Abstract: Novel, heterocyclic compounds having at least one ring nitrogen, disclosed side chains and, in some embodiments, an oxygen ortho to the ring nitrogen inhibit inflammatory responses associated with TNF-.alpha. and fibroblast proliferation in vivo and in vitro. The compounds of the invention neither appreciably inhibit the activity of cAMP phosphodiesterase nor the hydrolysis of phosphatidic acid, and are neither cytotoxic nor cytostatic. Preferred compounds of the invention are esters. Methods for the use of the novel compounds to inhibit ceramide-mediated intracellular responses to stimuli in vivo (particularly TNF-.alpha.) are also described. The methods are expected to be of use in reducing inflammatory responses (for example, after angioplasty), in limiting fibrosis (for example, of the liver in cirrhosis), in inhibiting cell senescence, cell apoptosis and UV induced cutaneous immune suppression.

Abstract: An in vivo method for depleting mammalian cells of adenosine 5'-monophosphate (AMP) useful in the treatment of certain cancers is provided. According to the method, a population of cells is obtained from a host and assayed for loss of methylthioadenosine phosphorylase (MTAse) activity. MTAse catabolizes methylthioadenosine to adenine for endogenous salvage incorporation into the intracellular AMP pool. The preferred method for assaying loss of MTAse activity is a hybridization technique for detection of a homozygous loss of the gene which encodes MTAse. Hosts having MTAse deficient tumors are treated with a therapeutically effective amount of an agent which inhibits the activity of adenylsuccinate synthetase, which converts inosine 5'-monophosphate to AMP, thus depleting the tumor cells of substrates for de novo AMP production. L-alanosine is the preferred ASS inhibitory agent for use in the method of the invention.

Abstract: This invention relates to methods for administering antigens and immunostimulatory peptides to a mammalian host by the introduction of one or more naked polynucleotides to operatively encode for the antigens and immunostimulatory peptides, preferably by non-invasive means.

Abstract: The invention is directed to methods for introducing biologically active peptides into a host by administration of polynucleotides which operatively encode for the peptide of interest. In a preferred embodiment of the invention, a mammal is desensitized to an antigen, in particular an allergen, through administration to the mammal of polynucleotides which operatively encode the antigen. The antigen-encoding polynucleotides are administered to host tissues which have a high concentration of antigen presenting cells in them relative to other host tissues. The method is particularly useful in treating allergies because the allergen-encoding polynucleotides of the invention to induce tolerance while suppressing IgE antibody formation. Devices and compositions for use in the methods of the invention are also described.

Abstract: Vaccine compositions useful in inducing immune protection in a host against arthritogenic peptides involved in the pathogenesis of rheumatoid arthritis are disclosed. Each vaccine composition provides antigenic dnaJp1 peptide (by including the peptide or a polynucleotide which encodes the peptide).

Abstract: Combinations of polymerization, non-competitive hybridization and assay techniques is disclosed. In one aspect of the method, one member of a regular or anchored primer pair is modified to include a coupling agent capable of forming a tight bond (resistant to uncoupling in an alkaline denaturing environment) with a reactant. Competitive PCR is performed and the PCR products are coupled via the coupling agent to a reactant on the surface of a solid phase support. The bond between the reactant and the solid phase support in this and all embodiments is also resistant to uncoupling in an alkaline denaturing environment. In another aspect of the method, a primer is tightly coupled to the bound reactant and a polymerization of the competitor and target nucleic acids is performed on the solid phase. A third embodiment uses at least three primers, one of which is internal to the PCR templates and is bound to the solid phase support on which the entire PCR takes place.

Abstract: A method is disclosed for delivering an isolated polynucleotide to the interior of a cell in a vertebrate, comprising the interstitial introduction of an isolated polynucleotide into a tissue of the vertebrate where the polynucleotide is taken up by the cells of the tissue and exerts a therapeutic effect on the vertebrate. The method can be used to deliver a therapeutic polypeptide to the cells of the vertebrate, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the vertebrate, or to provide transitory gene therapy. In particular, a method is disclosed for the generation of detectable antibodies by the direct administration to a tissue in a mammal a DNA sequence encoding a immunogen where the DNA is complexed to a cationic lipid.

Abstract: The invention is directed to methods for introducing biologically active peptides into a host by administration of polynucleotides which operatively encode for the peptide of interest. In a preferred embodiment of the invention, a host who has been identified as having a tumor bearing at least one tumor-associated antigen is the recipient of a polynucleotide which operatively encodes for a foreign mimic of the tumor-associated antigen or a mutation of the self-antigen. The antigen-encoding polynucleotides are administered to host tissues which have a high concentration of antigen presenting cells in them relative to other host tissues. The method is particularly useful in treating cancer through induction of antigen-specific cytotoxic T lymphocytes in the host for lysis of tumor cells bearing the antigen. Devices and compositions for use in the methods of the invention are also described.

Abstract: A method for delivering an isolated polynucleotide such as DNA or RNA, to the interior of a cell in a mammal comprising the injection of an isolated polynucleotide into a muscle of the mammal where the polynucleotide is taken up by the cells of the muscle and exerts a therapeutic effect on the mammal. The method can be used to deliver a therapeutic polypeptide to the cells of the mammal, to provide an immune response upon in vivo translation of the polynucleotide, to deliver antisense polynucleotides, to deliver receptors to the cells of the mammal or to provide transitory gene therapy.

Abstract: Polynucleotide sequences, comprising DNA and RNA molecules can be directly administered, for example by injection, to tissues, such as muscle, and expressed as a protein, polypeptide or polypeptide. The polynucleotides can be contained within liposomes or the polynucleotides can free from association with transfection-facilitating proteins, viral particles, liposomal formulations, charged lipids and calcium phosphate precipitating agents.

Abstract: An improved method for chemotherapy of mammalian malignant cells which have an absolute requirement for methionine but lack methylthioadenosine phosphorylase (MTAse). The method comprises detection of MTAse negative cells in a mammal, administration of methionine .gamma.-lyase in sufficient amounts to reduce the volume of MTAse negative cells in the mammal, and co-administration of methylthioadenosine in amounts sufficient to ensure the continued availability of methionine to the mammal's non-malignant cells. Means for detection of MTAse negative cells are provided. Means for production and use of recombinant chemotherapeutic agents are also provided.

Abstract: Novel adenine derivatives whose structures are represented by Formula I, are disclosed, as are methods of using those compounds and others of Formula II to treat monocyte-mediated disorders such as rheumatoid arthritis and multiple sclerosis.

Abstract: Novel adenine derivatives whose structures are represented by Formula I, are disclosed, as are methods of using those compounds and others of Formula II to treat monocyte-mediated disorders such as rheumatoid arthritis and multiple sclerosis.

Abstract: Novel adenine derivatives whose structures are represented by Formula I, are disclosed, as are methods of using those compounds and others of Formula II to treat monocyte-mediated disorders such as rheumatoid arthritis and multiple sclerosis.

Abstract: The present invention relates to the use of interferon and/or interleukin-6 to increase intravascular C1 inhibitor concentrations in patients exhibiting or at risk for a C1 inhibitor deficiency. Therapeutic compositions containing interferon and/or interleukin-6 are also disclosed.

Abstract: Antigens, immunogens, inocula, antibodies, and particularly diagnostic methods and systems relating to Epstein-Barr virus nuclear antigen (EBNA) are disclosed. The diagnostic methods and systems utilize a synthetic, random copolymer polypeptide containing about 8 to about 40 amino acid residues that includes the overlapping five and six amino acid residue sequences--Gly--R.sup.1 --Gly--R.sup.2 --Gly-- (i)wherein R.sup.1 and R.sup.2 are amino acid residues selected from Ala, Asn, Arg, Gly, Leu, Pro, Ser, and Thr with the provision that R.sup.1 and R.sup.2 are not both Gly; and--Gly--Ala--Gly--Gly--Ala--Gly--. (ii)The polypeptide contains at least 50 mole percent Gly residues. The diagnostic method and system are particularly useful for assaying for the stage of mononucleois disease, and the presence of nasopharynegeal carcinoma.

Abstract: Antigens, immunogens, inocula, antibodies, and particularly diagnostic methods and systems relating to Epstein-Barr virus nuclear antigen (EBNA) are disclosed. The diagnostic methods and systems utilize a synthetic, random copolymer polypeptide containing about 8 to about 40 amino acid residues that includes the overlapping five and six amino acid residue sequences(i) --Gly--R.sup.1 --Gly--R.sup.2 --Gly--wherein R.sup.1 and R.sup.2 are amino acid residues selected from Ala, Asn, Arg, Gly, Leu, Pro, Ser, and Thr with the provision that R.sup.1 and R.sup.2 are not both Gly; and(ii) --Gly--Ala--Gly--Gly--Ala--Gly--.The polypeptide contains at least 50 mole percent Gly residues. The diagnostic method and system are particularly useful for assaying for the stage of mononucleois disease, and the presence of nasopharynegeal carcinoma.

Abstract: Novel adenine derivatives whose structures are represented by Formula I, are disclosed, as are methods of using those compounds and others of Formula II to treat monocyte-mediated disorders and autoimmune diseases.

Abstract: Chemically synthesized polypeptides containing about 6 to 40 amino acid residues and having amino acid residue sequences that substantially correspond to the primary amino acid residue sequences of particular variable or hypervariable regions of immunoglobulins, when administered alone or as polymers or as conjugates bound to carriers, induce the production of anti-idiotype antibodies of predetermined specificities.

Abstract: Antigens, immunogens, inocula, antibodies, diagnostic methods and systems relating to Epstein-Barr virus nuclear antigen (EBNA) are disclosed. Each of the compounds, compositions, methods or systems contains a synthetic, random copolymer polypeptide having about 6 to about 40 residues, or an antibody containing site that immunoreacts with such a polypeptide. The polypeptide includes the five amino acid residue sequence -Gly-R.sup.1 -Gly-R.sup.2 -Gly-, wherein R.sup.1 and R.sup.2 are the same or different amino acid residues selected from the group consisting of Ala, Asn, Arg, Gly, Leu, Pro, Ser, and Thr, with the provision that R.sup.1 and R.sup.2 are not both Gly. The polypeptide contains at least 25 mole percent Gly residues, and when linked to a carrier and introduced in an effective amount into a mammalian host is capable of inducing production of antibodies that immunoreact with EBNA.