Abstract: Clustered antibiotic biosynthetic genes are employed for improvement of production of the antibiotic in microorganisms and for the isolation of other genes involved in the biosynthesis of the antibiotic. The invention is exemplified with improved production of penicillin in Penicillium chrysogenum, with the isolation of another clustered biosynthetic gene(s) and with the expression of penicillin biosynthetic genes in Acremonium chrysogenum.

Abstract: A human T cell clone containing an integrated copy of HIV in a latent state, but inducible to productive replication by an activating agent is provided. The clone of the present invention allows in vitro screening of anti-HIV drugs.

Abstract: The present invention relates to nucleic acid sequences encoding brain derived neurotrophic factor (BDNF), as well as BDNF protein produced in quantity using these nucleic acid sequences, as well as fragments and derivatives thereof. In addition, the invention relates to pharmacologic compositions and therapeutic uses of BDNF, having provided, for the first time, the means to generate sufficient quantities of substantially pure BDNF for clinical use. The invention also relates to antibodies directed toward BDNF or fragments thereof, having provided a method for generating sufficient immunogen. Further, by permitting a comparison of the nucleic acid sequences of BDNF and NGF, the present invention provides for the identification of homologous regions of nucleic acid sequence between BDNF and NGF, thereby defining a BDNF/NGF gene family; the invention provides a method for identifying and isolating additional members of this gene family.

Abstract: Monoclonal antibodies or paratope-containing portions thereof are disclosed that immunoreact with a meso diester substrate ligand and catalytically hydrolyze a single predetermined ester bond to form one of a pair of enantiomers. Methods of making and using the same are also disclosed.

Abstract: The present invention relates to nucleic acid sequences encoding brain derived neurotrophic factor (BDNF), as well as BDNF protein produced in quantity using these nucleic acid sequences, as well as fragments and derivatives thereof. In addition, the invention relates to pharmacologic compositions and therapeutic uses of BDNF, having provided, for the first time, the means to generate sufficient quantities of substantially pure BDNF for clinical use. In a specific embodiment, BDNF may be used to promote the survival of substantia nigra dopaminergic neurons and basal forebrain cholinergic neurons, thereby providing a method for treating, respectively, Parkinson's disease and Alzheimer's disease. The invention also relates to antibodies directed toward BDNF or fragments thereof, having provided a method for generating sufficient immunogen.

Abstract: A new method is described for the preparation of a safe, immunogenic and efficacious vaccine for protection against the disease pertussis. In development of this vaccine, specific functional sites of pertussis toxin have been identified, and using this information, defined mutant holotoxins have been produced by site directed mutagenesis of the toxin gene. A number of these holotoxin analogues are detoxified, retain an immunodominant S1 epitope, are immunogenic and are protective in the standard pertussis vaccine potency test in mice.

Abstract: The disclosure describes a method for incorporating into double stranded DNA and RNA base pairs composed of pairing units that fit the Watson-Crick geometry in that they involve a monocyclic six membered ring pairing with a fused bicyclic heterocyclic ring system composed of a five member ring fused with a six membered ring, with the orientation of the heterocycles with respect to each other and with respect to the backbone chain analogous to that found in DNA and RNA, but with a pattern of hydrogen bonds holding the base pair together different from that found in the AT and GC base pairs (a "non-standard base pair").

Abstract: The present disclosure relates to the application of genetic engineering to provide artificial .beta. cells, i.e. cells which can secrete insulin in response to glucose. This is achieved preferably through the introduction of one or more genes selected from the insulin gene, glucokinase gene, and glucose transporter gene, so as to provide an engineered cell having all three of these genes in a biologically functional and responsive configuration. Assays for detecting the presence of diabetes-associated antibodies in biological samples using these and other engineered cells expressing diabetes-associated epitopes are described. Also disclosed are methods for the large-scale production of insulin by perfusing artificial .beta. cells, grown in liquid culture, with glucose-containing buffers.

Abstract: An expression vector cDNA library derived from senescent cells has been used to isolate cDNA clones that encode inhibitors of DNA synthesis. Such inhibitors play a role in cellular senescence and aging. Antisense nucleic acids reduce the inhibition of DNA synthesis.

Abstract: Disclosed are polypeptides which antagonize the activity of platelet-derived growth factor (PDGF). These polypeptides include an amino acid sequence sufficiently duplicative of at least a portion of the amino acid sequence of an A chain of PDGF such that the polypeptides bind a cell membrane-bound receptor for native PDGF on a cell that responds biologically to the binding of PDGF. The binding of the antagonist to the receptor is effective to inhibit PDGF binding and activity. Also disclosed are methods of preparing and using these antagonists.

Abstract: Lymphocytes of NK phenotype were cultured with stimulator cell lines in the presence of growth factor containing medium. The resulting lines and clones derived from these lines expressed CD16 and/or Leu 19, but lacked detectable CD3 or T cell receptor .gamma./.delta. complexes on the cell surface. In addition to displaying potent cytolytic activity against K562 erythroleukemia cells (a classical NK target), the vast majority of these lines and clones lysed their specific stimulator cell lines to a significantly greater extent than irrelevant cell lines. These results indicate that some CD3- lymphocytes, phenotypically indistinguishable from NK cells, can recognize and lyse allogeneic targets in a specific manner.

Abstract: The subject invention concerns novel polynucleotide sequences which code for polypeptides which bind IgA. A further aspect of the invention are hybrid proteins (and genes encoding these hybrid proteins) which comprise binding domains for both IgA and IgG.

Abstract: Mammalian G protein coupled glutamate receptors are identified, isolated and purified. The receptors have been cloned, sequenced and expressed by recombinant means. The receptors and antibodies thereby may be used to identify agonists and antagonists of G protein coupled glutamate receptor mediated neuronal excitation, as well as in methods of diagnosis.

Abstract: The present invention relates, in general, to a method of screening agents. In particular, the present invention relates to a method of testing the cancer preventing activity of a drug and of testing an agent for its ability to prevent cell transformation.

Abstract: Herein described are variants of parathyroid hormone that retain significant PTH activity and are substantially resistant to trypsin and trypsin-like enzymes. The variants are useful pharmaceutically, to treat bone disorders such as osteoporosis and in other therapeutic applications. Specific embodiments of the invention include [His.sup.25 ]PTH and [His.sup.25 His.sup.26 Leu.sup.27 ]PTH.

Abstract: Systemin is an 18 amino acid peptide hormone that induces expression of defense genes in plants wounded mechanically or by predators including herbivores, insects, bacteria and viruses. The precursor for systemin is encoded as a 200 amino acid prosystemin molecule that has the systemin peptide sequence located near the carboxy-terminus. Both a 951 bp cDNA for prosystemin and 4526 bp genomic DNA were cloned and the organization of the gene was determined. Transgenic plants constructed with antisense prosystemin DNA fail to mount a defensive response to wounding. Transgenic plants constructed with increased copy number of prosystemin genes exhibit increase resistance to wounding. A tomato systemin polypeptide has an amino acid sequence NH.sub.3 --AVQSKPPSKRDPPKMQTD--COO--.

Abstract: A novel bronchial or bronchiolar epithelial cell from normal neonatal rat lung has been isolated, established and maintained for multiple passages in the absence of serum, without undergoing crisis or senescence. By careful manipulation of the nutritional/hormonal microenvironment we have been able to select, from a heterogeneous population, a single epithelial cell type which can maintain highly differentiated features in vitro. This cell type has characteristics of bronchiolar epithelial cells. A clonal line, RL-65, has been selected and observed for more than 2 years in continuous culture. It has been characterized by ultrastructural, morphological and biochemical criteria.

Abstract: Disclosed herein are methods and means of producing novel growth hormone-like proteins derived from the pituitary gland of fishes belonging to the order Pleuronectina, the family Paralichthydae, which are useful in the growth promotion for fishes, by genetic engineering using cloned genes.

Abstract: Chimeric proteins and DNA sequence encoding chimeric proteins are provided, where the chimeric proteins are characterized by an extracellular domain capable of binding to a ligand in a non-MHC restricted manner, a transmembrane domain and a cytoplasmic domain capable of activating a signaling pathway. The extracellular domain and cytoplasmic domain are not naturally found together. Binding of ligand to the extracellular domain results in transduction of a signal and activation of a signaling pathway in the cell, whereby the cell may be induced to carry out various functions relating to the signalling pathway. A wide variety of extracellular domains may be employed as receptors, where such domains may be naturally occurring or synthetic. The chimeric DNA sequences may be used to modify lymphocytes as well as hematopoietic stem cells as precursors to a number of important cell types.

Abstract: A new method is described for the preparation of a safe, immunogenic and efficacious vaccine for protection against the disease pertussis. In development of this vaccine, specific functional sites of pertussis toxin have been identified, and using this information, defined mutant holotoxins have been produced by site directed mutagenesis of the toxin gene. A number of these holotoxin analogues are detoxified, retain an immunodominant S1 epitope, are immunogenic and are protective in the standard pertussis vaccine potency test in mice.