Abstract: Substance which bind with high affinity to endotoxin (lipopolysaccharide [LPS]), and which are useful for the prevention or treatment of, for example, Gram-negative and Gram-positive bacterial sepsis, and for the treatment of bacterial and fungal infections as well as for neutralizing effects associated with heparin. The substances are LPS-binding peptides comprising an LPS-binding domain. DNA sequences encoding peptides, recombinant microorganisms containing the DNA, pharmaceutical compositions containing the peptides of the invention, and diagnostic kits. Methods for the detection and removal of bacterial LPS from solutions.

Abstract: Azlactone-functional supports are used to provide cell selection from a mixture such as bone marrow or peripheral blood having a desired target cell population. An azlactone-functional support is derivatized by covalently coupling to the support a biologically active substance that binds the target cells. A mixture containing the target cells is contacted with the derivatized support to bind the target cells to the biologically active substance, and unbound remaining mixture is removed from the support. Bound cells may be eluted from the support to obtain purified target cells. Biologically active substances include antibodies, lectins, proteins, antigens and avidin. The biologically active substance may directly or indirectly bind cells in the mixture. Indirect binding may be through a second, intermediary biologically active substance that is bifunctional.

Abstract: The present invention relates to the field of carbohydrate crosslinked glycoprotein crystals. Advantageously, such crosslinked glycoprotein crystals display stability to harsh environmental conditions, while maintaining the structural and functional integrity of the glycoprotein backbone. According to one embodiment, this invention relates to methods for concentrating proteins that have been modified by carbohydrates and for releasing their activity at controlled rates. This invention also provides methods for producing carbohydrate crosslinked glycoprotein crystals and methods for using them in pharmaceutical formulations, vaccines, immunotherapeutics, personal care compositions, including cosmetics, veterinary pharmaceutical compositions and vaccines, foods, feeds, diagnostics, cleaning agents, including detergents and decontamination formulations.

Abstract: A process for the preparation of polymers having nucleobases as side groups by means of multicomponent reactions, especially the Ugi reaction, is described. Because of the multicomponent nature of preparation, the properties of the polymers can be varied substantially better than has hitherto been possible and can be adapted to requirements for use as an antisense or antigen therapeutic agent or as a diagnostic agent.

Abstract: Methods and reagents are provided for specifically targeting biologically active compounds such as antiviral and antimicrobial drugs, or prodrugs containing the biologically active compound to specific sites such as specific organelles in phagocytic mammalian cells. The biologically active compound or prodrug is linked to a microparticle with a linker that is non-specifically or specifically cleaved inside a phagocytic mammalian cell. Alternatively, the biologically active compound or prodrug is impregnated into a porous microparticle or coated on a nonporous microparticle, and then coated with a coating material that is non-specifically or specifically degraded inside a phagocytic mammalian cell. The prodrug contains the biologically active compound linked to a polar lipid such as ceramide with a specific linker such as a peptide that is specifically cleaved to activate the prodrug in a phagocytic mammalian cell infected with a microorganism.

Abstract: Copolymers designed for use as particulate carriers containing functionalizable amino acid subunits for coupling with targeting ligand are described. The copolymers are polyesters composed of &agr;-hydroxy acid subunits such as D,L-lactide and &agr;-amino acid subunits such as serine or in the preferred embodiment, terpolymers of D,L-lactide and glycolide and &agr;-amino acid subunits such as serine. Stable vaccine preparations useful as delayed release formulations containing antigen(s) or antigen(s) and co-adjuvants encapsulated within or physically mixed with polymeric microparticles are described. The particulate carriers are useful for delivering agents to the immune system of a subject by mucosal or parenteral routes to produce immune responses, including antibody responses.

Abstract: Novel polymer-supported quenching reagents of Formula (I): P-L-Q, wherein P is a polymer of low chemical reactivity which is soluble or insoluble; Q is one or more quenching reagents, or an acid or base addition salts thereof, that are capable of selective covalent reaction with unwanted byproducts, or excess reagents; and L is one or more chemically robust linkers that join P and Q; are described, as well as methods for their preparation and methods for their use in the rapid purification of synthetic intermediates and products in organic synthesis, combinatorial chemistry and automated organic synthesis.

Abstract: Poly(ethylene glycol) (PEG), a highly biocompatible hydrophilic polyether, is tethered to poly(propylene fumarate) (PPF), a biodegradable polyester. To avoid change in molecular weight distribution of PPF, end hydroxyl groups of PPF are reacted with bis-carboxymethyl PEG after being treated with thionyl chloride. New end carboxyl groups of the PEG-tethered PPF are further reacted with N-hydroxysuccinimide (NHS) in the presence of dicyclohexylcarbodiimide (DCC) to couple bioactive molecules. Glutamine and glycine-arginine-glycine-aspartic acid (GRGD) are attached to the PEG-tethered PPF in 50 mM phosphate buffer of pH of 7.4. The method is valuable for the preparation of a triblock copolymer with PEG end blocks and the coupling of biologically active molecules.

Abstract: A method of preparing a polymer-protein composite based upon placing a protein in solution in an organic phase via the ion-pairing of the protein with a surfactant. The polymer-protein composites are useful, for example, as highly active and stable catalysts, in for example, paints and coatings, as well as in medical application.

Abstract: Activated support materials are provided containing oxirane or azlactone groups as substituents in linear polymers as activated groups. A base support containing hydroxyl groups is suspended in a solution containing cerium (IV) ions and a monomer containing an oxirane or azlactone group, and grafting polymerization is carrier out to produce a polymer containing oxirane or azlactone groups covalently bonded to the base support. Azlactone groups can be bonded to the base support via a thioether bond by using a base support containing thiol groups. The activated support materials can be used to prepare affinity supports containing an affinity ligand that is thiophilic or possesses a metal chelating group, or to prepare immobilized enzymes. The ligand can be iminodiacetic acid, or can be obtained by reacting an oxirane group of the support material with NaHS, and reacting the resultant product with divinylsulfone followed by reacting with mercaptoethanol.

Abstract: The invention relates to surfaces coated with streptavidin and avidin for use in immunoassays, wherein the surfaces comprise a layer of streptavidin and avidin which are bonded on a surface of a solid supporting material through a biotinylated adhering agent.

Abstract: Fiber-optic sensors and fiberless sensors are made for measuring analytes, in particular nitric oxide. The sensors contain a compound specific for the analyte such a nitric oxide-binding compound. Fiber-optic sensors contain the compound immobilized on the tip of the fiber. The tip may be coated with an inert coating such as a metal layer and the compound is immobilized on the coating. Nitric oxide-binding compounds include heme-binding proteins, porphyrin group-containing proteins, heme group-containing proteins, dye-labeled porphyrin group-containing proteins and dye-labeled heme group-containing proteins. In a specific embodiment, dye-labeled cytochrome c′ such as fluorescein-labeled cytochrome c′ is immobilized on a fiber tip containing a gold colloid layer. The fiberless sensors are small enough to enter a single mammalian cell relatively non-invasively.

Abstract: A method of attaching unmodified biopolymers, particularly, unmodified polynucleotides, directly to a solid support is provided. The method includes the steps of (a) providing unmodified biopolymers; (b) providing a solid support having at least one surface comprising pendant acyl fluoride functionalities, and (c) contacting the unmodified biopolymers with the solid support under a condition sufficient for allowing the attachment of the biopolymers to the solid support. The unmodified biopolymers may be nucleic acids, polypeptides, proteins, carbohydrates, lipids and analogues thereof. The unmodified polynucleotides may be DNA, RNA or synthesized oligonucleotides. The DNA may be single or double stranded. A device including a solid support and unmodified biopolymers attached to the solid support by reaction with the pendant acyl fluoride functionalities of the solid support is also provided. The methods and devices of the present invention may be used in performing hybridization assays and immunoassays.

Abstract: The present invention relates to the field of carbohydrate crosslinked glycoprotein crystals. Advantageously, such crosslinked glycoprotein crystals display stability to harsh environmental conditions, while maintaining the structural and functional integrity of the glycoprotein backbone. According to one embodiment, this invention relates to methods for concentrating proteins that have been modified by carbohydrates and for releasing their activity at controlled rates. This invention also provides methods for producing carbohydrate crosslinked glycoprotein crystals and methods for using them in pharmaceutical formulations, vaccines, immunotherapeutics, personal care compositions, including cosmetics, veterinary pharmaceutical compositions and vaccines, foods, feeds, diagnostics, cleaning agents, including detergents and decontamination formulations.

Abstract: Immobilization of SH group-containing compounds on a solvent-insoluble support is carried out in the presence of an antioxidant to prevent oxidation of SH groups to S—S bonds. This improves immobilization efficiency and suppresses deterioration of inherent characteristics of the SH group-containing compound. Antioxidants include sodium pyrosulfite (sodium disulfite), sodium sulfite, sodium hydrogensulfite, sodium hydrosulfite and L-ascorbic acid. SH group-containing compounds include cysteine, peptides or proteins containing cysteine and thiol compounds such as ethanethiol, aminoethanethiol, benzylthiol and thiophenol. Preferably, the SH group-containing compound has a molecular weight not more than 3×104. The support may be activated by a functional group such as glycidyl, imidocarbonato, tosyl, tresyl, carboxyl, amino, azido or hydroxyl. The support can be inorganic such as glass beads or organic such as a synthetic polymer or a polysaccharide.

Abstract: A composition for intracellular delivery of a chemical agent into an interleukin-2-receptor-bearing cell, e.g. an activated T cell, includes a chemical agent and at least one copy of an interleukin-2-receptor-binding and endocytosis-inducing ligand coupled to a water soluble polymer. The ligand binds to a receptor on the interleukin-2-receptor-bearing cell and elicits endocytosis of the composition. The composition also preferably includes a spacer for coupling the chemical agent and the ligand to the polymer. Chemical agents can include cytotoxins, transforming nucleic acids, gene regulators, labels, antigens, drugs, and the like. A preferred water soluble polymer is a polyalkylene oxide, such as polyethlene glycol and polyethylene oxide, and activated derivatives thereof. The composition can further comprise a carrier such as another water soluble polymer, liposome, or particulate. Methods of using these compositions for delivering a chemical agent in vivo or in vitro are also disclosed.

Abstract: Particles and methods for the detection or visualization of analytes using fluorescence energy transfer. Particles comprising an energy donor as a first component and a fluorescent dye as a second component positioned in said particles at an energy exchanging distance from one another, wherein the two components have a Stokes shift of greater than or equal to 50 nm, said particle having bound on its surface, a protein, polypeptide, nucleic acid, nucleotide or protein containing ligand analogue are disclosed and claimed.

Abstract: Spherically shaped polyvinyl alcohol (PVAL) polymer particles are prepared encapsulating a magnetic colloid that provides the particles with magnetic properties for use in binding biomolecules. The particles have a size of 1-10 &mgr;m that makes them particularly suitable for use in cell separation/sorting, cleaning biosubstances in suspension and diagnostic assays. The particles are prepared by dispersing a magnetic colloid containing a magnetic material such as a ferromagnetic or superparamagnetic substance in an aqueous solution of polyvinyl alcohol containing reactive hydroxyl groups, adding the resultant mixture to an organic phase containing a mixture of at least two emulsifiers, and adding a water-soluble cross-linking agent such as a dialdehyde that reacts with the hydroxyl groups of polyvinyl alcohol to form the polymer particles. The emulsifiers are miscible in the polyvinyl alcohol solution, and at least one emulsifier is semi-hydrophilic and at least one emulsifier is lipophilic.

Abstract: A cyclodextrin derivative, wherein at least 60 percent of the free hydroxy groups of said cyclodextrin are acylated with acyl groups where at least one of said acyl groups comprise a free carboxylic group.

Abstract: Described is a method and reagent kit for the detection of an analyte in a sample liquid by agglutination, wherein the sample liquid is contacted with an agglutination reagent in a reaction vessel that contains an inert matrix to form a reaction mixture that is then subjected to centrifugation. The reaction between the analyte and the agglutination reagent is determined based upon the penetration of the agglutination reagent into the inert matrix. The agglutination reagent includes synthetic particles having an average diameter and specific density chosen such that the particles' sedimentation behavior towards the matrix is essentially the same as that of erythrocytes under the same centrifugal conditions. Preferably, the surfaces of the synthetic particles have ligand molecules immobilized thereon for binding to the analyte.

Abstract: The invention pertains to an electrically conductive copolymer of the general formula I: wherein A is a first polymerizable monomer which produces an electrically conductive polymer when polymerized, and represents a polymerized unit of said monomer A in the electrically conductive polymer; B is a second polymerizable monomer which when copolymerized with monomer A produces an electrically conductive polymer, and represents a polymerized unit of said monomer B in the electrically conductive polymer; w is an integer greater than or equal to 0; x is an integer greater than or equal to 1; y is an integer greater than or equal to 0; z is an integer greater than or equal to I; 11, and 12 are each independently covalent linkers or spacer arms; 13 is substituent group having a desired chemical functionality; and Bt′ is selected from the group consisting of biotin and complexes of biotin with a molecule selected from the group consisting of avidin, streptavidin, derivatives of avidin

Abstract: Substantially non-antigenic polymers containing pI and/or pH optimum modulating moieties are disclosed. The polymers are useful as intermediates for synthesis of amine-based polymers and in the formation of activated polymers for conjugation with nucleophiles. Conjugates and methods of preparation and treatment with the conjugates are also disclosed.

Abstract: A synthetic polymer based surface is coated with polymer particles without the use of an adhesive. A top surface layer is swollen or semidissolved by contacting with a solvent such as acetone, polymer particles are contacted with the surface to partially embed the particles in the surface layer, and the surface layer is dried. The polymer particles are either dry or in a slurry when contacted with the surface, and contact with the polymer particles may be simultaneous or subsequent to contacting with the solvent. The particles may be particles for chromatography, and may be derivatized before or after contacting with the surface such as by coupling an enzyme, DNA, an antibody or an antigen.

Abstract: Polymers having multi-functional sites and a gel comprising a solvent swollen network of cross-linked polymer(s), of which at least one polymer comprises at least one multi-functional site. A multi-functional site is a sequence of more than one functional group. A multi-functional polymer is a polymer comprising one or more multi-functional sites and/or more than one functional group.

Abstract: Endothelial cell attachment to an intravascular stent is promoted by coating the stent with an endothelial cell specific adhesion peptide. Coating is preferably carried out by activating the intravascular stent using plasma glow discharge, applying on the stent a layer or plurality of layers of a polymer such as poly(2-hydroxyethylmethacrylate), applying a tresylation solution containing pyridine and tresyl chloride, and applying a five amino acid peptide having the sequence glycine-arginine-glutamic acid-aspartic acid-valine.

Abstract: Disclosed is a peptide for binding thereto a low density lipoprotein, which has an amino acid sequence represented by the formula (I) or (II) and which has an electric charge (E) satisfying the following requirement: +1.ltoreq.E.ltoreq.+4 wherein E is defined by the formula: E=(the number of positive functional groups present in the peptide)-(the number of negative functional groups present in the peptide): ##STR1## wherein each a is independently Phe or Trp; each p is independently Arg or Lys; each X.sup.1, each X.sup.2 and each X.sup.3 are individually, independently an arbitrary amino acid residue; and m, n, p, q and r satisfy the following requirement: 2.ltoreq.m+n+p+q+r.ltoreq.10, wherein m and n satisfy the following requirements: 2.ltoreq.m+n.ltoreq.10 and 1.ltoreq.m, n.ltoreq.9, and p, q and r satisfy the following requirements: 0.ltoreq.p+q+r.ltoreq.8, 0.ltoreq.p, r.ltoreq.8 and 0.ltoreq.q.ltoreq.5.

Abstract: A polybifunctional reagent is provided having a polymeric backbone, one or more pendent photoreactive moieties, and two or more pendent bioactive groups. The reagent can be activated to form a bulk material or can be brought into contact with the surface of a previously formed biomaterial and activated to form a coating. The pendent bioactive groups function by promoting the attachment of specific molecules or cells to the bulk material or coated surface. Bioactive groups can include proteins, peptides, carbohydrates, nucleic acids and other molecules that are capable of binding noncovalently to specific and complimentary portions of molecules or cells.

Abstract: A bio-active material such as heparin, urokinase or streptokinase is bonded via a hydrophilic spacer to a functionality on the surface of a hydrophobic, bio-compatible polymeric substrate to provide a coating of the bio-active material on the surface. The substrate surface is preferably the surface of an implantable medical device such as a vascular graft. An amine and/or hydroxyl functionality on the substrate surface is reacted with an isocyanate group at an end of the hydrophilic spacer to bond the spacer to the substrate, and the bio-active material is reacted with an isocyanate group at another end of the spacer to bond the bio-active material to the spacer. Polymeric substrates include expanded polytetrafluoroethylene and polyethylene terephthalate, and the hydroxyl and/or amine functionality may be provided on the substrate surface by plasma glow discharge. A preferred spacer is an isocyanate end-blocked poly(ethylene oxide).

Abstract: There are electrically conductive, electroactive functionalized conjugated polymers having formula (I): ##STR1## These electrically conducive, electroactive conjugated polymers may be covalently bonded to a first biological molecule or antiligand. Polymers bonded to a first biological molecule or antiligand may be used to form an electrode and may be used to assay for, detect and/or extract a second biological molecule or ligand.

Abstract: Compositions and methods are provided for adhering and binding biologically active proteins and protein-containing composites to substrates. Adhesive formulations comprising a nonproteinaceous polymer of monomeric units comprising an aromatic moiety substituted with at least one hydroxyl group such as poly(p-hydroxy-styrene) are applied to substrates and subsequently contacted with proteins. Beads comprising a nonproteinaceous polymer of monomeric units comprising an aromatic moiety substituted with at least one hydroxyl group are also provided, and the beads are coated with a protein. Substrates to which the adhesive formulations have been applied, as well as the beads, can be used to adhere cells and tissues, to sort cell types, to perform immunoassays, to perform chromatography and to remove protein from samples.

Abstract: The present invention provides methods for preparing, and compositions comprising, stabilized protein-polymer conjugates. More particularly, the present invention relates to the stabilization of individual subunits of multisubunit protein complexes by conjugation to polymers. Such conjugation acts to stabilize the individual subunit in its native conformation in liquid medium, which in turn acts to stabilize its biological activity.

Abstract: Methods and reagents are provided for specifically targeting biologically active compounds such as antiviral and antimicrobial drugs, or prodrugs containing the biologically active compound to specific sites such as specific organelles in phagocytic mammalian cells. The biologically active compound or prodrug is linked to a microparticle with a linker that is non-specifically or specifically cleaved inside a phagocytic mammalian cell. Alternatively, the biologically active compound or prodrug is impregnated into a porous microparticle or coated on a nonporous microparticle, and then coated with a coating material that is non-specifically or specifically degraded inside a phagocytic mammalian cell. The prodrug contains the biologically active compound linked to a polar lipid such as ceramide with a specific linker such as a peptide that is specifically cleaved to activate the prodrug in a phagocytic mammalian cell infected with a microorganism.

Abstract: Compositions, and methods of use thereof, for use as blood substitute products comprise aqueous mixtures of oxygen-carrying and non-oxygen carrying plasma expanders and methods for the use thereof. The oxygen-carrying component may consist of any hemoglobin-based oxygen carrier, while the non-oxygen carrying plasma expander my consist of any suitable diluent.

Abstract: Processes for improving the in vivo function of factor VIII by shielding exposed targets of the factor VIII comprise a) immobilizing the factor VIII by interaction with a group-specific adsorbent carrying ligands manufactured by organic-chemical synthesis, for preventing polymer coupling to reactive amino acids of the immobilized factor VIII, within or adjacent to interaction domains; b) activating a biocompatible polymer; c) conjugating the activated biocompatible polymer to external sites of the immobilized factor VIII; and thereafter d) eluting the conjugate from the adsorbent. Processes for administering factor VIII comprise subcutaneously, intramuscularly, intradermally or intravenously administering a conjugate of factor VIII and a biocompatible polymer, and methods for treatment of hemophilia A comprise subcutaneous, intramuscular, intradermal or intravenous administration of a conjugate of factor VIII and a biocompatible polymer.

Abstract: A biocompatible, heterofunctional, star-shaped poly(ethylene glycol) is described. Methods of making the heterofunctional star-shaped poly(ethylene glycol) and using it for conjugation with proteins are also described.

Abstract: Disclosed are compositions with tethered growth effector molecules, and methods of using these compositions for growing cells and tissues. Growth effector molecules, including growth factors and extracellular matrix molecules, are flexibly tethered to a solid substrate. The compositions can be used either in vitro or in vivo to grow cells and tissues. By tethering the growth factors, they will not diffuse away from the desired location. By making the attachment flexible, the growth effector molecules can more naturally bind to cell surface receptors. A significant feature of these compositions and methods is that they enhance the biological response to the growth factors. The new method also offers other advantages over the traditional methods, in which growth factors are delivered in soluble form: (1) the growth factor is localized to a desired target cell population; (2) significantly less growth factor is needed to exert a biologic response.

Abstract: Copolymers designed for use as particulate carriers containing functionalizable amino subunits for coupling with targeting ligand are described. The copolymers are polyesters composed of .alpha.-hydroxy acid subunits such as D, L-lactide and .alpha.-amino acid subunits such as serine or in the preferred embodiment, terpolymers of D,L-lactide and glycolide and .alpha.-amino acid subunits such as serine. Stable vaccine preparations useful as delayed release formulations containing antigen(s) or antigen(s) and co-adjuvants encapsulated within or physically mixed with ploymeric microparticles are described. The particulate carriers are useful for delivering agents to the immune system of a subject by mucosal or parenteral routes to produce immune responses, including antibody responses.

Abstract: Multiple layered functional thin films fixed on a solid support are provided which comprise multiple layers of functional molecules (such as enzymes and other proteins, pigments and dyes) admixed with polymer ions in combination with multiple layers of polymer ions without the functional molecules. The films are prepared by immersing a solid support having an electric charge in an admixed polymer ion-functional molecule solution having a net electric charge opposite to that of the solid support followed by immersing the solid support in a polymer ion solution having a net electric charge opposite to that of the admixed polymer ion-functional molecule solution, and repeating at least once the immersings of the solid support in the solutions.

Abstract: A composition suitable for use in diagnostic imaging or as a cell killing agent comprising a chelating residue linked via an amide linkage to a poly(alkylene oxide) moiety, said compisition having a molecular weight of at least 4,500; ##STR1## wherein: Z is a chelating residue;Q is a divalent poly(alkylene oxidylene) moiety having a carbon terminus at R and at L;L represents an amide linkage;E.sup.(b) is one or more counterions each having a charge of b;b is an integer from 1, 2 and 3;n is an integer selected from the group 1, 2, 3 and 4;w is zero or an integer from 1 to 5;M.sup.(+a) is a cation, having a charge of +a;a is an integer from 1 to 4;r is 0 or an integer from 1 to 3, provided that when r is 2-3, each M.sup.(+a) can be the same or different cation;d is the total charge on the chelating residue and is an integer from 0 to 10;d+.SIGMA.(b.multidot.w)+.SIGMA.(a.multidot.r)=O; andR is a capping moiety chosen from the group consisting of hydrogen, hydroxyl, C.sub.1 -C.sub.

Abstract: A material is provided for immobilization of biologically active substances which are reactive with a carbodiimide group. The material contains a carbodiimide group-containing polymer supported on a carrier such as a plastic, an inorganic polymer, a metal, a natural polymer or a ceramic. The carbodiimide group-containing polymer has 2 to 100 carbodiimide groups per molecule and a molecular weight of 1,000 to 100,000, and is prepared by carbodiimidization of an organic polyisocyanate in the presence of a catalyst. The polymer may be supported as a film on part or the whole area of the carrier. Biologically active substances that may be immobilized include enzymes, hormones, antibodies, antigens, heptenes, peptides, DNAs and RNAs.

Abstract: Methods are provided for forming a coating of an immobilized biomolecule on a surface of a medical device to impart improved biocompatibility for contacting tissue and bodily fluids. A 2-aminoalcohol moiety of a biomolecule is oxidized with a periodate to an aldehyde moiety which is reacted with an amine moiety on the surface of a medical device to form an imine moiety, and the imine moiety is reduced to form an amine linkage immobilizing a coating of the biomolecule on the surface. Conversely, the biomolecule can contain the amine moiety and the 2-aminoalcohol moiety can be on the surface. In another method, a biomolecule coating containing an amine moiety and a 2-aminoalcohol moiety is immobilized on the surface of a medical device, and the 2-aminoalcohol moiety is oxidized with a periodate to an aldehyde moiety which reacts with the amine moiety to crosslink the coating.

Abstract: The invention concerns the use, in the induction of an immune response, of a synthetic microparticle polymer carrying on the surface one or more covalently bonded proteins capable of carrying one or more epitopes, the molecular weight of the protein(s) on the surface of the microparticles, being adjusted so as to direct the immune response to the induction of a humoral and cellular response or to the induction of a mainly cellular response, said microparticles have an average diameter of approximately 0.25 to 1.5 .mu.m.

Abstract: A process for preparing solutions of hemoglobin hyperpolymers by fractionating hemoglobin hyperpolymers having a nonuniform molecular weight distribution according to molecular weight using a polyhydroxy compound to precipitate different fractions of hemoglobin hyperpolymers, wherein each fraction has a different but more uniform molecular weight distribution as compared to the starting hemoglobin hyperpolymers. Preferably, the polyhydroxy compound is a polyalcohol, especially polyethylene glycol.

Abstract: The peptide X-Arg-Gly-Asp-R-Y wherein X is H or at least one amino acid and Y is OH or at least one amino acid, and R is an amino acid selected from Thr or Cys, or other amino acid, having the same cell-attachment activity as fibronectin and the peptide X-Arg-Gly-Asp-Ser-Y, wherein X and Y, having said activity are disclosed.

Abstract: Link protein and cartilage matrix protein, which are two major components of the extracellular cartilage matrix, have been found to bind to each other. Polypeptide fragments of cartilage matrix protein and link protein are produced. A recombinant fusion polypeptide is prepared containing a fragment of cartilage matrix protein that binds to link protein and a fragment of link protein that binds to cartilage matrix protein. The cartilage matrix protein fragment may bind to collagen and contain the CMP-1 or CMP-2 domain, and the link protein may bind to a complex of hyaluronic acid and proteoglycan. The fragments or fusion polypeptide can be administered for repair of diseased or injured cartilaginous and non-cartilaginous tissue by promoting binding of a complex of proteoglycan and hyaluronic acid to collagen. The fragments or fusion polypeptide can be anchored to the surface of a prosthetic device, implant or tissue graft to promote adherence of tissue and biocompatibility.

Abstract: A substance possessing physiological activity is coupled to a styrene-glycidyl methacrylate polymer through a spacer, and is used to isolate from a mixture a substance that can adhere to the substance possessing physiological activity. Preferably the polymer is in the form of a microsphere, the substance possessing physiological activity is 3-[(5-(2,3-dimethoxy-6-methyl-1,4-benzoquinonyl)]-2-nonyl-2-propionic acid or derivative thereof, and the spacer is an ethylene glycol diglycidyl ether derivative. The mixture may be a cell extract and the substance isolated a protein that is a receptor to the substance possessing physiological activity.

Abstract: Compositions, and methods of use thereof, for use as blood substitute products comprise aqueous mixtures of oxygen-carrying and non-oxygen carrying plasma expanders and methods for the use thereof. The oxygen-carrying component may consist of any hemoglobin-based oxygen carrier, while the non-oxygen carrying plasma expander my consist of an oncotic colloid-like starch.

Abstract: A high surface area system is provided with latex particles for immobilization of substances containing nucleophilic groups. The high surface area system is formed by aggregating the latex particles or by bonding the latex particles to a porous support of high surface area. The latex particles contain groups such as oxirane groups that react with the nucleophilic groups. The substances containing nucleophilic groups may be enzymes or proteins such as albumin, immunoglobulins, blood-clotting factors, cell-membrane proteins or peptide hormones. The high surface area system may be used as a sorbent in removing pollutants, as a stationary phase in organic synthesis such as peptide synthesis, and in the therapeutic treatment of a patient.

Abstract: Conjugates containing a substance with coagulant activity, such as recombinant Factor IX, non-antigenic polymers, such as poly(ethylene glycol), are disclosed. Also disclosed are methods of forming the novel conjugates of this invention.

Abstract: Methods are provided for forming a coating of an immobilized biomolecule on a surface of a medical device to impart improved biocompatibility for contacting tissue and bodily fluids. A 2-aminoalcohol moiety of a biomolecule is oxidized with a periodate to an aldehyde moiety which is reacted with an amine moiety on the surface of a medical device to form an imine moiety, and the imine moiety is reduced to form an amine linkage immobilizing a coating of the biomolecule on the surface. In another method, a biomolecule coating containing an amine moiety and a 2-aminoalcohol moiety is immobilized on the surface of a medical device, the 2-aminoalcohol moiety is oxidized with a periodate to an aldehyde moiety which is reacted with the amine moiety to form an imine moiety, and the imine moiety is reduced to form a secondary amine and crosslink the coating.