Abstract: Novel polypeptides, designated Apo-3 and Apo-2LI, involved in apoptosis are provided. Compositions including chimeric molecules, nucleic acids, and antibodies are also provided.

Abstract: The present invention provides novel nucleic acids encoding human apolipoproteins, lipases, and lipoprotein receptor proteins; the novel polypeptides encoded by these nucleic acids; and uses of these and related products.

Abstract: The present invention relates to methods and compositions for lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides that are incorporated in a lipid matrix. The invention is exemplified in production of a prefolded membrane polypeptide embedded within a lipid matrix via stepwise chemoselective chemical ligation of unprotected peptide segments, where at least one peptide segment is embedded in a lipid matrix. Any chemoselective reaction chemistry amenable for ligation of unprotected peptide segments can be employed. Suitable lipid matrices include liposomes, micelles, cell membrane patches and optically isotropic cubic lipidic phase matrices. Prefolded synthetic and semi-synthetic membrane polypeptides synthesized according to the methods and compositions of the invention also permit site-specific incorporation of one or more detectable moieties, such as a chromophore, which can be conveniently introduced during synthesis.

Abstract: The invention provides a method for diagnosing Kawaski Disease (KD) in a patient suspected of suffering from KD by using as an index a ratio of the level (by weight/volume, w/v) of haptoglobin (Hp) to the level (by weight/volume, w/v) of apolipoprotein A1 (Apo A1) in a patient. A system for use with the method is also included. In addition, the invention also provides a method for diagnosing Atypical Kawasaki Disease (AKD) in a patient suspected of suffering from KD by identifying the phenotype of haptoglobin in said patient and correlating the presence of Hp2-1 or Hp1-1 haptoglobin phenotype with AKD and providing immediate treatment of the patient.

Abstract: The present invention presents novel leptospiral membrane lipoproteins, LipL1 and LipL2, associated with pathogenic strains of Leptospira. LipL1 is of about 35 kDa, and LipL2 is of about 41 kDa. Also disclosed are the method for purifying these proteins from Leptospira, their nucleotide and amino acid sequences, the cloning of the genes encoding the proteins and their recombinant proteins, methods for producing antibodies to these proteins, the resulting antibodies. These proteins, their immunogenic fragments, and antibodies against them, are useful for inducing an immune response to pathogenic Leptospira as well as providing a diagnostic target for leptospirosis.

Abstract: A method of diagnosing the stage or aggressiveness of cancer and particularly breast and prostate cancer by measuring the deviation of levels of fatty acid binding proteins in mammalian tissue or body fluids from normal levels of fatty acid binding proteins. The invention relates to a family of key proteins called fatty acid binding proteins which are involved in metabolism of AA and other lipids and how they affect the proliferation of cancer cells.

Abstract: An improved reagent system for preparation of cells for flow cytometry having a physiologically compatible salt solution composition including a lysing agent, an agent for minimizing white blood cell lysis, and optionally a preservative.

Abstract: This invention provides methods of lowering cholesterol, delaying the onset of atherosclerosis, or treating atherosclerosis in a mammal without inducing hypertriglyceridemia. These methods involve administrating to or expressing in a mammal, an apoE polypeptide or nucleic acid that, when administered to or expressed in a mammal, lowers the total serum cholesterol level without inducing hypertriglyceridemia.

Abstract: Hydrophobically-modified proteins and methods of making them are described. A hydrophobic moiety is attached to a surface amino acid residue of the protein. The hydrophobic moiety can be a lipid or a peptide. Alternatively, the protein can be derivatized by a wide variety of chemical reactions that append a hydrophobic structure to the protein. The preferred protein is of mammalian origin and is selected from the group consisting of Sonic, Indian, and Desert hedgehog. The hydrophobic moiety is used as a convenient tether to which may be attached a vesicle such as a cell membrane, liposome, or micelle.

Abstract: The invention provides the cyclic lipopeptide daptomycin and A-21978C analogs in crystalline form, methods of preparing the crystalline forms, compositions comprising the crystalline forms and methods of using these forms.

Abstract: The present invention relates to a process for purifying apolipoprotein A (ApoA) or apolipoprotein E (ApoE) from human plasma, by obtaining a fraction of human plasma containing said ApoA or ApoE, prepurifying said fraction in at least one step, binding said ApoA or ApoE to an anion-exchange chromatography gel, and thereafter eluting said ApoA or ApoE from said anion-exchange chromatography gel. The thus produced ApoA or ApoE can be used for the manufacture of a medicament in the treatment of atherosclerosis and cardiovascular diseases, or peripheral atherosclerosis and sepsis as well as in a method for treatment of atherosclerosis and cardiovascular diseases, or peripheral atherosclerosis and sepsis when administered in a therapeutically effective amount.

Abstract: Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a variant of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles.

Abstract: The invention is directed to novel compositions comprising an electroprocessed material and a substance, their formation and use. The electroprocessed material can, for example, be one or more natural materials, one or more synthetic materials, or a combination thereof. The substance can be one or more therapeutic or cosmetic substances or other compounds, molecules, cells, vesicles. The compositions can be used in substance delivery, including drug delivery within an organism by, for example, releasing substances or containing cells that release substances. The compositions can be used for other purposes, such as prostheses or similar implants.

Abstract: A method of inducing an immune response by applying an immune response inducing effective amount of a lipopeptide to a mucosal membrane of a subject.

Abstract: There is disclosed a process for purifying a natural product using a two-phase, multi-solvent system followed by vacuum concentration and back extraction. The method allows for the removal of impurities by controlling the polarity balance of a two-phase system by manipulating the proportions of the four solvents and subsequently the relative distribution of the product versus the impurities.

Abstract: Peptide-macromolecule complexes for delivery of nucleic acid to a cell. The nucleic acid carrier includes a binding complex. The binding complex contains a binding moiety which noncovalently binds to the nucleic acid. The binding complex can also contain a binding moiety which is associated with a surface ligand, nuclear ligand or a lysis agent. These may be associated with the binding moiety by spacers. In addition, the carrier may include a nucleic acid with a combination of the above binding complexes or binding moieties.

Abstract: A selective complex of a lipoprotein with hemoglobin or a hemoglobin analogue; a method of assaying hemoglobin or a hemoglobin analogue in a sample, comprising reacting the sample with a lipoprotein which is capable of selectively forming a complex with hemoglobin or a hemoglobin analogue; and a kit for assaying hemoglobin or a hemoglobin analogue, comprising a lipoprotein which is capable of selectively forming a complex with hemoglobin or a hemoglobin analogue.

Abstract: A method of producing separated lipid-rich lipid/protein complex and native proteins from oil seeds, by adding a substance having the ability to aggregate lipids with proteins to a water extract of oil seeds, sedimenting or floating a lipid/protein complex having a lipid content of 45% or more as an aggregate, and recovering it for separation from native proteins.

Abstract: Lipoprotein complexes comprising a lipase-inhibiting protein component, and/or amylase-inhibiting protein component and a phospholipid component, compositions containing said complexes in combination with a polysaccharide component, pharmaceutical formulations and foods containing said complexes or compositions, processes for the preparation of said complexes and compositions, which are capable of reducing the weight increase following hypercaloric diets and of exerting hypocholesterolemizing, hypotriglyceridemizing and antioxidizing activities.

Abstract: The present invention has its objects to provide an adsorbent capable of efficiently adsorbing and removing LDL and VLDL from various lipoprotein-containing solutions, as well as a lipoprotein adsorber in which the adsorbent is used. This invention is related to a lipoprotein adsorbent which comprises a water-insoluble carrier having, on at least one part of the surface of the carrier, at least one group (other than p-nitrobenzoic acid) selected from the group consisting of groups represented by the general formula, and groups represented by the general formula.

Abstract: Compounds that modulate the aggregation of amyloidogenic proteins or peptides are disclosed. The modulators of the invention can promote amyloid aggregation or, more preferably, can inhibit natural amyloid aggregation. In a preferred embodiment, the compounds modulate the aggregation of natural &bgr; amyloid peptides (&bgr;-AP). In a preferred embodiment, the &bgr; amyloid modulator compounds of the invention are comprised of an A&bgr; aggregation core domain and a modifying group coupled thereto such that the compound alters the aggregation or inhibits the neurotoxicity of natural &bgr; amyloid peptides when contacted with the peptides. Furthermore, the modulators are capable of altering natural &bgr;-AP aggregation when the natural &bgr;-APs are in a molar excess amount relative to the modulators. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.

Abstract: The present invention relates generally to a newly identified adaptor protein FRS2 and related products and methods. FRS2 links protein kinases to activating partners in cells. The invention also relates to nucleic acid molecules encoding portions of FRS2, nucleic acid vectors containing FRS2 related nucleic acid molecules, recombinant cells containing such nucleic acid vectors, polypeptides purified from such recombinant cells, antibodies to such polypeptides, and methods of identifying compounds that enhance or block FRS2 interactions with natural binding partners. Also disclosed are methods for diagnosing abnormal conditions in an organism with FRS2 related molecules or compounds.

Abstract: The present invention relates to the study and control of atherosclerosis through the modulation of LDL-proteoglycan binding at Site B (amino acids 3359-3369) of the apo-B100 protein in LDL. The invention encompasses methods of identifying compounds which modulate LDL-proteoglycan binding, methods of identifying compounds which modulate atherosclerotic lesion formation, and methods of modulating the formation of atherosclerotic lesions. The invention also encompasses mutant apo-B100 proteins and LDL which exhibit reduced proteoglycan binding while maintaining LDL-receptor binding, polynucleotides which encode these apo-B100 proteins, as well as cells and animals which express the mutant apo-B100 proteins.

Abstract: The present invention relates to the study and control of atherosclerosis through the modulation of LDL-proteoglycan binding at Site B (amino acids 3359-3369) of the apo-B100 protein in LDL. The invention encompasses methods of identifying compounds which modulate LDL-proteoglycan binding, methods of identifying compounds which modulate atherosclerotic lesion formation, and methods of modulating the formation of atherosclerotic lesions. The invention also encompasses mutant apo-B100 proteins and LDL which exhibit reduced proteoglycan binding while maintaining LDL-receptor binding, polynucleotides which encode these apo-B100 proteins, as well as cells and animals which express the mutant apo-B100 proteins.

Abstract: An antigenic preparation is provided containing an outer membrane protein associated with pathogenic strains of Leptospira. The protein has been designated “LipL46” for “lipoprotein from Leptospira” and because the isolated polypeptide migrates to a position corresponding to a molecular weight of 46 kD in a denaturing polyacrylamide gel. The invention provides polynucleotides encoding LipL46 and antibodies that bind the protein which are useful in the diagnosis of leptospirosis. In addition, LipL46 can be used immunologically as a vaccine for spirochete-associated pathologies.

Abstract: Chimeric proteins which comprise a ligand-binding domain of a first receptor and a carrier domain which tends a cell surface receptor other than the first receptor, useful in transporting a selected substance present in extracellular fluids, such as blood or lymph, into cells; quantitative assays for the selected substance using chimeric proteins; DNA encoding the chimeric proteins; plasmids which contain DNA encoding the chimeric proteins; mammalian cells, modified to contain DNA encoding the chimeric proteins, which express and, optionally, secrete the chimeric proteins; a method of producing the chimeric proteins; a method of isolating the chimeric proteins; a method of using the chimeric proteins to assay the selected substance; and a method of reducing extracellular levels of the selected substance through administration of the chimeric protein, which results in transport of the selected substance into cells.

Abstract: A method for preventing adverse effects associated with the use of a medical device in a patient by introducing into the patient a device of which at least a portion includes a prophylactic or therapeutic amount of a nitric oxide adduct. The nitric oxide adduct can be present in a matrix coating on a surface of the medical device; can be coated per se on a surface of the medical device; can be directly or indirectly bound to reactive sites on a surface of the medical device; or at least a portion of the medical device can be formed of a material, such as a polymer, which includes the nitric oxide adduct. Also disclosed is a method for preventing adverse effects associated with the use of a medical device in a patient by introducing the device during a medical procedure and before or during said procedure locally administering a nitric oxide adduct to the site of contact of said device with any internal tissue.

Abstract: The invention relates to lipopeptides with very homologous amino-acid sequences but different fatty acid residues (lipid portion) which are synthesized by Actinoplanes sp. during fermentation and are released into the culture medium, to a process for isolating the lipopeptides from the culture medium and purifying them, to the use of the lipopeptides as pharmacologically active substances, in particular against Gram-positive bacteria, and to Actinoplanes sp. DSM 7358 for producing the abovementioned lipopeptides.

Abstract: A complex comprising a lipid and a conjugate of GPIb and lipid having a functional group, and use thereof. The GPIb-lipid complex of the present invention is extremely useful as a platelet substitute, a pharmaceutical agent for the prophylaxis and treatment of angiopathy, vascular damages and thrombosis, a diagnostic for vWF deficiency and the like, a biological or medical reagent, a reagent for screening platelet aggregation suppressant or antithrombosis, and the like. The GPIb-lipid complex of the present invention is also useful as a diagnostic for finding the location of vascular lesion or thrombus formation, or a therapeutic agent therefor, since it accumulates at vascular lesions.

Abstract: This invention also provides a method of treating atherosclerosis in a subject, comprising administering to the subject an effective amount of a substance capable of binding to the amino-terminal region of apolipoprotein B, thereby treating the atherosclerosis. This invention also provides a method for inhibiting the binding of low density lipoprotein to blood vessel matrix in a subject, comprising administering to the subject an effective amount of a substance capable of competing with the amino-terminal region of apolipoprotein B for binding to blood vessel matrix, thereby inhibiting the binding of low density lipoprotein to blood vessel matrix. This invention also provides a method for identifying a compound capable of ameliorating atherosclerosis. Additionally, this invention provides a kit for inhibiting the binding of low density lipoprotein to blood vessel matrix, wherein the kit comprises a substance capable of binding to the amino-terminal region of apolipoprotein B.

Abstract: Disclosed and claimed are isolated polypeptides consisting of amino acid sequences derived form ospA and/or ospB of various B. burgdorferi or portions thereof and methods of making and using the same.

Abstract: Disclosed is a fine fibrous assembly having a molecular structure of a bola-form peptide lipid containing L- or D-valine residues which can be obtained by spontaneous crystallization precipitation when an aqueous solution of the peptide lipid compound of the general formula ##STR1## in which Me is a methyl group, the subscript m is 1, 2 or 3 and the subscript n is a positive integer in the range from 6 to 18, in the form of an alkali metal salt is kept standing over days under an atmosphere of a saturated vapor over a dilute aqueous solution of a vaporizable acid such as acetic acid.

Abstract: The invention provides heterobifunctional cross-linking reagents and methods of using the cross-linking reagents. The cross-linking reagents of the invention combine a nucleophilic hydrazide residue with an electrophilic maleimide residue, allowing coupling of aldehydes to free thiols. In the methods of the invention, human immunodeficiency virus (HIV) infected cells can be detected using conjugates that include CD4 molecules conjugated to detectable markers via the disclosed cross-linking reagents.

Abstract: The invention relates to novel Borrelia, and OspA antigens derived therefrom. These antigens show little homology with known OspA's and are therefore useful as vaccine and diagnostic reagents. Multicomponent vaccines based on OspA's from different Borrelia groups are also disclosed.

Abstract: The present invention relates to a process for purifying a hydrophobic or amphiphilic compound, by first mixing a starting material containing the hydrophobic or amphiphilic compound with a first polymeric material, water and at least one of a second polymeric material and a surfactant, wherein the first polymeric material and the second polymeric material and/or surfactant are immiscible in the resulting primary aqueous solution. The process further comprises maintaining the primary aqueous solution for a period of time sufficient for essentially separating the phases formed, and then removing the phase containing the main portion of the hydrophobic or amphiphilic compound and the second polymeric material and/or surfactant. The second polymeric material and/or surfactant are separated from the hydrophobic or amphiphilic compound, and subsequently recycled to the initial mixing step.

Abstract: The present invention is directed to a family of unique antimycotic lipopeptide compounds produced by Pseudomonas viridiflava. The lipopeptides are effective against both human and plant fungal pathogens, and are typically characterized by their ability to inhibit growth of Candida albicans. Representative lipopeptides of the invention have molecular weights of 1137, 1153, 1164 and 1181 daltons.

Abstract: The present invention relates to a process for purifying apolipoprotein A (ApoA) or apolipoprotein E (ApoE) from human plasma, by obtaining a fraction of human plasma containing said ApoA or ApoE, prepurifying said fraction in at least one step, binding said ApoA or ApoE to an anion-exchange chromatography gel, and thereafter eluting said ApoA or ApoE from said anion-exchange chromatography gel. The thus produced ApoA or ApoE can be used for the manufacture of a medicament in the treatment of atherosclerosis and cardiovascular diseases, or peripheral atherosclerosis and sepsis as well as in a method for treatment of atherosderosis and cardiovascular diseases, or peripheral atherosclerosis and sepsis when administered in a therapeutically effective amount.

Abstract: A composition for the transfection of higher eucaryotic cells, comprising complexes of nucleic acid, a substance having an affinity for nucleic acid and optionally an internalizing factor, contains an endosomolytic agent, e.g. a virus or virus component, which may be conjugated. The endosomolytic agent, which is optionally part of the nucleic acid complex, is internalized into the cells together with the complex and releases the contents of the endosomes into the cytoplasm, thereby increasing the gene transfer capacity. Pharmaceutical preparations, transfection kits and methods for introducing nucleic acid into higher eucaryotic cells by treating the cells with the composition are also disclosed.

Abstract: An essentially pure immunogenic composite capable of selectively inducing antibody production in an animal to a peptide that if administered by itself to the animal without being conjugated to or mixed with additional substance does not stimulate production of anti-peptide antibody in the animal. This immunogenic composite comprises: a lipid and an amphipathic peptide. The amphipathic peptide if administered by itself to the animal without being conjugated to or mixed with additional substance does not stimulate production of anti-peptide antibody in the animal. The amphipathic peptide is covalently bound to the lipid in a peptide-lipid complex. The immunogenic composite has a vesicular or an amorphous particulate structure. Another embodiment of this immunogenic composite comprises: a lipid, the amphipathic peptide, and a hydrophilic peptide covalently bound together.

Abstract: The invention relates to a method for the renaturation of denatured proteins in which they are treated with a renaturant which has on vicinal carbon atoms a hydroxyl group and at least one fluorine atom.

Abstract: This invention provides a method of inhibiting the transcription of a gene, which is activated by AP-1 or an AP-1 component, comprising binding AP-1 or the component with a nuclear receptor so as to prevent the binding of AP-1 to the gene. The nuclear receptor can be the retinoic acid receptor, glucocorticoid receptor, vitamin D3 receptor, thyroid receptor, or estrogen receptor. Also provided is a composition of matter comprising AP-1 or an AP-1 component bound to a nuclear receptor. These methods and compositions can be used to treat arthritis and cancer.

Abstract: In a method for assaying an anticardiolipin antibody in a sample utilizing .beta.2-glycoprotein I, a polypeptide having the same amino acid sequence as domain IV of .beta.2-glycoprotein I or a polypeptide partially different therefrom but functionally equivalent thereto is used in place of .beta.2-glycoprotein I itself. According to this method, an autoantibody from patients with antiphospholipid syndrome can be accurately assayed in a simple manner.

Abstract: This invention presents antigenic preparations of Leptospira species outer membrane proteins and their immunogenic fragments which are useful for inducing immune response in animals, e.g., for use as vaccines against diseases caused by leptospirosis. Also presented are methods and kits for diagnosing leptospirosis by detecting the presence of these proteins, their immunogenic fragments, antibodies to these proteins or their fragments, or polynucleotides which encode or are translatable into these proteins or their fragments. Further disclosed are methods for isolating these proteins.

Abstract: A substantially endotoxin-free ApoA or ApoE is produced by recombinant DNA technique, suitably in E. coli. Medicaments and methods for treatment of atherosclerosis or cardiovascular diseases employ ApoA or ApoE purified by a process comprising contacting a first aqueous solution comprising ApoA or ApoE and endotoxins with a matrix comprising an immobilized compound with an end group comprising two or three nitrogen atoms bonded to a carbon atom for attaching the endotoxins to the matrix, and subsequently treating the matrix comprising the immobilized compound with a second aqueous solution comprising a surfactant for releasing the ApoA or ApoE while the endotoxins remain attached to the matrix.

Abstract: The present invention is directed to a process for purifying alpha-1-PI. The process comprises providing an impure protein fraction which comprises alpha-1-PI. The impure protein fraction is suspended in an aqueous solution at pH 6. Insoluble proteins are recovered and resuspended in aqueous solution at pH 8.5. PEG is added to precipitate .alpha.-2 proteins. To the PEG supernatant precipitation, which comprises alpha-1-PI, is added ZnCl.sub.2 to precipitate crude alpha-1-PI. The crude alpha-1-PI is resolubilized and applied to an anion-exchange medium. A fraction comprising alpha-1-PI is recovered from the anion-exchange medium. Alpha-1-PI purified by the process has a specific activity about 1.0 units/OD.sub.280.

Abstract: A method of preventing the transmission of or treating herpesvirus, such as herpes simplex virus infection, or Chlamydia trachomatis comprising administering to a patient a composition which comprises: (i) a protein or peptide containing lysines and an N-terminal amino group, wherein at least one of the lysines or the N-terminal amino group of the protein or peptide, such as casein, .beta.-lactoglobulin, powdered milk or whey, is modified by contact with an aromatic acid anhydride compound, such as trimellitic anhydride, trimellitic anhydride chloride or 3-hydroxyphthalic anhydride and/or (ii) a protein or peptide containing arginines, which is modified by an arginine modifying agent containing at least one carboxyl group, such as p-carboxyphenylglyoxal.

Abstract: A lipoprotein particle and a therapeutic lipoprotein composition are disclosed. The lipoprotein particle consists essentially of lecithin phospholipids with low phase transition temperatures and human apoproteins A and C. A therapeutic composition for therapeutic administration to a subject, comprising the lipoprotein particles of the invention, is also disclosed. The composition is useful is treating disease conditions associated with elevated serum Lp(a) levels, as well as hypertension and acute renal failure.

Abstract: The invention relates to novet Borrelia, and OspA antigens derived therefrom. These antigens show little homology with known OspA's and are therefore useful as vaccine and diagnostic reagents. Multicomponent vaccines based on OspA's from different Borrelia groups are also disclosed.

Abstract: The present invention relates to compositions and methods for neutralizing lipopolysaccharide, and treatment of gram-negative sepsis based therein. Accordingly, the invention is directed to a composition of homogeneous particles comprising phospholipids and a lipid exchange protein, such as phospholipid transfer protein or LPS binding protein. The lipid exchange protein is characterized by being capable of facilitating an exchange protein of lipopolysaccharide into the particles. In a specific embodiment, exemplified herein, the lipid particles are high density lipoprotein particles comprising apolipoprotein A-I (apo A-I), a phospholipid, and cholesterol or a lipid bilayer binding derivative thereof. In a specific example, the phospholipid is phosphatidylcholine (PC). In a specific example, the ratio of phosphatidylcholine:cholesterol:apolipoprotein A-I is approximately 80:4:1.

Abstract: The invention provides heterobifunctional cross-linking reagents and methods of using the cross-linking reagents. The cross-linking reagents of the invention combine a nucleophilic hydrazide residue with an electrophilic maleimide residue, allowing coupling of aldehydes to free thiols. In the methods of the invention, human immunodeficiency virus (HIV) infected cells can be detected using conjugates that include CD4 molecules conjugated to detectable markers via the disclosed cross-linking reagents.