Abstract: Methods for probing multiple targets in a biological sample are provided. The methods include the steps of providing a biological sample containing multiple targets, binding at least one fluorescent probe to one or more target present in the sample, and binding at least at least one control probe to one or more target present in the sample. The methods include the steps of observing a signal from the fluorescent probe and a control signal from the control probe and applying to the sample a basic solution containing an oxidizing agent that selectively inactivates the fluorescent probe and not the control probe. The methods further include the steps of binding at least one fluorescent probe to one or more target present in the sample and observing a signal from the fluorescent probe. The methods disclosed herein also provide for multiple iterations of binding, observing, and oxidizing for deriving information about multiple targets in a single sample. An associated kit is also provided.

Abstract: The present provides compounds capable of modulating IL-4 receptor-mediated IgE production, as well as IL 4 induced processes associated therewith, methods and kits for identifying such compounds that utilize a chloride intracellular channel 1 (CLIC1) as a surrogate analyte and methods of using the compounds in a variety of in vitro, in vivo and ex vivo contexts.

Abstract: A gene expressed specifically in mesangial cells. A DNA expressed specifically in mesangial cells; a protein encoded by this DNA; an antibody binding to this protein, etc. These substances are indigenous to mesangial cells and, therefore, useful in, for example, identifying mesangial cells and detecting abnormalities in mesangial cells. Moreover, the above protein would be helpful for clarification of the functions of masangial cells and, in its turn, for clarification of the causes of diseases relating to masangial cells. This protein is expectedly applicable to the treatment and diagnosis of diseases relating to masangial cells.

Abstract: Markers for TSE that are present prior to formation of detectable pathological prion protein are useful to detect this infection prior to clinical signs. Additional markers are useful to detect the stage of TSE infection and distinguish it from other conditions which have similar clinical symptoms. Determinations on isolated cell preparations are particularly useful, especially those derived from peripheral (non-brain) sources.

Abstract: A method of detecting PS2V characterized by comprising reacting PS2V in a sample with a primary antibody which is bonded to a solid phase and specifically recognizes PA2V, then reacting with a secondary antibody recognizing PS2 or PS2V by any of the following procedures: (a) reacting with a secondary antibody having been enzyme-labeled and recognizing PS2 or PS2V; (b) reacting with a secondary antibody having been biotinylated and recognizing PS2 or PS2V and then reacting with an avidinylated or streptoavidinylated enzyme; (c) reacting with a secondary antibody having been biotinylated and recognizing PS2 or PS2V and then reacting with a biotinylated enzyme and avidin or streptoavidin; and (d) reacting with a secondary antibody recognizing PS2 or PS2V and then reacting with an antibody having been enzyme-labeled and recognizing the secondary antibody; then adding the substrate of the above enzyme and detecting the product formed by the enzyme reaction.

Abstract: Short peptides are provided, which bind to a body fluid sample obtained from a schizophrenic patient at a substantively higher level than to a body fluid sample obtained from a non-schizophrenic individual. The peptides are no more than 10 amino acids long and comprise a continuous sequence of at least 5 amino acids which consists of at least one positively charged amino acid at one of its ends. The provided peptides, which are the putative binding sites of autoantibodies found in high levels in schizophrenic individuals, are thus useful in diagnosis of schizophrenia.

Abstract: The invention concerns a peptide having the biological activity of an inhibitor of amyloid formation and its diagnostic and medical use.

Abstract: Disclosed are methods relating to cell membrane fragments associated with microbeads, so that the characteristics of the cells the fragments originated from can be determined. The fragments can be oriented with what was the outer surface of the cell membrane facing outwardly, so that the antigens associated with the membrane can be contacted with ligands (including antibodies) to antigens in the membranes which would be accessible to antibodies in vivo. The system is useful, inter alia, for detection of panel reactive antibodies in donor serum, as well as detection of other cell membrane antigens; or quantitation of particular cell membrane antigens.

Abstract: Antibodies to DC-SIGN are disclosed which are capable of modulating the interaction of dendritic cells and T cells. In some embodiments, the antibodies inhibit the interaction of dendritic cells and T cells. In other embodiments, the antibodies are combined with peptides which are internalized in dendritic cells and presented to T cells, thereby generating an immune response to the peptide. The antibodies of the present disclosure may, in some embodiments, be useful in blocking viral binding, infection, and transmission.

Abstract: Laminin and specific laminin-derived protein fragments are disclosed as potent inhibitors of Alzheimer's disease type amyloidoses. A specific region is identified within laminin which interacts with the Alzheimer's disease beta-amyloid protein and contributes to the observed inhibitory and therapeutic effects. A prominent ˜130 kilodalton band in laminin was found in human serum and cerebrospinal fluid which primarily interacted with A? as determined by ligand blotting methodology. This ˜130 kilodalton laminin fragment is known as the E8 fragment and is also believed to consist of the globular domains of the laminin A chain. The interaction of specific laminin fragments such as the newly discovered ˜130 kDa protein is believed to bind A? in biological fluids and keep it in a soluble state.

Abstract: The present invention relates to methods for screening molecules and methods to detect protein-protein interactions and means used therein. More specifically, the present invention relates to methods for screening candidate drugs for treating or detecting MIF (macrophage migration inhibitor factor) related diseases. In certain aspects, the present invention involves detecting MIF/Jab1 (c-Jun activation domain binding protein) interactions as a basis for modulating cellular regulatory pathways and for identifying candidate drugs for MIF-related diseases. The invention also provides methods for the identification of molecules which dissociate or prevent interaction or binding between MIF and Jab1.

Abstract: The present invention is related to novel nucleoli sequences encoding a louse allergen and a methods for diagnosing, treating and preventing lice infestation and associated allergic disease with the nucleoli sequences and protein allergen of the invention. The present invention also relates to kits for diagnostic assays.

Abstract: The present invention relates to methods for identifying agents that modulate the effect of cytokine class I receptor binding compounds, by inhibiting the interaction between the cytokine class I receptor and nuclear factors. The agents are useful for decreasing IGF-1 levels in a cell, and for the treatment of medical disorders caused by hormone dysregulation, such as growth hormone or prolactin dysregulation.

Abstract: Ligands of CCX-CKR2 and the biological role of CCX-CKR2 in cancer is described.

Abstract: Disclosed is a method of screening a substance for angiotensinogen receptor-modulatory activity. The method includes the steps of contacting placental-derived cells with labeled angiotensinogen and a candidate substance; and then determining whether the candidate substance inhibits the binding of angiotensinogen to the placental-derived cells relative to a control wherein the placental-derived cells are contacted with angiotensinogen in the absence of the candidate substance.

Abstract: The present invention encompasses methods and compositions useful in diagnosing and treating hepatic disorders, especially those characterized by inflammation. The method comprises administration of an agent which prevents the interaction of MAdCAM with a MAdCAM binding partner or ligand. These compositions are useful in treating diseases or disorders involving ?4?7/MAdCAM blockade, as well as inhibiting a primary event in the inflammatory response such as blocking interactions between intercellular adhesion molecules and their ligands. Disorders treatable using the methods disclosed herein include infections, especially viral infections, iatrogenic disorders, cholestatic disorders, hereditary disorders, sarcoidosis, organ transplant, and the like. The diagnostic methods of the invention can be employed to detect the presence of a disorder or to monitor the course of therapy used to treat the disorder.

Abstract: A method of producing antibodies comprising the step of encoding a peptide sequence from a Domain I perlecan splice variant, wherein the peptide sequence is used to produce anti-peptide antibodies.

Abstract: The current invention discloses nucleic acid and amino acid sequences for novel organic anion transfer proteins (“OATPs”). The invention encompasses the OATPs described herein, together with vectors containing the cDNA sequences, host cells containing the vectors and polypeptides having all or part of an OATP. Also encompasses are uses for OATPs for targeting drugs to specific organs and for modulating the concentration of endogenous substrates.

Abstract: In methods for screening treatments for, and treatment of, neurodegenerative diseases, aggregation in neurons of NACP/?-synuclein is measured and expression of a non-amyloidogenic protein is stimulated in order to reduce the level aggregration. For purposes of screening agents for treatment of neurodegenerative disease, oxidative stress in the neuronal cells is stimulated by introducing a mixture of metal-ions and hydrogen peroxide. Examples of appropriate metals include iron, aluminum, and copper. After introduction of the agent under evaluation for stimulation of expression of non-amyloidogenic protein, the effectiveness is measured by testing for a decrease in the level of aggregation of NACP/?-synuclein. In an exemplary embodiment, the non-amyloidogenic protein is ?-synuclein. The aggregation of NACP/?-synuclein is dependent upon the concentration of metal ions in the neuronal cells.

Abstract: The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

Abstract: The present provides compounds capable of modulating IL-4 receptor-mediated IgE production, as well as IL-4 induced processes associated therewith, methods and kits for identifying such compounds that utilize a BAP-37 as a surrogate analyte and methods of using the compounds in a variety of in vitro, in vitro and ex vivo contexts.

Abstract: The present invention provides compositions that enhance or inhibit the interactions of galectin-8 and galectin-8-like proteins with other extracellular matrix proteins or cell surface receptors, and methods for the use thereof as physiological modulators of cell adhesion and in treatment of tumors, both in vivo or ex vivo. It further provides compositions and methods for modulating the expression of galectin-8, and galectin-8-like proteins, particularly to novel antisense oligonucleotides.

Abstract: The invention relates to protein-protein interactions and methods for identifying interacting proteins and the amino acid sequence at the site of interaction. Using overlapping hexapeptides that encode for the entire amino acid sequences of the linker domains of human P-glycoprotein gene 1 and 3 (HP-gp1 and HP-gp3), a direct and specific binding between HP-gp1 and 3 linker domains and intracellular proteins was demonstrated. The method of the present invention was further validated with Annexin. The present invention thus demonstrates a novel concept whereby the interactions between two proteins are mediated by strings of few amino acids with high and repulsive binding energies, enabling the identification of high affinity binding sites between any interacting proteins.

Abstract: An assay method is disclosed which isolates and detects the presence of a disease related conformation of a protein (e.g., PrPSc) present in a sample also containing the non-disease related conformation of the protein (e.g., PrPC). The sample is treated (e.g., contacted with protease) in a manner which hydrolyzes the disease related conformation and not the non-disease related conformation. The treated sample is contacted with a binding partner (e.g., a labeled antibody which binds PrPSc) and the occurrence of binding provides and indication that PrPSc is present. Alternatively the PrPSc of the treated sample is denatured (e.g., contacted with guanadine) or unfolded. The unfolded PrPSc is contacted with a binding partner and the occurrence of binding indicates the presence of PrPSc in the sample.

Abstract: High affinity monoclonal antibodies for recognizing estrogen receptor (clone SP1) with immunohistochemistry and methods for creating such an antibody are disclosed. The lagomorph derived ER antibody provides a significant advantage over the currently available mouse ER antibodies in that there is no need for target retrieval when performing immunohistochemistry. Furthermore, the very low background when the lagomorph derived ER antibody is used in immunohistochemistry is also impressive. The immunohistochemistry comparative study with about fifty clinical specimens showed that the new ER (clone SP1) antibody had favorable results when compared to mouse monoclonal ER antibodies (clone 1D5). The lagomorph derived ER antibody may prove of great value in the assessment of ER status in human breast cancer. Humanized versions of the ER antibody may also provide therapeutic benefits.

Abstract: Disclosed are immunoassay methods for the diagnosis/prognosis of diseases and disease susceptibility traits associated with gene mutations that cause protein truncation or allelic loss. The levels of one or more targeted wild-type proteins expressed by a subject gene or genes are immunologically quantitated in biological samples. Results indicating that a targeted wild-type protein is not present in an assayed sample, or that approximately 50% of the normal amount of such a wild-type protein is present in an assayed sample are considered to be positive for a mutation in one or both alleles of a subject gene, and correlated with the disease or the disease susceptibility trait associated with that mutation or mutations. Normal cells, particularly normal peripheral blood lymphocytes, are preferred biological samples.

Abstract: The present provides compounds capable of modulating IL-4 receptor-mediated IgE production, as well as IL-4 induced processes associated therewith, methods and kits for identifying such compounds that utilize an adenosine kinase as a surrogate analyte and methods of using the compounds in a variety of in vitro, in vitro and ex vivo contexts.

Abstract: A method and kit of diagnosing endometriosis in a female patient suspected of having endometriosis. The method includes obtaining a sample from the patient. The sample is analyzed to detect the presence of a purified and isolated endometriotic haptoglobin designated ENDO-I and functional analogs thereof. A therapeutic for treating endometriosis by modulating the expression of a purified and isolated endometriotic haptoglobin designated ENDO-I and functional analogs thereof and a pharmaceutically acceptable carrier.

Abstract: A method of isolating and detecting the presence of a disease related conformation of a protein (e.g., PrPSc) is disclosed. The sample is treated such as by contacting it with a protease and then contacting the treated sample with a binding partner which binds the PrPSc which can be isolated and separated from the sample.

Abstract: The present invention provides reagents for use in an automated environment for removing or etching embedding media by exposing a biological sample to be stained in histochemical or cytochemical procedures without the dependence on organic solvents. The reagents comprise components optimized to facilitate removal or etching of the embedding media from the biological sample. The present invention also provides reagents for use in an automated environment for cell conditioning biological samples wherein the cells are predisposed for access by reagent molecules for histochemical and cytochemical staining procedures. The reagents comprise components optimized to facilitate molecular access to cells and cell constituents within the biological sample.

Abstract: Antibodies are disclosed which specifically bind to native PrPSc in situ. Preferred antibodies bind only to the native PrPSc of a particular species e.g., human, cow, sheep, pig, etc. Particularly preferred antibodies bind specifically to a particular isoform of human PrPSc. Preferred antibodies of the invention are (1) produced by phage display methodology, (2) bind specifically to native PrPSc, (3) neutralizes the infectivity of prions, (4) bind to PrPSc in situ and (5) bind 50% or more of PrPSc in a liquid flowable sample. Antibodies of the invention can be bound to a substrate and used to assay a sample (which has any PrPc denatured via proteinase K) for the presence of PrPSc of a specific species which PrPSc is associated with disease. Antibodies which specifically bind to human PrPSc can be labeled and injected carrying out an in vivo diagnostic test to determine if the human is infected with prions associated with disease.

Abstract: Methods of detecting novel therapeutically active compositions based on their ability to modulate the glycolipid metabolism and overcome multidrug resistance are described. These methods are particularly useful in screening for novel chemotherapeutic agents for the treatment of cancer, as well as chemosensitizers that are capable of enhancing the cytotoxicity of such chemotherapeutic agents. A combination of one or more of these compositions can be used in the treatment of a various cancers.

Abstract: New reactive dyes are described which can be used to fluorescently label bioorganic molecules such as amino acids, proteins, antibodies, nucleotides and also polymer particles. The color of the new dyes and conjugates thereof can be varied over a wide range. In contrast to known symmetric cyanine dyes, the dyes of the invention contain only one reactive group. Hence the labelling takes place without the interfering cross-linking that occurs with bireactive dyes. Their fluorescence quantum yields are very high (especially in the conjugated form). Conjugates thereof with proteins, oligonucleotides or particles can be used in fluorescence-based analytical methods of determination e.g. in immunoassays, in hybridization assays, in cytometry or for pharmaceutical screening.

Abstract: The present disclosure is directed to devices, arrays, kits and methods for detecting biomolecules in a tissue section (such as a fresh or archival sample, tissue microarray, or cells harvested by an LCM procedure) or other substantially two-dimensional sample (such as an electrophoretic gel or cDNA microarray) by creating “carbon copies” of the biomolecules eluted from the sample and visualizing the biomolecules on the copies using one or more detector molecules (e.g., antibodies or DNA probes) having specific affinity for the biomolecules of interest. Specific methods are provided for identifying the pattern of biomolecules (e.g., proteins and nucleic acids) in the samples. Other specific methods are provided for the identification and analysis of proteins and other biological molecules produced by cells and/or tissue, especially human cells and/or tissue.

Abstract: Methods for diagnosing and monitoring Alzheimer's Disease in a subject comprising measuring hK6 in a sample from the subject. hK6 may be measured using a reagent that detects or binds to hK6, preferably antibodies reactive with hK6.

Abstract: There is provided an apparatus for screening pharmacological agents for agents which induce regression of cancer. The apparatus includes an evanescent sensing device, at least one sensor having affixed to its surface molecules of a first type, which have affinity for molecules of a biological receptor, the surface molecule and receptor molecule combination having the effect that, in vivo, the binding affects the rate of transcription of gene products, and a molecular tag wherein the molecular tag is bound to the sensor wherein the binding between molecules of the first type and molecules the biological receptor cause the tag to produce a alteration in signal recorded by the evanescent sensing device, the tag also being bound to molecules of a second type, the molecules of the second type having affinity for the receptor molecules.

Abstract: A method to recover receptors without removing microenvironmental components associated with them is described. The membranes containing the receptors are first associated with ligand-coupled solid supports to achieve association of the membranes through a receptor/ligand complex which includes the microenvironment to the solid support and then removing the membrane from the receptor and its microenvironment by shear forces. The thus isolated receptors and their microenvironments can then be analyzed for their role in cellular differentiation, apoptosis, transformation and the like.

Abstract: The present invention provides a TADG-12 protein and a DNA fragment encoding such protein. Also provided is a vector/host cell capable of expressing the DNA. The present invention further provides various methods of early detection of associated ovarian and other malignancies, and of interactive therapies for cancer treatment utilizing the DNA and/or protein disclosed herein.

Abstract: Increased expression of resistance sequences is associated with drug resistance of certain cells (e.g., cancer cells). The invention provides methods for identifying drug resistant cells by measuring the expression or activity of resistance genes (e.g., semaphorin D, B94, mel-14 antigen, 24p3, proliferin, or maspin), methods for identifying modulators of drug resistance, and methods for modulating drug resistance by modulating the expression or activity of resistance sequences.

Abstract: Methods are described for the use of transferrin binding as the basis for a diagnostic assay to identify pathologies consistent with demyelinating diseases including Multiple Sclerosis. In a specific embodiment the evaluation of transferrin binding, in brain tissue, is used in a method for the detection of multiple sclerosis.

Abstract: A method for judging an autoimmune disease by detecting the existence of an anti-Reg protein autoantibody in a specimen; and a method for judging insulin-dependent or non-insulin-dependent diabetes mellitus. A method for detecting an anti-Reg protein autoantibody by bringing into a specimen into contact with an antigen component and detecting the formation of an immune complex. A reagent for diagnosing autoimmune disease which contain an antigen component capable of binding specifically to the anti-Reg protein autoantibody; and a reagent for diagnosing insulin-dependent or non-insulin-dependent diabetes mellitus.

Abstract: The present invention relates to fluorescent cobalamins and uses of these compounds. More particularly, this invention relates to fluorescent cobalamins that comprise a fluorescent, phosphorescent, luminescent or light-producing compound covalently linked to cobalamin. These fluorescent cobalamins can be used to as diagnostic and prognostic markers (a) to distinguish cancer cells and tissues from healthy cells and tissues, including identifying lymph nodes containing cancer cells, and (b) to determine if an individual will respond positively to chemotherapy using cobalamin-therapeutic bioconjugates.

Abstract: The present invention provides new methods for detecting, diagnosing, monitoring, staging, prognosticating, imaging and treating cancer.

Abstract: This invention relates to a remedy for neuropathy, such as nerve injury, nerve degeneration, and hypofunction upon nerve grafting, which contains as the active ingredient galectin-1 having an amino acid sequence represented by SEQ ID NO:1 or its derivative; a protein having the amino acid sequence represented by SEQ ID NO:1 or one having a homology of 90% or more at the amino acid level with the sequence of SEQ ID NO:1 and carrying a disulfide bond(s) at least between Cys at the 16-position (Cys 16) and Cys at the 88-position (Cys 88) among cystein residues at the 2-position (Cys 2), 16-position (Cys 16), 42-position (Cys 42), 60-position (Cys 60), 88-position (Cys 88) and 130-position (Cys 130); and a process for producing the galectin-1 or its derivative protein by using an affinity column having an antibody to the above protein.

Abstract: The invention relates to methods and compositions for the isolation of neural progenitor cells.

Abstract: A method of measuring the physical and chemical properties of tissue or cells and a device for the same is provided, with which the physical and chemical environment of the tissue or cells can be changed arbitrarily corresponding to experimental necessities. The device comprises a system 40 for keeping the physical and chemical environment surrounding the biological tissue or cells constant, a system 50 for arbitrarily changing the physical and chemical environment, observation systems 10 and 20 for observing the physical and chemical properties of the tissue or cells, and a system 30 for comparing the change of the physical and chemical properties of the tissue or cells before and after changing the physical and chemical environment. The observation system 10 is a potential measurement device for measuring the electrophysiological properties of the tissue or cells.

Abstract: The invention provides methods of screening for a compound for promoting wakefulness in a mammal. The method is practiced by providing a compound that is a PrRP receptor agonist and determining the ability of the compound to promote wakefulness. Also provided by the invention are methods of screening for a compound for promoting sleep in a mammal. The methods are practiced by providing a compound that is a PrRP receptor antagonist and determining the ability of the compound to promote sleep. In addition, the invention provides a method of promoting wakefulness in a mammal. The method is practiced by administering to a mammal an effective amount of a PrRP receptor agonist. The invention further provides a method of promoting sleep in a mammal. The method is practiced by administering to a mammal an effective amount of a PrRP receptor antagonist.

Abstract: An assay method is disclosed which isolates and detects the presence of a disease related conformation of a protein (e.g., PrPSc) present in a sample also containing the non-disease related conformation of the protein (e.g., PrPC). The sample is treated (e.g., contacted with protease) in a manner which hydrolyzes the disease related conformation and not the non-disease related conformation. The treated sample is contacted with a binding partner (e.g., a labeled antibody which binds PrPSc) and the occurrence of binding provides and indication that PrPSc is present. Alternatively the PrPSc of the treated sample is denatured (e.g., contacted with guanadine) or unfolded. The unfolded PrPSc is contacted with a binding partner and the occurrence of binding indicates the presence of PrPSc in the sample.

Abstract: The invention provides immunological reagents (antibodies) capable of binding to plasmacytoid dendritic cells (pDC), to cell lines which express such antibodies and to a process for identifying and purifying plasmacytoid dendriticcells from tissues containing pDC using such antibodies.

Abstract: This invention provides a method of measuring oxidative response of cells without recourse to preparation of cell culture. The process involves: 1) preparing suspensions of cells from a living host in isotonic solutions, 2) preparing samples of test materials in isotonic solution containing tagged choline, 3) adding the cells suspension prepared in step 1 to the samples prepared in step 2, 4) incubating the product of step 3 with shaking for 2-90 minutes, 5) extracting and drying the lipid phase from the product of step 4, and 6) subjecting the product of step 5 to a scintillation counter to measure choline which has been incorporated into phosphatidylcholine (PC). An increase in incorporation of choline into PC in the short term indicates oxidative stress or free radical induced damage. Because the method of the invention using the cell isolates does not require the expense of cell culture with concomitant expense and possibility of cell change, it is particularly useful for clinical evaluation.