Abstract: The gene associated and causative of classical late infantile neuronal ceroid lipofuscinosis (LINCL), CLN2, has been identified and characterized. The translation product of this gene is a novel protease and a deficiency in this activity results in LINCL. Identification of CLN2 will not only aid in the prevention of LINCL through genetic counseling but provides strategies and test systems for therapeutic intervention. In addition, further characterization of this previously unknown lysosomal enzyme may provide useful insights into other more common human neurodegenerative disorders. Finally, the utility of a general approach for determining the molecular bases for lysosomal disorders of unknown etiology has been demonstrated.

Abstract: Assay systems and specialized antibodies for the detection and quantitation of troponin I and troponin T in body fluids as an indicator of myocardial infarction are disclosed. Troponin I and T exist in various conformations and the ratios of monomeric troponin I and T and the binary and ternary complexes, as well as which form of troponin present in the blood, may be related to the metabolic state of the heart. Disclosed are systems to determine the presence of a troponin form or a group of troponin forms in whole blood, serum or plasma samples. Disclosed is a method for improving the recovery of troponin I or T from a surface used in immunoassays. Also disclosed are antibodies which recognize unbound troponin forms, the forms of troponin in binary complexes, the ternary complex of troponin I, T and C, and the conformations of troponin I having intramolecularly oxidized and reduced cysteines.

Abstract: The present invention relates to a method for detecting von-Willebrand factor (vWF) activity comprising assaying a sample in the presence of a soluble form or portion of glycoprotein Ib(?) (GPIb(?) and ristocetin, or a functionally equivalent substance. Additionally, the invention relates to the use of the aforementioned soluble form or portion of glycoprotein Ib(?), of ristocetin or a functional equivalent substance, of specifically reacting anti-GPIB(?) antibody(ies) and/or of specific binding partners, like specifically reacting anti-vWF antibody(ies) for carrying out the method of the invention. Furthermore, the present invention relates to kits for carrying out the method of the invention.

Abstract: A method having clinically sufficient degree of diagnostic accuracy for detecting the presence of coronary artery disease in a human patient from the general population and for distinguishing between the stages of the disease in that patient is disclosed. The stages are, first, the non-acute stage, which is either asymptomatic coronary artery disease or stable angina, second, the acute stage known as unstable angina, and, third, the acute stage known as acute myocardial infarction. The diseased state (as opposed to the non-diseased state) is indicated by the clinically significant presence of a first marker in a sample from the patient. The presence of one of the two acute stages, unstable angina or acute myocardial infarction, is indicated by the clinically significant presence of a second marker in a sample from the patient. The presence of the more severe acute stage known as acute myocardial infarction is indicated by the clinically significant presence of a third marker in a sample from the patient.

Abstract: Assay systems and specialized antibodies for the detection and quantitation of troponin I and troponin T in body fluids as an indicator of myocardial infarction. Since troponin I and T exist in various conformations in the blood, the ratios of the monomeric troponin I an T and the binary and ternary complexes, as well as which form of troponin present in the blood, may be related to the metabolic state of the heart. Disclosed is a system to determine the presence of a troponin form or a group of troponin forms in a sample of whole blood, serum or plasma. Disclosed is a stabilized composition of troponin; the stabilized composition can comprise a stabilized composition of troponin I, wherein the troponin I is oxidized, the troponin I can be unbound or the troponin I can be in a complex.

Abstract: The present invention provides humanized, chimeric and human anti-CSAp antibodies and anti-CSAp antibody fusion proteins that are useful for the treatment and diagnosis of various cancers, including colon cancer.

Abstract: A method for preventing or inhibiting non-specific binding reactions between a detection reagent and an antigen in an immunological assay is described. The method involves using tetrameric antibody complexes that can bind to the antigen and are comprised of two monoclonal antibodies of a first animal species linked to two monoclonal antibodies of a second animal species that can bind the antibodies of the first animal species. Preferably, the antigen is an Fc Receptor and the method reduces the binding of a detection antibody with Fc receptors present on the surface of many cells.

Abstract: Heart and brain fatty acid binding proteins (H-FABP, B-FABP) are markers for TSEs, especially CJD. The invention provides a diagnostic assay for either of these markers, preferably by enzyme immunoassay using a specific antibody thereto. Since H-FABP is also a marker for acute myocardial infarction (AMI), to distinguish CJD from AMI requires an assay specific to AMI, e.g. using troponin-1 or CK-MB as a marker, also to be carried out.

Abstract: A method having clinically sufficient degree of diagnostic accuracy for detecting the presence of coronary artery disease in a human patient from the general population and for distinguishing between the stages of the disease in that patient is disclosed. The stages are, first, the non-acute stage, which is either asymptomatic coronary artery disease or stable angina, second, the acute stage known as unstable angina, and, third, the acute stage known as acute myocardial infarction. The diseased state (as opposed to the non-diseased state) is indicated by the clinically significant presence of a first marker in a sample from the patient. The presence of one of the two acute stages, unstable angina or acute myocardial infarction, is indicated by the clinically significant presence of a second marker in a sample from the patient. The presence of the more severe acute stage known as acute myocardial infarction is indicated by the clinically significant presence of a third marker in a sample from the patient.

Abstract: The present invention relates to methods for separating cells using immunorosettes. The method involves contacting a sample containing nucleated cells and red blood cells with an antibody composition which allows immunorosettes of the nucleated cells and the red blood cells to form. The antibody composition preferably contains bifunctional antibodies or tetrameric antibody complexes.

Abstract: A method for preventing or inhibiting non-specific binding reactions between a detection reagent and an antigen in an immunological assay is described. The method involves using tetrameric antibody complexes that can bind to the antigen and are comprised of two monoclonal antibodies of a first animal species linked to two monoclonal antibodies of a second animal species that can bind the antibodies of the first animal species. Preferably, the antigen is an Fc Receptor and the method reduces the binding of a detection antibody with Fc receptors present on the surface of many cells.

Abstract: Carriers hold remote-acting bodies which can be manipulated by a remote force, and also hold a micro-substance which is a target substance of an assay. The remote-acting bodies are manipulated in order to control the positions of the micro-substances, so as to execute assays for various target substances efficiently, at low cost, easily, and reliably. Various aspects of interest include the carriers which hold the micro-substances, a system suspending the carriers, an apparatus for manipulating the carriers, and a method of controlling the position of the carriers.

Abstract: Antibodies and methods are described for the detection and quantitation of cardiac specific troponin I in samples. Cardiac-specific troponin isoforms exist in various forms in the blood, including free and complexed forms. By selecting antibodies that are insensitive and/or sensitive to these various forms, the present invention can provide immunoassays that more accurately reflect the clinical state of an individual. These described antibodies and methods can be used for providing indicators of myocardial infarction and other cardiac pathologies.

Abstract: New intracorporeal radiodense medicaments and certain medical uses and methods for use of such high energy phototherapeutic medicaments for treatment of human or animal tissue are described, wherein a primary active component of such medicaments is a halogenated xanthene or halogenated xanthene derivative. The halogenated xanthenes constitute a family of potent radiosensitizers that become photoactivated upon irradiation of the treatment site with ionizing radiation.

Abstract: Assay systems and specialized antibodies for the detection and quantitation of troponin I and troponin T in body fluids as an indicator of myocardial infarction. Since troponin I and T exist in various conformations in the blood, the ratios of the monomeric troponin I an T and the binary and ternary complexes, as well as which form of troponin present in the blood, may be related to the metabolic state of the heart. Disclosed is a system to determine the presence of a troponin form or a group of troponin forms in a sample of whole blood, serum or plasma. Disclosed is a stabilized composition of troponin; the stabilized composition can comprise a stabilized composition of troponin I, wherein the troponin I is oxidized, the troponin I can be unbound or the troponin I can be in a complex. Disclosed is a method for improving the recovery of troponin I or T from a surface used in immunoassays.

Abstract: Multifunctional, polyionic copolymers with molecular architectures and properties optimized for specific applications are synthesized on/or applied to substrate surfaces for analytical and sensing purposes. The coatings are particularly useful for suppression of non-specific interaction, adsorption or attachment of molecular or ionic components present in an analyte solution. Chemical, biochemical or biological groups that are able to recognize, interact with and bind specifically to target molecules in the material containing the analyte to be detected can be coupled to, integrated into, or absorbed to the multifunctional copolymers. These multifunctional copolymer coatings are compatible with a variety of different established methods to detect, sense and quantify the target molecule in an analyte.

Abstract: The present invention relates to methods for separating cells using immunorosettes. The method involves contacting a sample containing nucleated cells and red blood cells with an antibody composition which allows immunorosettes of the nucleated cells and the red blood cells to form. The antibody composition preferably contains bifunctional antibodies or tetrameric antibody complexes.

Abstract: The present invention relates to a method for the selected chemical activation of photo-activatable cross-linker molecules around ligand binding pockets and fluorescent groups in macromolecules, especially biological macromolecules, by using fluorescent ligands of the macromolecule and by selecting photo-activatable cross-linker molecules having specific activation energies so that a radiationless energy transfer (Förster transfer) from the fluorescent ligands to the cross-linker molecules, which become activated thereby, takes place.

Abstract: The invention provides assay methods and kits that in general measure the level of a first analyte in a sample reduced by the level of a second analyte present in the same sample. In one embodiment, where levels of a first analyte from a first source is desirably determined and first analyte in the sample released from a second source is accompanied by proportional co-release of a second analyte, the assay identifies the level of first analyte released only from the first source. For analytes within bodily fluids, the assay can differentiate between elevated levels of analyte specific to the particular physiological or pathological state and elevated levels not specific to the particular state, providing single tests with diagnostic utility.

Abstract: Methods and compositions are described for the detection and quantitation of cardiac specific troponin I and troponin T in samples. Cardiac-specific troponin isoforms exist in various forms in the blood, including free and complexed forms. By selecting antibodies that are sensitive and/or insensitive to these various forms, the present invention can provide immunoassays that more accurately reflect the clinical state of an individual. These described methods and compositions can be used for providing indicators of myocardial infarction and other cardiac pathologies.

Abstract: The invention concerns a home kit and a method for detection of food allergies by determining the presence of antibodies against specific antigens in a stool sample.

Abstract: A method for detecting or assaying one constituting member in a specific binding pair, for example, the antigen in an antigen/antibody pair, by utilizing specific binding such as binding between an antigen and an antibody, together with redox reaction for detecting a label, wherein an oxygen micro-electrode with a sensing surface area of 1 mm2 or less is used; and an apparatus to which the method is applicable. According to the method and by using the apparatus, redox reaction for assaying the label can be completed in such a short time as several minutes. Therefore, an inexpensive disposable apparatus for household use can be realized.

Abstract: Methods of treating and imaging diseased tissue having the steps of administering a radiosensitizer agent proximate to or into the diseased tissue; and treating the diseased tissue with x-rays or other ionizing radiation so as to activate the radiosensitizer agent in the diseased tissue. Preferably, the radiosensitizer agent is a halogenated xanthene.

Abstract: The invention relates to methods of determining the presence or amount of an analyte in a sample suspected of containing the analyte, said method comprising the steps of: (a) bringing together in an aqueous medium to form a mixture: (i) the sample; (ii) at least one specific binder for the analyte; (iii) a first binding agent coupled to either (1) exogenous analyte or (2) the specific binder for the analyte; (iv) a support comprising a second binding agent; b) adding an activator to the mixture, wherein the activator binds the first binding agent and the second binding agent of the support to immobilize the first binding agent; c)determining the amount of the analyte in the sample by detecting the immobilized first binding agent, the presence or amount thereof being related to the presence or amount of the analyte in the sample.

Abstract: A compound comprises a target cell-specific portion, such as an antibody specific to tumor cell antigens, and an inactivating portion, such as an enzyme, capable of converting a substance which in its native state is able to inhibit the effect of a cytotoxic agent into a substance which has less effect against said cytotoxic agent. The prolonged action of a cytotoxic agent at tumor sites is therefore possible while protecting normal tissues from the effects of the cytotoxic agent.

Abstract: This invention relates to a fluorescence-based immunoassay method for the detection of an analyte, or for the measurement of its concentration in a biological sample. The method is based on the ability of a multivalent analyte to induce aggregation of receptor molecules labeled with a fluorophore, which molecules are anchored to and are freely mobile on a lipid membrane, and thereby cause changes in the fluorescence.

Abstract: Assay systems and specialized antibodies for the detection and quantitation of troponin I and troponin T in body fluids as an indicator of myocardial infarction. Since troponin I and T exist in various conformations in the blood, the ratios of the monomeric troponin I an T and the binary and ternary complexes, as well as which form of troponin present in the blood, may be related to the metabolic state of the heart. Disclosed is a system to determine the presence of a troponin form or a group of troponin forms in a sample of whole blood, serum or plasma. Disclosed is a stabilized composition of troponin; the stabilized composition can comprise a stabilized composition of troponin I, wherein the troponin I is oxidized, the troponin I can be unbound or the troponin I can be in a complex.

Abstract: The invention relates in part to methods and compositions for identifying the presence, measuring the amount, stabilizing, and facilitating recovery of troponin complexes or individual troponin isoforms in a sample.

Abstract: A trifunctional conjugate is provided having three chemical moieties attached through a spacer moeity. At least two of the chemical moieties are relatively small molecules, usually less than about 7,000 Daltons in size. The spacer moiety is selected to impart certain steric properties to the conjugate. In one embodiment, the binding of a macromolecular specific binding partner to one of the chemical moieties sterically inhibits the binding of a different macromolecule to another chemical moiety. In another embodiment, the binding of a first chemical moiety to a macromolecule restricts the subsequent binding of a second chemical moiety to a proximate location on the same macromolecule. The three chemical moieties are preferably a nitrophenylazido residue, a phenyl boronic acid residue, and a solid support or a label such as biotin. The spacer is preferably cysteine, lysine, glutamic acid, pyroglutamic acid, S-acetylmercaptosuccinic anhydride or .omega.-carbobenzoxylysine.

Abstract: Assays and antibodies are disclosed for the detection and quantitation of cardiac specific troponin I and troponin T in body fluids as an indicator of myocardial infarction. Since troponin I and T exist in various conformations in the blood, the ratios of the monomeric troponin I and T and the binary and ternary complexes may be related to the metabolic state of the heart. More specifically, immunoassays for determining the presence or amount of free, binary and ternary complexes of troponin I and T are claimed.

Abstract: Methods and test kits are described which provide a reliable, sensitive and selective assessment of periodontal disease activity, peri-implantitis or HIV(+)-infection/AIDS-disease related periodontal diseases. The preferred methods and test kits are constructed to be easy and rapid chair-side tests. The method is based on the preparation and use of monoclonal antibodies which recognize the active mammalian matrix metalloproteinase-S (MMP-8) and is capable of differentiating between said active matrix metalloproteinase-8 and its inactive proform.

Abstract: The present invention provides a method of classifying an unclassified live poliovirus vaccine as having an acceptable or unacceptable level of neurovirulence, comprising, prior to vaccine administration, the steps of: a) selectively amplifying a region of an unclassified poliovirus vaccine genome containing a nucleotide position predictive for increased neurovirulence using selectively mismatched primers, whereby a restriction endonuclease site in the selectively amplified region is created by introducing a site-specific mutation into the amplified region; b) digesting an amount of the amplified region with a restriction endonuclease that specifically cleaves the amplified sequences in revertant viruses which contain a reversion at the nucleotide position predictive for increased neurovirulence; c) digesting an amount of the amplified region with a restriction endonuclease that specifically cleaves the amplified sequences in nonrevertant viruses which contain the nucleotide position predictive for increased

Abstract: A trifunctional conjugate is providing having three chemical moieties attached through a spacer moiety. At least two of the chemical moieties are relatively small molecules, usually less than about 7,000 Daltons in size. The spacer moiety is selected to impart certain steric properties to the conjugate. In one embodiment, the binding of a macromolecular specific binding partner to one of the chemical moieties sterically inhibits the binding of a different macromolecule to another chemical moieties. In another embodiment, the binding of a first chemical moiety to a macromolecule restricts the subsequent binding of a second tridentate member to a proximate location on the same macromolecule. The three chemical moieties are preferably a nitrophenylazido residue, a phenyl boronic acid residue, and a solid support or a label such as biotin. The spacer is preferably cysteine, lysine, glutamic acid, pyroglutamic acid, S-acetylmercaptosuccinic anhydride or .omega.-carbobenzoxylysine.

Abstract: A compound comprises a target cell-specific portion, such as an antibody specific to tumour cell antigens, and an inactivating portion, such as an enzyme, capable of converting a substance which in its native state is able to inhibit the effect of a cytotoxic agent into a substance which has less effect against said cytotoxic agent. The prolonged action of a cytotoxic agent at tumour sites is therefore possible whilst protecting normal tissues from the effects of the cytotoxic agent.

Abstract: A method and test kit using a hydroxyaryl cyclic diacylhydrazide, a peroxide and a peroxidase enzyme on a blotting membrane for detecting DNA, RNA or proteins (polypeptides) is described. The method and kit provides enhanced chemiluminescence in an assay because of the use of the membrane. The method and test kit is particularly useful in Western, Southern and Northern blotting type assays and DNA sequencing.

Abstract: Human red blood cells with antigenic determinants recognized by unexpected alloantibodies are mixed with serum from the potential recipient. Following incubation, multivalent monoclonal IgM antibodies specific to the antigenic determinant present on the test red blood cells are added. If the recipient's serum is negative for an unexpected antibody which would bind to the antigens present on the test red blood cells, then the multivalent antibody will agglutinate the red cells. Conversely, if an unexpected antibody specific to those determinants is present in the recipient's serum, hemagglutination will be inhibited.

Abstract: This invention relates to antibodies and is particularly, though not exclusively, concerned with diagnostic and therapeutic methods using monoclonal bi- or tri-specific antibodies. The invention also provides a method in which binding of a first antigen to a first antibody binding site causes release of a second antigen from an adjacent second antibody antigen binding site.

Abstract: An assay method, compositions and test kits using a hydroxyaryl cyclic diacylhydrazide is described. A hydrogen peroxide and peroxidase enzyme. The preferred compositions incorporate enhancer compounds and a chelating agent which suppresses light production prior to addition of a peroxidase enzyme. The assay method can test for a peroxidase enzyme, a peroxide or can be used in immunoassays and probe assays.

Abstract: A homogenous sample of identical bispecific antibody determinants, each determinant being composed of two L-H half-molecules linked by disulfide bonds, each L-H half-molecule being specific for a different antigenic determinant and including at least the F(ab') portion of a monoclonal IgG antibody. The bispecific antibody determinants are useful, e.g., in the formation of multilamellar assemblies and in enzymatic assays.

Abstract: A pyridinoline composition in which pyridinoline is derivatized specifically at its aliphatic hydroxyl group by a selected chemical group is disclosed. In various embodiments, the composition may be used as a standard for HPLC or immunoassay of pyridinoline, a pyridinoline immunogen for producing anti-pyridinoline antibodies, and a solid-phase reagent for use in an immunoassay kit. Also disclosed are methods for making and using the composition.

Abstract: Methods for functionalizing sensing surfaces to be used in systems for measuring simultaneously several properties of one biomolecule as well as for simultaneously measuring the concentrations of a plurality of biomolecules in a sample. The invention furthermore also relates to sensor units containing such surfaces, to the use thereof for surface characterization of biomolecules, and to a reagent kit for functionalization of sensing surfaces.

Abstract: In an erythrocyte agglutination assay, the agglutination reagent comprises at least one erythrocyte binding molecule coupled to at least one specific analyte binding molecule wherein the erythrocyte binding molecule does not cause agglutination when incubated with erythrocytes in the absence of analyte (in the case of a direct assay) or analyte binding reagent (in the case of an indirect assay). Preferably, the erythrocytes are endogenous to the blood sample to be tested, that is, a whole blood sample is assayed. Mixtures of conjugates and conjugates of analyte analogues with erythrocyte binding molecules may also be used as agglutination reagents. The reagents and their use in direct or indirect assays is disclosed.

Abstract: A process for preparing CMP-activated fluorescence indicator-labelled sialic acids is disclosed. According to the process, a 5-acylamido-9-amino-3,5,9-tridesoxy-.beta.-D-glycero-D-galactonoulosonic acid or 5-aminoacylamido-3,5-didesoxy-.beta.-D-glycero-D-galactonoulosonic acid is reacted with cytidine phosphate in the presence of a CMP-sialic acid synthase which is then reacted with a fluorescing compound to give a CMP-activated fluorescing sialic acid. Also disclosed are novel CMP-activated fluorescing sialic acids.

Abstract: In a process for the quantitative determination of the function and antigenic concentration of a substance contained in a biological liquid, the substance is immobilized, the function is determined by the addition of a specific substrate which is then removed by washing, and in a subsequent step the immunological concentration of the bound substance is determined using an appropriate specific detector system with or without the use of an antibody.

Abstract: A homogenous sample of identical bispecific antibody determinants, each determinant being composed of two L-H half-molecules linked by disulfide bonds, each L-H half-molecule being specific for a different antigenic determinant and including at least the F(ab') portion of a monoclonal IgG antibody. The bispecific antibody determinants are useful, e.g., in the formation of multilamellar assemblies and in enzymatic assays.

Abstract: The present invention has multiple aspects. In its first aspect the present invention is directed to a trifunctional antibody-like compound that has tissue, organ, cell or molecule specificity and which is capable of being bifunctional when immobilized, via binding, at the tissue, organ, cell or molecule for which it has specificity. In particular, the present invention is directed to a trifunctional antibody-like compound of Formula I:F.sub.1 ab'--L--F.sub.2 ab'--L--F.sub.3 ab' (1)wherein L is the same or two different moieties for cross-linking F.sub.1 ab', F.sub.2 ab' and F.sub.3 ab';wherein F.sub.1 ab' is an Fab'-like fragment of a polyclonal or monoclonal antibody having specificity for an antigen expressed by the organ, tissue, cell or molecule of interest;wherein F.sub.2 ab' is an Fab'-like fragment of a polyclonal or monoclonal antibody having the same specificity as F.sub.

Abstract: A simultaneous dual analyte assay for determining the fertile period of the human menstrual cycle. The assay utilizes a capture reaction component consisting of P-3-G immobilized on a microporous membrane, a blocking reaction component consisting of anti E.sub.1 -3-G antibody, a labelled reaction component consisting of gold particle labelled anti E.sub.1 -3-G antibody, and an ambifunctional reaction component consisting of a hybrid immunoreactive substance having an anti P-3-G antibody binding site and a plurality of E.sub.1 -3-G determinant binding sites. An aqueous sample containing P-3-G and E.sub.1 -3-G is contacted with the components and the assay is calibrated to provide a positive assay result only when the concentration of P-3-G in the sample is less than a predetermined concentration and the concentration of E.sub.

Abstract: An antigen antibody conjugate is provided including at least one antigen and at least one monoclonal antibody having a specificity for at least one major histocompatibility complex (MHC) class I or class II antigens and at least one monoclonal antibody having a specificity for at least one antigen other than a MHC class I or class II antigen. Each antibody is conjugated to at least one antigen.

Abstract: A novel bidentate conjugate has two different chemical moieties, or bidentate members, attached through an adequate spacer moiety. Each bidentate member acts as a small molecule ligand and is capable of specifically binding to a different macromolecular substance. The bidentate members are relatively small molecules, usually less than about 7,000 Daltons in size. The spacer moiety is selected so that both bidentate members can simultaneously bind to their respective specific binding partners. Where the specific binding partners are multivalent, large complexes can be formed. The formation of these complexes can be inhibited by the presence of an unconjugated monovalent bidentate member, such as free analyte from a test sample. The bidentate is of particular use in turbidimetric or nephelometric inhibition immunoassay procedures.

Abstract: A method for carrying out competitive displacement immunoassays which entails the use of an oligovalent labelled antibody having at least 4 binding sites for the analyte to be determined per label.