Abstract: The present invention relates to 9-substituted adenine derivatives represented by formula (I) wherein W is selected from the group consisting of H, halogen, azido and amino group; X is selected from the group consisting of O, S, N(H), CH2, CH and C; Y is selected from the group consisting of H, hydroxy, C1-4 alkyl, C1-4 alkoxy and halogen; R is selected from the group consisting of H, hydroxymethyl, C1-4 alkyl, and C1-4 alkoxy; R1is selected from the group consisting of O, NH and CH2; R2represents a radical selected from the group consisting of —(CH2)n—S—C(O)—R4 and —(CH2)n—S—S—R4, where n=1-4 and R4is a C1-4-alkyl or aryl group and R4 is optionally substituted with a halogen, amino, N-alkylamino, N, N-dialkylamino or C1-4 alkoxy group and wherein each of the R2radicals may be the same or different; and R3is O or S. The derivatives are useful as prodrugs for inhibiting adenylyl cyclase and lowering 3?:5?-cAMP in cells, thereby inhibiting adenylyl cyclase dependent effects within cells.

Abstract: The invention is directed to purified and isolated SIGIRR polypeptides and fragments thereof, the nucleic acids encoding such polypeptides, processes for production of recombinant forms of such polypeptides, antibodies generated against these polypeptides, fragmented peptides derived from these polypeptides, and uses thereof.

Abstract: The invention concerns the Notch3 gene and the corresponding protein, which are involved in CADASIL. The invention concerns, in particular, methods for demonstrating mutations in this gene, which are linked to the risk of developing CADASIL. The invention also concerns models and products for treating CADASIL and related diseases.

Abstract: The present invention provides a method for screening a compound or its salt that alters the binding property between MCH or its salt and SLC-1 or its salt, characterized by using MCH or its derivative or a salt thereof and SLC-1 or its salt is useful for screening an SLC-1 agonist which can be used not only as an appetite (eating) promoting agent but also as a prophylactic/therapeutic agent for weak pains, atonic bleeding, before and after expulsion, subinvolution of uterus, cesarean section, induced abortion, galactostasis, and the like, and an SLC-1 antagonist which can be used not only as an antiobestic agents (drug), an appetite (eating) modulator, and the like, but also as a prophylactic/therapeutic agent for hyperstimulation, ankylosing uterine contractions, fetal distress, uterine rupture, cervical laceration, preterm delivery, Prader-Wili syndrome and the like.

Abstract: A sensor is provided including a polymer capable of having an alterable measurable property from the group of luminescence and electrical conductivity, the polymer having an intermediate combination of a recognition element, a tethering element and a property-altering element bound thereto and capable of altering the measurable property, the intermediate combination adapted for subsequent separation from the polymer upon exposure to an agent having an affinity for binding to the recognition element whereupon the separation of the intermediate combination from the polymer results in a detectable change in the alterable measurable property, and, detecting said detectable change in the alterable measurable property.

Abstract: Melanin concentrating hormone receptor ligands (especially 1-benzyl-4-aryl-piperazines, 1-benzyl-4-aryl-piperidines and related compounds), capable of modulating MCH receptor activity, are provided. Such ligands may be used to modulate MCH binding to MCH receptors in vivo or in vitro, and are particularly useful in the treatment of a variety of metabolic, feeding and sexual disorders in humans, domesticated companion animals and livestock animals. Pharmaceutical compositions and methods for treating such disorders are provided, as are methods for using such ligands for detecting MCH receptors (e.g., receptor localization studies).

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: The invention concerns a novel gene, called NPHS2 gene coding for a protein involved in the cortico-resistant nephrotic syndrome, and diagnostic and therapeutic uses of the novel identified nucleotide sequences and amino acids.

Abstract: DNAs encoding the human histamine H3 receptor have been cloned and characterized. The recombinant protein is capable of forming biologically active histamine H3 receptor protein. The cDNA's have been expressed in recombinant host cells which produce active recombinant protein. The recombinant protein is also purified from the recombinant host cells. In addition, the recombinant host cells are utilized to establish a method for identifying modulators of the receptor activity, and receptor modulators are identified.

Abstract: The present invention is directed to a DNA element that enhances the translation of the human amyloid precursor protein (APP) gene. The enhancer may be incorporated into expression vectors to enhance recombinant protein production. In addition, the invention is directed to an assay that utilizes vectors containing the translation enhancer element for the purpose of identifying agents that modulate the expression of the human amyloid precursor protein. These agents will ultimately be used to suppress APP expression in patients with Alzheimer's disease.

Abstract: The present invention is directed to the radioligand compound, [35S]-radiolabeled (+)-N-[1?-(6-cyano-1,2,3,4-tetrahydro-2(R)-naphthalenyl)-3,4-dihydro-4(R)-hydoxyspiro[2H-1-benzopyran-2,4?-piperidin]-6-yl]methanesulfonamide. Also within the scope of this invention is a method for identifying compounds that bind to the IKr channel, and may have antiarrhythmic activity.

Abstract: The invention is directed to purified and isolated novel human IL-1 epsilon polypeptides, the nucleic acids encoding such polypeptides, processes for production of recombinant forms of such polypeptides, antibodies generated against these polypeptides, the use of such polypeptides in cellular and immune reactions, the use of such polypeptides in screening for agonists or antagonists of IL-1 epsilon activity, and kits comprising such polypeptides.

Abstract: The invention provided herein relates generally to purified genes encoding mammalian cytokines as well as reagents related thereto including purified proteins, specific antibodies, and nucleic acids encoding these molecules. In particular, the novel cytokine, IL-B30, is provided herein as well as methods and kits for the detection of the expression of IL-B30 polynucleotides.

Abstract: The synthesis of novel diketopiperazines, their use in inhibiting cellular events such as those involving NFK-&agr;, NFK-&bgr; and in the treatment of inflammation events, a combinatorial library of diverse diketopiperazines and process for their synthesis as a library and as individual compounds. In particular novel diketopiperazines are disclosed including their synthesis and use in cellular events such as activation of the transcription factor, nuclear factor, TNF-&agr;, TNF-&bgr; and also apoptosis.

Abstract: With respect to a range of 1.5 Mbp and more in the chromosome 19p13.3 region containing Peutz-Jeghers gene, a continuous cosmid contig is constructed and a restriction map is prepared. Next, genes mapped with this region are searched by using EST database and the locations of these genes are accurately determined. Based on the evaluation of biological data, etc., several highly likely candidates for Peutz-Jeghers genes are specified from the genes thus found. After successively analyzing variations in these genes in DNAs of patients with Peutz-Jeghers syndrome, it is found that one of these genes, i.e., “LKB1” has been specifically varied in these patients. Thus, the diseases caused by the variation in the LKB1 gene can be diagnosed and treated by using the LKB1 gene, primers and probes based on its base sequence, LKB1 protein, an antibody biding to this protein, etc.

Abstract: Provided are novel complexes containing a crosslinked avidin, an analyzing method and analyzing reagents and kits whereby a compound to be analyzed can be quickly, conveniently and accurately analyzed while taking advantage of the avidin-biotin reaction. The complexes contain at least two homogeneous or heterogeneous biotin-introduced products and one crosslinked avidin sandwiched therebetween. In the analyzing method, the homogeneous or heterogeneous biotin-introduced products and the crosslinked avidin are used. The analyzing reagent contains the crosslinked avidin. The analyzing kit contains the crosslinked avidin and a biotinylating agent.

Abstract: The invention provided sets of genes that are expressed differentially in normal and malignant endometrium. These sets of genes can be used to discriminate between normal and malignant endometrial tissues. Accordingly, diagnostic assays for classification of tumors, prediction of tumor outcome, selecting and monitoring treatment regimens and monitoring tumor progression/regression also are provided.

Abstract: Methods for detecting schizophrenia or related neuropsychiatric disorders based on modifications of the contribution of the D4 receptor to phospholipid methylation levels are described herein. Individuals with schizophrenia or related neuropsychiatric disorders have a deficiency in phospholipid methylation activity compared with normal individuals. Methods for screening therapeutic processes or agents for use in treatment of schizophrenia or related neuropsychiatric disorders are also described.

Abstract: A set of contiguous and partially overlapping cDNA sequences and polypeptides encoded thereby, designated as BU101 and transcribed from breast tissue, is described. These sequences are useful for the detecting, diagnosing, staging, monitoring, prognosticating, in vivo imaging, preventing or treating, or determining the predisposition of an individual to diseases and conditions of the breast, such as breast cancer. Also provided are antibodies which specifically bind to BU101-encoded polypeptide or protein, and agonists or inhibitors which prevent action of the tissue-specific BU101 polypeptide, which molecules are useful for the therapeutic treatment of breast diseases, tumors or metastases.

Abstract: A method for measuring free ligands in biological fluids in the presence of bound ligand and endogenous binding proteins, without disturbing the equilibrium between the free ligand and the protein-bound ligand, comprised of the following steps: (a) incubating a sample of biological fluid with (i) a ligand analog tracer which, due to its chemical structure, does not bind to some of the endogenous binding proteins, (ii) a specific ligand binder and (iii) specific chemical inhibitor reagents that alone or in combination inhibit the binding of the ligand analog tracer to other endogenous binding proteins; (b) separating the ligand analog tracer bound to the specific binder from unbound tracer; and (c) comparing the bound fraction in said sample to the bound fraction of a given set of known free ligand calibrators to determine the concentration of free ligand in said biological fluid.

Abstract: A method for assaying an analyte in a sample. The method comprising the steps of a) contacting the sample with material comprising a receptor which is present in a liposome and which liposome comprises a detectable functionality, said contact occurring under conditions resulting in binding of the receptor to analyte if present before or concomitant with step b, wherein step b) consists of contacting the sample with an immobilised ligand for the receptor said contact occurring under conditions resulting in binding of the receptor to the ligand, with steps a and b being followed by c) separating the resulting immobilised ligand-receptor fraction and the receptor fraction present in solution and d) assaying the detectable functionality of the receptor in a fraction from step c) in a manner known per se for its detection.

Abstract: A predictive test for rheumatoid arthritis comprises the detection of antibodies to collagen in a biological sample from a patient by contacting the biological sample with an antigen comprising the CB10 peptide of mammalian type II collagen, or an antibody-binding fragment or variant thereof, for a time and under conditions for an antibody-antigen complex to form, and detecting the antibody-antigen complex, for example by immunoassay. A diagnostic test kit is also disclosed.

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: A method of evaluating for the presence of a polypeptide in an analyte, using an addressable array of capture agents linked to a substrate. The analyte is exposed to the array and a set of fixed capture agents, such that the target molecules will bind to the array by means of the capture agents. After the target molecule has bound to the capture agents, it is modified using a label. The label does not interact or mark the capture agent. Kits using such arrays are further provided.

Abstract: The present invention encompasses methods for determining the likelihood that benign hyperplastic breast tissue or normal breast tissue adjacent to carcinoma tissue will become malignant. The methods comprise substantially isolating the tissue; and determining loss of heterozygosity (LOH) at chromosome 3p24 in the tissue. LOH at chromosome 3p24 is a prognostic indicator that the tissue may become malignant.

Abstract: An antibody that binds to a specific urogenital carcinoma tumor liberated protein (TLP) epitope, wherein the TLP comprises GlyProProGluValGlnAsnAlaAsn, is described. Also described are kits comprising the antibody, and methods of identifying TLP, and methods for diagnosing urogenital carcinoma.

Abstract: A method for labeling &bgr;-amyloid plaques and neurofibrillary tangles in vivo and in vitro, comprises contacting a compound of formula (I): with mammalian tissue.

Abstract: The present invention provides a method capable of simultaneous processing of plural test samples for the receptor binding property of a chemical substance, which does not require immobilization of the receptor or a special device, and a reagent to be used for this method. That is a method for assaying the receptor binding property of an assay target substance is provided, the method comprising the steps of (a) competitively reacting a known concentration of a ligand and the assay target substance with a known concentration of the receptor in a solution, (b) measuring, without physically removing the ligand bound with the receptor prior to the assay, the amount of a free ligand in the solution using one or more antibodies against the ligand, and (c) determining the receptor binding property of the assay target substance using the amount of the free ligand as an index.

Abstract: A method for diagnosis of pre-eclampsia is disclosed, which comprises measuring the hormone inhibin A in a biological sample such as maternal serum. The method allows non-invasive, early diagnosis and can be used to predict the onset of secondary symptoms.

Abstract: The present invention discloses a novel secreted polypeptide, termed Osteoprotegerin, which is a member of the tumor necrosis factor receptor superfamily and is involved in the regulation of bone metabolism. Also disclosed are nucleic acids encoding Osteoprotegerin, polypeptides, recombinant vectors and host cells for expression, antibodies which bind Osteoprotegerin, and pharmaceutical compositions. The polypeptides are used to treat bone diseases characterized by increased resorption such as osteoporosis.

Abstract: The present invention relates to compositions and methods for genetic analyses. More particularly, this invention provides compositions and methods for differential gene expression analyses on biological material, such as tissue sections. This invention discloses more preferably differential gene expression analyses on biological material using particular probes with distinct radioactive labels. The present invention can be used to detect or monitor gene expression, compare gene expression (e.g., differential gene expression screening) in particular in different tissues, and is suitable for instance in research, diagnostic, and many pharmacogenomics applications.

Abstract: Methods and systems for identifying material from a breast duct using one or more markers that can be identified in ductal fluid retrieved from the breast are provided.

Abstract: Mitochondrial mutations occur as a product of contact of a person with an environmental pollutant. Mitochondrial mutations are readily detectable in body fluids. Measurement of mitochondrial mutations in body fluids can be used as a dosimeter to monitor exposure to the environmental pollutant. Mitochondrial mutations can also be detected in cancer patients. Probes and primers containing mutant mitochondrial sequences can be used to monitor patient condition.

Abstract: This invention relates to a method of predicting pregnancy, particularly, in a cow, the method comprising taking a milk sample from the cow in which a milk progesterone concentration of >3 ng ml−1 by Day 4 post insemination is indicative that the animal is pregnant. The invention also relates to methods of improving pregnancy success by timely supply of progesterone or a functional equivalent thereof (progestagen); to methods of assessing suitability for progesterone replacement therapy; and to methods of embryo transfer.

Abstract: A sensor element is provided including a polymer exhibiting a measurable property from the group of luminescence and electrical conductivity, the polymer being complexed with a unit including a recognition element, a tethering element and a property-altering element bound thereto so as to alter the measurable property, the unit being susceptible of subsequent separation from the polymer upon exposure to an agent having an affinity for binding to the recognition element whereupon the separation of the unit from the polymer results in a detectable change in the measurable property.

Abstract: A method of producing a diagnostic or therapeutic conjugate of a protein, polypeptide or peptide containing at least one disulfide bond which is necessary to maintain its biological activity, and bearing at least one thiol-containing moiety linked thereto through a hydrazone or hydrazine linkage, is effected by contacting said protein, polypeptide or peptide with a thiol-reactive diagnostic or therapeutic agent, either preformed or generated in situ, to form a stable diagnostic or therapeutic conjugate of the protein, polypeptide or peptide without substantial cleavage of the disulfide bond. Diagnostic and therapeutic conjugates produced using the foregoing method, as well as kits for carrying out the method are provided.

Abstract: Quinazolinones of formulae 1a, 1b, 1c and 1d are disclosed. They are useful for treating cellular proliferative diseases and disorders associated with KSP kinesin activity.

Abstract: The full amino acid and DNA sequences of placental protein 13 (PP13) are disclosed. Also described are various PP13 derived peptide fragments, and a recombinant method for the production of PP13. PP13 may be used in a screening and a diagnostic method for pregnancy-related complications.

Abstract: A method of treating cancer in a patient deficient in p53 tumor suppression gene is described herein by administering to a patient a therapeutically effective amount if a polyamine such as DENSPM in combination with an anticancer agent. Also described is a method of selecting patients for cancer treatment with a polyamine, for example, DENSPM.

Abstract: An improved electrochemical method for disassociating a biological binding partner from a corresponding second biological binding partner associated with a waveguide surface, the electrochemical method involving the application of an electrical potential to said waveguide surface (118), the improvement comprising: applying the electrical potential to the waveguide surface (118) as a square wave polarization function. Preferably, the waveguide surface is comprised of indium tin oxide. The biological binding partners are selected from the group consisting of antigen-antibody, avidin-biotin, enzyme-substrate, cell receptor-substrate/analog, antibody/anti-antibody, DNA, RNA, and fragments thereof. The antigen may be comprised of an epitope. The epitope is produced by a solid phase peptide synthesis performed on said waveguide surface (118).

Abstract: The invention provides a method of measuring the level of two or more nucleic acid molecules in a target by contacting a probe with a target comprising two or more nucleic acid molecules, wherein the nucleic acid molecules are arbitrarily sampled and wherein the arbitrarily sampled nucleic acid molecules comprise a subset of the nucleic acid molecules in a population of nucleic acid molecules; and detecting the amount of specific binding of the target to the probe. The invention also provides a method of measuring the level of two or more nucleic acid molecules in a target by contacting a probe with a target comprising two or more nucleic acid molecules, wherein the nucleic acid molecules are statistically sampled and wherein the statistically sampled nucleic acid molecules comprise a subset of the nucleic acid molecules in a population of nucleic acid molecules; and detecting the amount of specific binding of the target to the probe.

Abstract: A drug screening assay for identifying compounds for their potential effects on the long chain fatty acid dependant intracellular membrane anchorage sites of lipoproteins. Membranes-anchoring-target are incubated in the presence of the compound to be tested and the proportion of the target that is released by the compound is detected and quantitated. The benchmark for this assay are the prenylated proteins such as the farnesylated and palmitoylated oncogenic ras trigger proteins which are displaced from their anchorage at the intracellular plasma membrane by derivatives of Farnesyl Thiosalicylic Acid (FTS). The assay is adaptable to flexibly assay a large variety of anchored targets using a wide range of labeling and detection techniques in test wells, tissue culture, and in animals as injected cells or transgenic, thereby directly addressing a wide range of pharmacologically relevant needs.

Abstract: In an automated analyzer containing a spectrophotometer for determining color changes in a urine sample the urine is admixed with a basic indicator effecting the first color change and an acidic indicator effecting a second color change, a surfactant and water. The spectrophotometer determines and prints whether a first or second color change has occurred.

Abstract: The invention provides a competition binding assay for detecting P2YADP receptor ligands.

Abstract: Methods are disclosed for treating heart failure. Methods are disclosed for screening pharmacologicals that inhibit the down-regulatory activity of AUF1 or AUF1-related polypeptide for &bgr;-adrenergic activity. Methods are disclosed for treating a patient with a high level of the AUF1 or AUF1-related gene.

Abstract: We have identified and purified to homogeneity from lymphatic tissues a 8.4 kDa immunophilin that specifically and avidly binds the immunosuppressant drugs FK-506 (Kd=0.8 nM) and rapamycin (Kd=0.08 nM) and their pharmacologically active metabolites and derivatives, but does not bind cyclosporin A. The isolated 8.4 kDa protein appears to be identical to authentic human and bovine ubiquitins in all measured respects (partial amino acid sequence, molecular weight, binding constants, binding specificity, biochemical aspects, and utility as the protein binding reagent in binding assays for immunosuppressant drugs in fluid samples, including patient blood). The availability of commercial quantities of human recombinant ubiguitin removes a supply barrier to the use of immunophilin protein binding assays for the estimation of FK-506, rapamycin and pharmacologically active metabolites and derivatives in the clinical setting.

Abstract: Growth differentiation factor-3 (GDF-3) is disclosed along with its polynucleotide sequence and amino acid sequence. Also disclosed are diagnostic and therapeutic methods of using the GDF-3 polypeptide and polynucleotide sequences.

Abstract: The invention provides isolated nucleic acids encoding a variety of nucleic acids and proteins having diagnostic, preventive, therapeutic, and other uses. These nucleic acids and proteins are useful for diagnosis, prevention, and therapy of a number of human and other animal disorders. The invention also provides antisense nucleic acid molecules, expression vectors containing the nucleic acid molecules of the invention, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a nucleic acid molecule of the invention has been introduced or disrupted. The invention still further provides isolated polypeptides, fusion polypeptides, antigenic peptides and antibodies. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided. The nucleic acids and polypeptides of the present invention are useful as modulating agents in regulating a variety of cellular processes.

Abstract: The present invention relates to methods for the detection of substances capable of modulating or inhibiting pathological tau-tau protein association. The methods of the present invention are particularly useful in screening substances for the prophylaxis and treatment of Alzheiemer's disease.