyperplasia.

Abstract: The present invention is directed to a method and pharmaceutical formulations for the treatment of systemic sclerosis in mammals, by oral administration of collagen, including type I collagen, or biologically active peptide fragments thereof.

Abstract: The present invention relates to a method of stimulating the proliferation and appropriate cell maturation of a variety of different cells and tissues in three-dimensional cultures in vitro using TGF-.beta. in the culture medium. In accordance with the invention, stromal cells, including, but not limited to, chondrocytes, chondrocyte-progenitors, fibroblasts, fibroblast-like cells, umbilical cord cells or bone marrow cells from umbilical cord blood are inoculated and grown on a three-dimensional framework in the presence of TGF-.beta.. Stromal cells may also include other cells found in loose connective tissue such as endothelial cells, macrophages/monocytes, adipocytes, pericytes, reticular cells found in bone marrow stroma, etc.

Abstract: The present invention provides an epidermal gel secretion of Arabian Gulf catfish which is useful in enhancing wound healing, alleviating muscle spasms and pain, and treating dermatological disorders.

Abstract: The present invention relates to a method of stimulating the proliferation and appropriate cell maturation of a variety of different cells and tissues in three-dimensional cultures in vitro using TGF-.beta. in the culture medium. In accordance with the invention, stromal cells, including, but not limited to, chondrocytes, chondrocyte-progenitors, fibroblasts, fibroblast-like cells, umbilical cord cells or bone marrow cells from umbilical cord blood are inoculated and grown on a three-dimensional framework in the presence of TGF-.beta.. Stromal cells may also include other cells found in loose connective tissue such as endothelial cells, macrophages/monocytes, adipocytes, pericytes, reticular cells found in bone marrow stroma, etc.

Abstract: This invention is directed to cryopreservation of harvested mammalian tissues and living cultured tissue equivalents made by in vitro technology. The invention involves immersing a mammalian tissue or cultured tissue equivalent in a cryoprotectant solution, agitating the cryoprotectant solution and the immersed tissue to achieve effective penetration of the cryoprotectant solution into the tissue, and then freezing the tissue at a very slow freezing rate at 0.3.degree. C. or less/min. In the freezing step, extracellular ice formation is initiated by seeding. The cryopreserved tissue may be stored for indefinite periods of time prior to use. The cultured tissue equivalent is an in vitro model of the equivalent human tissue, such as skin or cornea, which, when retrieved from storage can be used for transplantation or implantation in vivo or for screening compounds in vitro.

Abstract: The invention concerns fractions from echinoderms of the class Holothuroidea (sea cucumber) that can be used directly as active therapeutic agents or as raw materials in producing biologically active derivatives thereof. The fractions can be used alone or in combination and are derived from a) the epithelial layer, free of muscle and collagenous tissues, b) the isolated flower, or c) the whole body wall substantially free muscle, viscera and flower. The invention also concerns processes for obtaining these fractions that involve the use of thermal/mechanical and/or enzymatic means.

Abstract: Cultures of keratinocyte cells are provided which are free from nonautologous fibroblasts and organ extracts, and which have a high speed of cell amplification for a minimum seeding density. Preferably, a culture contains no more than about 10% autologous non-keratinocyte cells such as star-shaped, non-keratinocyte cells and no more than about 1% autologous fibroblasts. The cultures can be cryopreserved in a buffered isotonic medium containing serum and a cryoprotectant. The cultures are produced by a process that does not involve the use of a feeder layer and organ extracts. A culture medium used contains Medium 199, serum, epidermal growth factor, cholera toxin and/or hydrocortisone, and optionally insulin. A substance for wound healing and for cosmetic applications is derived from cultured human keratinocytes. Lyophilized keratinocyte cell cultures or an extract therefrom is used to provide a pharmaceutical composition. Confluent and cohesive keratinocyte sheets are prepared for use in wound healing.

Abstract: A core material such as animal tissue or cells is contained within a semipermeable vessel which may be a microcapsule, hollow fiber or plastic membrane having a semipermeable wall by a method that prevents the core material from incorporation into the wall of the vessel. This is accomplished by suspending the core material in a solution of polysaccharide gum such as an alkali metal alginate in an amount between about 0.2% and about 0.5%, removing and washing the core material to remove all but a thin layer of polysaccharide gum, and gelling the polysaccharide gum with multivalent cations or other means to form a pretreated core material.

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.

Abstract: A method of inducing resistance to tumor growth comprising placing tumor cells in culture supplemented with an agent in a diffusion chamber thereby producing a cell-containing chamber, inserting the chamber into a mammal for a therapeutically effective time, thereby inducing resistance to tumor growth.

Abstract: A food supplement comprises isolated animal mesenchymal matter of fetal origin and extracts of animal organs of fetal origin, the mesenchymal matter consisting of a network of loose connective tissue and the food supplement being free of chemical preservatives.

Abstract: Injectable implant compositions for soft tissue augmentation comprise elastin and collagen and a biocompatible carrier. An injectable implant composition for soft tissue augmentation is derived from the ligamentum nuchae which has been treated to remove non-collagenous and non-elastinous proteins. Methods of making an injectable implant composition for soft tissue augmentation from the ligamentum nuchae are described.

Abstract: There is provided a skin substitute that can suitably be used for covering the surface of a damaged skin area which is typically a wound produced by a traumatic local loss of the skin of the human body as a result of a burn or some other cause of damage. It is a skin substitute of a laminate comprising a squid chitin sheet and a fish skin collagen coat layer, which may be a salmon skin collagen coat layer. Such a skin substitute effectively exploits the suppleness and the effect of proving an environment for encouraging the production of lysozyme and defending the wound of squid chitin and, at the same time, compensate the disadvantage of poor adhesion of fibroblast cells that operate for curing the wound.

Abstract: A method of increasing the number of adult pancreatic islet cells available for transplantation by contacting the cells with laminin 5 extracellular matrix. When contacted with the deposited matrix produced by 804G rat bladder carcinoma cells, a 1,500 fold increase in cell number is observed after three passages in culture. Islet cell expansion also occurs when cells are contacted with 804G soluble matrix. The expanded islet cells contain insulin and respond to glucose challenge.