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Biomedical subjects

A Benedetto

Publications and source records attributed to A Benedetto.

At least 91 records · Page 5Linked to original sources
PubMed1980

Prostaglandin A compounds as antiviral agents.

Prostaglandins of the A series strongly inhibit the production of Sendai virus in African green monkey kidney cells and are able to prevent the establishment of persistent infection ("carrier" state). This action is specific for prostaglandin A and is not due to alteration in the host cell metabolism or in the virus infectivity. The possibility that this effect is mediated by interferon is discussed.

Animals↗
PubMed1979

Prostaglandin A1 induces differentiation in Friend erythroleukemia cells.

The effect of different prostaglandins and prostaglandin-metabolites on the growth and differentiation of Friend erythroleukemia cells (FLC) was evaluated. The prostaglandin-metabolites, thromboxane B2 and 6-keto PGF1 alpha, were completely inactive, while PGE1 inhibited slightly and PGF2 alpha stimulated the replication of FLC. PGA1 was found to be the most active compound. It profoundly inhibited the replication of both DMSO-treated and undifferentiated FLC. Most importantly, PGA1 alone induced differentiation in FLC, stimulating hemoglobin production over a five-day period. PGA1-stimulated differentiation was completely suppressed by the addition of 10(-6)M hydrocortisone. Finally, treatment of DMSO-differentiated cells with PGA1 (but no DMSO) prevented the return to the undifferentiated state.

Animals↗
PubMed1979

Effect of endogenous and exogenous prostaglandin E on Friend erythroleukaemia cell growth and differentiation.

The effect of exogenous and endogenous prostaglandins on the patterns of growth and differentiation of Friend erythroleukaemia cells (FLC) were studied. During the differentiation process, DMSO stimulated PGE synthesis by an average of 95%. The addition of a long-acting synthetic analogue of PGE2,16,16-dimethyl-PGE2-methyl ester (di-M-PGE2) to the culture medium only slightly and temporarily slowed cell growth, with no appreciable induction of differentiation. However, in the presence of DMSO, the same concentration of di-M-PGE2 produced 73% inhibition of cell growth and accelerated and potently stimulated haemoglobin production. The action of both di-M-PGE2 and DMSO on cell proliferation was dependent upon the state of cell growth at the time of the administration of these compounds. FLC cultures treated with DMSO + di-M-PGE2 produced considerable amounts of haemoglobin before even one duplication cycle was completed. Both DMSO and di-M-PGE2 stimulated endogenous PGE biosynthesis, and the biosynthetic effect of these compounds was synergistic. Inhibition of endogenous prostaglandin synthesis by indomethacin completely abolished the effects produced by DMSO + di-M-PGE2 on the growth, and substantially reduced the stimulated differentiation of FLC. These data suggest that an endogenously synthesized prostaglandin plays a significant role in both the inhibition of replication and in the stimulation of differentiation induced by DMSO and di-M-PGE2 in Friend erythroleukaemia cells.

Cell Differentiation↗
PubMed1979

Modulation by cell trypsinization of Sendai virus expression in African green monkey kidney cells: first infection and establishment of a carrier state.

Two African green monkey kidney (AGMK) cell lines, 37RC (interferon-producing) and Vero (non-interferon-producing), were infected by egg-grown Sendai virus passaged in eggs at high and low m.o.i. The appearance of haem-adsorption, and cytopathic effect (c.p.e.) as well as the presence of haemagglutinating virions in the supernates were much more pronounced with a virus seed obtained with 10(-3) diluted passages than with a seed obtained with undiluted inoculum. They were also independent of interferon production (data obtained in 37RC and Vero cells were almost superimposable). In studies carried out with the virus seed prepared at high dilution the establishment of infection was maximal when monolayers were infected as soon as 5 h after trypsinization and cell seeding, regardless of cell density. Virus in supernates obtained from cultures infected 5, 20 or 50 h after seeding exhibited a greatly reduced infectivity for monkey cells, but not apparently for chick embryos. Trypsin treatment of the virus supernates restored their infectivity for AGMK cells more efficiently for virus released from cells infected 5 h after seeding than for virus released from cells infected later after seeding. In keeping with these observations, virus in supernates from cultures infected 5, 20 or 50 h after seeding contained increasing amounts of auto-interfering virions. The decreased infectivity obtained in cell supernates was not accounted for by major differences in virus RNA synthesis. Similarly, the optimum infection established in cells seeded only for 5 h was not due to increased virus adsorption. Several lines of cells surviving first infection with egg-grown Sendai virus have been obtained and kept in cultures for 3 to 18 months. Virus release and c.p.e. apparently become reduced in the cells surviving the first infection until the newly repopulated monolayers must undergo trypsinization. Weekly protease treatments of the cells reactivate all parameters of virus infection which again will tend to disappear slowly and then reappear following each trypsinization ('intermittent' carrier state). The establishment and the 'intermittent' reactivation of these lines were not prevented by the inclusion in the medium of anti-Sendai virus serum. Temperature-sensitive ts functions do not seem to play an important role in this virus-host relationship.

Adsorption↗
PubMed1979

Resistance of African green monkey kidney cell lines to actinomycin D: drug uptake in 37 RC cells after persistent inhibition of transcription.

37 RC cells, a cultured line derived from African green monkey kidneys, survived long treatments with actinomycin D (AMD; 0.1 to 0.5 mug/ml) under strong inhibition of ribonucleic acid synthesis and blocking of cell division. One aspect of the complex cellular response to this treatment was a progressive lowering of the influx rate of AMD and, consequently, of its endocellular concentration, leading to a late resurgence of transcription. Overall protein synthesis decreased in AMD-treated cells, but more of the residual protein was exported to the cell surface, a fact associated with the development of numerous strands of endoplasmic reticulum and Golgi bodies in the cytoplasm. The lowering of AMD influx during the treatment was not simply due to the decay of protein synthesis, and there was no evidence for a carrier-mediated transport of the drug. It was paralleled by, but seemingly not related to, modifications in cellular microtubules and microfilaments. The rate of AMD influx was restored to levels comparable to those of untreated cells by short exposure to ethylenediaminetetraacetic acid and trypsin. It is concluded that the changes in plasma membrane of 37 RC cells, creating an obstacle to the influx of AMD after long treatment with this drug, probably consist of an accumulation and/or a different distribution of glycoproteins or other surface components on the cell surface.

Animals↗
PubMed1977

An electron paramagnetic resonance study of free radicals in cells.

An electron paramagnetic resonance study was performed on cell lines of the following strains: HeLa, 37RC, L, FLC, NRK/RSV, 3T3/SV40. Unsynchronized and synchronized HeLa cells were studied with particular attention paid to the relation between growth and free radical concentration. Free radical levels were shown to be a function of the growth stage and different phases of the cell cycle.

Cell Division↗
PubMed1977

Inhibition of transcription and translation of globin messenger RNA in dimethyl sulfoxide-stimulated Friend erythroleukemic cells treated with interferon.

The addition of appropriate doses of interferon (IF) to cultures of Friend erythroleukemic cells inhibits dimethyl sulfoxide (Me2SO)-stimulated erythroid differentiation. In this study, the synthesis of heme, hemoglobin, and globin mRNA in Me2SO-stimulated cultures, with or without IF added, was compared. Although the hemoglobin content in Me2SO+IF-treated cultures was reduced 6- to 9-fold compared to that of cultures treated with Me2SO alone, there was less than a 2-fold decrease in the amount of heme accumulated. Globin mRNA, although unchanged in size or base sequence, was reduced in content in the Me2SO+IF cultures. The level of reduction of globin mRNA was insufficient to account for the lack of globin synthesis. Thus, it appears that IF may operate on two levels--one involving the transcription of globin mRNA and the other involving its translation.

Animals↗
PubMed1975

Study on the reinitiation of transcription in 37 RC cells after actinomycin D inhibition. Spectrum of major RNA species resynthesized after maximal suppression by the drug.

The reinitiation of the synthesis of major RNA species has been studied in 37 RC cells after maximal inhibition of RNA synthesis by actinomycin D (AMD). During the period of recovery from AMD, resynthesized RNA (rec-RNA) is initially composed of almost exclusively light (4-14S) heterogeneous RNA species. All normal species of RNA can be detected in the rec-RNA spectrum as early as 3 h after AMD removal. The synthesis of low molecular weight methylated RNA species increases slightly during the early period after AMD removal, while the increase of low molecular weight unmethylated species is more significant during the same period. Much of the radioactivity in the polyribosomal fraction is EDTA and puromycin sensitive. Since polysomal, puromycin-sensitive RNA is polyadenylated (as evidenced by the binding of poly-U filters), and is heterogenous in size, it belongs to the m-RNA class. The synthesis of m-RNA increases immediately after AMD removal, whereas the reinitiation of the r-RNA synthesis occurs after a lag period of about 2 h. The kinetics of recovery of the synthesis of major RNA species from AMD inhibition show a size dependency comparable to the size-related sensitivity to AMD inhibition in other cellular systems. This dependency is most clearly seen in HnRNA, the AMD sensitivity of which is measured by the length of the lag period between AMD removal and the appearance of HnRNA fractions in a sucrose density gradient. Low molecular weight HnRNA reappears first, whereas heavier fractions of HnRNA appear in the spectrum after a lag period, the length of which is in direct relation to the position of the HnRNA fraction in the gradient.

Cell Line↗
PubMed1974

Inhibition of uridine transport in cultured mammalian cells by theophylline.

Theophylline (theobromine, caffeine) reversibly inhibits the incorporation of labeled RNA precursors both in confluent 37 RC and in exponentially growing HeLa cells. As measured in 37 RC after 2 h labeling, 20 mM theophylline reduces the incorporation of [3H]UTP and [14C]uridine into acid-precipitable material to 5% and 9% of the control, respectively. This reduction is paralleled by a comparably lowered incorporation of the same precursors into the acid-soluble pool. The initial rate of incorporation into total cell material is similarly affected by theophylline, the inhibition being of a simple competitive type. Theophylline does not alter the turnover rate of pulse labeled RNA during actinomycin D chase nor does it preclude the utilization of the endogenous pool of nucleoside phosphates. Upto a concentration of 10 mM, it does not inhibit uridine kinase neither in 37 RC nor in HeLa cells. The mentioned inhibitory effects of theophylline cannot be mimicked by exogenously added cyclic AMP. All the data support the conclusion that theophylline inhibits the transport of uridine into the cell.

Biological Transport↗
PubMed1974

A guanidine-sensitive step of the poliovirus RNA replication cycle.

It has been shown that the amount of viral RNA synthesized in synchronized HeLa cells 0-2 h after infection does not notably vary during the mitotic cycle. However, the amount of viral RNA synthesized 2-4.5 h after infection exhibited a sharp maximum in S-phase cells. Guanidine inhibited the incorporation of 3-H-uridine into the viral RNA synthesized 2-4.5 h after infection only in cells in the S-phase. It had no demonstrable effect on viral RNA synthesis 0-2 h after infection in cells in any phase of the mitotic cycle. Thus, additional indirect evidence has been presented in favor of the hypothesis that two different replicases or two different conformations of one enzyme are involved in poliovirus RNA replication. The one functioning 0-2 h after infection is cycle-independent and guanidine-sensitive, whereas the other functions exclusively in phase-S cells 2-4.5 h after infection and is inhibited by guanidine.

Cell Division↗