Abstract: A method for assaying bone resorption rates which consists of quantitating the concentration of peptide fragments derived from bone collagen, found in a body fluid is disclosed. The method includes immunometric assay, fluorometric assay and electrochemical titration. The structure of specific peptide fragments having 3-hydroxypyridinium cross-links found in urine of Paget's disease patients and procedures for making monoclonal antibodies is described.

Abstract: Method and test kit for assaying in a sample an analyte which is a bloodgroup antigen present on erythrocytes or an antibody binding to such a bloodgroup antigen. To that end, the sample is treated with a reagent containing a binding partner for the analyte, so that a complex of bloodgroup antigen present on erythrocytes and antibody bound thereto is formed if the sample contains analyte. The analyte is a bloodgroup antigen present on erythrocytes, the analyte binding partner is an antibody capable of binding to the bloodgroup antigen and if the analyte is an antibody binding to a bloodgroup antigen, the analyte binding partner is the bloodgroup antigen present on erythrocytes. Erythrocytes, complex or non-complexed, are then separated from non-bound antibodies using a separation medium with a density higher than that of the liquid containing the antibodies but lower than the density of crythrocytes.

Abstract: The present invention relates to the finding that antibodies bind to the &bgr;-amyloid peptide, and that &bgr;-amyloid peptide binds the hinge region of the immunoglobulin heavy chain, thereby preserving the ability of the immunoglobulin to bind antigen. Methods for binding compounds such as detectable groups to &bgr;-amyloid peptide are accordingly presented.

Abstract: The invention describes quality control devices for assays that measure analytes in cells and tissue samples, and methods of use thereof. In particular, the quality control device comprises a matrix affixed with synthetic controls in different concentrations, or different synthetic controls. The quality control device can be adhered to a microscope slide and processed simultaneously with a tissue sample.

Abstract: Disclosed is a colorimetric sensor comprising polydiacetylene membrane liposomes, a polydiacetylene membrane film or fine particles coated with a polydiacetylene membrane, in which the polydiacetylene membrane is incorporated with a protein having a reduced molecular weight low enough not to cause color change in the polydiacetylene membrane. The examples of the reduced-molecular-weight proteins include an antibody Fab′ fragment, an antigenic protein of molecular weight of 100,000 or less, and a peptide consisting of 3-20 amino acid residue, which undergo an antigen-antibody reaction with an antigen or antibody contained in a sample. As the reduced-molecular-weight protein is also employed a combination of single-stranded DNA of 100 bases or less which hybridizes with single-stranded DNA contained in a sample to form a double-stranded DNA, and an antibody which reacts with said double-stranded DNA but does not react with the single-stranded DNA contained in the sample.

Abstract: Small specific binding molecules, such as single variable domain antibodies (Dabs) and Fv fragments, can be coupled to solid plastics surfaces or to tracers such as enzymes by means of linkers comprising polypeptides containing from 5 to 20 amino acids and which are hydrophobic and/or contain at least one lysine residue. The coupling can be achieved without significant loss of specific binding activity. The combined Dab/linker or Fv/linker can be prepared by expression in genetically-modified organisms.

Abstract: Method for the determination of thyroid autoantibodies Method for the determination of thyroid autoantibodies in a biological sample obtained from a patient in the differential diagnosis of diseases which are associated with changes of the thyroid and/or disturbances of the normal thyroid function, the determination of the presence and/or amount of the thyroid autoantibodies in the sample being effected with the use of an inmunodiagnostic assay method in which a test signal which represents overall the presence and amount of at least two antibodies, including anti-TPO autoantibodies and anti-Tg autoantibodies, in the sample is obtained per determination. The method increases the selectivity and sensitivity of the detection of the autoantibodies typical of specific autoimmune diseases while reducing the effort required.

Abstract: A hybridoma cell line has been produced for secreting a monoclonal antibody that binds ractopamine and is effective to detect ractopamine levels of about 1 ng/mL or lower. This monoclonal antibody may be used for the detection and quantitative determination of trace amounts of ractopamine in samples, especially in animal tissue, body fluids and feed material.

Abstract: The invention relates to the development of a method for assaying an antigen which is associated with disorders caused by mental stress in a human body fluid by way of an immunoassay technique which utilizes an antibody against a mental stress related protein having the following properties or a fragment thereof: (1) having a molecular weight of about 14 kDa (measured by SDS-PAGE); and (2) having the N-terminal partial sequence represented by SEQ ID NO: 1; and a kit for diagnosing disorders caused by mental stress which contains the above-mentioned antibody or a fragment thereof. Thus, the accumulation of mental stress can be easily estimated and judged and the results can be applied to the diagnosis of disorders caused by mental stress.

Abstract: This invention provides methods of selecting antibodies that are internalized into target cells. The methods generally involve contacting target cells with one or more members of an antibody phage display library. The members of the phage display library are also contacted with cells of a subtractive cell line. The target cells are then washed to remove the subtractive cell line cells and members of the phage display library that are non-specifically bound or weakly bound to the target cells. The target cells are cultured under conditions where members of the phage display library can be internalized if bound to an internalizing marker and internalized members of the phage display library are then identified.

Abstract: A new class of cellular receptors extensively homologous but not identical to coagulation factors V and VIII is identified. These new cell surface receptors are designated effector cell protease receptors (EPRs) and include EPR-1, which is shown to bind protease ligands. The DNA and amino acid residue sequences of the receptor are also described. The invention also discloses methods, sequences and vectors useful in the purification and synthesis of cellular receptors of the present invention. Antibody compositions capable of immunoreacting with the receptor or with polypeptides containing the identified amino acid residue sequences and related therapeutic and diagnostic protocols are also described, as are polypeptides, compositions and methods relating to the inhibition of T lymphocyte proliferation using the antibodies disclosed herein. The receptors are also demonstrated to bind coagulation factor Xa, which binding is inhibited by various disclosed monoclonal antibodies to the receptors.

Abstract: The claimed invention is a method for determining whether a mammal is infected with Haemobartonella felis or for inducing an immune response against Haemobartonella felis using a polypeptide expressed by Mycoplasma. Preferably, the polypeptide is expressed by Mycoplasma gallisepticum. In a preferred embodiment the polypeptide is the pMGA protein expressed by the strain of Mycoplasma gallisepticum having ATCC deposit number 19610.

Abstract: Interstitial cystitis (IC) is a chronic bladder disease for which the exact etiology is unknown and for which there is no reliably effective treatment. However, it is known that the bladder epithelium is often abnormal in IC. We discovered that normal, adult, human bladder epithelial cells are inhibited from proliferating by an anti-proliferative fact (APF) present in IC urine specimens. Inhibited proliferation may cause epthelial abnormalities characteristic of IC such as ulcerations and multiple tears in the bladder epithelium. We further discovered that levels of heparin binding--epidermal growth factor-like growth fact (HB-EGF), a factor known be important for epithelial cell proliferation and wound healing in other tissues, are abnormally low in the urine of patients suffering from IC as compared to asymptomatic controls or patients with acute bacterial cystitis. The invention herein is directed to the use of urine levels of HB-EGF as a diagnostic marker for IC.

Abstract: A method for stabilizing analyses with antibodies and antibody fragments comprises dissolving the analyte in a liquid to form a solution, adding analyte-specific antibodies, fragments of such antibodies, or both to the solution, heating the solution, and then cooling and filtering the solution. The filtered solution may be diluted in a suitable matrix.

Abstract: A method of determining affinity and kinetic properties for the solution interaction between an analyte and a binding partner therefor, which method comprises: (a) mixing a solution of said analyte with a solution of said binding partner, contacting the resulting reaction solution with (i) immobilised binding partner, or analogue, for said analyte, and/or (ii) immobilised analyte, or analogue, and monitoring the binding of said analyte and/or binding partner in said reaction solution to the respective immobilised species to determine the variation with time of the concentration of free analyte and/or binding partner in said solution; and/or (b) contacting a solution of the reaction complex of said analyte and a binding partner therefor with (i) immobilised binding partner, or analogue, and/or (ii) immobilised analyte, or analogue, and monitoring the binding of said analyte and/or binding partner in said reaction complex solution to the respective immobilised species to determine the variation with time of the

Abstract: Disclosed is a high throughput compatible assay that is useful for the identification of specific antagonists of TRAF-receptor interactions. The modular flexibility of the assay makes it possible to introduce simple modifications in order to measure the interaction of any TNF receptor cytoplasmic domain (or TRAF-binding protein) with any of the six TRAF proteins, TRAF1, TRAF2, TRAF3, TRAF4, TRAF5 and TRAF6.

Abstract: Novel magnetic assay methods and systems, as well as systems for conducting spectrophotometric analysis therewith. According to a preferred embodiment, the magnetic assay methods and systems incorporate a chromatographic medium, such as an assay test strip, that is designed to be contacted with a test solution having activated magnetic particles. A magnetic field, generated by a magnet or electromagnet, is additionally provided that if selectively applied to a chromatographic medium which causes the charged particles to become substantially bound at a site all in the chromatographic medium specified by the position of the magnets, to thus form a captured line or zone. To the degree of magnetic force applied to the medium may be selectively adjusted to vary the width or surface area of the capture line or zone. Additionally, in a preferred embodiment, capture lines may be formed while test strips are in motion along a stationary magnetized rail.

Abstract: Disclosed are conjugates including a polymer backbone or microbead and binding molecules, such as Fv, Fab, or F(ab').sub.2 fragments of monoclonal antibodies or whole antibodies that are bound through their Fc carbohydrate moieties or have their Fc portion modified so that they cannot effect ADCC or complement-mediated cytolysis, and that are specific for a T cell surface antigen, such as CD3, TCR, CD4, CD8, or CD28 on T cells. The polymer or microbead is preferably made of cross-linked dextran, ficoll, latex, or agarose. The microbeads are preferably of 1 to 10 .mu.m in size, so that they can be suspended in in vivo fluids. These conjugates can be used to induce proliferation of T cells and immune stimulation, and to increase the antibody response against an administered antigen.

Abstract: Cell surface antigens from mammals, reagents related thereto, including purified proteins, specific antibodies, and nucleic acids encoding said antigens. Methods of using said reagents and diagnostic kits are also provided.

Abstract: A method and device are provided for the semi-quantitative and quantitative determination of an analyte in a sample. A non-competitive trap which can bind unreacted labelled receptor to analyte but has virtually no binding capabilities to receptor in the presence of analyte is used. Labelled receptor:analyte complex is trapped in a second trap. The relative amounts of unbound receptor in the non-competitive trap versus the amount of receptor:analyte complex in the second trap is a measure of the amount of analyte in the sample.

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: Methods, compositions and articles of manufacture are provided for conducting specific binding assays to determine the concentration or presence of at least one analyte in a sample. At least two dendrimer-reagent preparations with different analyte specificities may be immobilized on a solid phase. Alternatively, at least one dendrimer-reagent preparation having multiple specificities may be immobilized on a solid phase. Immobilization is facilitated by coupling specific binding assay reagents such as polypeptide receptors or analytes with water soluble polymers. Such water soluble polymers, for example star polymers such as dendrimers, provide production advantages of lot-to-lot uniformity and homogeneity, and can enhance sensitivity due to low non-specific binding to the solid phase.

Abstract: Methods for using modulating agents to enhance or inhibit occludin-mediated cell adhesion in a variety of in vivo and in vitro contexts are provided. Within certain embodiments, the modulating agents may be used to increase vasopermeability. The modulating agents comprise at least one occludin cell adhesion recognition sequence or an antibody or fragment thereof that specifically binds the occludin cell adhesion recognition sequence. Modulating agents may additionally comprise one or more cell adhesion recognition sequences recognized by other adhesion molecules. Such modulating agents may, but need not, be linked to a targeting agent, drug and/or support material.

Abstract: The invention provides a method of assessment of carbohydrate-deficient transferrin in a transferrin containing body fluid, said method comprising the steps of:i) obtaining a transferrin containing liquid sample of or derived from a said fluid;ii) contacting said sample with a source of iron ions;iii) subsequently contacting said sample with an anionic ion exchange resin at a pH such as to cause carbohydrate-deficient transferrin to be retained by said resin;iv) subsequently contacting said resin with an eluant serving to release carbohydrate-deficient transferrin into the eluate from said resin;v) collecting a volume of said eluate substantially free from tetra- and penta-sialo transferrin; andvi) assessing the transferrin variant content in said volume of eluate.By including at least a proportion of the trisialotransferrin in the eluate, it is possible to use relatively simple assessment techniques such as turbidimetry in the assay.

Abstract: An assay device for detection or determination of an analyte in a sample uses opposable components and is suitable for assay of human chorionic gonadotropin and other protein or glycoprotein hormones.

Abstract: A method of detecting an antibody in a sample using a labelling compound and comprising the steps of mixing a ligand antigen, antibody or hapten bound to biotin with the sample; an antibody directed against the antibody to be detected bound to paramagnetic particles; and a chemiluminescent acridinium compound bound to avidin or streptavidin to form a solid phase complex; separating the solid phase from the liquid phase; and analyzing the separated solid phase for the presence of chemiluminescent complex.

Abstract: The invention discloses the use of a new cell growth related peptide. More precisely, the invention serves as a marker for cell proliferation. The marker is a peptide which is an exposed part of a cellular enzyme. This peptide is as well particularly useful as an aid in production of highly selective reactive molecules. The peptide is a part of thymidine kinase TK1 and has the sequence of SEQ ID NO: 1 or SEQ ID NO: 2.

Abstract: Capsular polysaccharides containing multiple sialic acid residues, particularly the Group B polysaccharide of Neisseria meningitidis, are modified by chemical reaction to randomly introduce pendant reactive residues of heterobifunctional linker molecules to the polysaccharide backbone. The capsular polysaccharide is deacetylated and the heterobifunctional linker molecule is reacted with the deacetylated material and any residual amino groups are blocked by reaction with alkyl acid anhydride. The introduction of the linker molecules to the polysaccharide chain between the termini enables the polysaccharide to be linked to a carrier molecule, such as a protein, to enhance the immunogenicity of the polysaccharide. The conjugate molecule may be formulated as an immunogenic composition for raising antibodies in a host to the polysaccharide.

Abstract: The present invention is directed to peptides from the sequence of hPTH(1-37), which contain .alpha.-helical amino acid sequence regions and/or non-structured amino acid sequence regions, said peptides being capable of inducing antibodies when injected into animals. Furthermore, the invention is directed to a diagnostic agent and antibodies obtainable by immunizing animals using the peptides according to the invention.

Abstract: The invention relates to fluorescent dyes that are substituted or unsubstituted derivatives of 1-(isoindolyl)methylene-isoindole that are bound through both isoindole nitrogens to a boron difluoride moiety, forming a fluorescent dibenzopyrrometheneboron difluoride compound ##STR1## that is further substituted by bathochromic substituents that are aryl or heteroaryl moieties further substituted by an additional aryl or heteroaryl, that is itself optionally further substituted by an additional aryl or heteroaryl. These aryl and heteroaryl groups are separated by a covalent bond, or by an ethenyl, butadienyl or hexatrienyl linkage. The dyes of the invention are particularly useful as labels for carriers, particularly polymeric microparticles. The resulting microparticles have a long-wavelength fluorescence emission, and possess utility for tracing flow in biological systems, particularly in tracing blood flow.

Abstract: A method for a single-measurement quantification of multiple populations of white blood cells (WBC) is based upon the labeling of different pairs of cell populations, each pair containing mutually exclusive cell receptors which are expressed at substantially similar receptor densities with labeled ligands for each receptor. One cell population is labeled with a ligand capable of binding to a first cell surface receptor which ligand is directly conjugated to a fluorescent phycobiliprotein or tandem dye; and a second cell population is labeled with a ligand capable of binding to a second cell surface receptor, which ligand is cross-linked by an aminodextran to a fluorescent phycobiliprotein or tandem dye. The phycobiliproteins upon laser excitation produce a different detectable fluorescence intensity for each cell population. Use of such pairs of conjugates enable two populations of cells with similar receptor densities to be distinguished with the use of a single color marker.

Abstract: An antibody specific for a target analyte is purified by affinity chromatography on a substrate bearing a low-affinity analogue of the target analyte. The antibody is displaced from the substrate by contact with a second analogue of intermediate affinity, which remains complexed with the antibody. This complex can be used in a conventional assay for the target analyte, which displaces the intermediate-affinity analogue. The complexed antibody is rendered more storage-stable because the second analogue protects the antibody binding reagion.

Abstract: The invention provides a method of diagnosing Alzheimer's disease. The method utilizes presenilin-1, whose level is found to be substantially decreased in Alzheimer's patients. Included in the invention are diagnostic kits for Alzheimer's disease and methods of screening for effective therapeutics for the disease. The invention also provides a method of studying the function and regulation of presenilin-1 in brain by the use of primate retinoblastoma cells.

Abstract: A biologically recognizing layer on a solid phase consisting of biologically recognizing molecules comprising regions which recognize a substance to be analyzed and regions which do not recognize a substance to be analyzed.The biologically recognizing molecules are aligned on a suitably modified surface by means of molecular regions which do not recognize the substance to be analyzed. The biologically recognizing molecules are cross-linked with the aligning surface and are consequently covalently altered. The molecular regions recognizing the substance to be analyzed are not altered by the covalent bonding and retain their bonding activity.The layer is produced in a novel two-stage method. In the first step, the biologically recognizing molecules, the aligning molecules and carrier molecules are adsorbed. In the second step, the molecules are covalently anchored by cross-linking. Cross-linking is brought about by photolytic activation of a water soluble reagent bonded to the carrier molecules.

Abstract: Novel methods of detecting and treating breast cancer are described.

Abstract: Monoclonal antibodies which specifically bind to human interleukin-5 (IL-5) are described. The antibodies can be used in assays for IL-5, to purify IL-5, or to characterize IL-5.

Abstract: Disclosed is a method for detecting neoplastic cells in a tissue sample by examining the cells for centrosomal abnormalities such as ectopic localization of centrosomal proteins, hypertrophic centrosomes, and supernumerary centrosomes.

Abstract: This invention relates to antibodies or fragments thereof that can be used as indicators of apoptosis. More specifically, this invention relates to antibodies and fragments thereof that selectively bind GP46, a protein whose levels increase significantly upon induction of apoptosis. This invention also relates to the hybridomas that produce anti-GP46 monoclonal antibodies. This invention also discloses a method of detecting cell death by apoptosis in vitro or in vivo by detecting and quantifying GP46 present in biological samples, comprising contacting the sample with the antibodies or fragments to form GP46 immunocomplexes, which may then be detected by the use of known methods. This detection method is useful for research into apoptosis and research relating to diseases in which apoptosis is involved. This method could also be used to diagnose the extent of damage caused by a particular disease or to evaluate the efficacy of drug treatments.

Abstract: The invention concerns a composition composed of several different antibodies or/and antibody fragments which is suitable as a reagent to reduce interferences in an immunological method for the class-specific detection of antibodies from one or several of the immunoglobulin classes G, M, A, D and E.

Abstract: A method of diagnosing insulin resistance and related disorders is provided. Additionally, methods of treating animals with insulin resistance and related disorders if provided. The methods employ antagonists to an insulin receptor tyrosine kinase inhibitor protein.

Abstract: Methods and apparatus for evanescent light fluoroimmunoassays are disclosed. The apparatus employs a planar waveguide with an integral semi-cylindrical lens, and has multi-analyte features and calibration features, along with improved evanescent field intensity. A preferred embodiment of the biosensor and assay method have patches of capture molecules each specific for a different analyte disposed adjacent within a single reservoir. The capture molecules are immobilized to the patches on the waveguide surface by site-specific coupling of thiol groups on the capture molecules to photo-affinity crosslinkers which in turn are coupled to the waveguide surface or to a non-specific-binding-resistant coating on the surface. The patches of different antibodies are produced by selectively irradiating a portion of the waveguide surface during the process of coupling the photo-affinity crosslinkers the selective irradiation involving a mask, a laser light source, or the like.

Abstract: The invention relates to monoclonal antibodies (mAB) which bind to water-soluble complexones such as ethylenediamine tetraacetate (EDTA) or diethylenetriamine pentaacetate (DTPA) with high specificity and avidity and retain their high avidity and specificity for these complexones after complexing of EDTA or DTPA with metal ions. These mAB can therefore be used, e.g. coupled on filters or other supports, for removing toxic heavy metals which are complexed with EDTA or DTPA. Furthermore, these mAB are suitable as components of immunoassays (RIA, ELISA etc.) for the quantitative determination of EDTA or DTPA in aqueous solutions.

Abstract: Methods are provided for conducting specific binding assays to determine the concentration or presence of at least one analyte in a sample. Dendrimer-reagent preparations with particular analyte specificities are mixed in solution with a sample to form dendrimer-reagent-sample complexes. The complexes are then immobilized on a solid phase. Immobilization is facilitated by coupling specific binding assay reagents such as polypeptide receptors or analytes with water soluble polymers. Such water soluble polymers, for example star polymers such as dendrimers, provide production advantages of lot-to-lot uniformity and homogeneity, and can enhance sensitivity due to low non-specific binding to the solid phase.

Abstract: An analytical method for detecting the presence poly-beta-hydroxybutyrate (PHB), which can be used as an indicator of atherosclerotic risk is disclosed. In the method, antibodies to PHB are used to detect the PHB.

Abstract: The present invention relates to antibodies against an alpha interferon receptor, as well as to kits comprising such antibodies. The antibodies of the invention are suitable for the assay of the receptors or for their visualization in the case of imaging. The present antibodies and kits can thus be used as diagnostics or imaging agents, or as pharmacological models to test compounds derived from human alpha interferon.

Abstract: This invention describes methods for generating antibodies specific for activation antigen CMRF-44 on activated dendritic cells, and antibodies produced by the method. The use of such antibodies, including monoclonal antibody CMRF-44, in immunological-based processes and systems for purifying and/or identifying activated dendritic cells is also described.

Abstract: Gliotoxic factor in the isolated or purified state, characterized in that it possesses toxic activity with respect to human or animal astrocytic cells, having the effect of a cytomorphological disorganization of their network of intermediate filaments and/or a degradation of the proteins of said intermediate filaments and/or cell death, in particular by apoptosis.

Abstract: The present invention provides a membrane the conductivity of which is dependent on the presence or absence of an analyte. The membrane comprises a closely packed array of self-assembling amphiphilic molecules and two ionophore components. A receptor molecule reactive with the analyte is provided on one of the ionophore components. The binding of the analyte to the receptor molecule causes a change in the relationship between the ionophore components such that the flow of ion across the membrane is prevented or allowed. The ionophore components are preferably selected from the group consisting of amphotericin B, gramicidin A monomers and combinations thereof, with gramicidin A monomers being particularly preferred. The present invention also provides a membrane including receptors directed against the Fc region of antibodies. These receptors are preferably derived from polyclonal antibodies.

Abstract: An aggregate for qualitatively or quantitatively determining bindable substances. Said aggregate comprises an ultra small colloidal particle and a specific binding agent characterized in that the mean diameter of the colloidal particle is below 2 nm. Preferably the size of the metal particle is selected so that the aggregate is capable of penetrating in standard biological specimens. The invention further provides a universally applicable detection system for determining bindable substances in particular in living material. Further there is provided a process for preparing said aggregate.

Abstract: Methods and compositions are provided for specific binding assays in which specific binding reagents are immobilized on a solid phase. Immobilization is facilitated by covalently coupling specific binding assay reagents such as polypeptide receptors or analytes with water soluble polymers. Such water soluble polymers, for example star polymers such as dendrimers, provide production advantages of lot-to-lot uniformity and homogeneity, and can enhance sensitivity due to low non-specific binding to the solid phase.