Abstract: A cyanide-free lytic reagent composition and method for measuring the total hemoglobin concentration in a blood sample, for counting the number of leukocytes and for deferential counting of three leukocyte subpopulations including lymphocytes, monocytes, and granulocytes are described. The cyanide-free lytic reagent composition includes a hemolytic surfactant chosen from quaternary ammonium salts, pyridinium salts, organic phosphate esters, and alkyl sulfonates to lyse erythrocytes and release hemoglobin, and an organic ligand chosen from triazole and its derivatives, tetrazole and its derivatives, alkaline metal salts of oxonic acid, melamine, aniline-2-sulfonic acid, quinaldic acid, 2-amino-1,3,4-thiadiazole, triazine and its derivatives, urazole, DL-pipecolinic acid. isonicotinamide, anthranilonitrile, 6-aza-2-thiothymine, adenine, 3-(2-thienyl)acrylic acid, benzoic acid and alkali metal and ammonium salts of benzoic acid, and pyrazine and its derivatives to form a stable chromogen with hemoglobin.

Abstract: Disclosed is a method of inhibiting a rejection response by a primate to a transplanted organ. One exposes the primate to a mutant diphtheria toxin linked to anti-CD3 antibody so as to largely eliminate the host's peripheral blood T cell lymphocyte population. At the same time as, or after, the exposure step one administers to the primate's thymus gland donor lymphocytes. Transplantation of the organ follows. The primate is tolerized to the transplanted organ.

Abstract: Methods and materials for the treatment of humans suffering from hemorrhage due to trauma are provided, in which therapeutically effective amounts of BPI protein products are administered.

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: A plasma-buffy coat concentrate that comprises plasma, platelets at a concentration of at least 1.0.times.10.sup.9 cells/ml, and fibrinogen at concentration of at least 5 mg/ml is described. The plasma-buffy coat concentrate can be combined with a fibrinogen activator to form a platelet glue wound sealant. A method for processing blood to produce the plasma-buffy coat concentrate is also provided. The method comprises centrifuging anticoagulated blood to remove red blood cells and produce a plasma-buffy coat mixture. Water is removed from the mixture to produce the plasma-buffy coat concentrate. A fibrinogen activator is mixed with the plasma-buffy coat concentrate to produce a wound sealant, which can then be applied to a wound to facilitate sealing and healing of the wound.

Abstract: The present invention relates to novel pharmaceutical composition for skin diseases, in particular to novel pharmaceutical composition useful for treatment of skin diseases; e.g. burns, wounds, general operative wounds, pernio, decubitus, folliculitis, impetigo, intertrigo, radiation ulcer, acne vulgaris or infectious eczematous dermatitis comprising deproteinized dialysate of calf's blood with tissue regenerative activity and aminoglycoside antibiotic with bacterial infection inhibitory activity as active ingredients.

Abstract: Induction of an antigen-specific T-lymphocyte response in a T-lymphocyte culture, e.g. a primary cytotoxic T-lymphocyte (CTL) response, by loading antigen-presenting vehicles which carry empty MHC molecules with an antigen-derived T-cell-immunogenic MHC-binding peptide, culturing T-lymphocytes in the presence of the peptide-loaded antigen-presenting vehicles under specific T-lymphocyte response-inducing conditions. Optionally, an antigen-specific T-lymphocyte is isolated from the resulting culture and cultured. The process can be used for preparing CTL which are specific for viral or other foreign antigens, or CTL which are specific for autologous peptides. The process can also be used for the identification of peptides that are capable of binding to MHC and inducing a T cell response.

Abstract: A method of treating rheumatoid arthritis is provided which involves administering an effective amount of allogeneic mononuclear cells or a molecule derived from these cells to an individual having rheumatoid arthritis. Also provided are compositions for the treatment of rheumatoid arthritis.

Abstract: Leucocytes can be quickly and selectively separated from erythrocytes by subjecting a whole blood sample to a series of steps including lysing the erythrocytes and washing the remaining leucocytes with a solution containing ammonium chloride and a carboxylic acid or a metal carboxylate. The resulting white blood cells can be readily lysed and subjected to polymerase chain reaction to amplify and detect a target nucleic acid. The test kit useful in practicing the amplification method includes a labeled primer, a PCR reagent and a reagent mixture containing ammonium chloride and a carboxylic acid or a metal carboxylate for sample preparation.

Abstract: The invention provides a modified human cytotoxic T cell line, which is characterized by dual activity in vitro and in vivo against malignant cells and virus-infected cells. Also provided are effective and safe methods for use of the modified cells in adoptive therapy of cancer and untreatable vital diseases in MHC-mismatched recipients, and in marrow purging to achieve complete eradication of residual tumor cells from marrows of patients with leukemia and other types of cancer. Also provided are effective and safe methods for use of the cytokine stimulated, irradiated TALL-104 cells in the manufacture of a veterinary composition for adoptive therapy of canine and feline malignancies.

Abstract: Laboratory non-human animals in which the immune system of a donor is induced in and thrives in vivo and expresses the immune response of the donor animal in a recipient non-human animal of a different species than the donor, and wherein malignant immune system cells of the donor can be induced in the recipient non-human animal by injection of non-malignant donor into the recipient are disclosed.

Abstract: The invention provides a modified human cytotoxic T cell line TALL-104, which is characterized by dual activity in vitro and in vivo against tumor cells and virus-infected cells. Also provided are effective and safe methods for use of the modified TALL-104 cells in adoptive therapy of cancer and untreatable viral diseases in MHC-mismatched recipients, and in marrow purging to achieve complete eradication of residual tumor cells from marrows of patients with leukemia and other types of cancer. Also provided are effective and safe methods for use of the modified TALL-104 cells in the manufacture of a veterinary composition for adoptive therapy of canine lymphoma and feline leukemias.

Abstract: This invention relates to a cell enumeration immunoassay which uses a calibrated standard, i.e., a substance which behaves like the sample under study and the concentration of which can be correlated to the concentration of the cells. This immunoassay is an efficient alternative to flow cytometry.

Abstract: Methods and pharmaceutical compositions for modifying the immune response of a mammal to a specific antigen are provided. The methods include treating an antigen presenting cell to enhance expression of a major histocompatibility complex molecule and reacting the treated antigen presenting cell with the antigen extracorporeally to form an antigen-associated antigen presenting cell.

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: A method is disclosed for preparing lyophilized and frozen cells as cytometry standards.

Abstract: This invention provides a method of isolating an increased number of hematopoietic stem cells from a subject comprising a) administering interleukin-7 to the subject in an amount that mobilizes the hematopoietic stem cells to the peripheral blood; and, b) isolating a population of leukocytes enriched for hematopoietic stem cells from the peripheral blood. Also provided is a method of transplanting an increased number of hematopoietic stem cells from a donor to a recipient to enhance repopulation of the recipient's hematopoietic and immune cells comprising a) administering interleukin-7 to the donor in an amount that mobilizes the hematopoietic stem cells to the peripheral blood; b) isolating a population of leukocytes enriched for hematopoietic stem cells from the donor's peripheral blood; and, c) transplanting the isolated population of leukocytes enriched for hematopoietic stem cells to the recipient, thereby enhancing the repopulation of the recipient's hematopoietic and immune cells.

Abstract: A reagent for analyzing leucocytes comprises (a) at least one ionic surfactant, being either a cationic or an amphoteric surfactant, in an amount sufficient for lysing erythrocytes and causing damage to a part of cell membranes of leucocytes; (b) at least one organic compound having a hydrophobic group and an acidic group which has a negative charge in an aqueous solution in an amount sufficient for a preserving leucocyte morphology by combining with a cationic component in leucocytes; (c) a nonionic surfactant; and (d) a buffer for adjusting pH.

Abstract: Described are methods for: (a) suppressing the ability of T-cells from a mammal to proliferate in response to stimulation by nonself mammalian tissue; and (b) suppressing immune response which leads to allograft rejection in a mammal receiving an allograft from a donor mammal. The methods involve orally administering to the mammal to be thus treated a composition comprising at least one of: (i) a major histocompatibility complex Class II antigen from a second nonself mammal or from tissue of a mammal syngeneic to said nonself mammal; (ii) at least one synthetic peptide corresponding to a T-cell suppressive fragment of said Class II antigen, said composition being administered in an amount effective to suppress said proliferation. The foregoing compositions are also described.

Abstract: The present invention relates to a three-dimensional cell culture system which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. In accordance with the invention, cells derived from a desired tissue are inoculated and grown on a pre-established stromal support matrix. The stromal support matrix comprises stromal cells, such as fibroblasts actively growing on a three-dimensional matrix. Stromal cells may also include other cells found in loose connective tissue such as endothelial cells, macrophages/monocytes, adipocytes, pericytes, reticular cells found in bone marrow stroma, etc. The stromal matrix provides the support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts found in vivo.

Abstract: A method for isolating tissue repair promoting substances from human or animal blood, which method comprises collecting the human or animal blood from a single human or animal individual in a first container of a container system comprising at least first and second interconnected containers; centrifuging the container system containing the blood so as to separate the blood in various fractions including a plasma fraction; transferring at least part of the plasma fraction to the second container of the container system; subjecting the plasma fraction in the second container to a low temperature so as to obtain a precipitate comprising tissue repair promoting substances; concentrating the precipitate in the second container so as to obtain a first fraction comprising a major part of the non-precipitated material, and a second fraction comprising at least the major part of the precipitate and a minor part of the non-precipitated material; and separating the second fraction comprising the tissue repair promoting

Abstract: A cytokine composition is prepared for use in immunotherapy of various diseases. The composition is prepared by culturing leucocytes previously infected with a virus in a culture medium containing a transal composition isolated from plasma and a complex of proteinase inhibitors composition isolated from plasma, separating leucocytes from the medium, removing impurities from the medium, and recovering a cytokine composition containing the transal composition and the complex of protease inhibitors composition. The transal composition contains transferrin, albumin and a 40 kDa protein and the complex of protease inhibitors composition contains .alpha..sub.2 -macroglobulin, a 160 kDa protein, an 80-60 kDa protein and a 20 kDa protein.

Abstract: Methods and apparatus for separating red blood cells by density are described. Older red blood cells are more dense than younger ones. Certain changes in the physiology are recorded in changes in hemoglobin or the red blood cells. By assaying different aged red blood cells, one can determine the historical physiological changes over a period of many weeks. Improved separation of red blood cells is accomplished by using rigid capillary tubes having an inner surface which augments the density equilibrium of red blood cells and/or incrementally increasing the centrifugation forces, as well as by chemically treating red blood cells to improve their deformability.

Abstract: A hematology control product comprising leukocyte analogs and an aqueous solution of a plasma substance for use in a blood counting instrument is described. The instrument employs a lytic reagent system for the lysable red blood cells in the control product. The plasma substance is in an amount effective to enable the differentiation of each of said leukocyte analogs relative to the physical attributes of the analogs, said physical attributes of the analog are similar to human leukocytes. Preferably, the plasma substance comprises cholesterol or its derivatives.A method for using the cell suspension media comprising an aqueous solution of a plasma substance is also described. The method provides a quality control to determine whether an instrument is operating within manufacturer's specifications.

Abstract: Laboratory non-human animals in which the immune system of a human donor is induced in and thrives in vivo and expresses the immune response of the human donor in a recipient non-human animal, and wherein malignant immune system cells of the human donor can be induced in the recipient non-human animal by injection of non-malignant donor cells into the recipient are disclosed.

Abstract: Methods and pharmaceutical compositions for modifying the immune response of a mammal are provided. The pharmaceutical compositions include a pharmaceutically acceptable carrier and a plurality of cells containing psoralen-DNA monoadducts and substantially no psoralen-DNA crosslinks. The preparation is formed by irradiating a suspension of cells with visible light radiation in the presence of psoralen.

Abstract: A method and composition for fixing and stabilizing tissues, cells, and cell components such that the antigenic sites are preserved for a useful period of time. The fixative employs a formaldehyde donor that is non-toxic, non-flammable, and that stabilizes the cell with minimal damage to and alteration of the cell morphology. In particular, the cell antigenic sites are left intact so that studies with monoclonal antibodies may be conducted. The invention also discloses a method for developing a positive control for test reagents and for test instrumentation.

Abstract: The present invention relates to a three-dimensional cell culture system which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. In accordance with the invention, cells derived from a desired tissue are inoculated and grown on a pre-established stromal support matrix. The stromal support matrix comprises stromal cells, such as fibroblasts actively growing on a three-dimensional matrix. Stromal cells may also include other cells found in loose connective tissue such as endothelial cells, macrophages/monocytes, adipocytes, pericytes, reticular cells found in bone marrow stroma, etc. The stromal matrix provides the support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts found in vivo.

Abstract: A method is provided for inactivating viral and/or bacterial contamination in blood cellular matter, such as erythrocytes and platelets, or protein fractions. The cells or protein fractions are mixed with chemical sensitizers and irradiated with, for example, UV, visible, gamma or X-ray radiation. In particular, quaternary ammonium or phosphonium substituted, halo-psoralen compounds are described as being useful.

Abstract: A aqueous stock solution for preserving human cells, particularly leukocytes, which includes 20-40% modified gelatin by weight in a physiologically acceptable buffer at pH4-7.5.

Abstract: The invention describes the preparation of non-infectious control cells from normal, non-infectious, non-disease altered blood by depletion or augmentation of one or more cell types found in normal blood to reflect a specific disease state. The control cells so produced are preserved and thereafter reconstituted for use in immunological assays.

Abstract: The invention is concerned with the discovery, isolation and purification of an agent or factor named herein the CR3 modulator or CMF-1 that is synthesized by polymorphonuclear leukocytes (PMN) in response to agonists which enhance CD18 activity. The CR3 modulator binds to CD18 and activates its adhesion-promoting ability. The CR3 modulator appears to be transiently produced by PMN as an acidic amphiphilic lipid. The CR3 modulator can be assayed by adding dilutions of a CR3 modulator -containing solution to resting PMN and observing the ability of CR3 to mediate binding of erythrocytes coated with C3bi (EC3bi). The isolation of the CR3 modulator, its biological and physical properties and diagnostic and therapeutic uses are described.

Abstract: A method for isolating tissue repair promoting substances from human or animal blood, which method comprises collecting the human or animal blood from a single human or animal individual in a first container of a container system comprising at least first and second interconnected containers; centrifuging the container system containing said blood so as to separate the blood in various fractions including a plasma fraction; transferring at least part of the plasma fraction to said second container of the container system; subjecting the plasma fraction in said second container to a low temperature so as to obtain a precipitate comprising tissue repair promoting substances; concentrating said precipitate in said second container so as to obtain a first fraction comprising a major part of the non-precipitated material, and a second fraction comprising at least the major part of the precipitate and a minor part of the non-precipitated material; and separating said second fraction comprising the tissue repair pro

Abstract: A method of determining the level of immunosuppression in a mammal involves determining the level of expression of at least one selected TCR subunit protein, or protein in the T lymphocyte signal transduction pathway, and comparing the level to that found in healthy individuals. The method is useful to identify patients having T lymphocytes capable of activation for autologous adoptive immunotherapy and for identifying agents which cause or reverse immunosuppression.

Abstract: The invention provides cytotoxic T-ALL cell lines, and modified cytotoxic T-ALL cell lines which contain a heterologous DNA sequence. The DNA sequence may encode a product capable of stabilizing or potentiating the tumoricidal activity of the cytotoxic cell lines and a product capable of controlling the growth of the cell line. Methods for use of these cell lines are also provided.

Abstract: There is disclosed an immunotherapy method for treating an individual with cancer or a viral infection comprising obtaining lymphoid cells previously exposed to a specific antigen, culturing the lymphoid cells ex vivo in a culture medium containing an effective amount of an IL-7 polypeptide or a functional derivative thereof to induce CTL activity in the lymphoid cells and administering the lymphoid cells having CTL activity for cells displaying the specific antigen to an individual.

Abstract: Preservation of leukocytes by suspending in storage medium containing modified fluid gelatin, plasma, and a non-toxic buffer. Preferred additives include heterocyclic bases which occur in nucleic acids, or nucleosides or nucleotides containing the same.

Abstract: A method for isolating tissue repair promoting substances from human or animal blood which comprises collecting the human or animal blood from a single human or animal individual in a first container of a container system comprising at least a first and second interconnected containers; centrifuging the container system containing the blood so as to separate the blood in various fractions including a plasma fraction; transferring at least part of the plasma fraction to the second container of the container system; subjecting the plasma fraction in the second container to a low temperature so as to obtain a precipitate comprising tissue repair promoting substances; concentrating the precipitate in the second container so as to obtain a first fraction comprising a major part of the non-precipitated material; and separating the second fraction comprising the tissue repair promoting substances from said first fraction within the second container; and optionally heating the second fraction within one of the contai

Abstract: Immunoreactive cells sensitized for an antigenic marker associated with a malignant tumor are prepared in vitro by collecting the tumor patient's own mononuclear cells, depleting suppressor T-cells, suspending the mononuclear cells with serum, preferably autologous, and culturing the cells under conditions to activate and immunize the patient's mononuclear cells against the patient's tumor. Methods of treatment and immunized cells in pharmaceutical presentations are described.

Abstract: The treatment of blood product to inactivate or destroy infective viruses found in animal fluids and tissues, such as the cytomegalovirus, by mixing the blood product with an effective amount of glycyrrhizic triterpenoid compounds in combination with albumin is disclosed.

Abstract: A new immunotherapeutic method of treating cancer with a combination of tumor infiltrating lymphocytes and IL-2 has been described.

Abstract: Pharmaceutical preparations are provided for preventing or treating autoimmune diseases in which the active principle is activated T-lymphocyte cells, specific for the autoimmune disease to be treated, which cells have been treated by incubation with a photoactivatable psoralen cross-linking agent, such as 8-methoxypsoralen, and then photoactivated. The active principle may also be the membrane fraction of such cells. Such preparations may be formulated into pharmaceutical compositions and administered to prevent or treat autoimmune disesases.

Abstract: There is provided an improved process for enhanced LAK cell activation wherein the peripheral blood mononuclear cells are treated with an amino acid amide to yield depletion, prior to the lymphocytes being cultured at high density. Also provided are pharmaceutical compositions and methods of using them in combination with IL-2 to treat cancer in a mammal.

Abstract: The present invention provides a method of inhibiting lipopolysaccharide (LPS)-mediated stimulation of cells. This method comprises contacting the cells, in the presence of a cell-stimulating amount of lipopolysaccharide, with Bactericidal/Permeability Increasing Protein (BPI) in an amount effective to inhibit cell stimulation.

Abstract: There is disclosed a composition and process for disinfecting or essentially sterilizing blood fractions and components of blood. The composition is formed by adding a chlorine dioxide liberating compound with a weak organic acid and a heat activated saccharide.

Abstract: Ornithine decarboxylase inhibitors when administered in conjunction with autologous LAK cells and interleukin-2 provide for an enhanced treatment of neoplastic disease states. This enhancement is provided by the ability of an ornithine decarboxylase inhibitor to reduce tumor load and to enhance interleukin-2 production in T helper cells.

Abstract: New human T cell suppressor factors have been identified which suppress mitogen, antigen or alloantigen driven cellular proliferation of human peripheral blood leukocytes, as well as antibody synthesis and secretion and growth of human tumor cell lines.Such factors have potential use for the treatment of graft versus host disease, autoimmune disease and lympho-proliferative disorders such as leukemia as well as other malignancies.

Abstract: DTH-Effector cells are primed with carbohydrate antigens and used to enhance the cellular immune response. Tumors have been inhibited by DTH-Effector cells primed with epiglycanin and with synthetic T and Tn antigens. Either the DTH-Effector cells, or these tumor-associated carbohydrate antigens directly, may be used for tumor prophylaxis and therapy.

Abstract: The present invention relates to a three-dimensional cell culture system which can be used to culture a variety of different cells and tissues in vitro for prolonged periods of time. In accordance with the invention, cells derived from a desired tissue are inoculated and grown on a pre-established stromal support matrix. The stromal support matrix comprises stromal cells, such as fibroblasts, grown to subconfluence on a three-dimensional matrix. Stromal cells may also include other cells found in loose connective tissue such as endothelial cells, macrophages/monocytes, adipocytes, pericytes, reticular cells found in bone marrow stroma, etc. The stromal matrix provides the support, growth factors, and regulatory factors necessary to sustain long-term active proliferation of cells in culture. When grown in this three-dimensional system, the proliferating cells mature and segregate properly to form components of adult tissues analogous to counterparts found in vivo.

Abstract: A device for separating mononuclear cells from blood includes a collection tube, a first layer of a liquid density gradient material placed in the tube, a second layer of a gel-like substance placed in the tube and situated above the first layer, a porous foam member placed in the tube and situated above and in contact with the second layer of gel-like substance, and a third layer of a Newtonian gel-like substance placed in the tube above the porous foam member. The gel-like substance of the second layer has a lower specific gravity than that of the liquid density gradient material of the first layer so that it floats on top of the first layer. The gel-like substance of the second layer becomes less viscous when heated such that it is absorbed by the porous foam member and forms a hydraulic barrier between the liquid density gradient material of the first layer and a blood sample placed in the collection tube.