Abstract: A diagnostic site-specific imaging reagent in the form of a receptor and an indicating means selectively binds to a specific cell membrane-associated antigen of a blood platelet that is in a stimulated active state but does not substantially bind to a platelet that is in a non-stimulated resting state. In particular, prelabelled monoclonal antibodies and polyclonal antibodies are prepared that bind and image thrombospondin when it is cell membrane-associated on a thrombin-stimulated platelet, thereby providing means for detecting and discriminating between a stimulated active blood platelet and a non-stimulated resting blood platelet.

Abstract: A method for rapidly determining the presence of functional cellular steroid receptors by assaying a tissue sample for nuclear steroid or antisteroid binding is disclosed which comprises treating the tissue with collagenase, incubating the isolated cells with a labelled steroid or a labelled antisteroid capable of complexing said receptors and measuring the bound nuclear radioactivity and the DNA of the isolated cellular nuclei.

Abstract: Alzheimer's Disease (AD) sufferers may be diagnosed by examination of T-cells from their peripheral blood. AD is marked by increased appearance of alpha-1 acid glycoprotein (AGP) on the surface of such cells. Among AD subjects normal for AGP, a subpopoulation exists which show elevated AMLR response as compared to age-matched controls. These tests may be used to diagnose AD or to screen possible therapeutic agents.

Abstract: The present invention provides a method for detection of protozoan parasites in blood or other specimen from their mammalian hosts. The method comprises nucleic acid hybridization of repetitive nuclear DNA fragments of the parasites. Hybridization probes have been prepared for this purpose by cloning the repetitive nuclear elements that are species-specific in appropriate vectors. The sensitivity of these probes has been increased by further sub-cloning to make them capable of cascade hybridization. The assay is highly specific and sensitive for detection of disease-causing protozoan parasites of the commonly occurring Trypanosomatidae of the genus Leishmania and genus Trypanosoma, as well as for malaria-causing protozoan and other parasitic microorganims of mammals.

Abstract: Improved assays are provided for anti-acetylcholine receptor protein autoantibodies in the sera of patients with myasthenia gravis. The basis for the improved assays is the discovery that large quantities of acetylcholine receptor protein, that, for practical purposes in immunoassays, is immunologically indistinguishable from human muscle acetylcholine receptor protein, can be isolated from cells of the human medullablastoma-derived cell line TE671.

Abstract: It has been determined that nerve growth factor binds to a cell surface protein of human neural crest origin having a molecular weight of about 75,000 daltons. New monoclonal antibodies specifically imunoprecipitate these receptor molecules, and also inhibit binding of the hormone to the receptor. These monoclonal antibodies show significantly higher reactivity with primary and metastatic melanoma cell lines than with melanocytes. The antibodies are used in a diagnostic method for histochemical detection of human neural crest disease.

Abstract: A simple method for preparing highly radioactive 1,4-dihydropyridine and 1,4-dihydroquinoline derivatives labelled with .sup.125 I enables a specific radioactivity of approx. 2200 to 8800 Ci/m Mole to be achieved. In this way high sensitivity in medicament screening with the aid of radioreceptor assays and in determining plasma levels of 1,4-dihydropyridines, 1,4-dihydroquinolines and other substances that inter-react with receptors for 1,4-dihydropyridines and 1,4-dihydroquinolines is achieved, with the result that a substantially shorter exposure time in the auto-radiographic identification of the receptors for these substances is required. For this purpose an amino derivative of a 1,4-dihydropyridine or 1,4-dihydroquinoline is reacted with an acylating reagent radiactively labelled with .sup.125 I (2200-4400 Ci/mMole), and the .sup.

Abstract: Radiodinated and non-radiodinated 16.alpha.-iodo- and 17.alpha.-(2-iodovinyl)-19-nortestosterones are prepared and are used in progesterone receptor assays.

Abstract: The method of measuring circulating antigens or antibodies by using a ligand labeled specific antigen or ligand labeled specific antibody chemically attached to a soluble matrix or backbone, a differently labeled anti-antigen or anti-antibody and a solid phase anti-ligand directed at the ligand attached to the specific antigen or specific antibody. This is achieved by either one or two analytical schemes:(a) Reacting a patient sample with a ligand labeled specific antigen or a ligand labeled specific antibody in the liquid phase in the presence of a differently labeled specific anti-antigen or labeled specific anti-antibody. This immunological complex is reacted with an immobilized anti-ligand on a solid support which is directed against the ligand attached to the specific antigen or antibody through the liquid matrix. Subsequently the solid phase is washed and checked for the label on the anti-antigen or anti-antibody which is directly proportional to the concentration of specific antigen or antibody.

Abstract: A nucleic acid detection probe comprising a hybridizable single stranded portion of nucleic acid connected with a non-hybridizable, single or double stranded nucleic acid portion, the non-hybridizable portion preferably including a recognition site for binding by a particular protein. Such recognition site can be a region of singly or doubly stranded nucleic acid specific for a particular nucleic acid binding protein such as lac repressor protein or can be a modified nucleic acid region such as a unique antigenic determinant introduced by interaction of the region with a modifier compound such as an intercalating agent or a platinum-containing ligand. The probe-binding protein can be labeled for ease of detection and in the case of an antigenic determinant binding site can be labeled antibody.

Abstract: A method, reagents, and kit for determining the levels of D-1 receptor antagonistic activity of neuroleptic drugs. The method correlates competition between analyte and tritiated R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol for binding to D-1 receptors in mammalian brain tissue.

Abstract: An immunochemical assay, and compositions used therein, to determine the presence and/or amount of human chromogranin A, which is useful in diagnosis of disease associated with alterations in sympathoadrenal activity.

Abstract: Methods and compounds are disclosed for determining the presence, amount of, or association between substances of interest in samples suspected of containing same. The methods are based on the polymerization-induced separation of specifically-bound, reporter-labeled recognition reactants from free, reporter-labeled recognition reactants. The methods described are applicable to any substance for which suitable recognition reactants exist or can be made and are not limited by considerations such as chemical composition or molecular size.

Abstract: Methods and procedures are described for the isolation of human progestin receptors and for the use of human progestin receptors as immunogens in producing both monoclonal and polyclonal antibodies. These antibodies are used for the detection of progestin receptors, such as the progesterone receptor both normal and cancerous tissues.

Abstract: Monoclonal antibodies are provided capable of distinguishing DNA-RNA hybrid complexes from single stranded DNA and RNA and double stranded DNA and RNA. The antibodies find particular use in determining the presence of a specific nucleic acid sequence on a solid surface. Single stranded polynucleotide is fixed to a solid (gel) surface and then hybridized with the complementary probe. The hybrid complex specific monoclonal antibody is then added to bind to any hybrid complexes which have formed. By appropriate label, the hybrid complex may be visualized in a variety of ways.

Abstract: A method for rapidly determining the presence of functional cellular steroid receptors by assaying a tissue sample for nuclear steroid binding is disclosed which comprises treating the tissue with collagenase, incubating the isolated cells with a labelled steroid capable of complexing said receptors and measuring the bound radioactivity and the DNA of the isolated cellular nuclei.

Abstract: Immunoassay methods and compositions are disclosed for the detection of one or more analytes in fluid samples. The disclosure provides conjugates of analytes or reactants with polymerizable organic monomers. Specific binding reactions between reactants are detected by means of reporter/reactant conjugates. Free and specifically-bound reporter/reactant conjugates are separated by a polymerization reaction which renders the polymerized monomers insoluble.

Abstract: A junction-fragment DNA probe, a DNA probe cluster, and methods of preparing and using the probe and cluster to study gene localization and organization. The probe includes first and second gene segments which are derived from first and second, single-copy genomic-DNA gene regions, respectively, separated from one another, in the genomic DNA strand, by a selected distance of between about 20 and 2,000 kilobases. The two segments in the probe are connected at a jThe invention was supported in part by the National Institute of Health grant #NIH CA-30938 and the Government has certain rights to the invention.

Abstract: Certain substituted adenosines have been found to selectively occupy A.sub.1 adenosine receptors found in animal brain tissues.

Abstract: Methods and compositions for detecting the presence of tumors are provided, where a physiological sample is assayed for the expression product of a c-onc gene as diagnostic for the presence of the tumor. The method finds use in both pre- and postoperative situations with a host suspected of having transformed malignant cells.

Abstract: Human monoclonal antibodies (HmAbs) capable of reacting with cell surface antigens and intracellular components are disclosed. It has been found that HmAbs Ev248, Ch-5, Ch-13, Te-39, Hu44, Ge-1, Gr-431, Gr169 and Sp909 may be used to detect these antigens in various cells. By means of these HmAbs malignant cells may be determined. This information may be used to screen metastasized tumors and primary tumors for tissue source and greatly affects the management of these cancers.

Abstract: A method for detecting a minute quantity of an inorganic or organic target molecule by combining it with a composition of a detecting agent for the target molecule which carries, by direct or indirect means, a visualization polymer. The visualization polymer is composed of multiple units of a visualization monomer which are covalently linked together directly or indirectly covalently linked together by coupling agents which bond to chemical groups of the monomer. The monomer may be an enzyme, a tagged polypeptide, a tagged polyol, a tagged polyolefin or a tagged carbohydrate. The detecting agent may be an antibody, an enzyme, a lectin, strand of a DNA receptor protein, avidin, streptavidin and the like. The visualization polymer produces a high degree of amplification for the detection of the target molecule.

Abstract: A method for evaluating the fertility of a test male mammal relative to the fertility of a control male mammal. The method includes the steps of collecting samples of semen from the test male and the control male. The binding affinity of a selected glycosaminoglycan to the sperm of the semen samples is measured by a selected means for measuring binding affinities. The fertility of the test male may be evaluated as higher or lower than that of the control male by the degree to which the binding affinity of the glycosaminoglycan to its sperm is higher or lower than the binding affinity of the glycosaminoglycan to the sperm of the control male.

Abstract: A single-stranded deoxyribonucleic acid molecule having a length of less than about 25 kb comprises at least three distinct nucleotide sequences which are the sites for incorporation into a chromosome of a deoxyribonucleic acid molecule encoding a deleterious gene. Deoxyribonucleic acid probes have been prepared from such molecules and are useful as hybridization probes for detecting chromosomal deoxyribonucleic acid which has a deoxyribonucleic acid molecule encoding a deleterious gene, i.e. oncogene, incorporated therein.A single-stranded deoxyribonucleic acid molecule derived from human chromosome 22 which is about 5.8 kb in length contains sites for incorporation of a deoxyribonucleic acid molecule encoding the oncogene c-abl derived from human chromosome 9. Deoxyribonucleic acid probes have been prepared from this molecule and used to detect the abnormal Philadelphia chromosome and chronic myelocytic leukemia.

Abstract: A murine monoclonal antibody combining site produced by a hybridoma formed by fusion of cells from a myeloma cell line and lymphocytes that produce antibodies that react (1) with isolated human C3b receptor and (2) with C3b receptor-bearing cells from a mammal immunized with human C3b receptor is disclosed.

Abstract: A process for the detection of a biological substance immobilized on a support including(1) incubating, after washing, the substance immobilized on a support with the product of coupling of a specific ligand with a ligand capable of reacting with erythrocytes;(2) adding erythrocytes;(3) immersing the whole in a solution of a fixing agent and(4) measuring the erythroadsorption, after having turned the support over in order to permit the removal of the red cells which have not reacted.

Abstract: A new technique is disclosed for assaying for the presence of invasive cancer. While based on leukocyte adherence inhibition, it is improved by using relatively long lived radio-labeled leukocytes, fractionation of the leukocytes to separately treat T-cells and monocytes and by providing for human plasma or serum in the incubation medium.

Abstract: A novel polypeptide, Alzheimer's Amyloid Polypeptide (AAP), is provided in substantially purified form which is isolated from amyloid deposits in patients with Alzheimer's Disease. The polypeptide has the following amino acid sequence: ##STR1## The polypeptide, or fragments thereof, may be used to produce antibodies useful in a diagnostic test for Alzheimer's Disease. Nucleotide probes corresponding to portions of the polypeptide are also useful for diagnostic purposes.

Abstract: A process for the production of radioiodinated spiperone and certain derivatives thereof, and novel compositions made by the process. The process includes reacting spiperone, thallium trichloride and radioiodine in a sealed reaction vial. The novel compounds are useful for diagnosis of disease states resulting in quantitative changes in dopaminergic receptors.

Abstract: Liability in human individuals to develop non-insulin-dependent diabetes mellitus (NIDDM) and/or atherosclerosis is determined by restriction enzyme mapping of DNA from a human individual using a probe selected from the group consisting of(i) cDNA complementary to the mRNA coding for the human insulin,(ii) human genomic DNA containing the actual insulin gene,(iii) DNA sequences of human genomic DNA located within 20.times.10.sup.6 base pairs from the insulin gene in either direction,and examining the distribution of DNA fragments for the appearance of insertion sequences of approximately 1600 to 2300 base pairs (U alleles) the occurrence of which indicates a liability for said individual to develop elevated blood glucose concentrations and/or atherosclerosis and in homozygous form a liability to develop NIDDM.

Abstract: An improved radioimmunoassay test method and device based upon competitive binding test methods wherein immunoreactions are halted at a time when the rate of change of the quantity of bound radiolabeled analyte of interest is inversely proportional to the concentration of analyte of interest in an unknown sera. Based thereon, a test device is created having a single calibration curve 36 which is accurate throughout the shelf life of the device.

Abstract: A hybridization assay between two sets of parallel bands of DNA or RNA, one set labelled as a probe on a porous carrier sheet, the bands of the other set crossed with respect to the first and immobilized on a plurality of carrier sheets, is carried out with the sheets in contact and saturated with hybridization buffer in static condition. As many as ten sheets can be assayed simultaneously.

Abstract: Method of binding nucleic acid to a nucleic acid-binding support comprising depositing the nucleic acid onto the support and then contacting the nucleic acid and the support with a liquid binding solution which is compatible with the support and which contains an organic solvent which is capable of binding the DNA to the support, for a period of time sufficient to effect the binding.

Abstract: Methods and compositions are provided for detecting the presence of carcinomas in a mammalian host by measuring the level of normal surface antigens specific for a differentiated cell in the serum of the host as compared to the normal level of such antigen. The method finds particular use in detecting residual carcinomas after therapy or in detecting the recurrence of neoplastic tissue, and assigning a tissue of origin to the neoplastic tissue.

Abstract: HLA typing based on restriction length polymorphism is carried out by: digesting an individual's HLA DNA with a restriction endonuclease that produces a polymorphic digestion pattern with HLA DNA; subjecting the digest to genomic blotting using a labeled cDNA hybridization probe that is complementary to an HLA DNA sequence involved in the polymorphism; and comparing the resulting genomic blotting pattern with a standard. This technique may be adapted to make paternity or transplant or transfusion compatibility determinations or to make disease association correlations to diagnose diseases or predict susceptibility to diseases. Locus specific cDNA hybridization probes, particularly probes for genes of Class II loci (D and DR loci), for use in the typing procedure are described.

Abstract: An antibody of a human leukemia virus-related peptide obtained by collecting an antibody produced in a mammal body by administering to the mammal an antigen prepared by reacting a human leukemia virus-related peptide represented by formula (1):R-Pro-Val-Met-His-Pro-His-Gly-Ala-Pro-OH (1)whereinR is a hydrogen atom or a group shown by formula, H-Tyr-;as a hapten, with a carrier in the presence of a hapten-carrier binding agent.

Abstract: Determination of tumor-associated glycolinkage (TAG) by:(1) competitively reacting body fluid TAG to be measured and a definite quantity of insolubilized TAG or TAG-like material with a definite quantity of lectin labelled with a labelling agent, separating the insolubilized TAG or insolubilized TAG-like material bound to the labelled lectin and unbound labelled lectin from each other, and measuring the labelling agent activity of either of them;(2) competitively reacting the material to be measured and a definite quantity of TAG or TAG-like material labelled with a labelling agent with a definite quantity of lectin or insolubilized lectin, separating the labelled TAG or labelled TAG-like material bound to lectin or insolubilized lectin and unbound labelled TAG or TAG-like material from each other, and measuring the labelling agent activity of either or them; or(3) reacting the material to be measured with the insolubilized lectin to form a TAG-insolubilized lectin complex, reacting this complex with a defini

Abstract: A cell matrix receptor specific for laminin expressed on the surface of carcinoma and epithelial cells is provided. The binding of these cells to extracellular matrix is mediated by the laminin molecule, which has binding domains for type IV collagen of the matrix and the cell surface receptor. Fragments of the laminin molecule lacking the type IV collagen binding domain and antibodies to the receptor are useful in conjunction with the cell receptor as ligands in binding assays for cancer diagnosis and in cancer management.

Abstract: This invention relates to a kit for the detection of microbial nucleic acids and a method for identifying the nucleic acids using a one-step sandwich hybridization technique. The technique requires two complementary nucleic acid reagents for each microbe or group of microbes to be identified.

Abstract: Nucleic acid hybridization assay methods and reagent systems for detecting a particular polynucleotide sequence in a test medium. An aggregate is formed in the assay reaction mixture comprising intercalation complexes between a nucleic acid intercalator and double stranded nucleic acid associated with the hybridization product of the sequence to be detected and a nucleic acid probe sequence. Hybridization of the probe with the sequence to be detected can then be determined by addition of an antibody, or a fragment thereof, capable of binding with the intercalation complexes in the formed aggregate and measuring the antibody or fragment thereof which becomes bound to such intercalation complexes associated with hybridized probe. In one preferred embodiment, this method eliminates the need to chemically modify the probe in order to form a labeled reagent. In another embodiment, the method provides an advantageous method for labeling the probe by chemical modification.

Abstract: A method and test kit are disclosed for detecting the presence of hepatitis B virus in a test specimen containing at least a portion of the DNA of the virus. A test reagent comprises cloned hepatitis B virus-DNA that has been repurified by treatment with a restriction enzyme and labelled to high specific activity with a radioactive label. The sample to be tested is fixed to a solid matrix, incubated in the presence of the test reagent under hybridization conditions and detected by hybridization to the labelled DNA probe. The uncombined HBV-DNA (labelled) is removed from the substrate, and the hybridized HBV-DNA determined by scintillation counting or by autoradiography of the substrate.

Abstract: An assay method for the detection of a specific nucleotide target sequence in a polynucleotide test extract is disclosed which utilizes a polynucleotide modified probe including both a cDNA sequence substantially complementary to the specific target sequence and a protein binding sequence. The assay is conducted by exposing the modified probe to the polynucleotide test extract for hybridization and then exposing the complex to the protein which binds to the protein binding sequence. An assay, such as an immunoassay, can then be conducted on the test sample to indicate the presence of the specific target sequence by detecting the presence of the binding protein.

Abstract: Rearranged DNA fragments associated with oncogenes are detected by DNA hybridization to a labelled probe comprising DNA fragment subject to rearrangement.

Abstract: Experiments designed to define the differences between an oncogene isolated from human bladder cancer cells and its corresponding proto-oncogene are described herein. By a series of in vitro recombinations, the difference was initially isolated to a 350 kb segment of DNA; sequencing defined the difference as a change in the Gly.sup.12 codon causing the p21 protein of the oncogene to contain valine at a location where the p21 protein of the proto-oncogene contained glycine. Assays for detecting carcinogenesis based on such differences are also described. In one type of assay, a restriction enzyme specific for either the altered or non-altered DNA segment of the genes are employed to detect carcinogenesis. In another type of assay, seralogical reagents, such as antibody specific for either p21 protein expressed from the proto-oncogene or oncogene, or a common site therein, are described.

Abstract: There is provided an assay for the determination of the carcinogenicity of chemical and physical agents, by exposing a selected line of tumor virus transformed cells to the agent to be tested and determining whether such exposure induces endogenous viral DNA replication in such cells, which induction is indicative of the carcinogenicity of the tested agent by in situ hybridization. There is provided a kit for carrying out such assay.

Abstract: A process for preparing a stable receptor preparation suitable for the quantitative determination of substances able to bind to cerebral receptors in which a brain or brain-region material is homogenized with an aqueous solution of an inert substance soluble in water; the formed homogenizate is centrifuged at an acceleration of 800 to 110 g for 8 to 20 minutes to form a supernatant; the brain or brain-region material is isolated from the supernatant by centrifuging the supernatant at an acceleration of 18,000 to 22,000 g for 10 to 20 minutes, the thus-obtained solid substance is rehomogenized in distilled water; the homogenizate is frozen and then thawed and thereafter centrifuged at an acceleration of 7000 to 9000 g for 5-15 minutes; the supernatant is isolated, centrifuged at an acceleration of 35,000 to 45,000 g for 20 to 30 minutes; the obtained solid substance is washed with an aqueous buffer solution of a pH value between 6 and 8, and a suspension consisting of the solid substance and the washing liquid

Abstract: The present invention relates to a conjugate of a specific ligand and a lectin, by covalent bonding.The product of the invention may, for example, be the conjugate of Concanavalin A and an antigen, a hapten, an antibody, a hormone or its receptor, an enzyme or its inhibitor or a lectin. Coupling being effected by means of glutaraldehyde or p-benzoquinone.

Abstract: Ligand having at least two determinant or binding sites is contacted with a labeled first binder, an unlabeled second binder different than the first binder and a precipitating binder specific for the second binder, with such contacting precipitating a complex of the ligand and the first and second binders to thereby separate bound labeled binder from unbound labeled binder. The bound and/or unbound labeled binder is determined as a measure of the ligand.

Abstract: A method for measuring the level of organic calcium antagonist drug in a body fluid comprises preparing a mixture of a radioactive calcium antagonist drug, a body fluid containing a calcium antagonist drug and a calcium antagonist receptor material, measuring the radioactivity of the radioactive calcium antagonist drug bound to said calcium antagonist receptor material and deriving the concentration of the calcium antagonist drug in the body fluid from a standard curve indicating the concentration of calcium antagonist drug versus inhibition of binding of said radioactive calcium antagonist drug to said receptor sites caused by the calcium antagonist drug in said body fluid. A kit for measuring the level of an organic calcium drug comprises a receptacle containing a radioactive calcium antagonist drug, a calcium antagonist receptor material and a standard amount of a nonradioactive calcium antagonist drug.

Abstract: This invention relates to the detection of antibodies in sera of AIDS and pre-AIDS patients and describes the biochemical and immunological analysis of antigens associated with the virus HTLV-III Human T-Cell Leukemia Virus. It is shown that antigens associated with the infection of human cells by this virus are specifically recognized by antibodies from AIDS patients. Specifically, HTLV-III isolated from AIDS patients and transmitted by cocultivation with an HT cell line is specifically detected by antibodies from human sera taken from AIDS patients. The method of detection of antibodies preferred is a strip radioimmunoassay (RIA) based on the Western Blot technique or an ELISA (an enzyme-linked immunosorbent assay) or an indirect immunofluorescence assay.