Abstract: An envelope protein of the etiologic agent of acquired immune deficiency syndrome (AIDS) and a method for its preparation are disclosed. Proviral DNA is transferred into a host cell after engineering into an expression vector which produces the envelope protein. A method of testing human blood for the presence of antibodies to the AIDS virus using the AIDS envelope protein is disclosed.

Abstract: What is described are methods and apparatus for performing a binding assay for an analyte of interest present in a sample. The methods include the steps of: forming a composition containing said sample, an assay-performance-substance which contains a component linked to a label compound capable of chemiluminescing when triggered, and a plurality of coated magnetic particles capable of specifically binding with the analyte and/or said assay-performance-substance; incubating said composition to form a complex which includes a particle and said labeled component; magnetically collecting said complex at the surface of an electrode; inducing said label to luminesce by contacting it with a trigger, said trigger being formed in-situ by conversion of a precursor molecule upon introduction of electrochemical energy; and measuring the emitted luminescence to measure the presence of the analyte of interest in the sample.

Abstract: A method for interfering with the binding between p53 and MDM2 or a protein having a p53 binding site analogous to that of MDM2, which method comprises administering a effective amount of a compound, selected from the group consisting of a peptide having up to twenty eight amino acids which is able to disrupt or prevent binding between p53 and MDM2, or a functional peptide analogue thereof.Compounds for use in the method, methods for detecting such compounds and their application in the diagnosis and treatment of tumours is also described and claimed.

Abstract: Red blood cells are removed from whole blood or a fraction thereof by agglutinating whole blood with a mixture of a free agglutinating agent and nucleating particles having agglutinating agent intimately associated therewith to form clusters of red blood cells. High molecular weight polyethylene glycol may be added further to enhance agglutination. The clusters of red blood cells are much larger than the size of individual red blood cells, so that the clusters can easily be filtered through a porous medium. The plasma, which is substantially free of red blood cells, is further passed through a filter that optionally contains an additional agglutinating agent. Flow-delay additives may be provided to retain the fluid sample in contact with a reagent for a predetermined time.

Abstract: A combinatorial library is disclosed which is represented by Formula ##STR1## wherein: ##STR2## is a solid support; T'-L- is an identifier residue; and -L'-II' is a ligand/linker residue. This library contains hydroxypropylamines of the formula:Aa.sup.1 -Aa.sup.2 -(CH.sub.2 Ar.sup.1)-CH.sub.2 CHOH-CH.sub.2 XR.sup.1IIwherein:Aa.sup.1 and Aa.sup.2 is each an amino acid joined to each other through an amide bond;Ar.sup.1 is an aromatic ring system;--CH.sub.2 Ar.sup.1 is attached to N on Aa.sup.2 ; andR.sup.1 is H, C.sub.1-20 alkyl, alkenyl, alkynyl, aryl, heteroaryl, aryl or heteroaryl fused to a 3- or 4-membered moiety to form a non-aromatic second ring, or substituted C.sub.1-20 alkyl, alkenyl, or alkynyl.

Abstract: An assay for measuring activation (i.e., autophosphorylation) of a tyrosine kinase receptor of interest is disclosed.(a) A first solid phase is coated with a substantially homogeneous population of cells so that the cells adhere to the first solid phase. The cells have either an endogenous tyrosine kinase receptor or have been transformed with DNA encoding a receptor or "receptor construct" and the DNA has been expressed so that the receptor or receptor construct is presented in the cell membranes of the cells.(b) A ligand is then added to the solid phase having the adhering cells, such that the tyrosine kinase receptor is exposed to the ligand.(c) Following exposure to the ligand, the adherent cells are solubilized, thereby releasing cell lysate.(d) A second solid phase is coated with a capture agent which binds specifically to the tyrosine kinase receptor, or, in the case of a receptor construct, to the flag polypeptide.

Abstract: The present invention provides novel human polynucleotide sequences and the recombinant human DRADA proteins encoded thereby and methods of use thereof.

Abstract: Particles comprising an energy donor as a first component and a fluorescent dye as a second component positioned in said particles at an energy exchanging distance from one another, wherein the two components have a Stokes shift of greater than or equal to 50 nm, said particle having bound on its surface, a protein, polypeptide, nucleic acid, nucleotide or protein containing ligand analogue are disclosed and claimed. In addition, novel fluorescent dyes are described which exhibit intramolecular energy transfer for use to label various molecules, proteins, polypeptides, nucleotides and nucleic acids or to incorporate into particles.

Abstract: A method is provided for detecting an analyte in a liquid sample, the method using light energy propagational properties of an analyte-responsive polymer. The analyte-responsive polymer is interfaced with a means to detect changes in the light propagation of the analyte-responsive polymer and the changes are correlated to the amount of analyte in the liquid sample.

Abstract: A method of screening for the presence of a periodontal disease condition is disclosed. The method involves obtaining an oral fluid sample from a human subject being tested, and determining the level of native free pyridinium crosslinks (free pyridinoline and/or free deoxypyridinoline) from the subject. An above-normal level of crosslinks, when compared with a predetermined level characteristic of normal subjects, is an indication of the presence of a periodontal disease condition.

Abstract: An immunoagglutination reagent includes liposomes, as a carrier, with a covalently bound antigen or antibody immobilized thereon. The reagent is used to assay an antibody or an antigen on the basis of agglutination. The assaying can be done at a high sensitivity in the short wave region where the change in turbidity caused by the agglutination is enhanced. An antibody or an antigen is immobilized onto the surface of the liposome, and a water-soluble polymer compound or a gelled compound is entrapped in the liposomes. The substance entrapped in the immunoagglutination reagent enhances the change in turbidity via the agglutination caused by the antigen-antibody reaction.

Abstract: This invention pertains to a method of detecting, in a sample obtained from an individual, anti-heparin antibodies which inhibit the formation of the heparin accelerated antithrombin III-thrombin complex. In the present method, the presence of such anti-heparin antibodies are detected directly (by detecting the presence of anti-heparin antibodies themselves) or indirectly (by detecting the presence or formation of the heparin accelerated antithrombin III-thrombin complex). In one embodiment of the present method, antibodies which react with or interfere with the heparin pentasaccharide which binds antithrombin III in such a manner that binding to antithrombin III is inhibited are detected. In a specific embodiment of the present method, the anti-heparin antibody detected is one which reacts with or interferes with the disaccharide UA-2S/GlcNs-6 present in residues IV and V of the heparin pentasaccharide that binds antithrombin III.

Abstract: Disclosed is a method for determining the concentration of an analyte in a liquid test sample. The method involves the use of colloidal sized metal particles, which exhibit a spectral response in the agglomerated state which is detectably different than in their unagglomerated state, which bear specific binding partners for the analyte in question on their surface. The specific binding partner treated colloidal particles are combined in a buffered, aqueous medium with a destabilizer material capable of destabilizing the specific binding partner-colloidal particle conjugates thereby permitting the particles to agglomerate. Also included in the liquid medium is a polymer bearing multiple analyte or analyte analog molecules along its surface which serves to protect the specific binding partner coated metal particles from dissociation by the destabilizing agent.

Abstract: A variant of a LAV virus, designated LAV.sub.ELI and cable of causing AIDS. The cDNA and antigens of the LAV.sub.ELI virus can be used for the diagnosis of AIDS an pre-AIDS.

Abstract: A diagnostic test, and a device for conducting the test, for assessing whether patient chest pain is cardiac in origin and for differentiating between unstable angina and myocardial infarction as a cause of patient chest pain is described. The diagnostic test comprises simultaneously detecting at least three selected cardiac markers with the use of at least three different monoclonal or polyclonal antibody pairs, each member of which is complementary to a different marker, which is released by heart muscle at varying stages after the onset of chest pain and is indicative of the cause of the chest pain.

Abstract: A diagnostic test, and a device for conducting the test, for assessing whether patient chest pain is cardiac in origin and for differentiating between unstable angina and myocardial infarction as a cause of patient chest pain is described. The diagnostic test comprises simultaneously detecting at least three selected cardiac markers with the use of at least three different monoclonal or polyclonal antibody pairs, each member of which is complementary to a different marker, which is released by heart muscle at varying stages after the onset of chest pain and is indicative of the cause of the chest pain.

Abstract: A method and apparatus for determining qualitatively or quantitatively the presence of analyte bound to a separation media without doing a bound/free separation. In the method, the bound fraction is collected in an assay region of a body of liquid which includes the free analyte, and the assay is performed by comparing the radiant-energy response in the assay region to the radiant-energy response in a control region of the body of liquid which is free of bound analyte. The apparatus has a chamber which contains the body of liquid, one or more collection elements and a control element and position in the body of liquid parallel to an opaque wall which has a colliminating slit in registry with each element. Each slit enables sensing of the radiant-energy response from the body of liquid between the slit and its associated elements.

Abstract: A method is provided for preparing a labeled protein, immobilized protein or protein-bioactive agent composition by attaching a label, support or bioactive agent to a protein by exopeptidase catalysis at a site that is remote from the active site of the protein. More specifically, an amine or alcohol group of an amino acid, amine or alcohol nucleophile is reacted by exopeptidase catalysis with a C-terminus carboxylic acid group of a protein such as an antibody, enzyme or hormone to couple the nucleophile to the protein to form an adduct, and the adduct is bound to an auxiliary substance such as a support, label or bioactive agent or its combination with a linker arm by reacting a reactive substituent of the nucleophile with a reactive group of the auxiliary substance. Alternatively, the nucleophile is bound to the auxiliary substance or its combination with a linker arm to form an intermediate, and the intermediate is coupled by exopeptidase catalysis to the protein.

Abstract: Combinatorial libraries of labeled biochemical compounds and methods for producing such combinatorial libraries comprising the steps of producing labeled individual units, combining at least two of the labeled individual units so as to produce a labeled biochemical compound, and repeating this process at least once so as to produce a combinatorial library of labeled biochemical compounds. Also, methods for determining the conformation of a biochemical compound which comprise producing a combinatorial library of labeled biochemical compounds, contacting the combinatorial library of labeled biochemical compounds with a target receptor molecule so that a selected labeled biochemical compound binds to the target receptor molecule, and determining the conformation of the selected labeled biochemical compound when bound to the receptor molecule.

Abstract: A combinatorial library composition and method for using the library to construct oligomers effective to bind to a selected ligand is disclosed. The library composition includes at least two sets of ar oligomer libraries, each library set having selected oligomer subunit positions filled by known subunits, and other subunit positions containing permutations of subunits. In the selection method, oligomers from each library set are identified, and a new permutation library formed of subunits corresponding to the highest binding affinity oligomers in each library is screened for binding affinity to the selected ligand.

Abstract: A method of assaying bone collagen breakdown levels in a human subject useful to screen for the presence of bone resorption disorders. Also disclosed is a method for monitoring the progression and/or treatment response of a cancer condition which involves or has the potential to progress to a metastatic condition which involves abnormalities in bone resorption rates.

Abstract: This invention is directed to an m.times.n array of different chemical compounds wherein each of said compounds has at least one structural diversity element selected from a group of amines and ketones and wherein the scaffold structure is selected from a group consisting of aminimide, imidazolone, sulfonylaminimide and phosphonylaminimide.

Abstract: An immunodiagnostic reagent consists of magnetic balls covered with a substance binding specifically to a substance to be detected in suspension in a suitable liquid. The magnetic balls consist of an organic matrix enclosing a magnetic charge and having a magnetizable material mass/non-magnetizable material mass ratio between 60 and 70%.

Abstract: An assay for the identification of neutralizing botulinum antibodies in sera is provided which includes the steps of separating non-sodium dodecyl sulfate, non-trypsinized complex botulinum toxin in an arylamide gel by electrophoresis, the separation occurring on a basis of botulinum toxin protein size and charge. Thereafter, the separated protein is electrophoretically transferred onto a solid support, the transferred separated protein being bound to the solid support at spaced apart sites. Remaining sites on the solid support not occupied by bound protein are blocked and the solid support and bound protein are contacted with a sera sample containing an antibody directed against botulinum toxin. The contacted solid support is then exposed to a second antibody capable of reacting to produce an insoluble colored substrate of intensity relative to a quantity of antibodies present. Finally, the second antibody is reacted to produce the insoluble colored substrate which is visually identified.

Abstract: The present invention concerns a method and an analytical device for the simultaneous detection of at least two organisms selected from the group consisting of Chlamydia trachomatis (CT), Neisseria gonorrhea (NG), and Mycoplasma (M) from a single specimen.

Abstract: An allergen immunoassay method features the use of a combination of a) closely controlled 1) elevated temperatures for assay reactions, 2) low temperatures for reagents and samples, 3) times for assay steps and especially assay reaction times, 4) reagent concentrations, and 5) reagent amounts; b) the use of a fast and accurate method of sample preparation that removes dust and contaminants; c) the stabilization of samples to avoid auto- and antibody degradation and unwanted effects of sample contaminants; and d) the formation of a colored product to determine the amount of a specific allergen. This combination provides an assay that can be completed in a few hours while retaining the precision, accuracy, sensitivity and response curve of previous methods requiring much longer periods of time.

Abstract: A surface of specific reactivity is formed by adsorbing a modified block polymeric surfactant of the Pluronic-type, i.e., containing pendant poly(ethylene oxide) blocks attached at an end to poly(propylene oxide) center blocks and with specifically reactive groups at the unattached ends of the poly(ethylene oxide) blocks, upon a hydrophobic surface.

Abstract: Disclosed are devices and methods for performing an assay which determines the presence or quantity of an analyte in a fluid sample by detecting binding of the analyte to at least one immobilized analyte capture reagent and washing unbound material from the immobilized analyte capture reagent. The devices and methods an elongated solid phase flow matrix, including capillary channels capable of driving capillary fluid movement, and further including (i) a first region adapted for receipt of the fluid sample, (ii) a second region at which the analyte capture reagent is immobilized, (iii) a third region for application of a wash reagent capable of removing unbound substances from the second region; and (iv) an absorbent reservoir of high volume capacity. The second region is positioned intermediate to the first region and the third region and intermediate to the absorbent reservoir and the third region. The device also includes means to detect analyte bound at the second region.

Abstract: Device for capturing a target molecule for the purpose of detecting it and/or assaying it, including a solid support on which is immobilized a ligand, the ligand being provided in the form of a conjugate resulting from the covalent coupling of a polymer with a plurality of molecules of the ligand. The polymer is an N-vinylpyrrolidone copolymer, and the conjugate is immobilized on the solid support by adsorption.When the ligand is capable of forming a complex with the target, the device is specific for a given target. When the device comprises, in addition, a bifunctional reagent capable of forming a complex, on the one hand, with the ligand and, on the other hand, with the target, the support on which the ligand is immobilized constitutes a universal capturing system.

Abstract: The present invention relates to a binary assay method capable of providing wide dynamic range and a high degree of precision in which analyte and labelled ligand are reacted with two independently determinable forms of solid-supported binding partners having affinity for the analyte and labelled ligand, respectively. The analyte concentration is determined from signals deriving from the resulting two forms by reference to a double standard calibration curve. A kit for use in the method is also disclosed.

Abstract: The invention relates to a method of detection, a sensor and a test-kit which find application in immunological detection (e.g., immunoassay). The invention provides, inter alia, a method of detection, suitable for use in immunological detection of an entity, which method includes the use of a secondary species (as defined in the specification), the use of a first detectable species, and the use of a second detectable species. The method may include, for example, the use of a primary species, a secondary species, a first detectable species and a second detectable species. The primary species may be, for example, an antibody or a ligand. The secondary species may be, for example, an auxiliary species such as an auxiliary binder or an auxiliary ligand, or a species which has a part which is an auxiliary function. The entity to be detected may be an analyte species as such or may be an entity which carries or includes analytes species.

Abstract: The present invention provides a general purpose specific binding assay method which has the advantages of highly accurate and quick measurements which exclude the effects of various factors that decrease reliability of the measured values, such as non-specific reactants in test samples, assay conditions and inactivation and the like changes in the activity of reagents. The present invention is further drawn to a specific binding assay device suitable for the practice thereof.

Abstract: Encoded combinatorial chemistry is provided, where sequential synthetic schemes are recorded using organic molecules, which define choice of reactant, and stage, as the same or different bit of information. Various products can be produced in the multi-stage synthesis, such as oligomers and synthetic non-repetitive organic molecules. Conveniently, nested families of compounds can be employed as identifiers, where number and/or position of a substituent define the choice. Alternatively, detectable functionalities may be employed, such as radioisotopes, fluorescers, halogens, and the like, where presence and ratios of two different groups can be used to define stage or choice. Particularly, pluralities of identifiers may be used to provide a binary or higher code, so as to define a plurality of choices with only a few detachable tags. The particles may be screened for a characteristic of interest, particularly binding affinity, where the products may be detached from the particle or retained on the particle.

Abstract: A reagent for the detection of an antibody against an acid-fast bacterial antigen comprising at least one compound selected from the group comprising mycolic acids, mycolic acid salts, mycolic acid esters and esters of fatty acids having a carbon number of 14 or more other than mycolic acid with a mono- or disaccharide, a method of detecting an antibody against an acid-fast bacterial antigen using said reagent and a method of diagnosis of acid-fast bacterial infections by said detection method are simpler in procedures and offer much higher specificity in comparison with conventional reagents and methods, enabling identification of acid-fast bacterial genera (including the genera Mycobacterium, Nocardia and Rhodococcus) and acid-fast bacterial species, and thus it is possible to make diagnoses to identify the infecting acid-fast bacterium, which leads to the quick choice of therapeutic drug for the disease.

Abstract: Antibodies that are indicative of organ transplant rejection, for example, cardiac or kidney transplant rejection, and of associated pathological conditions, for example, accelerated (or transplant-associated) coronary artery disease (CAD) are identified, as are antigens that bind to such antibodies. The antigens are used in immunoassays to diagnose transplant rejection and associated pathological conditions, and in the treatment of transplant rejection. The antigens and antibodies are particularly useful in the diagnosis and treatment of chronic rejection and associated conditions, especially rapid onset vasculopathy.

Abstract: A dry immunoassay analytical element, for assaying a ligand is disclosed. The element comprises, in the following order, (a) a layer containing a labeled ligand, (b) a bead spreading layer, c) a cross-linked hydrophilic polymer layer and d) a support; wherein(i) a fixed concentration of an immobilized receptor for the labeled ligand is located in a zone at the interface of layers (b) and (c); and(ii) the receptors are immobilized by being covalently bonded to polymeric beads that are smaller than the beads in layer (c).

Abstract: A test strip for a rapid immunoassay containing specific immunochemical reagent zones (7, 8, 9) is described. The test strip (10) has a backing sheet (1) and attached thereto a receiving end pad (3) and at a distance therefrom a finishing end pad (5). A test membrane (2) is provided between said pads (3, 5). Said membrane (2) is positioned in parallel relationship to said backing (1) at a distance therefrom so that said backing (1) and said membrane (2) limit between themselves an air gap (4) which is open at its edges. Said gap (4) functions as a sheltered reaction chamber for the immunolgical reaction taking place as a liquid is made to flow through said membrane (2). The test strip is simple to manufacture by lamination and easy to use and it is suitable for both diagnostic and environmental immunoassays.

Abstract: The present invention relates to an optical solid-phase biosensor for the detection of molecules which can be labelled with a fluorescent dye for the identification of substances in solution, for which there exists a biomolecule (receptor) which specifically recognises these and is chemically bonded to the uppermost layer of one or more layers of polyions on the surface of the sensor, by measurement of the Forster transfer between another dye molecule which is bonded in one of the uppermost layers of the sensor, and the said dye molecule.

Abstract: This invention relates to a lateral flow immunochromatographic assay device without a plastic housing. The assay includes a sample receiving region, analyte detection region and end region all made of porous material and capable of lateral flow. The analyte detection region includes labeling reagents, a capture reagent and a control reagent. The back of the porous material is laminated with a semi-rigid material with adequate mechanical strength. The top is partially covered with a thin plastic material so as to leave a portion of the sample receiving region exposed for sample application.

Abstract: Cancerous cells and HIV- and influenza virus-infected cells secrete .alpha.-N-acetylgalactosaminidase into blood stream, resulting in deglycosylation of Gc protein. This inactivates the MAF precursor activity of Gc protein, leading to immunosuppression. Thus, .alpha.-N-acetylgalactosaminidase activity in patient bloodstream can serve as diagnostic and prognostic index. Antibody-sandwich ELISA method and kits for cancer, HIV and influenza specific .alpha.-N-acetylgalactosaminidase as an antigen were developed to detect serum or plasma .alpha.-N-acetylgalactosaminidase in cancer and AIDS/HIV-infected and influenza patients and used as a diagnostic/prognostic index.

Abstract: The present invention relates to a method of assaying for Alzheimer's disease in a human by determining the relative abundance of one or more forms of amyloid precursor protein (APP) or the enzyme responsible for said forms in circulatory fluid and to a method for treating the disease by modulating divalent cation, trivalent cation and/or heparin interaction with APP.

Abstract: The invention is directed to methods to assess connective tissue, especially bone, metabolism in disease or to monitor therapy, which method comprises assessing the levels of native free collagen-derived crosslinks in biological fluids, especially urine. The method can be enhanced by concomitantly determining the levels of an indicator of bone formation in biological fluids of the same individual and assessing the differences between the degradation marker and the formation indicator. Antibodies which are specifically immunoreactive with forms of crosslinks which occur free in biological fluids are also disclosed.

Abstract: The invention is directed to methods to assess connective tissue, especially bone, metabolism in disease or to monitor therapy, which method comprises assessing the levels of native free collagen-derived crosslinks in biological fluids, especially urine. The method can be enhanced by concomitantly determining the levels of an indicator of bone formation in biological fluids of the same individual and assessing the differences between the degradation marker and the formation indicator. Antibodies which are specifically immunoreactive with forms of crosslinks which occur free in biological fluids are also disclosed.

Abstract: The invention concerns a method for the non-radioactive detection of metabolically labelled DNA, in one aspect detecting labelled DNA indicative of cell lysis or apoptosis.

Abstract: Disclosed is a method of predicting the onset of fetal membrane rupture in a gestative female comprising the step of assaying a tissue or fluid sample of fetal membrane origin obtained from the female for the presence of pro-metalloproteinase-9 (pro-mmd-9). The presence of pro-mmd-9 in the sample is a positive indication of the onset of fetal membrane rupture. Also disclosed is a method of delaying the onset of female membrane rupture in a gestative female comprising the step of administering to the female an MMP-9 inhibitor in an amount effective to delay fetal membrane rupture. Further disclosed is a method of inducing labor in a gestative female comprising the administration of an MMP-9 activator or MMP-9 itself in an amount effective to induce fetal membrane rupture, and thus facilitate the onset of labor.

Abstract: A rapid and accurate test kit is discussed for the detection of antibodies to HIV in saliva. The identification of antibodies to HIV in the saliva of seropositive individuals is shown using a test kit that requires no special machinery or skill and can be conducted by a single person in the privacy of their own home.

Abstract: A technique for generating nonrandom combinatorial libraries on solid phase supports in which each of a set of predetermined species of test compounds is present on a predetermined number of solid phase supports, preferably on only one, and each solid phase support has only a single species of test compound. Each of the predetermined species of test compounds is prepared with absolute certainty because the technique does not employ any random division of the solid phase supports. Rather, the method is based on the stepwise division of a continuous solid phase support matrix prior to each synthetic step in which more than one type of subunit is added. Non-limiting examples of matrices of the solid phase supports include polypropylene membranes, polytetrafluoropropylene membranes and cotton thread. The combinatorial libraries made by the technique are also disclosed.

Abstract: An immunochemical method is provided for the detection and determination of an analyte. The zeta potential of a latex-particle loaded with an immunologically active substance is measured before and after bringing the loaded latex-particle into contact with an analyte. The difference in zeta potential is correlated with changes of zeta potential for known concentrations of the analyte in order to determine the presence and amount of the analyte.

Abstract: The invention provides an apparatus for performing a process for amplification of specific nucleic acid sequences based upon the separation of nucleic acid strands by an electromagnetic field. This means of separation allows the use of mesophilic polymerases in the amplification process, thereby increasing the speed and fidelity of the amplification process, as well as the size of target nucleic acid that can be amplified.

Abstract: The invention is a rapid, continuous test for glycated hemoglobin using a non-equilibrium affinity binding method. Agarose beads derivatized with 3-aminophenylboronic acid specifically bind glycated hemoglobin. This solid phase is incorporated into a sample processor card, modified to mix and to separate the test solution from the solid phase prior to absorbance readings. Two absorbance readings are made on the test solution, one immediately after mixing the reagent/diluent with the specimen, and one after a significant amount of binding has occurred. A linear correlation between total glycated hemoglobin and hemoglobin A.sub.1c permits standardization and reporting of units equivalent to % hemoglobin A.sub.1c. Stable glycated hemoglobin solutions for use as standards in the assay, and a method for preparing the standards are also disclosed.