Abstract: Methods for modifying polyhydroxylated materials by the direct covalent bonding of nucleophilic ligands to the former sites of hydroxyl groups on the material are disclosed. More specifically, methods for activating the surface of polyhydroxylated materials such as silica, which can serve as stationary phases in various chromatographic methods, are disclosed. The silica is first contacted with a reagent, e.g., a phosphorylating agent, effective to cleave the O--H bond of at least one of said hydroxyl groups and introduce through an --O-- linkage a moiety amenable to nucleophilic displacement; and the product of step (a) is then contacted with a suitable nucleophilic ligand.

Abstract: Methods are provided for the purification of interleukin-2 (IL-2) and chimeric proteins containing an IL-2 moiety from a wide variety of sources, including synthetic mixtures, cell culture conditioned medium and mammalian and bacterial recombinant expression systems. The methods of the invention employ IL-2 receptor-affinity adsorbents in which soluble IL-2 receptors have been immobilized on solid supports. Through the use of these affinity adsorbents, highly purified IL-2 and chimeric proteins containing an IL-2 moiety can be produced in a single step from bacterial extracts or conditioned medium. The proteins thus purified are largely free of aggregated forms, which are often present when other purification methods are used.

Abstract: Disclosed are biocompatible viscoelastic gel slurries formed from a polymeric gel, preferably a hyaluronan or a derivative thereof such as hylan swollen in an aqueous medium and a fluid phase which is an aqueous solution of a polymer which may also but not necessarily be a hyaluronan or derivative thereof. Also disclosed are methods of making such slurries, controlling their rheological properties and the uses thereof.

Abstract: Undesired immune responses are suppressed by administering a nonimmunogenic material which comprises one or more haptens or epitopes corresponding to the antigen which causes the undesired immune response, the number and spacing of the haptens or epitopes being insufficient to trigger an immune response but sufficient to inhibit it. Also disclosed is an improved vaccine from which low molecular weight suppressive polymer has been removed.

Abstract: Preparation of a composite of mannan binding protein attached to an insoluble, support matrix is accomplished by reacting cyanogen bromide activated beaded agarose with a buffered solution of mannan binding protein isolated from rabbit serum. The composite has utility as an affinity sorbent for IgM when divalent metal ions are incorporated in the binding buffer. The composite does not show cross-reactivity (binding) with immunoglobulins of the G class.

Abstract: Disclosed is a soluble, biocompatible, pharmacological agent for inhibiting thrombin generation and thrombus formation, and methods for producing the same. The pharmacological agent or conjugate includes a soluble, biocompatible carrier and a thrombogenesis inhibitor immobilized thereto via the carrier which binds the inhibitor. The thrombogenesis inhibitor is hirudin, or an active analog or active fragment thereof. The thrombogenesis inhibitor may be bound to the carrier via a bifunctional cross-linking reagent.

Abstract: A system for stabilizing fibroblast-derived growth factors, maintaining their bioactivity over a prolonged period of time and controllably releasing them for use is disclosed. The system uses growth factors bound to biocompatible substrates via heparin or heparin derived compounds to maintain the bioactivity of the growth factors. A growth factor bound to a heparin coated substrate can be used independently as a controlled release device, or can be incorporated into a reservoir or matrix type controlled release devices to further enhance the controlled release properties. The stabilized growth factors can be implanted into a patient, thereby providing a means for producing an in vivo controlled release of a growth factor to the patient.

Abstract: A cyclic peptide designated FR115224, administered parenterally in a cyclodextrin carrier, which exhibits antiallergic activity.

Abstract: Biological materials such as enzymes, proteins and peptides are encapsulated by forming a mixture of the material and an aqueous non-ionic polymer solution, spraying the mixture into a circulating water-immiscible nonsolvent for the polymer at a temperature sufficient to freeze the beads and drying the frozen beads to remove essentially all unbound water such as to provide a water content of about 1-2 weight percent. Suitable non-ionic polymers are poly(vinyl alcohol), polyvinylpyrollidone, dextran and derivatized cellulose. A densification agent such as alumina may be present in the polymer solution to enhance specific gravity of the beads formed. Encapsulated material such as microbes produced by this process provide useful agricultural agents which can be delivered to the market in a dormant state and suitable for delivery to soil or plant leaves. The beads can be applied dry, via a planting or an insecticide box, or wet via a spray nozzle.

Abstract: A method for the selective extraction of beta-lactoglobulin and other proteins from whey or milk by means of subunit exchange chromatography and for the deproteinization of whey by subsequent chromatography on an ion exchange resin.

Abstract: Thromboresistant materials are disclosed comprising hirudin or hirudin derivatives covalently linked to support materials such that the resultant composition has substantially the same biological activity as hirudin. Methods for making such compositions are also disclosed.

Abstract: An adsorbent for .beta..sub.2 -microglobulin is disclosed, which comprises a water-insoluble carrier having supported thereon, as a ligand, at least one electrolyte selected from the group consisting of a polyamino acid, a polysaccharide, a synthetic high polymer, collagen having an isoelectric point of 9.5 or more, and gelatin having an isoelectric point of 6.5 or more, wherein said electrolyte has a molecular weight not less than 1,000 and an X value of more than 2.0, wherein X is a relationship regarding the skeleton structure of said electrolyte and is the sum of A and B, wherein A represents (the number of carbon atoms of the skeleton structure)-(the number of hydrophilic groups)/(the number of hydrophilic groups); and B represents .vertline.(the number of cationic groups)-(the number of anionic groups).vertline./(the number of hydrophilic groups). The adsorbent exhibits adsorptivity for .beta..sub.2 -microglobulin at high efficiency and high selectivity.

Abstract: Homogeneous cyclophilin, a soluble binding protein, having a specific binding activity of above 50 ug cyclosporin A per mg protein and a molecular weight of about 17,600 daltons, reversibly binds immunosuppressants or antibodies thereto such as cyclosporin or anti-cyclophilin. It is isolated from the cytosol of several different mammalian tissues and can be used in various diagnostic and purifications procedures.

Abstract: The present invention provides a process for the production of a polysaccharide matrix to which haptens are covalently bound, wherein polysaccharide-containing material is rendered alkaline, dried to a water content of less than 5% and then reacted in an anhydrous medium with a hapten containing at least one activated functional group.The present invention also provides a device for carrying out this process, which comprises a winding core (3) in a container (1) for a reaction solution which has a tube (11), provided on its wall with a plurality of openings (7) and closed on one end (9), for the reception of a winding (13) of the material to be treated and two axial end walls (15, 17) for sealing off the axial ends of the winding (13) and feeds the reaction solution from the container (1) into the other end (21) of the tube (11) by means of a circulating pump cycle (19).

Abstract: Fixation of a physiologically active substance on a carrier through an alkylene oxide chain allows the physioactive function of the substance to be retained to a high degree. The fixed physiologically-active substances are useful for separation and purification of materials. The carrier is preferably a thin fiber of 1.0 denier or less, and may be formed from a polymer. The alkylene oxide chain has an amino or epoxy group at one end which bonds to the carrier and a functional group at the other end which bonds to a physiologically-active substance.The carrier is preferably a thin fiber of 1.0 denier or less, and may be formed from a polymer. The alkylene oxide chain has an amino or epoxy group at one end which bonds to the carrier and a functional group at the other end which bonds to a physiologically-active substance.

Abstract: Antibody is provided which is capable of neutralizing the in vitro anti-neoplastic cellular activity of lymphotoxin. This antibody, which preferably is produced of monoclonal fusions, can be used in assays for lymphotoxin or for immunoaffinity purification of lymphotoxin.

Abstract: New Amines and amides of carboxylated polysaccharides having the nitrogen of the amido and amino groups directly attached to the polysaccharides and method of making same, based on reacting in solution a material having carboxyl-containing polysaccharides, such as carboxymethyl cellulose, with ammonium donors having the general formula >NH such as primary and secondary amine reagents and with or without a reducing agent to obtain amides or amines. These products may be used for instance in biological separations, for the immobilization of proteins, for the removal of metal ions, a thickeners, and as suspension agents.

Abstract: Enzymes or microorganisms are immobilized by bringing a first aqueous solution into contact with a second aqueous solution containing metal ions having a valence of 3 or more. The first solution contains enzymes or microorganisms, and at least one immobilizing agent selected from the group consisting of Xanthan gum and derivatives thereof. The immobilizing agent is thereby hardened in a state to enclose the enzymes or microorganisms. Preferably, the metal ions are iron, tin, manganese or titanium ions.

Abstract: A channel protein has a Na.sup.+ /K.sup.+ selectivity of approximately 100 and capable of affecting Na.sup.+ membrane transport. Amiloride derivatives, and amiloride gel materials incorporating such derivatives, are useful in treating membrane transport, cellular volume and cellular pressure disorders and in isolating the channel protein. The channel protein is used in diagnostic assays and screening assays.

Abstract: Methods and materials are described for the preparation of novel immobilized membrane compositions. The described compositions are useful for evaluating membrane association charcteristics of chemical compounds, and as a chromatographic support material for separation/purification of biomolecules and particularly those expressed by genetically transformed cells as novel hybrid proteins having covalently bound membrane-binding peptides. Novel phospholipid carboxylates are useful intermediates for the preparation of chromatography supports having surfaces formed as covalently bound artificial membranes which simulate natural cellular membranes. The immobilized membrane compositions are adapted for use in chromatographic systems to study interactions of biologically active substances with membranes in vitro.

Abstract: A polysaccharide derivative having the structure Sacch--O--Z--Ar--CH.dbd.N--Y or ##STR1## where Sacch--O-- represents a polysaccharide molecule; Z is --(CH.sub.2).sub.n -- or ##STR2## Ar is a divalent aromatic group; Y is (a) a monovalent group derived from a water-soluble substituted or unsubstituted aromatic compound containing only one free primary amine group, or (b) a monovalent group derived from a water-soluble substituted or unsubstituted aliphatic or cycloaliphatic compound containing only one primary amine group, or (c) a multivalent group derived from a water-soluble protein containing more than one primary amine group; n is one or greater; and m is zero or greater, is prepared by first modifying the polysaccharide with a reagent to introduce free aromatic aldehyde groups and then reacting with a suitable amine-containing reagent. The siloxane-containing starch derivatives are useful in glass forming size compositions.

Abstract: A membrane mimetic structure having a hydrophilic outer portion and a hydrophobic inner portion is covalently bound to a surface having reactive functional groups. The membrane mimetic structure consists essentially of adjacent amphiphilic molecules independently covalently bound to the surface. The structures can be applied to surfaces and should find application in a wide variety of disciplines requiring surfaces exhibiting properties of biological membranes.

Abstract: A monoclonal anti-idiotypic antibody specific to a human IgG.sub.1 type monoclonal antibody possessing specificity to nicotinic acetylcholine receptor; a method for the production of the aforementioned monoclonal anti-idiotypic antibody by the steps of immunizing an animal with a human IgG.sub.1 type monoclonal antibody specific to nicotinic acetylcholine receptor, collecting antibody-producing cells from the animal, fusing the collected cells with neoplastic cells, selecting from the product of fusion a hybridoma capable of producing a monoclonal anti-idiotypic antibody specific to the human IgG.sub.1 type monoclonal antibody possessing specificity to nicotinic acetylcholine receptor, propagating the selected hybridoma thereby giving rise to said monoclonal anti-idiotypic antibody, and collecting the produced monoclonal anti-idiotypic antibody; and use of the monoclonal anti-idiotypic antibody as a reagent and as an adsorbent.

Abstract: A channel protein has a molecular weight of approximately 280 kD and is capable of affecting K.sup.+ and Cl.sup.- membrane transport. Furosemide and quinine derivatives, and polysaccharide or monosaccharide gels incorporating such derivatives, are useful in treating membrane transport, cellular volume and cellular pressure disorders and in producing the channel protein. The channel protein is used in diagnostic assays and screening assays is described.

Abstract: Thiol gels are prepared from hydroxyl containing polymers by forming a 2-fluoro-1-methylpyridoxy derivative of the polymer followed by reacting the derivative with sodium dimethyldithiocarbamate and reducing to produce a sulfhydryl substituted polymer. Alternatively, the derivative is reacted with dithiothreitol to produce a sulfhydryl substituted polymer having free sulfhydryl groups spaced from the polymer. The thiol gel can be activated by means of 2,2'-dipyridyl disulfide and reacted with a free sulfhydryl containing biologically active ligand in order to provide an insolubilized ligand which can be used for various purposes including use as an immobilized biologically active material or use as a matrix in covalent chromatography.

Abstract: A biological composition comprises a solid phase support matrix or marker molecule bound to protein, typically a glycoprotein such as an immunoglobulin through a linking group, spacer arm, and hydrazone group. The linking group is conveniently an ether linkage, while the spacer arm is a linear chain including six atoms, where at least one of the atoms is a tertiary amine which is protonated at a pH below about 8. The hydrazone is formed by reacting the solid phase or marker molecule having the linking arm and the spacer arm including a terminal hydrazide group with a glycoprotein oxidized to include a terminal aldehyde group. Immunological reagents prepared by linking an immunoglobulin (IgG) through a carbohydrate on the Fc or hinge regions have been found to provide very high binding capacity approaching the theoretical bivalent limit of two moles of bound antigen for every mole of bound immunoglobulin.

Abstract: Macromolecular monoclonal antibody compositions are provided which are capable of selectively forming stable bonds to cells having a predetermined concentration of at least one surface antigen, such concentration being greater in such cells than in other cells in the cell population, wherein the composition comprises a substrate and a plurality of monoclonal antibodies specific to said surface antigen or antigens, which antibodies are covalently bonded to the substrate.

Abstract: The invention relates to compositions comprising adducts of activated polysaccharides with biologically active growth hormones, somatomedins, growth factors and biologically active fragments. The invention also relates to a method for increasing and maintaining increased levels of these biologically active molecules in the blood of treated animals for extended periods of time, increasing weight gains in animals, and increasing milk production of lactating animals by the administration of a composition of the invention.

Abstract: The invention relates to a new method of immunological analysis for serum amyloid A protein (SAA) and serum amyloid P-component (SAP), kits therefor and a method of purification of SAA and SAP. These methods are based on the efficient binding of SAP to a plastic surface and to carriers bearing nitrated phenyl groups in the presence of calcium and related bivalent ions, and of SAA to a plastic surface and to carriers bearing nitrated phenyl groups with or without calcium ions. The method of immunological analysis allows for rapid and reliable screening of serum samples with a high sensitivity. SAA and SAP play a key role in the diagnosis and management of inflammatory diseases.

Abstract: A novel process for the isolation and purification of vancomycin class antibiotics which utilized affinity chromatography by the formation of a sorption complex between the antibiotic and an immobilizing ligand selected from -D-alanyl-D-alanine or -X-D-alanyl-D-alanine, wherein X is an amino acid radical and the novel affinity chromatography sorbent employed therein are disclosed.

Abstract: The process for the separation of antiVIII:C antibodies present in a liquid consists of contacting said liquid with a solid support constituted by a polymer or a copolymer having in its chain substitutable groups, whereof at least part is substituted by groups having an affinity for antiVIII:C antibodies and a selectivity for antiVIII:C antibodies compared with other immunoglobulins and then separating the liquid from the support on which have been adsorbed the antiVIII:C antibodies.Preferably use is made of polystyrene, to which have been fixed groups --SO.sub.3 Na and --SO.sub.2 Glu, --SO.sub.2 Threo, --SO.sub.2 OHPro or SO.sub.2 Lys. These supports can be used for ex-vivo purification in the column of the blood plasma of a type A hemophiliac.

Abstract: The invention relates to a process for producing a fucosyl antigen charcterized in that an oligosaccharide contaning an .alpha.-fucoyransoyl-(1.fwdarw.3)-, -(1.fwdarw.4)- or -(1.fwdarw.6)-galactoyransoyl group and serving as a hapten is reacted wtih a carrier protein to obtain a carbohydrate antigen and to a process for producing from the antigen an antibody having specific reactivity with cells of cancers of the digestive system, especially human colon carcinoma cells, and murine teratocarcinoma cells.The invention also relates to a method of determining a cancer associated crabohydrate linkage with use of such antibody capable of specifically recognizing specific carbohydrate linkage and to a cancer diagnosing kit containing the antibody.

Abstract: A method for selectively covalently linking a target moiety to a chemical moiety or carrier comprising attaching to the chemical moiety or carrier a reagent having a selector group capable of forming a specific bond with a receptor carried on the target moiety and attaching a latent reactive group which is capable upon activation of covalently bonding to the target moiety, reacting the selector group with the receptor on the target moiety, and activating the latent group to form a covalent linkage to the target moiety.

Abstract: A naturally occurring protein is chemically modified to provide the protein with activity of a selected enzyme. The protein does not contain activity of the selected enzyme before modification. Modification is carried out by partially denaturing the protein, contacting the partially denatured protein with an immobilized enzyme inhibitor of the selected enzyme, crosslinking the protein in the presence of the inhibitor and recovering a modified protein having activity of the selected enzyme.

Abstract: The invention relates to an allosterically active conjugate composition comprising one or more hemoglobin tetramers and one or more adducts of a physiologically safe macromolecular agent covalently linked to one or more ligands, such that the adduct is bound to the allosteric binding site of the hemoglobin in a reversible, non-covalent manner; the invention also relates to methods for producing such conjugate compositions; and to blood substitutes or plasma extenders containing such conjugates.

Abstract: The invention relates to monoclonal anti-idiotypic antibodies to human anti-DNA antibodies. Monoclonal, anti-idiotypic antibodies are produced using hybridoma technology. The antibodies are used as diagnostic reagents in methods to determine the presence of anti-native DNA antibodies in serum from patients suspected of having systemic lupus erythematosus.

Abstract: The invention relates to monoclonal anti-idiotypic antibodies to human anti-DNA antibodies. Monoclonal, anti-idiotypic antibodies are produced using hybridoma technology. The antibodies are used as diagnostic reagents in methods to determine the presence of anti-native DNA antibodies in serum from patients suspected of having systemic lupus erythematosus, and as therapeutic reagents in methods to remove the anti-native DNA antibodies from the serum of patients with systemic lupus erythematosus.

Abstract: Novel peptide hydroxamic acid derivatives having useful collagenase inhibitory activity and capable of forming affinity resins for the purification of vertebrate collagenase are defined by the following structural formula:R-Pro-Leu-Gly-NHOHwherein R=H or N-protecting group or agarose.

Abstract: A hybrid cell formed by the fusion of a mouse spleen cell with a mouse myeloma cell secretes an IgM class antibody. The antibody is useful as a preparative reagent in the isolation of three proteins, molecular weights 45,000, 49,000 and 53,000, from the parasite Trichinella spiralis and is also useful as a direct diagnostic reagent is a competitive serodiagnostic test.

Abstract: The drug such as antitumor agents or antibiotics can preferentially be carried to a morbid part, for example, injured tissue and tumor site by administering its complex with fibronectin combined through an oxidized dextran to repair the morbid part. The complex is prepared by reacting the drug, an oxidized dextran having a cleaved structure of aldohexopyranose ring, and fibronectin.