Abstract: The present invention relates to a dermatomyositis-specific auto-antigen, a DNA encoding it and a process for the preparation thereof as well as its use.

Abstract: A method for determining the existence and the amount of soluble fibrin contained in a specimen fluid is provided. The method includes the steps of precipitating soluble fibrin out of the opaque specimen fluid, aggregating the soluble fibrin precipitates in a limited region of a transparent container so as to render the precipitates optically detectable in the opaque specimen fluid, and optically detecting the precipitates. The amount of soluble fibrin may be determined by measuring the time from the addition of the precipitating regent to the detection of the soluble fibrin precipitates. Methods of the present invention allow one to measure soluble fibrin in whole blood, and therefore render the test useful in the operating room under conditions of major surgery and in the presence of severe trauma wherein DIC is likely to supervene.

Abstract: The invention relates generally to compositions of and methods for obtaining and using a polypeptide other than BCL-2 that affects programmed vertebrate cell death. The invention relates as well to polynucleotides encoding those polypeptides, recombinant vectors carrying those sequences, the recombinant host cells including either the sequences or vectors, and recombinant polypeptides. The invention further provides methods for using the isolated, recombinant polypeptides in assays designed to select and improve substances capable of altering programmed cell death for use in diagnostic, drug design and therapeutic applications.

Abstract: A method for preparing polypeptide ligands of target molecules wherein candidate mixtures comprised of ribosome complexes or mRNA&Circlesolid;polypeptide copolymers are partitioned relative to their affinity to the target and amplified to create a new candidate mixture enriched in ribosome complexes or mRNA&Circlesolid;polypeptide copolymers with an affinity to the target.

Abstract: The present invention provides an isolated or purified antibody or antigenically-reactive fragment thereof that specifically binds to a C-terminal phosphorylated serine in an H2A histone protein and a product comprising the same. The present invention further provides fusion proteins comprising the isolated or purified antibody or antigenically-reactive fragment thereof. Also provided by the present invention are a method and a kit for determining double-stranded breaks in DNA. The method comprises contacting a sample comprising H2A histone proteins with the isolated or purified antibody or antigenically-reactive fragment thereof and detecting binding of the antibody or fragment thereof to an H2A histone protein in the sample. The detection of the binding of the antibody or fragment thereof to the H2A histone protein indicates the presence of a DNA double-stranded break in DNA.

Abstract: Overexpression of a CRAF1 (CD40 receptor-associated factor 1) gene truncated by 323 to about 414 amino acids at the amino inhibits CD40-mediated cell activation, and is used to treat conditions characterized by an unwanted level of CD40-mediated intracellular signaling.

Abstract: A diagnostic drug and a diagnostic kit for autoimmune diseases including at least one of a polypeptide selected from an HMG-1 family, a polypeptide selected from an HMG-2 family, a fragment thereof which is reactable with an antibody of an autoimmune disease patient, and a method for detecting an antibody of an autoimmune disease patient using the same are provided.

Abstract: The present invention relates generally to a newly identified adaptor protein FRS2 and related products and methods. FRS2 links protein kinases to activating partners in cells. The invention also relates to nucleic acid molecules encoding portions of FRS2, nucleic acid vectors containing FRS2 related nucleic acid molecules, recombinant cells containing such nucleic acid vectors, polypeptides purified from such recombinant cells, antibodies to such polypeptides, and methods of identifying compounds that enhance or block FRS2 interactions with natural binding partners. Also disclosed are methods for diagnosing abnormal conditions in an organism with FRS2 related molecules or compounds.

Abstract: Nuclear matrix proteins (NMP) are useful markers in diagnosing and monitoring the stage of malignancy of a cell, and in treating cell proliferative disorders associated with the NMP.

Abstract: The present invention encompasses an SH3 domain-containing TADG5 protein (SEQ ID No. 1), allelic variants or functional fragments thereof, a novel TADG5 DNA segment coding for the TADG5 protein (SEQ ID No. 2), allelic variants or functional fragments thereof, chimeric cells comprising the TADG5 DNA segment, expression vectors and plasmids comprising the TADG5 DNA segment and methods for producing the TADG5 protein. The present invention further encompasses methods of using the TADG5 protein (e.g., for gene regulation, etc.).

Abstract: The invention relates to the discovery and purification of novel intracellular vitamin D binding proteins (IDBPs) and the isolation of polynucleotide sequences encoding the proteins. IDBPs are of interest because they mediate the vitamin D resistance, i.e., insensitivity, observed in new world primates. IDBPs are distinct from the vitamin D receptor and other intracellular receptors, e.g. estrogen receptor. One aspect of the invention is to provide purified IDBPs as pharmaceutical compositions to affect steroid hormone activity. Another aspect of the invention provides polynucleotides encoding the IDBPs of the invention for use in altering the expression of IDBPs. Yet another aspect of the invention is to provide assays for the detection or screening of therapeutic compounds that interfere with the interaction between IDBP and vitamin D (or other ligands that bind to IDBP), and the use of such compounds as pharmaceutical compositions.

Abstract: Agents which inhibit the Jak-Stat signal transduction pathway are identified in order to identify candidate drugs for treatment of proliferative disorders. Identification methods are alternatively based on inhibiting the interaction of: (1) the activated Stat3 and Stat5 transcription factors with an electrophoretic mobility shift assay probe, or (2) the Stat3 or Stat5 proteins with the IL-2R&bgr; chain of the IL-2 receptor.

Abstract: Described are DNA-repair fusion proteins of multiple, complementary DNA repair proteins and having the activity of each protein, and related polynucleotides and vectors. The proteins, when expressed in cells, e.g., hematopoietic cells, increase the survival rate of the cells when contacted with chemotherapeutic agents. Also described are transgenic animal models wherein these proteins are expressed in essentially all cells of the animal. Such animal models are useful for instance in testing chemotherapeutic agents.

Abstract: The present invention features a human Nkx-2.2 polypeptide and nucleotide sequences encoding Nkx-2.2 polypeptides. In a particular aspect, the polynucleotide is the nucleotide sequence of SEQ ID NO:1. In addition, the invention features polynucleotide sequences that hybridize under stringent conditions to SEQ ID NO:1. In related aspects the invention features expression vectors and host cells comprising polynucleotides that encode a human Nkx-2.2 polypeptide. The present invention also relates to antibodies that bind specifically to a human Nkx-2.2 polypeptide, and methods for producing human Nkx-2.2 polypeptides.

Abstract: Nuclear matrix proteins (NMP) are useful markers in diagnosing and monitoring the stage of malignancy of a cell, and in treating cell proliferative disorders associated with the NMP.

Abstract: The invention features a nucleic acid molecule encoding a chondrosarcoma associated polypeptide and methods for diagnosing patients with chondrosarcoma. the gene.

Abstract: Human REQUIEM polypeptides and DNA (RNA) encoding such REQUIEM and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such REQUIEM for the treatment of a susceptibility to viral infection, tumorogenesis and to diseases and defects in the control of embryogenesis and tissue homeostasis, and the nucleic acid sequences described above may be employed in an assay for ascertaining such susceptibility.

Abstract: The present invention relates to chromotropic nitrone spin trapping agents, methods of making these agents, compositions comprising same, and methods of their use. In particular, azulenyl nitrones of the present invention are effective agents for trapping free radical species and find use as efficient antioxidants in physicochemical and biological systems. Accordingly, the invention also relates to spin adducts formed from the combination of azulenyl nitrones with free radicals. The compounds of the present invention are readily prepared from available starting materials and find further use in assays and in a number of diagnostic, prophylactic and therapeutic applications, including but not limited to the alleviation, modulation and inhibition of the negative effects of carbon-centered or oxygen-centered radical species and other products of oxidation. Moreover, the combination adducts may be calorimetrically detected and, optionally, isolated and characterized to obtain valuable information (e.g.

Abstract: A method for preparing polypeptide ligands of target molecules wherein candidate mixtures comprised of ribosome complexes or mRNA•polypeptide copolymers are partitioned relative to their affinity to the target and amplified to create a new candidate mixture enriched in ribosome complexes or mRNA•polypeptide copolymers with an affinity to the target.

Abstract: The invention discloses a direct interaction between D-type cyclins and a novel myb-like transcription factor, DMP1, which specifically interacts with cyclin D2. The present invention also provides evidence that D-type cyclins regulate gene expression in an RB-independent manner. Also included is DMP1, the transcription factor composed of a central DNA-binding domain containing three atypical myb repeats flanked by highly acidic segments located at its amino- and carboxyterminal ends. The invention includes amino acid sequences coding for DMP1, and DNA and RNA nucleotide sequences that encode the amino acid sequences. A use of DMP1 as a transcription factor is disclosed due to its specificity in binding to oligonucleotides containing the nonamer consensus sequence CCCG(G/T)ATGT. In this aspect of the invention, DMP1 when transfected into mammalian cells, activates the transcription of a reporter gene driven by a minimal promoter containing concatamerized DMP1 binding sites.

Abstract: A protein consisting essentially of purified human minor vault protein p193 or purified biologically active variants thereof, or a combination of purified human minor vault protein p193 and biologically active variants thereof. Also, a polynucleotide molecule encoding a protein which consists essentially of human minor vault protein p193, or its complementary strands. Further, there is provided a method of diagnosing and a method of treating patients with multidrug resistant cancer.

Abstract: A pharmaceutical composition useful for nucleic acid transfection is disclosed. The composition contains, in addition to a nucleic acid and at least one transfection agent, at least one compound that combines DNA binding properties with a nuclear DNA vectorisation capability, and preferably belongs to the HMG ("High mobility group") protein family. The use of said composition for in vitro, ex vivo and/or in vivo nucleic acid transfer is also disclosed.

Abstract: A class of mutant forms of p53 protein, such as His273 and Lys285, which are defective in conversion from the latent to the activated state by casein kinase II, but with the ability to be activated for specific DNA binding by the action of ligands such as monoclonal antibody PAb421 and heat shock protein DnaK. Activation of these mutants, which are found at high levels in certain types of tumour, can potentially lead to selective growth arrest and induction of apoptosis in the tumor cells. p53 can be constitutively activated also by deletion of the C-terminal 30 amino acids. p53 activated in this way, or by ligand binding, can be administered for the purposes of tumour or cell growth suppression.

Abstract: This invention relates in general to a phosphoprotein product of the retinoblastoma susceptibility gene. In particular, this invention relates to a phosphoprotein ppRB.sup.110 primarily located in the cell nucleus which has a DNA binding activity. The invention also relates to the amino acid sequence of the phosphoprotein and to the specific purified anti-retinoblastoma phosphoprotein antibody. The invention further relates to a method of diagnosing retinoblastoma and other retinoblastoma gene involved cancers, treating such kind of cancers and regulating the oncogenicity of other genes.

Abstract: A monoclonal or polyclonal antibody directed against urokinase plasminogen activator receptor (u-PAR), or a subsequence, analogue or glycosylation variant thereof. Antibodies are disclosed which react with free u-PAR or with complexes between u-PA and u-PAR and which are capable of 1) catching u-PAR in ELISA, or 2) detecting u-PAR, e.g. in blotting, or 3) in radioimmunoprecipitation assay precipitate purified u-PAR in intact or fragment form, or 4) is useful for immunohistochemical detection of u-PAR, e.g. in immunostaining of cancer cells, such as in tissue sections at the invasive front, or 5) inhibits the binding of pro-u-PA and active u-PA and thereby inhibits cell surface plasminogen activation. Methods are disclosed 1) for detecting or quantifying u-PAR, 2) for targeting a diagnostic to a cell containing a u-PAR on the surface, 3) for preventing or counteracting proteolytic activity in a mammal.

Abstract: Complementary DNA encoding a 52 kDa form of a protein present in the human Ro/SSA ribonucleoprotein complex has been cloned. A lambda gt11 cDNA library made from human thymocyte mRNA was screened with serum from a SLE patient and two immunoreactive clones were isolated. These clones reacted with other patient sera which had anti-52 kDa Ro/SSA antibodies and with affinity purified anti-52 kDa Ro/SSA antibodies. Moreover, affinity purified antibodies eluted from fusion proteins of the isolated clones reacted only with the 52 kDa protein of lymphocytes in the Western blot. Ro/SSA RNAs were also precipitated with these affinity purified antibodies, further confirming that the clones encode a 52 kDa Ro/SSA antigen. The sequence differs from the previously reported 60 kDa Ro/SSA gene.

Abstract: Described is a process for detecting reverse transcriptase activity and, thereby, reverse transcriptase inhibitors using fluorescence polarization, comprising, mixing a DNA primer with an RNA template. Then forming an RNA/DNA duplex utilizing the reverse transcriptase and removing the RNA from the RNA/DNA duplex to form single-stranded DNA. Finally, adding a fluorescent-labeled oligonucleotide complementary to the single-stranded DNA for hybridizing to the single-stranded DNA; and, measuring the fluorescence polarization.

Abstract: The present invention provides novel human small nuclear ribonucleoprotein (snRNP) Sm proteins (collectively called HSMP) and polynucleotides which identify and encode HSMP. The invention also provides genetically engineered expression vectors and host cells comprising the nucleic acid sequences encoding HSMP. The invention also provides pharmaceutical compositions containing HSMP or antagonists to HSMP, and in the use of these compositions for the treatment of diseases associated with the expression of HSMP. Additionally, the invention provides for the use of antisense molecules to polynucleotides encoding HSMP for the treatment of diseases associated with the expression of HSMP. The invention also provides diagnostic assays which utilize the polynucleotide, or fragments or the complement thereof, to hybridize to the genomic sequence or transcripts of polynucleotides encoding HSMP or anti-HSMP antibodies which specifically bind to HSMP.

Abstract: The present invention relates to chromotropic nitrone spin trapping agents, methods of making these agents, compositions comprising same, and methods of their use. In particular, azulenyl nitrones of the present invention are effective agents for trapping free radical species and find use as efficient antioxidants in physicochemical and biological systems. Accordingly, the invention also relates to spin adducts formed from the combination of azulenyl nitrones with free radicals. The compounds of the present invention are readily prepared from available starting materials and find further use in assays and in a number of diagnostic, prophylactic and therapeutic applications, including but not limited to the alleviation, modulation and inhibition of the negative effects of carbon-centered or oxygen-centered radical species and other products of oxidation. Moreover, the combination adducts may be calorimetrically detected and, optionally, isolated and characterized to obtain valuable information (e.g.

Abstract: The present invention concerns a nuclear inhibitor which specifically inhibits the activity of sequence specific DNA enhancer binding proteins of Human Papilloma Virus (HPV) and the use of this nuclear inhibitor for the production of a medicament for treatment of human cervical cancer.

Abstract: An invention is described that permits the regulation of recombination in cells, organisms or appropriate cell-free systems. The invention involves creating fusion proteins between recombinase proteins, or components of recombinase systems, and ligand binding domains derived from nuclear receptors. The fusion proteins show little recombinase activity in the absence of the ligand that binds to the ligand binding domain. Upon binding of the ligand, recombinase activity is induced. The invention provides a practical means to regulate recombination in cells and organisms and, by linking ligand binding to recombination, provides a simple means whereby ligand binding can be measured as recombination achieved.

Abstract: The invention relates to a method for the renaturation of denatured proteins in which they are treated with a renaturant which has on vicinal carbon atoms a hydroxyl group and at least one fluorine atom.

Abstract: Receptor recognition factors exist that recognizes the specific cell receptor to which a specific ligand has been bound, and that may thereby signal and/or initiate the binding of the transcription factor to the DNA site. The receptor recognition factor is in one instance, a part of a transcription factor, and also may interact with other transcription factors to cause them to activate and travel to the nucleus for DNA binding. The receptor recognition factor appears to be second-messenger-independent in its activity, as overt perturbations in second messenger concentrations are of no effect. The concept of the invention is illustrated by the results of studies conducted with interferon (IFN)-stimulated gene transcription, and particularly, the activation caused by both IFN.alpha. and IFN.gamma..

Abstract: The present invention provides a transrepressing protein of the Fos proto-oncogene family. The protein, FosB2, is characterized by having a leucine zipper domain and forming a heterodimer with a Jun related protein. This heterodimer is capable of binding to an AP-1 site and suppressing transcriptional transactivation of a promoter containing the AP-1 site.

Abstract: The invention provides human cell cycle related proteins (CCRP) and polynucleotides which identify and encode CCRP. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for treating or preventing disorders associated with expression of CCRP.

Abstract: This invention provides a method of inhibiting the transcription of a gene, which is activated by AP-1 or an AP-1 component, comprising binding AP-1 or the component with a nuclear receptor so as to prevent the binding of AP-1 to the gene. The nuclear receptor can be the retinoic acid receptor, glucocorticoid receptor, vitamin D3 receptor, thyroid receptor, or estrogen receptor. Also provided is a composition of matter comprising AP-1 or an AP-1 component bound to a nuclear receptor. These methods and compositions can be used to treat arthritis and cancer.

Abstract: The invention provides a human zinc RING protein (ZIRI) and polynucleotides which identify and encode ZIRI. The invention also provides expression vectors, host cells, agonists, antibodies and antagonists. The invention also provides methods for treating disorders associated with expression of ZIRI.

Abstract: The present invention relates to methods of diagnosing peripheral neuropathies which comprises the steps of determining the titer of autoantibodies directed toward particular nervous system antigens. It also provides for substantially purified preparations of specific antigens, namely neuroprotein-1, histone H3 (neuroprotein-2), .beta.-tubulin (neuroprotein-3), neuroprotein-4, neuroprotein-5, and NP-9 antigen which may be used in such diagnostic methods.

Abstract: A method for the detection of a polynucleotide target sequence is described. The method involves the formation of a covalent or non-covalent bonded pair of nucleotide sequences formed in response to a target polynucleotide sequence, adding nucleotide sequence specific binding proteins each capable of binding one member of the pair of nucleotide sequences, and detecting the specific binding proteins complexed to the pair of nucleotide sequences.

Abstract: Disclosed are nucleic acid molecules encoding polypeptides that specifically bind telomerase RNA. Also disclosed are methods of preparing the nucleic acid molecules and polypeptides, and methods of using these molecules.

Abstract: Receptor recognition factors exist that recognizes the specific cell receptor to which a specific ligand has been bound, and that may thereby signal and/or initiate the binding of the transcription factor to the DNA site. The receptor recognition factor is in one instance, a part of a transcription factor, and also may interact with other transcription factors to cause them to activate and travel to the nucleus for DNA binding. The receptor recognition factor appears to be second-messenger-independent in its activity, as overt perturbations in second messenger concentrations are of no effect. The concept of the invention is illustrated by the results of studies conducted with interferon (IFN)-stimulated gene transcription, and particularly, the activation caused by both IFN.alpha. and IFN-.gamma..

Abstract: The present invention relates to complexes of the 53BP2 protein with proteins identified as interacting with 53BP2 by a yeast two hybrid assay system. The proteins identified to interact with 53BP2 are .beta.-tubulin, p62, hnRNP G, and three gene products, 53BP2-IP1, 53BP2-IP2, and 53BP2-IP3 encoded, in part, by the EST R72810 sequence. Thus, the invention provides complexes of 53BP2 and .beta.-tubulin, p62, hnRNP G, 53BP2-IP1, 53BP2-IP2, and 53BP2-IP3 and derivatives, fragments and analogs thereof. The invention also provides the 53BP2-IP1, 53BP2-IP2 and 53BP2-IP3 genes and proteins and derivatives, fragments and analogs thereof. Methods of screening the complexes for efficacy in treating and/or preventing certain diseases and disorders, particularly cancer, autoimmune disease and neurodegenerative disease are also provided.

Abstract: A substantially pure S2-6 protein (a) having a zinc binding LIM domain, (b) whose mRNA is preferentially expressed in nonproliferating or growth inhibited human diploid fibroblasts, (c) whose mRNA is overexpressed in senescent human diploid fibroblasts or human diploid fibroblasts derived from a patient with Werner Syndrome, and (c) whose mRNA expression is reduced or abolished in fetal human diploid fibroblasts, immortalized cells, cancerous cells and other highly proliferative cells.

Abstract: A tissue culture screening system to monitor a transcriptional response treated by a chemical signal interacting with a plasma membrane receptor is provided. The tissue culture screening system includes a cell line containing a membrane receptor, a target gene and a specific receptor selected from the group consisting of a steroid receptor, a vitamin receptor and an orphan receptor. The specific receptor regulates transcription of the target gene. Any of the target gene membrane receptor or specific receptor can be introduced into the cell by an expression vector. In addition to the screening system there is also provided assays for identifying test compounds and chemical signals that regulate transcription or are potential agonist or antagonist neurotransmitters or which regulate indirectly by a membrane receptor binding or regulate transription in the absence of a steroid, vitamin or orphan ligand. There is further provided kits for the assays.

Abstract: Through the use of the novel receptor NER in a screening procedure, TOFA (5-tetradecyloxy)-2-furan-carboxylic acid) has been found to modulate other receptors and to be a potent potentiator of other drugs. TOFA activates the NER receptor. The NER receptor is a novel member of the steroid hormone receptor family and has been prepared by cDNA cloning from a human osteosarcoma SAOS-2/B10 cell library. Also disclosed is the complete sequence of human NER cDNA; a COS stable expression system; the expressed NER protein; and an assay using the COS expression system. In addition, the invention relates to a method for identifying functional ligands of the NER receptor.

Abstract: Disclosed is a method for determining whether a test protein is capable of interacting with a retinoid X receptor protein. The method involves: (a) providing a host cell which contains (i) a reporter gene operably linked to a protein binding site; (ii) a first fusion gene which expresses a first fusion protein, the first fusion protein including a retinoid X receptor protein covalently bonded to a binding moiety which is capable of specifically binding to the protein binding site; and (iii) a second fusion gene which expresses a second fusion protein, the second fusion protein including the test protein covalently bonded to a gene activating moiety; and (b) determining whether the test protein increases expression of the reporter gene as an indication of its ability to interact with the retinoid X receptor protein. Also disclosed is purified DNA encoding retinoid X receptor-interacting proteins and the polypeptides expressed from such DNA.

Abstract: Less toxic agents for reversal of heparin or low molecular weight heparin anticoagulation which are synthetic protamine-like polycationic peptides having a total cationic charge which is less than that of n-protamine. In preferred embodiments, arginine residues of n-protamine are replaced with lysine residues for ease of manufacture. Selective positively charged arginine residues have been replaced with an uncharged amino acid residue or its analog, such as glycine or glutamine, in order to reduce the total cationic charge on the polycationic peptide to the range of about ?+14! to ?+18!, preferably ?+16! to ?+18!. In specific embodiments, there are sequences of 29 and 32 amino acid residues wherein 4 to 5 clusters of 2 to 4 positively charged amino acids are separated by 2 to 6 neutral amino acids. The C-terminus and the N-terminus can be modified to mitigate against in vivo degradation by carboxypeptidases and aminopeptidases. Another modification, specifically use of .alpha.

Abstract: The present invention provides an isolated altered vertebrate telomere repeat binding factor (A-TRFs). Also included are the corresponding nucleic acids that encode the A-TRFs of the present invention, as well as the heterodimers formed by the association of an A-TRF with a TRF. In addition, pharmaceutical compositions containing the A-TRFs for treatment of diseases such as ataxia telangiectasia are also included. Methods of making, purifying and using the A-TRFs of the present invention are described. In addition, drug screening assays to identify drugs that mimic and/or complement the effect of the A-TRFs are presented.

Abstract: Hybrid regulatory proteins are provided which contain amino acid sequences that are susceptible to cleavage by specific proteolytic enzymes. When acted upon by such enzymes, the hybrid regulatory proteins are rendered substantially less active, thereby altering the rate of production of products of indicator genes that are controlled by the regulatory proteins. Also provided are DNAs encoding such regulatory proteins, recombinant vectors and transformed eukaryotic cells containing such DNAs, and methods for identifying inhibitors of the specific proteolytic enzymes.

Abstract: The present invention relates to the discovery in eukaryotic cells, particularly mammalian cells, of a novel family of cell-cycle regulatory proteins ("CCR-proteins"). As described herein, these family of proteins includes a polypeptide having an apparent molecular weight of 16 kDa (hereinafter "p16.sup.INK4 " OR "p16") and which can function as an inhibitor of cell-cycle progression, and therefore ultimately of cell growth, and that similar to role of p21 and p53, the p16 protein may function coordinately with the cell cycle regulatory protein, retinoblastoma (Rb). Furthermore, the CCR-protein family includes a protein having an apparent molecular weight of 13.5 kDa (hereinafter "p13.5"). The presumptive role of p13.5, like p16, is in the regulation of the cell-cycle.