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At least 685 records · Page 38Linked to original sources
PubMed1988

Role of xanthine oxidase in the interferon-mediated depression of the hepatic cytochrome P-450 system in mice.

Interferon, interferon inducers, and a variety of other immunomodulators are known to depress the hepatic cytochrome P-450 drug-metabolizing system. Two concepts have been proposed to explain this phenomenon. (a) The steady-state of cytochrome P-450 is altered through decreased synthesis and increased degradation of cytochrome P-450 apoprotein. (b) Interferon induces xanthine oxidase; superoxide generated by interferon-induced xanthine oxidase destroys cytochrome P-450. The current study investigated the second concept. Administered polyribonucleotides [polyriboinosinic acid.polyribocytidylic acid (poly IC), polyriboinosinic acid.polycytidylic acid, polylysine and carboxymethylcellulose, mismatched poly IC], recombinant murine gamma-interferon, and a natural murine alpha/beta-interferon were shown to depress hepatic cytochrome P-450 and selected microsomal cytochrome P-450-dependent monooxygenase reactions and to induce hepatic xanthine oxidase activity. The feeding of tungstate in the drinking water largely depleted xanthine oxidase in mice; cytochrome P-450 levels and monooxygenase activities were not affected by tungstate treatment. Tungstate rendered the level of xanthine oxidase much below that in mice that had not received tungstate regardless of whether or not they had received poly IC or interferon; nevertheless, poly IC and interferon produced losses of cytochrome P-450 and monooxygenase activities in these tungstate-treated mice equivalent to those observed in mice that had not received tungstate. The administration of N-acetylcysteine did not prevent the loss of cytochrome P-450 induced by poly IC, as has been reported, nor did the incubation of microsomal cytochrome P-450 with buttermilk xanthine oxidase and hypoxanthine cause a loss of cytochrome P-450, which has also been reported. It is concluded from these studies that the induction of xanthine oxidase and the loss of cytochrome P-450 generated by interferon are coincidental rather than causally related phenomena.

Acetylcysteine↗
PubMed1978

Enhancement of T cell cytotoxic responses by purified human fibroblast interferon.

Purified polyribonucleotide-induced human fibroblast interferon (HFIF) was tested for its effects on proliferative and cytotoxic human T cell responses to alloantigens. The addition of HFIF (100 to 400 IFU/ml) to mixed leukocyte cultures decreased alloantigen-induced lymphocyte proliferative responses as determined by both recovery of responding cells and by 3H-thymidine incorporation into responding cells. However, HFIF, but not the mock interferon preparation, increased the cytotoxic response of T cells to allogeneic cells by 4- to 5-fold when expressed in terms of lytic units. Although fibroblast and leukocyte interferons have different physicochemical and biologic properties, the results reported here are in concert with previous findings concerning the effects of virus-induced leukocyte interferon on human T cell functions.

Cytotoxicity, Immunologic↗
PubMed1988

[Extracellular ribonuclease from Bacillus thuringiensis].

The ability of the strain Bacillus thuringiensis var. subtoxicus to produce extracellular ribonuclease (ribonuclease Bt) was studied. It was found that the culture medium possesses a RNA-depolymerizing activity whose maximum is observed 4-5 hours after the beginning of the linear growth phase. A three-step chromatography of the culture extract on phosphocellulose resulted in a homogeneous enzyme with a molecular mass of 12000 Da. The enzyme showed the maximum activity towards RNA at pH 8.5, catalyzed the hydrolysis of polyribonucleotides and guanosine-2',3'-cyclophosphate. Hence, the enzyme can be related to base-nonspecific cyclizing ribonucleases showing the guanylic specificity towards nucleoside-2',3'-cyclophosphates.

Bacillus thuringiensis↗
PubMed1985

Bacteriophage T4 regA protein. Purification of a translational repressor.

The bacteriophage T4 regA protein translationally regulates its own synthesis and the synthesis of several other T4 early proteins. In order to study the mechanism of translational regulation, we have purified the regA protein. Initially a mutant protein, incapable of autogenous repression, was placed under lambda PL transcriptional control and amplified to approximately 10% of total cell protein. The membrane-associated mutant protein was extracted with organic solvent mixtures and purified by reverse phase-high performance liquid chromatography. Polyclonal antibodies prepared against the mutant protein were used in Western blot assays to monitor purification of the wild-type protein from T4-infected cells. Phosphocellulose and poly(U)-agarose chromatography were important steps in its purification. The binding properties of regA protein to polyribonucleotides are discussed in relation to the mechanism by which the protein recognizes its mRNA targets.

Amino Acid Sequence↗
PubMed1985

Renal reduced nicotinamide adenine dinucleotide phosphate:cytochrome c reductase-mediated metabolism of the carcinogen N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide.

N-[4-(5-Nitro-2-furyl)-2-thiazolyl]acetamide (NFTA) metabolism was examined in vitro using microsomes prepared from rat liver and renal cortex and from rabbit liver and renal cortex and outer and inner medulla. NFTA nitroreduction was observed with each tissue. Three mol of NADPH were used per mol of NFTA reduced. Substrate and inhibitor specificity suggested that the microsomal nitroreduction was due to NADPH:cytochrome c reductase. Metabolite(s) formed bound to protein, RNA, DNA, and synthetic polyribonucleotides. Maximum covalent binding was seen with polyguanylic acid. A guanosine-NFTA adduct was isolated. Binding was inhibited by sulfhydryl compounds and vitamin E. The [14C]NFTA:glutathione or [3H]glutathione:NFTA conjugates obtained from microsomal incubations showed identical chromatographic properties as the product obtained by the reaction of synthetic N-hydroxy-NFTA with [3H]glutathione. Structures of synthetic N-hydroxy-NFTA and the microsomal reduction product 1-[4-(2-acetylaminothiazolyl)]-3-cyano-1-propanone were established by mass spectrometry. The latter reduction product did not bind macromolecules. These results suggest that renal NADPH:cytochrome c reductase reduces NFTA to an N-hydroxy-NFTA intermediate that binds nucleophilic sites on macromolecules.

Animals↗
PubMed1985

In vivo and in vitro covalent binding of chlorobenzene to nucleic acids.

At 22 hr after ip injection into male Wistar rats and BALB/c mice, chlorobenzene was covalently bound to DNA, RNA and proteins of the liver, kidney and lung, as has been found with various weak carcinogens. A microsome-mediated interaction with DNA occurred in vitro. The interaction was enhanced by pretreatment in vivo with phenobarbitone but was suppressed by addition of 2-diethylaminoethyl-2,2-diphenylvalerate HC1 in vitro. These results indicate the involvement of cytochrome P-450. Liver microsomes were efficient bioactivators, whereas cytosol was ineffective. The extent of in vitro interaction of chlorobenzene with synthetic polyribonucleotides was of the same order as that with DNA. Finally, ultraviolet irradiation (lambda = 254 nm or lambda max = 365 nm) activated this environmental contaminant to forms capable of interacting with DNA. The results represent evidence for genotoxicity of chlorobenzene.

Animals↗
PubMed1985

Antitemplate effect of polynucleotides and their hybrid complexes.

In continuation of efforts to correlate the antitemplate activities of modified polynucleotides with their structure, and to understand the factors governing both their potency and stability, a group of single-stranded poly(ribo- and deoxyribo-) nucleotides, and the "hybrid" double-stranded complexes were prepared and investigated. The double-stranded hybrid poly(A,hs5U).poly(dT) section was found to be more stable to murine blood nucleases than was the single-stranded poly(A,hs5U). In a comparative study as inhibitors of the DNA polymerase alpha from rat hepatoma, the results showed that the modified polynucleotides were more potent than the unmodified ones, in general, the polydeoxyribonucleotides were better antitemplates than their ribo counterparts and the poly(A70,hs5U30).poly(dT) hybrid was more active than either of the single-stranded components. Thus it is possible to increase the nuclease resistance of the modified polyribonucleotides by forming hybrid complexes with complementary polydeoxyribonucleotides, and at the same time, to augment their antitemplate activities.

Animals↗
PubMed1977

[Study of the antiviral activity of a poly I : poly-C complex with poly-L-lysine in monkeys].

Antiviral activity of poly-I-poly-C complex with poly-L-lysine was studied on macaco rhesus. The complex bifilamentous polyribonucleotide induced active production of serum interferon and provided pronounced protection of the monkeys infected intracutaneously with the variolovaccine virus (10 LD50 for the monkeys in intracutaneous infection). The effectiveness of the protective effect depended on the scheme and route of the drug administration. The highest prophylactic and therapeutic effect was provided by local administration of the complex in a dose of I mg per I kg of the body weight, the incubation period being increased 2--3 times and the period of the skin affections being decreased approximately 2 times. The results of the studies on the effect of poly-I-poly-C complex with poly-L-lysine were evident of definite prophylactic activity of the drug against experimental vernal encephalitis in the monkeys. The animals not treated with the inductor died on the 16th or 17th day after infection because of the paralysis of the trunc and extremities muscles. The clinical evidences of the disease in the animals treated with the drug were not uniform: from complete health to death.

Animals↗
PubMedDate not supplied

[Influence of a complex of poly(I). poly(C) and poly-l-lysine on the course of vaccinia in monkeys].

Experiments of 22 Macaca rhesus monkeys were carried out to study the interferon-inducing and antiviral activity of poly(I) - poly(C) and of its complex with poly-l-lysine. The complexed double-stranded polyribonucleotide induced active production of serum interferon and markedly protected the monkeys inoculated intradermally with vaccinia virus (10 monkey ID50 by intradermal inoculation). The effectiveness of the protective effect depended on the schedule and routes of administration of the preparation. The greatest prophylactic and therapeutic effect was achieved by local administration of the complex in a dose of 1 mg/1 kg of body weight. This also prolonged the incubation period by 2-3 times and reduced the duration of persistence of skin lesions approximately by half. By the intravenous route, the best protection was achieved by 2 injections of 2 mg/kg at an interval of 96 hours. Four daily injections of the complex exerted virtually no effect on the course of vaccinia infection. The animals receiving the complexed poly(I) - poly(C) developed virus-neutralizing antibody to the same titres as control animals and were resistant to reinfection with vaccinia virus. A second injection of the complexed poly(I)-poly(C) 96 hours after the primary inoculation induced the same interferon production as the initial administration of the preparation. The monkeys inoculated intravenously with 2 mg/kg poly(I) - poly(C) showed no interferon in their blood serum and were also poorly protected against vaccinia virus infection.

Animals↗
PubMed1972

Swine interferon. I. Induction in porcine cell cultures with viral and synthetic inducers.

The production of interferon by porcine kidney (PK(15)) cell culture in response to viral and synthetic inducers was studied. The inducers used included a synthetic double-stranded polyribonucleotide, polyriboinosinic-polyribocytidylic acid (Poly I:C), swine influenza virus and three strains of pseudorabies virus. Following exposure to these inducers cell culture fluids were examined for interferon by the plaque-reduction method. The Poly I:C and the swine influenza virus induced production of interferon by PK(15) cell cultures, whereas, all three strains of pseudorabies virus at the two concentrations tested failed to induce production of interferon in vitro. The antiviral substance produced in PK(15) cells was identified as an interferon because it was pH stable, non-dialyzable, sensitive to trypsin, non-sedimentable, relatively heat stable, host-species specific and it possessed broad-spectrum antiviral activity. The latter was demonstrated by inhibition of vesicular stomatitis, vaccinia and pseudorabies viruses. Differences in interferon activity against the different viruses were observed.

Animals↗
PubMedDate not supplied

[Accelerated method of determining the antiviral activity of interferon inducers in experimental infection].

By the example of trials of two typical interferon inducers: a double-stranded complex of synthetic polyribonucleotides poly (I).poly (C) and polyacrylic acid the use of the proposed rapid method for the determination of the antiviral activity of interferon inducers in an experimental infection of mice with an alphavirus is described. The method permits to perform a statistically treated evaluation of the antiviral effect of a group of preparations within 96 hours. The mean standard error of the method is +/- 0,333 1g PFU per 1 ml of 10% brain suspension.

Acrylates↗
PubMed1966

Isolation and properties of a testicular ribonucleic acid polymerase.

A procedure is described for isolation in a soluble form of a ribonucleic acid polymerase from rat testes. Evidence is presented that this enzyme catalyzes three distinct reactions: (a) deoxyribonucleic acid-directed synthesis of RNA in the presence of all four major ribonucleoside triphosphates; (b) DNA-primed formation of polyadenylic acid and other ribohomopolymers in the presence of single ribonucleoside triphosphate substrates; (c) synthesis of complementary polyribonucleotides in the presence of various ribohomopolymer primers. The properties of these reactions are discussed with respect to metal ion requirements, affinities for ribonucleoside triphosphates and primer polynucleotides, heat denaturation of DNA primers, and the effects of ionic strength, beta-mercaptoethanol, polyamines, temperature, and inhibitors on the rates and extent of the reactions. The testicular ribonucleic acid polymerase is a very unstable enzyme that can be stabilized by high concentrations of glycerol.

Animals↗
PubMed1980

Production by mouse spleen cells of factors stimulating differentiation of mouse myeloid leukemic cells that differ from the colony-stimulating factor.

Mouse myeloid leukemic M1 cells can be induced to differentiate into macrophages and granulocytes in vitro by a protein inducer, differentiation-stimulating factor (D-factor), and by various other compounds. Mouse spleen cells produced D-factors when treated with various mitogens, such as concanavalin A, phytohemagglutinin, pokeweed mitogen, lipopolysaccharide, and synthetic double-stranded polyribonucleotide copolymer of polyinosinic and polycytidylic acids. Concanavalin A, phytohemagglutinin, and pokeweed mitogen stimulated spleen lymphocytes, but not spleen macrophages, to produce a D-factor with an apparent molecular weight of 40,000 to 50,000. On the other hand, lipopolysaccharide and copolymer of polyinosinic and polycytidylic acids stimulated both spleen lymphocytes and spleen macrophages to produce D-factors. Spleen macrophages produced D-factors with molecular weights of 40,000 to 50,000 and 20,000 to 25,000, whereas spleen lymphocytes produced only the larger molecules. In addition to D-factor, colony-stimulating factor (CSF), which stimulates growth and differentiation of normal bone marrow cells, and interferon, were detected in conditioned medium of spleen cells treated with concanavalin A or lipopolysaccharide. On gel filtration of the conditioned medium with Sephadex G-100, CSF was eluted between the larger D-factor and the smaller one. The fraction with interferon activity overlapped that of the larger D-factor. Incubation of the conditioned medium at pH 2 abolished the activity of interferon but did not affect the activity of either D-factor or CSF. The addition of cytochalasin B suppressed the production of interferon but not of D-factor or CSF by the spleen cells. These results indicate that the D-factor is a different substance from CSF or type II interferon.

Animals↗
PubMedDate not supplied

[Factors of a nucleic nature in human blood plasma].

Total amount of nucleic acids, content of RNA and RNAase activity were measured in blood plasma of healthy persons and of patients with chronic lympholeukosis. Content of nucleic acids and RNA was increased in blood plasma of these patients as compared with normal persons. Polyribonucleotide from blood plasma exhibited several specific physico-chemical properties: it was resistant to the effect of pancreatic RNAase and had specific nucleotide composition. The RNAase activity in blood plasma of patients with chronic lympholeukosis was similar to the values found in blood of healthy persons.

DNA↗
PubMedDate not supplied

[The mechanism of action of aminoglycosides].

The mechanism of action of aminoglycosides depends on the inhibition of polypeptide synthesis. In fact, some of them such as Streptomycin, Sisomicin and Gentamicin are believed to cause codon misreading, by increasing the incorporation of certain aminoacids into polypeptide in the ribosome-polyribonucleotide system. Their primary site of action seems to be located in the bacterial ribosome system. Experiments with Sisomicin showed that this antibiotic arrest cell growth, aminoacid incorporation and Beta-galactosidase synthesis, but not incorporation of uracil in ribonucleic acid in E. coli cultures. When polypeptide synthesis is directed by endogenous messenger in cell-fre extracts, the antibiotic stimulates the incorporation of some amino acids into protein.

Amino Acids↗
PubMed1983

Effect of interferon on thoracic duct lymphocyte output: induction with either poly I:poly C or vaccinia virus.

Systemic inoculation of the interferon (IFN) inducer polyinosinic-polycytidylic polyribonucleotide (poly I:poly C) into CBA/J mice produces a significant decrease in the number of thoracic duct lymphocytes (TDL) collected 6 to 22 hr after injection. The number of TDL is restored to normal levels by 48 to 64 hr. Residual TDL collected during the inhibition period of poly I:poly C treatment showed a phenotypic profile similar to phosphate-buffered saline- (PBS) treated control groups when examined for Lyt-1.1, Lyt-2, Thy-1.2 and Iak surface markers. Interferon is implicated as the mediator of this phenomenon since: 1) Inoculation of exogenous IFN can induce a similar suppression in the number of recoverable TDL. 2) Pretreatment of mice with sheep anti-murine IFN serum can block this effect of poly I:poly C. Similar experiments with vaccinia virus demonstrate that although live virus can partially suppress the TDL output, almost complete suppression is achieved with ultraviolet (UV)-inactivated virus. Vaccinia virus-induced suppression of the number of TDL also appears to be caused by IFN since: 1) UV-inactivated virus induces significantly higher serum levels of IFN in comparison to live virus. 2) The suppression of TDL output by either live or UV-inactivated vaccinia virus can be blocked by pretreatment with anti-murine IFN. These findings suggest that the immunosuppression often associated with viral infections may be at least partially due to a decrease in lymphocyte recirculation mediated by the IFN initially released in response to the virus.

Animals↗
PubMed1980

Modification of the 5' end of mRNA. Association of RNA triphosphatase with the RNA guanylyltransferase-RNA (guanine-7-)methyltransferase complex from vaccinia virus.

Purified RNA guanylyltransferase . RNA (guanine-7-)methyltransferase complex from vaccinia virus contains RNA triphosphatase activity. The latter activity, which removes the gamma-phosphate from triphosphate-ended polyribonucleotides, co-chromatographed with the capping and methylating enzyme complex on seven different ion exchange or affinity columns and co-sedimented with the complex on a glycerol gradient. On a molar basis, the RNA triphosphatase was about 100 times more active than the associated RNA guanylyl-transferase. When the purified enzyme complex was incubated with poly(A) containing a 5'-triphosphate, removal of the gamma-phosphate preceded capping. Furthermore, there was no significant difference in the rate or extent of capping 5'-diphosphate- or 5'-triphosphate-ended poly(A). Physical association of the three enzymatic activities appears to be an efficient mechanism for carrying out the following successive steps in cap formation: (formula: see text).

Acid Anhydride Hydrolases↗
PubMed1981

Purification and characterization of DNase VII, a 3' leads to 5'-directed exonuclease from human placenta.

An exonuclease, DNase VII, has been purified 6000-fold from human placenta. The enzyme has an apparent molecular weight of 43,000, requires Mg2+ for activity, and has a pH optimum of 7.8. The enzyme hydrolyzes single-stranded and nicked duplex DNA at the same rate proceeding in a 3' leads to 5' direction liberating 5'-mononucleotides. It does not measurably hydrolyze polyribonucleotides.

Deoxyribonucleases↗