Abstract: Preclinical studies in mice and rats based on three microinfusions (12 hours apart) of specifically designed and synthesized adenosine A.sub.1 receptor antisense oligonucleotide with the sequence: (A.sub.1 Antisense: 5'-GGCCGAGATGGAGGGCGGCAT-3' (SEQ ID NO: 1)) and as a control, a mismatched antisense nucleotide with a sequence: (A.sub.1 Sense: 5'-ATGCCGCCCTCCATCTCGGCC-3' (SEQ ID NO: 1)) established that the "functional knock out" of A.sub.1 receptors protected the animals from the well known motor incoordination due to alcohol or .DELTA..sup.9 -tetrahydrocarnabinol(THC: the major psychoactive component of marijuana intake). The motor coordination in animals was evaluated by the mouse/rat rotorod treadmill. The antisense was microinfused in mouse cerebellum and in the rat motor cortex whereas ethanol was always administered systemically. However, unlike ethanol, the .DELTA..sup.9 -THC was microinfused into the mouse cerebellum following the cerebellar pretreatment with the antisense.

Abstract: A process using polymerize chain reaction (PCR) technology is described for the detection of spore forming bacteria in paper products and paper manufacturing streams and additives. Disclosed and claimed are novel nucleotide primers which specifically amplify sporulation genes common to spore forming bacteria. These primers produce gene fragments diagnostic for the presence of spore forming bacteria.

Abstract: A detector oligonucleotide having a sequence which forms an intramolecularly base-paired secondary structure is described for use in detecting nucleic acid target sequences and target sequence amplification. The detector oligonucleotide is further modified by linkage to two dyes which form a donor/acceptor dye pair. The two dyes are positioned on the detector oligonucleotide such that they are in close spatial proximity in the base-paired, folded secondary structure, thereby causing quenching of donor fluorescence. The detector oligonucleotide may optionally further comprise a restriction endonuclease recognition site (RERS) which remains partially or entirely single-stranded in the base-paired secondary structure. The RERS is flanked by the two dyes. In the presence of target, the base-paired secondary structure is unfolded or linearized, increasing the distance between the donor and acceptor dyes and causing a change in fluorescence of the donor and/or the acceptor.

Abstract: Single-stranded signal primers are modified by linkage to two dyes which form a donor/acceptor dye pair. The two dyes are positioned in sufficiently close spatial proximity on the signal primer that the fluorescence of the first dye is quenched by the second dye. The signal primer may further comprise a restriction endonuclease recognition site (RERS) between the two dyes. As the signal primer is initially single-stranded and remains single-stranded in the absence of target, the restriction endonuclease recognition site is not cleavable or nickable by the restriction endonuclease. In the presence of target, however, signal primer and the restriction endonuclease recognition site are rendered double-stranded and cleavable or nickable by the restriction endonuclease. Cleavage or nicking separates the two dyes and a change in fluorescence due to decreased quenching is detected as an indication of the presence of the target sequence or of target sequence amplification.

Abstract: The photocleavable cyclic oligonucleotide according to the invention is the one that possesses a base sequence having the hybridization ability toward DNA or RNA to targeted, and is further provided with the structure cyclized by a photocleavable group. Accordingly, the photocleavable cyclic oligonucleotide according to the invention, after having been introduced in vivo, is hardly susceptible to the nuclease decomposition reaction owing to its cyclic structure and thus it is capable of diffusing toward the predetermined sites in vivo with sufficient time. Moreover, by being irradiated with the light at an appropriate wavelength after a predetermined period of time, the photocleavable group as described above is cleaved photochemically, thus cutting the predetermined bond. This permits the oligonucleotide that was cyclic to be a linear oligonucleotide which expresses the function of an antisense oligonucleotide.

Abstract: Compositions and methods are provided for the treatment and diagnosis of diseases associated with protein kinase C. Oligonucleotides are provided which are targeted to nucleic acids encoding PKC. Oligonucleotides specifically hybridizable with a translation initiation site, 5'-untranslated region or 3'-untranslated region are provided. Oligonucleotides specifically hybridizable with a particular PKC isozyme or set of isozymes are also provided. Methods of treating animals suffering from disease amenable to therapeutic intervention by modulating protein kinase C expression with an oligonucleotide targeted to PKC are disclosed.

Abstract: The present invention relates to a system for the reversible anticoagulation of blood utilizing a nucleic acid ligand which binds thrombin and a reversing agent which has greater affinity for the nucleic acid ligand than does thrombin. When used with a blood sample, the nucleic acid ligand binds thrombin, preventing it from converting fibrinogen to fibrin, and thus anticoagulating the blood. Subsequently, the reversing agent may be added to the anticoagulated blood sample, and by competitive binding, replaces thrombin bound to the ligand, thus freeing the thrombin to convert fibrinogen to fibrin and allowing the blood to coagulate.

Abstract: Compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of expression of a gene encoding a Jun N-terminal kinase (JNK protein) are provided. Oligonucleotide are herein provided which are specifically hybridizable with nucleic acids encoding JNK1, JNK2 and JNK3, as well as other JNK proteins and specific isoforms thereof. Methods of treating animals suffering from diseases or disorders amenable to therapeutic intervention by modulating the expression of one or more JNK proteins with such oligonucleotide are also provided. Methods for the treatment and diagnosis of diseases or disorders associated with aberrant expression of one or more JNK proteins are also provided. The invention is thus directed to compositions for modulating, diagnostic methods for detecting, and therapeutic methods for inhibiting, the hyperproliferation of cells and formation, development and maintenance of tumors.

Abstract: A single stranded oligonucleotide complementary to a specific region of a gene promoter, methylated at carbon 5 of all cytosine residues in cytosine-guanine (CG) dinucleotides, is provided. The modified oligonucleotide provides DNA methyltransferase (MTase) enzyme with a hemimethylated substrate so that DNA MTase can methylate complementary CG sites using methylated oligonucleotides as the template. Such methylation prevents translation of the gene. An oligonucleotide complementary to the sense strand of c-Ha-ras promoter having a methyl group on all cytosine residues of its 6 CpG sites was specifically effective in inhibiting breast tumor cell proliferation and tumorigenicity.

Abstract: Antisense oligonucleotides optionally stabilized with phosphorotioate residues or analogues, or modified in the whole sugar-phosphate backbone--complementary to the human urokinase receptor messenger RNA--are able to prevent invasiveness of neoplastic cells by inhibiting the overexpression of the receptor itself, directly responsible of the invasive phenotype. Said oligomers are useful as medicaments for the treatment of primary and secondary neoplasias as well as of other pathologies wherein the urokinase receptor gene overexpression is a pathogenic event.

Abstract: A protein designated "Lg-Flo1" can be produced recombinantly and confers brewer's yeast-type flocculating property, for example, when Lg-FLO1 DNA is expressed in non-flocculent yeast strain. Conversely, a flocculent yeast strain can be rendered non-flocculent by eliminating or disrupting the ability of the strain to express Lg-Flo1.

Abstract: The invention relates to novel conjugates of tetrasaccharides, preferably of sialyl-Lewis X (SLeX) and sialyl-Lewis A (SLeA), having improved activity as inhibitors of cell adhesion, a process for the preparation of these compounds, and their use as pharmacological active compounds and as diagnostics and pharmaceuticals which contain these conjugates.

Abstract: The present invention provides a polynucleotide (hhp) which identifies and encodes a novel human hyaluronidase (HHP). The invention provides for genetically engineered expression vectors and host cells comprising the nucleic acid sequence encoding HHP. The invention also provides for the use of substantially purified HHP and its agonists in the commercial production of recombinant proteins and in pharmaceutical compositions for the treatment of diseases associated with the expression of HHP. Additionally, the invention provides for the use of antisense molecules to hhp in pharmaceutical compositions for treatment of diseases associated with the expression of HHP. The invention also describes diagnostic assays which utilize diagnostic compositions comprising the polynucleotide, fragments or the complement thereof, which hybridize with the genomic sequence or the transcript of hhp. The present invention also relates to anti-HHP antibodies which specifically bind to HHP.

Abstract: Single-stranded signal primers are modified by linkage to two dyes which form a donor/acceptor dye pair. The two dyes are positioned in sufficiently close spatial proximity on the signal primer that the fluorescence of the first dye is quenched by the second dye. The signal primer may further comprise a restriction endonuclease recognition site (RERS) between the two dyes. As the signal primer is initially single-stranded and remains single-stranded in the absence of target, the restriction endonuclease recognition site is not cleavable or nickable by the restriction endonuclease. In the presence of target, however, signal primer and the restriction endonuclease recognition site are rendered double-stranded and cleavable or nickable by the restriction endonuclease. Cleavage or nicking separates the two dyes and a change in fluorescence due to decreased quenching is detected as an indication of the presence of the target sequence or of target sequence amplification.

Abstract: The present invention relates, first, to the identification of novel nucleic acid molecules and proteins encoded by such nucleic acid molecules, or degenerate variants thereof, that participate in the regulation, control and/or modulation of G-protein-mediated signal transduction involved in T cell activation, including, but not limited to T helper (TH) cell and TH cell subpopulation activation. Specifically, the nucleic acid molecules of the present invention include the genes corresponding to the mammalian R11 gene, including the human R11 gene. R11 sequence analysis indicates that the R11 gene is a novel gene belonging to the RGS ("regulator of G-protein signalling") gene family, a gene family which encodes gene products involved in G-protein-mediated signal transduction.