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: The present invention provides internally calibrated competitive assays for use on a solid support. Additionally, the invention provides a method of using such assays.

Abstract: This invention relates to a method of detecting and diagnosing neurological disease or dysfunction using antibodies against a neurological form of Pancreatic Thread Protein (nPTP). Specifically, this invention is directed to a method of diagnosing Alzheimer's Disease, Down's Syndrome, and other neurological diseases or dysfunctions by using monoclonal antibodies, combination of those monoclonal antibodies or nucleic acid probes, to detect nPTP. The invention also relates to a recombinant DNA molecule encoding PTP and to the substantially pure form of nPTP. The invention additionally relates to a method of diagnosing pancreatic disease using antibodies against Pancreatic Thread Protein.

Abstract: Methods for the biochemical and immunohistochemical detection of cell apoptosis are described. The methods utilize the detection and measurement of polypeptide fragments generated during apoptosis. Conditions associated with apoptosis may be detected by the methods of this invention. Methods are also presented for the screening of potential therapeutic compounds which inhibit or stimulate apoptosis. Kits for detection of apoptosis and diagnosis of diseases are also provided.

Abstract: A non-competitive method for the determination of analytes. Initially the analyte is bound to a specific binding partner, after which the unoccupied binding sites of the binding partner are inactivated. The bound analyte is then dissociated from the binding partner and replaced by a labeled marker, after which the bound labeled marker is determined. The signal from the bound labeled marker is directly proportional to the initial amount of analyte in the sample, which makes the present method more favorable than the competitive assays.

Abstract: The invention deals with isolated human tau peptide epitopes of SEQ ID Nos: 1 to 4, 7 and 15 to 20 which have the capability of binding AT120 monoclonal antibody.

Abstract: The present invention provides hapten derivatives that are useful for the preparation of antigenic, antibody and label reagents having superior performance characteristics for use in immunoassays for the detection of d-propoxyphene and d-nor-propoxyphene. In the present invention the propoxyphene nucleus is derivatized out of the nitrogen center to form an aminoalkyl -carboxyl, or -hydroxyl haptenic derivative. The resulting hapten can then be further modified at the now functionalized position off the nitrogen for linking to an appropriate antigenic or labeling group to provide reagents for propoxyphene immunoassays having excellent sensitivity and selectivity for both d-propoxyphene and d-nor-propoxyphene.

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: Immunoassays for complement components, complement activation products or, preferably both, can be used to determine an acceptable level of anticomplement activity (AC) in plasma derived biologically active products intended for infusion into a mammal. In one application an ELISA for complement components (CC) such as C1q, C1r or C1s can be used to determine AC in an IgM-enriched immune serum globulin (ISG). In another application, an immunoassay for complement activation products (CAP) is used for a similar determination. In yet a preferred third application, assays for both a CC (such as measuring a decreasing amount of C1r) and a CAP (such as measuring an increasing amount of C4a) are used to assess the relative AC (and safety) of a biologically active, therapeutic preparation.

Abstract: The invention discloses novel fused-azacylic quinoxalinediones. These compounds may be employed as excitatory amino acid antagonists and as analogs for use in immunological assays. The invention is also directed to both a radioimmunoassay and enzyme immunoassay for detecting and quantitating 1,4,7,8,9,10,-hexahydro-9-methyl-6-nitropyrido[3,4-f]-quinoxaline-2,3-dion e PNQX and analogs thereof.

Abstract: Diagnostic/prognostic methods are provided for screening for pathologies wherein an alteration in estrogen metabolism is indicative of a pathology or a susceptibility thereto which comprise detecting and/or quantifying directly in tissues and body fluids of mammals abnormal levels of estrone metabolites and their glucuronide conjugates. Particularly preferred methods involve the use of the 16OHE1-glucuronide fraction, i.e., the fraction which contains 16.alpha.-hydroxyestrone (16OHE1) and its conjugates, 16OHE1-3-glucuronide. Methods of preparing reagents to detect said 16OHE1-glucuronide fraction in tissues and body fluids are disclosed as well as test kits for performing the disclosed assays.

Abstract: The present invention provides a topiramate immunoassay and reagents for use in the immunoassay. In particular, topiramate is derivatized at the sulfamate moiety or the 9-carbon or 10-carbon methyl group of topiramate to add a label bound directly or through a linking group for use as a tracer (competitive analyte analog) or to add a linking group bound to a carrier for use as an immunogen to induce anti-topiramate antibodies. Immunoassay methods and kits are also provided.

Abstract: An isolated nucleic acid sequence encoding major Yo paraneoplastic antigenic polypeptide is provided by this invention. This invention also provides a purified major Yo antigenic polypeptide and compositions containing the purified major Yo antigenic polypeptide. Further provided by this invention is a monoclonal antibody directed to an epitope on the major Yo paraneoplastic antigenic polypeptide. Compositions containing this monoclonal antibody also are provided by this invention. This invention also provides methods of diagnosis and treatment using the compositions described hereinabove.

Abstract: Diagnostic/prognostic methods are provided for screening for pathologies wherein an alteration in estrogen metabolism is indicative of a pathology or a susceptibility thereto which comprise detecting and/or quantifying directly in tissues and body fluids of mammals abnormal levels of estrone metabolites and their glucuronide conjugates. Particularly preferred methods involve the use of the 16OHE1-, 2OHE1- or 2MeoE1-glucuronide fraction, i.e., the fraction which contains the metabolite and its 3-glucuronide conjugate. Methods of preparing reagents to detect said 16OHE1-, 2OHE1-, and 2MeoE1-glucuronide fraction in tissues and body fluids are disclosed as well as test kits for performing the disclosed assays.

Abstract: A method for detecting an analyte of interest present in a mixture at an ultralow concentration includes selecting a radioactive derivatizing agent comprising a multiphoton-emitting radioisotope moiety and a moiety reactive with the analyte of interest, the radioisotope moeity being bound to the derivatizing agent by a bond that is stable under the conditions employed in the other steps of the method, derivatizing the analyte of interest with the derivatizing agent, separating the analyte of interest from other components of the mixture by chromatography, and detecting the analyte of interest using multiphoton detection. The derivatizing step may be performed before or after fractionation. A radiophore for multiphoton emission enhanced chromatography has a first moeity bound to a multiphoton-emitting radioisotope, and a second moiety that is reactive with a functional group of an analyte of interest.

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: The present invention discloses novel immunogens, antibodies prepared from such immunogens, and labeled reagents useful in immunoassays for the detection and quantification of testosterone in a test sample. Also disclosed are immunoassays using these reagents and methods for synthesizing these reagents. The immunoassays are preferably microparticle enzyme immunoassays (MEIAs) and fluorescence polarization immunoassays (FPIAs). Further disclosed are novel starting materials for making the above novel immunogens and labeled reagents. Methods for making the novel immunogens and labeled reagents from the novel starting materials are also disclosed.

Abstract: The present invention provides methods for detecting the presence of or determining the amount of a ligand in a fluid sample. The methods comprise providing a first reagent comprising a sol particle having a detectable physical property bound to the ligand or ligand analogue (in a competitive format) or a substance capable of specifically coupling with the ligand (in a sandwich format), providing a second reagent having a detectable physical property comprising a sol particle bound to a substance capable of specifically coupling with the ligand and/or ligand analogue, if present, combining the first reagent, second reagent and the fluid sample and detecting before, during or after the reaction, a change in the physical property of the sol particles, which provides a qualitative or quantitative indication of the ligand in the fluid sample.

Abstract: The present invention provides a labelled .beta.-amyloid peptide or a labelled active fragment of .beta.-amyloid peptide and methods of using the labelled peptides to screen for agents which affect the deposition of the labelled peptide onto amyloid plaques in tissue samples evidencing the presence of Alzheimer's amyloidosis.

Abstract: The invention relates to methods for making synthetic, photoreactive peptides and their use. A photoreactively labelled amino acid is incorporated into the peptide. The resulting peptide, when compared to the non-labelled form, is not impaired with respect to its ability to bind an MHC molecule.

Abstract: The present invention provides hapten derivatives that are useful for the preparation of antigenic, antibody and label reagents having superior performance characteristics for use in immunoassays for the detection of d-propoxyphene and d-nor-propoxyphene. In the present invention the propoxyphene nucleus is derivatized out of the nitrogen center to form an aminoalkyl -carboxyl, -amino, -thiol or -hydroxyl haptenic derivative. The resulting hapten can then be further modified at the now functionalized position off the nitrogen for linking to an appropriate antigenic or labelling group to provide reagents for propoxyphene immunoassays having excellent sensitivity and selectivity for both d-propoxyphene and d-nor-propoxyphene.

Abstract: The present invention provides novel peptides and vaccines containing them capable of inducing production of antibodies directed against Clostridium perfringens alpha-toxin (CPa) in animals to which they are administered and thereby providing prophylaxis against infection by Clostridium perfringens and/or the alpha-toxin itself. Particularly the present invention provides such a vaccine that is relatively safe and simple to produce. e.g. by genetic engineering means. Preferred peptides comprise theo amino acid sequence of Clostridium perfringens alpha-toxin from amino acid 247 to 370 but lack the epitopes necessary for phospholipase C and/or sphingomyelin hydrolysing activity found between amino acids 1 to 240 of that sequence. Further provided are antisera and antibodies raised to the peptides and vaccines of the present invention, and particularly monoclonal antibodies and hybridoma cell lines for their production.

Abstract: Additives are proposed for compositions comprising radiolabelled organic compounds e.g. 32P-labelled nucleotides. Stabilisers are selected from tryptophan, para-aminobenzoate, indoleacetate and the azole group. Dyes are selected from Sulphorhodamine B, Xylene Cyanol, Azocarmine B and New Coccine. Preferred compositions contain both stabiliser and dye.

Abstract: A compound according to the formula: ##STR1## and conjugates thereof.

Abstract: The present invention is directed to novel purified and isolated mite allergens possessing mite allergen activity with a molecular weight of about 94,000, about 40,000, about 16,000 or about 14,000 as determined by SDS-PAGE, which can be isolated from extracts of mite, and to a process for producing such mite allergens. The purified and isolated mites allergens of the present invention are useful as a pharmaceutical and a diagnostic composition for mite allergic diseases.

Abstract: It has been determined that HLA B27 is related to proteins of the Gram negative enteric bacteria. The hypervariable regions of the HLA B alleles were compared to the known sequenced proteins for short consecutive amino acid identities. It was found that, unique to the HLA B alleles,, HLA B27 shares an unexpected number of hexapeptides and pentapeptides with Gram negative bacteria proteins. The proteins from enteric organisms that share sequence with B27 tend to have sequences that satisfy protein sequence motifs which are thought to predict binding to B27. In addition, there is a sequence in B27, LRRYLENGK, which is predicted to bind as a peptide to B27. Binding of this peptide to B27 has been demonstrated. The disclosed peptides are useful for diagnostic and therapeutic purposes and can be used to design additional peptides from Gram negative enteric organisms can be identified to be important in the spondyloarthropathies.

Abstract: The present invention is directed to a method for detecting a mammal's prior exposure to radiation or radiomimetic agents. Labeled antibodies are employed to determine the quantity of transferrin receptors on the red blood cells of the mammal. The quantity of transferrin receptors on the red blood cells of the mammal is correlated to the mammal's prior exposure.

Abstract: Additives are proposed for compositions comprising radiolabelled organic compounds e.g. 32P-labelled nucleotides. Stabilizers are selected from tryptophan, para-aminobenzoate, indoleacetate and the azole group. Dyes are selected from Sulphorhodamine B, Xylene Cyanol, Azocarmine B and New Coccine. Preferred compositions contain both stabilizer and dye.

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: As method of determining an analyte is described, where a medium suspected of containing an analyte is drawn into a capillary tube by capillary action, such that if the analyte is present, it becomes immobilized in the tube. This medium is expelled from the tube and, optionally, one or more additional reagents are similarly drawn up and expelled. When the last fluid is expelled from the tube, a pendulous drop is caused to form at the opening of the capillary tube and is examined for the presence or intensity of the signal, which is related to the presence or amount of analyte in the medium.

Abstract: Detectably labelled annexines and compositions thereof are disclosed. Also disclosed are methods for diagnosing a disruption or activation of the hemostatic system or a prothrombotic state in an individual suspected of having a hemostatic disorder, by contacting the blood of said individual with an annexine, and detecting whether an annexine-platelet complex is formed.

Abstract: A method for improved measurement of a concentration of an analyte in a sample having an unknown concentration of the analyte includes using an affinity assay having an experimental indicator. Standard and control samples, each having a known concentration of the analyte are assayed and a response, an amount of experimental indicator emitted for each sample is detected. The unknown sample is also assayed and its response is detected. A prior probability density is supplied for the unknown concentration, along with a model for a standard curve relating an expected response to a concentration of the analyte. A posterior density, having a median, for the unknown concentration is generated based on the supplied prior density, the supplied model, and the responses for the standard samples, the control samples and the unknown samples, by applying Bayes' rule.

Abstract: The invention is an assay, including a series of peptides, which allow screening for inhibitors of C5a binding targeted to the subsite on the C5a receptor occupied by the C-terminus of C5a. These peptides allow compound testing efforts to be targeted to this same subsite so that C5a agonists and antagonists can be identified. These peptides have much greater affinity (Ki<10 nM) than does the natural C-terminus of C5a (Ki=300 .mu.M) and have been labeled to allow for detection of molecules which inhibit binding of these peptides at this receptor subsite. The invention is useful to develop agonists, partial agonists, and antagonists of C5a, and the invention includes compounds identified according to the method of this invention and methods of their use.

Abstract: A method for observing and determining the size of individual particles and for determining the weight distribution of a sample containing particles of varying size, which involves placing a deformable or nondeformable particle in a medium, subjecting the particle to an external force, thereby causing conformational and/or positional changes, and then measuring these changes. Preferred ways to measure conformational and positional changes include: (1) determining the rate at which a deformable particle returns to a relaxed state after termination of the external force, (2) determining the rate at which a particle becomes oriented in a new direction when the direction of the perturbing force is changed, (3) determining the rate at which a particle rotates, (4) measuring the length of a particle, particularly when it is at least partially stretched, or (5) measuring at least one diameter of a spherical or ellipsoidal particle.

Abstract: A sensitive chemiluminescence immunoassay method for field detection of the presence or the amount of low chlorinated biphenyl compounds in a solution is disclosed. The assay has a five minute analysis time and a working range of detection as low as about 1 part per billion chlorinated biphenyl. Kits for the detection of chlorinated biphenyls are disclosed.

Abstract: A method for reducing or eliminating tyramine interference from amphetamine and methamphetamine immunoassays, comprising treating the sample with aqueous tyramine oxidase for a time and at a temperature and pH sufficient to deaminate any tyramine present in the sample, is provided.

Abstract: A method is provided for detecting whether a test composition can inhibit cell fusion mediated by paramyxovirus infection. A method is also provided for identifying an antiviral peptide capable of inhibiting paramyxovirus-induced cell fusion. The methods are based on the discovery that the hemagglutination and fusion-inducing proteins of paramyxoviruses interact to form a complex termed HN:F, that is prerequisite to cell fusion. Antibodies to HN:F provide a novel means of providing improved immunity against paramyxovirus infection.

Abstract: For isotopes decaying by capture of an inner shell electron by the nucleus, coincident emission of X-ray and gamma photons may occur. The X-ray results from the drop of an outer shell electron to fill the S shell. The gamma results from the transition of the excited daughter nucleus to a lower energy state. The invention disclosed is a Coincident Gamma and X-ray Detector (CGXD) which achieves extraordinary background rejection by a synergistic combination of coincident counting and other background suppression measures. Whereas the background registered by single gamma counters is of the order of 20-40 counts per minute, a CGXD optimized for the electron capture radioisotope I.sup.125 has a background of about one count per day.

Abstract: The stereochemistry of sialylation of an acceptor saccharide to obtain an .alpha. (2-3) or .alpha. (2-6) linkage is controlled to favor the .alpha. anomer by use of an aromatic ester of the sialyl reagent. The resulting intermediate .alpha. (2-3) and .alpha. (2-6) sialylated intermediate disaccharide blocks are useful in the synthesis of antigenic substances which can be used to raise antibodies useful in diagnosis and therapy, and can themselves be used as reagents in various applications. The preparation of the tetrasaccharide antigens corresponding to the 19-9 and sialyl-X antigens characteristic of malignant tissue illustrates the application of this method.

Abstract: Novel derivatives of procainamide and N-acetylprocainamide (NAPA) are disclosed having the following formula: ##STR1## wherein: X=hydrogen or acetyl;n=1 to p where p=MW of Z/1000;Z=a poly(amino acid) or polysaccharide; andR3=a bond or ##STR2## wherein R2=an alkyl, cycloalkyl or aryl group having 2 to 10 carbon atoms. The derivatives include maleimide conjugates of proteins or poly(amino acids), enzymes, enzyme donor polypeptides and labeling substances. Novel activated hapten intermediates useful in the preparation of the conjugates and methods for synthesis of the hapten intermediates and derivatives are also disclosed.

Abstract: Antibodies raised against derivatives of inositol are used to assay for specific isomers of inositol in a sample by first converting any inositol present in the sample to the derivative that was used to raise the antibody and then conducting an immunoassay for the inositol derivative in a conventional manner.

Abstract: The present invention provides a novel immunoassay for the detection of multiple analytes such as amphetamine and methamphetamine in a single assay of a biological fluid sample. In this assay, a single labelled binding partner is utilized capable of cross reacting at differing sensitivities to antibodies derived from conjugate derivatives of the different analytes such that the presence of the analytes at selected levels of concentration of the analytes singly or in combination can be detected.

Abstract: New purified mite allergens useful as pharmaceutical and diagnostic compositions for the treatment and diagnosis of mite allergic diseases are provided. Both allergens are contained in fecal extracts of mites in culture. The high molecular weight allergen has a weight average molecular weight of 70,000 to 80,000 as determined by sedimentation equilibrium. This is a glycoprotein containing more than about 70% sugar, and possesses allergen activity. The low molecular weight antigen has a molecular weight of 1,500 to 5,000 as determined by Sephadex G25 gel filtration. This is a glycoprotein containing more than about 40% sugar, and also possesses allergen activity.

Abstract: Disclosed is a novel photo-activatable derivative of ryanodine 9-hydroxy-21-(4-azidobenzoyloxy)-9-epiryanodine. This novel ryanodine derivative has been conjugated to keyhole limpet hemocyanin (KLH) and used for the production of antibodies with high affinity and specificity to ryanodine. A radioimmunoassay specific for ryanodine was developed using the anti-ryanodine antibodies, and a dissociation constant for ryanodine of 1 nM was determined. Also disclosed is the binding of a labeled, photoactivatable derivative of ryanodine (ABRy) with the ryanodine receptor of skeletal, cardiac and brain membranes. Digestion of the labeled ryanodine receptor revealed a labeled 76 kDa tryptic fragment which is critical for the formation of the high affinity ryanodine binding site.

Abstract: An immunoassay method that integrates a sample processing component that enables the testing of samples for the presence of an immunologically non-remarkable compound, such as benzene, by the use of a monoclonal antibody having specific reactivity for an immunologically remarkable compound, such as nitrobenzene, which has been prepared by reacting the immunologically non-remarkable compound with derivatizing agent, and the components for performing the method, wherein one example of the immunoassay utilizes a monoclonal anti-nitrobenzene antibody to detect the presence or absence of benzene contamination in an aqueous sample when tested in a field or laboratory location.

Abstract: Novel derivatives of procainamide and N-acetylprocainamide (NAPA) are disclosed having the following formula: ##STR1## wherein: X=hydrogen or acetyl;R.sub.1 =an alkyl group having 1 to 3 carbon atoms;m=an integer from 2 to 10;R.sub.2 =an alkyl, cycloalkyl or aryl group having 2 to 10 carbon atoms;Z=a poly(amino acid); andn=1 to p where p=MW of Z/1000.The derivatives include maleimide conjugates of proteins or poly(amino acids), enzymes, enzyme donor polypeptides and labeling substances. Novel activated hapten intermediates useful in the preparation of the conjugates and methods for synthesis of the hapten intermediates and derivatives are also disclosed.

Abstract: The present invention provides: a labelled .beta.-amyloid peptide of active fragment; a composition including the labelled .beta.-amyloid peptide or active fragment thereof and a pharmaceutical carrier; a method for labelling the .beta.-amyloid peptide or an active fragment thereof, and methods of using the labelled peptide or peptide fragment for detecting or monitoring Alzheimer's disease in a patient.

Abstract: A kit and method of non-destructively radiolabelling a biomolecule substrate by halogenation, including the steps of: a) reacting a secondary amine with a chlorinating agent to produce an N-chloro secondary amine, (b) reacting the N-chloro secondary amine with a salt of a radiolabelled halogen to produce a radiolabelled halogenating agent, (c) reacting a solution of the biomolecule substrate with the radiolabelled halogenating agent, and (d) recovering a radiohalogenated biomolecule from the reaction of step (c). The kit and method allow for more complete iodination with a lessening of side reactions such as decomposition of the biomolecule substrate to be labelled.

Abstract: N-substituted azetidinones are a class of inhibitors of human leukocytes elastase which are known to be useful in the treatment of a wide variety of antiinflammatory and antidegenerative diseases. In inhibiting elastase, the therapeutic agents are shown to form a characteristic stable complex with the enzyme. In the assay disclosed herein, the inhibitor-enzyme complex is advantageously hydrolyzed and specific product(s) of the hydrolysis are measured. The assays are useful in a clinical setting, for determining appropriate dosage and assessing the effectiveness of treatment.

Abstract: The invention relates to a novel process for preparing immunoconjugates consisting of haptens which are sparingly soluble or insoluble in aqueous solution and proteins/polypeptides using special solvents, in particular diethylene glycol monoalkyl ethers.