Abstract: An affinity chromatographic matrix for purification of a biological material is provided having an ionically charged polymeric ligand such as glycoaminoglycan non-covalently bound directly by an ionic bond to an oppositely ionically charged group on a chromatographic matrix. Having the ligand non-covalently bound to the matrix by an ionic bond, allows the ligand to be easily washed off the matrix and replaced for subsequent purifications without having to replace the matrix. A biological material in a crude mixture is purified by non-covalently binding the material to the bound ligand and dissociating the material from the ligand. Matrices that may be used include crosslinked agarose, crosslinked dextran, crosslinked cellulose, crosslinked dextran and bisacrylamide, or matrices based on silica or plastic polymers. The charged group may be a quaternary amine or diethylaminoethyl group.

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

Abstract: A stromal cell-based three-dimensional cell culture system is provided which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. The stromal cells along with connective tissue proteins naturally secreted by the stromal cells attach to and substantially envelope a framework composed of a biocompatible non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells. Living stromal tissue so formed provides support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture and/or cultures implanted in vivo. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts in vivo, which can be utilized in the body as a corrective tissue.

Abstract: Microcapsules and composite microreactors are prepared that immunoisolate living cells such as islet cells or genetically engineered cells. A reduced volume microcapsule is formed by coating a gel matrix particle with a polyamino acid of 15,000 daltons or less molecular weight to reduce volume of the particle by at least 30% as compared to volume prior to coating. A composite microreactor includes the microcapsule containing cell embedded in a gel matrix and provides a molecular weight cutoff that prevents molecules larger than about 400,000 daltons from containing the living cell. A double composite microreactor includes an internal particle that includes an internal particle gel matrix containing a living cell and having a coating, a particle that includes the internal particle embedded in a particle gel matrix and a coating, and a gel super matrix in which the particle is embedded. At least one of the coatings is a volume reducing coating of polyamino acid of 15,000 daltons or less molecular weight.

Abstract: Composition comprising oxidizable galactose type of alcohol configuration containing polymer (such as guar) which is in solid state and galactose oxidase. Application of such oxidized polymers in the papermaking process results in superior paper strength characteristics.

Abstract: The present invention provides polypeptide conjugates with reduced allergenicity comprising a polymeric carrier molecule having two or more polypeptide molecules coupled thereto. The invention also provides methods for producing the conjugates, compositions comprising the conjugates, and the use of the conjugates in industrial applications, including personal care products and detergent compositions.

Abstract: Proposed is a mitogen-free substance comprising cross-linked copolymers including 10 to 90 mole % of guluronic acid, the balance being made up of mannuronic acid. The substance has a molecular weight of from 10,000 to 500,000 Daltons. Also proposed are methods for preparing such substances and their use.

Abstract: An immunoisolatory vehicle for the implantation into an individual of cells which produce a needed product or provide a needed metabolic function. The vehicle is comprised of a core region containing isolated cells and materials sufficient to maintain the cells, and a permselective, biocompatible, peripheral region free of the isolated cells, which immunoisolates the core yet provides for the delivery of the secreted product or metabolic function to the individual.

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: Penicillin G acylase is immobilized by covalent bonding to a crosslinked mixture of a gelled gelling agent such as gelatin and a polymer containing free amino groups such as alginate amine, chitosan or polyethylene imine. The immobilized penicillin G acylase provides a higher synthesis/hydrolysis ratio as compared to immobilizing with other carriers when producing .beta.-lactam derivatives by a condensing reaction of an amino .beta.-lactam with an acylating agent. The acylating agent may be a derivative of D-phenylglycine, a derivative of D-p-hydroxyphenylglycine or a derivative of D-2,5-dihydro-phenylglycine. Examples of .beta.-lactam derivatives that can be produced are amoxycillin, ampicillin, cephaclor, cephadroxil, cephprozil, cephalexin and cephradine.

Abstract: Microorganisms which may be in the form of homogenated anaerobic sludge are immobilized in a polymeric gel matrix containing chitosan and lignosulphonate. A mixture of chitosan solution and a microorganism is added dropwise to a solution of lignosulphonate to crosslink chitosan droplets and form beads of chitosan/lignosulphonate matrix membrane encapsulating the microorganism. Alternatively, the mixture is added to a water-insoluble organic phase to form chitosan beads in an emulsion, and to the emulsion is added a lignosulphonate solution to crosslink the beads and form a chitosan/lignosulphonate matrix membrane encapsulating the microorganism. In another embodiment, anaerobic bacteria in the form of granules are encapsulated in the chitosan/lignosulphonate matrix membrane and the membrane contains another bacterial specie(s).

Abstract: A two-phase partition system is provided for affinity separation of a composition containing a polysaccharide binding peptide from a mixture such as a fermentation broth. The peptide may be from an enzyme and lacking in polysaccharidase activity such as the binding domain of cellulase that binds to cellulose. The system contains a phase-forming oligosaccharide polymer such as a cellulose derivative to which the peptide binds with a Ka of 10.sup.3 M to 10.sup.7 M, and a phase inducing agent such as a polyethylene glycol polymer, or a salt present at sufficiently high concentration to induce phase separation. If the oligosaccharide polymer is thermoseparating, phase separation can be induced by heating. Using the system involves contacting a composition containing the peptide such as a fusion protein with the system, partitioning the composition into a phase containing the oligosaccharide polymer by binding to the polymer and recovering the polymer containing the bound composition.

Abstract: An improvement for enzymatically syhnthesizing a .beta.-lactam compound is presented. The improvement comprises catalyzing the acylation of an amino .beta.-lactam with an acylating agent for at least 5 hours with an amidase or acylase, wherein the concentration of each reactant is constantly higher than 70% of the lowest value of the saturated concentration of both reactants.

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: In a vertical down-flow fluid bed reactor, suspended particles in liquid proximal to an inlet in an uppermost part of the reactor are agitated to form a downward extending turbulent zone having vigorously moving particles and a non-turbulent zone distal to the inlet having essentially stationary particles in liquid below and adjoining the turbulent zone. In a vertical up-flow fluid bed reactor, an upward extending turbulent zone is formed proximal to an inlet in a lowermost part of the reactor and the non-turbulent zone is above the turbulent zone. The downward or upward extend of the turbulent zone is determined by the degree of agitation. The particles may contain an active substance and be in the form of a conglomerate of base particles having a desired density to control floatation or sedimentation. Particles in the turbulent and non-turbulent zones may be different such as having different specific gravities.

Abstract: Oxalate-degrading enzymes and bacteria were encapsulated for both enteric and intraperitoneal administration. We have shown that via alginate microencapsulation of Oxalobacter formigenes, enzymatic activity was retained for several months. A new process was developed which strengthened the aliginate microcapsules and their tolerance to citrate treatment. Much smaller (30-50 .mu.m) aliginate microcapsules were made for injection as means of impantation. For oral administration, multi-encapsulated microspheres of cellulose acetate phthalate in poly-2-vinylpyridine (pKa=3.5) were prepared to protect the enzymes from gastric juices.

Abstract: Improved fermentation activity of microorganisms in a polysaccharide gel such as an alginate gel is obtained after dehydration, staorage and rehydration by soaking the gel containing the microorganisms prior to dehydration in a sugar solution to provide in the gel an amount of sugar of at least 100 g/kg and less than 500 g/kg of gel, preferably less than 300 g/k of gel. The dehydration may be carried out in a fluidized bed or by lyophilization. The gel may be in the form of beads or fibers having a double layer structure formed by an internal layer or core of gel containing the microorganisms and an external lay er or envelope of gel essentially devoid of the microoraganisms. The sugar is preferably xylose, glucose, fructose, lactose or sucrose, and the sugar solution may contain a polyol such as sorbitol, inositol or glycerol to provide in the gel an amount of polyol of at least 30 g/kg of gel.

Abstract: Enzymes are immobilized by preparing an emulsion containing a continuous hydrophobic phase such as a triglyceride oil and a dispersed aqueous phase containing an amphiphilic enzyme such as lipase or phospholipase and carrier material that is partly dissolved and partly undissolved in the aqueous phase, and removing water from the aqueous phase until the phase turns into solid enzyme coated carrier particles. The undissolved part of the carrier material may be a material that is insoluble in water and oil, or a water soluble material in undissolved form because the aqueous phase is already saturated with the water soluble material. The aqueous phase may be formed with a crude lipase fermentation liquid containing fermentation residues and biomass that can serve as carrier materials. Immobilized lipase is useful for ester re-arrangement and de-acidification in oils.

Abstract: A stromal cell-based three-dimensional cell culture system is prepared which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. The stromal cells and connective tissue proteins naturally secreted by the stromal cells attach to and substantially envelope a framework composed of a biocompatible non-living material formed into a three-dimensional structure having interstitial spaces bridged by the stromal cells. The living stromal tissue so formed provides the support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture and/or cultures implanted in vivo. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts in vivo, which can be utilized in the body as a corrective tissue.

Abstract: An artificial pancreas is described herein which comprises one or more viable and physiologically active pancreatic islet cells capable of producing insulin, encapsulated within a semipermeable spheroidal membrane comprising agar gel. Further disclosed are a method for producing agar microbeads, a tissue implantation method and a reseeding method for the artificial pancreas.

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: The present invention generally relates to novel encapsulation compositions and methods. In particular, the invention relates to stabilized microcapsule compositions which comprise a layer of a crosslinked, mixed functionality, polymer matrix, and methods for their preparation. The encapsulated compositions may comprise the crosslinked polymer matrix layer as an inner layer, an outer layer, or an intermediate layer of an overall encapsulated composition. The compositions will generally also comprise a biological material, e.g., cells, proteins, and the like, encapsulated within the composition. The compositions and methods of the invention are useful in a variety of applications, including cell culturing and transplant therapy.

Abstract: A media additive for the promotion of the growth of anaerobic and aerobic bacteria is presented. The additive comprises lyophilized microorganisms exposed to ionizing radiation. The microorganisms are Escherichia coli ATCC 25922 and Escherichia coli ATCC 110303. Such microorganisms are incapable of multiplication, yet retain many of their metabolic pathways, enzymes, and biologically active compounds, permitting them to be utilized by the bacteria to be cultured.

Abstract: A crosslinkable macromer system that includes two or more polymer-pendent polymerizable groups and one or more polymer-pendent initiator groups. The polymerizable groups and the initiator group(s) can be pendent on the same or different polymeric backbones. The macromer system provides advantages over the use of polymerizable macromers and separate, low molecular weight initiators, including advantages with respect to such properties as nontoxicity, efficiency, and solubility.

Abstract: Compositions and methods for avidin or protein having affinity for biotin immobilized on an inert support material, e.g., agarose, are disclosed. The compositions have high activity levels for binding biotin and may include a bulking agent, e.g., maltose, and a protectant to maintain the stability and integrity of the composition during lyophilization and terminal sterilization processes. The compositions have applicability in any instance where avidin agarose and/or the avidin/biotin technology are useful. In particular, the present compositions are useful in an enzyme capture system to prepare fibrin monomers useful for fibrin sealants.

Abstract: Contact lens are cleaned and disinfected by contacting with an enzyme that functions as a cleaning agent by degrading deposits on the lens, and with an enzyme inhibitor that inhibits remaining enzyme activity and a mild disinfecting agent. If rinsing of the lens is not carried out after cleaning and disinfecting, this procedure prevents eye damage by inhibiting remaining enzyme activity and using a mild disinfectant. Preferred enzymes are proteases such as an acidic aspartic protease, a cysteine protease, a serine protease or a metalloprotease, and preferred enzyme inhibitors function both as an inhibitor and as a mild disinfectant such as chloramine-T, chloramine-B, bacitracin or aryl boronic acids. In a preferred method, the enzyme is subtilisin A and the enzyme inhibitor and disinfectant is chloramine-T.

Abstract: Epithelial cells are attached to microcarriers to form a transplantation material for treatment of skin wounds. Preferably, keratinocyte-covered microcarriers are prepared using microcarriers having a diameter of 50 to 500 .mu.m, and obtaining a coverage of keratinocytes of 30 to 100% of the maximum coverage. An optimum coverage is between 50 and 80% and preferably between 60 and 70%. Keratinocytes are selected from autologous cells, allogenic cells and a combination of these cells. The microcarriers may be pre-coated with eukaryotic cells or an extracellular matrix protein such as collagen before keratinocytes are attached. The keratinocyte-covered microcarriers may be combined with a cryoprotective substance for storage at +3.degree. C. to -196.degree. C. prior to use. Keratinocytes are attached to the microcarriers by pre-culturing the keratinocytes, and then culturing the keratinocytes in the presence of the microcarriers while intermittently stirring. A serum free culture medium may be used.

Abstract: A macroencapsulation device for somatic cells using ultrapurified Na alginate and polysulfone hollow fibers of 30 kDa molecular weight cutoff. Ultrapurified Na alginate material is used which has a high `G` content, low endotoxin content, low divalent metal toxins and low protein impurities. Islet cells prior to being encapsulated, are irrigated with Hank's modified solution (without Ca and Mg) containing gentamycin, vancomycin and amphotericin B and then passed through a leukoabsorb filter to reduce the donor antigen load of passenger leukocytes and to reduce the bioburden of microorganisms including viruses. Encapsulation is done in RPMI 1640 tissue culture fluid containing necessary nutritional supplements and ATP source of energy. The open ends of the fiber are covered with a porous membrane. To further improve biocompatibility, the outer wall of the polysulfone is lightly gelled with alginate gel.

Abstract: A method is described for the rapid, sensitive and accurate determination of sucrose in biological fluids. A substrate is pre-coated with a glucose or fructose polymer and a transglycosidase enzyme. When the coated substrate is incubated with biological fluids containing concentrations of sucrose, the transglycosidase enzyme transfers monomers of glucose or fructose from the sucrose to the glucose or fructose polymer. The dimensions of the polymer are increased in proportion to the sucrose concentration of the samples. Newly formed polymer is subsequently quantitated in an immunoassay which employs either a combination of a carbohydrate-binding protein (which may be an antibody) and a conjugate of a secondary antibody and a marker enzyme, or a conjugate of a carbohydrate-binding protein and a marker enzyme. The assay is accurate at sucrose concentrations below 1 .mu.g/mL. No interference was observed at glucose concentrations as high as 25 mM.

Abstract: A biodegradable particulate vector for transporting biologically active molecules is prepared containing a nucleus formed of a cross-linked polysaccharide or oligosaccharide matrix having grafted ionic ligands, a layer of fatty acid compounds covalently bonded to the nucleus and a layer of phospholipids hydrophobically bonded to the layer of fatty acid compounds. Dextran, cellulose or starch may be cross-linked with epichlorohydrin to form a cross-linked polysaccharide matrix. Ionic ligands may be grafted using an acidic compound such as succinic acid, phosphoric acid or phosphorous oxychloride, or a basic compound such as choline, hydroxycholine, 2-(dimethylamino)ethanol or 2-(dimethylamino) ethylamine fastened onto the grafted acidic compound. Phosphoric acid or phosphorous oxychloride in one step provide both cross-linking and ionic ligands. Co-cross-linking can be obtained using a protein such as keratin, collagen or elastase.

Abstract: A process for the efficient production of a D-amino acid from the corresponding DL-5-substituted hydantoin by one-step reaction which comprises using a composite immobilized enzyme at a pH about neutrality, said composite immobilized enzyme being obtained by immobilizing a hydantoinase having its optimal pH within an alkaline range and a D-N-carbamyl-.alpha.-amino acid amidohydrolase having its optimal pH about neutrality in a coexisting state on an immobilizing support, simultaneously, is disclosed.

Abstract: Fusion proteins or conjugates are provided containing an amino acid sequence having a substrate binding region of a polysaccharidase such as cellulase that binds to a .beta.-1,4-glycan matrix such as cellulose. The substrate binding region is essentially without polysaccharidase activity. In the fusion protein, the substrate binding region is fused or chemically linked to a polypeptide such as an enzyme, a hormone, an immunoglobulin or a protein dye. By contacting the fusion protein with a .beta.-1,4-glycan matrix, the substrate binding region binds to the matrix to immobilize the polypeptide on the matrix. The polypeptide or fusion protein can be removed from the matrix with a protease acting on a protease recognition sequence or with a solution having a low ionic strength or high pH. In the conjugate, the substrate binding region is joined such as by covalent bonding to a non-protein chemical moiety such as a dye, chromophore, fluorescor, radionuclide or enzyme co-factor.

Abstract: Disclosed are rationally designed mixed mode resins which are useful in recovering a target compound from an aqueous solution and methods for use of such resins. The resins described herein have a hydrophobic character at the pH of binding of the target compound and a hydrophilic and/or electrostatic character at the pH of desorption of the target compound from the resin and are specifically designed to bind the target compound from an aqueous solution at both a low and high ionic strength.

Abstract: Compositions and methods for avidin immobilized on an inert support material, e.g., agarose, are disclosed. The compositions have high activity levels of avidin and may further include a bulking agent, e.g., maltose, and a protectant to maintain the stability and integrity of the avidin agarose during lyophilization and terminal sterilization processes. A dry composition, and wet compositions such as a gel, slurry or suspension having avidin immobilized on an inert support material are disclosed. The dry composition has at least 1000 biotin binding units of activity, and the wet compositions have at least 50 units of binding activity. These compositions have applicability in any instance where avidin agarose and/or the avidin/biotin technology are useful. In particular, the present compositions are useful in an enzyme capture system to prepare fibrin monomer useful for fibrin sealants.

Abstract: Isomaltulose-forming microorganisms are immobilized on a carrier that is a weakly basic anion exchange substance in the form of a substantially non-compressible porous particulate solid material, and are used for isomerization of sucrose to isomaltulose. A preferred carrier contains microfibers or microparticles of diethylaminoethyl cellulose adherently bound by agglomeration with polystyrene. The isomerization may be a continuous conversion in one or more columns packed with the carrier. Isomaltulose may be hydrogenated to form isomalt for use in sweetening. Microorganisms can be immobilized on the carrier by feeding microorganisms to a column containing the carrier. After microorganism immobilization, the carrier may be treated with a crosslinking and/or flocculating compound. Regeneration of the carrier is carried out by removing microorganisms, washing and reloading with fresh microorganisms.

Abstract: A method of producing fatty acids and glycerol from oleaginous materials utilizing comminuted seeds as an immobilized lipase catalyst. The comminuted lipase-containing seeds are combined with an oleaginous material, an organic solvent and water with the resultant heterogenous mixture being agitated under non-energy intensive conditions to provide free fatty acids and glycerol. The lipase catalyst may be recovered and recycled.

Abstract: The present invention generally relates to novel encapsulation compositions and methods. In particular, the invention relates to stabilized microcapsule compositions which comprise a layer of a crosslinked, mixed functionality, polymer matrix, and methods for their preparation. The encapsulated compositions may comprise the crosslinked polymer matrix layer as an inner layer, an outer layer, or an intermediate layer of an overall encapsulated composition. The compositions will generally also comprise a biological material, e.g., cells, proteins, and the like, encapsulated within the composition. The compositions and methods of the invention are useful in a variety of applications, including cell culturing and transplant therapy.

Abstract: An immobilized enzyme preparation is disclosed which comprises a gelling agent which has been cross-linked and active carbon in an amount of 1 to 3%. The gelling agent may be egg white chitosan or alginate. The enzyme glucose isomerase may be employed. When used in packed bed columns in enzymatic glucose isomerization processes, the disclosed immobilized enzyme formulation allows for a bedheight that is twice as high, a syrup flow that is doubled, or a doubled syrup viscosity when compared to formulations without carbon.

Abstract: A method of distinguishing between microorganisms having different attributes comprises the steps of: encapsulating one or more cells within a polymeric bead; incubating the cell(s) within the bead in a growth-supporting medium for a time period sufficient for multiplication of viable cells within the bead; then non-invasively physically examining the bead or the adjacent vicinity of the bead for physical characteristics associated with the differing attributes of cells within the bead. Various forms of apparatus for carrying out the process are descried.

Abstract: The present invention is directed to a non-immunogenic cellular composition comprising: a cell having a cell surface and antigenic determinants on the cell surface; a linker molecule covalently attached to the cell surface; and a non-immunogenic compound (e.g., polyethylene glycol or derivative thereof) covalently attached to the linker molecule. In one embodiment, the linker molecule is covalently attached directly to the antigenic determinant on the cell surface. In an alternate embodiment, the linker molecule may be covalently attached to a non-antigenic site on the cell surface, but will camouflage the antigenic determinant on the cell surface by virtue of the long chain length of the non-immunogenic compound.

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: Antivenoms to snake, spider, scorpion and jelly fish venoms are produced for treatment of humans and animals, and for analytical use. Polyvalent antivenoms are produced containing immunoglobulin which is greater than fifty percent venom reactive. Purified polyvalent antivenom is derived from a first polyvalent antivenom having two or more monovalent subpopulations, and purified such that greater than fifty percent of the monovalent subpopulations are recovered by weight. The antivenoms can be horse or avian such as chicken antivenom. Chicken antivenom is obtained using a whole venom that is not glutaraldehyde pretreated, and the antivenom contains yolk immunoglobulin. Antivenoms are purified with an antigen matrix containing a single whole venom or a plurality of whole venoms covalently attached to an insoluble support such as aldehyde-activated agarose. Preferably, the whole venoms forming the plurality of whole venoms are selected from the four whole venoms of C. atrox, B. atrox, C. adamanteus and C.

Abstract: Implantable beads which contain agarose and optionally collagen, and are coated with agarose have incorporated within cells which produce diffusible biological products. The beads may be used as implants to modulate a recipient's immune response. The beads may also be used in an in vitro context to encourage specific types of cells to grow, to produce desirable products in culture, or to suppress growth of certain cells. The implants may also suppress growth of certain cells following administration to a subject. Cancer cells such as renal cancer cells when restricted by being entrapped in the beads produce more of a material that suppresses cancer cell proliferation.

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

Abstract: The present invention provides an improved affinity membrane device and method for the effective removal of target molecules in plasma. The affinity membrane device is designed for use in an extracorporeal blood circuit and can be employed concurrently with other therapeutic processes for the purification of blood. The device of the present invention consists of hollow fiber membranes having specified dimensions and transfer properties, ligand immobilized to the pore surface of the hollow fibers, and a housing to encase the hollow fibers and allow appropriate entry and exit of the blood. In a preferred embodiment, specific immobilization chemistries are utilized to attach the ligands to the hollow fibers for optimal function.

Abstract: Mature Human Growth Hormone is prepared by enzymatic hydrolysis of a soluble precursor with immobilized Factor Xa. The soluble precursor contains a cleavage recognition sequence, Ile--Glu--Gly--Arg, for Factor Xa. The Factor Xa is preferably immobilized on CNBr activated Sepharose Cl-4B containing cyclic imido carbonate groups. Immobilization is carried out by reaction of amine groups on Factor X with the cyclic imido carbonate groups of the CNBr activated Sepharose Cl-4B to form covalently immobilized Factor X, which is then activated to Factor Xa with a protein contained in Russell's viper venom (RVV) in the presence of Ca.sup.++ ions.

Abstract: A carrier for holding a microorganism in soil releases, from a constituting material thereof, an inducer for production of an enzyme of the microorganism for soil remediation. The carrier for holding a microorganism may comprise a combination of a microorganism holding carrier composed of a hydrophilic polymer for holding the microorganism with an inducer-holder composed of another polymer for holding inducer manifesting a biological action to the microorganism adjacent to each other. A method for remediation of soil comprises application of the microorganism-holding carrier into the soil. A soil-remedying agent comprises the microorganism-holding carrier and a microorganism held thereon which exhibits enzyme activity for decomposition of a polluting substance in the soil under action an inducer released by the carrier.

Abstract: A supported polyionic hydrogel is prepared by impregnating a support matel with a solution of anionic polysaccharide and a solution of cationic polysaccharide where the anionic polysaccharide and cationic polysaccharide react with each other to form a polyionic hydrogel impregnated in the support material. The hydrogel may be dried such as by lyophilization. Preferably, the anionic polysaccharide is xanthan, dicarboxystarch or dicarboxycellulose and the cationic polysaccharide is chitosan. Especially preferred is a polyionic hydrogel formed from xanthan and chitosan. A paper material or a textile material can be used as the support material. A dry supported polyionic hydrogel can be formed as a bandage without active material incorporated therein. The supported polyionic hydrogel may be formed containing a biologically active material by having the active material in either polysaccharide solution or in another solution impregnated into the support material.

Abstract: Methods and compositions are provided for controlling cell distribution within an implantable bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the bioartificial organ with extracellular matrix molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination. The bioartificial organ typically has a semipermeable membrane encapsulating a cell-containing core, and is preferably immunoisolatory.

Abstract: The present invention relates to a purified, easily produced poly-.beta.-1.fwdarw.4-N-acetylglucosamine (p-GlcNAc) polysaccharide species. The p-GlcNAc of the invention is a polymer of high molecular weight whose constituent monosaccharide sugars are attached in a .beta.-1.fwdarw.4 conformation, and which is free of proteins, and substantially free of single amino acids, and other organic and inorganic contaminants. In addition, derivatives and reformulations of p-GlcNAc are described. The present invention further relates to methods for the purification of the p-GlcNAc of the invention from microalgae, preferably diatom, starting sources. Still further, the invention relates to methods for the derivatization and reformulation of the p-GlcNAc. Additionally, the present invention relates to the uses of pure p-GlcNAc, its derivatives, and/or its reformulations.