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E Paez

Publications and source records attributed to E Paez.

26 records · Page 2Linked to original sources

Nature and mode of action of vaccinia virus products that block activation of the interferon-mediated ppp(A2'p)nA-synthetase.

In this report it has been shown that inhibition of the 2-5A synthetase in IFN-treated, vaccinia virus-infected mouse L and human HeLa S3 cells is related to specific viral functions. This inhibition occurs concomitantly with degradation of ATP and with dephosphorylation of ppp(A2'p)nA. At least two viral-mediated enzyme activities are thought to be involved in this process, an ATPase and a phosphatase. The ATPase activity was established after determining the extent of hydrolysis of ATP, the nature of 2-5A, and the relative abundance of the different oligomers. Cytoplasmic cell extracts and purified vaccinia virions were bound to poly (I):(C) agarose, incubated with [3H]ATP, [alpha-32P]ATP, or [gamma-32P]ATP, and the extent of hydrolysis of ATP was determined by TLC. Authentic 2-5A and the relative abundance of the various oligomers were characterized by enzymatic and alkali treatments and identification by TLC and HPLC analysis. The phosphatase activity was measured by TLC after determining the degree of dephosphorylation of 2-5A from the extent of labeling at the 5'-OH termini with [gamma-32P]ATP and polynucleotide kinase. While free 5'-OH termini were not observed in oligomers synthesized with bound poly (I):(C) agarose enzyme fractions from IFN-treated, uninfected cells, a strong phosphorylation was found in oligomers from IFN-treated, infected cells. These findings suggest that it is the contribution of these viral enzyme activities that renders vaccinia virus resistant to interferons.

2',5'-Oligoadenylate Synthetase↗

Effect of interferon on integrity of vaccinia virus and ribosomal RNA in infected cells.

The state of vaccinia and ribosomal RNAs in IFN-treated, vaccinia virus-infected mouse L cells grown in suspension is examined. In these cells a drastic inhibition (approximately 90%) of both viral and cellular protein synthesis occurs after virus infection of IFN-treated cells. The findings show that (1) primary transcription of vaccinia virus is not impaired by IFN, but is rather enhanced; (2) viral RNAs produced in IFN-treated, infected cells are predominantly of the early class; (3) these viral RNAs can be translated in a cell-free protein-synthesizing system; (4) in IFN-treated, infected cells there is extensive cleavage of 28 and 18 S rRNA at early times post infection, resulting in a characteristic cleavage pattern; (5) cleavage of rRNA is viral RNA dependent. The results indicate that in this virus-cell system the IFN-mediated inhibition of vaccinia and cellular protein synthesis is correlated with an alteration in ribosomal integrity.

Animals↗

Antiviral action of 5-amino-2-(2-dimethyl-aminoethyl)benzo-[de]-isoquinolin-1,3-dion e.

A newly synthesized imide derivative of 3-nitro-1,8-naphthalic acid, 5-amino-2-(2-dimethylaminoethyl)benzo-[de]-isoquinolin-1,3-dione (designated M-FA-142), was tested on chick embryo cells against herpes simplex virus type 1 (HSV-1) and vaccinia virus (VV), and on Vero cells against African swine fever virus (ASFV). At a concentration of 4 micrograms/ml the drug inhibited VV replication by about one order of magnitude, and that of HSV-1 by about three orders of magnitude. A minor effect was shown against ASFV. Virus inhibition was found to depend on the amount of drug and multiplicity of infection. No virucidal effect was observed on the viruses tested, except for a slight effect on HSV-1. Inhibition of virus growth could be reversed when the drug was removed from the cell culture medium. Serial passages of HSV-1 and VV in the presence of the drug caused the appearance of drug-resistant viruses.

Adenine↗

Indiscriminate degradation of RNAs in interferon-treated, vaccinia virus-infected mouse L cells.

In this report we used Northern blot hybridization analysis to characterize the fate of several species of viral RNA transcribed from internal and terminal regions of vaccinia DNA in interferon-treated, infected mouse L cells grown in suspension. All species of viral RNAs were expressed but were reduced in amount. Larger-sized RNAs were reduced more than smaller-sized RNAs. This reduction appears to be related to the activation of the interferon-mediated double-stranded RNA-dependent 2-5A synthetase-endoribonuclease system, as the rRNA cleavage pattern characteristic of this system was observed early in infection and in cell extracts in response to exogenous 2-5A. Thus, in interferon-treated, vaccinia-infected mouse L cells in suspension, there is indiscriminate degradation of viral and cellular RNAs, and this RNA breakdown might play a role in the interferon-mediated inhibition of protein synthesis.

Animals↗

The relationship between the antiviral action of interferon and prostaglandins in virus-infected murine cells.

The relationship between prostaglandins (PG) and interferon (IFN) was investigated. IFN induced the synthesis of immunoreactive PGE and PGA at early and late stages, respectively, of vaccinia virus infection in mouse L fibroblasts. Only species-specific IFN possessed this activity and PG synthesis was stimulated in virus-infected cells, while normal L cells were not affected. The vaccinia virus infection did not significantly alter PG synthesis in the absence of IFN. Indomethacin increased the rate of vaccinia virus replication and partially inhibited the IFN-induced protection of L cells. The addition of exogenous PGA1 only partially reversed this effect. Finally, short-term PGA treatment induced the synthesis of two enzymes (protein kinase and 2,5A synthetase) thought to be partially responsible for the antiviral action of interferon. These findings suggest that a prostaglandin or PG-related compound seems to mediate at least one aspect of IFN action.

2',5'-Oligoadenylate Synthetase↗

Imide derivatives of 3-nitro-1.8-naphthalic acid: their inhibitory activity against DNA viruses.

The antiviral action of a new drug, 5-amino-2-(dimethylaminoethyl)-benzo-[de]-isoquinolin-1.3-dione has been studied against herpes simplex type 2 (HSV-2) and adenovirus type 5 (Ad-5) grown in Vero cells. The concentration of the drug which gives a 5 log10 reduction in virus titer was 4 micrograms/ml (maximum tolerated concentration) for HSV-2. The anti-HSV-2 activity of this compound was one log. more powerful than that of iododeoxyuridine (IDU). At this concentration the drug shows virucidal activity against HSV-2. No inhibition was found when the drug was tested against Ad-5. The inhibition of virus production has been studied depending upon the amount of drug or virus, and drug addition-time after infection. Reversibility of inhibition after drug removal, and drug resistance in the presence of the drug have also been determined.

Adenine↗

Validation of the Cross-Cultural Alcoholism Screening Test (CCAST).

BACKGROUND: When screening instruments that are used in the assessment and diagnosis of alcoholism of individuals from different ethnicities, some cultural variables based on norms and societal acceptance of drinking behavior can play an important role in determining the outcome. The accepted diagnostic criteria of current market testing are based on Western standards. METHODS: In this study, the Munich Alcoholism Test (31 items) was the base instrument applied to subjects from several Hispanic-American countries (Bolivia, Chile, Ecuador, Mexico, and Peru). After the sample was submitted to several statistical procedures, these 31 items were reduced to a culture-free, 31-item test named the Cross-Cultural Alcohol Screening Test (CCAST). RESULTS: The results of this Hispanic-American sample (n = 2,107) empirically demonstrated that CCAST measures alcoholism with an adequate degree of accuracy when compared to other available cross-cultural tests. CONCLUSIONS: CCAST is useful in the diagnosis of alcoholism in Spanish-speaking immigrants living in countries where English is spoken. CCAST can be used in general hospitals, psychiatric wards, emergency services and police stations. The test can be useful for other professionals, such as psychological consultants, researchers, and those conducting expertise appraisal.

Alcoholism↗

The effect of supplemental copper on osteopenia induced by ovariectomy in rats.

OBJECTIVE: The effect of a copper supplement on preventing bone mass loss induced by ovariectomy in rats was investigated. DESIGN: Three groups of fifteen 100-day-old female Wistar rats, each with a mean initial weight of approximately 260 g per animal, were selected for a 30-day experiment. One group of 15 ovariectomized rats was fed a diet supplemented with 15 mg of copper per kilogram of feed. The other two groups: 15 ovariectomized and 15 Sham- ovariectomized rats did not receive the supplement. Morphometric (weight and length) and densitometric studies with dual-energy x-ray absorptiometry were performed on the whole femur and the fifth lumbar vertebra of each animal at the end of the 30-day period. RESULTS: The ovariectomized rat group fed a diet supplemented with copper did not show the bone mass loss at the axial (fifth lumbar vertebra) or peripheral (femur) level that was evidenced in the ovariectomized group. CONCLUSIONS: The results of the measurement of axial and peripheral bones show that a supplement of copper may have a potential therapeutic application in the treatment and prevention of involutional osteoporosis.

Absorptiometry, Photon↗