Abstract: This invention is directed to a composition for catalyzed oligonucleotide cleavage comprising a synthetic non-naturally occurring oligonucleotide compound. The compound comprises nucleotides whose sequence defines a conserved group II intron catalytic region and nucleotides whose sequence is capable of hybridizing with a predetermined oligonucleotide target sequence to be cleaved, such target sequence not being present within the compound. The composition also includes an appropriate oligonucleotide co-factor. Preferably, the conserved group II intron catalytic region is a group II intron domain I catalytic region. In one embodiment the conserved group II intron domain I catalytic region may further comprise a conserved portion of a group II intron domain II, a group II intron domain III, a group II intron domain IV, a group II intron domain V, or a group II intron domain VI. The invention is also directed to methods of treatment and methods of use of such compounds.

Abstract: A method is disclosed for determining the chromosomal identity of a sample of genomic DNA. The genomic DNA is amplified and labeled by polymerase chain reaction using primers substantially complementary to interspersed repetitive DNA sequences. The amplified and labeled genomic DNA fragments are then contacted with chromosomal DNA of known identity under conditions in which the chromosome-specific, but not the interspersed repetitive DNA sequences, of the amplified and labeled genomic DNA fragments are available for hybridization. Specific hybridization to chromosomal DNA of known identity determines the chromosomal identity of the sample of genomic DNA.

Abstract: A method for determining the presence of polymorphisms, including mutations, in nucleic acids by using mass spectrometry is presented. The method requires amplification of the nucleic acid region to be analyzed followed by analysis by mass spectrometry and comparison of the obtained spectrum with spectra obtained from wild-type sequences and/or sequences known to contain the polymorphism. Differences between the spectra, either the appearance or disappearance of one or more peaks indicating a change in mass or a change in the height of one or more peaks indicating a change in the amount of nucleic acid of a specific mass, indicate the presence of a polymorphism. Variations of the method involve digestion of the amplified nucleic acid, e.g., by using restriction enzymes, nucleases or chemical methods, prior to analysis by mass spectrometry. The method can be applied to any type of nucleic acid including genomic DNA, CDNA and RNA.

Abstract: In an assay method in which a member of a specific binding pair is detected by means of an optically detectable reaction, the improvement wherein the optically detectable reaction includes the reaction, with an enzyme, of a dioxetane having the formula ##STR1## where T is a cycloalkyl or polycycloalkyl group bonded to the 4-membered ring portion of the dioxetane by a spiro linkage; Y is a fluorescent chromophore; X is H, alkyl, aryl, aralkyl, alkaryl, heteroalkyl, heteroaryl, cycloalkyl, cycloheteroalkyl, or enzyme-cleavable group; and Z is H or an enzyme-cleavable group, provided that at least one of X or Z must be an enzyme-cleavable group, so that the enzyme cleaves the enzyme-cleavable group from the dioxetane to form a negatively charged substituent bonded to the dioxetane, the negatively charged substituent causing the dioxetane to decompose to form a luminescent substance that includes group Y of said dioxetane.

Abstract: An expression cassette, operable in a recombinant host, comprising a heterologous DNA coding sequence encoding a protein, which is functional, alone or in cooperation with one or more additional proteins, of catalyzing an oxidation step in the biological pathway for conversion of cholesterol into hydrocortisone, which step is selected from the group consisting of:the conversion of cholesterol to pregnenolone;the conversion of pregnenolone to progesterone;the conversion of progesterone to 17.alpha.-hydroxy-progesterone;the conversion of 17.alpha.-hydroxyprogesterone to cortexolone;the conversion of cortexolone to hydrocortisone, and thecorresponding control sequences effective in said host.

Abstract: The present invention provides a gene that encodes proteins associated with liver neoplastic diseases, such as liver cirrhosis and hepatocellular carcinoma. Significantly, these proteins are not expressed in normal, non-neoplastic liver. In accordance with the present invention there also are provided antibodies that are capable of binding to the invention proteins, as well as methods and kits for screening for liver neoplastic diseases.

Abstract: A kit including a dioxetane and an enzyme reactive therewith is useful in an assay method in which a member of a specific binding pair is detected by means of an optically detectable reaction, the improvement wherein the optically detectable reaction includes the reaction, with the enzyme, the dioxetane having the formula ##STR1## where T is a cycloalkyl or polycycloalkyl group bonded to the 4-membered ring portion of the dioxetane by a spiro linkage; Y is a fluorescent chromophore; X is H, alkyl, aryl, aralkyl, alkaryl, heteroalkyl, heteroaryl, cycloalkyl, cycloheteroalkyl, or enzyme-cleavable group; and Z is H or an enzyme-cleavable group, provided that at least one of X or Z must be an enzyme-cleavable group, so that the enzyme cleaves the enzyme-cleavable group from the dioxetane to form a negatively charged substituent bonded to the dioxetane, the negatively charged substituent causing the dioxetane to decompose to form a luminescent substance that includes group Y of said dioxetane.

Abstract: The invention provides genetic suppressor elements that confer upon a cell resistance to one or more chemotherapeutic drug, methods for identifying and obtaining such elements, and methods of using such elements. The invention also provides cloned genes associated with sensitivity to chemotherapeutic drugs, particularly a cloned human kinesin heavy chain gene involved in resistance to DNA damaging agents.

Abstract: Oligonucleotides and other macromolecules are provided that have increased nuclease resistance, substituent groups for increasing binding affinity to complementary strand, and subsequences of 2'-deoxy-erythro-pentofuranosyl nucleotides that activate RNase H enzyme. Such oligonucleotides and macromolecules are useful for diagnostics and other research purposes, for modulating protein in organisms, and for the diagnosis, detection and treatment of other conditions susceptible to antisense therapeutics.

Abstract: Methods and compounds for selective cleavage of nucleic acid are described. The compounds generally contain three functionalities: (1) an oligonucleoside portion which is substantially complementary to at least a portion of the target nucleic acid, thereby providing selectivity to the compound; (2) a non-complementary portion which replaces one of the otherwise-complementary nucleoside bases in the oligonucleoside and which serves to place the target nucleic acid strand into a conformation that favors the cleavage of a phosphodiester linkage opposite the non-complementary portion; and (3) a cleavage moiety which possesses one or more and preferably two or more of the features of (a) proton donation, (b) proton acceptance, (c) hydrogen bonding, (d) charge neutralization and (e) Lewis acidity. These compounds may be used for the study and treatment of diseases involving foreign genetic materials or alterations to or inappropriate expression of genomic DNA.

Abstract: The present invention relates generally to a novel CREBa polypeptide isoform, polynucleotides encoding the polypeptide, expression constructs comprising the polynucleotides, host cell transformed or transfected with the polynucleotides, methods for producing the polypeptide, and methods to identify inhibitors of binding between the CREBa and other polypeptides or polynucleotides.

Abstract: The present invention is directed to isolated amyloid precursor-like proteins (APLPs), nucleotide sequences coding for and regulating expression of these protein, antibodies directed against these proteins, and recombinant vectors and host cells containing the genetic sequences coding for and regulating the expression of these protein sequences. The invention is also directed to isolated genomic DNA, cDNA anti-sense RNA, and RNA containing the protein sequence. Antibodies can be used to detect an APLP in biological specimens, including, for example, fluid, serum or tissue samples. APLP1 and APLP2 are candidate genes for late onset familial Alzheimer's disease.

Abstract: A process is disclosed for inhibiting the amplification of a DNA template by subjecting a sample of biological material containing nucleic acid to the polymerase chain reaction (PCR) using a DNA polymerase deficient in 5' exonuclease activity. The method comprises forming a PCR admixture comprising the DNA template, first and second oligonucleotide primers which are complementary to separated regions of the nucleic acid template, a non-extendable oligonucleotide blocker which is complementary to the inter-primer region of the DNA, and the DNA polymerase lacking 5' exonuclease activity, and subjecting the PCR admixture to at least one PCR thermocycle. The DNA polymerase lacking 5' exonuclease activity is incapable of excising the non-extendable blocker which anneals to the DNA template during the PCR, thereby inhibiting amplification which would otherwise occur during the PCR. Preferably, the DNA polymerase lacking 5' exonuclease activity is the Stoffel fragment of Taq polymerase.

Abstract: An improved composition containing peptides and nucleic acids has active components, i.e., which heighten the phagocytic activity f neutrophils, consisting of molecules with a molecular weight of at least 8 kDa, and preferably at least 15 kDa. The active components comprise peptides without aromatic portions and will absorb light at an absorption band of .DELTA..lambda.=200-235 mn, .lambda..sub.max =205 nm, in the UV spectrum. The composition is nontoxic and is formulated using casein, blood albumin, beef peptone, nucleic acid (RNA) and a base such as sodium hydroxide. The composition stimulates phagocytic activity of neutrophils if used at sufficient concentrations. A separate composition is obtained using the same components of manufacture, but filtering or centrifuging the composition to a molecular weight of <8-15 kDa which inhibits phagocytic activity of neutrophils for application in treating auto immune diseases.

Abstract: The present invention provides a nucleotide sequence encoding carbamoyl phosphate synthetase II of Plasmodium falciparum. Carbamoyl phosphate synthetase II catalyses the first committed and rate-limiting step in the de novo pyrimidine biosynthetic pathway. P. falciparum relies exclusively on pyrimidine synthesis de novo because of its inability to salvage pyrimidines. Mature human red blood cells, however, have no recognised requirement for a pyrimidine nucleotide. Accordingly, this enzyme represents a prime chemotherapeutic locus. The present invention relates to the use of the sequence encoding carbamoyl phosphate synthetase II in the recombinant production of carbamoyl phosphate synthetase II and to antisense molecules, ribozymes and other gene inactivation agents designed from this sequence.

Abstract: A novel conserved amino acid motif ("PAS") which provides a binding site for homo and hetero protein interactions has been found in mammalian and insect proteins. Abnormalities in these protein interactions are believed to be responsible for a variety of human diseases or conditions, including behavioral disorders and epithelial tissue cancers. Methods for identifying persons who have a disposition towards these behavioral disorders or epithelial tissue cancers are described. Methods are also described for identifying agonists and antagonists of proteins or related peptides containing PAS domains. Screening such agents involves assessing the ability of candidate compounds to promote or interfere with the binding of certain biologic preparations comprised of PAS-containing proteins. Successful agonists or antagonists should be useful in modifying the effects of human behavioral disorders, as well as certain epithelial cancers.

Abstract: This invention is a method for treating diseases involving the mammalian kidney proximal tubule epithelium with naked antisense oligonucleotides and antisense compositions against the mRNA of mammalian kidney epithelial proteins.

Abstract: Oligonucleotides that inhibit Epstein-Barr virus functions, pharmaceutical compositions containing such oligonucleotides, and methods of using these compositions to treat Epstein-Barr virus-associated diseases.

Abstract: The invention provides devices and methods for use in detecting nucleic acid analytes in samples. The devices each include a solid support to which is bound a two-dimensional distribution or field of nucleic acid probes that each bind to a nucleic acid analyte, which is detected by use of amplification methods.

Abstract: This invention provides isolated nucleic acid encoding human MAD2, isolated human MAD2 protein. This invention further provides a method of detecting the presence of MAD2 in a tissue sample, a method of determining whether a tumor is susceptible to treatment with a mitotic spindle inhibitor by detecting the presence of MAD2 in the tumor and a method of suppressing tumor formation in a subject which comprises administering the nucleic acid encoding human MAD2 to the subject in an amount effective to enhance expression of MAD2. This invention also provides a nucleic acid reagent capable of detecting the MAD2 gene or gene product and a method for in situ identification of tumors which may be susceptible to treatment with mitotic spindle inhibitors by detecting the absence of nucleic acid encoding MAD2 in the tumor.