Abstract: The invention relates to methods and compositions for manipulating bacterial resistance to non-antibiotic antibacterial compositions, disinfectants and organic solvents. The invention provides methods for rendering bacterial cells susceptible to non-antibiotic antibacterial compositions. Also provided are methods to reduce the selection of bacterial mutants having an multiple antibiotic resistance phenotype by non-antibiotic antibacterial compositions. The invention also provides methods for testing the ability of non-antibiotic antibacterial compositions to select for or induce a multiple antibiotic resistance phenotype in bacteria. Also provided are methods for increasing or decreasing bacterial tolerance to organic solvents by increasing or decreasing the activity of bacterial organic solvent efflux pumps. Compositions useful in the foregoing methods are also provided.

Abstract: Antisense oligonucleotides that selectively hybridise with one or more genes necessary for Helicobacter pylori (H. pylori) activity, and particularly with the CagA cytotoxicity-associated immunodominant antigen, flagellin (flaA and flaB) or vacuolating cytotoxin (vacA), are disclosed. Pharmaceutical compositions containing said antisense oligonucleotides, and the use thereof for treating atrophic gastritis, peptic and duodenal ulcers, gastric atrophy or stomach cancer, are also disclosed.

Abstract: A novel human GTPase polypeptide intracellular molecular switch is described. A full length cDNA which encodes the signal transduction polypeptide is disclosed as well as the interior structural region and the amino acid residue sequence of the human GTPase. Methods are provided to identify compounds that modulate the biological activity of the native signal switch biomolecule and hence regulate cellular and tissue physiology.

Abstract: External guide sequence (EGS) molecules for eukaryotic RNAse P are engineered to target efficient and specific cleavage of target RNA. Engineered RNA molecules are designed and synthesized which contain specific nucleotide sequences which enable an external guide sequence for RNAse P to preferentially bind to and promote RNAse P-mediated cleavage of target RNA molecules. Short External Guide Sequence (SEGS) molecules have been constructed that, when hybridized to a target molecule, provide a minimal structure recognized as a substrate by RNAse P. The SEGS/target structure is comprised of a structures similar to the A stem and the T stem of a tRNA, the natural substrate of RNAse P. The SEGS makes up only half of these stem structures. The other half of the stem structures is provided by the target molecule. By allowing the target molecule to form more of the RNAse P substrate structure, the disclosed SEGS molecules can be significantly smaller than previous EGS molecules.

Abstract: This invention describes compounds active against TNF-.alpha. mRNA. It further describes RNA molecules capable of conferring stability to RNA in vivo through an endogenous ribozyme binding protein(s). Possible mRNA molecules to be stabilized include ribozymes, antisense molecules and mRNA encoding polypeptides useful for protein production. The ribozymes and antisense molecules described herein are useful in mammals and plants, particularly suited for viral diseases. Methods of production and methods of use are also described.

Abstract: The invention relates to a recombinant nucleotide sequence, characterized in that it comprises:a regulatory sequence of the initiation of transcription, this regulatory sequence containing a promoter in association with the motif GCACTC 9N GAGTGC, in which "N" signifies any one of the 4 bases thymine, guanine, adenine and cytosine;a sequence coding for a polypeptide, called "heterologous polypeptide", which is different from that naturally associated with the promoter; the coding sequence being positioned downstream from the regulatory sequence of the initiation of transcription at a site which, under suitable conditions, would allow the expression of the polypeptide under the control of the promoter.

Abstract: A process is provided for preparing crystalline fine powder of silk fibroin from a silk substance in an industrially advantageous fashion.The process for the preparation of fine powder of the silk fibroin is such that, after the silk substance is brought into an alkaline aqueous solution at a temperature of 95.degree. C. or higher in order to cause a strength of said silk substance to deteriorate, the resulting silk substance is subjected to treatment with alkali and dried, and the dry silk substance is pulverized into finely divided powder.

Abstract: The present invention discloses a novel approach to attenuating bacteria and for their use as live vaccines. The vaccines can be used in human and animal medicine.In particular, there is disclosed a method of attenuating a bacteria by mutating a gene concerned with the regulation of one or more genes concerned with expression of outer membrane proteins, particularly porin proteins.

Abstract: We have now discovered a helper virus free herpesvirus packaging system. This system can be used to package a wide range of desired nucleotide segments, preferably a DNA segment, into an empty herpesvirus particle because of the large genomes of herpesviruses. Preferably, the herpesvirus is an alpha herpesvirus. More preferably, the herpesvirus is an alpha herpesvirus such as Varicella-Zoster virus, pseudorabies virus, or a herpes simplex virus such as HSV-1 or HSV-2. Another preferred herpesvirus is Epstein-Barr virus.

Abstract: Oligonucleotides are provided which are effective in inhibiting the growth, metastasis and/or angiogenesis of tumors, including particularly melanoma and/or lung cancer. Methods are also provided for use of these oligonucleotides in the treatment of diseases.

Abstract: Compositions for enhancing the production of toxic polypeptides in prokaryotic hosts comprise a coding nucleic acid and a bacteriophage nucleic acid. The coding nucleic acid encodes a promoter operably linked to a gene encoding a selected toxic protein. The bacteriophage nucleic acid contains at least one gene from the early region of a T7-like bacteriophage other than an RNA polymerase. When both the coding nucleic acid and the bacteriophage nucleic acid are used to transform or transfect a prokaryotic host, the production of the toxic polypeptide is greater than the level of production of the same toxic polypeptide when the same host is transformed only with the coding nucleic acid.

Abstract: The present invention provides a method for the silencing of specific genes by DNA methylation. The method involves introducing into a cell a single stranded oligonucleotide containing 5-methyl deoxycytosine. The single stranded oligonucleotide has a sequence complementary to a portion of the DNA sequence of the gene to be silenced.

Abstract: A method for finding an agent which inhibits interaction between LIL-Stat protein and a nucleic acid having a LIL-Stat binding sequence is described. The LIL-Stat protein is contacted with the nucleic acid in the presence of an agent which inhibits or does not inhibit the interaction between the LIL-Stat protein and the nucleic acid. It is determined whether or not the agent inhibits this interaction. Also described are a method for treating an inflammatory response in a mammal, a therapeutic inhibitory agent suitable for treating or preventing an inflammatory response in a mammal, and DNA molecules having a DNA sequence encoding a binding site for the LIL-Stat protein.

Abstract: Disclosed are methods of reducing neovascularization and of treating various disorders associated with neovascularization. These methods include administering to a tissue or subject a synthetic oligonucleotide specific for vascular endothelial growth factor nucleic acid effective in inhibiting the expression of vascular endothelial growth factor.

Abstract: This invention relates to lymphotoxin-.beta., a lymphocyte membrane type protein. This protein is found on the surface of a number of cells, including phorbol ester (PMA) stimulated T cell hybridoma II-23.D7 cells. This invention also relates to complexes formed between lymphotoxin-.beta. and other peptides such as lymphotoxin-.alpha. and to complexes comprising multiple subunits of lymphotoxin-.beta.. These proteins and complexes are useful in holding LT-.alpha. formed within the cell on the cell surface where the LT-.alpha./LT-.beta. complex may act as an inflammation regulating agent, a tumor growth inhibiting agent, a T cell inhibiting agent, a T cell activating agent, an autoimmune disease regulating agent, or an HIV inhibiting agent. Furthermore, the antitumor activity of the LT-.alpha./LT-.beta. complex may be delivered to tumor cells by tumor infiltrating lymphocytes (TILs) transfected with the gene for LT-.beta..

Abstract: Nucleic acid sequences, particularly DNA sequences, coding for all or part of the high molecular weight subunit of microsomal triglyceride transfer protein, expression vectors containing the DNA sequences, host cells containing the expression vectors, and methods utilizing these materials. The invention also concerns polypeptide molecules comprising all or part of the high molecular weight subunit of microsomal triglyceride transfer protein, and methods for producing these polypeptide molecules. The invention additionally concerns novel methods for preventing, stabilizing or causing regression of atherosclerosis and therapeutic agents having such activity. The invention concerns further novel methods for lowering serum liquid levels and therapeutic agents having such activity.

Abstract: Hepatitis delta is used as a vector for inhibition of viral infection and to express proteins in vivo in a cell-specific manner. The scope of delta's use as a vector is broadened in the present invention in several important ways. For example, a delta RNA genome capable of self-replication is enlarged to carry additional information, either coding for messenger RNA for a protein, or for a targeted ribozyme, which can be delivered to liver cells using delta's normally infectious properties, or to other cell types using chimeric delta viral agents carrying altered surface proteins. In another embodiment, the delta vector is made self-limiting, so that its role in delivering targeted information is separated from its viral property of unlimited infectious replication. Targeting is achieved through the use of sequences flanking the delta sequences that have affinity for sites on RNA to be cleaved.

Abstract: A 12 to 30 nucleotide-unit long oligonucleotide that comprises at least one 5-substituted uracil or cytosine, where the 5-substituent is a C.sub.3-6 n-alkyl, a vinyl, a butenyl, an ethynyl, or a C.sub.4-12 n-1-alkynyl, with the proviso that the uracil moiety may not be substituted with an n-alkyl or a C.sub.8-12 n-1-alkynyl.

Abstract: Method to produce a more active ribozyme by introducing a modified base into a substrate binding arm of the ribozyme or its catalytic core.

Abstract: Disclosed is a process for forming a normalized genomic DNA library from an environmental sample by (a) isolating a genomic DNA population from the environmental sample; (b) analyzing the complexity of the genomic DNA population so isolated; (c) at least one of (i) amplifying the copy number of the DNA population so isolated and (ii) recovering a fraction of the isolated genomic DNA having a desired characteristic; and (d) normalizing the representation of various DNAs within the genomic DNA population so as to form a normalized library of genomic DNA from the environmental sample. Also disclosed is a normalized genomic DNA library formed from an environmental sample by the process.