Template properties of polyribonucleotides containing uracil or modified uracil in the RNA polymerase reaction.
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Serum from patients with inflammatory bowel disease (I.B.D.) and their unaffected spouses bound significantly more synthetic single-stranded (poly.rA) and double-stranded (poly.rA.poly.rU) R.N.A. but not KB cell D.N.A. than did serum from age-matched controls and their spouses. Binding activity resided in Ig fractions and was predominantly of IgM class. A significant corelation was observed between the amount of double-stranded but not single-stranded R.N.A. bound by serum from patients and from their respective spouses. These findings provide indirect support for the presence of R.N.A. viruses in patients with I.B.D. and the transmission of such agents to their close personal contacts.
Twelve anthraquinones (AQ) were evaluated for their ability to potentiate the antiviral activity of poly r(A-U) using a human foreskin fibroblast-vesicular stomatitis virus bioassay in which the AQ was combined with 0.2 mM poly r(A-U) to produce an AQ/ribonucleotide ratio of 1/4. Poly r(A-U) and the AQ alone were not effective antiviral agents. Five of the twelve AQs tested, mitoxantrone, adriamycin, ametantrone, carminic acid and daunomycin, enhanced the antiviral activity of poly r(A-U) 9- to 13-fold. The interferon-inducing activity of the five active AQ/poly r(A-U) combinations was equal to the sum of the interferon-inducing activities of their constituents. These five AQs appear to potentiate the antiviral activity of poly r(A-U) without superinduction of interferon.
Polyadenylic-polyuridylic acid (PAPU) has a wide range of effects on various immunological cells and functions. It has been shown to enhance cellular and humoral immunity, in particular anti-cancer host defences, in both animals and man. In a small number of clinical trials (breast and stomach cancers) it appears to have a beneficial adjuvant effect, in terms of prolongation of disease-free and overall survival. Side effects with PAPU are minimal. The precise mode of action of PAPU is unclear and the most beneficial therapeutic regimen has yet to be established. PAPU, therefore, merits further careful consideration and evaluation. This article reviews its present status and considers further priority areas for investigation.
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A series of novel N1 alkylated purine nucleic acids were polymerized either enzymatically or by automated synthesis to further establish the SAR requirements for HIV, RT, and HCMV activity. Out of the series, two constructs, 2'-O-methyl-1-allylinosinic acid phosphorothioate 33-mer (16) and an oligomer incorporating 1-propyl-6-thioinosinic acid residues (20), were found to be highly active under all three assay conditions. SAR studies indicate that sulfur incorporation, high molecular weight, and low steric bulk at N1 all can be important for activity.
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