Abstract: Disclosed are methods for treatment of humans exposed to bacterial endotoxin in circulation by administration of bactericidal/permeability-increasing (BPI) protein products. Serologically and hematologically verifiable alleviation of endotoxin mediated increases in circulating cytokines, fibrinolysis and coagulation factors and changes in lymphocyte counts are observed upon such treatment. Also observed is alleviation of endotoxin mediated decreases in systemic vascular resistance index (SVRI) and concomitant increases in cardiac index (CI).

Abstract: Opossum whole serum exhibits a life saving property by neutralizing the lethality of venoms from all major families of poisonous snakes, and therefore an injection of Opossum serum can used as a novel treatment for many types of envenomation. Preferably, the injectable treatment for envenomation should be a composition obtained from the fraction of Opossum whole serum which contains the LTNF, i. e. the so called "LTNF-n", in purity. A method is given for the manufacture of a LTNF from the serum of an opossum (Didelphis virginiana) serum, by fractionating the opossum serum and isolating this select fraction from the plurality of fractions having an N terminal amino acid sequence given by SEQ ID No: 1. A short peptide was synthesized having SEQ ID No: 1. The synthetic peptide having the sequence SEQ ID No: 1 shows lethal toxin neutralizing activity similar to the natural LTNF from opossum or mongoose sera. The synthetic LTNF also has life saving utility.

Abstract: In a method of producing a virus-safe biological preparation by heating while preserving a least 50% of its biologic activity, a biologially compatible tenside is added to the preparation before heating and heating is carried out in the presence of the same, whereupon the tenside, preferably, is eliminated.

Abstract: A composition comprising coagulation factor VIII and a non-ionic surfactant such as block copolymers, e.g., polyoxamers or polyoxyethylene (20) sorbitan fatty acid esters, e.g., polysorbate 20 or polysorbate 80 as stabilizer is provided. The composition can also comprise sodium chloride, calcium chloride, L-histidine and/or sugars or sugar alcohols.

Abstract: The invention relates to a process for producing a virus free preparation of thrombin, and the use of said virus free concentrate as a pharmaceutical. For example, the invention relates to a process for the production of a purified and virus free preparation of thrombin which comprises adding a soluble salt in a concentration of from 0.5 mol/l up to the saturation limit thereof, said soluble salt having an anion that forms a sparingly-soluble salt or a soluble complex with calcium, to a solution of a prothrombin complex which has been purified on an anion exchanger and subjected to virus inactivation, said solution having a catalytic amount of thrombin present as a result of the purification, the viral inactivation, or added thereafter at a concentration of greater than zero up to 200 units of thrombin per ml of solution.

Abstract: A multimolecular complex made up of a plasminogen activator conjugated to anti-ACE Mab 9B9 capable of delivering the plasminogen activator to the pulmonary endothelium is provided. Methods of using this complex to selectively deliver the plasminogen activator to the pulmonary endothelium to enhance fibrinolysis in the lungs of an animal are also provided. In addition, a method of prolonging the time a plasminogen activator is present in the circulation of an animal by conjugating the plasminogen activator to anti-ACE Mab 9B9 is also provided.

Abstract: A process for producing a fibrinogen concentrate for use as a tissue adhesive from mammalian plasma includes freezing the plasma to a temperature of at most about -20.degree. C. for less than four hours in a container having a surface to volume ratio of from about 4.38:1 to about 1.65:1 reciprocal centimeters, thereby producing frozen plasma; thawing the frozen plasma at a temperature of at least about 4.degree. C. for a time sufficient to attain about 5% to about 95% residual icing, thereby producing thawed plasma; and centrifuging the thawed plasma to produce a fibrinogen concentrate having a solids content of about 6% to about 44% solids by weight of the concentrate.

Abstract: In a method of producing a virus-safe biological preparation by heating while preserving a least 50% of its biologic activity, a biologially compatible tenside is added to the preparation before heating and heating is carried out in the presence of the same, whereupon the tenside, preferably, is eliminated.

Abstract: Peptide-based compounds containing six invariant cysteine residues are useful as preservatives and in preventing, treating, or ameliorating microbial infection in animals and plants. These compounds are of the formulas: ##STR1## wherein each B.sub.i is a basic amino acid and the N-terminal acylated and/or C-terminal amidated or esterified forms thereof, either in optionally --SH stabilized linear or in cystine-bridged form.

Abstract: A method for the inactivation of prions, viruses and other infectious agents, which might be present in a biological raw material (e.g. plasma for the preparation of albumin), leaving the desired biological product (e.g. BSA, HSA) intact. To achieve this, the biological raw material is treated with a chaotropic agent, e.g. urea or siodium thiocyanate for approx. 18 hours. Before this, a detergent, e.g. sodium dodecyl sulfate, as well as ethanol or methanol can be added, and the solution can be heated to 70.degree. C. and kept at this temperature for 30 minutes. After cooling and acidification, denatured globulins can be removed. By modifications of this process (e.g. different concentrations, pH-values, temperatures etc.) a wide range of biological products (serum, plasma, proteins, peptides, gangliosides etc.) can be treated and rendered free of viruses, prions and all other infectivity.

Abstract: The use of human Protein C for the prevention and treatment of deposition or aggregation of thrombocytes, microparticles of thrombocytes, and leucocytes is described. In addition, an improved method for the extra-corporeal treatment of body fluids is disclosed.

Abstract: The present invention relates to a virus-safe blood coagulation factor XIII preparation, which is obtained by heating an aqueous solution containing the blood coagulation factor XIII having a specific activity of at least 2 U/mg of total protein, wherein the solution containing less than 10% of known stabilizers selected from the group consisting of sugars, polyols, amino acids, peptides and carboxylic acids, as well as less than 0.5 mol ammonium sulfate per liter, wherein the heating is effected for a period of time sufficient to inactivate infectious agents, preferably for a period of time of from 30 min to 100 h.

Abstract: Cation chromatography with solutions at pH less than 6.0 and low ionic strength can be utilized to purify human .alpha.-1 proteinase inhibitor (.alpha.-1 PI) from biological fluids including plasma and plasma fractions. The cation chromatography takes advantage of the fact that active .alpha.-1 PI does not bind to the cation column under these conditions but other proteins, including denatured .alpha.-1 PI and albumin, do. The effect is that active .alpha.-1 PI flows through the chromatography column leaving the contaminating proteins behind. Recovery of .alpha.-1 PI is high and improvement of purity is dramatic.

Abstract: A method of making a platelet releasate product is disclosed involving performing an assay on a platelet releasate sample for a component of the releasate and forming platelet releasate product by comparing the assay results to a predetermined range of amounts of the component to be contained in the product. A method of treatment of tissue is disclosed involving the topical application of such product.

Abstract: The present invention relates to a naturally occurring, minimally modified LDL antigen which is present in human atherosclerotic lesions as well as in the serum of a high percentage of patients with coronary artery disease. The invention also comprises antibodies reactive with the antigen, hybridoma cell lines that produce the antibodies of the invention, and methods for using the antibodies in the diagnosis and treatment of atherosclerotic disease.

Abstract: A method and composition utilizing thrombopoietin for increasing platelet cell counts in thrombocytopenia is disclosed. The method and composition are suitable for treatments of patients suffering from medical conditions, such as HIV/AIDS or chemotherapy, which result in low platelet cell numbers. Also disclosed are the active moieties or domains of the thrombopoietin molecule.

Abstract: A virus-inactivated Factor-Xa preparation with at least 100 units coagulation factor activity per mg protein is described, wherein this preparation is produced by activation of a corresponding starting material and subsequent treatment for the inactivation of infectious agents, particularly viruses. By incubation, the preparation obtained in this manner is transformed into a stable beta-Factor Xa preparation. In addition, the use of the present preparation for the treatment of hemophilia A inhibitor patients is disclosed.

Abstract: A method for the preparation of a platelet factor-enriched biological adhesive comprising freezing a platelet-enriched plasma and isolating a cryoprecipinate from the frozen platelet-enriched plasma is disclosed. Also disclosed is a method for biological adhesion employing the prepared biological adhesive.

Abstract: Serum albumin crystal forms have been produced which exhibit superior x-ray diffraction quality. The crystals are produced from both recombinant and wild-type human serum albumin, canine, and baboon serum albumin and allow the performance of drug-binding studies as well as genetic engineering studies. The crystals are grown from solutions of polyethylene glycol or ammonium sulphate within prescribed limits during growth times from one to several weeks and include the following space groups: P2.sub.1, C2, P1.

Abstract: This invention is related to an adhesive composition which may be used to bond or seal tissue in vivo. The adhesive composition is readily formed from a two component mixture which includes a first part of a protein, preferably a serum albumin protein, in an aqueous buffer having a pH in the range of about 8.0-11.0 and a second part of a water-compatible or water-soluble bifunctional crosslinking agent. When the two parts of the mixture are combined, the mixture is initially a liquid which cures in vivo on the surface of tissue in less than about one minute to give a strong, flexible, pliant substantive composition which bonds to the tissue and is absorbed in about four to sixty days. The adhesive composition may be used either to bond tissue, to seal tissue or to prevent tissue adhesions caused by surgery.

Abstract: Analogs of blood factors which are transiently inactive are useful in treatment of diseases characterized by thrombosis. In addition, modified forms of activated blood factors that generate the active blood factor in serum but have extended half-lives are useful in treating hemophilic conditions. These modified forms of the blood factor may be acylated forms which are slowly deacylated in vivo.

Abstract: Stabilized and activated Factor VIII is used as a therapeutic agent to treat patients with a Factor VIII deficiency. This includes hemophilia A patients as well as patients with Factor VIII inhibitors which block the hemostatic activity of Factor VIII. The stabilized and activated Factor VIII is also prepared in a therapeutic composition with a therapeutically acceptable adjuvant.

Abstract: The invention relates to a method for determining platelet aggregation in the presence of an inhibitor of fibrin aggregation, which prevents the formation of an interfering fibrin clot, and to a diagnostic aid for determining the platelet aggregation-inhibiting action of thrombin inhibitors.

Abstract: Human .alpha..sub.1 -antichymotrypsin (ACT) can be purified from solutions containing human .alpha..sub.1 -proteinase inhibitor (PI) and antithrombin III (AT-III) using chromatography adsorption steps at carefully controlled pH and conductivity. The separated ACT retains in vitro inhibitory capacity and has potential therapeutic use.

Abstract: Highly stable plasma-derived therapeutic albumin solutions, having a turbidity level of 5 NTU or less can be made by adding sodium caprylate to Cohn fraction II+III or IV-1 effluent at relatively low temperatures. The sodium caprylate acts as a partitioning agent to separate albumin from unwanted proteins. In preferred embodiments, the albumin source solution temperature is elevated, increased in pH and reacted for approximately six hours under conditions sufficient to disrupt the initial solution colloid, and partition albumin-containing supernatant from a colloidal disperse phase, which retains unwanted globulins and manufacturing debris. Since it tends to be a scavenger molecule, albumin is selectively stabilized by diafiltration against a buffer containing sodium caprylate, thereby assuring a high albumin monomer content and low turbidity level. The amount of sodium caprylate required for selective stabilization is determined by the amount of available binding sites on the albumin molecule.

Abstract: A composition and methods for use thereof relating to polypeptides having the ability to act as an inhibitor of complement C5b-9 complex activity. The compositions contain an 18 kDa protein found on the surface of human erythrocytes, active derivatives or fragments thereof which act to inhibit the activity of C5b-9, anti-idiotypic antibodies mimicking the action of the inhibitor proteins or antibodies against C7 or C9 which block the formation of the C5b-9 complex. The compositions can be used in vitro to inhibit C5b-9 related stimulatory responses of platelets and vascular endothelium of perfused organs and tissues, thereby preventing the C5b-9 initiated cell necrosis or stimulated secretion of proteolytic enzymes and the exposure of the procoagulant membrane receptors during collection and in vitro storage. Further, immune disease states can be treated by administering an effective amount of a C5b-9 inhibitor to suppress C5b-9 mediated platelet activation in vivo.

Abstract: The invention provides methods for stimulating thrombocytopoiesis and for treating thrombocytopenia in a mammal comprising administering to the mammal an effective amount of modified C-reactive protein (mCRP).

Abstract: An immunological serum and method of making same. The serum essentially consists of purified and concentrated materials, sometimes known as transfer factor, and immunoglobulins, expressed from the clotted blood of a donor group having known immunity. To produce the serum, a group of donors is chosen which includes known immunity, preferably to a wide variety of ailments. Blood is drawn from the donor group and allowed to clot. Thereafter, the blood is filtered to remove all cellular material, producing raw serum. This raw serum is then concentrated by removal of water. The concentrated serum is then sterilized, but not denatured, by freezing and gamma irradiation.

Abstract: A composition and method for separating red blood cells from whole blood comprising a rouleaux-forming aggregator and an enhancer for enhancing the settling rate. The enhancer is a material which alters directly or indirectly the properties of the red blood cell and may alter the structure and/or reactivity of the aggregator, without adversely affecting the morphology and function of white blood cells. In most instances, the red blood cell enhancers of the invention are osmotic agents. Such agents create a hypertonic solution while not entering the cells themselves. Preferably the enhancer is a salt of oxalic acid, a salt of malonic acid, mannitol or sucrose. Potassium oxalate is most preferred. High molecular weight substances which are large enough to form molecular bridges between red blood cells form the aggregators used in the invention.

Abstract: An isolated and purified substance called Acta having the following features: (a) a molecular weight of 60 kd to 70 kd in SDS-PAGE using 12.5% gel, (b) reacts with a monoclonal antibody which is secreted by hybridoma FERM BP-3482, (c) binds to chymotrypsin and (d) binds to DNA. Acta is used to diagnose cancer and Alzheimer's disease.

Abstract: Mammalian adipogenic factors, including purified proteins or glycoproteins, capable of inducing the adipose differentiation of adipogenic cells are disclosed, as are antibodies to such proteins, DNA encoding the proteins and host cells expressing the proteins. A method for determining the susceptibility of a subject to obesity by measuring the levels of one or more adipogenic factors in a biological fluid or tissue extract is also disclosed, as is a method for evaluating an anti-obesity drug which comprises contacting the drug with cells capable of producing one or more adipogenic factors and measuring the amount of the factors produced.

Abstract: Cell-free or released T cell antigen receptors, immunoassays which allow the detection of the released T cell antigen receptor in cell culture supernatants, cell lysates, and biological fluids, as well as diagnostic and therapeutic compositions and methods for monitoring and treating certain diseases or disorders which elicit or involve a T cell response are described. The released T cell antigen receptors described herein differ from the cell membrane bound antigen receptors and appear to exist in a variety of forms, some of which may be complexed with other T cell determinants such as the T3 antigen. Despite the size heterogeneity of the released T cell antigen receptors or receptor/complexes, these may be reliably identified using anti-receptor antibodies, including, but not limited to, anti-major framework, anti-minor frarmework and anti-clonotypic antibodies which define particular epitopes of the released T cell receptor or receptor/complex.

Abstract: A method is provided for detecting carbohydrate-deficient glycoproteins in samples taken from subjects with metabolic disorders, such as alcohol abuse and subjects who display a syndrome of carrying abnormal levels of carbohydrate deficient glycoproteins. The method involves steps of reglycosylating with a fluorescent-conjugate deglycosylated glycoproteins in a sample of body fluid from a subject. A further step involves fluorometric detection of fluoresceinylated carbohydrates incorporated into truncated serum glycoproteins.

Abstract: Cryoprecipitated mammalian plasma proteins with associated glycoproteins, polysaccharides, and numerous other macromolecular entities are transferred directly in the course of controlled thawing and centrifuging from native plasma phase across the boundary layer into a pre-prepared substrate transfer medium at sustained solidus--liquidus equilibrium regulated to residual icing from about 5 weight percent to about 95 weight percent to produce cryoprecipitates with enhanced productivity and enhanced qualifications for in vivo tissue bonding applications.

Abstract: The invention relates to a method of producing virus-safe highly purified factor VIII. The method includes a combination of the following measures:a) chromatographic purification of a factor VIII-containing fraction,b) tenside treatment of factor VIII in an aqueous solution at a tenside/protein ratio of from 1:1 to 1000:1, andc) heat treatment of the factor VIII preparation in the solid state.

Abstract: The present invention describes a variant protein S protein that is substantially homologous in amino acid residue sequence to wild-type mature human protein S, which has in vitro anticoagulant activity and has a reduced ability to bind C4b binding protein (C4BP), compositions containing the variant protein S, and recombinant DNA vectors for expressing the variant protein. Also disclosed are therapeutic methods of using variant protein S for inhibiting thrombosis, inflammation and the like conditions ameliorated by protein S.

Abstract: A composition and method for separating red blood cells from whole blood including a rouleaux-forming aggregator and an enhancer for enhancing the settling rate. The enhancer is a material which alters directly or indirectly the properties of the red blood cell and may alter the structure and/or reactivity of the aggregator, without adversely affecting the morphology and function of white blood cells. In most instances, the red blood cell enhancers of the invention are osmotic agents. Such agents create a hypertonic solution while not entering the cells themselves. Preferably the enhancer is a salt of oxalic acid, a salt of malonic acid, mannitol or sucrose. Potassium oxalate is most preferred. High molecular weight substances which are large enough to form molecular bridges between red blood cells form the aggregators used in the invention.

Abstract: The invention describes protein S polypeptides and anti-PS antibodies capable of inhibiting the binding of proteins to C4BP. The peptides and antibodies are useful in diagnostic methods and systems for purifying or detecting free protein S. In addition, the polypeptides are useful in therapeutic methods as an anti-coagulant.

Abstract: The invention is directed to a method for the separation of gamma globulin from albumin contained in an aqueous solution of both having a pH of 8-10 by ultrafiltration using an altered substrate microfilter having a water permeability of no more than 20 gallons per square foot per day per pound per square inch.

Abstract: This present invention is directed to an artificial functional polypeptide represented by the following structural formula [I]:X--(Y)m--Z [I]wherein X represents a polypeptide having cell-adhesive activity like that of human FN, Y represents a spacer, Z represents a polypeptide having fibroblast growth promoting activity like that of FGF, and m is 1 or 0. This polypeptide is particularly useful for pharmaceutical purposes.

Abstract: A photoactive lanthanide complex of 2,2',2",9,9',9"-bis[nitrilotri(methylene)]tris(1,10-phenanthroline) and its functional derivative capable of bonding with substrate such as polymer and protein are provided. The lanthanide complex is usable for photosynthesis and photoimmunoassay.

Abstract: This invention provides methods and an apparatus for peroxidizing lipoproteins and introducing them into a person infected with a virus such as HIV to help that person fight the disease. Peroxidized low density lipoproteins are shown to preferentially kill HIV-infected cells as well as the HIV virus.

Abstract: Fragments of the factor VIII:C polypeptide have been discovered which exhibit highly specific factor VIII activity. Monoclonal antibodies to the polypeptide fragments and methods for the isolation and purification of said fragments are also disclosed.

Abstract: Novel polypeptides having Factor VIII activity are provided as well as compositions and methods for their preparation. The polypeptides comprise derivatives and fragments of Factor VIII and have sequences substantially similar to portions of naturally occuring Factor VIII. The polypeptides find use in treatment of Hemophilia A.

Abstract: A substantially pure, single chain plasma protein of approximately 120 kDa having an N-terminal amino acid sequence EKNGIDIYSLTD, and a mixture of protein fragments having vasodilatory activity which fragments are generated by activated Kallikrein cleavage of the 120 kDa protein.

Abstract: A megakaryocyte stimulatory factor (MSF), purified to homogeneity, is an acidic protein (pI=5.1) with an Mr=15,000 which stimulates PF4-like protein synthesis in rat promegakaryoblast cells by as much as 7-fold, and exhibits half-maximal activity at a concentration of 0.8 pM. MSF exhibits no biologic activity corresponding to other known hemopoietic growth factors, and appears to be specific for the megakaryocyte lineage.In the given examples, MSF was purified to homogeneity (as judged by SDS-PAGE and isoelectric focusing in the presence of 9.2 M urea) from serum-free conditioned medium obtained from cultured human embryonic kidney (HEK) cells, and to near homogeneity from thrombocytopenic plasma.

Abstract: Polypeptides which are derived from the Arg-Gly-Asp (RGD) binding portion of an Integrin beta subunit are disclosed as are their use for modulation of Integrin ligand binding. Anti-antibody peptides, hybridomas secreting these antibodies, as well as methods of making any using such antibodies, and recombinant DNA molecules that define the structural gene coding for the polypeptides are also contemplated within the scope of the present invention.

Abstract: Vitronectin produces very high therapeutic effects upon injuries of the corneal epithelium. When applied to lesions of the corneal epithelium in the form of eye drops, Vitronectin induces rapid cure of the lesions with regeneration of normal cells. Moreover Vitronectin can be sterilized by autoclaving.

Abstract: A composition and methods for use thereof relating to polypeptides having the ability to act as an inhibitor of complement C5b-9 complex activity. The compositions contain an 18 kDa protein found on the surface of human erythrocytes, a 37 kDa proteiThe U.S. Government has rights in this invention by virtue of certain government grants.

Abstract: Reagent for analysis of triglycerides contained in blood serum is provided, which comprises lipases and monoglyceride lipases capable of acting on monoglycerides having substrate specificity and capable of catalyzing the following enzymatic reaction: monoglyceride+H.sub.2 O.fwdarw.glycerol+fatty acids. The glycerol or fatty acids are measured to learn an amount of the triglycerides or fatty acid by any known analytical method.