Abstract: Disclosed are methods of identifying compounds which inhibit transcription activation by CIITA and thus inhibit MHC class II gene expression. Such compounds can affect the induction of an immune response. The methods employ, independently, the activation and interactions domains of CIITA. The methods also employ the activation and interaction domains of isotype-specific CIITA proteins, allowing for the identification of compounds which are isotype-specific inhibitors of transcription and which are useful for selectively affecting the immune system.

Abstract: A method for assaying a medium for the presence of a substance that affects an SH2-phosphorylated ligand regulatory system. The method employs an SH2-like domain or a subdomain thereof and a phosphorylated ligand. The phosphophorylated ligand is capable of interacting with the SH2-like domain or a subdomain thereof to form an SH2-phosphorylated ligand complex. The SH2-like domain or subdomain and/or the phosphorylated ligand are present in a known concentration. The SH2-like domain or a subdomain thereof and the phosphorylated ligand are incubated with a substance which is suspected of affecting an SH2-phosphorylated ligand regulatory system. The method is carried out under conditions which permit the formation of the SH2-phosphorylated ligand complex. SH2-phosphorylated ligand complex, free SH2-like domain or subdomains thereof, or non-complexed phosphorylated ligand are assayed.

Abstract: Phosvitin or a modified phosvitin immobilised and coupled to a suitable matrix may be used for the separation and purification of proteins or polypeptides and in the removal of metal ions from biological material. If desired the phosvitin or modified phosvitin may be in the form of a metal chelate complex.

Abstract: A novel system and method for sensitive antigen detection. The system utilizes immuno-polymerase chain reaction in which a specific biotinylated nucleic acid molecule is used as the marker. The biotinylated marker is attached to antigen-antibody complex through a streptavidin-protein A chimeric protein that possesses tight and specific binding affinity both for biotin and immunoglobulin G. A segment of the attached biotinylated marker is amplified by polymerase chain reactions with appropriate primers and the polymerase chain reaction products are detected by agarose gel electrophoresis. The method can detect any antigen and has a greater sensitivity than any existing antigen detection system.

Abstract: Doxorubicin resistance can be conferred on a host by transforming the host with a recombinant vector comprising a DNA having the configuration of restriction sites shown in FIGS. 1 or 2 of the accompanying drawings or a restriction fragment derived therefrom containing a gene coding for doxorubicin resistance.

Abstract: A biosensor detector method for detecting biological targets, using specific binding, or hybridization techniques coupled with enzymatic amplification and the mass sensing capability of a piezoelectric oscillator. An optical biosensor is also contemplated.

Abstract: .alpha.-Glycosyl hesperidin, a novel hesperidin derivative wherein equimolar or more D-glucose residues are bound to hesperidin via the .alpha.-bond, is formed by a saccharide-transferring enzyme in a liquid containing hesperidin and .alpha.-glucosyl saccharide. The .alpha.-glycosyl hesperidin is easily recovered from the reaction mixture with a synthetic macroporous resin. .alpha.-Glycosyl hesperidin is superior in water-solubility, substantially tasteless and odorless, free of toxicity, and readily hydrolyzable in vivo into hesperidin and D-glucose to exhibit the physiological activity inherent to hesperidin. Thus, .alpha.-glycosyl hesperidin is favorably usable in vitamin P-enriching agents, foods, beverages, tobaccos, foods, pet foods, pharmaceuticals for susceptive diseases, cosmetics and plastics.

Abstract: The ability to improve the conversion of .epsilon.-rhodomycinone to daunorubicin can be conferred on a bacterial host transformed with a recombinant vector comprising a DNA coding for an appropriate protein useful for that conversion. Furthermore, the bacterial host may have a mutation that blocks the function of a gene of daunorubicin metabolism.

Abstract: A method of assaying a sample of blood or blood components for the concentration of an immunophilin ligand comprising incubating the sample with a nonionic detergent and a protease, then inactivating the protease, and subsequently determining the concentration of the immunophilin ligand in the sample.

Abstract: The present invention relates to a complex comprising hepatocyte growth factor (HGF) and met proto-oncogene protein. The present invention also relates to methods for detecting the presence of HGF ligand, met proto-oncogene receptor and methods for isolating either the ligand or receptor or complex comprising both. The present invention further relates to methods of diagnostic proliferative disorders and diseases such as hepatitis or hepatocarcinogenesis by detecting these ligand-receptor pairs.

Abstract: Whole cell or cell-free test systems for screening and identifying compounds that modulate or alter Cyclin E activity. Whole cell assays measure the G1 phase of cells in the presence or absence of the test compound. Additional whole cell or cell-free assays measure binding of cyclin E to a cell division kinase, measure cyclin E activity directly, or measure the cell division kinase activity directly in the presence or absence of the test compound.

Abstract: A substantially pure preparation of a polypeptide, the sequence of which comprises the sequence of a CAIP polypeptide.

Abstract: A method of separating bound labeled indicator from free labeled indicator in a layer of a test element for immunoassay. The method comprisesa) depositing sample containing a target immunoanalyte capable of binding to the labeled indicator or to an immobilized antibody in competition with the labeled indicator, onto an exterior surface of a test element in the presence of the labeled indicator andb) adding an amount of wash liquid to the exterior surface to form a pool of the liquid having a meniscus on the surface, the liquid penetrating the surface over an area bounded by a closed intersect edge formed between the pool meniscus and the surface, so that penetrating liquid can push free labeled indicator away from bound labeled indicator in a volume of the layer below the bounded area.

Abstract: Hayumicin compounds, obtainable by cultivation of a strain of Actinomadura sp. designated ATCC 55432, and analogs of these compounds. The novel compounds have antitumor as well as antibiotic, particularly antibacterial, activity.

Abstract: The invention relates to cell-free receptor binding assays which permit the binding behavior of receptor proteins in the cell membrane toward natural or artificial ligands to be investigated. This entails the particular receptor being linked to a suitable carrier molecule, preferably the heavy chain of an immunoglobulin, and being bound via the carrier, with retention of its biological property, to a suitable solid phase.

Abstract: Compositions and methods are described for identifying inhibitors of mature protein hormone formation from a prohormone, and prophylactic and therapeutic uses of the inhibitors for treating diseases associated with elevated levels of the mature hormones, particulary sepsis, AIDS and autoimmune diseases.

Abstract: This invention provides methods of treatment and/or diagnosis and/or siting of viruses including the AIDS virus and others as well as the cells which they infect. The method comprises introducing near, into or onto the virus or the cell which the virus infects, or both, minute particles. These particles possess ferromagnetic, paramagnetic or diamagnetic properties. After being localized near, in or on the virus or the viral-infected cell, the particles are inductively heated by application of an alternating electromagnetic field. The inductive heating is continued for a period of time sufficient to bring about a temperature rise to a minimum necessary to kill the virus or cell or to desirably alter the behavior of the virus or infected cell. Prior to, during or after treatment, these particles can be used diagnostically to locate and/or map the virus in the living tissue.

Abstract: Diagnostic and therapeutic compositions which comprise the .alpha.Gal(1-4).beta.Gal subunit are described. These compositions permit the rapid diagnosis and treatment of enteric infections caused by E. coli that produce shiga-like toxins (SLT).

Abstract: Endotoxin binding/neutralizing proteins capable of binding endotoxin in vivo, thereby neutralizing the toxic effect or bioactivity of endotoxin which are isolated from a horseshoe crab such as Limulus polyphemus, pharmaceutical compositions and pharmaceutical uses of the proteins, a method of purifying the proteins and an assay for endotoxin based on the proteins, are disclosed.

Abstract: In accordance with the present invention, there are provided novel assays which allow the identification of compounds which block the ability of lentiviruses to infect non-dividing cells. Compounds discovered employing the invention methods can be employed to block the ability of HIV to infect non-dividing cells. In accordance with another aspect of the present invention, novel antibodies have been developed which are specifically immunoreactive with the phosphorylated form of HIV-1 MA. In accordance with yet another aspect of the present invention, novel kinases which phosphorylate HIV-1 MA have been discovered.

Abstract: This invention relates to improved methods and novel compositions for enzyme complementation assays for qualitative and quantitative determination of a suspected analyte in a sample. The use of enzyme-acceptor and enzyme-donor polypeptides prepared by recombinant DNA techniques, DNA synthesis or chemical polypeptide synthesis techniques which are capable of interacting to form an active enzyme complex having catalytic activity characteristic of .beta.-galactosidase is described. Both homogeneous and heterogeneous assays utilizing these polypeptides are described.

Abstract: A method of measuring the ambient concentration in a fluid, especially a body fluid, of an analyte, such as a hormone or other biologically active material, whose concentration in the fluid is dependent on thedilution of the fluid is disclosed. The fluid is contacted with a trace amount of a binding agent, such as an antibody, specific for the analyte, the proportional occupancy of binding sites on the binding agent is determined and from that figure the analyte concentration is estimated without the need to measure accurately beforehand the volume of the fluid or fluid sample being tested. It is therefore possible to design a concentration-measuring device for insertion into a body fluid of a living creature for in situ measurement of concentration.

Abstract: There are disclosed novel compounds having the formula ##STR1## which exhibit antifungal activity.

Abstract: A ligand-mediated immunofunctional assay (LIFA) method for detecting the presence and the concentration of polypeptide hormone binding proteins which comprises capturing the binding protein with a solid phase bound first antibody, saturating the bound hormone binding protein with the ligand polypeptide hormone, and detecting the bound ligand polypeptide hormone with a detectably labeled second antibody specific for the ligand polypeptide hormone. In the absence of added saturating polypeptide hormone, the LIFA measures the amount of hormone binding protein bound to the endogenous ligand polypeptide hormone. A growth hormone binding protein assay illustrates the method of the present invention. LIFA assay results indicate that increased binding protein substantially increases growth hormone activity. Methods of use and formulations of growth hormone binding protein, growth hormone, insulin-like growth factor-I and insulin-like growth factor binding protein are disclosed.

Abstract: There is disclosed a method for determining the presence of endotoxin or an endotoxin like substance in a sample, as well as a monoclonal antibody and test kit useful in the method.

Abstract: Disclosed are novel compositions and methods, based on ubiquitin subdomain fusion proteins, which are useful for studying the interactions of two members of a specific binding pair, both of which are predetermined. A preferred embodiment relates to the determination of a predetermined ligand in a sample.

Abstract: A method for the qualitative or quantitative determination of an analyte in a test sample wherein a labelled reagent is caused to be immobilized in bound form on a solid phase to provide an indication of the presence or quantity of the analyte in the same is disclosed and is characterized in that the labelled reagent comprises a gold sol bound to a substance capable of specifically binding to said analyte or to a specific binding partner therefor, at least 75% by weight of the gold particles of the gold sol having a mean diameter of less than 5 nanometers.

Abstract: Disclosed is a method of isolating a ligand from a sample, the method including: providing a hybrid molecule including the receptor for the ligand covalently bonded to the first member of a specific binding pair; contacting sample with the hybrid molecule to form an affinity complex between the ligand and the hybrid molecule; and isolating the affinity complex using the second member of the specific binding pair. Also disclosed is a c-kit ligand, nucleic acid encoding such a ligand, and recombinant cells containing such nucleic acid. The c-kit ligand may be used to stimulate hematopoietic cell growth.

Abstract: The invention relates to an agent for the preservation, storage and suspension of cells, especially erythrocytes, which contains a chelating agent for multiply charged metal ions, in addition to other substances known to those skilled in the art, such as, for example, electrolytes and sugars.

Abstract: A rapid diagnostic method for detecting the rupture of fetal membranes is disclosed. The presence of insulin-like growth factor binding protein 1 (IGFBP-1) in a vaginal secretion sample, resulting from the rupture of fetal membranes, is detected with the aid of at least one specific binding substance for IGFBP-1 .

Abstract: Compositions and methods are described for identifying inhibitors of mature protein hormone formation from a prohormone, and prophylactic and therapeutic uses of the inhibitors for treating diseases associated with elevated levels of the mature hormones, particulary sepsis, and autoimmune diseases.

Abstract: The invention features a method for inhibiting the ligand binding of an integrin in a cell involving introducing into the cell a compound which inhibits integrin activation, a method for identifying compounds which inhibit integrin activation, and chimeric integrin molecules.

Abstract: The invention involves an immunological method of separating specifically-targeted cells or molecular structures from a mixed population under conditions which minimize damage to the cellular structure or the molecular integrity. The method is based upon the specific interaction of a label and an antibody directed against the label and the ability of a competitor to inhibit the interaction between the label and the antibody.

Abstract: Disclosed herein are polypeptides of the formulaR.sup.1 --AA--A.sup.1 --A.sup.2 --A.sup.3 --A.sup.4 --A.sup.5 --A.sup.6 --A.sup.7 --A.sup.8 --A.sup.9 --A.sup.10 --A.sup.11 --A.sup.12 --A.sup.13 --R.sup.2 that are useful in treatment of diabetes mellitus, wherein:AA is a single bond or a polypeptide chain of 1 to 12 natural amino acid residues;A.sup.1 is seryl, A.sup.2 is phenylalanyl, A.sup.3 is arginyl, A.sup.4 is valyl, A.sup.5 is aspartyl, A.sup.6 is leucyl, A.sup.7 is arginyl, A.sup.8 is threonyl, A.sup.9 is leucyl, A.sup.10 is leucyl, A.sup.11 is arginyl, and A.sup.12 is tyrosyl, wherein one of A.sup.1 through A.sup.12 may be replaced with a natural amino acid residue, and wherein when A.sup.12 is phenylalanyl, tyrosyl or tryptophyl, its aromatic ring may be substituted with 1 or 2 iodo atoms;A.sup.13 is a natural amino acid residue other than tyrosyl, the D-form of a natural amino acid residue, --N(R.sup.4)--CH(R.sup.3)--C(O)--, or --N(R.sup.4)--CH(R.sup.3)--CH.sub.2 --;R.sup.

Abstract: We have discovered that growth hormones form ternary complexes with their receptors in which site 1 on the hormone first binds to one molecule of receptor and then hormone site 2 then binds to another molecule of receptor, thereby producing a 1:2 complex. We believe this phenomenon is shared by other ligands having similar conformational structure. Assays based on this phenomenon are useful for identifying ligand agonists and antagonists. Sites 1 and 2 are structurally identified to facilitate generation of amino acid sequence variants of ternary complex-forming ligands. Novel variants of growth hormone, prolactin placental lactogen and other related ligands are provided. As a result of our studies with the ternary complex we have determined that selected antibodies to the receptor for these ligands are capable of acting as ligand agonists or antagonists. Novel growth hormones and novel uses for anti-growth hormone receptor antibodies are described.

Abstract: Methods for detecting the presence or concentration of an analyte in a matrix by exploiting the specificities of the analyte's antibody and enzyme-substrate are disclosed. The analyte is first extracted from the matrix by binding it to its specific antibody which has been attached to a solid surface. The antibody-bound analyte is then separated from the matrix to remove it from any interfering substances. Next, the antibody-bound analyte is reacted with its specific enzyme-substrate to generate a signal proportionate to the amount of analyte bound to the antibody, which in turn is dependent on the quantity of analyte present in the matrix. Applications of the methods of the present invention to detect the presence and concentration of hemoglobin, a transferase, and a serine protease, are specifically disclosed. Further, kits useful for utilizing the methods of the present invention are also disclosed.

Abstract: A coupled pair of fiber optic fibers are used an immunoassay device. The fibers are first coupled and then drawn down to a single mode diameter. The coupler senses output ratio change due to chemical, biochemical, bioaffinity, immunogenic-type interactions and other molecular activity occuring within the evanescent field. The fusion joint of the coupler is coated with a first immunoassay component, and then surrounded with a second immunoassay component.

Abstract: Peptides that form lightly associated homodimers can be used to form dimers and multimers of other molecules and molecular motifs of interest. These association peptides can dimerize regardless of whether motifs are added to the amino-terminus of the peptide, or the carboxy terminus of the peptide, although additions to the carboxy-terminus of the association peptides require the presence of certain acidic residues.

Abstract: Disclosed herein are a novel strain of Streptomyces and a method for the production of aclacinomycins A, B, Y and aglycone thereof by cultivating the same. Streptomyces lavendofoliae DKRS(KCTC 0092BP) of the present invention is capable of producing aclacinomycins A, B, Y and aglycone with higher yield. Further, it is possible to selectively produce aclacinomycin A or Y by adjusting pH of the cultured broth of Streptomyces lavendofoliae DKRS to 4.4 or 4.6 with acetate buffer or hydrochloric acid, respectively.

Abstract: Methods of monitoring and detecting the early onset of organ injury incident rejection of a organ rejection in an animal are disclosed. The described methods are capable of distinguishing organ rejection injury from other organ tissue damage in the animal. Free secretory component levels in an animal biological fluid (e.g., bile, urine, blood, amniotic fluid) may be used to identify organ rejection in an animal. Multiple and single organ transplant patients may be monitored and diagnosed according to the claimed methods. Biological fluids, such as blood, (serum) or urine, are analyzed immunologically using a particularly adapted ELISA which are then compared to an FSC control concentration to identify elevated FSC values. Animals with test FSC above FSC control concentrations are diagnosed as having an ongoing organ rejection episode. The detection of congenital renal dysfunction in utero is also provided according to the present invention through the measurement of FSC in the amniotic fluid.

Abstract: A one reaction step method for determining hydrophobic analytes, such as free hydrophobic analytes, comprising the steps of mixing a solution suspected of containing the hydrophobic analyte, e.g. free fatty acid, with a reagent comprising a fluorescently modified specific-binding protein for the hydrophobic analyte, detecting a fluorescence difference between the fluorescently modified specific-binding protein in the bound and unbound condition, and relating said fluorescence difference to the amount of arialyre in the solution is disclosed.

Abstract: Disclosed herein are a novel strain of Streptomyces and a method for the production of aclacinomycins A, B, Y and aglycone thereof by cultivating the same. Streptomyces lavendofoliae DKRS (KCTC 0092BP) of the present invention is capable of producing aclacinomycins A, B, Y and aglycone with higher yield. Further, it is possible to selectively produce aclacinomycin A or Y by adjusting pH of the cultured broth of Streptomyces lavendofoliae DKRS to 4.4 or 4.6 with acetate buffer or hydrochloric acid, respectively.

Abstract: A previously isolated hepatitis B virus (HBV) integration in a 147 bp cellular DNA fragment linked to hepatocellular carcinoma (HCC) was used as a probe to clone the corresponding complementary DNA from a human liver cDNA library. Nucleotide sequence analysis revealed that the overall structure of the cellular gene, which has been named hap, is similar to that of the DNA-binding hormone receptors. Six out of seven hepatoma and hepatoma-derived cell-lines express a 2.5 kb hap mRNA species which is undetectable in normal adult and fetal livers, but present in all non-hepatic tissues analyzed. Low stringency hybridization experiments revealed the existence of hap related genes in the human genome. The cloned DNA sequence is useful in the preparation of pure hap protein and as a probe in the detection and isolation of complementary DNA and RNA sequences. The hap protein is a retinoic acid (RA) receptor identified as RAR-.beta.. The RAR-.beta.

Abstract: Novel tethered hapten intermediates and related conjugates based on carbazole and/or dibenzofuran, as well as methods for making and using such conjugates. Haptens based on the above core structures may be substituted at any position on the aromatic rings with a wide variety of substituents. Using tethered intermediates, immunogens, tracers, solid supports and labeled oligonucleotides are all described; as are methods for using the intermediates to prepare the conjugates, methods of using the conjugates to make and purify antibodies, as assay tracers, and in nucleic acid hybridization assays. Kits containing haptenated oligonucleotides and anti-hapten conjugates are also described.

Abstract: The present invention provides in vitro models of the in vivo rolling and arrest of leukocytes along the endothelial cell wall, which are important steps in the migration of leukocytes out of the blood stream and into tissue, as part of the inflammatory response. The in vitro models of the invention are functional under physiologic flow conditions resulting in physiologic shear stresses. In a specific embodiment, for modelling leukocyte rolling, the apparatus of the invention comprises a solid phase surface with rolling mediator molecules present thereon. Such rolling mediators are, for example, selectins and selectin ligands which have binding partners expressed on leukocytes. In another specific embodiment, for modelling leukocyte rolling followed by adhesion/arrest, the apparatus of the invention comprises a solid phase surface with both rolling mediators and integrin binding partners present thereon.

Abstract: A new homogeneous cytosolic binding protein (FKBP12.6), having a specific binding activity of about 4.8 mg FK-506 per mg protein and a molecular weight of about 10-12 kilodaltons, reversibly binds the immunosuppressant FK-506, but not cyclosporine A (CSA). The protein is unstable to heating at 56.degree. C. for 30 minutes losing its FK-506 binding affinity. The FKBP12.6 protein is isolated from the cytosol of mammalian tissues, preferably bovine or human brain tissue, and can be used in diagnostic and purification procedures involving FK-506-type macrolide immunosuppressants. The FKBP12.6 protein also has peptidyl-proline isomerase enzymatic activity, catalyzing the cis-trans isomerization of proline-containing peptide bonds. In addition, FKBP12.6 binds to and inhibits the phosphatase calcineurin in the presence of FK-506.

Abstract: This invention provides an imaging agent which comprises a polypeptide labeled with an imageable marker, such polypeptide having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin. The invention further provides a method wherein the imaging agent is used for imaging a fibrin-containing substance, i.e., a thrombus or atherosclerotic plaque. Further provided are plasmids for expression of polypeptides having an amino acid sequence substantially present in the fibrin binding domain of naturally-occurring human fibronectin and being capable of binding to fibrin, hosts containing these plasmids, methods of producing the polypeptides, methods of treatment using the polypeptides, and methods of recovering, refolding and reoxidizing the polypeptides.

Abstract: The present invention relates to iminium ion substituted cyanine dyes having a fluoresence absorbance of between about 500 and 900 nm, a reduced tendency to aggregate and enhanced photostability. The cyanine dyes of the present invention are represented by the formula ##STR1## wherein n is 0, 1, 2 or 3;m is 0, 1, 2 or 3;R.sub.1 and R.sub.2 are taken together to form an aromatic ring or a fused polycyclic aromatic ring;R.sub.3 and R.sub.4 are taken together to form an aromatic ring or a fused polycyclic aromatic ring;R.sub.5 and R.sub.6 are independently selected from the group consisting of (CH.sub.2).sub.p X where p is 1-18 and X is a functional group that reacts with amino, hydroxyl and sulfhydryl nucleophiles;R.sub.7 and R.sub.8 are independently selected from the group consisting of hydrogen, C1-C10 alkyl groups and where R.sub.7 and R.sub.8 are taken together to form a five- or six- membered heterocyclic ring;R.sub.

Abstract: Compounds are evaluated for their binding to naturally occurring receptors, by employing the natural ligand conjugated to an enzyme donor fragment of .beta.-galactosidase for competing with the sample compound for the natural acceptor binding site or in the absence of competition where the sample compound binds to an allosteric site. By adding the enzyme acceptor fragment of the .beta.-galactosidase and substrate, the binding affinity of the sample compound may be evaluated as a measure of agonist or antagonist capability.

Abstract: The invention provides a method for determining platelet function in a mammal comprising providing platelets from the mammal, contacting the platelets in suspension with at least one immobilised ECM protein or an effective fragment or analog thereof while applying to the platelets an effective mechanical stimulus for an effective period of time and determining the platelet activation produced.The invention also provides a method for detecting a bleeding disorder in a human. Further, the invention provides a method for monitoring the efficacy of pharmacological agents affecting platelet function in vivo.