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Biomedical subjects

R Wyler

Publications and source records attributed to R Wyler.

At least 19 recordsLinked to original sources

Increase of interferon antiviral activity by exogenous cyclic adenosine-3':5'-monophosphate (cAMP).

Some effects of cAMP on replication of Semliki Forest Virus in chick embryo fibroblast cell cultures are described. Depending on concentration, the incorporation of [3H]-uridine into viral RNA or the formation of plaque-forming units is inhibited; the highest concentration tested was 8 mM. Cyclic AMP has an effect of its own and increases the Interferon action in the lower concentration ranges of Interferon (up to 1 unit/ml). The effect of cyclic AMP is fast, needs no induction and is also visible in late phases of viral replication. However, these experiments do not establish a causal relation between cAMP and Interferon.

Cyclic AMP

Altered or increased transfer-RNA methylation in the course of Interferon action on cells in culture?

The induction of the antiviral state by Interferon might reflect the decrease of the rate of biosynthesis, the degradation or the alteration of one or several tRNAs. This could result in rate-limiting concentrations for codons common in viral RNA but rare in host mRNA. Altered methylation of tRNA could be the basis of such a phenomenon. However, we could not find an altered extent of methylation of total tRNA or an altered pattern of methylation, if mixed tRNAs were chromatographed on MAK- or BD-cellulose columns, despite a large range of conditions of pretreatment of chick embryo fibroblast cultures with interferon.

Animals

Physical characterization of a stomatitis papulosa virus genome: a cleavage map for the restriction endonucleases HindIII and EcoRI.

The genome of stomatitis papulosa virus (a parapoxvirus) was cleaved with the restriction endonucleases HindIII and EcoRI, each giving rise to 6 fragments respectively. Double digestion with both enzymes resulted in 8 bands, two of which contained DNA fragments in double molar concentrations as revealed by reciprocal digests of isolated DNA fragments. The genome size, estimated by summation of the molecular weights of the fragments, is approximately 86 X 10(6) daltons, some 30 X 10(6) daltons smaller than vaccinia virus (an orthopoxvirus) DNA. The cleavage sites of HindIII and EcoRI endonucleases were mapped on the genome by analysis of reciprocal digests of isolated DNA fragments and by cross-hybridization experiments. This yielded two mapped segments which were then oriented relative to one another by cleavage of isolated partial digestion products. The terminal restriction fragments show rapid renaturation after alkali denaturation and subsequent neutralization, indicating that stomatitis papulosa virus DNA contains terminal cross-links analogous to those found in vaccinia virus DNA.

Animals

An imidazole derivative (Econazole) as an antifungal agent in cell culture systems.

Econazole, an imidazole derivative, was tested as an antifungal agent in different cell culture systems. In comparison with Fungizone, Econazole has the following advantageous properties: higher stability, higher solubility, better antifungal activity against contaminants of cell cultures and a wider range between minimal inhibitory to cytotoxic concentration with Aspergillus fumigatus, Candida albicans and Penicillium sp., activity against gram-positive bacteria and lower price. Econazole exerts no antiviral effect and can therefore be used for virus isolation from heavily contaminated material. The antagonistic effect of serum on the antifungal effect of Econazole and Fungizone was comparable as was the inhibitory effect of both antimycotics on Mycoplasma growth. In view of the above mentioned properties Econazole lactic acid can be recommended as an antifungal agent for cell culture systems at a concentration of 1 microgram per ml.

Amphotericin B

High C + G content in parapoxvirus DNA.

The DNAs of eight parapoxviruses (four stomatitis papulosa viruses isolated from infected calves, a pseudocowpox virus isolated from a teat lesion of an infected cow and three orf viruses, one isolated from an infected sheep and two isolated from human infections) were analysed in CsCl gradients. The mole % of G+C was calculated from the buoyant density and found to be approx. 63% for all virus isolates examined. Parapoxvirus DNA thus has by far the highest G+C content of all poxvirus DNAs so far examined.

Animals

Mitochondrial calcium uptake during infection of chicken embryo cells with Semliki Forest virus.

The key role of the mitochondria in the regulation of cellular Ca2+ led to a study of mitochondrial Ca2+ uptake during the infection of chicken embryo cells with Semliki Forest virus. Mitochondrial Ca2+ uptake was stimulated during the first 5 h of infection but declined later in infection. The early stimulation suggests an increase of cytoplasmic ionized Ca2+, whereas the later decrease indicates mitochondrial injury. This functional deterioration was correlated with an increase of the permeability of the inner mitochondrial membrane. Polarographic experiments showed that electron transport is impaired, whereas transduction of energy to Ca2+ uptake is intact.

Calcium

[New aspects of the part of the vector played by Ixodes ricinus L. in Switzerland. Preliminary note (author's transl)].

The authors, after having recalled their recent work on Ixodes ricinus ecology, give the new results about the part played by this species in the transmission of different infectious agents in Switzerland. I. ricinus was already known to be the most important vector of the tick borne encephalitis virus, and of protozoans of the Babesia genus. In this article, we describe the existence in the hemolymphe of different I. ricinus populations, of a rickettsia species related to the RMST group (Rocky-Mountain Spotted Fever), of a trypanosome, which is close to T. theileri, and of an infectious larval form (L3) of Dipetalonema rugosicauda. An outline is suggested with the object of illustrating the functioning of a natural foci of tick encephalitis. The biological significance of the unusual presence of trypanosomes and of larval filariae in ticks is also discussed. The authors underline the fact that rickettsia, trypanosomes and filarial forms are observed for the first time in Swiss I. ricinus.

Animals

Kinetics of interferon action.

A kinetic analysis of the action of interferon with different preparations in chick embryo fibroblast cell culture gives additional evidence for interaction of interferon with the cell surface, compatible with the idea that interferon is not taken up by the cells. With certain assumptions the binding constant is in the range of 10(13) [l/Mol].

Cell Membrane

Permeability changes of plasma and lysosomal membranes in HeLa cells infected with rabbit poxvirus.

Infection of HeLa-cell monolayer cultures with rabbit poxvirus induces a marked decrease in cell-associated protein and in the activities of lactate dehydrogenase, acid phosphatase, and beta-glucuronidase. This effect begins to occur around 10 hours post-infection (p.i.) and is accompanied by a concomitant rise of these enzyme activities in the culture medium. Only few cells detach from infected monolayers and these cannot account for protein release. Virion release can be inhibited at 4 degrees C, whereas protein release cannot and it seems therefore that these events do not happen by a common mechanism. Moreover, penetration studies with [14C]-sucrose indicate that protein release reflects a true increase in plasma membrane permeability. Using the Gomori stain for acid phosphatase, a release of the enzyme into the cytoplasm around 8 hours p.i. can be confirmed rendering a causative role of lysosomal hydrolases in the pathogenesis of the observed plasma membrane permeability changes possible but not proving it.

Acid Phosphatase

Inverted terminal repeats in rabbit poxvirus and vaccinia virus DNA.

In both rabbit poxvirus and vaccinia virus DNA have demonstrated an identical distribution of eight HinfI. The length of the terminal repeats was found to be 3.4 to 3.6 megadaltons (Mdaltons) for rabbit poxvirus DNA and 7.4 to 8.0 Mdaltons for vaccinia virus DNA. Maps of the HinfI restriction sites within isolated EcoRI end fragments of rabbit poxvirus and vaccinia virus DNA PHAVE DEMONSTRATED AN IDENTICAL DISTRIBUTION OF EIGHT HinfI sites in an internal part (approximately 2 Mdaltons) of the EcoRI end fragments of the two genomes.

Animals

[Natural borna virus infection in rabbits].

Two spontaneous cases of Bornea disease in rabbits are reported. With the help of fluorescence-serological methods it was possible to detect virus-specific antibodies in the brain and serum of both animals. Demonstration of viral antigen in the brain is a valuable supplement to cell culture from brains. The findings confirm earlier reports that the natural host spectrum of Borna virus includes the rabbit, in addition to the horse and sheep.

Animals

[Interferon and herpes].

Interferon, a protein produced by cells, is the only non-toxic antiviral inhibiting virus multiplication in the cell. Although the industrial-technical production of the substance is more expensive the exogenic interferon treatment (interferon which is produced in cell cultures is being administered to the organism) is preferred to the endogenous interferon therapy (by application of slightly-toxic substances the organism is stimulated to produce interferon) since with the first therapy the factor toxicity can be neglected. Clinical trials with exogenous interferon treatment of herpes virus infections of men gave encouraging results, they must however be confirmed by double blind studies. Should it come to a clinical application of interferon on a large scale, first of all methods of production must be worked out to make available sufficient exogenous interferon for treatment of patients.

Herpes Simplex