Abstract: The invention provides a method for diagnosing in a subject a neoplastic condition which comprises (a) obtaining from the subject a sample of a biological fluid; and (b) detecting the presence in the sample of a mutant p53 polypeptide encoded by an activated p53 oncogene, the presence of the mutant p53 polypeptide in the sample indicating that the subject has the neoplastic condition.

Abstract: A novel signal amplification system for immunoassays that minimizes non-specific signals is disclosed. Immunoassay methods, reagents and test kits are described for obtaining immunoassays of enhanced sensitivity. The reagents include antibody-variant DNA conjugates, wherein the variant DNA is a substrate for an RNA-dependent RNA polymerase, such as, QB replicase. Immunoassay methods to detect, or to detect and quantitate, analyte in test samples comprise transcribing the variant DNA of said antibody-DNA conjugates that are bound to analyte, to RNA, and replicating the RNA transcripts, wherein the presence or quantity of variant RNA replication products can be correlated with the presence or quantity of analyte in the test samples. Further, methods are provided to detect, or to detect and quantitate, simultaneously two or more analytes in a test sample.

Abstract: An antibody targeted to an antigen is brought into contact with a body component in situ. The resulting antibody/antigen complex is labeled and may be amplified. The label is then detected either in situ or ex situ.

Abstract: The present invention provides methods and reagents for assessing lipoprotein metabolism. The methods provided are applicable for use on multiple samples in a clinical laboratory, thus obviating the need for sophisticated instrumentation, such as flow cytometry. Selected cell types in a test sample are uniformly labelled with a detectable reporter substance, so that they may later be enumerated. Pre-determined lipoprotein receptors associated with the cells of interest are labelled with a receptor-selective marker, thereby to determine the number of lipoprotein receptors per cell in the test sample. Selected cells of interest are conveniently separated from the test sample by binding thereto a specific binding substance attached to a solid support. The specific binding substance binds specifically with a characteristic determinant of the cell subset of interest. The remainder of the test sample may be washed away or discarded.

Abstract: A method of quantitating the activity of a selected protein kinase on a peptide substrate is provided. The peptide substrate is conjugated to a binding compound. The modified peptide substrate is then added to a solution containing the selected protein kinase. The protein kinase and the peptide are incubated along with a label for sufficient time to form a modified peptide product having the binding compound and the label. The modified peptide product is then bound to a matrix having a high binding compound affinity. The bound peptide is then washed and the activity of the protein kinase is measured. Also provided is a kit for the stated method.

Abstract: The present invention includes a method to detect canine IgE using a canine Fc epsilon receptor (Fc.sub..epsilon. R) to detect canine IgE antibodies in a biological sample from a canid. The present invention also relates to kits to perform such methods.

Abstract: The present process for producing a high .alpha.-monoglucosyl hesperidin content product is characterized in that it comprises the steps of contacting glucoamylase and .alpha.-L-rhamnosidase simultaneously or randomly with a solution containing .alpha.-glucosyl hesperidin and hesperidin to obtain a mixture; crystallizing and separating .alpha.-monoglucosyl hesperidin in and from the mixture; and collecting the resulting .alpha.-monoglucsyl hesperidin. From solutions containing .alpha.-glucosyl hesperidin and hesperidin, the present invention facilitates the production of a high .alpha.-monoglucosyl hesperidin content product which does not substantially contain hesperidin, .beta.-monoglucosyl hesperetin, and hesperetin, and has an extremely-superior water-solubility.

Abstract: Compositions and methods for avidin immobilized on an inert support material, e.g. agarose, are disclosed. The compositions have high activity levels of avidin and may further include a bulking agent, e.g., maltose, and a protectant to maintain the stability and integrity of the avidin agarose during lyophilization and terminal sterilization processes. These compositions have applicability in any instance where avidin agarose and/or the avidin/biotin technology are useful. In particular, the present compositions are useful in an enzyme capture system to prepare fibrin monomer useful for fibrin sealants. The fibrin is prepared by subjecting a fibrinogen-containing composition to a biotinylated enzyme to convert the fibrinogen in the composition to a corresponding fibrin monomer. A fibrin monomer/biotinylated enzyme mixture is formed.

Abstract: This invention provides novel antibodies and engineered versions thereof and methodology for monitoring biological media for protein fragments, especially collagen fragments resulting from collagenase cleavage of type II collagen.

Abstract: Avidin-binding azo reagents which alter the spectrophotometric properties of avidin and the use of such reagents in homogeneous assays are described.

Abstract: A method for detecting mutations, such as a single base change or an addition or deletion of about one to four base pairs, is based on the use of an immobilized DNA mismatch-binding protein, such as MutS, which binds to a nucleic acid hybrid having a single base mismatch or unpaired base or bases, thereby allowing the detection of mutations involving as little as one base change in a nucleotide sequence. Such a method is useful for diagnosing a variety of important disease states or susceptibilities, detecting the presence of a mutated oncogene and for isolating or removing by affinity chromatography duplex DNA molecules containing mismatches such as error-containing molecules in PCR-amplified DNA samples. Also provided are kits useful for practicing the methods of the present invention.

Abstract: Three novel macrolactam monosaccharides isolated from an antimicrobial complex 510 produced in fermentation under controlled conditions using a biologically pure culture of the microorganism Actinomadura fulva subsp. uruguayensis ATCC 53713.

Abstract: The present invention relates to a reagent for biomaterials assay of (fluorescent dye).sub.n --avidin--a compound having a plurality of reactive groups--a biomaterial, or a reagent in which avidin is bound to a compound having a plurality of reactive groups through biotin in the above, a method for preparing it, a plastic fiber optics necessary for utilizing this, an assaying device having a sensing portion utilizing this fiber optics and an assaying method of biomaterials by use of this reagent and device. The assay method can be used for immunoassay of biomaterials such as antigens, enzymes contained in extremely minute amounts in blood or body fluid in medical diagnosis, and improves detectable sensitivity to a great extent.

Abstract: A composition and method are provided for detecting and isolating antigen associated cancer cells. The composition and method utilize an antigen specific, immunomagnetic composition as the detecting and isolating agent. An illustrative immunomagnetic composition comprises avidin or streptavidin conjugated to paramagnetic beads and further conjugated to antigen specific, biotinylated antibody. A fluidic admixture of the antigen associated cancer cells with the immunomagnetic composition in an affinity column disposed in a magnetic field produces a cancer cell immunomagnetic composition conjugate which is deposited onto the inner wall of the column.

Abstract: Methods for determining whether a chemotherapeutic treatment is appropriate for patients afflicted with gastrointestinal cancers, comprising;(a) obtaining a solid tumor tissue sample from the patient;(b) measuring a thymidylate synthase expression level in the tissue sample; and(c) comparing the thymidylate synthase expression level with a group of standard tumor tissue samples, the standards having known thymidylate synthase expression levels and known responses to the chemotherapeutic treatment, to determine if that chemotherapeutic treatment is appropriate for the patient.

Abstract: Compositions and methods for avidin or protein having affinity for biotin immobilized on an inert support material, e.g., agarose, are disclosed. The compositions have high activity levels for binding biotin and may include a bulking agent, e.g., maltose, and a protectant to maintain the stability and integrity of the composition during lyophilization and terminal sterilization processes. The compositions have applicability in any instance where avidin agarose and/or the avidin/biotin technology are useful. In particular, the present compositions are useful in an enzyme capture system to prepare fibrin monomers useful for fibrin sealants.

Abstract: Peptide antigens derived from the carboxy terminus of somatostatin receptors and antibodies produced using the peptide antigens. The anti-somatostatin receptor antibodies are specific for a receptor subtype and are useful in characterizing receptor subtypes expressed by tissues.

Abstract: The invention provides platinum-based probe compounds having the structure: ##STR1## wherein: Pt is a platinum atom, PROBE is a probe biomolecule for associating to a target biomolecule, M is a detectable marker moiety, and X and Y are stabilizing substituents. Also provided are platinum-based labeling compounds having the structure: ##STR2## wherein: Pt is a platinum atom, M is a detectable marker moiety, A is a displaceable leaving group, and X and Y are stabilizing substituents. The invention further provides platinum-based linker compounds having the structure: ##STR3## wherein: Pt is a platinum atom, A and B are the same or different reactive moieties, and X and Y are stabilizing substituents. Other Pt.sup.II and Pt.sup.IV compounds are also provided. Moreover, the invention provides methods for the preparation and use of these compounds, as well as diagnostic kits which contain the compounds.

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: Biotin-binding modified avidin-type molecules are provided in which the essential tyrosine residue in the biotin-binding site is modified in such a way that its pKa is decreased in comparison to the pKa of the unmodified tyrosine residue in the corresponding unmodified avidin-type molecule. The avidin-type molecules include: (i) native egg-white avidin; (ii) recombinant avidin; (iii) deglycosylated forms of avidin; (iv) bacterial streptavidin; (v) recombinant streptavidin; (vi) truncated streptavidin; and (vii) derivatives of (i)-(vi) which are modified at sites other than the essential tyrosine residue. The modification is achieved by substitution at one or both ortho positions to the hydroxy radical of the tyrosine residue by radicals such as nitro, halogen, azo and amino. The modified avidin-type molecules can be used in all applications of the avidin-biotin technology.

Abstract: The present invention relates to methods for measuring endogenous cytokines in blood. The method accurately measures the cytokines in the blood in the presence of substances that bind the cytokines thereby causing the measurement of the cytokines by conventional methods to give inaccurate results. The present invention also includes the non-invasive measurement of cytokines in biological fluids such as saliva and nasal secretions. Finally, the present invention allows one to monitor the level of cytokines in the blood during treatment of a human or animal with cytokines.

Abstract: Compounds and methods are provided for use in purification of CD34.sup.+ cells and specific surface antigens thereof. The present invention discloses methods for releasing CD34.sup.+ cells, as well as compounds having a carbohydrate epitope of the CD34 surface antigen, from an affinity matrix, using carbohydrates having the structure:Neu5Ac.alpha.2-3Gal.beta.1-4(X)wherein (X) is GlcNAc, or a monosaccharide or a cyclohexane derivative that is structurally similar to GlcNAc.

Abstract: An improvement in in vivo pretargeting methods for delivering diagnostic or therapeutic agents to a target site in a mammal uses a clearing agent that binds to the target-binding site of the targeting species, whereby non-bound primary targeting species is cleared from circulation but the clearing agent does not remove the bound primary targeting species. Anti-idiotype antibodies and antibody fragments are preferred clearing agents. Fast clearance is achieved by glycosylating the clearing agent with sugar residues that bind to the hepatic asialoglycoprotein receptor.

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: An in vitro method of identifying or isolating fetal cells from a blood sample is described. Fetal nucleated erythrocytes or erythroblasts are identified by using an antibody or antibody fragment specific for embryonic hemoglobin or an embryonic hemoglobin chain. Once the fetal cells are identified, they can be treated to render the fetal nucleic acids or proteins available for identification or amplification. Detecting the occurrence or existence of selected fetal nucleic acids or proteins allows a quantitative or qualitative diagnostic or prenatal evaluation, including determining the sex of the fetus, determining chromosomal, single gene or protein abnormalities, and determining the presence or absence of particular genes, nucleic acid sequences or proteins.

Abstract: The present invention relates to a method and kit for carrying out a qualitative or semi-quantitative assay. The invention uses a multi-layer device including an an uppermost cover layer of a water-impermeable material having a hole therein with a diameter of approximately 1-5 mm, an intermediate insoluble porous support layer having a first substance bound thereon in a reaction zone, the hole exposing at least a part of the reaction zone, and a layer of a hydrophilic material in contact with and positioned on the side of the insoluble porous support layer opposite the side with the cover layer. The device permits transverse, but not substantial radial, diffusion of liquid through the reaction zone. Approximately 1-50 .mu.l of a test sample and a second substance are applied to the reaction zone through the hole. A colloidal gold label is attached to the second substance.

Abstract: The invention provides methods for screening libraries of complexes for compounds having a desired property, especially, the capacity to agonize, bind to, or antagonize a cellular receptor. The complexes in such libraries comprise a compound under test, a tag recording at least one step in synthesis of the compound, and a tether susceptible to modification by a reporter molecule. Modification of the tether is used to signify that a complex contains a compound having a desired property. The tag can be decoded to reveal at least one step in the synthesis of such a compound.

Abstract: A biosensor apparatus for detecting a binding event between a ligand and receptor. The apparatus includes an electrode substrate coated with a high-dielectric hydrocarbon-chain monolayer, and having ligands attached to the exposed monolayer surface. Binding of a receptor to the monolayer-bound ligand, and the resultant perturbation of the monolayer structure, causes ion-mediated electron flow across the monolayer. In one embodiment, the monolayers have a coil--coil heterodimer embedded therein, one subunit of which is attached to the substrate, and the second of which carries the ligand at the monolayer surface.

Abstract: The present invention relates to analytical devices for determining the presence or amount of an analyte in a test sample. The analytical devices comprise an inlet port, a vent, a channel, and an array of structures. The structures have immobilized reagent covalently or non-covalently attached to the surface of the structures. The immobilized reagent captures analyte in the test sample where it is detected by a detection system. The present invention also provides methods and reagents for performing assays utilizing the analytical devices of the present invention. The present invention also provides methods of manufacturing the analytical devices of the present invention.

Abstract: The invention addresses new photo-activatable biotin derivatives having the formula I ##STR1## wherein R=?(CH.sub.2).sub.n --O.sub.m !.sub.q --?(CH.sub.2).sub.r --O.sub.s !.sub.t --(CH.sub.2).sub.pwith n,r=2,3; m,s=0,1; q+t=1-4; p=1-4,wherein the sum of all CH.sub.2 groups does not exceed 10and wherein R1 as a single or multiple substituent is hydrogen, C.sub.1 -C.sub.5 alkyl, NH.sub.2, COOH, F, Cl, or Br.and their preparation, their use to inactivate streptavidin, the use of the inactivated streptavidin to reduce interference in immunoassays.

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: The present invention includes a method to detect IgE using a human Fc epsilon receptor (Fc.sub..epsilon. R) to detect IgE antibodies in a biological sample from a cat, a dog, or a horse. The present invention also relates to kits to perform such methods.

Abstract: Compositions and methods for avidin immobilized on an inert support material, e.g., agarose, are disclosed. The compositions have high activity levels of avidin and may further include a bulking agent, e.g., maltose, and a protectant to maintain the stability and integrity of the avidin agarose during lyophilization and terminal sterilization processes. A dry composition, and wet compositions such as a gel, slurry or suspension having avidin immobilized on an inert support material are disclosed. The dry composition has at least 1000 biotin binding units of activity, and the wet compositions have at least 50 units of binding activity. These compositions have applicability in any instance where avidin agarose and/or the avidin/biotin technology are useful. In particular, the present compositions are useful in an enzyme capture system to prepare fibrin monomer useful for fibrin sealants.

Abstract: Assay methods for performing non-competitive ligand-receptor assays, where said assays provide a sensible result when the target ligand identified by the assay is present at a concentration greater than a defined threshold concentration. The threshold concentration can be selected to be the upper limit of a normal range of values for a target ligand in a sample, so that an assay in accordance with the invention provides a sensible result only when the target ligand is present at elevated levels.

Abstract: The present invention is drawn to methods for the synthesis of sialyl Lewis.sup.x derivatives modified at the C-2 and/or C-6 position of GlcNAc employing chemoenzymatic synthesis. The derivatives find use in the treatment and prevention of diseases.

Abstract: The invention concerns a method for typing antibodies in a sample liquid by means of type-specific antigens and in particular a method for typing antibodies to the hepatitis C virus and peptide antigens suitable for this.

Abstract: The present invention relates to a method for selectively enhancing the production of factors A.sub.2 and/or A.sub.3 of antibiotic A/16686 either to isolate these single components or to enrich the complex in one or both the above components, which comprises adding an appropriate precursor of the desired antibiotic factor to an A/16686 producing culture during fermentation.

Abstract: Methods and apparatus are employed for determining interactions between different components, of the same or different type of composition. The apparatus provides for arrays of samples in tracks, where light emitting labels are excited and emitted light detected. Headers are provided for defining sites, so that particular interactions can be rapidly detected. Particularly, disks having circular tracks with headers defining sites on the tracks, so that positive signals can be interpreted in relation to the information provided by the header. Various modifications can be made, such as preprepared segments which may then be attached to the disk for assaying.

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: An immunoassay is provided which is selective for an analyte over immunologically related substances which may be present in a sample to be tested. The presence of the analyte is detected using a first binding substance, typically an antibody, in the presence of a second binding substance, typically another antibody. The first binding substance recognizes an epitope which is characteristic of the analyte and cross-reacts with a related epitope on the cross-binding substance. The second binding substance preferentially binds the common epitope on the cross-binding substance, thus reducing non-specific binding of the first binding substance.

Abstract: A biotin-antibiotin immunoassay comprises coating a solid phase with a ligand-specific binding material, reacting the solid phase with a test sample, reacting the solid phase with the biotin-labeled form of the ligand-specific binding material and antibiotin labeled with a suitable marker. The marker is then measured to detect the amount of ligand present in the test sample.

Abstract: An immunoassay plate for an immune complex transfer immunoassay, comprising a well type solid phase and a dip stick type solid phase which can be inserted into said well type solid phase, wherein the dip stick type solid phase is coated with either substance (A) or (B) to be mentioned below and the well type solid phase is coated with the other, remaining substance, and these solid phases are used as the two solid phases to be used for an immune complex transfer immunoassay:(A): a substance having a reactive group which specifically binds to a functional group previously introduced onto a substance, which specifically forms an immune complex with a test substance(B): a substance having a reactive group capable of specifically binding to the test substance in the immune complex, a substance which specifically forms an immune complex with the test substance, or a functional group conjugated in advance with said substance, provided that the moiety which binds to the reactive group of (A) does not bind to the rea

Abstract: This invention provides a novel chromanol glycoside which is a water soluble antioxidant excellent in heat and pH stability and production method thereof. It is a chromanol glycoside represented by the general formula (1): ##STR1## wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 independently are a hydrogen atom or a lower alkyl group, R.sup.5 is a hydrogen atom, a lower alkyl group, or a lower acyl group, X is a monosaccharide residue or an oligosacoharide residue, providing the hydrogen atom of the hydroxyl group of saccharide residue may be substituted by a lower alkyl group or a lower acyl group, n is an integer in the range of 0 to 4, and m is an integer in the range of 1 to 6.

Abstract: Aminoglycosides such as aminoglycoside antibiotics are detected and separated by non-immunoaffinity binding to an immobilized binding protein which is preferably lysozyme or .alpha.-lactalbumin. Aminoglycosides are detected in a biological sample such as milk or a fermentation broth by contacting the sample with the binding protein immobilized on a solid carrier such as particles of carboxylated latex to bind the aminoglycosides to the binding protein, adding a label that binds to the aminoglycosides and measuring the label. In another embodiment, the binding protein containing bound aminoglycosides is separated from the sample, the aminoglycosides are removed from the binding protein, a label is added to the aminoglycosides and the label is measured. Aminoglycosides are removed from a sample by passing the sample through a bioreactor containing the binding protein immobilized on a solid carrier to bind the aminoglycosides to the binding protein and recovering the sample free of aminoglycosides.

Abstract: Linker compounds for formation of stably-linked conjugates are disclosed. Such linker compounds are aminooxy-containing linker compounds useful in forming conjugates having stable oxime linkages. The stably-linked conjugates have utility in a variety of immunodiagnostic and separation techniques.

Abstract: A process for the production of sophorolipids by a stock of Candida bombicola or apicola in a medium that contains a source of nitrogen and a substrate is described. The process includes a first fermentation cycle that includes a stage of growth of the stock and a stage of production of a fermentation wort. The following stages are carried out at least once:a) a portion of the wort is drawn off;b) a mineral that contains nitrogen is added to the remaining portion to constitute a second medium;c) a new fermentation cycle is carried out from this second medium, and another wort is produced.Sophorolipids are recovered from these worts of stages (a) and (c). The duration of the first and new fermentation cycles is at least 30 hours.

Abstract: A method of synthesizing saccharide compositions is described. In this method, an acceptor moiety is contacted with at least one donor saccharide in the presence of at least one cell surface-bound glycosyltransferase specific for catalyzing the coupling of the acceptor moiety with the donor saccharide. The acceptor moiety used is a carbohydrate, a protein, a glycolipid, a lipid, or a glycolipid.

Abstract: A luminescent specific binding assay method is used for detecting an analyte in whole blood. The assay is a heterogeneous sandwich or competitive assay in which a first binding reagent is labeled with a luminescent photoprotein and an immobilized second binding reagent serves as a capture reagent. The luminescent photoprotein, upon activation, emits light which may be detected by a luminescence detector. The assay is rapid, sensitive and may be performed on small sample volumes.

Abstract: An improved method allowing for rapid sensitive and standardized detection of a target nucleic acid from a pathogenic microorganism or virus or normal or abnormal gene in a sample is provided. The method involves hybridizing a target nucleic acid to several non-overlapping oligonucleotide probes that hybridize to adjacent regions in the target nucleic acid, the probes being referred to capture/amplification probes and amplification probes, respectively, in the presence of paramagnetic beads coated with a ligand binding moiety. Through the binding of a ligand attached to one end of the capture/amplification probe and the specific hybridization of portions of the probes to adjacent sequences in the target nucleic acid, a complex comprising the target nucleic acid, the probes and the paramagnetic beads is formed. The probes may then ligated together to form a contiguous ligated amplification sequence bound to the beads, which complex may be denatured to remove the target nucleic acid and unligated probes.

Abstract: The present invention relates to a method for assaying transferase activity upon incorporation of an affinity ultrafiltration process as a separation means, which method comprises: (1) reacting the transferase to be assayed with a labeled substrate and an unlabeled substrate to yield a product having a label moiety from the labeled substrate and a binding site moiety either from the unlabeled substrate or existing as a specific structure of the product, (2) contacting the reaction mixture with a soluble macroligand capable of forming a specific complex with the product via the binding site moiety, (3) subjecting the complex mixture to ultrafiltration which retains the complex and passes the unreacted labeled substrate, (4) washing the retentate, and (5) determining the final retentate. The present invention also relates to a kit embodying the inventive concept of the affinity ultrafiltration assay for transferase activity.