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Biomedical subjects

B Schaeffer

Publications and source records attributed to B Schaeffer.

11 recordsLinked to original sources

Prion infection-impaired functional blocks identified by proteomics enlighten the targets and the curing pathways of an anti-prion drug.

Prion-induced neurodegeneration results from multiple cellular alterations among which the accumulation of a modified form of the host protein PrP is but a hallmark. Drug treatments need understanding of underlying mechanisms. Proteomics allows getting a comprehensive view of perturbations leading to neuronal death. Heparan sulfate mimetics has proved to be efficient to clear scrapie protein in cultured cells and in animals. To investigate the mechanisms of drug attack, protein profiles of the neuronal cell line GT1 and its chronically Chandler strain infected counterpart were compared, either in steady state cultures or after a 4-day drug treatment. Differentially expressed proteins were associated into functional blocks relevant to neurodegenerative diseases. Protein structure repair and modification, proteolysis, cell shape and energy/oxidation players were affected by infection, in agreement with prion biology. Unexpectedly, novel affected blocks related to translation, nucleus structure and DNA replication were unravelled displaying commonalities with proliferative processes. The drug had a double action in infected cells by reversing protein levels back to normal in some blocks and by heightening survival functions in others. This study emphasizes the interest of a proteomic approach to unravel novel networks involved in prion infection and curing.

Animals↗

Ovine chorionic somatomammotrophin (oCS) production by isolated cotyledon cells from sheep in early and mid gestation: auto-regulation by recombinant oCS.

We report the ability of sheep placental cotyledonary cells, isolated at different periods of pregnancy (40 to 90 days) to produce ovine chorionic somatomammotrophin (oCS) in in vitro culture conditions. This oCS production increased gradually with stage of pregnancy. Endogenous oCS net production by isolated placental cells was increased, in a dose-dependent manner, by addition of recombinant oCS (roCS). This effect was not observed after addition of recombinant ovine growth hormone. The roCS effect was more potent on cells collected during early pregnancy. Specific immunoprecipitation of oCS revealed that roCS treatment was associated with an increased dose-dependent incorporation of [35S]methionine-[35S]cysteine. These findings provide evidence that oCS may act in a paracrine/autocrine manner to up-regulate its own production during early gestation. We suggest that this autoregulation may be associated with morphological and functional differentiation of the trophoblast during the growth of the placenta.

Animals↗

Hemostasis activation in patients undergoing brain tumor surgery.

Patients undergoing brain tumor surgery are at high risk for the occurrence of a thromboembolic event. To identify a laboratory marker suitable for risk estimation the authors studied the perioperative time pattern of routine coagulation parameters and the specific hemostasis activation marker D-dimer in 28 consecutive patients at high risk (11 patients with glioma and eight patients with meningioma) and low risk (nine patients with metastases) for thromboembolism, as previously reported. As is typical during major surgery, most of the routine parameters declined, probably because of hemodilution, and recovered postoperatively to values higher than baseline, probably because of an acute-phase reaction. On Days 2 and 7 after surgery no difference in the routine parameters was recorded between patients at high (meningioma and glioma) and low risk (metastasis). The level of D-dimer was elevated at baseline in patients with metastasis, indicating a hemostatic hyperactivity that is usual in cancer patients. During surgery a marked increase in D-dimer levels occurred in patients with meningioma and glioma (pre- and postoperative median 90/2000 and 100/1020 ng/ml, respectively), but the increase was less pronounced in patients with metastasis (320/660 ng/ml). Postoperatively, D-dimer declined in patients with metastases to lower than preoperative levels (Day 7, 270 ng/ml); in patients with meningioma or glioma, however, D-dimer levels remained elevated until Day 7 (450 and 200 ng/ml, respectively). These results indicate that levels of D-dimer correlate with the reported high risk for thromboembolism in patients with meningioma and glioma, and D-dimer should be evaluated for its use in estimating individual risk and the efficiency of its use in the control of prophylactic treatment.

Acute-Phase Reaction↗

Acquisition of imitative speech by schizophrenic children.

Two mute schizophrenic children were taught imitative speech within an operant conditioning framework. The training procedure consisted of a series of increasingly fine verbal discriminations; the children were rewarded for closer and closer reproductions of the attending adults' speech. We found that reward delivered contingent upon imitation was necessary for development of imitation. Furthermore, the newly established imitation was shown to have acquired rewarding properties for the children.

Child↗