Abstract: Methods are provided for improving the microbial production of amphotericin B by the selective inhibition of amphotericin A by means of protein synthesis inhibitors.

Abstract: The present invention provides assay methods and kits for detecting the existence of, or the propensity toward the development of autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroiditis, Birdshot retinopathy and anti-coagulant deficiency due to autoantibodies.

Abstract: Compounds having the formula: ##STR1## wherein T is a polycycloalkylidene group (e.g., adamant-2-ylidene); R is a C.sub.1-20 alkyl, aralkyl or cycloalkyl group; and Y is a fluorescent chromophore (e.g., m-phenylene), produced by reacting a compound having the formula: ##STR2## with an R-ylating agent (e.g., R.sub.2 SO.sub.4) in the presence of an alkali metal alkoxide in a polar aprotic solvent. Also, compounds having the formula: ##STR3## are produced by reacting a compound having the formula: ##STR4## with ##STR5## wherein X is an electronegative leaving group (e.g., a halogen anion such as chloride ion) in the presence of a Lewis base (e.g., a trialkyl-amine) dissolved in an aprotic organic solvent (e.g., benzene or toluene). Also, compounds having the formula ##STR6## are produced by reacting a compound of the formula ##STR7## with a tetra-O-acylated-O-hexopyranoside halide, then hydrolyzing off the protective acyl groups.

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: Disclosed and claimed are methods for selecting a recombinant virus, phage or cell expressing a catalytic antibody or catalytic portion thereof, or for selecting catalytic activity by a moiety. The method employs reaction-based selection for catalytic activity. The method can also be used to concentrate (increase the proportion of catalytic to non-catalytic moieties) a sample containing a catalytic moiety or viruses, phages or cells expressing a catalytic moiety. The selection or concentrating can be by employing a mechanism-based inhibitor, catalysis-accelerated movement, surface binding, changes in enthalpic component of binding as a function of temperature, or changes in binding by competition, or combinations thereof. The invention also comprehends a method for producing a recombinant virus or a cell-line expressing a catalytic moiety such as a catalytic antibody or catalytic portion thereof; and, this method can include infecting a suitable host with viruses which are screened for the expression.

Abstract: Disclosed is a binding assay for proteases and phosphatases, which contain cysteine in their binding sites or as a necessary structural component for enzymatic binding. The sulfhydryl group of cysteine is the nucleophilic group in the enzyme's mechanistic proteolytic and hydrolytic properties. The assay can be used to determine the ability of new, unknown ligands and mixtures of compounds to competitively bind with the enzyme versus a known binding agent for the enzyme, e.g., a known enzyme inhibitor. By the use of a mutant form of the natural or native wild-type enzyme, in which serine, or another amino acid, e.g., alanine, replaces cysteine, the problem of interference from extraneous oxidizing and alkylating agents in the assay procedure is overcome. The interference arises because of oxidation or alkylation of the sulfhydryl, --SH (or --S.sup.-), in the cysteine, which then adversely affects the binding ability of the enzyme.

Abstract: A diagnostic kit, method, and apparatus for electrochemically determining the presence or concentration of an analyte in a sample. A mixture is formed which includes the sample, an enzyme acceptor polypeptide, an enzyme donor polypeptide, and a labeled substrate. The enzyme donor polypeptide is capable of combining with the enzyme acceptor polypeptide to form an active enzyme complex. The formation of such the active enzyme complex is responsive to the presence or concentration of the analyte in the fluid sample. The active enzyme hydrolyzes the labeled substrate, resulting in the generation of an electroactive label, which can then be oxidized at the surface of an electrode. A current resulting from the oxidation of the electroactive compound can be measured and correlated to the concentration of the analyte in the sample.

Abstract: A method for determining the complexed forms of immunologically determinable prostate specific antigen (cPSA) in a blood sample, e.g., by two-site immunometric assays, in which the blood sample is treated to render free PSA (fPSA) immunologically nondetectable. A particularly preferred immunometric assay method employs three anti-PSA antibodies: an antibody that binds to both cPSA and fPSA (anti-tPSA), a second anti-tPSA antibody which is characterized by the unique property that binding to fPSA is blocked by binding of fPSA-specific antibodies, and a third antibody which is a fPSA-specific antibody. Thus, binding of the fPSA-specific antibody to PSA in the sample allows only cPSA to be measured in the immunometric assay. Measurement of cPSA blood levels has been found to provide a method for aiding in the diagnosis and monitoring of prostate cancer that is highly sensitive and specific, and eliminates the need for a significant number of patients to undergo unnecessary prostate biopsy.

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

Abstract: An in vitro method for predicting the identity of distinct, first-generation, drug-resistant, biologically-active, HIV protease mutants that may emerge in vivo in response to a drug targeted thereagainst. In a preferred embodiment, the in vitro method comprises the steps of (a) preparing, in the presence of the drug, a comprehensive library of all first-generation mutants of the protease differing therefrom by at least one and preferably no more than three amino acid substitutions, each of the protease mutants being generated as part of a polyprotein with the HIV reverse transcriptase protein; (b) isolating, in vitro, first-generation, drug-resistant, biologically-active, mutant proteases from said library by assaying for biological activity of the reverse transcriptase protein; and (c) identifying the distinct, first-generation, biologically-active, mutant proteases so isolated.

Abstract: In accordance with the present invention, it has been discovered that CREB binding protein (CBP) cooperates with upstream activators involved in the activation of transcription of such signal dependent transcription factors as c-Jun (responsive to phorbol ester), serum response factor, and the like. It has also been discovered that CBP can be employed in an assay to identify compounds which disrupt the ability of such signal dependent transcription factors to activate transcription. In another aspect, it has been discovered that CBP can be employed in an assay to identify new signal dependent transcription factors. In yet another aspect of the present invention, it has been discovered that CBP can be employed in an assay to identify novel co-factor protein(s) which mediate the interaction between signal dependent transcription factors and inducer molecules involved in the activation of transcription.

Abstract: Tetrazolium salt compounds represented by the following general formula (1): ##STR1## wherein R.sup.1 and R.sup.2 independently represent hydrogen atom, nitro group, cyano group, carboxyl group or a halogen atom, preferably nitro group; R.sup.3 represents an alkyl group or an alkoxyl group, preferably methyl group or methoxy group; and M represents an alkali metal or an ammonium. The compounds are useful for quantitative measurement of a dehydrogenase, and characterized to have high water-solubility and excellent storage stability in the state of an aqueous solution.

Abstract: The present invention provides a novel method for the rapid isolation and identification of large numbers of novel enzyme substrates. The novel method provided by the present invention identifies substrates in tissue and/or cell extracts of a non-human model characterized as having an inactive enzyme. Without active enzyme, the substrates of this enzyme accumulate in the non-human model. The tissue or cell extract containing the enzyme substrate is then fractionated by passing the extract through an affinity column. The affinity column comprises an enzyme having similar specificity to the inactive enzyme, bound to a solid support. The affinity resin binds the enzyme substrate so that the substrate may be isolated from other proteins in the extract. The substrate of the enzyme may then be further identified by purifying and sequencing. Also provided by the present invention are novel substrates, and analogs of the substrates identified by the method of the present invention.

Abstract: A non-competitive method for the determination of analytes. Initially the analyte is bound to a specific binding partner, after which the unoccupied binding sites of the binding partner are inactivated. The bound analyte is then dissociated from the binding partner and replaced by a labeled marker, after which the bound labeled marker is determined. The signal from the bound labeled marker is directly proportional to the initial amount of analyte in the sample, which makes the present method more favorable than the competitive assays.

Abstract: The present invention relates to novel classes of compounds which are inhibitors of interleukin-1.beta. converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions containing these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against interleukin-1 mediated diseases, including inflammatory diseases, autoimmune diseases and neurodegenerative diseases. This invention also relates to methods for inhibiting ICE activity and methods for treating interleukin-1 mediated diseases using the compounds and compositions of this invention.

Abstract: The invention relates to novel methods and compositions for the detection of analytes using the nuclear reorganization energy, .lambda., of an electron transfer process.

Abstract: DNA sequences are described which on the codogenic strand code plant debranching enzymes, whose transcripts formed in transgenic plants code new proteins with the enzymatic activity of debranching enzymes which in transgenic plants reduce the degree of branching of amylopectin starch and DNA sequences which on the codogenic strand code plant debranching enzymes, whose transcripts formed in transgenic plants prevent the synthesis of proteins with the enzymatic activity of debranching enzymes, which in the transgenic plants increases the degree of branching of amylopectin starch, as well as plasmids on which these DNA sequences are localized, which can be introduced into plant cells and plants. Also described is a process for the production of plants changed by genetic engineering whose amylopectin starch is modified, and the modified starch obtainable from these plants.

Abstract: Method of assaying hapten in a sample, in which said sample is placed in contact with antibodies capable of recognizing hapten and with a predetermined quantity of a reagent capable of competing with said hapten-fixing antibodies. The reagent is a conjugate formed by a single-stranded fragment of nucleic acid with a compound capable of being recognized by said hapten-recognizing antibodies. The fixed or unfixed reactant is detected by antibodies capable of recognizing the nucleic acid fragment of said conjugate. Detection of said reactant by anti-fragment antibodies of said nucleic acid enhances, in particular, the sensitivity of the assay.

Abstract: E6-BP polypeptides, nucleic acids encoding E6-BP polypeptides, and uses thereof.

Abstract: Formation of an intramolecular cross-link in enzyme donor polypeptide fragments of .beta.-galactosidase, thereby forming a cyclic enzyme donor which is hindered from complementation with an enzyme acceptor fragment to form active of .beta.-galactosidase. The cyclic enzyme donor can be linearized by cleaving to restore complementation ability. Assays in which such cyclic enzyme donors are linearized by specific analytes are disclosed, as well as novel homobifunctional bis-maleimido cross-linking agents of the formula ##STR1## wherein R is hydroxy or acetate.

Abstract: The present invention provides a chimeric polypeptide comprising an epitope of GAD65 protein and a structural region comprising a polypeptide of the GAD family, wherein the chimeric polypeptide is a more specific diagnostic for insulin dependent diabetes mellitus than intact GAD65 and produces fewer false positives than intact GAD65. The invention further provides a method of screening a subject for risk of developing IDDM, comprising contacting the chimeric polypeptide of claim 1 with a biological sample containing antibodies from the subject and detecting binding between an antibody in the biological sample and the chimeric polypeptide, the detection of binding indicating the subject is at risk of developing IDDM.

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

Abstract: 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: Compositions and methods are provided for the treatment of diseases associated with mitogen activated protein kinase cascades. In particular, the mitogen-activated protein kinase p38-2, and polypeptide variants thereof that stimulate phosphorylation and activation of substrates such as ATF2, are provided. The polypeptides may be used, for example, to identify antibodies and other agents that inhibit or activate signal transduction via the p38-2 kinase cascade. Such polypeptides and agents may also be used for the treatment of diseases associated with mitogen-activated protein kinase cascades.

Abstract: Substantially pure C. albicans topoisomerase I protein is disclosed. Nucleic acid molecules that encode C. albicans topoisomerase I protein, recombinant expression vectors that comprise a nucleic acid sequence that encodes C. albicans topoisomerase I protein, and host cells that comprise recombinant expression vectors that comprise nucleic acid sequences that encode C. albicans topoisomerase I protein are disclosed. Fragments of nucleic acid molecules with sequences encoding C. albicans topoisomerase I protein and oligonucleotide molecules that comprise a nucleotide sequence complementary to fragment of a nucleotide sequence that encodes C. albicans topoisomerase I protein are disclosed. Antibodies which bind to an epitope on C. albicans topoisomerase I protein are disclosed. Methods of identifying inhibitors of C. albicans topoisomerase I protein are disclosed. Camptothecin analogs useful as inhibitors of C.

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

Abstract: The invention is directed to a method for generating novel catalysts; particularly high turnover rate enzymes or biocatalysts. Functional catalytic units may be integrated into the germline composition of an animal in order to generate such novel catalysts.

Abstract: A CHO-K1 cell line stably expressing a recombinant full-length human PDE IVa (rhPDEIVa) enzyme was established under hygromycin B selection. Inhibition of the expressed PDE IVa activity by selective PDE IV inhibitors was evaluated. The rank order of potencies of the inhibitors in elevating cAMP in the whole-cell assay was quite different from that on the soluble enzyme. The whole-cell rank order of potencies was also maintained when PKA activity ratios were measured in place of cAMP levels. When inhibition of soluble PDE IVa activity was examined in the presence of 100 mM MgCl.sub.2, the rank order of potencies of the inhibitors mirrored that obtained for the whole-cell assays (both cAMP and PKA). The observed "high-affinity" conformation of the enzyme was not dependent upon a specific cation or anion.

Abstract: The invention is directed to a method for generating novel catalysts, particularly high turnover rate enzymes or biocatalysts. Functional catalytic units may be integrated into the germline composition of an animal in order to generate such novel catalysts.

Abstract: Simplified calibration and improved dose-response linearity of the standard curve of competitive assays are obtained by adding a predetermined amount of unlabeled competitive binding compound (usually just the analyte itself) to a first reagent containing anti-analyte antibodies before the reagent is reacted with a sample containing an unknown amount of analyte.

Abstract: The invention is directed to a method for generating novel catalysts, particularly high turnover rate enzymes or biocatalysts. Functional catalytic units may be integrated into the germline composition of an animal in order to generate such novel catalysts.

Abstract: Methods and compositions for increasing the production of erythromycins are provided. In particular, the invention relates to the engineering of erythromycin-producing organisms to express a heterologous oxygen-binding protein.

Abstract: A process for separating a natural B avermectin from a natural avermectin containing fermentation broth by using an aqueous precipitation. The process comprises extracting natural avermectins from the fermentation broth with a water miscible solvent and adding sufficient water to precipitate the natural B avermetins. Preferably, the water miscible solvent is a C.sub.1 -C.sub.3 alcohol, acetone, or acetonitrile. In addition, an acid, base, salt or surfactant may be added to facilitate the precipitation. This invention provides an isolation technique that substitutes the use of an aqueous precipitation for nonaqueous solvent precipitations. The reduction in use of nonaqueous solvents provides economic, environmental and safety benefits.

Abstract: Disclosed and claimed are methods for selecting a recombinant virus, phage or cell expressing a catalytic antibody or catalytic portion thereof, or for selecting catalytic activity by a moiety. The method employs reaction-based selection for catalytic activity. The method can also be used to concentrate (increase the proportion of catalytic to non-catalytic moieties) a sample containing a catalytic moiety or viruses, phages or cells expressing a catalytic moiety. The selection or concentrating can be by employing a mechanism-based inhibitor, catalysis-accelerated movement, surface binding, changes in enthalpic component of binding as a function of temperature, or changes in binding by competition, or combinations thereof. The invention also comprehends a method for producing a recombinant virus or a cell-line expressing a catalytic moiety such as a catalytic antibody or catalytic portion thereof; and, this method can include infecting a suitable host with viruses which are screened for the expression.

Abstract: Transformed cell lines containing a reporter gene operatively linked to a genetic control element that is responsive to growth factor-stimulated cell proliferation and/or oncogene-mediated neoplastic transformation are provided. Also provided are methods for using such transformed cell lines to screen for growth factor antagonists and/or antineoplastic agents.

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

Abstract: This invention relates to a novel calpain having a proteolytic activity, its partial peptide or a salt either of them, a DNA coding for the protein, a recombinant vector comprising the DNA, a transformant carrying the recombinant vector, a process for producing the protein, a pharmaceutical composition comprising the DNA, an antibody against the protein, a method for screening for a compound which activates or inhibits a proteolytic activity of the protein, a kit for screening for the compound, and a compound which activates or inhibits a proteolytic activity of the protein which is identified by the screening method or the kit. The DNA coding for the protein of the present invention can be used as a therapeutic and prophylactic composition for a variety of diseases including tumor, cerebral apoplexy, cerebral infarction, subarachnoid hemorrhage, Alzheimer's disease, myodystrophy, cataract, ischemic heart disease, atherosclerosis, arthritis, and collagen disease.

Abstract: A method for selective targeted degradation of intracellular proteins in situ by inducing in cells a production of an agent comprising N-terminal domain as well as a C-terminal domain. The N-terminal domain destabilizes the target protein and directs its degradation when attached to it through the C-terminal domain acting as a linker between the target protein and between the protein agent of the invention. The protein degradation directing N-terminal domain is a subregion within 97 amino acids corresponding to the N-terminus of protein antizyme.

Abstract: A nucleic acid and corresponding polypeptide that aids in the regulation of the cell cycle in Pneumocystis carinii is described. Antibodies generated against a unique carboxyl-terminus region of the polypeptide have specific binding affinity for P. carinii Cdc2 polypeptide and are beneficial in diagnosing and monitoring P. carinii infection in patients. Expression of P. carinii Cdc2 polypeptide in cdc2-mutant yeast and other cdc2-mutant organisms provides a useful model for studying the life cycle of P. carinii and for identifying novel therapeutics.

Abstract: Isolated nucleic acids which can confer on a cell at least a 5-fold increase in cisplatin resistance relative to a cisplatin sensitive cell are disclosed. The nucleic acids of the invention can further confer on a cell resistance to heavy metals such as cadmium and copper. Isolated proteins encoded by the nucleic acids of the invention are also disclosed. The isolated nucleic acids and proteins of the invention are useful for conferring cisplatin resistance on a cell, for example non-malignant cells in a tumor bearing subject being treated with cisplatin. Alternatively, the cisplatin resistance of a cell can be inhibited by contacting the cell with an agent which inhibits the activity of the protein of the invention, for example to reverse the cisplatin resistance of a tumor cell. The invention also discloses methods for identifying substances which inhibit cisplatin resistance in a cell or which are chemosensitizers of cisplatin.

Abstract: The present invention provides nucleotide and amino acid sequences that identify and encode a human homolog of rat elastase IV (HEIV) expressed in pancreas tissue. The present invention also provides for antisense molecules to the nucleotide sequences which encode HEIV, hybridization probes or oligonucleotides for the detection of HEIV-encoding nucleotide sequences, and a diagnostic test based on HEIV-encoding nucleic acid molecules. The present invention further provides for genetically engineered host cells for the expression of HEIV, biologically active HEIV, antibodies capable for binding specifically to HEIV, and treatment methods comprising administration of compounds, such antibodies or inhibitors, capable of binding HEIV to alter its activity.

Abstract: Kits comprising 1,2-dioxetanes which can be cause to chemiluminesce by contact with an enzyme, and the enzyme, are provided for use in optically detectable assays. The assay calls for binding the enzyme to the substance to be detected in a sample, removing any unbound enzyme, and then combining the treated sample with the dioxetane. If the substance to be detected is present, enzyme bound thereto will cleave the protecting group of the dioxetane, causing the dioxetane to decompose and chemiluminescence. The intensity of luminescence is indicative of the concentration of the substance in the sample. The substance to be detected may be an enzyme, in which case no binding group is necessary.

Abstract: The present invention provides isolated human and bovine TNF-.alpha. convertases, nucleic acids and recombinant vectors encoding the same, host cells comprising the nucleic acids and vectors, and methods for making the convertases using the host cells. This invention further provides antibodies and antigen binding fragments thereof which specifically bind to the convertases and are useful for treating medical conditions caused or mediated by TNF-.alpha.. Also provided are screening methods for identifying specific inhibitors of mammalian TNF-.alpha. convertases, and for identifying nucleic acids encoding such convertases.

Abstract: Genomic DNA of cholesterol 7.alpha.-hydroxylase and a minigene are disclosed. The minigene is used for making a transgenic animal that produces functionally active cholesterol 7.alpha.-hydroxylase and functions as a disease model. A cholesterol 7.alpha.-hydroxylase promoter region and reporter gene construct is provided, as well as a transgenic animal that expresses the promoter/reporter gene.

Abstract: An aglucone isoflavone enriched vegetable protein whey, whey protein material, high genistein material, high daidzein material, and aglucone isoflavone material are provided, as well as a process for producing the same from a vegetable protein whey. Isoflavone conjugates in a vegetable protein whey are converted to isoflavone glucosides by treating the whey at a temperature and a pH for a period of time sufficient to effect the conversion. The isoflavone glucosides are converted to aglucone isoflavones by enzymatic reaction to produce an aglucone isoflavone enriched vegetable protein whey. Aglucone isoflavone whey protein material is recovered from the aglucone isoflavone enriched vegetable protein whey. A high genistein content material, a high daidzein content material, and an aglucone isoflavone material are produced from an alcohol extract of the aglucone isoflavone whey protein material.

Abstract: The present invention provides for the use of Tripterygium wilfordii Hook F extracts and purified components thereof in the treatment of inflammation or an immune disorder with concomitant lack of steroidal effect. Extracts of this plant (T2) bound to the glucocorticoid receptor and competitively inhibited glucocorticoid mediated cellular processes, such as dexamethasone binding to the glucocorticoid receptor, glucocorticoid mediated activation of target genes, dexamethasone dependent cellular growth, with concomitant inhibition of cyclooxygenase-2 induction and inflammatory processes such as the production of prostaglandin E.sub.2. The T2 extract components triptolide and tripdiolide were effective inhibitors. The particular advantage provided by the methods herein is the treatment or prevention of inflammation and the concomitant lack of steroidal agonist effects and NSAID side effects. Conditions treatable by the present methods include inflammation and immune disorders including autoimmune disease.

Abstract: Isolated nucleic acids which can confer on a cell at least a 5-fold increase in cisplatin resistance relative to a cisplatin sensitive cell are disclosed. The nucleic acids of the invention can further confer on a cell resistance to heavy metals such as cadmium and copper. Isolated proteins encoded by the nucleic acids of the invention are also disclosed. The isolated nucleic acids and proteins of the invention are useful for conferring cisplatin resistance on a cell, for example non-malignant cells in a tumor bearing subject being treated with cisplatin. Alternatively, the cisplatin resistance of a cell can be inhibited by contacting the cell with an agent which inhibits the activity of the protein of the invention, for example to reverse the cisplatin resistance of a tumor cell. The invention also discloses methods for identifying substances which inhibit cisplatin resistance in a cell or which are chemosensitizers of cisplatin.

Abstract: A method for identifying and selecting novel substrates for enzymes is provided. The method comprises constructing a gene fusion comprising DNA encoding a polypeptide fused to DNA encoding a substrate peptide, which in turn is fused to DNA encoding at least a portion of a phage coat protein. The DNA encoding the substrate peptide is mutated at one or more codons thereby generating a family of mutants. The fusion protein is expressed on the surface of a phagemid particle and subjected to chemical or enzymatic modification of the substrate peptide. Those phagemid particles which have been modified are then separated from those that have not.

Abstract: Novel derivatives of LSD having the formula ##STR1## wherein R.sub.1 is an alkyl, cycloalkyl or aryl group having 1 to 10 carbon atoms, preferably an alkyl group having 1 carbon atom;R.sub.2 is a bond or ##STR2## wherein R.sub.3 is alkyl, cycloalkyl or aryl group having 2 to 10 carbon atoms, preferably an alkyl group having 2 or 5 carbon atoms; Z is an immunogenic carrier substance, an enzyme donor polypeptide or a label selected from the group consisting of an enzyme, a substance having fluorescent or luminescent properties and a radioactive substance; and n is 1 to p where p equals MW of Z/1000. The derivatives include maleimide conjugates of an immunogenic poly(amino acid), an enzyme donor polypeptide or a labeling substance such as an enzyme, a fluorescent substance or a radioactive substance. Novel activated hapten intermediates useful in the preparation of the conjugates and methods for synthesis of the hapten intermediates and their conjugate derivatives are also disclosed.

Abstract: The present invention is directed to a method for selectively enhancing the production of factors A, and/or B.sub.0 of antibiotic A 40926 either to isolate these single components in better yields or to enrich the complex in one or both the above components, which comprises adding an appropriate precursor of the desired antibiotic factor to an A 40926 producing culture during fermentation.