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Biomedical subjects

S Mousset

Publications and source records attributed to S Mousset.

At least 19 recordsLinked to original sources
PubMed1995

The nonstructural proteins of the autonomous parvovirus minute virus of mice interfere with the cell cycle, inducing accumulation in G2.

The nonstructural (NS) proteins of the autonomous parvovirus minute virus of mice (prototype strain) are involved in viral DNA replication and in the regulation of parvoviral and heterologous promoters. By constructing cell lines having integrated the NS coding sequence under the control of an inducible promoter, we were able to demonstrate that NS proteins are toxic, once expressed in the transformed cells. Cell killing appears after several days of NS expression, suggesting that NS toxicity involved cellular factors. In this paper, we show that NS proteins are cytotoxic and interfere with the cell cycle in proliferating cells only NS expression is innocuous in resting cells, whereas in growing cells, it induces the accumulation of G2 cells. This cytostatic effect is enhanced upon neoplastic transformation, which sensitized the cells to NS killing. Moreover, as clones resistant to NS toxicity undergo no alteration of their cycle, this cytostatic effect of NS proteins could be an early step on the way to cell killing. These observations strongly suggest that NS toxicity involves cellular factors associated with the regulation of the cell cycle.

Animals↗
PubMed1994

Activation of the mitogen-activated protein kinase cascade by tyrphostin (RG 50864).

Tyrphostins are synthetic compounds which have been described as in vitro inhibitors of epidermal growth factor (EGF)-receptor tyrosine kinase activity. In NIH3T3 cells, stimulation of EGF-receptor tyrosine kinase leads to an increase of intracellular protein phosphorylations, among them the phosphorylation of mitogen-activated protein (MAP) kinase and the S6 kinases p90rsk and p70S6K. Phosphorylation of these proteins, either on tyrosine or serine/threonine residues or on both residues increases their protein kinase activity. Unexpectedly, treatment of NIH3T3 cells with both tyrphostin (RG 50864) and EGF results in an increase in the level of tyrosine phosphorylation of the MAP kinase. During this treatment, we also observed an increase in MAP kinase and S6 kinase p90rsk activities. Tyrphostin treatment diminishes the level of c-fos mRNA but has no effect on c-myc mRNA expression nor on S6 kinase p70S6K activity. Mitogenic signalling induced by EGF in NIH3T3 cells was blocked by tyrphostin, suggesting that the target(s) for this event may be elements downstream from the MAP kinase or independent of this signal transduction.

3T3 Cells↗
PubMed1994

The cytotoxicity of the autonomous parvovirus minute virus of mice nonstructural proteins in FR3T3 rat cells depends on oncogene expression.

The nonstructural (NS) proteins of the autonomous parvovirus minute virus of mice are involved in viral DNA replication and in the regulation of homologous and heterologous promoters. Moreover, NS products have proved to be cytotoxic, especially for transformed cells. We show here that intracellular accumulation of NS products is not sufficient to kill rat fibroblasts from the established cell line FR3T3, which is phenotypically normal in several respects. FRNS cell lines were obtained by stable transfection of FR3T3 cells by a vector carrying the NS genes under the control of the hormone-inducible long terminal repeat promoter of the mouse mammary tumor virus. In the presence of dexamethasone, the NS proteins were synthesized without associated cell death. Transformation of FRNS cells with the c-Ha-ras oncogene or polyomavirus oncogenes had little effect on their capacity for NS induction, as measured at both concentration and transactivating activity levels, yet the transformants were now dying within a few days in the presence of the inducer. The same results were obtained with cells stably transfected by a vector expressing the NS1 product alone, suggesting that in this system there is no cooperation between NS1 and NS2 for maximal cytopathic effect. Cell mortality after NS protein induction was quantitatively related to the yield of oncogene expression, while NS-1 was not limiting in this respect. Our results show that the NS1 protein is not lethal unless cellular factors that may depend on oncogene expression trigger its cytotoxicity.

Animals↗
PubMed1992

Cooperation of oncogenes in cell transformation and sensitization to killing by the parvovirus minute virus of mice.

The established line of normal Fisher rat fibroblasts (FR3T3) is naturally resistant to the parvovirus minute virus of mice (MVM), and was used as a model system to study the influence of stepwise transformation on the susceptibility of cells to this virus. When transformed with genes encoding the class I nuclear oncoproteins large T antigen of polyomavirus (PyLT) or v-myc, cells retained a normal appearance, but acquired some ability to form colonies in soft agar. On the other hand, the class II transforming oncogenes encoding the middle T antigen of polyomavirus (PyMT) and c-Ha-ras-1 induced both morphological alterations and a high capacity for anchorage-independent growth in transfected cells. The concomitant expression of oncogenes from both classes (PyLT-(+)PyMT; v-myc+c-Ha-ras-1) induced a supertransformed phenotype characterized by the piling-up of cells into poorly adherent foci, even in low density cultures. The progressive transformation of this cellular system was found to coincide with a gradual increase in its susceptibility to MVMp (MVM prototype strain) infection. Compared to parental cells, class I, class II and double transformants proved to be sensitized to killing by MVMp to a low, moderate and large extent, respectively. Thus, oncogenes from different functional classes appeared to cooperate in the responsiveness of cells to parvovirus attack. Interestingly, this cooperation exacerbated both the killing of infected cells and their capacity to produce viral non-structural (NS) proteins, in agreement with the reported cytotoxic activity of NS polypeptides. Therefore, in this system, parameters of the parvovirus life cycle may serve as indications of the overall progression of the transformation process.

Animals↗
PubMed1991

Early effect of BCNU on rat astrocytes. Inhibition of S6 kinase activation by growth factors.

In primary cultures of astrocytes, methylmethane, 2-N-methyl 9-hydroxy-ellepticinium acetate, ditercalinium, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1,3 bis (2-chloroethyl)-1-nitrosourea (BCNU) blocked to various extents the activation of S6 kinase by acidic fibroblast growth factor and insulin [or insulin-like growth factor 1 (IGF1)]. The effects of the most active agent, BCNU, were time and concentration dependent. Pretreatment of cells with 50 microM BCNU for 1 hr completely prevented S6 kinase activation by growth factors for at least 2 days. The S6 kinase activity of unstimulated cells was slightly affected. S6 kinase activation by 12-O-tetradecanoylphorbol 13 acetate was also strongly impaired by treating cells with BCNU whereas activation by 8-bromo-cyclic AMP was slightly reduced. Cyclic AMP-dependent protein kinase and phospholipid and Ca(2+)-dependent protein kinase were unaffected. BCNU had no direct effect on IGF1 binding to cell surface receptors or on the S6 kinase activity of cell cytosols.

Animals↗
PubMed1990

Selective killing of transformed rat cells by minute virus of mice does not require infectious virus production.

Fischer rat fibroblasts, naturally resistant to killing by the fibrotropic strain of minute virus of mice [(parvovirus MVM(p)], became sensitive to MVM when transformed by polyomavirus. This sensitization did not involve an increase in the percentage of cells which synthesized viral capsid antigens or in the percentage of cells which produced infectious virus. The addition of anti-MVM antiserum to the growth medium of MVM-infected cells had only a small effect on their survival rates, indicating that the majority of the killing effect of MVM occurs in a single cycle of infection. The data indicate that cell killing by MVM is independent of infectious virus production and thus support the notion that the preferential cytolytic effect is affected by viral cytotoxic gene products which accumulate to intolerable levels in transformed cells but not in normal ones. Finally, using cells transformed with polyomavirus and genomic and subgenomic clones of polyomavirus, we showed that the extent of sensitization to killing by MVM depended on the transforming agent used.

Animals↗
PubMed1988

Susceptibility to parvovirus Minute virus of mice as a function of the degree of host cell transformation: little effect of simian virus 40 infection and phorbol ester treatment.

Transformation of mouse fibroblasts by simian virus 40 (SV40) or certain oncogenes enhances their susceptibility to the lytic replication of Minute virus of mice (MVM), a non-defective parvovirus. It was investigated whether this cytotoxic action of MVM can also be potentiated by two types of incomplete and reversible cell transformation induced either by SV40 infection or by exposure to the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Although the latter two treatments trigger the expression of several traits of the transformed phenotype, they do not significantly enhance cell permissiveness to MVM.

Animals↗
PubMed1985

Genotoxicity of ochratoxin A in mice: DNA single-strand break evaluation in spleen, liver and kidney.

Ochratoxin A, a natural contaminant of feed and food, has been shown to induce experimental liver and kidney tumours. In vitro experiments on mice spleen cells showed evidence of DNA single-strand breaks induced by ochratoxin A. We measured single-strand breaks in the DNA of spleen, liver and kidney of ochratoxin A-treated animals. Ochratoxin A induced DNA damage in vivo. This damage reversed with time. The appearance and extent of the damage varied in different tissues. Except for spleen our data correlate with the tumours induced by ochratoxin in mouse liver and kidney. With regard to the spleen, there has been no report to date of experimental leukemia induced by ochratoxin A. Thus our results indicate that this possibility has to be considered.

Animals↗
PubMed1985

A study of intermediate filaments (cytokeratin, vimentin, neurofilament) in two cases of Merkel cell tumor.

In two cases of Merkel cell tumor, the study of intermediate filaments, using monoclonal antibodies (vimentin, cytokeratin, neurofilaments), confirmed the double differentiation (neuroendocrine and epithelial) of this tumor as previously observed in histological, electron microscopical and histochemical analyses. Labelling of the tumor cells was positive with monoclonal antibodies against neurofilament proteins and cytokeratin.

Adenocarcinoma↗
PubMed1985

[DNA damage in the spleen, liver and kidneys of mice treated with ochratoxin A].

Ochratoxin A a natural contaminant of feed and food has been shown to induce experimental liver and kidney tumors. Since there is a good correlation between the carcinogenic potency of chemicals and the DNA damages induced in mammalian cells treated either in vivo or in vitro by these compounds, we have measured single-strand breaks induced by ochratoxin A in DNA of liver, spleen and kidney. Our data clearly showed that ochratoxin A induced DNA damages in vitro as well as in vivo. Damages were dose-dependent, reversible and vary upon the time according to the tissue. In spite there is no report up to now on experimental leukemia induced by ochratoxin A, our results indicate that this possibility have to be considered.

Animals↗
PubMed1984

[Value of correlated immunofluorescence and immunoperoxidase study of monoclonal markers in 2 adult cases of histiocytosis X].

Two cases of adult histiocytosis X have been studied using monoclonal antibodies on skin sections by two techniques: indirect immunofluorescence and immunoperoxidase. This study confirm: --that histiocytosis X express two specific antigens Ia and T6, --the relations between Langerhans cell and histiocytosis X. Especially, it suggests that histiocytosis X cell would be a dedifferentiated cell with receptors OKT4 and OKT10.

Adult↗
PubMed1983

[Rothmund-Thompson syndrome with glaucoma. Endocrine study].

Two cases of Rothmund-Thomson syndrome in siblings are described. The elder patient, whose case was best documented and who was followed for several years, had the characteristic skin changes of poikiloderma congenitale with small stature and mental deficiency. Upon ophthalmologic examination, this patient was shown to have bilateral glaucoma which was treated surgically, while the cataract typically found in Rothmund-Thomson syndrome was lacking. Primary hypogonadism was confirmed by endocrinologic investigations; anterior pituitary hormones were normally released. With reference to this observation differential diagnosis is discussed; the medical literature is reviewed.

Abnormalities, Multiple↗
PubMed1983

[Histiocytosis X with partial antehypophyseal deficiencies. 2 cases].

Diabetes insipidus is the most common endocrine disturbance associated with chronic multifocal form of histiocytosis X. Involvement of the hypothalamus can lead to growth hormone deficiency and short stature in children. Two cases with hypogonadism, growth hormone deficiency and diabetes insipidus are reported. In a 22-year-old man plasma testosterone was low and increased after administration of human chorionic gonadotrophin. Cutaneous and lytic bone lesions disappeared after treatment with Vinblastin. Partial diabetes insipidus was treated with clofibrate. A 59-year-old woman was found to have low pituitary gonadotrophins that failed to rise after administration of gonadotropin-releasing hormone and hyperprolactinemia. Fatal outcome was associated with polyuria, bone, cutaneous, gut and hypothalamic infiltration by histiocytes. There was no direct involvement of the anterior pituitary gland.

Adult↗
PubMed1983

[Wells' syndrome or eosinophilic cellulitis. Apropos of 2 cases. Review of the literature].

In 1971, four cases of a new dermatosis were described by Wells, under the name of recurrent granulomatous dermatitis with eosinophilia. In 1978, eight additional cases were reported by Wells and Smith and three authors suggested a shorter title: eosinophilic cellulitis for this syndrome. Since then, four additional cases were published in the literature. We report here two additional cases. From these eighteen upto now published cases, there is no doubt that this dermatosis, as initially described by Wells, is a distinct entity. Clinical course is characterized by sudden eruption of large infiltrated, itchy and/or painful plaques. Blisters are often associated. During the two or three weeks following the initial rash, the inflammatory aspect disappears. Lesions become indurated, and may resemble morphea. Spontaneous resolution occurs after about six weeks. Recurrences are constantly observed. Histologic features are a striking eosinophilic infiltrate associated with eosinophilic deposits constituting flame figures. Blood eosinophilia is present in most cases. Etiology of this entity remains unknown.

Adult↗