Abstract: The present invention relates to the preparation and use of liquid formulations of plasma proteins, particularly blood coagulation factors. More specifically, the present invention relates to stable liquid formulations of Factor VIII and Factor IX that can be administered by injection or infusion to provide a constant level of the coagulation factor in the blood.

Abstract: A cell is subjected to apoptosis, a genetically programmed autolysis of the cell. Cells of a specific type, classified by function, maturity, source, etc. can be effectively removed from a mixture of cells in a tissue or cell suspension by their different sensitivities to the pressure-time treatment. Donor tissue immunogenicity is eliminated by induction of apoptosis in immunoactive cells, such as antigen presenting cells in the donor tissue. When tissues, for example, blood products containing leukocytes or solid tissues containing dendritic cells, are pressure treated to induce apoptosis in the leukocyte or dendritic cell population, the leukocytes or dendritic cells lose their immunoactivity. Viral particles within the target cells, such as cytomegalovirus particles within the apoptosing leukocytes, are destroyed. Apoptosis can be induced, for example, by subjecting a material containing the target cells to a high pressure.

Abstract: A non-human transgenic mammalian animal, as described above, contains an exogenous double stranded DNA sequence stably integrated into the genome of the animal, which comprises cis-acting regulatory units operably linked to a DNA sequence encoding human Factor VIII protein and a signal peptide, where the cis-acting regulatory units are active in mammary gland cells and the signal peptide is active in directing newly expressed Factor VIII into the milk of the animal. The promoter may be a milk protein promoter such as for whey acidic protein, casein, lactalbumin, or beta-lactoglobulin promoter. The transgenic mammals are preferably farm animals, for example, cows, goats, sheep, rabbits and pigs. Concurrent expression of a gene for human von Willebrand's Factor into milk may be used to stabilize newly-secreted Factor VIII.

Abstract: The present invention is directed to a computer controlled apparatus for perfusing, cooling, and warming a biological organ. The apparatus includes a programmable computer, selectively addressable arterial perfusate reservoirs having inputs and outputs in a recirculating fluid flow path, a main pump in the recirculating flow path for recirculating the fluid in said path, an organ pump that withdraws fluid from the recirculating fluid flow path and provides it to one or more organs in an organ flow path for subsequent return to the recirculating fluid flow path or discard, a temperature-controlled cabinet housing most components of the apparatus, and improvements that permit organ perfusion at temperatures below -10.degree. C., immersion cooling of the organ to allow organ temperature reduction to below -40.degree. C. to -140.degree. C., immersion warming of the organ, and elimination of stagnant fluid in the organ flow path by means of an organ bypass valve.

Abstract: The invention relates to the field of organ and tissue perfusion. More particularly, the present invention relates to a method for preparing organs, such as the kidney and liver, for cryopreservation through the introduction of vitrifiable concentrations of cryoprotectant into them. To prepare the organ for cryopreservation, the donor human or animal, is treated in the usual manner and may also be treated with iloprost, or other vasodilators, and/or transforming growth factor .beta.1. Alternatively, or additionally, the organ which is to be cryopreserved can be administered iloprost, or other vasodilators, and/or transforming growth factor .beta.1 directly into its artery. The invention also relates to preparing organs for transplantation by a method for the removal of the cryoprotectant therefrom using low (such as raffinose, sucrose, mannitol, etc.

Abstract: The invention relates to the field of organ and tissue perfusion. More particularly, the present invention relates to a method for preparing organs, such as the kidney and liver, for cryopreservation through the introduction of vitrifiable concentrations of cryoprotectant into them. To prepare the organ for cryopreservation, the donor human or animal, is treated in the usual manner and may also be treated with iloprost, or other vasodilators, and/or transforming growth factor .beta.1. Alternatively, or additionally, the organ which is to be cryopreserved can be administered iloprost, or other vasodilators, and/or transforming growth factor .beta.1 directly into its artery. The invention also relates to preparing organs for transplantation by a method for the removal of the cryoprotectant therefrom using low (such as raffinose, sucrose, mannitol, etc.

Abstract: This invention provides methods for inactivating pathogenic contaminants in whole blood, plasma, cellular blood components, or in any combination thereof, by adding a phenthiazin-5-ium dye(s) thereto and irradiating said dye-containing composition for an effective length of time with light of wavelengths from 560 to 800 nm or red light, of an effective intensity, whereby the irradiation in conjunction with the dye(s) inactivate substantially all pathogenic contaminants contained therein. The methods of this invention inactivate pathogenic contaminants, such as viruses, bacteria and parasites, without substantially altering the whole blood, plasma, cellular blood components, or combinations thereof, such that they are suitable for transfusion.

Abstract: The invention is a sterile, plasma-free storage medium for blood components including red blood cells and for platelets processed separately or together. The red cell storage medium includes adenine and a physiologically compatible, aqueous electrolyte solution. In one liter of this electrolyte solution there is between about 3.0 grams and about 25.0 grams of dextrose, between about 3.0 grams and about 6.0 grams of sodium citrate, and between about 2.0 grams and about 4.2 grams of sodium bicarbonate. The red cell storage medium is isotonic and has a pH in a range of between about 6.8 and about 7.4. The red cell storage medium is capable of storing and preserving red cells for at least 49 days.

Abstract: A computer-controlled apparatus and method for perfusing a biological organ, such as a heart, kidney, liver, etc. The apparatus comprises a plurality of fluid reservoirs and an organ container for holding the biological organ. A first fluid flow path is defined as a loop from the plurality of reservoirs to necessary sensors and temperature conditioning means and back to the plurality of reservoirs. The reservoirs are selectively connectable to the first fluid flow path. Pump means are interposed in the first fluid flow path for pumping fluid from the first fluid flow path to a second fluid flow path. The organ container is located in this second fluid flow path. Pump means may also be included in the second fluid flow path for pumping fluid from the organ container to one or more of the reservoirs or to waste. One or more sensors are interposed in the fluid flow paths for sensing at least one of the concentration, temperature, pH, and pressure of the fluid flowing in the first and second fluid flow paths.

Abstract: A novel anticoagulant/modulator factor isolated from the saliva of the meinal leech Hirudo medicinalis, specifically inhibiting bovine Xa factor but not inhibiting bovine thrombin.

Abstract: A safety device for collecting fluids for laboratory testing is disclosed. More particularly, the invention relates to an apparatus for collecting multiple undiluted blood samples for subsequent laboratory testing wherein the apparatus is provided with a safety overshield which precludes the individual taking the blood sample from sustaining a needle stick injury. The apparatus includes a vacutainer tube retainer to which a safety overshield is attached. The safety overshield has an upwardly projecting peripheral rim which prevents the depositing needle from sliding off the face of the overshield and contacting the hand of the individual holding the vacutainer tube retainer.

Abstract: This invention provides an improved method for prolonging the shelf life of transfusible red blood cells by decreasing the effective osmolality of the suspending solution and increasing the intracellular pH of the cells prior to storage thereof. This invention also provides methods whereby the intracellular pH may be increased. These methods include collecting the cells in an anticoagulant at pH 7.0 or higher and/or washing, diluting or resuspending the cells prior to storage thereof in a biologically compatible buffered solution that contains at least one non-penetrating or substantially non-penetrating anion or non-electrolyte and is substantially free of chloride ions.

Abstract: The invention is a sterile, plasma-free storage medium for blood components including red blood cells and for platelets processed separately or together. The red cell storage medium includes a physiologically compatible, aqueous electrolyte solution. In one liter of this electrolyte solution there is between about 3.0 grams and about 25.0 grams of dextrose, between about 3.0 grams and about 6.0 grams of sodium citrate, and between about 2.0 grams and about 4.2 grams of sodium bicarbonate. The red cell storage medium is isotonic and has a pH in a range of between about 6.8 and about 7.4. The red cell storage medium is capable of storing and preserving red cells for at least 49 days.

Abstract: A computer-controlled apparatus and method for perfusing a biological organ, such as a heart, kidney, liver, etc. The apparatus comprises a plurality of fluid reservoirs and an organ container for holding the biological organ. A first fluid flow path is defined as a loop from the plurality of reservoirs to necessary sensors and temperature conditioning means and back to the plurality of reservoirs. The reservoirs are selectively connectable to the first fluid flow path. Pump means are interposed in the first fluid flow path for pumping fluid from the first fluid flow path to a second fluid flow path. The organ container is located in this second fluid flow path. Pump means may also be included in the second fluid flow path for pumping fluid from the organ container to one or more of the reservoirs or to waste. One or more sensors are interposed in the fluid flow paths for sensing at least one of the concentration, temperature, pH, and pressure of the fluid flowing in the first and second fluid flow paths.

Abstract: Methods and systems for collection of blood components, such as plasma, from donors are provided. One method includes the steps of collecting a unit of whole blood froma donor; forcing the collected blood unit through a plasma separator; accumulating the plasma in a container; and returning concentrated cells to the donor. One system includes a disposable blood collection set and a reusable fixture into which the collection set can be mounted. The fixture is operated by a self-contained energy source, requiring no exterior electrical connection or other external source of energy.

Abstract: A protein C activator is purified from the venom of the Southern copperhead snake. The resultant enzyme is a very specific and efficient activator of protein C. The high efficiency and specificity enables the sensitive measurement of functional protein C levels in plasma and other biological fluids. The enzyme is attached to a solid support material and the resultant enzyme reactor is capable of producing activated protein C at a high yield and is stable under the conditions of use.

Abstract: A device and process for inducing membrane fusion under an electric field. The process comprises the steps of (a) suspending said membranes in an aqueous buffered medium in a manner so that the membranes are without contact with each other; (b) altering said membranes to a fusogenic state by applying 2-30 pulses of direct current at a rate of 2 to 5 pulses per second in an electrical field strength of about 500-1000 volts/mm in the medium, said pulses having a rapid rise time not exceeding about 10 micro seconds and an exponential decay half time of about 0.2 milliseconds to about 1.2 milliseconds; and (c) thereafter bringing said fusogenic membranes in contact with each other. A long-lived metastable fusogenic state of membranes can be obtained by the device and process.

Abstract: The present invention discloses the effect of ultraviolet (UV) radiation on platelet concentrates collected in a plastics container, particularly in a polypropylene bag. Samples irradiated at 310 nm for 30 minutes at a dose of 774 J/M.sup.2 show no loss of platelet function as determined by ADP, collagen, or ristocetin-induced aggregation. Lymphocytes isolated from irradiated units are unable to act as responders or stimulators in a mixed lymphocyte reaction. The invention provides a method of UV irradiation of platelet concentrates resulting in transfusible cell suspension unable to evoke immunological response while retaining normal platelet function.

Abstract: The present invention discloses a hypotonic suspension medium and a method for prolonged storage of red blood cells at about 4.degree. C. The suspension medium comprises about 80-150 mM glucose, 30-80 mM mannitol, 6-90 mM potassium citrate, 1-5 mM adenine and 10-200 mM ammonium chloride or acetate in an aqueous solution having a pH of about 6.8 to 7.2 and an osmolarity of about 180-220 milli-osmolar. The suspension medium and the method of the present invention allow viable storage of red blood cells at about 4.degree. C. up to 125 days or more.

Abstract: A method is provided for the successful cryopreservation of biological materials including whole organs, organ sections, tissues and cells, in a non-frozen (vitreous) state, comprising cooling the biological material to be preserved under pressure in the presence of a non-toxic vitrifable protective solution to at least the glass transition temperature thereof to vitrify the solution without substantial nucleation or ice crystal growth and without significant injury to the biomaterial. The invention also provides non-toxic protective vitrification solutions useful in the cryopreservation of biomaterials.